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READ FIRST!!!!

To the Children:
So here are the notes we poured our blood, sweat, and tears into.
Couple of things:
1) Disclaimer: If there is anything in these files that offends you or anyone else, we dont apologize, well, because
you got it for free
2) Disclaimer: W e still dont know if a lot of the questions on these files are right or not. You will soon find in your
studies that some exact questions have different answers from different test years, so say a prayer and guess if
you get it on your test. So dont come tell us if you have found any errors or mistakes because, a) we dont care
anymore, and b) just fix it, make the files better, and help someone else benefit from your criticism.
3) Contents:
a. Entire 2004 dental decks, typed up, and searchable (Control F for those who have been living in a cave)
b. Every single question/answer from the USC CD will all the various test questions. All of these items will
be highlighted in green I believe they go up to 2002
c. Random remembered questions after 2002, but definitely not all and most are from 2003 to 2005. All of
these answers are listed in yellow highlights.
d. A ton of explanations from both Kaplan and USMLE First Aid books on a lot of the tough topics and topics
they constantly hit over and over again.
e. A ton of sweet images, charts, graphs, etc. courtesy of Google images, inc.
f. A bunch of comedic relief intermixed in the pneumonic devices that helped us on the test.

DENTAL ANATOMY AND OCCLUSION


***Look to the book for eruption sequence
***Make a chart w/ # of canals by tooth start w/ 77 Q 97
79a Q44 confirm w/ correct eruption sequence, 85 review Pullinger
80 Q90 Bennett shift
TOOTH COMPOSITION & DEVELOPMENT REVIEW
Basically everything is from Ectomesenchyme except for Enamel, which is from Ectoderm
A quick review of Odontogenesis
Initiation
Induction interaction between ectomesenchyme and epithelium
6th week
Formation of dental lamina
Bud Stage
Proliferation both dental lamina and underlying ectomesenchyme
8th week
Dental lamina into 10 buds per arch
Shape of tooth is evident
Enamel organ starts to form
Tooth buds of the Maxilla appear 1st!
Cap Stage
Proliferation and Differentiation
Morphodifferntiation change into other shapes
Histodifferentiation branch into different tissues
9-10th week
***NOW tooth germ is complete
Bell Stage
Differentiation of Odontoblasts
For the whom the BELL TOMES
Differentiation to its furthest extent resulting in 4 different cell types in the bell-shaped enamel organ (makes enamel
and Hertwigs root sheath)
OEE cuboidal
IEE columnar (Think I looks like a column)
Stellate reticulum network of star-shaped cells

Stratum intermedium flat to cuboidal


Dental papilla (makes dentin and dental pulp) differentiate into 2 layers
Outer cells
Central cells
Dental sac (makes Cementum, PDL, and alveolar bone proper) increases in collagen fibers
11-12 weeks
Remember enamel organ makes Enamel
Appositional Stage
Cells that were differentiated into specific tissue-forming cells begin to deposit the specific dental tissues (i.e. enamel,
dentin, cementum and pulp)
Maturation Stage
Mineralization begins at the DEJ and continues until total development accomplished, taking approximately 2 yrs to
complete
Enamel
Ectodermal Origin
4 Layers of Enamel Organ
Outer enamel epithelium
Outer cellular layer
Inner enamel epithelium (IEE)
Innermost layer
Cells will become ameloblasts
Essential for the initiation of dentin formation
*NOTE: In a developing tooth, the junction of the dental papilla and the IEE becomes the DEJ
Stratum Intermedium Think I is next to I
Lateral to inner enamel epithelium
Essential to enamel formation (nutrients for the ameloblasts of inner enamel epithelium) during calcification
Stellate Reticulum
Central core and fills bulk of organ
Contains lots of intercellular fluid (mucous type rich in albumin) which is lost prior to enamel deposition
After enamel formation, all 4 layers become 1 and form the Reduced Enamel Epithelium
What is the reduced enamel epithelium made from??? Attached epithelial cuff???
Very important in forming the dentogingival jxn, where the enamel and epithelium meet as tooth erupts
This forms initial junctional epithelium
96% inorganic, 1% organic, 3% water
Inorganic
Hydroxyapatite
Calcium and Phosphate
Fluoride and Zinc (Minor)
Optically clear
Organic
Protein rich in Proline
Brittle, but can endure 100,000 PSI of pressure
Yellow to grayish
Selectively permeable membrane (water and ions via osmosis)
Enamel Rods or Prism
Fundamental morphologic primary unit
Aligned perpendicularly to the DEJ (except in cervical regions of primaryteeth)
A chamfer or long bevel is commonly used as a gingival finish line in permanent tooth preparations because the
direction of the enamel rods in the region of the CEJ is such that the rods deviate from the horizontal in an apical
direction
The direction of enamel rods in primary teeth is inclined in an occlusal direction in the cervical 1/3 of the crown
The direction of enamel rods in permanent teeth in the cervical 3rd of crown is apically
512 million per crown
Rods increase in diameter as they flare outward Tails (from 48 microns)
Begin at the future cusp and spread down the cusp slope
Oldest enamel is at DEJ under cusp or Cingulum
Good thermal insulator
They represent the path of a single ameloblast from CEJ to surface
Hunter Schreger bands??
Alternating light and dark bands seen in enamel that begin at DEJ and end before they hit the surface

Represent areas of enamel rods cut in x-section dispersed between areas of rods cut longitudinally
Lines of Retzius
As ameloblasts retreat in incremental steps, they create artifact lines
Where these lines terminate, they form tiny valleys on tooth surface called perikymata
The small ridges, perikymata, seen on facial surfaces of canines, are the result of normal development
Perikymata are the result of normal enamel apposition
A Neonatal line exists where enamel was formed before and after birth
Found in both perm and prim
Enamel tufts
Fan-shaped, hypocalcified structures of enamel rods that project from the DEJ into the enamel proper
Unknown fxn
Enamel Spindles
Elongated Odontoblastic processes (hair-like) that transverse the DEJ from the underlying odontoblast
They are parallel to rods and hypocalcified and arise from DEJ
Tomes fibers
May serve as pain receptors
Tomes processes are from Enamel at the DEJ
Tomes Granular Layer is found in radicular dentin and lies just beneath the cementum, and distinguishes root
dentin from crown dentin
Enamel lamellae
Defects in the enamel resembling cracks or fractures which transverse the entire length of the crown from the surface
to the DEJ
Contain mostly organic material and may be carious
Perikymata and lamellae are seen on the surface of enamel, where Tufts are not
DEJ
Remnant of the onset of enamel formation from the junction of the dental papilla & IEE
Ameloblasts secrete enamel matrix as they retreat away from the DEJ, then matrix mineralizes
Odontoblasts begin dentin formation immediately before enamel formation, by laying down collagen matrix and then moving
from the DEJ inwards towards the pulp (newest dentin always closest to the pulp)
Area at which calcification begins
Morphology determined at Bell Stage
Dentin
Composition
70% inorganic, 20% organic, and 10% water
Test Q says 20-30% organic
Organic
Mostly of collagen fibers, Type I
Inorganic
More mineralized than cementum or bone, but less than enamel
Hardsoft: enameldentincementum
Calcium Hydroxyapatite
Main cell is odontoblast derived from ectomesenchyme
Avascular
More flexible than enamel
Forms the greatest amount of tooth structure
Fxn
Nutritive
Sensory
Protective
Along with pulp tissue, is formed by the dental papilla
Dentinogenesis
Steps
The ectomesenchyme influences the oral epi to grow down into the ectomesenchyme
Elongation of inner enamel epithelium and differentiation into ameloblasts
(making it columnar, but outer is still cuboidal)
This triggers the mesenchymal cells to differentiate into odontoblasts
Differentiation of Odontoblasts
Deposition of first layer of dentin
Deposition of first layer of enamel
*Deposition of root dentin and cementum
Mantle Dentin

Peripheral or first layer of dentin adjacent to enamel or cementum


Consists of more coarse fibers (Korffs) Think Dorff on Golf
Peritubular Dentin (Intratubular Dentin)
Lines each dentinal tubule
More mineralized than intertubular dentin
Intertubular Dentin
This is the main bulk of dentin
Surrounds peritubular dentin
Less mineralized
Interglobular Dentin
Imperfectly calcified matrix of dentin situated between the calcified globules near the periphery of the dentin
**Each tubule contains a cytoplasmic process (Tomes fiber) of an odontoblast
Dead tracts are tubules with dead cytoplasmic fibers in them
Primary dentin
Layed down before apical foramen closure
Dentin laid down before birth???
Secondary dentin
Formed after foramen closure
Slower forming than primary, as functional stresses are placed on tooth
Following the initial period of functional activity, an appreciable alteration in the size of the pulp chamber is a
direct result of deposition of secondary dentin
Regular and uniform layer
**There is a sharp change in the direction of tubules at junction of primary and secondary
The tubules of secondary dentin are wavy
Reparative dentin
What indicates Trauma during Dentin Formation????
Forms in response to stimuli produced by carious penetration of a tooth
Formed very rapidly in response to irritants like attrition, abrasion, erosion, caries, etc.
The tubules of reparative dentin are twisted
Sclerotic dentin
From aging and slowly advancing dental caries
Tubules become obliterated, which blocks access of irritants
All the following are seen dentin except
Tomes granular layer, Odontoblastic processes, Stria of retzius, and contour lines of Owen
Odontoblasts are mesenchymal origin
Cementum
Formed by cementoblasts from PDL, not from odontoblasts from pulp
Slightly softer and yellower
Most closely resembles bone, except no Haversian systems or blood vessels
Avascular, No innervation
Fxn
Compensates for tooth loss
Protects from resorption
Reparative fxn
50% Inorganic, 40% Organic, and 10% Water
Has the Highest Organic Content
Organic
Collagen and protein
More resistant to resorption than alveolar bone (permits ortho movement of teeth w/o resorption)
2 Types
Acellular
No cells
Coronal 2/3rds
Cellular
Contains cementoblasts, cememtocytes, fibroblasts from PDL and cementoclasts
Apical 1/3rd
Thickest to compensate for attritional wear of the occlusal/incisal surface and passive eruption
Cementoid
Peripheral layer of developing cementum that is not calicified
Pulp
From Dental Papilla

Vascular and noncalcified


Composition
Cells
Fibroblasts (Majority)
Q: What cell is most found in pulp of 62 year old?
Fibroblasts
Odontoblasts no cementoblasts or ameloblasts
Histiocytes fixed macrophages
Lymphocytes
Undifferentiated Mesenchymal cells (reparative fxn)
NOT Adipocytes
Loose CT (collagen and reticular fibers there are no elastic fibers in the pulp)
Blood vessels & nerves & lymph vessels
Blood flow is most like it is in the cranium
Ground Substance (water and long carbohydrate chains attached to protein backbones)
Large when tooth first erupts, then gets smaller (usually from progressive trauma)
The size of the pulp chambers of the maxillary first premolars usually decreases with age due to thermal shock; normal
physiological & masticatory functions; excessive attrition and abrasion
The size of the pulp cavity within a tooth is influenced by the age of the tooth, parafunctional activity of the tooth, &
history of the tooth (abrasion, erosion, caries, etc.)
NOT related to sex
NOT related to ability of Ameloblasts to form dentin (duh, they dont, odontoblasts do)
Function
The primary function of the dental pulp is to form dentin
Transmission of pain stimuli
Production of a defensive reaction when tooth is exposed to irritation
Does not cause formation of the mesenchyme of the dental papilla
Does not innervate the enamel
Pulp does not have function of pressure
Anatomy of the pulp
Central zone Pulp proper or Pulp Chamber)
Pulp chamber
The space occupied by the dental pulp w/in the tooth crown
The pulp chamber of a mature tooth contains
Blood vessels and nerves
NOT Odontoblasts or enamel lining
Lined peripherally by a specialized odontogenic area which has the following zones (inner to outer):
Pulpal Core similar to cell rich zone
Cell-rich zone contains fibroblasts
Cell-free zone of Weil capillary and nerve plexus (Plexus of Raschkow)
Think Cell Free of Weil has to be next to odontoblasts for Sensory (Hydrodynamic)
Odontoblastic layer contains odontoblasts and lies next to predentin and mature dentin
Pulp canals
Radicular pulp is continuous with tissues of the periapical area via the apical foramen
Accessory Pulp canals
May be found in the cervical third of the root
Contain nervous and vascular tissues
May be found in furcation areas of molars
Allow the pulp tissue to communicate with the PDL space
Pain
All stimuli to the pulp result in pain sensation (heat, cold, chemicals, touch)
Free nerve ending is only type of nerve in pulp, so regardless of source, you get pain
Contains both myelinated and unmyelinated nerve fibers
Myelinated sensory
Unmyelinated Motor (regulate size of vessel lumen)
NOT to concerned with speed here
Afferent and sympathetic
Proprioception is NOT found in pulp
Pulp capping
More successful in young teeth because:
Apical foramen is large
More cells

Very vascular
Less fibrous elements
More tissue fluid
BUT young pulp does lack a collateral circulation
Old pulp is more likely to have denticle or pulp stone
True denticle complete with tubule and processes
False denticle amorphous in structure no dentin structure
Free denticle unattached to outer pulpal wall
Attached denticle attached at dentin-pulp interface
TOOTH TERMINOLOGY
Clinical crown
Part that is visible in oral cavity occlusal to the gingival margins
Anatomic crown
Part that is covered by enamel coronal to the cervical line
A V-shaped incipient enamel extension coronoradicularly on a crown may be found in bifurcated areas of any
multirooted teeth and commonly on Eskimo teeth
May be smaller or larger than clinical crown
Larger than clinical crown in gingivitis
Smaller (shorter) than clinical crown in gingival recession
Occlusal surface
Chewing surface of posterior teeth
Incisal edge
Cutting of anterior
Point Angles (4)
3 come together
Line Angles
Anterior (6)
Not mesioincisal or distoincisal (because they are rounded)
Posterior (8)
Ridge
Any linear elevation on the surface of a tooth
Oblique Mx M1s (& primary Mx M2s)
Labial Canines
Buccal PMs
Cervical Primary teeth
Marginal All teeth
The ridge that extends from the distoincisal angle to the cingulum is the distal marginal ridge
Triangular Posterior teeth
Transverse Union of a L triangular ridge of a B cusp & a B triangular ridge of a L cusp
Marginal ridges
Marginal ridges on adjacent teeth are usually at the same height
Occlusocervically, the height of the mesial marginal ridge of a perm Mn M1 is the same as the height of the distal
marginal ridge of a Mn PM2
NOT at the same height on the Distal of Mn PM1 and Mesial of Mx PM2
When restoring the marginal ridges of posterior teeth, their shape should be
Rounded to help form occlusal embrasures and improve food flow (decreases food impaction)
Wide enough for strength and to provide an occlusal platform when there are opposing cusps
The following marginal ridges have little or no contact in centric & eccentric relationships:
Mesial of Mx canine(I think Distal of Mx Canine is not getting a contact from the Mn PM1)
Mesial of Mn PM1
Distal of Mn PM2?????
Developmental grooves (Primary)
Sharply defined, shallow, linear depressions
Separate lobes or cusps
Buccal/lingual grooves
Separate cusp ridges from marginal ridges see Brand book, p.174, for an illustration
Pits are at the junction
Supplemental grooves (Secondary)
Small, less distinct, irregularly placed grooves
Do not demarcate major divisional parts of a tooth
The groove that extends from the mesial pit of Mx PMs towards the the MB line angle is the MB secondary groove

Cusp
Elevation of mound of enamel
Mamelons (Sean thanks a lot)
Small, rounded projections on incisors
Indicative of malocclusion in teenagers & adults
Anterior open bite is likely in a 10-year-old pt
Usually 3 mamelons
Tubercle
Extra formation of enamel
Cusp of Carabelli (it is NOT formed by a lobe, but it is a tubercle)
What is the thing called between 2 cusp ridges on a cusp?? Tubercle? Only answer making any sense
Cingulum
Bulbous elevation of enamel, from a lingual lobe on anterior
12 cingula in a complete dentition
Lingual cusp of Mn PM1 similar to growth of Cingulum of a canine both done by lobes
Sulcus
Long depression or a V-shaped valley on occlusal surface of a posterior tooth between ridges and cusps
Fossa
Irregular depression or concavity
Lingual
Central
Triangular
Pits
Jxn of developmental grooves
Fissure
Narrow channel or crevice
Sometimes deep
Depth of developmental groove
Embrasures (4 per contact)
Generally speaking:
Contacting surfaces have Bigger embrasure
Mx ant L > F
Mn ant F > L the oddball
Posteriors L > F (except for between Mx M1 and M2 molars)
Where is the smallest embrasure???
Incisal embrasure of Mn centrals, then Incisal of Mx centrals
Buccal/Facial
Rounding of the mesiofacial & distofacial line angles contributes to the formation of facial embrasures
The deflective function of mesiofacial & distofacial line angles protects the facial part of the interdental papilla
Is the biggest embrasure of the PM1 and the canine is on the F or L I think????
Lingual
Posterior embrasures are generally larger on the L than on the F w/ the contact w/ in the facial moiety, except between
Mx M1 & M2
Occlusal/Incisal
The widest is found between Mx canine & PM1 (1979b)
The largest is found between Mx lateral & canine (with Mx canine & PM1 as an optionhmm) (1996)
Cervical
This is the interproximal space
The apex of the triangular-shaped boundary of the IP space is the contact area of the adjacent teeth
Fxns
Spillways
Self-cleansing
Protect
Stimulate tissue
The largest incisal embrasure is between Mx lateral & canine (because canine-PM1 embrasure is not an incisal embrasure)
Posterior embrasures are generally larger on the lingual than on the facial, with the contact area within the facial moiety,
EXCEPT between maxillary M1 & M2
Arch stability
Cusps, root forms, contact areas, & periodontal fibers all contribute to arch stability
NOT Embrasures
Other contributors: Facial & occlusal embrasure, and horizontal & vertical overlap
Lobes:
One of the primary sections of formation in the development of the crown of a tooth

Represented by a cusp in posterior and mamelons and cingula in anteriors


Separated by developmental grooves or developmental depressions in anteriors
The minimum number of lobes any tooth can develop from is 4
Anteriors
3 labial, 1 lingual
The perm Mx central incisor has 3 mamelons & 4 developmental lobes
Premolars
3 Buccal, 1 lingual
The lingual cusp of a Mx PM1 is formed entirely by the lingual lobe
Except for Mand 2nd PM (3 Buccal, 2 lingual)
1st Molars (Mn)
5 lobes (by each cusp)
2nd Molars (Mx M1)
4 lobes (cusp)
3rd Molars
At least 4 lobes (variations exist)
TOOTH ERUPTION
Eruption
The movement of the tooth through the surrounding tissue so that the clinical crown gradually appears longer
NOT Exfoliation (Dont get clowned)
Tooth makes its appearance in the mouth when one-half of the root is completed
3 Stages of Dentition
Primary Dentition (6 ms to 6 yrs)
Mixed Dentition (6 yrs to 12 yrs)
Commences with the 1st Perm Molars
Permanent Dentition (12 yrs+)
Permanent Dental Formula
I 2/2 C1/1 B2/2 M3/3 = 16 x 2 = 32
An imaginary animal (I 2/2 C1/1 M2/2) has the same # of anterior teeth as are found in a humans permanent dentition
Deciduous Dental Formula
I 2/2 C1/1 M2/2 = 10 x 2 = 20
Succedaneous teeth
Centrals to 2nd PMs
When extracting a primary Mx incisor in which the root has been partially resorbed due to pressure from its developing
succedaneous tooth, the buccal aspect will usually be longest & attached most securely to the gingiva
The first evidence of root resorption on a primary incisor is seen on the lingual root surface
Primary Teeth
All 20 primary teeth in utero
Begin to form about 6 weeks in utero
Begin to calcify about 4-6 months in utero
Primary teeth show calcification in utero during the 2nd trimester
1st and 2nd molars show calcification during 5-6 months and completed by 3yrs
Primary roots are completed
14 months after emergence for Mn
Mn teeth erupt from 6-7 months to 20 months
15 months after emergence for Mx
Mx teeth erupt from 7 months to 24 months
Calcification of the roots is normally completed by 3-4 yrs old
Remember last tooth comes in at 24 months Primary Mx M2
At 1.5 yrs, roots are completed for Mn centrals and laterals and Mx Centrals???
Primary Calcification Initiation Sequence
Mx
(in weeks)
Centrals
14
Laterals
16
Canines
17
M1
15.5
M2
19
Mn
(in weeks)
Centrals
14
Laterals
16

Canines
17
M1
15.5
M2
18
Hypoplasia of primary teeth limited to the incisal thirds of incisors, incisal tips of canines, and occlusal portion of molars
indicates a metabolic disturbance during the prenatal period
If a women took tetracycline during the second trimester, what teeth would be affected???? (Week 13-27)
Primary teeth ONLY
Note Tetracycline affects teeth erupting 1-2 years after taking it
Eruption Sequence
Primary Eruption Sequence From the Tooth Bible
Mn central (6)
Mn laterals (7)
Mx central (7.5)
Mx lateral (9)
Mn M1 (12)
1 yr, you should have 10 teethUnless youre a girl then @13 months youll have 12 teeth!!!
Mx M1 (14)
Mn canine (16)
Mx canine (19)
Mn M2 (20)
Mx M2 (24)
Deciduous eruption sequence: Central, Lateral, M1, Canine, M2
The last primary tooth to erupt is the Mx M2
Also last to start and finish calcifying
The first primary teeth to erupt are the Mn R & L central incisors
At 1 year, a child is expected to have erupted prim Mx & Mn incisors & M1s
A parent notices a new primary tooth at 12 months, most likely a Mn M1 (12 month Molar)
Prim M2s are expected to erupt shortly after the childs 2nd birthday
Last anterior tooth to calcify
Most dramatic change to the Oral Flora occurs when primary teeth erupt
Exfoliation sequence for Primary Teeth
Centrals
6-8 yrs
Laterals
7-9 yrs
1st Molars
10-12 yrs
Canines
9-12 yrs (10-11 for Mx canine was the correct answer option)
2nd Molars
10-12 yrs
Primate Space
Occur in deciduous dentition
Mx: space between laterals & canines
Mn: space between canines & M1s
NOTE: Spacing always occurs, but these are most noticeable
The perm dentition differs from primary in that primary teeth develop arch diastemata
Occur in 50% of children
Spacing between anterior teeth in the dentition is most frequently caused by growth of the dental arches
Permanent teeth
Begin to form at 4 months in utero
Calcification Initiation Sequence
Mx
M1
Birth
Centrals
3-4 months
Canines
4-5 months
Laterals
10-12 months
The Last Permanent Anterior Tooth of the Mx to initiate calcification is the Lateral @10 months
PM1
18-21 months
PM2
2-2.5 years
M2
2.5-3 years
M3
7-9 years
Mn
M1
Birth
Centrals
3-4 months

Laterals
3-4 months
Canines
4-5 months
Dont get clowned, here its the Canine as the last anterior to initiate calcification
PM1
21-24 months
PM2
2-2.5 years
M2
2.5-3 years
M3
8-10 years
Mx & Mn M1s begin to calcify at birth
In development of the human permanent dentition, the first teeth to begin calcification are the Mn M1s
Initiation of calcification for the mandibular central incisors is 3-4 months
The incisal ridge is the 1st structure to begin to calcify in an anterior tooth
Perm M3s begin to calcify at 8-10 yrs of age
Active eruption of teeth occurs after of the root is formed (perm or primary)
50% of root calcification is complete at the time of eruption
The apex is usually fully developed by 2-3 years after eruption
Permanent Dentition Eruption Schedule
Permanent Dentition
Typical
Eruption
Age (yrs)
6
6
6
7
7
8
10
10
10
11
11
11
12
12
20
20

Range
6 to 7
6 to 7
6 to 7
7 to 8
7 to 8
8 to 9
9 to 10
10 to 12
10 to 12
10 to 12
10 to 12
11 to 12
11 to 13
12 to 13
17 to 21
17 to 21

Maxillary

Mandibular
1st molar

1st molar
central incisor
central incisor
lateral incisor
lateral incisor
Canine
1st premolar
1st premolar
2nd premolar
2nd premolar
canine
2nd molar
2nd molar
3rd molar
3rd molar

Calcification
Birth
Birth
3-4 mos
3-4 mos
3-4 mos
10 months
4-5 mos
1.75-2 yrs
1.5-1.75 yrs
2.25-2.5 yrs
2-2.5 yrs
4-5 mos
2.5-3 yrs
2.5 yrs
8-10 yrs
7-8 yrs

Root
Completion
9-10 yrs
9-10 yrs
9 yrs
10 yrs
10 yrs
11 yrs
12-14 yrs
12-13 yrs
12-13 yrs
13-14 yrs
12-14 yrs
13-15 yrs
14-15 yrs
14-16 yrs
18-25 yrs
18-25 yrs

Enamel
Completion
2.5-3 yrs
3-4 yrs
4-5 yrs
4-5 yrs
4-5 yrs
4-5 yrs
6-7 yrs
5-6 yrs
5-6 yrs
6-7 yrs
6-7 yrs
6-7 yrs
7-8 yrs
7-8 yrs
12-16 yrs
12-16 yrs

CRAP: The third pair of perm teeth to erupt in normal sequence is Mn lateral incisors (1996 Q53)???
UNLESS, they asked for 3rd pair of succedaneous!!!
(Looks like 5th pair to me, unless you go by molars centrals laterals, in which case, why specify Mn laterals?)
1st succedaneous to erupt is the Mn central incisor at 6-7 yrs old (dont get clowned Mn M1 is not succedaneous)
Permanent max centrals erupt just after at 7-8 yrs
Permanent max laterats erupt at 8-9 yrs
6 yr old
Presents with all 20 primary and 4 perm 1st molars
First sign of mixed dentition
Mn Molars at age 6
Ordinarily, a 6-year-old would have the following teeth clinically visible:
All primary teeth & permanent M1s
7 yr old (another Q said 6 year old)
Presents with 18 primary and 6 perm teeth
4 perm molars
2 mand perm central incisors
On a panoramic radiograph of a 7-year-old, the dentist will expect to see all of the following:
Primary Mx laterals w/ partially resorbed roots
Partially erupted Mx centrals w/ incomplete root closure at the apex
Partially erupted Mn laterals w/ incomplete root closure at the apex

10

Fully erupted Mn M1s w/ incomplete root formation & non-closure at the apex
Not fully erupted Mn centrals w/ complete root formation and closure at the apex (it takes 2-3 years)
At 8 years of age
The teeth normally present are perm central & lateral incisors, primary canines & molars, permanent first molars
The Perm Mx M1 has no distal contact (it does have a mesial contact with the primary Mx M2)
At 9 years of age,
12 primary teeth remain in the mouth (Primary C9 and 2 Molars per quadrant)
At 10 years of age
The perm teeth expected are central & lateral incisors, first premolars, and first molars (What about Mn Canines??)
One would expect the root of the perm M1s to be finished forming & calcifying
One would expect primary tooth H (primary Mx canine) to be mobile due to the erupting succedaneous tooth
BAD Q, hope you dont get it
CAREFUL, because J was also an option, which is the PM2 coming in to replace Primary M2
The first perm tooth to erupt is generally the Mn M1
The earliest indication of a mixed dentition consists of the primary dentition and the Mn M1s
The earliest indication is NOT the exfoliation of any primary tooth
The last perm incisors to erupt are the Mx laterals
Perm PM1 replaces primary M1
The earliest age by which the roots of the Mx PM1 are completely formed is 12-13 years
Typically eruption is 10, then 2-3 years for root completion
At age 26, the third molars are fully erupted with a complete root structure
The perm Mn arch is the only arch (prim or perm) in which the canine erupts before the tooth immediately distal to it
In Primary, Remember M1 is the distal tooth and it erupts at 12 months!!!!, canines in Mn at 16, Mx at 19 months
3 Cardinal Eruption Rules:
1) Girls teeth erupt BEFORE Boys
2) Mn erupt BEFORE Mx
3) Teeth of slender kids erupt BEFORE fat kids, (so much to get through)
Teeth usually erupt in pairs one on the left & one on the right
The follicles of the developing permanent incisors are in a position lingual to the deciduous roots
Eruption problems:
In cases of delayed resorption of primary incisors, the permanent incisors may be expected to erupt lingual to the normal arch
form

11

DENTAL ANOMALIES (new section ) see Ch 7 of book


Dens in dente
Occurs when enamel becomes invaginated
Most commonly found in permanent lateral and central incisors
Known for giving endo like symptoms, but no decay on crown, etc.
Retarded growth of a portion of a single tooth germ, or the proliferation of a segment of the odontogenic epithelium in
the dental papilla
Mesiodens
Supernumerary teeth arising in the midline of the maxillae (most common supernumerary)
A small, calcified radiopaque mass between the roots of #8 & #9 is most likely due a mesiodens
Tooth appears mesial to both Mx central incisors
Concrescence
The cemental union of two fully formed teeth that were originally separate entities
Can be mistaken for Subgingival calculus
Fusion

12

Union of 2 adjacent tooth buds


Upon examination, the dentist notices that there is an abnormally wide Mn incisor; further examination reveals that there are
only 3 Mn incisors present; most likely due to fusion
Gemination
Incomplete splitting of a single tooth germ
A pt has an extremely wide, notched tooth in the Mn incisor position; clinical & radiographic exam reveals 28 teeth have
erupted (4 M3s unerupted); most likely due to gemination
MISCELLANEOUS
Radiographically
Anterior Palatine Foramen
Radiolucent and circular in shape
Waxing
Must Consider
Guiding (non-supporting) cusps are related to the Interproximal areas or developmental grooves
Supporting cusps are related to the marginal ridge and fossae
Supporting cusps are aligned with supporting cups of the same quadrant
Guiding (non-supporting) cusps overlap facial to mandibular teeth and lingual to maxillary teeth
Attrition
Facets usually develop on
Linguoincisal of Mx centrals
Facioincisal of Mn canines
Attrition on a Mn Canine, what would the Mesial ridge look like?? M ridge would be shorter than D
Attrition of a Mx Canine, what would the Mesial ridge look like?? M ridge would be longer
Linguoincisal of Mx canines
Incisal edges of Mn laterals is done with Mx central AND lateral incisors, NOT Canines
Pt with Normal Class I, has wear facets on inner aspect of facial cusp of Mx PM2, these can only be caused by Mn PM2
LEAST likely spot for attrition is labioincisal area of Mx lateral incisor
Anodontia
Complete (usually with Ectodermal Dysplasia)
Partial
Usually 3rds (Max more) >Max laterals >Mand 2nd PMs
Rule: if only one or a few teeth are missing, the absent tooth will be the most distal (if molar, then 3 rd)
So if a premolar were missing, which primary tooth would most likely remain?
Mand. 2 molar
Oligodontia
Many, but not all teeth
A developmental abnormality characterized by the presence of fewer than the usual number of teeth
Hypodontia
Few gone
Old school classifications
Heterodont Human teeth, or several kinds of teeth, serving a variety of fxns
Diphyodont To produce 2 sets of teeth (perm/prim)
Monophyodont 1 set of teeth
Polyphyodont Teeth being replaced continually (amphibians)
Homodont teeth are all alike
A typical nonpoisonous reptile is a homodont (What a lame question!)
Hypsodont long teeth (High crowned)
Haplodont a primitive basic tooth form having a single conical crown and a single root
Selenodontic Longitudinal Mesiodistal Ridge formation (Grazing animals, along with Hypsodontic)
Teratogens affecting Dentofacial Development
Worse during first trimester
Teratogen
Effect
ASA, Valium, Dilantin, Cigarettes
Cleft Lip and Palate
CMV, Toxoplasma
Microcephaly, Hydrocephaly, Microphthalmia
Ethyl Alcohol
FAS Central mid-face discrepancy
Rubella Virus
Microphthalmia, Cataracts, Deafness
X-radiation
Microcephaly
Vitamin D excess
Premature suture closure
Dental hypoplasia
If it occurs, it will be present when the teeth erupt
Tetracycline staining

13

A 5-year-old child is treated with large doses of tetracycline over a one year period. The perm teeth least likely to show
staining are lateral incisors, canines, and premolars. Perm centrals & M1s are more likely to stain.
Kaplan gives this explanation: Since the child is 5 years old, the teeth erupting at 6 or 7 will be MOST likely to show
staining, and those erupting later are less likely. On average, centrals erupt at 7, laterals at 8, canines at 11, PM1s at 9,
and M1s at 6.
So most likely stains teeth erupting 1-2 years after tetracycline usage
Hypercementosis
Excessive calcified tissue formation at the root apices
Ankylosis
Fusion of the alveolar bone to a tooth
Also when different tooth obstructs
Dentin Islands
Most common in Mx 2nd PM and in Mn Canine
Caries/Dental decay
Areas susceptible to caries include pits & fissures, Facial surfaces cervical to the height of contour (Cervical Thirds), &
proximal surfaces
On molars, the L of Mx M1s & B of Mn M1s are most likely to develop caries (due to those fissured grooves)
Least likely to occur on cusp tips
Mandibular canine is most likely to resist invasion by caries
Periodontal Disease
The following morphologic variations tend to accelerate existing periodontal disease
Enamel projections, fused roots, and excessively short roots
Malpositioned teeth
If a Mn PM2 is linguoverted, there is an area of overcontour affecting the lingual gingival sulcus
Linguoversion means the tooth is lingual to the normal position
Supraeruption
Tendency of teeth to erupt into an empty space; tends to follow extraction of opposing teeth
An extruded Mn R M3 (Mx M3 extracted) will most often impede a protrusive Mn movement
Anterior open bite
More common in African Americans
Can be caused by thumb sucking
Protrusion of max incisors
Constriction of max arch
Lingual inclination of mand incisors
Rotation of max laterals
Class II Malocclusions
Can be caused by abnormal swallowing (tongue Thrust)
Can be caused by mouth breathing
Presents with facial gingival of Max bleeding, edematous, and red
Midline affected the most
Mx arch is slightly longer than Mn
Mx diameter is 128mm
Mn diameter is 126mm
Nerves:
3rd1st molars innervated by PSA nerve (from V2)
1st molarPMs innervated by MSA nerve (V2)
Canines & incisors innervated by the ASA (V2)
A branch of the cranial nerve V to the tongue may be anesthetized during administration of an IA block (think sensory CN
V) -- the Lingual Nerve
Dryopithecus pattern
shows up most clearly in the mandibular first molar
Its the name of the ape they think we descended from, blah, blah
Maxillary Molar of early Primate
Had a trigon made up of 3 cusp MB, ML, DB
Heart shaped/triangular
Rodents (Rodentia)
Mammalian order with continuously erupting teeth in which apices never form
How many times do we swallow in one day?
2,000 times a day
When does a person swallow the most??
Daytime, when theyre NOT eating
PRIMARY TEETH (look at pictures)

14

Primary vs. Permanent Teeth


Fewer molars (2 vs. 3) and no premolars
Primary teeth have proportionately larger pulp cavities than perm teeth
Distinguished by long, pointed pulp horns
Crowns of primary incisors are shorter incisocervically compared with MD dimension
Roots:
Roots of anteriors taper more rapidly
Are comparatively longer & slimmer than perm teeth
Are more divergent than perm teeth
Root trunks are less pronounced than perm teeth
Enamel ends abruptly
Are whiter than perm teeth
Are smaller than perm teeth
Crown : root Ratio is smaller than perm teeth meaning they have longer roots
Crowns are more bulbous & constricted than perm teeth appear shorter & fatter than perm teeth
Cervical ridges are more pronounced than perm teeth large facial buldge
No mamelons on primary teeth
Primary arch is more circular than the perm arch
Smoother occlusally (fewer pit/fissures)
Narrower occlusal table
1mm enamel (uniform thickness) on occlusal surface vs. 2.5mm of perm teeth
B and L surfaces are flatter than perm teeth (occlusal to the cervical ridge)
Leeway Space
The MD widths of the primary molars in any quadrant are greater than their perm successors (PMs) (by 2-4mm)
With respect to their permanent successors, the sum of the MD diameters of the deciduous M1 & M2 is generally
greater
All Prim Molars
Differ the most from the perm teeth that replace them (among molars, canines, lateral incisors, central incisors)
Lack an identifiable root trunk
All Prim 1st Molars
Cusps:
In Max Teeth
Prim MB > ML
Perm ML > MB
In Mn Teeth
Prim ML > MB
Perm MB > ML
Dont get clowned They are opposites in Primary vs. Permanent
Distal surface is shorter than the mesial, occlusogingivally
Has a transverse ridge
Prominent mesial marginal ridge
Prominent MB cervical ridge
Present with the greatest morphologic deviations from permanent teeth (especially Mn M1)
All Prim 2nd Molars
Larger than M1s & resemble perm M1s
Show up after childs 2nd Birthday (20 months Mn, and 24 n=months Mx)
Individual Primary Teeth
Prim Mx Central
Shapes
M/D view =
B/L view =
Occlusal =
MD dimension is wider than incisocervical dimension
Wider MD & shorter incisocervically than perm
Straighter incisal edge: SHARPER, more angled incisal edge
NO mamelons (same with laterals)
Prominent labial AND lingual cervical ridges!!!!! (This Q gave teeth A, F, J, L, & T I got clowned by L Mn M1)
Most damaged (with Mx laterals) by baby bottle tooth decay
Prim Mn Central
Shapes
M/D view =

15

B/L view =
Occlusal =
Prominent cingulum
Often has a developmental groove on distal of root
Has the smallest FL dimension of any crown
Prim Mx Canine
Shapes
M/D view =
B/L view = Pentagon
Occlusal =
4 lobes
3 facial, and 1 on the lingual
Widest primary anterior tooth
Appears wider and shorter than perm
Crown height is less than MD diameter
Diamond-shaped crown from facial aspect (Kaplan differs from the pentagonal outline mentioned above)???
Prominent cingulum
Cusp is much longer & sharper than perm canine
Cusp points distally
ODD BALL -- Mesial cusp ridge is longer than distal cusp ridge (opposite for perm Mx canines)
Opposite of what you think for Perm canines and Prim Mn Canines
Pulp chamber looks pointed at incisal tip
Prim Mn Canine
Shapes
M/D view =
B/L view = Arrow-shaped from the facial
Occlusal =
Smooth labial surface
Longer distal incisal ridge than mesial incisal ridge
Prim Max 1st Molar
Shapes
M/D view =
B/L view =
Occlusal = trapezoidal (peripheral); rectangular (table)
*Most atypical of all Mx molars*
Intermediate form between PM and Molar
Crown somewhat resembles a perm PM, but the root form is typical of a perm Molar
Of primary molars, prim Mx M1 bears the greatest resemblance to a perm PM
One Q gives resemblance to Mx PM2 as the correct answer
Smallest prim molar
Bicuspid (2 main cusps = MB & ML, 2 indistinct distals)
MB cusp > ML cusp
Cervical ridge in the MB area most prominent cervical ridge among primary Mx teeth!!!!!
The mesial surface is larger than the distal surface
From a facial view, BOTH Primary Mx M1 and M2 have a short root trunk
The cervical line on the mesial curves slightly toward the occlusal it does not have a straight cervical line
H-shaped occlusal pit-groove area
3 Roots (root structure corresponds to that of perm Mx M1)
Number and form of the roots corresponds to Mx M1
Short root trunk
Does the Prim Mx M1 has a lingual groove???
NO!!!

Prim Max 2nd molar


Shapes
M/D view =
B/L view =
Occlusal =

16

Right

Same characteristics as perm Mx M1 except:


MB cusp is almost same size as ML
MB pulp horn is longest and largest
Normally has a Cusp of Carabelli, just like Perm Mx M1
Most likely primary tooth to have an oblique ridge (looks like perm Mx M1)
Has the greatest FL dimension of all primary teeth!!!!!
The difference between Primary Mx M2 and Permanent Mx M1 is that the primary tooth has a much narrower
measurement at the CEJ compared to its contact area
They are similar in that both crowns converge to the distal and lingual
NOT that they both have well developed 4 cusps, oblique ridges, well developed marginal ridges, or rectangular outline
From a facial view, BOTH Primary Mx M1 and M2 have a short root trunk
Last Primary tooth to erupt
This is the primary molar that typically has a transverse ridge, oblique ridge, & a DL groove
3 Roots
Short root trunk
Primary Mx M2, roots are less curved than Permanent Mx M1

Right
Prim Mand 1st Molar
Shapes
M/D view =
B/L view =
Occlusal = Rhomboidal peripheral outline; Rectangular table (if you disregard the large MB ridge)
Unlike any other tooth
Both Prim Mn M1 and M2 have central and lingual grooves
Most normally exhibits a Distal Triangular Fossa
Based on morphology, a Class II MO prep would be the most difficult on a primary Mn M1 (of any teeth)
Because of HUGE MB pulp horn!!
4 cusps = 4 pulp horns (dont be thinking that it has 5 just because a Mn M1 has 5)
ML cusp is highest & sharpest!!!!!
MB and ML make up transverse ridge
Oval with MB expansion
Cervical ridge/Bulge in the MB area
Which primary tooth has a facial cervical ridge which is so distinctly prominent that it is uniquely different from ALL
other teeth? Primary Mn M1!!!!!
The CEJ is most apically positioned on the mesial 1/3 of the crown of a primary Mn M1
S Shaped cervical ridge
The Distal portion is shortest occlusogingivally
A prominent transverse ridge distinctly separates the mesial portion from the remainder of the occlusal table!!!!!
Roots
2

Left
Prim Mand 2nd molar
Shapes
M/D view =
B/L view =
Occlusal =
Closely resembles a perm Mn M1 occlusally
Same characteristics as perm Mn M1 except:
Has a more prominent facial cervical ridge
MB, DB, and D cusps of prim Mn M2 are about same size
The easiest way to distinguish between primary Mn M2 & perm Mn M1 is comparative size of D cusps
Not the widest in the cervical like the perm Mn M1 (primary teeth are constricted)
Has 3 occlusal fossae, like a perm Mn M1

17

5 cusps does not have 4 cusps (dont get clowned)


All 3 buccal cusps are the same size (unlike perm M1)

PERMANENT TEETH
All Teeth:
CEJ (cervical line) curvature is greater on mesial than distal side
Facial height of contour is in cervical third
The only thing that all teeth have is M/D marginal ridges
Some All Rule, w/ exceptions:
All teeth have a M and a D marginal ridge
All teeth are wider FL than MD except:
Mx centrals & laterals
Mn molars
Tilt:
All teeth tilt facially EXCEPT Mn PM2 & Mn Ms (tilt lingually)
Mn PM1 is Straight up and down
All teeth tilt mesially EXCEPT Mx centrals & Mn centrals & laterals (ever so slightly tilted distally)
Mx canine has greatest tilt; PMs are the straightest
All Anterior Teeth:
Incisal edge or 1 cusp
Cingulum & lingual fossae 12 teeth have cingula (per dentition i.e. primary/permanent)
Cingula centered mesiodistally on: Mx lateral, Mx canine, Mn central
Cingula off-centered to the distal on: Mx central, Mn lateral, Mn canine
Both Facial and Lingual height of contour are in the Cervical 1/3 rd
Marginal ridges parallel to long axis
1 root
Triangular outline viewed from M or D (wedge-shaped from M or D aspect)
Trapezoidal outline viewed from B or L (longest uneven side toward the occlusal or incisal)
Contacts are centered faciolingually
Usually mesial edge is sharper than distal (Distal is rounded like letter D & Mesial is pointy like the letter M)
The incisal edges & incisal thirds of F surfaces of Mn anteriors generally oppose L surfaces of Mx anteriors w/in the incisal
thirds
Viewed from the sagittal plane and progressing anteriorly, the axial inclination of the anterior teeth inclines facially
All Posterior Teeth:
2 or more cusps
Occlusal table with ridges & grooves
Occlusal table makes up 55-65% of the BL dimension of the tooth
Marginal ridges perpendicular to long axis of the tooth
Facial height of contour in cervical third
Maybe except for Mandibular Molars which have them at the jxn of cervical and middle
Lingual height of contour in middle third
Except for the Mn PM2s, which have their height of contour in the occlusal 1/3 rd
Mesial marginal ridge more occlusal than distal except for Mn PM1s
Contacts in middle 1/3
Contacts in the Faciolingual direction are located in the Buccal side of the center
Are mesially inclined
All posterior teeth have rectangular occlusal tables, EXCEPT PM1s, which have trapezoidal occlusal tables
This is NOT the same as Occlusal outline (aka crown profile) see Kaplan p.549
All Maxillary Posterior Teeth:
Wider BL than MD
1st is larger than 2nd (& also 2nd larger than 3rd for molars)
Trapezoidal outline viewed from M or D (shortest, uneven side is towards the occlusal)
The B cusps of the Mx arch are B to the B cusps of the Mn arch
From a frontal plane view, axial inclination of Mx teeth is Buccally

18

Are progressively more buccally inclined as one moves posteriorly


From a frontal view, the plane of occlusion of the Mn arch is a concave curve
If a root goes into Mx sinus, it is usually from Mx M1
A more recent Q: The structure in the Mx alveolar bone that Mx premolar roots occasionally penetrate is the antrum (aka
maxillary sinus)
All Mandibular Posterior Teeth:
Lingual inclination of buccal surface
Rhomboidal outline viewed from M or D has a design flaw that encourages cusp fracture
Kaplan says: Because the crown is rhomboidal, the L surface leans lingually. The overhanging L cusp is not well
supported by underlying tooth structure and has a higher tendency to fracture.
Facial cusps of Mn posteriors oppose the central fossa line in the Mx dentition
IN a sagittal view, both anterior (yes, anterior) & posterior teeth are mesially inclined (other options were wrong 02Q44)
All Incisors:
Incisal edge
Marginal ridges run parallel to long axis of tooth
M & D contact areas are approximately centered faciolingually
Are 1st succedaneous teeth to erupt
Viewed incisally, the cingulum, lingual fossa, marginal ridges, & mesiofacial developmental depression are visible (not CEJ)
On the crown, the facial developmental depressions separate the labial lobes
All Maxillary Incisors:
Mesioincisal edge is sharp
Distoincisal edge is rounder
Distinguish Mx incisors from Mn incisors
Both larger than Mn incisors
Central is larger than lateral except root length which could be quite similar
Cervical line is greatest of all teeth on mesial side of max. centrals
Incisal edge is centered labiolingually
Embrasures: L > F
Have distinct lingual anatomy & may contain pits
Both Mx centrals & laterals are wider MD than LL
Mx incisor roots more frequently contain a single root canal than Mn incisors, Mx PM1s, Mx Ms (MB root), Mn Ms (M root)
Roots are more rounded than on Mn incisors
All Mandibular Incisors:
Laterals are larger than centrals; Centrals are smallest of all teeth
Incisal edges are lingual to root axis line (Lingual to the LL midpoint)
Indistinct cingula w/o grooves and pits
Smooth, continous convexity incisoapically
Wider LL than MD
Embrasures: F > L
Alveolar process is thinnest facial to Mn central incisors (good for infiltration injection)
In anesthesia of the Mn arch, local infiltration is likely to be effective in the incisor area
Proximal Contact
Contact occurs in the incisal third
Tends to occur equidistant from facial and lingual surfaces
All Canines:
1 cusp
Longest tooth in the mouth
Favorable crown-to-root ratio
Crown very bulky labiolingually
Transitional form between anterior & posterior teeth (mesial like incisors & distal like premolars)
Longevity (know why)
Labial ridge, developmental depressions, mesial & distal cusp slopes or ridges
The slight incisocervical concavity on the labial crown surface of the canines that is found in the incisal third, just mesial
to the labial ridge (whew!) is the mesiolabial developmental depression
Mesioincisal ridge shorter than distoincisal ridge
Lingual ridge
Viewed from the incisal, one expects to see:
Cingulum
Lingual fossa

19

Distal cusp ridge


Mesiofacial developmental depression (Labial Side)
Not the cervical line
Mesial contact is more incisal than distal contact
Crown form from labial aspect is pentagonal
Root has triangular cross section
Only cusped teeth which feature functional lingual surface rather than a functional occlusal surface
All Premolars:
1 buccal cusp
1 or 2 lingual cusps
Transitional between canines and molars in function
Enamel is thickest in the occlusal third
Have their long axis most perpendicular to the horizontal plane Mx & Mn PMs are the most nearly vertically aligned teeth
The union of the F & L triangular ridges forms a transverse ridge
All Maxillary Premolars:
B & L cusps of nearly EQUAL heights (but on Mx PM1, the B cusp is slightly larger)
The L cusp tip is located more mesially than the B cusp tip
Wider BL than MD (wider BL than Mn PMs, although MD dimension of all PMs is about the same)
Trapezoidal outline viewed from M or D
From occlusal view, more rectangle
Lingual height of contour is ~ midway between the CEJ & the L cusp tip (Dumb way of saying Middle 1/3rd)
1st is larger than 2nd
Roots are more flattened MD than Mn PMs
Roots have mesial concavities
In development, Mx PMs show crown completion at the same time
All Mandibular Premolars:
Large buccal cusp & very small lingual cusp(s)
Nearly equal MD & BL
1st PM is smaller than 2nd PM
From proximal view, crown tilts lingually in relation to the long axis of the tooth
Occlusal table is lingually displaced (Mx PM table is centered FL)
Rhomboid when viewed from the interproximal
Mn PM B cusps are more toward the FL midpoint than are Mx PM B cusps
From occlusal view, more square
Mn PMs compared to Mx PMs:
Mn have more rounded roots and seldom bifurcated
Mn crowns are tilted to the lingual
Have crowns much more rounded
Mn have less developed lingual cusps
In development, crown completion of Mn PM1 is 5-6 years; for Mn PM2, crown completion at 6-7 years
All Molars:
Largest and strongest teeth
At least 2 buccal cusps
1st, 2nd, 3rd, 6 year, 12 year, and wisdom tooth respectively
3 to 5 cusps
2 or 3 roots
Are NOT Succadaneous
DL cusp gets smaller as you go posterior in the arch
Root canals usually join the pulp chamber apical to the CEJ
3 Root Types:
Single or 1 Root
Incisors
Canines
Max 2nd PM
Mand PMs
Bifurcating or 2 Roots
Max 1st PM (B/P)
Mand Molars (M/D)

20

Trifurcating or 3 Roots
Mx M1s & M2s (MB, DB, P)
Some M3s
All Maxillary Molars:
Wider BL than MD
Usually 4 cusps; ML > MB > DB > DL
2 lingual cusps of different size (again, ML > DL)
Oblique ridge extends between the ML & DB cusps
Formed by the union of distal cusp ridge of the ML cusp & the triangular ridge of the DB cusp
The transverse groove of the oblique ridge connects central & distal pits
The ridges that make up the oblique ridge meet near the center of the occlusal surface on a level w/ the marginal ridges
Slides through the angled sulcus (DB) found on the occlusal surface of Mn Molars
The three cusps that form the primary cusp triangle on a Mx molar are the MB, DB, & ML (not DL or Cusp of Carabelli)
Crowns are either rhomboidal or heart shaped
>Rhomboidal when viewed occlusal
The crown portion that differs the most in contour and size is the distolingual
Their arrangement and design allow room for the powerful masseter muscle
Distolingual Developmental Groove
Fissured groove usually exists on L of Max Molars prone to caries
As such, cavity preparations would most frequently have to be extended from the occlusal to the L of Mx
molars
(more so than to the B of Mn molars dont get clowned)
3 roots (P, MB, DB)
Root length: P > MB > DB
All Mx roots are inclined distally & lingually EXCEPT the DB root of Mx M1 (inclined bucally)
Floor of pulp chamber is triangular (DB, MB, P)
The line connecting the MB and P is the longest
Apex is formed by the P canal
Considering the formation of root and pulp canals, the root canal instrument would be placed from the MB to DB in an
apical direction to gain access to the DB root of the perm Mx M1
Orifice location
MB: under the mesial slope of the MB cusp
DB: under the B groove
P: slightly distobuccal to the ML cusp tip
Distinguish between Mx & Mn molars by occlusal outline, arrangement of roots, & number of roots
NOT by # of cusps, # of developmental grooves, or size of the crowns
All Mandibular Molars:
Wider MD than BL
NO oblique ridge
Rectangular when viewed occlusally
Rhomboid when viewed from the interproximal
4 or 5 cusps with lingual cusps
L cups usually same height
Lingual cusps oppose grooves and embrasures only
Crowns inclined lingually from proximal view and a little distally relative to long axis of root (15-20% Lingual)
Mn molars have long axes positioned with their root apices facial and their crowns lingual
Height of contour is at the jxn of the cervical and middle thirds
Roots
2 roots (M or D)
M is very thin MD, wider BL and concave on both M and D
Pulp horn is higher on M than D
All Mn roots are inclined distally & facially
2 pulp canals almost always in M root
MB canal curves more than ML
Larger kidney shaped canal is found in the D root
Smaller more circular canals are found in M root, because there is 2 of them
Characteristics of Individual Teeth
Maxillary Central Incisor:

21

Shapes
M/D view = Triangular
B/L view = Trapezoidal
Occlusal =
Longest and widest anterior crown
Longest of all Crowns Correction from old card
But not as thick labiolingually as the Mx canine
Average crown length is 10.5mm
Wider MD than FL (same with Mx lateral incisor)
Incisocervical & mesiodistal dimensions nearly equal
Mesioincisal is sharper
Narrowest incisal/occlusal embrasures of all Mx teeth
Of all teeth, the greatest incisal curvature of a cervical line is on the mesial surface of Mx centrals (more so than Mn
centrals)
Anatomic features include cingulum, mamelons, marginal ridges & cervical ridges (not triangular ridges or cuspal ridges)
Incisal ridge of the crown is on line with the center of the root
Prominent cingulum located off-center toward distal
Different from Mx lateral in that
Has a shallow, broad lingual fossa on the incisal one-half of the lingual surface
The cervical outline of the facial surface is a broad curve, sometimes described as part of a semicircle
Has a distally located Cingulum (Mx lateral has central Cingulum)
3 Mamelons & 4 Developmental Lobes
Greatest axial inclination relative to occlusal plane (the Mx centrals vary the most from a vertical inclination) its a
28 tilt
Wear facets can develop in the linguoincisal area
M & D pulp horns are more likely to be found in Mx centrals (than Mn centrals??, Mn canines, Mx PM1s, or Mn PM1s)
A cross-section at the CEJ has a round form??? (Book says rounded triangular form)
Kaplan says: round on cross section, but may show some ligual convergence, with the mesial being longer than the distal
1 Root
Triangular pulp chamber in x-section, with the base of triangle located facially, apex located lingually, mesial side longer
than distal side: the tooth is most likely a Mx central
Length is 13mm
One root, one canal
Among choices of Mx central, Mx PM1, Mx PM2, Mn central, Mn lateral, and Mn PM1, Mx central is LEAST
likely to have a divided pulp canal!!!!!
Conical with blunt apex; lends itself well to rotation w/ extraction forceps during surgical removal

Left
Mid-root
Pulp
Right
Maxillary Lateral Incisor:
Shapes
M/D view = Triangular
B/L view =
Occlusal =
Smaller than central, and resembles it
MD measurement > FL (same with Mx Central incisor)
Different from Mx central in that
It has a DL groove
Diffentiate from Mn lateral by its more pronounced lingual fossa
Mx lateral is the incisor most likely to have a L groove that extends from enamel to cementum (Know your grooves)
This radicular groove is prone to decay
The DL groove of the Mx lateral is the anatomic feature most likely to complicate root planing
Lingual surface
Lingual surface is most concave of any of the incisors
Lingual surface has most distinct anatomy of all incisors
Lingual fossa is more pronounced on a Mx lateral than a Mn lateral
Marginal ridges are more prominent on the L surface of Mx lateral than other incisors

22

Mx lateral is most likely tooth to have a carious developmental pit on the lingual surface
Crest of the Cingulum is slightly distal to the faciolingual bisector mmmm, because Cingulum is supposed to be
centered
Longer root relative to crown length
Root length is equal to or longer than that of Mx central (Only dimension like this)
Root is round to ovoid in x-section
Root usually deviates to the distal
More circular pulp outline in x-section
Incisal edges are a little more rounded than on central
Of the Mx incisors, the distoincisal angle of the lateral is the most convex incisal angle
Tooth most often in an abnormal relation and contact with adjacent teeth in the same arch
May be absent
LAST anterior to begin to calcify (10 months)
Among options of Mx canine, Mn canine, Mx central, and Mx lateral, a lingual pit is most common on a Mx lateral
M3s & Mx laterals have the greatest anatomic variation, variation in tooth mass, variation in crown size & form

Lingual view
Mandibular Central Incisor:
Shapes
M/D view = Triangular
B/L view =
Occlusal =
Smallest permanent tooth
Smooth lingual surface
Flat facial surface
Sharp mesioincisal & distoincisal edges
Incisal Edge
Flat incisal edge
The incisal edge crosses the tooth parallel & slightly lingual to a plane bisecting the tooth into F & L halves
The Mx were just in the middle
Intersecting a plane bisecting the tooth into mesial and distal halves at a right angle to that plane
NOT considered to be wider MD than FL
Most symmetrical tooth
Mn central is usually bilaterally symmetric when viewed labially and incisally
Mesial and distal characteristics of the Mn central are most difficult to distinguish hardest tooth to distinguish R/L
Look at CEJ to determine M or D
Cingulum is centered
Contact Mx centrals during protrusion and lateral protrusion
First succedaneous teeth to erupt
In ideal ICP, the distoincisal aspect will contact with the Lingual fossa of Mx central, NOT distal marginal ridge
The lingual cervical line positioned more apically than facial cervical line
(Also same as Mn Laterals, NOT Mn Canines or Mx anteriors)
Root
Shortest root of all Mn teeth
Thin MD & wide FL
Ovoid on x-section
Concavities on both M & D surfaces (this one gets used over & over again)
Also, B of Mn Molars and MB of Mx Molars
Most common lower anterior with multiple canals!!
(CAREFUL, Mandibular Canine is most likely anterior with multiple roots!! Or in other words Bifurcated)
Root canal:
A cross section at midroot of a perm Mn central is likely to show that the pulp cavity is flattened mesiodistally

23

OR
OR
Mandibular Lateral Incisor:
Shapes
M/D view = Triangular
B/L view =
Occlusal =
Slightly larger than central incisor wider MD than Mn central
Mesioincisal edge sharper than distoincisal
Cingulum slightly off center to the distal
Mesial marginal ridge slightly larger
Distal contact area slightly cervical to level of mesial contact area (incisal 1/3)
Viewed incisally, the crown looks twisted on the root base so that the distal is curved toward the lingual
This is the feature that is the most reliable criterion for differentiating perm Mn centrals from laterals
The incisal edge follows the arch curvature in relation to the faciolingual axis
The lingual cervical line is positioned more apically than facial cervical line
Viewed proximally, the greatest curvature of both the F & L outlines will be in the cervical 1/3 of the crown
The greatest FL crown curvatures extend 0.5 mm F or L beyond the FL diameter of the root
Not a big step up from cementum to enamel
Wear facets on the incisal edges of Mn laterals are caused by occlusion w/ Mx centrals & laterals
Root
Small % with 2 canals
Concavities on both M and D surfaces
Very narrow MD Ovoid root in x-section
Larger than central root in all directions

Lingual view of Right


Mesial View of Left Lateral
Maxillary Canine:
Shapes
M/D view = Triangular
B/L view = Pentagonal
Occlusal = Diamond
Longest tooth; longest root
BUT Longest Crown is Mx central > Mn Canine > Mx Canine
Wider FL than MD has the largest FL dimension of all anterior teeth
The only ones wider MD are Mx centrals and laterals
Bulky crown w/ prominent ridges
Wider MD dimension of the crown on the facial than lingual
Mx canine has the greatest labial convexity of all anterior teeth
Least often extracted (along with Mn canine)
When viewed from incisal, mesial and distal outlines are asymmetrical
BOTH Canines have a longer Distal MR
Remember Primary Mx Canine is the only one with Longer MR
When viewed from incisal, cusp tip is Facial and Mesial
When viewed from incisal, There is a distal portion that exhibits some concavity in the facial outline
NOT thinner mesially!
Gingival pits/grooves, although not type traits, are common features
Incisal margin occupies at least one-third of the crown height
When viewed from the Facial, M and D margins are NOT parallel
THINK Mn Canine is more Parallel (i.e. Straight margins)
Intermediate form between anterior & posterior tooth
Sharp cusp tip (before wear)
The middle facial lobe (of the 4 developmental lobes) is the lobe that includes the cusp tip

24

In occlusion, the cusp tips do not make contact, because the tips line up with the facial embrasure
COMPARED TO THE MN CANINE:
Mx cusp tip is more nearly centered over the root when viewed from the labial
NOTE: When viewed from the mesial, a line bisecting the root from the apex passes lingual to the cusp tip
In other words, Mx canine cusp tip is displaced Facially in a F/L direction, where Mn is Lingually
Again, Remember Buck tooth flare up top
OPPOSITE to Mn, which has its cusp tip displaced lingually
Mx crown shorter than Mn crown (but Mx still longer overall)
Mx cingulum more pronounced than Mn
Mx lingual anatomy is more distinct than Mn
BULKIER in Both Directions
Mx crown is wider MD than Mn
Mx crown is wider FL than Mn
Mn crown makes contacts more incisally than Mx!!!!!
THINK IM vs JM
Mn crown has a straighter mesial border (viewed from facial)
The cusp tip horizontally overlaps a Mn anterior & a posterior tooth
Mx canine is the only tooth with the potential to contact both anterior & posterior antagonists
Wear facets on the L surface of a perm Mx canine can be caused by contact with Mn canine & PM1
Enamel on the facial surface extends farther apically than the lingual
Normal lingual anatomy:
Cingulum, L ridge, M & D fossae, M & D marginal ridges
NOT prominent developmental grooves & NOT L cusp)!!!!!
There is some evidence of developmental grooves
Dont get clowned, Development Depressions are on the facial
The structure immediately mesial to the DL fossa is the lingual ridge
The structure immediately distal to the ML fossa is the lingual ridge (believe it or not)
The M & D fossae meet the proximal surfaces of the tooth at the M & D marginal ridges
The structure immediately mesial to the ML fossa is the M marginal ridge
The most likely anomaly of a Mx canine is a lingual tubercle??? (agenesis, dwarfed root, peg crown, root bifurcation)
Well developed lingual anatomy, ridges and fossa
Marginal ridges are heavy & prominent
Mesial & distal concavities/fossae are frequently found
Distal portion of the facial surface displays some concavity (viewed from incisal)
Cingulum is centered MD
Height of contour of both labial & lingual is in the cervical third
How to distinguish between R & L Mx canines:
The mesioincisal angle is less rounded than the distoincisal angle
The curvature of the cervical line (CEJ) is greater on the mesial than the distal
The mesial surface is straighter than the distal surface (distal surface is more convex than mesial)
Mesioincisal cusp ridge is shorter than distoincisal so, cusp tip is not centered over the root center (mesiodistally)
From a proximal view, the Mx canine tends to be positioned in the arch with its axis most nearly vertical
(This is from among answer choices Mx canine, Mx lateral, Mx central, Mn lateral, Mn central)
NOTE PMs were not an option, all incisors are flared (Look at the All PMs section for some clarity)
Pulp cavity has its widest dimension faciolingually in the cervical third of the crown (vs. middle third of the root, crown,
etc.)
SEE PICTURE
Another Q: In the cervical third of the root (vs. apical third of root, incisal third of crown, etc.)
In a MD x-section, the pulp cavity is pointed at its incisal limit
Root
One root, one canal
Least likely tooth to have two roots (among Canines & PMs)
Root has M & D concavities D is more distinct
More oval pulp outline in x-section
Longest
Canine eminence making it the thickest in the cervical 1/3rd
Roots of Mx canines dictate alveolar wall morphology, although they are under bone

25

Left
Mesial of Max Canine
Mandibular Canine:
Shapes
M/D view = Triangular
B/L view = Pentagonal
Occlusal = Diamond
Long, narrow crown (the only larger dimension on Mn canine than Mx canine is incisocervical)
Longest crown of all perm teeth Toss up with Mx Central
Crown is distally inclined relative to the root
Its greatest FL measurement > its greatest MD measurement (Same as Mx canine)
Less sharp cusp tip (before wear)
Cusp is displaced lingually (differentiate from Max canine, when looking from incisal)
The mesial cusp ridge shorter than distal so, cusp tip is not centered over the root center (mesiodistally)
Has greater bulk distal to a BL bisecting plane than mesial to the plane its the transition tooth !!
The Mx Canine Does NOT have a difference in bulk (M or D)
Height of contour: cervical third for labial & lingual (at the level of the cingulum)
Labial and lingual ridges less developed, great for caries resistance
This is the tooth most likely to resist invasion by caries
Flatter labial surface than on Mx
Lingual surface
Relatively flat in the fossa area
Poorly developed in the marginal ridge area
Poorly developed in the cingulum area
The lingual crown surface is the narrowest MD (among labial or lingual crown surfaces of Mx/Mn canines)
Facial outline (viewed from proximal) is made up of one continuous arc & differs from the outline of a Mx canine
Remember Mx Canine has 3 facial planes
Mesial outline (viewed from facial), from the contact area to the root apex, relatively straight
Mesial axial surface is almost parallel to long axis of tooth
Wear facets are likely to develop incisal 1/3 of the labial surface of a Mn canine
Root
Anterior tooth most likely to have a bifurcated root (facial & lingual)!!!
In x-section at the CEJ, the root is best described as ovoid, but wider mesiodistally at the labial
Irregularly oval
Developmental depression may appear on mesial root surface
Often has a divided pulp (2 canals) more often than Mx canine, Mx central, L root of Mx M1, DB root of Mx M2

Right Mn Canine
Maxillary 1st Premolars:
Shapes
M/D view = Trapezoidal
B/L view = Pentagonal
Occlusal = Hexagonal
B surface has a prominent buccal ridge running axially
B surface is wider than L surface
L cusp is mesially displaced
B cusp is distally displaced
B cusp slightly to the distal
(BUT Mx PM2 has B cusp offset to the mesial!!!)
So, the mesial cusp ridge is longer than the distal cusp ridge the only PM w/ this feature
Largest of all PMs
Has a greater cervico-occlusal crown height than Mx PM2, Mn PM2, Mx M1or M2, Mn M2
Clinically, a Mx PM1 has four point angles with one point angle located at each of the four corners of the occlusal surface

26

Marked mesial concavity that progresses onto the root surface


Angular occlusal table
Steepest cusp inclines (well, steeper than Mn PM2, Mx M1, Mn M1 or M2)
Deep Sulcus, meaning steep cusp angles
Mesial contact is towards the mesiofacial line angle its with a Canine
Widest of all PMs, but still greater BL than MD
Mesial marginal developmental groove & mesial crown concavity on the cervical
REMEMBER, MesioLINGUAL developmental groove for Mn (because its by the tongue)
Mesiomarginal developmental groove for Mx
Among PMs, Mx PM1 is characterized by a deepened concavity on the mesial surface of the crown & root
The mesial surface has the deepest concavity of any posterior permanent tooth
The groove is the morphologic feature that presents the greatest difficulty in restorative dentistry
B cusp slightly longer than L cusp
BOTH Mx PM1 and Mx PM2 have L cusps offset to the mesial, but B cusps differ
In a CUSP TO FOSSA contacting relationship in ICP, Mx PM1 is most likely to articulate w/ Mn PM1
NOT both Mn PM1 and PM2 (Dont get clowned)
Picket Fence Pulls it into the Distal Fossa!!!
Occlusal pattern has deep sulcus and long central groove (relative to PM2), but fewer supplemental grooves (than PM2)
Think Biggest PM has to be stretched so it doesnt look wrinkled
2 roots! (The ONLY PM w/ 2 roots) as such, Mx PM1 has a bifurcation
Also has two pulp horns
When viewed from proximal, the axial inclination of roots appears MOST vertical
Cervical x-sections of root outline & pulp chamber floor outline are both kidney-shaped
Among PMs, Mx PM1 generally poses the greatest problem when root canal therapy, extraction or apicoectomy is being
considered
Easiest to perforate
There are sharp demarcations between pulp chambers & pulp canals in Mx PM1s due to 2 roots
This is not the case for any anterior teeth or other premolars
More likely to present w/ 3 roots than Mn central, Mx canine, Mn canine, Mx PM2, or Mn PM2
If Mx PM1 has 3 roots, where would they be? 2 Buccal, 1 Lingual
CAREFUL, eventhough the Lingual is larger
Most common problemwhen extracting? Leaving a root tip
Mx PM1 differs from Mn PM2
It has 2 roots
Has a longer central developmental groove
Presence of a mesial marginal developmental groove
BUT it is the same in that both have a lower L cusp than B cusp (only slightly on Mx)

Crown Outline (Left)

OR Right

(Midroot)

OR

Max RIGHT 1st PM


(L canal is bigger)

Maxillary 2nd Premolar:


Shapes
M/D view = Trapezoid
B/L view = Pentagonal
Occlusal = Rounded (Hexagon)
B cusp slightly to the mesial
(BUT Mx PM1 has B cusp offset to the distal so from the buccal both cusps merge together!!!)
L cusp inclined mesially, just like Mx PM1
Difficult to tell M from D
Crown is wider FL than MD
Less prominent buccal ridge
Smaller than 1st PM
More rounded occlusal table than PM1
Proximal contact with PM1 is Facial to mesiodistal line bisecting the crowns
B & L cusps nearly equal in size and are in-line
Both are offset to the mesial

27

Distal buccal cusp ridge is longer than mesial buccal ridge (opposite of PM1)
No mesial groove & concavity
Characterized by the presence of a short central groove has more supplemental grooves than PM1
Known as the wrinkled occlusal appearance when compared to PM1
(Good comparative features between Mx PM1 & PM2)
Roots
1 root

Left
OR
Right
Mandibular 1st Premolar:
Shapes
M/D view = Rhomboidal
B/L view = Pentagonal
Occlusal = Diamond (like the canine)
Smallest of all PMs
Most resembles a canine transitional tooth
2 cusps
But, Mn PM1 is the only PM that frequently only has one pulp horn (think of the weak-sauce L cusp)
Cusp may have varying forms (from person to person)
Long, sharp B cusp centered directly over the root
Mesial cusp ridge is shorter than the distal cusp ridge (So B cusp more mesial) Just like Canine
L cusp is also more mesial
Very small L cusp, non-functioning L cusp contacts no Mx tooth in ideal ICP
L cusp is ~2/3 the height of the B cusp
L cusp is similar in development to the cingulum of a canine
Only PM that has a B cusp w/ triangular ridge so uniquely prominent as to frequently separate its mesial pit from its distal pit
HENCE, need for 2 different Preps
Usually no central groove, but may have pits
May have a central pit (but Mn PM2 has one more often)
Both M & D marginal ridges have little or no contact in ICP
More prominent B ridge than 2nd PM
In the Mn arch, the greatest lingual inclination of a crown from its root is seen in Mn PM1!!!!!
Masticatory function similar to that of canine
Facial Masticatory mucosa (attached gingiva) is the smallest
Mesial lingual developmental groove makes mesial marginal ridge run at a 45 degree angle
REMEMBER, MesioLINGUAL developmental groove for Mn (because its by the tongue)
Mesiomarginal developmental groove for Mx
This makes it the only posterior tooth that has higher distal marginal ridge than mesial marginal ridge
More occlusal surfaces can be seen from the mesial than from the distal in a Mn PM1
The groove originates in an occlusal pit & extends onto a proximal surface
Mesial marginal ridge is same height as distal marginal ridge of Mn PM2
1 Root
Has a shorter and pointed apex
Shape of pulp chamber
oval, & wider facial-lingual than mesial-distal
Broader facially than lingually
Usually free of marked distal curvature
Frequently seen with slight concave areas on M & D surfaces
Not flattened faciolingually
If a 2nd pulp canal is present, it is most likely found lingual to the 1st canal
A bifurcation is the most common root anomaly on Mn PM1 (not dwarfing, elongation, concrescence or trifucation)
The pulp chamber morphology of the FACIAL makes it most susceptible to exposure
The Lingual Angulation of the crown forces us to make an angle prep, so we dont hit the chamber

Left

28

Right

Mesial Right

Mandibular 2nd Premolar:


Shapes
M/D view = Rhomboidal
B/L view = Pentagonal
Occlusal = Pentagonal
CAREFUL Tests before 98 say Square (Maybe for the H version w/ only 2 cusps?????)
L Height of Contour is OCCLUSAL 1/3rd (THE ONLY ONE TO HAVE IT!!!!)
Most congenitally missing PM
May have 3 cusps; B > ML > DL
If Mn PM is not an option
Maybe Mx M2
B cusp is centered M/Distally
DIFFERENT THAN up top, where they converged
B cusp is shorter than for Mn PM1
L cusps are functional
Wider on L than B
L surface is wider MD than for Mn PM1
Frequently has central pit; other PMs do not
NO ML groove or transverse ridge
Differences between Mn PM2 & Mx PM2:
The tip of the L cusp of the Mn PM2 is closer to the lingual border of the crown Hence Occlusal HOC
The occlusal outline of the Mn PM2 is more nearly square
Mx PM2 is more rounded occlusally rounded hexagon, where this is a Pentagon
The root of the Mn PM2 is more circular in cross section
The B & L cusps of the Mx PM2 are more nearly the same height More so than Mx PM1
The Mx PM2 crown outline (viewed from mesial) is a trapezoid with the short parallel side at the cervix
Whereas Mn PM2 is Rhomboidal
Mental foramen is located most closely to Mn PM2
Another Q: Usually situated nearest the apices of Mn PM1 AND PM2
1 Root
Thicker and longer than PM1
Longer, with blunted apex
Rounded root; lends itself well to rotation w/ extraction forceps during surgical removal (also Max central incisor)
ONLY PM with NO mesial root depression
Occlusal schemes
Y-type
Most common type
The PM w/ the occlusal groove pattern that may simulate the letter "Y" is Mn PM2
5 lobes, 3 cusps
2 L cusps & 1 facial cusp (F > ML > DL)
This means the Mn PM2 is the only PM that usually has 2 L cusps
Shorter and wider than PM1
Square occlusal
*Because of this scheme, the Mn PM2 frequently has a central pit (the other PMs do not)
The total # of pits (3) on the occlusal surface of Mx M1 is the same as is found on a Y-type Mn PM2
The only premolar that may exhibit 3 occlusal pits
H-type
4 lobes, 2 cusps
More common than U-type
U-type
4 lobes, 2 cusps
Central developmental groove can look like a U or crescent
So, Mn PM2 is the tooth most likely to possess a crescent-shaped central developmental groove
Central developmental groove that is crescent shaped and extends out as a mesial and distal developmental groove
SIDEBAR:Leong PM
Dens Evaginatus most commonly on Mn PM2
May contain a pulp Horn
Maxillary 1st Molars:
Shapes
M/D view = Trapezoid

29

B/L view = Trapezoid


Occlusal = rhomboid
Cornerstone of Mx arch
Largest permanent tooth NOT Mn M1
Rhomboidal outline (obtuse ML and DB; acute MB and DL)
Broader lingually than buccally (unlike any other perm)
(Has a MD measurement greater lingually than facially)
This makes the lingual embrasures associated w/ the Mx M1 relatively small
Cusp of Carabelli on ML cusp (5th cusp)
The Carabelli or fifth cusp on a permanent Mx molar is found on the ML lobe of M1
ML > MB > DB > DL (same sequence for Mx M2)
ML cusp is the largest and longest?? cusp of perm Mx teeth!!!!!
DL cusp is largest DL cusp of max molars
The most significant difference in the occlusal surface anatomy of Mx M1, M2 & M3 is the DL cusp gets progressively
smaller
The ML cusp tip is located D to the MB cusp tip
The DB cusp tip is located L to the MB cusp tip
Central groove runs from mesial pit to central pit on the occlusal table
The central pit is formed at the bases of the triangular ridges of the ML, MB, and DB (not DL)
There are 3 pits in Mx M1 (Same as Mn PM2 Y type)
Oblique ridge
The occlusal surface is usually distinctly divided by a ridge from the ML to the DB cusp
Forms the distal boundary of the central fossa
Passes through the DF sulcus (or angular sulcus) of permanent Mn M1
Opposes the developmental groove between the DF and D cusps of Mn M1
Is at the level of the marginal ridges
Mesial contact area when viewed from the mesial is usually facial to the center of the crown F/Lingually
CAREFUL, distal contact is centered Just like anteriors
The M border is broader than the D border
Both Mx M1 and M2 have Mesial Inclination
Distal surface has pronounced cervical concavity hard to adapt a matrix band (Along with Mesial of Mx 1st PM)
There is also a Mesial concavity that requires special attention when removing calculus deposits (Mx PM1 has one, too)
2nd Perm to erupt after Mn M1s
From the distal aspect, one can see 4 cusps
Occlusal contact should be anticipated on the L slope of the F cusp, the F slope of the L cusp, and L slope of the L cusp (but
not the F slope of the F cusp)
Roots two facial, one lingual
Tripod splayed out, whereas Mx M2 are closer together
Triangle formed by the orifices of the canals, the line connecting the P (L) to the M is the Longest
Roots of Mx M1 are equal or longer than roots of Mx M2
All 3 visible from Buccal
Root length/size: P > MB > DB
P
Is the largest, longest and strongest
(3rd longest of Max after canine and 2nd PM root)
Wider MD, than BL
Often has concavities/depressions on facial and lingual surfaces of the root
Longitudinal depression on the lingual, Concave on the buccal
Viewed from B, in line with B groove
Viewed from L, in line with the midpoint of MD diameter
DB
Usually has 1 root canal
The shortest and smallest root
Little thicker B/L than M/D
Sharp apex
More inclined distal than 2nd Max Molar
Inclined Buccally
MB
Flattened MD and has root depressions on both its M & D surfaces
Thicker B/L than mesiodistally
Blunted apex

30

Often has MB1 and MB2 (60%)


If a Mx M1 has a 4th canal, it is located in the MB root MB root can have 2 canals
MB2 is just L to the orifice to the MB Canal
Pulp horns of MB (and ML, if present) usually higher than D or P
The pulp horns most likely to be accidentally exposed in a Class II prep are MB & ML
ML comes with a MB 2 canal
Furcations
Distance from cervical line (from farthest to closest): D > F > M
Remember Mn Molars have Bifurcations (F/L) and Mx Molars have TRIfurcations (F/ML/D)
Has a B developmental groove, starting at furca and ending at CEJ
If a root goes into Mx sinus, it is usually from Mx M1

Distal view
Mesial View
Cervical Cross
Mid-root
Maxillary 2nd Molars:
Shapes
M/D view =
B/L view =
Occlusal =
At cervical level = Irregularly Triangular
Parotid Duct (Stensons) opens opposite to Mx M2
Smaller than 1st
No Cusp of Carabelli
Smaller oblique ridge
DL cusp is smaller than Mx M1
DL can be absent this means that Mx M2 can have 3 cusps w/ a central pit (also Mn PM2 and Mx M3)
DL groove is shorter than on Mx M1
MB line angle is most acute (viewed from occlusal) due to rhomboidal shape (MB & DL are acute)
B broader than L Think you turned Heart Shaped
More angular than 1st Molar
Both Mx M1 and M2 have Mesial Inclination
B groove is shorter and does NOT have a pit
The most constant & valuable trait to differentiate among Mx M1, M2 & M3 is the relative position of the DL groove
Roots
Shorter than roots of Mx M1
Closer together (more potential for fusion)
Have a greater distal inclination and have longer root trunk
The axial inclination of the P root of Mx M2 is distal & lingual
P is straighter than P of Mx M1
Maxillary 3rd Molars:
Shapes
M/D view =
B/L view =
Occlusal = Heart shaped (Most often)
Most often congenitally missing tooth (along w/ Mn M3s, of course)
3 or 4 cusps (small or sometimes missing DL cusp, making it heart shaped with the apex lingually)
Among options of Mx M1, Mx M3, Mn M1, & Mn M3Mn M3 most frequently has 3 cusps
No Cusp of Carabelli
THE 1 constant
Always have BL wider than MD
Roots fused
The Mx tooth exhibiting the greatest statistical variation in root alignment is M3
The MB is noticeably larger than the DB
Shortest permanent tooth
Oblique ridge is often absent
May have paramolar attached
Crown tapers more from B to L
Has a single antagonist in ICP (NOTE: Mn centrals also occlude with only 1 tooth)

31

In a normal dentition, maxillary teeth having single antagonists are the M3s
Strange & extra anatomy (usually undersized anomalies)
Maxillary tooth exhibiting the greatest statistical variation in root alignment

Left M3
Mandibular 1st Molars:
Shapes
M/D view = Rhomboid
B/L view = Trapezoid
Occlusal = Pentagonal
Cornerstone of perm dentition
MD dimension > BL dimension (Only slightly says the answer)
Has the longest MD measurement of all perm molars
When viewed sagittally, Mn M1s have their long axes at an angle least perpendicular to the occlusal plane
DONT get clowned, because Mn M2 still has its roots set back most distally
Most often restored, extracted or replaced
5 cusps
3 buccal (MB, DB, D) & 2 lingual (ML, DL)
3 cusps can be seen from the buccal
Where is the Distal cusp located??? Distofacial
All about the same size: MB is the largest cusp & D is the smallest cusp
The distal pulp horn is the smallest on this tooth
The second largest Cusp is the ML
Lingual cusps are higher and more pointed
The position & height of L cusps of Mn M1 accommodate working movement
The L surface of each L cusp possesses a slightly convex shape in the occlusal third
5 cusps = 5 pulp horns
5 cusps = 5 triangular ridges (95% sure)
Distal cusp projects into the distal fossa of the Mx M1
The largest proximal crown surface of a Mn molar is the mesial of Mn M1
Buccal pits in the buccal groove common place for caries
Crooked central groove in MD course
4 Grooves on Mn M1
1 central, 2 Buccal grooves (B & DB); 1 Lingual groove
The developmental groove between the distofacial cusp & the fifth cusp of a perm Mn M1 is the distofacial
The Number of developmental grooves distinguishes Mn M1 from Mn M2 4 for M1 and 3 for M2
Of all molars, the mesial fossa of the Mn M1 is most distinctly separated from the remainder of the occlusal table by a
transverse ridge (not to be mistaken with the oblique ridge of Mx Ms)
Both marginal ridges have developmental grooves
Roots
2 Roots, usually 3 canals (2 mesial canals) 2 roots means Mn M1 has a bifurcation
Furcations are B and Lingual
Roots incline distally
Pulp chamber is wider MD than FL
Have Longitudinal grooves on Both M and Distal surfaces of Mesial root,
BUT no longitudinal groove on the Distal of the Distal root
What distinguishes Mn M1 mesial root from Distal root?
Larger, 2 canals, biconcave
Mesial root of Mn M1 is typically very thin MD, much wider FL, and concave on both M & D surfaces (also MF of Mx
M1)
Mesial root has a strong distal curvature in the apical 1/3rd
In a mid-root x-section, the mesial root of Mn M1 is larger than any other Mx or Mn M1 root
The distal is smaller than mesial (D before M!!)
Are strongly compressed in a MD direction
The root trunk of the perm Mn M1 is equal in length to the mesial furcation of Mx M1
Which was the shortest distance to furcation from CEJ

32

Right Mn M1
Mesial Root
Buccal of R
Distal of L
Mandibular 2nd Molars:
Shapes
M/D view =
B/L view =
Occlusal = Rectangular
4 cusps
Cusps are of approximately equal size
CAN see the Lingual cusps from the Facial view as a little taller (SEE PIC BELOW)
Perm M2 differs from perm M1 in number of cusps
The DB cusp is the centric holding cusp of this tooth, and it occludes in the central fossa of Mx M2
Use height of contour to distinguish between B & L
Viewed from the occlusal, The greatest FL diameter of Mn M2 is located in the mesial 1/3 of the crown
MOST SYMMETRICAL MOLAR, BE CAREFUL 18 vs 31
More occlusal surface is visible from distal than mesial view
Normally the crown of Mn M2 inclines mesially & lingually
Facial has slight cervical dip, Lingual does not
3 developments grooves (from occlusal aspect) Central, Buccal, and Lingual
B & L developmental grooves
B groove extends half way down B surface Hello, buccal pit anyone?
L groove barely extends onto L surface
B & L grooves form right angles with central groove makes a + shaped occlusal surface
Central groove straight groove
More secondary grooves than Mn M1
1 B groove and 1 B pit no DB groove, as is present in Mn M1
Has large MB cervical expansion (like primary M1)
Viewed from the occlusal, the greatest FL diameter of a perm Mn M2 is located in the mesial third of the crown
Root
2 roots (M & D) Distal is smaller again, D before M!
Closer together & inclined more distally than Mn M1 roots
Longer root trunk

Buccal view of R
Mandibular 3rd Molar:
Shapes
M/D view =
B/L view =
Occlusal = Ovoid
4 or 5 cusps
Bulbous crowns that taper M to D
Calcification begins at 8-10 yrs
Extra grooves
MB cusps are wider/longer than DB
Rectangular form MD dimension of the crown is greater than the BL
Perm molar w/ shallowest central fossa
Oversized anomalies are more common, undersized more common in Max M3s
This Q comes from the 2001 Pilot:
Q: A radiograph of tooth #32 shows two well-formed roots. When sectioning this tooth to separate the roots & simplify
extraction, which of the following best describes how the cut should be made?
A: Bucco-lingually through the crown & furcation
Root
Marked distal inclination of root trunk

33

Roots fused and shorter


Long root trunk
Mx

ROOTS REVIEW
Anteriors
Virtually always have one root & one canal
Centrals
Newly erupted have 3 pulp horns
Least likely to have divided pulp canal (among Mx PM1, Mn cent, Mn Lat, and Mn PM1)
Pulp outline is somewhat triangular at cervical level
Pulp chamber is wider M/Distally
Mesial and distal pulp horns are MOST likely
Mid-root is round
Laterals
Newly erupted have either 0 or 2 pulp horns
Pulp outline is round for both sections
Root length is the only dimension that is the same or bigger than Mx central
Canine
Pulp chamber has the greatest faciolingual width of any anterior tooth
Longest root/Longest root canal
Least likely tooth to have two roots (among Canines & PMs)
F/L longitudinal section has the pulp cavity its widest dimension in the cervical third
Pulp cavity in M/D section is pointed at its incisal limit
Cervical cross section is ovoid, wider labiolingually
Mid-root is less ovoid to round
Posteriors
Premolars
PM1:
70% 2 canals
2 pulp horns, buccal is larger
Possibility of 3 Roots (2 Buccal/1 Lingual)
Sharp demarcation between chamber and canals
Lingual canal is slightly wider, even though lingual root is usually small
Cervical cross section is Kidney shaped with concave side on M
Mid-root is figure 8 shaped, lingual canal still slightly larger
PM2:
30% 2 canals, usually just branches into 2 foramina in the apical third
2 horns, B is larger
Cervical cross section is oval
But remember, it still has a root depression MAND PM2 is only PM that DOES NOT have a mesial
root depression
Mid-root is ovoid and wider BL than MD
Molars
M1:
MB1&2, DB, Palatal
60% MB2 canal
Always assume there is an MB2, unless you dont find it (the root is so wide)
NO pulp horn for cusp of Carabelli
MB and ML pulp horns are most susceptible to exposure
Cervical cross section is rhomboid
Mid-root has 3 roots, M with 2 canals
Furcations (closest to the CEJ = Mesial more than Facial more than Distal is Farthest
Palatal
P root has a buccal curvature
P root has a concave lingual surface
Often has concavities/depressions on facial and lingual surfaces of the root
Longitudinal depression on the lingual, Concave on the buccal
M2
DL pulp horn is smaller than M1 to match DL cusp size decrease

34

When compared to M1, M2 roots are greater in distal inclination


The axial inclination of the P root of Mx M2 is distal & lingual
Opposite to Mandibular M1 and M2, where M1 has greater distal inclination
When crown is heart shaped, cervical cross section is more triangular
M3
Varies
Mn
Anteriors
70-90% are normal
10-30% 1 canal with branching into 2 canals
1-2% 2 fully formed root canals
Centrals
NO pulp horns
Cervical cross section is Thin M/D, Wide F/L, and Concave on both M/D surfaces (see both pics)
Mid-root is still ovoid, but canal is more constricted
60% 1 canal
40% 2 canals look for double PDL space
Often the canals join apically will usually heal if you seal off one canal
Very few of the two canal cases do not join apically
Laterals
NO pulp horns
Cervical cross section is ovoid
Mid-root is still ovoid, but canal is more constricted
Canines
6% with 2 complete root canals
Occasionally 2 roots (Labially and Lingually)
Cervical cross section is ovoid (irregularly oval)
Ovoid and wider M/D on the labial
Another Q: Flattened in a M/D direction
Mid-root is ovoid
Posteriors
Premolars
PM1:
25% 2 canals (or more)
Fast-beak phenomenon: apically the canal space disappears means you have 2 canals
During Endo on #21, you suspect a second canal, MOST likely on LINGUAL just like Canine
2 pulp horns, large pointed B horn, small rounded L horn
Sometimes L is missing, and then would look like a canine
Broader facially than lingually
Usually free of marked distal curvature
Frequently seen with slight concave M/D
Cervical cross section is ovoid
Mid-root cross section is round
PM2:
5% 2 canals
2-3 Pulp horns (Y type have 2 lingual pulp horns) with B a lot larger
Cervical cross section is ovoid
Mid-root cross section is ovoid
Molars
Always 2 mesial canals
70% have only 3 canals
30% have 2 distal canals, for a total of 4
M1
4-5 Pulp Horns
Mesial 2 are about the same size, Distal 2 are about the same, but the MB is a lot bigger than the DB
Pulp horns likely to be exposed in newly erupted Mn M1 are BOTH MF and ML
D horn is sometimes large enough to detect (usually only in newly erupted)
Cervical cross section follows crown shape with 5 humps in the chamber (Pentagonal)
Mid-root is usually elongated kidney of M with 2 canals and concave toward Distal, then D root has 1
canal kidney shaped with concave toward M

35

Watch for C shaped canals in Distal root


Mesial root is very thin M/D, much wider F/Lingually and concave on BOTH M/D surfaces
Mesial root has the greatest mid-root cross section of any first molar root
M2
Still usually 2 canals in M root
Usually just one canal per D root
M3
Varies, but usually same as M2
CONTACTS
Contacts
All Rules
All embrasures are greater on the Lingual EXCEPT
Mx M1, M2
Mn anterior (to the mesial of the Canine)
Viewed from occlusal, all posteriors have contacts slightly buccal to the faciolingual midpoint
EXCEPT DISTAL OF MX M1
Also, slightly to the occlusal from the center of the proximal surface
Viewed labially, anterior teeth have contacts in the incisal to middle 1/3, except for the D contact of Mx canines
All permanent incisors have M and D contact areas approximately centered faciolingually
Viewed from facial, the proximal contacts are as follows:
Max teeth
IJ, JM, JM, MM, MM, MM, MM, M (all Ms except 1st 5 contacts IJJMJ) I Jump Jump Michael Jordan
Mand teeth
II, II, IM, MM, MM, MM, MM, M (all Ms except 1st 5 contacts be sure to count each one)
***I = Incisal 1/3rd
***J = Junction of Incisal/Middle 1/3rd
***M = Middle 1/3rd
NOTE: Mx centrals & laterals and Mn laterals (???) have distal contacts apical to their mesial contacts (so do Mx canines)
Maxillary central & lateral IP contact
The contact is centered faciolingually
NOT incisocervically
The lingual embrasure is wider/larger than the facial embrasure
There was a PBL type question that basically stated the orthodontist would want the distal proximal contact of the Mx
central and the lateral to be in the incisal 1/3rd, (IN reality, it should be Junction)
Mn incisor IP contact
Contact tends to occur equidistant from F & L surfaces
Contact occurs in the incisal third of the crown
Mn Canine and Mn PM1
Centered faciolingually
The facial embrasure is smaller than the lingual
In the incisal third
Mandibular posteriors
In the Mn posterior segment of the arch, the contacts of Mn PM2 & all 3 Mn molars are aligned in a straight line
This is not the case in the Mx arch
Proximal contact of posterior teeth creates wear patterns that eventually cause reduced IP embrasure spaces
The following anterior teeth have a distal contact area in a more apical position than the mesial:
Mx central incisors; Mx lateral incisors; Mn lateral incisors more apical, yet still in I
The following permanent teeth have mesial & distal contact areas at about the same level occlusocervically:
Mn central incisors, Mx PMs, Mx molars, Mn molars
The contact area DOES
prevent food impaction
form embrasures
stabilize the dental arch
protect the periodontium
It does NOT
distribute occlusal forces
protect mucosal tissues
provide better retention for the restoration
provide spillways, maybe the embrasure does
guide food toward the occlusal surface

36

guide food over the free margin of the gingiva


Loss of the contact area can result in drifting of teeth, food impaction, bone loss, damage to the interdental papilla, unfavorable
occlusion
Contact areas between posterior teeth in normal alignment aid in preventing mesial and distal drift
NOT in preventing Rotation
When two proximal surfaces diverge from an area of contact, lingual, facial, occlusal & cervical embrasures are formed
A proximal surface is always next to an adjacent tooth (hence, proximal)
OCCLUSION
WHEN THE TEETH DONT MOVE
Occlusal table
Area of a tooth bordered facially & lingually by crests of the cuspal ridges of F & L cusps, and mesially & distally by crests
of the marginal ridges
Normally makes up 55-65% of B/L tooth dimension
Overbite (vertical overlap)
Is when incisal edges are w/in incisal third of mand incisors
Overjet (horizontal Overlap)
Pt with overjet has?? Decreased anterior disclusion??
Determinants of Occlusion
Posterior
R/L TMJ and suspensory ligaments and condyles
Anterior
Teeth (occlusal surfaces)
Neuromuscular system
Programmed by teeth and what nature/man do to them
4 Determinants of design for restoring complete and functional occlusal surface:
Amt of vertical overlap allows you to make the cusps bigger and fossa deeper
Contour of articular eminence
Amt & direction of lateral shift in working condyle
Position of tooth in arch
Equilibration (Occlusal Adjustment) Principles:
Maximum distribution of stress
Forces borne on long axis
Change surface to surface flat contacts to point-to-surface
We want DOTs not Smudges
Involves
Discing
Odonto-, Enamelo-, Coronoplasty
CR
Relationship of bones of the upper and lower jaws w/o tooth contact
CO (ICP) is slightly anterior to CR
Ligament Guided
CO (ICP)
Relationship between Max and Man occlusal surfaces that provides the Maximum Inter-locked Position MILP
Tooth Guided
Determined by tooth contacts
The VDO is smallest in a position of maximum intercuspation
ICP supports the mouth during empty mouth swallowing
During non-masticatory swallowing, the teeth are usually in contact in ICP
Rinses the mouth of saliva and helps moisten oral structures
Masseter muscles contract and the tip of the tongue touches roof of mouth
Tooth contacts are longer duration during swallowing than chewing
RCP
When the Mn moves from ICP (MILP maximum interlocking position??) to a more posterior position, any tooth contact
that occurs is called a retrusive contact
Placing the Mn in a retruded path of closure usually results in: (meaning you stop at Retruded Contacts)
Increased VDO, increased horizontal overlap (of incisors?), and decreased vertical overlap
In a retruded contact position, the Mx central does not contact any tooth
Terminal Hinge Axis
The center of rotation for the mandible when it opens from retruded contact position
Rest (postural) position of Mn
Muscle guided occurs when muscles of mastication are in tonic equilibrium

37

Determined exclusively by the behavior of the mandibular musculature


Usually there is no teeth contact
Occurs the neuromuscular system has the least amount of activity
Usual reflex is the tonic stretch reflex of Mn elevators (myotatic reflex)
If the mandible were forced into CR from the rest position, the pts reflex neuromuscular defense would resist the
applied force
Freeway Space or Interocclusal distance
Results from Rest Position of the Mn
When mandible is at physiological rest, the space that exists between the teeth, (should be no contact)
Averages between 2-6mm
All 8 muscles of mastication plus supra and infrahyoids are in equilibrium
Angle Classes of Occlusion
*Determined by MB cusp of Mx M1
Class I (70%)
*MB of cusp line up with MB groove
In terms of cusp/fossa relationship, the DB cusp of the Mn M1 rests in the central fossa of Mx M1
Mx centrals overlap Mn centrals
Mx canine lies in embrasure between Mn canine and PM1
Mn posteriors are positioned more lingually & mesially than Mx posteriors
Mx posteriors are positioned more facially & distally than Mn posteriors (hey, it was a question)
Which may occur in class I pt
ANSWER was NONE of these:
Cross tooth balance
Bilateral tooth contacts in excursives
Posterior tooth contacts in protrusive movements
If you move from a postural position to ICP, you will be using the temporalis (last bit of closure)
Class II (25%)
*MB cusp between Mn M1 & PM2
Mn incisors occlude even more posterior
In a protrusive movement (in a Class II relationship), Mn canines articulate w/ canines, if you are thinking Class
II shift back
Mn PM1 lies between Mx PM1 & PM2
Mx canine is mesial to Mn canine
MB cusp of Mn M2 would articulate in the central fossa of the Mx M2, NOT the normal marginal ridge areas
Increase/Decrease Condylar Distance, OR Increase/Decrease of Bennett Angle
One of these 2, game time decision ???
Class III (<5%)
*MB cusp falls between Mn M1 & M2
Chin protrudes
Mn incisors overlap anterior to Mx incisors
A patient w/ a true or pseudo-Class III (Angle) occlusal relationship has no incisal guidance
As the Mn retrudes, the Mx laterals contact Mn canines & laterals
In a Class III malocclusion, the MB cusp of Mn M1 occludes in the mesial fossa of Mx PM2
Mx canine is distal to Mn canine
Often found when Mn arch is larger than Mx arch
Guiding cusps = Balancing = Non-supporting = Non-centric = Shearing
Mand Lingual, Max Buccal
Supporting cusps = Working = Stamp = Centric (NOTE: This changes with posterior crossbite pts)
Mn Buccal, Mx Lingual
Centric stops are areas of contact that a supporting cusp makes with opposing teeth
i.e. ML cusp of max molar with central fossa
5 Characteristics
Contact opposing in ICP
Support VDO of the face
Nearer to the faciolingual center of the tooth
Outer incline has potential for contact
Broader, more rounder cusp ridges
In centric occlusion, opposing contact may be expected at B slopes of L cusps of Mx posterior teeth
Posterior crossbite:
Mx facial & Mn lingual cusps are considered supporting cusps
In a working movement, the inner aspects of Mn L cusps may contact (inner means twd the tooth midline, not inner
as in toward the lingual)

38

Anterior crossbite:
When Mx & Mn incisors are in crossbite, the contacting surfaces are Mn lingual & Mx facial
Supporting cusps vs. Guiding cusps
Supporting cusps make fossa or marginal ridge contact
Supporting cusps of the same quadrant line up with each other
Guiding cusps are related to IP areas or developmental grooves
Guiding cusps overlap facial to Mn teeth & lingual to Mx teeth
NOTE: Mx F cusps & Mn L cusps (Guiding or non-supporting cusps) require sufficient occlusal length & horizontal
overlap for soft tissue protection
Horizontal & vertical overlapping of teeth afford some degree of protection for lips, cheeks & tongue
PICKET FENCE (get your incisal edge/cusp tip stuff down)
Teeth occluding only 1 tooth in opposite jaw:
Mn centrals
Mx M3s (Dont get clowned by Mn M3s in a question!)
Maxillary
Mx lateral opposes incisal edge of Mn lateral & canine; but, opposes no teeth at its incisal edge!!!!!
Cusp tip of Mx canine is in direct alignment w/ a facial embrasure of the Mn teeth
Mx posterior teeth oppose F & L inclines of F cusps, and F inclines of L cusps (not L inclines of L cusps)
L cusps of Mx posterior teeth oppose marginal ridges and central & distal fossae
B cusps of Mx posterior teeth oppose grooves & embrasures (meaning buccal grooves, not central grooves)
L cusps of Mx PMs contacts the distal fossa of respective PMs (Mx PM2 distal fossa of Mn PM2)
F cusps of Mx PMs oppose Mn PM & tooth distal to it
Mx PM1 opposes Mn PM1 & PM2
Distal marginal ridge of Mx PM1 is in contact w/ the mesial ridge of the F cusp of Mn PM2
In LEFT lateral movement, the L cusp of Mx RIGHT PM1 may appear to pass toward the tip of Mn PM2
Mx PM2 opposes Mn PM2 & M1
In a CUSP TO FOSSA contacting relationship in ICP, Mx PM1 is most likely to articulate w/ Mn PM1
(This is due to the lingual inclination of Mx PM1 Mn PM2 is not involved in a CUSP TO FOSSA manner)
ML of Mx molars goes to central fossa
ML cusp of the perm Mx M1 opposes the central fossa of Mn M1
ML cusp passes through the LINGUAL sulcus if its on the same side as the working movement
ML cusp of LEFT Mx M1 slides through the sulcus between DB and D cusps on Mn M1 during a RIGHT
working movement
DL goes to distal marginal ridge of same numbered Mn molar and mesial marginal ridge of tooth distal to it
DL cusp of Mx M1 opposes the mesial marginal ridge of Mn M2
DL cusp of Mx M2 opposes the mesial marginal ridge of Mn M3 & the distal marginal ridge of Mn M2
MB cusp of Mx M1 opposes the B groove of Mn M1
NOTE: its the triangular ridge of this cusp, not the cusp tip that opposes the groove DONT GET
CLOWNED
But, in a more recent question, it was the tip of the MB cusp of Mx M2 that opposes the B groove of Mn M2
In left working movement, the MB cusp of Mx right M2 will pass through, NOTHING, its the buccal cusp
DB cusp of Mx M1 opposes DB developmental groove of Mn M1!!!!!
DB groove also serves as escape for ML in non-working
The DL cusp of Mx M2 has the potential to oppose the mesial portion of Mn M3
Oblique ridge of Mx M1 opposes the DB groove on Mn M1!!!!!
(The prior 3 lines work great together, since the DB cusp connects through the oblique ridge to the ML cusp)
Mandibular
Mn central opposes Mx central only distoincisal aspect of Mn central opposes the lingual fossa of Mx central
Mn centrals contact Mx centrals during protrusion and lateral protrusion
It is important to check protrusion when restoring the incisal edge of an anterior tooth
Mn lateral opposes the distal marginal ridge of a Mx central, mesial marginal ridge of Mx lateral, and maxillary lateral
incisor 2-3 mm cervically to the incisal edge
Mn canine (incisal 1/3 of facial surface) opposes a Mx lateral & Mx canine at the approximation of their marginal ridges
An older question gave opposes the incisal embrasure between Mx lateral & canine as the correct answer, but in
this question (1989Q63), that answer option was available and was incorrect
The mesial cusp ridge of a perm Mn canine opposes the distolingual of the Mx lateral
B cusp of Mn PM1 contacts the mesial marginal ridge area of the Mx PM1
L cusps of Mn molars oppose grooves & embrasures (meaning lingual grooves, not central grooves)
ML cusp of Mn molar opposes the lingual embrasure of the same numbered Mx molar and tooth mesial to it
ML cusp of Mn M2 opposes the embrasure between Mx M1 & M2
DL cusp tip of Mn M1 has no antagonist

39

***D cusp of Mn M1 projects into the distal fossa of Mx M1


DB cusp of Mn molar opposes the central fossa
The central fossa of Mx M2 would be contact with the DB cusp of Mn M2
MB cusp of Mn molar opposes the mesial marginal ridge of the same numbered Mx molar and the distal marginal ridge
of the tooth mesial to it
MB cusp of Mn M1 opposes the occlusal embrasure between Mx PM2 & M1
MB cusp of Mn M2 opposes the mesial marginal ridge of Mx M2
B cusp of PM1 lies directly below the contacting area of Mx canine & PM1
B cusp of PM2 opposes the mesial marginal ridge of the Mx PM2
Some teeth w/ little or no marginal ridge contact in ICP & eccentric relationships
M & D of Mn PM1, D of Mn PM2
Class II Picket Fence
In a patient with a Class II, Division I angle occlusal relationship in maximum ICP, the MB cusp of Mn M2 articulates
with the central fossa of Mx M2
WHEN THE TEETH ARE MOVING
3 Planes of Movement
Frontal (up/down)
Horizontal (side/side)
Sagittal (forwards and backwards)
5 Factors of Mandibular movement
Initiating Position (CR)
Most stable and most easily reproduced
Types of Motion
Rotation
When the mouth is open to any given degree, there is more interocclusal
distance anteriorly than posteriorly because of the rotary nature of the
opening movement
1st ~20mm of opening is rotational; then translational
Translational
Occurs when the Mn moves from a maximum intercuspal position to a
maximum protruded position
***NOTE: When the mandible is opened beyond the point where the
condyle begins to translate, the meniscus glides downward and forward on
the articular eminence
Opening the mouth maximally from retruded position causes the Mn to
rotate, then translate
Direction of Motion
3 Planes
Degree of movement
Clinical significance of movements
Each pt may have different relationships
Mandible is a Class III lever like a shovel
Fulcrum Condyle
Force Muscles
Workload Teeth
Functional Occlusion
All contacts during chewing, swallowing, or normal actions
Parafunctional
Those made outside normal range, may create wear facets or attrition
Bruxing, clenching, nail biting, thumb sucking, cheek biting
Jaw closure in parafunction varies from masticatory function in the following ways:
Teeth seldom, if ever, contact in mastication
Teeth are in tight contact during parafunction
Masticatory cycles are vertical and cyclic
Border Movements LOOK OVER PULLINGERS HANDOUT

40

Sagittal Plane Posselts Envelope (ABOVE)


The final movement of the Mn in tooth closure is directed by the cusp-fossa relationship of opposing teeth
The maximum intercuspal position is the most superior point #3
Postural or rest position is that black dot right under #3,4
Retruded contact position is #4
Terminal Hinge axis is #6F
Masticatory Cycle of mandibular central incisor is #5
Curve #7 is the pathway for a maximum opening both rotatory & translational (NOT a border movement)
From which point to which point is there the greatest change in anterior guidance? I think from 3 2 (OR from CR
(3) to Edge to Edge Contact (2)
Intercuspal position is determined almost exclusively by tooth contact
The maximum opening position is the most inferior
In a normal diagram in the sagittal plane, initial occlusal contact in RCP occurs at a more inferior position than ICP at #4
Mastication of food occurs primarily in lateral contacting movement
In 90% of the population, the average distance from 34 is ~1.25mm (ICP is anterior to RCP)
In the other 10%, 3=4 (RCP = ICP)
The left border above is the protrusive opening path
Frontal Plane
Viewed anteriorly, chewing stroke (masticatory movement) vertical & tear drop in appearance (RIGHT)
In Frontal Plane there is Posterior contacts only on A
Canines are cusp tip to cusp tip on B

Horizontal Plane (Gothic Arch)


This records the position of the Mn anterior teeth, in assessing condylar movement via the lateral pterygoids
The diamond shape results from 1) L lateral, 2) L lateral w/ protrusive, 3) R lateral, 4) R lateral w/ protrusive
Points 5 & 6 in the figure on the right (below) represent the R & L lateral contacting positions, respectively
The apex of the horizontal plane Gothic arch tracing represents CR (OR POINT 1 Below)
Diagram shows (1999 Q 197 SEE RIGHT)
Horizontal component of movement from retruded contact position (1) to ICP
(2)
Anterior component of movement from ICP (2) to maximum protrusive
position (4)
Lateral component of movement from retruded contact position (1) to ICP (2)
Mandibular movements occurring laterotrusively
This diagram does NOT show Vertical component of any of the
movements

41

Centric Relation
retrusion

Rt

laterotrusion

Lt

laterotrusion

protrusion
OR
Bennett Movement = Lateral shift = Immediate side shift
Best described as a bodily shift of the mandible in the direction of the working condyle
Occurs during the earliest stage of lateral movement
Influences the M/D position of the cusps on all molars
Thats how you know where to wax up your cusp tips
The greatest influence of Bennett movement is potentially on the working side teeth in lateral movement
Wrong answers include: on posterior teeth in RCP, ICP, or during protrusion
When an exaggerated Bennett component is present in lateral jaw movement, it will have its greatest potential for
interference with the MD positioning of cusp tips
Most influences the lingual concavity of the maxillary anterior teeth and the cusp height and groove direction of the
posterior teeth (2001 Test, but before we had Anterior Guidance, what gives???)
Bilateral Balanced Occlusion
The stable simultaneous contact of opposing upper and lower teeth in centric relation position with a smooth bilateral gliding
contact to any eccentric position within the normal range of mandibular function, developed to lessen or limit tipping or
rotation of the denture bases in relation to the supporting structures
Unilateral Balanced Occlusion AKA Group Protected or Group Function Occlusion
If you extract the mandibular canine, you then would have only posterior group fxn
The idea is to eliminate all Non-working contacts
*In unilateral balanced occlusion, contact between upper B & lower B cusps, along w/ simultaneous contact between upper L
& lower L cusps, will most likely occur in laterotrusive movement
Mutually Protected Occlusion (MPO)
Includes Anterior and Canine Guidance
None of the posterior teeth contact on the non-working side when the Mn moves laterally
Anterior teeth disclude all posterior teeth in eccentric movements
Condyles are in their most superoanterior position in closure
Axial loading of occlusal forces occurs in closure
Posterior teeth contact more heavily than anterior teeth
In mediotrusion, the posterior teeth disclude the anterior teeth; in protrusion, the anterior teeth disclude the
posterior teeth
Anterior Guidance (anterior coupling)
Results from both horizontal and vertical overlap
Provides protection in disclusion of posteriors
Plays the greatest role in disoccluding the posteriors in latero-protrusive movements
Anteriors have mechanical advantage because they are farther away from the fulcrum, so better leverage to offset the
closing musculature
Canine Protected Occlusion
Only canine is involved in MPO
Curve of Spee
Best described as the anterior-posterior curvature of the occlusal surfaces of the teeth, as seen in a facial view
Mx arch is convex; Mn arch is concave
Another: The line beginning at the tip of the canines & following the F cusps of posterior teeth (viewed from the facial)
Curve of Wilson
Tilting of the Mn posteriors lingually makes the Mn arch concave & the Mx arch convex, when viewed from the front
According to curve of Wilson which way do maxillary molar roots tilt?
Lingually
Compensating Occlusal Curvature or Sphere of Monson
The 3D curvature of the occlusal plane, which is the combo of Wilson and Spee
The line beginning at the tip of the incisors and following the facial cusps of the posterior teeth as viewed from the facial
aspect
Axial Position
Which describes the relationship of the teeth with the vertical axis?
Spee, Wilson, Monson, or Axial inclination (Position)

42

Normally described in terms of the roots inclination, which means that the crown is normally inclined in the
opposite direction
Cusp Height Potential
Less vertical overlap, shorter the cusps must be
Greater vertical overlap, longer the cusps may be
Increased overlap allows for higher cusp ridges and deeper fossae
Less horizontal overlap of anteriors, longer the cusps may be
Greater horizontal overlap, shorter the cusps must be
Teeth articulation
The following are alterable factors in tooth articulation:
Incisal guidance, compensating curve, cusp-fossa relationship, & posterior tooth morphology (not postural position)
EXCURSIVES
NOTE: Lateral movements are an asymmetrical Mn movement (retrusion, protrusion are symmetric movements)
Laterotrusion = Working movement
In a lateral excursion, the teeth that ideally provide the predominant guidance through the full movement are the canines
In a lateral excursion, the Mn canine cusp tip passes mesial to the Mx canine cusp tip
The lingual cusps of a Mn M1 must be restored to accommodate working movement
From R lateral relation to centric: DB cusp of Mn M2 moves through the buccal groove of R Mx M2
During a working movement, the F cusp ridges of the Mx PM1 on the working side oppose the distal cusp ridge of Mn
PM1 & the mesial cusp ridge of Mn PM2
In a R laterotrusive movement, the L cusp of R Mx PM2 passes through the embrasure between R Mx PM2 & M1
In a R lateral excursion, the ML cusp of the perm R Mx M1 passses between the L cusps of Mn M1
This ML cusp passes through the L groove of Mn M1
In a R working movement, the ML cusp of L Mx M1 moves through the sulcus between DB & D cusps of Mn M1
A broad, flat facet existing on the outer aspect of the ML cusp of a Mx M1, and running in a ML to DF direction, was
probably caused by a working movement??? I think NON working!
In a L working movement, MB cusp of L Mx M2 will pass through the B groove of L Mn M2
In a L working movement, MB cusp of R Mx M2 will pass through nothing (actually mediotrusion for this cusp)
Mediotrusion = Non-working = Balancing movement
On Mn M1, the DF groove serves as an escapeway for the ML cusp of the Mx M1 during non-working Mn movements
The non-working condyle moves downward, forward & medial
The non-working pathway of Mx cusps on Mn posterior teeth is toward the distofacial
In a patient with a left canine protection, the ML surface of the R Mx M1 contacts the DB surface of the R Mn
M1 during a left lateral excursion. This contact is a non-working side interference
On the non-working side in an ideal occlusion, interfering contacts on posterior teeth will be located on the inner incline
of Mx & Mn supporting cusps
When moving the Mn from ICP to a R lateral relation, the L cusp of L Mx PM1 movees through the F embrasure
between the L Mn PMs
If the L cusp of #5 breaks off during trauma, this is most likely due to a left mediotrusive movement
In a L lateral movement, The L cusp of the R Mx PM1 may appear to pass toward the B cusp of the Mn PM2
Protrusion
The most likely Mn movement that occurs in breaking a Mn central incisor is a protrusive movement??? (01 Pilot)
Dumb Q: In protrusion, which way do the Mx cusps go? Nowhere, but maybe it was posterior relative to the Mn cusps
Condylar movement
A bilaterally symmetrical condylar movement
Lateral pterygoids are primary movers
The condyle moves forward and carries the disk with it
The underside of the meniscus moves distally relative to the superior surface of the condyle
The disk tends to be tilted in a superior-inferior fashion on the condyle
Mn incisors
Make contact w/ Mx incisors in protrusive & lateral protrusive movements (but NOT working/nonworking)
Contacting surfaces are the lingual of the Mx & incisal edge of the Mn
In a protrusive contacting movement, Mx laterals contact the Mn laterals & canines
In a protrusive movement, the F cusp tip of Mn PM2 has the potential to contact the DF cuspal incline of Mx PM1
When a protrusive Mn movement (anterior teeth edge-to-edge) is achieved, the Mn M1 has the potential to contact Mx
PM2 AND M1
Protrusive pathway
The protrusive pathway of Mn cusps on Mx posterior teeth is toward the mesial
Remember arrows on the Mx teeth tell exactly where the Mandible is going.
Arrows on the Mn teeth are in opposite to actual direction of mandibular movement
Lateral checkbite record

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Using the lateral checkbite record to set a respective condylar inclination implies that:
The non-working side condyle has moved anteriorly & medially
SURROUNDING STRUCTURES
TMJ
TMJ structural elements:
Condylar process, articular disc, capsular ligament, & joint cavities (not sigmoid notch)
The TMJ has two synovial cavities
Dense avascular fibrous CT covers the articulating osseous structures of the TMJ
There are also a few elastic fibers present
Glenoid fossa an oval cavity/depression in the temporal bone, anterior to the auditory canal
The joint:
A bilateral (complex) diarthrosis between 1) the articular tubercle/eminence of the temporal bone & 2) the Mn condyle
One Q said: What type of joint is the TMJ? Ans: an atypical diarthroidal joint (atypical due to lack of hyaline
cartilage)
Condyles:
Oblong processes, wider mediolaterally than anteroposteriorly
Concave anterior aspect (fovea pterygoidea)
Articulating surface is the superoanterior aspect slightly convex
Movements:
Retrusive both condyles move upward & back into the Mn fossa
Protrusive both condyles move forward & down the articular eminence
Lateral contacting mvmt:
Working side condyle merely rotates
In laterotrusion, the working condyle rotates along a vertical axis and translates laterally (a little,
right?)
Non-working side condyle moves downward, forward & medially
Lateral protrusive mvmt:
Working side condyle rotates, moves forward & downward
Non-working side condyle moves forward & downward & medially
***See p. 587 in Kaplan for pictures I think this could be a dont get clowned thing
The articular disc:
Is the tissue intervening between the articulating bones of the TMJ
Effectively divides the TMJ into two separately functioning compartments
The disc is attached laterally to the Mn condyle
Collateral Ligaments
The disc (meniscus) is moved forward principally by the lateral pterygoid muscle
Some fibers of the lateral pterygoid m. attach to the anterior border of the disc
Kaplan says: the medial & lateral corners of the articular disc are directly attached to the poles of the condyle via the
collateral ligaments
As the mouth is opened widely, the articular disc moves anteriorly in relation to the articular eminence, but distally in
relation to the condyle
In the sagittal plane, the posterior border is the thickest section of the articular disc

Joint spaces:
Upper compartment:
The space between the disc and the articular fossa & eminence
More recent Q: The superior joint cavity of the TMJ is bordered by the Mn fossa & the superior surface of the disc

44

Translation occurs here


Lower compartment:
Rotation of the condyle primarily occurs in the inferior joint space
Ligaments:
Temporomandibular (lateral) ligament
Has an outer oblique portion which limits the extent of jaw opening and initiates translation of the condyle down the
articular eminence
With a fracture of the left condyle, the condylar head remains in the mandibular fossa due to the TM ligament (01)
Prevents posterior & inferior displacement of TMJ

Collateral ligament
Medial and lateral connectors from the disc to the condyle
Restricts the movement of the articular disc away from the condyle during function
Another Q: Discal ligaments (synonyms) restrict the movement of the disc away from the condyle during fxn
During lateral Mn movement, the articular disc is tightly attached to the condylar head by the collateral ligaments
When the cusp tips of left Mx & Mn canines are placed in contact, the right condyle is positioned down the slope of the
articular eminence
Ligaments associated w/ the TMJ serve to protect surrounding & supporting tissues from damages
During function and in traumatic situations, the TMJ is protected by the synovial fluid, durability of the fibrocartilage,
ligament suspension, and muscles of mastication
Whats under the fibrocartilage? Periosteum???
Undifferentiated Mesenchyme or Hyaline Cartilage??
A projection of the facial surfaces of Mn molars would be medial to the anterior border of the ascending ramus
The condyle on the working side generally rotates about a vertical axis and translates laterally (rotation is the 1 movement)
Innervated by PAM: Posterior deep temporal, auriculotemporal, masseteric
MUSCLES
Mandible position
Mn ALWAYS deviates to the side of the injury
Lateral pterygoid muscle (mandible deviation)
Hypoglossal nerve (tongue deviation)
Mn postural position is determined almost exclusively by the behavior of the Mn musculature
So its not alterable
Primary Muscles of Mastication (4 Pairs)
Temporalis
Origin: Lateral surface of temporal bone
Insertion: Coronoid process of Mn
Anterior fibers elevate the Mn (close the mouth)
Q says masseter & medial pterygoid hold the condyle in most superior anterior position
Posterior fibers contraction retrude the mandible
Temporalis muscle is the principal retractor of the Mn
They are assisted by the anterior and posterior bellies of digastric muscle
Masseter
Origin: Zygomatic arch
Insertion: Lateral side of angle of Mn
Closes the mouth (elevator of Mn)
The most powerful muscle of mastication??? (1999 Exam.pdf #177 & 02 #178 what about temporalis?)
Medial Pterygoid
Origin: Medial surface of lateral pterygoid plate, pyramidal process of palatine bone & tubercle of Maxilla
Insertion: Medial side of angle of Mn
Closes the mouth (elevator of Mn)

45

NOTE: the masseter & medial pterygoid position the condyle in the most superior anterior position
Lateral Pterygoid
Superior head:
Origin: Infratemporal surface of sphenoid bone
Insertion: TMJ capsule & disc [SUPERIOR HEAD];
Inferior head:
Origin: Lateral surface of lateral pterygoid plate
Insertion: Condyle of Mn
NOT an elevator of Mn
Simultaneous contraction: depress (open) & protrude the jaw
Unilateral contraction: side-to-side movement of Mn
The muscle of mastication primarily responsible for synchronizing the movement of the condyle & articular disc
Contraction results in moving the mandible in opposite direction of contracted muscle (working movement)
(right muscle contraction moves Mn to the left)
Contraction of both simultaneously results in protrusion
Lateral pterygoids are the prime movers to a protrusive position
Contraction produces a forward movement of the condyle from the articular fossa
Contraction also opens the jaw
Assisted by the anterior bellies of digastric and omohyoid
Brings the articular discs and condyles down and anterior
When the incisal edges of the anterior teeth are placed in end-to-end contact, the Mn condyles have moved
downward & forward
Subsidiary Muscles
Buccinator
Compresses the cheek holding food under the teeth
Suprahyoid Muscles (4)
Contract to raise the hyoid bone during swallowing
In swallowing, downward displacement of the Mn is prevented by contraction of the masticatory muscles
Also, teeth come into occlusal contact & the tip of the tongue touches the roof of the mouth
Assist lateral pterygoid in depressing the mandible (Opening the mouth)
Assist Posterior fibers of Temporalis during retraction
Stylohyoid
Pulls the hyoid superiorly and posteriorly during swallowing
Fixes the hyoid bone for infrahyoid action
Digastric
Anterior belly
Opens mouth (depresses Mn)
Arises from trochlea of hyoid bone & inserts into digastric fossa of Mn
Innervated by mylohyoid branch of V3
Posterior belly
Fixes the hyoid bone for infrahyoid action
Arises from mastoid process & passes through trochlea of hyoid bone
Innervated by digastric branch of VII
Mylohyoid
Elevates the hyoid bone
Raises the floor of the mouth (for swallowing)
Depresses Mn when hyoid is fixed
Forms the floor of the mouth in the lingual vestibule
Inserts into the mylohyoid line on the medial side of the Mn
Moves in an upward slanting direction to the posterior
In the Mand M2/M3 area, the root apices are inferior to the mylohyoid line
Apices of Mand PM1/PM2 are superior to the mylohyoid line
Innervated by mylohyoid branch of V3
Geniohyoid
Depresses Mn
Can also help to retract Mn
Works with mylohyoid
**Both genio and mylohyoid form floor of the mouth
Innervated by C1 via CN XII

46

Infrahyoid Muscles (4) [Strap Muscles]


Depressors of the larynx and the hyoid bone
Lie between deep fascia and visceral fascia covering the thyroid gland, trachea, and esophagus
Innervated by ansa cervicalis (motor plexus from the Ventral rami of C1-3)
Thyrohyoid
Pulls the hyoid downward and raises the larynx
Sternohyoid
Pulls the hyoid downward
Sternothyroid
Pullys the larynx downward
Omohyoid
Pulls the hyoid downward
Extrinsic Tongue Muscles (4) pg 405 Netters H&N anatomy
Genioglossus
Genial tubercle to dorsum of tongue
Protrudes the tongue and Depresses the tongue
The muscle fibers that extend into the lingual frenum are from the genioglossus
Also has inferior fibers that connect the tongue to the hyoid
Hyoglossus
Greater and lesser horn (cornu) of the hyoid bone to lateral aspects of the tongue
Depresses the lateral sides of the tongue
Styloglossus
Styloid process to lateral aspects of the tongue
Retracts and elevates the tongue
Palatoglossus
Palatine aponeuroses to the side of the tongue
Elevates the posterior tongue and closes the oropharyngeal isthmus
(aiding in the initiation of swallowing)
Does not retract the tongue
Intrinsic Tongue Muscles (3)
Alter shape of tongue
Longitudinal
Shortens tongue (curls tip)
Transverse
Narrows tongue
Vertical
Flattens and broadens tongue
Mastication
Incision By incisors
Prehension (grasping) by the canines
Trituration by PMs and Ms
**The masticatory function of incisors & canines is primarily biting
PERIODONTIUM
Comprised of 2 functional units:
1) Gingival Unit
Free gingiva + attached gingiva + alveolar mucosa
Lined by masticatory mucosa
2) Attachment apparatus
= Cementum + PDL + Alveolar bone proper
NOTE: a question gives cementum, PDL & bundle bone as the correct answer (not lamina dura) see below
What protects the attachment apparatus
Anterior teeth might be responsible for disarticulating the posterior teeth in parafunctional grinding
MUCOSA
Oral Mucosa is either keratinized or non-keratinized
Keratinized
Strata basale, spinosum, granulosum, corneum
Non-keratinized
Strata basala, spinosum

47

Lamina propria
Dense CT of variable thickness
CT papillae carry BVs & nerves
Epithelial rete pegs are found between the CT papillae
Submucosa
CT of variable thickness/density
Contains glands, BVs, nerves, adipose tissue
Types of Oral Mucosa
Masticatory Mucosa
Free gingiva (some), hard palate, attached gingiva, interdental gingiva, dorsum of tongue
The hard palate submucosa contains adipose tissue anteriorly & glands posteriorly
NOTE: the hard palate also has long rete pegs
Keratinized
Orthokeratinized true keratin, NO nuclei, Uneven surface --- Dentures??
Parakeratinized keratinized cells retain their nuclei Masticatory Gingiva??
Thick, dense, firm lamina propria
Of Mn teeth, the facial masticatory mucosa (attached gingiva) is narrowest on PM1
Non-masticatory Mucosa = Lining or Reflective Mucosa
Free gingiva (some), lips, cheek, vestibule, alveolar mucosa, floor of mouth, soft palate, ventral tongue
Nonkeratinized
Thin, movable
Specialized Mucosa
Covers the dorsum of the tongue and taste buds
Vermilion border
Transition zone vs. Skin of the lip
Keratinization ends
Longer papillae carrying large capillary loops
Fewer sebaceous glands
No sweat glands
Sidenote: the # of melanocytes per unit area of mucosa does not vary between races; the difference is in cellular activity
GINGIVA
Gingival fibers
Collagen fibers that provide support for the marginal gingiva including the interdental papilla
Found w/in the Free Gingiva
Continuous with the CT fibers and are often considered part of the ligament (PDL)
Types (5)
Circumferential (circular) fibers
Encircle the tooth around the most cervical part of the root and insert into the cementum and lamina propia
of the free gingival and the alveolar crest
Resist rotational forces
Transseptal fibers
Extend from tooth to tooth coronal to the alveolar crest & are embedded into cementum of adjacent tooth
Occurs through the Interproximal segment of the alveolus
NOT via the facial aspect of the alveolus
Not on the facial and no attachment to the alveolar crest
These are not PDL fibers (apical, oblique, principal, transverse, & interradicular fibers are PDL or
principal fibers)
Maintain dental arch integrity
Dentogingival fibers
From the cementum apical to the epithelial attachment and course laterally and coronally into the lamina
propia of the gingival
Dentoperiosteal fibers
From the cervical cementum over the alveolar crest to the periosteum of the cortical plates of bone
Alveologingival fibers
Insert in crest of alveolar process and spread out through the lamina propria into the free gingiva
Apical, Oblique, Horizontal & Alveologingival fibers are attached to bone
Gingival apparatus
Term used to describe the 5 gingival fiber types and the epithelial attachment
Gingival ligament
Includes the dentogingival, alveologingival, and circumferential fibers

48

Free Gingiva (aka Marginal gingiva)


Collar of tissue that is not attached to the tooth or alveolar bone
1-3mm wide and forms the soft tissue wall of the gingival sulcus next to the tooth
Described as forming the wall of the gingival sulcus
Extends from free gingival groove to gingival margin/crest
(The free gingival groove is what gives the gingival roll its appearance its the one Jake & Boom-Boom
overacccentuate separates the free gingiva from the attached gingiva)
The healthy free gingiva aids in the self-cleansing process by adhering closely to the tooth surface below the height
of contour of the cervical enamel
NOTE: If the cervical enamel ridge is too great, it will adversely affect the self-cleaning quality of a dentition
Structures:
Gingival Margin
Top edge or crest
1mm band of gingiva that forms immediate collar around the base of the tooth
Hence Marginal Bleeding
Gingival Sulcus
Areas between the unattached gingiva and the tooth (Popcorn kernels)
Above jxnal epithelium, continuous with, but structurally different
Epithelium is non-keratinized (same w/ gingival col)
Then your PMNs couldnt get out!!
Healthy sulcus should NOT have rete pegs (rete pegs indicates inflammation)
Epithelial attachment (Junctional epithelium)
Joins the gingiva to the tooth
Normally follows curvature of CEJ
Does NOT normally stay at the same level throughout adult life
Inner layer of cells of junctional epithelium attaches gingiva to tooth
***Hemidesmosomes & Internal basal lamina are referred to as the epithelial attachment
The epithelial attachment in always an actual part of the tooths periodontium
The junctional epithelium is thin & non-keratinized
Susceptible to bacterial metabolite breakdown
Lymphocytes & plasma cells are routinely seen in the bottom of the gingival sulcus
Interdental Papilla
Portion of the free gingiva that fills the gingival embrasures (below contact area)
Tent-shaped
Consists of 2 papillae that are connected by the concave-shaped interdental col
Interdental col
Conforms to the shape of the contact area
Not present in teeth w/o contact
Non-keratinized
Small proximal contact areas with firm well-formed interdental papillae tend to decrease caries
susceptibility when occlusal and environmental factors are favorable
When restoring coronal structure, the creation of excessively round buccoproximal line angles tends to
create abnormal function with the interdental papilla
Deflective fxn of mesiofacial and distofacial line angles protects the interdental papilla
The interdental papilla between the Mand 2nd PM and 1st Molar is the shortest
(all other answer choices were anterior to this answer what about between the molars?)
Incisive Papilla
The elevation of gingival tissue directly lingual to embrasure between Mx central incisors
Free Gingival Groove
Separates the free gingiva from the attached gingiva
Attached Gingiva
Part of the gingiva that is attached to the underlying periosteum of the alveolar bone and to the cementum by CT
fibers and epithelial attachment
Present between the free gingiva and the more movable alveolar mucosa
Stippled
Extends from Mucogingival jxn to free gingival groove
The attached gingiva on the facial of the Mand 1st PM is very narrow
Mucogingival Jxn
Separates the attached gingiva and the alveolar mucosa
Joins lining mucosa and masticatory mucosa
Separates Keratinized from Non keratinized

49

Attached Gingiva
Stippled, firm, thick
No separate Submucosa, hard palate?
Immobile
No glands, except posterior of hard palate
Epithelial ridges high
Epithelium thick, keratinized

Alveolar Mucosa
Thin, loosely attached to periosteum
Well-defined submucosa
Mobile
Many small glands present
Epithelial ridges low
Epithelium thin, non-keratinized

PERIODONTAL LIGAMENT

STOP
General Info:
0.2mm wide
Widest in the cervical region narrowest in the middle region
Thickness depends on:
Age (thickness decreases 0.1mm in old agefrom deposition of cementum and bone)
Stage of eruption
Fxn of the tooth
In loss of function:
PDL narrows it becomes taut like yarn
Regular arrangement is lost
PDL becomes a thin MB w/ irregularly arranged fibers
Cementum may become thicker
In occlusal trauma:
Alveolar bone is resorbed
PDL is widened (PDL space enlarges) -- inflammation
Tooth becomes loose
Health & ability of PDL to resist occlusal force depends on:
Anterior teeth have slight or no contact in ICP
The occlusal table is less than 60% of the overall FL width of the tooth
The occlusal table of the tooth is generally at right angles to the long axis of the tooth
Crowns of Mn molars are inclined about 20 toward the lingual
Derived from the dental sac
(which makes the entire attachment apparatus- cementum, PDL, and alveolar bone proper)
Forerunner of the PDL in mandibular development is the Dental Sac
Connects to cementum and alveolar bone (Directly adjacent)
Contains remnants of Hertwigs root sheath (Rests of Malassezcalled cementicles when calcified)
Sharpeys Fibers terminal portion
Diameter greater on bone side vs. cementum
PDL contains:
Cells
Blood vessels
Periosteal blood supply is the major source of blood to the PDL
Also gingival arteries & arteries of the periapical area
Lymphatics
Extracellular substance of fibers (gingival and principal)
Mostly collagen
Type I & III
Ground substance
Mostly proteins and polysaccharides
Oxytalan fibers
Related to the microfibrillar component of elastic fibers
Run parallel to root surface
Fxn of PDL:
Physical/Support
Attachment of tooth to bone via principal fibers
Formative
Formation of CT components by activities of CT cells (cemento-, fibro-, and osteoblasts)
Remodeling

50

By activities of CT cells (blast vs. clast of above cells)


Nutritive
Through blood vessels
Sensory
By Trigeminal nerve
Proprioceptive and tactile sensitivity
DOES NOT help to maintain the epithelial attachment
If you bite on a popcorn kernel, what causes relaxation of the jaw???
Mechanoreceptors in the PDL (Mesencephalic Nucleus)
Principal Fibers (5)
Main structural elements w/in the PDL
There are NO elastic fibers in the PDL
Composed of Type I collagen
Collagenous ONLY
Classified as belonging to general group of alveolodental fibers
Apical
Offer initial resistance to tooth movement in occlusal direction
Alveolar crest fibers
From cervical cementum of the tooth to the alveolar crest
Fxn to counterbalance the occlusal forces on the more apical fibers and resist lateral movement
Oblique fibers (33%)
Insertions into the cementum and extend apically and obliquely into the alveolus
Most resistant fibers to forces along the long axis of the tooth (masticatory)
Protects tooth from apical pressure
Reduce the probability of forceful impaction into the alveolus because of a blow to the crown
Group of fibers most likely to be found in the middle 1/3rd of root
Horizontal Fibers
Perpendicular from alveolar bone to the cementum and resist lateral forces
Interradicularr fibers
Only in multi-rooted teeth
Extend from cementum in furca are to bone w/in furca area
ALVEOLAR PROCESS
Part of alveolar bone that houses teeth
2 Main Parts:
1) Alveolar Bone Proper
AKA Cribiform Plate, Tooth Socket, or Lamina Dura
Immediately surrounds root of the tooth to which the PDL fibers attach
Has minute openings for vascular and nerve components (called Cribiform plate or lamina dura)
2 layers of Bone:
Compact lamellar bone
Layer of bundle bone layer PDL fibers insert into this bone
Tooth attachment via Cementum, PDL, AND Bundle Bone
2) Supporting Alveolar Bone
Bone which surrounds the alveolar bone proper and gives support to the socket
2 Types of Bone
Cortical plate compact bone forms the outer and inner plates of alveolar process (thicker in Mn)
Spongy Bone fills in area between cortical plates,
NOT present in anterior or in radicular bone of maxillary posteriors as the cortical plate fuses
with the cribiform plate
IN SHORT From tooth
Cementum PDL Bundle Bone Lamellar Bone Cortical Plate Spongy Bone Cortical Plate
The ratio of organic to inorganic material is approximately the same in alveolar compact & spongy bone
Normal interosseous architecture is influenced to the greatest extent by the level of adjacent CEJs (because the level of
the CEJs determines the height at which the PDL attaches to cementum)
During eruption of perm teeth, alveolar bone is resorbed & deposited intermittently
In health, the height of the IP alveolar crest is related to the position of the cementoenamel lines of adjacent teeth!!!!!
Alveolar crest & interdental septum can be altered by:
Tooth rotation, drifting, tilting, or eruption
When viewed occlusally, the alveoli of R & L Mn central/lateral incisors tend to be aligned nearest to a straight line
What causes formation of the alveolar process?

51

Formation of teeth
W/o teeth there is no process
Retromolar pad
A slight elevation of gingival tissue, normally found posterior to the most posterior Mn molar tooth
Nasopalatine canal
Its opening is located at the anterior midline of the palate
Circular
ARTICULATOR Qs
Random stuff added from recent Files
Most important thing in checking excursive
Lateral checkbite
Most important in checking protrusion
Condylar inclination
whats most important when checking articulation of teeth!!!!!
bennet angle
condylar inclination
ICP contacts I put this
Horizontal angle
Lateral check bite
Whats most important thing in mounting maxilla to articulator
bennet angle
condylar inclination
ICP contacts
Horizontal angle
Lateral check bite
Facebow record I put this
Whats most important thing in checking excursives
bennet angle
condylar inclination
ICP contacts
Horizontal angle
Lateral check bite
Facebow record
Whats most important thing in checking protrusives
bennet angle
condylar inclination I put this
ICP contacts
Horizontal angle
Lateral check bite
Facebow record
You change the settings on the condyle of the articulator on BOTH sides, what movement does it affect?
Left lateroprotsive
Right lateroprotsive
Left medioprotusive
Right Medioprotusive
Right laterotrusive this is what I put because it was the only one different from all the rest as it wasnt
lateroPROtrusive
adjusting condyler angle on articulator directly effects what movement on the excursives: posterior guidance (closer to articular
eminence) or Ant guidance (protrusion)
Questions with pictures (not added to notes)
77 Q07, 66, 78, 84; 79a Q01-05, 07, 30, 64, 71, 78, 81, 82, 90-93; 79b Q01-04, 07, 25, 32-36; 80 Q01-06, 20, 86, 91-94; 81 Q01-10,
18, 22, 25-27, 80, 87, 92; 84 Q01-08, 15, 26, 33, 35, 56, 70; 86 Q01-09, 10?, 28, 38, 57, 63, 67, 73, 85; 88 Q02, 08, 11, 16, 20, 26, 29,
32, 41, 43, 48, 56-7, 62, 68, 72, 75-6; 89 Q02, 07-09, 13, 24, 25, 36, 37, 54, 62, 69; 96 Q14, 16, 28, 32-4, 41, 43, 45, 51, 66
USC messed up the following questions:
1977 Q41; 83
1979a Q49 (E should read 2-4mm)
1979b Q47 (no picture)
1980 Q 1,2 wrong pics, 96??
1984 Q39 (wrong Ans should be (e), (f), (g)); Q81 (poorly worded should say toward the incisal at the (A) mesial aspect)
1989 Q19 (no correct Ans would be E); Q39 (wrong Ans should be C)

52

1996 Q35 (no picture); Q81 (no correct answer option given the correct answer is C)
Lame questions:
1977 Q35 (Dryopethecus pattern); Q50 (teeth of grazing animals); Q70 (dentin islands); 88
1979a Q19 (fossil teeth see 79b Q ); Q97 (rodent teeth)
1979b Q28 (biochem about muscles); Q43; Q79 (anatomy section)
1980 Q96

Random Stuff all from 2007 so know this you dummy


Teeth with least amount of angulation? premolars

53

ANATOMIC SCIENCES
ADD
More detail on thoracic duct lots of 2007 questions from that.
REVIEW
Arteries!!!
Exocrine organs
FACIAL VEINS
LYMPH
USC messed up the following questions:
1979 Q79 (all of these structures pass through the diaphragm)
Questions I just didnt include:
1982 Q92
-

CELLS
Components of cells
o Plasma MB:
Dynamic, selectively permeable MB enclosing the cytoplasm
Between cell wall & cytoplasm
Composition:
Lipids (phospholipids, cholesterol, glycolipids)
o Cholesterol increases mechanical stability; also decreases MB fluidity, but prevents freezing
o Increasing unsaturated FAs increases fluidity
Proteins (integral MB proteins & peripheral MB proteins)
o All transport proteins are integral MB proteins
One layer of charged lipids on either side of a layer of neutral lipids
Cell coat and microfilaments are attached to the cell membrane (golgi complex is not)
o Cell Wall:
Protects the cell from changes in osmotic pressure
Anchors flagellae
Maintains shape
o Fluid stuff:
Protoplasm:
Viscous, translucent, watery material that is a primary component of animal cells
Contains large % water & inorganic ions (K+, Ca2+, Mg2+, Na+) & naturally occurring organic compounds (e.g., proteins)
o Irritability
Property of protoplasm responsible for cell being sensitive to a stimulus
Nucleoplasm:
Protoplasm of the cell nucleus plays part in reproduction
Communicates with the cytoplasm by way of nuclear pores
o Molecules < 40kD can diffuse freely between nucleoplasm & cytoplasm thru the pores
Cytoplasm:
Protoplasm of the cell body that surrounds the nucleus, converts raw material into energy
Site of most synthesis activities
Contains cytosol (viscous, semitransparent fluid that is 70-90% water), organelles, and inclusions (metaplasm)
Metaplasm:
Name given to lifeless material stored in cytoplasm
EX: glycogen (an example of a cytoplasmic inclusion), fat deposits, pigment granulesincluding lipofuscin (yellowishbrown substance that in quantity as cells age), and melanin (abundant in epidermis of skin & retina)
o Lipofuscin is the wear & tear pigment
o Microtubules:
Specialized type of filament composed of polymerized tubulin (protein)
Cylindrical hollow structures in the cytoplasm of all eukaryotic cells
Provide support and assist in cellular locomotion
Flagella and cilia
o Flagella:
Present in humans only in the spermatozoa
Core composed of microtubules
9 double circumferential microtubules and 2 single centrally located microtubules
Much longer than cilia

Move w/ an undulating snake-like motion


Cilia:
Short, hair-like projection from the cell MB
Beat in coordinated waves
Core composed of microtubules
9 double circumferential microtubules and 2 single centrally located microtubules
9 + 2 arrangement of microtubules
o Similarities between Flagella and Cilia:
Nine sets of doublets, two singlets in center
Basal body
Essential to function of cilia and flagella
From the basal body, fibers project into the cytoplasm, possibly to anchor the basal body to the cell
Move by contraction of tubular proteins
o Axoneme: Inner core of the flagella or cillia
Characteristic 9+2 pattern
Peripheral pairs share common wall of 2-3 protofilaments
Central pair of tubules are separated from one another and are enclosed w/in a central (single) sheath. Doublets and
central sheath linked by nexins
o CenTRIoles:
Nine sets of triplets
The microtubule organizing center of the cell
o Centrosomes:
Contain centrioles
Microfilaments:
Much smaller than microtubules and have contactile and structure groups (a filament is much smaller than a tubule)
Contractile is made up of
o Double-stranded helices of polymerized actin
o Actin and myosin
Structural is made up of
o Tonofilaments support the cell and provide attachments for Desmosomes, which anchor contigous cells, and
terminal webs , which anchor microvilli
What layer are they found in???? are they used in hemidesmosomes at the basal layer = stratum germ/basale,
Im going with Spinosum?
They are found in ALL layers except for corneum This test Sucks!
If it said anything about desmesomes Id go with spinosum. Hemidesmisomes go w/ basale.
Involved in local movement, by sliding filament movement (as in muscle fiber microfilaments)
o Microvilli:
Think Microvillaments
Core of microfilaments
Intestines
Primary purpose is to increase functional surface area (not flagella or cilia)
o ***Hey: Microvilli have microfilaments; Cilia have microtubules dont screw it up!!! Since flagella and cilia are
for movement, you need a TUBE rather than a little filament. Actin and Myosin (the filaments) are in the intestinal
villi.
o Stereocilia:
Long, nonmotile microvilli that cover the free surface of some of the pseudostratified columnar epithelium which
line the inside of the Epididymis
S for Sex and Stereocilia
Different from Cilia in that they are Nonmobile and have microvilli (microvillaments) NOT microtubules
Facilitate the passage of nutrients from the epithelium to the sperm by increasing the epitheliums surface area
Also present in the ductus (vas) deferens, which is also lined with pseudostratified epithelium
Intermediate filaments
Attachments between IFs are by DESMESOMES
Rope-like filaments that function in structural roles
Barr body: The unused X chromosome in the XX female or the XXY (abnormal) male
Sex chromatin body
Genetic activity of both X chromosines is essential only during the first weeks after conception
Later development only requires one functional X
Inactivated X chromosome appearing in dense chromatin mass attached to nuclear MB of normal female
Absent in normal males
If a male has a barr body, then he has Klinefelters (XXY)
Sex of embryo determined if Barr body present, as early as eight weeks
o

o
o

o
o

o
o

o
o
o

Important in recognition in epi cells because it tells us sex


Cytoskeletal elements:
Form network of protein structures
Nucleus
DNA is found principally in the nucleus
Feulgen Reaction test to distinguish beween DNA and RNA
Tells us what the Nucleus is FEUL (full) of
Nucleolus: located within the nucleus and NOT MEMBRANE BOUND
Site of rRNA synthesis (not DNA, tRNA, or mRNA) Assembles ribosome components
NOTE: rRNA is the most abundant RNA in the cell
NOT bound by a membrane (unlike nucleus, lysosome, mitochondrion, & pinocytotic vesicle)
Ribosomes:
Site of protein synthesis
All protein synthesis begins on free polysomes
Smooth ER (ribosomes are absent): Stores Ca++ in muscle cells
Steroid synthesis (vs. Protein Synthesis for RER)
The Q reads: Smooth ER predominates in steroid producing cells, but not in protein producing cells
Protein synthesis for use inside the cell not sure about this isnt this done by free ribosomes.
Intracellular transport
Detoxification reactions (hydroxylation & conjugation)
Glycogen degradation & gluconeogenesis (glucose-6-phosphatase is an integral MB protein of the SER)
Lipolysis begins in the SER
***Hepatocytes & steroid hormone producing cells of adrenal cortex are rich in SER
Rough ER (ribosomes are attached):
Protein synthesis for use outside the cell aka, site of synthesis of secretory proteins
Also site of N-linked oligosaccharide addition to many proteins
Think Osteoblasts
Associated with RNA repeated again & again & again on tests (rRNA)
*Cytoplasmic RNA is localized in granular endoplasmic reticulum
Has regions that are smooth in appearance called transitional elements
***Mucus-secreting goblet cells & Ab-secreting plasma cells are rich in RER
Active cells characterized by an abundance of rough ER (fibroblasts, osteoblasts)
Golgi apparatus:
Flat, membranous sacs or cisternae arranged in stacks (the stacks are called dicytosomes) w/ two poles
The cis face receives material
The trans face is for transportation function
Packages, stores, modifies & sorts products post-translational
Packages secretory material and forms lysosomes
Forms glycoproteins for extracellular use
Proteoglycan assembly from proteoglycan core proteins
Modifies N-oligosaccharides on asparagine
Adds O-oligosaccharides to serine & threonine residues
Procollagen filaments formed here from polymerization of amino acids!!!!! KNOW THIS
Polymerization of molecules into collagen fibrils occurs in the Golgi
Lysosomes:
Cytoplasmic MB-bound vesicles containing glycoprotein hydrolytic enzymes that digest & destroy exogenous material
Lysosomes deal w/ biochemical breakdown & phagocytosis in the oral region
Are formed in the Golgi apparatus (they bleb off of it)
Are called to action when the cell produces too much proteins
Peroxisomes:
Contain oxidases, enzymes capable of reducing oxygen to hydrogen peroxide and hydrogen peroxide to water
Bile acid synthesis occurs in peroxisomes
Vacuoles:
Store & excrete various substances w/in the cytoplasm
Mitochondria:
Threadlike structures w/in the cytoplasm that provide ATP
Similar to bacteria in shape & size
Reproduce by dividing (also like bacteria)
The most important organelle or component of a cell for oxidative processes = mitochondrion
Contain a double MB (inner & outer MBs)
Outer MB:
o Smooth, continuous, permeable

o Contains a lot of porin (integral MB protein that forms channels in the outer MB)
Inner MB:
o Impermeable to small ions (due to high content of cardiolipin)
o Enzymes for ETC & Oxid Phos are embedded in the inner MB
Both mitochondria and nucleus have double-unit membrane (not lysosome, Golgi complex, or rough ER)
Maternal DNA Link
Contains cyclic DNA like bacteria
Crista of the Mitochondria folds of the inner membrane
Stores and provides more surface area for chemical reactions to occur (Protein NZs)
Embryonically early cell types/forms:
o Mesenchymal cells (mesoblastic cells)
Potential to proliferate & differentiate into diverse types of cells
Form a loosely woven tissue called mesenchyme or embryonic CT
o Mesectoderm (ectomesenchyme)
Derived from ectoderm, especially from the neural crest in the very young embryo
The primary source of cranial connective tissue cells is the ectomesenchyme
o Neural crest cells:
Give rise to spinal ganglia (dorsal root ganglia) and the ganglia of the ANS
Give rise to neurolemma cells (Schwann cells), cells of the meninges that cover the brain and spinal cord, pigment cells
(Melanocytes), chromaffin cells of adrenal medulla and several skeletal and muscular components of head
o Fetus Blood Cells
Developing fetus blood cells are found in the red bone marrow, liver, spleen, and lymph nodes
Important CellsFunction or Location
o Macrophagephagocytosis, defense against bacterial infection
Activated by gamma-IFN
Can function as APC
Kupffer cellliver
Splenocytespleen
Histiocyteloose CT
o Mastmediators of inflammation on contact w/ antigen, same as Basophil in that it secretes Heparin & Histamine
Mediates allergic reaction involved in type I hypersensitivity reactions
o Schwannform myelin sheath around axons of PNS
Derived from neural crest cells
o Sertoliproduce testicular fluid (not testosterone)
o Leydigproduce testosterone Ley-dig cells produce testosterone for the Lay-ds.
o Fibroblastproduces collagen and reticular fibers, most common cell of CT
o Osteoblastforms bone matrix and gives rise to osteocytes
o Sustentacularinternal ear (organ of Corti), taste buds, olfactory epithelium susten-spec-tacular cells b/c involved in ear,
taste and smell!
o Pyramidalcerebral cortex (cerebrum)
The pyramids contain upper motor neuron fibers only
o Endotheliallining blood and lymph vessels, endocardium inner layer
o Ependymallining brain ventricles and spinal cord
o Ganglionicin the ganglion of peripheral to CNS
o Globulartransitional epithelium (kidney, ureter, bladder)
o Pricklestratum spinosum of epidermis spiny = prickly
o Chromaffinadrenal medulla and paraganglia of Symp NS
o Purkinjecerebellar cortex (cerebellum) info out of the cerebellum
o Claraterminal bronchioles
o Goblet cellsmucous MBs of female reproductive tract, respiratory tract, and intestines, colon No Goblet cells in stomach
o InterstitialCT of ovary and testis
o Isletpancreas
o Juxtaglomerularrenal corpuscle of kidney
o Hepatocyteliver
Cell replication:
o Chromosomes:
= DNA + protein (histones)
Appear as chromatin granules called chromatids, attached to centromeres when replicating
o Chromatin:
A complex of DNA & proteins (the proteins are either histone proteins or non-histone proteins)
Histone proteins:
o (+) charged proteins enriched w/ lysine & arginine

o
o
o

o Involved in DNA packaging


Non-histone proteins:
o Enzymes involved in nuclear functions such as replication, transcription, & DNA repair
Is the cell component that is genetically continuous from one generation to the next (not nuclear membrane or golgi
complex)
Euchromatin: (Eu means Good and Loose!!)
Loose form of DNA & transcriptionally active
Heterochromatin:
Highly condensed & transcriptioinally inactive Heteros arent as kinky or sexually ACTIVE
Almost the entire inactive X chromosome somatic cells in a woman is in this form
Mitosis:
Splitting of nucleus & cytoplasmtwo diploid (daughter) cells w/ identical genetic constitutions
Keeps the same 2N (diploid) the Q reads: The diploid number of chromosomes is perpetuated in somatic cells by a
process of mitosis
M phase mitosis (karyokinesis) division of the nuclear parts of cell (no protein synthesis)
See Below (PMAT)
Cytokinesis division of the cytoplasm, accompanies mitosis
Interphase (inactive phase) period between one mitosis and the next
o G1 phase 1st growth phase
By far the most variable cycle period timewise among different types of cells
o S phase when DNA is replicated
o G2 phase 2nd growth phase
Four active phases of Mitosis:
Prophase
o Gradual coiling up of chromatin in nucleus
o Individualization of chromosomes, initiation of mitotic spindle w/ centriolar duplication
o Phosphorylation of the nuclear lamina during prophase initiates nuclear disassembly
Metaphase
o Disappearance of the nuclear envelope & nucleoli
o Chromosomes line up at the equatorial plate
o Spindle is complete
Anaphase
o The chromosomes split longitudinally and migrate to poles
o Beginning of cell division
Telophase
o Nucleolar restitution w/ nuclear envelope formation
o End of cell division
o # of chromosomes after telophase???
46?? Only if youre counting PAIRS BEFORE Cytokinesis
There would be 46 PAIRS or 92, BEFORE cytokinesis. 23 pairs or 46 total afterward.
Cytokinesis
o Splitting of the cytoplasm
o Occurs right after telophase
o NOT essential for Mitosis to occur
Meiosis:
Gametes genetic material between homologus chromosomes is intermixed
Two divisions separated by a resting phase
Total of 4 daughter cells, each w/ the original # of chromosomes
Goes to Haploid
Goes through meiosis I (where the reduction division happens) and then meiosis II (splitting of sister chromatids)
CONNECTIVE TISSUE

Types
Epithelial tissue
CT Proper
Muscle

Description & Function


May be one or several layers thick; lower surface bound to a supportive
basement MB of glycoprotein, mitotically active tissue; line all body
surfaces, cavities, and lumina and are adapted
Highly vascular (except cartilage); contain considerable intercellular
matrix; mitotically active tissue, support or bind other tissues and provide
metabolic needs
Limited mitotic activity; fibers are adapted to contract in response to
stimuli; movement of materials through the body, the movement of one
part of the body

Example
Outer layer of skin, linings of GI tract,
urinary bladder, ducts and vessels; alveoli
of lungs; and covering of viscera and body
Tendons and ligaments; cartilage and bone,
adipose, blood
Smooth, skeletal, and cardiac muscle

Nervous tissue

Limited mitotic activity; respond to impulses to and from all body organs

Neurons and neuroglia

CONNECTIVE TISSUE
- CT in general:
o Derived from mesenchyme (mesoderm)
o Contains more intercellular material than cells
o Most common cells are the fibroblasts & macrophages
- CT Types:
o Dense CT provides tendons & ligaments w/ strong, flexible support; has high [fiber]
Dense regular: think more linear structures
Consists of tightly packed fibers arranged in consistant pattern EXs include tendons, ligaments, & aponeuroses,
&surrounding muscle fascia (NOT DEEP fascia though)
Dense irregular: think more lining structures
Consists of tightly packed fibers arranged in an inconsistent pattern
Found in dermis, submucosa of the GI tract, fibrous capsules, and deep fascia
o Loose CT (aka areolar CT) contains large spaces separating the fibers & cells, and contains a lot of intracellular fluid
Hypodermis is loose CT
- Collagen Types:
o Type I: most abundant found in dermis, bone, tendon, dentin, fibrous cartilage, fascias, late wound repair
o Type II: mainly in hyaline & elastic cartilage, vitreous body Type II for 2 eyes
o Type III: major component of reticular fibers (in skin, BVs, uterus, granulation tissue) think three on the (BV)
Three on the BeeVee for the RE-ticular fibers
o Type IV: found in basal lamina of basement MBs think fo on the flo
o Type V: present in fetal MBs Type Five to come Alive
o Type X: epiphyseal plate
- Tendons/ligaments:
o Ligament band of CT that binds bone to bone
o Tendon band of CT that attaches bone to muscle
More specifically, it secures the muscle fascia to periosteum
Aponeurosis = a sheet-like tendon
o ***When a tendon or ligament attaches to bone, the attaching fibers are called Sharpeys fibers (its not just in teeth)
These are the periosteal collagen fibers that penetrate the bone matrix, binding the periosteum to bone
- Fasciculus
o A bound group of individual muscle fibers
o Fasciculi are the bundles of muscle fibers composing the muscle
- Fascia
o Each muscle is surrounded by fascia, which secures the muscle to a tendon
o Composed of dense regular CT Linear
- Intercellular Junctions:
o Six major types of cell junctions in humans:
1) Tight junctions (zonula occludens)
Greatest resistance to substances moving between cells
o Think Keep it tight so nothing gets through
2) Intermediate junctions (zonula adherens)
Belt-like connects two neighboring cells
3) Desmosomes (macula adherens) (Think macules are spots)
Spot-like connects two neighboring cells
o Tonofibrils (tonofilaments) are found in the desmosome (spinosum???) Just not in the corneum
4) Hemidesmosomes
Spot-like connects plasma MB of an epithelial cell to the underlying basal lamina
o Epithelium anchored to the basal lamina and thus to the underlying CT
Common in stratified epithelium of skin and junctional epithelium of the epithelial attachment
Part of the oral cavity which is directly attached to the periosteum??
Hemidesmosomes to the CT
Junctional epithelium has hemidesmosomes & gap junctions
Bullous pemphigoid:
o Involves disruption of hemidesmosomes & consequent separation of the epithelium from the basal lamina
5) Focal contacts
Spot-like connects plasma MB of a fibroblast to the surrounding CT
6) Gap junctions
Specialized areas of cell MB connects neighboring cells
Communicating junctions

Organized collections of protein channels that allow ions/small molecules to passively traverse between connected cells
Separate from components of the junctional complex
Exist in all multicellular organisms and in almost all cell types
Some exceptions skeletal muscle (Because you want recruiting ability), RBCs, & freestanding cells such as circulating
lymphocytes
EPITHELIAL TISSUE
- Classified according to cell shape & number/arrangement of cell layers
- Functions of Epithelium:
o Protection, absorption, excretion, and secretion
- Types of Epithelium:
o Simple squamous epithelium:
Found where diffusion & filtration occur
Endothelium lining BVs & mesothelium lining body cavities
Alveoli of the lungs
o Simple cuboidal epithelium:
Collecting ducts, as well as proximal & distal tubules of the kidney
Thyroid follicles
Respiratory Bronchioles
o Simple columnar epithelium:
Specialized for secretion or absorption
Lines the majority of the GI system
Small & large intestine, gallbladder, & stomach (epi associated with the tubular part of the GI tract)
There is a distinct epithelium change between the esophagus and the stomach
Uterine epithelium
Salivary gland striated ducts
o Stratified squamous epithelium:
Usually contains cuboidal cells in the deeper layers & squamous cells in the surface layer
This tissue is well adapted for abrasion and protection most resistant to trauma
Broadest classification of epithelium
Found on skin, linings of mouth, oropharynx, laryngopharynx, esophagus (usually not keratinized), anus, and vagina
When it thickens, rete pegs increase in size, and intercellular bridges become more evident
o Stratified cuboidal epithelium:
Ducts of the sweat glands
So simple cuboidal is kidneys, stratified cuboidal is for SWEAT!
o Stratified columnar epithelium:
Large ducts of salivary glands
Male urethra
o Specialized EXs:
Pseudostratified ciliated columnar epithelium:
Respiratory Mucous MB of nasal cavity, paranasal sinuses, nasopharynx, trachea, & bronchial tree
o Not the lining of the respiratory bronchioles, which lose their cilia and change to cuboidal and then to
squamous
Parts of the male reproductive tract
Transitional epithelium
Stratified tissue that lines the urinary bladder, ureter, and upper part of the urethra
Contains dome-shaped superficial cells that change form when contracted or stretched
When epithelium is damaged changes into transitional epithelium
When epithelial cells specialize so that a free border is characterized with the presence of microvilli, then the cell possesses
either a striated or brush border (not pseudopoda or cilia) (e.g. brush border of the small intestine)
Epithelium
Simple
Pseudostratified
Stratified
Special stratified: transitional

Cells
Squamous
Cuboidal
Columnar
Columnar
Squamous
Cuboidal
Columnar
Varies between cuboidal and squamous

Function
Diffusion and filtration (Endo and mesothelium)
Secretion, excretion, or absorption (Kidney)
Absorption, secretion, and protection (GI)
Secretion and transport of particles out of air passages
(Respiratory/Mucus MB of nasal cavity)
Protection, prevents water loss (skin/esoph/anus/Vag)
Protection and secretion (sweat glands)
Protection (urethra)
Permits expansion (bladder, urethra)

Functions of skin:
o Prevention of body dehydration
o Synthesis of Vit D
o Prevention of pathogen entry
o Regulation of body temperature
Skin
o Epidermis (outer) consists of stratified squamous epithelium
Develops from embryonic ectoderm
Avascular
Outer cells are dead, keratinized, & cornified
o SIDE BAR: Excessively thickened layer of the straum corneum composed of:
orthokeratin (hyperorthokeratosis): keratin layer without residual nuclei (Normal) and uneven surface (so you need ortho)
parakeratin (hyperparakeratosis): keratin layer with shrunken (pyknotic) residual nuclei (more even surface) para is with,
so WITH nuclei
In denture pt that continually wears them and eroded alveolar bone, the underlying alveolar mucosa is best described as
gingival mucosa becoming orthokeratinized mucosa
Basement MB:
o Thin structure that attaches epithelium to underlying CT in contact w/ the dividing layer of cells
o Consists of glycoprotein from the epithelial cells and a meshwork of collagenous and reticular fibers from the underlying CT
o Type IV collagen
o Contains Hemidesmosomes
o Consists of:
Basal lamina develops from epithelial cells
Basal epithelial cells are most likely to be in mitosis (stem cell layer)
Reticular lamina develops from CT
o Lamina Lucida/Densa??????
o Dermis (inner) deeper, thicker layer of the skin
Consists of dense irregular CT -sheetlike, layered. Not linear like dense regular.
Develops from embryonic mesoderm
Contains
BVs & lymphatics
5 types of nerve endings
o (one Q reads: The dermis contains a wider variety of nerve endings than does the epidermis)
Desmosomes
Mitotic cells
Sebaceous glands
Associated with hair follicles and derived from ectoderm
Not found on palms of hands/soles of feet (Not found on glabrous skin)
Sweat/oil glands and hair follicles sheath which are in the basal layer
Papillary layer:
Thin & less fibrous
Has projections (papillae) that extend up toward the epidermal layer (rete pegs)
Finely constructed, thin, loose CT So most of dermis is dense irregular CT, but papillary layer is LOOSE!
Contains fibroblasts, mast cells, & macrophages
Elastic fibers are abundant and provide the skin tone
Reticular layer: (Deepest layer)
Thick, fibrous, dense irregular CT
Continuous w/ the hypodermis
Reticular fibers are abundant (Type III collagen)
Collagenous fibers & elastic fibers are also present
More fibers & fewer cells than in the papillary layer
o Tissue fluid reaches the epithelium in the skin through the ground substance of CT from capillaries
Hypodermis:
o Subcutaneous layer found beneath the dermis that binds skin to underlying structures
Connects dermis w/ underlying fascia of muscle:
o Composed of loose areolar CT, adipose tissue and BVs & and lymphatics
Major site of fat deposition (50% of body fat)
The Q actually asks: Where is fat found? & the answer is NOT dermis; submucosa or CT layers are options, which
works for the hard palate (submucosa), but maybe not the skin???
o My understanding: There is more fat found beneath the skin (the hypodermis) than in the oral cavity below the
mucosa (the submucosa.) CT layers is not specific enough

Good blood supply


Epidermis: (BiG Stars Give Lots of Charity)
o Outermost portion of skin develops from embryonic ectoderm
What cell junction type in epithelium Tight junctions (aka Zona Occludens) this resists substance passing through
o Layers from INSIDE TO OUT:
o 1) Stratum Basale (= Stratum Germinativum):
Least cytodifferentiated
Contains cuboidal or low columnar cells that exhibit lots of mitosis
Contains tonofibrils in the cytoplasm
Melanocytes are located here
Forms epithelial root sheath of hair follicle
o 2) Stratum Spinosum: aka PRICKLE LAYER
= prickle cell layer
Contains cells called Langerhans cells (unknown function perhaps immune response) Arent they Antigen Presenting
Cells? THINK SO!
Cell junction type in stratum Spinosum desmosomes (aka Macula adherens)
Malpighian layer denotes the stratum basale and stratum spinosum together
In the prickle cell layer of sulcular epithelium, the space in between cells is occupied by a small amount of tissue fluid,
NOT keratin or capillaries. Keratin is intracellular, and there is no blood supply to the epithelium!
THICKEST LAYER??, except for Thick Skin YES it is look at histo x-sections.
The following 3 Layers are NOT present in NON-Keratinized Oral Epithelium hmm. Check this out not sure about that line.
o 3) Stratum Granulosum:
Contain keratohyaline granules in the cytoplasm (not melanin or keratin granules)
o 4*) Stratum Lucidum:
Clear band of cells containing eleidin which is transformed into keratin as this layer becomes part of the stratum corneum
Most prominent in thick skin (palms & soles)
Absent in the thin skin and (orthokeratinized oral mucosa, which is thin skin)
NOT present in the oral cavity
o 5) Stratum Corneum:
Composed of closely packed dead cells filled w/ keratin
Thickest stratum corneum is found in the palm
Some cells of epithelium
o Keratinocyte:
Cell type most common in epidermis of skin
Specialized to produce keratin (a protective protein)
Tonofibrils & desmosomes are especially well developed in keratinocytes anchor to one another
o Melanocytes: produce melanin.
In basal layer
o Langerhans cells: antigen presenting cells, part of immune system
In spiny layer
o Merkel cells: associated w/ nerve endings
o Inflammatory cells: lymphocytes, monocytes, neutrophils
Cutaneous appendages: (see Kaplan in Integument chapter for all the details on these)
o Eccrine (merocrine) sweat glands normal, clear sweat producing
o Apocrine sweat glands smelly
o Sebaceous glands waxy
o Hairs
o Nails
Oral epithelium:
o Some structures found in the oral mucous membrane:
Basal lamina, lamina propria, keratohyaline granules (deeply stained granules in cytoplasm), stratified squamous epithelium
o Covered w/ stratified squamous epithelium
Areas of oral stratified squamous keratinized: gingiva, hard palate (are of mechanical stress)
o Permeabilities of oral mucosa:
Sublingual > buccal > palatal
Is based on relative thickness & degree of keratinzation
EX: sublingual mucosa is relatively thin & non-keratizined and thin lamina propia (great for meds)
o Sublingual musosa is the thinnest epithelium of the oral cavity
o Oral cavity is highly acceptable for systemic drug delivery
Mucosa is relative permeable w/ a rich blood supply
Virtual lack of Langerhans cells makes the mucosa tolerant to potential allergens
Route also bypasses the first-pass-effect & avoids pre-systemic elimination in the GI tract

EX nitroglycerin tablets given sublingually for rapid absorption


NOTE: alveolar mucosa is similar to sublingual mucosa appears red due to the numerous BVs & thin epithelial covering
o CT of oral cavity (referred to as lamina propria): synonymous with dermis layer in skin
Forms mechanical support & carries BVs & nerves
Two layers:
Papillary layer directly under epithelial layer, more cells, tone
Reticular layer dense, fibrous layer located under papillary layer
Oral mucosa of the cheek has a thinner lamina propria then the outer surface of the lip non keratinized vs. keratinized
o Submucosa:
Located between CT and muscle tissue
Present only in areas requiring a high degree of compressibility & flexibility (cheeks, soft palate)
Kaplan states that it is defined Submucosa, but immovable because it is tightly bound to underlying periosteum
The Anterior part contains much adipose tissue, and posterior part of the hard palate is full of glands
o NOTE: the most outstanding difference between the gingiva and the mucosa of the hard palate is the presence of glands
CARTILAGE/BONE
- Cartilage is avascular heals slowly after injury
- No calcium salts are present cartilage doesnt appear on x-rays
- Can support great weight, yet it is flexible & somewhat elastic
o Firmness of cartilage depends on:
Electrostatic bonds between collagen fibers & GAG side chains of matrix glycoproteins
Binding of water to the (-) charged proteoglycan complexes
- Cartilage has a preponderance of amorphous ground substance over fibers
- Chondrogenic cells = undifferentiated mesenchymal cells important to growth & development of cartilage
- Chondrocytes:
o Reside in depressions in matrix called Howships lacunae
o The only blood supply is provided by BVs entering cartilage through the perichondrium
o Secrete a hard, rubbery matrix around themselves
- Three subtypes:
o Hyaline
Most common type
Matrix contains many, closely packed, fine collagenous fibers
Has a capsule around the chondrocytes which represents the youngest layer of intercellular substance
Covers & protects bone
Precursor to bone in long bones, hyaline provides a region for bone to grow in length
Found where strong support & some flexibility are needed
Forms nearly all of fetal skeleton Most common type think were ALL fetuses
May grow interstitially, where bone only can grow appositionally
In adults:
Articular cartilage smooth and slippery, it lines movable joints Except TMJ!!!
Costal cartilages at the sternal ends of the ribs
Respiratory cartilages movable external nose and septum, larynx, trachea, and the bronchial walls
Auditory cartilages external auditory meatus and pharyngotympanic tube
o Think HYdraulics on the ACuRA.
Ground substance of hyaline cartilage is basophilic because it contains sulfated proteoglycans called
glycosaminoglycans (GAGs are highly negative)Like DNA, negative charged, so will bind to basic basophilic die. (vs.
eosinophilic)
GAGs can readily bind & hold water allows tissue to assume a gelatinous nature resistant to compression and also
permit some degree of diffusion
Most abundant GAG is hyaluronic acid
o Fibrocartilage
Most closely resembles dense, irregular CT
Matrix contains dense collagenous fibers
Withstands tension & compression
Found in intervertebral discs (vertebra), knee joint, TMJ, & symphysis pubis
o Elastic
Matrix contains collagenous & elastic fibers
Similar to hyaline cartilage but the fibers are not as closely packed
More importantly, elastic cartilage contains many elastic fibers (elastin)
Forms the external ear (pinna) and is also found in the epiglottis, the auditory meatus, & larynx
- Tropocollagen
o Protein molecule in BOTH collagen and reticular fibers
- Perichondrium:

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o Consists of a fibrous outer layer (connective tissue MB) and a chondroblastic inner layer
o Very important to cartilage growth Only vascular part associated with cartillage
Cartilage growth:
o Interstitial chondrocytes divide w/in cartilage occurs in epiphyseal plates & articular cartilages
o Appositional where surface perichondrium lays down new layers results from differentiation of perichondrial cells
Mineralization of Bone
o All of the following are contributors to the mineralization of bone:
Holes or pores in collagen fibers
Release of matrix vesicles by osteoblasts
Alkaline phosphatase activity in osteoblasts and matrix vesicles
Degradation of matrix pyrophosphate to release an inorganic phosphate group
NOT Release of acid phosphatase by osteocytes trapped in lacunae
Bone growth:
o Appositional below the periosteum is a fibrous outer layer & a cellular inner layer of osteoblasts, which lay down bone
Because of bones rigid structure, interstitial growth is NOT possible
o Bone increases in size by way of appositional growth by osteoblasts (Not interstitial)
o Do not confuse bone growth w/ bone formation
Bone forms by either endochondral ossification or intramembranous ossification
Endochondral bone formation: (Think ENDO like long bones (files, etc.))
o Cartilage is precursor for bone in this type of growth
o The epiphyseal plate (disc) is a wedge of hyaline cartilage accounting for this increase
The plate is found between the epiphysis & diaphysis at each end of a bone
Cartilage cells of the epiphyseal plate form layers of compact bone tissue, adding to the bone length (by interstitial
growth in the cartilaginous epiphyseal plate) NOTE: Interstitial growth in bones, but of CARTILLAGE, NOT BONE!
The disc becomes inactive in most individuals by late teens/early 20s
o 1 ossification center near the middle of the diaphysis
o 2 ossification center in the epiphysis; forms later note: epi = on top ends of bone.
o Metaphysis the region between the 1 & 2 ossification centers
o The Diaphysis shaft
o Here are the steps, all concise-like:
1) chondrocytes proliferate in epiphyseal plate
2) chondrocytes hypertrophy on diaphyseal side of the area
3) matrix calcifies
4) chondrocytes die
5) osteoblasts lay down layer of primary bone along the bone spicules
Zones of the Epiphyseal Plate
o Zone of resting cartilage
Nearest to the epiphysis
Chondrocytes are disordered and are not dividing rapidly
o Zone of Proliferation
New cartilage is produced by interstitial growth
Multiple chondrocytes stack up forming columns
o Zone of Hypertrophy
Chondrocytes Mature and Enlarge Lacunae also appear swollen
More mature ones are at the diaphysis end and less mature are at the epiphysis end
o Zone of calcification
Thin layer of mineralized matrix
Death of hypertrophied chondrocytes occurs and the lacunae are invaded by blood vessels
Osteoblasts from the endosteum, travel with the connective tissue of blood vessels and aggregate on the calcified cartilage
surfaces
New bone matrix is deposited by appositional bone growth, then remodeled

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o *The width of the epiphyseal plate remains constant because as the bone elongates, there is remodeling inside the metaphysis
o Bones fuse between 12 and 25 depending on bone and leave an epiphyseal line
o Plate closes at age 18?? 24??
Bone Repair picture here? More text to explain at least!
o Blood Clot forms
o Bridging callus forms
o Periosteal callus forms
o New endochondral bone forms
o NOT new osteons grown across the callus

EMBRYOLOGY
General Embryology
- Cleavage
o Begins w/in 24 hours of zygote formation
o With each division, the daughter cells (blastomeres) become smaller (no cell growth)
o Compaction begins w/ the 8-cell stage blastomeres flatten & are held together by tight junctions
o Morula by day 3 or 4, consists of the 16-32 cells, Solid Mass
The First solid ball of cells to form in the embryo
- Blastocyst formation Hollow ball of cells with inter blastocele layer
o Blastocele
Fluid begins to accumulate in the intercellular space & forms a central cavity known as the blastocele
o Blastocyst
In what stage do the cells start to have an inner cell mass?
Blastocyst
Is the zygote, now free of its zona pellucida
Embryoblast inner cell mass projects into the cavity gives rise to the embryo proper
Which cells turn into the inner layer of the fetus?
I think Embryoblast
Trophoblast outer cell mass forms outer epithelial layer gives rise to the fetal portion of the placenta
Think Troph i.e. has affinity to travel to uterine wall!
- 1st Week: Implantation
o Begins by the end of the 1st week
o Upon implantation, the trophoblast produces hCG, a hormone that maintains the corpus luteum (which secretes
progesterone)
Excessive growth of the trophoblast results in hydatiform moles (hCG) which can fill the uterus and result in fetal
death
Also, the trophoblast can form the highly
malignant chorionepithelioma, a tumor of
the chorionic villi
o Ectopic pregnancy implantation outside the uterus
- 2nd Week: Bilaminar disc
o Epiblast primary ectoderm High columnar cells,
during 3rd week forms ectoderm and mesoderm
form the amniotic cavity On top
o Hypoblast primary endoderm Low cuboidal cells
contributes to primary yolk sac (or remaining
Blastocyst) On the bottom

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3rd Week: Trilaminar disc Pic to Right


o Primitive streak
Linear thickening of the ectoderm cells
Defines the cephalocaudal axis of the embryo
Delimited rostrally by the primitive node
o Epiblast cells invaginate between epiblast & hypoblast(epiblast cells go
through the primitive streak) forms the intraembryonic mesoderm
o Notochord formation: (Get your Honda acCORD on your 16th birth
day)
Day 16 cells of the primitive streak migrate rostrally & form the
tube-like notochordal process
The notochord is a rod-shaped body found in embryos of all
vertebrates
Composed of cells derived from mesoderm and defines the primitive
axis of the embryo
Found on the ventral surface of the neural tube
The notochord induces the the thickening of the ectoderm to form the neural plate
Turns in to the Nucleus Propulsus
o Neural plate begins to form
o Buccopharyngeal Membrane Ruptures
What causes the infolding of the head thing in embryology?
o Neural cells growing OR branchial arch formation?? Im 100% sure its from neural cells growing!
4th 8th Weeks: Embryonic Period
o Week 4
For the 4 chambers of the heart begins to beat; upper/lower limb buds begin to form for the 4 limbs, and 4 Visible
Branchial Arches
Neural Plate
The neural plate increases in length as the primitive knot and primitive streak move caudally
Invagination of the neural plate at day 18 forms the neural groove
The edge of each fold is known as the neural crest
Neural tube is formed when the crests fuse, starting at the 4th somite region (neck) and proceeding in cephalic and caudal
directions
The cephalic end of the neural tube will eventually dilate to form the forebrain, midbrain, and hindbrain
o The spinal cord is formed from the remainder of the neural tube
o Neurelation sequence pictures below

Neural crest cells (Ectomesenchyme) Mostly peripheral nerve associated structures


Form Posterior root ganglia, sensory ganglia of the cranial nerves, autonomic ganglia, meninges, Schwann cells,
suprarenal cells, and Melanocytes
Head and Tail Folds Picture of folding to RIGHT
The entoderm (endo) germ layer gives rise to the GI and depends on BOTH the cephalocaudal folding and the lateral
folding of the embryonic disc in a tubelike fashion
HEAD FOLD
Rapid longitudinal growth of the CNS causes the cephalic and caudal ends to bend and form head and tail folds
o As a result the brain comes to lie cranial to the cardiogenic area and septum transversum, which contributes to the
formation of the diaphragm.
o Part of the yolk sac becomes incorporated into the embryo as the foregut

13

o
o

14

This cavity opens into the midgut via the anterior intestinal
portal and is bounded anteriorly by the prochordal plate,
which is known at this stage as the buccopharyngeal
membrane
This membrane forms the back of the stomodeum and
ruptures at the end of the 3rd week to establish
communication between the amniotic cavity and the
primitive gut
TAIL FOLD
o Blah, blah
Lateral Folds
The continued growth of the somites causes the expanding lateral
margins of the embryonic disc to bend ventrally, forming lateral folds
o As a result, part of the yolk sac is taken into the embryo to form the
midgut
o In addition, this folding constricts the initially wide communication
between embryo and yolk sac to a narrow, long vitelline duct,
which eventually lies w/in the umbilical cord
What causes the infolding of the head thing in embryology?
Neural cells growing OR branchial arch formation?? Im
100% sure its form neural cells growing!
THIS is why I think the answer to the above yellow
question is neural cells growth
3rd-8th week fetus most susceptible to teratogens
Ectodermal derivatives:
Surface ectoderm
Otic placode & lens placode
Epidermis
Hair & nails
Subcutaneous glands
Enamel
Anterior pituitary gland
Mammary glands
Hair, enamel, sweat glands & salivary glands are all derived from ectoderm (dentin is not)
Neuroectoderm: CNS STUFF
Posterior pituitary gland
CNS neurons
Oligodendrocytes & astrocytes
Pineal gland
Neural crest:
ANS (e.g., autonomic ganglia)
Sensory ganglia of CNs
DRGs
Meninges
Schwann cells
Adrenal medulla (chromaffin cells)
Melanocytes
Odontoblasts
Mesenchymal (mesodermal) derivatives:
CT (bone, cartilage)
Muscle
Dermis
Urogenital system
Adrenal cortex
Spleen
Serous MBs lining the pericardial, pleural & peritoneal cavities
Endodermal derivatives: Liver, lungs, GI, pancreas, thymus and thyroids are all spongy like
GI system
Thyroid/parathyroids
Thymus
Lungs

Liver
Pancreas
Lining of respiratory tract, bladder & urethra
th
- 10 Week:
o Genitalia have M/F characteristics
Head & Neck Embryology
- Stomodeum = stomatodeum:
o Slight depression on the surface ectoderm
o Represents the primitive oral cavity
o Separated from primitive pharynx by buccopharyngeal MB (oropharyngeal MB)
Composed of ectoderm externally & endoderm internally (no mesoderm)
Covers the stomatodeum
Ruptures at 3 weeks (forming max palatal shelves)
o Prochordal Plate Look up more context here!
Consists of the endoderm of the roof of the yolk sac and embryonic ectoderm
Does NOT contain mesoderm
- Branchial Arches = pharyngeal visceral arches
o General features:
A series of rounded mesodermal (mesoderm cuz cartilage and muscle
from mesoderm) ridges on each side of head & neck of embryo at 4
weeks
Develop in the 4th week as neural crest cells that proliferate & migrate
into the future head & neck region
By end of the 4th week, FOUR well-defined pairs of branchial arches
are visible externally
o The 5th & 6th are small & cannot be seen on the embryo surface
Each branchial arch contains a cartilaginous bar or rod, a muscular
component, an artery, & a nerve
1st-3rd arch play role in formation of face & oral cavity
1st arch develops into Mn & large part of Mx
1st, 2nd & 3rd arches play role in tongue development
Contain striated muscle, not from somites
Branchial arches (are SVE special because they are striated, but not developed from body wall or somites)
o

From the above picture, the facial process indicated w/ the letter A gives rise to the secondary palate

Cartilages of each arch:


1st arch cartilage (M: Meckels, Mandible, Malleus, Muscles of Mastication, Mylohyoid)
1st arch develops into Mn & large part of Mx
A model for the Mn but does not form any part of Mn Meckels cartilage is scaffold only!
o What forms the Mn?? Intramembranous ossification of Meckels WHAT!?!?
o Fate is dissolution with minor contribution to ossification
Closely related to development of the middle ear
o Ossifies to form the malleus & incus
All 8 muscles innervated by V3 (4 mastication, 2 tensors, anterior belly of digastric, and mylohyoid)
NOTE: CN V supplies the muscles derived from the 1st pair of branchial arches
nd
2 arch cartilage (Reicherts)
Closely related to development of the middle ear
o Ossifies to form the Stapes (Second = Stapes)
Think S Second, Stapes, Styloid Process, Stylohyoid, Seven (VII), Smiling (Muscles of facial expression)
Forms part of the hyoid bone
Also forms Styloid process of the temporal bone
Also forms the stylohyoid ligament
Stylohyoid muscle is from the 2nd arch
All facial expression muscles innervated by CN VII
3rd arch cartilage
Ossifies to form part of the hyoid bone hyoid is second and third branchial arches!
Stylopharyngeus muscle
Derivatives of the 3rd arch are innervated by CN IX
Think Pharynx: stylopharyngeus & glosspharyngeal nerve
4th & 6th arch cartilages:

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o
o

Fuse to form laryngeal cartilages (except for the epiglottis)


All other pharyngeal and laryngeal muscles
XI via X:
o Spinal part of XI
Goes to SCM and trapezius
o Cranial part of XI
Joins X
Goes to pharyngeal muscles from vagal branches except stylopharyngeus
Goes to laryngeal muscles via recurrent laryngeal
NOTE: CN XII provides GSE fibers derived from the Occipital somites, not any arches
4th arch:
o Most pharyngeal constrictors, Except Cricopharyngeus
o THE EXCEPTION Cricothyroid which you would think is the area of 6th arch
o Levator veli palatini
o Innervated by superior laryngeal branch of CN X
6th arch:
o All intrinsic laryngeal muscles (except cricothyroid) superior laryngeal branch of X
o The EXCEPTION Cricopharyngeus which you would think is the area of 4th arch
o Innervated by recurrent laryngeal branch of CN X
5th arch
Absent (short-lived or not developed)
A little more about the arches: (yup, I know, I suck & youre pissed)
1st Arch:
Divides at 4 weeks embryonic development to form Mn & Mx processes
Mn (except condyles) & Mx are mostly formed by intramembranous ossification Condyles are endochondral!
Develops into two prominences or processes:
1) Mn process (larger) forms the Mn & lower lip
o Mn forms by merging of medial ends of Mn processes during the 4th week (Mn forms before Mx)
2) Mx process (smaller) forms the Mx, zygomatic bone, squamous part of the temporal bone, most of upper lip
o Mx forms by merging of Mx processes What about nasopalatine process?
o The upper lip is formed from the Mx processes and medial nasal processes
o The medial nasal process form the center of the nose and lateral nasal processes form the ala of the nose
o Maxillary teeth are developed from Arch I and a globular process
o NOTE: the intermaxillary arch is NOT a derivative of the 1st Arch what is the intermaxillary arch?
o The palatine shelf is a medial extension of the Mx process
o Lateral palatine processes of Mx process secondary palate (hard and soft palate)
What makes up the Maxillary Palate (hard and soft)/
The secondary palate; fusion of the maxillary processes ???
o Primary Palate is formed by the medial nasal processes and join the secondary palate at the jxn of the nasopalatine
canal
Lateral cleft lip results from failed fusion of Max & medial nasas processes
May be unilateral or bilateral
o ***Cleft palate failure of fusion of the lateral palatine processes, nasal septum &/or median palatine process
Most common in Asians
Corners of the mouth
Formed by fusion of Mx & Mn processes
Tuberculum impar: (median tongue bud)
Median, triangular elevation which appears in the floor of pharynx just rostral to foramen cecum
Forms from 1st branchial arch
Gives first indication of tongue development in embryo at 4 weeks
Lateral lingual swellings (two distal tongue buds):
Develop on each side of median tongue bud
Elevations are the result of proliferation of mesenchyme of 1st arch
Swellings fuse to form the anterior 2/3 of tongue (mucosa and all)
o Delineated by circumvallate papilla??
Bifid tongue:
Results from lack of fusion of distal tongue buds (or lateral swellings)
Common in South American infants
2nd Arch:
Copula (helps to form posterior 1/3rd)
rd
3 Arch:
o

o
o

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Posterior 1/3 of tongue is formed by two elevations: the copula (2nd arch) & the hypobranchial eminence (3rd arch)
SIDE BAR:
o Bifid uvula:
Results from failure of complete fusion of palatine shelves
Pharyngeal pouches: (NOT ARCHES) (PIC TO RIGHT)
o Paired evaginations of pharyngeal endoderm lining the inner aspects of the branchial arches in the neck region
NOTE: the parotid gland is NOT a derivative of a pharyngeal pouch
Messed up development of 3rd & 4th pouchesDiGeorge syndromeleads to T-cell deficiency & hypocalcemia
Pharyngeal Pouch
1st
2nd
3rd
4th
5th

Structures Derived
Tympanic MB, audtitory tube, and middle ear cavity, mastoid air cells
Lymphatic nodules and palatine tonsils
Inferior parathyroid gland, thymus gland (Hassalls Corpuscles)
Superior parathyroid gland, ultimobranchial body which gives rise to parafollicular cells (C cells)
of the thyroid gland (produce calcitonin)
Rudimentary structure, becomes part of the fourth pouch

Vestibular lamina
o Separates lips & cheeks externally & the jaw structures internally in the developing embryo
o Outer lamina of the 2 epithelial lamina in embryo that separate the palate from the lip!!!!!
Frontal nasal process (prominence):
o Produced by the growth of the forebrain
o Develops the forehead and nose
Nasal placodes
o Thickened areas of specialized ectoderm that form on each side of the frontal nasal process
o Elevations form at the margin of these placodes
o What makes up the nose? Medial and lateral nasal processes
Two lateral nasal processes form the sides (alae) of the nose
Two medial nasal processes form the bridge of nose, nostrils, philtrum (upper lip), & primary palate (anterior to incisive
foramen)
o Philtrum
What forms the philtrum? Medial Nasal Processes with Maxillary processes
See pics to right
Lips:
o Derived from Mn, Mx, & Medial Nasal processes
Tongue:
o Derived from 1st, 2nd, and 3rd branchial arches
Anterior 2/3
1st Arch
Ectoderm (Mucosa)
Tuberculum impar (median tongue bud of first arch)
Lateral Lingual Swellings primary developmental source of mucosa of the
anterior 2/3 of the tongue
Posterior 1/3
2nd and 3rd Arch
Endoderm
Copula (2nd)
Hypobranchial eminence (3rd)
Tongue NOT formed from macula What is macula? Its in the eye asshole!
o At the jxn of the body and root of the tongue is:
Foramen Cecum
Lies at the base of the V of the sulcus terminalis
Sulcus Terminalis
V-shaped demarcation that separates anterior 2/3 from posterior 1/3
Circumvallate Papilla located in the back center or laterally though?
NOT Lingual raphe
o Taste in tongue:
All innervation is from the solitary nucleus
Anterior 2/3: CN VII
Posterior 1/3: CN IX

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Extreme posterior and soft palate: CN X


-

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ENDOCRINE SYSTEM
Exocrine glands classified according to:
o 1) Type of secretion:
Mucous (water & mucin)buccal glands, glands of esophagus, cardiac & pyloric glands of stomach, palatine glands
Serous (enzymes)parotid, von Ebners glands (ONLY), pancreas & uterine glands
Mixedsubmand. & sublingual glands, glands of nasal cavity, paranasal sinuses, nasopharynx, larynx, trachea, and bronchi
o 2) Mode of secretion:
Merocrineonly the cell secretory product is released from MB-bound secretory granules EX: pancreatic acinar cells
Apocrinesecretion of product plus small portion of cytoplasm EX: fat droplet secretion by mammary gland
Holocrineentire cell w/ secretory product EX: sebaceous glands of skin & nose (Think Hol = Whole)
o 3) Structure of duct system:
Unbranchedsimple glands EX: sweat glands
Branchedcompound glands EX: pancreas
o 4) Shape of secretory unit:
Tubularcylindrical lumen surrounded by secretory cells EX: sweat glands
Acinar (alveolar)dilated sac-like secretory unit EX: sebaceous & mammary glands
Tubuloacinar (tubuloalveolar)intermediate in shape or has tubular & alveolar secretory units EX: major salivary glands
o NOTE: Salivary, sweat, sebaceous, and von Ebner's glands are all exocrine glands
Pituitary Gland (hypophysis cerebri):
o Master endocrine gland because it controls many other glands through release of tropic hormones
Tropic hormones = hormones that effect the activity of another endocrine gland
o Origin:
1) Upgrowth from ectoderm of the stomodeum roof of mouth (anterior pituitary, glandular portion from oral ectoderm)
Rathkes pouch diverticulum developing at 3 wks from the roof of stomodeum (primitive mouth) grows
toward brain
o The anterior lobe of the hypophysis develops from Rathkes pouch Think Antero = Adeno, not neuro origin
2) Downgrowth from the neuroectoderm of diencephalonfloor of brain (posterior pituitary, nervous portion) posterior,
or NEURO hypophysis, is of NEURO origin
o Positioned in the sella turcica of the sphenoid bone directly above the sphenoid sinuses
o Structure:
Adenohypophysis = Anterior Pituitary
Pars tuberalis, pars distalis, and pars intermedia the distal, intermediate, tube. DIT.
Pars intermedia is an avascular zone lying between the lobes but is considered part of anterior pituitary
Pars intermedia & tuberalis have no proven function in mammals Distalis Does the Damage
NO innervation
Contains alpha & beta cells
Hypothalamic-hypophyseal portal blood system not neural, so has the portal system
Neurohypophysis = Posterior Pituitary
Pituicytes Primary cell -Glial cells -of posterior pituitary, fusiform cell closely related to neuroglia Name says it all
Median eminence, infundibulum and pars nervosa The nervous, eminent, infundibulum. Nervous = Neuro-hypoph.
Infundibulum carries important nerve tracts from hypothalamus & substances to act on posterior pituitary
o The infundibular contains the hypothalamic-hypophyseal tract, which carries axons to the posterior pituitary
If you cut this stalk, lose the function of ADH (vasopressin) and oxytocin
Consists mainly of unmyelinated nerve fibers Doesnt need to go far, doesnt need the myelin to speed up cond.

Blood supply
From right & left superior and inferior hypophyseal arteries
Sinusoidal blood arrangement (sinusoidal arrangement of BVs also found in Liver and Spleen)
Forms a rich vascular portal system
Portal has two capillary beds
***Three portal systems in the body:
o 1) Hepatic portal system 1st capillary bed in intestines & 2nd in the sinusoids of liver
o 2) Renal portal system 1st capillary bed in glomerulus & ????
o 3) Hypothalamus-Hypophyseal portal system 1st bed in HTh & 2nd in Anterior Pituitary
Carries the Releasing Hormones produced in the hypothalamus to the anterior pit and have them release further
hormones
Synthesized peptide hormones:
Anterior Pituitary = pars distalis: FLAT PeG
The following tissues would be affected if the anterior lobe of the hypophysis were destroyed:
o Thyroid epithelium, zona fasciculata of adrenal gland, interstitial cells of testis, spermatogenic epithelium of testis
NOT adrenal medulla Affected by nerves that go straight here not hormones
B/C anterior lobe releases, TSH, ACTH, FSH/LH,
Hormones released from:
o Alpha cells GH & Prolactin (regular hormones) Alpha for acidic or Eosionophilic pEg
o Beta cells FSH, LH, ACTH, TSH (all tropic hormones)- meaning they act on other endocrine glands
Sidenote: The hypophysis is characterized by an anterior lobe w/ alpha & beta cells
Follicle stimulating hormone (FSH):
o Development of graafian follicles & estrogens in the ovary
o Promotes spermatogenesis in males
Luteinizing hormone (LH): L for LH for corpus Luteum and for Leydig cells
o Stimulates formation of corpus luteum & progesterone secretion
o Stimulates interstitial cells (Leydig cells) of testes to secrete testosterone
Corticotropin (ACTH):
o Controls secretion of adrenocortical hormones (glucocorticoids), which affect glucose, protein, & fat metabolism
Thyroid stimulating hormone (TSH):
o Controls secretion of thyroxine by thyroid, uptake of iodine, and synthesis
**Melanin Stimulating Hormone (MSH) and Beta-Lipotropin What is the deal with this MSH secretion, etc
o Secreted from the pars intermedia
Prolactin (Lactotropin):
o Promotes mammary gland development & milk production, breast development
The mammary glands are under direct control from the hypophysis
o Triggered by rising estrogen levels Need the estrogen
prolactin milk
Growth hormone (GH) aka somatotropin: Athletes take it cuz they want PTN building (muscles) and not fat/carb
o Growth in general; particularly skeletal system by stimulating aa uptake, protein synthesis, & CHO/fat breakdown
o Most plentiful of AP hormones

19

20

o Fusion of long bone epiphyses determines if excess GH will result in gigantism (children) or acromegaly (adults)
o Produced by acidophils in the anterior pituitary (pEg)
Posterior Pituitary Neurohypophysis or pars nervosa:
Consists of unmyelinated nerve fibers
Consists of 100,000 axons of the supraoptic and paraventricular nuclei of hypothalamus pg. 484 of blue neuroscience
book
Secretes ADH & oxytocin
Hormones are synthesized in hypothalamus & transported in axons to the poster lobe for storage and secretion
o Transport occurs via hypothalamo-hypophyseal tract
Antidiuretic hormone (ADH) aka vasopressin:
o Controls rate of water excretion into urine
Oxytocin:
o Helps to deliver milk from glands in breasts to nipples during nursing milk letdown and uterine contraction
Thyroid gland: LOOK AT MILLER POWERPOINTS FOR CLARIFICATION pg. 444 of Netter Head and neck anatomy book
o H-shaped structure two parts joined by a thin isthmus
The isthmus runs in front of the trachea and contacts it posteriorly
o It has rings of epithelial cells surrounding a space filled with colloid
o Characterized by the fact that it functions as the controller of general body metabolism
o In adults, the site of origin is seen as the foramen cecum
o Blood supply
External carotid superior thyroid artery (supplies thyroid gland) superior
laryngeal (enters thyrohyoid membrane) (top artery in pic)
Enters membrane with the internal branch of the superior laryngeal nerve (from the
vagus)
inferior thyroid artery from thyrocervical trunk) (Bottom artery in pic) (pg. 123 & 129
Netters H&N anatomy)
SIDENOTE: Vagus, has both the superior laryngeal nerve and the recurrent laryngeal
nerve (BOTH do sensory and muscle)
Pharyngeal branch Innervates the pharyngeal constrictors except the
Cricopharyngeus (VI arch)
THINK Cricos are the ODD balls
Recurrent Laryngeal Sensory/PS: Everything from the folds down
MOTOR: All the motors of the Larynx except Cricothyroid (IV
arch)
Superior Laryngeal Sensory/PS: (Internal branch) above the folds
MOTOR: (External branch) to the Cricothyroid
o Nerve supply glandular branches of cervical ganglia of sympathetic trunk
o Cell types:
Follicle cells:
Synthesize thryoglubulin (from tyrosine), which is stored in colloid of each follicle, and is a precursor to T3 & T4
When pituitary gland secretes thyrotropin (aka TSH), the colloid becomes active & thyroglobulin molecules are
released and taken back into the follicular cells where they become T3 & T4
Remain inactive at times of low thyroid hormone need can be activated when necessary for mobilization of colloid
found in thryroid
Colloid in the usual thyroid follicle stains acidophilic (PINK)
Metabolically active follicular colloid stains BASOPHILIC
Parafollicular cells: (C cells)
Produce calcitonin lowers calcium & phosphate levels in blood tones down the calcium
Thyroglossal duct a narrow canal connecting the thyroid gland to the tongue during development
Disappears but persists as the foramen cecum
An upward extension of the thyroid gland could be a remnant of the thyroglossal duct, a pyramidal lobe, or a muscular slip
question answer was all of the above
Cervical cysts in the midline of the neck is from Thyroglossal duct
Parathyroid gland:
o Four glands two superior (superior thyroid artery from external carotid) and two inferior (inferior thyroid artery from
thryocervical trunk) pairs of glands on posterior (dorsum) of thyroid gland
o Develops from 3rd & 4th pharyngeal pouches 4th is superior and 3rd is inferior!
o Blood supply is mostly from inferior thyroid artery (with contribution from the superior thyroid artery to the superior glands
only)
o Controlled by blood levels of calicum NOT TSH
o Cell types:
Principal cells (chief cells) secrete PTH, have clear cytoplasm

Oxyphil cells (acid secreting cells) granules in cytoplasm, unknown function


PTH:
Regulates calcium & phosphate metabolism
It is ESSENTIAL for LIFE
Innervention by superior cervical ganglion (sympathetic)
Low PTH leads to tetany & muscle weakness duel to lack of Ca 2+
Pineal gland:
o Located in the epithalamus of brain and releases the hormone melatonin
o Thought to play role in regulation of sleep-wake cycle, body temperature regulation, and appetite circadian rhythms
Adrenal gland:
o Aka suprarenal gland
o Embedded in adipose tissue above kidneys
o Adrenal Medulla:
Secretes Epi and Norepi
Secretion of Adrenal medulla is NOT ESSENTIAL FOR LIFE (unlike those of Parathyroids, Adrenal cortex, Anterior
pituitary, Pancreatic islets (Langerhans) Just think fight/flight not necessary
From neuroectoderm (neural crest cells which differentiate into medullary cells called chromaffin cells)
Same embryologic origin as sympathetic ganglia (neurocrest)
So, chromaffin cells of adrenal medulla secrete catecholamine (NE and E)
So, the adrenal medulla is an endocrine gland of ectodermal origin in the abdomen
Is composed of many cells containing MB-bound osmiophilic granules
Has an intrinsic stroma consisting primarily of reticular fibers***
NOT separated from the cortex by a capsule of collagen fibers what separates it then?
o Adrenal Cortex:
Outside to In: Zona GlomerulosaZona FasiculataZona Reticularis (GFR like Glomerular Filtration Rate)
Also outsidein: SaltSugarSex (aldosteroneglucocorticoidsandrogens) life gets sweeter
Each Zone of the cortex has endocrine cells:
Zona Glomerulosa
o Thin layer, clusters of cells beneath CT capsule
o Secretes mineralocorticoids, primarily aldosterone Affects minerals i.e. Na+
Zona Fasiculata
o Thick middle layer, cells arranged in parallel columns that run at right angles to surface
o Secretes glucocorticoids, primarily cortisol; also small amounts of estrogenic & androgenic-like substances
Zona Reticularis
o Inner layer, cells arranged in interconnecting cords
o Secretes small amounts of cortisol & Dehydoropiandrosterone (DHEA)
Derived from the mesoderm Weird because the outside is from Mesoderm and the Inside is from Ectoderm
Q was what is not derived from neural crest? all were correct except adrenal cortex
Endocrine Glands that are ESSENTIAL FOR LIFE: parathyroid, adrenal cortex, anterior pituitary, pancreatic islets (Langerhans)
o

Thymus:
o Major gland of immune system
o Two soft, pinkish-gray lobes lying in a bib-like fashion below the thyroid gland and above the heart
Encapsulated
o From 3rd branchial pouch
o Primary lymphoid organ (just like bone marrow. Secondary lymph tissue is: spleen, tonsils, lymph nodes, & Peyers
Patches)
o Site of T-cell maturation/education
o Outer cortex contains primarily lymphocytes
o Inner medulla contains T-lymphocytes & Hassalls corpuscles (thought to be vestiges of epithelium unknown function)
Are Mature in the Medulla
o The thymus is the immune system organ most isolated from blood Important to regulate blood b/c important lymphocyte
education is occuring
o Master organ in immunogenesis in the young some believe it monitors total lymphoid system throughout life
o Requires zinc most critical involved in all aspects of immunity: Vit B6, Vit C, carbonic anhydrase, & others
o No afferent lymphatics of lymphatic nodules
o Blood from the internal thoracic & inferior thyroid arteries
o Innervated by vagus & phrenic nerves
o Has double embryologic origin:
Lymphocytes derived from hematopoietic stem cells (mesenchyme)
Hassalls corpuscles (epithelium) derived from endoderm of 3 rd pharyngeal pouch
o Produces thymopoietin & thymosin

21

22

Both are thymic lymphopoeitic factors confer immunological competence on thymus-dependent cells & induce
lymphopoiesis
Also produces thymic humoral factor (THF) & thymic factor (TF)
Important in normal development of immune systemproliferation & maturation of T lymphocytes
Pancreas:
o Has both exocrine & endocrine function
o Retroperitoneal organ, except for small portion of tail which lies in the lienorenal ligament
o Head & neck nestle in the curve of the duodenum; body is behind stomach; tail extends to spleen***
o Characterized by groups of special cells scattered among glandular alveoli
o Endocrine (pancreatic islets Islets of Langerhans)
Endocrine glands secrete products (hormones) into interstitial fluid to diffuse into capillariesbloodstream
*Alpha cellsglucagon
*Beta cellsinsulin, carb metabs, most abundant (80% of cells)
Degeneration of Islets of Langerhans leads to diabetes mellitus
*Delta cellssomatostatin acts locally w/in islets of Langerhans to depress secretion of insulin & glucagon
o Exocrine (acini):
Exocrine glands secrete products into ducts, Trypsinogen
Centroacinar cellspancreatic juices lipases, carbohydrases & proteases (to digest fats, CHOs, & proteins)
Centroacinar cells are ONLY found in the Pancreas
o Duct of Wirsung:
Main excretory duct begins at tail & joins common bile duct to form hepatopancreatic ampulla (ampulla of Vater)
Ampulla opens into duodenum (into descending portion [2nd part] of duodenum)
o Accessory pancreatic duct (Santorinis duct) opens separately into duodenum (when present)
Wolffian duct: (mesonephric duct) embryonic duct that develops in the male into the deferent duct, in the female it is obliterated Wolf
are strong and manly, why its obliterated in females
SALIVARY GLANDS:
Major salivary glands are compound tubuloalveolar glands***
Innervation
By way of General Visceral Efferents from both the salivatory nuclei & the lateral horns of the spinal cord
o Adenomere: part of developing salivary gland destined to become responsible for function
Composed of:
Intercalated ducts transport saliva to larger ducts
Striated ducts think striated like muscle, does work (transport), needs mitochondria
o contain mitochondria for electrolyte & water transport; simple, low columnar epithelium
o Striations of salivary glands are related to a combo of foldings of basal cell MBs & radially arranged mitochondria
And maybe by the striated ducts?
Glandular cells synthesize glycoproteins
o Serous demilunes:
A muctous tubuloalveolar secretory unit that contains lysozyme (degrades bacterial cell walls)
Serous demilune cells: associated w/ mucous acini of the sublingual & submandibular glands (Mixed serous)
Secrete into intercellular canaliculi, not into striated ducts
o Mucus cells: clear granules mostly everywhere
Function to protect & lubricate for transportation
Characterized by large, clear secretory granules that occupy most of the cell & a flattened nucleus-containing, condensed
chromatin at cell base
o Serous cells: nucleus and rER at the bottom, clear zymogen granules at the apex
Rounded euchromatic nucleus surrounded by rough ER in the basal third of the cell w/ zymogen granules (clearly visible &
easily stained secretory granules) at cell apex
NOTE: there is an abundance of zymogen granules in the apical cytoplasm (NOT ribosomes or mitochondria)
Apical granules in the parenchyma of the salivary gland cells represents secretion precursors
Serous cells are found in acinar cells of pancreas, parotid, gastric chief cells and intestinal paneth cells (found at base of vili
in intestines)
What is common among the pancreas and parotid?
They both have serous secretory cells
o Ducts:
Parotid Stensons duct
Submandibular Whartons duct
Sublingual gland Rivian ducts (Bartholin duct -- See below)
o Parotid gland:
Largest salivary gland
PURELY SEROUS
High in amylase activity
Distinguished by having serous acini only, realtively long secretory ducts, and long intercalated ducts

No serous demilunes b/c these associated with Mucous, not serous


Divided by Mn ramus into deep & superficial lobes
PS secretomotor from CN IX by way of lesser petrosal nerve, the otic ganglion, & auriculotemporal nerve (branch of
V3)
Diminished salivation due to middle ear involvement most likely involves the lesser petrosal nerve
Lymphatics superior deep cervical nodes
Stensons duct crosses over masseter m., pierces buccinator m. & opens into vestibule opposite Mx M2
Things that PASS through the Parotid Gland
Facial Nerve (NOT Artery OR Vein)
Retromandibular vein
External Carotid artery
Superficial temporal artery
Branches of the great auricular nerve
o Sensory loss in the skin overlying the parotid gland could be caused by damage to the great auricular nerve
(C2-3)
Surgical excision of the parotid gland endangers the facial nerve, auriculotemporal nerve, & external carotid artery
Submandibular gland: (formerly submaxillary gland)
Mixed serous & mucous
Located in the submandibular triangle (digastric triangle)
Superficial part rests on mylohyoid muscle
To expose, you only need to cut the mucous membrane
Deep part is located around the posterior border of mylohyoid between the mylohyoid m. & hyoglossus m.
Whartons duct
Arises from deep portion of gland & crosses lingual nerve in the region of the sublingual gland
Runs anteriorly immediately deep to the mylohyoid muscle
Terminates on the sublingual caruncle (papilla) adjacent to the base to the base of the sublingual frenulum
o Sublingual caruncles are elevations that lie on either side of the lingual frenum
SIDENOTE: The lingual frenum is attached to the genioglossus
Facial artery enters the submandibular triangle deep to the posterior digastric & passes under to supply submandibular gland
Gives off submental branch as it emerges beneath the gland
PS secretomotor fibers leave CN VII in chorda tympani
Carries pre-G fibers to lingual nerve from which the submandibular ganglion is suspended
Fibers leave lingual nerve & synapse in ganglion w/ post-G
Also supply sublingual, lingual, von Ebners & inferior labial glands & glands of inferior portion of buccal mucosa
Post-G sympathetic fibers are from superior cervical ganglion
They gain access via the adventitia of the facial & lingual arteries
o Submandibular & sublingual lymph drainage is to the deep cervical lymph nodes look up all lymph drainage
o Sublingual gland:
Contains mostly mucous w/ some serous demilunes
Bartholins Duct major sublingual duct opens on sublingual papilla in floor of mouth (accompanies
submandibular duct)
Mylohyoid muscle supports the glands inferiorly
Innervated by PS of CN VII w/ chorda tympani from submandibular ganglion
Blood from sublingual artery (from lingual a. from external carotid a.)
o Von Ebners glands:
Located around the circumvallate papillae of the tongue
Function rinse food away from papilla after it has been tasted
PURELY SEROUS
o Parotid & Von Ebners are the only adult salivary glands that are purely serous
o Mucus-secreting glands
Palatine gland and Buccal glands (PURELY MUCOUS)
Submandibular (submax)
Sublingual NOT purely mucous
Mucus of the trachea
Glands of the esophagus
NOT parotid gland or mucosa of ureter
Parasympathetic innervation controlling salivation originated ONLY with VII and IX
Fordyces Granule
o Aberrant sebaceous glands ectopic (?)
GASTROINTESTINAL SYSTEM
Divisions:

23

Foregut esophagus, stomach, duodenum, liver, gallbaldder, pancreas


Celiac artery
o Midgut jejunoileum, cecum, ascending colon, transverse colon
SMA
o Hindgut descending colon, sigmoid colon, superior 1/3 of rectum
IMA
Peritoneum:
o Single sheet of simple squamous mesothelium that lines the abdominopelvic cavity and covers the abdominal and pelvic organs
o Parietal layer portion on the cavity wall
o Visceral layer portion on the organ
o Some of the organs are suspended from the body wall by a double fold of peritoneum called a mesentery
o Some organs are moved to or develop behind the peritoneum, hence retroperitoneal
Intraperitoneal structures:
o Usually have a mesentery or peritoneum
Stomach, jejunum, ileum, appendix, transverse & sigmoid colon, spleen, liver, and gallbladder
Retroperitoneal structures:
o Organs do not have mesenteries
o Structures on posterior abdominal wall are retroperitoneal:
Think all Vertical Organs and the Pancreas SAD PUCKER. (Suprarenal glands, Aorta, Duodenum, Pancreas, Ureter,
Colon, Kidney, Esophagus, Rectum
Duodenum, ascending & descending colon, rectum, kidney & ureters, pancreas, suprarenal glands, IVC, and abdominal aorta
NOT liver, spleen, other shit above
Parts of the large intestine in sequential order alternate between intra- & retroperitoneal:
o Ascending colon (retro)transverse (intra)descending (retro)sigmoid (intra)rectum (retro)
Vagus nerve innervates ascending colon and transverse (?) (but does not innervate the descending colon, sigmoid colon,
rectum or anus)
Esophagus:
o 10 inches, behind trachea in thorax, empties in cardiac portion of stomach through cardiac orifice
o Upper 1/3 has skeletal , Middle 1/3rd has skeletal + smooth muscle; lower 1/3 has smooth muscle only
What type of muscle is present in lower 1/3rd Smooth
Divided into 3 portions on basis of muscularis externa
o Receives blood from inferior thyroid artery, branches of descending thoracic aorta, and left gastric artery
o PS from esophageal branches of CN X
o Motor fibers from recurrent laryngeal of CN X & S innervation from esophageal plexus
Abdomen divided into 9 regions by 4 imaginary planes (Hollywood Squares, Tic-tac-toe):
o 1 Epigastricmidline region above umbilical region (contains most of stomach)
2 Hypochondriacregion to R & L of epigastric region. Located beneath the cartilage of the rib cage (spleen here)
o 1 Umbilicallocated centrally, surrounds the umbilicus
2 Lumbarareas to the R & L of umbilical region
o 1 Hypogastric (pubic)midline region directly below the umbilical region
2 Iliac (inguinal)regions on R & L of hypogstric region
Stomach:
o In upper part of abdomen, extending below the left costal margin into epigastric & umbilical regions, protected by lower ribs
o Connects w/ esophagus via cardiac sphincter & to small intestine via pyloric sphincter
The purpose of the Gastroesophageal sphincter is to prevent reflux of stomach contents
o 1.0 L capacity
o Receives blood from all 3 branches of celiac artery (L & R gastric, short gastric, and L & R gastroepiploic a.)
o Venous Drainage from the Portal vein & Splenic Vein
o Stomach regions:
Cardiaclies near junction of stomach & esophagus
Fundusenlarged portion above and left of esophageal opening into stomach dome
Bodymiddle or main portion of stomach
Pylorislower portion, lying near small intestines
o Rugae transient folds of the mucosa & submucosa present in an empty stomach but smoothen out in a distended stomach
o Gastric glands of stomach in the lamina propria:
Parietal (oxyntic)in fundus & body, secretes 0.16 M HCl and Gastric Intrinsic Factor (Dont want at cardiac or pyloris)
pH of stomach is <2, due to HCl secretion
Chief (zymogenic)in fundus & body, secretes pepsin Dont want pepsin at ends (cardiac or pyloris)
Enteroendocrinepresent throughout stomach; produce gastrin, serotonin??? (1989 Q26)
The G cell is an enteroendocrine cell that produce gastrin
o Lesser & greater omentum mesenteries that connect the stomach to other viscera (Lesserliver; Greater Guts (small
intestines))
o

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Greater Omentum
Connects transverse colon to the stomach
Lesser Omentum
A peritoneal fold connecting the lesser curvature of the stomach & the first part of the duodenum to the liver
Connects Liver to the stomach (Lesser = Liver)
Contains the common bile duct, hepatic artery, & the portal vein the hepatic triad makes sense cuz Lesser = Liver
o No Goblet cells in stomach (rest of GI tract below stomach were other options)
Trachea, small int & large intestine DO have goblet cells
Small intestine (D J I)
o Small intestine secrete:
Malatase, sucrase, lactase converts disaccs to monosaccs
Aminopeptidase & dipeptidase converts polypeptides to individual aa
Enterokinase converts trypsinogen to trypsin
o Small intestine mucosa:
Plicae circulares = tranverse folds of mucous MB increasing surface area of jejunum (aka valves of Kerckring)
Villi (numerous in entire small intestine) absorb via microvilli projections on the free surface of the cells lining villi
Each villus consists of a lamina propria that has vessels, nerves, and lacteals goes straight up into villus
The central lacteal absorbs chylomicrons into the lymphatic circulation through junctional gaps
Epithelial cells lining villi:
Show surface modification known as the striated border (or brush border) -- microvilli
o Disaccharidases & dipeptidases carry out their activity at the striated (brush) border aka brush border NZs
o Lactose intolerance is caused by deficiency of the disaccharidase lactase
Goblet cellsmostly in the ileum (become more numerous as one proceeds distally along the small intestine)
Absorptive cellssimple columnar cells w/ microvilli
Villi, microvilli, brush border, and circular folds all increase surface area in small intestine (NOT rugae stomach)
Enteroendocrine cellssecrete enterogastrones (secretin & CCK) into bloodstream found in duodenum
Paneth cells(stain red) found at bases of villi of tubular intestinal glands (crypts of Lieberkuhn) & secrete digestive
enzymes, lysosymes (Pan for gold at the base of the villi)
o Duodenum:
One foot longshortest but widest in small intestine, horseshoe-shaped curves around head of pancreas
Brunners glands (submucosal glands) secrete alkaline mucus Neutralizes acidic chyme
Small, branched, coiled, tubular glands in submucosa that secrete alkaline mucus to neutralize gastric acid (histologically
differentiates stomach & duodenum)
Retroperitoneal in the latter parts
Receives common bile duct & pancreatic ducts at the ampulla of Vater (small rounded elevation in wall of duodenum)
Duct of Wirsung:
Main excretory duct begins at tail & joins common bile duct to form hepatopacreatic ampulla (ampulla of Vater)
o Ampulla opens into duodenum (in descending portion [2nd part] of duodenum)
Accessory pancreatic duct (Santorinis duct) opens separately into duodenum (when present)
Blood supply superior pancreaticoduodenal artery (arises from gastroduodenal artery & inferior pancreaticoduodenal
arising from superior mesenteric)
Pre-G PS are in dorsal motor nucleus of CN X
o Jejunum Think WORKER of the intestine
Thicker muscular wall for more active peristalisis, mucosal inner lining of greater diameter for absorption
Has more plicae circulares (valves of Kerckring) & more villi for absorption
Plicae circulares are most characteristic of the jejunum
Tall columnar epithelium (like the rest of the GI tract!!!)
o Ileum: Think immune system and more individual functions
More mesenteric fat, more lymphoid tissue (Peyers patches), more complex vascularity, more goblet cells
Lymphoid tisse (Peyers Patches MALT for Ag presentation & secretory IgA) to handle waste and destroy bacteria
Preferred site for Vit B12 absorption
Ileocecal valve joins small & large intestines
Hormone

Gastrin
Cholecystokinin
Secretin
Gastric inhibitory polypeptide

Major activities
Stimulates gastric acid secretion
Stimulating secretion of pancreatic enzymes, and
contraction and emptying of the gall bladder
Stimulates secretion of water and bicarbonate from
the pancreas and bile ducts
Inhibits gastric acid secretion (HCl) and motility
and potentiates release of insulin form beta cells

Stimuli for release


Presence of peptides and amino acids in gastric
lumen. Distension of stomach
Presence of fatty acids and amino acids in the
small intestine
Acidic pH in the lumen of the small intestine
Presence of fat and glucose in the small intestine

25

in response to elevated blood glucose


concentrations
-

26

Large intestine:
o Three Parts:
1) Cecum vermiform appendix extends downward from cecum (appendix contains large amt of lymphoid tissue )
Infection at the vermiform appendix would spread by entering the bloodstream via the Brachiocephalic Vein
2) Colon ascending (shortest), transverse, descending, & sigmoid
3) Rectum no teniae coli
o Teniae coli:
Three thick, longitudinal bands of smooth muscle fibers that extend the entire length of colon
Function for peristalsis
Shorter than the large intestine therefore cause it to form small pouches called Haustra
o Epiploic appendages (appendices epiploicae) small areas of fat-filled peritoneum lacking in the small intestine
o Function of large intestines (colon):
Remove water from material entering it
Water removed by absorption
Large intestines do not secrete enzymes into lumen
o Colon epithelium: Yes microvilli, no regular villi
Simple columnar w/ border of microvilli to increase surface area for absorption of water from lumen
Goblet cells lubricate dehydrating fecal mass w/ mucous
Crypts of Lieberkuhn (intestinal glandsin stomach they are called rugae) invade lamina propria (L for L) (not same
as goblet cells)
o Note: Lieberkuhn are in Lamina Propia, but Brunners are in Submucosa
No villa formed in large intestines (no surface area increase) Distinguishes it from Small Intestine
o Colon muscularis externa: inner circle smooth muscle layer
o Innervation
Vagus nerve supplies PS to ascending & transverse colon
Pelvic splanchnic nerves to descending & sigmoid colon w/ rectum & anus (Think where you get SPANCHED)
o Anal canal:
Rectal columns of Morgagni = vertical folds, produced by the infolding of the mucous MB around the submucosa
The columns is separated by furrow-like rectal sinuses, which end distally in small valve-like folds called anal valves
Sphincters:
Internal = smooth muscle; External = skeletal muscle
Epithelium (from valves to opening):
Simple cuboidalstratified cuboidalstratified squamouskeratinized stratified squamous
Liver: (picture)
o Largest & most active organ, largest gland of the body
o Lies under right side of diaphragm
o Blood flow:
Blood supply hepatic artery & portal vein
The central hilus, or portal hepatis:
o Receives venous blood from the portal vein & arterial blood from
the hepatic artery
o Also transmits the common bile duct
o ***Portal Triad = Portal vein + hepatic artery + bile ducts (sometimes
lymph vessels) (3 things together at corners of hexagonal
hepatocytes)
The central vein lies outside the portal triangle (Central vein in
middle of hepatocytes)
Blood eventually drains via the three hepatic veins into the IVC which is
transported to heart
Esophageal veins serve as an important collateral circulatory unit to the
hepatic portal system
Cirrhosis esophageal varices Death
o Sinusoids: (Represented by straight black radial lines in the picture)
Irregular capillaries w/ round pores 100-200 nm in diameter. No basement MB
Allow macromolecules of plasma full access to the surface of liver cells through the space of Disse
o Autonomic nerve fibers from celiac plexus
o Divided into large right lobe & small left lobe by attachment of peritoneum of falciform ligament (PICTURE)
Right lobe of liver is further subdivided into quadrate lobe and caudate lobe by presence of gallbladder, fissure for
ligamentum teres (umbilical vein remnant), IVC, and fissure for ligamentum venosum

o
o

Coronary ligaments attatch liver to underside of diaphragm


Liver cells (hepatocytes): Are involved in:
Protein synthesis, storage
Transformation of carbs
Synthesis of cholesterol, bile salts, phospholids, and detoxification
Modification of endogenous & exogenous substances
Encircle a central vein and radiate outward (pic above)
Produce & excrete bile, excrete bilirubin (major end product of hemoglobin decomposition)
Contain large number of mitochondria and smooth ER
Contain lots of glycogen clustered near SER
20-30 micron polyhedral eosinophilic cells
6 or more surfaces may either contact another cell to form gap jxns and bile caniliculi or form a free surface with microvilli
exposed to the perisinusoidal Space of Disse
Bile canaliculi
o Tubular spaces limited by the plasma membrane of several hepatocytes
o Form a network that progresses along the plates of the liver lobule in the direction of the portal canals
o At the periphery of the lobule, these ducts empty into the Herings canals, which are small ducts of cuboidal cells
o Then these ductules terminate in the cuboidal or columnar lined bile ducts, which go on to form the right and left
hepatic ducts, which together constitute the common hepatic duct
o BILE FLOW: Bile Canaliculi Bile ductules (Herings) Right and left hepatic ducts
Common Hepatic
Duct
Produces prothrombin, fibrinogen, albumin etc.
Stores lipid and carbohydrates & vitamins
Converts lipids and amino acids into glucose via the enzymatic process of gluconeogenesis
Detoxifies and inactivates drugs by oxidation, methylation, and conjugation
Liver regeneration can be as much as 90% in about 2 weeks
Does NOT deal w/ phagocytosis of particulate matter Kupfer cells do this I guess not a function of the liver?
Secrete bile into common hepatic duct, joined by short cystic duct of gallbladder to form common bile duct
Bile is conducted away from the liver and into the cystic duct by the common hepatic duct
Kupffer cells:
Reticuloendothelial macrophages which line sinusoids of the liver. Come from monocyte lineage
Function to filter bacteria or small foreign particles out of blood
Originate from the mononuclear phagocyte system
Remove bacteria and toxins entering blood through the intestinal capillaries.
Have vacuoles, lysosomes, and granular ER

Gallbladder:
o Pouch-like organ that stores & concentrates bile by absorbing water & salts (bile continuously produces in liver)
o When small intestine is empty, sphincter of ampulla (Oddi) constricts forcing bile up the cystic duct to gallbladder
With food (particularly fats), CCK relaxes ampulla for bile to mix w/ chyme

27

o
o
o
o
o
o

Bile emulsifies neutral fats & absorbs FAs, cholesterol, & certain vitamins
Gallbladder has Simple Columnar Epithelium
Gallbladder does NOT contain a submucosa***
Colon, stomach, jejunum, & duodenum do have a submucosa present
Receives blood from cystic artery of the right hepatic artery
Is innervated by vagal fibers from celiac plexus
Lymph from gallbladder drains into a cystic lymph node, then into the hepatic nodes and then into celiac nodes

THE EYE:

28

SENSORY ORGANS

Eye Structure pg. 505 in Netters H&N anatomy book


o As if I were a ray of light, I would pass through:
Cornea
Anterior Chamber (filled with aqueous humor)
Pupil (made from the Iris which contains the sphincter muscles)
Lens (which is made more or less ovoid by the ciliary muscles in the ciliary bodies found at the periphery of the iris)
Vitreous body
Made of Type II Collagen Think type II for 2 eyeballs
3 Layers of back wall
Retina
o Rods (night visionuse your rod at night!) and Cones (C for Color)
o Continues all the way to just below the Ciliary Bodies
o Macula
Fovea centralis in the Macula
Avascular region that contains ONLY cones for most acute vision (What a perfect placeonly Cones)
Choroid
Sclera
o In other words, 3 layers to the eye
External Fibrous Layer
Sclera and Cornea
Middle Vascular Pigmented Layer
Uvea (consists of choroid, ciliary body, & iris)
Internal Neural Layer
Retina
Lacrimal Apparatus (Flow of drainage)

Lacrimal glands
In a picture is located on the Lateral side
o Lacrimal ducts
Superior and Inferior Fornix
Lacrimal puncta (tear duct)
o Lacrimal Canaliculi
o Lacrimal Sac
o Nasolacrimal Duct
Drains into the inferior nasal meatus behind the inferior nasal concha (I want my $50 dollars,..$50 dollars)
- Tears (Parasympathetic pathway)
o Under PS control:
CN VII the Greater Petrosal nerve which came to the Pterygopalatine ganglion then hopped a ride on the
zygomaticofacial branch of V2 then on the Lacrimal branch of V1 to the lacrimal gland
THE EAR: PG. 475 OF NETTERS H&N ANATOMY BOOK
- Ear consist of:
o External ear:
Receives sound waves
Auricle & external auditory canal
Innervation is Auriculotemporal does anterior part of external auditory meatus; Auricular branch of vagus does back of
auricle and posterior part of external meatus; Great Auricular does posterior part of auricle; Lesser Occipital does behind the
auricle
o Middle ear (tympanic cavity):
Air to bone conduction
Ossicles malleus (hammer) stapes (stirrup) and incus (anvil)
A stapedectomy surgery will improve hearing
Two muscles stapedius muscle (smallest skeletal muscle in the body) (att.
To stapes in pic) & tensor tympani muscle (cut in pic)
Medial wall oval & round windows
Lateral wall tympanic membrane left wall
Middle ear communicates posteriorly w/ the mastoid air cells and the mastoid
antrum through the aditus and antrum
Eustachian tube serves to equalize air pressures between the tympanic cavity
(middle ear) & the nasopharynx (anterior wall not shown in pic)
Middle ear infections (otitis media) are quite prevalent and may become
extensive due to connection to both the mastoid air cells and the nasopharynx by
way of Eustachian tube
Pt is clinically deaf but a tuning fork on mastoid process causes hearing there is
a problem of disarticulation of ossicles Just not a nerve problem!
NOT caused by a laceration of auriculotem, laceration of cn 8, or problem w stapedius muscle
o You would have no hearing ever if it was a nerve problem, and stapedius
dampens the sound.
o Inner ear: (PIC TO RIGHT) pg. 483 Netters H&N anatomy
Located in the Petrous Part of the Temporal Bone
Transmits to the nerves
Bony labyrinth
3 cavities: vestibule, semicircular canals, cochlea
Filled w/ perilymph (Na+ rich) Just like a regular extracellular environment
Membranous labyrinth
3 parts:
o Cochlear duct base of the cochlea = high frequency; apex = low frequency
o Saccule & utricle both contain maculae for sensing linear acceleration
o Semicircular canals contain ampullae for sensing angular acceleration Think ampitheatres(ampulla) are round,
Filled w/ endolymph (K+ rich) Just like an intracellular environment
Hair cells are found in both the cochlear & vestibular apparatus
o

URINARY SYSTEM
Urinary system:
o 2 kidneys, 2 ureters, 1 urinary bladder & 1 urethra
o Removes nitrogenous waste as urea from blood
Urea is produced when foods containing protein are broken down
o Lined w/ transitional epithelium
o Genital & urinary systems are supplied w/ PS fibers from pelvic splanchnic nerve

29

30

o Kidneys, ureters, & urinary bladder all located retroperitioneally (behind the peritoneum) All vertical organs!
Kidneys: pg. 246 of Clementes anatomy book, or pg. 65 of USMLE Kaplan vol.1
o Epithelium
Bladder and Ureters Transitional
Tubules Simple cuboidal
o Contain extensive vascularity & millions of nephrons w/in renal cortex & medulla
o Filter blood & regulate volume & composition of body fluids during urine formation
o Located retroperitoneally
Can be approached surgically w/o violating the continuity of the peritoneum (ovary, spleen, & gallbladder can not)
o Right kidney lies slightly lower than the left due to large size of the right lobe of liver
Right kidney is close to the Colon, Liver, and Duodenum (CLOSEST to Colon)
o Left kidney is in visceral contact anteriorly with the stomach
o Each is surrounded by a fibrous renal capsule & is supported by an adipose capsule
o Each has an indentation the hilum on its medial border through which the ureters, renal vessels, & nerves enter/leave
Point of entry/exit for renal artery, renal vein & ureter
o Divided into outer dark-brown renal cortex & inner light-brown renal medulla
o Derived from mesoderm of the intermediate cell mass 1994Q58
Intermediate cell mass into both kidneys & gonads
o Horseshoe kidney: when the inferior poles of both kidneys fuse
Bloodflow through the kidney:
o Renal arteryinterlobar arteriesarcuate arteriesinterlobular arteriesafferent arterioles
Internal features of kidneys:
o Cortex outer layer (glomeruli are located here)
o Medulla inner layer, consists of renal pyramids separated by renal columns
2-3 pyramids may unite to form a papilla
o Renal columns found between pyramids; cortical tissue
o Renal papilla apex of pyramids; the collecting ducts pour into minor calyces here
A renal papilla projects directly into the minor calyx
o Minor calyces unite to form major calyces, which then unite to form renal pelvis
Nephron:
o Functional unit of excretory system
Smallest unit of the kidney that makes urine
o Subunit of kidney that purifies blood & maintains safe balance of solutes & water
o >1 million nephrons per kidney
o Made up of a renal corpuscle, proximal convoluted tubule, loop of Henle, & distal convoluted tubule
Renal corpuscle aka Malpeeeeegian Corupuscle
Consists of a glomerulus (network of parallel capillaries) & the surrounding Bowmans capsule
Site of filtration (passage of plasma substances from glomerulus into Bowmans capsule)
o BP forces fluid into Bowmans capsule
Bowmans capsule has simple squamous epithelium (parietal layer)
Also has a visceral layer formed by podocytes
Where do you find podocytes? Glomerular epithelium
Between the layers is the urinary space
Renal tubule
Four regions:
o 1) Proximal convoluted tubule in cortex
o 2) Loop of Henle in medulla Thin part has thinner cells, and thick part has thicker cells!
Thin limb Simple squamous
Thick limb Simple cuboidal
o 3) Distal convoluted tubule in cortex
o 4) Collecting duct in medulla (Technically not part of the nephron)
After filtration, the tubules handle tubular reabsorption & tubular secretion
o Water, glucose & sodium are reabsorbed into blood
o Waste products are retained & emptied into collecting tubuleureters
Juxtaglomerular apparatus:
o JG cells
Modified smooth muscle of afferent arteriole
Secrete renin in response to low renal Blood flow, & BP, low Na+, & high sympathetic tone
Renin converts circulating angiotensinogen into AT I, which is then converted into AT II by ACE
Also secrete erythropoietin
o Macula densa
Na+ sensor

Part of distal convoluted tubule


o Afferent arteriole
o Polkissen cells
Ureters:
o Long, slender, muscular tubes that transport urine from renal pelvis to base of the urinary bladder
Urethra:
o Fibro-muscular tube that carries urine from urinary bladder to outside of the body
o In males it carries semen as well as urine (if youre lucky)
Urinary bladder:
o Distensible sac situated in pelvic cavity posterior to the symphysis pubis
o Slightly lower in females than in males
o Concentrates urine & serves as a reservoir
o Tonically Contracted
Urine:
o Adults pass ~1.5 quarts of urine each day
o Volume of urine formed at night that formed during day
o Normal urine is sterile contains fluids, salts, & waste products, but is free of bacteria, viruses & fungi
o Bladder tissues are isolated from urine & toxic substances by a coating that discourages bacterial attachment & growth on walls

I knowits HOT.
TEETH

Enamel
Mineral content

96%

Color
Formative cell
Embryology

Translucent yellow
Ameloblast
Epithelial (ectoderm)
NOT mesenchyme
No replacement, some
reminerilazation

Repair
Aging

Wear, staining, caries

Sensitivity
Cells in mature tissue

None
None

Comparison of Tooth Tissues


Dentin
Cementum
70%
50%
Light yellow
Odontoblast
Ectomesenchyme

Light yellow
Cementoblast
Ectomesenchyme

Pulp
None, except denticles or
pulp stones
Blood red
Dental papilla
Ectomesenchyme

Physiologically,
reparative 2dentin
(tertiary?)
Increased 2 & sclerotic
dentin
Yes, only as pain
Cytoplasmic extensions
from odontoblasts

New cementum
desposition

Can recover from mild


inflammation

Increased amount w/
age (apex)
No
Cementocytes

Reduces in size; may be


obliterated
Yes
Odontoblasts & other types

31

ENAMEL:
Hardest tissue in body
Richest in calcium highly mineralized
Secreted by ameloblasts totally acellular
Enamel has no possibility of self-repair because its formative cells are lost once it is completely formed
Content:
96% inorganic minerals of calcium and phosphorous as hydroxyapatite (HA)
1% (or 2%) organic material (protein which is rich in proline) for calcium sequestering?
3% water
Maturation of enamel is characterized by an increase in inorganic content & a decrease of BOTH water & organic material
Ectodermal origin (NOT ectomesenchymal)
ALL other tooth components are derived from ectomesenchyme (neurocrest cells)
PICTURE: Forming enamel/dentin layers

PICTURE: Shows tomes processes and odontoblast processes in picket fence arrangement in forming teeth

Enamel rod or prism:


Fundamental morphologic unit of enamel
Bound together by an interprismatic substance (interrod substance)
Each is formed in increments by a single ameloblast An enamel rod is the pathway of a single ameloblast from the DEJ to
the surface
At the time enamel matrix is first formed in a tooth, the nuclei of ameloblasts move to the non-secreting end of the
cell (Reverse polarization)
Ameloblasts have short extensions towards the DEJ called Tomes process when they are in their Secretory stage
These Tomes processes give the ameloblasts at the DEJ a picket-fence appearance
The Tomes processes from the enamel are picketed with enamel spindles of the dentin (odontoblastic processes)
CAREFUL, Odonotblastic processes are Called Tomes FIBERS
During Calcification, Ameloblasts get their nutrients from the Stellate Intermedium see pic above
The interface between pre-ameloblasts and pre-odontoblasts is most like the interface between Epi and Dermis???
Look at other answers here see if one is better.
Rods begin at DEJ & extend to outer surface
Rods normally diverge radially away from the DEJ
Exception: in the cervical portion of primary teeth, the rods diverge toward the occlusal
Enamel rods converge toward the surface in the area of fissures although they are still diverging from the DEJ
5-12 million rods per crown
Rods increase in diameter (4 up to 8 microns) as they flare outward from DEJ

32

Oldest enamel in a fully erupted tooth is located at DEJ underlying a cusp tip or cingulum
Is a good thermal insulator
Organic matrix decreases as tooth matures and inorganic increases (F & Zn are minor constituents)
Optically clear in a demineralized histologic section of a adult tooth due to low organic (high inorganic) content
Extremely brittle, but very strong in compression can endure crushing pressure of ~100,000 psi
Coupled w/ dentin has cushioning property
Semitransluscent yellow to grayish-white
Selectively permeamble MB allows water & certain ions to pass via osmosis (Remember Bleaching!)
Crystals (Inorganic)
Have their long axes parallel to the rods in the bodies of the rods & deviating increasingly in their tails
Their tails are at the surface, heads at the DEJ

The degree of calcification in C, compared to that of D, islower


This would be opposite for a x-section of dentinal tubule
Fluoride Topical Application
Acid solubility of the surface enamel is reduced by fluoride
Enamel Caries
Are thought to penetrate along the route of the rod sheath
Spreads parallel to enamel rods
Hunter-Schreger bands: (Everyones TIGER hunting riffles are pointed in
different directions)
Refers to alternating light & dark lines seen in dental enamel that begin at the
DEJ & end before they reach enamel surface
They represent areas of enamel rods cut in cross-section dispersed between
areas of rods cut longitudinally

Lines of Retzius: (Stria) (A) (Think Age Bands like a tree) pg. 186 in dental
histology book
Artifacts in enamel (not found in dentin) created by incremental steps of
Ameloblasts
Analogous with with Contour Lines of Owen in Dentin
Have increased organic content and are indicative of the rhythmic
variation in the calcification of the enamel matrix
They follow the appositional growth pattern
Neonatal line: 1985 Q87
One of the lines of Retzius is accentuated
Marks the division between enamel formed before & after birth
Found in decidous teeth and cusps of permanent 1st molars
Found in enamel of primary incisors, permanent canines, and
permanent 1st molars???
Found in dentin of permanent mandibular incisors and
permanent first molars??? (Check Calcification ages)
Perikymata: (Peri KY jelly) mata
Where lines of Retzius terminate on the tooth surface making a
small valley traveling circumferentially around tooth
Ribbed surface of the tooth (for her pleasure)
Imbrication Lines of Pickerill:

33

Depression or grooves formed when growth rings (lines of Retzius) are incomplete at the enamel surface
Enamel tufts: (B)
Fan-shaped, hypocalcified structures of enamel rods that project from the DEJ into the enamel proper (unknown function)
Never found at the outer surface of enamel (perikymata, enamel matrix, & enamel lamellae are) makes sense bc they come
from the CEJ
Enamel lamellae: (C)
Defects in the enamel resembling cracks or fractures which traverse the entire length of crown from surface to DEJ
Contain mostly organic material & may provide pathway for bacteria to enter
Hypomineralized structures extending from the DEJ to the surface of the enamel

A = Stria of Retzius; B = Enamel Tuft; C = Enamel Lamella; D = DEJ

For Pic above

Gnarled Enamel: (A) Right


Found most frequently in cusps, (pits and fissures?)
Wavy
Enamel spindles: (B?)Right
Careful, its not enamel, ITS a dentinal process
Elongated odontoblastic processes (hair-like) that traverse the DEJ from the
underlying odontoblasts they go up in the enamel and get trapped there
May serve as pain receptors
In a ground section of a permanent lateral incisor, the enamel spindle is the first
formed (other options were: perikymata, gnarled enamel, granular layer of Tomes)
Odontoblast is formed before the enamel and enamel defects
Enamel spindle (dentin) formation happens BEFORE Granular layer of
Tomes pg. 200 in Bibbs book
Serve as the counterparts to the Picket-Fence DEJ from the odontoblast side (Tomes
processes from ameloblastic side)
Primary Enamel Cuticle (aka Nasmyths MB) (Think Cellophane wrapping)
Delicate MB covering the crown of a newly erupted tooth
Produced by the ameloblast after it produces the enamel rods
Worn away by mastication and cleaning
Replaced by an organic deposit called the pellicle
Pellicle formed by salivary glycoproteins & invaded by bacteria to form plaque
**In a newly erupted tooth, the junction between the tooth surface and crevicular epi is a Basal lamina-like structure between
the enamel and the epithelium
Eruption:
During the early stage of eruption, the enamel matures
During eruption, the epithelial covering of the enamel unites with the oral epithelium and then degenerates
DENTIN:
Content:
70% inorganic (calcium hydroxyapetite), 20% organic (primarily Type I collagen), 10% water
More mineralized than regular bone, but less than enamel
The apatite crystal is oriented parallel to the collagen fibers in the dentin matrix (not parallel to dentinal tubules)???
Purposes of Dentin:
Nutritivekeeps organic components of the surround mineralized tissue supplied w/ moisture and nutrients
Sensoryextremes in temperature, pressure, or trauma to the dentin or pulp are perceived as pain
Pain originates in the pulp due to free nerve endings about the odontoblastic cells
*NOTE: in peripheral organs, the free nerve endings are receptors stimulated by pain (not touch, pressure,
temp)
Tactile receptors in tooth free nerve endings (A-delta & C fibers)
Protectiveformation of reparative(tertiary) or secondary dentin
Theory of Pain
Hydrodynamic phenomena involving fluid influx into the tubules which then stimulate receptors in the pulp
Formation
Formed from the dental papilla (so is dental pulp) (see picture- tooth formation in Cap Stage)
Mesenchymal dental papilla adjacent to the IEE differentiates into odontoblasts
Main cell is the Odontoblast, derived from ectomesenchyme

34

Cell body is in the pulp cavity Process goes into


dentinal tubules
**Ectomesenchyme is the primary source of
cranial connective tissue
Odontoblasts begin dentin formation before enamel
formation by the ameloblasts
ORDER OF IT ALL:
Preameloblast differentiation
Odontoblast differentiation
Predentin secretion
Ameloblast differentiation
Enamel matrix secretion
Dentin mineralization
Enamel mineralization

During the last part of active eruption the


odontoblasts are still functioning actively (ameloblasts are not) at this point they are now considered Reduced
Enamel Epithelium
Incremental lines of von Ebner (aka contour lines of Owen): pg 199 in Bibbs book
Lines in dentin that correspond to lines of Retzius in enamel
Also have a neonatal line which marks the transition between dentin formed before & after birth
Types: pg. 197 of Bibbs book
Mantle dentin
The 1st formed portion of the dentin thus closest to the CEJ
The peripheral portion of dentin adjacent to enamel (DEJ) or cementum (CEJ), consisting mostly of coarse fibers
(Korffs fibers)
Circumpulpal dentin the remaining dentin
During the lifespan of a multirooted tooth, dentin forms most rapidly on the floor and roof of the pulp chamber
Peritubular dentin (AKA intratubular dentin): intra meaning within the tubule
Lines each dentinal tubule most mineralized dentin; more than intertubular dentin ( inorganic salt content)
Intertubular dentin: (in between tubules)
Surrounds the peritubular dentin, less mineralized (has content of inorganic salts)
Interglobular dentin:
Imperfectly calcified matrix of dentin situated between the calcified globules near the periphery of the dentin
Primary dentin:
Dentin forming the initial tooth shape
Deposited before completion of the apical foramen
shouldn't it be
Secondary dentin:
secondary???
Dentin formed after completion of the apical foramen
Formed at a slower rate than primary dentin as functional stresses are placed on a tooth
Does not contain cells (primary cementum & cancellous bone BOTH do) cells are in the pulp!
A regular & somewhat uniform layer of dentin around the pulp cavity
Junction between 1 & 2 dentin is characterized by a sharp change in direction of dentinal tubules
Reparative dentin (Tertiary dentin):
Formed very rapidly in response to irritants such as attrition, abrasion, erosion, moderately advancing dental caries,
trauma
Forms at the pulp interface of the dentin in response to caries
Sclerotic dentin:
Results from aging & slowly advancing dental caries
The dentin tubules become calcified & obliterated, which blocks access of irritants to the pulp by way of tubules
On a histological Slide:
Dentin tubules appear dark/black due to air when sectioning
Dentinal Tubules
Dentinal tubules are S-shaped in the crown due to crowding of the odontoblasts
Each dentinal tubule contains the cytoplasmic cells of an odontoblast
Primary curvatures of the dentinal tubules is LESS in root dentin than in crown dentin More in CROWn due to
increased CROWding
Tomes fibers: (AKA Odontoblastic Fiber)
CAREFUL, Ameloblasts give off Tomes Processes
Long, slender, cytoplasmic extension arising from each odontoblast
Occupy the dentinal tubules
Dentin sensitivity is mediated by these fibers
Because of these fibers, odontoblasts are considered living tissue

35

Dead tracts:
Groups of dead, coagulated cytoplasmic processes of the dentinal tubules
Attributed to aging, caries, erosion, cavity preparation, or odontoblastic crowding
Shows up dark on ground section of tooth
A dead tract can form if odontoblastic processes disintegrate & leave open dentinal tubules
DEJ
Morphology of DEJ determined at the Bell stage Enamel Organ has also differentiated into four layers (oee, Iee, stellate
reticulum and stratum intermedium)
For whom, the BELL TOMES!
Interface between dentin & enamel
Where calcification of a tooth begins
Oldest dentin is next to DEJ Same with oldest enamel!
CEMENTUM: PG. 208 IN BIBBS BOOK
Slightly softer & lighter in color (yellow) than dentin
Avascular and not innervated but does have cells
Cementum is formed by cementoblasts from the PDL, as opposed to dentin which is formed from odontoblasts of the pulp
In order for cementum to form during root development, the epithelial root sheath (Hertwigs) must be fenestrated or
the continuity must be broken
Lines the apical foramen of a fully developed permanent tooth (Important for ENDO, dont perf the cementum)
Content:
50% inorganic (HA), 40% organic (collagen/protein), & 10% water
Similar to bone in the degree of mineralization
Collagen fibers formed from BOTH cementoblasts AND fibroblasts
Most closely resembles bone (more so than dentin) except there are no Haversian systems or BVs
Distinguished from enamel by presence of collagen fibers and the cellular component in mature tissue
Distinguished from dentin in that dentin was made by pulp cells and cementum by PDL cells
Similar to bone in that both contain cells in lacunae with canaliculi extending toward nutritional source
Secondary dentin does not contain cells
Cementum does NOT contain blood vessels
Important in orthodontics:
More resistant to resorption than alveolar bone, permitting orthodontic movement of teeth w/out root resorption
Two types of cementum (no functional difference)
Acellular cementum:
Usually predominates in the coronal 2/3 of the root. Thinnest at the CEJ
Cellular cementum: (Think C for laCunae)
Contains cementoblasts, inactive cementocytes, fibroblasts from the PDL, and cementoclasts
Occurs more frequently on the apical 1/3 of the root
Remember you need active Cementoblasts for attrition wear replacement
Usually the thickest to compensate for attritional wear of the occlusal/incisal surface & passive tooth eruption
Best differentiated from acellular cementum by the presence of lacunae (not by any functional difference) Makes
sense if its gonna have cells, gotta have a place for the cells to be- lacunae
Cementoid:
Peripheral layer of developing cementum (uncalcified)
Cementicles:
Calcified bodies sometimes found lying free w/in the PDL or fused w/ the cementum of the tooth
Primary cementum
Possesses lamellae (not lacunae, canaliculi, or cementocytes) so no cells, just rings in primary cementum
Functions:
Main function provides rough surface for attachment of Sharpeys fibers (PDL)
Compensates for loss of tooth surface due to occlusal wear by apical deposition of cementum throughout life (apposition of
apical cementum)
Protects the root surface from resorption during vertical eruption & tooth movement
Reparative function of cementum allows reattachment of CT following periodontal treatment
Replaces resorbed dentin or cementum
Pulp
Mature Pulp is composed of primarily Loose CT
In mature pulp, which cells predominate? Fibroblasts!
25 yr old has pulp characterized as Loose CT
Anatomy
Derived from Dental Papilla (mesoderm) Pic above of dental papilla
After the tooth is formed, the dental papilla remains as the dental pulp

36

Coronal pulp
Located in the pulp chamber and pulp horns
Radicular pulp
Located in pulp canals
Apical foramen
Communicates w/ the PDL
Local resorption/deposition of cementum & local resorption of dentin may change the position/shape of apical foramen
Accessory canals
Extend from pulp canals through root dentin to PDL
Formed by a break in the (Hertwig) epithelial root sheath from blood vessel trapped, etc.
Central Zone (pulp proper)lined peripherally by specialized odontogenic area which has these zones (inner to outer):
Pulpal core similar to cell-rich zone
Cell-rich zone contains fibroblasts (most abundant cell type in the pulp)
Cell-free zone (of Weil) Capillary and Nerve plexus (Plexus of Raschkow)
Odotoblastic layer contains odonotblasts and lies next to the predentin and mature dentin
Nerve Fibers
Principle types of nerves in the pulp are sympathetic & afferent fibers Sympathetic control blood, afferent tranmit the
pain from free nerve endings
Age changes in pulp:
Decrease in:
Intercellular substance, water, & cells
Size of pulp cavity due to secondary &/or tertiary dentin
Number of reticulin fibers
Increase in:
Number of collagen fibers
Calcifications w/in pulp (called denticles or pulp stones)
Denticles:
True: complete w/ tubule and processes
False: amorphous in structure
Free: unattached to outer pulpal wall
Attached: attached at dentin-pulp interface
Pulp capping
More successful in young teeth because:
Apical foramen of a young pulp is large
Contains more cells
Is very vascular
Has fewer fibrous elements
More tissue fluid
Does lack collateral circulation
Alveolar Process
Alveolar bone proper: (aka: cribriform plate or lamina dura) (SOCKET)
Part of alveolar process which immediately surrounds root of tooth & to which the fibers of PDL are attached
Has minute openings which provide passage for vascular nerve components NOT for attachment of sharpeys!
During growth and development of the alveolar process, osteoblasts, osteoclasts, and osteoid are present
Resorbs when subjected to pressure - thus orthodontics is possible
What causes alveolar bone development?
Tooth Growth, w/o teeth it wont grow
Consists of:
1) Compact lamellar bone
2) A layer of bundle bone
Sharpeys fibers insert into this layer
Supporting alveolar bone:
Surrounds the alveolar bone proper & gives support to the socket
Consists of:
Cortical plate (compact lamellar bone)
Lamellar bone has more what than woven bone? Collagen, (not cells, water, ground substance)
Forms outer & inner plates of the alveolar processes
Thicker in Mn than Mx Why we cant give infiltration injections in Mn
Spongy bone (cancellated bone):
Fills in area between cortical plates of bone
This type of bone is not present in anterior region of mouth here the cortical plate is fused to the cribriform plate

37

This is also true over the radicular buccal bone of the maxillary posteriors
NOTE: Alveolar bone proper is the only essential part of the bone socket supporting alveolar bone is not always present
Mandible
Growth is appositional like all bone!
Bone can only grow appositionally, but cartilage can grow appositionally or interstitially
Causes the formation of resting lines during growth of Mn B/C it grows appositionally
During active tooth eruption there is apposition of bone on all surfaces of the alveolar crest and on all walls of the bony socket???
The bone formed at the base of the socket is usually in the form of horizontal trabeculae See this on radiographs
The best theory describing the force needed for active eruption is from the cells and fibers of the PDL pulling the tooth out
Permanent teeth move occlusally and buccally when erupting
Break in the mandible from a baseball at the mental foramen, which way will the muscles
pull the fragments
Large anterior and superior Small Inferior and Posterior
When you open your mouth, the buccal vestibule is squashed by the Coronoid process
Apical abscesses
Mn M2s & M3s have a marked tendency to produce cervical spread of infection most
rapidly
Attachment of muscles may determine the route that an infection will take, channeling the
infection into certain tissue spaces
Mandibular Teeth
Infections perforate below the buccinator
Swelling of the lower of the face
Infection will spread medially (lingually) from the Mn into the submandibular space & masticatory spaces
It pushes the tongue forward and upward
Further spread cervically may involve the visceral space and lead to edema of the vocal cords and airway obstruction
Molar abscess will reach the floor of the mouth by continuous spread until the lingual attachment of the mylohyoid m.
Swelling at the angle of the mandible is from the deflection of exudates from the mylohyoid m.
Tooth #32 is infectedinfection spreads to parotid, buccopharyngeal, & masseteric fasical spaces, NOT the temporal
In Hep C pt, Tooth #28 needs to be extractedWhich is a life-threatening sequelae of that txLudwigs Angina -Life
threatening sequellae from infection nothing to do with heart Angina means Strangeling in greek!
Alpha delta fibers are responsible for sharp pain C fibers are for dull pain
Maxillary teeth
Perforate the bone above the buccinator attachment
Cause swelling of the upper of the face (which will eventually spread to the entire face)
Lingual spread
From infected Mn premolar or molar teeth into floor of mouth when above the level of attachment of the
mylohyoid m.
This is due to the mylohyoid line position relative to roots of premolars & molars search it in the Dental Anat file
Below the mylohyoid, it would drain into the submaxillary/submandibular space
Ludwigs Angina
Cellulitis, usually of odontogenic origin, bilaterally involving the submaxillary, sublingual, and submental spaces, resulting
in painful swelling of the floor of the mouth, elevation of the tongue, dysphasia, dysphonia, and (at times) compromise of the
airway hence the life-threatening part
Mesial Drift (or in mesial tilting during orthodontic movement):
Coronal half of the Mesial root wall shows resorption from osteoclastic activity
Coronal half of the Distal wall of the root shows deposition from osteoblastic activity
Similar situation: loosening & tightening of primary tooth before its lost
Alternate resorption (clasts) and apposition (blasts) of cementum and bone
TOOTH HISTOLOGY
First sign of tooth development (seen in histo sections) occurs in 6th week in utero (pictures)
Tooth development appears to be initiated by the mesenchymes inductive influence on the overlying ectoderm
In 6th week there is a thickening of the oral epithelium (derivative of the surface ectoderm)
These thickenings or U shaped bands are called the dental lamina and follow the curve of the primitive jaws (20)
At certain point on dental lamina, the ectodermal cells proliferate and produce swellings which become the enamel organ
Inside the depression of the enamel organ is an area of condensed mesenchyme becomes the dental papilla
Surrounding both the enamel organ and dental papilla is a capsule-like structure of mesenchyme called the dental sac
Enamel organ separates from the dental lamina AFTER the layer of dentin is deposited
Each tooth is the product of two tissues that interact during tooth development 1) oral epithelium & 2) underlying ectomesenchyme
The epithelium grows down into the underlying ectomesenchyme to form small areas of condensed mesenchyme, which become
tooth germs
Sequence of Tooth Histogenesis

38

The ectomesenchyme influences the oral epithelium to grow down into the ectomesenchyme
Elongation of inner enamel epithelium
This triggers the mesenchymal cells to differentiate into odontoblasts
Differentiation of odontoblasts
Deposition of first layer of dentin
Deposition of first layer of enamel
Deposition of root dentin and cementum
Stages of Histogenesis
Initiation (Bud Stage):
Initial interaction between oral epithelium and mesenchyme (ectomesenchyme), formation of dental lamina
Congenitally absence of teeth results from an interruption in this phase
Fused or geminated teeth occur during initiation and proliferation stages of tooth development
Proliferation (Cap stage):
Shape of tooth becomes evident, enamel organ is formed
Differentiation (Bell Stage):
Final shaping of tooth; cells differentiate into specific tissue-forming cells (amelo-, odonto-, cemento-, & fibroblasts) in
emanel organ I think this also means: IEE, OEE, Stellate Reticulum and stratum Intermedium
Histodifferentiation and mophodifferentiation occur during this stage ^^^^^
DEJ determined at this stage For whom the BELL TOMES
Forms the DEJ (the 1st structure formed by tooth but that remains in the fully developed tooth not IEE)
Apposition:
Cells that were differentiated into specific tissue forming cells begin to deposit the specific dental tissue
**Dentinogenesis imperfecta & amelogenesis imperfecta occur during histodifferentiation
Terms of Dentinogenesis
From Top of Diagram to bottom
Oral Epithelium
Epithelial layer on top
Dental Lamina
Stem connecting the Oral Epithelium to the Enamel Organ
Tooth Germ
Enamel Organ, Dental Papilla, Dental Sac (not successional lamina)
Enamel Organ
Derived from ectoderm
Gives rise to enamel and Hertwigs Root Sheath
4 Layers of Enamel Organ (not in order):
1) Outer enamel epithelium (OEE)
Outer cellular layer
Outlines the shape of future enamel organ
2) Inner enamel epithelium (IEE)
Innermost layer
Cells will become ameloblasts
Essential for the initiation of dentin formation (ameloblasts stimulate dentin formation)
1st formed in a partially erupted central incisor (among 1/2 cuticles, stellate reticulum, stratum intermedium)
3) Stratum Intermedium
Lateral to IEE
Essential to enamel formation (nutrients for the ameloblasts of IEE), but does not actually secrete the
enamel
Ameloblasts will only form enamel when stratum intermedium is present
4) Stellate Reticulum
Central core and fills bulk of organ
Contains lots of intercellular fluid (mucous type rich in albumin) which is lost prior to enamel deposition
Disturbances during morphodifferentiation of the enamel organ affect the shape of the tooth
IEE & OEE of enamel organ come together in the neck region and form Hertwigs root sheath
After enamel formation, all 4 layers become 1 and form the Reduced Enamel Epithelium
The reduced enamel epithelium & oral epithelium fuse to form the initial junctional epithelium
Very important in forming the dentogingival junction, where the enamel & epithelium meet as tooth erupts
This forms initial junctional epithelium (attached epithelium joining gingiva to tooth)

39

Dental Sac (aka Dental Follicle) Dental Sac Pic above a few pages
Derived from mesenchyme (derived from neural crest cells) NOT from oral epithelium
Gives rise to the cementum, PDL, and alveolar bone proper (aka attachment apparatus)
The embryonic precursor to cementoblasts
Surrounds the tooth germ (enamel organ/dental papilla)
Dental Papilla
Derived from mesenchyme (derived from neural crest cells)
Gives rise to the dentin and pulp
Triangular shaped inside the bell stage under the enamel organ
Peripheral cells of dental papilla differentiate into odontoblasts which produce predentin (calcifies to become dentin)
Center of dental papilla will become dental pulp
Epithelial Diaphragm
Multiple root formation follows unequal proliferation of the epithelial diaphragm okay
Hertwigs Epithelial Root Sheath
Sheath is formed by the joining of the IEE & OEE
After crown formation, the root sheath grows down
It shapes the root of the tooth & induces formation of root dentin (stimulates differentiation of odontoblasts)
Uniform growth of this sheath will result in the formation of a single rooted tooth
Medial outgrowths or evaginations of this sheath will produce multi-rooted teeth
???OLD TEST (1987) The # of roots formed is determined by the number of medial ingrowths of the cervical loop
Hertwigs epithelial root sheath is characterized by:
1) The formation of cell rests (rests of Malassez) in the PDL when the sheaths functions have been accomplished
2) The absence of stellate reticulum and a stratum intermedium IEE and OEE only!
Cementogenesis:
After first root dentin is deposited, the cervical portion of Herwigs root sheath breaks down
This new dentin comes in contact w/ the dental sac
This communication stimulates cells fibroblast cells from the dental sac to differentiate into cementoblasts which
produce cementum
Accessory root canals are formed by a break or perforation in the rooth sheath BEFORE the root dentin is deposited
Epithelial Rests of Malassez
Are remnants of Hertwigs epithelial root sheath
Fate
Some degenerate and others calcify or become cementicles
Persistent rests can be found as groups of epithelial cells in the PDL
Continuity of Hertwigs epithelial rooth sheath must be broken in order for cementum to be deposited during tooth development

Tomes Granular Layer


Formed by odontoblasts that produce an organic matrix
Found in radicular dentin and lies just beneath the cementum
So, the granular layer (Tomes) makes the root dentin readily distinguished from crown dentin
**Interglobular dentin differs from Tomes granular layer in that interglobular dentin usually occurs a short distance
inside the DEJ and represents uncalcified areas?????

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Partial Anodontia (Hypodontia)


Radiograph of 10 year pt where 2 succedaneous teeth are missing
PDL & GINGIVA
PDL pg. 225 in Bibbs book
0.2mm wide
Thickness depends on:
Age (decrease 0.1mm in old agedue to deposition of cementum & bone)
Stage of eruption
Function of the tooth
(PDL is thin and irregular principle fibers on teeth that lose their function) Like skel muscle use it or lose it!
Vital to the functional life of a tooth because it:
Contains nervous and vascular elements
Allows for physiologic movement of the tooth
Provides a cellular source for new cementurn and bone
Derived from the dental sac!!!!!
Connects cementum to alveolar bone
Contains remnants of Hertwigs root sheath (Rests of Malassezcalled cementicles when calcified)
Sharpeys Fibers terminal portion
Diameter greater on bone side vs. cementum
Only consist of Collagenous fibers, NOT reticular or elastic
Insert into Bundle Bone and Cementum
Function of PDL:
Physical
Attachment of tooth to bone via principal fibers
Formative
Formation of CT components by activities of CT cells (cemento-, fibro-, and osteoblasts)
Remodeling
By activities of CT cells (blast vs. clast of above cells)
Nutritive
Through BVs
Sensory
By CN V
Proprioceptive & tactile sensitivity
PDL and its hard tissue anchorage in terms of resisting occlusal force:
Anterior teeth have slight or no contact in the ICP
Occlusal table is < 60% of the overall faciolingual width of the tooth
Occlusal table of the tooth is generally at right angles to long axis
Crowns of Mn molars are 15-20 lingually inclined
Hence roots are positioned more facially for these teeth
Following loss of tooth function:
One may expect a reduction in width & loss of regular arrangement of principal fibers???
Like pulling a yarn taut???
PDL & nerves
2 Types
Free, unmyelinated endings convey PAIN think cold test takes a long time to react
Encapsulated, myelinated convey PRESSURE Think fast jaw jerk reflex
PDL contains:
Cells
Osteoblasts, fibroblasts, Macrophages, Cementoblasts, etc. And the various -clasts
BVs
Lymphatics
Extracellular substance of fibers (gingival and principal)
The principal fibrous elements of the PDL in adults is chiefly collagen And only
collagen in sharpeys fibers.
Ground substance
Mostly proteins and polysaccharides
Oxytalan fibers Like elastin, are part of elastic fibers
Related to the microfibrillar component of elastic fibers
Run parallel to root surface
Gingival fibers (5) (picture) name tells it all for these guys.
General features:

41

Collagen fibers that provide support for the marginal gingival including the interdental papilla
Found w/in the free gingiva
Continuous w/ the CT fibers and are often considered part of the ligament (PDL)
Circumferential (circular) fibers (A)
Encircle the tooth around the most cervical part of the root
Insert into cementum & lamina propia of the free gingiva & alveolar crest
Resist rotational forces
Transseptal fibers (BELOW A)
Extend from tooth to tooth (cementum to cementum), coronal to alveolar crest
Are embedded into the cementum of adjacent teeth
Not on the facial and no attachment to the alveolar crest
Maintain dental arch integrity
Classified w/ principal fibers of PDL (AKA collagenous fibers).
Are included in the Interdental Ligament pg. 228 of Bibbs book
Dentogingival fibers (B)
From the cementum apical to the epithelial attachment; course laterally & coronally
into gingival lamina propria
Dentoperiosteal fibers (C)
From the cervical cementum over the alveolar crest to the periosteum of the cortical
plates of bone
Alveologingival fibers (D)
Insert in crest of alveolar process and spread out through the lamina propria into the free
gingiva
Principal Fibers of the PDL(5) (picture) pg. 226 in Bibbs book
General features:
Composed of Type I collagen
Sometimes classified as belonging to general group of alveolodental fibers
Connect the cementum to the alveolar bone
Never found in contact w/ enamel
Alveolar crest fibers (B)
From cervical cementum to the alveolar crest
Function to counterbalance the occlusal forces on the more apical fibers and resist
lateral movement
Horizontal Fibers (C)
Perpendicular from alveolar bone to cementum
Resist lateral forces
Oblique fibers (33%) (D)
Most numerous
Insert into cementum and extend apically and obliquely into the alveolus I think this is backwards: Alveolus apical into
cementum
Resistant to forces along the long axis of the tooth (masticatory)
Found usually in middle 1/3 of root
Apical (E)
Offer initial resistance to tooth movement in occlusal direction extrusive movements
Interradicular fibers (F)
Only in multi-rooted teeth
Extend from cementum in furca are to bone w/in furca area
Gingival apparatus
Term used to describe the 5 gingival fiber types and the epithelial attachment
Gingival Ligament
Includes the dentogingival, alveologingival, and circumferential fibers
GINGIVA
The gingiva offers protection against bacterial invasion, the most important factor in this protection being that the surface
epithelium is highly impervious
Free Gingiva (aka marginal gingiva)
Collar of tissue that is not attached to the tooth or alveolar bone
1-3mm wide & forms the soft tissue wall of the gingival sulcus next to the tooth
Extends from free gingival groove to gingival margin
Structures: pg. 153 in Bibbs book
Gingival Margin

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1mm band of gingiva that forms immediate collar around the base of the tooth
Gingival Sulcus
Areas between the unattached gingiva and the tooth (where popcorn kernels go)
Above junctional epithelium (JE) continuous w/ JE, but structurally different
Epithelium is non-keratinized (same w/ gingival col)
Most vulnerable to inflammation
Healthy sulcus should NOT have rete pegs (rete pegs indicate inflammation)
Cells of the sulcular epi are joined TO EACH OTHER by desmosomes
Epithelial attachment (Junctional epithelium)
As supragingival plaque/calculus continues apically, it first would disrupt the attachment of the junctional epithelium
Joins the gingiva to the tooth
Inner layer of cells of JE attach gingiva to tooth
Cells of the epithelial cuff attach to enamel or cementum by means of hemidesmosomes
Internal basal lamina (**Basal lamina like structure)
Does NOT contain rete pegs as the superior apex of the free gingiva does
**Dentojunctional epithelium
Gingival epithelium that faces the tooth
Includes both Sulcular and Junctional
Interdental Papilla
Portion of the free gingiva that fills the IP embrasures below contact area
Consists of 2 papillae that are connected by the concave-shaped interdental col
Interdental col
Conforms to the shape of the contact area
Not present in teeth w/o contact
Non-keratinized Just as the rest of the free gingival/papilla is not keratinized as well
Blood vessels of the interdental papilla anastomose freely with BOTH periodontal & interalveolar vessels
Attached Gingiva
Part of the gingiva that is attached to the underlying periosteum of alveolar bone & to cementum by CT fibers & epithelial
attachment
NO submucosa
Present between the free gingiva & the more movable alveolar mucosa
Parakeratinized (means tissue with nuclear remnants in stratum corneum)
Masticatory Mucosa is Parakeratinized except with Dentures
Soft palate, skin of lips, floor of mouth & ventral tongue are NOT parakeratinized
Stippled
Extends from the mucogingival junction to free gingival groove
Mucogingival Junction pg. 139 in bibbs book
Separates the attached gingiva and the alveolar mucosa
Joins lining mucosa & masticatory mucosa
Free Gingival Groove pg. 153 in bibbs book
Separates the free gingiva from the attached gingiva
Is related to the arrangement of the supraalveolar fibers (not probe depth measurement, alveolar crest, or degree of PD health)
Oral Mucosa
Covers all oral surfaces except the teeth
2 Layers:
Stratified squamous epithelium
Keratinized
Nonkeratinized
Parakeratinized
Lamina Propria
CT that supports the epithelium
2 Layers
Papillary
Reticular
Attached to the periosteum or interposed over the submucosa (glands, BVs, nerves)
In the hard palate & gingiva, the lamina propria attaches directly to bone without an intervening submucosa
(not so for the soft palate) pg 153 in Bibbs book
Gingiva differs from alveolar mucosa in that it has high connective tissue papillae Makes sense more wear n tear, more
papilla
Specialized Mucosa
Covers the dorsum of the tongue and taste buds

43

Non-keratinized (most of the dorsum of the tongue is keratinized, right?)


Masticatory Mucosa No Sub mucosa???
Free gingiva, hard palate, attached gingiva, interdental gingiva
Keratinized
Beneath lies the lamina propria (dense, thick, firm CT containing collagenous fibers)
Lining or Reflective Mucosa
Inside of lips, cheek (buccal mucosa), vestibule, lateral surface of alveolar process, floor of the mouth, soft palate, ventral tongue
Thin, movable
Nonkeratinized, stratified squamous epi
Lamina Propia no glands in the lamina propria of the floor of the mouth
Submucosa
Periodontium
2 functional units:
Gingival unit
Free gingiva, attached gingiva, and alveolar mucosa
Attachment apparatus
Cementum, PDL, and alveolar bone proper
TMJ
TMJ pg. 325 in Bibbs book
A diarthrodial joint that has a fibrous CT (fibrocartilage) on its articular surfaces (NOT hyaline)
Most diarthrodial joints are covered by hyaline cartilage
The articular surface of the condyle AND the posterior slope of the articular eminence have the same fibrous CT covering
Joint cavity is lined by a synovial MB & enclosed by a fibrous capsule So everything else is normal, just the fibrocartillage
Divided into two compartments by an articular disc
The TMJ of a child contains Undifferentiated Mesenchyme cells, then Cartilage layer under the Fibrocartilage
TMJ Nutrients
Hyaluronic acid of the Synovial fluid, feeding the articular cartilage
12 weeks condylar cartilage is present at the most superior aspect of the ramus
The condylar cartilage persists as the cartilage zone of the mature condyle, contributing to its adaptation potential
12 weeks The embryonic CT (Mesenchymal) between the growing condyle and temporal bone condenses to form the articular
disc
13 weeks Cavitation forms the lower joint compartment then the upper compartment
14 weeks Joint development complete
Structures
Articular Surface of temporal bone
Articular fossa (or glenoid fossa or mandibular fossa) concave
In older people is covered with Fibrous CT with Chondrocytes chondrocytes for fibroCARTILAGE
In young adults the articular zone has
Articular zone of Fibrous CT
Proliferation zone of undifferentiated Mesenchymal cells UM
Cartilage zone
Articular Eminence convex
Is the anterior surface/boundary of the Mandibular (glenoid) fossa
42 yr old female with Hx of hyperPTHism, bilateral pain in TMJ, ears clogged and ringing
The region of the articular surface that is most likely missing is the Proliferative zone (I have no idea why!)
See 2001 Pilot Q 366

Condyle
Posterior aspect of the condyle is rounded & convex, whereas the anteroinferior aspect is concave
Posterior aspect of the condyle can be palpated by way of the external auditory meatus

44

Growth of the condyle allows for the space needed for erupting teeth It grows upward and backwards
Condyle is broken through the pt. fovea?, there is no necrosis, what artery is supplying the tissue?
Superficial
Temporal artery
Articular disc (meniscus) pg 326 in Bibbs book
Consists of fibrocartilagenous tissue, which resembles dense, irregular CT that may be associated w/ chondrocytes,
capable of providing smooth articulating surface
Meniscus is a biconcave oval plate
Divides the joint into two spaces:
Superior joint space bounded by articular fossa & articular eminence
Sliding Motion occurs between the disks & articular eminences in upper jt space, only disc and eminence
(thus the sliding cant rotate)
Upper compartment of the TMJ does
Translational movement
Inferior joint space bounded below by the condyle
Rotational Motion condyle rotates, and its on bottom.
Meniscus varies in thickness, the thinner, central intermedia zone separates the thicker anterior & posterior bands
Posteriorly, the meniscus is continuous w/ the posterior attachment tissues called the bilaminar zone which is vascular,
innervated tissue that plays an important role in allowing the condyle to move forward
NOTE: the bilaminar zone is the most vascular portion of the articular disc (NOT the posterior band)
Posterior-inferior lamina of bilaminar zone has a very dense collection of elastic fibers (1999Q23 confirmed
JC?) Pg. 258 in Netters H&N Anatomy
Retrodiscal Pad Area
Elastic fibers
Venous plexus well-vascularized structure of the TMJ
Collagen fibers
Loose connective tissue
NOT Hyaline Cartilage No hyaline cartilage there!
Nonarticular surfaces of the TMJ are covered w/ synovium or periosteum (dont get clowned by the non part)
Articular capsule
Surrounds the joint
Attached above to the articular eminence (tubercle)
Attached at margins of the mandibular fossa & below the neck of the Mn
Synovial MB lines the capsule in the superior & inferior spaces of the joint
It does not cover the articular surfaces of articular discs
Innervated by the auriculotemporal, the masseteric, and the posterior deep temporal (ALL V3)
Anterior portion is innervated by masseteric nerve ?? Netters H&N pg. 262 says
post. deep temporal innervates anterior part of TMJ
Ligaments (picture) pg. 259 Netter H&N anatomy
Temporomandibular ligament not pictured
Runs from articular eminence to the Mn condyle
Provides lateral reinforcements for the capsule
Is the only ligament that gives direct support to the capsule of the TMJ
Aka: lateral ligament
Prevents posterior & inferior displacement of the condyle
Sphenomandibular & stylomandibular ligaments
Are considered accessory ligaments responsible for limiting Mn movement
Sphenomandibular ligament attached to the lingula of the Mn and the spine of the sphenoid bone
Most often ligament damaged in an IA nerve block (tested again & again)- makes perfect sense since it attaches to
the lingula
Stylomandibular ligament attached at angle of the Mn
Muscles
Lateral pterygoid muscle: pg. 246 Netter H&N Anatomy
Superior head:
Origin: Infratemporal surface of sphenoid bone
Insertion: TMJ capsule & articular disc
Inferior head:
Origin: Lateral surface of pterygoid plate pterygoid plate is the inferior part of the sphenoid bone makes sense!
Insertion: Neck of the Mn condyle
Actions:
Protrude, depress (open), laterally move Mn depresses with superior head of lateral pterygoid
Innervation
Auriculotemporal nerve, Masseteric, and Posterior Deep Temporal in the capsule and around the periphery of the disc

45

NOTE: the auriculotemporal nerve carries pain, touch, temperature, & proprioceptive modalities to the TMJ
The TMJ, as w/ all joints, receives no motor innervation
The muscles that move the joint receive the motor innervations
Branchiometric motor fibers innervate the temporalis, pterygoids, anterior belly of digastric, mylohyoid, & tensors
Treatment
TMJ should be evaluated for tenderness and noise
The joint is palpated laterally (in front of the external auditory meatus) w/ the Mn in closed and open position
The joint is palpated posteriorly (through the external auditory meatus) w/ the Mn in closed and open position
Things to note:
Tenderness and sensitivity
Joint noises
Mn range of motion
Normal range of movement of adult Mn ~50 mm opening & ~10 mm protrusively & laterally
Magnetic resonance imaging (MRI):
Best imaging modality for identifying position of articular disc of the TMJ
Gold standard for soft tissue, especially the position of the articular disc
Utilizes magnetic field to alter energy levels of primarily the water molecules of soft tissue
Results in good visualization of various soft tissues, including articular disc
Major advantage of MRI is that there is no radiation involved
No harmful effects have been demonstrated
Panoramic, CT, & lateral transcranial radiographs are used to evaluate the bony structures of the TMJ
Problems
Dislocation (luxation)
May occur w/ one or both condyles
Relaxation of the supporting ligaments occasionally allows condyle to extend anteriorly beyond normal open position
May be manifested by true luxation that requires assistance for reduction
Or, it may be merely an overextended excursion anteriorly that is self-reducing (subluxation)
TMJ can only be dislocated anteriorly The post glenoid tubercle posterioly wont let it displace backward!
Anteromedial most common direction in which the articular disc in the TMJ can be displaced
A click sound is usually demonstrated when this happens
Articular disc is seated on condyle & held in place by collateral ligaments (attached to medial & lateral poles of the condyles)
Muscle fibers from the lateral pterygoid muscle are attached to the anterior portion of the articular disc
Reduction of the dislocation
Is done by standing behind pt w/ thumbs inside mouth and the index fingers below chin
Thumbs depress the back of the jaw, and the chin is elevated by the index fingers
The head of the condyle will then slide back into the articular fossa
42 yr old female with Hx of hyperPTHism, bilateral pain in TMJ, ears clogged and ringing
The region of the articular surface that is most likely missing is the Proliferative zone (I have no idea why!)
Sounds
Click best describes sound associated w/ a disc displacement w/ reduction
Crepitation sound (crepitus) usually associated w/ a degenerative process (osteoarthritis) of the condyle
Dull thud usually associated w/ self-reducing subluxation of the condyle
Tinnitus ear ringing
-

46

BLOOD
Fluids in general:
o Extracellular fluid (Na-142; K-4) vs intracellular (Na-10 K-140) KIN Potassium is in
o Fluid: 50-60% of body weight
Intracellular fluid (w/in cells) = 35-40% of body weight
Extracellular fluid (outside the cells) = 15-20% of body weight
Blood plasma = 4-5% of body weight
Interstitial fluid = 11-15% of boby weight. Most of extracellular fluid is interstitial fluid
o Transcellular fluids: CSF, intraocular, synovial, pericardial, pleural, peritoneal
o Tissue (interstitial) fluid contains a small % of plasma proteins of low MW that pass through the capillary walls as a consequence
of hydrostatic pressure of blood. This fluid bathes the cells
Blood
o 8% of total body weight
o Volume = 4-6 liters
o Temp = 38C
o pH = 7.35-7.45
Blood composition
o 55% plasma:

91% water
7 % protein
Albumins 55% Albumin is the most prevalent plasma protein
Globulins 38% Igs
Fibrinogen 7% Clotting ptns
2% other solutes
Metabolic end products, food materials, respiratory gases, hormones, ions
45% formed elements:
1) Erythrocytes 4.3-5.8 million/mm3
Proerythroblast erythroblast normoblast reticulocyte erythrocyte
o What increases when a proerythroblast becomes an erythrocyte? cytoplasmic acidophilia
Biconcave, enucleated discs 7-8m in diameter
o Contain heme (an endogenous pigment)
o Biconcave shape increases surface area 20-30%
o High surface area : volume ratio
No MB-bound organelles
Energy source is glucose
o 90% from anaerobic metabolism degraded to lactate no mitochondria
o 10% from HMP shunt
Function = O2 & CO2 transport
o Oxyhemoglobin = hemoglobin molecule + O2
o Carbaminohemoglobin = hemoglobin + CO2 (~70% of CO2 is transported as bicarbonate ions) Not this
Remember Carboxyhemoglobin is CO
RBC MB contains chloride-bicarbonate antiport allows transport of CO2 to lungs for elimination
Hematocrit = proportion of erythrocytes in a blood sample
o 46%, for males, 40% for females
Formed via erythropoiesis stimulated by erythropoietin produced in kidney
o In erythropoiesis, the cytoplasmic acidophilia increases (Duh, they become more red )
o In erythropoiesis, cells trend toward:
A progressively smaller size
A progressive loss of organelles
A progressive increase in cytoplasmic Hemoglobin concentration
Average life span = 120 days
o Normoblast is a developmental stage of the erythrocyte (not monocyte, lymphocyte, or eosinophil)
Shrink and crenate in hypertonic solution
Become ghost cells in hypotonic solution Become bigger probably whiter like a ghost!
Erythrocytosis = polycythemia = # of RBCs
Anisocytosis = varying sizes
Poikilocytosis = varying shapes
2) Platelets 250-400k/mm3
Cytoplasmic fragments of cells that promote clotting (as part of hemostasis)
o Thrombopoietin stimulates megakaryocytes to give rise to platelets
Minute, irregularly shaped, disk-like cytoplasmic bodies found in blood plasma
No nucleus, DNA or hemoglobin
Life span is 5-9 days removed in spleen & liver
Stop blood loss by forming a platelet plug
Contain secretory vesicles (granules), which release ADP & others chemicals when platelets adhere to collagen
o Induces changes that make platelet surface sticky
o Additional platelets adhere to original platelets to form plug
Thromboxane A directly promotes platelet Aggregation
o Where PGI inhibits Platelet grouping
3) Leukocytes 5-10k/mm3
Neutrophils 60-70% [of leukocytes] in a differential blood count
o More recent #s say 40-75%
o Lobed nucleus, fine granules
o Large, spherical azuriphilic 1 granules (lysosomes)
Contain hydrolytic enzymes, lysosyme, myeloperoxidase, & lactoferrin
o Function = phagocytosis (they love to ingest bacteria)
o Nucleus becomes more hyperchromatic during the development in the red bone marrow
o Neutrophils w/ > 5 lobes are called hypersegmented
Lymphocytes 20-30% (agranulocytes)

47

o
o
o

48

Round nucleus, little cytoplasm


Function = produce Ab, destroy specific target cells
T cells:
Differentiate in the thymus
Account for 70-80% of circulating lymphocytes
Produces cell-mediated immunity
Interact w/ specific antigen, become sensitized & differentiate into several types of daughter cells:
Helper T cell (CD4)helps activate other T lymphocytes and B cells
Cytotoxic T cell (CD8)combines w/ Ag on surface of foreign cell causing lysis & cytokine release
Suppressor T cellsuppresses activation of immune system maintains hemostasis & tolerance to self
Memory T cellremains inactive until 2nd exposure to same Ag then reproduce to mount a faster
reaction
o Aka delayed hypersensitivity T cell
o B cells:
Differentiate in bone marrow
20-30% of circulating lymphocytes
Antibody immunity
Once activated by/sensitized to Agdaughter cells that either make Ab/s or become memory cells
Memory B cellsplasma cells (after 2nd exposure to Ag)
Can function as an APC (to T cells) via MCH Class II
o Plasma cells:
Differentiated from B-cells
Found in bone marrow, CT and sometimes blood
Off-center nucleus & clock-face chromatin distribution
Short 5-10 day life
Specific immunity
Aid in the immunologic defense of the body (NOT mast cells, neutrophils, giant cells)
Plasma cells (NOT T-cells or B-cells) produce most of the bodys Ab/s
Contain large amount of rough ER & well-developed Golgi apparatus (Same with Mucous secreting Goblets)
Are found in the inner medullary center of lymph nodes (aka Medullary Cords) Maybe get a pic of this
Monocytes 2-6% (agranulocytes)
o Kidney-shaped nucleus (Crescent Moon shaped)
o Differentiates into macrophages in tissues
o Function = phagocytosis
Eosinophils 1-4%
o Lobed nucleus, red or yellow granules
o Function = may phagocytize Ab-Ag complexes
o Contain histimase, acid phosphatase, and aurosulfurnimase
Basophils 0-1% Never Let Monkeys Eat Bananas Neutrophils, Lymphocytes, monocytes, Eosinophils, basophils
o Obscured nucleus, purple granules purple or blue BASOphils
o Function = release histamine, heparin, serotonin, & SRS-A (slow reacting substance of anaphylaxis)
o Similar to mast cells w/ coarse cytoplasmic granules
Granules contain heparin (anticoagulant), histamine (vasodilator) and bradykinin, serotonin, & SRS-A (slow
reacting substance of anaphylaxis)
Heparin can prevent blood coagulation & can speed the removal of fat particles from blood after a fatty meal
Occur in most loose CT, especially along the path of BVs
NOTE: serum = blood plasma w/o fibrinogen

Bone marrow
o Produces WBCs, RBCs & platelets by hematopoiesis
o Red marrow:
Cavities of cranial bone, vertebrae, ribs, sternum, & ends of long bones
Prior to birth, other areas produce blood elements: liver, spleen, lymph nodes
Hemacytoblasts (pluripotent stem cells):
So, the principal site of granulocytic hemopoiesis in the adult human is red bone marrow
o Yellow marrow:
Found only in cancellous (spongy) tissue of certain bones:
Flat skull bones, ribs, sternum, vertebrae, portions of ossa coxae & proximal epiphyses of humerus & femur
Minor location of fat storage
ARTERIES
Blood vessel walls:
Tunica intima
Innermost layer
Consists of simple squamous epithelium (endothelium) and a thin CT basement MB
ONLY layer present in all vessels
In atherscletotic pt, this is the layer involved in the hypertrophy
Tunica Media
Middle Layer
Usually very thick in arteries (smooth muscle w/ some elastic fibers)
What keeps blood flowing during diastole
energy stored in elastic fibers of arteries
Tunica Externa (Adventitia)
Outer layer of CT w/ elastic & collagenous fibers
The tunica adventitia of the medium sized artery has mostly what?
collagen and elastin
In larger vessels, infiltrated w/ tiny BVs called vasa vasorum (vessels of the vessels) that nourish external tissues of BV
wall
Arteries
Highest BP found here
Greatest drop/change/gradient in BP is from the arteries to the arterioles
There are more elastic membranes in a large artery than there are in a medium-sized artery
Arterioles
Very small diameter (<0.5mm)
Small lumen, thick tunica media almost entirely of smooth muscle, little elastic tissue
Has the greatest proportion of smooth muscle thickness when compared to the size of the lumen Makes sense most
muscle = biggest pressure drop
Other choices: large arteries (dont get clowned), capillaries, veins
Smooth muscle (fibers, with single, centrally-placed nuclei) dilation/constriction is caused by neurochemical stimuli & has
profound impact on peripheral resistance

49

Can empty in toSinusoids in certain tissues (liver, spleen, pituitary, adrenal, carotid body, pancreas, parathyroid not in
kidneys, they just have a portal system
Sinusoids are wider & more irregular than capillaries
Walls consist of phagocytic cells, from part of reticuloendothelial systemdeal w/ phagocytosis & Ab formation
Capillaries
Exchange occurs here
Endothelium only (no tunica media or adventitia)
Which is seen continuously throughout Circulatory system?
ENDOTHELIUM
Constant lumen & complete endothelial lining (unlike sinusoids)
NO elastic fibers
One RBC at a time
Velocity of blood is slowest here
Aorta: pg. 133 in Clemente anatomy
Tunica media is composed primarily of elastic fibers (distinguishing factor between aorta & arteries)
Has four parts:
1) Ascending aorta:
Beginning portion, R & L coronary arteries branch from it (to supply heart muscle)
Syphilis aneurysm occurs here
2) Arch of Aorta:
Gives rise to 3 Branches that supply all of the blood to the head, neck, and
upper limbs:
Brachiocephalic
Extremely short
1st branch of aorta
At the neck it divides into the Right Common Carotid and right
Subclavian artery pg. 155 Clemente anat.
***Only 1 Brachiocephalic artery, BUT 2 Brachiocephalic
veins
Left common carotid
Along w/ right common carotid, supplies head and neck
SEE BELOW
Left Subclavian
Along w/ right subclavian, supplies upper limbs
SEE BELOW
3) Thoracic portion: pg 152 in Clemente anatomy
From T4T12 (lies in the posterior mediastinum)
All of the arterial branches from this part are small
Posterior Intercostals (pic to lower right arteries coming of aorta)
Supply intercostal, serratus anterior, and pectoral muscles
Anastomoses w/ Anterior Cutaneous Arteries which arise from the Internal Thoracic (which is from the
Subclavian)
At the mid-axillary line, give rise to Lateral Cutaneous artery
Subcostals
Supply the thorax & the diaphragm
Pericardial braches
Mediastinal branches
Esophageal branches
Bronchial branches
Superior Phrenic (at the level of the diaphragm)
4) Abdominal portion: (SEE BELOW) pg 152 in Clemente anatomy
Most common location for an atherosclerotic-induced aneurysm
From T12L4
Branches to:
(Unpaired)
Celiac Trunk
Superior Mesenteric
Inferior Mesenteric
NOTE: Spleen, stomach, pancreas & appendix are supplied by the 3 unpaired aortic branches (not
adrenals)
(Paired) (makes sense all structures above are unpaired, where Kidney, gonads, adrenals, are paired!)
Renal
If the renal artery is occluded, you are likely to get 2ndary HTN

50

Suprarenal NOT From upaired


Gonadal
Lumbar
Terminates w/ branching of:
Right Common Iliac arteries
Left Common Iliac arteries
Small Middle Sacral artery
Supply abdomen, pelvic region & lower limbs
Common Carotid: (FROM ABOVE)
Supplies head & neck
Branches into ICA & ECA at superior border of thyroid cartilage pg. 490 Clemente anatomy
Another Q: Branches at the level of C4 or the Hyoid bone
Carotid Sinus
Spindle-shaped dilation located at junction of ICA & ECA
Has baroreceptors for pressure when stimulated causes vasodilation, HR, & BP
Innervated by carotid sinus branch of CN IX (only 1 because its just a sinus, not a whole body) Sinus Ninus
Carotid sinus syndrome: temporary loss of consciousness accompanying convulsive seizures
Due to intensity of carotid sinus reflex when pressure builds in one or both carotid sinuses
Carotid body:
Lies posterior to the bifurcation of the Common Carotid
Innervated by CN IX & CN X (2 because its a whole body) Has X, because there are hot bodies in Vagus!
Sensitive to CO2 & O2 tension in blood BODY needs O2 in and CO2 out BODY doesnt like pressure
Carotid Sheath: pg. 479 Clemente anatomy
In it runs:
Common Carotid
Internal Jugular Vein
Vagus Nerve
NOT ansa cervicalis
NOT phrenic nerve
Branches of Common Carotid (2)
Internal Carotid: (3 Branches) pg. 490 & 524 Clemente anatomy
Inside the cranial cavity
Branches to:
Ophthalmic: pg. 526 Netters H&N anatomy
Supplies orbit & eye through optic foramen w/ optic nerve
Branches to:
Anterior ethmoidalSupplies the nasal cavity
Dorsal NasalAnastomoses w/ Angular branch (Facial)
Anterior Cerebral:
Great cerebral circle of Willis
Supplies:
Medial surfaces of hemispheres
Anterior & superior portions of frontal & parietal
lobes
Anterior portions of basal ganglia, internal capsule, corpus
callosum
Middle Cerebral: pg 526 Clemente anatomy
Great cerebral circle of Willis
Largest branch of ICA
Branches include Lenticulostriate Arteries
These are Arteries of Stroke (not the middle
meningeal)
Thin-walled, frequently rupture to cause cerebral
hemorrhage Makes Perfect sense!
Supply internal capsule, caudate, putamen
Supplies:
Lateral surface of the cerebral hemisphere
Posterior limb of the internal capsule & part of the basal
ganglia
NOTE: Circle of Willis: (aka cerebral arterial circle)
Rupture of a vessel in the circle of Willis causes
subarachnoid hemorrhage

51

The Basilar artery emits into 2 posterior cerebral arteries (Basilar artery is formed by both vertebrals joining)
Then posterior cerebral arteries emits posterior communicating artery
Then posterior communicating artery joins middle cerebral artery
Then middle cerebral artery emits anterior cerebral artery (Mid. cerebral is term. branch of int. carotid)
Finally anterior cerebral arteries joined by anterior communicating artery
From Front to Back
Ant. CommunicatingAnt. CerebralMiddle CerebralPost. CommunicatingPost. CerebralBasilar
Anterior Communicating:
Most common circle of Willis aneurysm may cause visual field defects
Posterior Communicating:
Common area of aneurysm causes CN III palsy
The basilar & anterior communicating arteries are the unpaired vessels of the Circle of Willis
Forms an important means of collateral circulation in case of obstruction
If the internal carotid is blocked, blood will still get to the brain via the vertebral arteries/Basilar
NOTE: Stroke warning signs
Sudden weakness; paralysis; numbness of the face, arm, & leg on one/both sides of body
Loss of speech or difficulty speaking or understanding speech
Dimness or loss of vision, particularly in only one eye
Unexplained dizziness, unsteadiness, & sudden falls
Sudden severe headache & loss of consciousness
SIDENOTE: Branches of the Vertebral Artery (these have nothing to do w/ the carotid arteries)
Meningeal branches
Anterior & posterior spinal
Posterior inferior cerebellar (see diagram above)
Medullary branches
The Superior Cerebellar artery is not part of the vertebral artery
Basilar artery:
Formed by the union of the two vertebral arteries
Gives several insignificant (to Boards studying) branches
Significant branches: Posterior cerebral arteries
Supplies:
Occipital pole
Inferomedial temporal lobes
Subthalamic nucleus
External Carotid: (8 Branches) pg 506 clemente anatomy
From the level of the superior border of the thyroid cartilage (or C4) to the neck of the Mn into the parotid
Supplies the muscles of the neck, face, thyroid gland, salivary glands, scalp, tongue, jaws, and teeth
Branches from Inferior to Superior SALFO PMS (Some Angry Lady Figured Out PMS)
Superior thyroid
Ascending Pharyngeal
Lingual
Facial
Occipital
Posterior auricular
Maxillary
Superficial Temporal
Terminal Branches
Maxillary and Superficial Temporal the most superior branch
ANTERIOR BRANCHES: (4)
Superior Thyroid:
Supplies thyroid gland
Originates just below the level of the hyoid bones greater cornu
Branches to:
The SCM
Superior laryngeal artery pg 453 netters H&N anatomy
Pierces thyrohyoid MB w/ the internal laryngeal nerve (aka internal branch of superior laryngeal n.)
CAREFUL (the artery is the superior thyroid, but then turns into superior laryngeal, whereas the nerve is
internal branch of superior laryngeal, then internal and external branches) pg 453 & 456 netters H&N anat
Lingual: (little Stub in picture near angle of Mn) pg 492 clemente anat or pg 374 & 414 H&N anatomy

52

Supplies tongue & floor of the mouth and tip of the tongue
Tongue also receives blood from Tonsillar branch (Facial) and Ascending Pharyngeal
Lingual artery does not follow the lingual nerve
Lingual artery does NOT pass between the medial pterygoid & the ramus of the Mn
Branches at the level of the tip of the greater horn of the hyoid bone in the carotid triangle
Passes Medial (deep) to the hyoglossus muscle and Superior to the Mylohyoid (Deep from the neck aspect)to enter
the oral cavity
So NOT between Hyoglossus and Mylohyoid
It passes between the Hyoglossus and the Genioglossus
Branches to: Which one supplies the dorsum of the tongue? Dorsal Lingual?
Suprahyoid
Dorsal Lingual
Sublingual
Deep Lingual
The terminal branch that supplies the anterior 1/3 of the tongue (tip)
Ascends between the genioglossus and the inferior longitudinal muscles
If you pierce the tip of the tongue with a bur, you most likely hit the Deep Lingual Artery You could also
hit lingual artery, or deep lingual vein
Facial: pg. 177, 289, netters H&N anatomy
Supplies face, tonsils, palate, labial glands, muscles of lips, ala and dorsum of the nose, muscles of facial expression,
and submandibular gland
Branches to: (8)
Cervical: (4) Facial to tonsils and to SubMn gland
a) Tonsillarto tonsils & some supply to the tongue pg. 433 & 434 Netters H&N anatomy
b) Ascending Pharyngealto pharyngeal wall & some supply to the tongue?????
c) Glandularto submandibular gland
d) Submentalto area below chin
Facial portion: (4) (can see these branches on pic above)
a) Inferior labialto the lower lip
b) Superior labialto the upper lip and vestibule of the nose
c) Lateral nasalto outer side of lateral nose (lateral wall)
c) Angularmedial side of eye
Terminal branch of facial artery
Anastomoses w/ the dorsal nasal branch of ophthalmic
Maxillary artery: (picture) pg 375 netters H&N anatomy & Infratemporal Fossa anatomy powerpoint
Supplies ALL teeth, muscles of mastication, hard/soft palate, and most of nasal cavity (NOT skin of forehead)
Branches from ECA at the posterior border of the Mn ramus
Terminal branch of ECA to region of infratemporal fossa and nasal cavity
Lateral pterygoid muscle divides maxillary artery into 3 parts: pg. 247 netters H&N anatomy
1) Mandibular portion before muscle (Doug And Mike Arent Inferior)
Gives rise to branches supplying the tympanic cavity and membrane, dura, and mandibular teeth
Deep Auricularto external auditory meatus
Anterior Tympanicto eardrum
Middle Meningealto cranial cavity (damage to this artery results in epidural hematoma/hemorrhage)
Accessory Meningealto cranial cavity
Inferior Alveolarto chin & Mn teeth (runs along w/ vein & nerve and lingual nerve in the
pterygomandibular spacebetween the pterygoid muscle and the ramus of Mn (lingual artery does not)
3rd Branch of Mx artery???Other Answer was Middle Meningeal,
IN Netters, they both come off at the same level!!! I
hate this test
2) Pterygoid portion passing over/under muscle (And Doug Poked
Mikes Behind)
Gives rise to branches that supply the muscles of mastication
Anterior Temporal
Deep Temporal aka Posterior Deep Temporal
Pterygoidmedial and lateral
Masseteric
Buccal
3) Pterygopalatine portion crossing muscle Sahand And Dave Popped
In, Played, Ate
Gives rise to branches that supply the max teeth, portions of
the face, orbit, palate, and nasal cavity

53

Sphenopalatine pg 299 & 301 netters H&N anatomy


Terminal branch of maxillary artery
Enters the nasal cavity through the sphenopalatine foramen along w/ the nasopalatine branch of the
maxillary nerve
Principal artery to the nasal cavity, conchae, meatus, and paranasal sinuses
Damage results in epistaxis (nosebleed)
Nasopalatine (Comes off the Sphenopalatine- which came through the Sphenopalatine
Formamen with the Nasopalatine Nerve)
Comes through incisive foramen
Supplies anterior hard palate
Anastomoses w/ Greater Palatine artery of the Descending Palatine
Artery of the pterygoid canal
Descending palatinegreater and lesser palatine
Branches to:
Greater Palatine Arterypasses to the palate through the greater palatine foramen
Supplies mucosa of hard palate posterior to maxillary canine
Supplies Maxillary M2
A laceration of the palatal mucosa in the area of Mx M1 is most likely to damage the G. P. artery
Anastomoses w/ nasopalatine artery
Lesser Palatine ArterySupplies soft palate & tonsils after emerging from the lesser palatine foramen
Pharyngeal
Infraorbitalcanine and incisor, Part of the 3rd Part of the Maxillary Artery pg 177 & 301 Netter H&N anat
Careful, the Infraorbital NERVE comes out from V2, but this is the artery
Posterior Superior Alveolar (Dental)maxillary molars and premolar
PSA is a direct branch off of Mx artery
Anterior and Middle Superior Alveolar Maxillary anteriors
POSTERIOR BRANCHES of External Carotid (4):
Ascending Pharyngeal
Supplies the pharyngeal constrictor muscles
Supplies the tongue!!!
Occipital pg 139 Netters H&N anatomy
Pharynx and suboccipital triangle
SCM
Hooks CN XII Landmark for finding XII
Posterior Auricular
Back of scalp
Superficial Temporal does supply the temporalis muscle (along w/ the maxillary
artery)
Supplies the TMJ
Transverse Facial does NOT supply the temporalis (it branches off too early)
The Scapular Anastomosis
subclavian a.
( 1st part )

thyrocervical trunk

transverse cervical a.
suprascapular a.
axillary a.

dorsal
scapular a.
intercostal
as.

( 3rd part )
posterior
circumflex
humeral a.

subscapular a.

circumflex
scapular a.

Subclavian (FROM ABOVE)


Divided in 3 parts by the scalene muscles pg 137-138 Netters H&N anatomy
1st Part Medial to the scalene m.
Vertebral (foramen magnum) Not pictured
FIRST BRANCH seems like it should be the third branch. See pg 16 Clementes anat. Then see pg. 138 Netters H&N
**If internal carotid becomes blocked, blood still reaches the brain via the vertebral arteries
Branches from vertebral artery found in section on circle of Willis

54

ThyroCERVical Trunk (3) comes off subclavian


Suprascapular
Transverse cervical
Inferior thyroid
Internal Thoracic: (mammary)
Descends directly behind the 1st 6 costal cartilages, just lateral to the sternum
Branches to:
Upper Anterior Intercostalswhich anastomose w/ the Posterior Intercostals (Thoracic Aorta)
This network provides muscular branches to the intercostal, serratus anterior, and pectoral muscles
MusculophrenicSupplies the diaphragm and lower intercostal spaces anteriorly
Superior EpigastricEnters the rectus sheath and supplies rectus muscles are far as the umbilicus
***NOTE: The inferior epigastric artery (External Iliac) anastomes w/ the Superior Epigastric in the
rectus sheath in the area of umbilicus
2nd Part Behind the scalene m.
Costocervical (2):
Supreme intercostal (High Intercostal)
Deep cervical
3rd Part Lateral to the scalene m.
Dorsal Scapular:
Supplies the back
Axillary Artery pg. 293-296 Essential clinical anatomy
Continuation of the Subclavian
Begins at the 1st rib and ends at the margin of the teres major
m., then turns into the Brachial artery (runs with Median
Nerve), then turns into the Radial and Ulnar arteries at the
Cubital fossa
Brachial Artery
Supplies the Posterior Compartment of the arm
Thoracodorsal
Supplies the latissimus dorsi m.
Divided into 3 Sections by the tendon of the pectoralis minor
m. (Screw The Lawyer Save A Patient)
1st Part (MEDIAL)
Supreme Thoracic artery
2nd Part (DEEP)
Thoraco-acromial -artery branches off the axillary
artery
Lateral thoracic artery
3rd Part (LATERAL)
Subscapular artery
Posterior circumflex humeral artery
Anterior circumflex humeral artery
Abdominal portion of descending aorta: (FROM ABOVE)
From T12L4
Branches to:
(UNPAIRED)
CSI pg 138 essential clinical anatomy
1) Celiac Trunk pg. 102 Essential clinical anatomy
Hepatic (Common) the common hepatic artery is a branch of the celiac artery
Liver, upper pancreas, duodenum, and gallbladder
Branches to:
Right Hepaticto right lobe of liver
Cysticto gall bladder
Left Hepatic
Right Gastriclesser curvature of the stomach (ALL Gastrics go to lesser curvature)
Gatroduodenalpancreas and duodenum
***[SEE Hepatic Circulation BELOW]
Left Gastriclesser curvature of the stomach and inferior part of the esophagus
Splenic spleen, stomach, and omentum
Branches to:

55

Left Gastroepiploicto greater curvature of the stomach (Epiploic appedanges of Greater omenum)
Short Gastricto ??lesser?? curvature of the stomach
**Stomach supplied by: R & L Gastric, Gastroepiploic & Short Gastric artery
2) Superior Mesentericsmall intestine (duodenum and jejunum), pancreas, cecum, ascending and transverse colons
Supplies the GI tract from the middle of the 2nd part of the duodenum to the distal 1/3 of the transverse colon
Supplies the right colic flexure
3) Inferior Mesenterictransverse, descending, & sigmoid colons and rectum
(PAIRED)
1) Suprarenaladrenal gland, Adrenals are not supplied by one of the 3 upaired branches
2) Renalkidneys
3) Gonadal
Testiculartestes
Ovarianovaries
4) Lumbarepaxial muscles of lumbar region -This is the only one that isnt obviously going to 2 paired structures
Terminates w/ branching of:
Right Common Iliac
Left Common Iliac
Small Middle Sacral

Cardiac Blood Supply


1st branch of the aorta is R/L coronary arteries
Right Coronary
Supplies right atrium, most of right ventricle, diaphragmatic surface of the left ventricle, part of AV septum, SA node
(60% of the time), and AV node (80% of the time)
Posterior interventricular (Aka posterior descending a)
Along with middle cardiac vein
Left Coronary
Supplies left atrium, most of left ventricle, some of the right ventricle, most of the IV septum, the SA node (40%), and
the AV node (20%)
Branches from the ascending aorta immediately above the anterior left cusp of the aortic valve
Anterior interventricular
Along with great cardiac vein
Necrosis on the anterior heart wall over both ventricles is likely due to occlusion of the ant.
interventricular a. (AKA L. Ant Descending)
Circumflex branch
Coronary Sinus pg 67 essential clinical anatomy
Receives

56

Great, Middle, and Small Cardiac veins


Hepatic Circulation
Hepatic portal vein
Brings food-laden blood from the abdominal viscera
Formed by union of Superior Mesenteric Vein & Splenic Vein
Blood from liver eventually drains into the hepatic veins and then to IVC
**Liver has mixture of arterial (hepatic) and venous blood (portal)
Blood supply to nose:
Sphenopalatine branch of maxillary artery
Anterior ethmoidal branch of ophthalmic artery to the dorsal nasal
Septal branch of superior labial branch of facial artery
VEINS
Veins vs. Arteries:
Less muscle, lower pressure, less elastic tissue, same general structure, larger diameter
>70% of blood is found in the venous system at any one time
Valves in veins of arms & legs prevent backflow
Veins & arteries have pulse present, none in capillaries
Veins have larger tunica adventitia when compared to arteries
Artery: Media is thickest layer
Vein: Adventitia is thickest layer
CapsVenulesVeinsVena Cava
Venules have very thin tunica adventitia
Larger veins have thicker tunica adventitia
Drainage from Brain to Right Atrium
Superficial region of head & neck drains into External Jugular Vein (EJV)
EJV Subclavian Vein (coming from the Axillary Vein of the shoulder)
Subclavian Vein joins the IJV (coming from the Sigmoid Sinus of the brain)
IJV & SCV join to form the Left Brachiocephalic Vein
The Left Brachiocephalic Vein then receives the Vertebral Vein from the posterior portion of the head
Left Brachiocephalic Vein meets the Right Brachiocephalic Vein to form the Superior Vena Cava Right Atrium
Veins (Individual Facts)
Superior Vena Cava (SVC):
Union of two Brachiocephalic Veins, has no valves, blood from head, neck, upper limbs, & chest; empties into Right Atrium
Inferior Vena Cava (IVC):
Larger than SVC
Guarded by a rudimentary non-functioning valve
When IVC gets slowly occluded, there are collateral routes through BOTH epigastric veins AND the total azygos
system
Brachiocephalic Veins:
Formed at the base of the neck from the joining of the IJV & SCV
Present on both sides of the neck
The R & L Brachiocephalics meet in the superior mediastinum to form SVC
Azygos vein (right side) joins the posterior aspect of the SVC just before it pierces the pericardium (thats why its collateral
circulation)
Infection of lower lip would first enter bloodstream at the Brachiocephalic Vein
Internal jugular vein (IJV):
Begins at jugular foramen as a continuation of the Sigmoid Sinus
Descends in the carotid sheath w/ common carotid and vagus nerve
Descends behind sternoclavicular joint w/ SCV to form Brachiocephalic Vein
Drain the venous sinuses of the skull
External jugular (EJV):
Drains the skin, parotid, & muscles of the face & neck
Formed by union of the Posterior Auricular Vein & the posterior branch of the Retromandibular Vein
Crosses the SCM vertically, under the platysma, and ends in the SCV (DIFFERENT than Artery)
Subclavian Vein (SCV):
Continuation of the Axillary Vein at the inferior margin of the 1st rib
Passes medially to join the IJV to form Brachiocephalic Vein
Crosses 1st rib anterior to the anterior scalene muscle (Subclavian goes Posterior)
So does the Phrenic
Subclavian tributaries are:
EJV on the left side at the angle of its junction w/ IJV

57

Lymphatics from the Thoracic Duct


On the right side it receives the Right Lymphatic Duct at the same location
Axillary Vein:
Begins at the lower border of the teres major muscle as the continuation of the Basilic Vein
Located in the Deltopectoral Triangle
(Think ABCs) Axillary Vein is really the union of the Cephalic (radial side) & the Basilic (medial side formed after
the Median Cubital Vein shoots off of the Cephalic Vein)
Brachial Veindrains venous blood from deep antebrachial regions and brachial regions to Axillary Vein
Cephalic Veindrains venous from radial side to the antebrachium and brachium into Axillary Vein
Superiorly the vein passes between the deltoid and the pectoralis major muscles and enters the deltopectoral triangle
where it joins to be the axillary vein
Damage in deltoid triangle damages cephalic vein
Becomes the SCV as it ascends to the inferior margin of the 1st rib
Basilic + Cephalic = AxillarySubclavian (receives EJV)Subclavian + IJV (Jxn for thoracic duct = Brachiocephalic
Id say this is a good thing to know!!!
Vertebral Vein:
Drains posterior portion of head
Then empties into the Left Brachiocephalic before it forms the Superior Vena Cava
Azygos Vein: (right side)
Drains posterior abdominal and thoracic body wall
Usually formed by union of the Right Ascending Lumbar and Right Subcostal Vein
Ascends through the aortic orifice of the diaphragm (A for A)
Lies in the posterior mediastinum & empties into the SVC at the junction of the 2 Brachiocephalic Veins
The Right Vagus nerve lies just posterior to the arch of the azygos
The Va-goose is most posterior
Azygos vein leaves an impression on the right lung as it arches over the root/hilum
Right Superior Intercostal Vein drains into Azygos vein
NOTE: the 2nd, 3rd & 4th R posterior intercostal veins drain from the R superior intercostal vein into the azygos vein
Left Superior Intercostal Vein drains into the Left Brachiocephalic Vein at level of ????
Hemiazygos Vein: (left side)
Formed by union of the Left Ascending Lumbar Vein & Left Subcostal Vein
Empties into the Azygos Vein
Ascends on the left side of the vertebral body behind the thoracic aorta, receiving the lower four Posterior Intercostal Veins
Accessory Hemiazygos Vein:
Formed by union of 4th -8th Intercostal Veins
Empties into Azygos Vein, sometimes meets up with the Hemiazygos first then crosses and joins the azygos
Face: Veins

Index

Main Menu

maxillary v.

superficial
temporal v.
facial v.

retromandibular v.
external
jugular v.
internal
jugular v.

superior labial v.
inferior labial v.
common facial v.
The veins of the face generally
follow the same pattern as the
arteries. The facial vein is the
major source of venous drainage for
superficial facial structures (or the
same areas that are supplied by the
facial artery).

subclavian v.
Superficial Temporal Vein: PIC
Drains the scalp & side of head
Descends anterior to the ear and plunges into the substances of the parotid gland
Maxillary Vein pg. 181 Netters H&N anatomy
Forms from the Pterygoid Plexus of Veins
Joins the Superficial Temporal Vein w/in the parotid gland to form the Retromandibular Vein
Retromandibular Vein: (Think Terminal Branches of Arterials)
Formed by union of Superficial Temporal & Maxillary vein w/in parotid pg. 204
Divides at the angle of Mn into:
Anterior Branch joins Facial Vein to form Common Facial Vein, which then drains into the IJV
Posterior Branch joins Posterior Auricular Vein (occipital) from behind ear to form EJV

58

Veins of Cervical Triangle: Retromandibular Vein, EJV & IJV


Facial Vein pg 528 Netters H&N anatomy
Begins as Angular Vein by the confluence of the Supraorbital and Supratrochlear Veins
Communicates w/ Superior Ophthalmic via the Supratrochlear and Supraorbital allowing infection from face to the Cranial
Dural Sinus
Drains directly into the IJV or joins the Anterior Branch of the Retromandibular Vein to form Common Facial Vein which
also enters IJV
The Facial Vein anastamoses w/ Retromandibular Vein below the border of the Mn & empties into the IJV, usually through
the Common Facial Vein
Angular Vein
Continues at the lower border of the orbital margin into the Facial Vein
Receives the Infraorbital and the Deep Facial Veins
Deep Facial Vein communicates between Facial Vein and the Pterygoid Plexus (which also becomes Max
Vein)
Superior Ophthalmic Vein is a communication between the Facial Vein & Cavernous Sinus
Deep Facial Vein (most inferior vein in pic to right shows communication with facial v (anterior) and pterygoid plexus
(posterior).
Communication between the Facial Vein & Pterygoid Plexus
Superior Ophthalmic Vein Top vein in pic going from facial vein (anterior)to cav sinus (posterior)
Communication between the Facial Vein & Cavernous Sinus
Inferior Ophthalmic Vein Middle v. in pic, shows splitting to cav sinus and pterygoid plexus.
Divides into two terminal branches
One to the Pterygoid Plexus
One to the Superior Ophthalmic Vein to the Cavernous Sinus
Pterygoid Plexus of Veins:
The pterygoid plexus is in between the temporal and pterygoid muscles
The pterygoid plexus and its tributaries are the venous parallel of the maxillary
artery
Infection that spreads posterior to Mx sinus enters here
Terminates posteriorly in the Maxillary Vein
Terminates anteriorly in the Deep Facial Vein (drains into Facial Vein)
The pterygoid plexus drains into the retromandibular vein
Retromandibular splits into Anterior and Posterior divisions:
Anterior joins Facial Vein to form Common Facial Vein and then
dumps into internal jugular vein Anterior to Internal!!!
Posterior receives the posterior auricular veins and forms the
external jugular vein, which then drains directly into the subclavian
vein
Direct communications of the Pterygoid Plexus:
Maxillary vein (cut in pic)
Deep Facial vein can see
Posterior Superior Alveolar vein cut?
Infraorbital vein Can see its the inferior infraorbital
NOT VertebralDuh! This drains into left
Brachiocephalic vein
Surrounds the maxillary artery occupying the infratemporal fossa
associated w/ pterygoid muscles
Receives veins that correspond to the maxillary artery

Dural Venous Sinuses. Pg. 528 Netters H&N anatomy


View is with the skull cap removed and the cranial cavity exposed.
A. Sphenoparietal at junction of sphenoid and parietal bones
B. Intercavernous
C. Sigmoid
D. Occipital
E. Confluence
F. Basilar
G. Transverse
H. Superior Petrosal

59

I. Inferior Petrosal
J. Cavernous
K. Superior Sagittal
The Cavernous Sinuses:
Paired, irregularly shaped Venous Dural Sinuses
Created by drainage of Superior & Inferior Ophthalmic Veins, the Cerebral Veins, & the Sphenoparietal Sinus
Located on either side of the sella turcica of sphenoid bone in middle cranial fossa
Empty by way of Superior Petrosal Sinuses into the Transverse Sinuses which become the Sigmoid Sinuses
The Sigmoid Sinuses then empty into the Jugular Foramen by becoming the IJV
These veins do not have valves and so can also drain anteriorly into Ophthalmic Vein
Internal Carotid Artery and abducens (CN VI) nerve pass through the Cavernous Sinuses (CN VI is free-floating)
All of the others are embedded in lateral wall of the Cavernous Sinuses: Pg. 528 Netters H&N anatomy
Oculomotor (CN III), Trochlear nerve (CN IV), Ophthalmic nerve (CN V1), Maxillary nerve (CN V2)
Think Cavernous s-EYE-nuses (III, IV, VI are eye movers, & V1/V2 are above & below the eye on the face)
The Sinuses
Superior Sagittal above picture is weak, look at pic to lower right = giant sinus at top of skull
At the top of the falx cerebri
CSF flows into the arachnoid villi then into the superior sagittal sinus
Which dura divides cerebrum sagitally?
Falx Cerebri
Inferior Sagittal pictured on right: in mid sagital plane, below the superior sag sinut
At the bottom of the falx cerebri
Straight sinus pictured right: from inferior sagital sinus to confluens
When the great cerebral vein meets the inferior sagittal sinus, they form the straight
sinus which takes them down to the Confluence
Occipital
In the falx cerebelli
Confluence of sinuses
Where the Superior Sagittal, Straight, Occipital, and both Transverse Sinuses meet in
the back
Transverse sinus
The 2 lateral sinuses that connect the Confluence to the Sigmoid Sinuses
Sigmoid
Connects to the Internal Jugular Vein via the jugular foramen of the skull
Also collects the Superior Petrosal Vein
Cavernous sinuses
Anterior and Posterior intercavernous sinuses surround the Infundibular stalk of pituitary
Drain the valveless ophthalamic & paranasal sinuses danger of infection
Sella turcica
Lies directly above the sphenoid sinuses
Middle cranial fossa
Diaphragma sellae
The tentorium cerebelli forms the roof of the posterior fossa (Perpendicular to falx cerebri- it runs
horizontal in picture to right)
Danger triangle of face:
Covers the nose and maxilla and goes up to the region of the eye
Superficial veins communicate w/ the Dural Sinuses
Facial Vein has no valves and backflow of infection can get into the sinuses via the Deep Facial Vein (via Pterygoid Plexus) and
Superior Ophthalmic Vein (via Cavernous Sinus)
Veins of the Skull:
Direct tributaries to the Dural Sinuses (Cerebral Sinuses, or the sinuses of dura mater)
Various venous channels located in the dura mater and lined w/ endothelium
Emissary Veins: (THINK you have to go THROUGH the checkpoint to get to the COMMISSARY on BASE (of skull)
Valveless, connect the dural sinuses w/ the veins of scalp
Differently worded: emissary veins connect the venous sinuses of the dura mater w/ the extracranial veins
Diploic Veins:
Lie in channels in the diploe of the skull & communicate w/ Dural Sinuses, the veins of the scalp, and Meningeal Vein
Lie w/in the bone of the calverium and join as tributaries to the Emissary Vein
Portal Vein (aka: Hepatic Portal Vein):
Formed by the union of the Splenic and the Superior Mesenteric Veins (splenic behind pancreas in pic, SMV in front of
duodenum) Note: Also shows duodenum going around heat of pancreas.
Tributaries are R & L Gastric Veins & the Cystic Vein

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Passes:
Anterior to the epiploic foramen in the free edge of the lesser omentum
Epiploic foramen is bounded anteriorly by the free border of the lesser omentum
Greater peritoneal sac communicates with lesser peritoneal sac by means of the epiploic foramen
Posterior to the bile duct and the Proper Hepatic Artery
Ascends in front of IVC
Divides into R & L branches before entering liver
Carries 2x as much blood as the Hepatic Artery
Drains stomach, intestines, spleen, pancreas, and gallbladder
Drains into Hepatic Sinusoids, which then drains into the Center Vein
Here the blood travels through the hepatic portal system & makes it possible for
the liver to perform many functions, (like remove substances from blood,
metabolize, detox)
After leaving liver, blood travels through Hepatic Vein to IVC
Splenic vein: Shown to right
Drains spleen
Receives tributaries from:
Stomach = R & L Gastroepiploic Veins and R & L Gastric Veins
Pancreas = Pancreatic Vein
Gallbladder = Cystic Vein
Joins the Superior Mesenteric to form the Portal Vein
2 abdominal anastomeses
Superficial
Superficial epigastric to the Lateral thoracic (off of subclavian)
Deep
Inferior epigastric from the external iliac to the Internal thoracic
Superior Mesenteric drains:
Small intestine, cecum, and ascending & transverse colon
Joins Splenic Vein behind the neck of the pancreas to form the Portal Vein
Inferior Mesenteric:
Drains rectum, descending colon of the large intestine
Usually joins the Splenic Vein behind the neck of the pancreas
Fetal vessels and their remnants:
One Q reads: Ligamentous remnants of the fetal circulatory system persisting in the adult include the ligamentum venosum,
ligamentum arteriosum, ligamentum teres of the liver (not ligamentum nuchae or ligamentum teres of the uterus)
Umbilical Vein (1) Ligamentum teres (aka: Round ligament of the liver):
Placenta to liver, forms major portion of umbilical cord, nutrient-rich blood from placenta to fetus
Forms the round ligament of the liver after birth (ligamentum teres)
Umbilical Arteries (2)Medial Umbilical Ligaments:
Arise from Internal Iliac arteries associated w/ umbilical cord
Transports blood from fetus to placenta, becomes adult medial umbilical ligament
AllantoisMedian Umbilical Ligament
Ductus ArteriosumLigmentum Arteriosum: (Ductus)
Between pulmonary trunk (left pulmonary artery) & aortic arch to bypass pulmonary circuitry
R to L shunt, we dont care about pulmonary circ. On way to lungs (pulm. Artery) gets shunted straight to aorta!
Does not carry fully oxygenated blood
Closes shortly after birth, atrophies, & becomes the ligamentum arteriosum
Ductus VenosusLigamentum Venosum
After Umbilical vein reaches the liver, then the Ductos venosus takes the blood to the IVC
Right Atrium foramen ovale
Carries Umblicial vein (O2 rich from momma) to the IVC (Just distal to where the bad blood was sent out in the iliac
arteries)
Only fetal vein to carry O2-rich blood and nutrients
Foramen OvaleFossa Ovalis:
Opening between R & L atria to shunt blood passed the pulmonary circuitry, closes at birth and becomes the fossa ovalis, a
depression in the interatrial septum
Notochord Nucleus Pulposus kinda in a pretty random spot, no?
NOTE: The following are immediate changes that occur in the cardiovascular system at birth:
Closure of foramen ovale
Closure of the ductus venosus
Constriction of the ductus arteriosus
Constriction of the umbilical arteries
Not closure of the interventricular foramen
Since were thinking about the umbilical cord:

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Contains 2 umbilical arteries de-O2d blood FROM fetus


Contains 1 umbilical vein O2d blood TO fetus (from placenta)
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LYMPH SYSTEM
Lymph
o Transparent, usually slightly yellow, often opalescent liquid found in lymphatic vessels
o Contains a liquid portion resembling plasma, as well as WBCs (mostly lymphocytes) & a few RBCs
o Absorbed from tissue spaces by lymphatic capillaries
o Flows through the filtering system (lymph nodes)
o Is eventually returned to venous circulation by lymphatic vessels
Functions of Lymphatic System:
o 1) Collect & return tissue fluids back to bloodstream
Fluid entering lymph capillaries is called lymph
Fluid enters due to differing osmotic pressure across capillary MB
Lymph is returned to venous system via 1) thoracic duct & 2) right lymphatic duct
Lymphatic system depends on:
Skeletal muscle contraction, presence of valves in lymphatic vessels, breathing & gravity to move fluid
Lymph vs. Veins
Walls of lymph vessels are thinner
Muscle layer is less developed
o 2) Transport absorbed fats
Lacteals transport fat products in small intestines from GI into circulatory system
Lacteals are lymph capillaries w/in villi of small intestine
o 3) Provide immunologic defense against disease-causing agents
Lymph filters through lymph nodes
Lymph nodes filter out microorganisms & foreign substances
Basic framework of all lymphoid tissues (EXCEPT Thymus) is primarily reticular fibers and lesser amount of collagen fibers
In the upper limb, the hallmark of lymph vessels is that they CONTAIN Valves Sean you got clowned Sean would get clowned, but
I never would because lymph needs valves to work! Idiots
Bone marrow is part of lymph system
Chief characteristic of lymphatic organ is presence of lymphocyte
Lymph nodes:
o Small, oval/round bodies of lymphatic tissue permeated by lymphatic channels
o Contains both afferent & efferent vessels (spleen, thymus, tonsils do not have both)
Contains numerous afferent lymphatic channels (spleen, thymus, palatine/pharyngeal tonsils do not)
The spleen, thymus, palatine & pharyngeal tonsils do not have numerous afferent vessels entering them as do lymph nodes
But wait, do spleen, thymus, tonsils, etc have afferent vessels?
o Primary function act as filters that remove & destroy Ag/s circulating in blood & lymph
Contain a lot of macrophages
o Lymphoid tissue in nodes produces Ab/s & stores lymphocytes
o Generally occur in clusters, particularly in armpits, groin, lower abdomen, & sides of neck
o Each node is enclosed in a fibrous capsules w/ internal trabeculae (CT) supporting lymphoid tissue & lymph sinuses
Trabeculae are specialized bands of CT that divide the lymph node
o Outer cortical region:
Contains separate masses of lymphoid tissue (called germinal centers, nodules)
source of lymphocytes
NOTE: The germinal center of a lymph nodule represents the area of
proliferation of lymphocytes
Also contains subscapular & cortical sinuses
Outer cortex B cells & nodules
Inner cortex T cells & NO nodules
o Inner medullary region:
Lymphoid tissue here is arranged in medullary cords source of plasma cells
What is not found within a medullary cord? Mast Cells. (macrophages, t-cells,
b-cells, plasma cells are found there)
Travel of lymph through nodes:
o Afferent lymphatic vessels carry lymph into node vessels enter on convex surface
of the node
Lymph is cleansed by macrophages, lymphocytes & plasma cells as it
circulates through cortical sinuses
o Efferent lymphatic vessels carry filtered lymph through the concave hilus region
into efferect collecting vessels

Collecting vessels converge into larger vessels lymph trunks (five in the body)
There are fewer efferents than afferents
o Lymph trunks empty into the thoracic duct or right lymphatic duct
Thoracic duct
Drains most of the body
Empties into junction of the LEFT internal jugular & LEFT subclavian veins (which becomes the L brachiocephalic v.)
Right lymphatic duct
Drains right side of head & neck, right upper limb, & right side of thorax
Empties into junction of RIGHT internal jugular & RIGHT subclavain vein
Deep cervical lymph nodes:
o Eventually receive all lymph of head & neck
o Form a chain along the internal jugular vein, from skull to root of neck
o Efferent vessels join to form the jugular lymph trunk then drain to thoracic duct or right lymphatic duct
o Mandibular 3rd Molars initially???
o Carcinoma of the larynx would most likely affect?
Deep cervical lymph nodes
Anterior cervical lymph nodes
o Drains internal structures of throat as well as post pharynx, tonsils, and thyroid
o What doesnt drain into ant cerv lymph nodes scalp, skin of neck and arm, thorax, axillary nodes
Parotid lymph nodes:
o Strip of scalp above parotid salivary glands
o Anterior wall of external auditory meatus
o Lateral parts of eye lids & middle ear
o **Drain into deep cervical lymph nodes
Submandibular lymph nodes:
o Lymph from most of the dental and periodontal tissues drains initially into the submandibular lymph nodes
o Front of scalp
o Nose & adjacent cheek
o Upper & lower lips (except center part)
o Drain the Oral Cavity
o Mx & Mn teeth (except Mn incisors) (dont get clowned by infraorbital lymph
node for drainage of Mx teeth)
o Anterior 2/3 of tongue (except the tip)
o Floor of mouth & vestibule & gingiva
o Angle of the mouth
o **Drain into deep cervical lymph nodes
Submental lymph nodes:
o Tip of tongue
o Anterior floor of mouth (beneath tip of the tongue)
o Mn incisors & associated gingiva
o Center part of lower lip & skin over chin
NOT Mn molars, upper lip, lateral portion of lower lip
o **Drain into submandibular & deep cervical lymph nodes
***NOTE: The primary lymph nodes draining the mandible are the submandibular
& submental nodes
Thoracic duct:
o Conveys lymph from lower limbs, pelvic & abdominal cavities, left side of
thorax, & left side of head, neck & left arm
o Begins below the abdomen as dilated sac the cisterna chyli
o Ascends through aortic opening in diaphragm, on the right side of the
descending aorta
o Empties into junction of the left internal jugular & left subclavian veins
o Contains valves & ascends between the aorta & azygos vein in the thorax (Azy goose and Thoracic DUCK touch)
How is it related to the esophagus and sympathetic chain?
Right lymphatic duct:
o Drains the right side of the head & neck, right upper limb, & right side of the thorax
o Empties into junction of the right internal jugular & right subclavian veins
Virchows node is a left supraclavicular node that gets lymph from most of the body via the thoracic duct
Spleen:
o Largest single mass of lymphoid tissue in body
o Ovoid organ ~size of a fist
o Develops from mesenchymal cells of the mesentery attached to primitive stomach weird
o Found in closest relation to the inferior surface of the diaphragm Spleen
o

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Lies in left hypochondrium of abdominal cavity between stomach & diaphragm


Important blood reservoir
Filters blood ONLY (No afferent lymphatics)
Phagocytosis of undesirable blood particles
Manufactures mononuclear leukocytes
White pulp
One card says: Contains lymphatic nodules & lymphocytes, like a lymph node
Another card: Contains compact masses of lymphocytes surrounding branches of the splenic artery
o Red pulp
Consists of a network of blood-filled sinusoids, along w/ lymphocytes, macrophages, plasma cells, monocytes & RBCs
Contains: splenic cords, numerous erythrocytes and blood vascular sinusoids
o PALS is the center zone of the spleen, surrounding the Central arteriole
*USMLE says: T cells are found in the PALS & the red pulp. B cells are found in follicles w/in the white pulp.
The B cells in the white pulp are analogous with the B cell outer cortical germinal centers in the lymph node
PALS is the most analogous the paracortex in the medulla of the lymph node blah blah
o Site of erythropoiesis in fetus & infant not in adults!!!
Fetal erythropoiesis takes place in the Yolk sac, Liver, Spleen, Bone marrow (Young Liver Synthesizes Blood)
o Travel of blood through spleen:
Enters at the hilum through the splenic artery
Drained by the splenic vein joins lesser mesenteric vein to form hepatic portal vein to the liver w/ greater mesenteric vein
*Nerves to spleen accompany the splenic artery & are derived from the celiac plexus
Thymus:
o Bilobed lymphoid organ located in the superior mediastinum has no lymphatics
o Main function to develop immature T-cells into immunocompetent T-cells
Tests new T cells for ability to recognize self-MHC molecules & self-epitopes these T cells are destroyed
o Thymus large in newborns, grows until puberty & then regresses in adults
o In the adult thymus blood supply is isolated from parenchyma blood thymus barriersupply is MOST isolated from the
parenchyma of the thymus (more than the other options: spleen, lymph node, Peyers patch, pharyngeal tonsil)
o In the childs thymus blood supply is NOT isolated from parenchyma
o Hassels corpuscle are characteristic of the thymus histologically Its a HASSEL for blood to get to parenchyma in thymus
Pharyngeal tonsils:
o When inflamed, they are called adenoids
o Collection of lymphatic tissue located in posterior wall & roof of nasopharynx
o No lymph, sinuses or crypts
o Surrounded partly by CT & partly by epithelium, which forms deep infoldings (which arent crypts??)
o Characteristically covered by ciliated pseudostratified columnar like respiratory epithelium
This is the distinguishing feature histologically from the palatine tonsils
Palatine tonsils:
o Two masses of lymphoid tissue one mass on each side of oropharynx
o Reach maximum size during childhood & diminish considerably after puberty
o Contain many crypts & lymphoid follicles no sinuses
Think Crypts are in between your Arch CAVES
o Surrounded partly by CT and epithelium
o Found between palatoglossus and palatopharygeus
Lingual tonsils:
o Found on posterior portion of dorsum of tongue
o Smaller & more numerous each has single crypt
Peyers Patches:
o Follicular-associated epithelium
Enterocytes & M cells
o Germinal center
IgA positive B cells, CD4 T cells & APCs
o Intestinal tonsils, similar in structure & function to tonsils
o Located in the lamina propria & submucosa of the ileum
o Destroy bacteria
o No Goblet cells
o USMLE: M cells take up Ag. Stimulated B cells leave Peyers patch & travel thru lymph & blood to lamina propria of
intestine, where they differentiate into IgA-secreting plasma cells. The IgA is transported across the epithelium to deal w/
intraluminal Ag
Peyers patches & tonsils considered subepithelial & nonencapsulated lymphoid tissue (not thymus, lymph nodes)
Lymph from lungs, bronchi, and trachea drain into the mediastinal lymph nodes
The spleen, thymus, & lymph nodes are similar in that they all contain lymphocytes
o
o
o
o
o
o

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o
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Not all three filter blood, have a medulla and a cortex, serve as filters for tissue fluid, have afferent & efferent lymphatic vessels

BONE
Function of bone:
o Support
o Protection
o Body movement
o Hemopoiesis
o Mineral storage
Inorganic bone matrix is composed primarily of minerals Ca & P
Give bone its rigidity & account for ~2/3 of its weight
95% of calcium & 90% of phosphorous in body is deposited in bone/teeth
In mineralization of bone inorganic material increases, water content decreases, but little change in collagen
Different than enamel, because bone has a DECREASE in Organic content (collagen, son)
o Not fat storage
Nutrition of bone reaches cells of compact bone via caniliculi, capillaries, & Volkmanns canals (not osseous matrix or lamellae)
Bone formation:
o 1st evidence of bone ossification 8th week of prenatal development
o Endochondral ossification: (ENDO think long bones, condyles Long like FILES)
Most long bones are endochondral derived
Begins as a hyaline cartilage model this doesnt happen in flat bones
Know Fxn of Hyaline Cartilage in bone growth
Calcified cartilage is replace by bone (dont get clowned: hyaline cartilage is not transformed into bone)
Bone replaces cartilage osteocytes replace chondrocytes
Short & long bones (bones of extremities & weight bearing bones)
Mandibular condyles
The list includes ethmoid, sphenoid, & temporal bones
Cranial Base portions of the occipital, sphenoid, temporal, and ethmoid
o Intramembranous:
Bone formed directly no cartilage precursor
Takes place w/in MBs of CT
Flat bones of skull (cranial vault) & face (e.g., nasal bone), & clavicle
Mandible (except condyles), Maxilla
In ORTHO tx, the type of new alveolar bone formation is intramembranous
Contributes to growth of short bones & thickening of long bones
Involves transformation of osteoblasts to osteocytes
o Once formed, bone grows by appositional growth
o A disturbance in cartilage formation in a fetus results in deformities of the axial skeleton and the base of the skull
Bones grow NOT formed by
o Appositional
Cells of bone formation & resorption:
o Osteoblasts:
Synthesize collagenous fibers, bone matrix & promote mineralization during ossification
Become trapped in their own matrix & develop into osteocytes
Derived from mesenchyme (fibroblasts)
Have high RNA content & stain intensely with basic dyes (blue) makes sense constantly transcribing/translating
o Osteoclasts:
Large, multinucleated Giant Cells containing lysosomes & phagocytic vacuoles
Reversal Lines:
o Seen on the Cribiform plate (aka alveolar bone proper) of the alveolar process
o Indicates cessation of osteoclastic activity
Originates from Mononuclear-phagocyte family (MONOCYTE)
Form Howships Lacunae The evil, bone destrying Osteoclasts of the Monocyte galaxy fly in on their How-SHIPs!!!
o Osteoid:
Newly formed organic bone matrix that has not undergone calcification
Differs from bone in that it has no mineralized matrix
o Osteocytes:
Maintain the bone tissue
Bone properties:
o Hard due to calcification of extracellular matrix
o Elastic due to presence of organic fibers
o Strong due to collagenous fibrils

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Bone components:
o Diaphysis
Cylindrical shaft of durable compact bone
o Epiphysis
Caps diaphysis
Location of secondary ossification center
Primary center is diaphysis
Spongy bone surrounded by compact bone
Contains red bone marrow
Erythropoiesis takes place mainly in the epiphysis says Sean
o Epiphyseal plate
Between epiphysis & diaphysis
Region of mitotic activity responsible for elongation of bone
o Medullary cavity
Centrally positioned space w/in diaphysis
Contains fatty yellow bone marrow (everywhere else)
NOTE: Red marrow = Blood cell formation
Cranial, vertebrate, ribs, sternum, epiphysis of long bones
o Nutrient foramen
Opening into diaphysis
Provides site for nutrient vessels to enter/exit medullary cavity
o Articular cartilage
Hyaline cartilage caps of each epiphysis
Facilitates joint movement
o Endosteum
Lines medullary cavity
Consists of supportive dense regular CT
o Periosteum
Dense regular CT covering surface of bone
Site for ligament & tendon-muscle attachment
Responsible for diametric bone growth
Has an outer fibrous layer and an inner osteogenic layer
o Compact bone (Lamellar)
Hard, outer layer of bone tissue
Covered by periosteum
Serves for muscle attachment
Provides protection & gives durable strength to bone
The component of bone tissue that gives a bone tensile strength is the collagenous fibrils of matrix
Consists of:
Matrix of compact bone is collagen plus salts of calcium & phosphorus
Osteocytes bone cells
Osteon a cylinder of compact bone composed of concentric lamellae (HENCE, lamellar or compact bone)
o The oldest lamella of the osteon is the most peripheral lamella
o Osteon canals are oriented parallel to the predominant direction of force like when you stand on an aluminum can
Lacunae depressions in the matrix where an osteocyte is located
Lamellae circular layers of osteocytes located in lacunae
Canaliculi processes connecting lacunae each
canaliculus resembles a miniature canal
Haversian canal central canal around which
concentric lamellae are located
o Contains BVs & nerves that serve the
osteocytes
o Exchange of substances between central canals
& osteocytes occurs along canaliculi
o Which part is the oldest? most peripheral
ring
Haversian system = Haversian canal + surrounding
structures
o Repeating system is found in compact bone of
diaphyses of long bones
Volkmanns canal = connects 2 Harversian canals, runs perpendicular to haversian canals

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Cancellous (spongy or trabecular)


Porous, highly vascular, inner layer of bone tissue branching network of trabeculae
Makes bone lighter & provides spaces for marrow
Seen as spicules or trabeculae
o Immature bone (woven bone, nonlamellar bone, or bundle bone)
Laid down fast
Bundle bone receives the Sharpeys fibers in the alveolar bone proper
Surface features of bone:
o Fissure
Sharp, narrow, cleft-like opening (groove) between parts of a bone that allows passage of BVs & nerves
o Sulcus
Shallow, wide groove on bone surface that allows passage of BVs, nerves, tendons
A shallower & less abrupt cleft/groove than a fissure
o Incisure (notch)
Deep indentation on the border of a bone
o Fovea
Small, very shallow depression
o Fossa
Shallow depression may or may not be an articulationg surface (e.g., glenoid fossa & subscapular fossa, respectively)
o Foramen
Opening through which BVs, nerves, or ligaments pass
o Meatus (canal)
Tube-like passage running through a bone
o Process
Bone projection that serves for attachment of other structures
o Epicondyle
Projection or swelling on a condyle
o Spine
Sharp, slender projecting process
o Tubercle
Small, rounded process
o Tuberosity
Large, rounded, roughened process
o Trochanter
Large blunt projection for muscle attachments on femur
o Crest
Prominent elevated right or border of a bone
o Linea (line)
Small crest, usually somewhat straighter than a crest
o Ramus
Major branch or division of the main body of a bone
o Neck
Slight narrowing of the body of bone that supports the head
o Lamina
Very thin layer of bone
Unpaired bones ethmoid, frontal, occipital, & sphenoid
Ethmoid bone:
o Sieve-like bone at base of skull, behind bridge of nose (behind septal cartilage)
o Straddles mid-sagittal plane & aids to connect the cranial skeleton to the facial skeleton
o Each sinus divided into anterior, middle & posterior air ethmoidal cells
o Horizontal plate (cribriform plate)
Perforated (olfactory foramina) on either side of crista galli for passage of olfactory
nerve bundles
Crista galli sharp, upward, midline projection for attachment of falx cerebri
o Lateral masses (right & left)
Project downward from horizontal plate
Contain ethmoid sinuses & lamina orbitalis (lamina papyracea located in the
orbital medial wall)
The thinnest portion of the orbit is the Medial wall
The roof of the orbit is made from the Frontal bone
Superior & middle conchae are curved plates of bone that form the medial surfaces of the lateral masses
o Perpendicular plate
Downward projection from midline on the undersurface of horizontal plate
o

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68

Forms upper portion of the nasal septum


Sphenoid bone: Pink bone in pic to right pg 35 Netters H&N anatomy
o Single bone that runs through the mid-sagittal plane
o Aids in connecting cranial skeleton to facial skeleton
o Consists of a hollow body & 3 pairs of projections:
Hollow body
Contains the sella turcica (houses pituitary gland) & sphenoid sinuses
Greater wing forms lateral wall of orbit (bottom pic) & roof of the infratemporal fossa (top pic)
Foramina in greater wing provide access to both pterygopalatine & infratemporal fossa
o Foramen ovale transmits V3
o Foramen spinosum transmits middle meningeal vessels & nerves to tissue covering brain
Lesser wing helps to form superior orbital fissure & roof of orbit
Contains optic canal (optic foramen) & ophthalmic artery
Superior Orbital Fissure
S.O.F. is located between greater and lesser wings of the sphenoid
o Left & right pterygoid processes Yellow bone to right, lateral pterygoid plates hanging down
Project downward from near junction of each of the greater wings w/in body of sphenoid bone
Run along posterior portion of nasal passage
Each proccess consists of a medial & lateral pterygoid plate
Lateral pterygoid plate
o Provides origin for both lateral & medial pterygoid muscles
Medial pterygoid muscle originates from medial surface
Inferior head of lateral pterygoid originates from the lateral surface
o ***Forms medial wall of infratemporal fossa
Medial pterygoid plate
o Forms posterior limit of lateral wall of nasal cavity
o Ends inferiorly as the hamulus (haMElus) for Medial pg 354 Netters H&N anatomy
Hamulus = small, slender hook acting as a pulley for tensor veli palatine tendon (from vertical to horizontal)
What is located directly behind Mx 3rd Molar?? Hamular notch, or Mx tuberosity Its gotta be!
TMJ components:
o Mandibular fossa
Oval depression in inferior surface of base of zygomatic process of the temporal bone
Articulates w/ condyle of Mn to form TMJ
o Articular eminence
Rounded bar of bone forming the anterior part of the Mn fossa
Posterior slope of eminence is lined by fibrous CT
o TMJ cavity
Divided into upper & lower compartment by articular disc
Upper disc glides forward on articular tubercle
Lower condyle rotates beneath the disc like a hinge
o This contains the condyle and capsule
Alveolar bone:
o Exists only to support teeth if tooth never erupts, it never forms if tooth is extracted, alveolus resorbs
o In children, it increases in height & length to accommodate developing dentition
o Position of tooth, not the functional load placed on it, determines the shape of the alveolar ridge
o Alternate loosening and tightening of primary tooth about to shed is from alternate resorption and apposition of cementum and
bone
o The primary mineral component of alveolar bone in the periodontium is Hydroxyapatite
Mandibular condyles:
o Provides space for erupting molars
o Major site of growth
Soft tissue development carries the Mn forward & downward
Condylar growth fills in the resultant space to maintain contact w/ the base of the skull
o Long axes of Mn condyles intersect at foramen magnum, which indicates that axes are directed posteromedially
o Growth at the mandibular condyles provides the space between the jaws into which the teeth erupt
Hard palate:
o Anterior 2/3 formed by palatine processes of maxilla
o Posterior 1/3 by the horizontal plates of palatine bones
o The portion of hard palate located directly posterior to the Mx central is derived from the medial nasal processes
o Forms the roof of the oral caviy & floor of nasal cavity
If you over-implanted Teeth #710, you would penetrate the nasal cavity
o Covered w/ a mucous MB beneath these are palatal salivary glands

o
-

Submucosa of anterolateral is characterized by adipose tissue, where posterolateral contains nests of mucous salivary
glands - this is the glandular tissue we compress with the posterior palatal seal in dentures!
Roof of the oral cavity formed by the maxilla & the palatine bones; specifically the palatine processes of the maxilla & horizontal
plates of the palatine bones. Same as the floor of the nasal cavity
Soft palate:
o Posterior to & continuous w/ hard palate
o Contains
Lamina propia of loose fibrous CT
Tough fibrous CT sheet the palatal aponeurosis
Salivary acini deep to the mucous membrane
Shallow, blunt rete pegs *this is only one not obvious
o Posteriorly, soft palate is suspended in the oropharynx ends in the midline uvula
o Most palatal muscles receive innervation from pharygeal nerve plexus
o Motor branchers of CN V3 to tensor mucles of palate
o Sensory innervation provided by CN V2
Nasal cavity:
o Bridge of nose is formed by two nasal bones
o Lateral walls formed by superior, middle, & inferior conchae
o Bony floor formed by palatine process of Mx & horizontal plate of palatine bone =hard palate
o Roof formed by nasal, frontal, body of sphenoid & cribiform plate of ethmoid
o Medial wall or nasal septum formed by the perpendicular plate of ethmoid bone, vomer bone, & septal cartilage (pic above)
o The rest of the framework for bone consists of several cartilage plates
Specifically, the lateral nasal cartilage and greater & lesser ala cartilage
These are held together by fibrous CT
o Opens on face through nares
o Communicates w/ nasopharynx through choanae (posterior openings of nasal cavity to nasopharynx)
o Nasal conchae: See pic on right they are cut in pic to left to show meatus
Three pairs of scroll-like delicate shelves or projections, which hang into nasal cavity from lateral walls
Increase surface area w/in nasal cavity & expose the olfactory nerve to inhaled odors
Superior & middle conchae part of ethmoid bone (yellow bone)
Inferior conchae separate bone (aka inferior turbinates)
o Meatus of the Conchae:
Space below & lateral to each concha
Superior meatus
Receives openings of the posterior ethmoidal sinuses
(Two dots most superior)
(also drains posteriorly into sphenoethmoidal recess)
Middle meatus
Receives the openings of:
o Frontal sinus drains into infundibulum of middle meatus (Straw going
from frontal bone/sinus)
o Middle ethmoidal sinuses drain onto ethmoidal bulla (rounded prominence
on lateral wall of middle meatus) (round thing in pic)
o Anterior ethmoidal & maxillary sinuses drain into middle meatus via
the hiatus semilunaris (just below ethmoid bulla)
Hiatus semiluminares groove on lateral wall continuous w/ the infundibulum
NOTE: the maxillary sinus must drain upwards against gravity makes
maxillary sinus infections hard to treat
Inferior meatus:
Receives the opening of nasolacrimal duct drains lacrimal fluid from eye
surface of into meatus for evaporation
(tiny little hole just posterior to nose)
Cranial fossae:
o Anterior cranial fossa
Formed by frontal & ethmoid bones white and yellow. Also lesser wings of
sphenoid, pink.
Contains:
Frontal lobes of cerebrum
Cribriform plate
Foramen cecum (contains emissary vein in fetal life)
Crista galli
o Middle cranial fossa

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70

Formed by sphenoid (greater wings), temporal, & parietal bones


Contains:
Temporal lobes of cerebrum
Hypophysis cerebri (pituitary gland)
Optic & carotid canal
Superior orbital fissure
Trigeminal impression for trigeminal ganglion
Separates the middle ear cavity & sphenoid sinus
Which foramen is not in the middle cranial fossa
Jugular
o Posterior cranial fossa
Formed by occipital & temporal bones
Contains:
Occipital lobes
Cerebellum, pons, & medulla oblongata
Internal auditory meatus
Jugular, condyloid, & mastoid foramen
Foramen magnum
Hypoglossal canal
o Petrous portion of the temporal bone:
Forms the floor of the middle cranial fossa
Separates the middle cranial fossa from the posterior cranial fossa
Zygomatic bone
o NOT part of the calvarium, because it comes from the 1 st Branchial arch
o Aka cheekbone, malar bone or zygoma
o Forms prominence of cheek & part of the lateral wall & floor of the orbital cavity
o NOT part of the calvarium (Temporal, Occipital, Parietal, Frontal all are)
o Anteriorly articulates w/ maxilla
o Posteriorly articulates w/ zygomatic process of temporal bone to form the zygomatic arch
Temporal fossa
o Shallow depression on side of cranium bounded by temporal lines
o Terminating below level of zygomatic arch
o Area above zygomatic arch, filled w/ temporalis muscle
o Lower margin is masseter muscle
Infratemporal fossa
o Lies posterior to maxilla (Green), between pharynx & ramus of mandible,
below infratemporal crest of greater wing of sphenoid bone (yellow)
o Boundaries of Infratemporal fossa:
Anterior wall posterior surface of maxilla
Posterior wall tympanic part & styloid process of temporal bone (pink)
Medial wall lateral pterygoid plate of the sphenoid bone (yellow)
Lateral wall ramus of the mandible
Roof (see lower pic) infratemporal surface of greater wing of sphenoid bone
Contains foramen ovale transmits V3 (in sphenoid bone yellow!)
Floor point where medial pterygoid muscle inserts into medial aspect of the Mn near the
angle
o Communicates w/ pterygopalatine fossa (medial- between pterydoid plates and posterior
maxilla) via pterygomaxillary fissure (IN, UP, BACK Just like PSA block)
o Other openings communicating w/ the infratemporal fossa: foramen ovale, foramen spinosum
(not foramen rotundum)
o CONTENTS of infratemporal fossa: lots of Qs on this stuff
See 1999Q04 I dont like this one
Temporalis muscle (lower portion)
Temporalis muscle passes medial to the zygomatic arch & inserts into coronoid
process
Medial & lateral pterygoid muscles (cut, sandwiching the inferiorly running
inferior alveolar and lingual nerves)
Between them runs the:
o IA nerve and artery
o Lingual nerve
NOT the nerve to the masseter (little tiny one piercing superior head
of lat pterygoid)
Maxillary artery & most branches (including middle meningeal artery)

MAJOR artery of the infratemporal fossa drawing on bottom right


Pterygoid plexus of veins
Mandibular nerve & branches including lingual nerve
Chorda tympani shown joining the lingual nerve, just deep to IA nerve in pic
Otic ganglion (PS ganglion associated w/ glossopharyngeal nerve)
Sphenomandibular ligament Think about it Mn to sphenoid gonna be in this space!
o In a fractured condyle, muscular contractions may result in displacement of the condyle into the
infratemporal fossa
*Temporal & infratemporal fossae communicate w/ each other deep to zygomatic arch
Infratemporal crest of greater wing of sphenoid bone
o Separates the temporal fossa from the infratemporal fossa below it
Pterygopalatine fossa (Think Sphenopalatine Fossa)
o Communicates laterally w/ infratemporal fossa by way of pterygopalatine fissure
o Formed by the sphenoid (posterior/superiorly), palatine (medially), and maxillary bones (anteriorly) (not temporal)
Infection in Maxillary Sinus that spreads posteriorly spreads to pterygopalatine fossa ??? Confirm this
o Pterygopalatine ganglion:
Lies in the pterygopalatine fossa just below CN V2
Receives preG PS fibers from facial nerve by way of greater petrosal nerve
Also receives PostG fibers via the deep petrosal - Sympathetic
Sends postG PS fibers to lacrimal gland & glands in palate & nose (NOT to parotid gland- otic)
o CN V2 & pterygopalatine portion of maxillary artery pass through the fossa
Pterygopalatine fissure communicates:
o 1) Medially w/ nasal cavity through sphenopalatine foramen
The Sphenopalatine foramen connets the pterygopalatine fissure with the nasal cavity
o 2) Posteriorly w/ middle cranial cavity through pterygoid canal and (3) the foramen rotundum
o 4) Posteriorly w/ the pharynx through the pharyngeal canal
o 5) Anteriorly w/ orbit through the inferior orbital fissure
o 6) Inferiorly w/ oral cavity via the Greater Palatine canal
NO communication with Facial Canal
Chest
o Ribs
True 1-7
False 8-12
Floating 11-12
Articulate with the spine at the superior articular process of the vertebrae of the same number and the inferior facet for one
number lower (higher on the spine) in a synovial joint and are surrounded by a radiate ligament
When the arched shaft of the ribs is elevated, transverse diameter of the pleural cavity is increased Think about it
when elevated, you are breathing in, so the cavity is gonna increase in size
o Sternum
Has 3 parts:
The manubrium (top), the body (middle), the xiphoid process (bottom)
Sternal angle (inbetween manubrium and body)
The bottom of the sternal shield (bottom of manubrium)
Used to locate 2nd rib
Level of the branching of the trachea (where it passes behind the aortic arch)
Same plane as T5
Body of sternum articulates directly w/ manubrium & xiphoid process (not clavicle, 1st rib,
11th rib)
Hip bone
o Formed by fusion of ileum, ischium, pubis
o Articulates w/ the sacrum at sacroiliac joint to form pelvic girdle
o Two hip bones articulate w/ one another anteriorly at the symphsysis pubis
o Ilium:
Upper flattened part of hipbone
Iliac crest ends in front at anterior superior iliac spine & behind at
posterior superior ilac spine
Greater sciatic notch a large notch call
o Ischium:
L-shaped w/ upper thicker part (body) & lower thinner part (ramus)
Bears weight of body when person is upright & seated
Ischial spine & ischial tuberosity
Obturator foramen formed by ramus & pubis

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72

Pubis:
Body, superior ramus, & inferior ramus
Bodies of the two pubic bones articulate in the midline at symphysis pubis
Medial to symphysis is pubic tubercle
Inguinal ligament connects the pubic tubercle to anterior superior iliac spine
Acetabulum:
Cup-shaped cavity on lateral side of hip bone
Receives the head of femur
Formed superiorly by ilium, posteroinferiorly by ischium & anteromedially by pubis

JOINTS
Three main classes of joints (articulations):
o Synarthroses: Think : these joints think it is a Syn to move!
Immovable joints (fibrous joints) EX: sutures
In a newborn, intervals between bones in the middle of the cranial base is Hyaline cartilage (see spheno-occipital15 lines)
o Diarthroses: These joints would rather sin (move) and DIE, than be still.
Freely movable joints (synovial joints)
Aneural & avascular
Covered in hyaline cartilage or fibrocartilage (TMJ)
o Amphiarthroses: amphi both.
Slightly movable articulations in which the contiguous bony surfaces are either connected by broad, flattened disks of
fibrocartilage or are united by interosseous ligaments (cartilaginous joints) EX: pubic symphysis, vertebrates
Joints can also be classified based on the associated CT type:
o Fibrousjoined by fibrous CT
1) Sutures
2) Syndesmoses between radius & ulna
3) Gomphosis tooth socket a synarthrosis joint that binds teeth to alveolar socket via the PDL
o Cartilaginousjoined by fibrocartilage or hyaline cartilage
1) Synchondroses epiphyseal plates w/in long bones
NOTE: The spheno-occipital synchondrosis in the midline of the cranial base of a newborn consists of hyaline
cartilage
2) Symphysis mental symphsis
o *Synovialjoint capsule containg a synovial MB that secretes a synovial fluid
Lined with either Hyaline cartilage or fibrocartilage
Most joints are synovial such as TMJ
*Synovial joints:
o Freely movable (diarthrodial) joints
o Limited by one joint surface, ligaments, muscles, or tendons
o Have 5 distinguishing features:
1) Articular cartilage:
Thin layer of hyaline cartilage that covers the smooth articular surfaces
Contains no BVs or nerves
NOTE: TMJ contains fibrocartilage not hyaline cartilage
2) Synovial cavity:
Small fluid-filled space separation the ends of adjoining bones
3) Articular capsule:
Double-layered capsule
o Outer layer fibrous CT encloses the joint.
o Inner layer thin, vascular synovial MB (because it needs blood supply to produce synovia)
4) Synovial fluid:
Clear, thick fluid secreted by synovial MB
Provides nutrition
Fills joint capsule & lubricates articular cartilage at the articulations
5) Supporting ligaments:
Capsular, extracapsular, & intracapsular ligaments
Maintain normal bone positioning
o Some synovial joints have articular discs (i.e., TMJ & sternoclavicular joint) that divide the cavity into two separate cavities
Bursa:
o Fluid filled sac lined w/ a synovial MB
o Function = reduce friction
o May be located between tendon & bone to reduce friction during muscle contraction
o Bursitis inflammation of lining of a bursa

Subacromial bursa
Large synovial membrane which is adherent to undersurface of coracoacromial ligament, acromion, & deltoid laterally, &
floor is adherent to rotator cuff & greater tuberosity;
It envelops proximal humerus, & facilitates gliding of proximal humerus under coracoacromial arch
Atlanto-axial joint:
o Allows for maximum rotational movement of head about its vertical axis
o Synovial articulation between:
1) the inferior & articulating facets of the atlas (1st cervical vertebra)
2) the superior articulating facets of the axis (2nd cervical vertebra)
o Movement of head in saying NO
Atlanto-occipital joint: (the upper one)
o Synovial articulation between:
1) the superior articulating facets of the atlas
2) the occipital condyles of the skull
o Pemits rocking & nodding movement in saying YES
o

MUSCLE
-

Muscle fibers:
o Sarcoplasm cytoplasm of muscle cells
Contains many parallel, threadlike structures called
myofibrils
o Myofibrils
Large, multinucleated skeletal muscle cells
Each is comprised of smaller strands called myofilaments
that contain contractile proteins: actin & myosin
An increase in #s of additional myofibrils causes muscle
fibers to hypertrophy
This is caused by progressively greater numbers of
both actin & myosin filaments in the myofibrils
The # of muscle fibers does not increase, the size of
each fiber increases
I Band
Gets smaller with contraction
Only Actin
o Z line
Separates adjacent sarcomeres
Where the T tubules lie
Desmin is also found at the Z lines
It aligns adjacent myofibrils in the myocyte, giving muscle its striated appearance
A Band (A for Alpha Male -- myosin, meaning it makes everyone come to it)
Doesnt change size with contraction
Both actin and myosin, but Myosin dictates borders this is because myosin (thick) is only present in the A Band
o H zone (Think HOT zone, where the ACTIoN is coming)
Gets smaller with contraction
Only Myosin
o M line Middle
o Sarcomere: (see figure)
Repeating contractile unit in the myofibril
Each sarcomere is enclosed between two Z lines (Think End of the alphabet)
Characterized by dark & light striations due to the arrangement of thick (myosin) & thin (actin) filaments
Dark bands = A bands (Anisotropic)
Contain myosin filaments throughout
o In normal light microscopy of striated muscle, the dark portion of the striation is caused by the presence of myosin
Outer regions contain both actin & myosin
H band central area of A band w/o actin/myosin overlap
Light bands = I bands (isotropic)
Bisected by dark Z lines, where actin filaments of adjacent sarcomeres join
o Sarcoplasmic reticulum:
Network of membranous channels, tubules & sacs in skeletal muscles
Analogous to endoplasmic reticulum of other cells
Extends throughout the sarcoplasm

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The organelles that releases & sequesters/stores Ca2+ during muscle contraction & relaxation
o Fibrous CT covering of muscle:
Epimysium:
The CT layer enveloping the entire skeletal muscle
Perimysium:
Continuation of the outer fascia, dividing the interior of the muscle into bundles of muscle cells
Fasciculus = bundle of cells surrounded by each perimysium
Endomysium:
The CT layer surrounding each muscle fiber
What immediately covers myofibrils?
o Endomysium or Sarcolemma?????
o Above it says sarcoplasm contains myofibrils so Id say sarcolemma is the answer for this one (if above is correct)
The 3 levels of fascia are interconnected, allowing vessels & nerves to reach individual fibers & cells
o Muscle-tendon junction
The union is made by a continuity of CT sheaths of the muscle with those of the tendon
Motor unit
o Def: alpha motor neuron + muscle fibers it innervates
o Axon of motor unit is highly branchedone motor neuron innervates numerous muscle fibers
o When a motor neuron transmits an impulse, all fibers it innervates contract simultaneously
Muscle contraction
o Tension develops because of interaction between actin & myosin filaments (see figure)
o Actin filaments (thin myofilaments, 5-8 nm diameter); composed of:
Actin globular actin (G-actin) molecules are arranged into double spherical chains called fibrous actin (F-actin)
*Tropomyosin (Like ROPE-Omyosin)long, threadlike molecules, lie along surface of F-actin strands & physically cover
actin binding sites during resting state
*Troponin (LIKE TRIP, i.e. tripped the SWITCH) a small oval-shaped molecule attached to each tropomyosin
o Myosin Filaments: (thick myofilaments, 12-18 nm diameter); composed of:
Light meromyosin (LMM) makes up rod-like backbone of myosin filaments
Heavy meromyosin (HMM) forms shorter globular lateral cross-bridges, which link to actin binding sites during
contraction
- Smooth muscle:
o Responsible for involuntary movements of internal
organs
o Much smaller than skeletal muscle fibers
o Composed of uninucleate, elongated, spindle-shaped
cells (fusiform cells)
Do not possess regularly ordered myofibrils & are
therefore NOT striated (myofibrils lack transverse
striations)
Nuclei are found in the widest part of each fiber
o Do NOT possess T-tubules & sarcoplasmic reticulum
is poorly developed
o Contraction process is slow & not subject to voluntary
control
Types of Smooth muscle
Single unit
Has numerous gap junctions (electrical synapses) between adjacent fibers
These fibers contract spontaneously
EX muscular tunica of GI tract, uterus, ureters, & arterioles
Multi-unit
Lacks gap junctions
Individual fibers are autonomically innervated
EX: ciliary muscle & smooth muscle of iris, ductus deferens & arteries
Skeletal muscle:
o Responsible for voluntary body movement
o Composed of bundles of very long, cylindrical, multinucleated cells
Possess regularly ordered myofibrils responsible for striated appearance (myofibrils have distinct transverse striations)
Striations consist primarily of actin & myosin proteins
Each fiber is innervated by an axon & motor neuron at a motor end plate
o Enlarges with prolonged activity as result of increase in sarcoplasm and in the number of myofibrils of existing muscle fibers
o

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Not from differentiation of myoblasts or mitotic division of muscle fibers


Nuclei are either slender ovoid or elongated & are situated peripherally
Only skeletal muscle has peripherally located nuclei
o Contain transverse tubules (T-tubules -- at the Z line) & the sarcoplasmic reticulum is very well developed
o Contraction is quick, forceful, & usually under voluntary control
o Myofibrils (actin & myosin) are the contractile element
o Triad consists of terminal cisternae and fingerlike invagination of sarcolemma
Cardiac muscle fibers:
o Make up thick, middle layer of heart known as the myocardium
o Have larger T-tubules & less-developed sarcoplasmic reticulum as compared to skeletal fibers
o Short, branched, & single or binucleated
o Have more mitochondria between myofibrils; richer in myoglobin than most skeletal muscles
o Contain large, oval, centrally placed nuclei
o Characteristic feature presence of intercalated discs
Strong, thin unions between fibers
Provide low resistance for current flow
Within the discs, desmosomes attach cells & gap junctions allow electrical impulses to spread from cell to cell
o Can contract spontaneously w/o nerve stimulation
o Respond to increased demand by increasing fiber size known as compensatory hypertrophy
o

HEAD/NECK MUSCLES

Muscle
SCM

Origin
Sternum; clavicle

Digastric

Inferior border of mandible;


mastoid groove

Mylohyoid
(Know how to
pick out of a
diagram)

Mylohyoid line of mandible


** the mylohyoid ridge/line is
located on the body of the
mandible
**The mylohyoid is the muscle
responsible for displacing
denture when extended too far
inferiorly
Styloid process of temporal
bone

Stylohyoid
Hyoglossus

Body and greater horn of hyoid


bone

Sternohyoid
Thyrohyoid

Manubrium
Thyroid cartilage

Omohyoid

Superior border of scapula

Muscles of Anterior Neck


Insertion
Action
Mastoid process of
Turns head to side; flexes
temporal bone
neck & head
Hyoid bone (sling)
Opens jaw;
elevated hyoid bone
Does move the mandible
(one Q asked about
aiding in protrusion)
BUT is NOT a muscle of
mastication
Median raphe
Elevates hyoid bone &
(It must attach to hyoid
floor of mouth
somehow!)
NOTE: in the submental
region, the mylohyoid is
the 1st muscle to be
penetrated from the skin
NOT involved in
mastication!!
Body of the hyoid
Elevates & retracks
(gotta have style for the
hyoid bone
body!)
Lateral and dorsal tongue Raises the hyoid, retracts
the tongue to the
LATERAL FLOOR
Body of hyoid
Depresses hyoid
Greater cornu of hyoid
Depresses hyoid;
bone
elevates thyroid cart.
Clavicle; body of hyoid
Depresses hyoid
bone

Innervation
Accessory nerve CNXI
Ant belly (V3)
Post belly (VII)

Trigeminal V3

CN VII
Hypoglossal n.
Ansa cervicalis
C1 via hypoglossal n.
Ansa cervicalis

Mandibular Movements and the muscles that make them! (courtesy of Dr. Millers PwrPts)
o OPENING
Lateral Pterygoids (1 )
Gravity
Mylohyoid
Digastric
Q reads The lat pterygoids, suprahyoid, & post digastric contract, what happens? Mandible opens
o PROTRUSION
Lateral Pterygoid

75

o
o
-

Medial Pterygoid
CLOSING
Masseter
Temporalis
Medial Pterygoid (2 )
RETRUSION
Temporalis (Posterior Fibers)
LATERAL MOVEMENTS
All four muscles of mastication- Moving at different times in a complex fashion

Only 3 muscles Depress the Hyoid TOS, Thyrohyoid, Omohyoid, and Sternohyoid
Superficial Muscles of the Neck???
o SCM
o Platysma
o Sternohyoid
o Maybe Splenius Muscles???
Muscles of the Deep Neck pg 113 Netters anatomy
o Often called the lateral vertebral muscles
o Form a large portion of the floor of the posterior cervical triangle

Muscle
Longus Capitus pg 134

Origin
Anterior Tubercles of
C3-C6 vertebral
transverse processes

Longus Colli

Bodies of T1-T3, bodies


of C4-7, and transverse
processes of C3-C6

Scalenes

Anterior: Anterior
tubercles of transverse
processes of C3-C6
Middle: Posterior
tubercles of the
transverse processes of
C2-C7
Posterior: Posterior
tubercles of the
transverse processes of
C4-C6

Anterior tubercle of the


atlas (C1), bodies of C24, and transverse
processes of C5-C6
Anterior: Scalene
tubercle of 1st rib
Middle: Superior surface
of 1st rib
Posterior: External
border of 2nd rib

Action
Flexes the neck
**In front of the cervical
vertebrae and are often
called prevertebral ms.
Flexes the neck (weakly),
and slightly rotates and
laterally bends the neck

Innervation
C1-C3 ventral rami

Anterior and Middle:


Elevate the 1st rib, when
the 1st rib is fixed, they
flex the neck forward and
laterally rotate it to the
opposite side

Anterior: C5-C7 ventral


rami

Posterior: Raises the 2nd


rib and flexes and
slightly rotates the neck

C2-C6 ventral rami

Middle: C3-C8 ventral


rami
Posterior: C6-C8 ventral
rami

Suboccipital Triangle
o Deep in the triangle passes the vertebral artery and the Suboccipital nerve (aka dorsal ramus of C1)
o Posterior Neck/Head Nerves
Greater occipital nerve (dorsal ramus of C2 spinal nerve)
Great auricular nerve (cervical plexus C2,3)
Lesser occipital nerve (cervical plexus C2,3)
Least occipital nerve (dorsal ramus of C3 spinal nerve)
Suboccipital nerve (aka dorsal ramus of C1)

Muscle
Rectus Capitus Posterior
Minor
Rectus Capitus Posterior
Major
Obliquus Capitus
Superior

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Muscles of Deep Neck


Insertion
Basilar portion of the
occipital bone

Muscles of Suboccipital Triangle


Origin
Insertion
Action
Arises from the tubercle
Medial part of the
Extends the head
of the posterior arch of
inferior nuchal line
the atlas
Arises from the spinous
Lateral portion of the
Extends head and rotates
process of the axis
inferior nuchal line
it to the same side
From the transverse
Occipital bone between
Extends the head and
process of the atlas
the superior and inferior
bends it laterally

Innervation
Suboccipital nerve (aka
dorsal ramus of C1)
Suboccipital nerve (aka
dorsal ramus of C1)
Suboccipital nerve (aka
dorsal ramus of C1)

Obliquus Capitus Inferior

Spinous process of the


atlas

Triangle
Anterior (there are two!)

Carotid (Superior) pg 120


Submandibular (Digastric, Submaxillary)
Pg 118 H&N
Submental pg 124
Muscular (or inferior carotid) Omotracheal
Posterior (THINK Os)
THE SCM divides the anterior and posterior
triangles, Pic Above
Occipital
Omoclavicular (Subclavian)
-

nuchal lines
Inferior and dorsal
portions of the transverse
process of the atlas

Rotates the atlas, turning


the face towards the
same side

Location & Contents of the Triangles of


the Neck
Boundaries
SCM muscle, medial line of neck, inferior
border of mandible
Jugular notch also a boundry, not
omoclavicular space
SCM (posterior), posterior digastric
(superior), & omohyoid muscle (anterior)
Superior border is the posterior digastric
Digastric muscle, inferior border of
mandible
***NOTE: mylohyoid makes up the floor
Digastric, hyoid bone (only unpaired
triangle of neck)
Floor = Mylohyoid
SCM & omohyoid muscles, midline of neck
SCM & trapezius muscles; clavicle

SCM, trapezius, & omohyoid muscles


SCM, & omohyoid muscles, clavicle

Suboccipital nerve (aka


dorsal ramus of C1)

Contents
Four lesser triangles, salivary glands,
larynx, trachea, thyroid glands, various
vessels & nerves.
Carotid Sheath (Carotid arteries, internal
jugular vein, vagus nerve,) CN XII (where
the IJV originates from) , Ansa Cervicalis
Salivary glands, CN XII
Muscles of the floor of the mouth, salivary
glands & ducts
Larynx, trachea, thyroid gland,
Floor: Medial and Posterior Scalenes,
Splenius capitus, Levator scapulae, Nerves
& vessels, Anterior belly of Omohyoid
(NOT sternohyoid)
Cervical plexus, accessory nerve
Brachial plexus, Subclavian artery

Triangles
o Anterior Triangle
Submental
Digastric
Carotid
Muscular
Not Omohyoid
o Posterior Triangle
Occipital and Omoclavicular
o CN XII (Hypoglossal) travels from the Carotid triangle into the subMandibular triangle
Muscles that pass:

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Medial scalene
Splenius capitis
Levator scapulae
-

Hyoid Bone
o Attached by muscles or ligaments to the mandible, clavicle, and tongue
Sternocleidomastoid (SCM)
o Origin
2 heads of origin
Sternal head arises from the anterior surface of the manubrium of the sternum
Clavicular head arises from the superior surface of the medial third of the clavicle
o ***Clavicle is first bone to calcify and is the most commonly broken
o Insertion
To the lateral surface of the mastoid process and the lateral half of the superior nuchal line
o Action
Tilts head to one side, flexes the neck, rotates the neck so the face points superiorly to the opposite side, both together flex
the neck
o Innervation
Spinal root of XI (and C2, C3)
Only Traps are also innervated by XI
o Sternocleidomastoid separates the anterior & posterior triangles of the neck
Platysma
o Innervated by CN VII Its so superficial, its almost a facial muscle so its innervated by facial nerve!!!

Muscle of Mastication
Origin
Insertion
Action
Floor of the temporal bone
Coronoid process of Mn
Elevates & retracts Mn
Zygomatic arch
Lateral ramus of the Mn
Elevates Mn to occlude teeth
Medial surface of the Lateral
Medial surface of angle of Mn
Elevates Mn & moves Mn
pterygoid plate & tuberosity of Mx &
laterally
pyramidal process of palatine bone
Lateral pterygoid
Superior head: Greater wing of the
Superior head: Articular disc & capsule Opens, protrudes, & moves Mn
sphenoid bone
Inferior head: Condylar neck of Mn
laterally
Inferior head: Lateral surface of
lateral pterygoid plate
- Muscles of mastication
o Two groups based on function:
Masseter, temporalis, medial pterygoid elevate Mn to close mouth
In the temporalis, most elevation is from the anterior fibers, but the posterior fibers do contribute to elevation of Mn
Lateral pterygoid depresses Mn to open mouth, translates jaw (side-to-side) & protrudes Mn
What about mylohyoid as an elevator of Mn see 2000 Q01
Kaplan says mylohyoid also depresses the Mn (bad Q!!!) Elevates the hyoid not Mn tho
o All receive blood supply from pterygoid portion of the Mx artery
o Innervated by trigeminal nerve (V3)
o Masseter & medial pterygoid form sling around angle of Mn
Superificial head of masseter inserts on lateral surface of angle & medial pterygoid inserts on medial surface of angle
Primary closing muscles provide lateral stabilization of Mn
Both muscles exert similar forces upon Mn
Nerve to the masseter passes through the mandibular notch, BUT does not reach the muscle by passing through the
mandibular foramen Uhhh No SHIT! Why would it pass through the mandibular foramen?
o Medial pterygoid muscle:
The lingual nerve, inferior alveolar nerve, & IA artery all pass between medial pterygoid & Mn ramus (not lingual artery)
If needle lies below mandibular foramen during IA block, it will pierce the Medial Pterygoid muscle
A diffuse swelling at the angle of the Mn & lateral neck of the condyle constrains the following muscle (NOT the medial
pterygoids)
Digastric, mylohyoid, lateral pterygoid, geniohyoid
o Lateral pterygoid muscle:
Condylar fracture or injury to lateral pterygoid results in deviation toward affected side
Damage to the articular disc of TMJ would result in paralysis of the lateral pterygoid muscle, which inserts on the articular
disc, joint capsule, & neck of the Mn. The patient would be unable to open his/her mouth
o Temporalis muscle:
Fan-shaped muscle originating from 1) the bony floor of the temporal fossa & 2) the deep surface of the temporal fascia
Inserts on the coronoid process of the mandible & the anterior border of the ramus of the mandible
Muscle
Temporalis
Masseter
Medial pterygoid

78

Anterior & superior fibers elevate Mn; posterior fibers retract Mn (these fibers also contribute to elevation of Mn)
Primary function of the temporalis muscle is to elevate & retrude the Mn
Innervated by deep temporal nerves (branches of V3)
Arterial supply by the maxillary & superficial temporal arteries
Passes medially (downward & deep) to zygomatic arch as a thick tendon before inserting
Posterior fibers retract Mn & maintain resting position of closure of mouth
o In a double vertical fracture at the mental foramina, muscle action will cause the small fragment to move inferiorly &
posteriorly
The small fragment would be the anterior part
Buccinator muscle:
o Does not move the jaw
o Innervated by CN VII
o Complex origin:
Maxilla along alveolar process superior to alveolar margin between 1 st & 3rd molars
Mandible along oblique line of Mn between 1st & 3rd molars
Pterygomaxillary ligament
Pterygomandibular raphe thin, fibrous band running from the hamulus of the medial pterygoid plate down to the Mn
(Along with Superior pharyngeal constrictor)
Marks the posterior border of the vestibular side of the cheek (posterior border of buccinator)
Connects the buccinator (ANTERIORLY) and the superior pharyngeal constrictor (POSTERIORLY)
o Inserts:
Orbicularis oris & skin at angle of mouth
o Pierced by the parotid duct
Parotid duct crosses the massetter and pierces the buccinator
o Proprioceptive fibers are derived from the buccal branch of V3
o Muscle innervation from the buccal branch of VII
o Actions:
Assists with mastication but NOT innervated by V3
Move boluses of food out of vestibules & back towards molar teeth
Tense the cheeks during blowing & whistling
Assist w/ closure of mouth
o Blood supply facial & maxillary arteries
IA nerve block injection
o Needle passes through mucous MB & buccinator muscle & lies lateral to medial pterygoid
o If needle passes posteriorly at level of Mn foramen penetrates parotid facial paralysis
o If needle passes well below Mn foramen penetrate medial pterygoid

Muscle
Genioglossus

Origin
Superior genial spine of
mandible

Styloglossus

Styloid process of
temporal bone

Muscles of Tongue
Insertion
Dorsum of tongue
Lateral side & dorsum of
tongue (some fibers go
into the hyoglossus m.)
Side of tongue
Side of tongue

Action
Protrudes apex of tongue
through mouth
Depresses ALSO
Elevates & retracts
tongue (during swallow)

Innervation
C1 via ansa cervicalis
via Hypoglossal nerve
XII
XII

Hyoglossus
Hyoid bone
Depresses side of tongue XII
Palatoglossus
Palatine aponeurosis
Pulls tongue upward &
XI via X (oddball alert!)
(Anterior Fauces)
backward
- Muscles of Tongue
o All muscles of tongue are innervated by CN XII (except palatoglossus muscle pharyngeal plexus [CN XI via X])
Damage to what CN leads to movement of the tongue toward the side of the damage?
CN XII
o Blood supply lingual artery; venous drainage into internal jugular vein
o Extrinsic muscles:
Anchor tongue to skeleton
Control protrusion, retraction, & lateral movements of tongue
Genioglossus, Hyoglossus, Styloglossus, Palatoglossus (Decks say
Palato IS an extrinsic, Netters doesntGo with Decks)
Lingual nerve, hypoglossal nerve, & submandibular duct are all
superficial to the hyoglossus (lingual artery is not)
o Intrinsic muscles:

79

Lie entirely w/in tongue itself


Named according to spatial plane: longitudinal, transverse, vertical
Fibers contract to squeeze, fold, & curl the tongue
NOTE the Exceptions C1 via XII Genioglossus (should be just XII)
for the extrinsic tongue muscles
Thyrohyoid (should be just ansa cervicalis) for the strap muscles
Geniohyoid!!
Taste buds: pg 402 Netters H&N anatomy
o Associated w/ peg-like projections on the tongue mucosa called lingual papillae
o Contain a cluster of 40-60 gustatory cells as well as many more supporting cells
o Each gustatory cell is innervated by a sensory neuron
o Have a turnover rate of 30 days, and are located on ventral and dorsum of the tongue??
o Kinds of Lingual papilla:
Filiform: (think MILI, like Millions)
Most numerous, small cones arranged in V-shaped rows paralleling the sulcus terminalis on anterior 2/3 of tongue
Characterized by absence of taste buds & increased keratinzation (DONT Taste, just like MILI didnt sing)
o Filiform papillae are the lingual papillae with the thickest keratin (think Mili Vanilli wore lots of Makeup)
Fungiform:, FUNGUS are on the Tip and SIDES
Mushroom-shaped, found on tip & sides of tongue
Most likely to be damaged by a tongue laceration
Taste buds innervated by CN VII (taste to anterior 2/3rds)
Circumvallate:
Largest but fewest in number (7-12), arranged in an inverted V-shaped row on back of tongue
Associated w/ ducts of Von Ebners glands
Have many taste buds, which are innervated by CN IX
Foliate:
Found on lateral margins as 3-4 vertical folds
Taste buds innervated by both CN VII & CN IX
Where are the taste buds found on the dorsum of the tongue?

Muscle
Stylopharyngeus

Longitudinal Muscles of Pharynx


Insertion
Styloid process
Posterior and superior margins of Thyroid
cartilage & muscles of pharynx
(Passes between the superior and middle
pharyngeal constrictors)
Hard palate; aponeurosis of soft palate
Thyroid cartilage & muscles of pharynx
Cartilage of auditory tube
Muscles of pharynx
Origin

Action
Elevates pharynx & larynx

Palatopharyngeus
Elevates pharynx
Salpingopharyngeus
Elevates nasopharynx??,
Pg 431
opens auditory tube
- Stylopharyngues innervated by the glossopharyngeal nerve (the other two are innervated by CN XI via X -- pharyngeal plexus)
- Soft palate:
o Blood supply lesser palatine artery/vein
o All muscles of soft palate (except one) are innervated by CN IX & X (pharyngeal plexus)
Exception: tensor veli palati m. innervated by nerve to the medial pterygoid, a branch of V3
o Anterior zone of the palatal submucosa contains fat
o Posterior zone contains mucous glands
o Attached inferolaterally to tongue by the glossopalatine archs
o Connected to lateral wall of pharynx by the pharyngopalatine arches
o Palatal salivary glands found beneath mucous MB of the hard & soft palate (mostly mucous)
o Five paired skeletal muscles of the soft palate:
1) Palatoglossus closes oropharyngeal isthmus
2) Palatopharyngeus
Elevates pharynx
Contraction during swallowing causes a fold in the posterior wall of the pharynx
3) Levator veli palatini pg 425 & 429 Netters H&N anatomy
Elevates soft palate during swallowing & yawning puts the soft palate against the oropharynx during swallowing
Innervated by X (XI via X)
Extrinsic muscle of the soft palate
Inserts in a palatine aponeurosis
From cartilage of Eustachian tube and petrous portion of temporal bone to the palatine aponeurosis of soft palate
4) Tensor veli palati

80

Tenses palate & opens mouth of the auditory tube during swallowing & yawning
Curves around the hamulus (if hamulus is fractured, actions of this muscle are affected)
From the scaphoid fossa of the medial pterygoid plate, spine of the sphenoid bone, and cartilage of Eustachian tube to the
palatine aponeurosis of the soft palate
Innervated by V3 its double weird in that its innervated by V3, and that it uses the hamuls as a pully
5) Uvular raises & shortens the uvula to help seal oropharynx from nasopharynx
o Uvula suspended from the soft palate
Innervated by pharyngeal nerve plexus (XI via X)
Unilateral nerve damage causes uvula to deviate to the opposite side (THE ODD BALL in that rule)
When uvular muscle contracts, the muscle on the intact side pulls the uvula toward that side
Bifid uvula:
Results from failure of complete fusion of palatine shelves
- Pharyngeal Constrictors (Circular Muscles)
o Superior Pharyngeal constrictor
From pterygoid hamulus, pterygomandibular raphe, posterior portion of the mylohyoid line and side of the tongue
All attach to the median raphe of the pharynx and the pharyngeal tubercle of the occipital bone
Constricts the wall of the upper pharynx during swallowing
Innervated by X
Forms the Fold of Passavant during swallowing
Lateral wall of the Oropharynx
Behind the Mandible
Superior and Middle Constrictors are split by CN IX (glossopharyngeal) and the
Stylopharyngeus musclepg 432 Netters H&N anatomy
o Middle Pharyngeal Constrictor
From the stylohyoid ligament and the greater & lesser horns of the hyoid bone to the median
raphe of the pharynx
Constricts during swallowing
Innervated by X
Behind the Hyoid bone
o Inferior Pharyngeal Constrictor pg 456
Arises from the oblique line of the thyroid cartilage and side of cricoid cartilage to the median raphe of the
pharynx
Constricts during swallowing
Innervated by X
Behind the Thyroid and Cricoid cartilages
The lower end is referred to as the cricopharyngeal muscle, which is continuous with the esophageal muscle fibers
Circular Muscles of Pharynx
Muscle
Origin
Insertion
Action
Superior constrictor
Medial pterygoid plate, pterygoid hamulus,
Median raphe & pharyngeal Constricts upper pharynx
pterygomandibular raphe; mylohyoid line of mandible, tubercle of skull
side of tongue
Middle constrictor
Greater & lesser horns of hyoid; stylohyoid ligament
Median raphe
Constricts lower pharynx
Inferior constrictor
Arch of cricoid & oblique line of thyroid cartilages
Median raphe of pharynx
Constricts lower pharynx
-

Styloid Process Muscles


o Stylohyoid
Innervated by VII
Perforated near its insertion at the hyoid bone by the tendon of the 2 bellies of the digastric bone
Elevates and retracts the hyoid bone that elongates the floor of the mouth
o Stylopharyngeus
Innervated by IX (only muscle IX hooks up)
Passes between superior and middle constrictors
Elevates the larynx and pharynx during swallowing and speaking
o Styloglossus
Innervated by XII
Some fibers interdigitate with hyoglossus muscle
Elevates and retracts the tongue during swallowing
One of the 4 Extrinsic muscles of the tongue
Fauces
o Anterior pillars form the glossopalatine arch (aka palatoglossal arch)
The arch attaches the soft palate laterally to the tongue
Within the arch palatoglossus muscle elevates tongue & narrows the isthmus of the fauces

81

Posterior pillars form the pharyngopalatine arch (aka palatopharyngeal arch)


The arch attaches the soft palate to the lateral wall of the pharynx
Within the arch palatopharyngues muscle elevates pharynx, helps close nasopharynx, narrows the isthmus of the fauces,
& aids in swallowing
o Palatine tonsils:
Consist predominantly of lymphoid tissue
Found between the two arches in an area called the isthmus of the fauces
- Retropharyngeal or Prevertebral space pg 424 Netters H&N anat
o Lateral boundary at level of oropharynx is the carotid sheath (not pterygomand. raphe, medial pterygoid, or stylopharyngeus m)
o NOTE: retropharyngeal space lies between buccopharyngeal fascia & prevertebral fascia
Infection can spread from pharynx to mediastinum
- Strap Muscles (Infrahyoid Muscles)
o Depressors of larynx & hyoid after they have been drawn up w/ pharynx to swallow (deglutition)
o Lie between deep fascia & visceral fascia over the thyroid gland, trachea, & esophagus
o Innervated by ansa cervicalis (aka cervical plexus) from C1,2,3 (except thyrohyoid C1 fibers via CN XII)
o Sternothyroid
o Sternohyoid
o Thyrohyoid ***Boards ? said it WAS innervated by ansa cervicalis, and Geniohyoid was only one not
Anatomy notes say Infrahyoids, EXCEPT thyrohyoid (C1 via CN XII)
Maybe that one Q thinks that C1 (via CN XII) counts as part of ansa cervicalis
o Omohyoid
Muscle
Origin
Insertion
Action
Innervation
Manubrium of the
Body of the hyoid
Depresses the hyoid after C1, C2, C3
Sternohyoid
sternum
swallowing
(ansa cervicalis)
Posterior
surface
of
the
Oblique
line
of
the
Depresses
the
larynx
C2, C3
Sternothyroid
manubrium of the
thyroid cartilage
after swallowing
(ansa cervicalis)
sternum
Inferior Belly: Superior
Superior Belly: Inferior
Depress the hyoid bone
C1, C2, C3
Omohyoid
border of the scapula
border of the hyoid bone after the bone has been
(ansa cervicalis)
near the suprascapular
elevated. Retracts and
notch
steadies the bone
* Then goes through a
fibrous attachment of the
clavicle
Oblique line of the
Inferior border of the
Depresses the hyoid bone C1 via XII
Thyrohyoid
**Does not raise the
lamina of the thyroid
body and the greater horn and if the hyoid is fixed,
(also to the Geniohyoid,
hyoid (its infrahyoid,
cartilage
of the hyoid
draws the thyroid
and to the
baby!)
cartilage superiorly
Genioglossus)
o

Suprahyoid muscles:
o Raise the hyoid during swallowing
o Assist lateral pterygoid in depressing Mn
o Assists posterior fibers of temporalis in retraction of Mn
Muscle
Origin
Insertion
Posterior Belly
Both bellies end in an
Digastric
(Longest): Mastoid
intermediate tendon that
notch of the temporal
perforates the stylohyoid
bone
muscles and is connected
Anterior Belly: Digastric to the horn of the hyoid
fossa of the mandible
Styloid process
Body of the hyoid
Stylohyoid
(Perforated by the
digastric intermediate
tendon)
Mylohyoid line of
Median fibrous raphe
Mylohyoid
mandible
and the body of the hyoid
bone
**If fall on nail in
submental region, first
muscle penetrated

82

Action
Elevates the hyoid and
helps lateral pterygoids
open the mouth by
depressing the mandible

Innervation
Anterior Belly: V3
(Mylohyoid n. branch)
Posterior Belly: VII
(SAME AS Stylohyoid)

Elevates and retracts the


hyoid to elongate the
floor of the mouth

VII

Elevates hyoid and raises


floor of mouth during
swallowing, pushes
tongue upward or
forward
**Can help depress the
mandible or open the
mouth

Mylohyoid n. branch
(V3)

**Sublingual gland is
located superior to the
mylohyoid muscle
Geniohyoid

Mental spine (Genial


tubercles)

Body of the hyoid

Elevates and draws the


hyoid forward shortening
the floor of the mouth
When hyoid is fixed, also
helps retract and depress
the mandible

C1 via XII
(also to the
Thyrohyoid)
**C1 Ventral primary
ramus contributes to the
superior root of the ansa
cervicalis, which then
jumps on XII to get to
the geniohyoid
(thyrohyoid also)

Muscles of the Larynx pg 451 Netters H&N anatomy


o ALL (but the cricothyroid) of the intrinsic muscles of the larynx receive their innervation from the inferior (recurrent) laryngeal
nerve (of CN X)
o Posterior cricoarytenoid
Helps maintain a wide airway through the larynx
Pics from left to right: 1) POSTERIOR VIEW. oblique and transverse arytenoids (superior) and posterior cricoarytenoid (inferior). 2)
Lateral Cricoarytenoid (inferior), Thyroarytenoid (just above- in middle). 3) Cricothyroid (both straps below thyroid cartilage)

Muscle
Cricothyroid

Origin
Anteriolateral part of
cricoid cartilage

Insertion
Inferior aspect and
inferior horn of the
thyroid cartilage

Action
Stretches and tenses
vocal cords

Posterior
Cricoarytenoid

Posterior surface of the


laminae of the cricoid
cartilage

Attaches to the muscular


process of the arytenoid
cartilage

Oblique Arytenoids

Arytenoid cartilages

Transverse Arytenoid

Arytenoid cartilages

Attach to opposite
arytenoid cartilage
**(Some fibers continue
superiorly as the
Aryepiglottic muscle)
Attach to opposite
arytenoid cartilage

ONLY muscle that


ABDUCTS the vocal
folds and widens the
rima glottidis (space
between the vocal folds)
Close the inlet of the
larynx by adducting the
rima glottidis

Aryepiglottic
Thyroepiglottic

Close the inlet of the


larynx by adducting the
rima glottidis

Innervation
External branch of
superior laryngeal nerve
of X
(**Superior laryngeal
continues as internal
branch that pierces
thyrohyoid membrane
and does sensory above
the vocal cords)
Recurrent laryngeal
nerve of the vagus
(Inferior Laryngeal)
Recurrent laryngeal
nerve of the vagus
(Inferior) This does
evrythin below vocal
cords
Recurrent laryngeal
nerve of the vagus
(Inferior)
Recurrent laryngeal
nerve of the vagus
(Inferior)
Recurrent laryngeal
nerve of the vagus

83

(Inferior)
Recurrent laryngeal
nerve of the vagus
(Inferior)
Recurrent laryngeal
nerve of the vagus
(Inferior)
Recurrent laryngeal
nerve of the vagus
(Inferior)

Thyroarytenoid
Lateral Cricoarytenoid

Derived from the


Vocalis
Thyroaryteniod muscle
Pulls on the True
**Located in the vocal
(cords?) and changes
folds themselves
pitch
- ALSO in the Larynx
o Conus Elasticus
Most superior portion is thickened and forms the vocal ligament
o Vocal Ligament
- The cricoid cartilage is cut twice in a sagittal plane (splits the body in left and right halves) is only one that forms a complete ring!
o Which cartilage would not be cut if larynx was cut in a sagittal plane? Arytenoids
o The thyroid cartilage, arytenoid cartilage, epiglottis & 2nd tracheal cartilages would not be cut twice
UPPER LIMB MUSCLES
- Axilla
o Boundaries: (Pyramid)
Medial wall upper 4-5 ribs & their intercostal muscles, and the serratus anterior muscle
Lateral wall humerus (specifically the coracobrachialis & bicep muscles in the biciptial groove)
Posterior wall scapula, subscapularis, teres major, & latissimus dorsi muscles
Anterior wall pectoris major, minor, & subclavius muscles
Base axillary fascia or skin
o Contents:
Axillary vessels
Branches of the brachial plexus
Both heads of the biceps brachii
Coracobrachialis
Muscles of the Axilla
Muscle
Nerve Innervation
Action
Pectoris major
Medial & lateral pectoral nerve from brachial plexus Flexes, adducts, & medially rotates arm
Pectoris minor
Medial pectoral nerve
Depresses the scapula
Latissiums dorsi
Thoracodorsal nerve from brachial plexus
Adduct, extends & medially rotates the arm
Deltoid
Axillary nerve (C5-C6)
Abducts arm, post. Fibers extend & anterior fibers flex
Teres major
Lower subscapular nerve from brachial plexus
Adducts, extends & medially rotates the arm
(medially rotates due to attchmnt on lateral humerus)
Teres minor
Branch of Axillary nerve
Rotates the arm laterally

Muscle
Serratus anterior

Origin
Outer surface and
superior borders of
first 8 to 9 ribs

Pectoralis minor

Ribs 3-5

Subclavius

Rib 1

Trapezius

Occipital bone and


vertebrae C7-T12

Levator scapulae
Rhomboideus major
Rhomboideus minor

Muscles of the Shoulder


Insertion
Action
Insert on the ventral
Pulls scapula forward &
aspect of the vertebral
downward preventing winging
border of the scapula
Also rotates scapula upward to
abduct the arm above 90 degrees
Coracoid Process of
Pulls scapula forward &
Scapula
downward
Ventral surface of
Draws clavicle downward
Clavicle
Inserts into the upper
Elevates scapula, draws head
and medial border of
back, adducts scapula, braces
the Spine of the
shoulder, draws scapula
Scapula, and Clavicle
downward
Elevates & draws scapula
medially
Elevates & retracts scapula
Elevates & retracts scapula
Muscle of the Arm

84

Innervation
Long thoracic nerve
(C5, C6, C7)
Medial pectoral nerve
Nerve to subclavius, C5,
C6
Accessory nerve

Dorsal scapular nerve


Dorsal scapular nerve
Dorsal scapular nerve

Muscle
Triceps Brachii

Origin
Scapula & humerus

Insertion
Ulna (olecranon process)

Nerve Innervation
Radial

Brachialis
Brachioradialis
Biceps Brachii

Humerus
Humerus
Scapula (coracoid
process & supraglenoid
tubercle)

Ulna (coronoid process


Radius (styloid process)
Radius (tuberosity)

Musculocutaneous
Radial
Musculocutaneous

Action
Primary Extensor of the
forearm
Flexes the forearm
Flexes the forearm
MEDIAL rotates the arm
Flexes the forearm &
arm, supinates the
forearm
**Primary supinator at
the radio-ulnar joint
**Flexion at the glenohumeral joint
**Flexion at the humeroulnar joint

Radial nerve is most commonly injured in a mid-humeral shaft fracture, because it runs in the radial (spiral) groove of the humerus
Coracoid Process
o A break would affect the biceps brachii and the pectoralis minor muscles (Pec major inserts into arm)
And one more factoid:
o The pronator quadratus m. is the primary pronator of the forearm (assisted by the pronator teres m.)
Triangle of auscultation
o Bounded by the upper border of the latissimus dorsi, the lower border of the trapezius, & the medial margin of the scapula
o Site where breathing sounds can be heard most clearly
o Floor is formed by the rhomboid major

ABDOMINAL & PELVIC MUSCLES

Muscle
Transversus abdominis
Internal abdominal
oblique
**Along with the
aponeuroses of the
transverses, forms the

Muscles of Anterior Abdominal Wall -- (TIRE from Deep to Superficial)


Origin
Insertion
Action
Compresses abdomen
Lateral half of the
inguinal ligament, the
iliac crest, and the
thoracolumbar fascia

Inferior borders of the


cartilages of the last 3
to 4 ribs, the linea alba,
pubic crest, and
pectineal line

Compresses abdomen; lateral


rotation, acting alone it bends
the vertebral column laterally
and rotates it to bring the
shoulder of the opposite side
forward

Innervation
Lower intercostal,
iliohypogastric &
ilioinguinal nerves
Lower intercostals (T7T11), subcostal (T12)
iliohypogastric, &
ilioinguinal nerves (L1)

85

conjoint tendon

Rectus abdominis
**Linea alba splits the
muscle and 3
tendinous bands
horizontally (6 pack)
External abdominal
oblique

2 tendons
Lateral attaches to the
pubic crest
Medial interlaces with
the tendon of the
opposite side to arise
from the pubic
symphysis
Fleshy digitations fro
the external surface and
inferior borders of
lower 8 ribs

Attaches to the 5th, 6th,


and 7th ribs and the
xiphoid process

**Nerves of the anterior


abdominal wall lie
immediately deep to this
muscle
Flexes vertebral column,
tenses abdomninal wall, and
depresses the ribs

Lower intercostal nerves


(T7-T11), and the subcostal
nerve (T12)

Attaches to the anterior Compresses abdomen; lateral


Lower intercostal nerves
half of the iliac crest,
rotation, acting alone it bends
(T7-T11)
anterior superior iliac
the vertebral column laterally
spine, and into a broad
and rotates it to bring the
aponeurosis along a line shoulder of the same side
from the 9th costal
forward
cartilage to the anterior
superior iliac spine.
The aponeurosis inserts
into the midline linea
alba
*TIRE going in to out; Ill miss the point if they ask about attachments; actions are straight forward, Innervated by lower intercostals
-

86

Cremaster muscle
o Arises from the middle of the inguinal ligament and is a continuation of the internal abdominal oblique muscle
o Draws testes upward
o Innervated by the genital branch of the genitofemoral nerve (L1 and L2)
o After passing through the inguinal ring, the muscle fibers of the cremaster form a series of loops making up the cremaster fascia
which surrounds the spermatic cord
Posterior abdominal muscles:
o Psoas major & minor innervated by lumbar plexus
o Quadratus lumborum
From the transverse process of L3-5, the iliolumbar ligament, and the iliac crest to the lower border of the last rib and the
transverse processes of L1-3 vertebrae
Flexes the lumbar vertebral column, fixes the 12th rib during inspiration
Innervated by lumbar plexus (Subcostal nerve T12 and L1-3)
Above the muscle, the diaphragm forms the lateral arcuate ligament
o Iliacus innervated by femoral nerve
o Dorsal rami innervate erector spinae muscles Dorsal Rami innervate ALL deep back muscles:
Splenus Capitus
SPlenus cervicis
Errector Spinae
Respiratory muscles:
o Diaphragm, internal & external intercostals, subcostals, & transverses thoracic
Diaphragm is innervated by phrenic nerve; the others are all innervated by intercostal nerves
o Diaphragm:
Muscle mostly responsible for quiet breathing
Flat muscle in a dome-like shape that separates chest & abdominal cavities
Arises from the xiphoid process, lower 6 costal cartilages and a lumbar portion (L1-L3)
Then the muscles converge and insert into the central tendon
o The tendon is drawn downward and forward during inspiration
Inhaling contraction of diaphragm pulls down on chest (via the central tendon), drawing in air via pressure differences
The vertical dimension of the thoracic cavity is increased chiefly by contraction of the diaphragm
Exhaling contraction of abdominal forces the relaxed diaphragm upwards
Upper surface contacts heart & lungs; Lower surface contacts liver, stomach, & spleen
Innervated by the Phrenic nerve (C3, 4, 5keep the diaphragm alive)
Travels through the thorax between pericardium & pleura (between heart and lungs)
o The phrenic nerve is the nerve lying in close relation to the surface of the pericardial sac (not the vagus nerve)
Right phrenic travels anteriorly to bronchial root and does NOT leave an impression (azygos v. does)
Sends off branches to innervate the parietal pericardium

Is in direct contact in the neck with the Infrahyoid fascia


Inability to move the diaphragm is associated with a total section of the spinal cord at C2 (or above prolly)
Phrenic nerve passes anterior to which muscle Anterior scalene!!!
Has three openings:
Caval opening (T8)
o IVC
o Right phrenic nerve
Esophageal opening (T10)
o Esophagus
o R & L vagus nerves
Aortic opening (T12)
o Aorta
o Azygos vein
o Thoracic duct
PNEUMONIC: I 8 10 EGGs AAT 12
o I = IVC T8; T10 EG = esophagus, G vaGus; A = Aorta, Azygos, T = Thoracic duct T12
o External intercostals: (Girls gone wild Externs lifting up their shirt!)
From rib to rib in a shoulder to belly button direction hands in pocket
Pass from rib to rib & run at right angles to fibers of the intenal & innermost muscles
Continue toward sternum as the anterior intercostal MB
Active during inspiration and elevate the ribs
Innervated by the intercostal nerve, i.e. between 4th and 5th rib is the 4th intercostal space, so innervated by the 4th intercostal
nerve meaning there are only 11 intercostal nerve
o Internal intercostals:
Right angle to External intercostals
Eleven on each side between ribs
From rib to rib in a sternum to pants pocket direction
Continue toward vertebral column as the posterior intercostal MB
The upper portions (upper 4 to 5 intercostal muscles) elevate the ribs
The lateral and posterior muscles, where fibers run more obliquely depress the ribs and are active during expiration
Innervated by intercostal nerves
o Innermost intercostals:
Run in same direction as internal intercostals but are separated from them by nerves & vessels
Thought to elevate the ribs
Innervated by the intercostal nerves
o Transversus thoracis:
From posterior surface of the lower portion of the body of the sternum and xiphoid process to the inner surface of costal
cartilages 2-6
Depress the ribs
Innervated by the intercostal nerves
Muscles of Inspiration
o SCM Accessory muscle
o Scalenes (Ant, Middle, Post) Accessory muscle
o External intercostals
o Interchondral part of internal intercostals
o Diaphragm
Muscles of Expiration
o Internal intercostals (except interchondral part)
o Abdominals (TIRE Transversus abdominis, Internal oblique, Rectus abdominis, External oblique)
NOTE : the nerves of the anterior abdominal wall lie between transversus abdominis & internal oblique muscles
Active Inspiration
o Diaphragm descends
o Rib joints are active
o Lateral diameter of thorax increases

LOWER LIMB MUSCLES


- Quadriceps femoris group
o Rectus femoris:
Crosses the hip & knee joints
Flexes thigh at hip & extends leg at knee
o Vastus lateralis, intermedius & medialis
All extend leg at knee

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88

Muscles of the thigh posterior group


o All three:
Flex the leg & extend the thigh
Innervated by tibial nerve
o Biceps femoris
o Semitendinousus
o Semimembranous
Muscles of the thigh anterior group
o Sartorius
Flexes leg & thigh
Abducts thigh
Femoral triangle:
o Contains the femoral V.A.N.
Unhappy triad: MCL, meniscus, & ACL
NERVOUS SYSTEM
Embryology:
o Neural PlateNeural Tube
Prominent growth of neural tissue causes folding of the embryo during the 4th week of development
This gives it a C-shaped curvature
Neural plate forms by Day 19 in the dorsal midline of the embryo
A rostrocaudal groove appears on the midline & invaginates as the lateral borders rise to form the neural folds
The neural folds begins to move together & fuse, converting the neural plate into a neural tube
The Notochord induces ectoderm to form neuroectoderm, hence promoting formation of the neural plate
The Prochordal Plate (Buccopharngeal) and the cloacal plate only have 2 layers epi and hypoderm
o Neural Tube
The neural tube develops into the CNS
Initially the neural tube is separated from the surface ectoderm by neural crest cells
Caudal end develops into the spinal cord
Basal plates motor part of CNS bottom, becomes ventral
Alar plates sensory part of CNS top, (like an altar), becomes dorsal
Rostral end develops into the brain
3 parts: rhombencephalon, mesencephalon, prosencephalon
o Neural crest:
Band of neuroectodermal cells that lies dorsolateral to developing spinal cord
Clusters of cells (neural crest cells) develop into: DRG cells, spinal autonomic ganglion cells, chromaffin cells, neurolemma
cells (Schwann cells), integumentary pigment cells (melanocytes), & meningeal covering of brain & spinal cord
Nervous tissue has two classes of cells:
o 1) Neurons: nerve cells
Transmit nerve impulses
Basic unit of the nervous system activities of the system are carried out it at the neuron level
o 2) Neuroglial cells: nerve glue
Provide support & nourishment for neurons
1) Neurons:
o Structure
Cell body (perikaryon)
Contains nucleus & most of the cytoplasm
Located mostly in the CNS as clusters called nuclei some found in periphery as ganglia
When the cell body is destroyed all of its fibers degenerate and die
Synthesizes axoplasm that is needed for increasing axon length
Contains Nissl bodies (rough ER); not found in axon or axon hillock
Dendrites
Process that send the impulse toward the cell body
May be one or many dendrites some neurons lack dendrites
Axon (nerve fiber)
Process that send the impulse away from the cell body
Only one axon per neuron
o Classified according to:
1) Structure (by number of processes)
Bipolar or Unipolar or Multipolar (most common)
2) Function

Motor or Sensory or Mixed


Myelination
Myelin formed by Schwann cells in PNS & oligodendrocytes in CNS
Node of Ranvier is junction between two Schwann cells
o Neurolemma
The outermost portion of a nerve fiber (Dont call the myelin sheath the outer!!!!)
The nucleated layer of Schwann cells that surrounds the myelin sheath
So, from inside out: axis cylindermyelin sheathneurolemma hmmm isnt myelin sheath just cell mb around
neurelemma???
o Motor Neurons
Babinski Sign has to do with feet?
In adults, a positive Babinski sign means damage to upper motor neurons
In newborns, a positive sign is normal
- 2) Neuroglia:
o Non-neuronal tissue of CNS that performs supportive & other ancillary functions
o Composed of various types of cells collectively called neuroglial or glial cells
o With the exception of the microglia, which derives from mesoderm, all other neuroglia cells form from ectoderm
Neuroglia
Cells that support neurons
Structure
Function
CNS
Astrocytes
Stellate w/ numerous processes
Form structural support between capillaries &
neurons w/in CNS, Blood Brain Barrier
Oligodendrocytes
Similar to astrocytes but w/ shorter & fewer
Form myelin in CNS, guide development of neurons
processes
w/in CNS myelinates multiple CNS axons
Microglia
Minute cells w/ few short processes
Phagocytize pathogens & cellular debris w/in CNS
Macrophage of CNS
Mesodermal origin (M for M, others are from
Ectoderm)
Ependymal
Columnar cells that may have ciliated free surface
Line ventricles & central canal w/in CNS where
CSF is circulated by ciliary motion
PNS
Satellite cells
Small, flattened cells
Support ganglia w/in PNS
Schwann cells
Flattened cells arranged in series around axons or
Form myelin w/in PNS only myelinates 1 axon
dendrites
Promote axonal regeneration
o

Spinal cord:
o Cylindrical, occupies ~ upper 2/3 of vertebral canal, & is enveloped by the meninges
o Centrally located gray matter & peripherally located white matter
o Ends at ~L1 in adults & at ~L3 in young children
Dura & arachnoid continue to S2 where arachnoids fuses w/ filum terminale (after fusion it is called the coccygeal ligament)
o Main areas of spinal cord:
Gray matter
H-shaped, centrally located, consists of nerve cell bodies & unmyelinated nerve fibers
Gray commissure center of the H connects two paired posterior (dorsal) horns & anterior (ventral) horns
Anterior hornmotor
o Cell bodies of somatic motor system lie w/in the ventral horn
o Cell body of a motor neuron in a spinal reflex arc is located in anterior gray column (ventral horn) of the spinal cord
o Patellar (knee-jerk) reflex: L4
o Biceps reflex: C5
o Triceps reflex: C7
o Achilles reflesx: S1
Lateral hornautonomic
Posterior hornsensory
Central canal:
w/in gray commissure & filled w/ CSF
White matter:
Composed primarily of myelinated axons (because its fatty)
Surrounds gray matter

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o Fasciculus gracilus legs (Think Graceful legs like a ballerina)


o Fasciculus cuneatus arms cunning, so closer to the brain
Spinal taps
o Lumbar puncture needle inserted in space between L3-L4 (or between L4-L5)
Needle enters subarachnoid space which is filled w/ CSF (pia is not pierced)
o CSF can be aspirated most safely by inserting the needle between L3 & L4 since the spinal cord usually does not extend below L2
Spinal nerves:
o 31 pairs; all spinal nerves are mixed made up of ventral & dorsal roots
8 cervical 12 thoracic 5 lumbar 5 sacral 1 coccygeal
The cauda equina consists of the roots of the lumbar & sacral spinal nerves
o Ventral and Dorsal roots leave the spinal cord, immediately join to form the Spinal Nerve, then 3 branches, 1 to sympathetic chain
ganglion(seen in pic), 1 to the Ventral Rami (i.e. intercostals), 1 to Dorsal Rami (i.e. intrinsic muscles of the back)
Then the anterior rami can branch to form Lateral and Anterior cutaneous branches
The intercostals nerves course between the innermost and the inner intercostal muscles
Intercostals (somatic nerves) are connected to the sympathetic chain ganglia via the rami communicantes
Like how the greater splanchnic nerve comes from rami communicantes from T5-9
o Ventral roots
Contain axons of motor neurons (also ANS stuff)
Cell bodies located in spinal cord
Upon exit, become anterior rami (mixed & long nerve in pic to right) supply body
wall & limbs
In cervical, brachial, lumbar, & sacral regions the anterior rami of the spinal
nerves unite to form plexuses
o These plexuses give rise to other nerves for distribution to muscle, skin, etc.
o Dorsal roots
Contain axons of sensory neurons
Cell bodies located outside spinal cord in dorsal root ganglia Can see in pic
Upon exit, become posterior rami (mixed) supply skin & deep back muscles
o Hey, if youre confused, look at a picture somewhere

Spinal Cord tracts


o Columns of white matter w/in spinal cord that conduct impulses to CNS (ascending) & away from CNS (descending)
SPINAL CORD TRACTS
Ascending tracts
Function
Anterior spinothalamic
Conducts sensory impulses for touch & pressure
Lateral spinothalamic (side of lateral horn)
Conducts pain & temperature impulses
Fasciculus gracilis (back in the midline) & fasciculus cuneatus
Conducts sensory impulses from skin, muscle, tendons, & joins;
(back offset) (THINK GRACEFUL LEGS)
also touch localization (conscious proprioception)
Posterior spinocerebellar (back corners)
Conducts sensory impulses from one side of body to same side of
cerebellum for subconscious proprioception
Descending Tracts
Function
Anterior corticospinal (Front Midline)
Conducts motor impulses from cerebrum to spinal nerves &
outward through anterior horn for coordinated movement
Lateral corticospinal (Just next to dorsal horn, inside Post.
Conducts motor impulses from hemisphere to spinal nerves through

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Spinocer.)
Tectospinal (Front offset) (Night at the Roxbury TECHNO head
shake)
Rubrospinal (In lateral grooves, in front of lat. Corticosp.)
Vestibulospinal (Front really offset)
Anterior & medial reticulospinal & lateral reticuloalspinal

anterior horns for coordinated movments


Conducts motor impulses to cells of anterior horns & eventually to
muscles that move the head
Conduct motor impulses concerned w/ muscle tone & posture
Regulate body tone & posture (equilibrium) in response to
movements of head
Control muscle tone & sweat gland activity

Meninges
o Three protective tissue layers covering CNS
o The structures involved in meningitis (inflammation of meninges) if severe can become encephalitis (inflammation of brain)
o Dura mater:
Outermost MB a fused, double layer of tough fibrous CT
Layers separate to form venous sinuses in the cranial cavity
Endosteal layer adheres tightly to inner surface of the cranium
Meningeal layer forms partitions (folds) that extend between regions of the brain
o Arachnoid:
Delicate middle MB adheres to dura mater but is separated from pia mater by subarachnoid space contains CSF
o Pia mater
Innermost MB delicate vascular MB of loose CT adheres closely to brain & spinal cord
Outside the skull: SCALP
o Skin, CT, Aponeurosis, Loose CT, Pericranium
Cerebrospinal fluid
o Clear, colorless fluid formed by the choroid plexuses w/in the lateral, 3rd & 4th ventricles
o Produced by filtration, primarily from tufts of capillaries that protrude into all four ventricles
Ependymal cells also produce CSF they line the ventricles, central canal of spinal cord, & choroid plexuses
o Fluid enters the subarachnoid space through three foramina of the 4th ventricle
o Choroid plexuses regulate intraventricular pressure by secretion & absorption of CSF
o CSF along w/ ligamentous walls of vertebral canal protect spinal cord from injury
Dura mater (continued):
o Two vertical folds
Falx cerebelli separates hemispheres of cerebellum; contains occipital sinus
Falx cerebri separates the cerebral hemispheres in a sagittal direction; contains inferior & superior sagittal sinuses
o Two horizontal folds
1) Tentorium cerebelli
Separates occipital lobes from the cerebellum

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Contains straight, transverse, & superior petrosal sinuses (NOT inferior petrosal sinus) look at pic on pg 59
2) Diaphragma sellae
Forms roof of sella turcica; a small central opening allows passage of infundibular stalk of the pituitary
-

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BRAIN
o Blood-brain barrier (BBB):
Protected by the CIA:
Choroid plexus epithelium
Intracerebral capillary endothelium
Arachnoid
Glucose & amino acids cross by carrier-mediated transport mechanism
L-dopa used to treat Parkinsons, since dopamine does not cross the BBB L dopa does because its AA like
o Consists of several regions: TDMMMS
Forebrain (prosencephalon)
Telencephalon & diencephalon derive from the
forebrain
Midbrain (mesencephalon)
Hindbrain (rhombencephalon)
Metencephalon and Myelencephalon derive from
the Hindbrain
o Each portion of brain consists basically of three areas:
Gray matter composed primarily of unmyelinated
nerve cell bodies
White matter composed basically of myelinated nerve
fibers
Ventricles spaces filled w/ CSF
o Cerebrum:
Located w/in telencephalon & is the higher forebrain
Consists of five paired lobes w/in two convoluted
cerebral hemispheres (connected by corpus callosum)
Accounts for 80% of brains mass
Deals w/ higher functions perception of sensory impulses, instigation of voluntary movement, memory, thought, reasoning
Two layers of cerebrum:
Cerebral medulla thickened core of white matter
Cerebral cortex thin, wrinkled gray matter covering each hemisphere
o Diencephalon:
Major autonomic region of forebrain almost completely surrounded by cerebral hemispheres of the telencephalon
Chief components thalamus, hypothalamus, epithalamus, & pituitary gland (just posterior pituitary)
The 3rd ventricle forms a midplane cavity w/in the diencephalon
o Hypothalamus:
Is the inferior portion of the diencephalon & forms roof & ventrolateral walls of the 3 rd ventricle
Endocrine control
Regulates hormone synthesis in anterior pituitary
Synthesizes & releases oxytocin & ADH water/salt balance\
ADH supraoptic nucleus; Oxytocin paraventricular nucleus -- (Think LOW oxygen when you PARAshute)
Regulation of ANS
Temperature control (anterior hypothalamus think A/C: Anterior = Cooling)
Eating behaviors
Lesions of ventromedial HThobesity
Lesions of lateral HThsevere aphagia
Lesions of supraoptic nucleidiabetes insipidus (polydipsia & polyuria result from deficient ADH)
Sexual maturation & childbirth
o Thalamus:
Thalamic nuclei:
DOESNT regulate Breathing Medulla Ob does
Lateral Geniculate nucleus visual
Medial Geniculate nucleus auditory (PUT your fingers in your ears POINT MEDIALLY)
Ventral posterior nucleus sensory posterior just like dorsal area is sensory in SC
o Medial part body senses
o Lateral part facial sensation
Ventral anterior/lateral nuclei motor Again, normal, ventral anterior = motor

o
o
o
o
o

A Lateral Ventricle
B Corpus callosum
Identify the thalamus in the sketch above: C
D Internal Capsule
E Basal Ganglia (Caudate, Putamen, Pallidum, Substantia Nigra, Nucleus accumbens, Subthalamic Nucleus)

Most of the fibers ascending or descending to the cerebral cortex transverse the internal capsule
The fiber tracts passing from the thalamus to the cortex are found in the internal capsule
= thalamus to cortex
Four ventricles:
NOTE: formation of the brain begins w/ differentiation of the cephalic
end of the hollow neural tube
Hollow spaces persist as ventricles w/in the brain
1&2) Two lateral ventricles
Hollow C-shaped spaces w/in right & left cerebral hemispheres
Large mass of gray matter that bulges into the floor and lateral
aspect of the ventricle is the caudate nucleus
3) Third ventricle
Forms a median cavity w/in the diencephalon (forebrain)
4) Fourth ventricle:
Located in the metencephalon (hindbrain).
Contains two openings in its walls called Lateral apertures
(foramina of Luschka)
Contains a single opening in its roof called Medial aperture
(foramen of Magendie)
The apertures connect the ventricular system w/ the subarachnoid space
After circulating throughout the subarachnoid space, CSF is returned to the circulatory system by filtration
through arachnoid villi (villi protrude mainly into the venous drainage sinuses of the cranial cavity) into the
Superior Sagittal sinus
Two interventricular foramina of Monro oval openings which provide communication between the third & lateral
ventricles
The cerebral aqueduct in the midbrain connects the third & fourth ventricles
Obstruction of the cerebral aqueduct causes enlargement of the two lateral & third ventricles (not the fourth)
Referred to as a non-communicating hydrocephalus which means lateral ventricles are not in communication w/
subarachnoid space
o Excessive CSF in the ventricles
Flow through ventricles:
First and Second ventricles Foramen of monro 3rd Ventricle cerebral Aqueduct out via Lateral foramen of
Luschka (2) or Medial formanen of Magendie (1)
Substantia Nigra (Black people are DOPE)
Uses dopamine as predominant neurotransmitter for S.N. (not for olivary nucleus or lateral reticular nucleus)
Cerebellum
Consists of the vermis (medial) & two cerebellar hemispheres
External anatomy:
Each hemisphere has an anterior lobe, posterior lobe, & flocculonodular lobe
Internal anatomy:
Cerebellar cortex
o 3 layers (think MPG): Medullary, Purkinje, Granular
Arbor vitae
o Subcortical white matter
Cerebellar nuclei
Circuitry:

o
o

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Mossy fibers = excitatory fibers from the spinal cord, pons, & vestibular nuclei
Climbing fibers = excitatory fibers from the inferior olive nucleus
Golgi cells = fibers receiving input from mossy fibers & parallel fibers of the granule cells
Purkinje fibers = fibers receiving input from the climbing & parallel fibers AND inhibitory input from basket cells
Each granule cell sends its axon into the molecular layer, giving off collaterals at 90 angles = parallel fibers
o The granule cell axons stimulate the distal dentrites for the Purkinje cells & Golgi cells
o Purkinje fibers are the final common pathway for cortical output
They can stimulate OR can send a single axon through the granular layer & arbor vitae to inhibit the deep nuclei
Common symptoms of cerebellar dysfunction
Ataxia, Dysmetria, Nystagmus, Hypotonia, Intention tremor
Cerebral cortex:
o Extensive outer layer of gray matter of cerebral hemispheres
o Cerebral lobes function primarily in voluntary movement, higher intellectual processes & personality (w/ the limbic system)
o NOTE: basal nuclei gray matter structures deep w/in each cerebral hemisphere help control muscle activity

Area of Cerebral Cortex


Precentral gyrus of frontal lobe
Postcentral gyrus of parietal lobe
(Think Dorsal meaning Sensory just like
Spinal Cord)
Medial surface of the occipital lobe
Parietal lobe (near base of postcentral gyrus)
Temporal lobe (transverse temporal gyri)
Frontal lobe

Parietal lobe
Temporal lobe (Medial surface)
-

Function
Motor area (initiates voluntary contractions of skeletal muscle
EX Highly skilled, discrete hand movements depend on activity of the precentral
gyrus
Sensory area (receives sensory info regarding temperature, touch, pain, proprioception)
Concerned with recognition of painful stimulus from the teeth
**Sensations from Left face and Teeth are interpreted in the Right Parietal Lobe
Visual area visual center of the cerebral cortex is found here
Taste area
Hearing area the primary auditory complex is found here
(Higher intellectual functions)
(Unable to Plan or Organize Behaviors)
(Lacks Self-Discipline)
(Anti-social Behavior) PHINEAS GAGE
Somatic associated area (Integration & interpretation center)
Smell

Limbic system:
o Includes brain structures involved in emotion, motivation, & emotional association w/ memory
o Responsible for 5 Fs:
Feeding, Fighting, Feeling, Flight, & Sex (Ha, Ha) (as quoted from USMLE)
Gate Theory of Pain (outdated???)
o A controller system modulates sensory input so that there is a selective and integrative action occurring before impulses reach the
first synapse for onward transmission.
The gate controller in this system is the substantia gelatinosa
Jello would fit through the gate
BRAINSTEM
o Picture: ID cross section of : pons, midbrain, medulla oblongata, spinal cord
o Corticobulbar tract bulb is old word for Medulla so this is the tract from cortex to medulla!
The fibers which separate from the corticospinal tract as it descends through the pons & medulla oblongata
Fibers of this tract innervate the motor nuclei CN V, CN VII, CN XII (perhaps also the nucleus ambiguus)
1) Which CN contralateral innvervation? CN 12 (also the upper part of 7 to the forehead, and most texts also say 2)
o I think it could be 5, 7 upper, 12 (& even nulceus ambiguus)
2) What CN crosses corticobulbar? 12
o Same answer
3) Which tract of the corticobulbar only innervates to the contralateral side of the face?
o I say its 7 lower
o Hypoglossal n. (not sure)
o From Neuroanatomy lecture: All cranial nerves have bilateral innervation with two exceptions:
1) Lower Face of VII is contralateral
upper face is bilateral
2) CN XII is contralateral

http://sprojects.mmi.mcgill.ca/cns/histo/systems/motor/main.htm - for explanations


Also see lab on desktop for explanation
CN XII receives bilateral innervation
CN V does, too

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CN VII lower is only contralateral


N. ambiguus receives bilateral
-

BRAINSTEM
o Lower extension of brain where it connect to spinal cord
o Neurological functions located in the brainstem include those necessary for survival
Breathing, digestion, HR, BP
o Most cranial nerves come from brainstem
o Motor nuclei are medial to sensory nuclei
o Pathway for all fiber tracts passing up & down between peripheral nerves & spinal cord to higher brain
o Midbrain:
Nerve pathway of cerebral hemispheres
Contains auditory & visual reflex centers
General anesthesia affects what system? The Reticular system which is located between medulla & midbrain, and is
responsible for state of consciousness
o Pons:
Bridge-like structure which links different parts of brain
Serves as a relay staion from medulla to higher cortical structures of brain
o Medulla oblongata:
Relay station for the crossing of motor tracts between spinal cord & brain
If the spinal tract of CN V were sectioned at the level of the caudal medulla, PAIN from the ipsilateral side of the
face would be most affected
Contains respiratory, vasomotor, & cardiac centers
Has many mechanisms for controlling reflex activities (e.g., coughing, gagging, swallowing & vomiting)
Medial lemniscus (from gracile and cuneate nuclei (of medulla) to the thalamus.
Large ascending bundle of fibers, composed of 2nd order neurons, carrying proprioception & discriminatory
touch sensations to the conscious
levels
o No where else to put this. the 3rd order
neuron in pain pathway comes from thalamus
BRAINSTEM NUCLEI:
o LOOK UP CROSS SECTIONS OF
MIDBRAIN, PONS, AND MEDULLA
ORIGIN OF CNS
BRAIN (2)
o I
o II
MIDBRAIN (2)
o III Oculomotor
o IV Only CN from Dorsal
Brainstem Trochlear
PONS (4)
o V (remember Spinal N. of V is
from Medulla) Tg motor
o VI Abducens
o VII Facial
o VIII Vestib/Cochlear
MEDULLA (4 5* if you count Spinal
of V)
o IX
o X
o XI
o XII
o CN III
Occulomotor
GSE fibers to all extraocular muscles except the superior oblique (trochlear nerve) and the lateral rectus (Abducens
nerve)
Edinger-Westphal Nucleus pg. 549 Netters H&N anatomy
PARA-PRE, which give rise to GVE fibers with terminate on cells in the ciliary gaglion
Innervates the papillary sphincter muscle, sends parasympathetic
Lesions
Ptosis, droopin of an eyelid, Mydriasis, and loss of accommodation

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96

CN IV
Trochlear nuclei
located near central gray matter of the lower midbrain at the level of the inferior colliculi
Located on the Dorsal side of the brain
Lesions
Double vision on looking downward and away from the affected side
CN V: pg 86 Netters H&N anatomy
Sensations from the Left face and teeth are interpreted in the Right Parietal lobe
Touch receptors are most numerous per unit area in the tip of the tongue
Motor nucleus of V:
*Sends SVE fibers to muscles of mastication
Lower motor neuron control of the muscles of mastication is by way of the Motor nucleus of V
Monosynaptic jaw closing reflexes might be disrupted in Motor nucleus of V
Just medial to the Main Sensory Nucleus
Fibers are SVE and supply the 8 muscles of V3
Joins sensory nuclear complex fibers to become Trigeminal Nerve
Trigeminal sensory nuclear complex:
Axons enter the pons through sensory root & terminate in 1 of 3 nuclei of trigeminal sensory nuclear complex:
1) Mesencephalic nucleus: (MeS for Muscle Spindle and Phalic for P-DaLic)
o Mediates proprioception (ex. Musclespindle) from the face
o Primary sensory neurons of mechanoreceptors in the PDL
o Cell bodies of the proprioceptive 1st order neurons are found in mesencephalic nucleus (not trigeminal ganglion)
o Mediates Jaw jerk reflex Only nucleus in the CNS that receives proprioceptive inputs from muscle
spindles
o Only example in which the primary sensory cell bodies
reside within the CNS instead of in ganglia
2) Main sensory nucleus: (The Main role of V is sensation)
o Discriminative touch of face
o Mediates general sensation (ex. Touch)
o **All sensory information from the face
fibers cross and
ascend in the ventral TTT (Trigeminalthalamic Tract) to the
VPM
From the rest of the body it goes to the VPL
3) Spinal trigeminal nucleus of V: (SPAINAL Spine pain/temp
in lateral cord)
o Mediates pain & temperature from head & neck (Oral Cavity)
o Mx bone fracture next to central incisornociception
terminates centrally in spinal subnucleus caudalis of V
o If the spinal tract of the fifth cranial nerve were sectioned at the level of the caudal medulla, PAIN from the face
would be most affected
o The primary sensory neurons' nucleus of termination for pain from a Mx M2 is the spinal nucleus of V
o The descending tract (down to the spinal nucleus) of V contains axons of primary sensory neurons
o Fibers then cross and ascend in the ventral TTT (trigeminothalamic) tract to the VPM as well
Lesions
Sensory deficits
Loss of tactile, Proprioceptive, pain sensation, temperature, etc.
Motor deficits
From lower motor neuron involvement involving the muscles of mastication
Temporalis and masseter causes weak jaw closure
Pterygoid weak jaw opening
CN VI
Abducens nucleus
Located in the lower pons, ventral to the floor of the fourth ventricle near the midline
Provides GSE to the lateral rectus muscle
Lesions
Paralysis causes lateral rectus palsy, leading to medial deviation of the affected eye and diplopia
CN VII pg 97 H&N anatomy
Main Motor Nucleus
To all the muscles of facial expression
NOTE the upper face receives bilateral innervation BUT the lower face receives contralateral innervation
REFER TO Bells PALSY
Superior Salivatory nucleus

Located posterolateral to the motor nucleus of VII


One group of fibers enters the superficial (greater) petrosal nerve and terminates in the ptergopalatine ganglion
Lacrimal glands
Another group of fibers travels in the chorda tympani nerve to reach the submandibular gangion
Submandbular
and Sublingual glands
Gustatory nucleus (Nucleus Solitarius) actually VII, IX, and X
Solitary tract gives rise to the geniculate ganglion
geniculate ganglion = sensory ganglion of 7 (?)
The rostral portion of the nucleus of the solitary tract receives all the SVA fibers for taste, which pass in the seventh,
ninth, and tenth CNs
The facial receives all the anterior 2/3rds of the tongue
The taste afferents in the facial nerve arise from cells in the geniculate gangion
Lesions
Flaccid paralysis of muscle of facial expression (upper and lower face)
Loss of corneal reflex (efferent limb)
Hyperacusis (due to stapedius muscle) paralysis
Loss of taste from anterior 2/3rds means lesion is proximal to the sytlomastoid foramen since the chorda tympani
joins the facial nerve in the middle ear
Bells Palsy
o Lower motor neuron damage = ipsilateral problems
o *Facial nerve:
Lower Motor Neuron lesion:
Affects BOTH upper & lower face
Causes an IPSILATERAL flaccid paralysis of facial musculature
A pt has a lower facial paralysis, where is the damage facial nerve in the facial canal!!!
o NOT after it leaves the stylomastoid foramen
Hyperactive Spastic Paralysis
Hypoactive Fasciculations, Atrophy, Flaccid Paralysis (Like in ALS)
Upper Motor Neuron lesion:
Affects ONLY lower face (upper face has backup innervation)
Most commonly affects CONTRALATERAL face below the eyeball Can still wrinkle forehead
Rt sided lower face paralysis caused by Contralateral (left side) Cerebrocortical damage
CN VIII
Vestibular Nuclei
Sensory from the Crista ampullaris of the semicircular canals and the maculae of the utricle and saccule
Cochlear Nuclei:
Input from the Organ of Corti, Spiral Ganglion
CN IX
Glossopharyngeal nuclei
SVE fibers from the rostral nucleus amibiguus and supply the stylopharyngeus muscle
GVA fibers to the nucleus solitarius and supply the baroreceptors of the carotid sinus you guessed it: Sinus Ninus!!!
SVA fibers carrying taste sensation from the posterior 1/3rd of the tongue and terminate in the nucleus Solitarius (aka
gustatory nucleus)
GSA Fibers supplying the posterior tongue and pharynx carry the sensory limb of the Gag reflex
o The motor limb of this reflex is carried by fibers from the nucleus ambiguous, which exits via the vagus nerve
o Lesion
Up CN IX results in unilateral ipsilateral loss of gag reflex
Down CN X results in bilateral loss of gag reflex
Inferior Salivatory
PARA-PRE nerve fibers to the Otic ganglion via Lesser petrosal nerve hitchhikes on V3 (auriculotemporal) to the
Parotid Gland
CN X
Main Motor Nucleus
(aka the vagal part of the nucleus ambiguous)
Located in the anterior portion of the reticular formation and extends throughout the medulla
Sends motor fibers through the
Dorsal Motor Nucleus
Located in the floor of the 4th ventricle and ventral to sulcus limitans
PARA=PRE fibers distributed to the PostG neurons supplying the viscera of the thorax and abdomen
Nucleus Solitarius (aka Gustatory nucleus) VII, IX, and X
GVA fibers from the larynx, esophagus, and baroreceptors in the aortic arch and visceral abdominal/thoracic viscera
SVA fibers from epiglottis taste buds (present in newborns)

97

98

Nucleus Ambiguus
Sends SVE fibers to larynx, pharynx all the XI via X crap
Lesions
Weakness of the palate, loss of gag, and nasal speech occurs and possibly nasal regurgitation of food
Bilateral lesions of the vagus leads to paralysis of the pharynx and larynx death from asphyxiation
Paralysis of an ipsilateal vocal cord may occur, because the recurrent laryngeal nerve supplies all of the laryngeal
muscles, except the cricothyroid, which is supplied by the superior laryngeal nerve
In a nut shell
Nucleus solitarius = sensory (taste, gut distension, etc) VII, IX, X
Nucleus ambiguus = motor (pharynx, larynx, upper esophagus) IX, X, XI
o Dorsal motor nucleus (parasympathetic) (to heart, lungs, upper GI) X only
Baroreceptors
o From IX Carotid Sinus
o From X Aortic Arch
Each CN has a nucleus of its own name, EXCEPT:
o I/II/VIII special sense only
o IX/X these share nucleus ambiguous
o VII/IX/X share nucleus solitarius (aka gustatory nucleus)
o XI arises from cervical spinal cord only called a CN because it sneaks up & exits skull w/ IX & X
o CN XI
Spinal accessory nerve (not nucleus):
*Sends SVE fibers to SCM & trapezoid
XI via X explanation
o Cranial root fibers originate from the caudal nucleus ambiguous to supply the intrinsic muscles of the the larynx
o The fibers join CN X and finally reach the intrinsic laryngeal muscles through recurrent laryngeal nerve
Lesions
Paralysis of the SCM (difficulty in turning head) and Trapezius (shoulder droop)
o CN XII
Hypoglossal Nucleus
Located near the midline below the floor of the 4th ventricle in the caudal medulla
GSE fibers to intrinsic muscles of the tongue, genioglossus, hyoglossus, and Styloglossus
Lesions
Ipsilateral paralysis deviateion TOWARD
o UMN Unilateral Tongue weakness W/O atrophy
Bilaterally innervated upper, so NO atrophy
o LMN Unilateral Tongue weakness W/ atrophy
Anatomic Divisions of Nervous System
o CNS
Brain & spinal cord
Control center of nervous system
Receives sensory input from PNS & formulates responses
o PNS
12 pairs of cranial nerves
31 pairs of spinal nerves 8 cervical, 12 thoracic, 5 lumbar, 5 sacral, & 1 coccygeal
Afferent division:
Somatic sensory neurons carry impulses from skin, fascia & joints
Visceral sensory neurons carry impulses from viscera of body (hunger pangs, BP)
Efferent division:
Somatic (voluntary) somatic motor neurons carry impulses to skeletal muscles
Autonomic (involuntary) visceral motor neurons transmit impulses to smooth & cardiac muscles & glands
o Sympathetic & Parasympathetic
o See next section
Autonomic Nervous System
o Innervation to organs not usually under voluntary control
o Cardiac muscle, smooth muscle, visceral organs/glands
o Preganglionic neurons
Cell bodies are in CNS
Synapse in autonomic ganglia
Parasymp originate in cranial nerves & craniosacral region
PreG PS fibers have their cell bodies in association w/ the nuclei of certain cranial nerves & in the anterolateral cell
column of the grey substance of S2-4, A for AL, as

o
o

o
o

Preganglionic PS nerve fibers to the urinary bladder have their cell bodies in the spinal cord at the S2,3,4 level
Symp originate in thoracolumbar (T1-L3) region
PreG S fibers to the head/neck have their cell bodies in the intermediolateral horns of the thoracic spinal cord
PostG S fibers to the head have their cell bodies in the cervical ganglia
Postganglionic neurons
Cell bodies in autonomic ganglia
Synapse on effector organs
SYMPATHETIC DIVISION:
Prepares body for intense physical activity in emergencies (fight or flight) through adrenergic effects
HR increases & blood glucose rises
Blood is diverted to skeletal muscles
Pupils & bronchioles dilate
Adrenal medulla releases Epi & NE
Preganglionic fibers
Release ACh
Carried by white rami
Postganglionic fibers
Release NE (except for BVs in skeletal muscles & sweat glands)
Carried by gray rami
***Synapse in paravertebral or prevertebral ganglia
PARASYMPATHETIC DIVISION:
Conserves energy (rest & digest)
Decrease HR
Papillary & bronchiolar constriction
No effect on adrenal medulla
Maintains normality of body functions
Preganglionic & postganglionic fibers release ACh
Synapses between neurons are made in autonomic ganglia
PS NS ganglia located in or near effector organs
Symp NS ganglia located in the paravertebral chain
NOTE: Most organs are innervated by both PS & Symp NS

Cranial Sutures
o Coronal Suture
Separates Frontal bone from BOTH Parietal Bones
o Sagittal Suture
Separates BOTH Parietal Bones
o Lambdoid Suture
Separates BOTH Parietal Bones from Occipital Bone
o Squamous Suture
Separates A Parietal Bone from the Temporal Bone

FORAMINA:

Anterior Cranial Fossa: I pg 54 Netters H&N anatomy


Cribriform plate (ethmoid) perforations
Located in ethmoid bone

99

100

Contains olfactory nerves (CN I)


Middle Cranial Fossa: II-VI
Optic Canal CN II, ophthalamic artery, central retinal vein
Superior Orbital Fissure CN III, IV, V1, VI, superior ophthalamic vein NOT ophthalamic artery
Between the slit light openings between lesser & greater wings of sphenoid bone
Foramen rotundum in sphenoid bone carries maxillary nerve (V2)
Inferior orbital fissure carries the maxillary nerve (V2) AFTER IT HAS EXITED THE BRAIN
Foramen ovale in sphenoid bone carries mandibular nerve (V3) & the lesser petrosal nerve and accessory meningeal
artery
Think: for CN V, its Standing Room Only (S. R. O.)
Spinosum middle meningeal artery
Foramen spinosum in sphenoid bone carries middle meningeal artery & vein
Posterior Cranial Fossa: VII-XII
Internal Auditory Meatus CN VII, VIII
Canal running through petrous portion of the temporal bone
CN VII enters meatus & emerges from stylomastoid foramen between styloid & mastoid processes of temporal bone
o Gives off five branches in the parotid gland supplies motor innervation to muscles of facial expression
o Anesthetic in parotid (during Mn block) paralyzes muscles of facial expression
o Gives chorda tympani (VE para/pre) branch thru the petrotympanic fissure, Q reads through which opening does
parasymp fibers run through? petrotympanic
CN VIII enters meatus, then remains w/in temporal bone
o Nerve fibers to cochlear duct (hearing), semicircular ducts & maculae (balance)
Jugular Foramen CN IX, X, XI, internal jugular vein (Found in the Posterior Cranial Fossa)
Passage between the petrous potion of the temporal bone and the jugular process of the occipital
2007 Q Jugular foramen is NOT found in middle cranial fossa
Hypoglossal Canal CN XII
Foramen magnum in occipital bone contains medulla oblongata, vertebral arteries, & spinal accessory nerve,
Mandibular foramen:
Location:
Above the occlusal plane & posterior to the Mn molars
On medial surface of ramus just below the lingula, midway between the anterior & posterior borders of the ramus
Lateral to the medial pterygoid muscle
Leads into Mn canal which opens into mental foramen below PM2
NOTE: incisive canal a continuation of the Mn canal beyond the mental foramen & below incisor teeth
NOTE: lingula bony projection that serves as the attachment for the sphenomandibular ligament pg 259
Contains inferior alverolar nerve, artery & vein
IA nerve ends at mental foramen by dividing into:
o 1) mental nerve supplies skin & mucous MB of mental region
o 2) incisive branch supplies pulp chambers of anterior teeth & adacent mucous MB
Other foramina:
Carotid canal
Located in temporal bone
Contains internal carotid artery & sympathetic nerves (carotid plexus)
Nasolacrimal canal
Located in lacrimal bone/maxilla
Contains nasolacrimal duct
Foramen cecum in frontal & ethmoid bones contains emissary vein in fetal life
Sphenopalatine foramen sphenopalatine artery/vein & nasopalatine nerve 270 netters h&n
Pterygoid canal deep & greater petrosal nerves (these form the nerve of the pterygoid canal) 270 netters h&n
Carries parasymp and sympathetic fibers
Pterygomaxillary fissure PSA artery/vein/nerve & maxillary artery
Pterygopalatine canal greater & lesser palatine artery/vein/nerve
Pharyngeal canal pharyngeal branch of V2
Greater palatine foramen in the palatine carries greater palatine nerve, artery & vein
Lesser palatine foramen carries lesser palatine nerve artery & vein
Stylomastoid foramen in temporal bone carries facial nerve
Mental foramen in mandible carries mental nerve, artery & vein
Petrotympanic fissure in temporal bone carries chorda tympani & anterior tympanic artery
Q asked: Which of the following contain ParaSymp nerves (not spinosum, rotundum, ovale)
Fracture involving petrotympanic fissure would affect the chorda tympani
Foramen lacerum in temporal & sphenoid bones carries artery of the pterygoid canal, greater & deep petrosal
nerves (through the occluded cartilage)

Supraorbital foramen in frontal bone carries supraorbital nerve artery & vein
Infraorbital foramen in sphenoid & maxilla carries infraorbital nerve (V2), artery, & vein
Incisive foramen in maxilla carries nasopalatine nerve
http://en.wikipedia.org/wiki/Cranial_nerves#Thirteen_cranial_nerves.3F
CN
CN Name
Nuclei
Site of exit from skull
#
I
Olfactory
Anterior Olfactory
Cribiform plate (ethmoid
bone)
II
Optic
Lateral Geniculate
Optic foramen
III
Oculomotor
Edinger-Westphal
Superior orbital fissure
Occulomotor
IV
V

Trochlear
Trigeminal

Trochlear
Mesencephalic, Main
Sensory, Spinal, and
Trigeminal Motor

Superior orbital fissure

V1 Ophthalmic
V2 Maxillary

Superior orbital fissure


Foramen rotundum

V3 Mandibular

Foramen ovale

Functions (M= motor; S = sensory)


S = smell
S = vision
M = levator palpebrae superioris, medial,
superior, inferior, inferior oblique, ciliary m. (lens),
sphincter m. (pupil)
M = superior oblique m.

Abducens
Facial, Solitarius
(Gustatory), Salivatory
Vestibular, Cochlear
Ambiguus, Inferior
Salivatory, Solitarius

Superior orbital fissure


Internal auditory meatus

Vagus

Ambiguus, Solitarius,
Dorsal Motor

Jugular foramen

XI

Accessory

Jugular foramen

XII

Hypoglossal

Ambiguus, Spinal
Accessory
Hypoglossal

S = cornea, skin of nose, forehead, scalp


S = nasal cavity, palate, Mx teeth, skin of cheek,
upper lip
S = tongue, Mn teeth, Mn, skin of chin, floor of
mouth, TMJ
M = mastication mm., tensors, anterior digastric, &
mylohyoid
M = lateral rectus m.
S = taste (anterior 2/3)
M = facial expression mm., lacrimation, salivation
S = hearing, balance
M = stylopharyngeus muscle
S = taste (posterior 1/3), pharynx, middle ear,
carotid sinuses
M = muscles of pharynx & larynx
M = smooth m. of thoracic & abdominal organs
S = taste (epiglottis)
S = thoracic & abdominal organs (viscera)
M = trapezius m. & SCM m.

Hypoglossal canal

M = intrinsic & extrinsic tongue mm.

VI
VII

Abducens
Facial

VIII
IX

Vestibulocochlear
Glossopharyngeal

Internal auditory meatus


Jugular foramen

CN IX
CN X

Parasympathetic Nuclei & Ganglia by Cranial Nerve


Pg 542 H&N anatomy
Nucleus
Ganglion
Effector
Edinger-Westphal N.
Ciliary G.
Pupillary sphincter m. meiosis
Ciliary m. accomodation
Superior Salivatory N.
Pterygopalatine G.
Lacrimal gland & nasal cavity/nose secretion
Submandibular G.
Submandibular & sublingual glands secretion
Inferior Salivatory N.
Otic G.
Parotid gland secretion
Dorsal Motor N. of Vagus
*None*
Viscera of thorax & abdomen

Ganglion
Ciliary

Location
Lateral to optic n.

Pterygopalatine

Pterygopalatine fossa

Cranial Nerve
CN III
CN VII

Autonomic Ganglia PS & Symp fibers


PS Fibers
Symp Fibers
PreG: CN III (inferior division)
Internal carotid plexus
PostG: Short ciliary nn.
PreG: CN VII greater petrosal n.,
nerve of pterygoid canal
PostG: Branches of V2,then V1

Internal carotid plexus


Deep petrosal n.

Chief Distribution
Para Ciliary m. &
sphincter pupillae
Symp Dilator pupillae
& tarsal mm.
Lacrimal gland & glands
in palate & nose

101

Submandibular

On hyoglossus m.

Otic

Below foramen ovale

PreG: CN VII (Chorda tympani)


PostG: Lingual n.
PreG: CN IX & lesser petrosal n.
PostG: Auriculotemporal n.

Plexus on facial artery


Plexus on middle
meningeal artery

Submandibular &
sublingual glands
Parotid gland

CRANIAL NERVES
- CN V, VII, IX, X are branchiomeric (nonsomitic) in origin because they originate from the branchial arches
- Olfactory (CN I)
o Exits Cribiform plate of ethmoid bone
o Enters nasal canal for smell
o Fracture of the cribiform plate typically results in loss of sense of smell
- Optic nerves (CN II) pg 82 netters h&n anatomy
o Arise from axons of the ganglion cells of the retina which converge at the optic disk
o Optic foramen (optic canal):
Area where nerve enters the cranial cavity through the sphenoid bone
o Optic disc (aka optic papilla):
Area where optic nerve exits eye
Made up of nerve cells
Small blind spot on surface of the retina no rods or cones
Located ~3mm to nasal side of the macula
Only part of retina which contains no photoreceptors
Optic tracts consists of axons from ganglion cells
Consists of axons of ganglion cells exiting the retina to form the optic nerve
The axons are accompanied by the central artery & vein of the retina
o After exiting eyes, optic nerves meet at the optic chiasm (in the floor of the
diencephalon)
o From optic chiasm, axons that perceive the left visual field form the right optic tract &
vice-versa
Fibers that arise from the nasal hemiretinas decussate & contribute to the
contralateral optic tract
o Optic nerve fibers from the nasal side cross the midline and enter the optic tract of the
other side by way of the optic chiasma (SEE PIC)
Optic tract fibers synapse in the lateral geniculate nuclei w/ geniculocalcarine
fibers (optic radiations) that terminate on the banks of the calcarine sulcus in the
primary visual cortex (Brodmanns area 17) of the occipital lobe
So, the right visual field is interpreted in the left hemisphere of the brain & vice versa
o Central artery of the retina (branch of ophthalmic artery), pierces the optic nerve & gains access to the retina by
emerging from the center of the optic disc
o If the retina were to detach this would decrease the length of the optic center and therefore the patient would be?
Farsighted
- Oculomotor nerve (CN III)
o Supplies: medial, superior, & inferior recti; inferior oblique; & levator palpebrae superiori
A deficit in the inferior oblique muscles can be revealed by asking the patient to elevate the adducted eye
This is the only muscle the elevates the eye from an adducted position. Sup rectus elevates it from an abducted position
o Post gang fibers leave the ganglion in the short ciliary nerves to supply the sphincter pupillae & the ciliary muscle
- Oculomotor nerve (CN III), trochlear nerve (CN IV) & abducens nerve (CN VI) and ophthalmic (V div 1) all exit the cranium through
the superior orbital fissure. They innervate the extrinsic ocular muscles, resulting in movement of the eyeball
- Trochlear nerve (CN IV):
o Supplies the superior oblique muscle Smallest nerve, supplies weirdest eye muscle, only one to exit from the back
o Smallest cranial nerve
o Only cranial nerve that emerges from dorsal aspect of the brainstem
- Trigeminal nerve (CN V):
o Exits inferolateral PONS as a sensory & motor root
o Largest of 12 cranial nerves
o Larger sensory root enters the trigeminal (semilunar, gasserian) ganglion in the middle cranial foss, Embeds in Meckels CAVE
o Three sensory divisions of the nerve arise from the ganglion & leave the cranial cavity through foramina in the sphenoid bone
o Smaller motor root passes under the ganglion & joins the mandibular division as it exists through the foramen ovale
- Semilunar ganglion (aka trigeminal or gasserian ganglion)
o Large, flattened, sensory ganglion of the trigeminal nerve
o Lies close to cavernous sinus in the middle cranial fossa
o Ophthalmic division (V1):
Enters orbit through superior orbital fissure

102

Sensory innervation to eyeball, tip of nose, skin on face above eyes


Three branches: lacrimal, frontal, & nasociliary
o Maxillary division (V2): pg 87
Passes through foramen rotundum
Sensory innervation to midface (below eyes & above upper lip), palate, paranasal sinuses, & maxillary teeth
o Mandibular division (V3): pg 90
Exits cranial cavity through foramen ovale
Motor innervation to tensor veli palatine, tensor tympani, muscles of mastication, and anterior belly of digastric &
mylohyoid
Has no ParaSymp component at its origin:
Sensory innervation to:
Skin on Lower face, skin of mandible, lower lip & side of the head
TMJ (Auriculotemporal (main one), and Masseteric (V3) and Posterior Deep Temporal), mandibular teeth, mucous
MBs of cheek, floor of mouth, & anterior part of the tongue
Lingual nerve branch of V3:
Descends deep to lateral pterygoid muscle, where it is joined by chorda tympani (branch of CN VII) which conveys
pregang PS fibers to submandibular ganglion & taste fibers from anterior 2/3 of tongue
Supplies general sensation for anterior 2/3 of tongue, floor of mouth, & mandibular lingual gingiva
Submandibular duct has an intimate relation to the lingual nerve, which crosses it twice
Is directly on the lateral surface of the medial pterygoid muscle
If you cut lingual nerve after its junction w/ chorda tympani, pt loses taste & tactile sense to anterior 2/3 of tongue
In the pterygomandibular space where is lingual nerve in relation to inf alveolar n.?
Anterior and Medial
Nerve to Masseter:
Passes through mandibular notch to enter muscle on medial surface
Also a branch of V3
Carries a few sensory fibers to the anterior portion of the TMJ
Anterior portion of TMJ also supplied by branches of the posterior deep temporal nerve (branch of V3)
Auriculotemporal nerve:
Arises from posterior division of V3
Provides posterior sensory innervation to TMJ
o Pain (TMJ pt) is transmitted in the capsule & periphery of the disk by the auriculotemporal nerve
Pain from a fractured mandible
The joint only sends sensory information it does not receive motor innervation (the muscles do, duh!)
Carries some secretory fibers from the otic ganglion to the parotid gland (from CN IX)
Referred pain from the TMJ to skin over the parotid region & side of head is based on the distribution of the
auriculotemporal n.
TMJ
o Innervated by: (Think PAM pic (From the office she has strong Jaw/TMJ))
Posterior deep temporal nerve (anterior portion) V3
Auriculotemporal (Primary) V3
Nerve to the masseter (anterior portion) V3
CN III, VII, IX use branches of CN V to distribute their preganglionic PS to the PS head ganglia
Abducens (CN VI):
o Supplies the lateral rectus of the eye
o NOT found within the walls of the cavernous sinus (III, IV, V1, and V2 are)
3,4,5 in the cave.
o Injury to abducens means what? Cant abduct eye
Facial nerve (CN VII): pg 97
o Contains sensory neurons that originate from taste buds on anterior 2/3 of tongue
The cell bodies are located in the geniculate ganglion, which lie in the facial canal, in the inner ear
o Associated with the second pharyngeal arch
o Innervates the facial muscles w/ motor fibers
o Supplies the Mimetic muscles (LIKE a MIME, facial expression)
o Lacrimal gland & salivary glands w/ PS fibers
o Anterior tongue w/ sensory fibers
o Originates in the pons
o Traverses the facial canal of the temporal bone & exits the stylomastoid foramen
o Also contains PS fibers to sublingual & submandibular glands (via submandibular ganglion)
o Facial nerve function:
Motor innervation:
Muscles of facial expression

103

104

Posterior belly of digastric muscle & stylohyoid muscle after CN VII emerges from stylomastoid foramen
Stapedius muscle w/in the middle ear
Damage just after it left stylomastoid foramen would cause loss of innervation to facial muscles (orbicularis oculi m.)
Which structure innervates the orbicularis oculi? Temporal and zygomatic branches of CN VII
Sensory: proprioceptive innervation: from the same muscles listed for motor innervation
Secretomotor: PS innervation. Secretion of tears from the lacrimal gland & salivation from the sublingual & submandibular
glands
Special sensory: taste impulses (sweet sensation) from the taste
buds on the anterior 2/3 of tongue, floor of mouth, & palate
o Bells Palsy
Damage to the facial nerve or its branches may cause weakness
or paralysis of facial muscles
Peripheral ipsilateral facial paralysis
Inability to close eye on affected side
Complete destruction of the facial nucleus itself OR its
branchial efferent fibers (facial nerve proper) paralyzes all
ipsilateral facial muscles
Upper motor neuron
Can wrinkle forehead (Inability to
smile he can still wrinkle forehead because upper face gets
innervation from the BOTH sides of the brain (See Pic)
Lower motor neuron lesion (i.e. Facial Nucleus Destruction)
Complete facial paralysis (Inability to smile OR wrinkle
forehead)
PS innervation controlling salivation originate in facial
& glossopharyngeal nerves
tympani
o Emerges from a small canal in posterior wall of
tympanic cavity & crosses medial surface of
tympanic MB
o Joins lingual nerve in the infratemporal fossa
Geniculate ganglion:
o Located w/in the facial canal (petrous portion of
temporal bones)
o Contains sensory neurons via chorda tympani of CN
VII (innervates taste buds on anterior 2/3 of tongue)
o Greater petrosal nerve:
Parasymp secretomotor branch of CN VII and
general visceral afferent fibers
No sympathetic fibers or general somatic
efferents
Also described as the parasympathetic root of
the pterygopalatine ganglion
Arises from the geniculate ganglion
Carries PS preG fibers to pterygopalatine ganglion
Exits cranial cavity through foramen lacerum
Enters pterygoid canal after joining w/ deep petrosal nerve to form the nerve of the pterygoid canal
o Deep petrosal nerve is carrying postG S from the superior cervical ganglion
o Both form the nerve of the pterygoid canal (Vidians)
In pterygopalatine fossa, the nerve of the pterygoid canal terminates in the pterygopalatine ganglion
PS pre-ganglionics from greater petrosal nerve synapse w/ post-ganglionics here
S (already post-ganglionics) just pass on through the ganglion w/out synapsing
Post-ganglionic autonomics distributed to lacrimal gland & glands of mucous MB of nasal cavity, pharynx, & palate
Also transmits taste centrally from palate through palatine nerves
These taste fibers also necessarily pass through the pterygopalatine ganglion & nerve of the pterygoid canal to
reach the greater petrosal nerve on their way to the tractus & nucleus solitarius in the pons
o Lesser petrosal nerve:
Pregang PS to the otic ganglion
parotid gland (via auriculotemporal nerve V3)
NOTE: the postG PS cell bodies to the parotid gland are found in the otic ganglion
Stimulation of lesser petrosal nerve causes secretion by parotid gland
Tympanic & lesser petrosal branches of CN IX supply preganglionic PS secretomotor fibers to the otic ganglion
o Preganglionic fibers leave CN IX as the tympanic nerve (SEE MIDDLE PIC)

Tympanic nerve enters middle ear cavity & participates in formation of the tympanic plexus (on the medial
Wall), where chorda tympani runs from posterior wall across lateral wall (aka medial surface of Tympanic MB)
o It reforms as the lesser petrosal nerve, leaves cranial cavity through foramen ovale, & enters otic ganglion
Diminshed salivary gland production from the parotid due to MIDDLE EAR damage has most likely affected the Lesser
Petrosal Nerve (NOT the auriculotemporal)
Glossopharyngeal nerve (CN IX):
o Originates from anterior surface of the medulla oblongata along w/ CN X & CN XI
o Passes laterally in posterior cranial fossa & leaves skull through the jugular foramen
o Splits the Superior and Middle Constrictors to enter the oral cavity
o Supplies sensation (including pain) to pharynx & posterior 1/3 of tongue
o Innervates derivatives of the 3rd branchial arch
o Innervates stylopharyngeus muscle (the only muscle supplied by CN IX)
Landmark for locating CN IX as CN IX enters pharyngeal wall, it curves posterior around the lateral margin of the
muscle
o Cell bodies of these sensory neurons are located in Superior & Inferior ganglia of this nerve pg 102
Cell bodies of pain fibers in CN IX are found in the superior ganglion of CN IX Pain no good, but its SUPERIOR in 9
o Descends through upper part of neck along w/ internal jugular vein & internal carotid artery
Reaches posterior border of the stylopharyngeus muscle supplies it w/ somatic motor fibers
o Caries 1 afferent neurons that cause the gag reflex (innervates mucous MBs of the fauces)
o ***NOTE: CN III, VII, IX, & X all carry pre-gang PS fibers
o Visceral sensory branches of CN IX:
Lingual branch of CN IX
Terminal branch of CN IX to posterior 1/3 of tongue conveying general sensation & taste to circumvallate
papillae
Also carries some secretomotor fibers to the glands
Pharyngeal
Distributed to mucous MB of the pharynx sensory limb of the gag reflex
Carotid sinus nerve
To carotid sinus (baroreceptor) & carotid body (chemoreceptor)
o Remember Sinus gets it from IX, but the whole BODY gets it from IX and X, aortic arch only from X
Otic ganglion:
o Pregang PS cell bodies originate in the Inferior Salivatory nucleus
o Small PS ganglion, functionally associated w/ CN IX
o Situated below foramen ovale; medial to V3
o Tympanic & lesser petrosal branches of CN IX supply preganglionic PS secretomotor fibers to the otic ganglion
Preganglionic fibers leave CN IX as the tympanic nerve
Tympanic nerve enters middle ear cavity & participates in formation of the tympanic plexus
It reforms as the lesser petrosal nerve, leaves cranial cavity through foramen ovale, & enters otic ganglion
o Postgang PS fibers leave the ganglion & join the auriculotemporal nervejump off at the parotid gland
Vagus Nerve (CN X):
o Leaves brain from medulla & exits cranial cavity through jugular foramen
o Contains PS pre-ganglionic fibers to thoracic & abdominal viscera
o Descends in neck in the carotid sheath behind the internal & common carotid arteries & internal jugular vein
o Both R & L Vay-Goose trunks pass through posterior mediastinum on the esophagus & enter abdominal cavity w/ the esophagus
o In the lower thorax, the esophageal branches of the right vagus branches are found mainly on the posterior esophagus
Just make the right hand turn on the wheel the left vagus goes to the anterior
o Supplies viscera of neck, thorax, & abdomen to the left colic (splenic) flexure of large intestine
Abdominal viscera below left colic flexure, & pelvis & genitalia supplied w/ pregang
PS fibers from pelvic splanchinc nerves
o Vasomotor sympathetic fibers are thought to end on BVs
o Possesses Two Sensory Ganglia:
Superior ganglion (lies on nerve w/in jugular foramen)
Meningeal supplies dura mater
Auricular supplies auricle, external auditory meatus
Inferior ganglion (lies on nerve just below the jugular foramen) pg 104
Pharyngeal
o Forms pharyngeal plexus
o Supplies:
Pharyngeal muscles, except stylopharyngeus (CN IX)
Soft palate muscles, except tensor veli palati (V3)
Superior laryngeal, divides into:

105

1) Internal laryngeal travels w/ superior laryngeal artery & pierces thyrohyoid MB Can see both artery and nere
piercing the MB in the pic to the right
Supplies mucous MB of larynx above vocal folds
o 2) External laryngeal travels w/ superior thyroid artery & supplies cricothyroid muscle In pic going to
cricothryoid muscle
Sensory Portion of CN X:
Somatic sensory fibers to skin of the ear
Cell bodies in the superior ganglion of CN X (somatic sensory nucleus)
Axons enter spinal tract & nucleus of CN V
Visceral sensory fibers to pharynx, larynx, & thoracic & abdominal viscera to the left colic flexure (hunger pangs)
Cell bodies in inferior ganglion of CN X (visceral sensory nucleus)
Axons enter tractus & nucleus solitarius
Visceral sensory fibers to epiglottis (taste)
Cell bodies in inferior ganglion
Axons enter tractus & nucleus solitarius
Motor Portion of CN X:
Branchiomeric motor fibers to skeletal muscle derived from visceral arch muscle in larynx, upper esophagus & pharynx
Cell bodies of these motor neurons are in nucleus ambiguus Think that its ambiguous whether or not they are from
CNX or CNXI
Visceral motor fibers to smooth muscles & glands of the organs of the neck, thorax, & abdomen
These are the PS preganglionic fibers w/ cell bodies in dorsal motor nucleus of vagus
o One Q asked about the preG PS fibers of the duodenum these are found in the dorsal motor nucleus of
vagus
Left vagus nerve:
Enters thorax in front of the left subclavain artery & behind the left brachiocephalic vein So between L. SCA and BCV!
SEE PIC!
Then crosses left side of the aortic arch (pic) & is itself crossed by the left phrenic nerve (R and L phrenic nerves in pic)
Then passes behind the left lung (bottom pic to right), forms the pulmonary plexus
(pic), & continues to form the esophageal plexus
Enters abdomen in front of the esophagus through the esophageal hiatus of the diaphragm
as the anterior vagal trunk
Right vagus nerve:
Crosses anterior surface of the right subclavian artery & enters thorax
posterolateral to the brachiocephalic trunk, lateral to the trachea, & medial (& just
posterior) to the azygos vein
Passes posterior to root of the lung (pic), contributing to the pulmonary plexus
Contributes to the esophageal plexus
Enters abdomen behind the esophagus through the esophageal hiatus of the diaphragm as
the posterior vagal trunk (At T10)
R&L vagus nerves lose their identity in the esophageal plexus
At lower end of the esophagus, branches of the plexus reunite to form the anterior vagal
trunk (anterior gastric nerve)
Anterior vagal trunk can be cut (vagotomy) to reduce gastric secretion
Right recurrent laryngeal nerve pg 123
Arises from right vagus nerve in neck
Hooks around subclavian artery (pics) & passes up/backwards behind artery & ascends in groove
between trachea & esophagus (tracheoesophageal groove)
Innervates:
All muscles of the larynx (except cricothyroid supplied by external laryngeal branch of superior
laryngeal nerve)
o The external laryngeal brach runs with superior thyroid artery to the cricothyroid
Mucous MB of larynx below the vocal folds
Mucous MB of upper part of the trachea
Comes in contact w/ thyroid gland & comes into close relationship w/ inferior
thyroid artery
Left recurrent laryngeal nerve
Crosses arch of the aorta, hooks around ligamentum arteriosum (PIC), &
ascends in groove between trachea & esophagus
Arises from left vagus
Innervates:
Same muscles as right recurrent, but on left side
A few cardiac branches arise from CN X & enter cardiac plexus
o

106

When BP goes up, then these branches increase firing


These are pre-gang PS nerves
Innervate heart mucle & conducting system (SA node, etc.)
Accessory Nerve (CN X1):
o Innervation to the SCM and Trapezius
Hypoglossal Nerve (CN XII):
o Motor nerve supplying all intrinsic & extrinsic muscles of the tongue (except palatoglossus CN X and Genioglossus C1 via XII)
o Leaves skull through hypoglossal canal medial to carotid canal & jugular foramen
o Passes above hyoid bone on the lateral surface of hyoglossus muscle deep to the mylohyoid muscle (Between Hyoglossus and
mylohyoid)
o Landmark Loops around occipital artery & passes between the external carotid artery & internal jugular vein
o Soon after it leaves the skull through the hypoglossal canal. it is joined by C1 fibers from cervical plexus
TO then supply Genioglossus, Geniohyoid, Thyrohyoid
o Unilateral lesions result in deviation of protruded tongue toward the affected side due to lack of function on diseased side
o Injury of CN XII eventually produces paralysis & atrophy of tongue on affected side w/ tongue deviated to the affected side
Dysarthria (inability to articulate) may also be found
IF tongue protrudes to left when you stick it out then Left Genioglossus is not
working
o NOTE: if genioglossus muscle is paralyzed, tongue has tendency to fall back & obstruct
oropharyngeal airway suffocation risk

PICTURE TO RIGHT: CNXII descending from inbetween external carotid and internal
jugular vein (and looping around occipital artery). Travels from carotid to
submandibular triangle of neck. Located in classical position just at inferior border of
posterior digastric. Gives off C1 to innervate thyrohyoid. Then dives into oral cavity
between hyoglossus and mylohyoid muscles.
- Cranial Nerve lesions:
o CN V (motor) jaw deviates TOWARD side of lesion
o CN X uvula deviates AWAY from side of lesion ODDBALL ALERT.
o CN XI head turns TOWARD side of lesion
o CN XII tongue deviates TOWARD side of lesion
**************************************************************************
- Sympathetic ganglia:
o Sympathetic trunks two long chains of symp ganglia on either side of vertebral column that extend from base of skull to coccyx
Damage to the sympathetic trunk causes Horners Syndrome
Horners = (drooping eyelid- loss of tarsal muscle innervation, flushing skin on affected side loss of constriction,
loss of sweating on affected side, no dilation of pupil on affected side)
Lie close to vertebral column & end below by joining to form a single ganglion the ganglion impar (unpaired)
Sympathetic ganglia are located at intervals on each sympathetic trunk alongside vertebral column
Generally there are 3 cervical, 12 thoracic, 4 lumbar, & 4 sacral
Gray rami connect sympathetic trunk to every spinal nerve
White rami are limited to the spinal cord segments between T1 & L2
Cell bodies of visceral efferent fibers (in visceral branches of the sympathetic trunk) located in lateral horn of spinal cord
Cell bodies of visceral afferent fibers located in dorsal root ganglia
o Sympathetic nerves arise from thoracic sympathetic ganglia (T5-T12) they all pass through diaphragm
o PreG Symp fibers may pass through ganglia on thoracic part of sympathetic trunk w/out synapsing
These myelinated fibers form the splanchnic nerves:
Greater symp fibers from T5-T9 pierce diaphragm & synapse w/ excitor cells in the ganglia of celiac plexus
o Nerves consist primarily of preganglionic visceral efferent fibers
o The thoracic splanchnic nerves to the celiac ganglion consist predominantly of preG visceral efferents
o PostG fibers arise from excitor cells in celiac plexus & are distributed to smooth muscle & glands of viscera
o Travels just posterior to the azygos vein
Lesser symp fibers from T10-T11 pierce diaphragm & synapse w/ excitor cells in aorticorenal ganglion
Least symp fibers from T12 pierce diaphragm & synapse w/ excitor cells in ganglia of the aorticorenal plexus
The fibers from the thoracic splanchnics (T5-12) and the lumbar splanchnics synapse largely in 3 ganglia:
1) Celiac ganglion
2) Superior Mesenteric ganglion
3) Inferior Mesenteric ganglion
o Some nerve fibers go even more inferior to the superior hypogastric plexus to provide sympathetic innervation to the
pelvic viscera
o NOTE: PS innervation of the upper 2/3 of the abdominal viscera comes via the vagus nerve which goes through the celiac plexus
w/o synapsing like the sympathetics do
o

107

The remaining inferior portions come by way of the parasympathetics from S2, S3, S4 via pelvic splanchnics
Cervical Ganglia:
Sympathetic innervation to head & neck structures is distributed via the blood vessels (NOT CN III, VII, IX, X)
Superior cervical ganglion
Uppermost & largest lies between internal carotid artery & internal jugular vein
Most of postG sympathetic fibers that go to head region have their cell bodies located here
o EX: The postG sympathetic fibers to the vessels of the SbMn gland arise from cells in the superior cervical ganglion
o This is where the preG and postG sympathetic fibers of the cervical region synapse
o Cell bodies of sympathetic fibers in the nerve of the pterygoid canal come from the superior cervical ganglion
o Postganglionic symp cell bodies that provide innervation to the submandibular gland is located in superior cervical
ganglion
Some fibers go to the upper 3 to 4 cervical nerves
Middle cervical ganglion
Fibers to the cervical nerves C5 & C6
Small, located at level of cricoid cartilage
Related to the loop of the inferior thyroid artery
Inferior cervical ganglion
Fibers to spinal nerves C7, C8, & T1
Most commonly fused to first thoracic sympathetic ganglion to form a stellate ganglion
Cervical plexus:
o Cervical nerves C1-C4 contribute motor fibers to plexus
o Motor nerves are branches of ansa cervicalis (loop formed by C1-C3)
o Positioned deep on side of the neck, lateral to the 1st four cervical vertebrae
o An important branch of each cervical plexus is the phrenic nerve (C3-C5) supplies diaphragm
o Provides cutaneous innervation to skin of the neck, shoulder & upper anterior chest
Supraclavicular nerves innervate skin over the shoulder
Transverse cervical nerve provides sensory innervation to anterior/lateral parts of the neck
o Provides motor innervation to infrahyoid (strap) muscles (except for the thyrohyoidC1 via XII & to the geniohyoid muscle)
o

Gives rise to the first 2 of 3 roots contributing to the phrenic nerve that innervates the diaphragm (C3, 4, 5)

The Brachial
Plexus: Structure
ventral
rami
C5
C6
C7
C8
T1

axillary
musculocutaneous

5 roots
3 trunks
6 divisions
3 cords
5 terminal branches

radial
median
ulnar

108

Brachial plexus (C5-T1)


o Formed in posterior triangle of the neck
o Extends into axilla, supplying nerves to the upper limb
o Axillary sheath contains the Cords of the brachial plexus and the axillary artery and vein2 (NOT subclavian artery???)
Sheet music contains Cords
o Think Robert Taylor Drinks Cold Beer
o Roots Trunks Divisions Cords Branches
(Question: What is terminal portion of brachial plexus called?)
o 5 Roots
o 3 Trunks:

o
o

Superior C 5,6
Middle C 7
Inferior C8, T1
Each splits into anterior and posterior division
3 Cords:
Lateral C5,6,7 From Superior and Middle Roots
Lateral pectoral nerve C5,6,7
Musculocutaneous nerve C 5,6,7
**Median nerve (forms from the medial & lateral cords) C5-T1
Posterior C5,6,7,8,T1 From All 3 Roots
Gives off Axillary nerve C5,6
Radial nerves C5-T1

o
o

Medial (C8, T1) From Inferior


Medial pectoral nerve C8,T1
Ulnar nerve C8,T1 ulnar nerve is a terminal brach of the medial cord
o Ulnar nerve is most sensitive at the elbow (not wrist, hands) think funny bone
**Median nerve (forms from the medial & lateral cords) C5-T1
o Brachial artery runs adjacent to and parallel with the median nerve in the arm
Branches
Think from Back to front to Medial ARMMU
Anteriors
**Arm & Forearm Flexors
Musculocutaneous biceps, brachialis,
coracobrachialis mm.
Median forearm flexors, thenar mm., radial
lumbricals
Ulnar Ulnar flexors, adductor pollicis,
hypothenar mm., interossei, lumbricals 4-5
Posteriors
**Arm & Forearm Extensors (posterior of the
arm/forearm)
Radial both arm & forearm extensors
o (triceps, brachioradialis, supinator, extensors
of wrist/fingers)
Hand
Thenar muscles:
Opponens pollicis, Abductor pollicis brevis,
Flexor pollicis brevis
Innervated by the median nerve (dont get
clowned by the radial nerve)
Numbness of Forefinger and thumb caused by
damage to the Median nerve
Hypothenar muscles: (all are ____ digiti minimi)
One Half LOAF
One and half Lumbricals,
Opponens d.m., Abductor d.m., Flexor d.m.
Innervated by Ulnar nerve
The lateral two lumbricals are also innervated by the
median nerve
The rest of the intrinsic muscles of the hand are
innervated by the ulnar nerve (i.e. interosseoi)

Lumbar plexus: L1-L4


o Formed in psoas muscle
o Supplies lower abdomen & parts of the lower limb
o Main branches are the femoral & obturator nerves
Sacral plexus: L4-L5 & S1-S4
o Lies in posterior pelvic wall in front of piriformis muscle
o Supplies lower back, pelvic, & parts of thigh, leg, & foot
o Main branches are the sciatic (largest nerve in body),
gluteal, & pelvic splanchnic nerves

109

Dermatome:
o Area of skin supplied by a single spinal nerve
o *Supplied by either cranial or spinal nerves
o Cranial nerves
All 3 divisions of CN V supply the skin of face, anterior scalp (V1) & ear (V3)
The ear receives additional innervation from CN VII, IX, & X
All but one of the spinal nerves anterior & posterior primary divisions innervate the remaining dermatomes of the body
The greater occipital nerve (C2) supplies posterior scalp because C1 usually does not supply a dermatome
No overlapping innervation of cranial dermatomes
o Spinal (peripheral) nerve innervation of the skin (cutaneous innervation):
Usually differs from cranial nerve skin innervation because ventral primary divisions of spinal nerves form plexuses
Allows multiple spinal nerves to constitute a peripheral nerve
o EX: C5-C7 form the musculocutaenous nerve
Spinal nerve dermatomes overlap 50%
Must anesthetize T4-T6 to block feeling in T5 dermatome
Functional Components of Nerves
Spinal Nerves
***Only contain 4 of 7 functional components (just the General, not Special components)
Efferent
GVE smooth muscle, cardiac muscle, glands
PreG S: C8L2 w/ cell bodies located in the intermediolateral nucleus
PreG PS: S2S4 w/ cell bodies located lamina VII (analagous to the intermediolateral nucleus)
GSE skeletal muscle arise from alpha & gamma motor neurons of lamina IX (anterior horn)
Afferent (all arise from DRGs)
GVA sensory info from the viscers (although technically not a part of the ANS)
GSA exteroceptive & proprioceptive sensation
Exteroceptive touch, pain, temp
Proprioceptive joints, muscle, tendons, fascia
Cranial Nerves
Afferent
GSA see above
*SSA Vision, Hearing & Equilibrium
GVA see above
*SVA Olfaction & Taste (Southern Virginia is OuT there!!!)
Special visceral afferent fibers for taste are conveyed in VII, IX, & X
Efferent
GSE skeletal muscle from myotomes
GVE PreG PS (no Symp): CN III, VII, IX, X
*SVE (Brachial Arches)
CN V mastication from motor nucleus of V
CN VII facial expression from facial nucleus
CN IX & X larynx, pharynx from nucleus ambiguus
CN XI trapezoid (lift shoulders), SCM
(turn head)
The ENTIRE Cranial Nerve MAP
CN I (Olfactory Nerve)
Special Visceral Afferent
Enter/exit cribriform plate
Conveys information from olfactory epithelium
CN II (Optic Nerve)
Special Somatic Afferent (Special Visceral Afferent
according to Moore pg. 644)
Enter/exit optic canal
Conveys information from retina
CN III (Occulomotor Nerve)
Part 1 - General Somatic Efferent

110

Enter/exit superior orbital fissure within annulus tendinus


Superior Division
Innervates superior rectus muscle
Innervates levator palpebrae superioris muscle
Inferior Division
Innervates inferior rectus muscle
Innervates medial rectus muscle
Innervates inferior oblique muscle
Part 2 General Visceral Efferent (PARASYMPATHETIC PART)
Carries preganglionic parasympathetic fibers along inferior division to ciliary ganglion
Fibers synapse in ciliary ganglion
Short ciliary nerves carry postganglionic parasympathetic fibers from ciliary ganglion to innervate sphincter of pupil and
ciliaris muscle
Ciliary ganglion also carries 1) postganglionic sympathetic fibers along short ciliary nerves to blood vessels of eyeball and
the tarsals, 2) Afferent fibers from nasociliary nerve (CN5 V1)
CN IV (Trochlear Nerve)
General Somatic Efferent
Enter/exit superior orbital fissure
Innervates superior oblique muscle
CN V (Trigeminal Nerve)
Exits the PONS
V1 (Opthalmic Nerve)
General Somatic Afferent
Enter/exit superior orbital fissure
Sensory nerve with 3 main branches
Frontal Nerve (Branch 1)
Enter/exit superior orbital fissure above annulus
tendinus

Nerves of the Orbit:


V1 Branches

supra-.
orbital n.

supra-.
trochlear n.

nasociliary n.

Summary of CN V1 branches:
Lacrimal Nerve
Frontal Nerve
Supraorbital N.
Supratrochlear N.
Nasociliary Nerve
Long Ciliary Ns.
Posterior Ethmoidal N.
Anterior Ethmoidal N.
Infratrochlear N.

long
ciliary ns.

Main Menu

infra-.
trochlear n.
ant.
ethmoid n.
post.
ethmoid n.

lacrimal n.
frontal n.

Supraorbital Nerve
Exit supraorbital foramen
Innervates frontal sinus, conjunctiva
upper eyelid, skin of forehead
Supratrochlear Nerve
Exit on medial side of supraorbital nerve
Innervates skin in middle of forehead to hairline

Index

Frontal Nerve cut here

Nasociliary Nerve (Branch 2) Seen beautifully in bottom of two pics


Enter/exit superior orbital fissure within annulus tendinus

pg 89 H&N

Infratrochlear Nerve
Exits of medial wall of orbit above upper eyelid
Innervates skin and conjunctiva of upper eyelid
Anterior Ethmoid Nerve
Courses w/ anterior ethmoid artery (ophthalmic artery) through anterior
ethmoid foramen
Innervates anterior ethmoid sinuses and anterosuperior part of nasal mucosa on both septum and lateral wall of
nasal cavity
Terminal branch is External Nasal Nerve, innervates skin on dorsum and tip of nose
Posterior Ethmoid Nerve
Courses w/ posterior ethmoid artery (ophthalmic artery) through posterior ethmoid foramen
Innervates posterior ethmoid sinuses and sphenoid sinuses

111

Long Ciliary Nerves (2)


Innervates (sensory to) iris, cornea, and ciliary body
Carry postganglionic sympathetic fibers to the dilator of the pupil
Sensory Root to Ciliary Ganglion
Sensory fibers to eyeball from nasociliary nerve pass through ciliary ganglion and course w/ short ciliary nerves
(CN 3)
Lacrimal Nerve (Branch 3) Seen great in both pics
Enter/exit superior orbital fissure above annulus tendinus
Gland is in the outer lateral side
Courses forward in lateral part of orbit to the lacrimal gland
Carries postganglionic parasympathetic fibers (secretomotor) from pterygopalatine ganglion via zygomaticotemporal
nerve (CN5 V2) from greater petrosal nerve (CN7)
[CN V1 via CN V2 via CN7]
Carries postganglionic sympathetic fibers (vasoconstrictive) from pterygopalatine ganglion via zygomaticotemproal
nerve (CN5 V2) from deep petrosal nerve (Superior Cervical Ganglion)
[CN V1 via CN V2 via Superior Cervical Ganglion]
V2 (Maxillary Nerve)
General Somatic Afferent
Enter/exit foramen rotundum then runs anterolaterally through pterygopalatine fossa
If anesthesia was injected into the pterygopalatine fossa, then V2 would be anesthetized
Within fossa gives rise to 3 branches:
Zygomatic Nerve (Branch 1) (below and on left) pg 92 Netters H&N anatomy
Arises in floor of orbit through inferior orbital fissure
Innervates skin over zygomatic arch and anterior temporal region
Best described as sensory branches of maxillary division of V
Gives rise to 2 terminal braches:
Zygomaticofacial Nerve
Exit zygomaticofacial foramen
Zygomaticotemporal Nerve
Exit zygomaticotemporal foramen
Carries postganglionic parasympathetic fibers (secretomotor) to lacrimal nerve (CN5 V1) from pterygopalatine
ganglion via zygomaticotemporal nerve (CN5 V2) from greater petrosal nerve (CN7)
[CN5 V1 via CN5 V2 via CN7]
Carries postganglionic sympathetic fibers (vasoconstrictive) to lacrimal nerve (CN5 V1) from pterygopalatine
ganglion via zygomaticotemporal nerve (CN5 V2) from deep petrosal nerve (Superior Cervical Ganglion)
[CN5 V1 via CN5 V2 via Superior Cervical Ganglion]
Other V2 Branches: Zygomatic Nerve

Index

zygomatotemporal n.
The zygomatic nerve arises
from V2 in the pterygopalatine
fossa. It divides into 2
branches: the zygomaticofacial
nerve and zygomatical
temporal nerve.

zygomatofacial n.

Main Menu

Pterygopalatine Ganglion:
Branches & Related Ns.

posterior
superior nasal ns.

V2

nasopalatine n.
( not depicted )

Vidians
nerve
greater
petrosal n.

zygomatic n.

deep
petrosal n.
pharyngeal
br.
lesser
palatine n.
greater
palatine n.

112

Ganglionic Branches (2) Supporting Pterygopalatine Ganglion (Branch 2 and 3) (above and right)
Convey general sensory fibers from maxillary nerve that pass through ganglion
(Note: all the braches of the pterygopalatine ganglion are mixed nerves with General Somatic Afferent fibers from the
maxillary nerve, and General Visceral Efferent fibers from the nerve of the pterygoid canal [see below])
Pterygopalatine ganglion gives off numerous braches:
Greater Palatine Nerve
Innervates gingivae, mucous membranes, glands of hard palate
Lesser Palatine Nerve
Innervates gingivae, mucous membranes, glands of soft palate
Nasopalatine Nerve (not depicted)
Courses through sphenopalatine foramen along posterior half nasal septum (along with the Sphenopalatine artery)
NOTE: The spenopalatine foramen is the hole on the MEDIAL wall of the pterygopalatine fossa
In other words it is the direct connection with the nasal region and the Ganglion region of V2
Innervates mucosa in this region then dives down through incisive canal
Innervates mucous membranes and gland of anterior part of hard palate
Nerve of the Pterygoid Canal (aka Vidians Nerve)
General Visceral Efferent
Carries preganglionic parasympathetic fibers from CN7 via greater petrosal nerve, these are secretomotor to mucosa
and glands and synapse in ganglion
Carries postganglionic sympathetic fibers from Superior Cervical Ganglion via deep petrosal nerve, these are
vasoconstrictive to mucosa and glands, do not synapse
Posterior Superior Lateral Nasal Nerve
Innervates mucosa on superior half of lateral wall of nasal septum
Posterior Inferior Lateral Nasal Nerve
Innervates mucosa on inferior half of lateral wall of nasal septum
Maxillary nerve then leaves pterygopalatine fossa through inferior orbital fissure
Henceforth it is known as the Infraorbital nerve (CAREFUL, youre still in bones)
Infraorbital nerve (continuation of V2 once zygomatic and branches to ganglion given off.)
It then gives rise to 3 large sensory branches:
Innervates the upper lip
Posterior Superior Alveolar Nerve
Sensory innervation to maxillary molars
Doesnt get MB of M1
Middle Superior Alveolar Nerve
Sensory innervation to maxillary molars and premolars
Anterior Superior Alveolar Nerve
Sensory innervation to premolars, a branch dives through the incisive canal and emerges as the Incisive Nerve to supply
the maxillary canines and incisors
(Note: nasopalatine nerve also courses through incisive canal)
Maxillary Nerve then continues along floor or orbit through infraorbital sulcus
It dives down through the infraorbital canal and emerges through the infraorbital foramen and serves to innervate
(sensory to) the skin of the cheek, lower lip, lateral side of nose and upper lip
Superior labial branches (skin over cheek and upper lip)
V3 (Mandibular Nerve)
Mixed nerve w/ General Somatic Afferent (sensory) and Special Visceral Efferent fibers (motor)
Enter/exit foramen ovale and enters infratemporal fossa
Divides into anterior and posterior trunks

113

Anterior trunk gives rise to:


Long Buccal Nerve
Innervates skin and mucosa of the cheek, vestibule, and buccal gingiva adjacent to 2nd and 3rd molars
Pain from Swelling of the gingiva would be transmitted via the Buccal nerve
Branches to Four of the Muscles of Mastication
Motor nerve to Masseter, Temporalis, Medial Pterygoid, Lateral Pterygoid muscles
Branches to Additional Muscles (not sure if these branches from anterior trunk)
Motor nerve to anterior belly of the digastric (accessory muscle of mastication), tensor veli palatini, tensor tympani, and the
mylohyoid
(Note: muscles of mastication and innervation derived from 1st pharyngeal gill arch)
Posterior trunk gives rise to:
Auriculotemporal Nerve
Passes between neck of mandible and external acoustic
meatus
Innervates skin anterior to ear and posterior temporal
region
Pain from fractured mandible
Carries postganglionic PS fibers (secretomotor) from
otic ganglion to the parotid salivary gland, these general
visceral efferent fibers come to the otic ganglion via the
lesser petrosal nerve (preganglionic parasympathethic)
from CN 9 (see below)
Marker: middle meningeal artery passes between
branches that make up auriculotemporal nerve
Inferior Alveolar Nerve
Enters mandibular foramen
Sensory innervation to mandibular teeth

V3 (Mandibular) Division:
Branches

deep temporal ns.

auriculotemporal n.

lateral
pterygoid
nerve

inferior alveolar n.
The V3 Branches are the
following:
Trunk Branches:
1. meningeal br. (not depicted)
2. m. pterygoid n.
Anterior Division Branches:
3. masseteric n.
4. deep temporal ns.
mylohyoid n.
5. lateral pterygoid n.
6. long buccal n.
Posterior Division Branches:
lingual n.
7. auriculotemporal n.
8. lingual n.
9. inferior alveolar n.
submandibular gland
a. mylohyoid n.

Mental Nerve
Terminal branch of mandibular nerve
Exits through mental foramen
Innervates skin of chin, lower lip, mucosa of lower lip
Pt with dentures has caused pain in the inner vestibule or something

buccinator

masseteric
nerve

long buccal n.

which nerve was irritated

Mental

Nerve of the Mylohyoid


Runs along the mylohyoid groove
Motor nerve to Mylohyoid muscle (accessory muscle of mastication)
Lingual Nerve
Enters mouth between medial pterygoid and ramus of mandible inferior to 3 rd molar
Sensory innervation to anterior 2/3 of the tongue, floor of the mouth, lingual gingiva
Carries Special Visceral Afferent fibers via Chorda Tympani:
Chorda Tympani
Special Visceral Afferen(taste), General Visceral Efferent (salivary gland)
Branch of CN VII, passes through middle ear over tympanic membrane
Joins lingual nerve in infratemporal fossa
Carries taste fibers to anterior 2/3 of the tongue
Carries preganglionic parasympathetic fibers (secretomotor) to submandibular ganglion for the submandibular and
sublingual salivary glands
CN VI (Abducens Nerve)
General Somatic Efferent
Enter/exit superior orbital fissure
Innervates lateral rectus muscle

114

What muscles Abducts the eye? Abducens Lateral rectus


Paralysis of lateral rectus muscle causes interference with?

Abduction of the eye

CN VII (Facial Nerve)


Motor and sensory nerve, see Moore pgs. 658-660
Supplies the Mimetic muscles (muscles of facial expression) Remember, the MIME.
Consists of two roots
Smaller root has taste (Special Visceral Afferent), parasympathetic (General Visceral Efferent) and sensory (General Somatic
Afferent) fibers
Larger root carries motor fibers to muscles from 2nd pharyngeal arch (Special Visceral Efferent)
Nerve enters internal acoustic meatus
Within facial canal it gives rise to:
Greater Petrosal Nerve
(General Visceral Efferent)
Carries preganglionic parasympathetic fibers to pterygopalatine ganglion
Joins the deep petrosal nerve as it passes through cartilage of foramen lacerum
(Note: These two nerves form the nerve of the pterygoid canal)
After synapse, postganglionic parasympathetic fibers
innervate lacrimal gland (See Above), and mucous
CN VII: Nervus
Intermedius VE Fibers
glands of nasal cavity, palate, upper pharynx
Nerve to Stapedius (not pictured)
(Special Visceral Efferent)
Innervates stapedius muscle in middle ear
Prevents excess movement of the stapes
Chorda Tympani Nerve
Passes through middle ear over tympanic membrane
Joins lingual nerve in infratemporal fossa
Carries taste fibers to anterior 2/3 of the tongue
(Special Visceral Afferent)
Carries preganglionic parasympathetic fibers
(secretomotor) to submandibular ganglion for the
submandibular and sublingual salivary glands
(General Visceral Efferent)
(Note: Sensory fibers (General Somatic Afferent) to
concha of auricle of external ear arise here)

Index

CN VII

Main Menu

greater petrosal n.

geniculate
ganglion

chorda
tympani n.
motor root
lingual
nerve
The nervus intermedius:
VE-para/pre fibers to the
pterygopalatine ganglion (via
the greater petrosal n.) and
submandibular ganglion (via
the chorda tympani). Also
TASTE SSA.
Motor root: SVE to
stapedius, muscles of facial
expression, stylohyoid

pterygopalatine
ganglion

submandibular
ganglion
muscles of facial
expression

Larger motor root (Special Visceral Efferent) exits stylomastoid foramen


Gives off motor braches to occipitalis and auricular muscles (via Posterior Auricular Branch)
Gives off motor branches to posterior belly of the digastric and stylohyoid muscles
Pierces parotid gland
Gives off five terminal motor branches to muscles of facial expression: (TZBMC)
Two Zebras Broke My Coccyx
Temporal Branch
Zygomatic Branch
Buccal Branch
Mandibular Branch
Cervical Branch
CN VIII (Vestibulocochlear Nerve)
Special Somatic Afferent
Enter/exit internal acoustic meatus
Conveys equilibrium, balance (Vestibular fibers) and hearing (Cochlear fibers) information from inner ear
CN IX (Glossopharyngeal Nerve)
Motor (General Visceral Efferent and Special Visceral Efferent) and sensory (General Somatic Afferent and Special Visceral
Afferent) nerve,
From Inferior Salivatory Nucleus
Goes to tympanic plexus as tympanic nerve, then turns into lesser petrosal nerve (carrying Pregang PS to the otic ganglion,
which then sends Postgang PS to the parotid via the auriculotemporal (V3)

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Enter/exit jugular foramen


Gives off two small branches:
Tympanic Nerve
Courses through middle ear
Forms tympanic plexus on promontory of middle ear
Provides sensory innervation (General Somatic Afferent) to the internal surface of the tympanic membrane
Clogged ears from pressure on the auditory tubes is sensed via CN IX (dont get clowned by vestibulocochlear)
Reforms as the lesser petrosal nerve
Carries preganglionic parasympathetic fibers (General Visceral Efferent) to the otic ganglion to supply the parotid gland via
the auriculotemporal nerve (CN5V3) (See Above)
Carotid Branch
Special Visceral Afferent
Provides baroreceptor innervation to the carotid sinus One more time SINUS NINUS!!!
Follows and gives motor innervation (Special Visceral Efferent) to Stylopharyngeus muscle (derived from 3rd pharyngeal arch)
Gives of Pharyngeal Branch to Pharyngeal Plexus of nerves (CN9 and CN10), this gives sensory innervation (General Somatic
Afferent) to the oropharynx
Passes b/w superior and middle constrictor muscles to reach oropharynx
Gives of two branches in oral cavity:
Tonsilar Branch
General Somatic Afferent
Provides sensory innervation to the palatine tonsil
Lingual Branch
Provides general sensory innervation (General Somatic Afferent) to posterior third of tongue
Provides taste fibers (Special Visceral Afferent) to posterior third of tongue
CN10 (Vagus Nerve)
Motor and sensory nerve,
Enter/exit jugular foramen
Joins with cranial root of CN11
Enters carotid sheath and continues to root of the neck
Gives off multiple branches:
Pharyngeal Branch
Innervation to pharyngeal constrictor muscles (Special Visceral Efferent), except cricopharyngeus, and pharyngeal
longitudinal muscles, except stylopharyngeus (Note: pharyngeal muscles derived form 4th through 6th pharyngeal arches)
Provides general sensory innervation (General Somatic Afferent) to laryngopharynx
(Note: motor innervation is really cranial root CN11 via CN10)
Superior Laryngeal Nerve
Divides into two terminal nerves:
Internal Laryngeal Nerve
Sensory (General Somatic Afferent) to root of tongue to vocal folds
Carries preganglionic parasympathetic (General Visceral Efferent) to mucous membrane in same area
External Laryngeal Nerve
Motor innervation (Special Visceral Efferent) to the cricothyroid muscle (ONLY laryngeal m. not done by
recurrent)
Recurrent Laryngeal Nerves
Sensory (General Somatic Afferent) and parasympathetic (General Visceral Efferent) to laryngeal mucous membrane from
vocal folds down
Motor innervation (Special Visceral Efferent) to muscles of larynx and cricopharyngeus muscle, Except Cricothyroid
Cardiac Branches
Provides sensory (General Visceral Afferent) and preganglionic parasympathetic fibers to heart
Passes through superior thoracic aperture into thorax

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Provides sensory (General Visceral Afferent) and preganglionic parasympathetic (General Visceral Efferent) innervation to
organs of thorax
Passes through esophageal hiatus as anterior and posterior vagal trunks
Provides sensory (General Visceral Afferent) and preganglionic parasympathetic (General Visceral Efferent) innervation or
organs of abdomen as far as left colic flexure
CN11 (Accessory Nerve)
Enter/exit jugular foramen
Motor nerve with many branches, see Moore pgs. 666-667
CN12 (Hypoglossal Nerve)
Enter/exit hypoglossal canal
Motor nerve with many branches, see Moore pgs. 667-669
CNs involved in swallowing:
V3, IX, X, XI, XII
HEART
A review of the principle body cavities:
Posterior (dorsal) cavity
Cranial cavity contains brain
Spinal cavity contains spinal cord
The two cavities communicate through foramen magnum
The cavities are lined by meninges
Anterior (ventral) cavity
Thoracic cavity:
Pericardial cavity surrounds heart
Pleural cavity (R & L) each surrounds a lung
The portion between the two pleural cavities is called the mediastinum (the heart & pericardial cavity are located
here)
Abdominal cavity:
Abdominal cavity contains the stomach, spleen, liver, gallbladder, pancreas, and small/large intestines
Pelvic cavity contains the rectum and urinary bladder
In the male, also the paried ductus deferens & seminal vesicle and prostate gland
In the female, also the paired ovaries & the uterus
Superior mediastinum:
Aortic arch w/ its branches, R & L brachiocephalic veins, upper of SVC, trachea, esophagus, thoracic duct, thymus,
phrenic nerve, vagus nerve, cardiac nerve, & left recurrent laryngeal nerve
Inferior mediastinum: (T4 to T12)
1) Anterior mediastinum
Part of the thymus gland
Some lymph nodes
Branches of the internal thoracic artery
2) Middle mediastinum
Pericardium & Heart
Phrenic nerves & its accompanying vessels
Parietal Pericardium forms a boundary
3) Posterior mediastinum
Think of the 4 birds in the back of the thoracic cage:
Va-goose, Esopha-goose, Azy-goose, & Thoracic duck
Descending (thoracic) aorta
Thoracic duct
Esophagus
Azygos system of veins (including hemiazygos vein)
Vagus nerves on the esophagus
Splanchnic nerves
Many lymph nodes
Sympathetic chain ganglia (sympathetic trunks)
NOT phrenic nerves
Cross Section at T8 of the Posterior Mediastinum

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From Back to Front


Vertebra
Splanchnic
Azygos vein
Thoracic duct (off-center to right)
Thoracic duct anterior to vertebrae. As it ascends, it has azygous vein to right, and aorta to left.
Descending aorta (off-center to left)
Esophagus
Vagus Nerve around esophagus
Trachea (but here its already bisected into bronchi)
HEART general info:
Size of a closed fist
Located in the middle mediastinum
Two thirds of hearts mass is to the left of body midline
The developing Heart is anterior to the notochord (It delineates the posterior part of the heart..
Surrounded by the Pericardium
Inner is the Visceral Pericardium (epicardium)
Outer is the Parietal Pericardium
Visceral and parietal pericardia are continuous at the veins & arteries entering & leaving the heart
Serous fluid fills in between to minimized friction went the heart beats
Close relation laterally to the phrenic nerves (which innervate the parietal pericardium)
The apex fits into a depression in the diaphragm
Chambers of the Heart
2 Atria
Separated by thin, muscular interatrial septum
Fossa Ovalis
Shallow depression
Site of foramen ovale in the fetus, which permitted blood flow from atrium to atrium, bypassing pulm circ.
The foramen eventually becomes closed with fibrous CT and becomes fossa
Valve of foramen ovale lies in the medial wall of the left atrium
Anulis ovalis forms the upper margin of the fossa
2 Ventricles
Separated by thick, muscular interventricular septum
Apex of the heart located at level of the 5th intercostal space (left)
Enlarge due to coarctation (constriction) from the aorta
Left ventricle is thicker
Layers of the heart:
Internal endocardium:
Homologous with the tunica intima of the blood vessles
Lines the surface with simple squamous endothelium and underlying loose CT with small blood vessels
Myocardium:
Homologous to the tunica media
Bulk of heart mass with cardiac muscle cells arranged in the spiral configuration
Allows heart to wring blood from the ventricles toward aortic and semilunar valves
Right and left coronary arteries supply myocardium, come from ascending aorta
Epicardium or pericardium:
Serous membrane
Externally, it is covered by simple squamous epithelium supported by thin layer of CT
The adipose tissue that surrounds the heart accumulates in this layer
Cardiac muscle:
Makes up myocardium
Intercalated discs to form a functional network
DOES NOT contract voluntarily
Fibers are separate cellular units, which dont contain many nuclei
Respond to increase demands by increasing fiber size (compensatory hypertrophy)
Pectinate muscles: The woven muscles on flapped R. Atrial wall
Located on the inner surface of the right atrium
They are prominent ridges of atrial myocardium in right atrium and both auricles
(which are small conical pouches projecting from the upper anterior portion of
each atrium)
Crista terminalis: The Ridge that the pectinate muscles are coming from

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Vertical muscular ridge that runs along the right atrial wall from the opening of the SVC to the IVC.
Provides origin of the pectinate muscle.
Represents junction btw the sinus venosus and the heart in the developing embryo
The line of junction between the primitive sinus venosus and the auricle
Also represented on the external surface of heart by the vertical groove called the sulcus terminalis
NOTE: There is also a Sulcus Terminalis in the tongue!
SA node is located in the crista terminalis near opening of SVC
Papillary muscles:
Cone-shaped muscles that terminate in tendinous cords (chordae tendineae that attach to the cusps of the AV valves)
Papillary muscles do not help the valves to close
Help prevent the cusps from being everted or blown out into the atrium during ventricular contraction
Chordae tendinae do the same thing
Sinus Venarum (Can see in pic)
Smooth portion of the right atrium
Develops from embryonic sinus venosus
Receives blood from sup. and inf. vena cavae, coronary sinus, and anterior cardiac veins
Separated from muscular portion by the Crista terminalis
Septomarginal Trabecula
Band of trabeculae carneae connect the interventricular septum to the base of the anterior papillary muscle
Contraction of this muscle prevents over distention of the ventricle
Interventricular Septum
Largely muscular, except for superior aspect, which is a small membranous portion that is common site for
ventricular septal defects
Ligamentum Arteriosum
Remanants of Ductus Arteriosum (fetal bypass of pulm. circ)
Connects Aortic arch to Pulmonary Veins
Left Recurrent Laryngeal hooks around it
Valves: (TPMA Tee Pee My Ass)
Tricuspid
best heard over the right half of the lower end of the body of the sternum
Anterior, Septal, Posterior cusps
Pulmonary
valve best heard over the second left intercostal space, just lateral to sternum
NO chordae tendinae or papillary muscles
Anterior, Right, and Left Semilunar cusps
More Anterior than Aortic Valve (Remember that because it has an Anterior Cusp, where Aortic has Posterior)
Mitral valve (bicuspid)
best heard over apex of heart, (Left 5th intercostal space at the mid clavicular line)
Only valve of the 4 that has 2 cusps
Posterior and Anterior Cusps
Aortic valve
best heard over the second right intercostal space, just lateral to the sternum
NO chordae tendinae or papillary muscles
Left, Right, and Posterior Semilunar cusps
Blood Flow
The cardiac veins lie superficial to the arteries
These all empty into the right atrium:
Coronary sinus
Largest venous pathway
Opens into the right atrium
Most of the cardiac veins empty here, except for anterior cardiac veins, which empty directly into the right
atrium
Superior Vena Cava
Opens into the upper part of the right atrium
Returns blood from upper half of the body
Inferior Vena Cava
Larger than Superior VC
Opens into the lower part of the right atrium
Blood from lower half
Anterior Cardiac Veins THINK ARTRIA Cardiac VEIN
Empty direct into R atrium

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Then blood goes through the Tricuspid valve into the R ventricle then through Pulmonary valve and goes to pulmonary
arteries/circulation
Blood gas exchange occurs and is return to heart via pulmonary veins
Increased resistance to pulmonary blood flow in
the lungs would cause a strain on the right
ventricle
Enters left atrium, passes through Mitral valve to left
ventricle, and out the aortic valve to the rest of the
body
After entering the aorta, immediately the blood can
leave the aorta through the right and left coronary
arteries, sending blood right back to the heart
This does NOT happen during contraction of
left ventricle
Coronary arteries fill during diastole
Obstruction of either artery can lead to anoxia to
the heart, resulting in MI, spasms, or death
The small and middle cardiac veins return blood
from the myocardial capillaries to the Coronary
Sinus
Small comes from right
Middle from back
The anterior interventricular (AKA the L.A.D.)
artery accompanies the great cardiac vein
The posterior interventricular artery accompanies the
middle cardiac vein
**Thrombosis in coronary sinus might cause
dilation in small, great, oblique, and middle
cardiac veins, but NOT THE ANTERIOR cardiac
vein
Anterior cardiac vein drains directly into the right atrium whereas all others drain into the coronary sinus.
Impulse-conducting system of heart:
Consists of specialized cardiac muscle (which contain modified cardiac muscle fibers) present in the SA node, the AV node, and
the Bundle of His (including the Purkinje fibers)
Fibers capable of depolarizing more rapidly than regular fibers, but are weakly contracting
The Sinoatrial node (SA node):
Located in the crista terminalis at the junction of the superior vena cava and the right auricle. Its the most rapidly
depolarizing (Pacemaker)
Depolarizes spontaneously at 70 to 80 per minute
The conduction system of heart is all modified cardiac muscle fibers and NOT NERVES
Innervation to the heart is by what???
the Vagus nerve and sympathetic nerves
SA Node Atria AV Node AV Bundle Purkinje fibers
Parasympathetic fibers from the vagus slow the heart where the sympathetic fibers from the sympathetic trunk speed up the
heart beat
Usually (60% of the time) the SA Node receives blood supply from the right coronary artery (AV node supplied by RCA, too)
Pericardial sac
With heart removed, look for the Transverse pericardial sinus (under the pulmonary trunk)
Also oblique pericardial sinus, is a col-de-sac behind the heart
RESPIRATORY SYSTEM
The Respiratory System:
Has two major partsa branching, tree-like set of hollow tubes (the conducting airways) and very thin-walled pouches (the
alveoli) at the ends of these tubes
Cartilaginous rings found in the main bronchi
Left lung has a smaller capacity than the right
BC that is where the heart is, less lung space
Alveoli form the functional unit of the lung
Assists in vocalization and olfaction
Consists of the nasal cavity , pharynx, larynx, trachea, and the bronchi, bronchioles, and alveoli within the lungs
Lungs
Developed from an outpocketing of the gut tube (so did liver, pancreas, & gallbladder not spleen)
Pair of resp organs that lie within the thoracic cavity and are separated by the mediastinum

120

Each lung is shaped like a cone


It has a blunt apex, a concave base (that sits on the diaphragm), a convex costal surface, and a concave mediastinal surface
At the middle of the mediastinal surface, the hilum is located
Which is a depression in which the bronchi, vessels, and nerves that form the root enter and leave the lung.
The small bronchial arteries also enter the hilum of each lung and deliver oxygen rich blood to the tissues
They tend to follow the bronchial tree to the respiratory bronchioles where they anastomose with the pulmonary vessels
Branches of the vagus nerve also pass the hilum of each lung
Innervation is by what???
the Vagus nerve and sympathetic chain ganglia nerves
Right lung:
Has 3 lobes (superior, middle, and inferior) and three secondary (lobar) bronchi
Contains ten bronchial segments (tertiary bronchi)
Usually receives one bronchial artery
Slightly larger capacity than the left lung
More common to aspirate foreign bodies into the Right lung (less acute angle)
Left Lung:
Has 2 lobes (superior and inferior) and two secondary (lobar) bronchi separated by an oblique fissure
Two lobes because the heart takes up too much space for a third lobe
Contains eight bronchial segments (tertiary bronchi)
Contains a cardiac notch on its superior lobe
VERY ODD Usually receives two bronchial arteries (Where Right only gets 1, eventhough 3 lobes)
Contains a lingulaa tongue-shaped portion of its superior lobe that corresponds to the middle lobe of the right lung.
A stab wound creating a pneumothorax on the left side would result in the collapse of the left lung only(Not pericardial sac)
Hilum
Pulmonary Veins usually anterior and inferior
Pulmonary Arteries are then Anterosuperior
Brochus usually most posterior
Structure of the Lung:
Each lung is enclosed in a double-layers sac called the pleura
One layer is called the visceral pleura, the other is called the parietal pleura
Between the two layers is the pleural cavity, which is filled with serous fluid
Root of the lung major structures found therein:
1) Primary bronchusarise from trachea and carry air to the hilum
Part of the conducting division of the respiratory system = pulmonary conduction system
2) Pulmonary arteryenters the hilum of each lung carrying oxygen poor blood
3) Pulmonary veinssuperior and inferior pair for each lung leave the hilum carrying oxygen rich blood
Top to Bottom:
Trachea:
Tube that begins below the cricoid cartilage (C6) of larynx and splits at the level of the sternal angle (T5) [about the same
level where the trachea passes behind the aortic arch] where it divides at the carina into primary bronchi (right and left
primary or mainstem bronchus, which lead to each lung and are part of the pulmonary conduction system
Two main bronchi branches divide into five lobar bronchi (secondary bronchi):
Right main bronchus divides into three lobar bronchi
Straighter, shorter, and larger than the left primary bronchus
It is also in a more direct line with the trachea (important in dental chair because if patient swallows an object it
tends to lodge in the right bronchus)
Left main bronchus divides into two lobar bronchi
Each secondary or lobar bronchus serves one of the five lobes of the two lungs
Secondary bronchi branch into tertiary bronchi (segmental bronchi) which continue to divide deeper in the lungs
into tiny bronchioles, which subdivide many times, forming terminal bronchioles
Each of these terminal bronchioles gives rise to several respiratory bronchioles
Each respiratory bronchiole subdivides into several alveolar ducts, which end in clusters of small, thinwalled air sacs called alveoli
These alveoli open into a common chamber called alveolar sac, which forms the lungs functional unit
Bronchus
Differs from a bronchiole by possessing cartilage plates & pseudostratified columnar epi
Main support provided by Hyaline Cartilage
Bronchioles
Characterized by:
Diameter < 1mm
Epithelium that progresses from ciliated pseudostratified columnar to simple cuboidal (respiratory bronchioles)
Small bronchioles have non-ciliated bronchiolar epithelial cells (Clara cells) that secrete GAGs that protect the lining
No glands, no hyalinecartilage, no lymphatic nodules

121

Smaller diameter prevents them from collapsing at end of expiration


Scattered goblet cells
Abundant smooth muscle to regulate the bronchiolar diameter
Variation of the size of the lumen of the bronchiole during inspiration and expiration is caused primarily by smooth
muscle and elastic fibers
Contraction is from parasymp stimulation
*Conduction bronchioles
Smaller extensions of bronchi (little bronchi)
Those devoid of alveoli in their walls are nearer the hilum of the lung
*Terminal bronchioles
Lined by low columnar epithelium
*Respiratory bronchioles
Continues to progress to low simple cuboidal
Continuing from terminal bronchioles, branch nearer the alveolar ducts and sacs and have occasionally alveoli in their walls
These bronchioles capable of respiring are the first generation of passageways of the respiratory portion of the bronchial tree
As air passes from the trachea into the lungs, the respiratory bronchiole is the 1st structure in which gaseous exchange through
the wall of an alveolus may occur
In proceeding from the bronchus to the respiratory bronchiole, there is a decrease in cartilage and an increase in
elastic fibers
In proceeding from the trachea to a respiratory bronchiole, the following structural changes occur:
Decrease in goblet cells, decrease in ciliated cells, total loss of cartilage from the walls
Not a progressive change from stratified squamous to cuboidal epithelial lining (from Columnar to cuboidal)
As you go down respiratory tract what is the last thing to go
Smooth muscle??? See physio book
Cells
Type I Pneumocyte
Account for 97% of alveolar lining
Extremely thin (as thin as 25 nm)
Provide minimal barrier to facilitate diffusion of gas
Type II Pneumocyte (GREAT cells)
Account for 3% of alveolar surface
Produce/secrete surfactant (a lecithin)
Phosphlipid-containing substance that reduces surface tension
Pharynx (throat) tube
Serves as passageway for respiratory and digestive tracts. Extends from mouth and nasal cavities to the larynx and esophagus.
Has three regions:
The Nasopharynx: Internal Structures
Main menu
Nasopharynx:
pharyngeal
Contains the eustachian canal (connects the nasopharynx to
tonsil
The nasopharynx is posterior to
the apertures of the nasal cavities
middle ear), salpingopharygeal fold, pharyngeal recess, &
torus
and above the soft palate. Most
pharyngeal tonsils (called adenoids when inflamed), (not
tubarius
superiorly it contains the
pharyngeal tonsil: a large
piriform recess) Which is on either side of epiglottis
auditory
collection of lymphoid tissue.
tube opening
Lies above the soft palate and is continuous with the nasal
On each lateral wall we see:
passage
pharyngeal
Opening of the auditory tube
recess
Torus tubarius: bulge on the
Lies directly behind the nasal cavities or choanae
pharyngeal wall formed by the
The pharyngeal tonsils may become inflamed & block
rim of the auditory tube opening
Salpingopharyngeal fold:
salpingothe choanae, causing pt to becoe a mouth breather
mucosal elevations and folds
pharyngeal
post. to the opening of the tube.
The tensor veli palatine and the levator veli palatine
fold
Pharyngeal recess: a deep area
muscles prevent food from entering the nasopharynx
posterior to the torus tubarius
and the salpingopharyngeal fold.
The uvular muscle does, too, but it wasnt an answer
The Oropharynx: Internal Structures
Main menu
soft palate
option
Index
The oropharynx is posterior to
Oropharynx:
the oral cavity, inferior to the soft
soft palate
palate and above the epiglottis.
Extends from the plane passing through the anterior pillars
The anterior wall is the posterior
to the beginnings of the laryngopharynx
third of the tongue, containing
the lingual tonsil: a large
It communicates with the oral cavity through the isthmus
palatoglossal
collection of lymphoid tissue.
arch
of the fauces
On each lateral wall we see:
Oral part of the Pharynx communicates directly with the
Lingual
Palatoglossal arch: boundary
tonsillar
tonsil
between the oral cavity and the
Nasopharynx and the Laryngopharynx
fossa (with
oropharynx;
the palatine
Receives food from mouth and air from nasopharynx
tonsil)
Palatopharyngeal arch:
posterior and medial to the
Contains palatine and lingual tonsils
palatoTongue:
palatoglossal arch;
pharyngeal anterior 2/3
Between the soft palate and the epiglottis
Palatine tonsil: a large
arch
collection of lymphoid tissue
Tongue:
Laryngopharynx (also hypopharynx):

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in the tonsillar fossa or bed.


Visible through the oral cavity.
Index

posterior 1/3

epiglottis

pharyngeal
wall

Extends from the oropharynx (tip of the epiglottis and inferior)


The SUBGLOTTIS receives sensory innervation from the Superior Laryngeal Nerve
Serves as a passageway for food and air
Air entering the laryngopharynx goes to the larynx while food goes to the esophagus
Food entering the larynx would be expelled by violent coughing
Swallowing
Food moves from oropharynx , prompting soft palate to rise and seal off the nasopharynx.
Epiglottis bends downward while the laryngeal apparatus moves upward, closing off the laryngeal inlet (Aditus)
Bolus of food cascades around the epiglottis and passes through the piriform fossae (recesses) on either side to enter the
esophagus
We swallow 2000 times a day
Mostly done during the daytime, NOT eating
Nose:
What makes up the nose? Medial and lateral nasal processes
Air enters through nostrils (external nares) lead to the vestibules of the nose
The bony roof of the nasal cavity is formed by the cribiform plate of the ethmoid bone
The lateral walls have bony projections called conchae that form shelves which have spaces beneath them called meatuses
The paranasal sinuses
(maxillary, frontal, ethmoidal, and sphenoidal) drain into the nasal cavity by way of these meatuses
The nasal bone does NOT contain paranasal sinuses
Maxillary is the Largest Paranasal sinus
NOTE: Sphenoidal sinus doesnt drain into any of the meatuses
The nasolacrimal ductdrains tears from surface of eyes, also empties into the nasal cavity by way of the inferior meatus
The floor is formed by the hard palate
Nasal cavity & oral cavity are connected by the incisive foramen??? (other options: gr. pal. & less. pal)
The nasal cavity opens posteriorly into the nasopharynx via a funnel-like opening called the choanae (posterior nares)
Epithelium:
Vestibules are lined with nonkeratinized stratified squamous epithelium
Conchae of the nasal fossae and the sinuses are lined with pseudostratified ciliated columnar epithelium
The cell of the maxillary sinus is pseudostratified ciliated columnar epithelium
The specialized columnar epithelium is very prominent in the upper medial portion of the nasal cavity
The nasal cavity receives sensory innervation from the olfactory nerve for smell and from the trigeminal nerve for other
sensations
Nasal cavities lined with specialized columnar epithelium (called olfactory epithelium)
Blood supply is from the branches of the ophthalmic and maxillary arteries
Emergency tracheotomy:
Tracheotomy allows for air to pass between the lungs and the outside air
Done in the cricothyroid space (between thyroid and cricoid cartilages) or through the median cricothyroid ligament
Most easily made by an incision through the median cricoid cartilage to the thyroid cartilage and is inferior to the space between
the vocal cords (rima glottides) where aspirated objects usually get lodged
If you cut below the cricoid cartilage you will damage the trachea
What type of epithelium is covering the vocal folds???
Upper vocal folds (FALSE folds)
Psuedostratified
Lower vocal folds (TRUE folds)
Nonkeratinized stratified squamous
REPRODUCTIVE SYSTEM
Organs of the Female Reproductive System
Ovaries
Are almond-shaped organs located on either side of the uterus, but vary with age.
Round, smooth, and pink at birth
Grow larger, flatten and turn grayish by puberty
During childbearing years take on almond shape and rough, pitted surface
After menopause, they shrink and turn white
Produce ova and steroid hormones:
Estrogenstimulates the development of the female sex organs, the breast, and various secondary sexual characteristics
Progesteronestimulates secretion of uterine milk by the uterine endometrial glands; also promote development of the
secretory apparatus of the breasts
Purpose of ovaries is to produce mature ova
Oogoniaserve as source of oocytes
1 oocytes begin meiosis I during fetal life & complete meiosis I just prior to ovulation
During the in between year, meiosis I is arrested in prophase
Meiosis II is arrested in METaphase until fertilization (until the egg has MET a sperm)

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Just prior to ovulation the preovulatory follicle produces and secretes large amounts of Estrogen
Primordal folliclescontaining oocytes in their sexually mature ovary are stimulated to develop by secretion of FSH from the
anterior lobe of the pituitary
Primary follicles (in first meiotic division) become secondary follicles with the formation of the antrum (cavity)
Fully mature Graafian follicles containing secondary oocytes (in second meiotic division) release the egg into the abdominal
cavity under the influence of LH to be swept into the ostium of the Fallopian tube (uterine tube, oviduct) to be fertilized and
subsequently implanted in the uterus or discarded if not fertilized
During maturation of the egg, four daughter cells are produced, one of which is the large fertilizable ovum, while the others
are small, rudimentary ova known as polar bodies or polocytes.
Zona pellucida is associated with a oocyte in a mature follicle
Atretric Follicles
A follicle that degenerates before coming to maturity; great numbers of such atretic follicles occur in the ovary before
puberty; in the sexually mature woman, several are formed each month
Corpus luteum
Endocrine body that secretes progesterone and is formed in the ovary at the site of a ruptured ovarian (Graafian) follicle
immediately after ovulation.
If pregnancy does not occur, the corpus luteum regresses to a mass of scar tissue (corpus albicans) which eventually disappears.
If pregnancy does occurcorpus luteum persists for several months until the placenta matures enough to produce the hormones
Develops directly from the cells remaining in the remnants of the preovulatory follicle after ovulation
In the ovary:
Progesterone production is primarily by the corpora lutea
Uterine/Fallopian Tubes
Convey secondary oocyte toward the uterus
Site of fertilization
Convey developing embryo to uterus
Uterus
The uterine cavity is roughly triangular in shape and compressed in an anteroposteriorly
Site of implantation
Blastocyst usually occurs in the upper portion of the uterine cavity
Protects and sustains life of embryo and fetus during pregnancy
Active role in parturition
What initiates menstruation? decreased estrogen and progesterone
Round ligament of the uterus normally found in the inguinal canal of the female.
It is a fibromusuclar band attached to the uterus on either side in front of and below the openings of the fallopian tube. It
passes through the inguinal canal to the labia majora
Vagina
Convoys uterine secretions to outside of the body
Receives erect penis and semen during coitus and ejaculation
Passage for fetus during parturition
Path of menstrual flow to outside
Mammary Glands
Produces and secretes milk for nourishment of an infant
Lie in the superficial fascia
Are actually a modified sweat gland
Contain myoepithelial cells (aka basket cells) (star-shaped)have processes that spiral around some of the secretory cells
of these glands
Contraction forces the secretion of the glands toward the ducts
Located in the spaces between the basement membrane and secretory cell!!!!!
The breast receives arterial blood through branches of the lateral thoracic (branch of the axillary artery) and internal thoracic
arteries
Coopers ligaments support breastsare strong, fibrous processes that run from the dermis of the skin to the deep layer of
superficial fascia through the breast
Nipple usually lies at the level of the fourth intercostal space
Breast cancer causes dimpling of the overlying skin and nipple retraction
Most of the lymph from the mammary glands goes to the axillary lymph nodes
Organs of the Male Reproductive System
Testis
Testis produce spermatozoa and secret sex hormones
They are firm, mobile organ lying within the scrotum
Each develops retroperitoneally and descends into the scrotum about time of birth
Seminiferous tubules
Sperm are produced in the seminiferous tubules and stored outside the testis in the epididymis until ejaculated
Meiosis occurs here (it does NOT occur in the ductus epididymis, stratum germanitivum, or ovarian germinal epi)

124

Lining consists of a complex stratified epithelium


Contain two cell types:
Sertoli cells
Produce spermatozoa
Form the blood-testes barrier with tight junctions connecting each cell
Spermatogenic cells germ cells found between Sertoli cells
The development of germ cells depends on pituitary FSH & testicular testosterone
Interstitial cells
Produce and secrete male sex hormones
Androgens, the most important one being testosterone, are synthesized and secreted into the blood stream by interstitial
cells (of Leydig) found in the interstitium of the testis between the seminiferous tubules
Testosterone is required for development of the testes and secondary sex characteristics and initiation and maintenance of
sperm production and secondary sex characteristics.
Epididymis
One found on each testis
Epididymis displays stereocilia
It is a tortuous, C-shaped, cordlike tube located in the scrotum
Tube emerges from the tail as the vas deferens, which enters the spermatic cord
Provides storage space for the spermatozoa and allows them to mature
Carries sperm from the seminiferous tubules of the testis to the vas deferens
Ductus Deferens (Vas)
Store spermatozoa
Conveys sperm from the epididymis to the ejaculatory duct
Cordlike structure
Contains Stereocilia also
Ejaculatory Duct
Receive spermatozoa and additives to produce seminal fluid
Passageway formed by the union of the deferent duct (vas deferens) and the excretory duct of the seminal vesicle
The ejaculatory duct opens into the prostatic urethra
Speaking of ejaculation: just think, Point & Shoot = Parasympathetic for erection, Sympathetic for emission
Seminal Vesicles
Secrete alkaline fluid containing nutrients and prostaglandins
Prostate Gland
Secretes alkaline fluid that helps neutralize acidic seminal fluid and enhance motility of spermatozoa
Scrotum
Encloses and protects testes
Penis
Conveys urine and seminal fluid to outside of the body
Sperm development:
Spermatogenesis occurs in Seminiferous tubules
Spermatogonium1 spermatocyte2 spermatocyteSpermatid
Diploid, 2NDiploid, 4NHaploid, 2NHaploid, N
What cell out of all the above is against the basement membrane?
Spermatogonium
Organs that produce semen:
Seminal vesiclespaired sacs at the base of the bladder
Bulbourethral gland (Cowpers gland)paired located inferior to the prostate
Prostate glandunder the bladder and surrounds the urethra. Continually secretes prostatic fluid, a thin, milky, alkaline fluid.
Copora amylacea are present in the alveoli of this gland
Inguinal canal:
It transmits the spermatic cord in males and the round ligament of the uterus in females; as well as the ilioinguinal nerve in both
sexes
It begins at the deep inguinal ring and extends to the superficial inguinal ring
It is much larger in males than in females:
The anterior wall is formed by aponeuroses of the external oblique and partially by the internal oblique muscle
Passes:
Cremaster muscle
Testicular artery
Internal spermatic fascia
Pampiniform plexus of vein
NOT the epidiymis
Spermatic Cord
Covered by 3 concentric layers of fascia derived from the layers of the anterior abdominal wall

125

Internal and external spermatic fascia


Cremasteric fascia (cremaster muscle and fascia)
Spermatic cord contents:
Testicular artery: branch of the abdominal aorta; supplies mainly the testis and cremaster muscle
Testicular veins: pampiniform plexus forms testicular veins; drains into the left renal vein on the left side and into the inferior
vena cava on the right side
Urethra
Passageway for urine between the urinary bladder and the outside of the body
Female urethra
4 cm
Females have more frequent bladder infections
Opens into the vestibule between the clitoris and the vagina
Male urethra
20 cm because it travels in the penis
Ureter
Paired passageway which transports the urine from the kidney to the urinary bladder for concentration and storage until voided
Reproductive Anatomy
See Kaplan pp. 515-521 for all the details
Hyoglossus and Mylohyoid Relationships
Lingual Nerve, Hypoglossal nerve, Submandibular Duct
SubMan duct and lingual nerve cross 2 x
ALL superficial (Lateral) to the Hyoglossus
ALL deep (medial) to the Mylohyoid
Lingual Artery
Deep to BOTH (Medial)
Which nerve does NOT follow its artery???
Lingual nerve
External Carotid
What nerve follows the external carotid??
Great Auricular Nerve???

Random Questions from 2007


Boundaries of the Axilla: Pectoralis major, subscapularis, serratus anterior, bicipital groove of the humerus
Which of the following is a feature of the Y Chromosome?

it is submetacentric

Sensory Nucleus for 5,6,7,9,10?


principal, abducent, geniculate, inferior petrosal, superior of X

126

BIOCHEMISTRY/PHYSIOLOGY
REVIEW PG 84-86
Circulatory System
Stretch receptors in carotid sinus
Most important for short term BP reg
High BP activates the Carotid Sinus nerve
Activation of parasympathetic nervous system and inhibition of sympathetic to drop BP
Stimulation leads to decreased heart rate, decreased arterial blood pressure and decreased venous return
Increased pressure in the carotid sinus increases the discharge of efferent fibers that travel in the 9 th CN
Then through local medullary circuitry, descending fibers are activated that inhibit sympathetic neurons
associated with the heart
Respond to actual stretching, not chemicals
Stretch receptors in the atria
Elicit Bainbridge reflex --- Think Bridging the gap from the heart to the Lungs
Initiated by excess blood volume in R atrium
Sensitive to both Pressure and stretch
Goal is to get heart to pump harder to transfer excess blood from pulm circ to systemic circ
A sudden increased inflow into the R atrium will cause an increased blood flow to the lungs in 2-3 heart beats
Afferent to the medulla via the vagus nerve
Stimulation of the heart by the vagus nerve keeps the HR down
The effect on basal HR of cutting successively the vagus & the sympathetic nerves in an animal reveals
predominance of vagal over sympathetic innervation in determining HR
Increased vagal activity also results in decreased cardiac oxygen consumption
Increased vagal activity does not result in decreased transit time through the AV node
Then efferent sympathetic increases the HR and strength of contractions
Chemoreceptors
Central (Think C for Central and CO2)
Medulla
MAJOR regulators of ventilation
Kaplan states central receptors are sensitive to low pH
Detect H+ changes in CSF (cerebrospinal fluid)
NO detection of PO2
Detect increase in PCO2
When PCO2 goes up, also increases H+ because CO2 + H2O forms carbonic acid, which then disassociates
to H+ and bicarbonate
Breathing a gas mixture with 5% CO2 ultimately leads to a stimulation of central chemoreceptors
Normally, air is 78% N2, 21% O2, and traces of other gases like CO2
CO2 affects central chemoreceptor the most
Peripheral
Located in carotid and aortic bodies
Detect change in blood PO2 (if <60mmHg), PCO2, and H+ (or pH) ion concentrations
Transmit to resp. center in brain to reg.
A marked fall in the oxygen tension in arterial blood would stimulate the receptors in the aortic & carotid bodies
Normal Hemoglobin concentration is about 15gm/dl blood and normal arterial oxygen content is about 20ml/dl
blood.
An anemic individual breathing room air with a hemoglobin concentration of 10 gm/dl blood is expected to have
Normal arterial oxygen tension and reduced arterial oxygen content
Breathing a gas mixture containing 10% O2 and 90% N2 will stimulate respiration because low oxygen tension has
an Excitatory effect on the peripheral chemoreceptors receptors
Different Q, but it reads administration of 90:10 N20 to O2 will DEPRESS RESPIRATION??? And it will
result in Respiratory Acidosis
NOTE Subanesthetic doses of nitrous (20-40% N2O) cause increased respiration
Blood Volume
64% in systemic veins
By far the most
13% in systemic arteries
7% in arterioles and capillaries
7% in heart
9% in pulmonary vessels

Liver
Largest share of systemic CO
Kidney
Highest blood flow per gram of tissue especially the adrenals
Heart
Large arteriovenous O2 difference
Increased O2 demand is met by increased coronary blood flow, NOT by increased extraction of O2
Total Peripheral Resistance (TPR)
Regulates the flow of blood from the sys. arterial to venus circulation
Resistance to blood flow from the entire circulatory system
Caused by accumulation of vasodilator local metabolites (lactate, K+ ions, & adenosine)
Organ
Factors determining Autoregulation of blood flow
Heart
O2, adenosine, NO (Unique in that when hypoxic causes vasoconstriction)
Brain
CO2, pH
Kidneys
Myogenic and tubuloglomerular feedback
Lungs
Hypoxia causes vasoconstriction (* Unique like the heart)
Skeletal Muscle
Local metabolites, Lactate, Adenosine, K+ (vasodilators)
Adenosine causes vascular smooth muscle to relax
Accumulate due to increasing metabolism of exercising muscle
Posseults Law
= Viscosity (of blood) x length (of vessel) / (Radius)4
Factors affecting blood resistance
Vessel Radius
Most Powerful relationship (Vasoconstriction is King)
Resistance is inversely proportional to the 4th power of vessel radius (= 1/r 4)
If you Half the vessel, then resistance goes up 16 times
Larger the vessel, the less resistance
Viscosity
Directly proportional to resistance
The vena cava contains the highest viscosity blood in the body (95% sure from the other answer options of
aorta, vasa recta, pulmonary vein, pulmonary artery)
Viscosity increases with polycythemia, Hyperproteinemic states (Multiple Myeloma), and Hereditary
Spherocytosis
May vary with hematocrit
Vessel Length
Directly proportional to resistance
Constant
Increasing the radius produces the greatest decrease in resistance in a single artery (versus changing the length or
reducing viscosity) due to the 4th power relationship
Cardiac Output (CO)
Regulates flow of blood from veins back into arterial side
CO = HR x SV
During exercise, CO increases initially as a result of an increase in SV
After prolonged exercise, CO increases as a result of an increase in HR
If HR is too high, diastolic filling is incomplete and CO drops (i.e. ventricular tachycardia, pulse >200)
Most important factor in relation to circulation
Average resting is 5.6 L /min for men
10-20% less for women
Heart Rate (HR)
The parasympathetic NS regulates HR
Stroke Volume (SV)
= End Diastolic Volume End Systolic Volume
Average is 70-80ml
CAP
Contractility (increases SV)
Increased with
Catecholamines (increased activity of Ca2+ pump in sarcoplasmic reticulum)
Sympathetic action of increasing HR, conduction velocity, and contractiility
Increased intracellular Ca2+
Decreased Extracellular Ca2+
Digitalis (increased intracellular Na+, resulting in increased Ca2+)

Resulting in bigger contractility, and slows down (more efficient)


Decreased with
B1 Blockers
Heart Failure
Acidosis
Hypoxia/Hypercapnea
Afterload (decreases SV)
Diastolic arterial pressure (proportional to peripheral resistance)
Vasodilators decrease afterload (i.e. hydralazine)
Preload (increases SV)
Ventricular EDV
Venous Dilators decrease preload (i.e. nitroglycerin)
Venous Return
Most important determinant of CO
A drop in BP results from decreased venous return
Assisted by:
Contraction of skeletal muscles (especially in legs)
Pressure changes in thorax and abdomen during breathing
Increase of thoracic/abdominal pressure will decrease VR
Valsalva Maneuver
VR would be reduced by a forced expiration with the glottis closed
Pressure of venous valves
Decrease venous compliance
Sympathetic action decreases compliance, and increases VR
NOTE: Peripheral vasodilation reduces venous return to the heart
Frank-Starling
Initial length of cardiac muscle fibers affects the strength of contraction
Matches CO with venous return
Greater the filler, the harder the contraction because of more linking of actin and myosin
Increased filling of the ventricle during diastole causes a more forceful heartbeat
This is due to the increase in end-diastolic fiber length
NOTE: in a denervated heart, adjustments to increased workload are mediated by mechanisms
associated with increased end diastolic volume
Another Q:In the completely isolated, blood perfused mammalian heart, adjustments to increase
workload appear to be mediated primarily by mechanisms associated w/ increased diastolic volume
Mean Arterial Pressure (MAP) = CO x TPR (Total Peripheral Resistance)
Similar to Ohms law = Voltage = Current x Resistance
ALSO MAP = Diastolic + 1/3 pulse pressure
Pulse Pressure = Systolic Diastolic
Pulse Pressure Stroke Volume
Example 120/80 MAP = 80 + (120-80)/3 93.33
This is why doctors say the Diastolic BP is more important to monitor
Ejection Fraction
= (EDV ESV/ EDV) = SV/ EDV (Whats leaves/ what you started)
An idex of of ventricular contractility
Is normally 60-70%
Ventricular Filling
Rapid Filling Phase
Rapid flow of blood into the ventricle actually produces a decrease in atrial and ventricular pressures, but a sharp
increase in ventricular volume
Diastasis (Slow Filling Phase)
Gradual rise in atrial, ventricular, venous pressures and ventricular volume
The volume of the ventricle is greatest at end diastolic volume
Compliance (Larger compliance, larger the dilation)
A measure of how much a vein reacts to an change in pressure
Highly compliant veins dilate a lot
Determines the amount of blood flow in the veins
Sympathetic decreases venous compliance and returns more blood back to the heart
Vascular compliance = Increase in volume/increase in pressure
Blood Flow
= Pressure difference/Resistance

BP

The greater the pressure gradient, the greater the flow


The flow rate decreases with increased resistance
CO = BP/TPR V = IR = (BP) Pressure = Flow (CO) x Resistance (TPR)

Measuring BP What indicates systole when using a sphygmomanometer? First sound


A fall in BP causes increased activity of the vasoconstrictor center and decreased activity of the cardioinhibitory center
BP = CO x TPR
Aorta
The characteristic of the aorta most responsible for the maintenance of diastolic BP is elastic distensibility
Systemic Arteries
High pressure
Systolic BP may be abnormally high when arterial compliance is decreased (think arteriosclerosis)
Another Q: Prior to surgery, an anxious patient has a higher systolic BP than previously noted the
most likely reason is decreased arterial compliance (From the NE, sympathetics??)
Strong muscular walls
Always carry blood A for Away from the Heart
The main factors directly involved in the maintenance of systemic arterial blood pressure are
cardiac output, blood volume, blood viscosity and peripheral resistance (not heart rate)
Another Q: A drop in BP results from decreased CO
Now think of things that could cause a decrease in CO, like venous return for example
The arterial blood pressure might be abnormally high in a cerebrovascular accident (not cardiac shock, heart
failure, anaphylactic shock, or ventricular fibrillation)
Arterioles
Greatest drop occurs in the arterioles
In the presence of a constant HR, changes in BP may be attributed mainly to alterations in resistance in
arterioles
Another Q: Postural hypotension is compensated by constriction of systemic arterioles
Another Q: The most likely cause of hypertension is generalized constriction of arterioles
Small vessels with diameter of 0.5 mm
Small lumen, but thick tunica media (almost all smooth muscle)
Primary resistance vessels, hence determine distribution of CO
Control valves for the capillaries
Local blood supply is regulated by tissue metabolism
Humoral factors affect diameter as well as sympathetic activation
Capillaries
Where exchange occurs
Walls are very thin
Only a single layer of endothelial cells
Surrounded by a thin basal lamina of the tunica intima
The amt of blood passing through the capillaries of the systemic circulation/min = amt of blood passing through
the aorta/min
More capillaries arranged in parallel
BP decreases as it flows through circulation
If two vessels are connected in parallel, their total resistance to blood flow is less than the resistance
of either vessel alone
Capillary diameter is directly influenced by byproducts of metabolism
Venules
Small veins which collect blood from capillaries
Gradually coalesce into larger veins
Systemic Veins
Conduits for blood to get back to the heart
The blood pressure of the circulatory system is the lowest in the veins
Greater osmolarity is in the IVC
Larger lumens and thinner walls than arteries
Higher compliance, act as reservoirs
Valves, especially in limbs to prevent backflow
The primary effect of substituting a rigid arterial system for a compliant arterial system would be that continuous flow in the
capillaries would change into pulsatile flow
Another Q: The continuous flow of blood in arteries during diastole is made possible by energy stored in arteries during
systole

Edema
From capillary fluid pressure and increased colloid osmotic pressure of interstitium
These two act in the same direction when it comes to movement of water between interstitium & plasma
Capillary pressure
Force out fluid by filtration
Determined by venous pressure and arterial pressure
Interstitial fluid pressure
Opposes cap pressure
Oncotic pressure (or colloid osmotic pressure of the plasma)
Pulls fluid back into the plasma (same axn as the interstitial fluid pressure)
Colloid osmotic pressure of the blood is important because it prevents excess loss of fluid from capillaries
Another Q: Plasma colloid osmotic pressure acts in the same direction as tissue pressure
Main protein contributing to oncotic pressue is albumin
Albumin
Is produced in the liver
Aldosterone and Vasopressin are NOT
Smallest, most abundant protein in the blood plasma
Type: a simple protein
Important buffer in the blood and is partly responsible for blood viscosity
The role of the liver in edema may be the result of diminished albumin synthesis
Forms a complex with free FAs to be transported in the blood
Kidney is main organ responsible for reg of osmotic pressure with reg of water resorption via ADH
When balance is off, edema occurs and lymphatics pick up the extra fluid left in the interstitium
Pulmonary Circuit
BP is much lower than systemic circuit
Pulmonary arteries are usually dilated and have little resistance are a lot of compliance
Compared with systemic circulation under normal conditions, pulmonary circulation is characterized by low
pressure, equal flow and low resistance (Great example of paralleling capillaries)
Think V = IR, aka pressure = current*resistance
From right side of the heart to the lungs and back to the left side of the heart
Only supplies the alveoli
Systemic Circuit
To all tissues except the alveoli
***Volume flow for BOTH circuits is 5 L/min (vol. flow/min is the same for both the systemic & pulmonary
circulations)
Blood
BY Total Body Weight
92% Body Fluids and Tissues
8% Blood
55% Plasma
45% Formed Elements
Serum
= Plasma Clotting Factors (i.e. fibrinogen)
Clear, thin, sticky fluid portion after removal of fibrin clot and blood cells
No platelets, RBCs, or Fibrinogen
Plasma
= Serum + Fibrinogen
= Blood Formed elements
Liquid portion of the blood
55% of the blood
No cells
Contains
Proteins (7%) albumins 55%, globulins 38%, and fibrinogen 7%
Water (91%)
Other Solutes (2%) Metabolic end-products, food materials, respiratory gases, hormones, and ions
Fibrinogen, prothrombin, calcium ion, and ascorbic acid are all found in plasma (thrombin is not)
Formed elements
The other 45%
RBCs

Leukocytes
PMNs 40-70%, Lymphocytes 20-40%, Monocytes 2-10%, Eosinophils 1-6%, Basophils <1%
Platelets
RBCs
Biconcave discs
7.5 microns in diameter
Function to transport O2 and CO2
No nuclei or mito
The membrane of the RBC
Composed of hemoglobin & other soluble proteins necessary for gaseous respiratory exchange
Has lipid membrane of A, B, or O antibodies
Blood Type
Blood groups
Antigens on RBC
Antibodies in Plasma
(Agglutonogens)
(Agglutinins)
O (Universal dOnOr)
Anti-A and Anti-B
A
A
Anti-B
B
B
Anti-A
AB (Universal Recipients)
A and B
Hematocrit
Proportion of RBCs in a sample of blood
46.2% -- Males
Hematocrit of 45% is a typical finding for a normal 23-year-old man
Abnormal: venous pH = 7.2, WBCs = 10,000/mm3, RBCs = 7 million/mm3, pulse pressure = 80
mmHg
Normal Venous pH
Venous = 7.36
Arterial = 7.41
40.6% -- Females
Bile excretion is a good indicator of RBC destruction per day
Hemoglobin (Hb)
Constitutes 33% of the cell weight in RBCs
1 RBC contains up to 300 million Hb molecules
Hb synthesis involves iron & copper
Heme synthesis occurs in the liver and bone marrow
The committed step is Glycine + Succinyl CoA
gamma-aminolevulinate (ALA)
This is done by the NZ aminolevulinate synthase (inhibited by product heme)
Another Q: Some parts of a hemoglobin molecule iron, protein, histidine, pyrrole ring (not magnesium)
Globin portion
Consists of 2 alpha and 2 beta chains
Exists in 2 Forms:
Taut (T) has low affinity for Oxygen
Increased Cl-, H+, Temp, CO2, and DPG favor the T form (Unloading O2)
CO2 binding favors the T form
CO2 transport binds to the amino acids in the globin chain (at the N-terminus) and not at the Heme site
Relaxed (R) has high affinity for Oxygen (300x)
Heme Portion
Consists of 4 ring-shaped heme molecules
N-containing organic pigment molecule that has single atom of Fe2+ (ferrous) in its center, which can combine
one molecule of O2
Hb is important due to its ability to combine reversibly with O2 at the ferrous heme prosthetic group (not
ferric heme group)
Attached to Globin polypeptide chains
Each Fe can bind reversibly with 1 molecule of O2, so Hb molecule can associate with 4 O2 molecules
(oxyhemoglobin)
Remember that O2 binds with positive cooperativity and negative allostery, meaning that the binding
of the first O2 helps with the binding of the other 3
This accounts for the sigmoid shape dissociation curve (unlike myoglobin)
Hb can bind CO2 and that decreases amount that can bind to O2
Carbon monoxide has a 200x greater affinity for hemoglobin than does O2
Carbon monoxide (CO) decreases the amount of O2 that can be transported by hemoglobin

CO competes w/ O2 for hemoglobin for hemoglobin binding sites this makes CO toxic
MetHemoglobin
Has its iron in Fe3+ (ferric) state and cannot function (NOT reduced hemoglobin)
Remember ferrOus (O for oxygen carrying)
So, the consequence of appreciable conversion of hemoglobin to methemoglobin is a noticeable decrease in
the ability of blood to transport oxygen
Fe

2/3rds of the bodys Iron is in Hb


Other 1/3rd is in liver, spleen, bone marrow, etc. in the form of ferritin or hemosiderin
Body normally has about 4 gms
Absorbed in the upper part of small intestine, primarily in duodenum
Combines in blood plasma with beta globulin apotrasferrin to form transferrin, which is then transported in
plasma
The major storage form of iron is ferritin So ferritin to store it, transferring to transport it in blood
Dominant factor controlling GI absorption of iron is saturation of mucosal cells
Hb Types
Hb A Normal type
Hb C Abnormal in which Lysine has replace glutamic acid causing reduced plastiCity of the RBCs
Hb H Abnormal composed of 4 beta chains (resulting in alpha-thalassemia)
Hb M Abnormal Hbs in which single amino acid substitution favors the formation of methemoglobin
Hb A1C Hemoglobin of a diabetic pt
Hb S (Sickle Cell anemia)
Abnormal Hb in which valine replaced glutamic acid in the beta chain
This causes Hb to become less soluble under low O2 tension & to polymerize into crystals that distort the
RBCs into a sickle shape (sickle-cell anemia)
Major effect of sickle cell anemia is from decreased solubility of the deoxy form of hemoglobin
This would cause an increase of the isoelectric pH
The pH at which number of positive charges equals the number of negative charges
Another Q: Sickle-cell anemia is caused by the presence of a valine substitution for glutamate in the sixth amino
acid from the N-terminal end of the hemoglobin B-chain. This amino acid substitution is the result of a base
change in the DNA of the B-chain gene
Involves a missense mutation
Another Q: The substitution of valine for glutamic acid is a result of a change in DNA coding (due to a genetic
mutation)
Hb test
Measures the grams of Hb contained in 1dl of whole blood and provides an estimate of carrying capacity of RBCs
Normal Concentrations
Women 12 to 16 gm/dl
Men 14 to 18 gm/dl
Infants 14 to 20 gm/dl
Value depends on # of RBCs and amount of Hb in each
Low value indicates anemia
An anemic patient breathing room air is expected to have normal arterial O2 tension & reduced arterial O2
content
Remember that arterial O2 tension has nothing to do with Hb & accounts for only 2% of total O2 content
It has to do with arterial saturation w/ O2, which occurs quickly in the blood
Oxygen transport
O2 picked up in the lungs forms oxyhemoglobin (HbO2)
Then in tissues, O2 splits away from Hb and creates reduced hemoglobin (HHb) or deoxyhemoglobin
A dental patient presents with a bluish discoloration of the mucous MBs indicative of cyanosis most likely the
result of increased levels of reduced hemoglobin
NOTE: Cyanosis, by definition, is a bluish discoloration of the skin due to the presence of deoxygenated Hb in
BVs near the skin surface
Axn is reversible
Depends of PO2
When PO2 is high, (in pulmonary caps), Hb has higher affinity for O2
Among the larger blood vessels, O2 tension is highest in the pulmonary veins
When PO2 is low, (in tissue caps), Hb has lower affinity and unloads O2

Conversion of HbO2 to Hb is the most important process in preventing a decrease of >0.2 units in
blood pH when CO2 enters
Causes of O2 unloading (Decreased affinity for O2) Curve shift to the Right
Low PO2
Bohr effect
The equilibrium expression for oxygen association to hemoglobin includes participation of H+ ions
Decreased pH = increased arterial [H+] = decreased affinity for O2
Increase in arterial pCO2 Causes oxyhemoglobin to shift to deoxyhemoglobin
Has the most effect in stimulating respiration
Increase in Diphosphoglycerate (DPG)
Hypoxia increases the formation of DPG
Increase in tissue temperature (exercise)
So basically, when CO2 enters the blood, pH drops, causing unloading of O2, which then keeps the
blood pH from dropping too much
In question form: The hemoglobin dissociation curve is shifted to the right by an increase in arterial
pCO2 & an increase in arterial H+ concentration
Curve shift to the left
This would be area representing times of Hypoxemia or cyanosis

Oxygen dissociation equation:


y = (pO2)n/[ (pO2)n + (P50)n]
y is the fractional occupancy of O2-binding sites
P50 is the pO2 at which 50% of sites are filled
n = 2.8 for hemoglobin (I have no idea where the 2.8 comes in)
Notes:
At 100mm Hg , Hb is essentially fully saturated (98%)
The PO2 must drop below 70 mmHg before there is a significant lowering of the total bound O2
At 40 mmHg, (venous blood), approximately 75% of heme sites are occupied (or 3 bound
molecules)
P50 (pressure where half the sites, or 2 molecules, are bound) is 27 mmHg
EX: Given P50 = 26 torr & pO2 = 30 torr, the average # of O2 molecules bound per Hb is greater than 2, since
the equation yields y = 0.6 or 60%
Blood leaving lungs is 98% saturated in O2
Blood returning is 75% saturated in O2
Carbonic anhydrase
CO2 is carried from tissue to the lungs in 3 ways
90% Bicarbonate
5% Bound to Hemoglobin as carbaminoglobin
5% Dissolved CO2
[CO2 + H2O H2CO3 H+ + HCO3-]
Present within tubular cells, and it catalyzes the formation of carbonic acid from carbon dioxide and water
Carbonic acid dissociates into hydrogen ion and bicarbonate
One of the fastest known enzymes and is found in great concentration in erythrocytes
Zinc is an essential component
The steps:

Waste CO2, released from respiring tissues into the blood plasma enters the erythrocyte
Within the erythrocyte, carbonic anhydrase facilitates the combination of CO 2 and water to form carbonic acid
[CO2 + H2OH2CO3]
Carbonic acid dissociates into hydrogen ions and bicarbonate ions [H2CO3H+ + HCO3-]
Carbonic anhydrase in erythrocytes increases the rate of dissociation of H2CO3
HCO3- reenters the blood plasma for transport to the lungs
Because the RBC membrane is not very permeable to cations, the HCO3- efflux is balanced with
a Cl- influx, which is known as the Cl- shift
Chloride passes from the plasma into the cell as HCO3- passes from cell into plasma
Because HCO3- is much more soluble in blood plasma than CO2, this roundabout route increases the
bloods capacity to carry carbon dioxide from the tissues to the lungs
In the lungs, HCO3- reenters the erythrocyte and combines with hydrogen ions to form carbonic acid,
which is split by carbonic anhydrase into CO2 and water
This CO2 diffuses into the alveoli and is exhaled
So, carbonic anhydrase in erythrocytes increases the rate of dissociation of H2CO3
Haldane Effect
In the lungs, oxygenation of Hb promotes dissociation of CO2 from Hb
Carbonic anhydrase in the kidney tubular cells is associated with reabsorption of bicarbonate ion
Although not required for CO2 and water to form carbonic acid, it greatly increase the reaction in both respects
Absence of carbonic anhydrase drastically reduces blood CO2 carrying capacity
Most of the CO2 is transported in the blood as bicarbonate ion (HCO3-)
It is converted to carbonic acid more rapidly in whole blood than in plasma
The reason: whole blood contains erythrocytes w/ carbonic anhydrase, while plasma does not contain RBCs
The greatest concentration of carbonic anhydrase is found in erythrocytes
The bicarbonate buffer system of blood is very efficient because CO2 is rapidly eliminated through the lungs
Oxygen Tension vs. Oxygen Content
A marked fall in the oxygen tension in arterial blood would stimulate the receptors in the aortic & carotid bodies
Normal Hemoglobin concentration is about 15gm/dl blood and normal arterial oxygen content is about 20ml/dl
blood. An anemic individual breathing room air with a hemoglobin concentration of 10 gm/dl blood is expected to
have
Normal arterial oxygen tension and reduced arterial oxygen content
NOTE: Hb concentration is about 15 g/dl, and each gram can combine with 1.36 ml O2, so blood can carry 20
ml/dl of O2, compared with only 0.3 ml of physically dissolved O2
Breathing a gas mixture containing 10% O2 and 90% N2 will stimulate respiration because low oxygen tension has
an excitatory effect on the peripheral receptors
Carbaminohemoglobin
Hb that is carrying CO2
Hb carries 97% of O2 transported
Hemostasis preventing or minimizing blood loss
Chain
Vasoconstriction
Platelet aggregation
The important role that platelets play in hemostasis is that they agglutinate and plug small, ruptured vessels
Thromboxane A2 is released by platelets & causes platelets to stick together
Increased bleeding (in a patient w/ leukemia) is most likely due to thrombocytopenia (when anemia, leukopenia,
Ca2+ deficiency, and Factor VIII deficiency are your other options
Basically all the blood progenitor cells are too busy making WBCs and so no energy to make platelets
Coagulation Cascade (picture)

Extrinsic pathway
Remember something else started it
Upon injury to endothelial cells tissure factor (factor III) rlsd
Which combines w/ factor VII & Ca+2 to form activating complex for factor X
Then activates factor IX to activated complex which becomes common pathway
3- 7- 10
Common:
Then activate factor X then factor II activated (prothrombin thrombin)
10- ProT(2)- Throm- Fibrinogen- Fibrin- x-linked fibrin
Also 10- ProT(2)- Throm- 13- Fibrin Monomer- x-linked fibrin
Intrinsic pathway:
When platelets adhere to injured subendothel region factor XII rlsd which becomes activated by
kallikrein and HMWK (high MW kininogen)
Which activates factor XI which activates IX then common pathway
12- 11- 9- 10
Notes
Factor X upon activation is first slow once thrombin made factor V is activated (back door from
Thrombin) speeds up Factor Xs rsn (prothromb thromb)
Speeds up HUGE (800,000 FOLD when V and Ca2+ added)
Also speeds up back door via activation of factor VIII from thrombin which joins IX making it stronger
Thrombin
Catalyzes: fibrinogen fibrin monomer rxn
In other words, fibrinogen represents the normal substrate of thrombin
Research has shown that thrombin acts upon the arginyl-glycine linkages in fibrinogen to produce
a fibrin monomer
Factor XIIIa catalyzes: fibrin monomer cross-linked fibrin reaction
When BVs are ruptured, usually both intrinsic and extrinsic pathways are activated
In severe degenerative disease of the liver (such as advanced alcoholic cirrhosis), prothrombin and
fibrinogen levels will be markedly deficient
Thromboxane A2
Release by platelets and causes them to stick together or aggregate
First thing to happen in formation of platelet plug? Adherence of platelet to subendothelium. This
happens before TbA2 is released
Things required for normal blood clotting:
Ca2+, thrombin, vitamin K, phospholipid, proteolysis
Vitamin K is cofactor 2 (prothrombin), 7,9,10
(Plasmin breaks down clots)
Another Q: Fe2+ is not involved in coagulation of blood

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Anticoagulants:
Heparin, dicumarol, sodium citrate, any antithrombin substance
Plasmin
Mediates dissolution of the fibrin clot during vessel repair
Bleeding disorders
Hemophilia A represents a bleeding disorder due to lack of factor VIII
Erythropoeitin
Stimulates RBC production in bone marrow
Glycoprotein hormone produced in the kidneys
Negative feeback mech sensitive to the amount of O2 in blood
Site of action
Hemcytoblast (a pluripotent stem cell)
Can have hypo (anemia) or hyper (polycythemia) secretions of erythropoietin
Plasma Calcium Levels
8.5 to 10.5 mg/dl
Regulated by PTH
Vit D3 regulates uptake in GI
Low Plasma Ca results in hyperirritability of nerves and muscles
High Plasma Ca results in CNS and Cardiovascular depression
Plasma Phosporus levels
3.0 to 4.5 mg/dl
Regulated by PTH
Causes kidneys to increase the rate of phosphate excretion
Blood glucose levels
80-100 mg/dl
Reg. by insulin and glucagons
Glucose normally does not appear in urine although it is filtered because it is reabsorbed in the proximal convoluted
tubule
Heart
Valves
TPMA (Toilet Paper, My A**)(Tricuspid/Pulmonary/Mitral/Aortic)
Tricuspid
Between Right A and V
Tough, fibrous tissue flaps of endocardium
Secured to papillary muscle via chordae tendineae
Damage to the tricuspid valve results in blood leakage from the right V to the right A
Pulmonary
Entrance of pulmonary artery
3 cusps
Mitral (bicuspid)
Between Left A and V
Tough, fibrous tissue flaps of endocardium
Secured to papillary muscle via chordae tendineae
Aortic
Entrance of ascending aorta
3 cusps
Sounds
First Heart Sound
Lub
Closure of the AV valves at beginning of ventricular contraction
Immediately following the closure of the AV valves is the period of isometric contraction, (not isotonic)
Louder and stronger
Systole starts with 1st sound
Diastole ends with 1st sound
Second Heart sound
Dub
Closure of semilunar valves (pulmonary and aortic)
Aortic closes before pulmonary, so sound can be split
The second heart sound is related to closure of aortic valve

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Systole ends with 2nd sound


Diastole starts with 2nd sound
Sounds heard in the antecubital space during systole are produced by turbulent blood flow through the artery
All 4 valves are NEVER open at the same time
Cardiac Cycle
Phases
1 Atrial Systole
2 Isovolumetric Contraction
Period between mitral valve closure and aortic
valve opening, so all valves are closed
Period of highest oxygen consumption
3 Rapid Ejection
4 Reduced Ejection
5 Isovolumetric relaxation
Period between aortic valve closing and mitral
valve opening
6 Rapid Ventricular Filling
7 Reduced Ventricular Filling
Sounds
1 Mitral and Tricuspid Valve Closure (Lub)
2 Aortic and Pulmon. Valve Closure (Dub)
3 Start of Ventricular filling
4 High atrial pressure/stiff ventricle
Diastole
Isovolumetric ventricular relaxation
Pulmonary and aortic valves close
Ventricular pressure decreases
During this period, blood flow to the coronary arteries is the greatest in a resting individual
Another Q: During early diastole, blood flow to the left coronary artery is greatest
Opening of tricuspid and mitral (bicuspid) valves [Passive Filling]
Atrial Systole
Following SA node depol, atria depol and contract [Active Filling]
The wave of depol slows in the AV node, allowing time for blood filling of ventricles
Ventricular volume is greatest at end of atrial systole = at the end of ventricular diastole
Systole
Isovolumetric ventricular contraction
Mitral and tricuspid valves close (All valves are closed during isovolumetric ventricular contraction)
Another Q: Ventricular pressure rises rapidly
Ventricular ejection
Opening the aortic and pulmonary valves
Empty rapid at first, then rate slows and ventricular pressure drops
Ventricular pressure is greatest at beginning of ventricular ejection
The largest volume flow of blood through the left coronary artery occurs during diastole
An immediate effect of diminished oxygen tension in the myocardium is vasodilatation of coronary vessels
Chronotropic State (Heart Rate)
Positive = Increase in Rate
Epinephrine administration causes both Positive Chronotropy and Inotropy
Inotropic States (Myocardial Contractility)
Term used to describe the degree to which the fibers are activated at a given preload and afterload
Positive Inotropy
Most commonly related to increased availability of intracellular Ca2+
Agents include:
Epi, NE, other Beta-1 agonsists
Increase the probability that a Ca channel is open
An injection into the left ventricular wall increases cardiac output and is a positive inotropy
Increased Extracellular [Ca2+]
Causes an increased influx of Ca during phase 2 of the action potential
Cardiac glycosides (Digitalis)
Inhibit the Na+/K+ ATPase, causing an increased intracellular [Ca2+]
Digitalis is given to increase strength of contractions & decrease HR

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I think this makes it a positive inotrope & a negative chronotrope


Negative Inotropy
Related to decreased availability of intracellular Ca2+
Agents:
Ca channel blockers
Acidosis
Which blocks Ca2+ channels
Beta-1 receptor antagonists
Which decrease the probability that a given Ca2+ channel is open
Myocardial ischemia
Alcohol
Acetylcholine
Decreases Ca2+ influx in the atria, but not in the ventricles
Exercise
3 major effects are essential for proper circulation during exercise:
Mass discharge of sympathetic NS
Constricts vegetative muscles
Vasodilates skeletal muscles
Increase heart stuff, etc.
Moderate exercise increases HR & coronary blood flow
Increase in CO
Skeletal muscle contraction facilitates more venous return, so stroke volume goes up, CO goes up
Increase in arterial BP
From symp action, increasing CO
Heart Muscle Refractory Periods
Ventricular Muscle 0.25 - 0.30 seconds
Atrial Muscle 0.15 seconds
Types of refractory periods
Absolute
Another AP is not even possible (H gate stuck)
Interval in which no stimulus is effective in creating an AP
Another Q: Absolute refractory period is determined by duration of Na gate inactivation
Limits the maximum frequency of effective nerve stimulation (maximum # of impulses a nerve can carry)
Relative
Begins at end of absolute and continues until membrane potential returns to resting level
Another AP is possible if stimulus is larger than usual
Excitation time for total heart 0.22 seconds
Skeletal muscle cells have short refractory periods
Also can undergo tetanus, which increases strength of contraction
Cardiac muscle does not tetany because of its long refractory period
Autonomic NS and the heart
Controlled in medulla oblongata of brain stem
Sympathetic
NE
Increase in HR
Fibers are from T1-T4 (accessory nerves)
Parasympathetic
Ach
Decrease in HR
Parasympathetic nervous system regulates heart rate
Fibers in the vagus nerves
Right vagus nerve SA node (pacemaker)
Left vagus nerve AV node (slowest conductor in the heart)
***NOTE: Vagal stimulation in the mammalian heart has
primarily a rate effect because there are few vagal endings
distributed to the mammalian ventricles
Myocardial Action Potential (RIGHT)
Phase 0
Rapid upstroke
Voltage-gated Na+ channels open

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Phase 1
Initial Repolarization
Inactivation of voltage-gated Na+ channels
Voltage-gated K+ channels begin to open
Phase 2
Plateau Ca2+ influx through voltage-gated channels balances K+ efflux
Ca2+ influx triggers myocyte contraction
Phase 3
Rapid repolarization
Massive K+ efflux due to opening of voltage-gated slow K+ channels and closure of voltage-gated Ca2+ channels
Phase 4
Resting Potential
High K+ permeability through K+ channels
Cardiac Conduction
SA Node
Pacemaker
The following changes in the electrical properties of a pacemaker cell can slow down the rate at which the cell
initiates impulses:
The threshold potential becoming more positive
The rate of spontaneous depolarization decreasing
The maximum diastolic potential becoming more negative
In posterior wall of R atrium by the opening of superior vena cava
The rate of the heart beat in a human is determined by the SA node
Internodal pathways
0.04 Seconds
Transmit depol to L atrium and AV node
AV Node
In the lower R interatrial septum
Delays impulse 0.13 seconds so atria can contract first
The slowest rate of conduction velocity
AV Bundle (of His)
Orginates in AV node
Divides into 2 bundle branches to 2 sides of interventricular septum
Purkinje fibers
Originate in right and left bundle branches and extend to papillary muscles and lateral walls of the ventricles
Very fast depol through bundle branches and purkinje fibers 0.03 seconds
ECG or EKG Know the P, QRS, & T waves

P wave
activation of the atria
PR segment
the duration of the AV conduction
QRS complex
activation of both ventricles
ST-T wave
ventricular recovery
Each 1 mm square represents 0.04 sec (40 ms)
Rate: 300 # of large boxes between 2 consecutive R waves
P wave
Atrial depolarization
P waves occurring in ST segment indicating ectopic beats originating in the atria
AV Blocks
1st Degree
Prolonged PR interval (>200msec)
2nd Degree
Type I (Wenckebach) shows a progressive prolongation of PR interval until a P wave is blocked and
not followed by a QRS complex
Type II (Mobitz) shows sporadic/episodic dropped QRS complex
Extra P waves before each QRS complex on an EKG are indicative of partial heart block (second
degree block)

14

Another Q: An EKG showing a consistent rhythmical ratio of three P waves to each QRST complex
indicates an AV node partial block
3rd Degree
Complete AV block with P waves completely dissociated from QRS complexes
Another Q: When the P wave and QRS complex are dissociated, it is indicative of complete (3rd
degree) heart block
QRS Complex
Ventricular depol
T wave
Ventricular repol
S-T segment
Ventricles are completely depolarized??? (Only point where this happens in ECG)
Isoelectric
P-R interval
What is the PR interval
Length of time between depol of atria and depol of ventricles
The P-R interval is related to propagation of the cardiac impulse between the SA node and the AV node
Index of the conduction time between the atria and the ventricles
Index of the atrial depolarization and conduction through the AV node
Another Q: When an increased PR interval is observed, this represents slow conduction of impulses through the
AV node
Approx 0.16 seconds (0.13 + 0.03, see above)
Q-T interval
Period between ventricular depol and repol
Approx 0.35 seconds
T-P section
Isoelectric (aka ventricle is at resting membrane potential) no electric signal to the heart during this section
Ventricle is filling with blood
Shortens a lot at high HRs
Leads
Standard Bipolar Limb Leads
I
Right Arm (-)
Left Arm (+)
II
Right Arm (-)
Left Leg (+)
III
Left Arm (-)
Left Leg (+)
Standard Unipolar Limb Leads
AVR
Right Arm (+)
AVL
Left Arm (+)
AVF
Left Leg (+)
Doesnt matter which one you used for cardiac arrythmias, BUT it does w/ voltage abnormalities & axis deviations
Chest Leads
V1, V2, V3, V4, V5, V6
Represent 6 places on the anterior chest wall
Heart NZs:
Creatine kinase (CK) also called creatine phosphokinase (CPK)
The first heart enzyme to appear in blood after a heart attack
Glutamate oxaloacetate transmaminase (GOT)the second to appear
Glutamate pyruvate transmaminase (GPT)
Lactate dehydrogenase (LDH) different isozyme characteristic of heart muscle
The plasma levels of these enzymes are commonly determined in the diagnosis of myocardial infarctions
They are particularly useful when the ECG is difficult to interpret
NEW GOLD STANDARD for Dx of a MI Troponin C
Congestive heart failure
Causes bulging veins in the neck
A person with left heart failure might show signs of dyspnea when placed in the supine position because of edema caused by
excessive pulmonary capillary hydrostatic pressure
Respiratory System
Gas exchange
Oxygen passes from alveolar air into blood by diffusion
Depends on:

15

Thickness of the membrane


Thin is better
Rate of diffusion is inversely proportional to the diffusion distance
Surface area of the respiratory membrane
Rate of diffusion is directly proportional to the surface area
Increasing the cross-sectional area can increase the rate of oxygen diffusion at the alveolar membrane
Solubility of gas
Gas dissolved in liquid exerts partial pressure
So partial pressure includes both gas particles and liquid gas particles
CO2 is 20x more soluble than O2
Partial pressure difference between two sides of a membrane
Net diffusion from high to low pressure
In addition to the respiratory system, the exchange of gases between plasma & tissue fluid is a function of
partial pressures (NOT due to osmotic pressure differentials or differences in volume % of the gases)
Another Q: The actual diffusion of gases is 1 controlled by differentials in partial pressures of the gases
Alveolar PO2 is greater than pulmonary arterial pressure
Alveolar PCO2 is lower than pulmonary arterial pressure
The diffusion coefficient for the transfer of each gas through the respiratory membrane depends upon BOTH
solubility and molecular weight
Partially pressures of respiratory gases found in arterial blood most closely correspond to partial pressures found in
the alveoli
So, O2 removal from the alveoli is facilitated by low PO2 of alveolar blood, increased total alveolar surface area, and
increased blood flow through alveolar capillaries
Another Q: As blood passes through alveolar capillaries, blood PO 2 rises, hemoglobin releases CO 2 & H+ (blood
PCO2 does not rise)
NOTE Hb does release H+, but NOT into the blood, only to be available in the RBC to make Carbonic acid
with the influxed bicarb
Pulmonary Circulation
Normally a low-resistance, high compliance system
PO2 and PCO2 exert opposite effects on pulmonary and systemic circulation
A decrease in PAO2 causes a hypoxic vasonconstriction that shifts blood away from poorly ventilated regions of the
lung to well-ventilated ones
A consequence of pulmonary hypertension is cor pulmonale and subsequent right ventricular failure (Jugular venous
distention, edema, hepatomegaly)
Pulmonary Ventilation
Total volume of gas per minute inspired or expired
Coordinated in the brain stem (medulla)
V/Q Mismatch
Ideally Ventilation is matched to perfusion such that V/Q = 1
Actual is 0.8
Lung zones
Apex of the lung = V/Q = 3 (wasted ventilation)
Just think blood is flowing through the base of the lungs, so base of the lungs, and air rises so V is greater
in the apex
Base of the lung = V/Q = 0.6 (wasted perfusion)
BOTH ventilation and perfusion are Greater at the base of the lung than at the apex
V/Q = 0 (means airway obstruction)
V/Q = infinity (means blood flow obstruction)
Minute ventilation
Volume of air moved in to the respiratory passageways in one minute
= Tidal volume x Breaths/min
Alveolar ventilation
Is the actual air that reaches the alveoli and can participate in gas exchange
Expressed in per minute OR per breath
= Respiratory Rate x (Tidal volume Dead air space volume)
Dead air space
Air that is filled in the non-gas exchange areas of the lung (all but alveoli)
~150ml
Is the best criterion for effectiveness of breathing
Lung Volumes and Capacities

16

FVC

FVC = Forced Vital Capacity

Tidal volume (VT)


Amount of air entering the lungs with each breath
Normal is 12/min
~500ml
Inspiratory capacity (IC)
Amount of air entering lungs with maximal inhalation
Vital capacity (VC)
Maximum volume a person can exhale slowly
= Vt + IRV + ERV
Functional residual capacity (FRC)
This is the volume left in lungs at the end of a normal quiet expiration
At FRC the tendency of the lungs to collapse is exactly balanced by the tendency of the chest wall to expand
= ERV + RV
One should expect Nitrous sedation to take longer than normal in a person with functional residual capacity
larger than normal
Residual volume (RV)
Volume left in lungs at the end of a forced maximal expiration
ANATOMIC Deadspace
Inspiratory Reserve Volume (IRV)
Extra volume of air that can be inspired in addition to Vt
Approx 3000ml
Expiratory Reserve Volume (ERV)
Extra volume of air that can be exhaled after normal expiration of Vt
Approx 1100ml
Total lung capacity (TLC)
Vital capacity + residual volume
Forced vital capacity (FVC)
Maximum volume a person can exhale with maximal force
Forced expiratory volume in one second (FEV1)
Volume of air forcefully exhaled in one second
Note, this is a measure of flow whereas FVC is a measure of volume
FEV1/FVC
This ratio is useful in differentiating obstructive and restrictive lung conditions
TLC =
IRV + VT + ERV + RV
FRC + IC
VC + RV
A patient with emphysema exhibits increased FRC & increased compliance
Compliance
is the measure of distensibility of a chamber expressed as a change in volume per unit change in pressure
Spirometry
You cant measure RV, FRC, and Total lung capacity
Lung Receptors
Lung stretch receptors

17

Located in smooth muscle of airways


During inspiration (when distended):
Stimulate Hering-Breuer reflex, which prevents overinflation
The adequate stimulus for the Hering-Breuer reflex is the stretching of alveoli
Think Bruer Hockey Gear to keep your lungs tight
Send stimuli over afferent vagus nerve to resp center in medulla
LungVagusMedullaSpinal cordRespiratory muscles
Not used much in normal breathing, only protective
Expansion of the lungs stimulates vagal nerve endings in the lung parenchyma & inhibits inspiration
J Receptors
Located in the alveolar walls
When stimulated, cause rapid, shallow breathing
Jake is a shallow person
Irritant Receptors
Located between airway epi cells
Stimulated by noxious substances
Joint and muscle receptors
Are activated during exercise to stimulate breathing
NOTE: PCO2 is the most important stimulus for the respiratory center in medulla
An increase in arterial CO2 has the greatest effect in stimulating respiration
Another Q: After a period of voluntary hyperventilation, respiration becomes depressed mainly due to reduced blood
PCO2
Another Q: Apnea occurring after hyperventilation of an anesthetized patient results from decreased CO 2 tension
Respiratory Products
Surfactant:
Dipalmitoyl Phosphatidylcholine (Lecithin)
Collapsing Pressure = 2 (tension)/Radius
Decreases alveolar surface tension and increases compliance
Difficulty breathing in neonates due to deficient surfactant resulting in increased surface tension
Prostaglandins
Histamine
Angiotensin Converting Enzyme (ACE): cleaves AI AII, inactivates bradykinin and causes cough, angioedema)
Kallikrein: Activates Bradykinin
Respiratory Terms
Apnea cessation of breathing
Hypercapnea Excess CO2 in arterial blood
Hypocapnea Duh
Hyperpnea Abnormally deep and rapid breathing
Resp Arrest Permanent cessation of breathing
Hyperventilation Increased ventilation in excess of metabolic requirements
Results in loss of CO2 from blood, causing a decrease in BP and may result in fainting (Brown Bag it)
Results in decreased CO2 and increased pH (decrease in H+)
Another Q: Voluntary overventilation of the lungs results in decreased [H+]
Hypoventilation
decreased ventilation
The most important test for hypoventilation is the determination of arterial CO2 tension
Caused by:
Drugs that depress respiratory center in the medulla (barbiturates)
Obstruction paraylysis of the respiratory muscles
Lung Disease
Pressures in the respiratory system:
Atmospheric Pressure
= 760mmHg = same pressure in alveoli when lungs are at rest (aka after a normal expiration)
Collapsing force of lungs
By the elastic CT of the lungs and surface tension from surfactant
NOTE: Pulmonary surfactant acts to increase both lung compliance & vital capacity
So obviously w/o it you have decreased both compliance and vital capacity
Expanding force of the lungs
***Both forces are equilavent at FRC or the end of expiration, or the point of rest
Here, both inspiration or expiration would require muscle involvement

18

Partial Pressures (in mmHg)


Venous Blood
PO2
40
PCO2
46

Arterial Blood
100
40

Alveoli
105
40

Atm
160
0.3

In the resting state, the average difference between O2 content of arterial & venous blood is 5 volume percent
Jake: how does this correlate with the 40 vs. 100mmHg thing above? Does it have to do with total content, and
not PO2, which changes drastically
Another Q: When the partial pressure of oxygen in arterial blood is lower than that in alveoli, this suggests
thickening of the alveolar membrane??? (Sounds normal to me)
Another Q: The partial pressures of respiratory gases found in arterial blood correspond most closely to those partial
pressures found in the alveoli
Another Q: In a pulmonary AV shunt, the O2 partial pressure in arterial blood is low
Another Q: Under physiological conditions the lowest partial pressure of oxygen is in Venous Blood NOT expired
Air
Intrapleural Pressure
Pressure w/in the pleural cavity
In resting position, approx 4 mm Hg less than the atm pressure (so 756mm Hg)
Intrapleural pressure is always less than the intrapulmonary pressure
Another Q: Intrapleural pressure during normal respiration is subatmospheric
Simultaneous contraction of the external intercostal muscles & the diaphragm results in a decrease in
intrapleural pressure
(the pressure becomes more negative thats a decrease)
Physiologic Dead Space
= Anatomic dead space + any part of the lung that should be ventilated and perfused but is not
= the volume of the conducting pathways (trachea and Bronchiosomething)
Establishing a tracheostomy results in decreased respiratory work
Non perfusing alveoli, PHYSIOLOGIC dead space
Work, which is defined as P x V is reduced because volume is reduced
You would decrease anatomic dead space with a tracheostomy
Another Q: The RQ for a man who uses 4 liters of oxygen and produces 3 liters of CO is 0.75
Respiratory Quotient
= The rate of Vco2/ Rate of vO2 How much CO2 you make/ How much O2 you use
RQ = CO2/O2 remember the 0.8
RQ quotient for a person taking pure glucose as food source is higher than normal (normal is 0.8, with pure
glucose is 1.0)
NOTE the RQ may be used to calculate the basal metabolic rate via the technique of indirect calorimetry
RQ: for fat = 0.7; for carb = 1.0
If the respiratory quotient is 0.7, the primary energy source is: fat, ketone bodies, glucose, etc.
Asthma
Signs/Symptoms of asthma attack
Airway Edema
Brochospasm
Increased Mucous secretion
Increased airway resistance
NOT Decreased Surfactant
Tx
Adrenergic Beta-2
Consequences of pts respiratory difficulty
Causes, Hypoxia, Hypercapnia, Tachycardia, Acute Respiratory Acidosis
NOT Increased Renal Bicarbonate Production
(Because Increased CO2 already shifts the equation back to having lots of Bicarb, so no need for
more)
Muscle
Motor Unit
Alpha motor neuron and all of the muscle fibers it innervates
Each muscle has several muscle fibers
Each muscle fiber is innervated by a single alpha neuron

19

Each alpha neuron innervates many muscle fibers


All of the fibers innervated by a motor neuron contract when that motor neuron fires an AP
In other words, when a nerve arrives at a motor unit, it will cause all of the motor unit to contract
Size Principle
Motor neurons are recruited in order of size
If small force is needed, only small fibers activated, etc.
Fractionation
You do NOT need to activate all motor units in a muscle at once
Recruitment with respect to motor neurons refers to progressive increase in the number of motor units involved

SEE http://www.sci.sdsu.edu/movies/actin_myosin_gif.html for a sweet Animation


Muscle Contraction (ABOVE PICS)
Controlled by nervous system
The sarcomere represents the basic contractile unit of muscle myofibril
APs traveling down somatic alpha motor neurons cause depolarization of the skeletal fibers at which they terminate
Neuromuscular junction = junction between the terminal of the motor neuron and a muscle fiber
When an AP arrives at a neuromuscular junction, calcium ions enter the nerve terminal causing the release of Ach
from synaptic vesicles within the motor neuron
Ach then binds to the nicotinic cholinergic receptors in the muscle fiber plasma membrane. This causes
depolarization which triggers an AP (the action potential travels along the membrane t-tubules)
Acetylcholine esterase is the NZ that is involved in the termination of the neuromuscular transmission
The depolarization of the skeletal muscle cell membrane by motor nerves is directly produced by the
change in end plate potential level to a critical value
Transmission of impulses from the motor nerve to the muscle cell regularly produces an action potential in
the muscle cell
This AP triggers the release of calcium ions from the sarcoplasmic reticulum
The calcium release form the S.R. into the cytoplasm is the 1st measurable event in the myofiber
following generation of an AP in the sarcolemma
Calcium is sequestered/stored in Sarcoplamic Reticulum
This leads to crossbridge formation between actin and myosin. These interactions are responsible for
the development of tension and the shortening of the fibers
The length-tension diagram shows that the maximum active tension of a muscle occurs when there
is maximum overlap of crossbridges
The excitation-contraction coupling is measured by the release of calcium from the sarcoplasmic
reticulum
Calcium binds to troponin C on the thin filaments Think C for calcium
Calcium ions trigger contraction of muscles when they bind to troponin
The stimulation of muscle contraction (via calcium) is mediated via troponin C (not mediated by
actin, tropomyosin, troponin I, or the sarcoplasmic reticulum)
Cardiac muscle only needs 1 Ca to activate, other muscles need 2 Ca2+
2 sites are always filled by Mg
Causes a conformational change in troponin that permits Troponin I to release from tropomyosin
and then tropomyosin changes allowing myosin and actin to bind
After calcium binds with troponin, tropomyosin moves from its blocking position permitting actin
and myosin to interact

20

High energy myosin binds weakly to actin subunits, however, when inorganic phosphate is
released from the myosin, the myosins bind tightly to the actin subunits
High energy myosin has ATP bound to it; upon release of Pi, myosin can bind tightly to actin
Energy stored in the high-energy myosin is discharged, and the myosin head swivel, pulling on the
thin filaments
Mg2+ comes in to Activate the ATPase, which then gives the energy to stroke
This repeated pulling of the thin filaments past the thick filaments toward the centers of the
sarcomeres draws the Z lines closer together, and the muscle fiber shortens (contracts)
During an isotonic contraction, the A band does not change in width or length
HIZ contracts!!!
H band, I band, and consecutive Z lines, sarcomeres, & series elastic elements do change
dimension
This process is repeated as long as calcium ions are bound to troponin and ATP is available
Once calcium ions are returned to the sarcoplasin reticulum, tropomyosin moves back into its
blocking position and prevents further interaction between high-energy myosins and actin subunits
Then contraction ceases and the muscle fibers relax
The dissociation of the actomyosin complex results from ATP replacing ADP on the myosin head
NOT rephosphorylation of ADP
Submaximal direct stimulus to skeletal muscle will cause some fibers to contract, but not the whole
muscle
Another Q: Ratio between the amount of work done & total energy expended determines the mechanical
efficiency of muscular contraction
A muscle devoid of tonus is atonic

Muscle Energy Sources


Another Q: ATPADP + Pi is the reaction providing the immediate source of energy for muscular contraction (1-2
seconds)
Then, creatine phosphate is used to rephosphorylate the now unbound ADP to ATP (next 2-5 seconds)
Glycogen is then the 3rd participant and is used to reconstitute both ATP and creatine phosphate
At moderate levels of muscle activity (>20 minutes), the predominant source of ATP is from FAs
Another Q: FAs is the predominant source of ATP at MODERATE levels (>60 min) of activity
During prolonged period of starvation, the primary fuel is NOT glycogen
Another Q: ATP is essential to the transformation of G-actin to F-actin
Types of muscle fibers:
Extrafusal fibers:
Fibers that make up the bulk of the muscle
Innervated by alpha-motor neurons (efferent neurons)
Provide the force for muscle contraction
Intrafusal fibers AKA muscle spindles
Are encapsulated in sheaths to form muscle spindles
Innervated by gamma-efferent (motor) neurons, slow conducting
Two types of fibers:
Nuclear bag fibers:
Detect fast, dynamic changes in muscle length and tension
Innervated by group 1a afferents fastest in body
Nuclear chain fibers:

21

Detect static changes in muscle length and tension


Innervated by the slower group II afferents
Chain gangs are slow
*NOTE:
Discharge of impulse in small motor (fusiform) neurons innervating muscle spindle serves to sustain
extrafusal muscle contractions
Another Q: the gamma efferent system controls the excitability of the muscle spindle
Spinal Reflex
*The spinal cord is the only structure in the CNS necessary for a simple reflex
Two important spinal reflexes influence the contraction of skeletal muscles
Stretch reflex:
It is initiated at receptors called muscle spindles that are sensitive to muscle length and tension
This reflex stimulates the stretched muscle to contract
Stretch reflex is monosynaptic (not withdrawal)
Another Q: The sensory endings serving the stretch reflex are classified as propriocecptors
An example is the patellar reflex (knee jerk reflex) in which the striking of the patellar tendon at the knee causes
the quadriceps muscle to contract and swing the leg forward
Another example of a spinal reflex is reflex shivering upon application of a local, cold stimulus applied to
an extremity but not leading to lowering of body temperature
Another Q: The tone of masseter muscle is maintained by stretch reflex (via muscle spindles)
Another Q: Strong stimulation of spindles in the masseter muscle results in contraction
Another Q: Tapping on the side of the face elicits a contraction of the masseter muscle; this is an example of a
stretch reflex
Fxns:
Maintain muscle tone for
posture
Increase efficiency for
locomotion
Postural reflexes are
maintain by muscle
spindles
Smooth out movements
Act as site of
coordination for higherorder inputs
Muscle spindles: (muscle
length and tension)
Are found within the
belly of muscles
Connective tissue sheath
that encloses 2-12
intrafusal muscle fibers
Consists of two afferent
fibers, group Ia and
group 2 fibers
Encapsulated intrafusal fibers that run in parallel with the main muscle fibers so that the spindle will stretch
when the muscle relaxes or stretches
Detect both static and dynamic changes in muscle length
The stretrching gives rise to a generator potential and ultimately to an action potential in the group Ia and 2
fibers that arise from the spindle
The intrafusal fibers in addition to being innervated by sensory fibers also receive motor innervation
from gamma efferents
The activation of these gamma fibers stretches the intrafusal muscle fibers and gives rise to an action
potential in the group Ia fibers
Relaxation of intrafusal muscle fibers decreases impulse activity in the group Ia fibers
Finer movements require greater number of muscle spindles in a muscle
3 components:
Specialized muscle fibers (intrafusal) see below
Separate from the exrafusal fibers, that make up the bulk of the muscle fiber
Sensory terminals: group Ia and II afferents
Wrapped around specialized muscle fibers (intrafusal fibers)

22

Motor terminalis: gamma motor neurons


Activation maintains the spindle sensitivity
Muscle spindles are the sensory organs concerned with maintenance of skeletal muscle tone
Another Q: The annulospiral (primary) ending of the skeletal muscle spindle is stimulated when the
muscle is stretched
Another Q: Frequency of impulse activity in the afferent nerve from a muscle spindle (Group Ia
afferent fibers) is increased by an increased activity in gamma efferent fibers AND a passive stretch
of the muscle
Spasticity is best characterized by exaggerated stretch reflexes
Constant stimulation of muscle spindle, leads to spastic paralysis
Golgi Tendon reflex:
Initiated at receptors called neurotendinous organs (golgi tendon organs)
Sensitive to tension which occurs as a result of muscular contraction or muscle stretch
Stimulates the contracted muscle to relax
Reverse of stretch reflex
Also depolarize in response to stretch, but this reflex inhibits alpha neuron causing the muscle to relax
Golgi tendon organs (tension):
Innervated by a single group Ib sensory fiber
Reciprocal inhibition
When the stretch reflex stimulates the stretched muscle to contract, antagonistic muscles that oppose the
contraction are inhibited
The neuronal mechanism that causes this reciprocal relationship is called reciprocal innervation
Reciprocal innervation is the process by which motor neurons to extensor muscles acting at a particular
joint are inhibited by stretch of the flexor muscles acting at the same joint
Jaw opening reflex
When a person bites down rapidly on an unexpectedly hard surface while chewing, the result is cessation of motor unit
recruitment in jaw closing muscles by causing a stimulation of periodontal mechanoreceptors
Jaw Jerk reflex
Is an example of a dynamic stretch reflex
Is seen when you tap on the chin, causes the masseter to jerk close
Reflex after-discharge????
Can be explained in terms of internuncial pool circuits
Internunial A neuron functionally interposed between two or
more other neurons
Types of muscle:
Smooth muscle
Contraction
First a hormone combines with a hormone receptor and activates a
G protein
Then the alpha subunit goes and opens the Calcium channel
Calcium comes in and binds to Calmodulin
Then the CaCM complex binds to Myosin kinase and
activates it
MK attaches phosphate from ATP to myosin
heads to activate the contractile process
A cycle of cross-bridge formation, movement,
detachment, and cross-bridge formation
occurs
Relaxation occurs when myosin phosphatase
removes phosphate from myosin
Characterized by:
Slow Ca2+ channels
NO transverse T tubules
NO Troponin
Ach Stimulates Think glands and rest and digest muscles
from Parasympathetic
Spontaneous activity in the absence of nervous stimulation
(Hormones arent nervous!)
They have intrinsic nerves that are contained within
plexuses (GI myenteric plexus)

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Sensitivity to the chemical agents either released locally from nerves, or carried in the circulation
They could cause the release of more Ca2+
Another Q: Slow wave potentials are commonly observed in smooth muscle
Another Q: The contractile process in smooth muscle involves actin & myosin
Another Q: Smooth muscle contraction can be maintained for a longer time than skeletal muscle contraction
Another Q: Smooth muscle contains each of the following muscle proteins:
Actin, myosin, tropomyosin (but not troponin)
Another Q: In smooth muscle contraction, myosin kinase is responsible for initiating cross-bridge cycling
Skeletal muscle
Has the greatest membrane potential difference across the membrane
NO slow Ca2+ channels
Has Transverse T tubules
NOT inhibited by Ach
Cardiac muscle
(Calcium-induced Calcium release)
Contraction is dependent on Extracellular Ca2+, which enters the cells during plateau of action potential and
stimulates Ca2+ release from the cardiac muscle Sarcoplasmic reticulum
Cardiac is different than skeletal because:
Action potential has a plateau, which is due to the Ca2+ influx
Cardiac nodal cells spontaneously depolarize, resulting in automaticity
Cardiac myocytes are electrically coupled to each other by gap jxns
A type of striated muscle containing transverse tubules, a slow rate of calcium sequestration, & is inhibited
by Ach
The strength of cardiac muscle contraction is increased when extracellular Ca 2+ is increased
Muscle Cells/Energy
Use the Phosphorylated form of creatine to store energy
Normal metabolism cannot supply energy as quickly as a muscle cell can use it, so an extra storage source is needed
The phosphate group can be quickly transferred to ADP to regenerate ATP necessary for muscle contraction
Autoregulation of bloodflow in muscle determined by muscle metabolites (PAL: K+, lactate, adenosine)
Adenosine causes vascular smooth muscle to relax
Your muscles relax because ATP has been broken down to adenosine
Phosphate compounds found in living organisms can be divided arbitrarily into two groups based on their standard free
energy hydrolysis:
Higher phosphate group-transfer potential than ATP:
Phosphoenolpyruvate
Acetyl phosphate
1,3-diphosphoglyceric acid
Carbamoyl phosphate
Creatine phosphate
***1,3-diphosphoglyceric acid & creatine phosphate are energy-rich phosphate carriers
Lower phosphate group-transfer potential than ATP: (Sugars and De-Pi Creatine)
Glucose-1-phosphate
Fructose-1,6-diphosphate
Glucose-6-phosphate
Creatine
ATP and muscle contration
Hydrolysis of ATP (ATPADP + Pi) provides immediate source of energy for muscle contraction
Although muscle fibers contain only enough ATP to power a few twitches, its ATP pool is replenished as needed
Sources of high-energy Pi:
Creatine Pi
Glycolysis of glucose from stored glycogen
Cellular respiration in the mitochondria of muscle fibers
Slow vs. Fast Twitch
Fast twitch are twice as large
Twice for Type II
Characteristic
Slow Twitch (type I) Think Fast twitch (type II)
O2
Myosin-ATPase activity
Low
High
Speed/intensity of contraction
Slow/low
Fast/hight

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Resistance to fatigue
Oxidative capacity
Enzymes for anaerobic Glycolysis
Mitochondria
Sarcoplasmic reticulum
Capillaries
Myoglobin
Glycogen content

High
High
Low
Many (Youve got time for
Krebs)
Less extensive
Many
High
Low

Low
Low (Burn out quickly)
High
Few
More extensive
Few (white muscles)
Low
High

CNS
Spinal Cord
Gray Matter
Dorsal Horn (DRGanglia)
Sensory impulses
Anterior Horn (Ventral)
Motor impulses
White Matter
Consists of myelinated nerve fibers, which form the ascending and descending tracts
A tract represents a group of axons within the CNS having the same origin, termination, and function, and is
often named for its origin and termination (i.e., spinothalamic tract)
Sensory impulses
Travel via the afferent of ascending neural pathways to the sensory cortex in the parietal lobe of the brain
where they are interpreted
Sensory information is processed on the contralateral side
Spinothalamic tract (anterior and lateral)
Travel in the anterolateral quadrant of the spinal cord and are also called the anterolateral system
Sensations originate in the dorsal horns of the spinal gray mater, cross to the opposite side of the
cord and ascend via the spinothalamic tracts through the anterior and lateral white columns of the
cord to terminate at the levels of the brain stem and in the thalamus
Lateral spinothalamic tracts
Impulses concerned with pain and temperature
Anterior (ventral) spinothalamic tracts
Impulses from receptors sensitive to light touch
Dorsal Column-Medial Lemniscal System:
Carries sensations mainly in the posterior (dorsal) columns of the cord and them, after synapsing and
crossing to the opposite side in the medulla, upward through the brain stem to the thalamus by way
of the medial lemniscus
Conveys well-localized sensations of touch, pressure and vibration
Fasciculus gracilus
In the medulla, nerve fibers from the fasciculus gracilis synapse in the nucleus gracilis
Fasciculus cuneatus
Fibers from the fasciculus cuneatus synapse in the nucleus cuneatus also in the medulla
**Processes from the two nuclei cross to the other side of the medulla and give rise to a tract
called the medial lemniscus
Nerve fibers from the lemniscus synapse in the thalamus
**Spinocerebellar tract
Destruction of the left spinocerebellar tract at T2 would eliminate positional sense on the LEFT side of
the body below T2
Tract is IPSILATERAL
Motor impulses
Travel from brain to muscles via motor (efferent or descending) pathways
Originate in the motor cortex of the frontal lobe
These impulses reach the lower motor neurons of the PNS via the upper motor neurons
Two systems:
Pyramidal system (corticospinal)
Composed of lateral (70 90%) and anterior or ventral (10 30%) corticospinal tracts
Impulses in this system travel from the primary motor cortex through the internal capsule to
the medulla, where they cross to the opposite side and continue down the spinal cord
This system is responsible for fine, skilled, movements of skeletal muscle

25

Section of the pyramidal tracts produces loss of fine voluntary movements


Think it took fine, skilled movements to build the pyramids
Extrapyramidal system:
Impulses originate in the premotor area of the front lobe (and other areas) and travel to the
pons, where they cross to the opposite side
Then the impulses travel down the spinal cord to the anterior horn, where they are relayed to the
lower motor neurons. These neurons, in turn, carry impulses to the muscles
This system controls gross motor movements for posture and balance
Tracts in this system include
Rubrospinal, reticulospinal, olivospinal, vestibulospional, and tectospinal (neck muscles)
Flaccid Paralysis
Damage to the spinal nerves or to the cell bodies of lower motor neurons resulting in reduced
muscle tone, depressed stretch reflexes, and atrophy

Cerebellum
Situated below and posterior to the cerebrum and above the pons and medulla
Divided into two lateral hemispheres and a middle portion
Fxns:
Maintain equilibrium
Muscle coordination (voluntary movement)
Another Q: The cerebellum modifies the pattern of muscular response in reflex and voluntary contractions
Cerebrum
Divided into right and left hemispheres, which are connected by nerve fibers called the corpus collosum
Majority of the cortex is involved in associative and higher order functioning such as ideation, language, and thought
Frontal lobes: control skilled motor behavior (think pyramidal tract)
Parietal lobes: interpret somatosensory input
Occipital lobes: interpret visual input
Temporal lobes: interpret auditory input
Hypothalamus
Controls many homeostatic processes, which are often associated with the ANS
The major center in the brain for ANS regulation is the hypothalamus
Fxns:
Body temperature
A patients internal temperature is monitored by central thermoreceptors located in the hypothalamus
Stimulation of the anterior hypothalamus by a reduction in core temperature will produce shivering
Water balance
Appetite
Gastrointestinal activity
Carbohydrate metabolism (Gets out epi, which triggers glycogenolysis, etc.)
Sexual activity
Sleep
Emotions such as fear and rage
Growth
Ovulation
Does not control respiration (medulla does)
Does not control pupillary diameter
Does not control PTH
Also regulates release of hormones of the pituitary gland thus, it greatly affects the endocrine system
The hypothalamus-pituitary complex controls hormonal secretions of the corpora lutea, ovarian follicles, and interstitial
cells of the testes (NOT the parathyroids)
Thalamus
Large ovoid mass of gray matter that relays all sensory stimuli (except olfactory) as they ascend to the cerebral cortex
Output from the cortex also can synapse in the thalamus
Located in the lower region of the brain
Contributes to the subconscioius activities of the body, like controlling BP and respiration
Basal Ganglia
Includes:
Caudate nucleus
Putamen
Globus pallidus
Substantia nigra

26

Subthalamic nucleus
Function is control complex patterns of voluntary motor behavior
Basal ganglia & Cerebellum are large collections of nuclei that modify movements on the minute-to-minute basis
Cerebral cortex sends information to both, & both structures send information back to the cortex via the
thalamus
Output of the cerebellum is excitatory, while the basal ganglia are inhibitory
Balance between these two systems allows for smooth, coordinated movement, and a disturbance in either system
allows for smooth, coordinated movement, (i.e., Parkinsons, Huntingtons, Dysmetria and Ataxia)
Hippocampus
Functions in the consolidation of memories and in learning
Sea Horse Shape
Brain stem
Lies immediately inferior to the cerebrum, just anterior to the cerebellum
Consists of:
Midbrain
Connects dorsally with the cerebellum
Contains large voluntary motor nerve tracts
Pons
Connects cerebellum with the cerebrum and links the midbrain to the medulla oblongata
Serves as the exit point for cranial nerves V, VI, and VII
Medulla oblongata:
Lowermost portion of the vertebrae brain, continuous with the spinal cord
Joins the spinal cord at the level of the foramen magnum
Contains the cardiac, vasomotor, and the respiratory centers of the brain
Responsible for blinking, coughing, vomiting, and swallowing (not patellar reflex)
Breathing ceases upon destruction of the medulla oblongata
The activity of the respiratory center is decreased directly by increased pH (increased pH means there is
not excess CO2 causing increased H+ [ pH])
Things that can alter the function of the medullary centers for respiration:
1)The central & peripheral chemoreceptors
Nucleus tractus solitarius and nucleus retro ambiguus are the nuclei in the medulla responsible for
generating the respiratory rhythm
Peripheral chemorectors from the aortic and carotid bodies synapse onto the NTS in the medulla to
increase respiration
2)The apneustic & pneumotaxic centers in the pons
Apneustic center
Initiates respiration by activating the inspiratory center in the medulla
Inhibited by lung stretch receptors (Hering-Bruer Reflex)
Remember Hockey, and the Ducks play on the PONd (Pons)
Pneumotaxic center
Inhibitory center in the upper pons
Stimulated by medullary inspiration neurons during inspiration to inhibit the apneustic
center until inspiration stops and expiration begins
3)The CNS at the conscious level
A note on swallowing (no where else to put it):
In swallowing, the larynx is elevated, respiration is inhibited, the epiglottis covers the trachea, & the
eustachian tubes open
Before swallowing can be initiated, afferent information must be received from mucosal mechanoreceptors,
indicating the consistency of soft bolus of food
Trouble swallowing pills
Limbic system
Primitive brain area deep within the temporal lobe
Located in the mid-basal region of the brain
Initiates basic drives (hunger, aggression, emotional feelings and sexual arousal)
Emotional feelings are most closely linked to the limbic system in the brain
Screens all sensory messages traveling to the cerebral cortex
Nerve
Lets put this one 1st, in case it shows up: Tetrodoxin blocks sodium channels in nerve-axon MBs (its the puffer fish
poison)
Membranes

27

Action potential is initiated by a depolarizing stimulus:


If it reaches threshold (about 20 mV positive to resting membrane potential) an excitable cell will fire an AP
If neuron does not reach this critical threshold level, then no AP will occur (all or none)
So long as they can reach the threshold, suprathreshold stimuli produce the same AP that threshold stimuli do
Excitable cells include neurons and muscle cells

Depolarization
Makes membrane potential less negative (interior of cell becomes less negative)
Following a depol, a membrane is then more permeable to Na+, which causes a further depol and the opening of
Na+ channels
Membrane potential actually reverses (becomes positive inside the overshoot) as the Na+ influx drives membrane
potential towards Na+ equilibrium potential
If an axonal MB transiently becomes very permeable to Na + ions, the cell MB potential approaches +60mV
Another Q: A depolarized membrane is more permeable to ion flow
Another Q: The generation of an action potential is attributed to a rapid but brief increase in Na+ conductance
Another Q: an AP is related to the entry of Na+ followed by the exit of K+
Another Q: Under normal conditions, the resting potential across a muscle cell membrane is lower than the
equilibrium potential for potassium because the membrane has a low permeability to the sodium ion
Another Q: Sodium permeability of an axon membrane is maximal during the ascending limb of the action potential
Another Q: The primary ionic movement during the depolarization phase of a nerve AP is best described as sodium
ions moving from outside the MB to inside the MB
Another Q: The generation of the spike or action potential is attributed to a rapid but brief increase in Na+
conductantce
If a nerve cant produce ATP, then the intracellular level of Na+ will slowly rise cant use Na+/K+ ATPase!!
Repolarization
Occurs due to:
Rapid decrease in membrane perm to Na+ (stop flowing in)
Slower increase in membrane perm to K+ (start leaking out)
Hyperpolarization
Membrane potential becomes more negative
Happens because K+ conductance is greater than at rest (relative refractory period)
if you have high extracellular potassium, what occurs?
SAME AS Failed Pump
SAME as Digoxin which prolonges contraction and wrings out the heart longer and more efficiently
SAME as HyperKalemia
Gradual hyperpolarization this is what I put Because K+ cant rush out and make cell more neg
again
Case in point Hypokalemia can produce a hyperpolarized cell membrane potential
Many K+ channels remain open for several milliseconds after repolarization of the membrane is complete
Increased K+ conductance allows for additional K+ efflux, leaving the interior of the cell more negative (the
overshoot)
This opening of K+ channels, although delayed, is due to the initial depolarizing stimulus

28

Relative refractory period


The phase at which Sodium activation is ending
In order to trigger a second AP, the depolarizing stimulus must be of a greater magnitude to achieve
threshold
Increased K+ permeability (not change in Na+ perm) has primary control over the relative refractory period
The relative refractory period of a nerve corresponds to increased potassium permeability
Absolute refractory period
Determined by the duration of Na+ inactivation gate closure
No matter how strong the second stimulus, the AP cannot be propagated, as H ball is stuck, inactivating the
Sodium channel
The length of the absolute refractory period limits the maximum frequency of effective nerve stimulation
Resting membrane potential (RMP):
Difference in electrical charge between the inside and the outside of the cell membrane of an unstimulated
(nonconducting) neuron
Due to an imbalance of charged particles (ions and proteins) between the extracellular and intracellular fluids
More positive ions (cations) outside the membrane and more negative ion (anions) on the inside
The membrane is said to be polarized (a voltage exists [called the RMP] across the membrane)
RMP varies, but in excitable cells runs between (-) 40 and (-) 85 millivolts
If one could extract the cytoplasm from a resting neuron and measure it, the electrical charge would be negative
Comes from 2 activities:
There is a resting K+ membrane potential which allows (+) charges to leave cell down their electrochem. gradient
In most excitable cells this is the most important determinant of RMP
The Na+/K+ pump establishes the Na+ and K+ gradients across the membrane using ATP
This pump is electrogenic, i.e., it exchanges two K+ ions into the cell for every three Na+ ions it pumps out of
the cell for each ATP that binds to the cytoplasmic-side ATP binding site, resulting in a a net loss of positive
charges within the cell
Cardiac Glycosides (digitoxin) block this pump and keep the inside of the cell more positive and closer to
its threshold, thus increasing cardiac contractility
Ouabain inhibits by binding to the K+ site
The resting potential of a nerve membrane is maintained by active transport of Na + & K+ ions
Another Q: an example of primary active transport is the movement of potassium into a nerve cell
Another Q: Visceral smooth muscle & cardiac pacemaker cells both lack a stable RMP
Another Q: The gradual (phase 4) depolarization in a pacemaker cell is generated by progressively
decreasing K+ conductance, meaning leaky K channels are becoming less leaky
Another Q: At rest, the potential difference across the membrane of skeletal muscle is the greatest (more than the
sinoatrial node & visceral smooth muscle)
Which changes can slow down the rate of the pacemaker cell?
Threshold becomes more positive
The rate of spontaneous depolarization decreases
The maximum diastolic potential (resting potential) becomes more negative
Nernst Equation

n is the number of electrons transferred in the half-reaction.


E0' is the formal electrode potential
E is the electrode potential
Allows you to compute the electric potential difference required to produce an electrical force that is equal to and
opposite to the force of the equilibrium
At the peak of the action potential, the rapid increase in sodium conductance causes the membrane to move toward the
equilibrium potential for sodium
Another Q: The limit of the peak of the AP is solely determined by the Nernst equilibrium potential for Na+ between the
inside of the axon and the surrounding tissue fluid
Think K+ controls the Baseline (RMP)
Think Na+ controls the Changes
Local anesthetics and the membrane
Reversibly block impulse conduction and produce reversible loss of sensation at their administration site
Small, myelinated nerve fibers which conduct pain and temperature sensations are affected first, followed by touch,
proprioception, and skeletal tone

29

Bind to the inactivation gates of fast voltage gated Na+ channels, stabilizing them in a closed position, effectively
prolonging the absolute refractory period
This decreases Na+ membrane permeability, and therefore reduces membrane excitability
Local chemical anesthetics block nerve conduction by preventing the increase in membrane permeability to Na+
When the excitability has been reduced below a critical level, a nerve impulse fails to pass through the anesthetized
area
K+, Ca2+, and Cl- conductances remain unchanged
When anesthetics are applied to a neural membrane:
K+ flux remains unchanged
Pores of the membrane become "frozen"
There is a Ca2+ flux through the membrane?????
Resting potential does not drop to a more negative value
Conduction
An impulse can travel from one nerve to another in only one direction because the synapse limits the direction of travel
Another Q: An AP initiated at the midpoint along the length of an axon will propagate towards BOTH the soma & the
nerve ending
NOTE: The impulse from the 2nd Q will terminate at the soma, because of the reasoning in the 1st Q
Unmyelinated neurons
Impulse travels along the entire membrane surface and is known as continuous conduction
It is relatively slow (1.0 m/sec)
Myelinated neurons
Myelin sheath decreases membrane capacitance and increases membrane resistance Makes you jump,
preventing movement of Na+ and K+ through the membrane
Conserve energy since the Na+ and K+ pumps have to re-establish concentration differences only at the nodes of
Ranvier (spread .2m and 2mm apart)
Travels up to 100 m/sec
Saltatory conduction:
Increase the velocity of nerve transmission along myelinated fibers
Allow repolarization to occur with little transfer of ions
Depends on the presence of nodes of Ranvier
Conduction velocity depends on:
Diameter of nerve fiber an increase in diameter reduces resistance to current flow down the axon
Presence of myelin sheath
Neurilemma (aka sheath of Schwann or Schwanns membrane)
Thin membrane spirally enwrapping the myelin layers of certain fibers, especially those of peripheral nerves, or the
axons of certain unmyelinated nerve fibers
All axons of PNS have a neurilemma (made up of the outer layer of Schwann cells) around them
When a Schwann cell is wrapped successively around an axon it becomes a myelin sheath
Peripheral fibers can sometimes regenerate if the soma (cell body) is not damaged and some of the neurilemma
remains intact
The neurilemma forms a regeneration tube through which the growing axon reestablishes its original connection
If the nerve originally led to a skeletal muscle, the muscle atrophies in the absence of innervation but re-grows when
the connection is re-established
Regeneration of severed axons does not take place in the CNS because of the absence of a neurilemma
***NOTE:
Right-sided lesions of the spinal cord result in loss of motor activity on the same side, and pain &
temperature sensation on the opposite side
Remember Motor crosses above in the medulla, where pain crosses right away at the spinal cord
Synapse
Anatomical junction between 2 neurons depolarization of presynaptic cell initiates a response in postsynaptic cell
An axon terminal of a presynaptic neuron closely approaches a dendrite or cell body of a postsynaptic neuron
But, the two cells are separated by a small synaptic cleft
Neurotransmitters are stored within the axon terminal of a presynaptic neuron in synaptic vesicles
When an AP depolarizes the presynaptic MB, voltage-gated calcium channels are opened causing an increase in
intracellular calcium
Calcium causes the synaptic vesicles to empty the neurotransmitters into the synaptic cleft
Neurotransmitters diffuse across the synaptic cleft and bind to specific receptors on the postsynaptic cell
This process is called synaptic transmission and the time required is called synaptic delay
Synaptic delay explains the following phenomenon:

30

When an impulse is carried by a chain of two or more neurons, the total transmission time is greater than
the sum of the transmission times for each neuron
Electrotonic or Subthreshold potentials examples:
Inhibitory post-synaptic potentials
Excitatory post-synaptic potentials
Generator potentials in Pacinian corpuscles
Endplate potentials at the neuromuscular jxn
End Plate Potentials
Depolarization of the skeletal muscle cell membrane by motor nerves is directly produced by the change in the endplate potential level to a critical value
Another Q: If AChE is inhibited, there will be prolongation of the endplate potential
Miniature End-Plate Potentials (MEPP)
Due to the release of subthreshold amounts of Ach
Spatial Summation
Occurs when two excitatory inputs arrive at a postsynaptic neuron simultaneously converging circuits
This increases probability of causing an AP in the postsynaptic neuron (excitatory postsynaptic potential = EPSP)
Results from the convergence of several afferent impulses on the same postsynaptic nerve soma
Another Q: Spatial summation in spinal reflexes is dependent upon simultaneous arrival of impulses from a large
number of receptors
Temporal Summation
Occurs when two excitatory inputs arrive at a postsynaptic neuron in rapid succession
There is an increase in the frequency of nerve impulses in a single presynaptic fiber
The amplitude of the AP may be increased by increasing the extracellular concentration of Na+
Tetany
Point at which nerve signals are arriving fast enough to cause a big steady contraction, not just individual twitches
A tetanic contraction results from a high frequency stimulation

**When are nerve fibers hypoexcitable


During Positive after-potential:
Spontaneous or inducible increase in transmembrane potential following the completion of repolarization
In the heart, this usually corresponds to the U wave on the EKG
Excitatory neurotransmitters in the CNS
Depolarize the postsynaptic membrane bringing it closer to threshold and closer to firing an AP
The altered membrane potential is known as an excitatory postsynaptic potential (EPSP)
Includes: Ach, NE, Epi., Dopamine, Glutamate, Serotonin
Inhibitory neurotransmitters (including glycine and GABA) in the CNS
Hyperpolarize the postsynaptic membrane moving it away from threshold and farther from firing an AP
An inhibitory postsynaptic potential (IPSP)
could result from either an increase in membrane permeability to Cl-, which must run into the cell, or an
increase in membrane permeability to K+ out of the cell
GABA
GABA increases the permeability of postsynaptic membranes to chloride ions ClGlutamate decarboxylase, which catalyzes formation of GABA by decarboxylation of glutamate, is unique to
nervous tissue
Cl- then hyperpolarizes the cell, making it harder to feel pain
Secreted by nerve terminals in the spinal cord, cerebrum, basal ganglia, and in the cortex
Glycine
binds to specific receptors (mainly in the spinal cord) opening chloride channels
Glycine is the immediate precursor for creatine, purines & porphyrins
CNS (= spinal cord + brain)
Peripheral Nervous System (afferents from sensory receptors to CNS + efferents from CNS to muscles, organs, glands)
Somatic nervous system
Consists of:
12 pairs of cranial nerves and 31 pairs of spinal nerves
Autonomic nervous system: has two subdivisions:

31

Actions of the ANS are largely involuntary (in contrast to those of the somatic system)
Also differs from the somatic system in using two efferent neurons from the CNS to the effector
Preganglionic neurons arise in the CNS and run to autonomic ganglia in the body
Here they synapse with postganglionic neurons, which run to the effector organ (cardiac muscle, smooth
muscle, visceral organs, or glands)
Preganglionic autonomic nerve fibers are exclusively cholinergic
Postganglionic neurons have their cell bodies in the autonomic ganglia and synapse on effector organs
Sympathetic nervous system
Ganglia located in the paraverterbral chain or prevertebral ganglia
Preganglionic neurons originate in the spinal cord segments T1L3 (thoracolumbar)
Pregang symp cell bodies are found in thoracic & lumbar segments of the spinal cord
Uses Ach (cholinergic)
Majority of sympathetic post G are noradrenergic (NE)
Exception: BVs in skeletal muscle, terminal fibers to the adrenal medulla (Ach) & sweat glands
use Ach at muscarinic cholinergic receptors
When the sympathetic nervous system is activated, arterial pressure, mental activity, blood glucose
concentration and blood flow to skeletal muscles all increase (blood flow to the skin does not increase)
NE is NOT used at the terminal sympathetic fibers to the heart epinephrine is
High ratio of postganglionic sympathetic to preganglionic is indicative that stimulation of the sympathetic
NS leads to widespread effects
Sympathetic Stimulation most likely produces Bronchial Dilation
Parasympathetic nervous system
Ganglia located in or near effector organs
Preganglionic neurons originate in the nuclei of cranial nerves in spinal cord segments S2S4 (craniosacral)
Uses Ach (cholinergic)
Postganglionic fibers are all cholinergic
Innervation of salivary gland cells in humans is predominantly parasympathetic postganglionic
Main nerves of the PNS are the vagus nerves
They originate in the medulla oblongata
Each preganglionic PS neuron synapses with just a few postganglionic
The synapses in the CNS are the most susceptible sites in the nervous system to acute anoxia
Absence or almost complete absence of oxygen from inspired gases, arterial blood, or tissues; to be
differentiated from hypoxia.
Receptors/Neurotransmitters
Cholinergic receptors
Use Ach as neurotransmitter
Membrane receptor proteins located on autonomic postganglionic neurons or on effector organs regulated by Ach
They are always excitatory in preganglionic
Effects of postganglionic PS can be either excitatory or inhibitory (PS fibers innervating heart cause a slowing)
Preganglionic autonomic neurons (both Symp and PS) and all postganglionic PS
Ach is released at sympathetic ganglia, parasympathetic ganglia, somatic efferents to skeletal muscles, & terminal
sympathetic fibers to the adrenal medulla (but not at terminal sympathetic fibers to the heart) Nor is NorEpi
Muscarinic:
Located on all effector organs innervated by postG neurons of the PS division
Located on those effector organs innervated by postG cholinergic neurons of the Symp division (e.g., sweat
glands)
Nicotinic:
Located at the ganglia of both the Symp and PS divisions
Neuromuscular junction:
Ach is the neurotransmitter released from the presynaptic terminal and the postsynaptic membrane
contains a nicotinic receptor
Ach opens Na+ channels in the motor endplate resulting in depolarization and the opening of voltage
gated Na+ channels in the sarcolemma
Leads to an AP in the skeletal muscle fiber which travels down the transverse tubules resulting in
a release of calcium from the sarcoplasmic reticulum and muscle contraction
Ach Synthesis
Synthesized in the neurons from which it is released
Choline acetyltransferase catalyzes formation of Ach from acetyl CoA & Choline in the
presynaptic terminal
Stored in the synaptic vesicles

32

Following its release form the presynaptic terminal, Ach is rapidly broken down into acetate and
choline by the enzyme Actylcholinesterase (AChE)
AChE is responsible for the termination of neuromuscular transmission
Another Q: If AChE is inhibited, there will be prolongation of the endplate potential
Receptors: structures that are generally activated by changes (stimuli) in either the internal or external
environment of the body. As a result of the activity of these receptors, nerve impulses are initiated within
the sensory nerve cells
Adrenergic receptors:
Membrane receptor proteins located on autonomic effector organs that are regulated by catecholamines (Epi & NE)
Two main types:
Think 1s are Cons, and the 2s are both Relaxers
Alpha
Alpha 1: located on smooth muscle, produces excitation (contraction or constriction)
Alpha 2: located in presynaptic nerve terminals, platelets, fat cells, and the walls of the GI tract; produce
inhibition (relaxation or dilation)
Beta
Beta 1: located in the heart; produces excitation (increased HR, and contractility)
Beta 2: located on smooth muscle; produce relaxation (dilation)
Treatment of asthma symptoms requires activation of the adrenergic beta-2 pathway
NE stimulates mainly alpha receptors (remember NE doesnt go to the Heart)
Epi stimulates both alpha & beta receptors
Epi at high concentrations B 1 predominates, like Anesthesia, but at low, its B 2 and does vasodilation
Monoamine oxidase (MAO)
Enzyme that catalyzes the oxidative deamination of monoamines such as NE, serotonin, and Epi
Normally NE is uptaken into the nerve endings via active transport or diffused away into body fluids and then
into the blood, but if there is some left over, MAO takes care of it
This deamination process aids in metabolizing excess neurotransmitters that may build up at post-synaptic terminals
MAO is present in the nerve endings themselves
MAOIs increase the available stores of serotonin, NE and epi
Two classes of receptors:
Exteroceptors:
Respond to stimuli from the body surface, including touch, pressure, pain, temperature, light, and sound
Two-point discrimination requires that two sensory receptors are innervated by two different axons
Interoceptors:
Sensitive to pressure, pain, and chemical changes in the internal environment of the body
Baroreceptors
Aortic Arch
Transmits via vagus nerve to medulla
Carotid Sinus
Transmits via glossopharyngeal nerve to medulla
Specialized types of receptors:
Photoreceptors:
Specialized receptors that are sensitive to light energy
Located only in the retina of the eye (specifically the rods and cones)
Mechanoreceptors:
Sensitive to pressure or stretch
Pacinian corpuscles, muscle spindles, golgi tendon organs, Meissners corpuscles, and hair cells which transduce the
senses of hearing and balance
Tactile Sensation
Meissners corpuscles, found in demal papillae
Meissners corpuscles are rapidly adapting touch receptors for 2 point discrimination
Merkels and Pacinian are slowly adapting
Thermoreceptors
Free nerve endings sensitive to changes in temperature
Chemoreceptors
Stimulated by various chemicals (in food, the air, or blood)
Receptors for:
Taste (taste receptors)
Sensations of taste are generated in the taste buds and conveyed to the CNS through CN VII & IX and X
Low threshold of taste for BITTER
Smell (olfactory receptors)

33

Monitoring pH & gas levels in the blood (osmoreceptors and carotid body O2 receptors)
Peripheral
Carotid and Aortic bodies
respond to decrease in PO2, increased PCO2, and decreased pH
Peripheral carotid body receptors are stimulated most effectively by low arterial O2 tension
Another Q: Increased pulmonary ventilation at high altitudes results directly from the effect of
hypoxia on the carotid body
Central
Respond to changes in PCO2 and pH of CSF, which are influenced by systemic PCO2
DO NOT directly respond to PO2
NOTE on taste/smell: The following are similar characteristics of taste & smell: ??? from 2001 pilot
Receptors are replaced regularly
There are primary classes of taste & odor
Receptors are located on cilia or microvilli at the apical ends of cells
Molecules must be dissolved in saliva or mucus to interact with receptor membrane proteins
Not correct: Receptors initiate APs directly to respective cranial nerve sensory fibers
Smell does have directly firing AP cells with ciliary sensors
BUT TASTE uses G Protein mechanism, Do NOT have axons, and do NOT generate own APs
Nocioceptors
Free nerve endings sensitive to painful stimuli
Proprioceptors
Type of interoceptor that provides information concerning the position of body parts, without the necessity of
visually observing the parts
Located in muscles, tendons, joints, and the vestibular apparatus
These sensory receptors serve the stretch reflex
Intracellular Receptors
Remember, steroid hormones can go directly into the cell w/o using an Extracellular receptor and cAMP, etc.
Primary recognition of B-estradiol by its target cell, depends upon the binding of its hormone to a specific
cytoplasmic receptor
The principal mechanism by which glucocorticoids stimulate their target cells is by activating specific genes
Adaptation (to constants They both have 2 Ts)
is a property of certain receptors through which they become less responsive or cease to respond to stimuli of constant
intensity
Accomodation (to change)
the property of a nerve by which it adjusts to a slowly increasing strength of stimulus, so that its threshold of excitation
is greater than it would be were the stimulus strength to have risen more rapidly
Facilitation
The enhancement or reinforcement of a nervous activity by the arrivals of signals from other neurons
Another Q: The generator potential of a receptor is characterized by being graded according to strength of the stimulus
Special Sensory Organs
Retina:
Innermost layer of the eye
Receives visual stimuli and sends the info to the brain
Photoreceptors called rods and cones compose the visual receptors of the retina and contain photopigments
Four different types of photopigments, each consisting of a protein called opsin to which a chromophore molecule
called retinal is attached
Opsins differ from pigment to pigment and confer specific light-sensitive properties on each photopigment
Retinal (retinaldehyde) is produced by vitamin A
Rods and Cones:
Rods:
Contain a photopigment called rhodopsin
Their response indicates different degrees of brightness characterized by relative lack of color discrimination
They are numerous in the periphery of the retina
Visual purple is seen with rhodopsin in the retina
Usually formed in the retina
During dark adaptation (night vision) rhodopsin is synthesized in the rods of the retina
NOT part of accommodation for near vision
Rods are more abundant, have higher sensitivity, and lower acuity compared to cones
Cones:

34

Primarily responsible for color vision


Three different types of cones (red, green, blue)
Each one contains a different photopigment and is selectively sensitive to a particular wavelength of light
Concentrated in the center of the retina especially in the fovea
Principal photoreceptor during daylight or in brightly lit areas
Intraocular structure:
Sclera:
Tough white outer layer; maintains size and form of the eyeball
Cornea:
Transparent dome on surface of the eye
Serves as a protective covering & helps focus light on the retina at the back of the eye
Iris:
Circular colored area of the eye
Amount of pigment in the iris determines the color of the eye
The ciliary body is made up of three muscles and the iris
It controls the lens thickness
Pupil:
Circular opening (black area) in the middle of the iris, through which light enters the eye
Pupil size is controlled by the papillary sphincter muscle, which opens and closes the iris
Lens:
Situated directly behind the iris at the papillary opening, by changing its shape, the lens focuses light onto the retina
Choroid:
Lines the inner aspect of the eyeball beneath the retina; very vascular
The eyeball itself is divided into two segments, each filled with fluid
Anterior segment
Has two chambers (anterior and posterior)
Filled with aqueous humor (watery fluid)
Posterior segment
Filled with vitreous humor (thick, gelatinous material)
Made with Type II Cartilage
Eyes:
Changes during accomodation for near vision:
Constriction of pupils
Convergence of eyeballs
Contraction of ciliary muscle
Problems with eyesight:
Myopia (nearsightedness) (My opia, its what I have)
The primary effect of myopia is related to eyeball length relative to refractive power of the lens
The eye is too long for the refractive power of the lens, and far objects are focused at a point in front of the
retina
The eye can focus on very near objects
Tx with concave lenses
Hyperopia (farsightedness)
The eyeball is too short for the lens, and near objects are focused behind the retina
A slight detachment of the retina results in a decrease of length from the optical center, and the subject
therefore exhibits farsightedness (99% sure that farsightedness is the answer)
So in a detached retina, you cant read!
Distant objects are focused correctly
Tx with convex lenses
Astigmatism
Occurs when the curvature of the lens is not uniform
Tx with cylindric lenses
Presbyopia
Inability of the eye to focus sharply on nearby objects
Results from the loss of elasticity of the lens with advancing age
Tx with bifocals
Miosis
The constriction of the pupil of the eye
Can be caused by a normal response to an increase in light, certain drugs or pathological conditions

35

Mydriasis
Prolonged abnormal dilation of the pupil of the eye induced by a drug or caused by a disease
Parts of the ear: Pg. 474 Netters h&n anatomy
External ear:
Auricle (pinna)
Directs sound waves
External auditory canal (meatus)
Contains hair and cerumen (brown earwax) serves as a resonator
Middle ear:
Air-filled cavity in the temporal bone
Auditory (eustachian) tube:
Equalizes pressure
Ear aches may develop as a result of blockage of the eustachian tube because pressure in the middle ear is not
equalized with atmospheric pressure
Ossicles (malleus, incus, stapes)
Link together to transmit sounds to the oval window
Inner ear:
Formed by a bony labyrinth and a membranous labyrinth
Vestibule (saccule and utricle):
Associated with sense of balance
Responsible for static positioning (affected by gravity)
Responds to LINEAR acceleration or deceleration
Semicircular canals:
Concerned with equilibrium, angular acceleration and deceleration
Each one contains an enlarged region called the ampulla containing the receptor organ, the Crista ampullaris
The receptor contains hair cells whose processes are embedded in a gelatinous matrix
Rotary acceleration in any plane will cause a sense of rotation opposite to the direction of the endolymph
displacement
An angular (NOT LINEAR) acceleration or deceleration represents an adequate stimulus for semicircular canals
Cochlea (contains two membranes, vestibular and basilar):
Portion of inner ear responsible for hearing
The spiral organ (organ of Corti)
Responsible for perception of sound
Contains receptors (called hair cells) for hearing
Basic functional unit of hearing it transforms fluid vibration from sound waves (mechanical energy) into
a nerve impulse (electrical energy)
Impulses for hearing are transmitted to the brain from receptors in the cochlea
Low pitch, low frequency (Bass) at the apex or middle of the snail
High pitch, High frequency at the big base of the snail
The Elderly lose which type first? High pitched or at the base

GI System
Ptyalin AKA amylase
NZ in the saliva for digesting starches
The regulation of Gastric Secretion
Cephalic stage:
Eating, tasting, smelling, and thinking about food increases the rate of gastric secretion via activation of the PS
nervous system, specifically the vagus

36

The cephalic phase of gastric secretion is a reflex mediated by the vagus nerve
What allows your stomach to become bigger?
Receptive relaxation is an increase in the stomach volume before the arrival of food
Vagotomies are sometimes used to control gastric ulcers
Vagus nerve also causes contraction of the gallbladder (not part of the cephalic stage)
Gastric stage:
Stretch associated with a volume of food filling the stomach also increases the rate of gastric secretions
This phase accounts for about 70% of the total gastric secretion
Involves both neural reflex pathways and the release of gastrin
Gastrin:
Enteroendocrine cells (gastrin or G cells) of the pyloric glands of the stomach mucosa secrete it
Absorbed in the blood and carried to the oxyntic glands (gastric glands) in the body of the stomach
There it stimulates the parietal cells to secrete HCL
Relaxes the pyloric sphincter, activates the pyloric pump, and contracts the esophageal sphincter
THINK opposite to the enterogastric reflex
Intestinal stage:
The delivery of acidic, high osmolarity food/stuff into the small intestine
Inhibits gastric secretion via the enterogastric reflex and hormonal mechanisms (secretin)
Esophagus
Nitrous Oxide
Causes smooth muscle relaxation (lower esophageal sphincter)
Gastric glands of stomach mucosa:
Stomach glands produce as much as 23 liters of secretions per day
The pH of gastric secretion is 1.03.5
Gastric juice usually has a [H+] > 1x10-3 M (among answer choices of bile, urine, saliva, & pancreatic juice)
The mucus produced by mucus-secreting cells is very alkaline and protects the stomach wall from being exposed to the
highly acidic gastric secretion
G cell
Secretes Gastrin
Stimulates secretions of Acid, IF, and Pepsinogen
Stimulates Gastric motility
Inhibited by secretin or stomach pH <1.5
Stomach emptying is enhanced by gastrin & the presence of food in the stomach
Mucous neck cells (pyloric glands):
Secretes Mucus and some pepsinogen
Adheres to the stomach walls, lubricates the walls and protects the gastric mucosa from acidic secretions
Chief (peptic or zymogenic) cells:
Secretes Pepsinogen
Formed inside chief cells in the inactive form (pepsinogen)
In the upper part (Fundus) of the stomach
Once pepsinogen is secreted & comes in contact with previously formed pepsin in the presence of HCl, it is
converted to form active pepsin
Begins protein digestion
The most important function of HCl is activation of pepsinogen
Then that active pepsin, activates its other pepsinogen buddies
Does NOT secrete Bicarbonate
Parietal (oxyntic) cells:
K+ and Cl- go out of the cell via a cotransporter
Then K+ goes back down the gradient formed by that cotransporter via the H+/K+ ATPase and H+
goes out causing gastric acid
Secretes HCl
Kills bacteria, breaks down food, activates pepsinogen to pepsin
Sterilizes chyme
Stimulated by histamine, Ach, and gastrin
Inhibited by Prostaglandin (PGI2 and PGE2) and GIP
NOT essential for digestion
Secretes Intrinsic factor
Vitamin B12 absorption in terminal ileum
So no parietal cells, you get pernicious anemia
Secretion is increased by Ach, gastrin and histamine

37

Peptic ulcers can result either from the oversecretion of acid and pepsin or a diminished ability of the mucosal
barrier to protect against these secretions
Intestinal secretions
Mainly mucus, are secreted by goblet cells and enterocytes
The pH of the secretions in the small and large intestines is 7.5-8.0
Surface cells (duodenum)
Bicarbonate
Neutralizes acid
Stimulated by secretin (potentiated by vagal input) CCK
I cells (duodenum and jejunum)
Cholecystokinin (CCK)
Stimulates gallbladder, and pancreatic enzyme secretion
Inhibits Gastric emptying
Stimulated by FAs and AAs
Augmented flow from the gallbladder during feeding results in part from the release of CCK
Stimulates gall bladder contraction, releasing bile
Bile
pH ~7.8
Produced by the liver and stored in the gallbladder
Composed of bile salts, phospholipids, cholesterol, bilirubin, and water (97%)
Aids in the emulsification, digestion, and absorption of fats
S cells (duodenum)
Secretin
Natures antacid
Stimulates pancreatic Bicarb secretion
Inhibits gastric acid secretion
Stimulated by FAs and AAs
D cells (pancreatic islets and GI mucosa)
Somatostatin
Inhibits Gastric acid and pepsinogen secretion, Pancreatic and intestine fluid secretion, Gallbladder contraction,
and Release of both insulin and glucagons
Stimulated by acid and inhibited by the vagus
Vasoactive Intestinal Peptide (VIP)
Secreted by smooth muscle and nerves of the intestines
Relaxes intestinal smooth muscle
Causes pancreatic bicarb secretion
Inhibits gastric H+ secretion
Pancreatic secretions
From pancreatic acinar cells include enzymes involved in protein breakdown including:
Alpha-amylase starch digestion, secreted in active form
Proteases protein digestion, secreted as proenzymes
Trypsin Converted from trypsinogen by enterokinase, then trypsin activates the other proenzymes
Chymotrypsin
Elastase
Carboxypolypeptidase
Lipase Fat digestion
Bile salts aid in the action of pancreatic lipase
Activated by?
Acid, Trypsin, Enterokinase , bile salts
Cholesterol esterase
Phospholipase A Fat digestion
Pancreatic enzymes are secreted in an inactive form and are then activated in the small intestine
Pancreatic duct cells (I cells?) secrete a fluid that is high in bicarbonate ion concentration (pH of 8.0 8.3)
Pancreatic secretions stimulated by:
Ach Major stimulus for zymogen release, poor stimulus of bicarb
CCK Major stimulus for enzyme-rich fluid by pancreatic acinar cells
Secretin Stimulates ductal cells to secrete bicarb-rich fluid
Somatostatin Inhibits the release of gastrin and secretin
Gastric empyting:
Foodstuff entering the duodenum, especially fats and acidic chyme, stimulates hormone release
Hormones released in duodenum:

38

Gastric inhibitory peptide (GIP)


Inhibits the pyloric pump
So, fat ingestion most markedly affects (inhibits) the rate of gastric emptying
ParaSympathetic activation
Usually excitatory in the GI tract
Increases production of saliva
Increases H+ secretion
Increases pancreatic enzyme and Bicarb secretion
Stimulates enteric nervous system to create peristalsis and relax sphincters
Sympathetic activation can have either excitatory or inhibitory effects
Increases the production of saliva (serous watery, parotid)
Decreases splanchnic blood flow in flight or fight response
Decreases motility
Constricts sphincters
Stimulation of the sympathetic nervous supply to the gastrointestinal tract generally causes inhibition of motility
Chyme
Semifluid contents of the stomach, consisting of partially digested food and gastric secretions
The volume and composition of chyme that enters the duodenum (beginning of the small intestine) exerts a major
influence on gastric motility and the rate of gastric emptying
When a portion of the small intestine becomes distended with chyme, the stretch of the intestinal wall elicits localized
rhythmic contractions, called segmentation
Segmentation (aka rhythmic segmentation)
Occurs at a rate of 11 to 12 cycles/min in the terminal ileum
The contractions chop the chyme many times a minute
In this way they promote progressive mixing of the food with digestive secretions of the small intestine
Intensity can be influenced by mechanical, neural, and hormonal inputs
For example, distension of the intestine by chyme and
PS neural activity both increase the contractile force,
while Symp neural activity decreases it.
Two major types of contractions in the GI tract:
Peristalsis:
Contraction generates propulsive movements
Starts when food enters the stomach
Mixing contraction:
Serve to spread out the food and increase the surface area
available for digestion and absorption
***Smooth muscle control in the GI tract is under the
control of the myenteric plexus of the enteric NS
Entering the intestinal mucosa:
Fatty acid:
In the lumen of the small intestine, dietary TGs are
emulsified by bile salts into smaller fat droplets (micelles)
where they are enzymatically digested into free FAs and 2
monoglycerides
The free FAs and monoglycerides readily diffuse across
the brush border by simple diffusion
Then are reconstituted in the ER into TGs and finally
transported by lymphatics
Dipeptides and amino acids
The end-products of protein digestion
The final digestive stage occurs by brush border peptidases
and absorption immediately follows
Absorption across the brush border occurs by multiple
secondary active transports utilizing either the Na+ or
H+ gradients
Disaccharides and small glucose polymers
Occurs at duodenum and proximal jejunum
Hydrolyzed at the brush border by lactase, sucrase,
maltase and alpha-dextrinase

39

The resultant monosacchariades, glucose and galactose are then absorbed by secondary active transporters
driven by the Na+ gradient this is an example of a co-transporter
The immediate energy source for glucose transport into
intestinal endothelial cells is a Na+ gradient across the
luminal MB
The Odd-ball Fructose absorption is mediated by
Facilitated diffusion (F for F)
The following secrete HCO3- into the GI tract:
Colon mucosa
Salivary glands
Stomach mucosa
(NOTE: Chief cells do not)
Liver
Functions of liver:
Bile formation
Protein metabolism (deamination of aa, , formation [not
elimination], plasma protein formation, synthesis of aa)
Another Q: Death from advanced liver disease caused by
Hepatitis C is PRIMARILY due to inhibition of urea
synthesis
Steroid conjugation
Carbohydrate storage
Prothrombin synthesis and fibrinogen production
Another Q: Thrombin itself is not found in blood plasma, only its precursor prothrombin
Liver disease results in missing prothrombin and fibrinogen (not thrombin)
Detoxification
Gluconeogenesis
Formation of plasma proteins
Regulation of blood sugar level
NOT Secretion of digestive NZs
Bile is NOT an NZ, it is an emulsifying agent
NOT elimination of urea
Gluconeogenesis:
Occurs mainly in the liver (90%), but the kidney is a minor contributor (10%)
During prolonged starving the kidney becomes the major glucose-producing organ
Is the synthesis of glucose from compounds that are not carbohydrates
Glucose can be made from lactate, glycerol, pyruvate, and fructose (but not acetyl CoA, which comes from
FAs)
Glucokinase
Found only in the liver and functions at a significant rate only after a meal
This enzyme uses ATP to catalyze the phosphorylation of glucose to glucose-6-phosphate during glycogen synthesis
Then the G-6-phosphate cannot diffuse back out of the cell membrane and can be used to make glycogen
**Other tissues use hexokinase to do the same thing as glucokinase
ONLY hexokinase is feedback inhibited by Glucose-6-Phosphate
**Liver does not participate in the regulation of immediate blood glucose
Functions of liver in protein metabolism:
1. Deamination of amino acids:
Required before they can be used for energy or before they can be converted into CHO or fat
2. Formation of urea for removal of ammonia from the body fluids:
The liver is the organ pimarily responsible for the formation of urea
Removes ammonia from body fluids if the liver fails to do this, the result is a hepatic coma and death
Urea cycle
Ordinarily, Careless Crappers Are Always Freaks About Urination
Ornithine + Carbamoyl phosphate
Citrulline + Aspartate Argininosuccinate (Fumarate),
Arginine Urea

40

Occurs almost exclusively in the liver


It represents the fate of most of the ammonia that is channeled there
Ammonia is converted to urea in the liver for eventual excretion
The level of non-protein nitrogen in the blood is due primarily to the level of urea
Another Q: The major component of non-protein nitrogen in the blood is urea
Another Q: The main product of protein nitrogen metabolism in urine is urea
The two nitrogen atoms that are incorporated into urea enter the cycle as ammonia and aspartate
1 from GLUTAMATE (ammonia), 1 from an AA (aspartate)
Urea is produced by the hydrolysis of arginine, which is ureas direct precursor
Another Q: Arginase directly catalyzes urea formation in a cell
Carbomyl Pi is formed from carbon dioxide and ammonia
The first two reactions (ammonia to carbamoyl Pi then added to Ornithine to form Citrulline) occur in the
mitochondria, whereas the remaining cycle enzymes are located in the cytosol****
Ordinarily Careless Crappers
Nitrogen can also come from Carbomyl Pi : Glutamic acid goes to NH3 + CO2 = carbamyl phosphate
Urea that is formed in the urea cycle is passed via the blood stream to the kidneys & is excreted into urine
Carbamoyl Pi is added to ornithine to become citrulline
Aspartate is added to citrulline to make argininosuccinate
Fumarate is released resulting in arginine
Arginine is hydrolyzed and yields urea and ornithine
3. Formation of plasma proteins:
Accounts for 90% of all plasma proteins
4. Ability to synthesize certain amino acids and other important chemical compounds from amino acids
The nonessential amino acids can all be synthesized in the liver
To do this for most aa, a keto acid having the same chemical composition (except at the keto oxygen) as that of
the aa is first synthesized
Then the amino radical is transferred through transamination from an available aa to the keto acid to take the
place of the keto oxygen
Cholesterol
Most abundant non-phospholipid component of the cell membrane
Least Polar
Fxns:
1) Primarily used by mammalian cells as a component of the cell membrane
2) Secondarily used as the immediate precursor of bile acid
3) Thirdly, used as precursor to various steroid hormones
Mainly synthesized in the liver from acetyl CoA
NADPH is necessary for the de novo synthesis of cholesterol AND FA SYNTHESIS
NADPH is used in the reduction of cholesterol
Key intermediates in biosynthesis of cholesterol are:
HMG CoA, mevaolonic acid, isopentyl pyrophosphate, and squalene

41

NOT Cholic acids


The major regulatory enzyme is HMG CoA reductase
Rate Limiting Enzyme of Cholesterol Synthesis HMG CoA Reductase
Statins inhibit HMG-CoA reductase
Bile salts are formed from cholesterol (via cholic acid)
Most endogenous cholesterol in the liver is converted into cholic acid
Another Q: In certain endocrine tissues cholesterol is converted to steroid hormones:
Testosterone
Cortisol
Progesterone
Estradiol
The most potent naturally occurring human estrogen
Estrogens a class of steroids that contains 18 carbon and an aromatic ring
Vitamin D is also formed from cholesterol by a series of reactions requiring the skin, liver and kidney
UV activation of precursors in the skin are required for vitamin D3 synthesis
Cholesterol absorption depends upon the presence of bile salts in the intestinal lumen
Cholesterol is mostly esterified with FAs when circulating in blood plasma
Circulating cholesterol is taken up into liver cells
Here it inhibits synthesis of additional cholesterol from acetyl CoA via allosteric inhibition of HMG CoA reductase
This provides intrinsic feedback control system to reduce excess cholesterol synthesis
Glucose
Liver releases glucose back into the circulating blood during exercise
The skeletal muscle and the brain take up this extra glucose
Liver has the major responsibility for maintaining blood glucose levels
Releases glucose into the blood during muscular activity and in the interval between meals
The released glucose is derived from two sources:
1) Breakdown of stored glycogen
2) Formation of new glucose by gluconeogenesis
Fasting State vs. Fed State
Fed State
Digestive System
Glucose (liver)
Glu-6-P Glycogen OR Glycolysis OR HMP Shunt
Amino Acids (liver)
Proteins OR Glycolysis
Chylomicrons (liver) Fatty Acids Glycolysis OR Fats VLDLs
Fasting State
Fatty Acids (liver)
Acetyl CoA Ketone Bodies
Amino Acids/Glycerol/Lactate (liver)
TCA Cycle Acetyl CoA Ketone Bodies
(liver) Glycogen
G6P Pyruvate Acetyl CoA Ketone Bodies
OR (liver) Glycogen
Glucose (out of the liver) Glucose
So, fasting for several hours leads to decreased liver glycogen
NOTE: Heres a question that uses info from all over the place:
Each of the following occurs during prolonged starvation:
Circulating T4 is converted to rT3 (reverse T3)
Ketoacidosis develops progressively
Insulin levels are depressed
(Primary fuel is not glycogen)
Glucose is required particularly by tissues such as the brain and RBCs
RBCs oxidize glucose to pyruvate and lactate
Glucose is the major fuel for the brain
It oxidizes approximately 140 g/day to CO2 and water, producing ATP
The brain contains no significant stores of glycogen, and is therefore completely dependent on the availability
of blood glucose
In skeletal muscle
Glucose is phosphorylated, then degraded by glycolysis to pyruvate, which is converted to acetyl-CoA and oxidized
via the citric acid cycle
Glucose is the major end-product of CHO ingestion
Liver enzymes:
Glutamate-pyruvate transmaminase (GPT): also called alanine animotransferase (ALT)
Glutamate-oxaloacetate transmaminase (GOT): also called asparatate aminotransferase (AST)

42

Kidney
Countercurrent mechanism: (picture)
The countercurrent theory is used to explain the functioning of the kidney
Essential for the concentration of urine
This is the mechanical system employed by a kidney dialysis machine (Counter current)
System in the renal medulla that facilitates concentration of the urine as it passes through the renal tubules
Responsible for secretion of hyperosmotic urine in response to elevated plasma osmolarity and requires that the
penetration of the loop of Henle into the renal medulla for the development of the medullary osmotic gradient
The loops of Henle are responsible for the establishment of an osmotic gradient within the medulla of the kidney
Depends on the special anatomical arrangement and transport properties of the loops of Henle
Countercurrent multiplier in the loops of Henle is dependent upon:
Active reabsorption of sodium ions by the thick ascending limb of the loop of Henle
Osmotic equilibrium between interstitial fluid and tubular fluid in the descending limb of the loop of Henle
Continued inflow of new sodium chloride from the proximal tubule into the loop of Henle
The sodium chloride reabsorbed from the ascending loop of Henle keeps adding to the newly arrived sodium chloride,
thus multiplying its concentration in the medullary interstitium
Countercurrent exchange in the medullary BVs, called the vasa recta
The vasa recta do not create the medullary hyperosmolarity but do prevent it from being dissipated and can carry
away the water which has been reabsorbed
Nephron
The kidneys basic structural and functional unit
Parts: pg 384 in First Aid
Proximal convoluted tubule:
Workhorse of the nephrons
Requires the greatest amount of ATP
80% of ATP is used for Na+ reabsorption
67% occurs in the PCT
Water Permeable!!!, as solutes get pumped actively, water follows
Reabsorption of ALL glucose and AAs, most of the bicarbonate, water, and Na+, chloride, phosphate, calcium
Secretes Ammonia which acts as buffer for secreted H+
Approximately 2/3 of the glomerular filtrate is reabsorbed in the proximal convoluted tubule
This includes 100% of the filtered glucose and amino acids
Another Q: The osmotic pressure of the filtrate at the end of the proximal convoluted tubule is about the same
as that of plasma
Another Q: Most fluid reabsorption by the kidney occurs here
Thin Descending limb of loop of Henle:
Reabsorption of solutes and water
Impermeable to Na+
Thick Ascending limb of loop of Henle (Thick and Thin)
Has a thick wet suit on
Impermeable to Water
Reabsorbtion Actively of Na+, Cl-, and K+
Indirectly induces the reabsorption of Mg2+ and Ca2+
This, in the thick portion, is the basis for the countercurrent multiplier activity
Henles loop is the segment of the nephron wherein the tubular fuid has the highest osmolarity &
osmolality
Osmolarity of 1400 at the bottom
Dont get clowned the Collecting duct is not part of the nephron
Distal convoluted tubule:
(controlled by aldosterone)
Secretion of H+ and K+
Proximal Secreted Ammonia
Reabsorption Actively of Na+ and ClReabsorption of Ca2+ is under control of PTH
Collecting duct
Where the distal ends of each distal convoluted tubule join
Reabsorbs Na+ in exchange for secreting K+ and H+ (controlled by aldosterone)
Secretes H+ and reabsorbs water (controlled by ADH = vasopressin)
Osmolarity of medulla can reach 1200-1400mOsm
Juxtaglomerular vs. Cortical Nephrons

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Juxtaglomerular
Have their renal corpuscles close to the base of the medullary pyramid
Have Long loops of Henle and long thin segments that extend into the inner region of the pyramid
Cortical
Have their renal corpuscles in the outer part of the cortex
Have Short Loops of Henle and the hairpin turn occurs in the distal thick segment
Intermediate
Inbetween the other two, duh!
Juxtamedular & cortical nephrons differ primarily in length of the thin segment of the loop of Henle
Glomerular filtration
Filtration process as blood flows through the kidney
Some of the plasma (16-20%) is filtered out of the glomerular capillaries and into the glomerular capsules of the renal
tubules as the glomerular filtrate
Formation of glomerular filtrate does not rely on diffusion
Another Q: Energy for filtrate formation is derived from the hydrostatic pressure of the blood
Glomerular filtrate contains everything contained in plasma (urea, glucose, NaCl) except plasma protein
Glomerular filtrate contains the same concentration as plasma does of urea, glucose, amino acids, and plasma
electrolytes
NOT Steroid hormones
Glucose & sodium chloride are filtered and subsequently reabsorbed
The fact that increased concentration of colloids in plasma diminishes the formation of filtrate supports that the
glomerulus acts like a simple physical microfilter
Glomerular Filtration Barrier
Composed of:
1. Fenestrated capillary endothelium (size barrier)
2. Fused basement membrane with heparan sulfate (negative charge barrier)
The charge barrier is lost in nephritic syndrome, resulting in albuminuria, hypoproteinemia,
generalized edema, and hyperlipidemia
3. Epithelial layer consisting of podocyte foot processes
Inulin:
A starch that is given by mouth
NOT natural, thats the creatinine one
Is freely filtered from the glomerular capillaries into Bowmans capsule, but does not undergo tubular secretion or
reabsorption
If the clearance of a substance which is freely filtered is < inulin, then there is a net reabsorption of the substance
If the clearance of a substance which is freely filtered is > inulin, then there is a net secretion of the substance
Measures Clearance Rate
Glomerular filtration rate (GFR)
Can be calculated by the clearance of inulin from plasma
GFR may be measured by a substance that is filtered but not reabsorbed or secreted (not creatinine)
A substance that is actively secreted by the kidney is not useful in measuring GFR; it is useful is measuring:
Renal blood flow
Renal plasma flow
Filtration fraction
Tubular Maximum
The rate at which a substance is cleared from plasma
Renal clearance equation
Cx = UxV/Px
Cx Volume of plasma cleared
Ux Urinary [ ] of x
V Urine Volume
Px Plasma [ ] of x
= (plasma volume completely cleared)/(unit time) = (urinary concentration of the substance * urine volume) /
(plasma concentration of the substrate)
Assessment of blood urea nitrogen (BUN) and serum creatinine can also be used to estimate the GFR
Creatinine is freely filtered, is not reasorbed, slightly secreted, and produced endogenously at a constant rate
Q: Creatine is not slightly reabsorbed
Another Q: Creatinine is the natural metabolite measured clinically as a predictor of GFR
(Dont mix this Q up with inulin)
Clearance rate for a substrate that is completely removed in one pass through the kidney = renal plasma flow

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Simply put, the amount of the substance removed correlates to the amount of plasma that flows through the kidney
Decrease in GFR is caused by:
Constriction of afferent arteriole:
Decreases the glomerular capillary hydrostatic pressure and decreases the renal blood flow (RBF)
Relaxation of efferent arterioles:
Decreases the glomerular capillary hydrostatic pressure
Increased plasma protein concentration of glomerular capillary blood:
Increases plasma oncotic pressure
Ureteral blockage (increased hydrostatic pressure in Bowmans capsule):
Blockage of urine transport through the ureters will increase hydrostatic pressure in Bowmans capsule
Capsule hydrostatic pressure is the major force causing glomerular filtration
Excessive constriction of the efferent arteriole will decrease RBF and GFR
Another Q: A proportionate increase in resistance of afferent and efferent arterioles of the kidney would
result in a decrease in RBF with no change in GFR
Increase in GFR is caused by:
Decreased plasma oncotic pressure (synonym with osmotic)
Vasodilation of afferent arterioles
Decreased pressure in Bowman's capsule
Moderate vasoconstriction of efferent arterioles
The most likely cause of an increase in filtration fraction is efferent arteriolar constriction
PAH used to measure eefective renal plasma flow
Both filtered and secreted and is used to estimate renal plasma flow
(Filtration of PAH is also know as Effective Renal plasma flow (RPF))
Secreted in proximal tubule
Secondary active transport system
Mediated by a carrier system for organic acids
Competitively inhibited by probenecid
Filtration Fraction
= GFR/RPF or Cinulin/CPAH
The most likely cause of an increase in filtration fraction is efferent arteriolar constriction
NSAIDs
Prostaglandins dilate afferent arterioles ( RPF and GFR, so FF stays the same)
So NSAIDs can cause renal failure because they inhibit the renal production of prostaglandins, which
normally keep the afferents dilated to maintain GFR
ACE Inhibitors
Angiotensin II constricts efferent afterioles ( RPF and GFR, so FF would increase)
End in PRIL
So if you inhibit ACE, no Angiotensin II and FF would be less)
Free Water Clearance
CH2O = V - Cosm
V = Urine flow rate
Cosm = Uosm V/Posm
Glucose Clearance
At a normal level, all glucose is reabsorbed in proximal tubule
At plasma glucose level of 200mg/dL, glucosuria begins (Threshold)
At plasma glucose level of 300mg/dL, transport mechanism is completed saturated (Tm)
Glucosuria can be caused by low insulin level, high blood sugar level, impaired tubular reabsorption, & high
GFR
The best explanation why glucose does not appear in the urine is that glucose is freely filtered, but is removed
by reabsorption in the proximal convoluted tubule
The normal clearance of glucose is 0 mg/min
Glucose transport from the lumen of the nephron depends on Na + transport (via a cotransporter)
The presence of glucose in the urine proves a person has exceeded his/her renal threshold for glucose
So a High renal threshold usually wont result in glucosuria
Amino Acid Clearance
Resorption by at least 3 different carrier systems, with competitive inhibition within each group
Secondary active transport occurs in proximal tubule and is saturable
Kidney normally excretes 1-2 L urine/day

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When tubular secretion and reabsorption processes are completed, the fluid remaining within the tubules is transported to
other components of the urinary system to be excreted as urine
Urine consists of water and other materials that were filtered or secreted into the tubules but not reabsorbed
Although about 180 L per day of glomerular filtrate are produced, the kidneys only excrete 1-2 L
Approximately 99% of filtrate is returned to the vascular system, while 1% is excreted as urine
Water and substances the body needs are returned to the blood, whereas waste products and excess fluid and solutes
remain in the tubules and are excreted form the body as urine
In response to elevated plasma osmolarity, a small volume of concentrated urine will be produced
If plasma osmolarity is lower than normal, a large volume of dilute urine will be excreted
Excretion rate = filtration rate reabsorption + secretion
Reabsorption
Movement of solutes from the tubular fluid into the interstitial fluid
Occurs in the following:
Proximal tubule
Loop of Henle
Distal convoluted tubule
Collecting duct
Processes include: 1 active transport, 2 active transport, facilitated diffusion, simple diffusion, and solvent drag
Transport can be either transcellular or paracellular
***The osmolarity of the renal fluid at the end of the proximal tubules equals that of plasma
Secretion
Movement of solutes from the interstitial fluid into the tubular fluid
Urine
Normal urine
Consists of Na+, Cl-, K+, calcium, magnesium, sulfates, phosphates, bicarbonate, uric acid, ammonium ions,
creatine, and urobilinogen
The main route of calcium excretion from a normal human adult is FECES
Is clear, straw-colored, slightly acidic, and has the characteristic odor of urea
Normal specific gravity of urine is between 1.005 and 1.030
Formation is important in the regulation of acid-base balance, maintenance of ECF volume and BP, and in
maintaining the normal osmolarity of ECF
Diuresis:
Results from a decrease in the tubular reabsorption of water (often after ingesting a large quantitiy of water)
Another Q: An osmotic diuresis is observed during diabetes mellitus
Causes of dilute urine:
Absence of ADH, diabetes insipidus
Causes of concentrated urine:
Decreased plasma volume, cellular dehydration, diabetes mellitus, excess ADH
Think in DM, all of the glucose in the urine, so it still is concentrated even though you get osmotic diuresis
to go with it
In cellular dehydration water moves from interstitial and Extracellular to inside the cells, now you have a
decrease in plasma volume
This decrease produces action potentials to the supraoptic hypophyseal tract and into the neural lobe of
the posterior pituitary resulting in the release of ADH
ADH of course gets water reabsorbed and leaves the urine more concentrated
***Na+ has the greatest influence on water retention, even more than Cl- & K+
The ability to concentrate urine is most closely related to the length of the loop of Henle
Ammonia
Produced from the metabolism of a variety of compounds
Amino acids is the most important because most Western diets are high in protein and provide excess aa, which are
deaminated to produce ammonia
Sources of ammonia:
From amino acids:
Many tissues, but particularly the liver, form ammonia from amino acids by the aminotransferase and glutamate
dehydrogenase reactions
From glutamine:
The kidney (specifically, the tubular cells) form ammonia from glutamine by the action of renal glutaminase
Most of this ammonia is excreted into the urine as NH4, which is an important mechanism for maintaining the
bodys acid-base balance
From amines:

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Amines obtained from the diet and monoamines that serve as hormones or neurotransmitters give rise to
ammonia by the action of amine oxidase
From purines and pyrimidines:
The catabolism of purines and pyrimidines, amino groups attached to the rings are released as ammonia
Amino acids are the source of most of the nitrogen in purines
Ammonia & the alpha amino acids:
Ammonia NH+ is formed from glutamine in the kidney
Cellular levels of ammonia must be maintained at low concentrations due to its toxicity
Glutamate dehydrogenase can catalyze the formation of glutamate from ammonia and a-ketoglutarate using NADPH
as a cofactor (SEE UREA CYCLE CHART)
Formation or urea in the liver is qualitatively the most important disposal route for ammonia
Urea travels in the blood from liver to kidneys, where it passes into the glomerular filtrate
Ammonia is excreted in high amounts after prolonged acidosis
Endocrine Fxns of the Kidney
Conversion of 25-OH vitamin D to 1,25-(OH)2 vitamin D via 1alpha-hydroxylase, which is activated by PTH
JG cells secrete erythropoietin to stimulate bone marrow and also secretes renin in response to decreased renal arterial
pressure and increased renal nerve discharge (Beta 1 effect)
Secretion of prostaglandins that vasodilate the afferent arterioles to increase GFR
Hormones that act on the Kidney
Vasopressin (ADH)
Induced by increased plasma osmolarity and decreased blood volume
Actions: H2O permeability, urea absorption in collecting duct, and Na+/K+/2Cl- transporter in thick
ascending limb
Aldosterone
Induced by decreased blood volume (via Angiotensin II), and by plasma [K+]
Actions: Na+ resorption, K+ secretion, H+ secretion in distal tubule
Angiotensin II
Induced by Decreased blood volume (via Renin)
Actions: Contraction of efferent arteriole ( GFR), Na+ and HCO3- reabsorption in proximal tubule
Atrial Natriuretic peptide (ANP)
Induced by Increased atrial pressure
Actions: Decreased Na+ reabsorption, GFR
PTH
Induced by Decreased plasma [Ca2+]
Actions: Ca2+ reabsorption, 1,25 (OH)2 vitamin D production, Decreased PO 43- reabsorption
Acid/Base Regulation
Kidneys regulate acid-base balance by the secretion of hydrogen ions (H+) into the renal tubules and the reabsorption of
bicarbonate ions (HCO3-).
Measured by urine pH, ammonium excretion and phosphate excretion
Secretion of ammonia is aid to the kidney in the elimination of H+ ions
Another Q: The kidney is the organ chiefly responsible for resistance to change in the blood pH
Hydrogen ions are secreted into the tubules by tubular cells
Secretion mechanism derives hydrogen ions from carbonic acid
Carbonic anhydrase
[CO2 + H2O H2CO3 H+ + HCO3-]
Present within tubular cells, and it catalyzes the formation of carbonic acid from carbon dioxide and water
Carbonic acid dissociates into hydrogen ion and bicarbonate
One of the fastest known enzymes and is found in great concentration in erythrocytes
Carbonic anhydrase in the kidney tubular cells is associated with reabsorption of bicarbonate ion
Although not required for CO2 and water to form carbonic acid, it greatly increase the reaction in both respects
Absence of carbonic anhydrase drastically reduces blood CO2 carrying capacity
Phosphate compounds (HPO) and ammonia (NH3)
The kidney can eliminate cations due to the high ratio of HPO42- to H2PO4Eliminating Cations, i.e. H+, just like HCO3- to H2CO3
Mechanism for recovering from metabolic acidosis
Act as buffers to tie up hydrogen ions in the tubular fluid
Ammonia is formed in the tubular cells by the deamination of certain aa, particularly glutamic acid
Ammonia interacts with the H+ and forms the ammonium ion to be removed from the body
It acts in the elimination of H+ in the kidney and allowing for the reabsorption of Na+ into blood
Secretion of ammonia aids in the elimination of hydrogen ion from the kidney

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Ammonia helps to reduce the Hydrogen Ion concentration in body fluids. This mechanism involves the
reabsorption of Sodium into the blood
Phosphate and ammonium excretion measurements provide good information on how much acid is being
eliminated by the kidneys because phosphate and ammonium buffer the acid
Phosphate compounds are excreted in combination with a cations such as Na+
Ammonium ions are excreted in combination with anions such as ClNormal blood bicarbonate:carbonic acid ratio is 20:1. A patient with 10:1 ratio is in uncompensated acidosis
SO basically you have a 20:2 ratio, more carbonic acid, so H+ needs to go out!!!!
The most important secretory mechanism for conservation of Na+ by kidney is H+ secretion for the reabsorption of
Na+ & HCO3- (1st Na+ is reabsorbed into epi cell from lumen via countertransport against H+, then the Na+
gets into the blood vessel via a cotransport with Bicarb)
Reproductive System
Male puberty:
During early childhood, a boy does not secrete gonadotropins, and thus has little circulating testosterone
During puberty, the penis and testis enlarge and the male reaches full adult sexual and reproductive capability
In males, growth and development of secondary sex organs are under direct control of testosterone
Puberty also marks the development of male secondary sexual characteristics
Secretion of gonadotropins from the pituitary gland, which usually occurs between the ages of 10 and 15, marks the
onset of puberty
The normal delay in sexual development until puberty is attributed to lack of hypothalamic stimulation of
gonadotropin release
Pituitary gonadotropins stimulate testes functioning as well as testosterone secretion
At puberty, an alteration in brain function leads to an increased production of gonadotropin-releasing hormone (Gn-RH)
by the hypothalamus
GnRH stimulates the secretion of FSH and LH (gonadotropins) by the anterior pituitary gland
The birth control pill inhibits the release of GnRH which thereby stops ovulation
It also alters endometrial lining so no implantation, and alter the cervical mucus making sperm less penetrable
These gonadotropins stimulate the growth and function of the testes
(FSH & LH act on both ovaries & testes)
FSH
promotes the maturation of sustentacular cells (Sertoli cells)
in females it does ovarian follicle development and secretion of estrogen from ovaries
(FSH, S for Sertoli & Sperm)
which are involved in sperm development and maturation
produce ABP (Androgen Binding Protein) which ensures that testosterone (testes?) is high in seminiferous
tubules
produce Inhibin, which inhibits FSH (negative feedback)
LH
stimulates the interstitial (Leydig cells) of the testes
(Leydig for LH)
to produce testosterone secondary sex characteristics
Anabolic Steroid Use
A person who used anabolic steroids, but who has recently stopped will experience
Low FSH, and LH levels
Low Testosterone levels
Decreased number of spermatids
NOT Sterility (Looked it up, it may take a few months, but gonads will get back to full production)
Androgens
DHT> Testosterone> Androstenedione
Testosterone is converted to DHT by 5alpha-reductase
Testosterone and androstenedione are converted to estrogen in adipose tissue by the NZ Aromatase
Functions
Differenetiation of wolffian duct system into internal Gonadal structures
Secondary sexual characteristics and growth spurt during puberty
Required for normal spermatogenesis
Anabolic effects: increased muscle size, increased RBC production
Inhibits GnRH (negative feedback)
Fuses epiphyseal plates in bone
Increased Libido (Whoo-whee!)

48

Female Puberty
Female reaches puberty 1 or 2 years earlier than males
Puberty is marked by the first episode of menstrual bleeding, which is called the menarch
An alteration in brain function leads to increased gonadotropins-releasing hormone (GnRH) secretion by the
hypothalamus
GnRH stimulates the secretion of FSH and LH by the anterior pituitary gland, which ultimately leads to an increased
production of estrogens (androgen hormone) by the ovaries
The events of puberty in the female (such as enlargement of the vagina, uterus, and uterine tubes; deposition of fat in the
breasts and hips) are largely a result of increased production of estrogens by the ovaries
Estrogen
Estradiol> Estrone> Estriol
Estradiol from the Ovary
Estriol from the Placenta
Functions:
Causes the development of female 2 sex characteristics (genitalia)
Causes the development of the breast
Maintains pregnancy
Growth of the follicle
Endometrial proliferation, myometrial excitability
Female Fat distribution
Hepatic synthesis of transport proteins
Feedback inhibition of FSH
LH Surge (Estrogen feedback on LH secretion switches to positive from negative just before LH surge)
Is effective at very low concentrations & generates a slowly developing long-term response in target tissues by binding
to an intracellular receptor
Contains 18 Carbons and an aromatic ring
Androgens do NOT (19 carbons, no ring)
Progesterones, Glucocorticoids, Mineralcorticoids (NO ring 21 Cs)
Estrogen Hormone Replacement Tx
Decreases risk of heart disease
Decreases hot flashes and postmenopausal bone loss
Unopposed Estrogen Tx
Increases risk of endometrial cancer
Decreased risk when used with Progesterone
Progesterone
Funtions:
Stimulation of endometrial glandular secretions and spiral artery development
Maintenance of Pregnancy
Elevation of progesterone levels is indicative of pregnancy
Decreased myocardial excitability
Production of thick cervical mucous which inhibits sperm entry
Increased body temp
Inhibition of Gonadotropins (LH, FSH)
Uterine smooth muscle contraction
Promotes secretory changes in the endometrium during the latter half of monthly period, thus preparing
endometrium for implantation of fertilized egg
hCG
Synctiotrophoblast of placenta
Maintains the corpus luteum for the 1st trimester by acting like LH
In 2nd and 3rd trimesters, the placenta synthesizes its own estrogen and progesterone and the corpus luteum
degenerates
Used to detect pregnancy because it appears in the urine 8 days after successful fertilization (blood and urine Testing)
Elevated hCG in women with hydatidiform moles or choriocarcinoma
Precocious puberty
A condition in which the changes associated with puberty begin at an unexpectedly early age
Results from hyperactive adrenal cortex
Is due to an excess of androgenic (in boys) & estrogenic (in girls) substance produced by the adrenal cortex
NOTE: Androgens are produced in the testis & the adrenal cortex
These substances resemble the male and female sex hormones
Menopause

49

Cessation of estrogen production with age-linked decline in number of ovarian follicles


Average age of onset is 51 (earlier in smokers)
Therapy - Estrogen replacement
HAVOC Hot flashes, Atrophy of Vagina, Osteoporosis, Coronary heart disease
Menstrual cycle:
Ovulation occurs 14 days before menses, regardless of cycle length
Average menstrual cycle usually occurs over 28 days, although the normal cycle may range from 22 to 34 days
Menstrual phase:
Aunt Flow begins the cycle
Cycle starts with menstruation (cycle day 1), which usually lasts 5 days
Proliferative (follicular) phase:
Lasts from cycle day 6 to day 14
LH and FSH act on the ovarian follicle (mature ovarian cyst containing the ovum)
This leads to estrogen secretion from the follicle, which in turn stimulates buildup of the
endometrium
Development of ovarian follicles to the point of ovulation is stimulated primarily by FSH Follicle
stimulating hormone
Late in this phase, estrogen levels peak, FSH secretion declines, and LH secretion increases, surging at midcycle (around day 14)
LH Surge (Estrogen feedback on LH secretion switches to positive from negative just before LH surge)
The LH surge leads to final maturation of follicle, rupture of follicle and ovulation
Another Q: ovulation is believed to be caused by a shift in anterior pituitary gonadotropin secretion with LH
predominating in the mixture
Without the LH, even though large quantities of FSH are available, the follicle will not progress to the
stage of ovulation
FSH and LH are both glycoproteins and act in both the ovaries (in females) and the testis (in males)
FSH is a polypeptide
FSH exerts its action on germinal epithelium
Then, estrogen production decreases, the follicle matures, and ovulation occurs
Ovulation:
Day 15 14 days after Day 1 of menstruation, BUT does VARY
Occurs as a result of the estrogen-induced LH surge
The discharge of an mature ovum (oocyte) from the follicle (Graafian follicle) of the ovary
The ovum generally disintegrates or becomes nonviable if it is not fertilized within 4 days
Progestins
Being used as oral contraceptive substance due to their ability to suppress ovulation
Remember Progesterone is usually the maintainer of pregnancy, so body is fooled into thinking its prego
Luteal (secretory) phase:
Lasts about 14 days
FSH and LH levels drop
The corpus luteum begins to develop, and it synthesizes estrogen and progesterone
hCG is promoting this in the 1st trimester
The blood concentration of estradiol does NOT increase as corpus luteum develops
This is why prego women are not horny in the 1st trimester, the corpus luteum is taking care of
itself and there is no circulating estradiol to stimulate them to go find their man!!
But the 2nd Trimester is Great The Madonna period
Ruptured mature follicle forms the corpus luteum, which secretes progesterone and estrogen
If fertilization does not occur, the corpus luteum degenerates (become nonviable)
As a result, estrogen and progesterone levels decrease until their levels are too low to keep the
endometrium in a fully developed secretory state
The endometrial lining is shed as menstrual fluid during menstruation or menses
Decreasing estrogen and progesterone levels stimulates the hypothalamus to produce GnRH, and the cycle beings
again
Two significant results of the female sexual cycle:
Only a single mature ovum is normally released from the ovaries each month so that only a single fetus can begin to
grow at a time
Lipids
Lipids:
Organic compounds that do not dissolve in water but do dissolve in alcohol and other organic solvents

50

Are not able to move in body fluids due to their hydrophobic nature so they are packaged in micellar structures called
lipoproteins
Various lipoproteins are classified in terms of density
Since lipids are much less dense than proteins there is an inverse relationship between lipid content and density
(i.e., high lipid content means low density particle) HDL good because little lipid content
The major components of lipoproteins being transported are phospholipids and proteins which make up the micellar
membrane (the protein component alone is called apolipoprotein)
The major lipids include triacyglycerols or TGs (the most common lipids) phospholipids, and steroids
Lipid is required in the average diet because it provides essential fatty acids
Another Q: Among cellular components, lipids are most characteristic of membranes
Another Q: Which of the following is least descriptive of lipids:
Hydrophilic (among answer choices of nonpolar, carbon-containing, and amphipathic)
Lipids that are relatively polar, contain more Oxygen
Triglyceride: (TGs)
Provide more than half the energy requirements of some organs, particularly the liver, heart, and skeletal muscle
When hormones signal the need for metabolic energy, TGs stored in adipose tissue are brought out of storage and
transported to those tissues (skeletal muscle, heart, renal cortex) in which FAs can be oxidized for energy production
TGs are not membrane constituents
TG is the principal lipid stored in adipose tissue
Phospholipids
Type of lipid that contains a phosphate group
Major lipid that makes up cell membrane
Would likely form a micelle when mixed with water & agitated
Like a phospholipid bilayer, but its only one layer, small circular
Another Q: Lipid micelles have spherical structures that are stabilized by hydrophobic interactions of lipid groups
The major driving force for formation of a liquid micelle is hydrophobic interaction between hydrocarbon tails
Three major types of Body Phospholipids:
Lecithins: (aka phosphatidylcholine)
Major component of cell membrane of RBCs, of myelin, of bile, and of surfactant (DPPC)
Phospholipid present in liver bile
They are water soluble emulsifiers
Are a group of phospholipids that upon hydrolysis yields:
1) Two fatty acid molecules
2) One molecule each of glycerol, phosphoric acid, and CHOLINE
Lipotropic effect of lecithin upon fatty liveralso produced by choline
Choline:
Another Q: Choline is an important lipotropic substance
Lipotropic substance one that promotes taking fat out of the liver
Another Q: Outer lamella of cell MB contains sphingomyelin & phosphatidylcholine (not
phosphatidylethanolamine)
Both choline and lecithin are lipotropic substances
A compound synthesized by the body and is found in most animal tissues
Is essential for the metabolism of TGs, particularly lipoprotein secretion, in the liver
A deficiency of choline in the diet can cause abnormalities in fat/lipid metabolism
Is a natural amine that is often classified with the B vitamins, although it is not a vitamin, and is a
constituent of many biologically important molecules such as Ach and lecithin
It prevents the deposition of fats in the liver and facilitates the movement of fats into the cells
When converted to betaine, is also a source of transferable methyl groups in metabolism
A deficiency of choline in animals leads to fatty liver disease and eventually hepatic cirrhosis
W/o choline you cant put fat in the other cells, because no choline no lecithin so no
lipotropic effect
Choline, choline phosphate and cytidine diphosphocholine are involved in the synthesis of
phosphatidylcholine, a major phospholipids constituent of membranes and lipoproteins. It is
synthesized de novo in liver cells
The cephalins:
A group of phospholipids having hemostatic properties and found especially in the nervous tissue of the brain
and spinal cord
They resemble lecithin, except they contain either 2-ethanolamine or L-serine in the place of choline
The sphingomyelins:
Phospholipids that are found especially in nerve tissue and yield:
Sphingosine, choline, a fatty acid, and phosphoric acid upon hydrolysis

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They are membrane constituents


Basic structure of phospholipids: glycerol + fatty acids + phosphate group + R group
Types of Lipoproteins:
Lipid-binding proteins, responsible for the transport in the blood
Chylomicrons:
Least dense lipoprotein
Most triglyceride and the least protein content
Transport primarily dietary triacylglycerols around the body and dietary cholesterol to the liver
Secreted by intestinal epithelial cells
Remember micelles emulsify in water to give phospholipids, (NOT TGs SEE PICTURE ABOVE)
Another Q: triglyceride absorbed into the lymphatic system is transported to the liver as chylomicrons
They are the largest of the lipoproteins
Are plasma lipoprotein
Carry FAs obtained in the diet to the tissues in which they are consumed or stored as fuel
Remnants of chylomicrons, depleted of their tracylglycerols but still containing cholesterol, move through the
bloodstream to the liver, where they are taken up, degraded in lysosomes, and their constituents recycled
VLDLs (very low-density lipoproteins):
More dense than chylomicrons
High content of triacylglycerides
Secreted by the liver
Transport endogenous (hepatic) triacylglycerols to various tissues (primarily muscle and adipose tissue)
LDLs (low-density lipoproteins):
Large spherical particles made of a core of esterified cholesterol surrounded by a lipid bilayer containing protein
Denser than VLDLs
Less TG and more protein content
High phospholipids content
Highest cholesterol content
Delivers hepatic cholesterol to peripheral tissues
They are the primary plasma carriers of cholesterol for delivery to all tissues carrying cholesterol, cholesterol esters,
and phospholipids from liver to body
Another Q: LDLs are transported into the cells by way of receptor-mediated endocytosis
When cholesterol is needed, a cell will make a receptor for LDL and insert the receptor in the plasma membrane
Then LDL binds to the receptor and is engulfed (via endocytosis)
When the cell has enough cholesterol, gene regulation for the LDL receptor is down regulated
Which one adjusts the Cholesterol level in blood?
LDL
HDLs (high-density lipoproteins):
Most dense lipoproteins
Has the lowest triglyceride and highest protein content
Transfers cholesterol as an acyl ester derivative from other tissues back to the liver
Mediates reverse cholesterol transport (from periphery to liver)
Secreted from both liver and intestine
Familial Hypocholesterolemia
The key problem is a decrease in LDL receptors
Comes with Xanthomas (Achilles heel)
Fats/TGs:
Contains three molecules of fatty acid combined with one molecule of glycerol
Neutral fats contain mixtures of one or more fatty acids esterified with glycerol
Is a long chain compound with an even number of carbon atoms and a terminal COOH group
Can be saturated, monounsaturated, or polyunsaturated
Classified by the number of double bonds between carbon atoms in their fatty acids molecules:
Ending in -ic
Saturated fat:
No double bonds between carbon atoms
Arachidic(spelled right) acid, behenic acid, butyric, capric, caproic, caprylic, lauric, myristic, palmitic, stearic
Upon complete hydrogenation, oleic, linoleic and linolenic acids yield stearic acid (20 cs)
Monounsaturated fat:
One double bond between carbon atoms
Erucic, oleic, palmitoleic
Polyunsaturated fat:

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Multiple double bonds between carbon atoms


Arachidonic, linoleic, linolenic
Prostaglandins are made within cells from polyunsatured fats
***Stearic oleic linoleic linolenic (arachidonic): a sequence that shows increasing number of double bonds
Arachidonic acid has the most double bonds, among oleic, stearic, and palmitic
Fatty acids:
Essential FAs cannot be synthesized because we lack the lack the enzymes to place double bonds at certain
positions (omega 3 and omega 6) and must therefore obtain them from the diet
Essential FAs:
Arachidonic, linoleic, and linolenic Polyunsaturated fats
Linoleic is a polyunsaturated fatty acid commonly found in animal cell MBs (thats why we eat those
animals)
All fatty acids are building blocks of phospholipids and glycolipids and are therefore needed for the synthesis of MBs
Cells derive energy from them through beta oxidation
The predominant source of ATP at moderate levels of activity (>20 min) are fatty acids
Freeing stored fat/Free fatty acids:
Epinephrine and glucagons
Increase glycogen and lipid breakdown
Activate adenylate cyclase
Lies in the adipocyte plasma membrane
Raises the intracellular concentration of cAMP
Activated by Epi, Glucagon, and PTH, NOT Insulin
A cAMP-dependent protein kinase, in turn, phosphorylates & thereby activates hormone-sensitive
triacylglycerol lipase
Mobilization of fat stored in adipocytes involves activation of triglyceride lipase by a cAMP dependent
protein kinase
cAMP is broken down by cAMP phosphodiesterase
Methyl xanthines such as caffeine & theophylline enhance lipolysis in adipose tissue by
inhibiting cAMP phosphodiesterase
Triglyceride Lipase
This NZ initializes the hydrolysis of the ester linkages of TGs forming 3 free FAs and glycerol
SIDE BAR Fat, monoglycerides, and Proteins are broken down by Hydrolysis
The 3 FAs that are released bind to serum albumin and travel to the tissues where they dissociate from
albumin and diffuse into the cells in which they will serve as fuel
Glycerol released by lipase action
Is phosphorylated by glycerol kinase, and the resulting glycerol-3-phosphate is oxidized to
dihydroxyacetone phosphate
This compound is then converted to glyceraldehyde-3-phosphate by the enzyme triose phosphate
isomerase
G3P is then oxidized via glycolysis to go on to make Pyruvate
Acetyl CoA Krebs
Insulin causes activation of a phosphorylase which dephosphorylates the hormone-sensitive lipase and thereby
diminishes lipolysis
Fatty acid degeneration occurs in the mitochondria and uses FADH+/NAD+ --- Think FAD Fatty Acid Degeneration
Degeneration occurs where its product (Acetyl CoA) will be used in Krebs!!
Fatty acid synthesis occurs in the cytosol and uses NADPH, other different enzymes, and Malonyl CoA
Both require phosphopantothenic acid (the Q discussed the 2 previous lines)
Fatty Acid Catabolism
Involves beta oxidation
Transported to the liver by employing carnitine as a carrier substance, which is inhibited by cytoplasmic MalonylCoA
Once inside the mitochondria, the fatty acid is transferred from the carnitine to a CoA and is oxidized (via beta
oxidation) to acetyl CoA
Acetyl CoA molecules enter into the citric acid cycle (Krebs cycle) to form carbon dioxide and reducing equivalents
(NADH, FADH2)
The reducing equivalents are then reoxidized by electron transport system and the energy released by that process is used
by the oxidative phosphorylation system to form ATP
18 carbon FA 9 molecules of acetyl CoA when broken down
Ketone bodies:
Acetoacetate
Synthesized by cleavage of B-hydroxy-B-methyglutaryl CoA

53

Which of the following is a ketone body? Acetoacetate (not glycerol, glucagon, acetyl CoA, and
phosphatidylcholine)
Beta-hydroxybutyrate
Sometimes referred to as D-Beta-hydroxybutyrate or 3-hydroxybutyrate
Acetone
Not utilized by the body as fuel
May normally leave the body via the lungs
Fruity smell of the breath
During conditions of low glucose availability (starvation or fasting, or a case of diabetes mellitus), adipose
tissue breaks down its triacylglycerol stores into FAs and glycerol, which are released into the blood
Glycerol is converted into glucose, by first getting converted to Glyceraldehye 3 Phosphate, which is an
intermediate in glycolysis, it makes Pyruvate, then because the brain needs energy, you get
gluconeogenesis happening to send glucose out of the liver to the brain
When there is inadequate insulin, utilization of fat for energy in increased
Through the process of -oxidation, the LIVER converts the FAs to acetyl CoA
Acetyl CoA is used by the liver mitochondria for the synthesis of the ketone bodies
The liver is the site for production of ketone bodies
Another Q: In relative insufiicient insulin, acetyl CoA is usually channeled into ketone-body formation
They are transported in the blood to peripheral tissues, where they can be reconverted to acetyl CoA and
oxidized by the citric acid cycle (Krebs cycle)
They are important sources of energy for the peripheral tissues
They are soluble in aqueous solution and therefore do not require carriers in blood
Unlike fatty acids, ketone bodies can be oxidized by the brain
Metabolized to 2 molecules of Acetyl-CoA by the brain
Under circumstances that cause acetyl-CoA accumulation (starvation or untreated diabetes, for example),
thiolase catalyzes the condensation of two acetyl-CoA molecules to acetoacetyl-CoA, the parent of the
three ketone bodies
High concentrations in the blood result in keto acidosis
Ketosis:
Condition characterized by an abnormally elevated concentration of ketone bodies in the body tissues and fluids
Occurs when fatty acids are incompletely metabolized, a complication of untreated diabetes mellitus, starvation,
fasting and alcoholism
In severe diabetic acidosis, one would expect an increase in plasma keto acids
Another Q: Excessive ketone bodies in blood & urine are possible indications of diabetes mellitus
Another Q: Ketosis may be produced experimentally by fasting
Characterized by ketones in the urine (ketonuria), K+ loss in urine, and a fruity odor of acetone on the breath
Acetone is a compound that may leave the body by way of the lungs
A diabetic coma can be caused by the buildup of ketone bodies
It is commonly fatal, unless appropriate therapy is instituted promptly
Glucose is the only effective substance in reversing ketosis in a non-diabetic patient
Another Q: Excessive use of fat as energy source can lead to ketosis, acidosis and ketonuria (but not alkalosis)
Fatty Acid Biosynthesis
WRITE OUT THE PROCESS: A good reference is pg. 66 in the blue Kaplan book called Biochemistry notes
Summary of fatty acid synthesis: Acetyl CoA malonyl CoA malonyl-ACP acetyl ACP acetoacetyl
ACP butyryl ACP fatty acid
Occurs in the cytosol, and gets there via a citrate shuttle
Active processes during FA biosynthesis: TCA cycle, pyruvate dehydrogenase, amino acid catabolism, glycolysis (not oxidation) these arent necessarily a part of FA biosynthesis; the Q is going for us knowing about -oxidation
Is not a simple reversal of -oxidation used for the catabolism of fatty acids
Involves two carbon additions from acetyl CoA and an acyl carrier protein (ACP)
Acetyl CoA is the immediate precursor for fatty acid synthesis
The important step
The first one in which acetyl CoA, ATP, and bicarbonate form malonyl-CoA
A key intermediate in the synthesis of FAs is malonyl-CoA, a 3-carbon intermediate, which is formed from acetylCoA, bicarbonate, and ATP
This is the committed step, the essential control point
Acetyl CoA is carboxylated by Acetyl CoA carboxylase to Malonyl-CoA
Similar to the carboxylation of Pyruvate to start gluconeogenesis
The pathway for synthesis of even-numbered fatty acids differs from that of the catabolism of fatty acids in that
malonyl CoA is an intermediate in synthesis
Another Q: CO2 is incorporated into acetyl coenzyme A, forming malonyl coenzyme A (2 Carbon 3 carbon)

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This irreversible reaction is the committing step in fatty acid synthesis and is the principal regulator Acetyl
Co A carboxylase
Kaplan
The diet is the primary source of FAs
The next source is from the biosynthesis
In many instances, the saturated straight chain 16 carbon acid palmitic acid is first synthesized and all other
FAs are made by modification of palmitic acid
Important points:
Glucose is first degraded to pyruvate by aerobic glycolysis in the cytoplasm
Pyruvate is then transported into the mitochondria, where pyruvate forms acetyl CoA (by pyruvate dehydrogenase)
and oxaloacetate (by pyruvate carboxylase)
Acetyl CoA and oxaloacetate condense to form citrate
Then Oxaloacetate can either go up the Gluconeogenesis tract to PEP via PEPCKinase (the committed Step)
OR Oxaloacetate plays an important role in the body by reacting with acetyl CoA to form citrate in the first step
of Krebs
Citrate, in turn, can be transported out of the mitochondria to the cytoplasm (where fatty acid synthesis occurs), and
there it splits to generate cytoplasmic acetyl CoA for fatty acid synthesis
Citrate is a positive modulator that allosterically regulates the enzyme catalyzing the rate-controlling step in the
de novo synthesis of fatty acids
Another Q: The enzyme that catalyzes the 1st step in the fatty acid synthesis pathway is acetyl CoA carboxylase
It is an allosteric enzyme & is the principal regulator of the pathway
So, for a little clarity, the 1st step of FA biosynthesis is the conversion of acetyl CoA to malonyl CoA
Citrate is a positive modulator of acetyl CoA carboxylase in this step
Acetyl CoA Carboxylase is the principal regulator of FA synthesis
Coenzyme A (CoA)
A pantothenic acid containing coenzyme that is involved in both fatty acid synthesis and catabolism
*Coenzyme A participates in activation of carboxyl groups
*Acetyl CoA is a common intermediate of the metabolism of fatty acids, amino acids and CHOs
Transporting FAs in the blood
The body uses 3 mechs for transporting FAs in the blood
1) FAs to albumin
2) Chylomicrons (Cholesterol binds to fat and phospholipids to form chylomicrons)
3) Ketone bodies (aceto-acetate and beta hydroxyl butyrate
Bile Salts:
Are sodium salts composed of cholic acid (cholate & deoxycholate most abundant) conjugated with glycine or taurine
to form glycocholate and taurocholate respectively
Sodium taurocholate/glycocholate are necessary for absorption of fatty acids. These are conjugated bile components
Bile salts are amphipathic (hydrophilic and hydrophobic)
Bile salts are synthesized in the liver and pass, via the bile duct, into the duodenum and then into the jejunum
They aid in intestinal digestion and absorption of lipids by emulsifying and solubilizing them in micelles
Reabsorption of the bile salt micelles occurs in the ileum, from which a large proportion return via the blood to
the liver
The bile ducts carry bile salts from the liver to the gallbladder, where they are stored; excreted (excess) cholesterol is
dissolved in the bile salt micelles
Overall 90% of bile salts involved in absorption of lipid from w/in the jejunum are recycled in a process called
enterohepatic circulation they are reabsorbed into the portal circulation and reused
Actions of bile salts:
Help in absorption of FAs, monoglycerides, cholesterol, and other lipids from the intestinal tract (form water-soluble
complexes [micelles] with FAs and glycerides)
Aid in the absorption of ADEK Vitamins
NOTE on micelles:
The major driving force for forming a lipid micelle is hydrophobic interaction between hydrocarbon tails
Have a detergent action on the fat particles in the food, which decreases the surface tension of the particles and
allows agitation in the intestinal tract to break the fat globules into minute sizes
Membrane
Cytoplasmic membrane = cell membrane:
Function is to regulate the flow of material into and out of the cell
A selectively permeable barrier, meaning that the movement of molecules across the MB is selectively restricted
Some small (<75), uncharged, nonpolar molecules move across the membrane quite readily
Molecules and ions that are large, highly charged &/or polar move across the membrane via transport systems

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Mammalian cell membranes do NOT have endotoxin (but they do have LPS)
Passive Diffusion
Simple diffusion
Simple diffusion is movement down its concentration gradient
No transport or carrier system is needed
Facilitated diffusion (aka Mediated Diffusion)
A form of passive diffusion that uses the assistance of transport or carrier proteins
Requires no energy & moves molecules down the concentration gradient
Mediated diffusion of substances across cell membranes differs from simple diffusion in that mediated
diffusion exhibits saturation kinetics
Because the carrier can become saturated by the presence of large solute concentrations
Another Q: Facilitated diffusion differs from active transport in that facilitated diffusion requires a concentration
gradient
Another Q: What characterizes both active transport & facilitated diffusion? Competitive inhibition
Another Q: The process involving nonpenetrating solutes (e.g., proteins) best describes facilitated diffusion
(The other answer options were osmosis, diffusion, & epithelial transport)
Active transport
Primary active transport uses energy derived from ATP
EX: sodium-potassium pump
Secondary active transport uses the gradient of one molecule to move another no direct ATP coupling is used
EXs: sodium-calcium exchanger (counter-transport), glucose symporter (co-transport)
The rapid movement of a substance across a biologic membrane against a concentration gradient requires the
participation of an energy-requiring active transport system
***Another Q: the movement of Ca2+ across many cell MBs involves a Ca2+/Na+ countertransport system
Active transport systems generally involve specific binding molecules that are protein (not lipid, lipoprotein, CHO)
Another Q: Active transport is distinguished from facilitated diffusion by its requirement of metabolic energy
Which of the following occur when active transport is involved in the movement of a solute across a biologic
membrane?
Expenditure of metabolic energy
A gain in free energy by the system (Because basically you are creating a potential energy state)
A unidirectional movement of the solute
Movement of the solute against a concentration gradient
Polar & hydrophilic
Molecules or groups that are soluble in water (e.g., ions, glucose, and urea)
Hydrophilic molecules require a carrier protein to cross the cell membrane
Nonpolar, hydrophobic
Molecules or groups that are poorly soluble in water (e.g., O2, CO2, and alcohol)
The cell MB is more permeable to O2, CO2, H2O, ethanol & palmitic acid than to Na+
Hydrophobic molecules are transported across cell membranes by simple diffusion
Cholesterol
Most abundant non-phospholipid component of the cell membrane
The least polar molecule when listed with ethanol, palmitic acid, & glycocholic acid
Another Q: Lipids that are relatively polar contain more oxygen
Amphipathic = amphiphilic
Both polar and nonpolar functional groups are essential for a substance to act an amphipathic molecule
An example of an amphiphilic molecule is phospholipid
Is a fluid mosaic model of lipids and proteins
The plasma membrane is described best as a fluid mosaic composed primarily of phospholipids, cholesterol and
glycoproteins
Another Q: The chief constituents of biologic membranes are lipids & proteins
Another Q: The most abundant nonphospholipid component of the cell membrane is cholesterol
The phospholipid forms the bilayer component
The hydrophilic head groups interact with water on both the extracellular & intracellular surfaces
The hydrophobic fatty acyl chains in the central portion of the membrane
Globular Proteins
Peripheral proteins are embedded at the periphery
Integral proteins
span from one side of the membrane to the other side & are associated with the hydrophobic phase of the
bilayer
May move freely within the plane of the membrane

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Integral proteins are the reason for the selective permeability of biological membranes
Leucine & valine are found on the interior of globular proteins (LV is the center of the Globe)
CHOs are attached to proteins and lipids on the exterior side of the cell membrane
The membrane mosaic is fluid because the interactions among lipids and between lipids & proteins are noncovalent,
leaving individual lipid and protein molecules free to move laterally in the plane of the membrane
The primary force stabilizing the lipid-protein complex in cell membranes is the hydrophobic interaction
Bilayers arise through the operation of two opposing forces:
1) attractive forces between hydrocarbon chains (van der Waals forces) caused by the hydrophobic effect forcing
such chains together
2) repulsive forces between the polar head groups
Lipid classes commonly incorporated into the cell membrane:
Phospholipids:
Sphinogomyelin
Phopsphatidylcholine
Gangliosides
Glycolipids found on various cell surfaces; have N-acetylneuraminic acid residues in addition to sphingosine
Named so because many cells in CNS ganglia have them
Cholesterolprimarily used as component in cell membrane
Six common features of biological membranes:
1. Sheetlike structure: only a few molecules thick (60-100 angstrom)
2. Consists mainly of lipids and proteins (CHOs are attached to exterior)
3. MB lipids small molecules with hydrophobic and hydrophilic groups that form lipid bilayers in aqueous media
The hydrophobic center of the bilayer forms a barrier to the flow of polar molecules across the membrane
4. The proteins function as transporters, enzymes, receptors, etc.
5. Are noncovalent assemblies: the proteins and lipid molecules are held together by many noncovaelnt interactions
6. Are asymmetric: inside and outside faces are usually different
The plasma membrane has most of the CHOs (as glycoproteins and glycolipids) on the outer face while
The lipids phosphatidylethanolamine and phosphatidylserine are more concentrated on the cytoplasmic face
Two examples describing an asymmetric model of membrane assembly:
Some membrane proteins may have their N-terminal residues predominately on one side of the membrane
The polar head groups of the phospholipids may be primarily oriented toward one side of the membrane
Proteins in cell membrane function as:
Transporters transport substances across the membrane
Enzymes catalyze biochemical reactions
Receptors bind hormones or growth factors
Mediators aid in triggering a sequence of events
pH

Buffer systems:
Most commonly consist of a weak acid (the proton donor) and a salt or conjugate base of that acid (the proton acceptor)
These systems minimize the pH changes brought about by a change in the acid or base content of the solution
These buffer systems reduce the effect of an abrupt change in H+ ion concentration by:
1) releasing H+ ions when pH rises
2) accepting H+ ions when pH drops
Major buffer systems include:
Sodium bicarbonate carbonic acid buffer system:
The major buffer in extracellular fulid
Is very important in the oral cavity for acid neutralization in foods & those produced by oral bacteria
Phosphate buffer system:
The minor buffer in the extracellular fluid
Protein buffer system:
Intracellular proteins absorb hydrogen ions generated by the bodys metabolic processes
Proteins contain many functional groups with diferring pKs, making them able to buffer over a wide pH range
An increase in pK means a stronger ability to bind hydrogen ions (better base or proton acceptor)
pK High pK means very low [H+] (1.0 x 10-14), so it will accept H+ faster
Hemoglobin is a major intracellular buffer
*** H2CO3, NaHCO3, Na2HPO4, NaH2PO4 all function in buffer systems in blood
Blood:
Is slightly basic, between pH 7.35-7.44

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Acid-base balance is controlled precisely because even a minor deviation from the normal range can severely affect
many organs
The body uses three mechanisms to control the acid base balance:
1. Excess acid is excreted by the kidneys as H+, NH4+ or combined with phosphate
2. The body uses pH buffers in the blood to guard against sudden changes in acidity
The major blood buffers are bicarbonate, hemoglobin, and albumin
The most important buffer system in maintaining physiological pH of plasma is carbonic
acid/bicarbonate
3. The excretion of CO2: the blood carries carbon dioxide to the lungs where it is exhaled
Respiratory control centers in the brain regulate the amount of carbon dioxide that is exhaled by controlling the
speed and depth of breathing
An abnormality in one or more of these pH control mechanisms can cause one of two major disturbances in acid
base balance: acidosis or alkalosis
From the Henderson-Hasselbach relationship we can see how plasma pH is determined by the plasma levels of carbon
dioxide and bicarbonate. 6.1 is the pKa of the bicarbonate-carbon dioxide buffer system
pH = 6.1 + log [bicarbonate]/ (0.03 x partial pressure of carbon dioxide)
Henderson-Hasselbach equation:
pH = pKa + log[A-]/[HA]
ph = pkA WHEN [HA] = [A-]
Or when the acid is Half Neutralized
Describes the relationship between the pH, pK (the negative log of the dissociation constant) and the concentration of an
acid and its conjugate base (aka, the salt of the acid)
EX: If adrug has a pK of 6.4, at pH = 7.4, the ratio of A- to HA is 10
7.4 = 6.4 + log[A-]/[HA] 1.0 = log[A-]/[HA] 101.0 = [A-]/[HA] = 10:1 ratio
A useful way of restating the expression for the dissociation constant of an acid (K a)
Ka = [H+][A-]/[HA]
The larger the Ka, the stronger the acid, because most of the HA has been converted into H+ and A-.
Conversely, the smaller the Ka, the less acid has dissociated, and therefore the weaker the acid
Shows that pH = pK when an acid is half neutralized
Because from our equation pH = pK then 0 = log[A-]/[HA] 100 = ratio 1 = ratio
The pH of a buffer system depends on the pK of the weak acid & the ratio of molar concentrations of salt and
weak acid
At pH = pKa, there is maxiumum buffer capacity i.e. half neutralized, and could then go either way
Another Q: The optimum pH for an enzyme is the pH of the most rapid reaction rate
This type of problem is solved by using the following equation: Kw = [H+][OH-]
Kw is the ion product of water and always equal 10-14
[H+] is the hydrogen ion concentration (pH = -log[H+])
[OH-] is the hydroxide ion concentration (pOH = -log[OH-]
14 = pH + pOH
Use the pH scale
14 = pH + 4
pH = 10
EX: The pH of a solution having a 10-5 M concentration of OH- ion is 9 (from 14 5 = 9)
EX: The pH of a solution of 0.01 M HCl = 2
pH = -log[0.01] -pH = log[0.01] 10(-pH) = 0.01 10-2 = 0.01 pH = 2
EX: If the pH = 5.7, the [H+] = 1x10-6
EX: Solution A has a pH = 7.0; Solution B has a pH = 6.0; volumes are equal; A has 1/10 as many H + ions than B
This just recapitulates that pH is a fxn of log, or powers of 10!!!
Isoelectric point
The pH at which number of positive charges equals the number of negative charges
The amino acid composition of a protein having an isoelectric pH of 10 has more basic than acidic amino acids
The pH at which a solute has no net electric charge & thus does not move in an electric field (i.e., during electrophoresis)
It is designated pl for that solute
For example, at its isoelectric pH of 6.06, glycine will not move in an electric field
Another Q: Electrophoresis is a procedure that depends primarily on electrostatic net charge
A protein in an electrophoretic system, has the pH lowered below its isoelectric point
then protein would
migrate to negative pole
This means you have more H+ and will move Negative
This information has practical importance for a solution containing a mixture of amino acids, the different amino acids
can be separated on the basis of the direction and relative rate of their migration when placed in an electric field at a
known pH. The same applies to protein molecules and is frequenly used to separate proteins

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Example: Glycine has a net negative charge at any pH above its pl, so it will move toward the positive electrode
At any pH below its pl it has a net positive charge and moves towards the negative electrode
The farther the pH of a glycine solution is from its isoelectric point (pl), the greater the net electric charge of the
population of glycine molecules
At physiologic pH, all amino acids have both a negatively charged carboxyl group (COO-) and a positively charged
amino group (NH3+) They are therefore dipolar ions (zwitterions)
In aqueous solution at pH 7, a peptide containing 1 amino group side chain & 2 carboxyl group side chains, the net
charge would be (-1)
pH Problems
Metabolic acidosis:
Excessive blood acidity characterized by an inappropriately low level of bicarbonate in the blood
Major causes chronic renal failure, diabetic ketoacidosis, lactic acidosis, poisons and diarrhea
Ketoacidosis can result from a sustained, severe CHO deficiency in the diet
Ammonia is the nitrogenous product that is excreted in high amounts after prolonged acidosis
The kidney responds to metabolic acidosis by synthesizing NH3 to then pull out H+ and make NH4+ and
excrete it
Respiratory acidosis:
Excessive blood acidity caused by a buildup of CO2 in the blood as a result of poor lung function or slow breathing
Major causes hypoventilation, emphysema, chronic bronchitis, severe pneumonia, pulmonary edema, & asthma
In respiratory acidosis, CO2 content increases and pH decreases
Signs/symptoms of elevated PCO2:
Acute pain, anxiety, hyperventilation (to attempt to compensate), dizziness, signs of loss of consciousness
Administration of a 90:10 nitrous oxide:oxygen mixture causes respiratory depression. Respiratory acidosis is likely
to result (from the respiratory depression or hypoventilation). Dont misunderstand this one.
In respiratory acidosis, there would not be increased production of renal bicarbonate
Having all that CO2 would shift the equation back to HCO3- + H+
There would be hypoxia, hypercapnia, and a response of tachycardia
Metabolic alkalosis:
A condition in which the blood is alkaline because of an inappropriately high level of bicarbonate
Major causes vomiting acidic gastric contents or as a result of ingestions of alkaline drugs
Renal compensation for chronic metabolic alkalosis involves a partial reabsorption of the filtered HCO3Normally, over 99% of bicarb is reabsorbed to continue as a buffer, but in alkalosis, there would be an excess
of bicarb, so the kidney secretes more than usual into the urine to get the alkaline serum back down to
normal
Respiratory alkalosis:
A condition in which the blood is alkaline due to rapid or prolonged deep breathing
Results in a low blood CO2 level, which causes H+ and HCO3 to shift to make CO1, hence reducing the
H+ Low HCO3
Alkalosis can cause hypocalcemia and tetany by promoting the binding of calcium to albumin, hence reducing
the ionized Calcium in blood
Major causes hyperventilation (most common cause), pain, cirrhosis of liver, & low levels of oxygen in the blood
(high altitude)
Hyperventilation causes some degree of temporary alkalosis
Another Q: Hyperventilation often produces muscle spasms because the loss of CO 2 has caused alkalosis
Chronic respiratory alkalosis
Low CO2, Low HCO3, normal venous pH
High Altitude Respiratory Resopnse
Acute increase in ventilation
Increased pulmonary ventilation at high altitudes results directly from the effect of hypoxia on the carotid body
Chronic increase in ventilation
Increased erythropoietin increased hematocrit and hemoglobin
Increased 2,3-DPG (binds to Hb so that Hb releases more O2)
Cellular changes (increased mitochondria)
Increased renal excretion of bicarbonate (to compensate for respiratory alkalosis)
Chronic hypoxic pulmonary vasoconstriction results in right ventricular hypertrophy
In water intoxication, most of the excess water will be found in the intracellular compartment (as opposed to extracellular,
intravasacular, or interstitial compartments)
Hormones
Types of Hormones
Steroid hormones:

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Derivatives of cholesterol
PET CAT
Pet for heavy Petting (Sex Hormones) and Cat for Catabolism Hormones
**Progesterone, Estradiol, Testosterone, and Cortisol, Aldosterone, Thyroxine
NOT relaxin
Not water soluble and bind to intracellular receptors, forming complexes that activate or inactivate genes
Best characterized by binding to intracellular receptors
Adrenal Steroids
CholesterolPregnenoloneProgesterone11DoxycorticosteroneCorticosteroneAldosterone
This is the Main chain, first NZ is Desmolase, which is controlled by ACTH and inhibited by ketoconazole
Pregnenolone17-Hydroxypgregnenolone11-DeoxycortisolCortisol
Progesterone17a-HydroxyprogesteroneAndrostenedioneEstrone
AndrostenedioneEstradiol
AndrostenedioneTestosteroneDHT
Mineralocorticoids Aldosterone ( 21 Cs)
Glucocorticoids Cortisol (21 Cs)
Androgens Testosterone (19 Cs)
Estrogens Estrone/Estradiol (18 Cs)
Amine hormones:
Derived from tyrosine, an essential amino acid found in most proteins
They include thyroid hormone (T3 and T4) and the catecholamines (epi and NE and dopamine)
Polypeptide hormones:
Proteins with a defined, genetically coded structutre
Synthesized in precursor form (a pre-prohormone)
Usually transported unbound in plasma
Stored in secretory vesicles
Act by binding to a plasma MB receptor & generating second messengers
Another Q: Polypeptide hormones usually exert their effect by binding to receptors on the cell MB & altering the
specific activity of certain enzymes
Another Q: Hormones that exert there effects through the activation of second messengers are usually water soluble
peptide/protein hormones thats like a definition!!!
They include:
Anterior pituitary hormones (GH, TSH, FSH, LH, & prolactin)(FLAT PEG)
Thyroid hormones, glucocorticoids & gonadal steroids are similar in that each is released in response to
signals from the hypothalamic-anterior pituitary complex
Posterior pituitary hormones (ADH & oxytocin)
Pancreatic hormones (insulin and glucagon)
PTH
Somatostatin
Inhibitory of GH, TSH, Insulin, Glucagon, and Gastrin
Elaborated primarily by the median eminence of the hypothalamus and by the D for delta cells of
pancreatic islets
There is a positive N2 balance following administration of GH (somatotropin)
A particular hormone does not necessarily affect all cells; only its target cells
Target cells of a hormone possess receptors to which molecules of a hormone can attach
These receptors can be located either on the plasma membrane or within the cell itself
Second messenger:
A molecule found inside a cell which responds to the presence of a hormone outside the cell
cGMP and cAMP are second messengers that carry signals from the cell surface to proteins within the cell
cAMP is the intracellular, "second" messenger for many peptide and polypeptide hormones
Another Q: cAMP (adenosine-3, 5-monophosphate) is directly invovled in the action of hormones on target cells
Another Q: cAMP increases the rate of glycogenolysis by promoting the phosphorylated form of glycogen
phosphorylase
Frequently they act to stimulate protein kinase
They are rapidly broken down in cells (to terminate response) by enzymes called phosphodiesterases
Some hormones that use cAMP as a second messenger are:
Glucagon
Epinephrine
ACTH
Parathyroid hormone
TSH

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FSH
FL
Glucagon, epinephrine, & PTH induce activation of cAMP (insulin does not)
This increases the rate of glycolysis & gluconeogenesis
cAMP is formed from ATP in a reaction catalyzed by adenylate cyclase
Adenylate cyclase is an integral protein of the plasma membrane
Many hormones act by way of stimulation of the MB-bound adenylate cyclase
Signal Molecule Precursors
ATP cAMP via adenylate cyclase
GTP cGMP via guanylate cyclase
Glutamate GABA via glutamate decarboxylase (requires Vitamin B6)
Choline Ach via choline acetyltransferase (ChAT)
Arachidonate Prostaglandins, thromboxanes, Leukotrienes via cyclooxygenase/lipoxygenase
Fructose-6-Phosphate Fructose 1,6-bisphosphate via phosphofructokinase (PFK), the rate limiting NZ of glycolysis
1,3-BPG 2,3-BPG via bisphosphoglycerate mutase
Hypothalamus:
Located on the floor of the forebrain
ADH and oxytocin are synthesized in certain hypothalamic nuclei (supraoptic --ADH and paraventricular -- Oxytocin) of
the brain, which contain the cell bodies of neurosecretory cells
Hormones are then transported along the axons of the neurosecretory cells to the pars nervosa (posterior pituitary)
Neural inputs to the brain influence their release
Secretions of the anterior pituitary are controlled by hormones called hypothalamic releasing and inhibitory factors,
which are secreted within the hypothalamus itself
These tropic hormone releasing factors conduct to the anterior pituitary through minute BVs called the
hypothalamic-hypophyseal portal system
The function of hypophyseal portal vessels is to carry hypothalamic releasing factors to the adenohypophysis
Center of the brain regulating body temperature Anterior Hypothalamus (A/C)
Center of the brain for ANS regulation
Factors include:
Gonadotropin releasing hormone (GnRH) stimulates release of both FSH and LH
Thyrotropin releasing hormone (TRH) stimulates release of TSH
Corticotrophin releasing hormone (CRH) stimulates release of ACTH
Stimulated by: low plasma cortisol, hypoglycemia, pyrogen, and stress
Suppressed by: high plasma glucocorticoids
Growth hormone releasing hormone (GH RH) stimulates release of GH
Dopamine (DA) inhibits release of prolactin
Somatostatin inhibits release of GH
Pituitary (Hypophysis)
Has direct hormonal control over the mammary glands (among many things)
Posterior Pituitary = pars nervosa = neurohypophysis
The neurohypophysis produces vasopressin & oxytocin, which both affect contraction of smooth muscle
Antidiuretic hormone (ADH) = vasopressin
Produced in the Hypothalamus (specifically in the supraoptic nuclei)
Vasopressin is a peptide that is stored and released into the bloodstream by the posterior pituitatry
End organ resistance to ADH is called nephrogenic diabetes insipidus
Kidneys fault for not absorbing the water
This results in the inability to concentrate urine, polyuria, and increased serum osmolarity (resulting from
the loss of free water in the urine)
Urine Osmolarity of less than 200 mOsm/L
Decreases the urine volume by increasing the reabsorption of water by the renal tubules (increases the
permeability of the collecting ducts and distal convoluted tubules to water)
ADH receptors are located on the membranes of these collecting ducts and distal tubules
Released in response to:
Increased plasma concentration of Na+
Most important variable regulating ADH is plasma osmolarity
Most sensitive hormone to plasma osmolarity
Decreased blood volume
Hypotension
Ethanol and caffeine decrease ADH release, while nicotine increases its release
Sweating causes an increase in ADH, while drinking large amounts of water causes a decrease in blood ADH

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Hyposecretion of ADH results in diabetes insipidus (polyuria, polydipsia and polyphagia)


Diabetes insipidus would also result from the hypoactivity of the posterior pituitary
Infusion of vasopressin results in a decrease in osmolality
Oxytocin
Causes muscle of the uterus and milk ducts in the breast to contract
What causes contraction of the uterus oxytocin
Released from the posterior pituitary in response to dilation of the cervix and to suckling
Stimulates smooth muscle cells of myoepithelium of mammary gland alveoli
Oxytocin is responsible for causing contractions of the uterine smooth muscle during labor
ADH and oxytocin are stored and released form the pars nervosa, but neither hormone is produced there
Produced by the paraventricular nuclei in the hypothalamus
Anterior Pituitary (FLAT PEG) = pars distalis = adenohyposphysis
Complete destruction of anterior pituitary would result in Addisons disease, myxedema, & hypogonadism
FSH (Follicle Stimulating Hormone)
Stimulates graafian follicle development and induces secretion of estrogens
Polypeptide
Exerts its action on the germinal epithelium
LH (Luteinizing Hormone)
Stimulates ovulation and the development of the corpus luteum
FSH and LH work together to cause ovulation & the formation of the corpus luteum
GnRH (produced by the hypothalamus) stimulates release of both FSH and LH
Adrenocorticotropic hormone (ACTH)
Called the stress hormone
Controlled by the hypothalamus
When body is stressed, corticotropin-releasing hormone (CRH) produced by the hypothalamus travels
through a portal system to the anterior lobe of the pituitary, where it induces the production and secretion of
ACTH by the basophils of the pars distalis
ACTH stimulates the adrenal cortex to synthesize cortisol
Cortisol influences CHO, lipid, & protein metabolism
The mineralcorticoid aldosterone and the glucocorticoids are collectively called corticosteroids
Aldosterone secretion from the adrenal cortex is induced by elevated plasma K+ & angiotensin II, not by
ACTH
IV injections of KCl would increase the secretion of aldosterone
Aldosterone primary effect is on the kidney tubules, where it stimulates Na+ retention and K+ excretion
Results in high Na & low K in plasma
Another Q: Aldosterone causes increased renal tubular reabsorption of sodium
Another Q: Reabsorption of sodium chloride is controlled in the kidney tubules by an adrenal cortical
hormone (aldosterone)
Another Q: Aldosterone is normally associated with partial regulation of sodium balance
Another Q: Aldosterone increases K+ secretion into the urine
The following statements describe aldosterone:
It is a mineralocorticoid
It increases Na+ uptake from the kidneys
Its production is stimulated by angiotensin II
NOTE: it is not produced in the zona fasciculata of the adrenal cortex (its made in the zona glomerulosa)
Thyroid Stimulating hormone (TSH)
Aka thyrotropin
Secreted by basophils of the pars distalis of the anterior pituitary gland
Controls the rate of secretion of thyroid hormones (thyroxine and triiodothyronine)
Thyroxine in turn controls the rates of many metabolic processes and the metabolic rate
Exposure to cold increases the rate of TSH secretion
Thyroid secretion is stimulated by prolonged exposure to a cold environment
Stress can inhibit TSH secretion, most likely by way of neural influences that inhibit the secretion of TRH
from the hypothalamus
TSH is stimulated by TRH. There are several negative feedback loops which regulate:
High levels of circulating thyroid hormone decreases the secretion of both TRH and TSH
Elevated levels of TSH decreases secretion of TRH
Disease:
Hypersecretion of TSH results in Graves disease (and Plummers)
Hyposecretion of TSH results in Cretinism (in young people) and Myxedema (in adults)

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**NOTE ACTH and TSH are pituitary tropic hormones


Prolactin (aka lactogenic or luteotropic hormone)
Produced by eosinophils (remember PeG e is for Eosins) of the pars distalis of the anterior pituitary gland
Stimulates milk production by the mammary glands (during pregnancy for breast development and after
delivery of the child for lactation)
Basically, Prolactin increases dopamine synthesis, then Dopamine inhibits Prolactin secretion
Hypothalamus synthesizes a prolactin inhibitory factor (dopamine)
Under normal conditions, large amounts of dopamine are continually transmitted to the anterior pituitary
gland so that the normal rate of prolactin secretion is slight
This is why prolactin is said to be under predominant inhibitory control by the hypothalamus
This is also why blocking the hypothalamic-hypophyseal venous portal system increases the release of
prolactin
During pregnancy and lactation, the formation of dopamine itself is suppressed, thereby allowing the
anterior pituitary gland to secrete an elevated amount of prolactin
Most anterior pituitary hormones are enhanced by the neurosecretory releasing factors transmitted from the
hypothalamus, but not prolactin
Blocking the hypothalamic-hypophyseal venous portal system increases the secretion of prolactin
But, it does not increase the secretion of ACTH, TSH, and oxytocin
Not oxytocin, because it is a hormone of the posterior pituitary
Not ACTH & TSH, since release is stimulated by CRH & TRH, respectively from the hypothalamus
Prolactin secretion increases, because release is inhibited by dopamine from the hypothalamus
In females, Prolactin inhibits GnRH synthesis and release, which inhibits ovulation (Breast feeding CAN be
birth control)
Growth Hormone (aka Somatotropin)
From the anterior pituitary alpha cells:
Does not function through a target gland but instead exerts effect on all or almost all tissues
GH causes the liver (and to a much lesser extent other tissues) to form several small proteins called
somatomedins (also called insulin-like growth factors) that in turn have the potent effect of increasing all
aspects of bone growth Somatomedin is increased by somatotropin
Insulin-like growth factor 1 (IGF-1) is secreted by the liver; IGF-1 secretion is stimulated by GH in
blood
Basic metabolic effects:
Increased rate of protein synthesis in all cells of the body
Decreased rate of carbohydrate utilization throughout the body
Increased mobilization of fats and the use of fat for energy
Causes cells to shift from using carbohydrates to using fat for energy Think you lose your baby Fat
Secretion is increased by: sleep, stress, starvation, exercise, hypoglycemia, hormones related to puberty
Secretion is decreased by: somatostatin, somatomedins, obesity, hyperglycemia, and pregnancy
The rate of GH secretion increases and decreases within minutes
Most of the time it is in relation to the persons state of nutrition or stress
GH is released in a pulsatile fashion
Acidophile Hormone of Hypophysis??
GH
GH is also released in response to a decline in plasma glucose concentration and an elevated plasma level of
certain amino acids, particularly arginine
Growth hormone undersecretion produces pituitary dwarfism in children
Oversecretion of GH causes gigantism in children or in adults, acromegaly
Hypersecretion of GH causes hyperglycemia
This is because GH stops usage of CHOs and makes you use FAs for energy
Nitrogen Balance
Positive Nitrogen Balance
Means that nitrogen intake exceeds nitrogen output
Patients taking GH are likely to exhibit a positive nitrogen balance
A positive nitrogen balance is likely to take place following administration of GH
Growth, Protein Synthesis because the ammonia is incorporated into the alpha amino groups of amino
acids and therefore less nitrogen will be secreted
Negative Nitrogen Balance (BAD for wasting or NOT growing)
Means the nitrogen output exceeds nitgrogen intake
A negative nitrogen balance is most likely to occur during old age
Negative nitrogen balance may be caused by a dietary lack of essential amino acids
Not during fetal growth or adolescence for obvious reasons
Not during convalescence, which is a period of recovery from injury, surgery, etc

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Nitrogen can be used as a measurement of protein level in meat


An example of synergism is GH & thyroxine on skeletal growth
Ovaries (From F for FSH and L for LH)
Produce ova, the female sex hormones (progesterone and estrogen) and follicles
The corpus luteum
Is a yellowish mass of cells that forms from an ovarian follicle after the release of a mature egge
If the mature egg is not fertilized and pregnancy does not occur, the corpus luteum retrogresses to a mass of scar
tissue (corpus albicans) which eventually disappears
If the mature egg is fertilized and pregnancy does occur, the corpus luteum does not degenerate but persists for
several months. Human chorionic gonadotropins HCG which is produced by the placenta stimulates the corpus
luteum to produce estradial and progesterone
Granulosa cells in the corpus luteum produce progesterone and estrogen
It produces more progesterone than estrogen
Ovulation
Oral contraceptives prevent ovulation:
Most contraceptives are combined pills which contain synthetic estrogen-like (ethynl estradiol, mestranol) and
progesterone-like (norethindrone, norgestrel) substances
Progestins
Being used as oral contraceptive substance due to their ability to suppress ovulation
It stops LH, but does NOT decrease FSH secretion
Preventing the rise in LH prevents ovulation
Primary recognition of B-estradiol by its target cell depends upon the binding of the hormone to a specific
cytoplasmic receptor
Exact mechanism is thought to be as follows:
In presence of either estrogen or progesterone, the hypothalamus fails to secrete the normal surge of LH
releasing factor
This inhibits the release of LH from basophils of the anterior pituitary gland
Subsequent ovulation does not occur
Ovulation occurs as a result of the estrogen-induced LH surge
Unlike other steroid hormones, all estrogens have an aromatic A ring
Adrenal Medulla (From A for ACTH)
Specialized ganglion of Symp NS
Preganglionic fibers synapse directly on chromaffin cells in the adrenal medulla
These cells secrete epi (80%) and NE (20%) into the circulation
Both of these hormones are direct-acting adrenergic agonists and are biosynthesized from tyrosine
Tyrosine is a metabolic precursor for epinephrine
Epinephrine is most closely related structurally to Tyrosine
NE and its methylated derivative epi act as regulators of CHO and lipid metabolism
NE & epi increase degradation of triacylglycerol & glycogen, AND increase heart output (specifically, epi) & BP
These effects are part of a coordinated response to prepare the individual for emergencies fight or fright reactions
Increase in response to fright, exercise, cold, low levels of blood glucose
The adrenal medulla is supplied by cholinergic preG Symp neurons that release Ach
In terms of origin & function, the adrenal medulla is comparable to a postganglionic sympathetic nerve
In response to this, the adrenal medulla releases mainly epi (and some NE) into the bloodstream, which carries the
secretions to the effector organs
The pathway of Origin (NE and Epi)
Tyrosine L-Dopa Dopamine NE Epi
Dopamine is synthesized in 2 steps from which of the following compounds (Tyrosine)
Epinephrine (adrenalin):
The release of epinephrine is controlled mainly by nerve impulses
Stimulates glycogenolysis and gluconeogenesis (except in the liver), which tend to raise blood glucose levels
When injected, epinephrine causes an increase in blood sugar
Another Q: Sympathetic stimulation affects CHO metabolism because epinephrine increases liver
glycogenolysis
Also stimulates lipolysis in adipose tissue (breakdown of TGs into glycerol and fatty acids)
Increases rate, force, and amplitude of heart beat
Administration of local anesthetic w/ epinephrine will most likely produce an increased heart rate
Constricts BVs in skin, mucous membranes, and kidneys
Sympathetic stimulation dilates bronchioles in the lungs & relaxes bronchiolar smooth muscle
Another Q: Increased parasympathetic activity causes bronchiolar smooth muscle contraction

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Another Q: Epi activates muscles glycogen phosphorylase


Tags glycogen to be degraded
Norepinephrine (noradrenalin):
Increases heart rate and the force of contraction of heart muscle
Promotes lipolysis in adipose tissue
Constricts blood vessels in almost all areas of the body, thus increasing total peripheral resistance
Has the LEAST effect on Calicum Metabolism
NE can be released in two ways:
1. By the adrenal medulla into the bloodstream
The effects are more widespread when NE is released into the bloodstream by the adrenal medulla as
opposed to directly onto an organ by the postganglionic sympathetic neuron
2. Directly onto an organ by a postganglionic sympathetic (adrenergic) neuron which stores NE
Cortisol (hydrocortisone)
Has direct inhibitory effect on hypothalamus and anterior pituitary gland
Is a glucocorticoid
The principal mechanism by which glucocorticoids stimulate their target cells is by activating specific genes
Release of cortisol is controlled primarily by ACTH, which is secreted by basophils in the pars distalis of the
anterior pituitary
Release of ACTH is influenced by corticotrophin-releasing hormone (CRH) from the hypothalamus
Cortisol exerts an inhibitory influence on both ACTH and CRH by way of negative feedback
Main glucocorticoid produced and secreted by the cells of the zona fasciculata in the adrenal cortex
Fxns:
Allows glucagon and epi to work more effectively at their target tissues, but antagonizes the action of
insulin
Increases hepatic glycogen content, gluconeogenesis, protein breakdown, & adipose tissue breakdown
Anti-inflamatory properties
Impairs cell-mediated immunity
Influences behavior (decreasing stress)
Stimulates leukocytosis
Inhibits synthesis of nucleic acids (except liver)
Affects immune system, bone, calcium absorption from the GI tract, and the CNS
Effects:
blood glucose (by stimulating gluconeogenesis and inhibiting glucose uptake)
Cortisol stimulates synthesis in the liver of pyruvate carboxylase (NZ of gluconeogenesis)
amino acids (by stimulating protein breakdown)
fatty acids (by stimulating lipolysis)
Decreases glucose utilization from the cells
A patient taking cortisol for a long period of time may experience atrophy of the adrenal cortex due to inhibition of
ACTH production
15-30 mg released daily in diurnal rhythm, mostly in morning, same is true for ACTH
90% is bound to transcortin (corticosteroid binding globulin = CBG)
Cushings syndrome
Metabolic disorder resulting from the chronic and excessive production of cortisol
The most common cause of this syndrome is a pituitary tumor that causes an increased secretion of ACTH
Characterized by hypertension, hyperglycemia, hypokalemia, increased androgen levels, and increased
protein catabolism (All the things a pheochromoctyoma does)
NOT increased protein anabolism
Thyroid (From T for TSH)
Thyroglobulin:
TSH from the pituitary gland stimulates synthesis and the release of thyroid hormones
Thyrotropin releasing hormone (TRH) from the hypothalamus promotes TSH secretion
Glycoprotein prohormone (10% carbohydrate)
Contains iodine which is attached to tyrosine molecule
The follicle cells of the thyroid gland synthesize thyroglobulin and secrete it into the colloid-containing regions of
the follicle
Here the thyroglobulin undergoes iodination and coupling processes that produce the thyroid hormones
Thyroglobulin molecules containing these hormones are then stored in colloid-containing regions of the follicle
So if your body needs iodine, then it breaks down thyroglobulin and releases iodinated T3 and T4

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When the thyroid is actively secreting, these thyroglobulin molecules are then taken back into the follicle cells
and broken down into the two hormones (T4/T3)
An iodine deficiency will increase the secretion of thyroglobulin (not T3, T4, or TSH)
Thyroid hormones:
Thyroglobulin (stored)
Hydrolysis of thyroglobulin liberates a number of iodinated compounds, only 2 are considered thyroid
hormones
T3 (Triiodothyronine)
T4 (Thyroxin)
T3 (triiodothyronine) has several times the biologic activity of T4 (thyroxine)
T4:T3 = 20:1
T4 could be said to act primarily as a pro-hormone for T3; T4 is converted to T3 primarily in the kidney
and liver, also can be converted to rT3, which is produced during illness, malnutrition or induced by
some drugs
0.03% of T4 is free and 0.3% of T3 is free, the rest are bound to thyroxine binding globulin (TBG)
4 Bs of T3
Brain Maturation
Bone Growth
Beta-adrenergic effects
BMR increased (Basal Metabolism Rate)
Thyroid secretes two iodine containing amine hormones that have a structural differences of one iodine atom
The majority of T4 is converted peripherally by target cells to T3 which is a more potent hormone
This is done by the enzymatic removal of one iodine atom
Iodine is important in the biochemical synthesis of thyroxin (T4)
Thyroid hormones are lipophilic hormones which exert their effects via transcriptional processes
Thyroid hormones are synthesized from Tyrosine
Fxns:
Important for normal growth and development (especially for brain)
Affect many metabolic processes and the metabolic rate
Basal Metabolism Rate is an increase in H2O, related to surface area???
Increased BMR is done via increasing Na+/K+ ATPase activity = increased O2 consumption,
increased body temp
Increase glycogenolysis, gluconeogenesis, and lipolysis, protein degradation (SAME AS CORTISOL)
This is why removal of the anterior pituitary (TSH) would result in a drop of blood glucose level
Regulate metabolism by speeding up cellular respiration
Beta-adrenergic effects
CV: increased CO, HR, SV, contractility, and RR
Stimulate bone maturation as a result of ossification and fusion of the growth plates
Calcitonin:
Synthesized and secreted by the parafollicular cells (C cells) of they thyroid gland that are located in the interstitium
Its secretion is stimulated by a increase in serum calcium
The immediate effects of calcitonin secretion are decreased serum levels of both calcium and phosphate
Most significant immediate result of lowered serum calcium is hyperirritability of nerves and muscles
It acts on bone cells to suppress bone resorption and enhance bone formation
Along with parathyroid hormone 1,25 DHC, it is a regulator of calcium metabolism
Is a linear polypeptide consisting of 32 amino acids
Is not required in adult humans
Although it is important during bone development, the major regulator of plasma calcium level in the adult is PTH
Parathyroid hormone (PTH)
Phosphate Trashing Hormone (Decreases Serum Phosphate, but increases Urinary Phosphate)
Secreted by Chief Cells in the parathyroid glands in response to decreased plasma calcium levels
NOT in response to Hypothalamus-Pituitary Complex
Plasma calcium level is the major controller of PTH, NOT Hormonal
Another Q: Bone resorption seen in elderly patients with low dietary calcium is enhanced by PTH (not insulin,
estrogen, aldosterone, or TSH)
The principal controller of calcium and phosphate metabolism and is involved in the remodeling of bone
The most prominent function of bone is a calcium reservoir
Increases the plasma calcium concentration and decreases the plasma phosphate concentration
In a parathyroidectomized animal, plasma calcium is low and plasma phosphate is high
PTH modes of action: daddy

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The major target tissues of the calcium regulating hormones are: bone, intestine, kidney
Stimulates BOTH osteoclasts and osteoblasts
Bone cells (osteoclasts) increase bone resorption, leading to release of calcium & phosphate into blood
plasma
Accelerates removal of calcium and phosphate from skeleton, but NOT from teeth
Q: Theories of the effect of PTH on bone:
PTH influences the rate of bone resorption
The action on bone is related to its action on phosphate excretion
The effect of parathyroid extract is to influence osteoclastic activity
PTH does NOT cause a decrease in new bone formation
Increases Kidney reabsorption of Calcium in DCT
Acts on the kidney to decrease calcium excretion and increase phosphate excretion in the urine
Also stimulates 1-alpha-hydroxylase in the kidneys Activates Vitamin D
Causes an increase in 1,25 hydroxycholecalciferol formation, which then causes an increase in Calcium
absorption from the intestine
Increases the absorption of calcium in the GI tract
Diseases associated with PTH
Hyperparathyroidism (von Recklinghausens disease)
Causes extensive bone decalcification
A patient w/ hyperparathyroidism is predisposed to an increased likelihood of bone fracture
Is marked by extremely high blood calcium levels and low blood phosphate levels
BOTH PTH and Calcitonin lead to Low serum phosphate levels
This leads to muscular weaknesses
The low serum phosphate level in hyperparathyroidism is caused by increased renal loss of phosphate
Renal calcium excretion is increased in hyperparathyroidism
Seems a little counterintuitive, but websites confirm it must be due to the excess of PTH, since
normal PTH levels would decrease calcium excretion
This is the stones part of moans, groans, stones, bones & psychiatric moans symptoms
Hypoparathyroidsim
(tetany) (hyperirritability of neuromuscular areas )
Causes decreased bone resorption, decreased renal calcium reabsorption, increased renal phosphate
reabsorption, and decreased production of the active form of vitamin D (1,25 dihydroxycholecalciferol)
Together these effects decrease serum calcium & increase serum phosphate
Marked reduction in serum calcium will result in increased muscular irritability
***Another Q: the movement of Ca2+ across many cell MBs involves a Ca2+/Na+ countertransport
system
Another Q: Complete removal of the parathyroid glands leads to tetany
Hormonal Calcium Metabolism
Androgen, Estrogen, Thyroid Hormone, and Parathyroid Hormone all have effects
Norepinephrine is the LEAST involved
Pancreas
Secretions are stimulated by blood levels of certain molecules
A piece of pancreas transplanted under the skin (re-established circulation) would secrete after ingestion of food
A piece of parotid gland would not secrete
Insulin:
Proinsulin is converted to insulin (a segment of proinsulins polypeptide chain is removed) This segment is called
C-peptide
Secreted by beta cells in the islets of Langerhans of the pancreas in response to a rise in the blood glucose level
Insulin is secreted more in the absorptive state than the post-absorptive state
Fxns:
It causes glycogenesis in the liver
Insulin lowers the blood glucose level by stimulating and facilitating the uptake of glucose and the utilization of
glucose as an energy source by many cells
A principal action of insulin is to enhance cell permeability to glucose
It also promotes the synthesis of glycogen, triglycerides, and proteins
GLUT List
GLUT 1 receptors are found on RBCs, Brain, Renal Cortex
GLUT 2 receptors are found in Beta cells
GLUT 4 receptors are found in muscle and fat
Has NO effect on glucose uptake by the brain
Inhibits lipolysis (it enhances triglyceride synthesis)

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Stimulates protein synthesis (inhibits protein breakdown)


Increases entry of glucose into muscles & adipose tissue
Brain uptakes Glucose Independent of Insulin
Enhances cell permeability to glucose
Another Q: Insulin increases the rate of anabolic (biosynthetic) reactions
Another Q: Insulin conserves protein, carbohydrate, & fat stores in the body
Another Q: Insulin increases the activity of phosphofructokinase
Basically, tells to cell to get storing the energy and also pushes the glucose down the chain faster
Remember the Factory, and the Truck that showed up analogy
Secretion inhibited by:
Decrease in blood glucose
Secretion of somatostatin
Secretion of either epi or NE
BUT NOT by secretion of glucagons - I guess insulin is KING
Insulin released by beta cells is promoted by:
Rise in blood glucose: this is the major factor governing insulin release
Elevated level of amino acids (especially arginine, lysine, and leucine) in the blood plasma
Glucagons, GH, and cortisol because all of the following blood glucose levels
PS stimulation
Removal of the anterior pituitary gland increases the sensitivity to insulin
(To pick up what little glucose there is!!) Because w/o Anterior Pituitary, Blood glucose goes down
Another Q: The blood glucose level in diabetes mellitus is decreased by removal of the anterior pituitary
gland
I think this might be due to the absence of T4, GH, and ACTH, which would normally elevate blood glucose,
hence activating Insulin
Insulin stimulates the tyrosine kinase receptor
Insulin vs. Glucagon
Insulin (If your house is insulated, you can take stuff off, i.e. Phosphates)
Dephosphorylates stuff
Turns Glycogen Synthase (A) ON, but Phosphorylase (B) OFF
Glucagon
Phosphorylates stuff
Turns Glycogen Synthase (B) OFF, but Phosphorylase (A) ON
The A Form is ON FORM
Glucagon:
Secreted by the alpha cells in the Islets of Langerhans of the pancreas in response to blood glucose level
Fxns:
Most important function = ability to cause glycogenolysis in the liver (which, in turn, plasma glucose)
Cyclic AMP rate of glycogenolysis by promoting formation of phosphorylated form of Glycogen
phosphorylase
cAMP PKA P form of glycogen phosphorylase glycogen-P glycogenolysis
The phosphorylation of phosphorylase b to phosphorylase a operates in liver cells to regulate
breakdown of glycogen
Glucagon is found in standard medical emergency kits because it promotes glycogenolysis in hypoglycemic pts
Does not stimulate glycogen degradation in muscle Because it cant leave the cell anyway (No G-6-P)
Frequently called the hyperglycemic factor
Hyperglycemic affect of glucagon is mediated primarily through the liver glycogenolysis
Glucagon released by Alpha cells is promoted by the following:
A fall in blood glucose level (hypoglycemia): this is the major regulator of glucagon
NOTE on hypoglycemia: clinical manifestations of hypoglycemia include:
Dizziness, confusion, convulsion, coma (not hyperventilation)
Same Pt has a seizure
Most likely due to Hypoglycemia
Sympathetic stimulation
Epinephrine and norepinephrine secretion
Elevated level of amino acids (especially arginine) in the blood plasma
Cholecystokinin secretion
Factors that decrease glucagon secretion
Rise in the blood glucose level
Insulin

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Somatostatin
Free FAs
Ketoacids
Kidneys
Aldosterone:
Exhibits main effect on the distal convoluted tubule and the collecting duct to increase Na+ permeability
Stimulates Na+ retention and K+ excretion
This restores extracellular fluid volume and blood volume to normal
Is the principle mineralcorticoid
Secreted by cells located in the zona glomerulosa of the adrenal cortex
Secretion is induced by 1) plasma K+ levels and 2) the renin-angiotensin system
Decreased [Na+] causes JG cells of the kidneys secrete renin
(Reduced renal blood flow causes hypertension by the release of renin)
Your kidney thinks BP is down, so it kicks out renin to preserve Na+, which preserves fluid, which
raises BP
Renin-Angiotensin System
Renin is released by the kidneys upon sensing decreasing BP
Renin cleaves angiotensinogen to angiotensin I (in the blood)
ACE cleaves Angiotensin I to angiotensin II primarily in the lung capillaries
Angiotensin II
Stimulates the adrenal cortrex to release aldosterone
Potent vasoconstrictor
Release of ADH from posterior pituitary
Stimulates Hypothalamus (increase thirst)
**ANP (Atrial Natriuretic Peptide) released from the atria may serve as a check
Addisons disease
Caused by the hyposecretion of aldosterone and cortisol
GI Hormones:
NEED TO STUDY
Gastrin
Stimulates gastric acid secretion (HCl) by parietal cells coupled with the release of pepsinogen by chief cells
Released caused by:
Presence of peptides and amino acids in gastric lumen
Distension of stomach
Synthesized and stored in the cells of the antrum and duodenum (Antrum is the distal end of the stomach)
Secretion of gastric acid inhibits gastrin secretion an example of feedback regulation
Also inhibited by secretin
Enterogastrone:
Includes secretin, cholecystokinin, and gastric inhibitory peptide, GIP
Are released by the small intestine in response to the acidity of the duodenal chyme and the presence of amino acids
and free fatty acids
The hormones enter the blood and are carried to the stomach, where they depress the pyloric pump (pumping action
of the stomach), thus inhibiting gastric motility, which slows down gastric emptying
The enterogastric reflex
Initiated when the duodenum fills with chyme, also inhibits the pyloric pump, thereby inhibiting gastric motility
and emptying and secretions
The rate of gastric slow waves is unchanged but gastric emptying is reduced
The enterogastric reflex produces a decrease in gastric motility
Fats have the largest control over the release of the gastrones and the subsequent rate of gastric emptying
Fat in the small intestine inhibits gastric emptying through activity of enterogastrone
Cholecystokinin:
Produced in the small intestine in response to the presence of certain amino acids and free fatty acids
Functions:
Stimulates the release of pancreatic enzymes (trypsin, chymotrypsin, and carboxypeptidase)
Stimulates the contraction & emptying of the gallbladder
Delays gastric emptying following fat ingestion
NOTE: although secretin also inhibits gastric emptying, the Q was asking about it in relation to fat
intake
Secretin:
Secreted in the duodenum, and is an enteroendocrine cell

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Is released when the gastric contents (especially, H+) are delivered to the duodenum
In turn secretin stimulates pancreatic duct cells to secrete a fluid high in bicarbonate (HCO3-), which neutralizes
the H+ in the duodenum
Functions of secretin:
Inhibits stomach motility and gastric acid secretion
Stimulates the pancreatic duct cells to secrete a fluid which contains a lot of bicarbonate ion but is low in
enzyme
Stimulates the secretion of bile from the gallbladder
Secretin functions in digestion of proteins by increasing flow of pancreatic juice (which contains trypsin,
chymotrypsin, carboxypeptidase)
Gastric inhibitory peptide:
Like secretin, is secreted from the mucosal cells in the duodenum
Functions:
Inhibits gastric acid secretion (HCl) and motility and stimulates the release of insulin from the beta cells in
response to elevated blood glucose concentrations
Release stimulated by presence of fat & glucose in small intestine
Enterokinase (enteropeptidase)
This hormone causes the release of pancreatic zymogens (e.g., trypsinogen, chymotrypsinogen, proelastase, and
procarboxypeptidase A & B) and the contraction of the gallbladder to deliver bile to the duodenum when chyme comes
into contact with the mucosa
Enterokinase is found in the succus entericus but NOT found in the pancreatic juice
Converts trypsinogen to trypsin
Pancreatic proteases are secreted in inactive forms (zymogens) that are activated in the small intestine:
Site of Synthesis
Zymogen
Active NZ
Stomach
Pepsinogen
Pepsin
Pancreas
Chymotrypsinogen
Chymotrypsin
Pancreas
Trypsinogen
Trypsin
Pancreas
Procarboxypeptidase A
Carboxypeptidase A
Pancreas
Procarboxypeptidase B
Carboxypeptidase B
Pancreas
Proelastase
Elastase
Pepsinogen:
Secreted by the chief cells of the body (or Fundus -- BOTH) of the stomach (Pepsinogen)
Activated by pepsin and low stomach pH
The most important fxn of Hydrochloric acid in the stomach is activation of pepsinogen
Pepsinogen is not found in pancreatic juice (but lipase, amylase, trypsinogen, and chymotrypsinogen are)
Trypsinogen:
Activated to trypsin by enterokinase
Trypsin: THINK TRYPs the SWITCH
Cleaves peptide bonds in which the carboxyl group is contributed by lysine and arginine (basic amino acids)
Converts trypsinogen, chymotrysinogen, proelastase, and procarboxypeptidase A and B to their active form
Serine is an important aa in the active site of both chymotrypsin & trypsin
Chymotrypsin:
Hydrolyzes peptide bonds on the alpha carboxyl side of aa residues with large polar side chains, like Tyrosine,
Tryptophan, Phenylalanine, Methionine, and Leucine
Phenylalanine, Tyrosine, Tryptophan are AROMATIC
Serine is an important aa in the active site of both chymotrypsin & trypsin
Elastase
Cleaves at the carboxyl end of aa residues with small, uncharged side chains such as alanine, glycine or serine
Carboxypeptidase A
Has little activity on aspartate, glutamate, arginine, lysine, or proline
Carboxypeptidase B
Cleaves basic amino acids: lysine and arginine
Sub
Eicosanoids: prostaglandins and the related compounds of thromboxanes and leukotrienes
Prostaglandins:
20-carbon FAs that contain a five carbon ring
Chemical messengers present in every body tissue
Differ from true hormones in that they are formed in almost all tissues rather than in specialized glands
Act as primarily as local messengers that exert their effects in the tissues that synthesize them

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Have a very short half-life


Synthesis can be inhibited by a number of unrelated compounds including aspirin, indomethacin, ibuprofen,
phenybutazone, which are all NSAIDs
Major Classes
PGA, PGB, PGE, and PGF
Seem to modulate the action of hormones rather than act as hormones
They enhance inflammatory effects, whereas aspirin diminishes them
Arachidonic acid:
A polyunsaturated fatty acid
The major compound from which prostaglandins, prostacyclins, thromboxanes, and leukotrienes are derived
Prostaglandins are made within cells from polyunsaturated fatty acids
Linoleic & arachidonic acids serve as precursors to prostaglandins
Upon complete hydrogenation, oleic, linoleic, linolenic acids yield steric acid
It is part of phospholipids in the plasma membranes of cells
When a cell is stimulated by a neurotransmitter or hormone, a plasma membrane enzyme called phospholipase A is
activated, and this enzyme splits arachidonic acid from the phospholipids
Cortisol inhibits phospholipase A activity which results in the formation of arachidonic acid from MB lipids
Different metabolic pathways utilize different enzymes that convert arachidonic acid into:
Cyclooxygenase: prostaglandins, prostacyclins, and thromboxanes
Lipooxygenase: Leukotrienes
Prostacyclin (PGI2) (Platelet Gathering Inhibitor)
Acts to prevent platelet formation and clumping
Also a potent vasodilator
Physiologic Anticoagulant
Contrast to Thromboxane A2 which is secreted by platelets
Heparin:
Is a heteropolysaccharide that serves as a powerful anticoagulant that prevents the formation of active thrombin
Another Q: Heparin administration results in symptoms similar to vitamin K deficiency increased bleeding time due to
lack of thrombin formation
Unlike other glycosaminoglycans that are extracellular compounds, heparin is an intracellular component of mast cells
These mast cells line arteries, especially the liver, lungs, and skin
Mast cells are abundant in the tissue surrounding lung capillaries & to a lesser extent in liver capillaries
Small quantities are produced by basophils functionally almost identical with mast cells
Used in treatment of certain types of lung, blood vessel, and heart disorders, and during or after certain types of surgeries
(open heart or bypass surgeries)
Concentration in the blood is normally slight, so that only under limited physiological conditions does it have significant
anticoagulant effects
HEPARIN Think Hugh Heffarin with his PERFECT 10 girls stops 10 from doing its thing
Administration of heparin will result in an increase in bleeding time due to the activation of antithrombin, a
major protease inhibitor, which rapidly inhibits thrombin.
It is used in treating pts who have suffered a coronary thrombosis
Heparin can also enhance the removal of lipoproteins from the blood by binding apolipoprotein E (protein found on
some liposomes) and by activation lipoprotein lipase
Histamine:
Causes:
Vasodilation (particularly the arterioles by the decarboxylation of histidine)
Decarboxylation of the aa histidine results in formation of a vasodilator (histamine)
Secretion of HCL H2
Bronchoconstriction
Decreased blood pressure
Increased vascular permeability (particularly in the capillaries and venules)
Found in tissues, mast cells, basophils (and is in highest concentration in the lungs)
Secreted by mast cells as a result of allergic reactions or trauma
When tissue is injured, histamine is liberated by the damaged tissue into the surrounding fluids
This increases the local blood flow as wells as capillary & venule permeability, allowing large quantities of fluid
protein to leak into the tissue characteristic wheal
Powerful pharmacologic action from two receptors:
H1 receptors:
Mediate the typical allergic and anaphylactic responses to histamine bronchoconstriction, vasodilation, and
increased capillary permeability

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H2 receptors:
Mediate other responses to histamine, such as the increased secretion of gastric acid and pepsin
Serotonin: (aka 5HT)
Synthesized from the aa tryptophan (also secretes another tonin melatonin and Niacin NAD)
Released from platelets upon damage to the blood vessel walls
Acts as a potent vasoconstrictor and increases vascular peripheral resistance
In gastric mucous membranes it is secreted by the enteroendocrine cells and causes the smooth muscle to contract
(TONIN)
In brain it acts as a neurotransmitter
Lysergic acid diethylamide interferes with the action of serotonin in the brain
Disorders
Diabetes mellitus:
The most common pancreatic endocrine disorder
A metabolic disease involving mostly carbohydrates (glucose) and lipids
In uncontrolled DM,
Infection
Delayed Wound Healing
Type I DM pt scheduled for extractions, dentist should be most concerned about Increased potential for
infection
Caused by:
(Type I)
An absolute deficiency of insulin
Defective or absent beta cells in the pancreas
(Type II)
Resistance to insulins actions in the peripheral tissue
Results from loss of the insulin receptor fxn in the target tissue
80-90% of diagnosed cases
Polygenetic etiology
Middle aged, obese
Insulin is present at elevated or near normal levels
Cardinal symptoms include: polydipsia, polyuria, polyphagia, weight loss, loss of strength
In untreated diabetes mellitus, polyuria is related to the osmotic effect of glucosuria
Another Q: Glucosuria with hyperglycemia usually occurs in diabetes mellitus
Characteristics
Level of insulin secretion
Typical age of onset
Percentage of diabetes cases
Basic defect
Associated with obesity
Speed of development of symptoms
Development of ketosis
Treatment

Type 1
None or almost none
Childhood
10 20%
Destruction of B cells
No
Rapid
Common if untreated
Insulin injections, dietary mgmt

Type 2
May be normal or exceed normal
Adulthood
80 90%
Reduced sensitivity of insulins target cells
Usually
Slow
Rare
Dietary control, weight reduction,
occasionally oral hypoglycemic drugs

Diabetes insipidus:
A disorder in which insufficient levels of antidiuretic hormone (ADH) cause excessive thirst (polydipsia) and excessive
production of very dilute urine (polyuria)
Results from hypoactivity of the posterior pituitary gland or destruction of the supraoptic nuclei of the hypothalamus
ADH deficiency results in failure of tubular water reabsorption (kidney) and the consequent passage of a large amount of
dilute urine and great thirst
Body fluid volumes remain close to normal so long as the pt drinks enough water to make up for increased H2O
clearance
Nephrogenic diabetes insipidus:
Congenital and familial form of diabetes insipidus due to failure of the renal tubules to reabsorb water
Excessive production of ADH but the tubules fail to respond
Shock:
Inadequate perfusion of tissue
Symptoms:

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Tiredness, sleepiness, and confusion


Skin becomes cold and sweaty and often bluish and pale
Pulse is weak and rapid
Blood pressure drops as well
Stages of shock:
Compensated:
Compensatory mechanisms
Activation of the sympathetic nervous system, increased cardiac output, and increased total peripheral
resistance in order to maintain perfusion to vital organs
If blood has been lost & the pt is in shock, the following are likely to occur:
Decrease in GFR
Decrease in urine formation
Progressive:
Decreased heart perfusion leads to cardiac depression and decreased cardiac output
Irreversible:
Depletion of high energy phosphate reserves
Death occurs even if treatment can restore blood flow
Major categories of shock:
Hypovolemic:
Produced by a reduction in blood volume
Results from severe hemorrhage, dehydration, vomiting, diarrhea, and fluid loss from burns
Results in a decrease in GFR and a decrease in urine formation
A patient is dehydrated due to severe vomiting; a symptom he/she might present with is an increased pulse rate
Cardiogenic:
Circulatory collapse resulting from pump failure of the left ventricle
Most often caused by massive myocardial infarction
Septic:
Due to severe infection
Causes include endotoxin from G- bacteria
Neurogenic:
From severe injury or trauma to the CNS
Anaphylactic:
Occurs with severe allergic reaction
Jaundice:
Yellow discoloration of the skin and white of eyes caused by abnormally high levels of the bile pigment, bilirubin, in the
bloodstream
Bilirubin
Heme is scavenged from the RBC (after their 120 day life span) and the Fe2+ is reused
Actively taken up by hepatocytes
Heme Biliverdin Bilirubin
Sparingly water soluble, toxic to CNS, and transported by albumin
Bilirubin is the product of heme degradation
Another Q: RBC destruction is measured by the bilirubin (bile pigments) excreted from the liver each day
Another Q: The amount of bile pigment secreted by the liver is deteremined by the amount of hemoglobin
destruction
Heme portion of the hemoglobin, the part of the red blood cells that carries oxygen is broken down into bilirubin
Bilirubin is carried to the liver as unconjugated and bound to albumin
UNconjugated is INdirect and INsoluble
Free bilirubin-albumin complex
Converted to the diglucuronide derivative (conjugated bilirubin) in the liver
Conjugated is Direct
Conjugated version is water-soluble
Conjugated is then ready to be excreted via bile
Then
excreted into intestines as a component of bile
OR excreted by the kidneys as urobilirubin
Bacterial conversion to urobilinogen in the colon (precursor for urobilirubin???)
Some excretion as stercobilin in feces
But most is recycled via enterhepatic circulation of urobilinogen
If the excretion from the liver is hindered, excess conjugated bilirubin passes into the bloodstream, resulting in jaundice

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Very common the leading manifestation of liver disease


Can occur at any age and in either sex
Symptom of many disorders liver disease, gallstones, pancreatic cancer, and acute biliary obstruction
Normal plasma concentration of bilirubin averages 0.5 mg per 100 ml of plasma
In jaundice it can rise to as high as 40 mg per 100 ml
Causes of jaundice:
Increased destruction of red blood cells with rapid release of bilirubin into the blood
Obstruction of bile ducts or damage to liver cells causes inability of bilirubin to be excreted into the GI tract
Phenylketonuria (PKU):
An abnormal presence of phenylketone and other metabolites of phenylalanine in the urine
PKU is caused by the absence of or a deficiency of phenylalanine hydroxylase, the enzyme responsible for the
conversion of the amino acid phenylalanine into tyrosine
Metabolic defect in phenylketonuria results in failure to hydroxylate phenylalanine adequately
Tyrosine lessens the need for Phenylalanine
Tyrosine becomes essential
Phenylalanine is the amino acid that can be converted to Tyrosine most easily in the human body
Accumulation of phenylalanine is toxic to brain tissue
It will impair normal development of the brain causing severe retardation
Signs: mental retardation, musty smell, fair skin, excema NO melanin
Alkaptonuria (aka homogentisuria): Think AKU
Due to the failure to catabolize tyrosine beyond the intermediate, homogentisic acid, which is excreted in the urine and
makes it appear black
THINK you make melanin from tyrosine, so of course its intermediate is dark colored
Homogentisic acid accumulates in the urine
Results from a deficiency of a dioxygenase (homogenetisate)
Usually, the condition does not result in any serious ill effects
Cystinuria:
A hereditary disorder characterized by excessive urinary excretion of cystine and other amino acids
COLA Cysteine, Ornithine, Lysine, and Arginine
Caused by a defect in the renal tubules that impairs the reabsorption of these amino acids
Excess cysteine in urine can lead to kidney stones
Albinism:
Due to the failure to convert tyrosine to melanin, as a result of a deficiency of the enzyme, tyrosinase
Tyrosine is a precursor of the pigments of the skin, hair & nails
Albinos do not have problems with epinephrine synthesis, despite melanin and epinephrine having DOPA as a common
intermediate, because of different enzymes used in malanocyte for DOPA synthesis
Teeth/Mouth
Enamel:
Highly mineralized structure containing approximately 95% inorganic matter
Hydroxyapatite (HA) crystals
Made up of calcium & phosphate
Are the largest mineral constituent (90-95%) of enamel
Have a multi-ionic structure
Solubility is pH-dependent (as pH , solubility )
Tends to bind polar substances
Substitution of carbonate into HA increases the solubility (instead
of phosphate) around the Ring
Fluorapatite forms during hard tissue formation by a substitution
of OH ions by F ions in the center of the Ring
The distribution of carbonate within dentin and enamel follows the same
surface to DEJ pattern as NONE of the above??? (Not Lead, Calcium,
Fluoride, or Strontium) maybe the same as phosphate as it
substitutes in HA
Ameloblasts produce an enamel matrix (organic matrix) with protein
components called amelogenins and enamelins
Amelogenin forms the collagen Rods by which are then calcified by Ca,
PO4 and OH minus
AMELOGENIN disappears makes the rods, but then disappears when
collagen and water decrease

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Enamelins stay behind as an interrod structure and are the MOST abundant
This organic matrix makes up about 1-2% of enamel and water makes up about 4%
Protein content of enamel from mature teeth is approximately 0.1-1%
The tooth becomes more resistant to acid-producing bacteria because fluorapatite has lower solubility product
constant than hydroxyapatite
Fluorapatite is less soluble than hydroxyapatite in solutions with low pH
What LEAST contributes to Fluorides anti-caries effectiveness??????
Substitutes for PO4, because it doesnt
Enamel is harder than bone
The main reason for this is that enamel hydroxyapatite crystals are larger and more firmly packed
These tightly packed masses of hydroxyapatite crystal are called enamel prisms and they are structural units of
enamel
These crystals in enamel are four times larger than those in bone, dentin, and cementum
Dentin
Dentin is not metabolically inert it is in dynamic equilibrium with blood and metabolites
Another Q: Collagen is the major protein produced by odontoblasts & is contained in the organic matrix of dentin
Another Q: Phosphophoryn is the noncollagenous protein component that best characterizes dentin matrix
Cementum
Collagen is the major protein component of cementum
Enamel Hypoplasia
A defect in the formation of enamel matrix
The enamel of primary and permanent teeth appear pitted, yellow to brown and have open contacts
Radiographically the enamel is either absent or very thin over tips of cusps and IP areas
Can be caused by nutritional deficiencies, hereditary
Vitamin A and C deficiency may cause it as well as inadequate intake of calcium, fluorosis, congenital syphilis, high
fever, rickets, injury or trauma to the mouth
Vitamins A and D are primarily responsible for enamel tooth formation
A vitamin A deficency in a developing tooth most likely affects enamel (more than dentin, pulp, & cementum)
Hypoplasia results only if the assault occurs during the time the teeth are developing
So, a prolonged vitamin A or D deficiency, Rickets, or inadequate intake of calcium can produce enamel hypoplasia
The Least important in producing enamel hypoplasia is Fluoride intake of less than 0.2ppm in the water
Another Q: Vitamins A, C, & D are all involved in tooth development & calcification; Vitamin B1 is not
Another Q: The lack of Vitamins A & D during tooth formation induces enamel hypoplasia
Enamel Hypocalcification
A defect in the mineralization of the formed enamel matrix
Pulp
Proprioceptors are not found in pulp
The hemodynamics of flow in the tooth pulp are most likely analagous to those in the cranium
Caries activity is directly proportional to:
Consistency of fermentable carbohydrates ingested
Frequency of ingesting fermentable carbohydrates (most important factor)
Oral retention of fermentable carbohydrates ingested
Caries development:
The first event in the development of caries is the deposit of plaque on the teeth
Plaque arises primarily as a result of bacterial enzymatic reaction using sucrose & saliva (fermentable CHOs)
SUCROSE is the most important factor for caries
Large numbers of bacteria (mainly S. mutans and Lactobacilli) inhabit plaque and are readily available to cause caries
However, these bacteria depend to great extend on CHOs (sucrose) for their food
When carbohydrates are available, their metabolic systems are strongly activated and they also multiply
As a result of the metabolic activity they release acids, particularly lactic acid, and proteolytic enzymes
When the acidity level (pH level) of the mouth drops below 5.5, demineralization of the teeth can occur
Carbonated Beverages
Carbonic acid, H2CO3, is a weak acid, but when ingested in large quantities can slowly decalcify teeth due to
low pH (They also contain Phosphoric acid which has the same effect)
Drinking large quantities of carbonated cola type beverages could lead to enamel decalcification due to low pH
Another Q: Tooth erosion in bulimic (bulimia) patients is due to solubility of hydroxyapatite in acid
Extracellular dextrans
An extracellular polysaccharide synthesized by cariogenic streptococci (not a mucopolysacch) in the presence of
sucrose
The structural component of plaque

75

Are formed from sucrose by bacterial enzymes (glycosyl trasferase GTF ) which are located on the cell surface of certain
lactic acid bacteria (e.g., S. mutans and Lactobacilli)
Another Q: Sucrose most directly contributes to the addition of polysaccharides to dental plaque
Dextrans are essential for the cariogenicity of these bacteria
Acquired Pellicle
Essentially absent of microorganisms
Brownish structureless film that accumulates on the surfaces of the teeth
Brownish color from tannin
Forms the interface between tooth structure and dental plaque and calculus
Calcium phosphate is NOT in the pellicle
The acquired pellicle is primarily composed of salivary glycoproteins
Most similar to organic composition of plaque????
Saliva:
pH of saliva is between 6.0 and 7.0
Saliva is able to neutralize acids mainly due to its bicarbonate content
Another Q: The principal buffer system in stimulated parotid saliva is carbonic acid/carbonate
Approximately 2/3 of the ~1 L/day produced by an average adult comes from the submandibular glands
~1/4 comes from the parotid glands & the remainder is produced by the sublingual & buccal glands
Occurs Most inbetween Meals
Saliva production drops at night
Composition of saliva:
97% to 99.5% water, contains electrolytes (Na+, K+, Cl-, and HCO3- ions; not F-)
Some chemicals, like Potassium, Iodine, and Mercury are excreted in part by the saliva
High K+ and HCO3- concentration (at least in the mucous portion)
Low Na+ and Cl- concentration
Hypotonic due to the fact that the salivary ductal cells reabsorb Na + and Cl- in exchange for K+ and
HCO3Also contains proline-rich proteins which have antimicrobial properties
Saliva supplies calcium and phospate for remineralization
Control of salivary secretion:
Both PS & Symp stimulations cause secretion
PS has the greatest effect
Vagal stimulation increases saliva production, so a vagotomy inhibits saliva production xerostomia
Atropine also prevents saliva secretion (normally stimulated by chorda tympani)
Sidenote: The chorda tympani nerve contains preganglionic parasympathetic secretory fibers
This isnt all it contains see Anatomy section for notes on its taste fibers, etc
It prevents the action of Ach on the secreting cells (anticholinergic competitve inhibitor of Ach)
Salivary Secretions:
Mucous secretion:
Contains mucins, which are proteins w/ polysaccharides attached to them lubricates mouth and food
Mucins are glycoproteins
Sublingual & buccal glands produce mucous secretions
Serous secretion:
Contains salivary amylase (ptyalin)
This enzyme splits starch into alpha dextrin, maltotriase, and maltose (see below)
So, -amylase ptyalin is secreted by the parotid glands
NOT produced from a zymogen
NOTE: The digestive action of salivary amylase continues for some time after swallowing, because the
amylase inside the bolus is protected from the inactivating action of gastric HCl
A number of proteins (proline-rich proteins, statherin, etc.) play important roles in maintaining the enamel
surface and preventing calculus formation
Parotid glands produce serous secretions
Parotid saliva is believed to be hyposmolar because reabsorption of water by striated duct cells is less
than reabsorption of sodium
Submandibular produce both mucous & serous secretions
Functions of Saliva:
1) Lubrication for the mastication and swallowing of food
2) Protection prevents dehydration of the oral mucosa
3) Oral hygiene antimicrobial properties and washes away food particles
Salivary lysozymes have bactericidal activity

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4) Digestion starch digestion by alpha amylase (ptyalin) [not required]


Amylases:
Digest starches by hydrolysis
Types:
Alpha amylase:
Converts starch to oligosaccharides
Salivary amylase (ptyalin) and pancreatic amylase are this type
They both hydrolyze 1,4 glycosidic bonds in starch yielding alpha-dextrin, maltotrios, and maltose
Malatase, alpha dextrinase, and sucrose in the intestinal brush border then hydrolyze the
oligosaccharides to glucose
Salivary amylase is inactivated by acidic environment of the stomach
Beta amylase:
Converts starch to maltose and dextrin
Glucamylase:
Converts starch to glucose
Monosaccharides are absorbed in the small intestines
Disaccharides
Maltose
Glucose + Glucose
Must be digested into an absorbable form that can be ingested by the enterocytes
Sucrose
Glucose + Fructose
Degraded by sucrase
Lactose
Glucose + Galactose
Isomaltase cleaves a glucose-linked 1,6 to another glucose as is found at branch points in starch/glycogen
The belief that the secretion of saliva is an active process is supported by the observation that secretion continues even
when the pressure within the salivary duct is higher than the blood pressure
Xylitol increases salivation
DNA/RNA
DNA double helix:
The two antiparallel polynucleotide chains of double helical DNA are not identical in base sequence or composition
Instead they are complementary to each other
Because strands are complementary, separated strands are able to reassociate
Wherever adenine appears in one chain, thymine is found in the other
Watson and Crick deduced this specificity of base pairing because of stearic and hydrogen bonding factors
In their structure the two chains or strands of the helix are antiparallel one strand runs 5 3 & the other runs 3 5
The DNA double helix is held together by two sets of forces:
1) hydrogen bonding between complementary base pairs
2) base stacking interactions
The two chains of dsDNA are so arranged that hydrophobic aromatic nitrogen bases are held close to each other
The helix structure results in a major and minor groove being formed along the DNA molecule
The major groove is the binding region for many proteins which control the transcriptional activity of the DNA
DNA backbone: picture

77

It is constant throughout the molecule


Monomeric units of nucleic acids are linked by phosphodiester bonds
The 3 hydroxyl group of one nucleotide bonds to the 5 hydroxyl group of the next nucleotide by a phosphodiester
linkage
The covalent backbones of a nucleic acid consists of alternating phosphate & pentose residues, w/ a purine or a
pyrimidine base is attached to each pentose
Phosphodiester bond connects the pentose hydroxyl groups of DNA and RNA are always 3 to 5
Bond formed from the esterification of 2 or 3 hydroxyl groups of phosphoric acid to adjoining nucleotide residues
Two free hydroxyl groups are present on the 3C and 5C
Is hydrophilic and highly polar
The hydroxyl groups of the sugar residues form hydrogen bonds with water
The ribose phosphate portion of purine & pyrimidine nucleotides comes from 5phosphoribosyl-1-pyrophosphate
(PRPP)
PRPP is synthesized from ATP and ribose-5-phosphate, which is primarily formed by the pentose phosphate
pathway
So, ribose phosphate needed for nucleic acid synthesis can be derived from the pentose phosphate pathway
What happens when DNA is denatured? (from 2 Qs)
UV light absorption increases
Complementary strands become random coils
Base stacking becomes disrupted
Hydrogen bonds are broken
Peptide bonds are broken
Loss of native conformation, 2 & 3 structure
Loss of biological activity
*Total G-C or A-T content does not change
Nucleic acids
Store and transmit information to synthesize the polypeptides and proteins present in the bodys cells
Nucleic acids are complex molecules composed of structures known as nitrogenous bases (purines and pyrimidines), five
carbon sugars (pentoses) and phosphates groups (which contain phosphorous and oxygen)
The backbone of nucleic acids is made up of alternating phosphate and pentose units, with a purine and pyrimidine
attached to each
Nucleotide = a single base sugar phosphate unit
The nucleotide is the basic unit of DNA
NOTE: catabolism of nucleotides yields no energy production in the form of ATP (unlike lipid, protein & CHO)
Another Q: An example of a nucleotide is thymidylate (dTMP); urate, uracil, ribose, adenosine are not nucleotides
Nucleoside = a single base sugar phosphate unit w/o a phosphate group

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These individual nucleotides are linked together to form a polynucleotide chain (the link or bond is between a phosphate
group of one nucleotide and the sugar of the next)
If the polynucleotide chain contains the sugar ribose, the chain is called a ribonucleic acid (RNA); if it contains the sugar
deoxyribose, the chain is called deoxyribonucleic acid (DNA)
2-deoxyribose is always found in DNA
Hydrolysis of nucleic acids yields
Ribose, adenine, deoxyribose, phosphoric acid, NOT acetic acid
Bases
PURINES (PURe As Gold)
Have 2 rings
Guanine has a ketone
Adenine (A) and guanine (G)
The C-G bond results from 3 H-bonds
The A-T bond results from 2 H-bonds(AT (annual training) is 2 weeks long)
Purine bases consumed in the human diet in the form of DNA or RNA are mostly excreted in the form of uric acid
Another Q: The end product of the catabolism of purine is uric acid
Another Q: Xanthine oxidase catalyzes this formation of uric acid from purine bases (NOT hydrolysis)
Xanthine oxidase is involved in the last step of purine degradation changing xanthine to uric acid
What is inhibited by allopurinol? Xanthine oxidase
Hypoxanthine and xanthine are also purine bases
Nucleoside derivatives of these bases will contain either ribose or 2 deoxyribose linked to the purine ring
through a beta N-glycosidic bond at N9
The link between Ribose (Sugar) and Purine (Base) is via a glycosidic bond
In the final rxn of the de novo synthesis of purine ribonucleotide, inosine monophosphate (IMP) is formed
IMP is converted to adenosine phosphates and guanosine phosphates
Purine ribonucleoside phosphates are all synthesized de novo from the common intermediate inosine
phosphate
PYRIMIDINES (CUT the PY)
Have 1 ring
Thymine has a Methyl
Uracil does not
In DNA, pyrimidine bases are thymine (T) and cytosine (C)
In RNA, pyrimidine bases are uracil (U) and cytosine (C)
Uracil is the pyrimidine base that is present in RNA, but not in DNA
Three H bonds are formed between G and C, but only two form between A and T
The melting temperature of the double helix is a function of the base composition
Higher GC content having a higher melting temperature and an increased stability of the double helix
If the molar % of A in a native DNA specimen is 22%, then the molar content of G is28% (do the math)
Bacteria found in hot springs, high G-C content for high Bpoint, from 3 bonds
The weaker bonding between A and T is used in transcription to aid in the release of the newly formed RNA from the
DNA template
Remember U substitutes T in RNAthey both bind to A
The use of tetrahydrofolic acid (TFA) by several of the enzymes in purine and pyrimidine synthesis have made TFA
metabolism a prime target for a number of antimetabolites such as methotrexate, used in cancer chemotherapy
Methotrexate works in the S phase
Tetrahydrofolic acid is a coenzyme required in the general reaction for the transfer one-carbon fragments
Another Q: DNA damage by ultraviolet light is due to induction of dimerization by way of covalent bonds
between adjacent thymine groups
Just Like SAM???
The pyrimidine dimers then interfere with replication and transcription
Replication: Good review in blue book called Biochemistry pg. 123
The process of completely duplicating the DNA within a cell
The process is semi-conservative
Each new double helix will consist of one old and one newly synthesized strand
The primary enzyme in this process is DNA polymerase
The polymerase that initiates the primary synthetic reaction is polymerase 3
But first needs primer to initiate synthesis. Note: RNA replicaion does not require a primer
Reads a single strand of DNA from 3 to 5 while forming the new, complementary, continuous strand from 5 to 3
As the DNA polymerase complex moves along the DNA molecule, the original complementary stand (lagging
strand) is also duplicated

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DNA polymerase moves along the lagging strand from 5 to 3 and thus cannot form a continuous copy
of the lagging strand
Instead, it forms ~1000-5000base long multiple segments (Okazaki fragments)
The fragments are joined together by DNA ligase to form a continuous strand
DNA Ligase
Involved in DNA Replication, Repair, and Recombination (The 3 Rs)
NOT transcription
Immediately following the production of Okazaki fragments, the gap between fragments becomes
connected through the action of DNA-ligase
Another Q: DNA ligase seals single stranded nicks in DNA
DNA polymerase can only add nucleotides to a pre-existing piece of nucleic acid (primer)
During replication the primer is provided by RNA polymerase (which has no primer requirement)
The short 10-base segments created by RNA polymerase are removed, once the DNA has been added to it, by an
exonuclease and the gap in the sequence is filled in by a DNA polymerase
RNA polymerase
is an enzyme that synthesizes polynucleotide sequences from nucleotides and does not require a primer chain
(opposite to DNA polymerase)
No proofreading fxn
RNA polymerase binds to TATA box on ssDNA
But can initiate chains
RNA polymerase II opens DNA at promoter sites (A/T rich upstream sites, i.e. TATA and CAAT)
DNA Repair
First a special glycosylase recognizes the error
Endonuclease cuts internal phophodiester bonds cuts DNA into pieces
Exonuclease removes jacked-up pieces
Cuts at the end of the chain
DNA polymerase fills the gaps
DNA Ligase seals

FROM PIC, read it 3- 5 and Make 5 FIRST


The Genetic Code
Degenerate nature of the genetic code:
Implies that many amino acids are designated by more than one codon
Unambigous = only one codon for that amino acid (Tryptophan, Selenocystein, and Methionine)
The other 18 amino acids are coded by 2+ codons
Codons (sometimes referred to as a triplet)
A sequence of three adjacent nucleotides (AUG, for example) in a nucleic acid that codes for a specific aa
How many nucleotides are required to code for a protein with 150 amino acids? Ans: 450
Codons that specify the same amino acid are called synonyms
Multiple codons for an amino acid usually differ in the third base (at the 3 end)
Several of the Codons Serve Special Functions:
Initiation codon (AUG or rare GUG):

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Signals the beginning of polypeptide chains and codes for methionine (all proteins begin with methionine)
Starts the inAUGural Methionine (In prokaryotes its f-met)
Termination codon (UAA, UAG, and UGA):
Signals the end of polypeptide chain sythnesis
These codons are also referred to as STOP codons or Nonsense codons
Selenocysteine is the 21st genetically coded aa
The codon UGA occurring in the correct contex, leads to the incorporation of this serine derived aa
Anticodon
A specific sequence of three nucleotides in transfer RNA complementary to a codon for an amino acid in a
messenger RNA
The aa inserted in a polypeptide chain during protein synthesis is determined by a complementary
relationship between mRNA & tRNA
The two RNAs are paired antiparallel:
DNA Polymerase reads from 3 to 5 on the DNA, and makes 5 to 3 mRNA to match
Then, tRNA matches the 5 to 3 mRNA by its anticodon which is a 3 to 5, BUT anticodons are
ALSO read 3 to 5
The first base of the codon pairs with the third base of the anticodon (both are read in the 5 to
3 direction)
EX: If the codon on mRNA is CGU, then the corresponding anticodon on tRNA is ACG
Dont get clowned by simply lining up the codon & anticodon and giving that as your answer
Its really 5CGU3 and 5ACG3
So, you could just match up 5CGU3 and 3GCA5, then switch it up to 5ACG3 for your answer, got it?
Transcription
Process in which DNA serves as a template for the assembly of molecules of RNA (all three types)
Cellular process of making RNA from DNA
This process involves the enzyme RNA polymerase
From way out in right field: Rifampin is effective in treating active TB because it targets transcription
Translation (L for last step)
Is the process by which genetic information flows from RNA to protein
Involves 4 steps
Activation
Involves joining the correct amino acid to the correct tRNA (AUG)
Initiation
Small subunit of ribosome binds to the 5 end of the mRNA
Uses the help of Initition factors
The first step in the utilization of amino acids for protein synthesis requires aminoacyl-tRNA synthetase
Elongation
Next AA in line will form complex with Elongation factor and GTP
In prokaryotic protein synthesis, the elongation factor G serves to translocate the growing peptide chain and to
move the ribosome along the mRNA
At the end of each elongation cycle, the growing polypeptide is found as peptidyl-tRNA bound to the P site
Termination
When A site faces nonsense codons (UAA, UAG, UGA), no tRNA can recognize it, but releasing factor will
recognize it and release the newly synthesized protein
Types of RNA:
Messenger RNA (mRNA or RNA polymerase II):
M for Massive
Single-stranded; made in the nucleus; made as a complement to one strand of DNA; template for protein synthesis
Molecules carrying information (genetic code) from DNA in the nucleus to ribosomes in the cytoplasm, where
polypeptides and proteins are synthesized (translationmRNA is the template for protein synthesis)
Random Q: Addition of synthetic polyuridylic acid to a cell-free system capable of protein synthesis results in
greatly enhanced incorporation of phenylalanine into peptide linkages. In this system, polyuridylic acid is
performing a function normally performed by mRNA.
A landmark experiment was formed where polyuridylic was dumped into a cell-free, but protein synthesizing
system. It resulted in the production of polyphenylalanine, and lead us to the breaking of the genetic code, so
here the polyuridylic acid served as the mRNA that brought in the instructions for translation
Splicing
Small lariot shaped intermediate is formed
Then a SnRNP (small nuclear ribonucleoprotein particle splices out the intron)

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Intron vs Exon
Exons stay in the mRNA to EXIT the nucleus
Another Q: During nuclear processing of hnRNA to mRNA the portion of the molecule that is removed is
the intron
Processing
Occurs in the nucleus
Capping on the 5 end (7 methyl G)
What is the reason for the GGG repetition in prokaryotes
Protects the mRNA from degradation outside the nucleus
For the ribosome movement, translation process
Polyadenylation on 3 end (300 As)
Pre-processed transcript is called hnRNA heterogenous RNA, where post is called mRNA
Transfer RNA (tRNA or RNA polymerase III):
T for Tiny
Made in the nucleolus
Molecules carry the amino acids to ribosomes, where the amino acids are linked together in the order specified by
mRNA to form particular polypeptides and proteins
Clover shaped, with the amino acid covalently bound to 3 end
Amino acyl-tRNA synthetase
is a group of ligases (enzymes) that ensures that the correct amino acid is attached to the tRNA with the correct
anticodon to be used during protein synthesis
Uses ATP for its monitoring energy
SO, ATP is used for Activation tRNA
BUT, GTP is used to bind tRNA to ribosome
tRNA activates and selects specific amino acids for protein synthesis
Individual enzymes are highly specific for one amino acid
No error checking occurs during the translation process on the ribosome
Ribosomal RNA (rRNA or RNA polymerase I):
R for Rampant
Made in the Nucleolus
Molecules are the major component of ribosomes, which are the physical and chemical structures on which protein
molecules are actually assembled
rRNA is the most abundant of the three types of RNA (rRNA > tRNA > mRNA in abundance)
mRNA is the largest (Massive mRNA, Rampant rRNA, and Tiny tRNA)
Ribosomes:
Small structures found floating free in the cytoplasm (polyribosomes) that contain rRNA and protein
Translation (aka protein synthesis)
At a ribosome, amino acids are linked together in the order specified by mRNA to form a polypeptide or protein
Have E, P, and A sites for Translation
Come in on A site, shift to P site to be added to, and then bumped out on the E site
Ribosomes have enzymatic activity
They catalyze the formation of peptide bonds, which link amino acids to one another
Rough ER
Carboxy-terminal of protein attaches to the RER????
Some are attached to the cytosolic suface of the endoplasmic reticulum membrane
Proteins formed by ribosomes attached to the RER are destined for secretion from the cell, incorporation into the
plasma membrane, or formation of lysosomes
Since all protein synthesis begins on free ribosomes, attachment of a ribosome to the ER requires the presence of a
specific sequence at the amino end of the growing protein chain to signal the attachment of the ribosome to the ER
70s ribosomes are the sites of protein synthesis (translation) in bacterial cells and chloroplasts
80s ribosomes are the sites of protein synthesis (translation) in eukaryotic cells
Most protein synthesis occurs on polyribosomes
Hydrolysis of DNA will yield:
Phosphoric acid
Deoxyribose (sugar)
Nitrogenous bases (A,G,T,C)
Hydrolysis of RNA yields the same stuff (but U instead of T and ribose instead of deoxyribose)
Ribose and uracil are the only differences between the products of RNA and DNA hydrolysis
Another Q: Hydrolysis of nucleic acids produces pentoses, phosphates, amino acids, purine bases, pyrimidine bases
Replication forks are sites at which DNA synthesis (replication) is occurring

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Helicases unwind the helix


Topoisomerases act to decrease the degree of supercoiling of the helix, aiding in unwinding the DNA at the replication forks
DNA gyrase, a topoisomerse found in prokaryotes, in addition to reducing the supercoiling prior to replication induces a
negative supercoil following replication
Secures the replication fork
Primase
Reverse transcriptase:
Certain RNA viruses contain within the viral particle a unique RNA-directed DNA polymerase which is called reverse
transcriptase
Building DNA from RNA
On infection, the single stranded RNA viral genome and the enzyme enter the host, and the reverse transcriptase
catalyzes the synthesis of a DNA strand complementary to the viral RNA or mRNA (different question)
This enzyme is found naturally in certain viruses called retroviruses
These viruses in which the genetic information is carried on an RNA molecule
When one of these viruses infects a host cell, it uses this enzyme to make a complementary DNA (cDNA) copy of
its genetic information which is then incorporated into the host DNA
cDNA Library
A collection of DNA sequences generated from mRNA sequences
This type of library contains only protein-coding DNA (genes) and does not include any non-coding DNA
*NOTE: The distinguishing feature of a cDNA library is the presence of multiple copies of RNA transcriptase
*NOTE: Reverse transcriptase is used in vitro to make cDNA from mRNA
The human immunodeficiency virus (HIV) the causative agent in AIDS, is a retrovirus
The drug AZT (a thymidine analog) is a competitive inhibitor of the HIV reverse transcriptase
NOT Flurouracil antineoplastic drug used in carcinoma pts to interfere with DNA and RNA
NOT Methotrexate Antineoplastic drug that interferes with DNA synthesis, repair, and cellular
respiration
Inhibits dihydrofolate reductase, inhibiting formation of THF, which inhibits thymidine
synthesis, which inhibits DNA synthesis, etc.
Methotrexate works in S phase
The wild-type reverse transcriptase seems to have a higher affinity for AZT and other base analogs
Reverse transcriptase is one of the enzymes used in genetic engineering, where it can be used to obtain a copy of a
particular gene from the relevant mRNA
NOTE on viruses: Certain viruses isolated in crystalline form have been found to be nucleoproteins
This didnt fit anywhere else in the document
Mutations
Nonsense
Worst
Results in termination of protein, usually mutation to a stop codon
Missense
Changed AA, but similar in strucure
Silent
Same AA, but codon was changed
Usually in 3rd position of codon
Frame shift
Results in entire misreading down-stream
Usually results in truncated protein
Transition vs Transconversion
Transition = purine for purine
Transconversion = purine for pyrimidine or vice versa
Genetic recombination experiments:
Depend heavily upon the action of DNA ligase and endonucleases
*NOTE: Restriction enzymes are best described as site-specific endonucleases
Purpose of Restriction Endonuclease? Fragment DNA
Nuclease
Used to cleave both the DNA to be clones and a plasmid DNA
The specificity of the nuclease is such that when mixed, the DNA to be cloned and the plasmid DNA will
anneal (base pair) and can then be joined together by a DNA ligase
The first organism used for DNA cloning was E. Coli and it is still the most common host cell
Bacterial cloning vectors plasmids, bacteriophages, and cosmids
Plasmid vectors suitable for cloning have 2 genes conferring resistance to different antibiotics (its true!)

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Commercial products of recombinant DNA technology include:


Human insulin (for diabetes)
Anticoagulants (tissue plasminogen factor)
Erythropoietin for anemia
Human growth factor (for dwarfism)
Some other enzymes that are used in recombinant DNA technology include:
DNA polymerase I (not RNA polymerase) fills in gaps in duplexes by step-wise addition of nucleotides to 3end
Reverse transcriptase makes a DNA copy of an RNA molecule
Exonuclease removes nucleotides from 3 ends of a DNA strand
DNA ligase, DNA polymerase I, restriction nucleases, reverse transcriptase are involved in gene cloning
RNA polymerase is not Huh???
Restriction Nucleases (Site specific Endonucleases)
Find specific sites to cut open in the DNA
Usually work in dimers and create palindromic 5 to 3 segements
Used for the Introduction of recombinant DNA into a bacterial cell
*NOTE: Restriction enzymes are best described as site-specific endonucleases
Southern Blotting (S for Same)
The type of blotting used to identify DNA restriction fragments is Southern blotting
DNA-DNA Hybridization
Northern Blotting
DNA-RNA hybridization (northeRN)
Which is used for mRNA
Western Blotting (Think Western society with their protein bars/shakes, etc.)
Antibody-Protein Hybridization
Southwestern Blotting
DNA-protein interaction
ELISA (Enzyme linked immunosorbant assay)
Basically test the blood with an antigen, it it links with an antibody, it luminsces a bright color
HIV test
PCR (Polymerase chain Reaction)
Used to synthesize many copies of desired DNA
Steps
Heat DNA to denature it
Then cool it with added premade primers
Then a heat stable DNA polymerase copies
Then repeat
The polymerase chain reaction is most useful for amplifying a specific DNA sequence
Sanger Methods
You throw a bunch of dideoxynucleotides, that lack OH at the 2 and 3 position, and they are used to terminate DNA
synthesis at specific bases
Four separate reactions are carried out, when the dideoxynucleotide is incorporated, DNA synthesis stops, so each of the
4 reactions would yield a series of products extending from the primer to the DNA terminating dideoxynucleotide
Products are then separated by electrophoresis and analyzed by autoradiography to determine the DNA sequence
Basic principles for sequencing DNA in the Sanger procedure derive from Replication

Proteins/Amino Acids
Proteins
A polypeptide chain of ~100 or more amino acids linked by peptide bonds

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10+ amino acids linked in a chain by peptide bonds form a polypeptide


Proteins function as hormones, catalysts, structural elements, & oxygen carriers
NOT carriers of genetic information
Proteins are able to buffer physiologic solutions over a wide range of pH because they contain many functional groups
with varying pKs
Deficiency in proteins may be indicative of: lack of vigor and stamina, weakness, mental depression, poor resistance to
infection, impaired wound healing, slow recovery from disease
Primary structure
Amino acid sequence (linked together by covalent peptide bonds)
From N-amino terminal to carboxy terminal of the protein chain
Always linked from N to C
The primary structure of proteins is best described as the polymer formed by amide linkages between alphacarboxyl group and alpha-amino groups
The Amide bond links amino acid residues to form proteins
Secondary structure
Refers to the spatial arrangement of a portion of a polypeptide chain determined by the amino acids present
The most common types of secondary structures are:
Alpha helix (coiled conformation of a peptide chain)
Beta pleated sheets (an extended, zigzag arrangement of a polypeptide chain)
Beta bends (reverse turns)
Secondary protein structures are stabilized by hydrogen bonds
Tertiary structure
Stabilized by hydrophobic interactions, then hydrogen bonds
Refers to the irregular folding of a polypeptide chain
The overall 3D conformation of the polypeptide (globular, fibrous, and pleated sheet)
Proline contributes to the tertiary structure of a protein by causing a bend when it occurs in the primary
sequence
Cysteine can stabilize the tertiary structure by forming a covalent bond in its side chain
Quaternary structure
Refers to the spatial arrangement of subunits in a protein consisting of >1 polpeptide chain
Two EXs of proteins with quaternary structures are 1) hemoglobin and 2) Ab molecules found in blood
This is the level of protein structure in which 2+ individual polypeptides interact to form a noncovalent complex
Protein Bonds
Noncovalent
Ionic, Hydrogen, and Hydrophobic
Covalent
Peptide (Amide)
X-ray diffraction
Requires a protein in crystalline form
Beam of x-rays is diffracted by the electrons around each of the atomic nuclei in the crystal and with an
intensity proportional to the number of electrons around the nucleus
Another Q: The best method for determining the 3D structure of a protein is by x-ray diffraction
Electrophoresis
Used to separate various proteins based on protein size and charge
Procedure that depends primarily on electrostatic net charge
Ultracentrifugation
Separates and characterizes proteins based on molecular weight and size
Peptide bond:
A specific type of amide bond
Because a peptide bond is a form of an amide bond, amide bonds link amino acid residues to form
proteins
Covalently joins the alpha-carboxyl group of one aa and the alpha-amino group of another aa
Formation of peptide bond results from the removal of a molecule of water between the carboxyl group of one
amino acid and the amino group of a second amino acid
Extremely stable and cleavage generally involves the action of proteolytic enzymes
Characteristics of peptide bonds:
No freedom of rotation around the bond
Has partial double-bond character means it is shorter than a single bond and is therefore rigid & planar
Bonds involving the alpha carbon can rotate freely

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Is generally a trans bond (instead of a cis bond)


Is uncharged but polar
Proline, due to formation of a tertiary amine, restricts the range of rotation of the -carbon in the peptide bond
Disulfide bond:
Another type of covalent bond that occurs in many proteins
Formed from the sulfhyrdyl group (SH) of each of two cysteine residues, to produce a cystine residue
(A residue is a single aa unit within a polypeptide chain)
It is widely thought that these strong, covalent bonds help stabilize the structure of proteins and prevent them from
becoming denatured in the extracellular environment
EXs insulin & immunoglobulins
Cysteine is the aa that can stabilize the 3 structure of some proteins via a covalent bond involving its side chain
Protein Denaturation
Denaturation usually destroys hydrogen, hydrophobic, & electrostatic bonds (but not covalent bonds)
Characterized by
Loss of native conformation, secondary and tertiary structures
Loss of biological activity
Breakage of H bonds
Amino Acids (AAs) I need pictures/diagrams
Have a central or alpha carbon to which is attached a H atom, a COOH carboxyl group, an NH2 amino group, and a 4 th
group, Rwhich determines the AAs identity
Except Glycine, which has 2 H groups (in other words, R = H for glycine)
Used for Energy
First the AA loses its amino group and is converted to alpha-keto acids that can enter Krebs cycle
An alpha-keto acid is similar to an AA, except that is has O2 rather than an amino group bonded to its
alpha carbon
When proteins are broken down for energy, most of the energy is derived from the oxidation of the alpha-keto
acids (Pyruvate, Oxaloacetate, and alpha-ketoglutarate)
Negative nitrogen balance (nitrogen output exceeds intake) may be caused by a dietary lack of essential AAs
Another Q: Total urinary nitrogen excretion is least when an individual is on a diet containing adequate fat & CHO
but no protein
Higher temperatures facilitates the increase intake of salts
Metabolism of carbohydrates serve as a principal source of carbon for nonessential AAs
All are stereoisomers (aka optical isomers or enantiomers) EXCEPT Glycine
All have a chiral center (4 different groups attached to a central carbon)
Non-superimposable mirror images of each other
Glyceraldehyde
The reference compound for naming all other compounds is the smallest sugar w/ an asymmetric carbon
(An asymetric carbon is characterized by having 4 different groups attached to it)
In other words, the arrangement of sugars into D- and L- configurations is based upon their resemblance
to D- and L-glyceraldehyde
Established by x-ray diffraction analysis
All AAs are L designated compared to glyceraldehydes (except for some D in ABX and bacteria cell
walls)
(aLL for L)
Grouped by their R Group (5)
Nonpolar, aliphatic R groups:
alanine, valine, leucine, isoleucine, glycine and proline (All Gay Lovers Lay w/ Vernas pussy)
Aromatic (generally nonpolar):
phenylalanine, tyrosine, and tryptophan
Forming tyrosine from phenylalanine only requires hydroxylation of the benzene ring at carbon 3
That is why it is most easily converted in the human body
Polar, uncharged R groups:
serine, threonine, cysteine, methionine, asparagines, and glutamine
(the polarity of cysteine and methionine is contributed by their sulfur atom, and that of asparagines
and glutamine by their amide group)
Negative charged:
aspartate and glutamate (Aspartic ACID and Glutamic ACID)
Positively charged: (Think HAL plays the Bass)
lysine, arginine, and histidine

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Arg and Lys have an extra NH3 and are found in large amounts in Histones, which bind to negatively
charged DNA
**Arg is the most basic AA
Essential vs. Nonessential
Essential AAs (9):
PriVaTe TIM HArgLL
Phenylalanine, Valine, Tryptophan, Threonine, Isoleucine, Methionine, Histidine, Arginine, Lysine,
Leucine
**Arginine and Histidine are required during periods of growth
Methionine is a thio-ether
One question lists groups of 3 AAs & asks which group contains only essential AAs
Phenylalanine
Is an essential AA needed for optimal growth in infants and for nitrogen equilibrium in adults
Tryptophan
Forms 5 HT (serotonin), melatonin, niacin, and the nicotinamide moiety of NAD and NADP
NOTE: proteins obtained from corn are poor in nutritional values for man because they are low in lysine
& low in tryptophan both are essential AAs, get the drift?
Nonessential AAS (11):
Glutamate, glutamine, proline, serine, glycine, aspartate, asparagines, alanine, cysteine, & tyrosine
Ten of the nonessential amino acids contain carbon skeletons that can be derived from glucose
What makes glutamine from glutamate? Glutamine synthase
They are not needed in the diet
Can be synthesized from:
The corresponding alpha keto acid
An alpha amino acid (as the NH3 donor)
A specific transaminase enzyme
And the coenzyme pyridoxal phosphate (vitamin B6)
These AAs include alanine, aspartate, and glutamate
The other nonessential AAs are synthesized by amidation (glutamine and asparagine)
Glutamate, glutamine, proline, arginine, serine, glycine, aspartate, asparagines, alanine, cysteine, &
tyrosine
Cysteine and tyrosine become essential when their precursors, methionine and phenylalanine, are
restricted
In a phenylketonuric person, tyrosine is an essential aa
Cysteine and methionine have sulfur containing side chains
Cysteine
Although its carbon skeleton can be formed from carbohydrates, requires the essential amino acid
methionine to supply the sulfhydryl group
Tyrosine
Is synthesized by hydroxylation of the essential amino acid phenylalanine
Presence of tyrosine lessens the need for phenylalanine
Another Q: Phenylalanine can most easily be converted to tyrosine in the human body
Synthesizes dopamine, the thyroid hormones (triiodothyronine and thyroxine), melanin,
norepinephrine and epinephrine
Dopamine is synthesized in two steps from tyrosine
Alanine
can be synthesized by transamination directly from pyruvic acid, using glutamic acid as an
amino group donor
Glycine
Glycine is the immediate precursor for creatine, purines & porphyrins
Serine
Has a hydroxyl group that often participates in NZ reactions
Classified as ketogenic, glucogenic, or both according to the nature of their metabolic end-products:
Ketogenic:
Amino acids whose catabolism yields either acetoacetate or one of its precursors, acetyl CoA or acetoacetyl
CoA
EXs leucine and lysine
Glucogenic and ketogenic:
Amino acids whose catabolism yields both ketogenic and glucogenic end-products
EXs tyrosine, isoleucine, phenylalanine, and tryptophan
Glucogenic:

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Amino acids whose catabolism yields pyruvate or one of the intermediates of the citric acid cycle (alpha
ketoglutarate, oxaloacetate, fumarate, and succinyl CoA)
EXs the remaining amino acids
Synthesis of Amino Acids:
Alpha ketoglutarate gives rise to glutamate (think a comes first ate before ine)
-ketoglutarate + alanine glutamate + pyruvate
which in turn is the precursor of glutamine, proline, and arginine
3 phosphoglycerate gives rise to serine
which, in turn, is the precursor of glycine and cysteine
Oxaloacteate gives rise to aspartate
which in turn is the precursor of asparagines, methionine, threonine and lysine
Threonine along with pyruvate is the precursor of isoleucine
Pyruvate gives rise to alanine, valine, leucine, and isoleucine
*Isoleucine can be formed by either pyruvate or threonine
Phosphoenolpyruvate and erythrose 4 phosphate produces shikimate
which is converted to Chorismate
Chorismate gives rise to tryptophan, tyrosine and phenylalanine
Tyrosine is synthesized from phenylalanine in humans
Ribose 5 phosphate gives rise to histidine
Catabolism of Amino Acids????
The first step in the catabolism of most AAs involved the removal of the alpha amino group
Once removed, this nitrogen can be incorporated into other compounds or excreted
The enzymes that catalyze these reactions are known as transaminases or aminotransferases
Transamination:
Involve the transfer of amino group from one AA to an alpha keto acid
Glutamate and alpha ketoglutarate are often involved in these reaction, serving as one of the amino
acid/alpha keto acid pairs
ALL transaminases require the coenzyme pyridoxal phosphate (PLP) = vitamin B6
Transamination of the alpha amino to a keto acid is the 1st step in the catabolism of many amino
acids
Pyridoxal phosphate (PLP) derived from vitamin B6 & serves as the cofactor for these reactions (required in all
transaminase reactions)
Vitamin B6 (pyridoxal phosphate) acts as a coenzyme in transamination reactions
PLP functions as the intermediate carrier of amino groups at the active site of aminotransferases
It undergoes reversible transformations between its aldehyde form, pyridoxal phosphate (PLP) which can accept
an amino group, and its aminated form, pyridoxamine phosphate (PMP) which can donate its AA to an alpha
keto acid
Glutamate Dehydrogenase: (Top of the Urea Cycle Chart)
Catalyzes the oxidative deamination of glutamate to form alpha ketoglutarate, using either NAD+ or
NADP+ as an electron acceptor
The reversible reaction has major function in both the synthesis and degradation of glutamic acid and via
transaminases, other AAs as well
These reactions (oxidative deamination) occur primarily in the liver and kidney and provide alpha keto
acids (for energy) and ammonia (source of nitrogen in urea synthesis)
Histidine is deaminated by histidase to form ammonium ion (NH4+) and urocanate
Serine and threonine are deaminated by serine dehydratase
Serine is converted to pyruvate
Threonine to alpha ketobutyrate; NH4+ is released
Glutaminase deaminates glutamine to glutamate and NH4+
Asparaginase deaminates asparagines to aspartate and NH4+
In synthesis, you add the amine group to the acid (-ate) to make it an (ine)
In catabolism, its backwards, you pull off amino group from the (ine) and get the acid for (ketone body)
energy and ammonia goes to the urea cycle
Amino Acid Derivatives
Phenylalanine Tyrosine
Thyroxine
Dopa Dopamine
Melanin
NE Epi
Tryptophan

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Nicin NAD+/NADP+
Serotonin (5-HT)
Melatonin
Histidine
Histamine
Glycine
Porphyrin Heme
Arginine
Creatine
Urea

Collagen
General facts:
Collagen is 35% glycine, 21% proline, & 11% alanine (hydroxyproline & hyroxylysine are also present see
below)
The unique aa composition of collagen is reflected in the high content of glycine, proline, & hydroxyproline
Hydroxyproline can be used as an estimatation of the amount of collagen present in a tissue of meat
Collagen is Unique because of its Hydroxyproline
Mature collagen lacks aromatic & sulfur-containing amino acids
The amino acid composition of mammalian collagen (Type 1) is characterized by the presence of
glycine (nearly 1/3 the total # of aa residues)
hydroxyproline & hydroxylysine
no sulfur-containing amino acids
The basic structural unit of collagen is tropocollagen
Tropocollagen is the longest known protein and is formed from procollagen, which is secreted by fibroblasts into the
Extracellular space
The Process http://depts.washington.edu/bonebio/ASBMRed/collagen/collagen.swf for a good review
Gly-x-y is formed in the RER (called preprocollagen)
Then this gets hydroxylated in the Golgi to procollagen
Procollagen is wound into a triple helix, then this gets exocytosed
Procollagen peptidases cleave terminal regions of procollagen, which transforms it into tropocollagen which
then aggregates to form collagen fibrils
The fibrillar structure is reinforced by the formation of covalent lysine-hydroxylysine cross-linking between
tropocollagen molecules, done by enzyme LYSYL OXIDASE

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Tropocollagen is also present in reticulin, which is a component of reticular fibers


Almost 1/3 of all proteins found in the body is collagen
Collagen is the most abundant protein (by weight) in the human body
Collagen biosynthesis
Intracellular events include
translation, hydroxylation, glycosylation, and peptide bond formation
Extracellular events include
Intermolecular cross-linkage
Fibrin Formation
Another Q: Intermolecular cross-linkage is a collagen synthesis post-translational event occurring
extracellulary by lysyl oxidase
Mitochondria is NOT involved in Collagen synthesis, but RER, Golgi are!!
Each collagen molecule consists of 3 polypeptide chains which are wound tightly around each other to give a triple
helix
This gives the molecule a structure which is very resistant to stretching, a vital property, for example, for its
functions in tendons and as a component of the matrix of bone and cartilage
Vitamin C influences the formation of collagen, which is the organic matrix found in dentin and cementum
Another Q: Collagen is the major protein produced by odontoblasts & is contained in the organic matrix of dentin
Another Q: Increased aging is associated w/ increased crosslinking of collagen
Collagen and reticular fibers make up the stroma of all lymph tissues except the thymus
Hydroxyproline and hydroxylysine
Are nonstandard AAs that are present in few proteins other than collagen
For this reason their concentration in a particular tissue is a good estimate of collagen content
Are not used directly in the reactions of protein synthesis
Are formed by the hydroxylation of proline and lysine
Proline becomes hydroxylated in the synthesis of collagen
Another Q: The hydroxylation occurs after translation
Another Q: The hydroxylation involves -ketoglutarate, ferrous iron, oxygen, & vitamin C (ascorbic
acid)
Does not involve ergosterol or vitamin K
Another Q : Procollagen proline hydroxylase & procollagen lysine hydroxylase require vitamin C for their
activity
Another Q: The best explanation of why vitamin C is essential in the diet of patients recovering from
periodontal surgery is that it is an essential cofactor in the hydroxylation of proline
Another Q: Vitamin C deficiency primarily affects connective tissue
Collagen has a trihelical structure
The molecular weight of tropocollagen is above 100,000 tropo is the longest known protein
Destruction of collagen can be caused by collagenases
Collagen contains both hydroxyproline and hydroxylysine residues
Elastin:
Is rich in small, nonpolar aliphatic residues such as glycine (1/3 of all residues), proline, alanine, valine, leucine, and
isoleucine
Elastin & collagen are both ~1/3 glycine
It contains a small amount of hydroxyproline????
Is a CT protein with rubber-like properties, in contrast to collagen, which forms high tensile strength fibers
Can stretch several times their normal length gives these fibers the capacity of returning to their original lengths after
being stretched
Fibers are found in the skin, ligaments and in the walls of arteries where their elastic properties are important
The polypeptide subunit of elastin fibrils is tropoelastin (as opposed to tropocollagen)
Elastin fibers are formed as a 3D network of cross-linked polypeptides
The crosslinks involve lysine and oxidized lysine residues (allysine), which are covalently linked to produce a
desmosine crosslink
NOT Disulfide crosslinking
The oxidation of lysine residues in both collagen and elastin is an extracellular process catalyzed by lysyl
oxidase a copper requiring enzyme
So, collagen, elastin, and reticulin are types CT fibers; chitin is not
Histones:
Fairly low molecular weight and contain a large portion of the simple, positively charged AAs arginine and lysine
(Part of HAL playing the Bass Lysine, Arginine, and Histidine)
Chromatin of eukaryotic cells consists of DNA complexed with histones in nucleosomes
There are five major classes of histones: H1, H2A, H2B, H3, H4

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H1 connects the nuclesomes together in a string like, the others bind the DNA to form the blocks of histone
Because of their positive charge, they form ionic bonds with the negatively charged DNA
Histones help neutralize the large negative charge of the DNA phosphate groups
The major function of histones is to stabilize DNA in a compact form
Histones are proteins rich in basic amino acids, such as lysine and arginine, which bind strongly to DNA
Chromatin:
Is the chromosomal material that is randomly dispersed throughout the nucleus
Consists of fibers that contain protein (histones) and DNA in approximately equal masses
These histones package and order the DNA into structural units called nucleosomes
Nucleosomes are repeating subunits of chromatin, consisting of a DNA chain coiled around a core of histones
Gene Regulatory Proteins
Nonhistone proteins found in chromatin
These proteins are important in controlling the interactions of DNA with other molecules
Activation of DNA for replication or transcription requires break up of the nucleosome structure
Phosphorylation of serine and threonine residues in histones is part of the process for replication, while acetylation
of lysine residues in the histones is used for transcriptional activation
Plasma proteins:
Act as buffers that help stabilize the pH of the internal environment
Intracellular proteins absorb H+ generated by the bodys metabolic processes
Conversion of tissue protein to plasma proteins occurs in the liver
The three major types of plasma proteins are albumin, globulins, and fibrinogen
Globulin: (alpha, beta, and gamma):
Main function of plasma globulin is to provide body for both natural and acquired immunity
Alpha and beta function as transport molecules
Gamma globulins (immunoglobulin) are circulating antibodies that act in the immune response
Fibrinogen
A blood clotting protein
Synthesized in the liver (also prothrombin)
Albumin:
Simple Protein
Transports many small molecules (that otherwise are usually absorbed) in the blood (for example, bilirubin,
calcium, Na+, Cl-, progesterone, and drugs)
Transports free FAs in human blood
The body uses 3 mechs for transporting FAs in the blood
1) FAs to albumin
2) Chylomicrons (Cholesterol binds to fat and phospholipids to form chylomicrons)
3) Ketone bodies (aceto-acetate and beta hydroxyl butyrate)
Most bound calcium is transported in blood as an albumin complex
Various substances are transported in the blood as protein complexes, Calcium/Albumin is an example
Is also of primary importance in maintaining the oncotic pressure of the blood
Albumin is the major contributor to colloid osmotic pressure
This is because, unlike small molecules such as Na+ and chloride, albumin is impermeable across the
capillary membrane
Is synthesized in the liver
Albumin is most commonly associated with transport of free fatty acids in human blood
Another Q: Free fatty acid level in blood is affected by serum albumin levels, the anti-lipolytic action of insulin,
and intestinal absorption of fatty acids (not by the action of calcitonin)
Albumin is most commonly associated with transport of free FAs and bile acids in the blood
Other plasma proteins include:
Lipoproteins (chylomicrons, VLDL, LDL, HDL)
Responsible for the transport of triglycerides, phospholipids, cholesterol, and cholesterol esters
Transferrin
The plasma protein that transports ferrous iron
Another Q: The most abundant form of iron in human blood plasma is found associated with transferrin
Another Q: After being absorbed from the intestine, iron is carried through the blood, associated with transferrin
Prothrombin
A blood clotting protein
Phospholipids and proteolysis are required for blood clotting
Myoglobin:
An oxygen-storing pigment found in muscle

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Chemically very similar to Hb as it is made up of a polypeptide chain associated with an iron-containing heme group
Myoglobin is also called muscle hemoglobin
Has a much greater affinity for oxygen than Hb
This makes it well suited for its biological function within muscle cells, which is to store oxygen and make it available
to the mitochondria
Myoglobin is, in fact, much better at this than Hb because its very high affinity for oxygen at low pO2 enables it to bind
and store oxygen effectively
Cytochrome:
A protein which is combined with another chemical group containing iron or copper
Fe is an essential element found in all cytochromes
Found on the membranes inside mitochondria of chloroplasts
The electron transport chain (ETC) is the final common pathway by which electrons derived from different fuels of the
body flow to oxygen
Electron transport and ATP synthesis by oxidative phosphorylation procede continuously in all cells of the body that
contain mitochondria cells in the blood do NOT contain an active mitochondrial electron transport system
Receive electrons from the reduced form of coenzyme Q (ubiquinone)
Each contains a heme group made of porphyrin ring containing an atom of iron
This cytochrome iron atom is the electron carrier and is reduced when the cytochrome accepts an electron (Fe3+, Fe2+)
These differences are a result of the heme prosthetic group
The prosthetic groups of cytochromes have four five-membered, nitrogen-containing rings in a cyclic
structure called a porphyrin
The four nitrogen atoms are coordinated with a central Fe ion that can be either Fe2+ or Fe3+
These porphyrins are also found in the heme proteins hemoglobin and cytochrome P450
Iron-porphyrin protein structures are components of cytochromes
Cytochromes a3 & a the terminal members of the ETC
They exist as a complex, which is called Complex IV or cytochrome oxidase complex
Glycine and succinyl-CoA are the precursors to the biosynthesis of these rings
NOTE: Glycine is the immediate precursor for creatine, purines & porphyrins
G-proteins
SUMMARIZE http://en.wikipedia.org/wiki/G_protein, & include the answer to the 2000 Exam, Q 110
The biologically active conformation of trimeric G-protein requires the alpha-subunit to bind GTP
Steps:
Hormone binds extracellularly and causes conformational change intracellulary
Then the Inactive G Protein moves laterally and interacts with the changed receptor protein
This causes a change of so GDP is kicked off and GTP is then bound and Activates the G Protein
Then the active G Protein moves back laterally on the membrane, and with its terminal Pi from GTP
activates an enzyme
The Active Enzyme is now able to catalyze other reactions, i.e. 2 nd messengers
The G Protein, now with only GDP bound returns to inactivity

Carbohydrates
Fructose, glucose & glyceraldehyde are all monosaccharides; amylose is not
Another Q: Saccharin (Nutri-sweet) is a non-nutritive, non-cariogenic sweetener
Monosaccharides:
Common monosaccharides fructose, galactose, glucose, mannose, ribose, and xylose
The simplest of carbohydrates, which are classified according to the # of carbon atoms they contain:
Trioses: those with three carbons, EX glyceraldehydes and dihydroxyacetone
Tetroses: four, EX erythrose

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Pentoses: five, EX ribose


Hexoses: six, EX glucose, fructose
Fructose has 1 anomeric carbons present
BUT Sucrose is the sugar that is NOT a reducing sugar
Naturally occuring fruit sugar D-fructose has a specific rotation of -88.5.
It is a sugar in spite of the negative rotation because of its structural relationship to D-glyceraldehyde
Aldoses
Monsaccharide with an aldehyde as their most oxidized functional group
For example glyceraldehydes
Ketoses
Those with a keto group as their most oxidized functional group
For example dihydroxyacetone
Naming
Based on the absolute configuration of glyceraldehydes
The symbols L and D refer to the absolute configuration of the four consitituents around a specific chiral
carbon (asymmetric carbon) in monosaccharides and AA
In a Fisher projection the D form has the hydroxyl group on the right, the L form has it on the left
Sugars of the D form, which are related to D-glyceraldehyde, are the most common in nature
Dont get clowned AAs are mostly L form
Disaccharides:
A carbohydrate whose molecules contain two sugar units
Maltose:
Consists of two glucose molecules jointed together by a reaction (condensation reaction) in which a molcules
of water is removed
This reaction produces a bond between two glucose molecules call a glycosidic bond
The intestinal enzyme maltase promotes the conversion of maltose into glucose
Maltose must be digested before being in a form that can be absorbed by enterocytes
Lactose:
Consists of glucose and galactose
The intestinal enzyme lactase promotes the conversion of lactose into glucose and galactose
Sucrose:
Consists of glucose and fructose
Fructose has 1 anomeric carbon
Is a glycoside to a-D-glucopyranosido-B-D-fructofuranoside
The intestinal enzyme sucrase (invertase) promotes the conversion of sucrose into glucose and fructose
Carbohydrate Digestion
Salivary Amylase
Starts digestion, hydrolyzes the alpha 1,4 linkages to give maltose, maltotriose, and alpha-limit dextrans
Pancreatic amylase
Highest concentration in duodenal lumen, hydrolyzes starch to oligosaccharides, maltose, and maltotriose
Oligosaccharide hydrolases
At brush border of the intestine, the rate-limiting step in carbohydrate digestion, produce monosaccharides
(glucose, galactose, and fructose)
The final digestion of these substances (disaccharides) to absorbable monosacharides is completed by enzymes of the
small intestine (maltase, sucrase, and lactase).
These monosaccharides can then be absorbed by enterocytes
Monosaccharides can be linked by glycosidic bonds to create larger structures (disaccharides, oligosaccharides, and
polysaccharides)
These bonds form when the hydroxyl group on the anomeric carbon of a monosaccharide reacts with an -OH or -NH
group of another compound (typically an alcohol, purine, pyrimidine, or in this case another sugar)
Maltose, lactose and sucrose consists of monosaccharides joined by an O-glycosidic bone
If oxygen is involved, this bond is classified as O-glycosidic, if nitrogen is involved this bond is classified as Nglycosidic
Polysaccharides (aka glycans):
Carbohydrates which are polymers of monosaccharides
Made up of many sugar units joined by condensation reactions (which results in glycosidic bonds)
Polysaccharides are converted to monosaccharides by hydrolysis of glycosidic bonds
Since they have large molecules, they are insoluble
Their main functions in living organisms are to act as storage molecules (starch and glycogen) or as structural materials
(cellulose)

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Homopolysaccharides (starch, glycogen, dextrans, and glucans) contain only a single monosaccharide species
Heteropolysaccharides (glycosaminoglycans) contain a number of different monosaccharide species
The two most important storage polysaccharides are starch and glycogen
Starch:
A large, insoluble carbohydrate which forms an important energy store in plants
It is a polymer and consists of a large number of alpha glucose molecules joined together by condensation
reactions
It consists of two main components which may be present in different proportions
Amylose:
Is unbranched & forms long straight chains (alpha-1,4 linkages)
Amylopectin:
A glucose polymer (alpha-1,4 linkages) with highly branched chains (alpha-1,6 linkages)
Both amylose and amylopectin are rapidly hydrolyzed by alpha-amylase, which is secreted by the
parotid glands and the pancreas
Glycogen:
1,4 = glucose residues linked in glycosidic bond
1,6 = branching in glycosidic bond
More highly branched (with alpha-1,6 linkages) and very compact
The predominant linkages between glucose units are alpha-1,4 linkages (these linkages make linear chains)
Carbohydrate is stored in the body principally as glycogen
The two major sites of glycogen storage are the liver & skeletal muscle
Another Q: The major storage form of carbohydrates in the liver is glycogen
Glycogen is the CHO in highest concentration in resting muscle
Glucose units of glycogen can enter the glycolytic pathway after removal by the action of glycogen
phosphorylase
The cleavage of glycogen beyond a branching point requires the activity of glucantransferase and amyloalpha-1,6 glucosidase
Dextrans:
Water soluble, High molecular weight Polysaccharides of glucose obtained from yeast and bacteria
Dextrans are produced from sucrose (by S. mutans)
Is a sticky polymer of glucose molecules linked together in alpha 1-6 linkages with some alpha 1-3 branches
It is produced outside of bacterial cells by the enzyme dextran sucrase (glycosyl transferase)
Substrate for GTF is sucrose (glucose and fructose)
This enzyme splits sucrose into glucose and fructose and links the glucose molecules into a dextran polymer.
The dextran is deposited as a thick glycocalyx around the cell and seems to be essential for the cariogenicity of S.
mutans
The glycocalyx is located extracellularly
Dextran-like glucans are extracellular polysaccharides synthesized by cariogenic streptococci in the presence of
excess sucrose
Levans (fructans):
Also increase the adhesion of bacteria to surfaces of the teeth and promote the formation of dental plaque
A polyfructose synthesized by plaque bacteria
Stimulator of B cells and an individual with periodontal disease exhibits greater response to this
polysaccharide than do normal control individuals
A soluble polysaccharide found in dental plaque that is formed from the fructose moiety of sucrose by the enzyme
levan sucrase
Considered to be reserve nutrients for bacteria
Polymer and their components??
Dextran
Sucrose
Levan
Sucrose (Fructose moiety of sucrose)
Glycogen
UDP-Glucose
Glycogen
Fructose
Reducing Sugars:
Lactose, Maltose, Glucose, Galactose, and Fructose
Contain one free anomeric carbon that can be oxidized
A fructose molecule has one anomeric carbon present
The anomeric carbon itself becomes oxidized
If the oxygen on the anomeric carbon (the carbonyl group) of a sugar is not attached to any other structure, that
sugar is a reducing sugar
A reducing sugar can react with chemical reagents and reduce the reactive component

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This reaction is the basis of a reducing sugar test (that is, free glucose test), which was classically used by clinical
laboratories to screen for diabetes and other inborn errors involving the inability to metabolize other reducing sugars
Most current clinical tests for blood glucose utilized glucose oxidase-linked reactions
Some carbohydrates convert Cu2+ ions to Cu+ ions; this property is related to their ability to act as a reducing
agent
Remember the reducing agent gets oxidized and the oxidizing agent gets reduced
Because the reducing groups of both glucose and fructose are involved in the glycoside bond,
Sucrose is not a reducing sugar.
In other words, sucrose contains no free anomeric carbon
Glocusuria
The presence of glucose in the urine
Can be caused by low insulin levels, high blood sugar levels, impaired tubular reabsorption, or a high GFR
Glycosaminoglycans (GAGs):
Contain mostly carbohydrate (95% or more)
Most abundant heteropolysaccharide in the body
Are long unbranched polysaccharides containing a repeating disaccharide unit
of the disaccharide is always an amino sugar derivative, either NAM or NAG
*** Bacterial cell walls contains a heteropolysaccharide made up of alternating NAG and NAM units
The other is usually a uronic acid, such as glucuronic acid, giving a negative charge
GAGs are highly negatively charged molecules, with extended conformation that imparts high viscosity to the solution
Located primarily on the surface of cells or in the extracellular matrix
Along with the high viscosity of GAGs comes low compressibility, which makes these molecules ideal for a lubricating
fluid in the joints
At the same time, their rigidity provides structural integrity to cells and provides passageways between cells, allowing
for cell migration
GAGs function as important structural components of CT (which includes adipose tissue, cartilage, and bone as well as
collagenous, elastic, and reticular fibers)
Most important physicochemical property of CT which is regulated by its mucopolysaccharide molecule is
Viscosity
The extracellular space
In animal tissues is filled with a gel-like material, the extracellular matrix, also called ground substance, which holds the
cells of a tissue together and provides a porous pathway for the diffusion of nutrients and oxygen to individual cells
Chondroitin sulfate & hyaluronic acid are components of extracellular matrix
Hyaluronidase is most likely to promote depolymerization of the ground substance or Extracellular Matrix
(different Q)
The ground substances is composed of an interlocking meshwork of heteropolysaccharides (glycosaminoglycans) most
covalently linked to protein forming proteoglycans and fibrous proteins
GAG
Hyaluronic acid
Chondroitin sulfate
Heparan sulfate
Heparin
Dermatan sulfate
Keratan sulfate

Localization
Synovial fluid, vitrous humor of the eye,
ECM of loose CT
Cartilage, tendons, ligaments and aorta
Basement membranes, components of cell
surfaces
Component of intracellular granules of
mast cells that line the arteries of the
lungs, liver and skin
Skin, blood vessels, heart valves
Cornea, bone, cartilage aggregated with
chondroitin sulfates

Comments
Large polymers, serves as a lubricant and
shock absorber
Most abundant GAG of extracellular
matrix
Contains higher acetylated glucosamine
than heparin
Serves as an anticoagulant

Most heterogenous GAG

Which one is NOT a GAG???


The are all Sulfates, Except, Heparin and Hyaluronic Acid
So know all of the above!!!
Hyaluronic acid/Hyaluronate
Is a repeating polymer of a disaccharide of glucuronic acid and N-acetylglucosamine
Is a lubricating material in the synovial fluids of joints such as the elbow or knee
Acts as the cement substance of tissue
Synthesized in the golgi apparatus
is a highly polar polyanion

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Is unique among the GAGs in that it contains no sulfur and does not covalently link to protein to form
proteoglycans
Is found in extracellular matrix, and is a very long filament structurally
So it does not have compact folded structure
Another Q: Depolymerization of ground substance occurs via hyaluronidase (not collagenase)
Hyaluronidase is an enzyme that hydrolyzes hyaluronic acid
Chondroitin sulfate:
Primarily found in cartilage, however, small amounts are found in bone
Fxns as part of the ECM
Is a polymer of a repeating unit comprising alpha (1-3) linked disaccharide of glucuronic acid and Nacetylgalactosamine
Galactosamine is largely sulfated on the hydroxyl of carbon 6
Keratan sulfate (aka keratosulfate):
Is found in the cornea of the eye and in cartilage
Occurs primarily in cartilage
Consists of alternating units of sulfated N-acetylglucosamine and D-glucuronic acid
Heparan sulfate:
Occurs in the cell membrane of most cells
Is type IV collagen Basement Membrane
It consists of alternating units of a sulfated N-acetylglucosamine and either L-glucuronic acid or L-iduronic acid,
which also may be sulfated
Dermatan sulfate:
Found mostly in the skin
It consist of alternating units of a sulfated N-acetylgalactosamine and L-iduronic acid, which is sometimes sulfated
Proteoglycans:
Consist of a Large Hyaluronate fiber (polymer of disaccharide) and attathed to it is core proteins with
glycosaminoglycan (GAGs) attached in a brush like fashion
The ground substance of the extracellular matrix is a highly hydrated gel containing large polyanionic proteoglycans
molecules, which are about 95% polysaccharide and 5%
protein
The linkages of GAGs to the core protein involves a specific
trisaccharide composed of two galactose residues and one
xylose residue
The carbohydrate chain is referred to as a
glycosaminoglycans, which can bind covalently to a protein
core
The protein cores are rich in serine and threonine
residues (-OH groups), which allows multiple GAG
attachments
The large # of alcohol groups on the polysaccharide
chains contributes to the water-binding properties of
proteoglycans via hydrogen bonding
Another Q: Each of the following applies to proteoglycans:
Polyanion
Hydrophilic
Highly charged
Sulfated sugars
Linear structure
Glycoproteins:
Are proteins that have a carbohydrate covalently attached to them
The carbohydrate portion of most glycoproteins differ from that of proteoglycans in that it is shorter and
branched
Serve as enzymes, hormones, antibodies, and structural proteins
Are often components of cell membranes and are involved in cell-to-cell interactions
Glycolipids (or sphingolipids):
Are found in the cell membrane with the carbohydrate portion extending into the extracellular space
Found in Schwann cells
Are derived from the lipid ceramide; this class of compounds includes cerebrosides and gangliosides (gangliosides
are found in the cell membrane)
Minerals/Vitamins

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A person who lacks fruits & vegetables in his/her diet is likely to develop a dietary deficiency in Vitamins A & C
NOT
Vitamin B1 found in cereal, unpolished rice, and wheat products
Vitamin B12 Animal origin
Vitamin K K1 is from VEGETABLES but K2 is from intestinal bacteria
No vitamins have been shown to influence the dental caries rate, if given in amounts greater than the RDA
Fat Soluble vitamins: ADEK
A
Vitamin A (retinol):
Dietary sources:
Widely distributed in green and yellow vegetables and fruits
Major body functions:
Think Retin-A (Skin/acne medicine)
Antioxidant
Constituent of rhodopsin (visual pigment
Structural component of rhodopsin
Maintenance of epithelial tissues, has a role in mucopolysaccharide synthesis, bone growth, and
remodeling
Vitamin A functions to promote differentiation of epithelial cells
A deficiency of rhodopsin is most likely caused by decreased dietary intake of vitamin A
Vitamin A and C are required for osteoblasts to form the organic matrix of bone prior to
calcification of the tissue
Deficiency:
Xerophthalmia (keratinization of ocular tissue), night blindness
Along with vitamin C & D, it is required for the normal production of sound dentin and enamel
A deficiency of vitamin A will most likely affect enamel more than dentin (Epithelial origin)
A deficiency of vitamin C will affect the dentin more due to the role of vitamin C in collagen synthesis
Involved in the formation of the gingival collagen
Is the most toxic of all vitamins
D
Vitamin D
Involved in calcium metabolism along with PTH increasing serum calcium
D3 = Cholecalciferol (sun-exposed skin)
7-dehydrocholesterol, an intermediate in cholesterol synthesis, is converted to cholecalciferol in the dermis
and epidermis of humans exposed to sunlight
The metabolite, 25-hydroxycholecalciferol, is derived MOST immediately from 7-dehydrocholesterol
Cholecalciferol is converted to 25-hydroxycholecalciferol in the liver
25-hydroxycholecalciferol is converted to 1,25-dihydroxycholecalciferol in the kidney (active)
This conversion consists of hydroxylation at the 1 position of 25-hydroxycholecalciferol in the
kidney
Another Q: The conversion of circulating vitamin D metabolite to its most active form take place
in the kidney
In short
UV activation in skin
Hydroxylation in the liver
Hydroxylation in the kidney
**24,25-(OH)2 is the Inactive Form
Dietary sources: (D2 = ergocalciferol)
Plants
Fish-liver oil, eggs, diary producs, fortified milk, margarine
Major body functions:
Promotes growth & mineralization of bones and teeth, calcium and phosphorous metabolism
(bone formation)
Deficiency
Causes a net demineralization of bone resulting in Rickets in children and Osteomalacia in adults
Vitamin D can be supplied to humans by the normal action of intestinal flora
Vitamin D is a steroid hormone and acts on nuclear receptors
E
Vitamin E (tocopherol):
Is the least toxic of all vitamins
Dietary sources:

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Vegetable oil and seeds, green leafy vegetables, margarines, shortenings


Major body functions:
An antioxidant preventing free radicals from oxidizing compounds such as polyunsaturated fatty acids
E is for Erythrocytes
Deficiency:
Is almost entirely restricted to premature infants
Supplementation has been proposed to be a benefit in prevention of heart disease and cancer, however
controlled studies have been unable to show a link
K
Vitamin K: phylloquinone or antihemorrhagic factor
Is synthesized in the intestinal bacterial, therefore Vitamin K deficiency can occur with prolonged use
of broad-spectrum ABX
The Vitamin K clotting factors are II, VII, IX, X, Protein C and S
Warfarin is a synthetic analog of Vit K, which acts as a competitive inhibitor of prothrombin formation
Warfarin is a vitamin K antagonist
A derivative of Vit K is the coenzyme for the gamma carboxylation of glutamate side chains
(Glu Gla), NOT crosslinking of fibrinogen that would be Factor XIII
Vit K decreases coagulation time and is present in low concentrations in milk
Dietary sources:
Green and yellow vegetables, small amount in cereals, fruits, and meats
Major body functions:
Required for synthesis of prothrombin and certain other clotting factors in the liver
Vit K serves as a coenzyme in the carboxylation of inactive prothrombin to form active
prothrombin
Deficiency:
Leads to increased bleeding time
Would affect blood clotting chiefly by decreasing prothrombin production
Water Soluble Vitamins:
B-complex
This complex occurs chiefly in yeast, liver, eggs, and some vegetables
Thiamine (B1) (ITs the Beri-beri 1st Vitamin B)
Dietary sources:
Meat (especially pork and organ meats), grains, dry beans and peas, fish, poultry
Major body functions:
Involved in the metabolism of carbohydrates and many amino acids
In thiamine pyrophosphate, a cofactor for oxidative decarboxylation of alpha-keto acids
(pyruvate and alpha-ketoglutarate)
Cofactor for the transketolase in HMP shunt
Deficiency:
Adult Beriberi characterized by
Polyneuritis, muscular atrophy, edema, and cardiovascular changes
Dry skin, irritability, disorderly thinking, and progressive paralysis
Beriberi is associated with a deficiency in thiamine
Seen in alcoholism and malnutrition
Converted to the coenzyme thiamine Pyrophosphate, TPP
TPP is required for the key rxns catalyzed by pyruvate and alphaketoglutarate dehydrogenase
Its the 1st, so 1st thing needed to start KREBs
Riboflavin (B2) (Its the Rival, so 2nd best)
Dietary source:
Milk, leafy vegetables, fresh meat, egg yolk
Major body functions:
Constituent of two flavin nucleotides, coenzymes (FAD Fatty acid Degradation and FMN) that
function with some enzymes (flavoproteins) which catalyze oxidation-reduction reactions
A function of riboflavin is to form part of the coenzyme FAD
Vitamin B2 = 2 ATP (FAD)
Derivatives of riboflavin and niacin function as coenzymes in redox reactions
Deficiency:
Cracks at corner of mouth (cheilosis), dermatitis, glossitis/magenta tongue (tongue appearing smooth
and purplish)
Cheliosis, angular stomatits, glossitis, and red, iching eyes Its where your FLAVor is!

98

Niacin (B3 -- nicotinic acid): (Dont deNI-your-SINS at the PLAYGRound of pooping and scratching and
being retarded)
Dietary sources:
Liver, meat, fish, grains, legumes, poultry, peanut butter
Included in a breakfast of eggs, steak, white bread & butter, orange juice, and milk
Major body functions:
NZ specific not interchangeable
Component of NAD+ and NADP+, which are involved in Glycolysis, the Krebs cycle, and other
reactions
Vitamin B3 = 3 ATP (NAD)
Derivatives of riboflavin and niacin function as coenzymes in redox reactions
Deficiency:
Pellagra (The 3 Ds)
The clinical symptoms of dermatitis, diarrhea, and dementia suggest a deficiency in niacin
High supplemental doses are effective in treating hyperlipidemia
Can be formed from the amino acid tryptophan
A diet rich in tryptophan offsets a deficiency of niacin (because its derived from tryptophan)
A pyridine carboxylic acid
Converted to 2 major coenzymes (NAD+ and NADP+) which are used in oxidation-reduction rxns
NAD+
Generally used in Catabolic processes to carry reducing equivalents away, i.e. NADH
NADPH
Generally used in Anabolic processes as a supply of reducing equivalents
Produced from the HMP shunt and the malate dehydrogenase rxn
Used also in Respiratory Burst and P450
NADPH is not used in gluconeogenesis
Pantothenic acid (B5) (Think PENTothenic)
Is an integral part of coenzyme A (Pantothen-AAA, like acetyl CoAAAA)
Dietary sources
In all foods, eggs, liver, and yeast
Major body functions:
Component of Coenzyme A (fxns in the entry of pyruvic acid in to the Krebs cycle and in the
degradation of FAs)
Deficiency
Fatigue, sleep disturbances, impaired coordination, diarrhea, GI, and renal problems
Pyridoxine (B6) (Think TRANS-AM has a B6 engine)
pyridoxine, pyridoxal, pyridoxamine
All are naturally occurring forms of Vitamin B6
These forms are converted by the body into pyridoxal phosphate, which is required for synthesis,
catabolism, and interconversion of amino acids
Pyridoxine is a vitamin
Are all derivatives of pyridine, differing only in the nature of the functional group attached to the ring
Dietary sources:
Meats (liver), vegetables, whole grain cereals and egg yolk
Major body functions:
All three compounds can serve as precursors of the biologically active coenzyme, pyridoxal phosphate
Pyridoxal phosphate functions as a coenzyme for a large number of enzymes, particularly those
that catalyze transamination reactions involving amino acids (i.e. ALT and AST)
Another Q: A component of the coenzyme required in a transamination process is pyridoxine
Another Q: The coenzyme for glutamic-pyruvic transaminase is pyridoxal phosphate
Deficiencies
Rare but have been observed in women taking oral contraceptives and in alcoholics
Cobalamin (B12, cyanocobalamin)
Dietary sources:
Muscle and organ meats, eggs, dairy products, (not present in plant foods)
Major body functions:
Involved in the formation of methionine
Involved in the conversion of methylmalonyl to succinyl CoA
Deficiency:
Pernicious anemia, neurologic disorder, glossitis
Usually owing to the absence of intrinsic factor

99

Intrinsic factor (produced in the stomach) is necessary for absorption of Vit B12 from the GI tract
Vitamin B12 binds to R protein produced in the saliva and which is also in gastric juice and
bile
R protein/B12 complex is then hydrolyzed by pancreatic NZs
B12 then binds to intrinsic factor, which is produced by oxyntic cells of the glandular mucosa of
the stomach
Then the B12/Intrinsic factor complex binds to receptors on the terminal ileum for absorption
into the bloodstream
Vit B12 is used to treat pernicious anemia
Pernicious anemia is frequently associated with a deficiency of vitamin B 12 & folic acid
Is the only water soluble vitamin stored in the kidney (Folic acid is stored in the liver)
It is the only vitamin that contains essential mineral elements and is the first substance containing cobalt
that is found to be vital to life
May be present in inadequate quantities in a strictly vegetarian diet
Biotin (vitamin H) (Think BioTINthesis of FAs)
Required as a coenzyme in the initial steps of fatty acid synthesis
Dietary sources:
Liver, kidney, milk, egg yolk, yeast
Major body functions:
Essential for the activity of many enzyme systems that are involved in AA and protein
metabolism
Required for the carboxylation of acetyl CoA to malonyl CoA, an intermediate in fatty acid
synthesis
Eventhough the answer was just Malonyl CoA
Cofactor for carboxylations (i.e. Pyruvate Oxaloacetate, Acetyl CoA
Malonyl CoA)
Deficiency:
Fatigue, depression, nausea, dermatitis, muscular pains, loss of hair
Also synthesized by intestinal bacteria
Avidin (Rhymes) AVIDly binds to Biotin
is a protein found in uncooked egg whites that binds to and inactivates biotin and which, when
present in abundance, can result in a deficiency of biotin
Avidin is an important dietary component because of its influence on biotin
WEIRD ? What does N-terminal glutamic acid do??? I think it acts in the synthesis of Biotin
Folic acid (folate or folacin) (SEAN only FrOLICs with 1 Chica)
Dietary sources:
Liver, kidney, yeast, mushrooms, green vegetables
Folate is from Foliage
Missing from a breakfast of eggs, steak, white bread & butter, orange juice, and milk
Major body functions:
Involved in the synthesis of purines and thymine, which are required for DNA formation
Plays a key role in one-carbon metabolism, and is essential for the biosynthesis of the purines and
the pyrimidine thymine
Coenzyme involved in the transfer and utilization of a the single carbon moeity
Deficiency:
Megaloblastic anemia, diarrhea, glossitis
Folic acid is stored in the liver and may be synthesized by the bacterial flora of the GI tract
Folic acid deficiency is probably the most common vitamin deficiency in the U.S., particularly among
pregnant women and alcoholics
Because of folic acids importance in the synthesis of purines and thymine its metabolism is the target
of a number of antimetabolite drugs such as methotrexate (Think THF)
Usually occurs as polyglutamate derivatives with 2-7 glutamic acid residues
These compounds are taken up by the intestinal mucosa, and the extra glutamate residues are removed
by conjugase
The free folic acid is then reduced to tetrahydrofolate by NZ dihydrofolate reductase
Then they circulate in the plasma primarily as free N5 methyl derivative of tetrahydrofolate
N5-methyl THF is the immediate source of methyl groups in AA synthesis
Various 1 carbon tetrahydrofolate derivatives are used in biosynthetic rxns
I.E. required for the synthesis of choline, serine, glycine, methionine, and purines
C (ascorbic acid)
Effective reducing agent, that is essential for activating prolyl hydroxylase for collagen formation

100

Essential for normal elaboration and maintenance of bone matrix, cartilage, and dentin
Dietary sources:
Citrus fruits, tomatoes, green peppers, broccoli, spinach, strawberries, melon
Major body functions:
Synthesis of CT, essential for hydroxylation of lysine and proline in collagen synthesis, essential for
integrity of capillaries and oral mucosa, needed for normal bone matrix formation, needed for normal
phagocytic function and Ab synthesis in host defense system
Facilitates iron absorption by keeping iron in its Ferrous 2+ state
Necessary cofactor for Dopamine
NE
Deficiency:
Scurvy
(degeneration of skin, teeth, blood vessels, epithelial hemorrhages), delayed wound healing,
anemia
Associated w/ sore swollen joints, bleeding swollen gums, loose teeth, anemia & improper
development of dentin
Cessation of bone growth
Is an antioxidant
Avitaminosis of the gingiva is likely to be caused by vitamin C
Minerals:
Inorganic substances that are essential to life
Serve for both structural and regulatory functions
Major minerals:
> 0.005% of body weight
Calcium, chloride, magnesium, phosphorous, K+, Na+, and sulfur
Much of the bodys sodium content is readily exchangeable except for that portion found in bone
Another Q: Calcium metabolism is regulated by androgen, estrogen, thyroid hormone, PTH, but not
norepinephrine; is also regulated by calcitonin
Trace minerals:
< 0.005% of body weight
Chromium, cobalt, copper, fluoride, iodine, iron, manganese, molybdenum, selenium, and zinc
General functions of minerals:
Maintenance of acid-base balance
Coenzyme or catalysts for biologic reactions
Components of essential body compounds
Transmission of nerve impulses and regulation of muscle contractions
Maintenance of water balance
Growth of oral and other body tissues
Copper:
Is important in the maturation of collagen and elastin as it is a cofactor for enzyme lysyl oxidase
A copper deficiency can cause collagen & elastin to be defective due to diminished activity of lysyl oxidase
The oxidized lysine residues formed in collagen and elastin by this enzyme form the cross links which stabilize
these molecules
Zinc:
Fxns:
Stabilizes cell membrane
Taste acuity
Collagen formation
Cell-mediated immunity
Carbonic anhydrase
Zinc is an essential component of carbonic anhydrase
Calcium
A diet deficient in calcium will result in production of PTH and bone resorption
Another Q : < 50% of dietary calcium is normally absorbed from the gut of an adult man
Absorption of calcium from the small intestine is increased by lowering the pH of the intestine
Absorption of calcium from the small intestine through active transport
Another Q: In the regulation of calcium balance, the greatest elimination of calcium occurs in the GI tract
<50% absorbed and the rest eliminated
The main route of calcium excretion is in the feces
Another Q: Recommended daily dietary allowances for Ca and P provide a Ca/P intake of approximately
1.0

101

Calcium performs
Muscle contraction
Blood clotting
Nerve transmission
NOT maintenance of membrane fluidity
Calcium/Phosphate/Alkaline Phosphatase
HyperParaThyroidism and Pagets Disease
Vitamin D intoxication and Osteoporosis
Renal Insufficiency
Nutrient/Mineral
Iron
Iodine
Calcium
Phosphorous
Sulfur
Potassium
Sodium
Magnesium
Cobalt
Copper
Zinc

Ca2+ and Alk Phosphatase


Ca2+
Phosphate

Phosphate
Phosphate
Ca2+

Functions
Constituent of hemoglobin and enzymes involved in energy metabolism
Constituent in thyroid hormones, regulates energy metabolism
Bone and tooth formation, blood clotting (Factor IV), nerve transmission, muscle
contraction
Bone and tooth formation, acid-base balance, release of energy (ADP, ATP)
Constituent of active tissue compounds, cartilage and tendon
Acid-base balance, body water balance, nerve function, muscle relaxant
Acid-base-balance, body water balance, nerve function
Activates enzymes involved in protein synthesis
Constituent of vitamin B12
Constituent of enzyme associated with iron metabolism and nerve function, and
collagen formation (lysyl oxidase)
Stabilizes cell MB, taste acuity, collagen formation, & cell-mediated
immunity, Carbonic Anhydrase

Some notes:
Proteins that contain trace elements of essential nutrients for biological action include:
Myoglobin (Fe), thyroglobin (I), and carbonic anhydrase (Zn)
Another Q: Ca and Fe are lacking in the U.S. diet
Iron deficiency leads to Chronic Bleeding
Another Q: Major controlling factor of iron absorption is saturation of mucosal cells
Another Q: Iron is an important nutrient present in low concentration in milk
Lack of milk consumption leads to iron deficiency, not Ca2+ or protein deficiency
Fluoride:
Does not make enamel harder
NOT a primary or major electrolyte in the saliva
Sodium, Calicum, Potassium, and Bicarbonate ARE
Reduces the solubility of enamel due to the incorporation of fluoride into the apatite structure of the enamel
Fluoride acts by ion exchange
Increases the remineralization of incipient caries
Concentration in body fluids is regulated by an equilibrium relationship between bone and urinary excretion
Rate of fluoride incorporation into bone depends on
water/mineral ratio, age, rate of bone remodeling, amount of ionizable F in diet
Deficiency in fluoride can lead to an increased incidence of dental caries
Toxicity leads to tooth enamel mottling and discoloration, increased density (chalky white), and calcification
Other facts:
Excreted rapidly by the kidney
Deposited in calcified tissues
Passes the placental barrier slowly
1 ppm is tasteless, colorless, and odorless
NOTE: in plasma it does not only occur in the ionic form
Absorption
In the stomach, as Hydrofluoric acid
In the small intestine, Fluoride
Flouride Most electronegative ATOM
Hydroxyapatite
Calcium Phosphate/Calcium Hydroxide Compound
Fluoroapatite

102

The substitution of F- for OH ions makes enamel less susceptible to caries attack
can form during hard tissue formation by a substitution of OH ions by F- ions
Fluoride calculation

determine % F in compound
multiply by molecular weight ratio for the compound
multiple F by 10 to convert to mg/ml
convert to ppm by multiplying mg/ml by 1000
(1ppm = 1mg/liter)

% Fluoride
Product
NaF
SnF2
(APF) Na2FPO3

Example
1 mL of 2% NaF * 1/2.2 = .91% F
.91% * 10 = 9.1 mg F/mL
9.1 * 1000 = 9100 mgF/L = 9100 ppm
SHORTCUT Multiply by ratio, then multiple by 10,000 = ppm
0.2% NaF 900ppm
2% NaF 9100ppm
1.23% APF 12,000ppm
8% SnF2 19,369 ppm

Molecular Weight
Ratio
1/2.2
1/4.1
1/7.6

STUDYYY
Metabolism
Overview
Substrate-level phosphorylation:
*More details below
High-energy phosphate intermediates are formed and are transferred to ADP to produce ATP
Glycolysis
The Citric Acid cycle (Krebs cycle)
Oxidative phosphorylation:
*More details below
ETC
Electrons move down the electron transport chain and chemiosmosis occurs because the electrochemical gradient
generated by the transfer of electrons through the ETC to O2 is used in the production of ATP
ADP, inorganic phosphate, an electron donor, and O2 are all required (CO2 is not) for cellular respiration
Cellular Respiration = Coupled respiration
Energy for ATP synthesis is derived from the electron transport system by the process of oxidative phosphorylation
It is the third and final phase of the respiratory metabolism of glucose and other substrates
Reduced coenzymes (NADH and FADH2) generated earlier in Glycolysis and the Krebs cycle are reoxidized
The electrons they release are transported through a serires of MB-bound carriers (flavoproteins, iron sulfur
proteins, coenzyme Q, and cytochromes) to establish a proton gradient across a membrane
The energetically unfavorable proton gradient is created using energy from electron transfers
A terminal acceptor such as oxygen is reduced, and ATP is synthesized by chemiosmosis
Chemiosmosis is the diffusion of ions across a membrane, specifically the synthesis of ATP with the
H+ gradient
Oxidative P is the major source of ATP in aerobic organisms
Photophosphorylation:
Occurs as a result of photosynthesis (which also involves an ETC)
Aerobic breakdown of a single molecule of glucose produces a net profit of:
3638 ATP
4 ATP are produced by substrate level phosphorylation
(2 ATP) Glycolysis
(2 ATP) Krebs cycle (From GTP)
3234 ATP are produced by oxidative phosphorylation during electron transport
Oxidation of one NADH = 3 ATP, closer to 2.5; of FADH2 = 2 ATP, closer to 1.5
38 Total ATP if use Malate Shuttle
36 Total ATP is use G3P Shuttle
NOTE: ATP yields the most energy per mole
Anaerobic only produces 2 ATP per glucose molecule
ATP
Made of Adenosine + Deoxyribose + 3 Phosphates

103

Glycolysis:
Occurs in the cytoplasm
Embden-Meyerhof pathway: glucose is converted to pyruvate (THE OXygen is in the Mirer you cant get it)
Most common pathway and is used by a large number of anaerobic and facultative anaerobic bacteria
Oral bacteria use this pathway
Pyruvate is reduced to lactic acid via fermentation
Lactic acid is a cariogenic product of bacterial glycolysis
Another Q: In fermentation, the final electron acceptor is an organic compound (not O2, as in the
ETC)
This glycolytic pathway results in the net production of 2 lactic acid & 2 ATP per glucose metabolized
BE CAREFUL, the end products of alcohol fermentation are 2 molecules of Ethyl alcohol and 2 ATPs
This pathway is found in many yeasts and certain bacteria
During strenuous exercise, the energy required for the skeletal muscles is supplied largely from anaerobic
transformation of glucose to lactic acid from glycogen
(Lactic acid = CH3-CHOH-COOH)
Entner-Doudoroff pathway:
A glycolytic pathway used by many obligate aerobic bacteria
Results in the net production of only 1 ATP per glucose metabolized (compared to 2 ATP in EmbdenMeyerhof)
Pathway ends with the formation of a pyruvate and a glyceraldehyde-3-phosphate, which is converted by enzymes
outside the pathway to pyruvate
These bacteria lack one of the key enzymes of the EM pathway: 6-phosphofructokinase OR aldolase

104

Enzymes of Glycolysis: Pic in USMLE Biochem book. Vol. 2 pg. 178


ATP involved steps (aka the kinases) 1,3,6,9
NADH involved steps
5
1) Hexokinase (Glucokinase in Liver): ATP used
G G6P
2) Phosphoglucose isomerase:
G6P F6P
3) Phosphofructokinase: ATP used
AMP Increase Glycolysis
F6P F1,6BP
The most important control point in glycolysis
Rate-limiting step of glycolysis phosphofructokinase
This is a physiologically irreversible
Does not function in association with a membrane
Allosteric enzyme stimulated by ADP or AMP & inhibited by high energy molecules (ATP and citrate)
ATP inhibits phosphofructokinase even though ATP is also a substrate for the enzyme; this is an
example of allosteric inhibition
SIDEBAR: Fructose-2,6-bisphosphate
Allosteric activator of phosphofructokinase
Allosteric inactivator of fructose-1,6-bisphosphatase
***(In other words, it promotes Glycolysis & inhibits Gluconeogenesis)
4) Aldolase:
F1,6BP GA3P + DHAP (One 6C into Two 3Cs)
This is called the aldolytic reaction
Aldolase is the enzyme that brings about the transition from 6-carbon metabolites to 3-carbon metabolites
Plentiful in skeletal & heart muscle
4a) Triose phosphate isomerase:
DHAP GA3P
5) Glyceraldehyde 3-phosphate dehydrogenase: NADH made
GA3P 1,3BPG
(high energy phosphate compound is formed)
6) Phosphoglycerate kinase: ATP made
1,3BPG 3PG
1st ATP generating step
7) Phosphoglyceromutase:
3PG 2PG
A mutase is an enzyme that catalyzes an intramolecular shift of a chemical group
8) Enolase:
2PG PEP

105

Sodium Fluoride inhibits enolase (hence inhibiting glycolysis)


9) Pyruvate kinase: ATP made
PEP Pyruvate
(2nd ATP generating step)
Irreversible NZ
Possible fates of pyruvate:
Branch point molecule of Glycolysis is pyruvate
1) Conversion to lactate:
Lactate dehydrogenase (LDH) converts pyruvate to lactate in the cytosol
Major fate for pyruvate in RBC, the lens and cornea of the eye, the medulla of the kidney, the testes, and
leukocytes
The Cori Cycle

The cycle refers to the recycling of lactate produced by muscle during anaerobic metabolism
During recovery, the lactate formed in muscles is transported to the liver and used to form glucose,
which is released to the blood and returned to the muscles to replenish their glycogen stores
This pathway (glucoselactateglucose) is called the Cori cycle
Nets 2 ATP
The pathway resulting in glucose formation in the liver from lactate produced in muscle is the Cori
cycle
Anaerobic Glycolysis:
Enzymes that catalyze the anaerobic processes of CHO metabolism are found predominantly in the
cytoplasm
Provides ATP energy quickly, supplementing the basal ATP production resulting from the aerobic
oxidation of other fuels via the citric acid cycle
The end-product of glycolysis under anaerobic conditions is lactic acid
Another Q: Anaerobic glycolysis yields 2 ATP per glucose degraded (& 2 lactic acid molecules)
Another Q: Under strenuous exercise, the stored muscle glycogen is broken down to lactate by
anaerobic glycolysis
Another Q: During the period following exercise (when ventilation is in excess of the metabolic
requirement), the level of lactic acid in blood decreases
Another Q: During exercise, muscle tissue accumulates lactic acid.
As a result, erythrocytes passing through capillaries in the muscle absorb more CO2 & release
more O2
Another Q: After prolonged muscular exercise (when oxygen debt is being repaid), most lactic acid
undergoes gluconeogenesis in the liver
NOTE: nicotinamide (in the form of nicotinamide adenine dinucleotide = NAD) is a vitamin (B3) derivative
concerned with conversion of glucose to lactic acid
Another Q: Adenine is a molecule common to NAD+ & FAD
2) Conversion to acetyl CoA:
Pyruvate dehydrogenase converts pyruvate to acetyl CoA in the mitochondria
Formation of Acetyl-CoA from pyruvate is best described as Oxidative Decarboxylation
Dont be clowned because the NZ is called Dehydrogenase, whereas the 1 st NZ for Gluconeogensis is
Pyruvate Carboxylase to get Oxaloacetate from Pyruvate
Causes backup of substrate (pyruvate and Alanine) causing lactic acidosis
Can be seen in alcoholics due to B1 deficiency (Beriberi)
Tx with increasing ketogenic nutrients (Lysine and Leucine are the only 2 purely ketogenic AAs)
Rxn = Pyruvate + NAD+ + CoA
Acetyl-CoA + CO2 + NADH
Cofactors
B 1-5
thiamine pyrophosphate (B1-decarboxylation),

106

FAD (B2-riboflavin),
NAD+ (B3),
Pantothenic acid (B5)
Lipoic acid,
Coenzyme A
Biotin (Pyridoxine) is NOT a cofactor repeated again & again!!!!!
This acetyl CoA can then enter the Krebs cycle or be used as the building block for fatty acid synthesis
Acetyl CoA is the immediate precursor for fatty acid synthesis
Acetyl CoA is the principal allosteric regulator of pyruvate metabolism in the liver

3) Conversion to oxaloacetate:
Pyruvate carboxylase converts pyruvate to oxaloacetate
This is not the irreversible step of gluconeogenesis, the next step, i.e. Oxaloacetate PEP via PEP
carboxykinase is the rate limiting/committed step of gluconeogenesis
This replenishes the citric acid cycle intermediates and provides substrate for gluconeogenesis
Pyruvate carboxylase is found in the liver and kidney, but not in muscle
4) Conversion to ethanol:
Pyruvate is reduced to ethanol
Yields only 1 ATP whereas the Lactic and Glycolysis yield 2 ATP
Occurs in yeast and certain microorganisms, but not in humans
Krebs cycle: Pg. 194 in Kaplan USMLE vol. 2
Aka tricarboxylic acid cycle (TCA) or citric acid cycle
Starts with the 4-carbon compound oxaloacetate, adds 2 carbons from acetyl CoA, loses 2 carbons as CO2, and regenerates
the 4-carbon compound oxaloacetate
The TCA cycle is initiated by the condensation of acetyl coenzyme A & oxaloacetate
Malonate is an effective inhibitor of metabolism
Its competitive inhibition can be overcome by succinate
Pyruvate that enters this cycle is generated by the Glycolysis of glucose or protein catabolism
Oxaloacetic acid and a-ketoglutaric acid are acids found in the citric acid cycle
This cycle is controlled by regulation of several enzyme activities
The most important of these regulated enzymes are citrate synthase, isocitrate dehydrogenase, and alpha
ketoglutarate dehydrogenase complex
Final step in complete metabolism of fat carried out by the Krebs or TCA cycle
Aspartic acid and oxaloacetic acid are interconvertible
Aspartic acid is the most immediate source of oxaloacetic acid during metabolism
Enzymes of the citric acid cycle are found in the mitochondria
CIKSSFMO = Citrate Is Krebs Starting Substrate For Mitochondrial Oxidation
Citrate
Citrate Officer Can I Keep Selling Sex For Money *******
Is
Isocitrate
OUT = CO2 and NADH Isocitrate dehydrogenase is rate limiting enzyme
Isocitrate dehydrogenase produces
-Ketoglutarate
Krebs
-Ketoglutarate
OUT = CO2 and NADH
**The alpha ketoglutarate dehydrogenase complex uses the same cofactors as pyruvate
dehydrogenase
Starting
Succinyl-CoA

107

OUT = GTP and CoA


Succinate
OUT = FADH2
For
Fumarate
Mito.
Malate
OUT = NADH
Oxidation Oxaloacetate
THE MATH: 3 NADH + 1 FADH2 + 2 CO2 + 1 GTP/per acetyl CoA = 12 ATP (then x2 per glucose)
Substrate

Glyoxylate cycle
Replenishes Krebs cycle intermediates
Acetate
Done in many bacteria, including Azotobacter vinelandii
Oxidative Phosphorylation
Biologic oxidative-phosphorylation enzymes occur in the cell primarily as highly
organized multi-enzyme units in the mitochondria
Electron Transport Chain (ETC):
The final steps in the aerobic generation of ATP:
Involve the transfer of electrons from the reduced coenzymes NADH and
FADH2 to oxygen and the combination of protons (H+) with the oxygen to form
water and regenerate NAD+ and FAD
These coenzymes pass electrons to the ETC
In this chain, flavin mononucleotide (FMN) and coenzyme Q (ubiquinone) pass the electrons to hemecontaining cytochromes, which transfer the electrons to oxygen
Ubiquinone is a lipid that participates in mitochondrial electron transport
During the movement of the electrons along the ETC, H+ is moved across the inner membranes to the space
between the inner and outer membrane
In respiration, the removal of hydrogen ions from a substrate is always accompanied by the removal
of electrons
Chemical energy generated by e- transport results from an H+ gradient across the inner MB
The electrochemical gradient created provides the energy for the production of ATP from ADP and Pi by the
oxidative phosphorylation complex
FMN is derived from riboflavin; NAD is derived from niacin
Coenzyme Q is not derived from a vitamin (the body synthesizes it)

108

Each cytochrome consists of a heme group associated with a protein; cytochrome a + a3 (aka
cytochrome oxidase)
Oxygen is the ultimate electron acceptor and is reduced to water
A coenzyme is a nonprotein substance (organic cofactor) that combines with an apoenzyme (the protein
portion of a complex enzyme) to form a haloenzyme (a complete, catalytically active enzyme system)
Electron transport complexes:
There are four, each representing a fraction of the entire respiratory chain
Each is separate and has its own unique composition, and each is capable of catalyzing electron transfer
through a portion of the chain
Complexes I and II catalyze electron transfer to ubiquinone from two different electron donors:
NADH (Complex I) and succinate/FADH2 (Complex II)
Complex III carries electrons from ubiquinone to cytochrome c
Complex IV completes the sequence by transferring electrons from cytochrome c to oxygen
Remember all of them are associated with membranes (i.e. succinate dehydronase and q reductase)
THE MATH = 1 NADH 3 ATP; 1 FADH2 2 ATP
Complex
Protien components
I
(NADH dehydrogenase complex)
NADH dehydrogenase
II (Succinate/FADH2 dehydrogenase complex)
Succinate dehydrogenase
III (Ubiquinone-cytochrome c oxidoreductase complex)
Ubiquinone-cytochrome c oxidoreductase
IV (cytochrome oxidase complex)
Cytochromes a and a3
The last stage of biological oxidation is accomplished with cytochrome oxidase

Pentose phosphate pathway: (Think nadPH as in PHATTY acid synthesis) Pg. 214 in Kaplan USLME vol.2
Other names: the pentose shunt, the hexose monophosphate shunt, or the phosphogluconate pathway
The major role production of NADPH for reductive biosynthetic reactions (e.g., fatty acid synthesis) and the
production of essential pentoses, particularly D-ribose, used in the biosynthesis of nucleic acids
Another Q: The pentose phosphate pathway is a metabolic pathway that generates significant amounts of NADPH
Ribose phosphate needed for nucleic acid synthesis can be derived from Pentose phosphate p-way
Produces CO2
Can produce 5-carbon sugars (used for DNA and RNA) for nucleic acids
ALL rxns of this pathway occur in the cytoplasm
Occurs in all sites of FA or steroid synthesis, i.e. Lactating mammary glands, Liver, Adrenal cortex
Controlled by inhibition of glucose-6-phosphate dehydrogenase by NADPH (SEE PIC BELOW)
(Normally G6PDH makes NADPH)
Deficiency of glucose-6-phosphate dehydrogenase results in reduced NADPH
NADPH is needed to keep Glutathione reduced, which in turn detoxifies free radicals and peroxides
Reduced NADPH lead to hemolytic anemia, due to poor RBC defense against oxidizing agents
NOTE: Any glycolitic NZ deficiency is associated with hemolytic anemia because RBCs metabolized glucose
anaerobically and solely depend on glycolysis
In the irreversible oxidative reaction of the pathway, one carbon of G6P is released as carbon dioxide; NADPH is
generated; and ribulose-5-phosphate is produced
In the reversible nonoxidative reaction, pentose phosphates produced from ribulose-5-phosphate are converted to the
glycolytic intermediates fructose-6-phosphate and glyceraldehyde-4-phosphate

109

Prominent pathway in tissues actively carrying out biosynthesis of fatty acids & steroids from small precursors
Particularly the mammary glands, adipose tissue, the adrenal cortex, and the liver
Large amounts of NADPH are required in the reductive synthesis of fatty acids from acetyl CoAspecifically the
reduction of double bonds and carbonyl groups
Other tissues less active in synthesizing fatty acids, such as skeletal muscle, are virtually lacking the pentose
phosphate pathway

Glycogen synthesis:
UDP glucose is the substrate for glycogen synthesis
Fructose is also a component precursor of glycogen
Glucose enters the cell and is phosphorlyated to glucose-6-phosphate by hexokinase (in most tissues) or by
Glucokinase (in the liver)
To initiate glycogen synthesis,
1st, the glucose-6-phosphate is reversibly converted into glucose-1-phosphate by phosphoglucomutase
This takes us away from Glycolysis and starts us up the path of Glycogen synthesis
2nd, This glucose-1-phosphate is then converted to UDP glucose by the action of UDP glucose pyrophosphorylase
3rd, Glycogen Synthase transfers glucose residues from UDP glucose to the nonreducing ends of the glycogen
molecule
Glycogen synthase
The key regulatory enzyme for glycogen synthesis
Transfers glucose residues from UDP glucose to the nonreducing ends of the glycogen molecule
Is responsible for making the 1,4 linkages of glycogen
Occurs in both phosphorlyated and dephosphorylated forms
The active enzyme glycogen synthase A is the dephosphorylated form
Remember
As are always on
Insulin (House is warm, takes off Pis)
Glucagon (Tags Pis for breakdown)
Glycogen synthase B is the phosphorylated form inactive form of the enzyme
Kaplan states
The I form is the active form (ADP) (Just think I for insulin initiated!!!)
The D form is the inactive form (ATP)
Phosphorylation of some enzymes by ATP results in conversion of the enzyme from an active to an inactive
form. This is illustrated by the conversion of glycogen synthetase I to glycogen synthetase D???
VOWELS are turned ON

110

Glycogenolysis pg. 14 in blue Kaplan Biochem book


Glycogen phosphorylase
Breaks down glycogen into Glucose-1-Pi
Works only on linear chains, and breaks glycogen down until you get to within 4-5 glusoce units of a branchpoint
For full degradation of glycogen you would still need an alpha 1,4 glucan transferase, then an alpha 1,6 glucosidase
Last NZ in Glycogenolysis? FOR sure Last Step of Gluconeogeneis
G-6-Phosphastase??
OK, if the ? asks for the last NZ in glycogenolysis of the LIVER, then yes G-6-Phosphatase,
BUT if its just in muscle, then its Phosphoglucomutase (G-6-Pi G-1-Pi) to then be used in
Glycolysis
Breaks down glycogen, also has two forms (A) and (B)
Phosphorylation of this enzyme forms the active enzyme (A); dephosphorylation forms the inactive enzyme (B)
Muscle glycogen phosphorylase is activated by epinephrine, not glucagons
Glucagon knows muscle cant release glucose anyway!
Liver glycogen phosphorylase is activated by both Glucagon and epinephrine
Another Q: Epinephrine causes a rise in cAMP levels in muscle cells, which in turn activates glycogen
phosphorylase
Keep a carpule of glucagon in the office for Hypoglycemic attacks
If insulin decreases, the glycogenolysis increases in the liver and Glycogen decreases
Both enzymes glycogen synthase and phosphorylase are phosphorylated at specific serine residues
The following are required for the activation of glycogen phosphorylase:
ATP, adenylate cyclase, glucagon or epinephrine, phosphorylase kinase (but not phosphofructokinase)
The ATP is needed to create the cAMP, from the activated adenylate cyclase
Glycogen storage diseases
Type I
Von Gierkes disease
Glucose-6 phosphatase deficiency
Type II
Pompes disease
Lysosomal alpha 1,4-glucosidase deficiency
Type III
Coris
Alpha 1,6-glucosidase deficiency (debranching NZ)
Type IV
McArdles Disease
Skeletal muscle glycogen phosphorylase deficiency
Cant break down glycogen to in muscle
VPCM = Very Poor Carbohydrate Metabolism***
Gluconeogenensis:
Biochemical process in which glucose is made from molecules which are not CHOs (primarily from AAs but not FAs)
Process occurs primarily in the liver, and its role is to provide glucose for export to other tissues when other sources of
glucose are exhausted

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Occurs in Liver, Kidney, Intestinal Epithelium, BUT NOT Muscle!!


Glucose-6-phosphatase is found associated with the
Liver AND Kidney
Hypoglycemia can be caused by a deficiency in any of the below
NZs (Von Gierkes Glucose-6-phosphatase)
Typically it involves the conversion of lactic acid or amino acid into
pyruvate or phosphoenolpyruvate, which is then converted to glucose.
Irreversible NZs (PPFG-Pathway Produces Fresh Glucose)
Pyruvate Carboxylase (irreversible, just not the committed step)
In Mitochondria
Pyruvate Oxaloacetate
PEP Carboxykinase
In Cytosol
Oxaloacetate Phosphoenolpyruvate
Fructose-1,6-bisphosphatase
In Cytosol
Fructose-1,6-bisphosphate Fructose-6-Phosphate
Glucose-6-phosphatase
In Cytosol
Glucose-6-phosphatase Glucose
Last Step of Gluconeogenesis
Essential for this transformation, it catalyzes the last step of
this process in which glucose-6-phosphate is hydrolyzed into glucose
Is found associated with the liver (primarily) and the kidney (NOT in muscle)
Essentially absent from normal mammalian muscle (and brain)
Muscle glycogen does not yield blood glucose directly because glucose-6-phosphatase is not present in muscle
Does not contain a high energy bond

Key reactions of Gluconeogenesis: Pg. 211 In Kaplan USMLE vol. 2


Pre-step
Some amino acids to Oxaloacetate
Some amino acids or Lactate to Pyruvate
EX of an amino acid that can be used is alanine
The conversion of [AlanineLactic AcidGlucose] is an example of gluconeogenesis
1)Pyruvateoxaloacetate (catalyzed by pyruvate carboxylase)
2)Oxaloacetatephosphoenolpyruvate (catalyzed by phosphoenolpyruvate carboxykinase)
Phosphoenolpyruvate carboxykinase production is inhibited by insulin

112

Phosphoenolpyruvate Carboxykinase (PEPCK) is the Rate-limiting step in gluconeogeneis


Remember Insulin is for storage, except it stimulates glycolysis
Think Gluconeogenesis only happens when were out of energy, Insulin says hey, we have energy, so
dont go playing me like that!
3)Fructose-1,6-bisphosphatefructose-6-phosphate (catalyzed by fructose 1,6 bisphosphatase)
4)[Last Step] Glucose-6-phosphateglucose (catalyzed by glucose-6-phosphatase)
CAREFUL in glycolysis its Hexokinase that gets Glucose to Glucose-6-phosphate

Pyruvate
Directly can go to:
Gly, Ser, Ala, Cys
Acetyl-CoA
Oxaloacetate
Lactic Acid
Ethanol

113

Enzymes
General Properties:
Enzymes have enormous catalytic power accelerate reactions by factors of at least 106
Highly specific, both in the reaction catalyzed and in their choice of reactants
Their activity is somewhat regulated
The rate of product formation is affected by: pH, temperature, ionic strength, [substrate] (but not isoelectric
point)
Enzyme-catalyzed reactions are characterized by formation of a complex between substrate & enzyme (an ES complex)
The binding occurs in a pocket on the enzyme called the active site
Equilibrium of a reaction is unaffected by the enzyme
This means that an enzyme accelerates the forward and reverse reaction precisely by the same factor
Enzymes function is to lower the activation energy for the reaction they catalyze and thereby enhance the reaction rate
Many enzymes require cofactors that frequently are metal ions or derivatives of vitamins
Boards Q: Methods of regulating enzyme activity: allosterism, zymogen activation, competitive inhibition
NOT induction and repression
Each of the following represents a key regulatory feature of an ezymatic cascade:
Amplification of an initiating signal
Coordinated control of enzyme activity in the target cell
Enzymes controlling the activity of other enzymes
***Secretion of protein kinases outside the cell does NOT
Michaelis-Menton Kinetics pg. 135 in Kaplan USMLE vol. 2

114

V = Vmax*([S]/([S] + Km)
Constant Km:
Numerically equal to the [substrate in moles/liter] that gives half-maximal velocity, expressed as Km = [S], when Vo
= Vmax
Km is equivalent to that substrate concentration at Vo (initial reaction velocity) is one half of Vmax
Km has units in molarity
Values range widely: from most enzymes Km lies between 10-1 and 10-6 M
Km value for an enzyme depends on the particular substrate and also on environmental conditions such as the
temperature and ionic strength
Frequently incorrectly said to be the equivalent to the dissociation constant of the enzyme substrate complex
For most reactions it is a complex function of many different reactions constants, but it does give a means of
comparison of the affinity (reciprocal of dissociation) of an enzyme for different substrates or different enzymes
for the same substance
The lower the Km the higher the relative affinity
Km values for substrate reactions:
Increase in the presence of competitive inhibitor
Another Q: If the presence of a specific compound, C, increases the K, for an enzyme-substrate reaction, C
would be a competitive inhibitor of the enzyme
Are not affected in the presence of noncompetitive inhibitor
EX problem: for Km = 1mM, when the [S] doubles from 10mM to 20mM, the velocity of the reaction increases slightly
NOTE the math: V = Vmax*(10/(10 + 1) = Vmax*0.90 V = Vmax*(20/(20 + 1) = Vmax*0.95 (slight increase)
The velocity of a reaction increases with the substrate concentration if the enzyme concentration is constant
At Vmax, all of the active sites of the enzyme are saturated with substrate
So, the limited value of Vmax of the reaction rate is due primarily to saturation of the enzyme with substrate
The velocity of a reaction i
ncreases with temperature until a maximum is reached, above which the enzyme will denature
Lineweaver-Burk plot: (SEE ABOVE GRAPH)
The y-intercept of a Lineweaver-Burk plot represents Vmax
Inhibition Types: (SEE GRAPH)
Competitive inhibition:
The competitive inhibitor resembles the substrate and binds to the active site of the enzyme
The substrate is then prevented from binding to the same active site
Inhibitor and substrate compete for the same binding site on the enzyme
Is overcome by increasing substrate
In other words, it just takes a bunch more substrate to get to half the max velocity!
Vmax is unchanged
Km is increased
Noncompetitive inhibition:
The inhibitor and substrate both can bind to the NZ on different sites
Cannot be overcome by increasing substrate and is by definition an allosteric inhibitor (SEE BELOW)
The noncompetitive inhibitor binds to either a free enzyme or the ES complex
In other words, we blocked off and ruined allosterically some NZs, so we still can get to half velocity just fine
with substrate, but even if we keep adding substrate well never hit our max velocity
Vmax is decreased

115

Km is unchanged
Uncompetitive inhibition:
Like noncompetitive, the inhibitor and substrate bind at different sites which do not overlap
But, uncompetitive inhibitors only bind to an enzyme which has a substrate already attached (ES complex)
Irreversible inhibition:
Those that combine with or destroy a functional group on the enzyme that is essential for its activity
Classic EX irreversible inhibition of cyclooxygenase (COX) by aspirin (acetylsalicylate) which acetylates the
active site serine residue
Allosteric enzymes:
Frequently catalyze a committed step early in the metabolic pathway
Often have two or more subunits each with substrate binding sites that exhibit cooperativity
An allosteric modifier alters enzymatic reaction rate by interacting with the enzyme at non-active sites
Allosteric activators cause the enzyme to bind substrate more readily
Allosteric inhibitors cause the enzyme to bind substrate less readily
A number of catabolic pathways are allosterically inhibited by an increase in the concentration of ATP
Show a complex relationship between the velocity and substrate concentration
Do NOT follow Michaelis-Menton kinetics Because we altered NZ
The most common form of covalent modification is phosphorylation / dephosphorylation
Kinases and phosphatases involved are themselves allosterically regulated
Protein kinases are the enzymes that phosphorylate certain AA residues in specific proteins
Through this process of phosphorylation, protein kinases act to regulate the activities of other enzymes
Zymogens
Inactive precursors of proteolytic NZs (i.e., digestive NZs)
Become active by removal of a peptide fragment
EXs: pepsin, trypsin, chymotrypsin area all secreted as zymogens (amylase is not)
Phosphatases
Are any of a group of enzymes that liberate inorganic phosphate from phosphoric esters
Alkaline phosphatase and pyrophosphatase are two enzymes that play an important role in calcification
Pyrophosphatase also may play a role in the mineralization of bone
Alkaline phosphatase: (ALP)
Believed either to increase the local concentration of inorganic phosphate or to activate the collagen fibers in such a
way that they cause the deposition of calcium salts
Involved in bone mineralization, hydrolysis of phosphoric esters, and functions optimally at pH 8.6
Secreted from osteoblasts that are actively depositing bone matrix
High levels are seen in Pagets disease and osteosarcomas; low levels are seen in cases of hypophosphatasia
Acid phosphatase:
A phosphatase with optimum functioning at pH 5.4 and is present in the prostate gland
High levels are seen in carcinoma of the prostate gland
Creatine phosphate:
Aka phosphocreatine
An organic compound found in muscle tissue and capable of storing and providing energy for muscular contraction
During increased muscle activity, ATP is resynthesized from phosphocreatine
Oncogene
Produced when a mutation occurs in an NZ controlling a signal pathway involved in cell growth processes
Miscellaneous
Heat
Principle energy laws:
Govern every organization; are derived from the two famous laws of thermodynamics
First Law of Thermodynamics (Energy Conservation)
Heat, being a form of energy, is subject to the principle of energy conservation
Total energy, incuding heat, in a closed system is conserved
Second Law of Thermodynamics: (restriction for heat)
Heat, being a form of energy, can be transformed into work and other forms of energy and vice versa
This transformation of heat energy is subject to a very important restriction:
Heat flows spontaneously from a hot body to a cool one
One cannot convert heat completely into useful work
Every isolated system becomes disordered in time
Entropy
is a measure of the degree of randomness or disorder in a system

116

*Enthalpy
Heat content of a system (Heat has an H in it)
Gibbs Free energy change:
In thermodynamics, GFE is the energy portion of the thermodynamic system available to do work
This is thermodynamic potential and is a state function
G = H TS
Final Initial =
G = gibbs energy
H = Enthalpy
T = Temperature
S = Entropy
When is the free energy of a system at a minimum?
When the free energy of the final state is less than the free energy of the initial state
Certain chemical reaction proceed spontaneously until equilibrium is reached
Exergonic
Reactions that proceed with the release of energy
Because the products of such reactions have less free energy than the reactants, the free energy
change is negative
Endergonic
Chemical reactions in which the products have more free energy than the reactants are endergonic
For these reactions the positive free energy change
Reactions that have unfavorable energetics (+ delta Go) in metabolic pathways may be driven to
completion by coupling
Remember Positive G is going uphill, and G is going down!!
Calorimetry:
Method of measuring heat loss or energy loss
Putting a person in a tank of water and noting the temperature change in the water can measure human body heat
The body heat causes this change
Direct calorimetry:
The measurement of the amount of heat made by the bodys processes
This is a method of measuring energy released by the cells
Oxidative reactions (e.g., evaporation, radiation, conduction and convection) produce heat
Indirect calorimetry:
Human calorie use can also be measured in terms of the amount of oxygen inhaled and the amount of carbon
dioxide exhaled during a given time
HENCE:
RQ = CO2/O2 remember the 0.8
RQ quotient for a person taking pure glucose as food source is higher than normal (normal is 0.8, with
pure glucose is 1.0)
NOTE the RQ may be used to calculate the basal metabolic rate via the technique of indirect
calorimetry
Heat regulation:
Heat generating mechanisms increased voluntary activity, shivering, and increased secretion of epinephrine from
the adrenal medulla
Shivering is the most important
Vasoconstriction of cutaneous blood vessels prevents heat loss (does not generate heat)
Another Q: Mechanisms that raise body temperature include shivering, ATP hydrolysis, exothermic reactions, and
increased thyroxine release (not peripheral vasodilation)
Heat loss includes vasodilation of cutaneous BVs & increased sympathetic outflow to the sweat glands
Both heat generating and heat loss mechanisms are activated by the posterior hypothalamus
Mechanisms of panting, sweating, loss of appetite & cutaneous vasodilation are activated in response to heat
Human body temperature generally remains constant, thus heat gained equals heat lost
Heat is transferred between the body and environment via:
Radiation:
Emission of heat in the form of infrared rays
The body is continually exchanging heat by radiation with objects in the environment
Surface body temperature is usually higher than the surface temperature of most objects in the environment
Conduction:
Transfer of thermal energy as a result of direct contact between two objects; aided by convection
Body only loses heat when outside air is cooler than body heat

117

Convection:
When air molecules exchange heat with the body surface and move away to be replaced by other molecules
Evaporation:
Conversion of a liquid into a vapor
Heat is lost when water evaportates from the body surfaces
Water is lost from body surfaces in two ways:
1) Insensible water loss occurs by way of exhaled air and through the skin
2) Sweating active fluid secretion by the sweat glands
It must evaporate to produce its cooling effects
More effective means of cooling in low humidity than in high humidity environments
If the air temperature is 105o F and the relative humidity is 10 percent, evaporation is the
primary cause for loss of body heat
Another Q: Someone working under conditions of high temperature should increase NaCl intake
Another Q: In prolonged sweating, the the extracellular fluid compartment experiences a decrease
in volume & an increase in osmotic pressure
Man sweats a lot, you see Low sodium retention (Right then, not what happens next to maintain
BP)
Osmosis:
The net diffusion of water through a semipermeable membrane caused by a concentration difference
Osmotic pressure:
The pressure that develops in a solution as a result of net osmosis into that solution
It is affected by the number of dissolved particles per unit volume of fluid
Intracellular and extracellular fluids have similar total osmotic pressures
Another Q: The distribution of fluids between intracellular and extracellular compartments is mainly achieved by
unrestricted movement of water to achieve osmotic balance
Albumin affects osmotic pressure the most
NaCl and KCl will ionize two ions therefore their osmotic pressure will differ from a single mole of glucose
One side contains 0.2 mol NaCl and other side has 0.2 mol glucose, which way does the water go
toward NaCl
Osmolarity:
Osmotic pressure of a solution expressed in osmols/kg of solution
Calculating Molarity
Molarity = # of particles in solution x [] of each particle in solution
Ex: What is the molarity of 1M CaCl2 solution?
1 Ca2+ x 1M + 2Cl- x 1M = 3 M/Liter
If a solution of 700 mOsm/L & one of 500 mOsm/L are separated by a membrane only permeable to water, there will be
a net movement of water from the 2nd solution to the 1st
Osmolality:
Osmotic pressure of a solution expressed in osmols/kg of water
Tonicity:
Due to the presence of solutes which are impermeable across the cell membrane, which determine cell volume
Isotonic solution
A solution that when placed on the outside of a cell will not cause osmosis
The cell neither shrinks nor swells: 0.9% NaCl or 5% glucose solutions are both approximately isotonic to
plasma
A 0.9% solution of NaCl is isotonic to blood since it exhibits the same osmotic pressure (osmolarity) as blood
Another Q: a 0.85% solution of NaCl is isotonic with respect to blood. It would also be isosmotic.
Hypertonic solution
A solution that when placed on the outside of cell will cause osmosis out of the cell and lead to shrinkage of the cell
NaCl solutions of > 0.9% concentration are all hypertonic
Infusion of hypertonic NaCl solution will decrease intracellular volume and increase extracellular volume
Hypotonic solution
A solution that when placed on the outside of a cell will cause osmosis into the cell & lead to swelling and cell lysis
Any solution of NaCl with < 0.9% concentration is hypotonic
Systems of diffusible ions (Gibbs-Donnan equilibrium)
The presence of impermeable ions on one side of the membrane will result in
Osmotic pressure
Transmembrane potential
Asymmetric distribution of diffusible ions across the membrane
Sometimes the trapped ions are negatively charged, then the diffusible positively charged ions are drawn to
them and gives an asymmetrical distribution of diffusible ions

118

Because the negative proteins cannot diffuse, the potential that is set up would not disappear as the two sides
cannot equilibrate
Body Water
Body water:
Humans weight is due 50-60% because of water
Intracellular fluid: 2/3
The largest amount of body water can be found in intracellular fluid
33% of total body water by weight
Major cations are K+ and Mg+. Major anions are protein and organic phosphates.
Extracellular fluid: 1/3
Made up of interstitial fluid and plasma.
Major cation is Na+. Major anions are Cl- and HCO3Plasma
Interstitial fluid
Largest component of extracellular fluid volume
27% of total body water by weight
Fluid surrounding and bathing the cells
Its composition is the same as that of plasma except it has a lower concentration of protein
If you subtract the Extracellular Fluid, you can calculate the intracellular body fluid
Edema:
Occurs when the volume of interstitial fluid exceeds the capacity of the lymphatics to return it to the circulation
Physical cause of edema is positive pressure in the interstitial fluid space
Conditions that will cause extracellular fluid edema:
Increased capillary pressure due, for example to blockage of a vein
Decreased plasma colloid osmotic pressure, due to decreased plasma protein concentration
Increased interstitial fluid colloid osmotic pressure (oncotic pressure) caused by a lymphatic obstruction
NOTE: Decreased lymphatic drainage promotes edema
Increased capillary permeability which may occur in certain allergic responses
Venous constriction and standing cause increased capillary hydrostatic pressure and tend to cause edema
Inflammation causes local edema by dilating arterioles and increasing permeability
This may be due to vasodilating kinins
Constriction of arterioles causes decreased capillary hydrostatic pressure and, as a result, decreased net pressure across
the capillary wall. Arteriole dilation increases the likelihood of edema
Administration of a plasma volume expander could be beneficial in reducing edema in the arms of women who have had
a radical mastectomy with removal of axial lymph nodes (this draws fluid from the interstitium to the blood)
Know how to calculate Net Filtration
Immunoglobulins:
Glycoproteins found in blood serum; synthesized by plasma cells in the spleen and lymph nodes in response to the
detection of a foreign antigen; they mediate anaphylaxis, atopic allergies, serum sickness, and Arthus reactions
IgG:
The most abundant; the only Ig which crosses the placenta; main defense against various pathogenic
organsisms
IgA:
2nd most abundant; occurs in body secretions and protects surface tissues; synthesized by the plasma cells in the
mucous membranes of the GI, respiratory and urinary tracts
IgA is the plasma protein subfraction that contains antibodies found bathing mucous surfaces (mouth, bronchial
passages, small intestine)
Another Q: Secretory IgA is involved in bacterial aggregation & subsequent elimination from the oral cavity
sIGA is Polymeric 2 IgAs joined by J chain
Another Q: IgA is the characteristic immunoglobin present in human external secretions
IgD:
Makes up < 1% of Igs; present on MB of many ciruculating B-cells; function is unknown or not fully understood
IgM: (M for Massive and iMMediate)
Largest Ig; 1st Ab produced in response to infection; powerful activator of complement system
IgE:
Present only in trace amounts in serum; reagenic activity resides in this Ig; protects external mucosal surfaces;
Tightly bound to its receptors on mast cells and basophils; responsible for Type I hypersensitivity reactions
(allergic and anaphylactic)
A sound can be characterized according to its pitch, loudness, and timbre (quality)
Pitch:

119

Related to sound wave frequency


In general, the higher the frequency of a sound wave, the higher the pitch of the sound wave
Frequency is measured in hertz (Hz) or cycles per second
Loudness/Intensity:
Usually the greater the amplitude of a particular sound, the greater the intensity of the wave and the louder the sound
Intensity is measured in decibels (dB)
A 100 dB sound is 100,000 times greater than the human threshold for sound???
I think this is right: dB = 20 log (x); if dB = 100, then 100/20 = log (x), which means x = 10^5 = 100,000
The Threshold of hearing is O dB 0 = 20 Log x 0/20 = log x 10^0 = x or 1
Timbre or quality:
Related to the presence of additional sound-wave frequencies superimposed on the principal frequency
Bonds
Covalent bonds:
Forces that hold atoms together
Forces are formed when the atoms of a molecule share electrons
Two examples of covalent bonds are peptide and disulfide
Hydrogen, oxygen, nitrogen, and carbon are capable of forming one, two, three, and four covalent bonds
respectively
Carbon is very versatile and can form single, double, and triple bonds
Not normally broken under biologic conditions unless by enzymatic catalysis
Weak bonds:
May be easily broken but are very important becaue they help to determine & stabilize shapes of biological
molecule
EX important in stabilizing the 2 structure (alpha helix and beta sheets) of proteins
Hydrogen bonds keep complementary strands of DNA together and also participate in enzymatic catalysis
These interactions are individually weak but collectively strong
Denaturing agents (organic solvents, urea, and detergents) act primarily by disrupting the hydrophobic interactions
that make up the stable core of globular proteins
Are easily broken under normal biological conditions of temperature and pressure
Isotopes:
Same chemical properties but different weights
Are stable or radioactive forms of an element
The radioactive forms of isotopes are often used as tracers
Naturally occurring elements are usually mixtures of isotopes so that atomic weight is an average of values for the
mixture
Isotopes have the same atomic # but different mass #
The atomic # is the number of protons; mass number is the sum of protons and neutrons
Therefore, isotopes have the same # of protons but differ in the # of neutrons
Bone matrix:
Are affected by age, race, and gender:
Blacks commonly have denser bone whan whites, and men commonly have denser bones than women
Bone density and structural integrity (ability to withstand stress) decease after age 30 in women and 45 in men
Thereafter, a relatively steady quantitative loss of bone matrix
The intercellular matrix of bone contains both organic components (glycosaminoglycans in the ground substance and
collagen fibers) and inorganic salts
Inorganic salts consist primarily of Ca2+ phosphate, which is present in the form of highly insoluble HA crystals
According to chemical & x-ray diffraction studies, the structure of bone mineral is HA
These salts allow bone to withstand compression
Organic matrix is composed largely of collagen and GAGs
Collagen fibers provide bone w/ great tensile strength
Bone is an important calcium reservoir
Osteoblasts:
Secrete the organic components of the intercellular matrix bone, including GAGs (5%) & collagen (makes up 95%
of the intercellular matrix)
Within the period of days, the intercellular matrix calcifies via the deposition of insoluble calcium salts w/in it
Some of the common GAGs present in the intercellular matrix of bone include hyaluronic acid and chondroitin sulfate
Form organic matrix and require Vitamin A and C
The intercellular matrix also contains a calcium-binding protein called osteocalcin as well as a calcium & collagenbinding protein called osteonectin
Osteonectin =

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Bone specific protein


Found in bone AND non-mineralized tissues
Provides sites of growth for the calcium crystals and anchors them to the organic matrix
Ca and collagen
What is more common in enamel??? Hyaluronate or Osteonectin????
Osteocalcin = only Calcium
Osteogenin
Matrix protein of bone
No binding affinity for Calcium to collagen
Amelogenin
Matrix protein of enamel
No binding affinity for Calcium to collagen
Fibronectin
Glycoprotein found in Extracellular matrix, on cell surface
Functions as adhesive-ligand like molecule
Promotes cell adhesion
Does NOT facilitate calcium and collagen binding
Ehlers-Danlos syndrome
a group of inherited generalized connective tissue diseases characterized by overelasticity and friability of
the skin
hypermobility of the joints, and fragility of the cutaneous blood vessels and sometimes large arteries, due to
deficient quality or quantity of collagen
Also associated with Berry Aneurysms
the most common is inherited as an autosomal dominant trait;
some recessive cases have hydroxylysine-deficient collagen due to deficiency of collagen lysyl hydroxylase,
and two tentatively ascribed to X-linked inheritance.
Coumadin
Rx to prevent Stroke
Cyandide Poisoning
Cyanide affects virtually all body tissues, attaching itself to ubiquitous metalloenzymes and rendering them inactive.
Its principal toxicity results from inactivation of cytochrome oxidase (at cytochrome a3), thus uncoupling mitochondrial
oxidative phosphorylation and inhibiting cellular respiration, even in the presence of adequate oxygen stores.
Cellular metabolism shifts from aerobic to anaerobic, with the consequent production of lactic acid.
Consequently, the tissues with the highest oxygen requirements (brain and heart) are the most profoundly affected by
acute cyanide poisoning.
Acute cyanide poisoing most likely results in decreased oxygen extraction by peripheral tissue
Fainting (Vaso-vagal)
Associated with Pallor, Diaphoresis, Decreased Heart Rate, Decreased Cerebral Flow
NOT Increased Systemic Blood Pressure
SWEET NUGGETS FROM USMLE
Activated Carriers
Phosphoryl (ATP)
Acyl (Coenzyme A, Lipoamide)
Electrons (NADH, NADPH, FADH2)
CO2 (Biotin)
One-carbon units (Tetrahydrofolates)
CH3 groups (SAM)
Aldehydes (TPP)
Glucose (UDP-Glucose)
Choline (CDP-Choline)
Metabolism Sites
Mitochondria (Energy)
Fatty acid oxidation (Beta-oxidation)
Acetyl-CoA production
Krebs cycle
Cytoplasm
Glycolysis
Fatty acid synthesis
HMP shunt
Protein synthesis (RER)

121

Steroid synthesis (SER)


Both
Gluconeogenesis
Urea cycle
Heme synthesis
Alcohol Dehydrogenase
Ethanol
(via Alcohol Dehydrogenase) Acetaldehyde (via Acetaaldehyde Dehydrogenase) Acetate
Both Rxns go via NAD+
NADH
So NAD+ is the limiting reagent
Alcohol Dehydrogenase operates via zero order kinetics
Ethanol metabolism increase NADH/NAD+ ratio in the liver, causing diversion of pyruvate to lactate and OAA to malate
This inhibits gluconeogenesis and leads to hypoglycemia
This altered NADH/NAD+ ratio is responsible for the hepatic fatty change seen in chronic alcoholics
Pruvate
Lactate
(Via NADH to NAD+)
Oxaloacetate
Malate
(Via NADH to NAD+)
Kwashiorkor vs. Marasmus
Kwashiorkor
Results from a protein-deficient MEAL
Malabsorption, Edema, Anemia, Liver (fatty)
Clinically, a small child with swollen belly
Marasmus
Protein-calorie malnutrition resulting in tissue wasting
Cell cycle Phases
M
When is DNA conc inside a cell lowest? I phase, between G1-S phase, M phase
In what phase does nondisjunction occur most rapidly??
Mitosis (PMAT)
Usually shortest phase
Protein & RNA synthesis occur in each of the following phases of the cell cycle, except M (does occur in G0, G1, S &
G2)
Interphase (G1, S, G2)
G1
Growth Phase
Rapidly dividing cells have a shorter G1 Phase
Most variable phase in the cell cycle
S
Synthesis of DNA
G2
Growth Phase
G0
Quiescent Phase
Most cells are in this phase
S-adenyl Methionine (SAM or AdoMet)
Contains an active (labile) methyl group
SAM synthetase synthesizes SAM from Methionine and ATP
SAM is the methyl group donor for most of the methylation reactions in all organisms
Examples: synthesis of phosphocreatine, high-energy phosphate active in muscle ATP production
Regeneration of methionine (hence SAM) is dependent on Vitamin B12
The methyl group of methionine is transferred to the substrate and then the demethylated SAM or AdoMet is released

Random Qs
Oncofetal antigen
Tumor associated antigen present in the fetal tissue, but not adult
Examples: alpha-feto protein (kidney) and carcinoembryonic antigen
Cyclin proteins do what in the cell cycle?
Activate protein kinases (cyclin-dependent kinases) at various stages throughout mitosis
Allows it to go From G1 to S phase

122

Destroyed by the ubiquination/proteasome pathway


Part of the Mitosis Promoting Factor (MPF cyclin/cyclin DK)
Ksp
A compound is soluble when what is greater than its solubility constant (Ksp)?????
Add info on Streptomycin
Streptomycin is an antibiotic which inhibits the process of transcription in prokaryotes
Add somewhere???
Electronegativity in living cells requires that a potential for charge separation exists
USC messed up the following questions:
1978 Q91 (options (c) & (d) should be iron & copper, respectively then the listed answer is correct)
1979 Q03 (answer should be (c) compare w/ 81 Q05); Q05 (the answer is in the question it shouldve been option (a)) Q 89 (In the lungs, HCO3- comes in and Clgoes out, then HCO3- goes to H2CO3 and pushes out CO2 and H20)
1982 Q25 (should be (e) decreased venous return compare w/ 85 Q36)
Lame questions:
1979 Q88
1982 Q24 (None of the above lame-o); Q28 (2 correct answers (b) & (d))
Huh?
1979 Q40; Q53; Q70
1981 Q22
Questions I have a problem with:
78 Q51 (ADH cells of the posterior hypophysis? NO!) 55 (NO!, its PTH that increases Ca absorption in intestine), 59
85 Q02 (wrong 1,25-etc), 15 (none of the above), 66, 85 (ACTH?), 89
89 Q06 (look closely at #6 CO2), 26 (same problem in B), 43 (B12, not B2)
96 Q53 (should be 10 -5)
Questions to review (add to notes)
78 Q50 (Volume per cent?) 82 Q74, 81
85 Q03, 38
87 Q17 (not covered), 53, 73, 80, 90, 91, 99
89 Q09, 14, 25 (just read), 81, 85, 89, 92
96 Q63, 84

123

124

MICROBIOLOGY AND PATHOLOGY


USC messed up the following questions:
1979Q94 wrong Should be Decreased
1981Q61 wrong should be (c) fibroblasts & endothelial cells
1981Q68 wrong should be basophils & mast cells, not eosinophils & mast cells
Questions to Find
Which of the following affects the widest organ range?
Herpes, rubella, varicella, Moluscam m.
CELLS/ORGANELLES
Cell parts:
Mitochondrion double MB structure responsible for cellular metabolism powerhouse of the cell
Nucleus controls synthetic activities and stores genetic information
Ribosome site of mRNA attachment and amino acid assembly, protein synthesis
Endoplasmic reticulum functions in intracellular transportation
Gogli apparatus/complex composed of membranous sacs involved in production of large CHO molecules & lysosomes
Lysosome organelle contains hydrolytic enzymes necessary for intracellular digestion
Membrane bag containing digestive enzymes
Cellular food digestion lysosome MB fuses w/ MB of food vacuole & squirts the enzymes inside
Digested food diffuses through the vacuole MB to enter the cell to be used for energy or growth
Lysosome MB keeps the cell iself from being digested
Involved mostly in cells that like to phagocytose
Involved in autolytic and digestive processes
Formed when the Golgi complex packages up an especially large vesicle of digestive enzyme proteins
Main function of lysosomes in steroid producing cell? cleave the ester from cholesterol ester to make free cholest.?
Phagosome vesicle that forms around a particle (bacterial or other) w/in the phagocyte that engulfed it
Then separates from the cell MB & fuses w/ lysozome to receive contents
This coupling forms phagolysosomes in which digestion of the engulfed particle occurs
Microbodies:
Smaller lysosomes that contain catalase includes peroxisomes and glyoxysomes
Contain catalase
Bounded by a single MB
Compartments specialized for specific metabolic pathways
Similar in function to lysosomes, but are smaller & isolate metabolic reactions involving H2O2
Two general families:
Peroxisomes: transfer H2 to O2, producing H2O2 generally not found in plants
Glyoxysomes: common in fat-storing tissues of the germinating seeds of plants
Contain enzymes that convert fats to sugar to make the energy stored in the oils of the seed available
Inclusions transitory, non-living metabolic byproducts found in the cytoplasm of the cell
May appear as fat droplets, CHO accumulations, or engulfed foreign matter
The cell cycle
1) Labile cells (GI tract, blood cells)
Described as parenchymal cells that are normally found in the G0 phase that can be stimulated to enter the G1
Undergo continuous replication, and the interval between two consecutive mitoses is designated as the cell cycle
After division, the cells enter a gap phase (G1), in which they pursue their own specialized activities
If they continue in the cycle, after passing the restriction point (R), they are committed to a new round of division
The G1 phase is followed by a period of nuclear DNA synthesis (S) in which all chromosomes are replicated
The S phase is followed by a short gap phase (G2) and then by mitosis
After each cycle, one daughter cell will become committed to differentiation, and the other will continue
cycling
2) Stable cells (Hepatocytes, Kidney)
After mitosis, the cells take up their specialized functions (G0).
They do not re-enter the cycle unless stimulated by the loss of other cells
3) Permanent cells (neurons)
Become terminally differentiated after mitosis and cannot re-enter the cell cycle
Which cells do not have the ability to differentiate?
Cardiac myocytes
Enzymes:
Serum lysozyme:
Provides innate & nonspecific immunity
Lysozyme is a hydrolytic enzyme capable of digesting bacterial cell walls containing peptidoglycan

In the process of cell death, lysosomal NZs fxn mainly to aulolyze necrotic cells (NOT mediate cell degradation)
Attacks bacterial cells by breaking the bond between NAG and NAM
Peptidoglycan the rigid component of cell walls in most bacteria not found in archaebacteria or eukaryotic cells
Lysozyme is found in serum, tears, saliva, egg whites & phagocytic cells protecting the host nonspecifically from
microorganisms
Superoxide dismutase: catalyzes the destruction of O2 free radicals protecting O2-metabolizing cells against harmful effects
Catalase:
catalyzes the decomposition of H2O2 into H2O & O2
Aerobic bacteria and facultative anaerobic w/ catalase are able to resist the effects of H2O2
Anaerobic bacteria w/o catalase are sensitive to H2O2 (Peroxide), like Strep
Anaerobic bacteria (obligate anaerobes) lack superoxide dismutase &/or catalase
Staph makes catalase, where Strep does not have enough staff to make it!!
Coagulase
NOT an NZ, its an adhesin
Converts Fibronogen to fibrin
Coagulase test is the prime criterion for classifying a bug as Staph aureus from other Staph species
Coagulase is important to the pathogenicity of S. aureus because it helps to establish the typical abscess lesion
Coagulase also coats the surface w/ fibrin upon contact w/ blood, making it harder to phagocytize
NOTE: this is NOT a polysaccharide capsule that forms
Cell Functions:
Autolysis:
degradative reactions in cells caused by indigenous intracellular enzymes usually occurs after cell death
Irreversible (along with Coagulative necrosis or infarcts) reversible: fatty degeneration, & hydropic degeneration
Autolysin:
Ab causing cellular lysis in the presence of complement
Autolytic enzymes produced by the organism degrade the cells own cell wall structures
In the presence of cephalosporins & penicillins, growing bacterial cells lyse
W/o functional cell wall structures, the bacterial cell bursts
Heterolysis: cellular degradation by enzymes derived from sources extrinsic to the cell (e.g., bacteria)
Necrosis: sum of intracellular degradative reactions occurring after individual cell death w/in a living organism
Lymph nodes
If a foreign antigen enters through the skin, it will first hit the lymphoid system in the lymph nodes
NOT the MALT, liver, spleen, or thymus
Lymphocytes
Motile
Immunoglobulin production
Produce MIF (Macrophage inhibiting factor)
If a T-lymphocyte from a pt with chronic periodontitis were cultered in vitro with dental plaque antigen, production of
MIF would occur
DO NOT PHAGOCYTIZE
When T cells from people with chronic PD are reacted with certain plaque bacterial antigens, they produce:
MIF, OAF, & lymphotoxin (aka TNF ) (NOT Ab, collagenase, or C3)
B-lymphocytes:
Are WBCs that complete maturation in bone marrow then migrate to lymphoid organs
Search out, identify, & bind w/ specific Ag/s
Recognize specific antigens by virtue of membrane-bound immunoglobulin
Committed to differentiate into Ab-producing plasma cells involved in Ab-mediated immunity
When an immature B cell is exposed to a specific Ag (they recognize Ag by MB-bound Ig), the cell is activated
It then travels to spleen or lymph nodes, differentiates, and rapidly produces plasma & memory cells
Mature B cells have surface IgM & IgD that bind Ag & cause release of immunoglobulins
B-cell immunodeficiency can be treated with injections of gamma-globulin
Need to dump the IgG in if you have none!
Plasma cells:
The predominant cell in synthesis of Ab/s
More common in chronic inflammation than acute inflammation
Cells of Chronic inflammation are Lymphocytes, Plasma cells, and Macrophages
T-lymphocytes:
Affected by IL-4???
WBC that complete maturation in thymus & become thymocytes
Responsible for initially recognition of antigen
In pts with chronic PD, when the T cells react with certain plaque bacterial antigens, they produce:
IL-2, TNF-alpha, IFN-gamma

NOT Immunoglobulin
Responses to viral infections:
Production of lymphokines
IL-2s, etc.
Direct cell-mediated cytotoxicity
CD8s
Helper activity to B cells to make Abs
Major classes include helper T-cells, suppressor T-cells, & cytotoxic (killer) T-cells
T helper cells:
CD4+
NOT antigen-specific
(Antigen-specific cells are):
B cells, Macrophages, Dendritic, and Langerhans
Two classes of helper T cellsTh1 & Th2 cells
Distinguished by the types of cytokines they secrete
Th1: release IL-2 & IFN-gamma
Cell mediated immunity IL-2 activated CD8, NK
Stimulate proliferation & cytotoxic responses
Th2: release Il-4, IL-5, IL-6, Il-10
Humeral Immunity
Stimulate B cell maturation, differentiation & class-switching
Cytotoxic T-cells
CD8+
First activated w/ IL-2, which is secreted by active helper T-cells
Act by recognizing foreign Ag & MHC I molecules w/ their TCR
Toxic Terrel Owens: 8-1
Natural Killer (NK) cells
Also activated w/ IL-2
Recognize foreign Ag w/o need for Ag presentation on MHC molecules
NON specific immunity
Activated by cytokines, such as IFN-gamma
Deficiency in T-cells can predispose a person to candidiasis (NOT a deficiency in basophils/eosinophils/plasma cells/Ms)
Eosinophils
Release histaminase & aryl sulfatase to help control allergic reactions is this right!?!?!?!?
Basophils
Have receptors for the Fc portion of IgE
IgE binding promotes degranulation = release of histamine, etc, which lead to symptoms seen in atopic allergies
Mast Cells
IgE has an affinity for the Fc portion of Mast cells
Type I Hypersensitivity
Secrete
Histamine
Heparin
ECF-A (Eosinophil Chemotactic Factor of Anaphylaxis)
SRS-A (Slow-Reacting Substances of anaphylaxis (SRS-As)
Leukotrienes
Whats inside a mast cell? Course cytoplasmic granules that release histamine and heparin
Lymphocytes
T helper cells (Th)
Cytotoxic T cells (Tc)
T suppressor cells (Ts)
T memory cells
B lymphocytes
B memory cells
Natural killer cells (NK)
Plasma cells

Function
Help or assist other T cells and B cells to express their immune function
Kill target cells expressing foreign Ag/s (cells containing obligate intracellular parasistes & tumor cells)
Suppress or inhibit the immune function of other lymphocytes
Long-lived cells that recognize previously encountered T dependent antigens
Differentiate into antibody-producing plasma cells and B memory cells in response to an antigen
Long lived cells that recognize a previously encounter antigen
Kill and lyse target cells that express foreign antigens
Actively secrete antibody

Cells that maintain latent capacity for mitotic division:


Blood (RBCs live for 120 days, WBCs only 2-5 hours), bone marrow, liver, and salivary glands
Liver undergoes regeneration: occurs as adaptive mechanism for restoring a tissue or organ
After removal of 70% of liver, numerous mitoses of hepatocytes occur reaching a peak at 33 hours
By day 12 the mass of liver is totally restored
Liver is the least common site for infarcts (than brain, heart, kidney, adrenals)
NOTE: Bone cartilage & intestinal mucosa are also able to regenerate

Cells that do not have ability to undergo mitosis:


Nerve cells (least ability to regenerate) in the CNS, skeletal, cardiac, & smooth muscle cells, lungs
Striated muscle is harder to regenerate than smooth muscle
Heart, brain, & lungs are very vulnerable to hypoxia & anoxia
They die & are unable to regenerate
The heart can undergo hypertrophy in response to injury
BACTERIA
A quick note on organisms in general:
Commensalism:
Interaction between two populations of different species living together in which one population benefits from the
association, while the other is not affected
Symbiosis:
An obligatory interactive association between members of two populations
Produces a stable condition in which the two organisms live together in close physical proximity
It may, but does not necessarily, benefit each member
Mutualism:
Form of symbiosis both members live together w/ mutual benefit
Cell types:
Eukaryote
Has a true nucleus surrounded by a nuclear MB & uses a mitotic apparatus in allocating chromosomes
Contains organelles & larger (80S) ribosomes
Mitotic replication
EXs: plants, animals, protozoa, fungi
Prokaryote
No nucleus, organelles, or cytoskeleton
Think of the cytoskeleton as an organelle
Nuclear material NOT contained w/in a nucleus
Naked, single circular molecule of losely organized dsDNA
Single chromosome
Located in nucleoid (membraneless structure/region containing DNA little resemblance to eukaryotic nucleus)
Contains no MB-bound organelles & smaller (70S) ribosomes
Has a rigid external cell wall containing peptidoglycan (mycoplasmas lack a cell wall)
EXs: BACTERIA, mycoplasmas, rickettsia, chlamydia
Gram-staining
Based on interaction w/ cell wall
Limitations:
Treponema (too thin to be visualized) Use Darkfield for Syphilis
Rickettsia (intracellular parasite)
Mycobacteria (high-lipid content cell wall) Use acid-fast
Mycoplasma (NO cell wall) M. pneumoniae (walking pneumonia)
Legionella Pneumophila (Primarily Intracellular)
Use Silver stain
Chlamydia (intracellular parasite)
Acid-fast organisms appear red against blue background (due to lipids/waxes [mycolic acids] in the cell wall)
Staining in tubercle bacilli is due to lipid/waxes mycolic acid
Mycobacteria & Nocardia are acid-fast Thus they will look red!
True bacteria multiply by binary fission
NOTE: viruses are not cells they are obligate intracellular parasites
Either RNA or DNA; no organelles; protein capsid & lipoprotein envelope
Classification:
Neutrophiles (pH = 7.0)
P. aeruginosa
Clostridium sporogenes
Proteus species
Acidophiles (pH < 7.0)
Thiobacillus thiooxidans
Sulfollobus acidocaldaarius
Bacillus acidocaldarius
Alkaliphiles (pH > 7.0)
Nitrobacter species
Streptococcus pneumoniae
Bacterial growth

1) Lag phase (Think lagging behind)


Metabolically active, non-dividing
Increase in mass, but not in number
2) Log phase = logarithmic phase (Log Growth)
Exponential growth
Most of the cidal Abx work best in this phase
i.e. Ampicillin
Best phase for staining bacterial cultures
For uniform staining rxn, morphology, and biochemical activity
3) Stationary phase
# of cells are dying = # of cells being produced
4) Death phase/phase of decline
More death than new cell production
Logarithmic decrease in cell #
Glucose metabolism (respiration)
Oxidative phosphorylation involves the Cell MB in bacterial cells
BUT, ETC in Eukaryotes happens on the inner mitochondrial MB
Aerobic respiration
Results in greatest release of energy
The primary result of bacterial carbohydrate metabolism is production of energy (NOT heat, alcohol, or acetone)
Involves a cell MB respiratory chain (electron transport chain = ETC)
O2 is the terminal hydrogen acceptor, with final end products of H2O and CO2
Fermentation
Substrate phosphorylation
Formation of ATP not coupled to electron transfer
Occurs when final electron acceptor is an organic compound
An intermediate glucose product (i.e., pyruvate) is the final hydrogen acceptor
Takes place in cytoplasm
How Anaerobic bugs get their energy
Aerobic metabolism (obligate aerobes & facultative anaerobes) They have the Faculty to be Aerobes too
Toxic byproducts: H2O2 & free superoxide radicals
Final endproducts are H2O and CO2
Cells possess a defense system to destroy these endproducts:
Enzymes include superoxide dismutase & catalase
1) Superoxide dismutase catalyzes the decomposition of free superoxide radicals into H2O2 & H2O
2) Catalase then catalyzes H2O2 H2O + O2
Cytochromes:
Respiratory enzymes capable of undergoing alternate reduction & oxidation
Contain central iron atom which can be cycled between oxidized ferric state (Fe 3+) & reduced ferrous state (Fe2+)
Chemically related to hemoglobin
Aerobic organotropic (heterotrophic) bacteria which oxidize a substance to CO2 and H2O in the final electron transport, use
NZs containing cytochromes
EXs:
Cytochrome oxidase terminal enzyme in chain of events constituting cellular O2 consumption found in mitochondria
Cytochrome P450 important in metabolism of many drugs found in liver microsomes (small particles typically
consisting of fragmented endoplasmic reticulum to which ribosomes are attached)
Cytochrome b cytochrome of respiratory chain
Cytochrome b5 cytochrome of endoplasmic reticulum
Transcription
Synthesis of mRNA from DNA by DNA-dependent RNA polymerase
Occurs in cytoplasm of prokaryotes (nucleus of eukaryotes)
Two strands of DNA are temporarily pulled apart to allow RNA polymerase to access DNA as a template
Translation
Process where in nitrogenous bases are used to determine the aa sequence of a protein
Reverse transcription
Formation of DNA from RNA template
Retroviruses (HIV, RNA tumor viruses) use this process
RNA genome is used as a template for RNA-dependent DNA polymerase
The virion-associated reverse transcriptase makes DNA copies from RNA
This DNA is then integrated into the host genome
**Retrovirus is an oncogenic RNA virus (papillomavirus is NOT because it is a DNA virus dont get clowned)
3 types of RNA:

1) rRNA combines w/ proteins to form ribosomes


2) mRNA dictates sequence of aa assembly
3) tRNA transports aas to ribosomes for protein assembly
Genetic Transfer in Bacteria 3 processes:
1) DNA TRANSFORMATION
Process in which DNA is released by lysis of one bacterium & taken up by a second, leading to a change in
phenotype
Another Q: Transformation is best described as acquisition of an inheritable trait by bacteria mediated by DNA
Transfer of inheritable characteristics among bacteria is dependent upon DNA
Rough pneumoncocci grown in the presence of DNA from smooth pneumococci developed capsules
The most primitive mechanism for gene transfer among bacteria
Used in lab to create recombinant DNA & to map gene locations
No cell-to-cell contact required
Involves the uptake of naked DNA molecules (the other processe of genetic transfer do NOT involve)
The DNA picked up by the recipient cell must be dsDNA
Intracellular DNAase (endonuclease) degrades one strand, providing energy for uptake of the other ssDNA
Uptake depends on presence of protein called competence factor
The ssDNA inserts into homologous regions of recipient chromosome
2) TRANSDUCTION
NEED A TRANSDUCER THE VIRUS!
Transfer of genetic material from one bacterial cell to another by viral infection
No cell-to-cell contact required
Least susceptible to DNAase DNAase is the thing that will mess up transformation, b/c that has just pieces of dna
sitting around
Transfer of DNA via a bacteriorphage = phage-mediated
3) CONJUGATION (THINK Conjugal Visit)
A form of sexual reproduction in which ssDNA is transferred from one live bacterium to another through direct contact
Pili establish the physical contact
Does NOT require flagella for pair formation
NOTE about pili: The most important function of bacterial pili in causing human infectious disease is by allowing
bacteria to adhere to human cells, and NOT in the transfer of DNA between bacteria although pili do both
This process transfers the greatest amount of genetic information (compared to transformation & transduction)
Ability to grow in the presence of ABX is passed in vivo from one bacterium to another
The pattern of resistance is transferred to other bacteria via conjugation
F factors
Plasmids transferred from a donor cell (F+ cell) to a recipient cell (F cell) during conjugation
Integration of the F factor plasmid into the chromosome is essential in order for the F factor to be transferred
during conjugation
An Hfr (high freq of recombination) is a cell w/ an F plasmid incorporated into the chromosome
During conjugation, portions of the Hfr chromosome are transferred from the Hfr bacterium to the F bacterium
NOTE: all 3 processes contribute to increase in genetic variation w/in a population
Cell Parts (insideout):
Nuclear material
Single, double stranded DNA molecule not confined within a nuclear membrane
Plasmid
Contains a variety of genes for ABX resistance, enzymes, and toxins
DNA
Ribosome
Protein Synthesis
RNA and protein in 50S and 30S subunits
Cell MB = Cytoplasmic Membrane = Plasma MB
Dynamic, selectively permeable MB involved in energy transformations (i.e., oxidative phosphorylation)
Regulates movement of substances, including water, into/out of the cell
Most active cellular structure of bacteria that controls the intake of solutions
Encloses the cytoplasm
Bordered externally by the cell wall
In gram + bacteria, the teichoic acid induces TNF and IL-1 (acute phase)
Periplasm
Space between the cytoplasmic membrane and outer membrane in gram bacteria
Contains many hydrolytic NZs, including Beta-lactamases
Cell Wall see notes below on G+ & G- cell wall contents
The basic difference between G+ & G- bacteria is the cell wall structure

Surrounds plamsa MB
Protects cell from changes in osmotic pressure
Anchors flagella
Maintains cell shape
Controls transport of molecules into/out of the cell
N-acetylmuramic acid (NAM) is intermediate (also NAG) in cell wall biosynthesis
In gram - bacteria, the Lipid A induces TNF and IL-1 (acute phase)
so teichoic as and lipid as for Acute resp.
Capsule
Gelatinous (polysaccharide) coat often used 1) as an indicator of virulence (Enables them to stick to other cells) & 2) to
determine bacterial pathogenicity
**All are polysaccharide, except for Bacillus anthracis, which is D-glutamate
Surrounds cell wall of certain bacteria
Protective against phagocytosis by eukaryotic cells
Loss of capsule promotes phagocytosis
Prevents opsonization by complement
1) The capsule is slimy, making it hard for phagocytes to hold onto the bacterial surface
2) Complement receptors are masked by the capsule, making it difficult/impossible for complement to bind
Capsule must be first coated w/ specific anticapsular antibodies & complement
EXs of bacteria w/ capsules:
Streptococcus pneumoniae
Hemophilius influenzae
Klebsiella pneumoniae
Cryptococcus neoformans
Pilus/Fimbria
Mediates adherence of bacteria to cell surface THE MOST IMPORTANT THING IT DOES.
Sex pilus forms attachment beween 2 bacteria during conjugation
Glycoprotein
Flagellum
Motility
Protein
Spore
Provides resistance to dehydratin, heat, and chemicals
Keratin-like coat
Dipicolinic acid
Glycocalix
Mediates adherence to surfaces, especially foreign surfaces (i.e. catheters)
Polysaccharide
Extracellular
NOTE: Protoplasts usually from penicillin and lysozyme makes sense two things that target cells walls!
A bacterial cell that is free of a cell wall and a capsule
Spherical body produced under appropriate conditions from certain bacilli by the axn of lysozyme or PCN
Cells that have their cell walls & capsules removed by enzymatic (lysozyme) or Abx (penicillin) Tx
G+ cell envelope (insideout):
Inner Cell Membrane
Cell Wall components:
Thick murein (peptidoglycan) layer
The backbone biochemical of the bacterial cell wall (makes up ~90% of the cell wall)
Peptidoglycan (murein):
The rigid component of the cell wall in most bacteria not found in archaebacteria or any eukaryotic cell
Two parts of molecule:
Peptide portion: short, attached, cross-linked peptide chains containing unusual amino acids
Glycan portion: alternating units of amino sugars N-acetylglucosamine and N-acetylmuramic acid
The NAG-NAM backbone is attacked by the enzyme lysozyme
Lipoteichoic acids
Teichoic acids
Unique to G+ bacteria
Polysaccharides that serve as attachment sites for bacteriophages
No outer membrance
Capsule (sometimes)
G- cell envelope (insideout):
Inner Cell Membrane

Outer Membrane
Cell Wall components:
More complex than G+ cell wall
Thin murein layer (~10% of cell wall)
Lipoproteins are an integral part of cell wall
Lipopolysaccharide (LPS) layers (= endotoxin)
Located in the outer MB of G- bacteria
Basic chemical structure consists of:
Somatic O Polysaccharide, Core Polysaccharide, and Lipid A (and Keto-deoxy-octanoate!!!)
NOT Teichoic acid (That is only in G+ cell wall !!!)
Lipid A is the most responsible for the endotoxins toxic activity
Induces TNF alpha and IL-1 Also activates complement
Endotoxin is made of Lipid A
NOT Protein A, O antigen, or core polysaccharide
Only released (toxic) after cell dies & outer MB is broken down (i.e., not secreted)
Pathogenic effects occur via activation of complement cascade
Has a chemotactic effect on neutrophilic granulocytes induces phagocytosis
Host response includes: chills, fever, weakness, aches, shock, death
Accumulates in the gingival crevice in the absence of gingival hygiene
Dont get clowned by bacterial metabolites including enzymes accumulating in the crevice
Shwartzman reaction
In this reaction, endotoxin elicits the response
Rabbit is injected intradermally with a small quantity of lipopolysaccharide (endotoxin) followed by a second
intravenous injection 24 hours later and will develop a hemorrhagic and necrotic lesion at the site of the first
injection
Phospholipids
Proteins
Other Cell Contents:
Granules (inclusion bodies) storage areas for nutrients
Volutin reserve of high energy stored in the form of polymerized metaphosphate that can be used in synthesis of ATP
Commonly associated w/ Pseudomonas aeruginosa & Cornybacterium diphtheriae
Where does cornybacterium get its exotoxin? lysogenic conversion via a temporate bacteriophage
Sulfur granules
Metachromatic granules Diphtheria
Plasmids
Extrachromosomal, circular, dsDNA molecules capable of replicating independently of the chromosome
Molecules of DNA that are separate from the bacterial chromosome
Confer conjugal fertility shooting blanks
Carry genetic information between bacteria
Example: R (resistance) factor
Replicate while attached to the bacterial cell membrane
Do NOT exist as circular RNA molecues
They are DNA!!!
Multiple drug resistance is related most closely to plasmids (NOT viruses, transformation, or cell chromosomes)
ABX Resistance
Most antibiotic resistance in bacteria is caused by genes that are carried on plasmids
Plasma-mediated antibiotic resistance has been observed with all of the following EXCEPT one:
S. aureus, B. pertussis, and H. influenzae, N. gonorrhea, S. pyogenes???
(Google says they all do!!!)
PCN resistance in N. gonorrhea is explained by its production of a plasmid encoded beta-lactamase
Strep pyogenes is resistant to erythromycin (plasma-mediated??), but is sensitive to bacitracin & penicillin
Determine traits not essential for the viability of the organism but that change the organisms ability to adapt
Transposons
Consists of two insertion sequences flanking an ABX resistance gene
Pieces of DNA that move readily from one site to another, either w/in or between the DNAs of bacteria, plasmids, or
bacteriophages
Genes that often encode proteins necessary for ABX resistance and that can change positions on a chromosome or
jump from a plasmid to a chromosome
Frequently associated w/ formation of multiple-drug resistance plasmids
Encapuslated Bacteria
Polysaccharide capsule is antiphagocytic virulence factor

IgG2 necessary for immune response


Capsule serves as antigen in vaccines (Pneumovax, H. influenzae b., Meningococcal vaccines)
Quellung Rxn = Caspsular Swellung rxn
capsule swells when specific anticapsular antisera are added
Streptococcus Pnuemoniae
Haemophilus influenzae
Neisseria meningitides -BIodome
Klebsiella pneumoniae
Cryptococcus Neoformans Inside the Crypt
Exotoxin Vs. Endotoxin
Property
Source
Secreted
Chemistry

Location of genes
Toxicity/Potency
Clinical effects
Mode of action
Antigencity
Vaccines
Heat Stability
Typical Diseases
Specificity
Miscellaneous

Exotoxin
Some Gram + and Gram Yes (Diffuse out)
Polypeptide

Plasmid or bacteriophage
High (fatal if dose on the order of
1microg)
if you shoot it, its more
deadly!
Various
Various
Induces high titer antibodies called
antitoxins
Toxoids are used
Destroyed rapidly at 60 degrees C (except
Staph enterotoxin) (Heat Labile)
Tetanus, botulism, diphtheria, anthrax
High
Detoxified by formalin
Highly immunogenic - antigenic

Endotoxin
Cell wall of most Gram ONLY
No (Just a breakdown product)
Lipopolysaccharide
Most bacterial endotoxins are
composed of lipoproteinpolysaccharide complexes
Bacterial chromosome
Low (fatal dose on the order of hundreds
of micrograms)
Fever, shock
Includes TNF and IL-1
Poorly antigenic
No toxoids formed and no vaccine avail.
Stable at 100 degrees C for 1 hour
Mb
is more stable thus heat stable
Meningococcemia, sepsis by Gram- rods
Different from exotoxins in that they
activate complement via the alternate
pathway
Play a role in PD because the role
endotoxins play in inciting an
inflammatory response
Found in gingival crevice?

Effects of Endotoxin
1. Activates Macrophages
Produce IL-1 (acts on T + B cells) Fever
Produce TNF Fever, Hemorrhagic tissue necrosis
Produce Nitric Oxide Hypotension (shock)
2. Activates Complement (Alternative Pathway)
Produce C3a Hypotension, Edema
Produce C5a Neutrophil Chemotaxis
3. Activates Hageman Factor (Clotting Factor)
Coagulation Cascade DIC (Disseminated Intravascular Coagulation)
Some Protein Toxins (Exotoxins) Produced by Microorganisms That Cause Disease in Humans
Organism
Exotoxins
Disease
Action
Gram +
Clostridium botulinum
Several neurotoxins (A,B,E)
Botulism
Paralysis, blocks neural transmission
(Gram +)
Blocks release of Ach just like
Lambert Eatons
Spores found in Canned Food, Honey
Clostridium perfringes
a-toxin (a lecinthinase)
Gas gangrene
Destroys integrity of cell MBs
(Gram +)
K-toxin (a collagenase)
Breaks down fibrous tissue
Get double zone of hemolysis on blood
agar
Clostridium tetany
Neurotoxin (tetanospasmin)
Tetanus
Spastic paralysis interferes w/ motor

(Gram +)
Corynebacterium
(Gram +)

Diphtheria toxin
*a lysogenic phage encodes it

Streptococcus Pyogenes
(Group A Strep)
(Gram +)

Various hemolysis
Streptolysin O
Streptolysin S
Erythrogenic
Enterotoxin Very fast food
poisoning

Staphylococcus aureus
(Gram +)

Diphtheria

Rheumatic fever
Scarlet fever
Food poisoning
Toxic Shock
Syndrome

TSSTright?
Bacillus anthracis
(Gram +)
Gram Shigella dynsenteriae

Anthrax
Neurotoxin

Escherichia coli

Bacterial (bacillary)
dysentery
Diarrrhea

Vibrio Cholerae

Rice-water diarrhea

Bordetella pertussis

Whooping Cough

neurons
Blocks release of inhibitor glycine
Causes Lockjaw
Blocks protein synthesis at level of
translation
Inactivated E2-F by ADP ribosylation
(similar to Exotoxin A of Psuedomonas)
Causes Pharyngitits/Psuedomembrane
Lysis of RBCs
Causes symptoms of rheumatic fever
Causes rash of scarlet fever
Intestinal inflammation
Toxin is a superantigen that binds to
MHC II and T cell receptor, inducing IL1 and IL-2 synthesis in toxic shock
syndrome
One toxin in the toxin complex is an
adenylate cyclase
Hemorrhage, paralysis
Heat labile toxin stimulates adenylate
cyclase by ADP ribosylation of G
protein
Stimulates adenylate cyclase by ADP
ribosylation of G protein, increasing
pumping of Cl- and H20 into the gut
Stimulates adenylate cyclase by ADP
ribosylation
Inhibits chemokine receptor, causing
lymphocytosis

Two other examples:


Pyrogenic exotoxin A similar to the staphylococcal toxic shock syndrome toxin
Exotoxin B a protease that rapidly destroys tissue
NOTE: one Q reads, tetanus & diphtheria are similar in nature w/ respect to production of exotoxins
Botulism:
Uncommon, life-threatening poisoning (not infection)
An intoxication, not an infection THINK BOTU TOXU
Caused by the toxins produced by the G+ anaerobic bacillus Clostridium botulinum
Heat-labile neurotoxin usually from improperly canned food
These exotoxins (neurotoxins) are the most potent poisons known to humans
Can severely damage nerves & muscle
Bind to presynaptic nerve & block release of ACh from CNS nerve cells
Causes flaccid paralysis of skeletal muscle
Cause loss of motor function, including respiratory failure = death
Occurs w/ botulism food poisoning, wound botulism, & infant botulism
Infant botulism = floppy baby syndrome leads to failure to thrive
Foods most commonly contaminated home-canned vegetables, cured pork/ham, smoked/raw fish, & honey or corn syrup
Cannot grow in human body only the toxin causes disease
So another Q reads: It does NOT require the presence of a live organism
Mortality from botulism is ~25% death usually caused by respiratory failure during the 1st week of illness
Symptoms appear 8-48 hours after ingestion of toxin:
Initial CN paralysis w/ diplopia (double vision), dysathria (difficulty speaking), & pupil dilation
Followed by limb & trunk muscle weakness or paralysis
Antitoxin is given, along w/ respiratory support
Cannot undo damage, but may slow/stop further physical & mental deterioration body can heal itself over months
Diphtheria
ABCDEFG
ADP ribosylation
Beta-prophage (exotoxin is encoded by)
Club Shaped (Coryne means club shaped)

10

Diphtheria
Elongation Factor 2 (Exotoxin inhibitrs protein synthesis via ADP ribosylation of EF-2)
Granules (Metachromatic Granules)
Causes pseudomembranous pharyngitis
Grows on tellurite agar
Bacteria Groupings
The following diseases are transmitted by droplets or droplet spray:
Whooping cough
Meningitis
Diphtheria
Pneumonia
VSV
NOT Condylatum acuminatum Get this by dipping the stick
Gram + (purple/blue)
Rods
Clostridium (tetany, botulism, difficile psuedomemb. Colitis, Gas gangrene - perfringes) SPORE FORMING
The bacteria that causes gas gangrene also has lecithinase
Corynebacterium (Diphtheria)
Listeria (Fetal Death, cholera, dysentery, meningitis)
Bacillus (Anthrax) SPORE FORMING
Cocci
Catalase +
Staphylococcus
Coagulase +
S. aureus
Coagulase
S. epidermidis (Nosocomial with valves/joint replacement)
S. saphrophyticus (UTIs in sexually active women)
Catalase
Streptococcus
Hemolysis
Alpha
Capsule (optochin sensitive)
S. Peumoniae (Pneumonia)
NO Capsule (optocin resistant)
Viridans Streptococci (i.e. S. mutans) (Endocarditis, caries, Brain abscess)
Beta
Group A (Bacitracin Sensitive) -- according to carb found in cell wall
S. Pyogenes
Group B (Bacitracin Resistant)
S. agalactiae (Neonatal meningitis, pneumonia, sepsis)
Gamma
Enterococcus (E. Faecalis and Peptostreptococcus)
**Can be either gamma or alpha
Gram - (Pink)
Cocci
Neisseria
Maltose Fermenter
N. meningitidis (Meningitis and Septicemia)
Non-Maltose Fermenter
N. gonorrhoeae
Coccoid (rods)
Haemophilus influenzae
Pasteurella (Cat and dog bites Cellulitis)
Brucella (Brucellosis fever)
Bordetella pertussis (whooping cough)
Rods
Lactose Fermenter (pink on MacConkeys)
Fast Fermenter
Klebsiella (Bronchopneumonia and Nosocomial UTIs)

11

Escherichia coli (UTIs, Diarrhea)


Enterobacter (Diarrhea)
Slow Fermenter
Citrobacter
Serratia (Makes make red pigment)
Others
NON-Lactose Fermenters
Oxidase Shigella (Bloody Diarrhea, Paralysis)
Salmonella (Enteric Fever, Typhoid Fever, Bloody Diarrhea, Osteomyelitis in Sickle Cell pts)
Proteus (UTIs)
Oxidase +
Pseudomonas (Pneumonia, Burn wound infection, Osteomyelitis, UTI, Contact lens infection)
MORE on G- aerobic rods and cocci:
Pseudomonas family (really just P. aeruginosa):
G-, straight or curved rods, most are obligate AERobes (PETS -- AIR)
Think PSEUdomonas Pneumonia (in CF pts), Sepsis (black skin lesion), External Otitis (swimmers ear), UTI
Motile by means of polar flagella
Produce characteristic fluorescent pigments (P. aeruginosa), but others do not
Has ability to adapt and thrive in many ecological niches, from water to soil to plants & animals, including humans
Exotoxin A
Inhibits protein synthesis (not DNA synthesis)
Inactivates E2-F
Important nosocomial infection in immunocompromised & chronically ill patients
People w/ cystic fibrosis, burn victims, individuals w/ cancer & pts requiring extensive care in hospitals
Nosocomial infections often caused by:
Staph, Strep, E. coli, & P. aeruginosa are common bugs in hospital-acquired infections
Once established, produces a number of toxic proteins which cause not only extensive tissue damage, but also
interfere w/ the human immune defense mechanisms
An infection followed a serious skin burn that is characterized by greenish pus and is resistant to ABX is
probably caused by P. aeruginosa (think P. aeru-green-osa)
Pyocanin pigment
Gentamicin is a broad spectrum aminoglycoside antibiotic effective in treating bacteremias caused by P. aeruginosa
Volutin (aka metachromatic granule) is a reserve of high energy stored in the form of polymerized metaphosphate
that can be used in synthesis of ATP
Metachromatic granules are commonly associated w/ Pseudomonas aeruginosa & Corynebacterium
diphtheriae (Remember ABCDEFG)
Burn victims
Which of the following will not affect burn victims?
P. aeruginosa, Mycobacterium ulcerans, C. tetany, Staph aureus --- VERIFY
Bordetella
Neisseria
Brucella
Legionella
Gram rod
Stains poorly, use Silver stain
Grown on charcoal yeast extract culture with iron and cysteine
Aerosol transmission from water source habitat
Legionella pneumophilia is transmitted via aerosolized organisms in air conditioning cooling towers
French Legionnaire with his Silver Helmet, sitting around a campfire (charcoal) with his iron because he no
Cissy (cysteine) and his atypical Pontiac Car parked out front with the A/C on
Young Healthy person exposed to Legionella Pneumophilia, what happens
Initial symptoms are flu-like, including fever, chills, and dry cough. Advanced stages of the disease cause
problems with the gastrointestinal tract and the nervous system and lead to diarrhea and nausea
Causes Pontiac fever and Legionnaires disease and Atypical Pneumonia
Treat w/ erythromycin
Haemophilus Influenzae
haEMOPhilus causes Epiglottitis, Meningitis, Otitis, Pneumonia
Large Capsule
Small gram coccobacillary coccoid rod

12

Aerosol transmission
Most invasive disease is caused by capsular type b (b=bad)
Vaccine contains type b capsular polysaccharide conjugated to diphtheria toxoid or other protein
Tx with Cephalosporin
Think use CEPH because its your brain (MENINGITIS)
Produces IgA protease
Culture on chocolate agar requires Factor V (NAD) and X (hematin) Go to the FIVE (V) and DIME (X) store to
buy chocolate
Does NOT cause the Flu that is a VIRUS
Helicobacter pylori
Gram rod
Causes gastritis and 90% of duodenal ulcers
Risk factor for peptic ulcer and gastric carcinoma
Urease positive (cleaves urea to ammonia) along with Proteus
Bacteria in the mouth use all for nutrients except????
Bicarb or Urea
Tx with Triple Tx
Bismuth
Pepto-bismal (think Stomach)
Metronidazole
Tetracyclin or Amoxicillin
G- anaerobic rods:
Bacteroides
Fusobacterium
Prevotella
Facultative anaerobic, G- rods
Highly invasive & can readily become resistant to Abx
Enterobacteria
All have endotoxin
All are found in GI tract (except Y. pestis)
All are motile (except Klebsiella & Shigella)
All ferment glucose and are oxidase negative
Think COFFEe
Capsular Related to the virulence
O-antigen, and Oxidase Negative All have Somatic O-antigen (Polysaccharide of Endotoxin)
Flagellar antigen The Flagellar H antigen is found in motile species
Ferment glucose
Enterobacteriaceae
Escherichia pg 56 Micro made simple
Short, G-, facultative anaerobic rods
Motile via a peritrichous flagella
Normally present in intestines
Contaminates water supply
DONT Giardia is NOT in our water supply
Capable of causing mild to severe forms of enterocolitis
The most common cause of UTIs (cystitis)
The most common causative organism in G- sepsis
Etiologic agent of travelers diarrhea
Use ELISA assay to detect an enterotoxin produced by E. coli
ELISA can also detect:
An enterotoxin produced by Vibrio cholerae (a curved, G- bacillus)
An enterotoxin produced by S. aureus, which toxin causes acute-onset food poisoning
Viral gastroenteritis
Shigella vs. Salmonella (not usually found in human GI???)
Both cause bloody diarrhea
Both non-lactose fermenters
Both invade intestinal mucosa
salMonella is Motile and can invade heMatogenously
Symptoms of Salmonella can be prolonged if tx with ABX
Salmon (animal reservoir)

13

Oh, Shiii, Shigella is more virulent


Shigella is transmitted via food, fingers, feces, and flies
Klebsiella
Causes severe lobar pneumonia in people w/ underlying conditions like alcoholism, diabetes, COPD
Yersinia intracellular
Enterobacter
Vibrionaceae Vibrio
Pasteurellas Haemophilus, Gardnerella, Pasteurella
Gram - and PCN
ALL gram - are resistant to PEN-G, but may be susceptible to PCN derivatives, like ampiciliin
The gram outer membrane layer inhibits entry of PEN-G and Vancomycin
SPIROCHETES Treponema & Borrelia
Treponema pallidum pg 91 Micro made simple
Found elsewhere in the file syphilis
Darkfield exam
Dx
FTA-ABS
Specific for Treponema, and turns positive earliest in disease
Find The Antibody- ABSolutely
VDRL
Many false positives
Viruses, Drugs, Rheumatic fever, Lupus/Leprosy
Borrelia Burgdorferi Lyme Disease:
B for Big
Only Borrelia can ve seen using aniline dyes (Wright or Giemsa stain) in light microscopy
Named after Lyme, Connecticut
Most commmon vector-borne disease in the northern hemisphere (from arthropods)
Signs/symptoms: skin rashes, arthritis, & neurological symptoms
Hallmark: erythema chronicum migrans red macule w/ central clearing bullseye at site of bite
Organism found in tick vectors that have fed on infected deer or mice reservoirs
After hiking through the woods, pts presents with polyarthritis, paresthesias, and a skin rash
You also can see Heart problems DONT SEE Night Sweats
RICKETTSIAE & CHLAMYDIAE Rickettsia, Coxiella, Chlamydia
Both rickettsia & chlamydia:
Can cause human disease
Posess both DNA & RNA -- Bacteria
Growth can be inhibited by antimicrobial drugs
Are inactivated by heat, drying, and chemical agents
NOT multiply in bacterial cells
Both are obligate intracellular pathogens
Both are not insect vector transmitting only Rickettsia is (remember the Rickettsia Rockets)
CHLAMYDIA:
C. trachomatis
Lots of info found elsewhere in file
C. psittaci
Transmitted by inhalation of organisms from infected birds & their droppings
Birds + pneumonia = think C. psittaci
RICKETTSIA: causes spotted mountain fever
Small G- aerobic coccobacillary bacteria that are obligate intracellular parasites
Rickettsia and viruses have in Common they are both intracellular parasites
The only bacteria that are IPs are Rickettsia and Chlamydia (they stay inside when its Really Cold)
This means they only survive by establishing residence inside animal cells and utilizing the hosts ATP
Both Rickettsia and Chlamydia have this ATP/ADP translocator to assist them in stealing ATP
Rickettsia still can oxidize certain molecules and create ATP, whereas Chlamydia does not have a
cytochrome system and can not produce ATP
Rickettsia needs CoA and NAD
Results from insect bites arthropod transmission
Requires an insect vector in the transmission to humans think Rickettsia = Insectsia
Triad:
Headache, Fever, Vasculitis

14

Most rickettsial diseases produce severe illness in humans because rickettsiae are destructive for endothelial cells
NOT because they produce potent exotoxins, cause extensive CNS damage, or are destructive to epithelial cells
For Dx and culturing
You can inoculate into living tissues (chicken embryo yolk sac or cell culture)
Target cell: endothelial cell of capillaries and other small blood vessels
Produce severe illness in humans because they attack the endothelial cells
Present as systemic symptoms of headache, myalgias, and fever, followed by rash
Maculopapular rash appears on palms of hands & soles of feet
Rash spreads to the trunk
Can be dx with certain strains of Proteus vulgaris because they both have certain antigens in common
Rickettsia and Viruses have the following in common:
Growth environment both require living cells for growth
Small Size
Being obligate intracellular parasites
NOT in common with virus (in other wordswhat they have in common with fellow bacteria):
Have BOTH DNA and RNA (viruses only have one or the other)
Synthesize their own proteins (viruses do not)
Are sensitive to ABX (obviously viruses are not)
Reproduce by a complex cycle w/ Binary Fission (Bacteria = Binary Fission; Viruses = synthesis & assembly)
Possess an energy yielding, autonomous enzyme metabolism (Rickettsia only)
Divided into two groups:
Spotted-Fever Group Rash is inward (from palms inward)
Rocky mountain spotted fever
tick
R. rickettsii (which accounts for 95% of rickettsial diseases in U.S.)
Endemic in East Coast, that is why its a fever only in the Rockies
Queensland tick fever
tick
Boutonneuse fever, Kenya tick fever
tick
Siberian tick fever
tick
Rickettsial pox
mite
Is the rickettsia disease that may have oral manifestations (NOT Brills disease, or epidemic typhus)
Typhus Group Rash is outward spread
Louse-borne tymphus (epidemic typhus)
louse
R. prowazekii
Murine typhus (endemic typhus)
flea
R. typhi
Scrub typhus
mite
R. tsutsu-gamushi
Q fever (Queer has no rash)
inhalation
Coxiella burnetii
Does NOT cause a skin rash
Does NOT require an arthropod vector
**Only rickettsia that is via aerosol
Tx: tetracycline & chloramphenicol
Mycoplasmas Mycoplasma, Ureaplasma
Lack a cell wall resistant to beta-lactam ABX
Has ergosterol in cell membrane
Require sterols for growth
M. pneumoniae
Transmitted by respiratory droplets
Frequent in military recruits and prisons
Cause atypical pneumonia walking pneumonia= #1 cause of pneumonia in young adults
Cold agglutinins used in presumptive dx (IgM)
PCN resistant so tx with Ery or Tetra
G+ cocci Staphylococcus, Streptococcus, Enterococcus, Peptostreptococcus
Endospore forming rods & cocci Bacillus, Clostridium
Regular non-spore forming G+ rods Lactobacillus
Irregular non-spore forming G+ rods Corynebacterium, Actinomyces
Actinomycetes Streptomyces, Nocardia, Rhodococcus
STAPHYLOCOCCUS
G+ coccus that grows in grape-like, usually occur in irregular clusters in culture (NOT in pairs, chains, etc)

15

Kaplan says they CAN occur in pains & short chains


Facultative
Posess both superoxide dismutase & catalase
Bacteria most commonly found on the skin
Most common manifestation of staph infections in humans is cutaneous abscesses
One answer option, Scalded skin syndrome, is staph-related, but not the most common manifestation of staph
Resistance to PCN
Most frequently develops resistance to PCN
Gains resistance to PCN by an having an NZ that attacks PCN
Staph infections are suppurative infections usually caused by S. aureus
Abscess formation is characteristic
EXs: abscesses, endocarditis, impetigo, osteomyelitis, pneumonia, septicemia, cavernous sinus thrombosis
S. aureus
Not part of normal flora
Can cause acute-onset food poisoning via enterotoxins
Most common cause of suppurative infections involving the skin, joints, & bones
Osteomyelitis is most commonly caused by S. aureus
Causes Acute Bacterial Endocarditis
Most commonly causes skin infections (pyoderma)
Most often associated with fatalities following influenzal infection
Coagulase(+) [other Staphylococci are coagulase(-)]
Coagulase test is the prime criterion for classifying a bug as Staph aureus from other Staph species
Coagulase is important to the pathogenicity of S. aureus because it helps to establish the typical abscess lesion
see 2000 Q56 to discuss w/ Jake
Coagulase also coats the surface w/ fibrin upon contact w/ blood, making it harder to phagocytize
NOTE: this is NOT a polysaccharide capsule that forms
Resistant to PCN
Tx: methicillin, nafcillin, oxacillin [or for MRSA vancomycin]
Protein A
Binds the Fc receptor of IgG, thereby blocking complement activation by the classical pathway and inhibiting
phagocytosis
(cell wall component) may be responsible for virulence
Antiphagocytic
Elicits Hypersensitivity
Causes Platelet injury
Staphylokinase cleaves plasminogen to plasmin (Streptokinase & Urokinase do, too) Kind of anti-coagulase
Staphylococcal food poisoning:
Food contaminated w/ toxins of certain types of Staph; generally results in diarrhea & vomiting
Gastroenteritis is principal feature
Incubation period of 2-4 hours (NOT the case for cholera, botulism, salmonellosis)
STREPTOCOCCUS
General Info
Facultative anaerobic G+ cocci that grow in pairs or chains in culture
Does have some aerobics, so:
If you pull human saliva out and let it grow on agar in air for 24 hours, strep will have the most out of the other
Facultative Anaerobics (Lactobacillus, Staph, Fusobacterium, and Actinomycetes)
When growing glucose in an unbuffered medium, will cause pH to drop
Most numerous group in the oral cavity
Most predominant bug in dental plaque
Streptococcal pharyngitis infections are preferentially treated w/ Abx affeecting cell wall synthesis
Lack catalase although they can live in conditions where O2 is present
1) -hemolytic Streptococcus
Produce a zone of incomplete hemolysis around the colony & adjacent green discoloration
Most common organism producting subacute bacterial endocardititis (S. sanguis, under Viridans Streptococci,
below)
Most often associated w/ infective endocarditis
Most oral Streptococci are alpha-hemolytic streptococcus
S. pneumoniae (aka Pneumococcus ) (Optochin sensitive)
Think breathing in through the nose, because its AFRAID of the CHIN)
Most common cause of community acquired bacterial pneumonia in the U.S.
Very well known for its large polysaccharide capsule (so is Cryptococcus neoformans)

16

Strains of Strep pneumonia are distinquished by their polysaccharide capsules


Host response are chiefly mediated by opsonins
Antigens
Capsular
Virulence of pneumococcus is associated with its capsular polysaccharide
C-polysaccharide
F-antigen
M-protein
NOT erythrogenic toxin (thats strep pyogenes Scarlet fever/Rheumatic Fever)
Treatment/Prevention:
Vancomycin or erythromycin
PCN resistance on the rise due to transformation
Vaccine: 23-valent vaccine available
Viridans Streptococcus (optochin resistant)
NOT afraid of the CHIN
Normal flora of the oropharynx and cause dental caries and bacterial endocarditis
S. sanguis the major cause of subacute endocarditis in those w/ abnormal heart valves
Lots of Blood in heart
S. mutans causes dental caries
Treat w/ PCN
2) -hemolytic Streptococcus
Produce a clear zone of hemolysis around the colony = complete hemolysis
How do you classify Strep? By Hemolysis, BUT if it says How do you classify Beta hemolytic Strep? Lancefield
Group A, B, C, etc., based on CHO found in the cell wall (C Carbohydrate) (Lancefield groups)
1) Group A -hemolytic Streptococcus
Most likely Pathogenic for humans (among Strep bacteria, or what?)
M-protein: -- JUST like S. PneuMoniae
Is closely associated w/ the virulence of the bacteria
Specific antigenic subtypes based on the cell wall M-protein
Affects the host by inhibiting phagocytosis
Antibody to M-protein enhances host defenses against S. pyogenes
Consists only of S. pyogenes
Streptococcus pyogenes
G+ coccus that occurs in pairs or chains
Frequently part of the endogenous microflora that colonizes the skin & oropharynx
But NOT usually found in plaque
Cause of several acute pyogenic infections in man (Scarlet fever, erysipelas, sore throat [strep throat])
Pyogenic pathogens are associated with acute suppurative inflammation type
Toxins:
Erythrogenic exotoxin (aka pyrogenic exotoxin)
Causes the rash of Scarlet fever
A Strep virulence factor that acts like a superantigen, mediating a variety of cytokine-induced
effects that can result in life threatening disease
Streptokinase
Cleaves plasminogen to plasmin
Hence has the ability to dissolve a preformed blood clot (same with Staphylokinase and Urokinase)
Streptolysin O
A hemolysin that is inactivated by oxidation (oxygen-labile); antigenic
Streptolysin S
a hemolysin that is not inactivated by oxygen (oxygen-stable); not antigenic
Hyaluronidase
The spreading factor produced by certain streptococci
NOT involved in Arthus reaction, Shwartzman phenomenon, or localization of staph infections
Streptokinase, Streptodornase, deoxyribonuclease
Diseases of S. pyogenes : scarlet fever & nephritis
Glomelular nephritis caused by Group A beta hemolytic strep(S. pyogenes)
Toxigenic
Scarlet Fever
Toxic Shock Syndrome
Suppurative

17

Strep throat
Erysipelas acute contagious disease marked by a circumscribed red eruption on the skin +
chills/fever
Impetigo localized, intraepidermal skin infection seen in preschool-aged children
Cellulitis
Results from traumatic inoculation
Diffuse inflammation of soft tissue painful swelling from purulent exudates that spread along the
facial planes and separate the muscle bundles
Not circumscribed
Not confined to one area
Non-Suppurative (Immunologic)
Rheumatic fever (search rheumatic fever more info elsewhere in the file)
PECCS
Polyarthritis, Eythema marginatum, Chorea, Carditis, Subcutaneous nodules
Begins w/ sore throat, then progresses to rapid temperature rise, prostration, joint inflammation
The heart is often affected
Can be a sequela of Scarlet Fever
Can result in pathologic changes in the heart valves
Acute poststreptococcal glomerulonephritis
Symptoms: fluid retention, dark tea-colored urine, BP elevation
Occurs primarily in children
Allergic reaction of glomerular and vascular tissue to beta-hemolytic streptococcal products
The two most important post-streptococcal diseases are:
1) Rheumatic fever
2) Glomerulonephritis
Different Q: Which of the following are related to streptococcal cross-antigenicty
Rheumatic fever & acute glomerulonephritis
Remember they are from Hemolytic sequelae
2) Group B -hemolytic Streptococcus
Consists of S. agalactiae
Leading cause of neonatal pneumonia, meningitis, & sepsis
***Although not Streptococci, BOTH Staph aureus and Listeria are ALSO Beta hemolytic
3) -hemolytic Streptococcus
Produce no hemolysis
Enterococci
Pen G resistant
Major concern with enterococci in the hospital
Cause UTI and Subacute endocarditis
Part of normal fecal flora
Lactic Acid bacteria
General
Use lactic acid fermentation pathway (pyruvate lactic acid)
Aciduric can tolerate acid environment
Acidogenic acid-forming
NOTE: lactic acid is the main cause of enamel decalcification
Lactobacillus
Labeled as cariogenic because of ability to produce acid
Significant secondary invader of dental caries
In coronal caries, causes progression of existing caries
Found in deep dental caries and increases in the saliva during periods of caries activity
Regular, non-sporing, G+ bacteria
Most likely to tolerate the lowest pH (lower than even Streptococci)
Found in vagina, GI tract, mouth
L. acidophilus added to milk products to aid in digestion of milk products
Bacterial enzymes convert milk sugars to digestible products
Streptococcus
Streptococci are the predominant bacteria found in saliva
S. mutans
Smooth surface caries
First stable organism to colonize oral cavity and remains in significant numbers??? LOOK-UP 2002 Q05

18

In the presence of sucrose, produces deposits of a gummy polysaccharide called glucan


Produces Glycosyltransferase from Sucrose
this degrades glucose
End product of glucose metabolism is lactate
Lactic acid forms in large quantities during the degradation of glucose
Capsule has importance virulence factor that enhances oral accumulation
Can be distinguished from other Streptococci by:
Production of adherent Extracellular polysaccharide
Fermentation of mannitol or sorbitol
(The previous two are the two most important factors for initiation of caries)
Production of intracellular polysaccharide
Colonial morphology on mitis-salivarius agar
NOT gram stain (theyre all G+)
Actinomyces root surface caries
MYCOBACTERIA
M. tuberculosis Often resistant to multiple drugs
M. kansasii Pulmonary like TB symptoms
M. scrofulaceum Cervical lymphadenitis in kids
M. avium-intracellulare Causes disseminated disease in AIDS
M. leprae leprosy (M. leprae = Hansens bacillus)
Form mycolic acids, which are unusual acids associated w/ the cell wall
Mycolic acids:
Localized in the inner leaflet of the mycobacterial cell wall
Involved in maintaining rigid cell shape
Contribute to resistance to chemical injury
Protect against hydrophobic Abx (isoniazid inhibits mycolic acid biosynthesis)
NOTE: also present in cell walls of actinomycetes
G+, nonmotile, rod-shaped bacteria
Produces neither exotoxins nor endotoxins
Acid-fast staining
Important in the early diagnosis of active mycobacterial infections
Smear is stained w/ carbol-fuschin stain, decolorized w/ acid alcohol, counterstained w/ methylene blue
Acid-fast organisms appear red against blue background (due to lipids/waxes [including mycolic acids] in the cell wall)
Has highest lipid count in cell wall
Remember Gram + is normally BLUE, but here it is RED
Classic skin test (PPD skin test)
May indicate an infection, but not whether the infection is active
A PPD (purified protein derivative) from M. tuberculosis is injected subcutaneously
Observation of a delayed (Type IV) hypersensitivity reaction indicates a hypersensitivity to tuberculoproteins
M. tuberculosis TB
Obligate aerobe
Cord Factor
Glycolipid found in the cell wall of M. Tb and allows them to grow in serpentine cords
Slow-growing 20-60 days before growth can be visualized
NO exotoxins or endotoxins
Tubercle (Ghon focus)
A small, rounded nodule produced by infection w/ M. tuberculosis
Primary lung lesion in the periphery
Usually in lower lobes
Primary lung lesion of pulmonary TB
Primary TB
Nonimmune host (usually child)
Ghon Focus Ghon complex (from there it can go to below options)
Heal by fibrosis
Immunity and Hypersensitivy Tuberculin positive
Progressive lung disease (HIV) Death (rare)
Severe bacteremia Miliary TB Death
Preallergic lymphatic or hematogenous dissemination
Dormant tubercle bacilli in several organs
Reactivation in adulthood Extrapulmonary TB (See below)
Secondary TB
Partially immune hypersensitized host (usually adult)
From either Reinfection or Reactivation tuberculosis in the lungs
Causes fibrocasseous cavitary lesion in upper lobes

19

Goes to Extrapulmonary TB
CNS (parenchymal TB or meningitis
Vertebral body
Lymphadenitis
Renal
GI
Hypersensitivity (IV) to M. tuberculosis is manifested by necrosis
Tuberculosis is produced by an agent that does NOT produce exotoxin NOR endotoxin
M. tuberculosis has the highest lipid content in the cell wall (compared to E. coli, L. casei, S. aureus)
Granulomas w/ multinucleate giant cells and caseation necrosis characterize lymph node involvement w/ M.
tuberculosis in the lateral neck
M. leprae leprosy (M. leprae = Hansens bacillus)
Also induces delayed-type hypersensitivity in patients
Cannot grow in vitro on any culture medium (same for syphilis)
Likes cool temperatures
Reservoir in US Armadillos
LEthal
Spore-forming bacteria
Spores are specialized resistant cells produced by many microorganisms to enhance the survival potential of the organism
Spores are primitive, usually unicellular cells by which bacteria, fungi, green plants reproduce
Spores grow into new organisms via asexual reproduction (w/o uniting w/ another reproductive cell)
Active spores are thin-walled; dormant spores are thick-walled
Spores contain large amounts of Calcium Dipicolinate = calcium + dipicolinic acid
Calcium dipicolinate is thought to be responsible for the heat resistance of the spore
Spores are a problem in sterilizing instruments & equipment because they are resistant to physical & chemical agents
EX: bacterial endospore heat-resistant spore
More difficult to destroy than HIV, HBV, TB virus
Requires autoclaving at 121C for 20 min at 15 psi
Most important endospore producers: Bacillus & Clostridium genera (perfingens and tetany)
Difference between Clostridium and Bacillus is that Bacillus is aerobic (Nice Pets Must BBBBreath)
Clostridium
C. Botulism
Botulism is caused by C. botulinum
From Bad Bottles of food or honey from Bees
Floppy Baby
C. Perfringens
Gas gangrene is caused by C. perfringens
Gas gangrene is produced by a G+, spore-forming anaerobic bacillus
Perforates a gangrenous leg
C. Difficile
Produces a cytotoxin, an exotoxin that kills enterocytes, causing pseudomembranous colitis
Often secondary to ABX use, especially clindamycin or ampicillin Clostridium Dificile is very difficult to give
patients antibiotics, because they get pseudomembranous colitis
Causes Diarrhea
Tx with Metronidazole
C. tetani
Tetanus is caused by C. tetani
Exotoxin blocks glycine release, which normally is a neurotransmitter inhibitor, so paralysis ensues
Lockjaw
Bacillus Think B for Breathing!!
Anthrax is caused by B. anthracis
The antiphagocytic capsule is composed of D-glutamate, NOT polysaccharide
Contact via malignant pustule (painless ulcer), but can progress to death
Black skin lesions vesicular papules covered by black eschar
Inhalation can cause life-threatening pneumonia
Septicemia = sepsis
Happens when there are too many bacteria in the bloodstream to be removed easily
Symptoms include: fever, weakness, nausea, vomiting, diarrhea, chills
Can lead to septic shock
Associated w/: S. aureus, E. coli, Klebsiella
The most common causative organism in G- sepsis is E. coli

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Bacteremia
Refers to the presence of viable bacteria in circulating blood
Clinical signs/symptoms usually not present
EX: From dental prophy, bugs around teeth enter the blood streambacteremia
Viremia
A viral infection of the bloodstream
Major feature of disseminated infections
The infecting virus is most susceptible to circulating antibodies
Some enzymes:
Streptodornase (DNAase) depolymerizes DNA in exudates or necrotic tissue
Hyaluronidase degrades HA, which is the ground substance of subcutaneous tissue
Produced by Streptococcus, Staphylococcus, Clostridium (Think Perfringens)
The purposes of Hyaluronidase are
Avoid the immune system
Cause disease in host
Disseminate
NOT for Nutrition
The spreading factor produced by some Strep
Some Extracellular Enzymes Involved in Microbial Virulence
Action
Example of Bacteria producing enzymes
Hyaluronidase
Breaks down hyaluronic acid
Strep, Staph, and Clostridium
Coagulase
Converts fibrinogen to fibrin
Staph. Aureus
*coagulase is actually an adhesin, not an
enzyme. It results in a clot formation so
the bug can establish residence
Destroys RBC and other tissue cells
Lecithinase
Clostridium
Breaks down collagen (CT fiber)
Clostridium, Bacteroides, Actinobacillus,
Collagenase
AA, and Bacillus (Think PD bugs)
Phospholipase
Lyses RBC
Staph. Aureus
Fibrinolysin, staphlokinase, streptokinase Dissolve blood clots (Plasminogen
Staph and Strep
Plasmin)
Enzyme

Body site
Oral cavity (saliva, tongue, plaque)
Gastrointestinal tract
Upper respiratory tract (nasal cavity and nasopharynx
Lower respiratory tract
Upper urinary tract (kidney and bladder)
Genitourinary tract (urethra and vaginal tracks)

Normal Microbiota
Streptococcuus, Veillonella, Bacteriodes, Fusobacterium,
Peptostreptococcus, and Actinomyces
Lactobacillus, Streptococcus, Clostridium, Veillonella,
Bacteroides, Fusobacterium, Escherichia, Proteus vulgaris
(natural to intestinal flora), Klebsiella, and Enterobacter
Streptococcus, Staphylococcus, Moraxella, Neisseria,
Haemophilus, Bacteroides, and Fusobacterium
None
None
Streptococcus, Lactobacillus, Bacteroides, and Clostridium

Predominant subgingival bacteria associated w/ gingival health:


Streptococcus mitis & S. sanguis
Actinomyces viscosus & A. naeslundii
Rothia dentocariosus
Staphylococcus epidermidis
Small spirochetes
Periodontal disease:
IgG is found in the highest concentration in serum samples from pts w/ PD disease
Prevotella melaninogenica and Prevotella intermedia (NEW NAMES)
[Bacteroides melaninogenicus = OLD NAME]
Anaerobic bug from gingival scrapings
Forms a black pigmented colonies on hemin-containing culture media hence the name melaninogenicus
Found in higher concentrations in the gingival crevice than on the tongue or in plaque
Collagen degradation is observed in chronic periodontal disease, which occurs by collagenase NZs
from.Porphyromonas species
Juvenile periodontitis: (Now called Aggressive Periodontitis)

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1) Generalized
P. intermedia & E. corrodens predominate
12-25 y.o.
Prevotella Intermedia
(Intermediate, think Juvenile)
First detectable in the oral cavity in adolescence
is a collagenase producing bug associated with PD disease
Rapid, severe perio destruction around most teeth
Associated w/ DM type 1, Down syndrome, neutropenias, Papillon-Lefevre syndrome, leukemias
2) Localized
A. actinomycetemcomitans & Capnocytophaga ochraceus predominate
12-19 y.o.
Severe perio destruction around Mx/Mn 1st molars or Mx/Mn Anteriors
Relative absence of local factors (plaque) to explain it
A.actinomycetemcomitans & C. ochraceus are also associated w/ periodontitis in juvenile diabetes
Adult periodontitis: now called chronic periodontitis
Porphyromonas gingivalis
High levels of antibodies are seen in adult periodontitis against P. gingivalis (these antibodies are IgG)
Known for its collagenase NZs in breaking down collagen in chronic PD
G-, so causes inflammation by endotoxin (lipopolysaccharide)
Prevotella intermedia
Bacteroides forsythus
Campylobacter rectus
Fusobacterium nucleatum
Spirochetes
**When T cells from people with chronic periodontitis react with certain plaque bacterial antigens they produce:
MIF & Lymphotoxin
Lymphotoxin is synonymous with TNF-beta
MIF = (macrophage) migration inhibitory factor
Heres the story:
T cells produce lymphokines as a result of interaction w/ bacterial antigens
In PD disease, these lymphokines include IL-1, TNF, MAF, MIF & CTX
Refractory periodontitis: (SAME AS ADULT)
Porphyromonas gingivalis
Bacteroides forsythus
Campylobacter rectus
Prevotella intermedia
Rapidly progressive periodontitis:
Features:
Most commonly seen in young adults (20-35 y.o.)
Marked inflammation, rapid bone loss, periods of spontaneous remission
Most of these pts have depressed neutrophil chemotaxis
Predominant bugs:
Porphyromonas gingivalis
Eubacterium
Prevotella intermedia
Fusobacterium nucleatum
Campylobacter rectus
Eikenella corrodens
ANUG = acute necrotizing ulcerative gingivitis
Principal bacteria: 1) Prevotella intermedia & 2) Spirochetes
An anaerobic infection of gingival margins causing ulcerations & ultimately destruction of gingiva & underlying bone
IP areas affected first
Spirochetes invade the epithelium & CT
SOME BACTERIAL STDs
CHLAMYDIA:
Any of several common, often asymptomatic, STDs
Most common cause of STD in the U.S.
Caused by C. trachomatis:
An obligate intracellular parasite (NOT a virus)
Along with Rickettsia Only bacteria to be
Cannot survive on the host extracellularly
Also causes ocular trachoma & inclusion conjunctivitis (described elsewhere in file)

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Serotypes
A,B,C
Africa, Blindness, Chronic infection
D-K
Everything else
L1, L2, L3
Lymphogranuloma venerum
2 Forms
Elementary Body (small, dense) Kids get tons of infections in Elementary school
Infectious agent of Chlamydia elementary body
Enters cell via Endocytosis
Initial or Reticulate Body
Replicates in cell by fission
Young women w/ chlamydia may also acquire salpingitis (inflammation of the fallopian tubes)
Most common chlamydial disease in the U.S. is nongonococcal urethritis
There is a large number of asymptomatic carriers, women are often asymptomatic
Frequent co-infection w/ gonorrhea
Most infections of Chlamydia are located on the eyes, genitals, and inside human cells
Tx newborns with Ery eye drops as soon as their born
Cell wall lacks muramic acid (NAM) beta-lactam resistant
What is not caused by Chlamydia trachomatis? DOES NOT CAUSE PRURITIS
Inclusion conjunctivitis
Ocular trachoma
LGV
Lymphadenopathy ??
Pruritus Means ITCHINESS --- Asymptomatic remember
Chlamydia trachomatis. Which is false?
Most women are Symptomatic FALSE, More men are Sx-atic than women, causes keratoconjunctivitis
Does Chlamydia cause keratoconjunctivitis? Hell yes mother sucka
GONORRHEA: (the clap) BIODOME with Rock Climbers get arthritis
STD caused by bacterium Neisseria gonorrhea
Species of Neisseria are differentiated by sugar fermentation
MeninGococci ferment Maltose and Glucose
Gonococci ferment Glucose
Virulence factor is Endotoxin along with capsule & IgA protease
NOT a virulence factor
enterotoxin Duh!!! Enterotoxin would have to be in GI tract
Most common cause of septic arthritis in adults is caused by Neisseria gonnorrhea
Neisseria gonorrhea has affinity for mucous membrane (NOT skin)
Portal entry of the nasopharynx (in one question, could be other membrane-like questions)
One of the most common infectious bacterial diseases
2nd only to chlamydial infections in # of cases
~50% of women w/ gonorrhea have no symptoms
Symptoms appear 210 days after infection
Treated w/ a single injection of ceftriaxone or spectinomycin
REMEMBER EMOP was also tx with CEPH
No longer susceptible to PCN:
Plasmid-mediated beta-lactamase
Chromosomally mediated decrease in affinity of PCN-binding proteins
What makes gonorrhea pathogenic? PCN resistance via Beta-lactamase??
Often occurs together w/ chlamydia and syphilis
Not an intracellular pathogen (Histoplasmosis, Ricketsia, Chlamydia all are!)
Intracellular bugs Salmonella, Neisseria, Bruciella, Mycobacterium, Legionella ,Yersinia
Some Nasty Bugs May Live in Yer cells
Ophthalmia neonatorum
A very serious complication of an infant delivered of mother with gonorrhea
Pt who has minimal resistance to a gonococcal infection most probably has:
Deficiency in cell-mediated immunity
Women
1st symptoms:
Bleeding associated w/ vaginal intercourse
Painful or burning urination

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Yellow or bloody vaginal discharge


More advanced symptoms (may indicate PID):
Cramps and pain
Bleeding between menstrual periods
Vomiting or fever
Men
Have symptoms more often than women
Pus from the penis
Painful, burning urination (may be severe)
SYPHILIS:
STD caused by infection w/ Treponema pallidum (a spirochete)
Produces neither endotoxins nor exotoxins (unlike cholera, gonorrhea, brucellosis, and gas gangrene)
SAME WITH M. TB
Congenital infections in neonates & infants can occur
Late manifestations include Hutchinsons triad abnormal teeth, interstitial keratitis, 8th nerve deafness
Cannot be grown on artificial media (neither can M. leprae) -- armadillos
Also disrupts the vasa vasorum of aorta with consequent dilation of aorta and valve ring, often affects the aortic root and
ascending aorta, Associated with tree bark appearance of the aorta, Responsible also for some Aortic anuerysms
3 stages of Syphillis:
PRIMARY:
Non-painful chancre reddish lesion w/ raised border (appears in 3-6 wks at the site of local contact)
Lips are most common site for chancres to appear in 1 oral syphilis
SECONDARY:
Characterized by:
Cutaneous lesions
Positive VDRL test
Mucous membrane lesions
Presence of Spirochetes in the lesions
NOT Development of a gumma (tertiary)
Highly infectious stage 6 wks after non-treatment of 1 syphilis
Maculopapular rash
Rash appears on palms of hands & soles of feet just like in Rocky Mountain spotted fever
Condyloma latum/lata secondary syphilis
Flat-topped papules (mucous patches) appearing on moist skin/mucosal surfaces
LATENT:
Develops in 30-40% of infected individuals
Mucocutaneous relapses are most common
TERTIARY:
Occurs in 30% of infected persons many years after non-treatment of 2 syphilis
The gumma (focal nodular mass) typifies this stage. Most commonly occurs on the palate and tongue
Neurologic symptoms are also evident at this stage
Gumma:
Infectious granuloma characteristic of tertiary syphilis
Characterized by a firm, irregular central portion, sometimes partially hyalinized, & consisting of coagulative
necrosis in which ghosts of structures may be recognized; a poorly defined middle zone of epithelioid cells,
w/ occasional multinucleated giant cells; and a peripheral zone of fibroblasts and numerous capillaries, w/
infiltrated lymphocytes and plasma cells
Causes irreversible heart failure, dementia, and disability (CNS & cardiac involvement)
Good prognosis for early Dx/Tx
Parenteral Penicillin G is the drug of choice for treating all stages
Dx: Darkfield microscope useful in examining blood for T. pallidum
USMLE RANDOM ADD-ONS
Pigment-producing Bacteria
Staph aureus Yellow (Gold Au)
Pseudomonas Aeruginosa Blue-green
Serratia marcescens Red (Maraschino cherries are red)
IgA Protease Bacteria
IgA normally prevents attachment
Streptococcus pneumoniae
Neisseria meningitidis

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Neisseria gonorrhoeae
Haemophilus influenzae
Culture Requirements
H. influenzae Chocolate agar with Factors V (NAD) and X (hematin)
N. gonorrhoeae Thayer-Martin (VCN) media
B. pertussis Bordet-Gengou (potato) agar
C. diphtheriae Tellurite agar
M. tuberculosis Lowenstein-Jensen agar
Lactose fermenting MacConkeys agar (PINK)
Legionella pneumophila Charcoal yeast extract agar buffered with increased iron and cysteine
Fungi
Sabourauds agar
Stains
Congo Red
Amyloid; apple-green birefringence in polarized light
Giemsas Borrelia, trypanosomes, Chlamydia
PAS (Periodic Acid Schiff)
Stains glycogen, mucopolysaccharides, Dx Whipples disease
Ziehl-Neelson Acid-fast bacteria (miliary TB) or Kinyouns acid-fast stain Think German Military
India ink Cryptococcus neoformans
Obligate Aerobes
Use O2 dependent system to generate ATP
Nice Pets Must Breathe
Nocardia
Psuedomonas aeruginosa Seen in burn wounds, nosocomial pneumonia, and Cystic Fibrosis pneumonia
Mycobacterium tuberculosis
Bacillus The spore forming bug that DOES breath
BOTH Nocardia an Psuedomanas Aeruginosa are both surrounded by mycolic acid
Obligate Anaerobes
Lack catalase and/or superoxide dismutase, and are thus susceptible to oxidative damage
Generally the foul smelling, difficult to culture, and produce gas in tissue (CO2 and H2)
Normal flora in GI tract, pathogenic elsewhere
They DONT know the ABCs of Breathing
Actinomyces -- Sulcus Dwellers
Bacteroides
Clostridium Spore forming that doesnt breath
Food Posioning Bugs
Staph aureus
(Meats, mayonnaise, and custard) THE FASTEST!!
Vibrio parahaemolyticus and Vibrio vulnificus
(Seafood)
Bacillus cereus
(Reheated Rice)
Clostridium perfringens
(Reheated Meat dishes)
Clostridium botulism
(Canned foods)
E. coli
(Undercooked meat)
Salmonella
(Poultry, meat, eggs)
Diarrhea Bugs
E. coli
Ferments lactose
No Fever
Watery/Bloody
Vibrio cholerae
Comma-shaped organism
No Fever
Watery
Salmonella
No lactose fermentation, mobile
Fever
Bloody
Shigella
No lactose ferm, nonmobile,
Fever
Bloody
Campylobacter jejuni
Comma or S shaped organism
Fever
Bloody
Vibrio parahaemolyticus
Transmitted by Seafood
Fever
Yersinia enterocolitica
From Pet feces (puppies)
Fever
Bloody
Cholera vs. Pertussis
Vibrio cholera
Toxin permanently actives Gs, causing rice water diarrhea
Turns the on on
Pertussis
Toxin permanently inactivates Gi, causing whooping cough
Turns the off off
Lactose-fermenting enteric bacteria
Think pink colonies growing on MacConkeys agar
Think MacKonKEEs
Klebsiella
E. coli

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Enterobacter
Zoonotic Bacteria
Think BBugs From Your Pets
Borrelia burgdorferi
Lyme Disease
Tick bites (living on deer and mice)
Brucella
Brucellosis Fever
Dairy products, contact with animals
Francisella tularensis
Tularemia
Tick bites; rabbits, deer
Yersinia pestis
Plaques
Flea bite; rodents; especially prairie dogs
Pasteurella multocida
Cellulitis
Cat, Dog bites
Normal Flora
Skin
S. epidermidis
Nose
S. aureus
Oropharynx
viridans Streptococcoi (S. mutans)
Dental Plaque
S. mutans
Colon
B. fragilis, and S. young
Vagina
Lactobacillus, colonized by E. coli, group B strep, J. Cragun

VIRUSES
Virion: the complete infectious viral particle
A viral nucleic acid (genome) is composed of DNA or RNA (NOT both) encased in a protein coat called a capsid
Capsid or Protein coat
Composed of polypeptide units called capsomers capsomeres make up a capsid
Makes protective vaccines a possibility
The capsid surrounds viral DNA NOT a nucleocapsid
Cellular tropism of viruses is dependent upon cell surface receptors
NOTe: the nucleocapsid = the protein shell + the nucleic acid
Naked or enveloped (an envelope is a lipid bilayer surrounding the capsid)
Almost all are haploid contain a single copy of their geneome (exception: retrovirus family diploid)
Replicate only in living cells obligate intracellular parasites
The only bacteria are Rickettsia and Chlamydia (they stay inside when its Really Cold)
Not sensitive to antibiotics but are sensitive to interferon, which inhibits their replication
Depend on host cells for energy production
Cannot be observed w/ a light microscope they are smaller than cells (duh!)
Pass through filters that retain bacteria
Peplomers:
Protein spikes (glycoproteinaceous projections) found in the envelope of some viruses
The spikes contain hemagglutinin, neuraminidase, OR a fusion protein that causes cell fusion & sometimes hemolysis
EXs: orthomyxoviruses & paramyxoviruses
Viriods:
Consist solely of a single molecule of circular RNA w/out a protein coat or envelope
Cause several plant diseases but are not implicated in any human disease
Prions:
Infectious protein particles composed solely of protein (No RNA or DNA)
Cause certain slow diseases such as Creutzfeldt-Jakob disease in humans & scrapie in sheep
Mad Cow Disease
Associated with spongiform encephalopathy
Harder than spores to get rid of
Host cell: cell w/in which a virus replicates
Once inside the host cell, the viral genome achieves control of the cells metabolic activities
The virus then uses the metabolic capacity of the host cell to reproduce new viruses
Host cell provides the metabolic NZs, and the virus provides the genetic information
Often the replication of these new viruses causes death of the host cell
Viruses must first adsorb to the cell surface of the host cell
This involves a specific interaction between a viral surface component and a specifice cell receptor on the cell membrane
Adsorption does NOT involve insertion of virally specified glycoproteins into the host cell membrane
Cellular tropism by viruses is dependent upon cell surface receptors (they interact with the spikes on the viruses)
For a retrovirus, what precedes integration into the host?
Synthesis of complement DNA from RNA
NOT synthesis of viral protein, capsid from nuclear membrane, or budding

26

Identifying viruses:
Whether or not antisera neutralize the virus
The most generally accepted laboratory method for dx of most common viral infections
Morphology of protein coat
Nature of viral nucleic acid (RNA or DNA)
The ability of ether or chloroform to inactivate the virus
NOT the ability of virus to grow on complex media Just Like M. leprae and Treponema (syphilis)
Viruses cause disease by any of the following:
Lysing many cells of the host
Transforming cells to malignant cells
Making vital target cells nonfunctional
Disrupting the normal defense mechanisms of the host
Viral antigens
Viral antigen recognition by CD4+ T-Helper cell from an APC LOOK UP!!! 2002 Q6
Each of the following is necessary:
Cleavage of viral proteins into small peptides
Internalization of the virus or viral protein by an antigen presenting cell
Transport of viral peptides to a cell surface by MHC II molecule
Binding of the TCR to a MHC II bound viral peptide
Viral replication in host NOT necessary by T-Helper cell
Most viral Ag/s of diagnostic value are proteins
Bacteriophage (aka phage)
Virus that can only replicate w/in specific host bacterial cells
Very delicate bacterial virus which may attach to & destroy bacterial cells under certain conditions
Contains a nucleic acid core (DNA or RNA) & a protein coat
Some have tail-like structures for injecting the nucleic acid into host cell
Phage Conversion
Responsible for conversion of erythrogenic toxin by Strep pyogenes!!!!!
Responsible for production of a pyrogenic toxin
Serological & phage typing of pathogenic bacterial species are used to identify bacterial strains in disease outbreaks
The best evidence for causal relationship between a nasal carrier of staph and a staph infection in a hospital is the
demonstration that both bugs are of the same phage type thats how disease spreads
Bacteriophage follows one of two courses:
1) Lysis: virus multiplies w/in the host cell & destroys it
The virus is said to be a lytic or virulent phage (lyses & kills host)
2) Lysogeny: virus does not replicate but rather (prophase) integrates into the bacterial chromosome
The virus is said to be a temperate or lysogenic phage (replicates to incorporate phage genome into host genome)
Temperate phage persists through many cell divisions w/o killing host
Can spontaneously become lytic
Presence of the integrated virus (called a prophage) renders the cell resistant to infection by similar phages
Lysogenic bacterium
Harbors a temperate bacteriophage
Example is Corynebacterium diphtheriae
Lysogenic conversion
Alteration of a bacterium to a virulent strain by the transfer of a DNA temperate bacteriophage
Presence of temperate phage renders C. diphtheriae pathogenic (harmless w/o the phage)
Toxin released from low iron concentration and is associated with bacteriophage infection
The following may be transmitted by respiratory droplets:
Rubeola, Adenoviruses, Influenza virus, Varicella-zoster virus, Diphtheria, Bordetella Pertussis
Arthropods:
Transmission by arthropod vectors occurs in:
Malaria
Typhus fever NOT Q fever
Dengue
Rocky mountain spotted fever (Tick)
NOT Diphteria
Viral Replication
For RNA viruses:
Transcription occurs in the cytoplasm except for retroviruses and influenza viruses nucleus
Transcription involves an RNA-dependent RNA polymerase except for retrovirus, which has a reverse transcriptase
enzyme (RNA-dependent DNA polymerase)

27

All RNA viruses have Continuous single stranded RNA, except for 4 (BOAR) which are Segmented
Bunyaviruses, Orthomyxoviruses (Flu virus), Arenaviruses, Reoviruses
The influenza virus (Orthomyxo) has 8 segments that can reassort a lot, and is the reason for worldwide
epidemics of the flu
Antigenic shift of influenza is caused by Genetic reassortment (then you get new surface receptors)
Polarity:
Positive polarity = RNA w/ same base sequence as the mRNA
Use RNA genome directly as mRNA
Negative polarity = complimentary sequence to mRNA
Must transcribe its own mRNA using the negative strand as template
The virus must carry its own RNA-dependent RNA polymerase
EXs orthomyxoviruses & paramyxoviruses
Only HIV does not function as a positive or negative sense molecule
It acts as a template for the production of viral DNA
For DNA viruses:
Transcription occurs in the nucleus except for poxviruses in a box
Transcription involves a host-cell DNA dependent polymerase (to synthesize mRNA)
All DNA viruses consist of dsDNA except for the parvoviruses, which have a ssDNA
(Sean has only made a SINGLE PARhole is whole life)
All DNA viruses consist of Linear dsDNA except for Papovavirus and Hepadnavirus, which have circular
Viral Genetics
Recombination
Exhchange of genes between 2 chromosomes by crossing over within regions of significant base sequence homology
Reassortment
When viruses with segmented genomes (influenza virus) exchange segments
High frequency recombination
Cause of worldwide pandemics
Complementation
When 1 of 2 viruses that infect the cell has a mutation that results in a nonfunctional protein
The nonmutated virus complements the mutated one by making a functional protein that serves both viruses
Phenotypic Mixing
Genome of virus A can be coated with the surface proteins of virus B
Type B protein coat determines the infectivity of the phenotypically mixed virus
However, the progeny from this infection has a type A coat and is encoded by its type A genetic material
Late proteins synthesized in viral replication:
Makes sense, because the last thing you do when you go outside is put on
your rain jacket!
Include viral structural proteins
One-step growth curve:
Lysis of bacterial cell release a large number of phages simultaneously
Consequently, the lytic reproduction cycle exhibits a one-step growth curve
Growth curve begins w/ an eclipse period:
Period in which there are no complete infective phage particles
Characterized by absence of demonstrable virus particle
Eclipse period is the time between the injection of the viral DNA & formation of the first complete virus w/in host
Eclipse period is the 1st portion of the latent period, which ends when the 1st assembled virus from the infected cell
appears extracellularly
Cytopathic effect (CPE): (old term was cytopathogenic effect, I think)
Is characteristic of each virus and can be used for detection of that virus, it is a hallmark of viral infection
This change starts w/ alterations of cell morphlogy accompanied by marked derangement of cell function
Culminates in cell lysis
The cytopathic reactions include: necrosis, hypertrophy, giant cell formation, hypoplasia, and metaplasia
These changes provide useful evidence for the Dx of the viruses that induce the CPEs seen
Not all viruses cause CPE
Slow Growth Viruses
In most slow viruses, tissue damage occurs in the brain
Dermatotropic viral diseases:
Measles, Smallpox, and Chickenpox
Latency:
State of dormancy may be latent for extended period of time & become active under certain conditions
Interval of time between an exposure to a carcinogen and emergence of a neoplasm
Existing as a potential, as in TB or HSV infection

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HOW TO REMEMBER DNA vs. RNA


Remember the DNA viruses the rest are RNA
Think HHAPPP: (* = exception)
Herpes
HepaDNA
(* Circular but incomplete DNA)
Adeno
Papova
(* Linear DNA)
Parvo
(* ssDNA)
Pox
(* Circular but supercoiled DNA)
(*NOT Icosahedral)
(*Replicates in Cyto [Own DNA-dep RNA polymerase])
CAREFUL (picorna & paramyxo are RNA, but start w/ P, clown)
PAP = Naked DNA viruses
Girls are naked when they get a PAP smear
HPH = Enveloped DNA (Think Pox in a Box)
Hepatitis viruses
Include DNA & RNA viruses
Detailed info is found in the section on the Liver
RNA VIRUSES
RNA ENVELOPED VIRUSES
Orthomyxovirus
ssRNA Segmented
Influenza A, B, C
Causes influenza, duh!
Composed of unique segmented ssRNA genome, a helical nucleocapsid, and an outer lipoprotein envelope
Envelope is covered w/ two different types of spikes that contain either hemagglutinin or neuraminidase
Causes a fever, runny nose, cough, headache, malaise, muscle ache
Fever distinguishes flu from common cold
Classified as type A, B, or C depending on the nucleocapsid Ag
Passed on via respiratory droplets
Microorganism characteristic of requiring a specific receptor site to infect a host
(incorrect options included anthrax, syphilis, dysentery, gas gangrene)
Influenza A:
Most common flu; causes the most severe disease
Ability to cause epidemics depends on antigenic changes in the hemagglutinin & neuraminidase
Two types of changes:
Antigenic shifts
which are major changes based on reassortment of genome pieces
This leads to new surface molecules (change in envelope)
Antigenic drifts
which are minor changes based on random mutations
Amantadine/Rimantadine
Inhibits replication of influenza A virus by interfering w/ viral attachment & uncoating
Effective in prophylaxis & Tx of influenza A
Main mode of prevention is vaccine consists of killed influenza A & B viruses
Staph aureus is associated with fatalities post influenzal infection
One serious complication associated w/ outbreaks of influenza is the development of Reyes syndrome, which is an
acute pathological condition affecting the CNS
Seems to be associated w/ outbreak of influenza B virus for unknown reasons
This syndrome is principally associated w/ children who have take aspirin to treat the trivial infection
No cause-and-effect relationship between ASA use & Reyes syndrome
Reyes syndrome is characterized by vomiting for one week after infection and either recover in 2 days or go
into coma w/ intracranial pressure
Paramyxovirus
Para of Ms
ssRNA -- Exception
Cause respiratory infections in children
Differ from orthomyxoviruses in that the genomes are not segmented, have a larger diameter & different surface spikes
Cytopathic effect for paramyxoviruses is syncitia formation (they induce cells to form multinucleated giant cells)
Multinucleated giant cells of the foreign-body type originate from fusion or division of mononuclear cells
Parainfluenza viruses
Cause croup (acute laryngotracheobronchitis) & pneumonia in children
Characteristic barking cough

29

Surface spikes include hemagglutinin, neuraminidase, or fusion proteins


Disease resembles common cold in adults
Transmitted by respiratory droplets & direct contact
Has 4 serotypes
Neither an antiviral therapy nor a vaccine is available
RSV
Disease primarily in infants
Most common cause of pneumonia & bronchiolitis in infants
Only one of the paramyxovirus lacking the glycoproteins hemagglutinin & neuraminidase (surface spikes)
RSV surface spikes are fusion proteins
Fusion proteins cause cells to fuse, forming multinucleated giant cells (syncitial, as in RSV)
Multinucleated giant cells of the foreign-body type originate from fusion/division of mononuclear cells
Aerosolized ribavirin is used to treat severely ill, hospitalized infants
Mumps
Transmitted via respiratory droplets
Occurs worldwide peak incidence in the winter
Most noticeable symptom painful swelling of the parotid glands PAROTITIS (unilateral or bilateral)
Typically benign & resolves w/in a week
10 yr old child had case of mumps when she was 5 yrs old
Her specific memory cells are B cells, CD4+ T cells, and CD8+ T cells maybe only CD8+ T cells, maybe
only CD4+ only
Complications:
Orchitis (Lumps in my Man Bumps from Mumps)
Chief complication in males
Painful swelling of the testicles in postpubertal males, which can result in sterility
Deafness in children
Measles (=Rubeola)
Caused by Rubeola virus (RNA paramyxovirus)
Rubeola is characterized by skin rash w/ Kopliks spots in the oral cavity (BAD cops in Mexico)
Kopliks spots small, bluish-white lesions surrounded by a red ring; occur opposite the molars
So, Koplik spot = measles = paramyxovirus
Pt can have:
A cold and red & runny eyes
Blotchy reddish rash behind ears and on the face
3 Cs Cough, Coryza, Conjunctivitis
Transmitted by respiratory droplets
what are features of measles except:
koplik
negri bodie this is the answer seen in Rabies
synctial formation happens in all Paramyxos
Rash
measles can affect lots of organs because:
lots of cells are tropic for its receptor
Arbovirus
Colorado tick fever virus
Transmitted by arthropods (mosquitoes, tics) (Also Flavivirus, Bunyavirus, and Togavirus)
Dengue fever
Yellow Fever
Togavirus
Alphaviruses (Think Alpha Males wearing Red Togas in Germany)
Eastern equine encephalitis
Weatern equine encephalitis
Rubivirus = rubella
Aka German measles - Think kiLLa virus, germans are killers
Caused by rubella virus (RNA virus)
Etiologic agent is a myxovirus
Enveloped virus composed of an icosahedral nucleocapsid and a positive, ssRNA genome
Transmitted by respiratory droplets
The only togavirus not transmitted by an arthropod vector

30

Initial replication occurs in the nasopharynx & local lymph nodes


From there it spread via the blood to the internal organs & skin
Incubation period of 2-3 wks followed by prodromal period of fever & malaise
This is followed by a characteristic maculopapular rash (appears first on face, then extremities), lasts 2-3
days
Prevention involves immunization w/ live, attenuated vaccine
mostly eradicated???
Posterior auricular lymphadenopathy is characteristic
Milder, shorter disease than measles
A teratogen in 1st trimester causes malformation of an embryo or a fetus (TORCH)
NOT Kopliks spots Thats Regular measles (Rubeola not Rubella)
Congenital rubella syndrome:
When a nonimmune women is infected during the 1st trimester, especially the 1st month, significant
congenital malformations can occur in the fetus
The malformations are widespread & involve primarily:
The heart (e.g., patent dutus arteriosus)
The eyes (e.g., cataracts)
The brain (e.g., deafness & mental retardation)
Flavivirus (Flavi = Yellow)
Yellow fever a mosquito-borne flavivirus infection
Has a monkey or human reservoir
Symptoms: fever, black vomit, jaundice (yellow)
a skeeter on a monkeys peeter, bites it, then you and
makes you nice and yeller
Councilman bodies (acidophilic inclusions) may be seen in liver
Dengue fever also a mosquito-borne illness characterized by fever, rash, arthralgia, lymphadenopathy
Hepatitis C
Transmitted via blood and resembles Hep B in course and severity
Common cause of IV drug use hepatitis in US
C = Chronic, Cirrhosis, Carcinoma, Carriers
Bunyavirus and Arenavirus
California encephalitis virus
Hantavirus
Rodent born virus. (Remember the BUNNYs playing with the RODENTS in the ARENA.
Rhabdovirus
Rabies virus
Has the longest incubation period (up to 3 weeks to months)
HBV, HIV????
Use of vaccines for preventing clinical symptoms after introduction of the virus is most likely to be effective against
rabies virus (NOT influenza, poliomyelitis, or herpes zoster)
You can administer vaccine even after inoculation!
Administer Human rabies immunoglobulin (HHIG) immediately in probable cases of rabies
Affects warm-blooded animals reason for human/dog infections
More commonly from bat, raccoon, and skunk bites in areas of vaccinated dogs, otherwise worldwide dogs are most
common
Bullet-shaped virus transmitted by the bite of a rabid animal
Virulence shown is due to??
Envelope (presence of arginine or lysine residue at position 333 in glycoprotein
residue)
Negri bodies
Characteristic cytoplamic inclusions in neurons infected by rabies
are pathogenic for the infection
Negri bodies = Rabies = rhabdovirus (Blacks shoot bullets)
Retrovirus
Enveloped, linear, positive-polarity ssRNA virus
Their genome surrounded by an inner protein envelope & an outer envelope that contains lipid & glycoprotein spikes
The spikes serve to attach the virus to host cells
Retro refers to the enzyme reverse transcriptase (an RNA-dependent DNA polymerase)
RT is packaged w/ the viral RNA genome
RT transcribes RNA to DNA during the process of viral nucleic acid syntheseis
The viral DNA integrates into the host cell genome
Reverse Transcriptase is unique to RNA tumor viruses
The viral genome encodes 3 groups of proteins:
Pol, Env, Gag

31

Three groups:
1) Oncovirus group (HTLV): produces leukemias, lymphomas, breast carcinomas, & sarcomas
HTLV III (HIV) is least likely virus to be spread in dental office
HTLV III is an obsolete term for HIV
2) Lentivirus group: causes AIDS
HIV occurs primarily by sexual contact and by transfer of infected blood
Virus infects/kills helper (CD4) T cells, resulting in the depression of both humoral & cell-mediated immunity
It travels throughout the body, particularly in macrophages
Induces a dinstinctive CPE (cytopathic effect) called giant cell (syncytial) formation
3) Spumavirus group: there are no known pathogens
HIV
Only virus with Diploid
Gp41 = Envelope protein
gp120 glycoprotein spike protrudes from the
envelope
This is the ligand for CD4 molecules
p24 = rectangular nucleocapsid protein (surrounds
RNA)
Black balls = Reverse Transcriptase
Directly affects:
Neurons, Macrophages, CD4 (helper)
lymphocytes
NOT CD8 (suppressor) lymphocytes
Transmitted by:
Semen, Serum, Amniotic fluid, Breast milk
NOT Saliva
Initial manifestation of Early, acute HIV infection
Mononucleosis-like syndrome
HIV is responsible for resurgence of
Mycobacterium Tuberculosis
Opportunistic Infections
Bacterial
Tuberculosis, M. avium-intracellulare comlex
Viral
Herpes simplex, Varicella zoster, CMV, Progressive mulitfocal leukoencephalophaty (PML), Hairy
Leukoplakia
NOT Adenovirus (conjunctivitis)
Fungal
Candidiasis, Cryptococcus (meningitis), Histoplasmosis, Pneumocystic carinii pneumonia (PCP)
Most common cause of pneumonia in HIV pts is from PCP
Protozoan
Toxoplasmosis, Cryptosporidium Enterocolitis
NOT Adenovirus conjunctivitis
Strains
New strains of HIV are the result of errors in transcription (remember, reverse transcriptase!)
In other words, by frequent errors induced by viral reverse transcriptase
NOT the result of genomic recombination or errors in translation
Dx
Made with ELISA High false positive rate, simply a Rule Out test
Positive ELISA are then confirmed with Western blot assay, Rule In test
HIV is NOT oncogenic
AIDS
Info available elsewhere in file
RNA NON-ENVELOPED VIRUSES
NAKED CPR (Calicivirus, Picornavirus, Reovirus)
PicoRNAvirus = picornavirus
Very small, non-enveloped; composed of positive stranded, ssRNA genome
NOT capable of causing cell transformation (naked DNA)
Retrovirus, Herpes, Hepatitis B, and Human Papilloma are capable of causing cell transformation
Subdivision: Enteroviruses

32

Poliovirus
Causes poliomyelitis
RNA is the Only nucleic acid presentduh
Transmitted by the fecal-oral route via consumption of water w/ fecal contaminants
Replicates in the mucosa of the oropharynx and GI tract before entering the blood Think swimming in
stomach POOL
Travels to the spinal cord & infects the anterior horn cells (motor cells) leading to Lower Motor
Neuron destruction
Uncommon in the U.S. due to successful vaccination program initiated in the 1950s
Initial symptoms: headache, vomiting, constipation, and sore throat
Does NOT form a latent infection
Paralysis may follow and is asymmetric & flaccid
Findings include CSF w/ lymphocytic pleocytosis w/ slight elevation of protein
Virus recovered from stool or throat
Two vaccines used currently:
Inactivated polio vaccine -- salk (IPV) vaccine & trivalent oral live virus vaccine (OPV)
Polio vaccine uses acquired artificial immunity (and Active)
Effective Polio Vaccine forms what kind of antibodies??
Membrane bound IgG??? I think
This is why SABIN (OPV or live) is better because it ALSO induces sIgA synthesis
Vaccine for Polio would be most affective if directed at Intestinal Mucosa
These immunize against polio in more than 90% of recipients
Coxsackie A & B virus
Most commonly isolated virus in the feces
Incorrect options: Hep C, influenza, rubella, herpes simplex
NOTE: you can get avian influenza from bird fecesjust food for thought; Coxsackie is right fo sho
Group A:
Causes herpangina and hand-foot-and-mouth disease
Summer illness that produces nodular lesions of the uvula, anterior pillars, and posterior pharynx
Location of the oral lesions distinguishes these two diseases:
1) Herpangina
Throat, palate, or tongue, the oral lesions
A viral disease with oral manifestations
3-yr-old w/ fever, vesicles / ulcers on soft palate, pharynx herpangina
Another: Fever over 100, erythematous oropharyngeal ulcers Herpangina
Herpangina & Coxsackie virus you can make the connection, right
2) Hand-foot-and-mouth disease buccal mucosa and gingiva
Group B:
Causes focal necrosis of skeletal muscle & degeneration in brain & other tissues
Pleurodynia (pain in chest), myocardidits, and juvenile diabetes
Cause mild infections in human
Replicates in mucosa of the pharynx & GI tract before entering the blood
Echovirus
Echoviruses cause aseptic (viral) meningitis, upper respiratory infections, and severe diarrhea in newborns
Subdivision: Rhinoviruses
Rhinovirus
Main cause of the common cold
There are >100 different serotypes hence, development of a vaccine is very difficult
The common cold also caused by coronaviruses in adults
NOT a persistant virus
Hepatitis A
RNA virus
Causes infectious hepatitis
Transmitted via Fecal-oral route Just Like Hep E
Short incubation (3 weeks)
A for Asymptomatic usually
Reovirus
Have a double-shelled icosahedral capsid containing 10 or 11 segments of dsRNA
Replicate in cytoplasm
Produce minor respiratory tract infections & GI disease
Rotavirus

33

Segmented (BOAR) (Bunya, Orthomyxo, Areno, Reo)


ROTA Right Out of The Anus
Causes infantile diarrhea
Most common cause of viral gastroenteritis in children (2 & under)
A self-limiting disease (aka, 24-hour flu or intestinal flu not caused by influenza virus)
Sudden onset of GI pain, vomiting, diarrhea
Dehydration is a major concern, especially in infants (can be fatal)
DNA VIRUSES (HHAPPPY)
DNA ENVELOPED VIRUSES
Herpesvirus
Herpes simplex virus
General
All are large (120200 nm diameter) 2nd only to poxvirus in size
Are medium-sized enveloped viruses w/ an icosahedral nucleocapsid containing linear, dsDNA
Replicate in the nucleus of the host cell and are the only viruses to obtain their envelopes by budding from the
nuclear membrane
Cause acute (primary) infections and secondary recurrent infections
Produces a latent virus (ECHO, measles, smallpox, coxsackie all do NOT)
Latency in the ganglion (SENSORY GANGLION)
Most common site of latent infection to 1 oral infection by HSV I is in the sensory trigeminal ganglion
Characterized by latency and then clinical symptoms that can follow trauma, fever, and nerve damage
For the majority of individuals, the initial infection results in a subclinical disease
HSV 1&2 and varicella-zoster cause vesicular rash
Often associated with recurrent attacks of dermatitis herpetiformis
NOT aphthous stomatitis or erythema multiforme
HSV Type 1 = primary herpetic gingivostomatitis = recurrent herpes labialis
May involve primary infection (gingivostomatitis) or a recurrent infection (cold sores)
First clinical manifestation is usually gingivostomatitis
Affects children under 10 y.o. & 15-25 y.o.
Transmitted by direct contact
Nearly all infections are subclinical (but they range from subclinical to severe systemic infection)
Many children have asymptomatic primary infections
Pt has small ulcers all over mouth, fever, and general malaise
has Primary herpes (gingivostomatitis)
Associated with oral and ocular lesions
Pt may have acute symptoms
Affects the lips, face, skin, & oral mucosa (above the waist)
Recurrent herpes most likely found on the labial mucosa
Fever; irritability; cervical lymphadenopathy; fiery red gingival tissues; small, yellowish vesicles
Most serious potential problem is dehydration due to child not wanting to eat/drink
Often reappears later as the familiar cold sore, usually at the mucocutaneous junction of the lips
Disease is referred to as recurrent herpes labialis
Emotional stress, trauma, and excessive exposure to sunlight have been implicated as factors for the
appearance of the recurrent herpetic lesions on the lip
May be diagnosed by a Tzanck smear for rapid identification when skin lesions are involved
Enveloped that was acquired by budding through the nuclear membrane WOW!!!!!
Supportive tx relieve acute symptoms
Acyclovir 5% ointment (Zovirax) has been successful in reducing the duration and severity of these sores
Acyclovir preferentially inhibits viral DNA polymerase when phosphorylated by viral thymidine
kinase (which is far more effective in phosphorylation than cellular thymidine kinase)
Clinical use: HSV, VZV, EBV, mucocutaneous & genital herpes lesions
Healing takes 2-3 weeks; non-scarring
Recurrent infection in otherwise healthy people
Occurs in people who have been infected with the herpes virus AND do have Abs against the virus
Recurrent infections include: keratoconjunctivitis & encephalitis
Herpes conjunctivitis
Specific chemotherapy is used in tx (NOT used to tx measles, hepatitis, herpangina, or infectious mono)
Recurrent Herpes
Similar to recurrent apthae in that symptoms are similar, but dont include apthous stomatitis
HSV Type 2 = Genital herpes
Spread by sexual contact

34

Affects the mucosa of the genital and anal regions (below the waist)
HSV-2 becomes latent in the lumbar and sacral ganglion
May have serious consequences in pregnant women
The virus may be transmitted to the infant during vaginal delivery
Can cause damage to the infants CNS &/or eyes
What causes cervicitis?
HSV 2, syphilis, HPV, chlamydia
Has been shown to have relationship to carcinoma of the cervix
Candidate virus for the induction of cervical cancer (carcinoma)
Varicella-zoster virus
Member of the herpes virus group
Causes 2 distinct diseases in different age groups
Very contagious and may be spread by direct contact or respiratory droplets
90% of cases of chickenpox occur in children under 9 years of age
Chickenpox (varicella)
Local lesions (vesicles) occur in the skin after dissemination of the virus through the body
Lesions become encrusted & fall off in ~1 week
Shingles (herpes zoster)
Unilateral
Pain along a dermatome (usually 1-3)
Only occurs in an individual having a latent VZV infection
More common in individuals that are Immunocompromised
DOES NOT occur repeatedly in Immunocompromised pts
Reactiviation of latent varicella-zoster that may have remained w/in the body from previous chickenpox
Reaches the sensory ganglia of the spinal or cranial nerves (most frequently the trigeminal nerve) producing an
inflammatory response
Latent In the sensory ganglia
Characterized by painful vesicles on the skin or mucosal surfaces along the distribution of a sensory nerve
Characterized by individual, blister-like lesions affecting specific dermatomes, usually causing burning pain
Tzanck Test
Smear of an opened skin vesicle to detect multinucleated giant cells
Used for HSV-1, HSV-2, and VZV
Epstein-Barr virus
Causes infectious mononucleosis
Infects B lymphocytes & some epithelial cells
Latent EBV is called SBV
Hodkins Lymphoma
Associated w/ development of Burkitts lymphoma & nasopharyngeal carcinoma
Assocated w/ hairy leukoplakia a whitish, nonmalignant lesion on the tongue (seen especially in AIDS pts)
Has splenomegaly and elevated heterophile titer
Heterophile agglutination test greater than 1:128
You get a sploner (splenomegaly) when you acquired the kissing disease (IM) from a GIRL (heterophile)
Associated w/ production of atypical lymphocytes & IgM heterophile antibodies IDd by the hereophile test
(aka: mononucleosis spot test or monospot test)
Ab eventually appears in serum of > 80% of pts w/ IM, hence it is highly diagnostic
Infectious Mononucleosis (IM):
Viral infection causing high temperature, sore throat, & swollen lymph glands, especially in the neck,
necrotizing pharyngititis, and splenomegaly
Typically caused by EBV Which infects B lymphocytes & causes Infectious mononucleosis
Often transmitted by saliva
Occurs most often in 15-17 y.o. (may occur in any age) most often diagnosed between ages 10-35
Hematologically a relative lymphocytic leukocytosis w/ atypical lymphocytes & a positive heterophile
test (increased)
Heterophile agglutination test greater than 1:128
EBV commonly produces a positive heterophile Ab test
After 1 week, many pts develop heterophile Ab/s, which peak at 2-5 wks may persist for several months
to 1 yr
Ab eventually appears in 80% of pts highly diagnostic
Serum of the pt will agglutinate sheep red cells

35

Spontaneous recovery usually occurs in 2-3 weeks


No antiviral therapy necessary for uncomplicated IM; there is no EBV vaccine
NOTE: EBV is associated w/ Burkitts lymphoma, nasopharyngeal carcinoma, & hairy leukoplakia
Cytomegalovirus
Congenital abnormalities
CMV is the major viral cause of birth defects in infants in developed countries
C in TORCH
HHV-6
6th disease = roseola infection
Virus
HSV-1
HSV-2
Varicella zoster
Epstein-Barr
CMV

Usual site of latency


Cranial sensory ganglion (CN V)
Lumbar or sacral sensory
Cranial/thoracic sensory ganglia
B lymphocytes
Uncertain

Recurrent infection
Herpes labialis, encephalitis, keratitis
Herpes genitalis
Zoster
None
None

Route of transmission
Via respiratory secretions and saliva
Sexual contact, perinatal infection
Via respiratory secretions
Via respiratory secretions and saliva
Intrauterine infection, transfusions,
sexual contact, via secretions (eg
saliva and urine)

HepaDNAvirus
Hepatitis B
Blood borne virus
Parenteral, sexual, maternal-fetal
Long incubation period (3 months)
Reverse transcription occurs?????
Poxviruses
DNA viruses the largest & most complex animal viruses
Brick shaped particles containing enveloped linear dsDNA genome
Multiply in the cytoplasm of host cell & are usually associated w/ skin rashes
Smallpox
Caused by variola virus
An acute, highly infectious, often fatal disease
Characterized by high fever, prostration, & a vesicular, pustular rash
Man is the only reservoir for the virus
Smallpox has been eradicated by global use of the vaccine which contains live, attenuated vaccinia virus
Protection against smallpox afforded by prior injection with cowpox
This represents antigenic cross reactivity
Vaccinia virus
A related poxvirus used to eradicate smallpox
Vaccinia used for Vaccine of smallpox like one of first
vaccinated viruses
Molluscum contagiosum
Causes umbilicated wart-like skin lesions
DNA NON-ENVELOPED VIRUSES
Papovavirus
Pa = Papilloma virus
Po = Polyoma virus
Va = Vacuolating virus
HPV (Human Papilloma Virus)
Most common cause of VIRAL STD
Cause papillomas (warts) on skin & mucus MBs
A DNA oncogenic virus (NOT RNA oncogenic, thats retrovirus)
Associated with the induction of cervical carcinoma (16,18)
Virus most commonly associated with oncogenesis
Condyloma Acuminatum
NOT passed on via respiratory droplets
Adenovirus
Naked, medium sized, icosahedral nucleocapsid & linear dsDNA genome
Have hemagglutinin spikes
Frequently cause subclinical infections
Cause upper & lower respiratory infections cold think of A-DEN full of coughing sneezing children w/ pinkeye

36

Transmitted via aerosol droplets, fecal-oral route, or direct inoculation


Can be transmitted via ocular secretions
Diseases associated w/ adenoviruses:
Acute respiratory infections
Acute contagious conjunctivitis (pink eye)
NOT associated with HIV opportunistic infection
Pharyngoconjunctival fever characterized by fever, pharyngitis, & conjunctivitis
Parvovirus (PAR V Fifths disease)
Erythema infectiosum (slapped-cheeks syndrome, 5th disease)
Transient aplastic anemia crisis
Fetal infections
Virus
RNA viruses
Influenza A
Parainfluenza
Respiratory synctial
Rubella
Measles
Mumps
Rhinovirus
Coronavirus
Coxsackie
DNA viruses
Herpes simplex type1
Epstein barr
Varicella
Adenovirus
Portal of Entry
Respiratory tract

Gastrointestinal
Skin
Genital

Blood

Disease

Vaccine available

Treatment

Influenza
Croup
Bronchiolitis and pneumonia in
infants
Rubella
Measles
Parotitis, meningitis
Common cold
Common cold
Herpangina, hand foot and mouth

Yes
No
No

Amantadine/Rimantadine
None
Ribaviron

Yes
Yes
Yes
No
No
No

None
None
None
None
None
None

Gingivostomatitis
Infection mononucleuosis
Chickenpox, shingles
Pharyngitis, pneumonia

No
No
No
No

Acyclovir in immunodeficient pt
None
None
None

Virus
Adenovirus
Cytomegalovirus
Epstein barr
HSV type 1 (more direct
contact)
Influenza
Measles viremia
Mumps viremia
Respiratory synctial
Rhinovirus
Rubella virus viremia
Varicella zoster
Hep A
Polio
Rota
Rabies bite in the skin
HPV
HPV
Hep B
HIV
HSV type II
Hep B
Hep C
HIV
Cytomegalovirus

Disease
Pneumonia
Mononucleosis syndrome most common
pneumonia in bone marrow transplant pt
Infection mononucleosis
Herpes labialis
Influenza
Measles
Mumps
Bronchiolitis and pneumonia in infants
Common cold
Rubella
Chickenpox
Hep A
Poliomyelitis
Diarrhea
Rabies
Papillomas (warts)
Papillomas (warts)
Hep B
AIDS
Herpes genitalis and neonatal herpes
Hep B
Hep C
AIDS
Mononucleosis syndrome or pneumonia

USMLE ADD-ONS
Naked/Enveloped Viruses

37

Naked
Most dsDNA (Not Pox) and (+) strand ssRNA viruses are infectious positively infectious
Naked nucleic acids of (-) strand ssRNA and dsRNA are not infectious
Enveloped
Usually acquire their envelope from plasma membrane when they exit from the cell
Except Herpes, which gets it from the nuclear membrane
Virus Ploidy
All are Haploid! (one copy of DNA or RNA)
Except for Retroviruses, which have 2 identical ssRNA molecules (diploid)
Nosocomial Infections
Newborn Nursery
CMV, RSV
Urinary Catheter
**E. Coli, Proteus
Respiratory Equipment
P. aeruginosa
Work in renal dialysis
HBV
Hyperalimentation
Candida
Water aerosols
Legionella
Wound Infection
**S. aureus
**2 most common nosocomials
If all else Fails
Pus, emphysema, abscess
S. aureus
Pediatric infection
H. influenzae
Pneumonia in CF, burn infection P. aeruginosa
Branching rods in oral infection
Actinomyces israelii
Traumatic open wound
C. perfringens
Surgical wound
S. aureus
Dog or cat bite
Pasteurella multocida
Sepsis/meningitis in newborn
Group B strep

FUNGI
Fungi:
Eukaryotic, all are G+; contain both DNA & RNA
Grow in Sabourauds agar medium
Cell walls contain chitin, glucans, & protein
Cell MB contain sterols (ergosterol)
Two types:
Yeasts grow as single cell that reproduces by asexually budding
Molds grow as long filaments (hyphae) and form a mat or mass which is referred to as mycelium
Hyphae can be septate or nonseptate
All fungi (except for zygomycetes) are septate
Dimorphism is characteristic of some fungi
Dimorphism = the fungus forms different structures at different temperatures
Can exist as either filamentous (mold) or yeast (spore) forms Yeast in tissue / Mold outside tissue
Cold = Mold/Mycelial (soil) Heat = Yeast (tissues)
Characterized by the capability to produce both a yeast & a mycelial phase
Exist as molds in the saprophytic, free-living state at ambient temperatures
Exist as yeasts in host tissue at body temperature
These fungi include the major pathogens Blastomyces, Histoplasma, Coccidioides, and Candida
Reproduction
Asexual:
Most fungal spores are asexual
Asexual spores (conidia) form through mitosis
Differentiating conidia help to ID various fungi
Sexual:
They mate & form sexual spores
Mechanism for disease is through type IV hypersensitivity reaction
Fungal spores:
Morphological characteristics (e.g., shape, color, & arrangement) of conidia help to ID fungi
Conidium is an asexually formed fungal spore
Fungal spores cause allergies in some people

38

Most fungal spores are completely killed when heated at 80 for 30 min (unlike bacterial spores)
Examples of asexual spores (conidia)
Arthrospores: formed by fragmentation of the ends of hyphae; are the mode of transmission of Coccidioides immitis
Think ARTHRitis creakity spores formed by hyphae fragmentation
Chlamydospores: thick walled & quite resistant; characteristic of C. albicans
A CLAM has thick outer walls and is resistant to things the C in clam for the C in C.albicans
Blastospores: formed by budding, as in yeasts; multiple buds are called pseudohyphae (also characteristic of C. albicans)
Sporangiospores: formed w/in a sac on a stalk by molds such as Rhizopus and Mucor
A spore in a spore sac
Example of sexual spores:
Zygospores: single large spores w/ thick walls
Zygote is a sexual thing
Ascospores: formed in sacs which are called an ascus
Ass is sexually related too!
Basidiospores: formed externally on the tip of a pedestal called a basidium
Think Buzum sexy. Also, our culture puts boobs on a pedestal!
Many fungi respond to infection by forming granulomas (as seen in coccidioidomycosis, histoplasmosis, blastomycosis)
Nosocomial infections:
Infections acquired during hospitalization, unrelated to the pts primary condition
Often caused by: C. albicans, Apsergillus, E. coli, Hepatitis viruses, Herpes zoster virus, P. aeruginosa, Strep, & Staph
Ability to become resistant to ABX is most important characteristic of enterobacteria in hospitals
CUTANEOUS MYCOSES
DERMATOPHYTES:
EXs: Trichophyton, Epidermophyton, and Microsporum
Cause superficial skin infections (Trichophyton) think Tineafrom Dr. Christensens Path course
Infect only the skin, nails, and hairs
Athletes Foot caused by Trichophyton
Trichophyton also is involved in ALL types of Tineas
Tx Griseofulvin (You have to be greasy to have these diseases)ringworm(tinea corpora)
Responsible for causing dermatophytosis
Common among people who live in communities w/ low standard of sanitation
Source from soil & dust
Characterized microscopically by intracytoplasmic microorganisms of Reticuloendothelial system
Epidemiology of Dermatomycoses
Disease
Causative agent
Examples of sources
Tinea capitis (ringworm of scalp)
Microsporum, Trichophyton
Lesions, combs, toilet articles, headrests
Tinea corporis (ringworm of body)
Epidermophyton, Microsporum,
Lesions, floors, shower stals, clothing
Trichophyton
Tinea pedis (ringworm of feet (athletes foot)
Epidermophyton, Trichophyton
Lesions, floors, shoes & socks, shower stalls
Tinea unguium (ringworm of nails) think
Trichophyton
Lesions
Under nails
Tinea cruris (ringworm of groin [jock itch])
Trichophyton, Epidermophyton
Lesions, athletic supports
Think crotch
9 yr old boy has tinea capitis
For tx, he should be given an anti-mycotic agent
SUBCUTANEOUS MYCOSES
SPOROTRICHOSIS:
Caused by Sporothrix schenckii
Classically associated w/ rose thorns
Cigar-shaped budding yeast visible in pus
MYCETOMA:
Lesions usually occur on feet or hands
Caused by infection w/ several fungi
SYSTEMIC MYCOSES Can mimic TB granuloma formation ALL 3 can come from Soil
HISTOPLASMOSIS:
Caused by Histoplasma capsulatum a dimorphic fungus
Found in bird & bat droppings Dont get clowned C. neoformans too!
Exists 1) as a mold in soil & 2) as a yeast in tissue
Endemic in Central and Eastern U.S., especially in the Ohio & Mississippi River valleys
Principal source of endemic form is from soil and dust
Infection results from inhaling contaminated air
Infection is usually asymptomatic, but may produce a benign, mild pulmonary illness (primary form of disease)

39

Infection with Histoplasma capsulatum in normal, healthy individuals results in a self-limiting, benign disease
systemic disease, most commonly of the lungs, characterized by production of tuberculate chlamydospores in
culture
Frequently causes pulmonary nodules
An oral lesion that may appear as an ulcer, nodule, or vegetative process, and is often mistaken for SCC
Uncommon disseminated form of the infection is quite serious
Intracellular Parasite of Macrophages --- Have in common with Viruses
In infected tissues, yeast cells of Histoplasma capsulatum are found w/in macrophages so intracellular
Characterized microscopically by intracytoplasmic microorganisms in the RE (reticulo-endothelial or macrophage)
system (incorrect options were: intranuclear inclusion bodies, flask-shaped ulcers of the ileum, focal liver abscesses)
Often mistaken for TB in the lungs because it can cause calcifications in the lungs also
Resembles TB, causing a granulomatous, tuberculosis-like infection both clinically and pathologically
Produces tuberculate chlamydospores in culture
Histoplasmosis and blastomycosis are rarely acquired from another individual (along with Sporotrichosis)
COCCIDIOIDOMYCOSIS:
Caused by the inhalation of dust aerosols containing Coccidioides immitis arthrospores (highly infectious)
Fungus that grows as a saprophyte (MOLD) in the soil
Endemic in hot, dry regions of the Southwest U.S. & northern Mexico
Referred to as Valley Fever or San Joaquin fever
Primary infection or lesion is in the lung
It is by and large an inapparent and self limiting infection in endemic areas
Amphotericin B is the drug of choice in treatment of fungal infection
Fluconazole, Amphotericin & itraconazole are also used to treat various fungal infections by inhibiting ergosterol
synthesis
BLASTOMYCOSIS: (aka Gilchrists disease or North American blastomycosis)
Caused by Blastomyces dermatidis a dimorphic fungus that exists 1) as a mold in soil & 2) as a yeast in tissue
Causes necrotic skin and bone lesions Blasted through my Skin to my Bone
Think B for Big, Broad-Based Budding
Considered a superficial fungus??? Make sure, sounds more like it should be trychophyton
Grows in moist soil rich in organic material (poop), forming hyphae w/ small, pear shaped conidia
Inhalation of the conidia cause human infection
Rarely, if ever acquire from another individual (Along with Histoplamosis, and Sporotrichosis)
OPPORTUNISTIC MYCOSES
CANDIDA:
C. albicans most important species of Candida
Characterized by white patches on buccal mucosa, consisting of pseudomycelia & minimal erosion of MBs
Psuedo cause not in mold
Causes thrush, vaginitis, and other diseases
An oval yeast w/ a single bud Not dimorphic
NOT an airborne fungus that causes opportunistic infections in debilitated individuals
Rhizopus, Aspergillus, and Cryptococcus ARE
Overgrowth of C. albicans in those w/ impaired host defenses produces candidiasis
Chlamydospores thick walled & quite resistant; characteristic of C. albicans
Genus of fungi most frequently recovered from healthy mucous membranes
Prolonged ABX (antibacterials) tx can predispose to infection from indigenous oral microorganism Candida albicans
Pts exposed to chemotherapy for leukemia are particularly prone to widespread oral infection caused by c. albicans
Pt comes in w/ xerostomia and sore mouth covered red and white patches it is candida
Next question: the cause of the infection is the xerostomia (not vitamin deficiency)
Pts with deficiency in T lymphocytes are predisposed
Pt exposed to long-term corticosteroids are predisposed to candidiasis
Candidiasis:
An infection of the oral cavity or vagina, usually by C. albicans
Common in patients 1) w/ a T-cell deficiency, 2) receiving chemotherapy & 3) who are immunosuppressed
C. albicans causes an inflammatory, pruritic infection characterized by a thick, white discharge
This yeast-like fungi is a normal inhabitant of the oral cavity & vaginal tract
Normally held in check by indigenous bacteria
Chemotherapy for leukemia predisposes for oral infections by C. albicans
Which type is the deep fungal infection type? Who the f*ck knows
Oral Candidiasis:
Acute
Pseudomembraneous (thrush) creamy, loose patches of desquamative epithelium containing numerous matted
mycelia over an erythematous mucosa that is easily removed; common in patients with more severe predisposing factors

40

Pseudomembrane (false MB) = desquamative and necrotic epithelial cells and matted and tangled mycelia
Tx = Ketoconazole or Fluconazole (not Nystatin)
Atrophic (erythematous) the mucosa is thinned, smooth, and bright red with symptoms of burning and increased
sensitivity commonly found on the palate under a denture but also on the tongue and other mucosal surfaces
Areas of superficial erosion and petechiae necrosis
Tongue: beefy red appearance due to loss of filiform & fungiform papillae, generalized thinning of the epithelium
and excessive inflammation of the CT
Chronic mucocutaneous candidiasis
Chronic Hyperplastic (candidal leukoplakia) white plaques or papules against an erythematous background
containing hyphae in the parakeratin layer of the thickened epithelium.
Firmly adherent white plaque to the oral cavity
Differential diagnosis is required: termed candidal leukoplakia resembles speckeled leukoplakia or speckled
erythroplasia conditions which are epithelial dysplasia
MUST BIOPSY!
Usually unilateral, dont rub off like pseudomembranous candidiasis
Oral Lesions
Angular Cheilitis (perleche)
Symptomatic bilateral fissures of the corners of the mouth that are common in patients with C. albicans infection
Intensified with mouth overclosure
Tx = antifungal medication (nystatin ointment)
Median Rhomboid Glossitis
An asymptomatic, elongated, erythematous patch of atrophic mucosa of the middorsal surface of the tongue due to a
chronic C. albicans infection
Gradually enlarges
May have on the midline of palate opposite the tongue lesion
Chronic Mucocutaneous Candidiasis
Persistent and refractory candidiasis occuring on mucous MBs, skin & nails of the affected patients
Watch out for w/ diabetic pts
Tx = topical clotrimazole troches
CRYPTOCOCCUS:
Cryptococcus neoformans causes Cryptococcosis
Latex agglutination test detects polysaccharide capsular antigen
Antiphagocytic polysaccharide capsules (along with strep pneumoniae think opsonins)
An oval, budding yeast not dimorphic
Narrow-based, unequal budding
Found in soil, pigeon droppings
More common than other fungal infections
Severe only in people w/ underlying immune system disorders such as AIDS
May spread to the meninges, where the resulting disease is cryptococcal meningitis
***Think Cryptococcus for immunocompromised pts and meningeal signs
Culture
Sabourauds agar, Stain with India ink Cryptic message with India ink
ASPERGILLUS:
Species exist only as molds and are not dimorphic
Septate hyphae that branch at V-shaped 45 degree angle
Branching Septate Hyphae
Aspergillus fumigatus causes an aspergilloma (fungus ball) in the lungs & Aspergillosis
Aspergilliosis is most commonly caused by A. fumigatus, A. niger, or A. flavus
Aspergilliosis takes one of three forms:
Mycetoma (grows in the lung cavities)
Fungus Ball
Invasive aspergillosis (begins in lungs, spreads to other organs)
Aspergillus can perforate the palate
Allergic bronchopulmonary aspergillosis (allergy to spores that produces asthmatic attacks)
One clinical manifestation is eosinophila
Cause pulmonary infections in AIDS pts or have undergone organ transplantation
Aflatoxin: (A. Flavus)
Aspergillus produces Aflatoxin B
Coumarin derivatives produced by Aspergillus flavus
Causes liver damage & tumors in animals
Ingestion of food contaminated with Aspergillus is associated with carcinoma of the liver
Think As for LIVER problems
Toxin binds to DNA & prevents transcription of genetic information

41

Ingested w/ spoiled grains and peanuts and are metabolized by the liver to epoxide (a potent carcinogen)
ZYGOMYCOSIS (MUCORMYCOSIS): (aka phycomycosis)
Relatively rare fungal infection caused by saprophytic mold (e.g. Mucor, Rhisopuz, and Absidia)
These fungi are not dimorphic Mold
Are morphologically characterized by the lack of septa in their hypha the ONLY non-septate fungus
Characterized by Hyphae growing in and around vessels
Pts w/ diabetic ketoacidosis, burns, or leukemias are particularly susceptible to this fungal infection
Pts w/ uncontrolled DM presents with nasal obstruction, proptosis, & perforation of the palate
Results in:
Fungi proliferate in the walls of blood vessels and cause infarction of distal tissue
Hemorrhagic infarction and necrosis following fungal infection
Massive necrotizing lesions of palate w/ poorly controlled DM
Black, dead tissue in the nasal cavity and blocks the blood supply to the brain
Leads to neurologic symptoms such as headaches and blindness
NOTE: other infections associated w/ AIDS pts: candidiasis, hairy leukoplakia, and cryptosporidium enterocolitis
PNEUMOCYSTIS CARINII
Causes Pneumonia (PCP)
Originally classified as protozoan, but its a yeast
Inhaled
Most infections are asymptomatic, but due to AIDS, etc.
Most common cause of pneumonia in HIV pts is PCP
Tx when CD4 drop below 200 cells/mL in HIV pts
What do deep fungal infections look like microscopically??? yeast in tissue & mold outside tissue. granulomatous
PARASITES/PROTOZOA
Protozoa
Diverse group of eukaryotic, typically unicellular, nonphotosynthetic microorganisms generally lacking a rigid cell wall
Infestation = presence of parasites on the body (e.g., ticks, mites, lice) or in the organs (e.g., nematodes or worms)
Balantidium coli: non-pathogenic, nonflagellated protozoan
Selective Cytotoxicity
A drug action which affects the parasite more strongly than host cell
INTESTINAL/MUCOCUTANEOUS PROTOZOA
Cyst = environmental form of a protozoa
Once inside the intestine, the organisms excyst & colonize
Trophozoite = motile, feeding, colonizing form found w/in intestine
GIARDIASIS:
Infection of the small intestine caused by a flagellated protozoan Giardia lamblia
One of the most common parasite infections of the small intestine
More common in male homosexuals & people who have traveled to developing countries
See in campers & hikers who present w/ diarrhea, bloating, flatulence, etc.
AMEBIASIS:
Infection of the large intestine caused by a flagellated protozoan Entamoeba histolytica
Acute intestinal amebiasis presents w/ dysentery (bloody, mucous-containing diarrhea)
Can also produce liver abscess
TRICHOMONIASIS:
STD of the vagina or urethra (men) caused by flagellated protozoan Trichomonas vaginalis
Transmitted sexually
Causes vaginitis in women; can lead to urethritis or prostatitis in men
Symptoms are more common in women
One of the most common infections worldwide
Exists only as a trophozoite
Entamoeba and Trichomonas species are found in the oral cavity (appear to be nonpathogenic in the O.C.)
NOT found in O.C.: giardia, plasmodium, leishmania, balantidium
CRYPTOSPORIDOSIS:
Caused by Cryptosporidium parvum
Main symptom is watery diarrhea accompanied sometimes by abnormal cramps, nausea, & vomiting
Most severe in immunocompromised pts may be fatal in these pts
BLOOD/TISSUE PROTOZOA
MALARIA:
An infection of RBC by parasite Plasmodium vivax, ovale, falciparum & malariae
Drugs taken for prevention are not 100% effective
Symptoms can begin a month after the infecting female mosquito bite, Anopheles

42

Early symptoms are nonspecific & often mistaken for influenza


Rapid Dx & early Tx are important, particularly for falciparum malaria, which is fatal in up to 20% of infected people
P. vivax & P. falciparum are more common causes of malaria than P. ovale & P. malariae
Often first symptoms are a mild fever, headache, muscle aches, and chills (flu-like symptoms)
Enlarged spleen characteristic of malaria due to congestin of sinusoids w/ RBCs
Total WBC count is usually normal but, hyperplasia of the lymphocytes & macrophages
Antimalarial drugs chloroquine, mefloquine, & pirmaquien
BABESIOSIS:
Caused by Babesia microti
Common in the Northeast U.S. Think about babes at the hamptons
LEISHMANIA:
Transmitted by the sandfly Dr. Fleishman riding on a Sand-Fly
TRYPANOSOMIASIS:
Cause by the trypanosoma species
1) African sleeping sickness = African trypanosomiasis
2) Chagas disease = American trypanosomiasis
TOXOPLASMOSIS:
Caused by Toxoplasma gondii
Teratogenic (Remember ToRCHeS)
Toxoplasma
Rubella
CMV
HSV, HIV
Syphilis
Sexual reproduction by this parasite occurs only in the cells lining the intestine of cats
Eggs are shed in the cats stool
People become infected by eating raw/undercooked meat containing the dormant form (cysts) of the parasite
May resemble a mild cold or infectious mononucleosis in adults
Treated w/ Sulfadiazine (an ABX)
Intracellular Parasite
Nematodes:
Roundworms w/ a cylindrical body & a complete digestive tract
Two categories based on primary location of body:
Intestinal nematodes: enterobius (pinworm), trichuris (whipworm), ascaris (giant roundworm) and Necator and
Ancylostoma (the two hookworms)
Tissue nematodes: Wuchereria, Onchocerca, and Lao are called filarial worms
Bx of tongue mass small, coiled, encysted larvae of nematode worms: Trichinae
Infections caused by certain nematodes cause marked eosinophilia (abnormally large numbers of eosiopnils in the blood)
Eosinophils do not ingest the parasites they attach to the surface of parasites via IgE & secrete cytotoxic enzymes
contained w/in their eosinophilic granules
Cestodes
Tapeworms
Trematodes
Flukes
ANTIMICROBIAL AGENTS
ANTIBIOTICS:
Broad-spectrum antibiotics: Tetracycline, Chlormycetin, & Cephalosporins
(NOT isoniazid, PCN, Dihydrostreptomy, or streptomycin)
Prolonged use of streptomycin can result in damage to auditory nerve
Steptomycin is an ABX which inhibits the process of transcription in prokaryotes
The indiscriminate use of broad-spectrum ABX is contraindicated because
They interfere with indigenous bacteria (NOT produce dependency rxns Susan Kinder Haake would be pissed)
Possible toxic effects of the antibiotics
Allergic reactions induced in patients
Development of drug resistance by an infectious agent
Secondary effects experienced due to creation of an imbalance in the normal body flora
Alteration of the immune response
Mechanisms of Action:
Cell wall inhibitors:
***Inhibit terminal step in peptidoglycan formation NOT cell membrane

43

***The first 4 in this list are beta-lactams


Penicillins
Cephalosporins
Carbapenems
Monobactams
Vancomycin
Bacitracin
Cycloserine
Protein synthesis inhibitors:
TAs are usually 30 yrs old
30S Tetracyclines
30S Aminoglycosides
30s Streptomycin
CLEC
50S Chloramphenicol Protein synthesis inhibition by inhibiting translocation by binding to 50S subunit
50S Lincomycin
50S Erythromycin ABX of choice for a dental pt w/ a heart valve abnormality AND a PCN allergy
If you have a bact sensitive to penicillin but pt is allergic what would u use instead
Cephalosporin NO: cross-allergenic
Amoxicillin NO, duh!
erythromycin
clindamycin would have been a better choice???
tetracycline
50S Clindamycin
Antimetabolites:
Sulfonamides (sulfa drugs)
Trimethoprim
Cell MB inhibitors:
In G- bacteria: Polymyxin & Colistin
In fungi: Amphotericin B, Nystatin, Fluconazole, Clotrimazole, Ketoconazole
Nucleic acid synthesis inhibitors:
Fluoroquinolone (e.g., ciprofloxacin)
Represents a DNA gyrase inhibitor with a broad spectrum of activity
Affects Replication, NOT a metabolic pathway
Quinolones
Blocks DNA topisomerase (which normally helps in the breakage and linkages of phosphodiester linkages) -Bacteriocidal
Rifampin
Binds to DNA-dependent RNA polymerase and inhibits RNA synthesis
PENICILLINS
The ABX of choice for prophylactic dental work
Cephalosporins are related both structurally & by mode of action
Penicillin will work only on growing cells that contain peptidoglycan in their cell wall
It inhibits the terminal step in the peptidoglycan synthesis (cell wall synthesis)
Usually non-toxic to humans because humans lack peptidoglycans
Greatest bacteriocial activity against growing G+ bacteria (thick peptiodoglycan layer)
Dont use with Erythromycin Because Ery stops growth and PCN only works if bacteria is growing
Penicillinase is produced by certain bacteria (e.g., some strains of Staphlococcus) that degrade the -lactam ring structure
Certain penicillins have a structural modification that provides resistance to penicillinase
This may also narrow the spectrum of action, limiting the primary use of such Abx to tx of Staph infections
Penicillinase-resistant penicillins:
Used during Log Phase
Methicillin, cloxacillin, dicloxacillin, nafcillin, oxacillin, amoxicillin/clavulonate potassium (Augmentin),
ampicillin/sulbactim (Unasyn), piperacillin/tazobactam (zosyn), ticarcillin/clavulonate potassium (Timentin)
Penicillin G:
Used for growing Gram + bacteria
Penicillin V:
Methicillin:
Prescribed primarily in the treatment of severe penicillinase-producing staphylococcal infections
Given IV
Not frequently used due to:

44

Incidence of interstitial nephritis


Availabitily of equally efficacious alternatives (nafcillin & oxacillin)
Methicillin-resistant Staph aureus (MRSA)
Group of resistant Staph bacteria that can be life threatening
Resistant to all penicillinase-resistant penicillins & cephalosporins
Usually resistant to aminoglycosides, tetracyclines, erythromycins, & clindamycin
In past vancomycin has been used against MRSA but there are some organisms resistant to it (VRE)
Broad-spectrum penicillins:
Ampicillin:
Amoxicillin
Amoxicillin Rxn:
Pt becomes hypotensive, itchy, and having difficult breathing
Amox reacts with IgE and activates cytotoxic T cells that release lymphokines
BOTH TYPE I and IV activate cytoxic cells????
CEPHALOSPORINS
Cefactor (Ceclor) is a broad-spectrum antibiotic
Bactericidal antibiotics
Act like penicillins affect the bacterial cell wall during cell division, preventing closure
Bacteria eventually lyse & die
Act against a wide range of G+ & GThere are four generations of cephalosporins
Progression from the first through the fourth is associated w/ a broadening of action against more G- bacteria and a
decreased activity against G+
1st cephalexin, cephradine, cefadroxil, cefazolin
2nd cefaclor, cefuroxime, cefoxitin
3rd cefixime, cefoperazone
4th cefepime
Approx. 10% of individuals w/ a penicillin allergy have cross allergenicity to cephalosporins
MONOBACTAMS:
CARBAPENEMS:
VANCOMYCIN:
CLINDAMYCIN:
Binds to 50S ribosomal subunit, blocking bacterial protein synthesis
Restricted use due to severe diarrhea, GI upset, & pseudomembranous colitis
Pseudomembranous colitis is a major adverse effect of prolonged therapy with clindamycin
Side effects are caused by overgrowth of Clostridium difficile (95% of Pseudo cases caused by C. difficile)
Bacteriostatic & active against most G+ & many anaerobic organisms, including Bacteroides fragilis (anaerobic G-)
Is alternate antibiotic used in dentistry when:
Amoxicillin cannot be used for bacterial endocarditis prophylaxis
Tx of common oral-facial infections caused by aerobic G+ cocci & susceptible anaerobes
For prophylaxis for dental patients w/ total joint replacement
Can be given to patients allergic to penicillins since there is no cross allergencitiy
AMINOGLYCOSIDES:
TETRACYCLINES:
Tetracycline
No tetracycline for pregnant women or children under 9 years of age
Causes pigmentation of developing teeth how about bone though LOOK UP
Doxycycline & Minocycline
MACROLIDES & LINCOSAMIDES: CLEC
***These three bind to 50S ribosomal subunit
Erythromycin
Clindamycin
Chloramphenicol
Prophylaxis Dental Treatment
All are given orally, 1 hour prior to the appointment
If no amoxicillin allergy:
Amoxicillin
Adults: 2g
Children: 50 mg/kg
Amoxicillin allergy:
Clindamycin

45

Adults: 600 mg
Children: 20 mg/kg
Cephalexin
Adults: 2g
Children:: 50 mg/kg
Azithromycin
Adults: 500 mg
Children: 15 mg/kg
Most likely mechanism for the increased occurrence of drug-resistant bugs is R factor transfer of resistance
Dont get clowned by increased mutation rate
ANTIMYCOBACTERIAL AGENTS
RIPE:
For TB
Rifampin
Isoniazid
Pyrazinamide
Ethambutol
ANTIVIRALS
For herpesviruses:
Acyclovir
Vidarabine
Ganciclovir
Foscarnet
For respiratory viral infections:
Amantadine & Rimantadine
Ribavirin
For HIV:
Zidovudine (AZT)
ddC & ddI
3TC
Protease inhibitors
ANTIFUNGALS
Antifungal drugs affect cell MB permeability
Cause leakage of cellular constituents, leading to death of affected cells
Antifungal drugs inhibit ergosterol in the fungus cell wall
AMPHOTERICIN B:
Given orally or by IV for tx of severe systemic fungal infections caused by fungi such as Candida species, Histo, Crypto,
and Coccoidio (NOT Nocardiosis)
Bacitracin, polymyxin-B & neomycin are not anti-fungal agents they are antibiotics
Amphotericin B & Nystatin are polyene Abx which impair ergosterol synthesis
Ergosterol is the major sterol of fungal MBs
Systemic administration is associated w/ a high incidence of kidney toxicity
NYSTATIN & CLOTRIMAZOLE:
Two antifungals that are used as swish & swallow to treat oral candida infections
Nystatin (Mycostatin) is taken as an oral suspension
NOT For psuedomembranous (Use Diflucan)
Clotrimazole (Mycelex) is taken as a troche (lozenge)
They work by binding to sterols in the fungal cell MB
Increase permeability & permit leakage of intracellular contents leads to cell death
IMIDAZOLES:
Aspergillus is very resistant to imidazoles
Treat aspergillus w/ amphotericin B

Topical agent
Clotrimazole
Nystatin
Topical agents (cream)
Amphotericin B
Ketoconazole
Nystatin
Systemic agents

46

Summary of Some Antifungal Agents


Use
Mechanism on fungal cell
Oropharyngeal candidiasis
Alters cell membrane
Oral cavity candidiasis
Alters cell membrane

Form
Troche
Oral suspension

Cutaneous & mucocutaneous Cand


Cutaneous and muco Cand
Cutaneous and muco Cand

Cream
Cream
Ointment

Alters cell membrane


Alters cell membrane
Alters cell membrane

Fluconazole
Ketoconazole
Amphotericin

Oral, esophageal, oropharyngeal Cand


Oral, esophageal, oropharyngeal Cand
Systemic candidiasis

Alters cell membrane


Alters cell membrane
Alters cell membrane

Tablets
Tablets
IV injection

VACCINES
Toxoids Name says it all they are Toxin Vaccines not toxic to organism bc treated w/ form. Induce AB production!
Are antigenic and Non-toxic
Are most often prepared by treating toxins with formaldehyde
Weakened bacterial toxins that are no longer toxic but do induce Ab production
Bacterial vaccines: (3 general classes Toxoids, Killed Organisms, and Attenuated)
Given routinely to children
Diphtheria, pertussis, (tetanis too right?) vaccine (Dont get clowned by the VIRAL pediatric vaccines MMR)
Capsular polysaccharide vaccines:
Streptococcus pneumonia vaccine pneumonia
Neisseria meningitidis vaccine meningitis
Haemophilus influenzae vaccine meningitis
Most common cause of acute purulent meningitis in kids 3 months to 2 years Think EMOP
Antigenic component of Haemophilus influenzae vaccine is from a capsular antigen (polysaccharide capsule)
Little Bobby H. Influenzae wears a CAP, and that CAP is a maker for his parents (Igs) to find him!
Inactivated protein exotoxins (toxoids)
Corynebacterium diphteriae diphtheria
Exhibits pathogenicty through toxemia (NOT via bacteremia or septicemia)
Clostridium tetani tetany
Killed bacteria vaccines:
Bordetella pertussis vaccine whooping cough Cough got his ass whooped, he dead now
Salmonella typhi vaccine fever
Typhoid Fever
Asymptomatic carriers are a major hazard Think about the dead fish being a vaccine
Vibrio cholerae vaccine cholera
Live attenuated bacterial vaccines: The cow, the rabbit (francis) and carol burnett are all living!!!
Mycobacterium bovis vaccine Tb
Francisella tularensis vaccine tularemia
Coxiella burnetii vaccine Q fever
Active immunity induced by vaccines prepared from bacteria or their products
Passive immunity provided by the administration of preformed ab in preparations called immune globulins (toxoids)
Provides immediate protection & a vaccine to provide long-term protection
Rabies and Clostridium tetani vaccines:
Result in artificially acquired active immunity
Can use vaccine after introduction of the virus to stop clinical symptoms
Longest incubation period
Used to elicit an immune response before the onset of disease symptoms
Effectiveness of this type of vaccine depends on:
Slow development of the infecting pathogen prior to the onset of symptoms
Ability of the vaccine to initiate Ab production before the active toxins are produced/released
Viral Vaccines
Live attenuated
Induce humoral immunity AND cell mediated immunity but have reverted to virulence on rare occasions
MMR, Sabin Polio, VZV, Yellow fever (flavaflav)
Killed
Only induce humoral immunity, but are stable
Rabies, Influenza, Hepatitis A, SalK (K for Killed) Polio
Recombinant
HBV (antigen = recombinant HBsAg)

Disease
Smallpox
Yellow fever (viral hepatitis)
Hepatitis B
Measles
Mumps

SOME CURRENT VIRAL VACCINES


Type of Vaccine
Attenuated live virus
Attenuated live virus
Purified HBsAg: recombinants HBsAG
Attenuated live virus
Attenuated live virus

47

Rubella
Polio
Polio
Influenza
Rabies
Varicella (chickenpox)
Hepatitis A

Attenuated live virus


Attenuated live virus (Sabin)oral
Inactivated virus (Salk vaccine)injection
Inactivated virus
Inactivated virus
Attenuated live virus
Inactivated virus

Adjuvants:
Non-specific, mildly irritating substances
Purpose: to enhance Ab response
Enhance Ag uptake by APCs
Added to vaccines to slow down absorption & increase effectiveness
Freunds Adjuvant:
Common experimental adjuvant consists of killed M. tuberculosis suspended in lanolin & mineral oil
Used to elicit stronger T- & B-cell mediated responses when Ag/s alone fail to evoke sufficient response
Human vaccines contain aluminum hydroxide or lipid adjuvants
Alum-precipitated Ag/s:
Formed from protein Ag/s mixed w/ aluminum compounds
Serves as a local inflammatory stimulus
A precipitate is formed that is more useful for establishing immunity than are the proteins alone
Released more slowly in the body, enhancing stimulation of the immune response
Adjuvants eliminate the need for repeated booster doses of Ag & permits use of smaller Ag doses in the vaccine
Toxoid (aka immune globulins):
Inactivated protein exotoxin (bacterial toxin)
Induce formation of specific antitoxin Ab/s that serve as the basis for the specific protection from the toxin
Used for diphtheria, tetanus, and other diseases
Prepared by treating toxins w/ formaldehyde
Not all toxins can be converted to toxoids by treatment w/ formaldehyde
But is strong enough to induce formation of antibodies & immunity to the specific disease
Antigenic, non-toxic
Antitoxin:
An Ab formed in response to a specific toxin
Antitoxins in serum Tx or prevention of certain bacterial diseases
Can neutralize unbound toxin to prevent the disease from progressing
Tetanus antitoxin Tx or prevention of tetanus
Botulinum antitoxin Tx of botulism
An intoxication rather than an infection
Diphtheria antitoxin Tx of diphtheria
Routine Vaccines
Infants are routinely immunized against:
Bordetella pertussis, Corynebacterium diphtheriae, and Clostridum tetani (NOT Brucella abortus or H. Influenzae)
DPT vaccine (diphtheria-pertussis-tetanis):
BCG vaccine avirulent bacteria (TB vaccine), not recomd in us cuz of low chance of infectivity, ruins PPD test
Unlike DPT, BCG vaccine consist of avirulent bacteria
DPT pertussis is killed whole bact, in US now suggest DTaP (pertussis Ag/s, not killed bact); diph / tetanus
Rubeola (measles), pertussis, smallpox, poliomyelitis, mumps & tetanus are all prevented by active immunization

INFECTION CONTROL
The most effective means of preventing disease transmission in a dental office is based on the concept of Universal Precautions
Dont get clowned by sterilization, asepsis, or barrier techniques Universal precautions encapsulates all of these
FIND OUT
OSHAs blood borne pathogen protocol is used to protect whom?????
To protect the employees!!!
OSHAs Bloodborne Pathogens Standard 29 CFR 1910.1030 recommends the use of a tuberculocidal disinfectant for
surfaces/objects that may be contaminated with blood and/or body fluids. (this represents an intermediate level
disinfectant)
FIND OUT
Dental personnel are most at risk for transmission of TB?? Dental Instruments Or Aerosolization
FIND OUT
What does OSHA stand for? Occupational Safety and Health Administration

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FIND OUT which disinfectant is lipophilic and lipophobic (isopropyl alcochol, iodophor, chloride, BENZ-something???)
Some general notes/definitions:
Concentration & contact time: critical factors that determine effectiveness of an antimicrobial agent
Any/all of the 3 major portions of microbial cells can be affected: cell MB, cytoplasmic contents (particularly enzymes)
& nuclear material
It is not possible, nor necessary to sterilize all environmental surfaces which become contaminated during patient care. In
many instances, because of the relatively low risk of microbial transmission, thorough cleaning of the surfaces is sufficient to
break the cycles of cross-contamination and cross-infection
Bactericidal:
Antibacterial solution w/ directly kills bacteria
Cidal agents & processes are designed to ensure microbial inactivation
EXs: Glutaraldehyde, betabropiolactone, ethylene oxide, formaldehyde are all bacteriocidal
Bacteristatic:
Inhibit their metabolism and replication
Affected organisms can remain viable but inactive for extended intervals
Not directly kill or inactive microbes
Organism resistance: highlow
PrionsBacterial sporesMycobacteriaParasitic bacteriaSmall, non-enveloped
virusesTrophozoitesNon-sporulating G- bacteriaFungiLarge non-enveloped virusesNon-sporulating
G+ bacteriaEnveloped viruses
STERILIZATION:
The use of physical or chemical procedure to destroy all microbial life, including bacterial endospores
Limiting requirement is removal of spores
Filtration:
Liquids are generally sterilized by filtration
The most commonly used filter is composed of nitrocellulose and has a pores size of 0.22 m
This size will retain all bacteria and spores
Filters work by physically trapping particles larger than the spore size
Used for liquids that will be destroyed at temps over 90C
Pre-cleaning:
The most important step in instrument sterilization
Debris acts as barrier to the sterilant and sterilization process
Ultrasonic instrument cleaning is the safest and most efficacious method of precleaning
2 purposes of cleaning:
Reduction in concentration/number of pathogens
Removal blood, tissue, bioburden, & other debris which can interfere w/ disinfection
Heat sterilization is recognized as the most efficient, reliable, biologically monitorable method of sterilization
All reusable items that come in contact w/ pt must be sterilized
DISINFECTION:
Less lethal than sterilization
Use of chemical agents to destroy virtually all pathogenic microorganisms on inanimate surfaces (headrests, light
handles,etc.)
Does not include destruction of all pathogen or resistant spores
Submerging dental instruments for 15 minutes in a cold disinfectant is unacceptable as a sterilizing method because
spores are not killed during that time
Immersion of instruments for 30 minutes in cold disinfectant is expected to destroy strep and staph, NOT spores or
Hep B
Glutaraldehyde is approved as an immersion sterilant, but takes a long time
Not considered safe for use on living tissue
Disinfectant: vs. Anti-septic (which is form human tissue use)
Antimicrobial agents that kill (germicide) or prevent growth (microbiostatic) of pathogenic microorganisms
Not safe for living tissues (antiseptics are safe) applied only to inanimate objects
Chlorine: a powerful oxidizing agent that inactivates bacteria and most viruses by oxidizing free sulfhydryl groups
Active component of hypochlorite (bleach), which is used as a disinfectant
Phenol: original disinfectant used in hospitals, but is rarely used as a disinfectant today because it is too caustic
DNP 2,4-dinitrophenol
P:O = Phosphorylation : Oxygen ratio = amount of ATP produced from ADP + Pi / per nanogram of O2 consumed
DNP disrupts coupling in mitochondria
DNP decreases the P:O ratio in mitochondria, so NOT allowing it to make energy w/ O2
We want the bugs P:O ratio to do down

49

Formaldehyde: (37% solution in water = formalin) denatures protein and nucleic acids
A high level sterilant (disinfectant) is characterized by what?
Capable of killing all microorganisms and low concentrations of bacterial spores. Used mainly as a sterilant for critical
medical devices; monitored by the FDA
Examples: glutaraldehyde, formaldehyde, peracetic acid, hydrogen peroxide
Intermedial levels agents:
Phenols, iodophors, hypochlorite, certain preparations containing alcohols & others
These are able to penetrate the wax and lipid outer layers surrounding mycobacteria
M. tuberculosis recognized as a benchmark criterion for disinfectant effectiveness
Morphology/structure of tubercle bacilli make them relatively resistant to penetration by a # of low-level
disinfectants
Examples: chlorine compounds, alcohol, phenol compounds, iodophors, quaternary ammonium compound
Low level agents
Effective against most bacteria, some viruses and fungi, but NOT TB or Spores
These disinfectants contain a lower concentration of active ingredients
ANTISEPSIS:
Antiseptics:
Chemical agents similar to disinfectants but may be applied to living tissue (i.e., handwashing)
Can be applied to external body surfaces or mucous MBs to decrease microbial #s not to be taken internally
Temporarily lowers the concentration of normal, resident flora
Alcohol
is the most widely used antiseptic
Used to reduce the # of microorganisms on the skin surface in wound area
Denatures proteins, extracts MB lipids & dehydrates
Dissolves lipids
Inactivates some viruses (only lipophilic viruses)
Disadvantages:
Evaporates too quickly
Has diminished activity against viruses in dried blood, saliva & other secretions
So, not regarded as effective surface cleansing agent
Isopropyl alcohol (90-95%) major form used in hospitals
Isopropyl alcohol 70%
Disinfectants against herpes simplex but NOT rhinovirus
Ethanol (70%) widely used to clean skin prior to immunization/venipuncture
Iodine most effective skin antiseptic used in medical practice (oxidizing agent & combines irreversibly w/ proteins)
Handwashing
Primary disease prevention measure in healthcare
Significantly reduces the # of transient & normal microorganisms that colonize host tissue
Soap is only good for removal of bugs from the skin
Handwash agents include: chlorhexidine gluconate & triclosan
Both have been shown to exhibit an antimicrobial effect when used as handwash agents in health care settings
They also show substantivity = a residual action on washed tissues for extended periods
Hand hygiene (not handwashing)
Isopropyl alcohol for hand hygiene procedures products containing 60-80% alcohol DO NOT use water
SANITATION:
Tx of water supplies to reduce microbial levels to safe public health levels
PASTEURIZATION:
Tx of dairy foods for short intervals w/ heat, to kill certain disease-causing microorganisms
Target of pasteurization is the destruction of M. tuberculosis
Pasteurization of milk targets what microbes?
Mycobacterium Tuberculosis & Coxiella Burnetti
Spaulding Classification
Rule of thumb is anything that can be sterilized should be, but for plastics and other, see below
BONE/BLOOD Mucous
Skin No contact
Spaulding Inanimate Objects Classification
Category

50

Level

Risk

Objects

Critical

Heat Sterilization

Very high

Touch bone or penetrate tissue; blood


present (scalpels, forceps, scalers, probes,
implants)

Semi-Critical

Sterilization, High-level
disinfection

Moderate

Touch mucous membrane but not


penetrate; no blood, (mirrors, burnishers,
amalgam carriers, etc.)

Non-Critical

Intermediate Level

Low

Unbroken skin contact; no blood; (masks,


clothing. b.p. cuffs)

Environmental surfaces:
Equipment housekeeping

Low Level disinfection;


sanitation

Minimal

No direct patient contact, no blood units,


knobs, light floors, walls, counters

Saturated steam sterilization (autoclave):


Most practical & economical & most currently effective sporicide
Most efficient method for destruction of viral & fungal microorganisms
Moist heat destroys bacteria by denaturation of the high protein-containing bacteria via heat under pressure
121C (250F) at 15 psi for 20 min
Used for wrapped instruments
To positively destroy all living organisms, the minimum required temperature is 121C
So, a case with solder that melts at 175C is OK
134C (270F) at 30 psi for at least 3 minutes (flash cycle)
Indicated for unwrapped instruments
Usually only 10 min required to destroy all bacteria
Additional time is allowed for penetration when the instruments are wrapped
Spore forming pathogens provide the ultimate test for efficacy of sterilization
Resist boiling at 100C at sea level they must be exposed to higher temperatures
Cannot be achieved unless the pressure is increased
Kills even the highly heat resistant spores of Clostridium botulinum
Clostridium and Bacillus anthracis spores used to check effectiveness of autclaving
Weekly spore testing of autoclave units is recommended
Using calibrated biological indicators remains the main guarantee of sterilization
Spores from Bacillus stearothermophilus should be used to verify heat in autoclave
These preparations contain bacterial spores more heat resistant than vegatiative bacteria, viruses & other microbes
Best method of avoid cross-contamination of Hepatitis B is by autoclaving or using dry heat on all instruments used in
Tx
Dry heat sterilization:
320F (160C) for 2hrs at 15 psi
340F (171C) for 1hr also effective
According to Spaulding Classification
Semi-critical items should be reprocessed by heat stabilization if the material is heat stable
Items which are usually sterilized by dry heat can be autoclaved
Remove immediately after cycle to diminish possibility of corrosion & dulling sharp points/edges (carbon steel
instruments)
Dry heat destroys microorganisms by causing coagulation of proteins
Advantages:
Effective & safe for sterilization of metal instruments
Does not dull or corrode instruments
Disadvantages:
Long cycle
Poor penetration
Ruins heat-sensitive material
Rapid Dry Heat Sterilization
Can NOT be WET
12 minutes at 350 F/177C for Wrapped
6 minutes at 350 F/177C for Unwrapped
Internal Air control
Provides a very fast cycle time, no dulling of cutting edges, & dry instruments after cycle
Forced air, dry heat convection ovens used for sterilization of heat-stable instruments
Higher temperature is used; shorter duration
Ethylene Oxide: (Unsaturated chemical vapor)
Used extensively in hospitals for sterilization of heat-sensitve (heat-labile) materials such as surgical instruments & plastics

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Kills by alkylating both proteins & nucleic acids irreversibly inactivates them
Primarily inactivates cellular DNA!!!!!
Most reliable gaseous sterilizing agent available for dental instruments
Limited use because:
Fairly toxic to humans and is also flammable unsafe
Slow process (10-16 hours) depending on the material to be sterilized Kaplan says 8-12 hours
The method of sterilization that takes the Longest
Advantages:
Highly penetrative
Does not damage heat sensitive materials (rubber, cotton, plastic)
Evaporates w/out leaving a residue
Works well for materials that cannot be exposed to moisture
NOTE: instruments must be dry before both ethylene oxide & dry heat sterilization water interferes w/ sterilization
process
Glutaraldehyde 2%:
Can be used as a disinfectant or sterilant
An alkalizing agent highly lethal to essentially all microorganism
Chemical with broadest antimicrobial spectrum of activity
Recommendend for disinfecting dental units & handpieces
Requires sufficient contact time (12-15 hours)
Requires absence of extraneous organic material
Advantages:
Most potent category of chemical germicide
Can kill spores (after 10 hours)
EPA registered as chemical sterilant
Approved as an immersion sterilant
Can be used on heat sensitive materials
Disadvantages:
Long period required for sterilization
Allergenic
Not an environmental disinfectant
Extremely toxic to tissues
In hospitals, glutaraldehydes are used to sterilize respiratory therapy equipment
Other Disinfectants:
Alcohols, chlorhexidine, & quaternary ammonium compounds
Immersion of dental instruments in cold disinfectants will not destroy spores or the hepatitis viruses (they are
resistant to physical and chemical agents) This is true because it says DISINFECTANT
Quaternary ammonium compounds (e.g., benzalkonium chloride):
Cationic detergents and have the narrowest range of effectiveness
Quaternary ammmonium compounds have the narrowest antimicrobial spectrum
Used as disinfectants & antiseptics
G+ bacteria are most susceptible to destruction
These compounds are not sporicidal, tuberculocidal, or viricidal
Inactivated by anionic detergents (soaps & iron in hard water)
Mechanism of action is against the cytoplasmic membrane
UV Sterilization
UV light at germicidal wavelengths (185 -254 nm) causes thymine molecules in the DNA to dimerize and become inactive
Bacteria is rendered useless, though it may not die
Only used as supplementary sterilization in conjunction with other methods
Irritation dermatitis:
Most common form of adverse epithelial reaction noted for health-care professionals
2030% of HC workers suffer from occasional or chronic dermatitis on their hands
Most common manifestation of the condition is irritation dermatitis, a non-specific immune reaction caused by contact w/ a
substance that physically or chemically damages the skin
Aggravated by frequent hand washing, residual glove powder left on hands, & harshness or repeated use of some antiseptic
handwash agents
More common in cold climates during winter months
Face masks should be changed between patients and more often if heavy spatter (becomes moist w/in or w/out) is generated
Personal protective equipment clinical jackets should be long sleeve, high neck and are required to minimize the potential for
exposed skin to contact, and therefore become contaminated w/ a pts blood, saliva, or other potentially infectious material
Antigens most responsible for an immediate Type I reaction to natural latex are: Proteins

52

Only a few of over 250 proteins found in sap from rubber tree Hevea brasiliensis are responsible for Type I immediate IgE
mediated reactions to natural rubber latex
These are water-soluble macromolecules that can leach out of latex gloves when a person perspires, or be detected on the
surface of other products containing natural rubber latex
Vinyl or nitrile gloves are worn to treat individuals who develop Type I immediate allergic reaction to latex
Hypoallergenic latex gloves are still latex w/ a chemical coating
Not an appropriate latex alternative, as allergic manifestation can still develop
Latex allergy risks factors include: person w/ multiple surgeries, atopy (type I), rubber industry workers, persons w/ an
allergy to bananas but NOT a person w/ a pollen allergy Pollen has nothing to do w/ latex ptn allergens
Hepatitis and Sterilization
HBV is the most infectious target of Standard Blood Precautions
HBV is the most infectious bloodborne pathogen known = greatest occupation health care risk of bloodborne disease
Infection control precautions aimed at preventing this viral transmission have also been shown to be effective in
preventing HBV & HCV cross-infection
Responsible for infection in 1030% of exposed, susceptible HC workers
Concentration of HBV in chronic carrier ranges between 106 & 109 virions per ml, it is significantly lower for AIDS
Viral concentration of HCV infected individuals is between HIV & HBV
Transmission of Hep B parenteral, dirty instruments, microabrasions, and blood, feces, saliva
Hepatitis C transmitted by accidental needle sticks, blood transfusions, drug addicts sharing contaminated syringes
Anionic surface acting substances (soaps/detergents):
These substances alter the nature of interfaces to lower surface tension & increase cleaning
Their primary value appears to be their ability to remove microorganisms mechanically from the skin surface
So the cationic agents disrupt the MBs of the bugs, while the anionic ones pull the bugs away from the skin
Include synthetic anionic detergents & soaps
Detergents:
Are surface-active agents composed of long-chain, lipid-soluble, hydrophobic portion & a polar hydrophilic group
which can be a cation, an anion, or a nonionic group
These surfactants interact w/ cell membrane lipids through their hydrophobic chain and w/ the surrounding water through
their polar group and thus disrupt the cell MB
Nonionic chemicals do not possess any antimicrobial properties
The WORST way to tell if a virus is susceptible to a chemical or some other disinfectant is:
By its nucleic acid type
The amount of saliva with the virus
The amount of blood with the virus
If it has an envelope or not
IMMUNOLOGY
Immune system
Main function = to prevent or limit infection by microorganisms such as bacteria, viruses, fungi, and parasites
Protection is provided primarily by the cell-mediated & Ab-mediated arms of the immune system
The other two major components of the immune system: 1) complement and 2) phagocytes
Opsonization
***Opsonin helps prepare bacteria for phagocytosis (NOT intracellular microorganisms or viruses)
Phagocyte locates microorganism via chemotaxis
Adherence sometimes facilitated by opsonization:
Opsonization is the coating of the microbial cell w/ plasma proteins
This speeds up phagocytosis!!!
Opsonins = C3 & the Fc portion of the Ab
The Fc receptors on macrophages react w/ the Fc region of IgG & hold the microbe close to the phagocytic cell MB,
thus facilitating the engulfment process
Pseudopods then encircle/engulf the microbe
The phagocytized microbe, enclosed in a vacuole (phagosome), is killed by lysosomal enzymes & oxidizing agents
Remember, the capsule protects bacteria from phagocytosis
Neutralization
Ab prevents bacterial adherence
Example is sIgA in the mouth
Complement Activation (more below)
Ab activates complement enhancing opsonization and lysis
Phagocytosis
Involves ingestion/digestion of: microorganisms, insoluble particles (like tattoo ink!), damaged/dead host cells, cell debris,
activated clotting factors
Mediated by macrophages & PMNs

53

Both will phagocytize bacteria coated w/ Ab & complement


The C3b fragment of complement binds to bacteria opsonized by Ab
Then the C3b binds to receptors on phagocytic cells & signals them to phagocytize the organism
Stages:
Chemotaxis movement of cells up a gradient of chemotactic factors
Adherence works well for whole bacteria/viruses; less so for proteins or encapsulated bacteria
Pseudopodium formation protrusion of MBs to flow around the prey
Phagosome formation fusion of the psuedopodium w/ a MB enclosing the prey
Phagolysosome formation phagosome-lysosome fusion
Lysosome contains H2O2, free radicals, peroxidase, lysosyme, hydrolytic enzymes
Elimination via exocytosis
Phagocytes:
Includes PMNs, Macrophages, Dendrititic cells and Langerhans, and apparently Eosinophils
Bacteria are ingested by Neutrophilic Lymphocytes
Fixed do not circulate (fixed macrophages & cells of the reticuloendothelial system)
Free circulate in bloodstream (PMNs & macrophages)
One Q said: PMNs and Eosinophils (remember granulocytes are not part of RE system)
Eosinophils CAN phagocytose antigen/antibody complexes
Macrophages
Macrophages are activated by lymphokines (mostly IFN-gamma)
Chemotactically, C5a and various cytokines are chemoattractants for activated macrophages
Macrophages have MHC II molecules that present antigenic peptides to T cells
Macrophages present Ag to antigen-specific T cells (CD4 T helper cells)
See discussion below on MHC MQs are APCs!!!
Hemosiderin:
Insoluble, iron-containing protein derived from ferritin
Normally occurs in small amounts w/in macrophages of bone marrow, liver, & spleen
Can accumulate in tissues in excess amounts, causing:
Hemosiderosis:
Occurs when hemosiderin builds up in tissue macrophages
Usually does not cause tissue or organ damage
Often associated w/ thalassemia major (beta)
Think H for Hb H and tHalassemia for Hemosiderin and Histoplasmosis
Hemochromatosis (aka bronzed disease):
More extensive accumulation of hemosiderin throughout the body
Tissue & organ damage
Increased ferritin and increased transferritin saturation
Most often is hereditary disorder develops in men >40 y.o.
Classic triad micronodular cirrhosis, pancreatic fibrosis, & skin pigmentation bronze diabetes
Results in CHF & increase risk of hepatocellular carcinoma
Disease may be primary (auto recessive) or secondary to chronic transfusion therapy
Immunologic Tolerance
Self vs. Non-self --- How the body knowswhy individuals do NOT have an immune response to self proteins
Clonal deletion:
Immature lymphocytes that make self reactive receptors, are deleted before they are released to do their thing
In the medulla of the thymus
1 of 3 current theories to explain why we dont attack ourselves and Kaplan describes it
Lack of co-stimulatory signals:
Foreign & self peptides are the same, so both are able to bind to MHC molecules (so, not the answer)
In order for an immune response to occur, the APC presents the Ag to the TCR
It must ALSO have a secondary signal, or costimulatorthis is all part of Congitive Recognition, which
is the reason Frogs dont snap at every black particle, it must act like a flywhich is the same thing as
why our bodys cells must have dual signals to know when to attack
Humoral vs. Cellular Immunity (i.e. Differentiation of B/T cells)
Microorganism activates either:
Cell Mediated Immunity TH1 Cells and IL-12!!!
Macrophage
via IL-12 Activates Nave Helper T-cell (Th-0) via IL-12 Activates Th-1 cells
Then Activated Th-1 either
via Gamma Interferon Activates Macrophage (maybe nat. killer cells)
via IL-2 Activates Cytotoxic T cell (CD8)
Humoral Immunity TH2 Cells and IL 4, 5, and 6!!!

54

(No name cell) via IL-4 Activates Nave Helper T-cell (Th-0) via IL-4
Activates Th-2 cells
Then Activated Th-2 cell via IL-4 or Il-5 Activates B cell Plasma cell Produces antibodies
Summary
Th1 (cell mediated)
Produce IL-2 and gamma interferon, activate macrophages and Tc cells
Th2 (humoral)
Produce IL-4 or IL-5, IL-6, IL-10 and help B cells make Ab daddy
Cellular immunity:
Cellular responses involve T-cells, and result in production of helper T cells & cytotoxic T cells
Mediated by T-cells either through 1) release of lymphokines or 2) exertion of direct cytotoxicity
Immunologic resistance to MOST intracellular pathogens is manifested with Cellular immunity
NOT humoral immunity, wheal & flare reactions, or non-specific serum protection
Host defense against M. tuberculosis, viruses, and fungi, Allergy (only poison oak contact), Graft and tumor rejection, and
regulation of antibody response (Help/Suppression)
It comprises delayed-type (type IV) hypersensitivity reactions
Specific acquired immunity involving T-cells
Acts to resist most intracellular pathogens (bacteria & viruses)
Humoral (Ab-mediated) immunity:
Humoral responses are generated against most antigens and require the secretion of Ab by plasma cells (activated B-cells)
The primary response is always IgM
IgM is always first to respond
IgM is initially produced (after a 3-5 day lag phase Ig/s undetectable), followed by class switching & a decline in
IgM
Later, IgG & sIgA become detectable
The secondary response is the result of isotype or class switching, resulting in synthesis of IgG, IgA, &/or IgE
An anamnestic response to previously encountered Ag
Memory B & T cells are responsible for this phase
IgG levels rise more rapidly than in 1 phase (requires less Ag to elicit response)
This response explains the efficacy of booster injections of vaccines
May produce high levels of IgE
B-cells (like T-cells) have surface receptors which enable them to recognize the appropriate Ag
Do not themselves interact to neutralize or destroy the Ag
After Ag recognition, B-cells reside in the 2 lymphoid tissue & proliferate to form daughter lymphocytes
These B-cells then develop into short-lived plasma cells
The plasma cells produce Ab/s & release them into blood at the lymph nodes
Some activated B-cells become memory cells instead of plasma cells
They continue to produce small amounts of Ab long after beating the infection
The key to humoral immunity = ability to react specifically w/ Ag/s
Accomplishes neutralization and inactivation of bacterial toxins
Provides protection against encapsulated bacteria Think that the ABs can bind to the capsule
Opsonization may occur as a component of the humoral immune system in response to virulent Strep pneumoniae
If B cells were eliminated, how would you achieve humoral immunity???
Injections of gamma globulin???
Natural (innate) immunity:
Present at birth
Occurs naturally as a result of a persons genetic constitution or physiology
Does not arise from a previous infection or vaccination
Comprised of skin, mucous MBs, secretions such as saliva & tears, phagocytic cells & NK cells
Nonspecific
An example of innate immunity is the alternative pathway of complement, which is demonstrated by phagocytosis of
microbes by neutrophils and macrophages
See 2000 Q1 & 2001 Q309
Response does not improve after exposure to the organism
Processes have no memory
EX: HCl in stomach, fever, phagocytosis by PMN (NOT sIgA in mothers milk)
Acquired immunity:
Develops in response to Ag exposure
Comprised of Ab/s (IgG, IgA, etc) and sensitized lymphocytes (T cells & B cells)
Specific
Improves upon repeated exposure to the organism
Long-term memory
May have an anamnestic response subsequent response is faster & bigger
Due to memory T cells & B cells

55

Active or passive
Active immunity
Host actively produces an immune response consisting of Ab/s & activates helper and cytotoxic T-cells
Main advantage resistance is long-term (years)
Major disadvantage slow onset
Rubeola, pertussis, poliomyelitis, and mumps
Toxoid still give active
Passive immunity
Ab/s are performed in another host
Main advantage immediate availability of Ab/s
Rapid onset
Major disadvantage short duration of active immunity (Thats why you need the tetanus shot every 10
years)
Think To Be Healed Rapidly
Tetanus toxin, Botulism toxin, Hbv, Rabies (After exposure, pts are given preformed antibodies)
Antitoxin is Passive
Occurs naturally or artificially
Natural Active
REGULAR
Person is exposed to an Ag & body produces Ab/s
EX: Recovery from mumps infection confers lifelong immunity
Natural Passive
EX: Ab/s (IgG) passed across placenta from mother to fetus
EX: IgA passes from mother to newborn during breast-feeding
Resistance of new-born to whooping cough
E.g. Baby born resistant to Whooping Cough
Artificial Active vaccination w/ killed, inactivated or attenuated bacteria or toxoid
Administration of tetanus toxoid which is a watered-down toxin
Injection of a killed viral vaccine
Artificial Passive injection of immune serum or -globulin
If person were given tetanus antitoxin
NOTE Toxin = ANTItoxin
NOTE: Hypersensitivity an exaggerated immunological response upon re-exposure to a specific antigen
EX positive skin test after having a disease
See below for more info on the four types of hypersensitivity reactions
Immunogens & Antigens:
Antigen = any substance that can be specifically bound by Ab or a TCR
Immunogen = an antigen that induces an immune response
Include all proteins (they are the most antigenic), most polysaccharides, nucleoproteins, and lipoproteins
Epitope
ON the AntiGEN The antigen binds the AB via the antigens Epitope!
the Ab binding site of the Ag for a specific Ab
Antibodies: (See below)
Able to bind to epitopes on a wide variety of molecules
T-cell receptors (TCR):
CD3 molecules link noncovalently to the TCR
This causes internal signaling, triggering the T-cell
Only able to recognize peptides bound to MHC proteins
Cannot recognize Ag alone only in the context of MHC molecules
Haptens: Think HALF-tens they are halfway there to eliciting a response, but need carrier ptns to do so.
Small molecules that act as an Ab epitope, but will not induce immune responses since they are not recognized as Tcell Ag/s
Have antigenic determinants, but are too small to elicit the formation of Ab/s by themselves
Can do so when covalently bound to a carrier protein
Many allergens (e.g., penicillin) are haptens
The catechol in the plant oil that causes poison oak is a hapten
Usually responsible for contact sensitivity
Not immunogenic because they cannot activate helper T cells
Ab production involves activation of 1) B lymphocytes by the hapten & 2) helper T cells by the carrier
MHC (major histocompatibility complex):
Glycoprotein MCH = ptn + sugar
A collection of polymorphic genes encoding for proteins that regulate immune responses

56

In humans, the MHC genes are termed HLA (human leukocyte antigens)
MHC is an antigen located where?
6th Human chromosome (I dont know if this is what they really asked)
Fxns Present exogenous antigens to T cells and determine tissue type
*Antigen processing = mechanism for internalization & re-expression of Ag on APC MBs by MHC I & II
MHC I: (Think whistle blower, broadcasting that the factory is making something they are not supposed to)
Found on the surface of all nucleated cells & platelets
HLA-1 is found on all nucleated cells
Bind peptides processed from protein synthesized in the cell cytosol
Endogenous Ag/s are presented by MHC I molecules to CD8 T cells
T-lymphocytes (not B) recognize Ag on the surface of APCs in the context of HLA-B
Cytotoxic T cells (CD8) recognize MHC I on infected cells (Product is 8)
MHC II: (Think Public Health InspectorAte something that made them sick, so the APCs, via MHC II to CD4s to B
cells to post their Poor Health Grade (Ab) everywhere)
Found on some cells, including APCs, B cells, and thymic epithelial cells invovled in T cell maturation
Bind peptide epitopes from endocytosed molecules
Exogenous Ag/s are processed & presented by MHC II molecules to CD4 T cells
Are necessary for Ag recognition by helper T cells
HLA Class II = HLA-DR, HLA-DQ, HLA-DP
CD4 cells recognize viral, bacterial, parasite, or injected proteins in association w/ class II (Product is 8)
Are the main determinant of organ rejection
MHC II Ag loading occurs in acidified endosome
Short Story for Clarification REVIEW OF IT ALL!!!
1st Virus or bug infects the cell
2nd APC (macrophage, B cell, or Dendritic cell) eats part of the produced virus or protein from the infected cell and grabs a
viral epitope and then displays it on its MHC II in hopes that a Helper CD4 cell will come to the rescue
3rdCD4 T cell recognizes the viral epitope on the APC with its own TCR and receives costimulation via IL-1 from the
APC to verify the distress signal
The Costimulatory signal is given from APC (B7) to the Helper T-cell (CD 28)
4thWith the newly confirmed distress signal, the CD4 cell either:
Activates Cellular immunity (Tags a CD8 cell with IL-2 to go find a cell with such and such epitope and kill it)
Activates Humoral immunity (Tags a B cell with IL-2,IL-4, IL-5 to start making antibodies against such and such
epitope in the lymph node
Interleukins (largest group of cytokines):
Fundamental function appears to be communications between (inter-) various populations of WBCs
Group of well-characterized cytokines produced by leukocytes & other cell types
Have broad spectrum of functional activities that regulate the activities & capabilities of a wide variety of cell types
Particularly important as members of cytokine networks that regulate inflammatory & immune responses
Act as messengers between leukocytes involved in the immunologic or inflammatory response
Think mmmm, T-Bone stEAk
IL-1:
A macrophage-derived factor
Stimulates activites of T-cells, B-cells, & macrophages (mmmmm for Macrophage)
Stimulates IL-2 secretion
Pyrogenic (HOT)
IL-2:

Produced by activated T cells (T- in T-bone)


Stimulates antigen-activated T helper & NK cells pg 191 path book(as well as cytotoxic T cells)
Also stimulates B cells

IL-3:

T-cell product that stimulates the growth & differentiation of various blood cells in bone marrow
(B in T-Bone)
Secreted by activated T cells

IL-4:

Secreted by activated helper T cells & mast cells


Stimulates B-cells
Increases IgG & IgE (E in stEAk)

IL-5:

Secreted by activated helper T cells


Promotes B cell maturation
IL-5 is a B-cell growth & differentiation factor
Increases IgA & synthesis of Eosinophils (A in stEAk)

57

Acute Phase cytokines


IL-1, IL-6, and TNF alpha (secreted by macrophage to do a bunch of stuff, like suppress viral
replication)
IL-6, 7, 8, 10, 12: see Kaplan, p. 152 for thie summaries
Immunoglobulins = Antibodies:
Glycoproteins found in blood serum
Synthesized by plasma cells in the spleen & lymph nodes in response to detection of a foreign Ag
Two functions:
Bind epitopes on Ag/s direct attack
Stimulate other biologic phenomena such as activating
complement & binding Fc receptors on other
lymphoid cells
Mediate anaphylaxis, atopic allergies, serum sickness, and
arthus reactions
Structure:
Consist of two heavy chains & two light chains
Heavy chain contributes to both Fc and Fab fragments
Light chain only contributes to Fab
Fab (Antibody)
Contains Antigen binding site
Area from the Hinge region and up
Hypervariable Region
Ag binding to the Fab is noncovalent (so its
reversible)
Fc (Cell)
The Stem of the Y
Binds to the Phagocytes, Mast cells, Basophils, Eosinophils, etc.
Think C Constant, Carboxy, Complement binding, and Carbohydrate side chains
The variable part
VH and VL (amino terminal side) recognizes the antigens
Constant regions
In IgG and IgM, it fixes complement
Carboxyl terminal side
Disulfide Bonds (See picture)
Between 2 Heavy Chains
Between Heavy and Light Chains
Ig Epitopes
Allotype (polymorphism)
Ig epitope that differs among members of same species
Can be on light or heavy chain
Isotype (IgG, IgA,etc.) DETERMINED BY HEAVY CHAIN (VARIABLE REGION)
Ig epitope common to a single class of Ig (five classes, determined by heavy chain)
An immune cell posseses IgM and IgD on its cell surfacewhich of the following differs between them?
Heavy Chain Variable - VH
Idiotype (specific for an antigen)
Ig epitope determined by antigen-binding site
Think Idio are unique
Immunoglobulin functions (condensed):
IgG: Opsonization, Placental passage, Complement activation, 2ndary Response
IgA: Mucosal (secretory) immunity, prevents attachment, Gets secretory portion from epi cells first
IgM: Complement activation, 1ary Response, does NOT cross placenta, Ag receptor on B cells attacks a foreign blood
type
IgE: Basophil & mast cell sensitization, Type I hypersensitivity, Immunity to worms
IgD: Antigen triggering of B cells
Ig Isotypes (detailed):
IgG:
Most abundant
Only Ig that crosses the placenta
Activates complement
Predominant serum Ig found during a memory response
Main defense against various pathogenic organisms
As the severity of Periodontal Disease increases, there is an increase in plasma cells that produce IgG

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Secondary or amanestic response to protein antigen


Characterized by production of IgG Ab/s with High Titer
T1/2 = 1 month
Where is it activated????
IgA:
2nd most abundant
Remember that IgA produces more than all of the others combined, but SHORT half life, that is why IgG is
most abundant
Polymeric IgA
Present in body secretions, such as (saliva, tears, breast milk, especially colostrums)
Protects surface tissues
Synthesized by plasma cells in mucous MBs of the GI, respiratory & urinary tracts
Important in these areas plays a major role in protecting surface tissue against invasion by pathogenic
microorganisms
Provides 1 defense at mucosal surfaces bronchioles, nasal mucosa, vagina, prostate, & intestine
sIgA
Found in tears, colostrum, saliva, & milk Found in gingival crevicular fluid
Producd by plasma cells in lamina propria of Gi & respiratory tracts
A week old baby has sIgA antibodies already, where does the B cell first get exposed to the Antigen?
In spleen of baby
In spleen of mom
In intestine of baby
Intestine of the mom If it says for the B cell that made the plasma cell that made the IgA
In breast of mom only if they ask us where the sIgA comes from
Primary fxn:
To bond w/ surface Ag/s of microorganisms, preventing the adherence and ingress of Ag through the
mucosa
Aggregates microorganisms, and prevents colonization
Acts against bacteria in the oral cavity
Resistant to hydrolysis by microbial proteolytic NZs (IgA, IgE, IgG are NOT)
J chain is for Dimeric IgA
J chain is for pentamic IgM
Polymeric 2 IgAs joined by a J chain
(Think J for Joining)
This happens just below the ductal
epithelium (lamina propia)
J chain is added by the Plasma
cell (step 10)
J chain also connects up the
IgM Pentamer
Then the dimer diffuses to the
intraepithelial space and binds to Pig
R (polymeric Ig Receptor)
Then that complex is
endocytosed, then the Pig R
becomes the Secretory
Component (SC)
Secretory portion added by the
epi cell
Enterosalivary Pathway (SEE PIC)
We absorbed antigen in the gut (via
M cell of Peyers patch)
Stimulates B cells via CD4+ T-cell
Switch cell
B cells then migrate back to salivary
glands
Gut has inducer site
Salivary gland has effector site
IgD:
Makes up < 1% of Ig/s

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Present in high levels in MBs of many circulating, mature B-cells


Functions in Ag recognition by B cells (but function is not fully understood)
IgM:
Largest Ig
First Ab produced in response to infection or after primary immunization (M for priMary iMmunization)
3 days ago, a pt received her 3rd immunization w/ tetanus toxoid, you would expect to see Low IgM and High IgG
If type A blood is transfused into a type B recipient, the immediate hemolytic reaction would be the result of IgM
against the A antigen (NOT IgA or IgG)
Efficient activator of complement
IgE:
Present only in trace amounts in serum
Has reagenic acivity
Protects external mucosal surfaces
Tightly bound to its receptors on mast cells and basophils
Responsible for Type I hypersensitivity reactions (allergic & anaphylactic)
IgE is responsible for atopic allergy
Complement:
Collective term for a system of ~20 plasma proteins, which are the primary mediators of Ag-Ab reactions
Present in normal human serum
Plays a role in humoral immunitiy & inflammation
Participates in lysis of foreign cells, inflammation, & phagocytosis
Acts in a cascade w/ one protein activating another
Synthesized mainly by the liver some are made in macrophages C1 is made in GI epithelium
Chemotactic component of complement attracts PMNs
Is not an Ig
Is heat labile
Complement system:
Functions to destroy foreign substances
Either directly or in conjunction w/ other components of the immune system
Components of complement bind to IgG, NOT IgA, IgM, Endotoxins, mast cells 1999 Q78 Are you sure? Maybe not
IgA
What does complement NOT bind to??? (If it says Alternate pathway then Immune complexes is the answer!!)
Consists of ~20 plasma proteins that function as enzymes or binding proteins
Activated by C1 (classical) or C3 (alternative)
Includes multiple distinct cell surface receptors specific for physiological fragments of complement proteins
These receptors occur on inflammatory cells & cells of the immune system
Two pathways:
Alternate pathway:
Activated by:
C3 Think 311 is an alternate band
LPS (endotoxin)
Aggregated IgA, IgG, IgE, IgM
Cobra venom factor
Example of innate immunity because you dont need Ab to work like Classical does
This pathway protects the body in the absence of antibody
Seems to be of major importance in host defense against bacterial infection
Activated by invading microorganisms
Ab independent
Classical pathway:
Activated by IgG and IgM (Think GM makes classic cars)
Activated by Ab-Ag complexes (immune complexes)
Activated by C1 binds to a specific part of the Ab
C1 composed of three proteins (C1q, C1r, & C1s); Ca2+ is required for activation
Ab dependent
NOTE: both pathways lead to cell lysis by terminal components (C8 & C9); initiation differs
NOTE: C1 esterase deficiency leads to angioedema (overactive complement)
Membrane attack complex (MAC)
End product of the activation
Contains C5b, C6, C7, C8, & C9
Makes holes in the MBs of G- bacteria & RBCs, resulting in cytolysis
Biologically important C proteins:

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C2a, C4a = weak anaphylatoxins


C3a, C5a = strong anaphlatoxins (bigger numbers, bigger response)
C5a = potent chemotaxin
C3b = potent opsonin (think C3b-O, like C3PO, O for opsonin)
Complement fixation:
Binding of complement as a result of its interaction w/:
1) Immune complexes (classic pathway) OR
2) Particular surface (alternative pathway)
Used in detecting Ag or Ab (e.g., Wassermann test [for syphilis])
Only IgM and IgG fix complement meaning activate
Antigen Detection Techniques
Immunofluorescence (fluorescent antibody)
Most frequently used diagnostic lab technique for microscopic detection of Ag/s in tissue secretions & cell suspensions
Fluorescent dyes (fluorescein & rhodamine) are covalently attached to Ab molecules
Made visible by ultraviolet light in the fluorescence microscope
Labeled antibody can be used to identify bacterial surface Ag/s
Radioimmunoassy (RIA)
Used for the quantification of Ag/s or haptens that can be radioactively labeled
Enzyme-linked-immunosorbent assay (ELISA):
Used for the quantification of either Ag/s or Ab/s in pt specimens
Precipitation (precipitin):
Ag is a solution in this test
The Ab cross-links Ag molecules in variable proportions & precipitates form
Agglutination:
The antibody that attacks in agglutination is IgM
Ag is a particulate in this test (e.g., bacteria & RBCs)
Remember agglutination in a mis-matched transfusion would happen on the donors RBCs in the pt
The most common side effect of a blood transfusion is ALLERGIC Rxn, NOT agglutination
Because Ab (agglutinin) is divalent or multivalent, it cross-links the multivalent Ag particles & forms a latticework
Clumping (agglutination) can be seen
Hemagglutination when clumping results from addition of Ab to RBCs (Ag/s must be present on surface of
RBCs)
Is the basis for blood typing & distinguishing the presence of A type Ag or B type Ag on the surface of RBCs
So agglutination occurs when blood type matches the type antiserum (e.g. A antiserum with blood A) and same for
Rh factor as well:
If blood mixed with A antiserum, and Rh Positive antiserum and NO agglutination occurs, then they are TYPE B
and Rh Negative
If blood mixed with A antiserum, B antiserum, and Rh Positive antiserum and NO agglutination occurs, then they
are TYPE O and Rh Negative
If blood mixed with anti-A serum, anti-B serum, and anti-Rh serum, and agglutination DOES occur, this pt has
Rh(+) type AB
Prozone ????
Immune systems with high titers of agglutination often fail to agglutinate homologous bacteria in low dilution
How things leave blood vessels:
Cellular adherence to vascular endothelium
Upregulation of endothelial adhesion molecules (ICAM-1 and VCAM-1) is in part response to cytokine stimulation
ICAM-1 & LFA-1 are specific receptors that make endothelial adherence of leukocytes possible
T cells use LFA-1 to bind to ICAM-1 of the endothelial cell
Margination
Lining up of the leukocytes along the wall of a dilated vessel
Transendothelial migration
Active passage of the leukocytes through the capillary wall happens by means of endothelial pores
Things that happen inside the blood & things that happen outside the blood:
Extravascular events:
Chemotaxis (totally extravascular)
Movement of cells towards chemicals (positive) or away from chemicals (negative)
Intravascular events:
Stasis (Stagnation of the blood or other fluids)
Hyperemia (Presence of increased amount of blood in a part or organ
Margination (Lining up of the leukocytes along the vessel walls in inflammation)
Pavementing flattening of a cell against the interior wall of the venule Just like it sounds!

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Anaphylatoxins:
Family of peptides C3a, C4a, & C5a produced in the serum during complement activation
Probably mediated indirectly via histamine release from mast cells & basophils
C5a most powerful
100x more effective than C3a1000x more effective than C4a
Most important chemotactic factor from the complement pathway
Chemotactic accumulation of inflammatory cells where immune complexes are deposited is most probably
due to the presence of C5a
Produce smooth muscle contraction, mast cell histamine release, affect platelet aggregation, & act as mediators of the local
inflammatory process
Anaphylaxis caused by complement components is less common that caused by Type 1 (IgE mediated) hypersensitivity
Sensitization
All of the following require prior sensitization:
Anaphylaxis (TYPE I), Arthus rxn (TYPE III), Erythroblastosis fetalis, and Contact Dermatitis (TYPE IV)
Anaphylactoid reactions do not require prior sensitization
Uticaria = Hives
Skin reaction characterized by wheals (small, smooth, slightly elevated areas that are redder or paler than surrounding skin)
Can be allergic reaction to food, medicine, or other substance
1st symptom is usually itching quickly followed by wheals
Angioedema:
Related to & sometimes coexistant w/ uticaria
The swelling covers large areas & extends deep beneath skin
Involve part or all of the hands, feet, eyelids, lips, genitals, or even oral mucosa, throat, & airways (makes breathing difficult)
Uticaria & angioedema are anaphylactic-type reactions limited to skin & underlying tissues
Uticaria & angioedema are of rapid onset & can either be just annoying or life-threatening
Histology of angioedema:
edema w/ Sparse Mast Cells, etc.
Therapy use of epinephrine, antihistamines or steroids
Deficiency of C1 esterase inhibition
Angioneurotic edema (Absence of the inhibitor of the C1 component of complement same as above)
Hereditary angioedema:
Absence of C1 esterase inhibitor
In other words, absense of the inhibitor of C1 component of complement may result in angioneurotic edema
HYPERSENSITIVITY REACTIONS:
Think ACID 1, Anaphylaxis/Atopic 2, Cytotoxic 3, Immune complex 4, Delayed
TYPE I: (Anaphylaxis and Atopic) pg 196 path book
Think First and Fast
Antigens (allergens) combine w/ specific IgE Ab/s bound to MB receptors on tissue mast cells & blood basophils
Requires previous exposure that sensitizes mast cells & basophils
The Ag-Ab reaction causes rapid release of potent vasoactive & inflammatory mediators
Mediators are preformed (histamine, tryptase) OR newly generated from MB lipids (leukotrienes &
prostaglandins)
Leukotrienes & prostaglandins
Anaphlatoxins C3a & C5a are generated via tryptase action
Bradykinin generated from kininogen by the action of kallikrein, activated Hageman factor (XIIa) or
trypsin
Common allergens foods, pollen, drugs, insect venom, animal dander, house dust
Severe anaphylaxis (anaphylactic shock):
Physiological shock from anaphylactic hypersensitivity reaction
Occurs suddenly (seconds or minutes) in an allergic individual after Ag exposure
EXs: bee bites or penicillin reaction
PCN rxn is Type I
Anaphylaxis is inducible in a normal host, unlike atopy
Anaphylactic reaction involves degranulation of mast cells
Release of histamine, heparin, platelet-activating factors, SRS-As & serotonin into bloodstream
Histamine is responsible for the principle symptoms of anaphylaxis
1st symptoms anxiety, weakness, sweating, SOB, & generalized urticaria
Associated with immediate rxn, passive transfer by serum, participation of Abs, smooth muscle spasm and
capillary damage
NOT associated with delayed rxn
Constriction of the bronchioli and BP are the usual causes of death
EX: after an injection of penicillin into a penicillin-sensitized person may lead to death by the above means

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Immediate treatment:
Maintain airway
Inject epinephrine
Drug of choice for shock
Opens airways & raises BP by constricting BVs
Conscious pt IM or subcutaneous
Unconscious pt IV
Which of the following causes vasoconstriction and vasodilation when administered IV?
Epinephrine
Antihistamines (e.g., diphenhydramine) & corticosteroids (e.g., prednisone)
May be given to further reduce symptoms
Atopic allergies:
Predisposition of an individual to sensitization is characteristic of atopy
Result from a localized expression of Type I hypersensitivity reactions
Interaction of Ag/s (allergens) w/ cell-bound IgE on the mucosal MBs of the upper respiratory tract & conjunctival
tissues initiates a localized type I hypersensitivity reaction
Most allergy sufferers are atopic
Possible to become allergic w/out being atopic
Heredity plays an important role
Allergies can jump a generation
Atopy can only occur in genetically predisposed individuals, unlike anaphylaxis
Atopic individuals are genetically programmed to produce an abundance of IgE Ab/s
IgE strongly reacts against allergens in the environment (poolen, moulds, household dust, etc)
Risk for becoming allergic
One parent w/ allergies = 30% risk
Both parents w/ allergies = 60% risk
Three principal kinds of atopic allergies: (Triad)
Atopic dermatitis (eczema):
Chronic skin disorder categorized by scaly & itching rashes
Most common in infants at least of the cases clear by 3 y.o.
In adults chronic or recurring condition
A hypersensitivity reaction occurs in the skin, causing chronic inflammation
Result: skin becomes itchy & scaly
Rhinitis (hay fever & year-around symptoms):
When the allergen interacts w/ sensitized cell of the upper respiratory tract
Symptoms coughing, sneezing, congestion, tearing eyes, & respiratory difficulties
Histamine is the 1 mediator released from sensitized mast cells & basophils
Allergic asthma:
Allergic reaction primarily affecting the lower respiratory tract
Common in children
Characterized by SOB & wheezing
Specific IgE Ab/s & nonspecific inhaled irritants provoke mast cell degranulation
Release of histamine & leukotrienes (SRS-As) cause bronchospasm & bronchial mucus secretions
Allergic desensitization is produced by competitive inhibition
Basis for allergy shots
FIND OUT
What kind of hypersensitivity is it if you take multiple doses of Pen G for syphilis, and then the ABX
seeps into the RBCs?????? I think Type I
TYPE II: (Cytotoxic)
Think Cy-2-toxic
IgG, IgM
Cytotoxic reactions resulting when Ab reacts w/ antigenic cell components or tissue elements or w/ antigen or hapten
coupled to a cell or tissue.
Ab reacts w/ cell-surface epitopes
Complement-mediated lysis or phagocytosis
The Ag-Ab reaction may activate certain cytotoxic cells (killer T cells or macrophages) to produce Ab-dependent cellmediated cytotoxicity, usually involving complement activation
Examples:
Certain drug allergies
Blood transfusion reactions (red cell lysis)
Hemolytic disease of the newborn
Autoimmune hemolytic anemia
Goodpastures syndrome

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TYPE III: (Immune complex, Serum Sickess, Lupus, and Arthus Rxn) pg 201 path book
Immune complex (IC) reactions result from deposition of excessive soluble circulating Ag-Ab ICs in BVs or tissue
Think 3 Things stuck together in a complex (Ag Ab-complement)
Most commonly deposited in kidneys, joints, skin & BVs
Glomerular lesions in the immune complex disease result from IgG
The ICs activate complement & thus initiate sequence of events resulting in PMN cell migration & release of lysosomal
proteolytic enzymes & permeability factors in tissues, thereby producing acute inflammation
Active mechanism for damage to BVs in an immune complex disorder is phagocytosis of immune complexes by
the RE system (macrophages)
The chemotactic accumulation at the site of the immune complex deposition is a result of complement
Reticuloendothelial system typically clears ICs
NOTE: Histamine does not play a major role in these Type III hypersensitivity reactions
Clinical features:
Urticaria, lymphadenopathy, edema, fever
Serum sickness
The hallmark of Type III hypersensitivity
Results from IC deposition in small vessels
Appears some days after injection of a foreign serum or serum protein
Local & systemic reactions uticaria, fever, general lymphadenopathy, edema & arthritis
Type of systemic arthus rxn
Arthus rxn: pg 204 path book
Is the cutaneous reaction of type III responses
Highly localized, appears w/in 1 hour, resolves w/in 12 hours
Type III hypersentivity local subacute type III rxn, intradermal injx of ag induces AbsAg-Abs complex in
skin
Immediate type of reaction where Histamine or IgE does NOT play a major role
EX: When horse serum is injected into a rabbit and again into the skin 2 to 3 weeks later, the necrotizing rxn that
results at site of injection is an Arthus reaction
Not Serum sickness!
Serum Sickness is a type of an systemic Arthus rxn, so says an old Q, but Kaplan doesnt mention it
What is not involved in serum sickness? IgE (NOT IgG, complement, PMNs)
TYPE IV: (Delayed, cell-mediated) pg 204 path book
Think 4th and Last (Delayed)
Cellular, cell-mediated, delayed, or tuberculin-type reactions caused by sensitive T-cells after contact w/ a specific
Ag
Circulating Ab/s are neither involved in nor necessary for development of tissue injury
Delayed type of hypersensitivity demonstrated by a positive tuberculin skin test
Hypersensitivity to M. Tuberculosis is manifested by necrosis
Delayed type of hypersensitivity can be transferred by sensitized lymphocytes encounter Ag and release
lymphokines hence the term cell-mediated
Cellular infiltrate in a fully-developed delayed hypersensitivity reaction consists mainly of macrophages &
lymphocytes
Th1 cells and macrophages
Contact dermatitis
Usually Latex is Type I (think allergic or atopic contact URTICARIA), but if the questions says its a TYPE IV rxn,
which would mean Allergic contact DERMATITIS, then go with the following!!!
Type IV reaction due to latex gloves, consists of Macrophages, Lymphokines, and T lymphocytes
Allograft rejection
When a 1st rejected allograft is followed by a 2nd allograft from the same donorthe 2nd rejection occurs more
rapidly than the 1st
Hence, a reminder that you need presensitization
Primary tissue transplant, such as allogenic skin, kidney or heart, are most commonly rejected due to
Cell-mediated immune responses to cell-surface autoantigens
Similarities between Type I and IV???
Complement OR Response after 24 hours???
Thymectomized and nude mice:
Have reduced numbers of T-lymphocytes
Cant reject allografts
Have reduced Ab production to most antigens no helper Ts
Have decreased or absent delayed type IV hypersensitivity

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Type
Type I (anaphylactic type):
Immediate hypersensitivity
Type II (cytotoxic type):
Cytotoxic antibodies
Type III (immune complex type):
Immune complex disease
Type IV (cell mediated type):
Delayed type hypersensitivity

Classification of Hypersensitivity Reactions


Immunologic Mechanism
IgE antibody mediated mast cell activiation &
degranulation
Cytotoxic (IgG, IgM) antibodies formed against
cell surface antigens. Complement is usually
involved
Antibodies (IgG, IgM, IgA) formed against
exogenous or endogenous antigens. Complement
and leukocytes (neutrophils, macrophages) are
often involved
Mononuclear cell (T lymphocytes, macrophage) w/
interleukin and lymphokine production
*Q answer: sensitized lymphocytes

Blood Group
O (universal donor)
A
B
AB (universal recipient)
Autoantibodies
Anti-nuclear antibodies (ANA)
Anti-dsDNA, anti-Smith
Anti-histone
Anti-IgG
Anti-neutrophil
Anti-centromere
Anti-Scl-70
Anti-mitochondria
Anti-gliadin
Anti-basement membrane
Anti-epithelial cell
Anti-microsomal

Ag/s (agglutinogens) on erythrocytes


*none*
A
B
A & B (alloantigens both A & B)

Example
Hay fever, asthma, anaphylaxis, atopic
dermatitis, eczema
Autoimmune hemolytic anemias,
antibody-dependent cellular cytotoxicity
(ADCC), Goodpastures syndrome
SLE, rheumatoid arthritis, most types of
glomerulonephritis, arthus rxn, serum
sickness
Granulomatous disease (Tuberculosis,
Sarcoidosis, Crohns, Fungus), contact
dermatitis, graft rejection

Antibodies (agglutinins) in plasma


Anti A & Anti B
Anti B
Anti A
*none*

Systemic Lupus
Specific for Systemic Lupus
Drug-induced Lupus
Rheumatoid arthritis
Vasculitis
Scleroderma (CREST)
Sclerderma (diffuse)
1ary biliary cirrhosis
Celiac disease
Goodpastures syndrome
Pemphigus vulgaris
Hashimotos thryoiditis

INFLAMMATION & NECROSIS


Inflammation overview:
Exudative component:
Involves the movement of fluid, usually containing important proteins like fibrin and immunoglobulins
BVs are dilated upstream of an infection (causing redness and heat) and constricted downstream
Capillary permeability to the affected tissue is increased, resulting in a net loss of blood plasma into the tissue
This gives rise to edema or swelling
The swelling distends the tissues, compresses nerve endings, and thus causes pain
Cellular component:
Involves the movement of WBCs from blood vessels into the inflamed tissue
The WBCs (leukocytes) take on an important role in inflammation
They extravasate (filter out) from the capillaries into tissue & act as phagocytes
They may also aid by walling off an infection and preventing its spread
If inflammation persists:
Released cytokines IL-1 & TNF will activate endothelial cells to upregulate receptors VCAM-1, ICAM-1, Eselectin, and L-selectin for various immune cells
Receptor upregulation increases extravasation of PMNs, monocytes, activated T-helper and T-cytotoxic cells, as well as
memory T and B cells to the infected site
Inflammation can lead to anemia, because shift to making more inflammatory cells rather than RBCs
Cytokines:
Soluble mediators that play an important role in immunity
Small molecular weight peptides or glycopeptides

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Many produced by multiple cell types such as lymphocytes, monocytes/macrophages, masts cells, eosinophils, even
endothelial cells lining BVs
Each individual cytokine can have multiple functions
Depends upon the cell that produces it & the target cells upon which it acts (pleotropism)
Several different cytokines can have the same biologic function (redundancy)
Exert their effect:
1) on distant targets through the bloodstream (endocrine)
2) on target cells adjacent to those that produce them (paracrine)
3) on the same cell that produces them (autocrine)
Most important effect of most cytokines is paracrine & autocrine functions
Major functions appear to involve host defense or maintenance and repair of blood elements
Four major categories of cytokines:
Interferons:
A family of inducible glycoproteins produced by eukaryotic cells in response to viral infections
The fact that eukaryotic cells produce interferon can be used to distinguish viral infections from other microbial
assaults!!!!!
Interfere w/ virus replication
Act to prevent the replication of a range of viruses by inducing resistance
Elaborated by infected host cells that protect non-infected cells from viral infections
Induce viral resistance in adjacent, non-infected cells
Do not block the entry of the virus into a cell, but rather prevent the replication of viral pathogens w/in protected
cells
Are not antiviral antibodies
Have no direct effect on viruses
Antiviral action is mediated by cells in which they induce an antiviral state
Considered a non-specific innate resistance factor (as are lysozyme, complement, etc.)
Interferon proteins do not exhibit specificity toward a particular pathogen
Means interferon produced in response to one virus is also effective in preventing replication of other viruses
Alpha and Beta Inhibit viral protein synthesis
Gamma Increase MHC I expression and Antigen presentation in all cells
Tumor Necrosis Factors (TNF):
Injecting them into animals causes a hemorrhagic necrosis of their tumors
Secreted by activated macrophages Easier to eat dead stuff
Interleukins (largest group of cytokines): Lots of questions on 2006/2007 exam w/ interleukins
Fundamental function appears to be communications between (inter-) various populations of WBCs
Group of well-characterized cytokines produced by leukocytes & other cell types
Have broad spectrum of functional activities that regulate the activities & capabilities of a wide variety of cell types
Particularly important as members of cytokine networks that regulate inflammatory & immune responses
Act as messengers between leukocytes involved in the immunologic or inflammatory response
Think mmm Hot T-Bone stEAk
IL-1:
A macrophage-derived factor study page 73 path book
Stimulates activites of T-cells, B-cells, & macrophages
Stimulates IL-2 secretion
Pyrogenic (HOT)

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IL-2:

Produced by activated T cells (T- in T-bone)


Stimulates antigen-activated T helper & NK cells (as well as cytotoxic T cells)
Also stimulates B cells

IL-3:

T-cell product that stimulates the growth & differentiation of various blood cells in bone marrow
(B in T-Bone)
Secreted by activated T cells

IL-4:

Secreted by activated helper T cells & mast cells


Stimulates B-cells
Increases IgG & IgE (E in stEAk)

IL-5:

Secreted by activated helper T cells


Promotes B cell maturation
IL-5 is a B-cell growth & differentiation factor
Increases IgA & synthesis of Eosinophils (A in stEAk)

Acute Phase cytokines


IL-1, IL-6, and TNF alpha (secreted by macrophage to do a bunch of stuff)
IL-6, 7, 8, 10, 12: see Kaplan, p. 152 for thie summaries
Colony Stimulating factors (CSF):
They support the growth and differentiation of various elements of the bone marrow
Neutrophils: (aka polymorphonuclear leukocytes or PMNs)
Most numerous WBC (5075%)
Increase dramatically in response to infection/inflammation
Fxns:
Phagocytosis of bacteria
Elaboration of proteolytic NZs
1st cells to infiltrate the inflammation cite
PMNs kill by 1) toxic O2 metabolites & 2) digestive enzymes from lysosomal granules
Oxygen-dependent killing of bacteria by PMNs involves:
Superoxide, Myeloperoxidase, Hydrogen Peroxide, NADP Dehydrogenase
NOT collagenase
Remember in Gingivitis you have lots of PMNs,
In order get to PD, you need Collagenase, which comes from Lymphocytes!!!!
Enzymes include myeloperoxidase (azurophilic granules) & lactoferrin (specific granules)
Primary constituent of pus
Highly mobile cells attracted to areas of inflammation by chemotaxis
They reach the tissues by diapedisis
Identify, attach to & begin engulfing the invading organisms in attempt to contain the infection
If infection continues, monocytes arrive (better engulfing ability)
NZs responsible for suppuration in an abscess are derived from PMNs
Inflammatory substances:
Process of attraction and recruiting cells in which a cell moves toward a higher concentration of a chemical substance
The Vasodilators:
Histamine
Bradykinin
C3 and C5 (via mast cells/Histamine)
Prostaglandins
Histamine:
Formed from histidine by decarboxylation
Released from the coarse cytoplasmic granules of tissue mast cells & basophils
In early stages of acute inflammation, histamine mediates the contraction of endothelial cells
Histamine is liberated by degranulation triggered by the following stimuli:
Binding of specific Ag to basophil & mast cell MB-bound IgE
TEST wording: Histamine release requires antibodies (IgE) attached to mast cells and reacting with
antigen
Binding of anaphylatoxins (C3a & C5a) to specific cell-surface receptors on basophils & mast cells
Release causes: increased capillary permeability, bronchial constriction, increased gastric secretion, and a drop in BP
Responsible for the principal symptoms of anaphylaxis
Serotinin has similar actions
Serotonin:
Also called 5-hydroxytryptamine
Synthesized from the aa tryptophan by enteroendocrine cells in the gut & bronchi
Plays a role in temperature regulation, in sensory perception, and in the onset of sleep
Powerful vasoconstrictor Downstream??? And vasodilator
Stimulates platelet aggregation (blood clotting)
Largest amount is found in cells of the intestinal mucosa
Smaller amounts in platelets & in CNS
In CNS:
Acts as a neurotransmitter in the brain
Inhibitor of pain pathways in spinal cord
Lysergic acid diethylamide interferes w/ action of serotonin in the brain
Secreted in tremendous quantities by carcinoid tumors (tumors composed of chromaffin tissue)
Kaplan says, 5-HIAA is secreted, which is a metabolite of serotonin
Bradykinin:
Vasoactive kinin potent vasodilator
Mediates vascular permability, arteriolar dilation, & pain
Pain in inflamed tissue is associated with the Bradykinin mediator

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Produced by the action of kallikrein (generated by activated Hageman factor, factor XIIa) on an alpha-2 globulin
(kininogen)
Chemical mediator of acute inflammation that is generated through the activation of an enzyme precursor (Kallikerin)
that requires activated Hageman factor
Hageman factor helps to create Bradykinin
May be involved in BP regulation
Arachidonic acid:
An unsaturated fatty acid generated by inflammatory cells and injured tissue
Major compound from which prostaglandins, prostacyclin thromboxanes, & leukotrienes are derived
Part of phospholipids in plasma MBs
When a neurotransmitter or hormone stimulates a cell, activating phosholipase A (a plasma MB enzyme)
PLA splits arachidonic acid from the phospholipids
Different metabolic pathways utilize different enzymes that convert arachidonic acid into the different messengers:
1) Cyclooxygenase: prostaglandins, prostacyclins, & thromboxanes (NOT leukotrienes)
Prostaglandins chemical messengers present in every body tissue
Act primarily as local messengers that exert their effect in the tissues that synthesize them
*PGG2 is converted to PGH2, which is ultimately converted to TxA2
2) Lipooxygenase: leukotrienes, HETEs, diHETEs
Leukotrienes:
A group of compounds derived from unsaturated FAs (arachidonic acid & other polyunsaturated FAs)
Extremely potent mediators of immediate hypersensitivity reactions & inflammation
Leukotrienes C4, D4, & E4
Collectively known as slow-reacting substances of anaphylaxis (SRS-As)
Responsible for development of many symptoms associated w/ allergic-type reactions
100-1000x as potent as histamine or prostaglandins in constricting bronchi
In asthma, the allergic reaction occurs in the bronchioles of lungs
The most important products released by mast cells are SRS-As (the 1 mediators of asthma)
SRS-As causes bronchiolar smooth muscle spasms
Anaphylatoxins C3a & C5a induce physiological response that results in BV dilation, hypotension, vascular permeability
Acute Inflammation:
The initial response of tissue to injury, particularly bacterial infections, involving vascular and cellular responses
What is involved in the early phase of wound repair?
Inflammatory
bacteria and debris are phagocytosed and removed, factors are released that cause the migration
and division of cells involved in proliferative stage
Proliferative and Maturation are more in chronic
Three major phenomena:
1) Increased vascular permeability tissue exudate forms
Mean capillary pressure decrease and osmotic pressure decreases in acute inflammation
2) Leukocytic cellular infiltration mainly PMNs via C5a & C3a
3) Repair regeneration or replacement
Chemotactic accumulation of mononuclear cells which occurs at the sites where immune complexes were deposited is
probably the result of C3 (only if C5a is not an answer)
Local signs:
Redness = rubor, Heat = calor, Swelling = tumor, Pain = dolor, organ dysfunction
Systemic effects:
Fever, Tachycardia, Leukocytsosis (esp. PMNs)
Vascular phase:
Vasoconstriction (temporary) seen as blanching of skin
What happens before Vasodilation in inflammation??? Vasoconstriction
Only transient
Vasodilation increased blood flow to infected area
Happens immediately after vasoconstriction
Done by Histamine, Bradykinin, and Serotonin
The 1st vascular reaction (following transient vasoconstriction) to injury in the sequence of events in inflammation
Increased permeability allows diffusible components to enter the site
Congestion in the early stages of inflammation is caused by active hyperemia (NOT ischemia, venous dilitation,
venous constriction, lymphatic obstruction)
Cells
Basophils, Mast cells, Platelets present in vascular phase all release histamine
Vasodilation and increased permeability lasting for several days in an area of inflammation indicate
Endothelial cell damage and dysfunction

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Cellular phase:
Leukocytes (mainly PMNs) are the 1st defense cell to migrate to the injured tissue chemotaxis
Leukocytes engulf particulate matter by phagocytosis
Engulfed matter becomes a phagosome combines w/ lysosomal granules to form a phagolysome for digestion
Cells
PMNs predominate
Macrophages appear late & mark transition between acute & chronic inflammation
NOTE: Eosinophils predominate in allergic reactions & parasitic infections
Chronic Inflammation:
Develops at a site of injury that persists longer than several days
Cells: Lymphocytes, Macrophages, and Plasma Cells not PMNs or Mast Cells
Necrosis commonly occurs & recurs
EXs: chronic hepatitis, pyelonephritis, and autoimmune diseases
Granulomatous inflammation:
A subtype of chronic inflammation characterized morphologically by granulomas
Proliferative processes dominate (NOT exudation, transudation, and congestion)
Characterized by a circumscribed collections of lymphocytes, macrophages, epitheliod cells with a background of
fibroblasts, capillaries, and delicate collagen fibers
EXs: TB, sarcoidosis, & silicosis
Vasodilation & vasopermeability lasting several days in inflamed area indicate formation of granulation tissue
Initial vasodilation of inflammation is due to serotonin, histamine, bradykinin
SIDENOTE
Chronic Granulomatous Disease
Hereditary disease where neutrophil granulocytes are unable to destroy ingested pathogens
Neutrophils normally require a set of enzymes to a reactive oxygen species to destroy bacteria after their phagocytosis
These NZs are called phagocyte NADPH oxidase complex, which is responsible for initiating the respiratory burst
SO in CGD, PMNs ingest baceria but then cannot kill them
MOST infections are caused by Staph Aureus, or CATALSE + bugs
Hence bugs that destroy the respiratory burst are left behind to cause chronic GD
Inflammatory Infiltrate
Fluids, PMNs, and Macrophages
Exudates:
Principally water also contains nutrients, oxygen, Ab/s & WBCs
Characterized by being protein-rich, cell-rich, glucose-poor & has a high specific gravity (> 1.020)
First role flush away any foreign material from site of injury
If fluid is cloudy/discolored strong indication of infection
Acts as a carrier to bring fibrin, etc., to the site of injury
Acts as a carrier for leukocytes provides oxygen/nutrients for ingestion of bacteria & debris
Nutrients are used by the new tissue to help in the generation of granulation tissue
Act as a lubricant, speeding up epithelial cell migration across wound surface to complete initial repair
Types of imflammatory exudates:
Suppurative
Purulent
Fibrinous
Pseudomembranous
Serous
NOT Fibrous
Acute inflammatory exudates
Includes Plasma fluid, plasma proteins and WBCs
NOT Plasma cells
Transudates: think of transudate as being pushed trans the filter thus lower ptns etc
Result from intravascular hydrostatic pressure or from altered osmotic pressure
Thin & watery characterized by few blood cells, low protein content, & low specific gravity (< 1.020)
Differs from Exudate by having a lower protein concentration
Present in non-inflammatory conditions, such as cardiac failure
Most common acute inflammatory reactions
Contain large # of PMNs
Termed suppurative (produce purulent matter)
Suppuration is the result of tissue necrosis, proteolytic enzymes, WBCs, & fluid buildup
NZs responsible for suppuration are found in the PMNs
NOT the result of the presence of lymphocytes suppurative does not simply = Lymphocytes!!!
Abscess:

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Confined collection of pus, which consists of dead WBCs & necrotic tissue
Surrounded by a wall of proliferation fibroblasts (produce collagen) bodys attempt to limit spread of infection
Cyst:
Abnormal sac w/in the body containing air or fluid
Lined w/ epithelium
Granulation Tissue:
Newly formed, highly vascularized CT associated with inflammation
Composed of:
Lymphocytes
Fibroblasts
Macrophages
Endothelial cells
Newly Formed Collagen
Capillary Buds
NOT Giant cells, Nerve cells, or Epithelioid cells, or Plasma cells these are Granulomatous
Granuloma:
Differentiate!!!!
Central necrosis surrounded by macrophages, lymphocytes, plasma cells, and occasional giant cells
Nodular collections of epithelioid cells specialized macrophages
Epithelioid cells are characteristic of granulomas (NOT granulation tissue)
Rim of lymphocytes, plasma cells, & fibroblasts surround the nodule of epithelioid cells
Produced by multinucleated giant cells (aka Langerhans giant cells & foreign body giant cells)
Multinucleated giant cells of the foreign-body type originate from fusion/division of mononuclear cells
(macrophages)
Characteristically associated w/ areas of caseous necrosis produced by infectious agents, particularly M. tuberculosis
Granulomatous inflammation is a subtype of chronic inflammation
Etiologic agents associated w/ granulomatous inflammation:
Infectious agents:
Mycobacterial diseases TB & leprosy
Girl with ulcerated lesion on tongue has Langerhans cells and granulomatosis, what is the disease???
Tuberculosis Granuloma???
Fungal infections blastomycosis, histoplasmosis, & coccidiomycosis
Spirochetes: T. pallidum, which causes syphilis
Cat scratch disease caused by Bartonella henselae
Foreign material suture or talc
Sarcoidosis unknown etiology, NON-caseating, NON necrotizing (whereas tuberculosis is caseation necrosis)!!!!!
Crohns disease NON-caseating, NON-necrosis, granulomatous inflammation of the gut wall
Healing:
The restoration to integrity to an injured tissue
After the inflammatory phase, wound healing is accomplished by three mechanisms; contraction, repair, and regeneration.
In most instances, all three mechanisms occur simultaneously
Healing by 1st intention:
Healing by fibrous adhesion, w/out suppuration or granulation tissue formation
Occurs when wound margins are nicely apposed, such as in surgical repair of a surface wound
With well-approximated wounds, there is little granulation tissue & the final scar is minimal
Healing by 2nd intention:
Large wound defects
CT repair occurs when the wound is large & exudative large amount of necrotic tissue & suppuration formed
Site fills in w/ a highly vascular, pinkish tissue known as granulation tissue
This produces large, irregular scars
Uncomplicated healing of a wound by secondary intention, observed microscopically after 3 days is most likely to
show...
Ulceration of the epithelial surface
NOT granulomatous inflammation, lack of acute inflammation, or keloid formation
Healing by 3rd intention:
Slow filling of a wound cavity or ulcer by granulations, w/ subsequent cicatrisation (the process of scar formation)
Which hormone establishes the greatest effect on granulation tissue in healing wounds?
Cortisone
Glucocorticoids have been shown to have the greatest effect on granulation tissue
Tensile strength of healing wound depends upon the formation of collagen fibers
Whether a wound heals by 1 or 2 intention is determined by the nature of the wound, rather than by the healing process
Keloids (cheloids):

**

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A nodular, firm, movable, nonencapsulated, often linear mass of hyperplastic scar tissue, tender and frequently
painful
Consist of wide, irregularly distributed bands of collagen fibers
Thick scar that looks like a tumor, and is more common in blacks
Tumor:
Growth of tissue that forms an abnormal mass
Caused by abnormal regulation of cell division
Generally provide no useful function & grow at the expense of healthy tissue
Necrosis:
Set of morphologic changes that accompany cell death w/in a living body
Differs from autolysis a process of cell death outside a living body
May manifest in different ways, depending on the tissue or organs involved
Coagulative necrosis is the most basic and most common type of necrosis
After a kidney infarct you will see coagulative necrosis
When larger areas of tissues are dead, the tissue is called gangrene
Types
Coagulation necrosis
Liquefaction necrosis (infarct to brain)
Caseous necrosis (Caseation)
Gangrenous necrosis

Causes
Ischemia (loss of blood supply)
Suppuration, abscesses & ischemic CNS injury
Granulomatous inflammation (typical of TB)
Calcification and Soapy Think Cheesy
TB Lesion
Putrefactive bacteria acting on necrotic bowel or
extremity
Immune-mediated vascular damage
Injured pancreas, trauma to adipose tissue

Most likely sites involved


Heart & kidney (renal & cardiac infarcts)
Brain or spinal cord
Granulomatous inflammatory sites
Lower extremities or bowel

Fibrinoid necrosis
Arterial walls (RA, Scleroderma, RF)
Fat necrosis
Adipose tissue, pancreas
Basic Types of Necrosis
Two types of necrosis are recognized and are based on the degree of preservation of the architecture of the cells and tissues.
These are as follows:
Coagulative necrosis
Coagulative necrosis is characterised by the preservation of cellular and tissue architecture.
Microscopically, the nucleus, cytoplasm, and cellular outlines including the arrangements of cells in the necrotic
tissue are still intact.
This type of necrosis is often difficult to detect grossly, except probably when the affected area is large where subtle
changes in tissue colour may be recognized. It usually results from acute disease conditions such as acute toxicity
(chemical toxicants or biological toxins) and sudden deprivations in blood supply.
Heart and renal Infarct (MI)
Characteristic nuclear changes:
Pyk- = condense
Kary- = nucleus
Karyolysis destruction of dissolution of the cell nucleus w/ fading of chromatin
Karyolyis of myocardial cell (& probably any other cell type) is irreversible
Think nuclear lysis easy
Karyopyknosis = pyknosis shrinkage of the cell nuclei & condensation of the chromatin
Another Q reads: condensation & shrinking of the cell nucleus w/ chromatin clumping
Think nuclear and pygmy Nuclear shrinking
Karyorrhexis fragmentation of the cell nucleus & chromatin
Karyorrhexis follows karyopyknosis during the process of apoptosis
NOTE: the key point is that these nuclear changes are morphologic hallmarks of irreversible cell injury and
necrosis
Liquefactive or Lytic necrosis
Rapid enzymatic dissolution of the cell that results in complete destruction is called liquefactive or lytic necrosis
(or colliquative necrosis).
It is seen in bacterial infections that lead to pus formation in which proteolytic enzymes are released from leucocytes
Pus is the evidence of liquefactive necrosis Think suppurative, abscesses, and brain injury
In a pt who had an infarct in the middle cerebral arteryanticipated type of tissue alteration would be liquefaction
necrosis
Brain or spinal cord
Suppuration
Acute pyogenic infections are associated with suppuration
Strep Pyogenes Causes liquefactive necrosis

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Special Forms of Necrosis


1) Fat Necrosis - occur in two forms:
Traumatic Fat Necrosis result from rupture of fat cells because of trauma
Enzymic Fat Necrosis occurs following the enzymic splitting of fat into fatty acid and glycerol by action of lipases
(seen in chronic pancreatitis)
Causes soap formation and calcification
2) Zenker Necrosis (Zenker degeneration) - loss of striations in muscles following necrosis (a type of coagulative necrosis in
striated muscles)
3) Caseation Necrosis - the presence of friable, cheesy or pasty, amorphous material in necrotic area, usually reserved but
not limited to those seen in tuberculous lesions
4) Fibrinoid Necrosis - a special form of necrosis associated with the accumulation of fibrinoid (see protein overload) in
connective tissues and blood vessel walls
5) Gangrenous Necrosis (See Below) - necrosis of tissue following deprivation of blood supply, and putrefaction following
invasion by saprophytic bacteria. If it is moist, it is called Wet Gangrene. If moisture is not present, it is called Dry Gangrene
6) Infarct - a form of coagulative necrosis resulting from a sudden deprivation of blood supply (process: infarction, see under
haemodynamic changes)
Other Terms Used in Association with Necrosis
1) Malacia - an area of liquefactive necrosis of the nervous tissues. Literally mean "softening"
2) Slough - a piece of necrotic tissue separating from viable tissue. Applied to necrosis of surface epithelia.
3) Ulcer - shallow area of necrosis, applied to epithelial surfaces.
4) Sequestrum - an isolated area of necrosis warded off from viable tissue. Applied to isolated necrosis of bones.
Gas Gangrene:
Results from local infection w/ the anaerobic, spore-forming, G+ rod Clostridium perfringens
C. perfringens produces toxins that kill nearby cells
Rare infection generally occurs at site of trauma or a recent surgical wound (devitalized tissues)
Results from compromised arterial circulation
Onset is sudden & dramatic
Inflammation begins at infection site a pale to brownish-red & extremely painful tissue swelling
Gas may feel as a crackly sensation when the swollen area is pressed on
Margins of infected area expand rapidly changes are visible over a few minutes
Involved tissue is completely destroyed
Gangrene is the death of tissue usually associated w/ loss of blood supply to the affected area.
A form of necrosis combined w/ putrefaction (decomposition, rotting)
Systemic symptoms sweating, fever & anxiety
If untreated, pt develops a shock-like syndrome w/ BP, renal failure, coma, & death
Prevented by proper wound care
Clostridium bacteria:
Produce many different toxins (alpha, beta, epsilon, iota)
Most important toxin is alpha toxin (lecithinase) damages cell MBs, including erythrocyte MBs (hemolysis)
Dont know where this should go: But hypoxia can lead to increased intracellular Na
GASTROINTESTINAL TRACT
ORAL CAVITY
Normal healthy mouth:
Consists of mainly obligate & facultative anaerobes, aerobes, and acidogenic bacteria
1979 reads: anaerobic, facultative, & acidogenic (NOT anaerobic, aerobic & facultative)
1989 reads: the single most numerous group of microorganisms in the oral cavity is facultative streptococci
Most oral streptococci are alpha-hemolytic
Least likely bacteria in the mouth is Mycobacterium
(other options were: Fusobacterium, Prevotella, Actinobacillus, Porphyromonas)
Bacteria with limited range of habitats in the oral cavity are:
Treponema and Bacteroides (Streptococcus & Actinomyces do not have a limited range in the O.C.)
After two teeth were extracted, a foul smelling, purulent material drains, which bugs are responsible:
Bacteroides and Peptostreptococcal (NOT salmonella, clostridium)
Essentially the same bacteria found healthy gingival sulcus become opportunistic & influence the course of PD disease
Obligate anaerobes are found in the oral cavity as part of the normal flora; they are opportunistic
ABX, Anticancer therapy, & corticosteroids all would affect the oral microflora
Progression from a healthy gingival sulcus to gingivitis is associated with a shift towards more G- anaerobic rods (not cocci)
Most dramatic change to the Oral Flora occurs when primary teeth erupt dont have s. mutans till then
Gingival sulcus (Periodontal Pocket):

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Principal oral site for growth of Spirochetes, Fusobacteria, & other G- anaerobes
Endotoxin (LPS) accumulates in the gingival crevice in the absence of gingival hygiene endotoxin since bact are gm Inhabitants
Normally G- anaerobic Rods and Fusobacteria
Treponema, Bacteroides, Actinobacillus, and Fusobacterium
NOT Mycobacteria
Actinomyces naeslundii
Branching, filamentous microorganism that is a normal inhabitant of the gingival crevice and tonsilar crypts
Crevicular Fluid
Contains:
IgA, IgG, Lymphocytes, PMNs
NOT IgE
Most numerous Leukocyte is the Gingival Crevicular Fluid is the Neutrophil
Area of stagnation & bacterial proliferation; due to:
1) increase in crevicular gingival fluid
2) desquamation of epithelial cells
3) bacterial acid products
Microbial population of the perio pocket is of a low order of intrinsic pathogenicity means they are opportunistic
The fact that oral microorganisms can enter the body by way of gingival sulci and perio pockets is evidenced by.
The transient bacteremias following dental procedures
Aerosolizatoin
Dental instrument causing aerosolization of large numbers of bugs is the.ultrasonic scaler
The aerosolization produced during dental procedures usually cotains gram POSitive bugs
Most of the the bugs in the dental operatory come from the pts mouth
Xerostomia
Lost taste can be from medication induced xerostomia
Most pronounced effect on reduced salivary flow is a shift toward more acidogenic microflora
Caries:
Strep bacteria (G+, facultative anaerobes):
Most numerous group of bacteria in oral cavity
S. mutans major cariogenic property is ability to produce dextrans & GTF (glucosyltransferase)
First stable colonizer of the OC
S. sanguis the most frequently isolated Strep in the oral cavity; produces H2O2; usually 1st to colonize plaque
S. salivarius found consistently in saliva & oral soft tissue (including under tongue)
Found commonly on the dorsum of the tongue (NOT S. mutans, L. acidophilus, P. melanginogenica)
S. mitis produces H2O2
Properties necessary for caries formation:
Adhere to tooth surface (colonize)
Produce lactic acid (from degradation of glucose)
Produce a polymeric substance (from CHO metabolism) causes acid to remain in contact w/ tooth
Produce dextran sucrase (GTF)
Caries process:
GTF catalyzes the formation of extracellular glucans from dietary sucrose
Glucan production contributes to the formation of the dental plaque
Dental plaque holds lactic acid (produced by Strep bacteria) against the tooth
The acid eats through enamel creating caries
Acidogenic microorganisms are the most important causative agents of dental caries (Lactobacillus and
Streptococcus families)
The ability of certain oral bugs to produce caries appears to be correlated with their capacity to produce an extracellular
polysaccharide dextran-like substance involved in the formation of dental plaque
Prerequisites for caries development:
Cariogenic bacteria
Susceptible host
Supply of substrate for lactic acid production
Bacteria that may be etiologically related to dental caries:
S. mutans, salivarius, sanguis (not S. mitis, although it is found in dental plaque)
A. viscosus, naeslundii, israelii
A. viscosus & A. naeslundii cause root-surface caries
NOT israeli
L. casei acidogenic
Bacteria that initiate caries must have ability to produce extracellular insoluble glucans

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Dextrans & mutans polymers of glucose (Extracellular polysaccharides)


Produced by S. mutans, sanguis, salivarius, & Lactobacillus species
Levans (fructans) polymers of fructose
Produced by S. mutans, sanguis, salivarius & L. casei, acidophilus
Dextrans, mutans & levans are synthesized from dietary sucrose by cariogenic & plaque bacteria
S. mutans acts on sucrose to produce levans and dextrans
In S. mutans, the end-product of glucose metabolism is lactate
Plaque
Features:
Key etiologic agent in initiation of gingivitis & PD disease
For a bacterium to be seriously considered in the etiology of dental caries, it must exist regularly in the dental plaque
Accumulation of a mixed bacterial community in a dextran matrix
Forms on a cleaned tooth w/in minutes
Composed of 80% solids (95% bacteria) & 20% water
Two categories: supragingival & subgingival
Proportions of varying plaque bacteria (cocci, rods, & filaments) change w/ time, diet & location
Direct association between amount of bacterial plaque and amount of gingival inflammation
Stages of plaque formation:
Formation of the pellicle (acquired pellicle):
Surface coating of salivary origin primarily protein in nature w/ some CHO complexes
Essentially structureless & bacteria free
Forms w/in minutes on a clean tooth surface due to its salivary origin
Also forms on crowns, dentures, & porcelain
Bacterial colonization:
Bacteria attach to pellicle in a somewhat orderly fashion
Cocci (Streptococci) first colonize in tremendsouly large #s
After a tooth erupts, what increases most rapidly??
aerobic gram + makes sense, now in aerobic
environment
Facultative Gram + (choose this if listed as an option)
Rods (Bacteroides & Fusobacterium) then colonize tooth surfaces
As plaque matures, shift in morphology to include filamentous types (Actinomyces)
Maturation stage:
Saliva continues to provide agglutinating substances & other proteins to the intercellular matrix
Bacterial intercellular adhesion results
The crystalline structure increases & eventually calcifies
Average time for whole process is 12 days for calculus
Supragingival plaque
Attached or tooth associated
Consists primarily of G+ facultative anaerobic cocci
Fewer anaerobes than subgingival plaque
S. sanguis, A. viscosus & A. naeslundii predominate?????
With time, Vibrio species, Spirochetes, & G- bacteria predominate
Subgingival plaque:
Attached or loosely adherent (epithelium associated)
Dominated by G- rods as pockets form
More anaerobes than supragingival plaque
Actinomyces species, F. nucleatum, Treponema species (spirochetes), and Veillonella (sulcus)
Young plaque: -- REVIEW
G+ cocci (40-50%) Streptococcus I think gm + and gm and rods and cocci are ~ equal
G+ rods (10-40%) Lactobacillus
G- rods (10-15%) Fusobacterium, Actinobacillus (not many until plaque matures)
Filaments ( 4%) Actinomyces & Veillonella
As plaque age:
50% G+
30% G+
# of cocci # of rods then filaments
# of aerobic bacteria
# of anaerobic bacteria
Calculus:
Calcified/mineralized bacterial plaque
Forms by bathing plaque in saliva high [Ca] & [P]
Surface is very rough & is covered by a layer or bacterial plaque
Inorganic components

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70-90% of the composition


Ca & PO4 w/ small amounts of Mg & CO3 (derived almost entirely from saliva); also hydroxyapatite & F
Organic components & water
Remainder of composition
Includes an abundance of Microorganisms (same as plaque), desquamated epithelial cells, leukocytes, & mucin
Main role in PD disease serves as a collection site for more bacteria
Subgingival calculus is dark due to pigments from blood breakdown
Root Canals
Preferred Bacteriologic media for culturing root canals:
Thioglycollate broth I dont know why youd ever want to culture those root canals, but if ye did, yed use a
thioglycollate broth!
Periodontal Disease
Gingivitis
Oral bacteria play a role in gingivitis is proven by.a reduction of inflammatory states with ABX OR by reduction in
inflammation after removal of the bacteria
Periodontitis
The normal oral microflora causes PD
Most likely source of bacteria playing a role in PD is from the Subgingival plaque
Bacterial endotoxins play a role in PD due to their role in inciting an inflammatory response
As the severity of PD increases, there is an increase in plasma cells that produce IgG makes sense because this is
just going from acute to chronic inflammation
In pts with chronic PD, when the T cells react with certain plaque bacterial antigens, they produce:
IL-2, TNF-alpha, IFN-gamma
NOT Immunoglobulin duh t cells NEVER produce Ig
Actinobacillus:
G- coccobacillary rods
A. actinomycetemcomitans
Part of normal flora in upper respiratory tract
Rare opportunistic pathogen causes endocarditis on damaged heart valves & causes sepsis
Most commonly implicated w/ the etiology of:
Localized juvenile periodontitis (LJP) now called Aggressive Localized Periodontitis
17 yr old with sparse plaque and periodontitis (A. actinomycetemcomitans)
Periodontitis in juvenile diabetes
Acute necrotizing ulcerative gingivitis (ANUG): Vincents infection or trench mouth
Condition which presents rather pathognomonic (indicative of disease) clinical signs/symptoms
Pathognomonic = Characteristic of a single disease
Two most important clinical sings:
1) Interproximal necrosis & pseudomembrane formation on marginal tissues
This is why we know its P. intermedia think Interproximals
P. intermedia messes with the Papilla INTERproximially
2) History of soreness & bleeding gums caused by eating & brushing
Other signs/symptoms fetor oris (offensive odor), low grade fever, lymphadenopathy, & malaise
PMN predominates in inflammatory infiltrate of ANUG
Because its a gingivitis
Occurs most often in adults between 18-30 y.o.
Predisposing factors Hx of gingivitis, tobacco smoking, gross neglect, fatigue, & stress
Associated bacteria:
Prevotella intermedia you get this as a teenager
Fusobacterium species
Intermediate-sized Spirochetes
Selenomonas species
Topical Antimicrobials:
Chlorhexidine:
Most effective antimicrobial agent for long-term reduction of plaque & gingivitis
Leaves greatest residual concentration in mouth after use
Rapidly absorbed onto teeth & pellicle slowly released
Characterized by a cumulative antimicrobial effect substantivity!!!
ADA: approved as antimicrobial & antigingivitis agent
Peridex & PerioGard
Stannous fluoride:
Antimicrobial action related to the tin ion rather F

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Available in gel form (e.g., Stop, Gel-Kam)


ADA: approved as anticaries but not antiplaque/antigingivitis
SIDE NOTE: Fluoride is most effective and safest as a prophylactic measure when its added to the water supply
Phenolic compounds:
ADA: approved as antimicrobial & antigingivitis agent
Listerine
Quaternary ammonium coumpounds:
Not as effective as others in reducing plaque or gingivitis
Best at eliminating halitosis
Scope & Cepacol
Mechanism of action is against the cytoplasmic membrane
Mandible Infection
Soft tissue infection speading along the mandible and into the floor of the mouth would likely involve:
Eikenella corrodens, Staph aureus, Strep pyogenes, Peptostreptococcus anerobius, and Bacteroides!!!!!
Ludwigs angina:
Aka submandibular space infection or sublingual space infection
Not often seen
An extension of infection from the Mn molar teeth into the floor of mouth
Characteristics:
First brawny induration that doesnt pit on pressure. No fluctuance is present
Secondly three facial spaces are involved bilaterally: submandibular, submental, and sublingual spaces
Thirdly the patient has a typical open-mouthed appearance
It has a rapid onset
Dysphagia, dyspnea, and fever are present
May swell to block airway = emergency
Goal of emergency Tx is to maintain open airway (intubation or tracheostomy, if needed)
Abx (usually penicillin-like drugs) are given via IV to treat until symptoms diminish then given orally
Most cases appear to be mixed infection Streptococci almost always present
Cervicofacial actinomycosis (Aka lumpy jaw):
Chronic infection w/ Actinomyces, usually A. israelii
Actinomyces and Nocardia are gram + rods forming long branching filaments, LIKE FUNGI
SNAP
Sulfa for Nocardia, Actinomyces use PCN
Branching, G+, microaerophilic, filamentous
NOT dimorphic Duh of course its not, its a bacteria!
Causes very hard, deep infections with broad swelling and draining fistulas
Slow growing, deep, lumpy pyogenic cutaneous abscesses that extrude a thin, purulent exudate through multiple sinuses
A. Israeli causes abscesses
Develops chiefly in the jaws and neck, less frequently in the lungs and alimentary tract
Occurs following tissue damage that is contaminated w/ endogenous organism (also found in healthy oral cavities)
Can be treated w/ long-term PCN therapy SNAP Dont worry lumpy treatment is a SNAP!!!
Actinomyces are G+ filamentous bacteria that are normal inhabitants of the oral cavity and GI tract
Lesion have characteristic sulfur granules Actually misnomer
These are actually colonies of infecting actinomycotic organism
Osteomyelitis is a common occurrence
Infection after pulled tooth from Actinomyces lumpy jaw
Behcets syndrome:
Chronic, relapsing inflammatory disease that can produce recurring, painful mouth sores, skin blisters, genital & ocular sores,
& swollen joints
Involves oral, ocular, and genital lesions (incorrect: herpetiform & recurrent aphthous)
Formation of a pus-like fluid in the anterior chamber of the eye
Pyodermas (pus-producing disease of the skin) are common
Often there is CNS involvement in a variety of forms
Aphthous-related condition w/ associated genital lesions and a genetic predisposition
A multisystem disease of uncertain pathogenesis, consisting of multiple oral, anogenital and ocular apthouslike lesions
Uveitis inflammation of the uveal tract of the eye, including the iris, ciliary body & choroid
Frequently w/ arthralgia (1 ankles and knees), thrombophlebitis, macular and pustular skin lesions and associated CNS
involvement
Hypersensitivity to minor scratches or other irritations
Pharyngitis
Inflammation of the pharynx
Main symptom is a sore throat

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Other symptoms Inflammation, exudates, fever, leukocytosis, lymphadenopathy


Caused by a variety of viruses (adenoviruses & coxsackie viruses)
ESOPHAGUS
Acid reflux:
Backflow of stomach contents upward into the esophagus; most obvious symptom is heartburn
Gastroesophageal reflux:
Clinical symptoms related to reflux of the stomach or duodenal contents into esophagus
Cause: Inappropriate relaxation of lower esophageal sphincter
Crural diaphragm important anti-reflux function, especially w/ increased pressure.
Hiatal hernia interferes w/ crural diaphragm
Crural may be damaged by bile and pancreatic secreations
Associated w/ smoking, some foods and juices
A person with chronic bleeding ulcer in the stomach will most likely present with what?? Esophageal reflux???
Maybe Hematemesis I cant see why itd be esophageal reflux
Heatburn most common sign, also accompanies by dysphagia, regurgitation and bleeding if excessive erosion is present
Dx: w/ barium swallow, ambulatory 24 pH monitor, endoscoopy
Complications include esophageal ulcers, aspiration, and barrett esophagus metaplasia w/ columnar epithelium
increasing incidence of adenocarcinoma. Chronic GERD is associated w/ esophageal carcinoma
Tx: lose weight, use antacids, H2 blockers, and surgery
Barretts esophagus: BARRetts = Becomes Adenocarcinoma, Results from Reflux
Glandular (columnar epithelila) metaplasia: replacement of nonkeratinized squamous epithelium w/ gastric
(columnar) epithelium in the distal esophagus
Achalasia (A-chalasia = absence of relaxation): Makes it A-CHALleng to to swallow food with the distal stenosis
Nerve related disorder of unknown cause that can interfere w/ two processes:
1) Rhythmic waves of peristalsis
2) Opening of lower esophageal sphincter [due to the loss of myenteric (Auerbachs) plexus]
Main symptom: difficulty swallowing both solids & liquids (progressive dyshpagia)
Barium swallow shows dilated esophagus w/ an area of distal stenosis
Associated w/ increase risk of esophageal carcinoma
Hiatal hernia:
Protrusion of a portion of the stomach through the diaphragm
Cause is unknown; most people have minor symptoms
Plummer-Vinson syndrome Notice Plumber is spelled wrong its plummer, thus the problem is with iron deficiency, not lead
Atrophic glossitis, esophageal webs, dysphagia
Associated w/ iron deficiency anemia Which is the most common type of nutrition deficiency
Mallory-Weiss syndrome: Drunk MALLARD (male) ducks always throwing up
Mild to massive, usually painless bleeding due to a tear in the mucous MB at junction of esophagus & stomach
Also characterized by hematemesis (vomiting of blood)
Most common in men > 40, especially alcoholics
Tears are usually caused by severe retching & vomiting
Most common after excessive intake of alcohol DRUNK DUCKS
Treatment varies w/ severity of bleeding
GI bleeding usually stops spontaneously
Tear usually heals in ~10 days w/o special Tx surgery rarely required
Esophageal varices:
Found elsewhere in file
Esophageal cancer:
Risk factors include ABCDEF: achalasia, Barretts esophagus, Corrosive esophagitis/Cigarettes, Diverticuli (eg., Zenkers
diverticulum), Esophageal web/EtOH, Familial
Most common malignant neoplasm of the esophagus is a squamous cell carcinoma not adenocarcinoma from
Barretts. Think that more people drink alchohol than get barrets esophagus!
STOMACH
Pyloric stenosis:
Associated w/ polyhydramnios, hypertrophy of the pylorus causes obstruction
Palpable mass in epigastric region and projectile vomiting at 2 weeks of age. Tx = surgery
Acute Gastritis
Alcoholics?? Yes, and associated with other drugs, stress, trauma, post surgery, etc.
NOT associated with Smoking???? Nope it is not! You think smoke gets all the way into your stomach? Stupid!
Chronic gastritis:
Type A (fundal): (most superior part)
Think 4 As Autoimmune disease, Autoantibodies to parietal cells, pernicious Anemia, Achlorhydria
Type B (antral): (End part of the stomach)

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Think B for Bug


Caused by H. pylori infections
Both increase risk of gastric carcinoma
Not caused by Cigarette Smoke
Peptic ulcers: (Duodenal)
Circumscribed lesions in the mucosal MB from gastric acid & pepsin
80% occur in the duodenum can also develop in lower esophagus, stomach (lower part), pylorus, or jejunum
Most commonly occur in men between ages 20-50
Most commonly located in the first part of the duodenum
Most common symptom = pain
Temporarily relieved by eating
Diet changes dont help
If erosion is sufficiently severe, stomach wall BVs are damaged, & bleeding occurs into stomach itself
Complications:
Duodenal peptic ulcer causes bleeding, stricture, perforation, NOT cancer
This is my good ulcer, pain relieved with eating and NO cancer
Hemorrhage
Most common complication of chronic peptic ulcers
Most likely with duodenal peptic ulcers
Perforation
Most common complication destructive for endothelial cells of peptic ulcers that RESULTS IN DEATH
Perforation with peritonitis
In extreme cases a peptic ulcer can lead to perforation (a hole entirely through the wall of the GI tract
Causes acute peritonitis can lead to death
Stenosis
LEAST common complication is malignant degeneration
Esophageal ulcers:
Caused by repeated regurgitation of stomach acid (HCl) into lower esophagus
Gastric ulcer:
Affect stomach mucosa
Most common in middle-aged & elderly men
Most are benign but carcinoma must be ruled out
Think G Pain Greater w/ meals, which leads to weight loss
Caused by H. pylori infection in 70%; NSAIDs is also implicated
Due to decrease in mucosal protection against HCL
Duodenal ulcer: (Peptic from above)
Erosion in the duodenum lining
Type of peptic disease caused by an imbalance between acid & pepsin secretion and the defenses of the mucosal lining
Inflammation may be precipitated by aspirin & NSAIDs
Commonly associated w/ presence of H. pylori in the stomach
Risk factors aspirin, NSAID use, cigarette smoking, older age
Due to increase in gastric acid secreaion or decrease in mucosal protection
Think D Pain Decreases w/ meals, leading to weight gain
Hypertrophy of Brunners glands
Tend to have clean punched out margins unlike the raised/irregular margins of carcinoma
Not associated w/ corticosteroids and alcohol
20% arent related to H. pylori (other source says that almost 100% are caused by H. pylori), NSAIDs or elevated gastrin
& are idiopathic
Tx of H. pylori w/ triple therapy:
metronidazole, bismuth salicylate, & amoxicillin or tetracycline
Zollinger-Ellison syndrome (uncommon):
Gastrin-producing tumor leading to increased HCl & multiple persistant ulcers
Usually located in the pancreas
May be associated with MEN Type I
50% are malignant
A decubital ulcer is an example of tissue destruction caused by ischemia
A chronic ulcer that appears in pressure areas of skin overlying a bony prominence in debilitated patients confined to bed
or otherwise immobilized, due to a circulatory defect, hence the ischemia
Stomach cancer:
Almost always adenocarcinoma Think about it how many squamous cells line the stomach NOT MANY!
Esophagus is SCC
LUNG is Adenocarcinoma

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Early aggressive local spread and node/liver metastasis


It is associated w/ dietary nitrosamines, achlorhydra, chronic gastritis
Is NOT etiologically associated w/ smoking Continued trend smoking does NOT get into the stomach! Different pipe!
BUTSmoking about doubles the risk of stomach cancer for smokers American Cancer Society
Termed linitis plastica when diffusely infiltrative (thickened, rigid appearance)
Associated:
Virchows node: involvement of suprclavicular node by metastasis from stomach
Krukenbergs tumor: bilateral metastasis to ovaries. Abundant mucus, signet-ring cells
SMALL INTESTINE
Meckels diverticulum
A true diverticulum due to persistence of the omphalomesenteric vitelline duct
True meaning it has the muscularias propria layer
Most are acquired, and False
Atresia congenital absence of a region of bowel
Stenosis narrowing, which may lead to obstruction
Diarrhea:
Types:
Osmotic: secondary to poorly absorbable solutes, (laxatives), slows w/ fasting
Secretory: caused by toxins like enterotoxigenic E. Coli or cholera, large amounts of water, doesnt slow w/ fasting
Drinking water is usually checked for E. Coli
You treat Cholera by replacing fluids (Vibrio cholera)
Exudative: secondary to invasive bacteria like shigella, includes inflammatory bowel diseases. Mainly involves colon.
White cells in stool Makes sense inflamm bowel disease has inflamm cells!
Motility disorder: irritable bowel syndrome, surgical bypass
Tx: treat underlying cause, opiates to slow peristalsis (except in acute infx), replace lost fluids
Bismuth subsalicylateinhibit colonization of enterotoxins
Antibacterial and anitprotozoal
Malabsorption:
Impaired intestinal absorption of dietary constituents
Can cause deficiencies of nutrients, proteins, fats, vitamins, or minerals
Symptoms vary depending on the deficiency
Clinical features: diarrhea, steatorrhea, weakness, weight loss
Steatorrhea results in deficiency of A, D, E, K, and calcium
Vitamin B12 malabsorption occurs in pernicious anemia (due to the absence of intrinsic factor) & in Crohns disease
Summary of Fat-Soluble Vitamins
Vitamin
Physiologic function
Result of deficiency
A
Helps maintain normal body growth & health of specialized
Night blindness, skin lesions, xerophthalmia
tissues (esp. retina); production of rhodopsin (photopigment) (keratinization & dryness of eye tissues)
Promotes differentiation of epithelial cells
D
Essential in bone formation
Rickets in children; osteomalacia in adults
E
Antioxidant
Possible neurologic dysfunction
K
Involved blood clotting
Tendency to hemorrhage
*Helps Produce Prothrombin
Vitamin
Vitamin B1
(thiamine)
Vitamin B2
(riboflavin)
Vitamin B3
(niacin)
Vitamin B6
(pyridoxine)

Deficiency Leads To
Wet beriberi, dry beriberi

Vitamin B12
(cobalamin)

Megaloblastic anemia (i.e.,


pernicious anemia) Neurologic
dysfunction
Megaloblastic anemia
Neuroligic dysfunction is not a
feature
Scurvy, defective formation of

Folic acid
Vitamin C

Cheilosis; glossitis
Pellagra
Cheilosis; glossitis, anemia

Characteristic of Deficiency
High cardiac output; peripheral
neuropathy
Skin fissures at angle of mouth;
inflammation of tongue
Dementia, dermatitis, & diarrhea
Skin fissures at angles of mouth;
inflammation of tongue; # of
RBCs is below normal
Anemia in which there is a
predominant # of megaloblasts &
few normoblasts
Anemia w/ a predominant # of
megaloblasts (abnormally large
nucleated RBCs)
Swollen, bleeding gums, muscle,

Symptoms
Pins and needles sensation, especially
in feet
Sore tongue and cracks at edge of
mouth

Anemia, pins and needles sensation


Anemia
Weakness, bleeding gums

79

(ascorbic acid) mesenchymal tissue & osteoid


joint, & bone pain, abnormal
matrix; defective wound healing
bleeding
Essential in
Impaired collagen formation
bone
formation
Other nutrient deficiencies
Iron anemia
Calcium bone thinning
Vitamin D Bone thinning (Rickets, Osteomalacia, Rachitic Rosary
Vitamin K Tendency to bruise & bleed
Protein Tissue swelling, usually in legs
Malabsorption syndromes:
Develop when nutirents are not absorbed properly into blood
Main characteristic finding = steatorrhea light-colored, soft, bulky, & foul-smelling stool
Celiac sprue = celiac disease:
Autoantibodies to gluten (gliadin) in grains leading to steatorrhea
Associated with people of North European decent
Villus flattening (blunting of villi) and lymphocytic infiltrate, and abnormal D-xylose test
Think you flattened out the Spruce trees
Tends to affect the jejunem, associated w/ dermatitis hepretiformis
10-15% lead to malignancy, often T-cell lymphoma, can be fatal in adults due to development of lymphoma in intestine
Some people develop symptoms as children & others as adults
The longer a person was breastfed, the later the symptoms appear
Other factors the age at which one began eating gluten-containing foods & how much gluten was eaten
Tropical sprue:
Cause is unknown may be related to an infectious organism (E. coli) since it responds to Ab/s
Affects residents of or visitors to the tropics Pretty easy bad shits for ppl in tropics
Typical symptoms steatorrhea, diarrhea, weight loss, & a sore tongue from Vit B deficiency
Disaccharidase deficiency:
Most common is lactase deficiency
Whipples disease: Pooping disease from the whippelii bug
Rare, causes malabsorption due to intestinal infection
Caused by infection w/ Tropheryma whippelii
Contains PAS positive macrophages
Primarily affects middle-aged white men
Slow onset of symptoms skin darkening, inflamed & painful joints, & diarrhea
May be fatal w/o Tx
Intestinal lymphgiectasia:
Disorder of children & young adults in which lymph vessels supplying the lining of small intestines enlarges
Main symptom = massive fluid retention
LARGE INTESTINE
Hirschsprungs disease:
Think your bowels Have SPRUNG out of control (Parasympathetic)
Congenital megacolon characterized by lack of enteric nervous plexus in segment (Auerbachs and Meissners plexuses) on
intestinal biopsy
Due to failure of neural crest cell migration
Presents as chronic constipation early in life.
Dilated portion of the colon proximal to the ganglionic segment, resulting in transition zone
Diverticular disease:
Diverticulum:
Blind pouch leading off the alimentary tract, lined by mucosa, muscularis, and serosa, that communicates w/ the lumen
of the gut
Most diverticula (esophagus, stomach, duodenum, colon) are acquired and are termed false in that they lack or have an
attenuated muscularis propria
Meckels is TRUE
Diverticulosis:
The prevalence of diverticulosis (many diverticula) in pt older than 60 approaches 50%
Caused by increase intraluminal pressure and focal weakness in the colonic wall
Most frequently involve the sigmoid colon
Associated w/ low-fiber diets
Most often asymptomatic or associated w/ vague discomfort
Diverticulitis: duh, the itis means inflammation!
Inflammation of diverticula classically causing lower left quadrant pain (Sigmoid area)

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May be complicated by perforation, peritonitis, abscess formation, or bowel stenosis


Inflammatory bowel diseases
Crohns disease & Ulcerative colitis
Crohns Disease
Ulcerative colitis
Infectious
Possible etiology
Autoimmune
May involve any portion of the GI tract, usually the
Colitis = colon inflammation. Continuous
Location
ileum, small intestines, and colon. Skip lesions, rectal
lesion w/ rectal involvement
sparing
Transmural inflammation. Cobblestone mucosa,
Mucosal inflammation. Friable mucosal
Gross morphology
creeping fat, bowel wall thickening (string sign on x
pseudopolyps w/ freely hanging
ray) linear ulcers, fissures
mesentery
Crypt abscesses and ulcers
Microscopic morphology
Noncaseating granulomas
Strictures, fistulas, perianal disease, malabsorption
Severe stenosis, toxic megacolon,
Complications
nutritional depletion
colorectal carcinoma
Migratory polyarthritis, erythema nodosum
Pyoderma gangrenosum, sclerosing
Extraintestinal
cholangitis
manifestation
Crohns disease = Granulomatous enteritis
Chronic granulomatous inflammation involving any part of the GI tract ileocolitis most common usually skip-lesions
Characterized by non-necrotizing granulomatous inflammation w/ ulcers, strictures, fistulas
Transmural (not limited to mucosa/submucosa)
Etiology unknown; no cure
Think Fat old Crone skipping down a cobblestone road looking at mural
Symptoms:
Cobblestone fissuring of buccal mucosa
Presence of anal fissures
Abdominal pain often right lower quadrant; diarrhea, weight loss, bleeding is uncommon, rectal abscess and fistula
Complications -intestinal obstruction, fistulas, malabsorption, extra intestinal similar to U.C.
Treatment antibiotics, immunosuppression, anti-TNF antibody, surgical -only w/ complications, since disease may recur,
hyperalimentation if significant absorptive problems are present
Ulcerative colitis:
Chronic disease in which the large intestine becomes inflammed & ulcerated
Not transmural
Leads to episodes of bloody mucous diarrhea, abdominal cramps, & fever
Increased familial incidence, decreased incidence in Blacks and increased in Jews
Onset often occurs after smoking stopped, etiology is unknown
Increased incidence of colon cancer w/ pancolitis and duration of more than 10 years
Complications include massive hemorrhage, colonic stricture, polyp, greater risk of adenocarcinoma than Crohns, toxic
dilation and perforation; extra intestinal pyroderma gangrenosum, and erythema nodusm, arthritis, and kidney stones
Pseudomembranous colitis
Clindamycin use allows for proliferation of C. difficile
Tx: vancomycin or metronidazole
Hemorrhoids
External or internal hemorrhoids
Familial polyposis
Familial adenomatous polyposis = familial polyposis coli
Colon becomes covered w/ adenomatous polyps after puberty
Progresses to colon cancer unless resected, associated w/ Gardners syndrome
Deletion on chromosome 5; 5 letters in polyp
Polyps appear in 20s, become symptomatic by 30s, and become adenocarcinoma by age 40 (100% of the time)
Gardners syndrome:
Type of hereditary polyposis
Autosomal Dominant
Various types of noncancerous tumors occur in intestines & elsewhere in the body
Characterized by polyposis of the colon
Carries a high risk of colon cancer
Peutz-Jehgers syndrome: (Polyps Jejunum Syndrome)
Condition in which many small lumps (juvenile polyps) appear in a variety of sites in the GI tract
Most common site = small intestine (esp. jejunum)
Hereditary condition affecting males/females equally
Characterized by melanin pigmentation of oral mucosa, especially of lips & gums- in the pigmented lesion study guide
Polyps are hamartomas not true neoplasms
They do not increase risk of cancer in intestinal tract

81

Pts are at increased risk for cancer of pancreas, breast, lung, ovary, & uterus
Turcots syndrome:
Characterized by polyps along w/ tumors of the CNS
Gastrointestinal Cancer:
Most commonly associated with villous adenoma (NOT diverticulosis, Meckels diverticulum, or duodenal peptic ulcer)
Makes sense that the cancer is associated with the adenoma, not the diverticulum or ulcer right? Sure!
Colon Cancer:
Adenocarcinoma is the most common type of colon cancer assoc. with villous adenoma
Presents w/ rectal bleeding, changed bowel habits, weight loss
Tumors of the L side are more likely to cause symptoms
More common in industrialized nations
Sigmoidoscopic exam can disclose a majority of tumors
Symptoms generally only in late disease
Transverse is NOT most common (Sigmoid)
Another Q says: Adenocarcinomas are most common in Rectosigmoid section hence, then Roto-rooter job
NOT etiologically associated with cigarette smoke (Along with STOMACH)
(Lung, Esophageal, Oral, Laryngeal and Urinary bladder ARE)
BUTRecent studies have shown that smokers are 30-40% more likely to die of colorectal cancer than nonsmokers
American Cancer Society
Intussusception: telescoping of one bowel segment into distal segment; can compromise blood supply (Like a telescope)
Volvulus: twisting of portion of bowel around its mesentery; can lead to obstruction
APPENDIX
Appendicitis:
Possible sequelae of acute appendicitis: general peritonitis, periappendiceal abscess formation, pylephlebitis, hepatic
abscess
Sudden inflammation of the appendix
One of the most common causes of emergency abdominal surgery in children
More common in males peak in the teens & early 20s
Leukocytosis is a Sign of appendicitis
Generally follows obstruction of the appendix by feces, a foreign body, or a tumor (rare)
1st symptom is typically crampy or colicky pain around the navel.
Usually a marked reduction in or total absence of appetite
Often assocatied w/ nausea and occasionally vomiting & low grade fever
As inflammation in increase, pain moves down & to the right localizes directly above the appendix
Appendix is found at McBurnerys point 2/3 of the way from the navel to the right superior iliac crest
Momentary increase in pain when abdomen is pressed, held momentarily, & then rapidly released
Rebound tenderness suggests inflammation has spread to the peritoneum
If rupture, pain may disappear briefly & pt may feel suddenly better
However, once peritonitis sets in, pain returns & pt becomes progressively more ill
Abdomen may become rigid & extremely tender
Appendectomy performed ASAP after Dx
Differntial Dx for acute appendicitis:
Crohns (Left)??? Says right 1 page up
Meckels diverticulitis (Duodenum)
Pelvic Inflammatory Disease
Gastroenteritis with mesenteric adenitis
NOT Duodenal Peptic Ulcer (heart burn) relieved pain with eating in differential for heart attack
Carcinoid tumor
The most common neoplasm of the appendix rarely metastasizes
Tumors secrete high levels of 5HT that does not get metabolized by the liver due to the liver metastases
Results in recurrent diarrhea, cutaneous flushing, asthmatic wheezing, and right-sided valvular disease
PANCREAS (non-endocrine)
Pancreatitis:
Inflammation or infection of the pancreas
Often caused by digestion of parts of pancreas by pancreatic enzymes normally carried to small intestine w/ pancreatic ducts
Acute hemorrhagic pancreatitis:
Caused by obstruction of normal pathway of secretion of pancreatic juice into intestine leads to AUTODIGESTION!!!
Causes
GET SMASHeD
Gallstones, Ethanol, Trauma, Steriods, Mumps, Autoimmune disease, Scorpion sting, Hyperlipidemia, Drugs
Zymogens of proteolytic enzymes are converted into catalytically active form prematurely inside pancreatic cells
Causes painful & serious destruction of the organ can be fatal

82

Associated w/ alcoholism & biliary disease


Manifestations/consequences
Enzymatic hemorrhagic fat necrosis w/ calcium soap formation & resultant hypocalcemia
Hemmorrhage
Inlammation
Fat necrosis
Parenchymal necrosis
NOT Fibrosis
Outstanding symptom severe, knife-like, upper abdominal pain
Dx made by noting the type of pain & by detecting elevated serum lipase (mostly) & amylase enzymes in pts serum
& urine
Chronic pancreatitis:
Strongly associated with alcoholism
Presents w/ steatorrhea, diabetes, and abdominal mass (pseudocyst)
Dx elevated amylase and alkaline phosphatase
BRAIN / NERVOUS SYSTEM
Counterparts
Thyroid
CAUSE:
Hyper (Thyrotoxicosis)
Graves/Plummers
Hypo (Myxedema/Cretinism)
Hashimotos
Adrenal
Hyper
Cushings
Hypo
Addisons
HEAD / BRAIN PROBLEMS
One out-of-place congenital problem:
Neural tube defects:
associated w/ high levels of alpha fetoprotein in the amniotic fluid and maternal serum. Their incidenc is decreased
w/ maternal folate ingesting during pregnancy
Spina bifida occulta:
failure of bony spinal canal to close, but no structural herniation. Usually seen in lower vertebral levels in
association w/ tuft of hair (associated with increased levels of AFP)
Meningocele:
meninges herniate through spinal defect
Meningomyelocele:
meninges and spinal cord herniate through spinal canal defect
Anencephaly: no development
Concussion:
Transient paralysis of cerebral function immediately after head trauma
Manifested by dizziness, cold perspiration, visual disturbance & loss of consciousness
Most people recover completely w/in a few hours or days
Contusion:
Bruise of the brain parenchyma typically involving the subunit of the gyrus
Brain Tumors
Adult
70% above Tentorium (i.e. cerebral hemispheres)
Incidence: Metastases > Astrocytoma (including glioblastoma) > Meningioma
Child
70% below Tentorium (i.e. cerebellum)
Incidence: Astrocytoma > Medulloblastoma > Ependymoma
Subdural head injury:
Traumatic subdural hematomas are among the most lethal of all head injuries, common during abuse cases
See in 15% of head traumas
Tiny bridging veins running between brain surface & its outer covering stretch & tear, allowing blood to collect
These veins rupture due to sudden change in velocity of head during trauma
Signs/symptoms confusion, headaches, disorientation, fluctuating levels of consciousness or coma
Develop gradually over time, occurring several hours or even days after initial injury
Intracranial hemorrhage:
Epidural hematoma
Rupture of middle meningeal artery, often secondary to fracture of temporal bone
Lucid interval; CT shows biconcave disk not crossing suture lines
Subdural hematoma

83

Rupture of bridging veins.


Venous bleeding (less pressure) w/ delayed onset of symptoms.
Seen in elderly individuals, alcoholics, and blunt trauma.
Crescent shaped hemorrhage that crosses suture lines
Pt lapses into a coma and fluctuating levels consiousness hours after blunt traumadx: subdural hematoma
Among most lethal head injuries!
Subarachnoid hemorrhage
Rupture of an aneurysm (usually Berry aneurysm) or AV malformation
Patient complains of worst headache of my life
Bloody or xanthochromic spinal tap
Berry aneurysms:
Aka saccular aneurysms
Most common cause of nontraumatic subarachnoid hemorrhage
90% are in the anterior part of the circle of Willis
MOST common site is the anterior communicating artery (Or branch of the middle cerebral)
In the past, middle meningeal
Rupture, is the most common complication, causes severe headache, and leads to hemorrhagic stroke
Associated with adult polycystic kidney disease, Ehlers-Danlos syndrome, and Marfans syndrome
May result in cerebrovascular accident
Damage to circle of willis, likely from: Berry Aneuysm
Parenchymal Hematoma
Caused by HTN, amyloid angiopathy, DM, and Tumor
Meningioma:
Intracranial tumor arising from arachnoid, usually occurring in adults >30 y.o.
Cerebral infarction (stroke):
Infarction of cerebrum due to arterial occlusion by a thrombus or embolus from the heart or carotid artery
Common signs/symptoms sudden paralysis & numbness on one side of body
Encephalitis:
An uncommon inflammation of the brain
Most commonly caused by VIRAL infection Like HSV
Exposure to viruses via:
Insect bites, food/drink contamination, inhalation of respiratory droplets, skin contact
In rural settings arboviruses carried by mosquitos or ticks or that are accidentally ingested
St. Louis encephalitis is transmitted via mosquito vector (its an arborvirus)
In urban settings enteroviruses are most common (Coxsackie virus, poliovirus, & echovirus)
Other causes:
HSV, varicella, measles, mumps, rubella, adenovirus, rabies, West Nile virus
Once virus is in blood it can localize in brain tissue causing inflammation
WBCs invade to try to fight off infection brain swells can cause destruction of nerve cells, bleeding & brain damage
Symptoms fever, headache, vomiting, photophobia, stiff neck/back, confusion (disorientation, drowsiness, clumsiness)
Meningitis:
Brain & spinal cord meninges become inflamed
May be bacterial OR may be caused by a number of viruses (Echovirus, Coxsackie, Mumps, etc.)
Bacteria are the most common cause of Meningitis thick Neisseria meningitides is BActeria
Dont get clowned, because Encephalitis is from VIRAL
Viral meningitis rarely results in permanent neural damage
CSF Findings in Meningitis
Type
Pressure
Cell Type
Protein
Sugar
Bacterial
Up
PMNs Up
Up
Down
Fungal/TB
Up
Lymphos Up
Up
Down
Viral
Normal/Up
Lymphos Up
Normal
Normal
May be transferred by respiratory droplets
Most common in adults Neisseria meningitidis & S. pneumoniae
N. meningitidis:
Transmission via respiratory droplets
Key virulence factor in N. meningitidis is its antiphagocytic capsule, same as S. Pneumoniae
IgA protease also in an important virulence factor
Treat it w/ PEN G
Most common in children < 2 y.o. H. influenzae
Most common in adults Neisseria meningitidis & S. pneumoniae
Most common in the elderly S. pneumoniae

84

NOTE all 3 of the most common have Capsules


Common Causes of Meningitis
Newborn (0-6 m) Group B Strep, E. coli, Listeria
Listeria Monocytogenes might cause Fetal Death or meningitis (Think the baby goes LISTless)
Dont confuse with Floppy baby (Botulism)
Also causes Dysentery, Cholera, and Gastroenteritis
Children (6 m 6y) S. pneumoniae, N. meningitidis, H. influenza B, Enteroviruses
Adults (6y 60y)
N. meningitides, Enteroviruses, S. pneumoniae, HSV
Adults (60+) S. pneumoniae (#1 in eldely), Gram rods, Listeria
Infecting organism enters body through nose & throat
Signs & symptoms high fever, severe headache, & neck stiffness
Arnold-chiari Malformation Arnold is a MAGNUM man, brain goes through foramen magnum
Brain coming through Foramen Magnum
Syringomyelia
Softening and cavitation around central canal of spinal cord
Crossing fibers of spinothalamic tract are damaged
Bilateral loss of pain and temperature sensation in upper extremities with preservation of touch sensation
Most common C8-T1
Common in Arnold Chiari malformation
Tabes Dorsalis
Degeneration of dorsal columns and dorsal roots due to tertiary syphilis, resulting in impaired proprioception and
locomotor ataxia
Associated with Charcot joints, shooting lightening pain, Argyll-Robertson pupils, and absence of deep tendon reflexes
One out-of-place disorder:
Fetal alcohol syndrome:
Newborns of moms who consumed significant amounts of alcohol (teratogen) during pregnancy (highest risk at 3-8
wks)
Have increased incidence of congenital abnormalities, including pre- & postnatal developmental retardation,
microcephaly, facial abnormalities, limb dislocation, and heart and lung fistulas
Mechanism may include inhibition of cell migration Think that the cells are too drunk to drive where they need to
go!
The #1 cause of congenital malformations in the U.S.
Pt has flat midface, flat nose, and short bridge of nose
NERVOUS SYSTEM
Degenerative disease:
Cerebral cortex:
Alzheimers disease:
Most common cause of dementia in the elderly
Multi-infarct dementia is the 2nd most common cause
Associated w/ senile plaques (beta amyloid core) & neurofibrillary tangles (abnormally phospharylated tau
protein)
Gross cortical atrophy
Familial form (10%) associated w/ specific genes
Picks disease: Think whatd happen if you took an ice pick to the frontal and temporal (two accessible) lobes
Associated w/ Pick bodies (intracytoplasmic inclusion bodies) & is specific for the frontal & temporal lobes
Basal ganglia and brain stem:
Huntingtons disease:
Autosomal dominant inheritance, chora, dementia
Atrophy of caudate nucleus (loss of GABA neurons)
Parkinsons disease:
Think TRAP for being trapped in your body
Tremor (at rest), Rigidity, Akinesia, Postural Instability
Associated w/ Lewy bodies and depigmentation of the substantia nigra
Due to loss of dopaminergic neurons in the caudate & putamen
Rare cases have been linked to exposure to MPTP, a contaminant in illicit street drugs
Signs/symptoms:
Bradykinesia, rigidity, resting tremor, masked faces, dementia
Motor Neuron
Amyotropic Lateral Sclerosis (ALS) (AKA Lou Gehrigs Disease)
Associated with BOTH lower and upper motor neurons (Think ALLS the motor neurons)
Werdnig-Hoffmann Disease
Present at birth as a floppy baby --- Botulism

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Tongue fasciculations
Polio
Lower motor neuron signs
Think Cant play water polio because no lower motor neurons to tread water
Demyelinating Diseases
Multiple Sclerosis:
Demyelinating disease
Disorder of brain & spinal cord (CNS) caused by progressive damage to myelin
Cause is unknown
Results in nerve functioning leads to a variety of symptoms
Spontaneous exacerbations & remissions
90% of pts develop pyramidal tract dysfunction (hyperreflexia, weakness, spasticity)
Disease involves repeated episodes of inflammation of nervous tissue in any area of CNS
Episodes occur when bodys own immune cells attack nervous system
Inflammation destroys myelin sheath in that area, leaving multiple areas of scar tissue (sclerosis) along the
myelin
Results in slower transmission of nerve impulse, leading to symptoms of MS
Affects approximately 1/1000 women more commonly affected
Commonly begins between 20-40 y.o.
Characterized by paresthesia, unsteadiness of gait, incontinence, paralysis, and plaques of demyelination
Plaques are evident in the white matter
Large amounts of protein are found in CSF
Injectable interferon reduces frequency of MS relapses
Periventricular plaques, preservation of axons, loss of oligodendrocytes, reactive astrocytic gliosis
Patients present w/ sudden loss of vision
Classic triad is: Think SIN
Scanning speech, Intention tremor, and Nystagmus
Increase incident w/ increased distance from equator
Progressive multifocal leukoencephalopathy:
Associated w/ JC virus and seen in 2-4% of AIDS patients (reactivation of latent viral infection)
Postinfectious Encephalomyelitis
Metachromatic Leukodystrophy
Guillain Barre syndrome: (Guillen cant lift the Barre)
Inflammation and demyelination of peripheral nerves & motor fibers of ventral roots (sensory effect less severe than
motor)
Causing symmetric ascending muscle weakness beginning in distal lower extremities
Facial diplegia in 50% of cases
Autonomic function may be severly affected (eg., cardiac irregularities, hypertension)
Findings include: elevated CSF protein w/ normal cell count (albumino-cytologic dissociation) and elevated
protein papilledema
Associated with C. jejuni or herpesvirus, but non definite link to pathology
Seizures:
Causes
Children Genetic, infection, trauma, congenital, metabolic
Adults Tumors, trauma, stroke, infection
Elderly Stroke, tumor, trauma, metabolic, infection
Partial seizures: 1 area of the brain
They can secondarily generalize
Simple partial (awareness intact): motor, sensory, autonomic, psychic
Complex partial (impaired awareness)
Generalized seizures:
Absence: blank stare (petit mal)
Myoclonic: quick, repetitive jerks
Tonic clonic: alternating stiffening and movements (grand mal)
Tonic: stiffening
Atonic: drop siezures
Aphasia:
Brocas (expressive): nonfluent aphasia w/ intact comprehension: Brocas areainferior frontal gyrus
Think Broca for Broken speech
Wernickes (receptive): fluent aphasia w/ impaired comprehension. Wernickes areasuperior temporal gyrus
Wernickes encephalopathy is characterized by confusion, ocular disturbance & ataxia of gait
Results from vitamin B1 deficiency
Think W for Wordy, but makes no sense

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Beriberi peripheral neuropathy:


Results from vitamin B1 deficiency
An axonal degeneration w/ 2 demyelination
Mechanism unknown
Myasthenia Gravis:
Neuromuscular disorder characterized by variable weakness of voluntary muscles
Often improves w/ rest & worsens w/ activity
Condition is caused by an abnormal immune response
Immune system produces auto Ab/s that attack ACh receptors that lie on the muscle side of the nm junction
This decreases responsiveness of muscle fibers to ACh released from motor neuron endings
Characterized by:
Muscle atrophy
Thymic hyperplasia or neoplasm (THYMOMA)
Antibody to acetylcholine receptors
NOT CNS degeneration
Pts have higher risk of having other autoimmune disorders (e.g., thyrotoxicosis, RA, & SLE)
Affects ~3/10,000 people most common in young women & older men
~10% of the pts develop a life-threatening weakness of muscles needed for breathing (called myasthenic crisis)
Eaton-Lambert syndrome:
Similar to myasthenia gravis in that its also an autoimmune disease that causes weakness
Caused by inadequate release of ACh rather than by abnormal Ab/s to ACh receptors
(Think they were Eaton up all the Ach!!!)
Similar to Clostridium Botulism (FLOPPY BABY) Inhibits Ach Release
CNS infections with AIDS
Toxoplasma Diffuse (intracerebral calcifications)
Cryptococcus Periventricular calcifications
LIVER / BILIARY / GALLBLADDER
LIVER
Chronic Passive Liver Congestion
nutmeg liver, from Right sided failure leads to liver congestion, and widening of sinusoids and central veins
Think about it: backed up liver will squeeze the blood back thus widening all the vessels
Portal hypertension:
High BP in the portal vein
Portal vein receives blood drained from entire intestines, spleen, pancreas, & gallbladder
After entering the liver, the blood divides into tiny channels
Blood drains back into the general circulation via central vein hepatic vein
Indicators/Complications of portal HTN:
Esophageal varices (first sign) diluted tortuous veins in the submucosa of the lower esophagus
Common complications of cirrhosis (varices are NOT a complication of other liver disorders/diseases)
Esophageal varices is the sequelae of fatty nutritional cirrhosis that is the most likely to result in death AND
exsanguination
Obstruction of portal circulation
Most common cause of esophageal varices is Portal HTN
Most common cause of massive hematemesis in alcoholics
Hemorrhoids
Testicular atrophy
Enlarged veins on the anterior abdominal wall (caput Medusae)
Ascities (fluid w/in abdominal cavity)
Splenomegaly single most important sign of portal HTN
Factors increasing BP:
Increased blood volume flowing through vessels
Increased resistance to blood flow through liver most common cause of portal HTN
Jaundice (aka icterus):
Yellow discoloring of skin, mucous MBs & eyes, caused by excessive amount of bilirubin dissolving in subcutaneous fat
Bilirubin waste product resulting from breakdown of heme moiety of hemoglobin molecules (from worn out RBCs)
Ordinarily excreted from body as chief component of bile
Conjugated bilirubin formed by the conjugation of bilirubin w/ glucuronic acid
Unconjugated (free) bilirubin toxic (unlike that bound to albumin or conjugated)
High bilirubin levels in blood can cause kernicterus (permanent damage to certain areas of the brain of newborns)
This can cause a characteristic form of crippling athetoid cerebral palsy

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Normally, liver cells conjugate bilirubin and excrete it into bile, where it is converted by bacteria to urobilinogen (some of
which is reabsorbed)
Some urobilinogen is also formed directly from heme metabolism
Termed unconjugated (indirect) bilirubin before conjugation and conjugated (direct) after.
Conjugated can enter urine and is soluble
Defects in bile excretion produce elevated levels of conjugated or unconjugated bilirubin
BUT Acute biliary obstruction causes a rise in conjugated bilirubin in the serum
Common in newborns in 1st week of life
All types (except physiologic jaundice in newborns) indicate:
Overload or damage to the liver
Inability to move bilirubin from the liver through the biliary tract to the gut
Very common; leading manifestation of liver disease
Common causes:
Increased destruction of RBCs w/ rapid release of bilirubin into the blood (unconjugated)
Obstruction of bile ducts or damage to liver cells causing inability of bilirubin to be excreted into GI tract (conjugated)
Pathogenesis of jaundice in patients with infectious hepatitis is the result from damage to liver cells
Gallstones, hemolytic anemia, infection hepatitis, carcinoma of common bile duct, carcinoma of head of the
pancreas -weird
Hemolysis of any cause usually results in unconjugated bilirubin predomination
NOT Causes:
Aplastic anemia Dont have the cells
Fibrosis of the liver INTERESTING!!!!
Vitamin K Deficiency
Obstructive jaundice:
Often caused by gallstones blocking the common bile duct
Hepatomegaly:
Most common cause of hepatomegaly w/o other signs and symptoms is fatty change (NOT ascites, hepatitis, etc)
Hepatic Failure:
Attributed to:
Tremor (Encephalitis), Gynecomastia, Hypoalbuminemia, Asterixis, and Spider Telangiectasia
NOT Mallory Bodies
Mallory bodies are large, poorly defined accumulations of eosinophilic material in the cytoplasm of damaged
hepatic cells in certain forms of cirrhosis and marked fatty change especially due to alcoholism
DRUNK DUCKS
Budd-Chiari syndrome:
Occlusion of IVC or hepatic veins w/ centrilobular congestion and necrosis, leading to congestive liver disease (heptomegaly,
ascites, abdominal pian, and eventual liver failure)
Associated w/ polycythemia vera, pregnancy, hepatocelluar carcinoma
Ascites:
Accumulation of free serous fluid in the peritoneal cavity
Almost pure plasma containing tremendous quantities of protein
Typically results from liver disease
Disorders that may be associated w/ ascites
Cirrhosis, hepatitis, portal vein thrombosis, portal HTN, constrictive pericarditis, CHF, liver cancer, nephritic syndrome,
pancreatitis, Decreased protein production by the liver (no albumin to maintain capillary osmotic pressure)
Does NOT develop as a result of esophageal varices but they are probably seen together!
Cirrhosis:
Chronic liver disease characterized by generalized disorganization of hepatic architecture w/ scarring & nodule formation
Normal hepatic architecture is destroyed & replaced by bands of fibrous scar tissue
Characterized by diffuse destruction & fibrotic regeneration of hepatic cells
Most common chronic liver disease
2x more common in men
Among people 45-65 y.o., cirrhosis is 3rd most common cause of death (after heart disease & cancer)
Signs/Symptoms/Complications:
Ascites
Bleeding disorders (coagulopathy, i.e. hemophilia)
NOTE: PT (not PTT) is used to assess coaguopathy due to liver disease
Portal hypertension
Complication of Cirrhosis is obstruction of portal circulation
Confusion or change in level of consciousness (hepatic encephalopathy) TREMORS asterixis (hand tremor)
Splenomegaly
Indicates portal HTN, which in turn causes esophageal varices

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Esophageal varices are most common source of massive hematemesis in alcoholics


Hematemesis Vomit
Hemoptysis Lung
Esophageal varices is the sequelae of fatty nutritional cirrhosis that is the most likely to result in death and
exsanguination
Spider angiomas are common in alcoholics
Sudden onset of upper GI bleeding w/ massive hematemesis (vomiting of blood)
Jaundice
Causes:
Alcohol abuse (most common 75%), use of certain drugs, and the exposure to certain chemicals
Infections (includig Hep B & C)
Biliary obstruction
Hemochromatosis (iron overload)
Congestive heart failure
Wilsons disease
(A hereditary accumulation of copper in the liver, kidney, brain, and cornea) Including green pigment in the
cornea
Other inborn metabolism errors: galactosemia, glycogen storage disease, or alpha1-antitrypsin deficiency
alpha1-antitrypsin deficiency affects BOTH the Lung and the Liver
Associated w/ an increased incidence of hepatocellular carcinoma
Is especially prevalent among malnourished persons >50 y.o. w/ chronic alcoholism
Mortality is high; many patients die w/in 5 years of onset
Nodular Regeneration
Types:
Micronodular: nodules < 3mm, uniform size, due to metabolic insult (e.g., alcohol)
Macronodular: nodules > 3mm, varied sized. Usually due to significant liver injury leading to hepatic necrosis (eg.,
postinfectious or drug induced hepatitis). Has increase risk of developing hepatocellular carcinoma
Tx: portacaval shunt between splenic vein and left renal vein may relieve portal hypertension
Fatty Liver
Fat is deposited in the hepatocytes (Intracellularly)
Hepatocellular carcinoma: (hepatoma)
Most common primary malignancy in liver of adult
Risk factors include: Hep B and C, Wilsons disease, hemochromatosis, alpha-1 antitrypsin deficiency, alcoholic
cirrhosis, and carcinogens (aflatoxin B1)
Commonly spread through hematogenous dissemination yielding alpha fetoprotein (AFP)
Reyes syndrome:
Involves brain damage (encephalopathy) & fatty liver changes
Most often seen in children 4-12 y.o. (peak = age 6)
Associated w/ use of ASA in children to Tx chickenpox or influenza
Typically follows an upper respiratory infection or chickenpox by ~1 week
Rapid onset & varying symptoms
Changes in mental status occur including delirium, combative behavior, & coma
Frequently begins w/ vomiting persistent over many hours
Vomiting is rapidly followed by irritable & combative behaivior
As condition progresses, child may become semi-conscious or stuporous
Ultimatley, seizures & coma develop can quickly lead to death
Is associated w/ the use of aspirin in children to treat chickenpox or influenza
Wilsons disease:
Think Wilson in Castaway He was so hungry he ate copper
Aka hepatolenticular degeneration
Inherited disorder of copper metabolism
Results in excessive deposits of copper in liver cells
Copper fails to enter circulation in form of ceruloplasmin
Characterized by
Think ABCsD Asterixis, Basal ganglia degeneration, Ceruloplasmin decrease, Cirrhosis, Corneal Deposits,
Copper Accumulation, Carcinoma, Choreiform movements, Dementia
cirrhosis, degeneration of basal ganglia, & deposition of green pigment in the periphery of the cornea
HEPATITIS A:
A picoRNAvirus
A FOR ASYMPTOMATIC
Aka viral, infectious, or short-incubation hepatitis (15-40 days)
Least serious, most mild among Hep A, B & C

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High morbidity, low mortality


Highly contagious infectious disease involving liver
Usually transmitted by the fecal-oral route
Also transmitted parenterally or sexually
May also be transmitted via blood products
Usually from ingestion of contaminated food, milk, or water
Outbreaks often traced to ingestion of seafood from polluted water
Also caused by an RNA enterovirus
Occurs most often in young Adults
Does not lead to chronic liver disease, only 0.5% suffer from fatal liver necrosis
Symptoms fever, malaise, abdominal pain, anorexia, jaundice
Appear after incubation period of 3-6 wks
Jaundice
Pathogenesis by Hepatitis A characterized by damage to the liver cells
Damage to liver cells results in increased serum levels of enzymes (e.g., transaminases) in liver cells
Detection of increases enzyme levels used to diagnose Hep A
Most cases are self-limiting and recovery occurs w/in 4 months
Surface Ag (A or B) in pts serum indicates the pt is potentially infectious for Hep (carrier state)
Hepatitis viruses are very heat resistant (more so than AIDS virus)
Proper autoclaving kills Hep
IgM-anti-HAV diagnostic of acute active or recent infection
IgG-anti-HAV indicates immunity to Hep A
Vaccine is available and should be taken when traveling to endemic areas
A = Asymptomatic (usually), young Adults, Arrives Quickly
HEPATITIS B:
Transmitted by a DNA virus
Aka Serum Hepatitis Hep B for Blood
HB5 antigen in the plasma is associated with Serum Hepatitis
Infectious disease producing liver inflammation & necrosis
Commonly transmitted by blood-derived products (more so than CMV, Hep A, herpes simplex keratitis)
Including perinatal, parenteral of sexual exposure, or mucous or skin openend and exposed to blood, saliva, or feces
Not by fecal-oral route
Severity varies from an asymptomatic carrier state to fulminate hepatitis
Chronic Hep is common, as are hepatomas
Less easily transmitted than Hep A
Can be transmitted through blood or by contact w/ human secretions & feces
Common among injection drug users who share needles, as well as between sexual partners
Signs/symptoms similar to Hep A (fever, abdominal pain, nausea etc.)
Longer incubation period of 6-8 weeks (one Q says: 1-6 months)
Symptoms are slower in developing, but longer in duration
Clinical manifestations:
Elevated transaminases, hyperbilirubinemia, elevated alkaline phosphatase
Most patients recover fully
Some develop chronic persistent hepatitis or chronic active hepatitis
Markers: KNOW THESE YOU STUPID IDIOT
A patient recovering from Hep B:
Detection of the Hep B antigen in serum is indicative of the carrier state
EX: Pts lab results show both the HBs and anti-HBsmeans pt is a carrier
HBsAg surface antigen
Indicates active infection with HBV
Earliest marker of virus in serum
Continued presence indicates carrier state (Both HBsAg and anti-HBsAg)
It usually disappears with antibody IgG for the sAg
If IgG comes and takes out HBs-Ag
Confers immunity (IgG anti-HBsAg) and affords protection
If no antibody (IgG) develops:
sAg remains high and the person is a carrier and potentially infectious
Persisting for more than six months indicates chronic hepatitis B
HBsAb
Indicates successful immunization
HBcAg (core antigen)

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Is found in the capsid


HBeAg (e-antigen)
Indicates active HBV replication making patient highly infective
IgM-anti-HBc
Indicates acute Hepatitis B
IgG-anti HBc
Indicates previous exposure to hepatitis B (may confer immunity)
How does Hep B cause disease in the liver???
Type III-- Ag/Ab complexes lead to extrahepatic problems like rash, urticaria, arthritis, vasculitis and
glomerulonephritis
Vaccines available and all health care professionals should be vaccinated and children
Hepatitis B immune globulin (HBIG) conferes passive immunity
B = Blood borne
Non-A and Non-B Hepatitis [HEY: this is actually Hepatitis C]
Type of infection most commonly transmitted via transfusion of properly screened blood
HEPATITIS C:
Serum hepatitis that is caused by a virus antigenically different from Hep A or B
Most likely results in chronic hepatitis
Most often transmitted through blood-transfusions (or via needle stick in a dental office)
Death from advanced liver disease caused by hepatitis C infection is primarily due to inhibition of urea synthesis
Accounts for 85% of post-transfusion hepatitis but w/ screnning for anti HCV it is reduced
Much milder than A or B but is otherwise clinically indistinguishable from them
Higher incidence of chronic disease (85%), cirrhosis (20%)
Increased risk of Hepatocellular Carcinoma
Most common reason for liver transplantation in the U.S.
Extrahepatic manifestations: rash, arthritis, glomerulonephritis, all mediated by cryoglobulins
Anti-HCV and RT-PCR available for dx and genotyping
Interferon plus ribavirin used in therapy
C = Chronic, Cirrhosis, Carcinoma, Carriers
HEPATITIS D:
Found in pts w/ acute or chronic episodes of Hepatitis B
Makes Hep B infection more severe
Drug addicts are at relatively high risk
Depends on host having been previoiusly infected with Hep B
Prevention of Hep B also prevents Hep D
D = Defective, Dependent on HBV
HEPATITIS E:
RNA Calcivirus (NAKED CPR)
Transmitted enterically much like Hepatitis A
Causes occasional epidemics similar to those of Hepatitis A
Hep E epidemics have only occurred in underdeveloped countries
Responsible for most waterborne outbreaks
Self limited illness but can be fulminant (worse) in pregnant women
E = Enteric, Expectant, Epidemics
A and E by Fecal-Oral Routes
The vowels hit your bowels
Alcoholic hepatitis:
Swollen and necrotic hepatocytes, neutrophil infiltration
Mallory bodies (hyaline), fatty change, and sclerosis around central vein
DRUNK DUCKS Eosinophils in the liver of drunkies
AST is elevated. AST ratio to ALT is > 1.5
Think A Scotch and Tonic
BILIARY
Cholelithiasis (Gallstones):
Stone or calculi in gallbladder result from changes in the bile component
Virtually all gallstones are formed w/in the gallbladder
Bile:
Composed of water, bile salts, lecithin, cholesterol & some other small solutes
Primary component is Cholesterol
Changes in relative concentrations may cause precipitation & formation of a nidus, or nest, around which gallstones form
Risk Factors:
Think 4 Fs Female, Fat, Fertile, Forty

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Signs:
Pt with conjugated hyperbilirubinemia and an absence of urobilinogen
Urobilinogen is low because the bile cant get down into the intestine where it is made
(pt does NOT have aplastic anemia, hemolytic anemia, acute hepatitis, or alcoholic cirrhosis)
Types:
Cholesterol stones (radiolucent w/ 10-20% opaque due to calicifications):
Associated w/ obesity, Crohns disease, cystic fibrosis, advanced age & Native American origin
Mixed stones (radiolucent):
Have both cholesterol and pigmented components
Most common type
Pigement stones (radiopaque):
Seen in patients w/ chronic RBC hemolysis, alcoholic cirrhosis, advanced age, & biliary infection
Choledocholithiasis term for gallstones are in bile duct
Size from grain of sand to > 1 inch
Color from yellow to other pigment, depending on what it is made of
GALLBLADDER
Cholesterolosis (strawberry gallbladder):
Characterized by small, yellow, cholesterol-containing flecks highlighted against a red background in the gallbladder lining
Polyps may form inside gallbladder & require its removal
Diverticulosis of the gallbladder:
Small, finger-like out-pouchings of the gallbladder lining may develop as a person ages
May cause inflammation & require gallbladder removal
KIDNEY DISEASE
Renin:
Renal hormone associated with HTN (dont get clowned by angiotensin)
Does not directly invoke vasodilation
Proteolytic enzyme formed in kidney & released into bloodstream where it has an important role in activating angiotensin
Produced by & stored in the juxtaglomerular apparatus that surrounds each arteriole as it enters a glomerulus
Release is controlled by activity of sympathetic nerves to kidney & renal arterial BP (if pressure, renin secretion )
Acts on angiotensinogen (manufactured by the liver & present in the blood)
Converts angiotensinogen to angiotensin I
In turn AT I is converted to AT II by ACE associated w/ capillary walls, particularly in the lungs
AT II stimulates aldosterone release from the zona glomerulosa of the adrenal cortex
Aldosterone causes Na+ retention by enhancing Na+ reabsorption by distal convoluted tubules & collecting ducts
Nephrolithiasis (Kidney Stones)
Presence of renal calculi (kidney stones) w/in renal pelvis or calyces
Calcium stones are the most commonly occurring form of nephrolithiasis
Most likely the result from Hyperparathyroidism Duh, increases Ca levels in blood!
Many stones are asymptomatic until they pass into the ureter causes renal colic (characterized by severe pain)
Complications:
Obstruction of the ureter
Acute or chronic pyelonephritis
Hydronephrosis
Stone formation w/in urinary tract represents a potential complication of many different diseases
4 types of stones:
Composed of Calcium salts, Uric acid, Cystine , and Ammonium Magnesium Phosphage (struvite)
Each has its own group of causes & specific management
All are caused by excessive supersaturation of the urine w/ a poorly soluble material
Stones grow upon the surfaces of the papillae, which detach & accompany the urine through the collecting system
Many stones are too large to negotiate the narrow circuit they obstruct flow of urine & can cause severe pain
More common in men; rare in children
Exact cause is unknown
Predisposing factors: dehydration, infection, changes in urine pH, obstruction of urine flow, immobilization causing bone
reabsorption, metabolic factors (such as hyperparathyroidism [leads to hypercalcemia]), renal acidosis, eleveated uric acid, &
defective oxalate metabolism
Kidney stones are not caused by diabetes insipidus
Painless hematuria as a common early clinical sign in acute diffuse glomerulonephritis, carcinoma of the bladder, focal
glomerulonephritis, and renal cell carcinoma
BUT NOT Nephrolithiasis (because that mofo hurts)
Hydronephrosis:
Abnormal dilation of the renal pelvis & calyces

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Caused by an obstruction of urine flow in the genitourinary tract


Not a separate disease entity
Rather, a physical manifestation of the disease process that causes impairment of urine drainage
Nephrosis describes kidney disease usually of the tubules, NOT the glomeruli
Urolithiasis:
Urinary calculus, formed in any part of the urinary tract
Associated with obstruction of urine flow
Composed of calcium oxalate &/or calcium phosphate
Calcium stones account for 80-90% of urinary stones
Associated with:
Gout, Hypercalcemia, Renal Infection, and Hyperparathyroidism
NOT systemic HTN
Pyelonephritis:
Bacterial infection (usually E. coli) of the renal pelvis & ureters
Fever, chills, flank pain, CVA tenderness
Acute active infection of the renal pelvis the pelvis may become inflamed & filled w/ pus
One feature is costovertebral angle tenderness
Chronic extensive scar tissue forms in the kidney renal failure becomes a possibility
Most often result from UTIs (from urinary reflux), particularly in the presence of occasional or persistent backflow or urine
from the bladder into the ureters or kidney pelvis (vesicoureteric reflux); abscesses often develop
Cystitis:
UTI
Dysuria, Frequency, suprapubic pain
Most common causing bugs are E. Coli and Proteus
Staph saprophyticus is 2nd common cause in young ambulatory women
Think SEEK PP Serratia marcescens, Staph saprophyticus, E. coli, Enterobacter, Klebsiella, Proteus,
Pseudomonas Aer.
Women have it 10x as much as men (short urethra)
NOT associated with blocked urinary flow (Hydronephrosis and Pyelonephritis are!!)
Kidney infections are usually caused by microorganisms ascending from the lower urinary tract
Nephrosis generally implies renal disease associated w/ the tubules Bc nephron is tubules son
Tubulointerstitial disease: tubular defects
From a variety of conditions and may be acute or chronic
Causes include drugs, obstruction, infections, toxins and vascular problems
Urine contains RBC, WBC, and WBC casts but proteinuria is less common w/ low molecular weight proteins
Can lead to renal tubular acidosis, aminoaciduria, salt, potassium magnesium wasting, and concentrating defect
Glomerulopathies:
Kidney disorders in which inflammation affects mainly the glomeruli
Nephrosis is only Tubules
Causes vary glomerulopathies are similar since glomeruli respond similarly to several types of injury
Four major types of glomerulopathies:
1) NephrOTIC syndrome:
Subtypes:
Membranous glomerulonephritis
Minimal change disease (lipoid nephrosis)
Focal segmental glomerular sclerosis
Diabetic nephropathy
SLE Wire loop appearance
Collection of symptoms caused by many diseases that affect the kidneys
Condition characterized by marked prOteinuria, generalized edema, hypOalbuminemia
Signs/symptoms: result from increased permeability of glomerular capillareis
PrOteinuria
Severe loss of protein into the urine (>3.5 grams/day)
Hypoalbuminemia & decreased levels of other blood proteins
Generalized edema
Hyperlipidemia
Hypercholesterolemia
Retention of excess salt & water
NOT anemia, hematuria, hypertension, or red cell casts in the urine
Not a disease itself results from a specific glomerular defect & indicates renal damage
Caused by:

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Amyloidosis, cancer, diabetes, HIV, glomerulopathies, leukemia, lymphomas, multimple myeloma and SLE
75% of cases result from primary glomerulonephritis
Can occur at any age
In children it is most common between ages 18 months & 4 years
Affects more boys than girls
In older people the sexes are more eqully affected
Early symptoms:
Loss of appetite, malaise, puffy eyelids, abdominal pain, muscle wasting, tissue swelling (excess salt & water
retention), & frothy urine
2) Acute nephrITIS syndrome
Subtypes:
Acute poststreptococcal glomerulonephririts Glomeruli large and bumpy with hypercellular neutrophils
Rapidly progressive Glomerulonephritis, crescent, moon-shaped
Goodpastures syndrome
Type II Hypersensitivity, Linear pattern, anti GBM antibodies
Membranoproliferative glomerlonephritis Subendothelial humps, tram track
IgA Nephropathy (Bergers disease)
Mesangial deposits of IgA
Glomerluar inflammation resulting in sudden appearance of hematuria w/ clumps of RBCs (casts) & variable
proteinuria
Most common in 3-7 y.o. boys
Starts suddenly and usually resolves quickly
Associated with destruction of basement membranes via PMNs (NOT lymphokines, eosinophils, or IgE Ab/s)
Elevated antistreptolysin O (ASLO) titers
Low serum complement
3) Chronic nephrotic syndrome
Aka chronic glomerulonephritis
Slowly progressive disease characterized by glomerular inflammation resulting in sclerosis, scarring & renal failure
Conditions that can lead to chronic GN SLE, Goodpastures syndrome, & acute GN
4) Rapidly progressive glomerulonephritis (RPGN)
Aka rapidly progressive nephritic syndrome or crescentic GN
May be idiopathic or associated w/ a proliferative glomerular disease such as acute GN
Uncommon disorder in which most of the glomeruli are partly destroyed, resulting in kidney failure
Starts suddenly & worsens rapidly
Occurs most commonly in 50-60 y.o. people
Glomerular diseases:
Damage to glomeruli caused by antibodies directed against glomerular basement membrane or antibody-antigen
complex deposition in which complement helps or hurts condition
Hematuria, proteinuria, and renal insufficiency are hallmarks and renal biopsy is needed to establish diagnosis
Renal Insufficiency
May produce Parathyroid Hyperplasia
I think it has to do with lacking the Vitamin D formation, so PTH has to work harder to increase serum Ca
May have a hemorrhagic tendency
RENAL FAILURE
Failure to make urine and excrete nitrogenous waste
Consequences
Anemia (no erythropoietin), Renal osteodystrophy (No active Vit D), Hyperkalemia (Leads to
cardiac arrhthymias, Metabolic acidosis (due to decreased acid secretion and decreased generation of bicarb), Uremia
(increased BUN and creatinine), Sodium and H20 excess, Chronic pyelonephritis, HTN
Acute renal failure:
Often due to hypoxia
acute reduction in renal excretory capacity causing nitrogenous waste retention
Various causes classified according to location:
Prerenal: intravascular and extracellular volume loss (dehydration, bleeds, burns); decreased intravascular volume
but increased extracellular volume (congestive heart failure, cirrhosis); in all cases renal perfusion is diminished
Renal: diseases of the renal parenchyma (glomerulonephritis, interstitial disease, drug toxicities, vasculities, acute
tubular necrosis or renal artery)
Post renal: might occur in tubules (uric acid nephropathy, or stones or enlarged prostate)
Characteristics and dx:
use of blood urea nitrogen (BUNnormal levels 8 20 mg/dL) and creatine (normal levels 0.7 1.5 mg/dL) to
estimate change in GFR
RBC, WBC, protein, casts, Na, urea, or urine
Structural evaluation using ultrasound, radionuclides scanning
Chronic renal failure:

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Often due to HTN and DM


GFR decreased by 25% and leads to uremia. It is most likely caused by diabetes mellitus and hypertension and a
decrease in protein intake will slow progression.
Uremia: clinical condition from renal failure w/ no underlying chemical basis.
Causes many problems including: fluid and electrolyte imbalance (acidosis, hyperkalemia) metabolic (osteomalacia,
hyperuricemia), neuromuscular neuropathys and myopathies, cardiovascular pericarditis and hypertension, pruritis and
anemia
Treat w/ hemodialysis and peritoneal dialysis or renal transplant
Hematuria:
Blood in urine (more than 5 erythrocytes per high power field)
Many causes including infections, stones, malignancies, connective tissue ds, renal disease that originate anywhere in
genitourinal tract
Polycystic kidney (PKD):
Inherited kidney disorder in which multiple cysts form on the kidneys
Exact mechanism triggering cyst formation is unknown
Early stages of disease
Cysts enlarge the kidney & interfere w/ function
Results in chronic high BP, anemia, & kidney infections
Cysts may cause kidneys to increase production of erythropoietin
Results in increased # of RBCs rather than the expected anemia
Bleeding into a cyst can cause flank pain
Increases incidence of kidney stones
HTN caused by polycystic kidneys may be difficult to control
Slowly progressive eventually results in end-stage kidney failure
Also associated w/ liver disease, including infection of liver cysts
An autosomal recessive form of PKD exists & appears in infancy or childhood
Tends to be very serious & progresses rapidly
Results in end-stage kidney failure & death in infancy or childhood
Medullary cystic disease:
Disorder in which kidney failure develops along w/ cysts deep w/in kidneys (in medulla).
Uncommon & affects older children
Medullary sponge kidney:
Congenital disorder in which urine-containing tubules are dilated, causing the kidney tissue to appear spongy
Malignant HTN:
A medical emergency condition where there is a severe rise in BP
Cause is unknown often a prior Hx of HTN, especially HTN resulting from kidney disorders (2 HTN)
More common in younger adults, especially African American men
Also occurs in women w/ toxemia of pregnancy & people w/ renal or collagen vascular disorders
Can cause severe, permanent, life-threatening consequences from pressure damage to brain, eyes, BVs, heart, & kidneys
If left untreated usually leads to death in 3-6 months
Characterized by:
Marked elevation levels of plasma renin A cause, not a compensatory mechanism!
Generally younger pts than benign HTN
Corresponding renal lesion is known as Malignant nephrosclerosis
May arise as de novo, or appear suddenly in a pt w/ previous mild HTN
NOT that pts will live a normal lifespan if untreated This shizz jacks you up!!!
Benign Essential HTN:
Constriction of arterioles is most likely the cause
Hyaline arteriosclerosis (see below: nephrosclerosis) is the renal lesion most commonly associated w/ benign essential
HTN
Chronic HTN:
Leads to reactive changes in the smaller arteries & arterioles throughout the body
These changes are collectively referred to as arteriosclerosis
The vascular changes are particularly evident in the kidney
They result in a loss of renal parenchyma, refered to as benign nephrosclerosis
Nephrosclerosis: (aka: arteriolonephrosclerosis = hyaline arteriosclerosis)
Renal impairment secondary to arteriosclerosis or HTN
Disease most commonly related to benign HTN (incorrect: renal atresia, acute pyelonephritis & chronic pyelonephritis)
Benign Nephrosclerosis is the most common autopsy find of essential HTN
Three types:
1) Arterial atrophy & scarring of the kidney due to arteriosclerotic thickenings of walls of large branches of renal artery

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2) Arteriolar renal changes associated w/ HTN in which the arterioles thicken & the areas they supply undergo
ischemic atrophy & interstitial fibrosis
3) Malignant rapid deterioration of renal function caused by inflammation of renal arterioles
This type accompanies malignant HTN
Von Gierkes disease: Think VON GlyKes
Massive accumulation of glycogen in the liver and the kidney
The most common of the glycogen storage diseases
Genetic disease resulting from deficiency of glucose-6-phosphatase, which helps to make glucose from glycogen
Deficient in the last NZ of Glyogenolysis
Renal Cell Carcinoma
Most common renal malignancy
Most common in men 50-70
Increased incidence in smokers
Associated with von Hippel-Lindau and gene deletion in chromosome 3
Originates in renal tubule cell polygonal clear cells
Signs Hematuria, palpable mass, 2ndary Polycythemia, Flank Pain, and Fever
Invades IVC and spreads hematogenously normally carcinomas spread lymphatically
Associated with paraneoplastic syndromes
LUNG DISORDERS
Pulmonary edema:
Accumulation of fluid in the extravascular spaces of the lungs
Increased pressure in lung veins due to backup from failing left ventricle (CHF)
Increased intravascular hydrostatic pressure
Fluid is pushed into the air spaces (alveoli)
Fluid becomes a barrier to normal O2 exchange resulting in SOB
Physiologically, caused by increase in intracapillary hydrostatic pressure or increase in capillary permeability
Early symptoms dyspnea, orthopnea, and coughing
Clinical signs tachycardia, tachypnea, dependent crackles, & neck vein distension
Causes arteriosclerosis, HTN, cardiomyopathies, valvular heart disease, & left-sided heart failure
Treatment reduce extravascular fluid & improve gas exchange & heart function (oxygen, diuretics, vasopressors, positive
inotropic agents, & antiarrhythmics)
Chronic passive congestion of the lungs
Characterized by thickening of the alveolar walls and hemisiderosis
Another Q said.by edema of the alveolar walls and heart failure cells
Is secondary to atherosclerotic heart disease Heart gets jacked thus the hemisderosis and heart failure cells leads to
fluid backup thus the edema and thickening of alveolar walls
Productive cough present in:
Chronic lung abscess
TB
Lobar pneumonia
Bronchogenic carcinomas
Pulmonary embolism
Brochiectasis
Sputum contains mucus, cellular debris, bacteria, & may contain blood or pus
Infarcts (Red vs. Pale)
Red RED LILly (Lung, Intestine, Liver)
Occur in loose tissues with collaterals, such as lungs, intestine, or following reperfusion (REd for REperfusion)
Hemorrhagic (red) infarcts most commonly found in the LUNG (NOT brain, spleen, or kidney)
Even if theres a stoppage, think red is still all around
Pale
Occur in solid tissues with single blood supply, such as the brain, heart, kidney, and spleen
Bronchiectasis
Irreversible, abnormal dilatation of bronchi/bronchioles caused by destruction of supporting structures by a chronic
necrotizing infection
Common in children w/ cystic fibrosis
Most common symptom chronic, productive cough w/ a foul-smelling, purulent sputum
Chronic dilation as result of inflammatory disease/chronic obstruction obstruction, hydothorax, pneumothorax
Atelectasis:
Shrunken & airless state of the lung, or portion thereof
Due to a failure of expansion or resorption of air from the alveoli
Common in premature infants due to a lack of surfactant

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Collapse of alveoli
May be secondary to:
Blockage of bronchus to aspirated foreign body
Blockage of bronchus by mucous
Hydrothorax
Pneumothorax
PNEUMONIA
General info:
Very common lung infection involving the alveoli & the tissues around them
Most common fatal infection acquired in hospitals
Characterized by chills & fever, productive cough, blood-tinged sputum, & hypoxia w/ SOB
Interstitial pulmonary inflammation is most charactistic of viral pneumonia Think Viruses are IN
(interstilial/intracellular)
Clinical signs: crackles are heard when listening to the chest w/ a stethoscope (auscultation)
Caused by various organisms: bacteria, viruses, & fungi
Autoimmune pt has endo done, develops chills, malaise, rales, difficulty breathing and increased WBCs they have:
Pneumonia
Bacterial pneumonia:
Tend to be the most serious cause of pneumonia
Streptococcus pneumonia (aka Pneumococcus) most common cause in adults
Most common cause of community acquired bacterial pneumonia in the U.S.
Well known for its large polysaccharide capsule (so is Cryptococcus neoformans)
Strains of Strep pneumonia are distinquished by their polysaccharide capsules
Antibodies formed against encapsulated bacteria, like strep pneum., initially fxn as Opsonins
Viral pneumonia:
Aka atypical pneumonia or interstitial pneumonia
Legionella pneumophilia causes pneumonia (atypical)
Most common causes of pneumonia in young children (peak between ages 2-3)
Viral pneumonia is most characteristic of interstitial pulmonary inflammation (IN is IN)
Diffuse and patchy (>1 lobe)
No alveolar exudate
Dry hacking cough
Elevated cold agglutinins
Bronchopneumonia:
Affects infants & elderly
Inflammation of the walls of the smaller bronchial tubes
Also spread of inflammation into alveoli & alveolar ducts
Patchy distribution of lobular inflammation; not just the bronchus itself
B for Bacteria
S. aureus, H. flu, Klebsiella, S. Pyogenes
Lobar pneumonia:
Diffuse distribution of inflammation
Pneumococcus most frequent (Strep pneumoniae)
Affects middle-aged people
Marked by fever, chest pains, cough & blood-stained sputum
Rusty sputum
Inflammation & consolidation of one or more lobes of the lunugs
Chest pain associated w/ lobar pneumonia attributable to coexistent pleurisy (inflammation of pleura)
Diplococcus pneumoniae
The essential antigen which determines both its virulence & its specific type is the distinct capsular polysaccharide
Common Causes of Pneumonia
Children (6 wk 18 y) Viruses (RSV), Mycoplasma, Chlamydia pneumoniae, S. pneumoniae
Adults (18 y 40 y)
Mycoplasma #1 in Young Adults (THEY WALK a LOT), Chalymdia pneumoniae, S. pneumoniae
Adults (41 y 65 y)
S. pneumoniae, H. influenzae, Anaerobes, Viruses, Mycoplasma
Elderly (65+) S. pnuemoniae, Viruses, Anaerobes, H. influenzae, Gram rods
Special Types of Pneumonia
Nosocomial
Staph, Gram rods
Immunocompromised
Staph, Gram rods, Fungi, Viruses, PCP
Aspiration
Anaerobes
Alcoholic/IV drug user
S. pneumoniae, Klebsiella, Staph
Postviral
Staph, H. influenzae
Neonate
Group B Strep, E. coli

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Atypical
Mycoplasma, Legionella, Chlamydia
Pneumocystis carinii pneumonia:
Originally thought to be a protozoa
But is a YEAST
Caused by Pneumocystis carinii in immunocompromised pts (commonly seen in AIDS pts)
Causes interstitial pneumonia often fatal
Type
Organism
Characteristics
Lobar
Intra-alveolar exudate consolidation, may involve
S. pneumoniae (Pneumococcus)
Its got a big capsule, to go
entire lung
everywhere
Bronchopneumonia
S. aureus, H. influenza, Klebsiella, S.
Acute inflammatory infiltrates from bronchioles into
pyogenes
adjacent alveoli; patchy distribution involving > 1 lobes
Interstitial (atypical) pneumonia Viruses (RSV, adenoviruses), M.
Diffuse patchy inflammation localized to interstitial
pneumoniae, Legionella, Chlamydia
areas at alveolar walls; distribution involving primary
psittaci (Birds)
lobes
Inflammatory exudates in pneumonia
Definitely present in lobar pneumonia, & bronchopneumonia
Least likely to occur in primary atypical pneumonia (walking pneumonia) 1999 Q100
Pulmonary Tuberculosis:
Contagious bacterial infection caused by M. tuberculosis
NOT from endotoxin or exotoxin (Histoplasmosis is another answer)
Lungs are involved, but the infection can spread to other organs
Histo:
Granulomas with giant multinucleated cells and caseation necrosis
Can develop after inhaling droplets from a cough or sneeze by infected person
Symptoms minor cough, mild fever, fatigue, weight loss, hemoptysis, night sweats & a cough w/ phlegm
Primary TB:
Immediately follows invasion by tubercle bacilli
Characterized by the Ghon focus 2002 Q8
Lesion at the pulmonary site of primary TB infection
Usually in middle or lower lung (Micro made simple, Dr. Cragun, and UCSF)
Other sources say subpleural parenchyma (U. of Utah, U. of Delhi)
Kaplan says, The primary lung infection is usually found subadjacent to the pleura in the lower part of an
upper lobe or in the upper part a lower lobe in one lung due to high air flow to these areas
Then the immune system ramps up in 2-4 weeks & now forms a similar caseation granuloma in hilar lymph
nodes
When this happens, it is now called the Ghon Complex
Calcifications in pulmonary parenchyma from earlier TB not to be confused w/ Ranke Complex
Ranke Complex is a lung lesion w/ calcified lymph nodes
Secondary TB:
Disease that develops long after the 1 infection due to reactiviation of the 1 infection
Characterized by tubercle formation (caseous granulomas)[unlike sarcoidosis] & subsequent cavity lesions
Lungs are the most common site for secondary TB
Miliary TB :
Results from spread of tubercle bacilli by way of hematogenous spread
Results in the seeding of several organs w/ multiple, small, millet, seed-like lesions
Disseminated TB
Treatment of TB:
Generally prolonged & involves daily oral doses of multiple drugs
May include combinations of rifampin, isoniazid, pyrayzinamide, ethambutol = RIPE
Possible serious adverse reactions of these drugs
Ototoxicity, nephrotoxicity, muscle weakness, & allergic reaction
CHRONIC OBSTRUCTIVE PULMONARY DISEASE
General info:
Group of lung diseases characterized by increased airflow resistance
Chronic airway obstruction resulting from emphysema, chronic bronchitis, asthma, or a combo of any of these diseases
In most cases, bronchitis & emphysema occur together
Secondary pulmonary HTN is most often caused by COPD
Chronic Obstructive Pulmonary Disease
Disorder
Characteristics

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Bronchial asthma
Chronic bronchitis
Emphysema (pulmonary emphysema)
Bronchiecstasis

Dyspnea and wheezing expiration


Productive cough characterized by hypersecretion of mucus
Often coexists w/ chronic bronchitis, labored breathing, and an increased
susceptibility to infection
Copious purulent sputum, hemoptysis, and recurrent pulmonary
infection

Bronchial asthma:
1st definition: disease in which inflammation of the airways causes restriction of airflow
2nd definition: chronic reactive airway disorder that causes episodic airway obstruction
Results from bronchospasms, mucus secretion, airway edema, & airway resistance
NOT decreased surfactant
NOT enlarged air spaces (thats emphysema)
NOT associated with purulent sputum-producing cough (only chronic bronchitis & chronic lung abscess)
Caused by the interaction of Ag & IgE on the surface of mast cells with the release of histamine
Heres what happens:
Prostaglandin D elicits bronchoconstriction & vasodilation
Chemotactic factors recruit & activate eosinophils & neutrophils
Platelet-activating factor (PAF) aggregates platelets & induces histamine release
Leukotrienes C4, D4, & E4 cause prolonged bronchoconstriction & mucin secretion
Found in 3-5% of adults & 7-10% of children
of cases develop before age 10; most before age 30
Reversible; symptoms can decrease w/ time
Recurring bronchial asthma attacks may predispose pt for future emphysema
Two types: 1) allergic asthma (most common) & 2) idiosyncratic asthma
Intrinsic: drug induced; overcompensation of autonomics. Extrinsic: from allergens
Common condition can strike at any age of all cases first occur < 10 y.o. (2x as often in boys)
Findings cough, characteristic wheezing expiration, dyspnea, tachypnea, hypoxeia, & decreased I/E ratio, pulsus paradoxus
Symptoms may be triggered by:
Inhaled allergens pet dander, dust mites, molds, pollens
Respiratory infections, exercise, cold air, tobacco smoke, stress, food or drug allergies
Aspirin/NSAIDs in some pts
Tx of an acute asthmatic attack inhalation of a selective 2-agonist (terbutaline, albuterol)
Status asthmaticus
Particularly severe episode of asthma
Usually requires hospitalization
Does not respond adequately to ordinary therapeutic measures
Emphysema: (pink puffer)
Form of COPD that involves damage to the air sacs (alveoli)
Air sacs are unable to completely deflate (hyperinflation) unable to fill w/ fresh air to ensure adequate O2 supply to body
Characterized by normal or increased lung capacity
Lack of elastic recoil in the lungs
Generally bilateral
More common in males
May lead to cardiac failure
Is a significant public health problem
Does NOT show hemoptysis
A tissue change, rather than mucous production (seen in asthma & chronic bronchitis)
Cigarette smoker with gradual onset of progressive, labored breathing, with prolonged expiratory effort
Labored breathing
Show Pursed Lips
Dyspnea, decrease in breathing sounds, tachycardia and decreased I/E ration
Increased susceptibility to infection
May be fatal, results from degenerative atrophy; and may be secondary to bronchial inflammatory disease
Two problems:
1) Lungs are fixed in inspiration
2) Respiratory surfaces of lungs have deteriorated so much that they no longer adequately exchange gases
Complete blood count likely shows polycythemia O2 will be low, so need to make more RBCs
Recurring attacks of bronchial asthma may predispose to emphysema
Most commonly caused by cigarette smoking
Tobacco smoke & other pollutants are thought to cause lungs to release chemicals that damage the walls of alveoli
Damage worsens over time, affecting O2 & CO2 exchange in the lungs
A naturally occurring substance in the lungs called alpha-1 antitrypsin may protect against this damage

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People w/ alpha-1 antitrypsin deficiency are at increased risk


Alpha-1 antitrypsin deficiency affects both the Lung and Liver
Two important types:
Centrilobar upper lobes of lungs most affected cigarette smoking is major cause
Panlobular lower lobes of lungs most affected familiar antiproteinase (caused by alpha-1 antitrypsin deficiency)
Chronic bronchitis: (blue bloater)
Common, debilitating respiratory disease, characterized by mucous production by the glands of trachea & bronchi
Characterized by:
Productive cough, often w/ wheezing (universal factor in all cases)
Produces purulent sputum for 3+ months in at least 2 consecutive years w/o any other disease that could account for
symptom
Dyspnea on exertion
Ventilation-perfusion imbalance
NOT decreased airway resistance
Strong association w/ smoking
Common results of chronic bronchitis:
Cor pulmonale (enlargement of the right ventricle) from working too hard to push blood through pulmonary
system
Airway narrowing
Obstruction of the bronchial tree along w/ squamous metaplasia
Squamous metaplasia is most commonly encountered in the bronchial mucosa (NOT stomach, oral mucosa, etc.)
Characteristic pathologic change:
Hyperplasia of bronchial submucosal glands & bronchial smooth muscle hypertrophy makes sense more mucus =
more glands
Hypertrophy quantified by the Reid index (ratio of glandular layer thickness to bronchial wall thickness) of > 50
Predisposed to bronchogenic carcinoma
Predisposition is based on bronchitis causing squamous metaplasia of bronchial epithelium
Wheezing, crackles, cyanosis
RESTRICTIVE LUNG DISEASE
General info:
Restricted lung expansion causes decrease in volumes (decreased Vc and TLC)
PFTs FEV1/FVC Ratio = >80%
In other words, your ratio of blowing volume out at 1 sec vs FVC is greater because the volumes dropped
But in Obstructive, your ratio is less than 80%, because you cant blow as fast, so less than 80% of the volume is out
at 1 second
Types:
Poor breathing mechanics (extrapulmonary): poor musclar effortpolio, myasthnia gravis; poor apparatusscoliosis
Interstitial lung disease (pulmonary): adult respiratory distress syndrome, neonatal respiratory distress syndrome,
pneumoconiosis, Sarcoidosis, Goodpastures
Adult respiratory distress syndrome
Pneumoconioses
Lung diseases caused by prolonged inhalation of foreign material
Lead to fibrosis of the lungs
Main symptoms chronic dry cough & SOB
Coal workers pneumoconiosis
Blackened sputum
Progressive massive fibrosis
Coal dust macules = aggregated macrophagescreates intensely pigmented areas
Silicosis:
Aka Stone Masons disease (S for Stone for Serious)
Progressive disease characterized by nodular lesions commonly progress to fibrosis
The most common & most serious pneumoconiosis (NOT siderosis, calcinosis, or anthracosis)
Characterized by massive fibrosis of the lung
Production of fibroblast growth factor (FGF)
Associated w/ increased susceptibility to TB
Asbestosis:
Characterized by diffuse interstial fibrosis caused by inhaled asbestos fibers
Can develop up to 15-20 yrs after regular asbestos exposure long latency
Results in marked predisposition to bronchogenic carcinoma & malignant mesothelioma of the pleura & peritoneum
Histologically ferruginous bodies found in lung (asbestos fibers coated w/ hemosiderin) & w/ ivory pleural plaques
Berylliosis:
A systemic granulomatous disorder w/ dominant pulmonary manifestations

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Anthracosis:
Aka Coal Workers pneumoconiosis, Black Lung disease
NOT known to predispose a pt to cancer
Progressive nodular pulmonary disease caused by deposits of coal dust in lungs
Ocurrs in two forms:
1) Simple small lung opacities
2) Complicated aka progressive massive fibrosis masses of fibrous tissue occasionally develop in pts lungs
Goodpastures syndrome:
Anti-glomerular basement membrane antibodies produce linear staining on immunofluorescence
Findings: pulmonary hemorrhage leading to hemoptysis; renal lesions lead glomerulonephritis w/ hematuria
This is a type II hypersensitivity
Think GP Good Pasture, Glomerular and Pulmonary
Most common in men between ages 20-40
Cystic Fibrosis
Autonomic recessive disorder heterozygotes unaffected
Generalized dysfunction of the exocrine glands affecting multiple organ systems
Inherited disease caused by a defective gene, chromosome 7q
The gene encodes a MB-associated protein called cystic fibrosis transmembrane regulator (CFTR)
Is thought to regulate Cl & Na+ across epithelial MBs
Results in defective Cl- channels, leading to very thick mucous secretions
Has elevation of Na+ and Cl- secretions
Affects mucus & sweat glands & Na+ channels
Causes respiratory & digestive problems
Thick mucus forms in breathing passages of lungs & predisposes pt to chronic lung infections
Effects males & females life expectancy = 28 yrs
Present usually in 1st year of life w/ steatorrhea
Most common fatal genetic disease in white children
Dx with Sweat Chloride test (elevated Cl- in sweat)
Complications include:
Pulmonary disease, pancreatic insufficiency, & meconium ileus (form of intestinal obstruction in newborns)
Lung abscess:
Pus-filled cavity in the lung surrounded by inflamed tissue & caused by infection
Most common cause is aspiration often in the settings of altered consciousness
Associated with aspiration of material from caries teeth
Alcoholism is the single most common condition predisposing to lung abscess
Also at risk: persons suffering from drug OD, epileptics, & pts w/ neuroloic dysfunction impairing the gag reflex
Almost all pts w/ a lung abscess present w/ cough & fever:
Characteristic symptoms:
Production of large amounts of foul-smelling sputum
Also dyspnea, chest pain, & cyanosis may be present
Common causes:
Most common aspiration of anaerobic bacteria (decayed teeth, vomitus, foreign material) from the oral cavity
Staphylococcus (most common bacterial cause) NOT strep which you would think
Inhaled Endo File, you may get a lung abscess
Also Pseudomonas, Klebsiella, & Proteus
Complications of pneumonia or bronchiestasis
Septic arterial embolus from a heart valve
Aspiration of Food
May cause Pneumonia, Lung abscess, Atelectasis, and Asphyxiation
NOT Pneumothorax
A collapsed Lung!!!
Adult respiratory distress syndrome
Might be caused by each of the following:
Shock
Heroine overdose
Viral pneumonia
Breathing 100% O2 Too much O2 causes respiratory depression, same result as heroine person may go into
respiratory arrest; because person is not breathing, respiratory acidosis occurs = bad news
NOT cigarette smoking Youre not going to immediately die due to smoking a cig
Neonatal respiratory distress syndrome:
Surfactant deficiency leading to increase surface tension, resulting in alveolar collapse
Surfactant is made by type II pneumocytes most abundantly after 35 weeks in gestation. The lecithin to sphingomyelin
ratio in the amniotic fluid, a measure of the lung maturity, is usually less than 1.5 in neonatal respiratory distress syndrome.

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Surfactant = dipalmitoyl phosphatidylcholine


Tx with maternal steroids before birth, artificial surfactant for infant
Kartageners syndrome:
Think Cant move your grocery KART
Immotile cilia due to a dynein arm defect. Results in sterility (sperm also immotile) bronchiectasis, and recurrent sinusitis
Bronchogenic cancers:
Lung cancer usually develops in the wall or epithelium of the bronchial tree such cancer is called bronchogenic
carcinoma
Lung cancer that starts in the bronchoepithelium
Tumors that arise centrally:
Epidermoid (squamous) carcinoma:
Most arise in the central portion of the lung
Appears as a hilar mass & frequently undergoes central cavitation.
Clearly linked to cigarette smoking
SCC is also linked to increase in PTH, and endocrine effect of hyperparathyroidism
Pulmonary neoplasm to which the endocrine effect of hyperparathyroidism is attributed!!!
Small cell (oat cell) carcinoma:
Most arise in the central portion of the lungs
Most aggressive & highly malignant
Most commonly affects men (80%), 90% of whom are cigarette smokers
Clearly linked to cigarette smoking
Oat cell that is observed in these carcinomas is a short, bluntly spindle-shaped, anaplastic cell containing a relatively
large hyperchromatic nucleus w/ little or not cytoplasm
Associated w/ ectopic hormone production (ADH, ACTH)
May lead to Lambert Eaton syndrome (muscle weakness due to Ag against motor nerve)
Wiki says its due to Abs against Ags of at NM junction.
Tumors that arise peripherally:
Adenocarcinoma:
Most common bronchogenic cancer
Tends to arise in the periphery, usually in the upper lobes of the lung
Develops on site of prior pulmonary inflammation or injury (old TB, scars, healed infarcts)
Less clearly linked to cigarette smoking
Large cell (anaplastic) carcinoma:
Tends to arise in the periphery
Very poorly differentiated
Bronchioalveolar Carcinoma
Only about 14% of patients w/ lung cancer survive 5 years after Dx
The Cancer with the best 5 yr prognosis is Lungs 15%, Stomach 21%, Colon 60%, Pancreas 4%, Esophagus15%
What is thyroid cancer survival rate that was on option too!
Metastases is very common to brain, bone, & liver
Pancoasts tumor:
May result from intrathoracic spread of bronchogenic cancer
Carcinoma that occurs in apex of lung and may affect cervical sympathetic plexus, causing Horners syndrome:
Ptosis (slight drooping of eye)
Anhidrosis (absence of sweating) and flushing (rubo of affected side of face)
Miosis (pupil constriction)
A person has ptosis, anhydrosis & a red face. What problem?? Sympathetic sup. cervical ganglion lesion??
3 neuron oclusosympathetic pathway above projects from the hypothalamus to intermediolateral column of the spinal
cord, then to the superior cervical (sympathetic ganglion, and finally to the pupil, the smooth muscles of the eyelids, and
the sweat glands of the forehead and face
Interruption of these pathways result in Horners syndrome
CONGENITAL HEART DEFECTS:
Infective endocardititis
The following are predisposers:
Tetraology of Fallot
Congenital aortic stenosis
Patent ductus arteriosus
Ventricular septal defect

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HEART DISORDERS

Right-to-left shunts cyanotic congenital heart disease (Blue Babies)


Think the 3 Ts Tetralogy, Transposition, Truncus
Eisenmengers
Tetralogy of Fallot (most common cause of early cyanosis) PROVe: Has these four things presenting together:
1) Pulmonary stenosis
2) Right ventricular hypertrophy
3) Overriding aorta (overrides the ventricular septal defect) aorta partly connected to rt ventricle
4) Ventricular septal defect patient suffers from cyanoic spells
Caused by anterosuperior displacement of infundibular septum
Transposition of great vessels:
Aorta leaves the right ventricle and pulmonary trunk leaves the left ventricle which separates the systemic and the
pulmonary circulations. Pt will die
Due to failure of aorticopulmonary septum to spiral, common in babies to diabetic mothers
Persistent truncus arteriosus: an embryonic structure
Left-to-right shunts acyanotic congenital heart disease (Blue Kids)
Ventricular septal defect (most common congenital cardiac anomaly)
Atrial septal defect: has loud S2; wide, fixed split S2
Patent ductus arteriosus: (embryonic structure)
there is a minor vessel that connects the blood from the aortic arch to the pulmonary artery
Lung resistance decreases and shunt becomes left to right w/ subsequent right ventricular hypertrophy and failure
Associated w/ continuous machine-like murmur. Patency maintained by PGE synthesis and low O2 tension
Indomethacin is used to close patent ductus arteriosus, and PGE is used to keep it open to sustain life in case of
transposition of greater vessels
Eisenmengers syndrome:
Uncorrected ventricular septal defect, arterial septal defect & patent ductus arteriosus leads to progressively
pulmonary HTN
As pulmonary resistance increases, the shunt changes from left to right to right to left, which causes late cyanosis
(clubbing and polycythemia)
Coarctation of aorta:
Infantile type (preductal): aortic stenosis proximal to insertion of ductus arteriousus. Male to female 3:1
INfantile: IN close to the heart (associated w/ Turner syndrome)
Adult type (postductal): stenosis distal to ductus arteriosus, associated w/ notching of the ribs, hypertension in upper
extremities, weak pulses in lower extremities
aDult: Distal to Ductus
PERICARDITIS:
Causes infection, ischemic heart disease, chronic renal failure, CT diseases
Effusions are usually serious; hemorrhagic effusion are associated with TB and malignancy
Findings Pericardial pain, friction rub, EKG changes, Pulsus paradoxus
Can resolve w/o scarring or lead to chronic adhesive or chronic constrictive pericarditis
Acute Pericarditis:
Inflammation of pericardium that begins suddenly & is often painful
Inflammation causes fluid & blood products (e.g., fibrin, RBCs, & WBCs) to pour into the pericardial space
Constrictive Pericarditis:
Post-inflammatory thickening & scarring of the pericardial MB constricts chambers
Can be caused by TB
Serous Pericarditis:
Caused by SLE, rheumatoid arthritis, infection, uremia, renal failure
Fibrinous Pericarditis:
Caused by uremia, MI, rheumatic fever, renal failure
Hemorrhagic Pericarditis:
Caused by TB or malignancy
Findings pericardial pain, friction rub, ECG changes (diffuse ST elevations in all leads), distant heart sounds
Can resolve w/out scarring or lead to chronic adhesive or chronic constrictive pericarditis
Cardiac Tamponade:
Heart compression caused by blood or fluid accumulation in the space between myocardium & pericardium leads to
CO
Blood cannot flow into the right atrium pt can die suddenly of decreased CO
Most likely to cause sudden arrest of heart fxn (incorrect answers: cardiac cirrhosis, mitral stenosis, constrictive
pericarditis)
Can occur after large myocardial infarction
Dead heart musculature of a ventricle can rupture, causing blood loss into the pericardial space

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Signs distended neck veins, hypotension, decreased heart sounds, tachypnea, & weak or absent peripheral pulses
The most serious complication of percarditis
Aneurysms
Berry aneurysm
Atherosclerotic aneurysm
Syphilitic aneurysm
Microaneurysm
Dissecting aneurysm:
Most frequently occur in the aorta
Characteristically results in aortic ruptures, most often into the pericardial sac, causing fatal cardiac tamponade
ISCHEMIC HEART DISEASE = Coronary artery disease (CAD):
Leading cause of death in U.S.
Usually caused by atherosclerosis
Condition in which fatty deposits (plaques) accumulate in cells lining coronary artery walls obstructs blood flow
As coronary artery obstruction worsens, ischemia to heart muscle can develop damages heart
Primary effect is loss of O2 & nutrients to myocardial tissue cue to diminished blood flow
NOTE: right coronary artery supplies blood from aorta to right side of heart
Characteristic features:
Represents an imbalance between myocardial oxygen demand and available blood supply
Has a peak incidence in men over 60 years and women over 70
Contributing factors include chronic HTN and high levels of LDLs
NOT Usually results from complete occlusion of one or more coronary arteries
Doesnt have to be complete occlusion
Risk factors high BP, hyperlipidemia, smoking, being overweight, inactivity
Dx based on pt Hx, especially Hx w/ characteristic risk factors
Major complications of CAD = 1) angina pectoris & 2) myocardial infarction
1) Angina:
Specific type of chest discomfort caused by inadequate blood flow through BVs of heart
Usually described as burning, squeezing or tight feeling in substernal chest
May radiate to left arm, neck, jaw, or shoulder blade
Most people w/ chronic angina feel pain only during exercise
Occurs when heart load becomes too great relative to coronary blood flow
Relieved by rest or nitrates (myocardial infarction is not)
2) Myocardial Infarction:
Heals by way of organization of collagen
Most frequently characterized by coagulation necrosis (eosinophilic masses w/ nuclei; result protein coagulation)
Most commonly caused by coronary atherosclerosis interrupts blood supply to heart
The most common autopsy finding in sudden death caused by a M.I. is coronary thrombosis
Very common in males & postmenopausal females
Signs & symptoms crushing pain in chest area over the heart, pain in left arm and/or jaw, sweating, GI upset,
fatigue, shortness of breath
Prognosis is fairly good if pt reaches hospital most deaths occur outside hospital due to arrhythmias
Most acute MIs are caused by coronary artery thrombosis
Coronary artery occlusion
LAD (left anterior descending) > RCA > circumflex
Acute MI is the most common cause of death in industrialized nations
Pain from an MI is NOT relieved by vasodilators such as nitroglycerin
Thrombolytic agents such as streptokinase often limit the size of infarction
Mycardial necrosis usually begins 20-30 min after coronary artery occlusion ***20-30 min***
Dx of a MI
First 6 hours, EKG is the gold standard
ST elevation (transmural ischemia)
Q Waves (transmural infarct)
There is death of heart muscle tissue causes leakage of enzymes into blood
Elevated enzyme levels following a myocardial infarction:
Cardiac troponin GOLD STANDARD w/in 1st 4 hours up to 7-10 days, more specific than other protein
markers
Serum Glutamate-Pyruvate Transaminase (SGPT) = AST, nonspecific and can be found in cardiac, liver,
and skeletal muscle cells
Serum Glutamic-Oxaloacetic Transaminase (SGOT)
Serum Lactic Dehydrogenase (LDH) former test of choice is also elevated from 2-7 days post-MI
Creatine Kinase (CK), or CK-MB test test of choice in 1st 24 hours post- MI

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Evolution of a MI
First Day
Occluded artery Infarct Pallor
Coagulative necrosis w/in the first (20-30min) 24 hours leads to release of contents of necrotic cells into
bloodstream with the beginning of neutrophil emigration
2 4 Days
Pallor Hyperemia
Tissue surrounding infarct shows acute inflammation
Dilated vessels (hyperemia)
Neutrophil emigration
Muscle shows extensive coagulative necrosis
5 10 Days
Hyperemic border; central yellow-brown softening, maximally yellow and soft by 10 days
Outer zone (in growth of granulation tissue)
Macrophages, and Neutrophils
7 weeks
Now its Grey-white
Contracted scar is complete
Infarcts heal by organization
ECG changes:
ST elevation (transmural infarct), ST depression (subendocardial infarct), & Q waves (transmural infarct)
Complications of myocardial infarctions:
Cardiac arrhythmia (90%), highest rise 2 days postinfarct
LV failure and pulmonary edema (60%)
Thromboembolismmural thrombus (a thrombus produced as a result of damage to the ventricular
endocardium)
Death from MI and Bx reveals thromboembolism
From the Right Ventricle
Cardiogenic shock (large infarcthighest risk of mortality)
Rupture of ventricular free wall, interventricular septum, papillary muscle (4 10 days post MI), cardiac
tamponade
Fibrinous pericarditisfriction rub (3-5 days post MI)
Dressler syndromeautoimmune phenomenon resulting in fibrinous pericarditis (several weeks post MI)
3) Sudden cardiac death
Death from cardiac causes within 1 hour of onset of symptoms, most commonly due to lethal arrhythmia
But acute MI leading cause of death is thrombo-embolism splitting hairs so dont get clowned!
4) Chronic ischemic heart disease
Progressive onset of congestive heart failure over many years due to chronic ischemic myocardial damage
RHEUMATIC FEVER:
Acute inflammatory disease w/ systemic manifestations & particular involvement of heart valves
Follows an upper respiratory infection w/ a Group A, -hemolytic streptococcus
Secondary infection from Group A strep, due to autoimmune, not from bacteria
Can be a sequelae to Scarlet Fever
Most common in children 5-15 y.o.
Onset is usually sudden
Occurs 1-5 symptom-free wks following recovery from sore throat or scarlet fever
Mild cases may last 3-4 wks, severe cases may last 2-3 months
Treatment penicillin & rest
Although RF may follow a streptococcal infection, it is not an infection
It is an inflammatory reaction to an infection
Heart is damaged because of a hypersensitivity rxn to group A, Beta Hemolytic streptococci
Clinical Dx requires 2 major criteria or 1 major + 2 minor (the Jones criteria)
Major carditis, arthritis, chorea, erythema marginatum & subcutaneous nodules
Minor fever, arthralgias (joint pain w/o inflammation), Hx of RF, EKG changes & lab tests
Heart inflammation
A pt with rheumatic heart disease would most likely develop congestive heart failure due to valvular insufficiency
Disappears gradually, usually w/in 5 months
May permanently damage heart valves resulting in rheumatic heart disease
Mitral valve (between left atrium & ventricle) is most commonly damaged
Valve may become leaky (mitral valve regurgitation) abnormally narrow (mitral valve stenosis) or both
Classic lesion of rheumatic fever is the Aschoff body FEVER Causes ASHES
An area of focal interstitial myocardial inflammation

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Characterized by fragmented collagen & fibrinoid material by large unusual cells (Anitschkow cells) & by
occasional multinucleated giant cells (Aschoff myocytes)
NOTE: Most common characteristic lesion of rheumatic fever, scleroderma and RA is fibrinoid degeneration
Think FEVERSS Fever, Erythema marginatum, Valvular damage, ESR increase, Red-hot joints, Subcutaneous
nodules, St. Vitus dance (chorea)
VALVULAR HEART DISEASE:
Mitral valve prolase
Mitral valve leaflets billow into the left atrium during systole, leading to insufficiency
High pitched murmur, & mid-systolic click are characteristic of MVP
Mitral stenosis
Due to scarring, calcification, or fusion of the mitral valve
Early diastolic opening snap is characteristic of MS
Aortic valve insufficiency
Insufficiency = regurgitation
Backflow thru aortic valve leads to increased LV volume, raising filling pressure, leading to LV failure
Aortic valve stenosis
CONGESTIVE HEART FAILURE (CHF):
Disorder in which heart loses ability to pump blood efficiently
Almost always a chronic, long-term condition it can sometimes develop suddenly
May affect the right &/or left side
Left ventricle usually fails first right-sided failure soon follows
Earliest & most common signs:
Exertional dyspnea bc right side is first
Paroxysmal nocturnal dyspnea (pt wakes up up grasping for air)
Other signs:
Peripheral edema (ankle edema), cyanosis, high venous pressure (back-up), passive congestion of the liver (back-up),
and orthopnea (sitting or standing in order to breath comfortably) pt. has to sleep sort of upright
Left-sided failure:
Common causes:
Coronary heart disease
Leading cause of cardiac death in the U.S.
HTN causes left ventricular hypertrophy
Aortic & mitral valvular disease
Myocardial disease
Rheumatic heart disease 1988 Q96
Presence of hemosiderin-laden macrophages (heart failure cells) w/ pulmonary congestion in LV failure
Complications of left-sided failure:
Life-threatening complication = pulmonary edema
Most reliable post mortem indicator is chronic passive congestion of the lungs
Presence of hemosiderin-laden macrophages (heart failure) cells
Orthopnea pooling of blood in lungs in supine position adds volume to congested pulmonary vascular system
Dyspnea Failure of LV output to increase during exercise
Pleural effusion just means excess fluid in pleural cavity
Bacterial pneumonia
Paroxysmal nocturnal dyspnea
NOT Myocardial hyperplasia (HYPERTROPHY!!)
Right-sided failure:
Most common cause = left-sided failure
Most common cause of pure RS-CHF = cor pulmonale (Rt heart problem from respiratory disorder)
Cor pulmonale
Enlargement of the right ventricle
Most commonly direct result of pulmonary HTN due to resistance to blood flow thru lungs
Right sided heart failure w/out involvement of the left side of the heart occurs most often w/ cor pulmonale
Most conspicuous sign is systemic venous congestion & peripheral edema
Clinical hallmarks of right-sided failure:
Jugular venous distension
Hepatomegaly Increased venous pressure, leads to increased portal resistance
Splenomegaly
Generalized edema
Affects the kidneys by causing: (All because BP is Down) these are all related and make sense
Renal hypoxia

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Venous congestion
Retention of H2O and NaCl
Decreased GFR
Cells of Heart Failure:
Hemosiderin-laden macrophage in alveoli, aka siderophore
Hemosiderin in the lungs is caused byHeart Failure!
INFECTIOUS ENDOCARDITIS:
Type of inflammation of heart valves
Vegetations on the valves usually consist of fused platelets, fibrin, and masses of bacteria
Most likely valve damaged is the MITRAL
Can affect the heart muscle (myocarditis) or lining of the heart (pericarditis)
Mitral valve is most commonly involved, followed by aortic valve
Source of infection:
Transient bacteremia (presence of bacteria in the blood)
Common during dental, upper respiratory, urologic, & lower GI diagnostic & surgical procedures
Most common: Streptococcus viridans -hemolytic strep causes ~ of cases
Most common cause from a dental procedure S. viridans
Other common organisms: Staph, Group D Strep
Less common organisms: Pseudomonas, Serratia, Candida
Can cause growths on heart valves, lining of heart or lining of the BVs
Fused platelets, fibrin, bugs are found in vegetation due to bacterial endocarditis
Growths may be dislodged & send clots to brain, lungs, kidneys or spleen
Health care provider may hear changing murmurs & detect enlarged spleen & mild anemia
Murmurs result from changes in valvular blood flow when clumps of bacteria, fibrin & cellular debris collect on valves
Self-infection (esp. by IV drug users) w/ S. aureus causes most severe damage (acute endocarditis)
Endocarditis on right side of the heart suggests IV drug abuse
Symptoms:
Fever is hallmark may be present daily for months before other symptoms appear
Fatigue, headache, malaise, night sweats
Janeway lesions (small red lesions on palm/sole) Roths spots (round white spots on retina surrounded by hemorrhage)
Nail bed (splinter) hemorrhages Oslers nodes (tender raised lesions on finger or toe pads)
Fever Anemia Murmur Emboli
Think JR = NO FAME Janeway Lesions, Roths spots, Nail-bed hemorrhage, Osler nodes, Fever, Anemia,
Murmur, Emboli
TYPES OF ENDOCARDITIS:
Acute bacterial endocarditis: HIGH VIRULENCE
STAPHylococcus aureus
Large vegetations on previously normal valves, rapid onset
Subacute bacterial endocarditis: LOW VIRULENCE
STREPtococcus viridans
The most common organism producing subacute bacterial endocarditis is alpha-hemolytic streptococcus
(S. sanguis, which is a Viridans Streptococcus) S. aureus is much worse in other cases, makes sense it is
worse w/ endocarditis
Smaller vegetations on congenitally abnormal or diseased valves
Sequela of dental procedures
More insidious onset than Acute
Tetralogy of Fallot, Congenital aortic stenosis; Patent ductus arteriosus; & Ventricular septal defect are all at risk of
developing secondary endocartitis
MYOCARDITIS = Cardiomyopathy:
Disease of myocardium w/ unknown etiology
Dilated (congestive) cardiomyopathies: heart dilates and looks like a balloon on chest X ray
Systolic dysfunction ensues
most common 90% of casts
Think ABCsDs Alcohol, Beriberi, Coxsackie B, Cocaine, Chagas disease, Doxorubicin, Diastolic Dysfunction
Hypertrophic cardiomyopathy (formerly IHSS):
Diastolic dysfunction ensues
often asymmetric and involving the intraventricular septum.
50% of cases are familial and are inheritied as an autosomal-dominant trait
Cause of sudden death in young athletes
Walls of LV are thickened and chamber becomes banana shaped on echocardiogram
Not due to HTN and other shit like that

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Restrictive/obliterative cardiomyopathy:
major causes include sacroidosis, amyloidosis, scleroderma, hemochromatoisis, endcardial fibroelastosis, and
endomyocaridal fibrosis (Lofflers)
Cardiac tumors:
Myxomas are the most common primary tumor in adults.
90% occur in the atria (mostly LA)
Myxomas are usually described as a ball-valve obstruction in the LA
Rhabdomyomas are the most frequent primary cardiac tumor in children
Metastases most common heart tumor
Cardiac muscle:
Following injury, restores fxnal capacity via hypertrophy
Creatine phosphokinase:
Found in heart, brain & skeletal muscle NOT found in liver
If total CPK level is substantially elevated, usually indicates injury/stress to one or more of these tissue
Heart Murmurs
Aortic stenosis Crescendo-decrescendo systoslic ejection murmur, with LV >> aortic pressure during systole
Aortic Regurgitation
High-pitched blowing diastolic murmur. Wide pulse pressure
Mitral Stenosis Rumbling late diastolic murmurs. LA >> LV pressure during diastole. Opening snap
Mitral Regurgitation High-pitched blowing holosystolic murmur
Mitral Prolapse Systolic murmur with midsystolic check. Most frequent valvular lesion, especially in young women
VSD (Ventricular Septal Defect) Holosystolic murmur
PDA (Patent Ductos Arteriosus) Continous machine-like murmur
Buergers Disease
Known as smokers disease and thromboangitis obliterans
Idiopathic, segmental, thrombosing vasculitis of intermediate and small peripheral arteries and veins
Findings Intermittent claudication, superficial nodular phlebitis, cold sensitivity, severe pain in affected part, may lead to
gangrene
Tx with Cessation of Smoking
Dont smoke in Burger King
VS. Raynauds Disease
Symmetric asphyxia (impaired oxygen exchange); idiopathic paroxysmal bilateral cyanosis of the digits due to
arterial and arteriolar contraction
Caused by cold or emotion
Takayasus Arteritis Korean Dr. saying to pt when feeling pulse: What Say You Takay A Su? I no hear Pulse!
Pulseless Disease
Thickening of aortic arch and/or proximal great vessels, causing weak pulse in upper extremeities and ocular disturbances
Associated with elevated ESR
Think FAN MY SKIN Fever, Arthralgia, Night sweats, MYalgia, SKIN nodules
HEMODYNAMIC DYSFUNCTION
Edema
Abnormal accumulation of fluid in the interstitial spaces or body cavities
Edema due to hemodynamic dysfunction may result in the brain, lung, subcutaneous tissue, peritoneal cavity
NOT the pancreas
May result from:
Increased capillary permeability (principal factor)
Elevated capillary pressure
Increased interstitial fluid colloid osmotic pressure
Decreased plasma colloid osmotic pressure
Increased sodium retention
Increased venule blood pressure
Lymphatic obstruction
Types of edema:
Anasarca Cant see your Sarcs (Muscles because youre so swollen)
generalized swelling or massive edema; generalized infiltration of edema fluid into subcutaneous CT
NOT usually associated with CHF
Hydrothorax excess serous fluid in the pleural cavity
Usually from cardiac failure
Hydropericardium excess watery fluid in the pericardial cavity
Ascities (hydroperitoneum) excess serous fluid in the peritoneal cavity
Transudate noninflammatory edema fluid resulting from altered intravascular hydrostatic or osmotic pressure

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Exudate inflammatory edema fluid from increased vascular permeability


Right sided CHF leads to peripheral edema
Most conspicuous clinical sign of right sided heart failure
Left-sided CHF leads to pulmonary edema
A person with left heart failure might show signs of dyspnea when placed in the supine position from the edema and
excessive pulmonary capillary hydrostatic pressure
Edema may described as:
1) Pitting edema press against swollen area for 5 sec, then quickly remove it indentation left that fills slowly
2) Nonpitting edema press against swollen area for 5 sec, then quickly remove it no indentation left in skin
Thrombus:
Solid mass of clotted blood that develops in & is attached to a BV wall
Formation enhanced by endothelial injury, alteration in blood flow (turbulence), & hypercoagulability
Arterial thrombi show alternating red & white laminations (lines of Zahn)
Venous thrombi are more uniformly red w/ distinct lines
Conditions predisposing to venous thrombosis:
Heart failure, extensive tissue damage, bed rest, pregnancy, oral contraceptives, age, obesity, & smoking, Just
had surgery, bound to wheelchair, cirrhosis/Increased Portal HTN
Except COPD
A whole thrombus may detach to form a large embolus or fragments may break off to generate small emboli
Different types of Thrombi:
Agonal forms in heart during the dying process after prolonged heart failure
Mural
forms as a result of damage to ventricular endocardium (usually left ventricle, following myocardial infarct)
A major complication is a cerebral embolism
It complicates myocardial infarctions, atrial fibrillation, & atherosclerosis of the aorta
White composed chiefly of blood platelets
Red rapidly forms by coagulation of stagnating blood composed of RBCs rather than platelets
Fibrin formed by repeated deposits of fibrin from circulating blood usually does not completely occlude the vessels
Ten days after hospitalization for a large, incapacitating myocardial infarct, a 50-year-old man suddenly develops paralysis of
the right side of his body. The best explanation for his brain damage isdetachment of a mural thrombus from the left
ventricle
Stroke following MI is caused by arterial thrombi (not venous) venous would end up in heart, or lung
Thrombosis:
Formation or presence of a blood clot inside a blood vessel or cavity of the heart
Deep Vein Thrombosis
Predisposed by Virchows triad
Stasis, Hypercoagulability, and Endothelial damage
Thrombotic occlusion in a coronary artery may result in:
Infarction
Fibrosis
Conductive changes
Nothing
Thrombolysis:
Breaking up of a blood clot
Embolus:
Blood clot that moves through the bloodstream until it lodges in a narrowed vessel and blocks circulation
Mass of solid, liquid, or gas that moves w/in a BV to lodge at a site distant from its origin
Most emboli are thromboemboli
Can lodge in the vascular beds of vital organs, occluding blood flow & possibly causing infarction
Splenic infarcts most commonly result from emboli originating in the left side of the heart
56-yr-old with atrial fibrillation and hx of MI 2 yrs ago, experiences a right flank pain and hematuria, paralysis of the right
side of the body and ischemia to the left foot
DUE to arterial emboli (NOT septicemia, venous thrombi or venous emboli)
I think youd have edema and not ischemia if it was a venous issue
A pt w/ cardiovascular disease has chronic atrial fibrillation. She is prescribed warfarin (Coumadin) to prevent stroke
Think FAT BAT Fat, Air, Thrombus, Bacteria, Amniotic fluid, Tumor
Fat embolism
Associated w/ long bone fractures marrow from inside long bones
More info found elsewhere in file
Pt breaks femur dies hours later, whats the cause? Fat embolism!
Air Pulmonary thromboembolus = pulmonary embolus
Very common occurrence

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Occurs during times of venous stasis (prolonged bed rest or sitting, CHF)
Most common source of a pulmonary embolism is thrombophlebitis (a thrombus formed w/in a vein)
95% of pulmonary embolus come from Deep Leg Veins
In this case, a deep leg vein is the common source for the origination of the thrombus
A thrombotic embolus originating in the femoral vein usually becomes arrested in the pulmonary circulation
Saddle Embolus:
A large embolus that may occlude the bifurcation of the main pulmonary artery
Usually results in sudden death (NOT pulmonary embolism)
Symptoms:
Sudden shortness of breath, tachycardia, hyperventilation, cardiognenic shock
May result in:
Atelectasias
Cardiogenic shock
Pulmonary hemorrhage
Pulmonary HTN
NOT absence of symptoms
Diagnosis:
Ventilation/perfusion scan
Amniotic Fluid embolus
Can lead to DIC, especially postpartum
Atherosclerotic Brain Infarction
Most likely warning sign of impending brain infarction is transient ischemic attacks
So, heres the story on TIAs:
TIAs are caused by a temporary disturbance of blood supply to a restricted portion of the brain
TIAs are called mini strokes, because their neurological symptoms last < 24 hours
TIAs are often called a warning sign for an approaching cerebrovascular accident, or stroke
Strokes last > 24 hours
The most common cause of a TIA is an embolus, which most frequently arises from an atherosclerotic plaque OR
from a thrombus
Phlebitis:
Inflammation of a vein
Pylephlebitis:
Inflammation of portal vein or any branches
Congestion:
Accumulation of excessive blood w/in BVs
Shock:
Set of hemodynamic changes reducing blood flow below a level providing adequate O2 for metabolic needs of organs/ tissues
Requires immediate medical Tx can worsen very rapidly
Clinical signs:
Reduced cardiac output is the main factor in all types of shock
Tachycardia, hypotension, pallor, diminished urinary output, & muscular weakness
Anoxia most severly affects brain & heart
The body produces excess acid in the advanced stages of shock, when lactic acid is formed through the metabolism of sugar
Major classes of shock:
Hypovolemic
Produced by a reduction of blood volume
Causes include hemorrhage, dehydration, vomiting, diarrhea, & fluid loss from burns
Cardiogenic
Due to the sudden reduction of cardiac output
Main cause is myocardial infarction
Septic
Due to severe infection
Most frequently caused by endotoxins from G- bacteria!!!!!
Minor classes of shock:
Neurogenic
Results from injury to the CNS
Anaphylactic
Shock that occurs w/ severe allergic reactions
Stages of shock:
1) Non-progressive (early)
Compensatory mechanisms maintain perfusion of vital organs ( HR & peripheral resistance)

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2) Progressive
Metabolic acidosis occurs (compensatory mechanisms are no longer adequate)
3) Irreversible
Organ damage survival not possible
Tx:
Epinephrine is the drug of choice
Amoxicillin Rxn
Pt becomes hypotensive, itchy, and having difficult breathing
This means Amox reacts with IgE and activates cytotoxic T cells that release lymphokines
BLOOD DISORDERS
Purpura spots: Petechiae < Purpura < Ecchymosis
Purplish discolorations in the skin produced by small bleeding BVs near skin surface
Petechiae = small purpura spots, small pinpoint hemorrhages
Ecchymoses = large purpura spots
Both ecchymosis & purpura are manifestations of hemorrhage
May also occur in the mucous MBs (e.g., lining of mouth) & in internal organs
By itself is only a sign of other underlying causes of bleeding
May occur w/ either normal platelet counts or decreased platelet counts
Kinds of Purpura:
Thrombocytopenic Purpura (Werlhofs disease):
Autoimmune disorder
Bleeding disorder characterized by deficiency in platelet #
Results in multiple bruises, petechiae, & hemorrhage into the tissues
Thrombotic Thrombocytopenic Purpura (TTP):
Severe & frequently fatal form characterized by low blood platelet count
Due to consumption of platelets by thrombosis in terminal arterioles & capillaries of many organs
Melena:
Presence of dark, tarry stools, due to the presence of blood altered by the intestinal juices
Refers to digested blood in the stool a manifestation of hemorrhage
BLEEDING/CLOTTING DISORDERS:
Laboratory values:
PT = prothrombin time
Measures Factors I, II, V, VII, X
PTT = partial thromboplastin time
Measures Factor XII, prekallikrien, kininogen, Factors I, II, V, VII, IX, X, XI
TT = thrombin time
Measures Factor I
Clotting/Clot lysis
Process:
Prothrombin converted to thrombin (in presence of thromboplastin & calcium ions)
Thromboplastin is released by damaged cells, thereby initiating the formation of fibrin
Prothrombin is produced in the liver with help from Vitamin K
Thrombin in turn converts fibrinogen to fibrin
Fibrin threads then entrap blood cells, platelets, & plasma to form a blood clot
Fibrinogen:
Plasma protein that is essential for the coagulation of blood and is converted to fibrin by thrombin & ionized
calcium
NOT in serum
Fibrin:
Stringy, insoluble protein responsible for the semisolid character of blood clot
Serves as a template for fibroblasts to repair tissue & walls of the area to infection
The product of the action of thrombin on fibrinogen in the clotting process
Plasminogen:
Inactive precursor to plasmin that is present in tissues, body fluids, circulating blood, & w/in clots
Converted by Steptokinase, Staphylokinase, and Urokinase
Fibrinolysin = Plasmin:
A proteolytic enzyme derived from plasminogen
Essential in blood clot dissolution
Not a component of the bodys nonspecific disease mechanism

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Lysozyme, complement, interferon & properdin ARE components of the bodys nonspecific disease mechanism
The most important fibrinolytic protease
Fibrinolysis:
Restores blood flow in the vessels occluded by a thrombus and facilitates healing after inflammation and injury
Aspirin
Marked with normal clotting time and normal platelet count, but prolonged bleeding time
It just inactivates them, meaning they are still there, but dont work
Factors causing delayed blood clotting:
**Pt taking Heparin (anticoagulant) acts as an antithrombin by preventing platelet agglutination
Heparin is found in the blood
**Pt w/ leukemia often has thrombocytopenia (reduced # of platelets)
Spontaneous gingival bleeding with leukemia
**Pts w/ cirrhosis have hypoprothrombinemia (abnormally small smounts of prothrombin in circulation)
In pts w/ liver disorders, it is difficult to curb hemorrhage due to hypoprothrombinemia
Prothrombin is formed & stored in parenchymal cells of liver
In cirrhosis, these cells are profusely damaged
Pts w/ severe liver disease may have hemorrhages due to a deficiency in prothrombin
**Scurvy
**Thrombocytopenia:
Condition in which there is a reduced number of platelets
Causes bleeding states wherein blood loss occurs through capillaries & other small vessels
Most common cause of bleeding disorders
Causes spontaneous bleeding
Most common sign is petechiae and purpura
Platelet count must reach a very low value (15,000 20,000/mm) before generalized bleeding occurs
Is the cause of prolonged bleeding time in pts w/ leukemia
Bleeding time increases but neither PT or PTT are affected
They dont change because they measure FACTORS, not platelets
**Von Willebrands disease:
Characterized by spontaneous bleeding from mucous MBs & excessive bleeding following trauma
Deficiency of vWf resulting in impaired platelet adhesion (although theres nothing wrong w/ the platelets)
Autosomal dominant bleeding disorder equal frequency in both sexes
Prolonged bleeding time; Normal platelet count & PT; Prolonged PTT
Results in a functional Factor VIII deficiency, because vWf serves as a carrier for factor VIII (hence prolonged PTT)
**Long-term ASA (cyclooxygenase inhibitor) Tx
Rsults in impaired thromboxane production (important platelet aggregants)
**Dicumarol:
An anticoagulant that inhibits formation of prothrombin in liver
Interferes w/ metabolism of Vit K (needed for prothrombin synthesis)
Used to delay blood clotting especially in preventing & treating thromboembolic disease
Has largely been replaced by Warfarin
**Bernard-Soulier disease hereditary platelet adhesion disorder
**Glanzmanns thombasthenia defect of platelet aggregation
Hemophilia:
Hereditary bleeding disorder causing 1) increase in clotting time & 2) abnormal bleeding
Normal PT (Prothrombin time) but Prolonged PTT (Partial Thromboplastin Time)
Hemophilia A & B are inherited as a sex-linked recessive trait
Males are affected & females are carriers
Majority of people have type A & it presents under age 25
Excessive bleeding form minor cuts, epitaxis, hematomas, & hemarthroses
Classifications of hemophilia:
A classical type&most common type deficiency of coagulation factor VIII (antihemophilic factor)
10 yr old boy dies post tooth extraction. He also had bleeding into his joints, especially his knees, maternal
uncle and male cousin had similar experience
B (Christmas disease) deficiency of factor IX (plasma thromboplastin component)
C (Rosenthals syndrome) not sex-linked, less severe bleeding deficiency of factor XI (plasma thromboplastin
antecedent)
True hemophiliac is characterized by:
Prolonged partial thromboplastin time (PTT) because it measures Intrinsic Pathway 12-11-9-10
Normal prothrombin time (PT)

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Normal bleeding time


HYPERTENSION:
Usually has no symptoms at all (called the silent killer) millions of people w/ high BP dont even know they have it
Factors age, obesity, DM, smoking, genetics, race (black > white > asian)
Predisposes to Coronary heart disease, CVA, CHF, renal failure, and aortic dissection
Pathology Hyaline thickening and atherosclerosis
The following may be evident:
Tiredness, confusion, visual changes, nausea, vomiting, anxiety, perspiration, pale skin, or an angina-like pain
Hypertensive heart disease is usually associated with left ventricular hypertrophy as an anatomic finding
Heart has to work harder against a higher afterload
Organs damaged due to prolonged HTN:
Heart 60% die of complications
Kidneys 25% die to complications
Brain 15% die of complications
Essential HTN:
High BP from no identifiable cause
Accounts for 90-95% of HTN cases (related to increased CO or increased TPR)
If left untreated can lead to retinal changes, left ventricular hypertrophy, & cardiac failure
Genetic factors include family Hx of HTN more common & usually more severe in blacks
Benign Nephrosclerosis (HARDENING) is the most common autopsy find of essential HTN
Environmental factors stress, obesity, cigarette smoking & physical inactivity
Secondary HTN:
Kidney failure = most common cause
Others causes: Obstructive sleep apnea, Aldosteronism, Renal artery bruits (suggests renal artery stenosis)
If renal artery is occluded, you get secondary HTN
Others causes still: Renal parenchymal disease, Excess catecholamines, Coarctation of the aorta, Cushings syndrome
Even more other causes: Drugs, Diet, Excess erythropoietin, Endocrine disorders
Findings in HTN
Findings
Cardiovascular
BP persistently >140/90
Angina pain
Dyspnea on exertion
Edema of extremities
Intermittent claudication
Neurologic
Severe occipital headaches w/ nausea & vomiting;
drowsiness, giddiness; anxiety; mental impairment
Renal
Polyuria; nocturin; diminished ability to concentrate
urine; protein & RBCs in urine
Ocular
Retinal hemorrhage & exudates

Basis of findings
Constricted arterioles cause abnormal resistance to blood flow
Insufficient blood flow to coronary vasculature
Left-sided heart failure
Right-sided heart failure
Decrease in blood supply from peripheral vessels to legs
Vessel damage w/in brain, characteristic of severe HTN
Arteriolar nephrosclerosis (hardening of arterioles w/in kidney)
25% die of renal failure
Damage to arterioles that supply retina

Preeclampsia (Pregnancy-Induced HTN)


Triad HTN, proteinuria, and Edema
When seizures are added, its called Eclampsia
Affects 7% of pregnant women from 20 weeks gestation to 6 weeks postpartum
Increaed incidence in pts with preexisting HTN, DM, Chronic renal disease, and autoimmune disorder
Can be associated with HELLP Hemolysis, Elevated LFTs, Low Platelets
Clinical features
Headache, blurred vision, abdominal pain, edema of face and extremities, altered mentation,
hyperreflexia,
Tx Deliver fetus ASAP
ANEMIA:
Condition in which # of RBCs is lower than normal
Measured by a decrease in hemoglobin
Body gets less O2 & therefore less energy than it needs
Symptoms fatigue, weakness, inability to exercise, & lightheadedness
Megaloblastic anemia:

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Any anemia usually caused by deficiency of vitamin B12 or folic acid


Deficiency in Folic acid is most common
Characterized by macrocytic erythrocytes (same as below under macrocytic)
Includes pernicious anemia & anemias caused by folic acid deficiency (sprue & megaloblastic anemia of pregnancy)
Pernicious anemia:
Caused by lack of intrinsic factor (needed to absorb Vit B12 from GI tract)
Vit B12 is necessary for formation of RBCs
Vit B12 also needed to help by nerve cells function properly
Best Tx with Vit B12
Causes a wide variety of symptoms fatigue, SOB, tingling sensation, difficulty walking & diarrhea
Characteristics
Reduction in acid secretion by the stomach
An increased tendency toward gastric carcinoma
Atrophic glossitis
Myelin degeneration in the spinal cord
Easy fatigability
Peripheral neuropathy
NOT Microcytic or hypochromic
A type of megaloblastic anemia
Erythrocytes produced are macrocytic & appear hyperchromic
Atrophic glossitis AND Atrophic gastritis is common
Aplastic anemia:
Result of inadequate erythrocyte production due to inhibition or destruction of red bone marrow
A stem cell defect, leading to pancytopenia
Results from drug-induced bone marrow suppression
Can be caused by radiation, various toxins, & certain medications
In drug-induced aplastic anemias:
RBCs appear normochromic (normal [hemoglobin]) & normocytic (normal size)
Just Few in #
Pancytopenia characterizd by severe anemia, neutropenia, and thrombocytopenia caused by failure or destruction of
multipotent myeloid stem cells, w/ inadequate production of differentiated lines
Tx: withdrawal of offending agent, allogenic bone marrow transplant, RBC & platelet transfusion w/ G-CSF & GM-CSF
Hemolytic anemias:
Anemias due to shortening of RBC life span ( RBC destruction)
Problems often result from the subsequent increase in bilirubin levels (breakdown product of hemoglobin)
Elevated levels of urobilinogen (compound formed in intestine by reduction of bilirubin)
Elevated kernicterus Jaundice of the KERNAL your head
Elevated levels of unconjugated bilirubin (water-insoluble bilirubin)
Unconjugated bilirubin normally combines w/ serum albumin in the liver to become water-soluble (conjugated)
Conjugated bilirubin is then secreted w/ other bile components into the small intestine
Kernicterus = toxic accumulation of unconjugated bilirubin in the brain & spinal cord pg 474 of path book
EXs of hemolytic anemia: 1) Erythroblastosis fetalis, 2) Sickle cell anemia, 3) Thalassemias, 4) Hereditary spherocytosis
By the way, these are all red cell disorders
1) Erythroblastosis fetalis:
Not an autoimmune Disease
Fetus is Rh-positive because the father passed along the dominant trait
Mother is Rh-negative & responds to the incompatible blood by producing Ab/s against it
High risk = Dad is Rh-positive and Mom is Rh-negative
In a case of Erythroblastosis fetalis, the mother has very high levels of serum complement and anti-Rh IgE
Antibodies cross placenta into fetus circulation, where they attach to & destroy the fetus RBC leads to anemia
Can also result from blood type incompatibilities (i.e., mother may be type O & fetus may be type A or B)
2) Sickle Cell anemia:
Caused by Hemoglobin S an abnormal type of hemoglobin
Autosomal recessive
Heterozygous get the trait
Homozygous get the disease (You know Homos are bad)
So if pt homozygous, bad
Globin portion of Hb S is abnormal valine is substituted for glutamic acid in the 6th position of Hb molecule
Valine replacing glutamic acid is a MISSENSE mutation base substitution leading to different AA
When Hb molecules are exposed to low [O2], they form fibrous precipitates w/ the erythrocytes

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This distorts the RBCs into a sickle (crescent) shape


Sickle cells function abnormally & cause microvascular occlusion & hemolysis
The clots give rise to recurrent painful episodes called sickle cell pain crisis
Also characteristic non-healing leg ulcers & recurrent bouts of abnormal chest pain
4 yr old black kid, long bones, enlarged spleen and liver, Lesion of skull Hair on end pg 613 path book
Homozygotes have sickle cell disease
Occurs primarily in blacks
Heterozygotes have sickle cell trait
Relatively malaria resistant (balanced polymorphism)
Becomes life-threatening when:
1) Damaged RBCs break down (hemolytic crisis)
2) The spleen enlarges & traps the RBCs (splenic sequestration crisis)
3) A certain type of infection causes the marrow to stop producing RBCs (aplastic crisis)
**Repeated crises can cause damage to kidneys, lungs, bones, eyes, & CNS
Blocked BVs & damaged organs can cause acute painful episodes (occur in almost all pts at some point)
Episodes can last hours to days, affecting bones of the back, long bones, & the chest
Complications aplastic crisis due to B19 parvovirus infection, autosplenectomy, increase risk of encapsulated
organism infection, Salmonella osteomyelitis, painful crisis (vaso occlusive) & splenic sequestration crisis
3) Thalassemias:
Group of inherited disorders resulting from imbalance in production of 1 of 4 chains of aa/s making up
hemoglobin
Characterized by low levels of erthhyrocytes & abnormal hemoglobin
Common in Mediterranean populations (ThalaSEAmia)
Alpha Thalassemias:
Due to gene deletion
No compensatory increase of any other chain. Some forms result in hydrops fetalis and intrauterine fetal death
Beta Thalassemias: pg 617 path book
Due to defect in mRNA processing
Beta chain is underproduced
In beta thalassemia major (homozygous), the beta chain is absent results in severe anemia requiring blood
transfusion. Cardiac failure is due to secondary hemochromatosis
In both cases, fetal hemoglobin production is compensatorily increased but is inadequate
HbS/beta thalassemia heterozygotes has mild to moderate disease
4) Hereditary Spherocytosis
Macrocytic anemia/Megaloblastic:
Any anemia in which average size of circulating RBCs is greater than normal
Frequently caused by deficiency of folic acid & Vit B12 (cyanocobalamin)
These are associated w/ hypersegmented PMNs
Unlike folate deficiency, Vitamin B12 is associated w/ neurologic problems
Folate deficiency can develop w/in months
Vitamin B12 deficiency takes years to develop
Also caused by drugs that block DNA synthesis (sulfa drugs, AZT)
Marked by reticulocytosis
Microcytic anemia:
Any anemia in which average size of circulating RBCs is smaller than normal
Frequently associated w/ chronic blood loss or nutritional anemia as in iron deficiency anemia
Iron deficiency anemia NO iron, then theyre SMALLER
Most likely caused by chronic blood loss to a long standing peptic ulcer
Total iron binding capacity increases while ferritin and serum iron decreases
Hypochromic, microcytic, MCV < 80
MCV = mean corpuscular volume
Diagnosis commonly made by demonstrating low serum iron, high TIBC, , & low serum ferritin
Normocytic normochromic anemias:
Include: Size is still normal
Myelophthisic
Acute hemorrhage
Enzyme defects (G6PH, PK deficiency)
RBC membrane defects (eg., hereditary spherocytosis)
Bone marrow disorders (aplastic anemia, leukemia, drug-induced bone marrow suppression)

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Hemoglobinopathies (eg., sickle cell disease)


Autoimmune hemolytic anemia
Anemia of chronic disease
Disseminated Intravascular Coagulation (DIC):
Activation of coagulation cascade leading to microthrombi & global consumption of platelets, fibrin, & coagulation factors
Splenic embolism most likely stems from DIC
Caused by obstetric complications (most common), G- sepsis, transfusion, trauma, malignancy, acute pancreatitis,
nephritic syndrome
Increased PT, PTT, fibrin split products (D dimers), low platelets, low fibrinogen
Characterized by helmet shaped cells on blood smear
Several days after an extraction, pt comes in with malaise and splinter hemorrhages beneath the fingernails
Caused from DIC or ENDOCARDITIS????? Endocarditis you fucking idiot
Arteriosclerosis:
Hardening of the arteries arterial walls become thicker & less elastic (harder)
Aorta & coronary arteries most affected
Abdominal aorta is the most common location for an atherosclerotic induced aneurysm
Atherosclerosis:
Is a form of arteriosclerosis
Disease of elastic arteries and large and medium sized muscular arteries
Most important & common form of arteriosclerosis
Fatty material (atherosclerotic plaque) accumulates under inner lining of arterial wall
Eventually the fatty tissue erodes arterial wall, diminishing elasticity (stretchiness) & interfere w/ blood flow
Plaques can also rupture, causing debris to migrate downstream w/in an artery
Signs & symptoms Angina, claudication, changes in skin color & temperature, headache, dizziness, & memory defects
Consequences of atherosclerosis:
Ischemic heart disease (coronary artery disease) & heart attack (myocardial infarct)
Stroke or aneurysm formation
Described as degenerative changes in the walls of the arteries
Microscopically:
Fibrous cap of smooth muscle cells, collagen, CT matrix, leukocytes
Cellular zone of necrotic cells, lipid-filled foam cells, plasma proteins
Proliferating capillaries in advanced lesions
Location
Abdominal aorta > Coronary artery > Popliteal artery > Carotid artery
More common in men in all age groups & in post-menopausal women
In very advanced cases, atherosclerotic plaques can become calcified & ulcerated
Risks smoking, HTN, heredity, nephrosclerosis, diabetes, & hyperlipidemia NOT alcoholism
Glass of wine a day
Arteriolosclerosis:
Diffuse thickening of the arterioles & small arteries
The kidney is particularly vulnerable to arteriolosclerosis
Carbon monoxide poisoning:
Very dangerous, colorless, odorless gas, generally associated w/ fumes from a car or a home heating system
Attaches to hemoglobin & blocks their ability to carry O2
Severe CO poisoning can cause a coma or irreversible brain damage because of O2 deprivation
Hemoglobin has higher affinity to CO than to O2, even when minute amounts of CO is inhaled (Carboxyhemoglobin)
Hemoglobin-CO bone is strong that very little is ever removed from blood
Patients w/ acute CO poisoning exhibit cherry-red discoloration of the skin, mucosa, & tissues
Think CO from your Cherry-red Porsche!!!
Death is ultimately due to hypoxia
Symptoms of low-level CO poisoning are easily mistaken for a common cold, flu or exhaustion proper Dx can be delayed
Chronic toxicity results in fatty changes in the heart, liver, kidney
Other environmental & chemical agents & their manifestations if ingested:
Carbon tetrachloride hepatocellular damage (also CNS, but think Liver and kidneys)
Mercury poisoning
Inactivates enzymes & damages cell MBs
Acute toxicity: severe renal tubular necrosis & GI ulceration
Chronic toxicity: excessive salivation, gingivitis, gastritis, cerebral & cerebellar atrophy
Cyanide poisoning prevents cellular oxidation, results in odor of bitter almonds
Methyl alcohol blindness
Lead Poisoning
Basophilic stippling of RBCs
Anemia, poorly localized abdominal pain (Abdominal colic)

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Peripheral neuropathy due to myelin degeneration primarily affects motor neurons


Wrist and Foot drop (makes sense radial nerve is MOST affected)
Lead lines in bone
Acetaminophen
Acetaminophen toxicity causes severe centrilobular hepatic necrosis
Hepatic failure 2-6 days after ingestion
Polyarteritis nodosa:
Serious BV disease wherein small & medium-sized arteries become inflamed & damaged when certain immune cells attack
Result is reduced blood supply to organs
Typically involves renal and visceral vessels
Symptoms Fever, weight loss, malaise, abdominal pain, headache, myalgia, HTN
Findings Cotton-wool spots, microaneurysms, pericarditis, myocarditis, palpable purpura, Increased ESR,
Associated with Hep B in 30% of pts
P-ANCA is often present in serum and correlates with disease activity, primarily in small vessel disease
Tx Corticosteroids
Temporal arteritis:
Chronic inflammatory disease of large arteries
Usually branches of the carotid artery
Findings Unilateral headaches, jaw claudication, impaired vision
Half of pts have systemic involvement and syndrome of polymyalgia rheumatica
Associated with elevated ESR, Responds well to steroids
Raynaud's syndrome:
Symmetric asphyxia (impaired oxygen exchange); idiopathic paroxysmal bilateral cyanosis of the digits due to arterial and
arteriolar contraction
Caused by cold or emotion
Differentiate from Buergers caused from smoking
Phlebitis:
Inflammation of the veins
Most common in the legs
Common causes local irritation (IV line), infection in or near a vein, & blood clots
Thrombophlebitis:
Vein inflammation related to a blood clot
Most common source of pulmonary embolism
Symptoms:
Tenderness over the vein
Pain in the affected part of the body
Skin redness or inflammation (not always present)
Specific disorders associated w/ thrombophlebitis:
Superficial thrombophlebitis affects veins near skin surface
Deep venous thrombosis affects deeper, larger veins
90% of cases occur in the deep veins of the leg
Pelvic vein thrombophlebitis
Congestion (hyperemia):
Localized increase in the volume of blood in the capillaries & small vessels
Active congestion results from localized arteriolar dilation (e.g., inflammation, blushing)
Passive congestion results from obstructive venous return or increased back pressure from CHF
Occurs secondary to venous obstruction
1) Acute occurs in shock or right sided heart failure
2) Chronic
a) of the lung (mostly caused by left-sided failure)
b) of the liver (mostly caused by right-sided failure) Leads to Nutmeg Liver
Myeloproliferative disorders:
Conditions in which myeloid stem cells develop & reproduce abnormally
Characteristics peak incidence in middle-aged persons, in blood basophils, serum uric acid, & prominent splenomegaly
Polycythemia vera:
Aka primary polycythemia or erythemia
A myeloproliferative syndrome characterized by a marked increase in erythrocyte mass
Rare disorder of blood precursors results in excess of RBCs (opposite of anemia)
Pts may later develop anemia or acute leukemia due to bone marrow burn out
Folate deficiency may also develop for the same reason
Characteristics

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Clubbing and cyanotic digits, erythrocytosis, leukocytsosis, thrombocytosis, & splenomegaly, along w/
[erythropoietin]
2 polycythemia an excess of RBCs caused by conditions other than polycythemia vera
EXs: chronic hypoxia associated w/ pulmonary disease, residency at high altitudes (Oskers disease), & heavy smoking
or secretion of erythropoietin associated w/ adult polycystic kidney & tumors
Myelofibrosis: Think that the Myeloid Cells are Fibrosed.
Disorder in which fibrous tissue may replace precursor cells in marrow
Results in an # of immature RBCs & WBCs & abnormally shaped RBCs, anemia & splenomegaly
CML disease in which a bone marrow cell becomes cancerous & produces a large # of abnormal granulocytes
White cell count
Differential Think that younger people tend to be more liberal TO THE LEFT, while older people tend to be more TO
THE RIGHT.
Increase in juvenile immature neutrophils or bands (shift to the left) suggests bacterial infection
Increase in mononuclear cells (shift to the right) suggests viral, occasionally fungal infections
Increase in eosinophils suggests parasitic infections among others
Leukocytosis:
Abnormally large # of leukocytes
Found as a result of a systemic bacterial infection
Most often there is a disproportionate increase in PMN # (called Neutrophilic Leukocytosis)
Scarlet Fever, Appendicitis, Staphylococcal Septicemia, Tularemia & acute abscesses all cause leukocytosis
Present in Acute abscess and Osteomyelitis
Not all bacterial infections show this characteristic
EX: typhoid fever & brucellosis actually result in a depression of PMNs
Many viral infections result in leukopenia, particularly of PMNs
Leukocyte count: a general indicator of bacterial vs. viral infection
Normal range for leukocytes: 5k10k/mm3 blood
Leukemoid reaction when circulating levels of leukocytes reach very high levels (up to 100k/mm3)
Sometimes difficult to differentiate from leukemia
Parasitic infections cause an increase in eosinophil # in peripheral blood
Pyemia: septicemia due to pyogenic organisms causing multiple abscesses
BONE & JOINT DISORDERS
BONE
Long bones
May be affected by Rickets, osteopetrosis, chondrodystrophy, fibrous dysplasia, osteogenesis imperfecta
Fracture:
A break in the bone, usually accompanied by injury to surrounding tissues
Occurs when force against bone exceeds bone strength
Described as:
Complete bone breaks into two pieces
Greenstick bone cracks on one side only (not all the way through )
Single bone breaks into 2 pieces
Comminuted bone breaks into 3+ two pieces (or is crushed)
Bending bone bends but doesnt break (only happens in kids)
Open bone sticks through skin aka compound?
Three phases of fracture healing:
1) Inflammatory phase characterized by bloot clot formation
2) Reparative phase: characterized by formation of a callus of cartilage (replaced by a bony callus)
3) Remodeling phase: cortex is revitalized
Reasons for failure of a fracture to heal:
Ischemia navicular bone of wrist, femoral neck, & lower 1/3 of tibia are all poorly vascularized & therefore subject to
coagulation necrosis
Inadequate immobilization after fracture pseudoarthrosis or a pseudojoint may occur
Presence of a sequestrum
Interposition of soft tissue between fractured ends
Infection most likely w/ compound fractures
Fat embolism:
Most often a sequela of fracture
Due to mechanical disruption of bone marrow fat & by alterations in plasma lipids
18 yr old male sustains a fracture to the femur, 24 hours later, after manipulating the fragments to help them heal better,
the pt dies suddenly.Fat embolism
Osteomyelitis:

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Acute pyogenic bone infection most often caused by Staph. Aureus


Sexually active
N. gonorrheae
Druggies
Pseudomonas Aeruginosa
Sickle Cell
Salmonella
Prosthetic Replacement
S. aureus and S. epidermidis
Vertebral
M. tuberculosis
The infection causing osteomyelitis is often in another part of body spreads to bone via blood
Affected bone may have been predisposed to infection due to recent trauma
In children long bones usually affected
In adults vertebrae & pelvis are most commonly affected
Infected bone usually produces pus may causes an abscess
Abscess derpives the bone of blood supply
Presents w/ pain, redness, swelling; also fever & malaise
Risk factors recent trauma, diabetes, hemodialysis, IV drug abuse, & people w/ removed spleen
Chronic osteomyelitis
Results when bone tissue dies as a result of lost blood supply
Can persist intermittently for years
Osteoporosis:
Thinning of bone tissue & loss of bone density over time
Most common type of bone disease
Occurs when 1) body fails to form enough new bone, 2) too much old bone is reabsorbed, or 3) both happen
Calcium & phosphate two minerals essential for normal bone formation
With age, minerals may be reabsorbed into body from bones, weakening bone tissue
End result in brittle, fragile bones that are subject to pathologic fracture even in absence of trauma
Type I
Postmenopausal, increased bone resorption fue to decreased estrogen levels, Tx with estrogen replacement
Type II Senile osteoporosis, affects men and women >70 years
Affects whites > blacks > Asians
Causes:
Leading cause
Drop in estrogen in women at time of menopause -estrogen inhibits RANK-L Pway
Drop in testosterone in men
Corticosteroids
Prolonged immobilization
Chronic malnutrition
Advanced age
NOT hypervitaminosis D -would be HYPO Vit D
Women, especially > 50 get it more often than men
Can result from prolonged corticosteroid administration
Can it cause bone to appear blue/gray? FIND OUT!!!
Osteomalacia: (in adults)
Softening of bones caused by Vit D deficiency or problems w/ Vit D metabolism
In children = Rickets
Bones become bowed in rickets because of failure of osteoid tissue to calcify (failure of bone matrix calcification)
Conditions leading to osteomalacia:
Inadequate dietary intake of Vit D
Inadequate exposure to sunlight (UV radiation) normally produces Vit D in body
Malabsorption of vitamin D by intestines
Hereditary or acquired disorders of Vit D metabolism
Kidney failure & acidosis
Phosphate depletion associated w/ low dietary intake of phosphates
Kidney disease or cancer (rare)
Side effects of mediations used to treat seizures
Characterized radiographically by diffuse radiolucency can mimic osteoporosis
Bone biospsy is often only way to differentiate between osteoporosis & osteomalacia
Symptoms: diffuse bone pain (esp. in hips), muscle weakness, & bone fractures w/ minimal trama
More common in women
Softening of bones occurs because bones contain osteoid tissue which has failed to calcify due to lack of Vit D
Teeth in child w/ Rickets delayed eruption, malocclusion, developmental abnormalities of dentin/enamel, & caries
rate
Osteopetrosis = Albers-Schonberg disease = marble bone disease Think FAT ALBERtS BONE
May be inherited as a dominant OR recessive trait
Marked by bone density, brittle bones, & in some cases skeletal abnormalities

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Often initially asymptomatic, trivial injuries may cause bone fractures due to bone abnormalities
Adult type is milder than the malignant infantile & intermediate types
Main features:
Overgrowth & sclerosis of bone
Thickening of cortex
Narrowing (or obliteration) of medullary cavity
Liver & spleen may become enlarged, blindness & progressive deafness may occur
Achondroplasia:
One of the most common causes of dwarfism
Autosomal dominant disorder characterized by short limbs w/ normal-sized head & trunk
Due to defect of fibroblast growth factor (FGF)
Best known form of dwarfism: Short limbs, large body, frontal bossing, & saddle nose
Osteogenesis imperfecta: Unbreakable MR GLASS!
Hereditary disorder (aka brittle bones)
Rare but demonstrates the effect of inadequate osteoid production
Defect in synthesis of type I collagen
Results in skeletal fragility, thin skin, poor teeth, thin blue sclera, tendency towards macular bleeding, & joint hypermotility
Joint hypermobility = ligamentous laxity
Teeth are poor because of malformation of dentin (dentinogenesis imperfecta)
Teeth are gray/yellow??? Check yes pg 1222 in path book
Patients have Hx of multiple fractures
Fibrous dysplasia:
Characterized by replacement of normal bone w/ fibrous tissue
Three classifications depending on extensiveness of skeletal involvement:
Monostotic = 1 bone involved
Polyostic = 2+ bones involved
Polyostic associated w/ endocrine disturbances (Albrights syndrome)
NOTE: Albrights syndrome is a disease where two of the following three are present:
Caf-au-lait spots
Fibrous dysplasia
Endocrine hyperfunction (includes precocious puberty)
Pathologic fractures are often presenting complaint
Pagets Disease (aka Osteitis deformans):
Metabolic bone disease involving bone destruction & regrowth resulting in deformity
Diffuse, cotton-wool opacities
Cause is unknown early viral infections (possibly w/ mumps) & genetic causes have been theorized
Characterized by excessive breakdown of bone tissue, followed by abnormal bone formation
Reversal lines with mosaic pattern
New bone is structurally enlarged, but weakened & filled w/ new BVs
Predisposition for osteosarcoma
Irregular resorption of bone with a poorly mineralized osteoid matrix
NOT decreased serum Ca & elevated serum P
May localize or be widespread frequently in pelvis, femur, tibia, vertebrae, clavicle, or humerus
Skull may enlarge the head size & cause hearing loss if cranial nerves are damaged by bone growth
Intraorally the teeth are spread
Lab findings:
Anemia
Markedly increased serum ALP (alkaline phosphatase NOT acid phosphatase) levels
ALP is an index of osteoblastic activity & bone formation
Elevated 24-hr UHP (urinary hydroxyproline), an index of osteoclastic hyperactivity
Von Recklinghasuens disease:
Disease of bone (osteitis fibrosa cystica) caused by hyperparathyroidism
Characterized by serum phosphorus & serum calcium & alkaline phosphatase
Condensing Osteitis (Sclerosing osteitis):
Unusual reaction or inflammatory response of dental pulp of the tooth to a low-grade infection
Osteochondroma:
Big mushroom-like neoplasm of bone showing peripheral cartilage cap in metaphyseal area of young person
Most common benign bone tumor
Usually seen in men < 25 y.o.
Commonly originates in the long metaphysic
Malignant transformation to chondorsarcoma is rare
Osteochondroses:

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Group of diseases in children & adolescents (years of rapid bone growth)


Localized tissue death (necrosis) occurs, usually followed by full regeneration of healthy bone tissue
Blood supply to growing ends of bones (epiphyses) may become insufficient resulting in necrotic bone, usually near joints
Avascular necrosis is used to described osteochondrosis
Necrotic areas are most often self-repaired over period of weeks or months
Characterized by degeneration & aseptic necrosis followed by regeneration & reossiffication
Affects different parts of body categorized by one of three locations:
1) Physeal:
Aka Scheuermanns disease
Occurs in the spine at intervertebral joints (physes), esp. in thoracic region
2) Articular:
Occurs at the joints (articulations)
Legg-Calv-Perthes disease occurs at the hip
Kohlers disease foot
Freibergs disease 2nd toe
The only type of osteochondrosis more common in females all others affect sexes equally
Panners disease: elbow
3) Non-articular:
Occurs at any other skeletal location
EX: Osgood-Schlatter disease of the tibia relatively common
JOINTS
Suppurative arthritis:
Usually monoarticular
Primarily a hematogenous seeding of joints during bacteremia (mostly Staph, Strep, or Gonococci)
Tender, swollen, erythematous joints requires rapid intervention to prevent permanent damage
Cloudy synovial fluid & high PMN count
Rheumatoid arthritis:
Chronic inflammatory disease primarily affecting the synovial joints & surrounding tissue can also affect other organ
systems
Cause is unknown there is a genetic predisposition
Characterized by the classic microscopic lesion called pannus
What is pannus, you ask? it is a hanging flap of skinthat sounds a lot like another kind of hanging flap of skin
Usually starts in the small joints of hands & feet usually symmetric involvement
Classic presentation: Morning stiffness (gross think Pannus) improving with use, symmetric AND systemic symptoms!!
RA involves an attack on body by its own immune cells (may be an autoimmune disease)
80% have positive rheumatoid factor (anti-IgG Ab)
Marked by proliferative inflammation of the synovial MBs leading to deformity, ankylosis, & invalidism
Primarily attacks peripheral joints & surrounding muscles, tendons, ligaments, & BVs
Synovia are the sites of the earliest changes in RA
Begins most often between ages 25-55
More common in older people women are more affected (2.5x)
Affects ~1-2% of population course & severity can vary considerably
Stills disease = type of RA occurring in young people
Gradual onset fatigue, weakness, morning stiffness (lasting >1hr), diffuse muscular aches, loss of appetite
Joint pain eventually appears w/ warmth, swelling, tenderness, & stiffness of joint after inactivity
NOTE: RA, SLE, polyarteritis nodosa, dermatomyositis & scleroderma are all classified as collagen diseases
All have common inflammatory damage to CTs & BVs w/ deposition of fibrinoid material
NOTE: Most common characteristic lesion of rheumatic fever, scleroderma and RA is Fibrinoid degeneration
Osteoarthritis (OA):
Chronic inflammation that causes:
1) articular cartilage of affected joint to gradually degenerate
2) development of bony spurs, osteophytes
NOTE: Osteophyte (bony spur) formation is a cardinal feature of osteoarthritis not RA
Most common form of arthritis
Inflammation is accompanied by pain, swelling, & stiffness
Most commonly affects joints constantly exposed to wear & tear
Classic presentation: is pain in weight-bearing joints after use, improving with rest, but no systemic symptoms
X-rays show loss of joint space
Higher incidence in women, most often >50 y.o.
Joints most often affected intervertebral joints, phalangeal joints, knees, & hips
Heberdens nodes: (Heber City is far away -- distal)

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Hard nodules/bony swellings which develop around the distal IP joints in patients w/ osteoarthritis
Produced by osteophytes of articular cartilage at the base of terminal planges in OA
2nd & 3rd fingers are most often affected
More common in females onset in middle life
Bouchards nodes
Same as Heberdens, but
Found in the proximal IP joint
Characteristic morphologic changes in OA (in addition to Heberdens & Bouchards nodes):
Eburnation of bone polished ivory like appearance of bone
Osteophyte formation bony spur formation
They fracture & float into synovial fluid along w/ fragments of separated cartilage & are called joint mice
Gout
Inherited disorder of purine metabolism occurring predominantly in men
Marked by uric acid deposits in the joints
There is hyperuricemia, too
Can be characterized by acute arthritis of big toe
Asymmetric
Caused by a metabolic defect resulting in either:
1) Overproduction of uric acid (monosodium urate crystals) OR
Uric acid end-product of purine metabolism, specifically xanthine metabolism
Overproduction due to hyperuricemia (caused by Lesch-Nyhan syndrome, decreased uric acid excretion, or G6P
Deficiency)
2) Reduced ability of the kidney to eliminate uric acid
Almost 25% of all people who have gout develop kidney stones
Exact cause of the metabolic defect is unknown
May also develop in people w/ diabetes, obesity, sickle cell anemia, & kidney disease, or it may follow drug therapy
(Thiazide Diuretics inhibit the secretion of uric acid)
Crystals are needle shaped and negatively birefringent Picture a gout needle going into someones big toe! OUCH!
Gout has 4 stages:
1) Asymptomatic
2) Acute
Causes painful arthritis especially in joints of feet & legs
Symptoms develop suddenly & usually involve only one or a few joints (asymmetric)
Pain frequently starts at night described as throbbing, crushing or excruciating
Joint appears infected signs of warmth, redness, & tenderness
Attacks may subside in several days, but may recur at irregular intervals
Subsequent attacks usually have a longer duration
Acute attack tends to occur after alchol consumption or large meal
Some pts progress to chronic gouty arthritis others may have no further attacks
Tophus formation often on external ear or Achilles tendon
Tophi are pathognomonic of gout
3) Intercritical
4) Chronic
Pseudogout:
Disorder characterized by intermittent attacks of painful arthritis caused by deposits of calcium pyrophosphate crystals
Usually occurs in older people affects both sexes equally
Forms basophilic, rhomboid crystals (as opposed to the negatively birefringent, needle shaped of gout)
Usually affects large joints
Ankylosing spondylitis:
CT disease characterized by inflammation of spine & large joints, resulting in stiffness & pain, along w/ aortic regurgitation
Associated w/ HLA-B27, gene that codes for HLA-MHC I
Reiters syndrome:
Inflammation of joints & tendon attachments at the joints, often accompanied by inflammation of conjunctiva & mucous
MBs (mouth, urinary tract, etc.) & by a distinctive rash
Males Cant see (conjunctivitis), cant pee (urethritis), cant climb a tree (arthritis)
Common in post GI or Chlamydia infections
NEOPLASMS
Changes in Cell Growth
Atrophy:
Decrease in organ or tissue size resulting from a pathological decrease in mass of preexisting cells

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Most often results from disuse, aging, or a disease process


Long standing gradual ischemia of an organ or tissue most likely result in atrophy
General causes of pathologic atrophy are:
Disuse
Pressure
Loss of innervation
Lack of nutrition
NOT chemical stimulation or oversstimulation w/ hormones fundamentally the opposite
Hypertrophy (reversible):
Increase in organ or tissue size due to an increase in cell size
Cardiac muscle
Following injury, restores functional capacity via hypertrophy
Increase in ventricular wall thickness in pt with HTN
Increase in the size of a heart of an athlete
Hyperplasia:
An increase in the size of the organ caused by an increase in the number of cells
Hypoplasia:
Decrease in cell production less extreme than aplasia
Example is the underdevelopment of an organ, NOT an acquired reduction in the size of the organ
Aplasia:
Failure of cell production
During fetal development, aplasia results in agenesis (the absence of an organ)
Abnormal cells lacking differentiation, often equated w/ undifferentiated malignant neoplasms
Tumor giant cells may be formed
NOT a feature of malignancy (Anaplasia is)
Anaplasia:
Absence of cellular differentiation (which is a measure of tumors resemblance to normal tissue)
When malignant cells resemble more primitive undifferentiated cells
Metaplasia:
Process whereby one cell type changes to another cell type in response to stress
Change of a more specialized cell type to a less specialized cell type
Generally assists the host to adapt to the stress
Does NOT change the number of cells involved only type of cell
Examples:
The most common type of epithelial metaplasia involves replacement of columnar cells by stratified squamous
epithelium (respiratory tract smokers)
Early bronchial mucosal alteration most likely seen in cigarette smokers
Bone production in scar tissue
Transformation of mucous secreting bronchial epithelium to a squamous epithelium
Dysplasia (reversible):
Type of nonmalignant cellular growth it may precede malignant changes (preneoplastic)
Epithelial change most predictive of cancer
Associated w/ chronic tissue irritation by:
1) chemical agents (e.g., cigarette smoke) OR
2) chronic inflammatory irritation (e.g., chronic cervitis)
Tissue appears somewhat structureless/disorganized & may consist of atypical cells w/o invasion
Abnormal tissue development
Epithelium exhibitis acanthosis (abnormal thickening of the prickle cell layer)
Changes in epithelial dysplasia: hyperchromatic nuclei, mitosis near the surface, pleomorphism of cells
EX: squamous cells exhibiting acanthosis, disorganization & atypical cells w/o invasion is diagnostic of dysplasia
May be reversed if causative factor is removed
Desmoplasia:
Excessive fibrous tissue formation in tumor stroma
Neoplasia
Clonal proliferation of cells that is uncontrolled and excessive
When cells grow out of control and proliferate
Tumor grade vs. stage:
Grade: (Think missing Histo by 1 point)
Histologic appearance of tumor
Usually graded I IV based on degree of differentiation & # of mitoses per high power field; character of tumor itself
Stage:

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Based on site & size of primary lesion, spread to regional lymph nodes, presence of metastases
Spread of tumor in a specific pattern
Has more prognostic value than grade
TNM staging system: T = size of tumor; N = Node involvement; M = Metastases
Whats more important???? STAGE Like everyone says GRADES arent important!!!
Neoplasm vs. Inflammatory Overgrowth
Most characteristic feature of neoplasm as opposed to inflammatory overgrowth is that there is still progressive growth
after removal of causative stimuli (NOT abnormal mitosis, tendency to grow rapidly, or tendency to recur after removal)
Oncogenes
Proteins that serve in normal control, but can be mutated or come in contact with a retrovirus and then growth occurs
uncontrollably
C-myc
Burkitts lymphoma
Bcl-2
Follicular and undifferentiated lymphomas (inhibits apoptosis) Think Blood Cell Lesion -2
Erb-B2
Breast, ovarian, and gastric carcinomas
Ras
Colon carcinoma Its in your Ass
Protooncogene
Gene sequences (in human cells) that are homologous to virus genome sequences known to cause cancer in animals
Tumor Suppressor Genes
Gene
Chromosome
Tumor
Rb
13q
Retinoblastoma, osteosarcoma
BRCA-1 and 2
17q, 13q
Breast and ovarian cancer
P53
17q
Most human cancers, Li-Fraumeni syndrome
Genetic Hypothesis of Cancer:
Implies that a single progenitor cell is damaged, resulting in a tumor mass of Monoclonal cells
Mutation:
Stable, heritable change in nucleotide sequence of DNA
Results in an alteration in products coded for by the gene
Result from 3 types of molecular change:
1) Base substitutions one base is inserted in place of another results in either a missense or nonsense mutation
Missense mutation:
Results in substitution of one aa for another
Example Val to glut in Sickle Cell
Nonsense mutation:
When base substitution generates a termination codon that prematurely stops protein synthesis
These mutations almost always destroy protein function
Transverse mutation:
Point mutation involving base substitutions in which the orientation of purine and pyrimidine is reversed
A purine is replaced by a pyrimidine or vice versa
Transition mutation:
Point mutation involving substitution of one base pair for another by replacing one purine by another purine
& one pyrimidine by another pyrimidine no change in the purine-pyrimidine orientation.
Caused by base analogues
2) Frame shift mutation
occurs when 1+ base pairs are added or deleted
3) Transposons
(insertion sequence) or deletions are integrated into DNA
Caused by:
Chemicals nitrous oxide & alkylating agents alter the existing base
Ionizing radiation (gamma & x-rays) produce free radicals that attack DNA bases
UV radiation has lower energy than x-rays, causes cross-linking of adjacent pyrimidine bases to form dimers
Nucleic acids in bacteria and viruses are most sensitive to UV radiation (versus protein, lipid, CHOs)
Thymine dimers result in inability of the DNA to replicate properly
THINK UV STERILIZATION
Viruses bacterial virus Mu (mutator bacteriophage) causes either frame-shift mutations or deletions
Bacterial mutation leading to the requirement for a single amino acid is due to absence of a single NZ activity
Radiosensitivity
High radiosensitivity cells: lymphocytes > blood-forming cells >reproductive cells > epithelial cells of GI tract
Low radiosensitivity (radioresistant) nerve cells, mature bone cells, muscle cells
Most to least radiosensitive: spermatogonium > intestinal mucosa > endothelial > skeletal muscle > osteocytes
Most closely related to mitotic rate
X-radiation

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Repeated exposure of low dose x-radiation can cause:


Genetic mutations
Carcinogenesis
Basic effect on living tissues is ionization (NOT denaturation, etc)
Benign tumor:
Localized, has a fibrous capsule, limited potential for growth, a regular shape, & well differentiated cells
Does not invade surrounding tissue or metastasize to distant sites
Grow by expansion
Causes harm only by:
Pressure, hormone overproduction, or hemorrhage following ulcerations of overlying mucosal surface
Usually do not recur after surgical excision
BENIGN neoplasms:
Adenoma, Fibroma, Hemangioma, Lipoma
Malignant tumors spread by local invasion and metastasis
MALIGNANT neoplasms:
Hepatoma, Lymphoma, Melanoma, Myeloma, Seminoma
Metastasis occurs via bloodstream or lymph system
Lymphatic tumor 1st spreads to local & regional lymph nodes then disseminates via blood
Hematogenous 2 tumor nodules develop in liver, lung, brain, bone marrow, & sometimes spleen & soft tissue
Benign
Well-differentiated (neoplastic cells resemble
comparable normal cells meaning blasts are still
making it to cytes, etc.)
Slow growth
Encapsulated; well circumscribed
Localized
Movable

Malignant
Less well differentiated (anaplastic: loss of structural difference)
**Can be either (Can either be well or poorly differentiated)
Rapid growth
Invasion
Metastasis most important distinguishing characteristic
Immovable

Host response to a malignancy is best reflected by lymphocytic infiltration at the edge of the tumor
Malignancy differentiated from inflammation in that malignancy will grow after removal of the causative agent
Most important characteristic of malignant neoplasms (distinguishing them from benign neoplasms) ability to invade &
metastasize
Seed vs. Soil Metastasis
Soil = Target organ liver, lungs, bone, brain, etc.
Seed = Tumor Embolus
Implantation or seeding metastasis
Most often seen in stomach, ovary, colon (NOT in tongue, skin)
These most often send out SEEDS
B and L are always Breast and Lung for Pneumonics
Metastasis to brain:
Lots of Bad Stuff Kills Glia: Lung, Breast, Skin (melanoma), Kidney (renal cell carcinoma), GI
~50% of brain tumors are from metastasis
Metastasis to liver:
Cancer Sometimes Penetrates Benign Liver: Colon>Stomach>Pancreas>Breast>Lung
Liver & lung are the most common sites of metastasis after the regional lymph nodes
Metastasis to liver are much more common than primary liver tumors
Metastasis to bone:
BLT2 w/ Kosher Pickles: Breast, Lung, Thyroid, Testes, Kidney, Prostate
Primary tumor of the tongue is LEAST likely to metastasis to bone
Brain tumors also tend NOT to metastasize to bone
Lung = lytic
Prostate = blastic
Breast = both lytic & blastic
Metastases from breast & prostate are most common
Metastisis to jaw: breast > lung (breast & prostate greatest)
Most likely to metastasize to jaw Breast Its a mans world always getting the boobs into the mouth!
Metastatic bone tumors are far more common than 1 bone tumors
MOST common organ receiving metastasis Adrenal Glands (Rich blood supply) then lungs, liver, bone
Usually first in medulla and then rest of gland
MOST common organ sending metastasis LUNG>Breast>Stomach

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Neoplasm
Small cell lung carcinoma (oat cell)
Small cell lung carcinoma and intracranial
neoplasms
Squamous cell lung carcinoma, renal cell
carcinoma, breast carcinoma, multiple
myeloma, & bone metastasis (lysed bone)
Renal cell carcinoma
Thymoma, bronchogenic carcinoma
Various neoplasms

Cell type
Epithelium
Mesenchyme
Blood cells
Blood vessels
Smooth muscle
Skeletal muscle (voluntary m)
Bone
Fat
>1 cell type

Paraneoplastic effects of tumors


Effects of tumors
ACTH or ACTH-like peptide
ADH or ANP

Effect
Cushings syndrome ( cortisol w/ ACTH)
SIADH

PTH-related peptide, TGF-alpha,


TNF-alpha, IL-2

Hypercalcemia

Erythropoietin
Antiboides against presynaptic Ca
channels at neuromuscular junction
Hyperuricemia due to excesss nuclei
acid turnover (cytotoxic therapy)

Polycythemia
Lambert-Eaton syndrome (muscle
weakness)
Gout

Benign
Adenoma, papilloma

Malignant
Adenocarcinoma, papillary carcinoma

Hemangioma
Leiomyoma (uterus)
Rhabdomyoma
Osteoma
Lipoma
Mature teratoma

Leukemia, lymphoma
Angiosarcoma
Leiomyosarcoma
Rhabdomyosarcoma
Osteosarcoma
Liposarcoma
Immature teratoma

Predisposers of cancer:
Abestosis
mesothelioma
Hepatitis C liver cancer
Gardners syndrome colon cancer
Ulcerative colitis Colonic adenocarcinoma
NOT Anthracosis
Histological features of malignancy:
Anaplasia
Absence of differentiation (which is a measure of tumors resemblance to normal tissue)
When malignant cells resemble more primitive undifferentiated cells
Invasion
Hyperchromatism
Pleomorphism
Abnormal mitosis
Diseases associated w/ neoplasms
Condition
Down syndrome
Xeroderma pigmentosum
Chronic atrophic gastritis, pernicious anemia
Tuberous sclerosis (facial angiofibroma, seizures, mental
retardation)
Actinic keratosis
Barretts esophagus (chronic GI reflux)
Plummer-Vinson syndrome (atrophic glossitis, esophageal webs,
anemia; all due to iron deficiency)
Cirrhosis (alcoholic, hepatitis B or C)
Ulcerative colitis
Pagets disease of bone
Immunodeficiency states
AIDS

Neoplasm
Acute lymphoblastic leukemia ALL We DOWN
Squamous cell and basal cell carcinoma of the skin
Gastric adenocarcinoma
Astrocytoma and cardia rhabdomyoma
Squamous cell carcinoma of skin
Esophageal adenocarcinoma
Squamous cell carcinoma of esophagus
Hepatocellular carcinoma
Colonic adenocarcinoma
Secondary osteosarcoma and fibrosarcoma
Malignant lymphomas
Aggressive malignant lymphomas (non-Hodgkins & Kaposis)
(Q asked : Which cancer is most associated w/ AIDSs)

Autoimmune disease (e.g., Hashimotos thyroiditis, myasthenia


gravis)
Acanthosis nigricans (hyperpigmentation and epidermal
thickening)

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Benign and malignant thymomas


Visceral malignancy (stomach, lung, breast, uterus)

Dysplastic nevus

Malignant melanoma

Tumor markers: should not be used as primary tool for cancer diagnosis. They may be used to confirm diagnosis, to monitor for
tumor recurrence, and to monitor response to therapy:
Marker
Tumor
PSA (prostate-specific antigen)
Prostatic carcinoma
Carcinoembryonic antigen. Very nonspecific but produced by
Carcinoembryoonic antigen (CEA)
70% of colorectal and pancreatic cancers; also produced by
gastric and breast carcinoma
Alpha fetoprotein (AFP)
Normally made by fetus. Hepatocellular carcinomas.
Nonseminomatous germ cell tumors of the testis (yolk sac tumor)
Human Chorionic Gonadotropin (Beta hCG)
Think HCG Hydatidiform moles, Choriocarcinomas, and
Gestational trophoblastic tumor
CA-125
Ovarian, malignant epithelial tumors
S-100
Melanoma, neural tumors, astrocytomas
Alkaline phosphatase (OSTEOBLASTS)
Metastases to bone, obstructive biliary disease, Pagets
disease
Acid phosphatase
Prostate tumors extenting outside prostate capsule (Stage C or D)
Bombesin
Neuroblastoma, lung and gastric cancer
TRAP
Tartate-resistant acid phosphatase. Hairy cell leukemiaa B cell
neoplasm
Oncogenic Virus
HTLV-1
HBV, HCV
EBV
HPV
HHV-8 (Kaposis sarcoma associated herpes virus)

Associated Cancer
Adult T-cell leukemia
Hepatocellular carcinoma
Burkitts lymphoma, nasopharyngeal carcinoma
Cervical carcinoma (16,18) penile/anal carcinoma
Kaposis sarcoma, body cavity fluid B cell lymphoma

Chemical Carcinogens
Aflatoxins, vinyl chloride
Nitrosamines
Asbestos
Arsenic
CCl4
Naphthalene (aniline dyes)

Associated Cancer
Liver
Esophagus, stomach
Lung (mesothelioma and bronchogenic carcinoma)
Skin (squamous cell)
Liver (centrilobular necrosis, fatty change)
Bladder (transitional cell carcinoma)

Carcinoma in situ:
Pleomorphism
Disorderly maturation
Hyperchromatic nuclei
BUT Basement membrane remains intact
Carcinoma:
Malignant tumor of epithelial origin just think squamous cell CARCINOMA
Usually metastasize via lymphatics
Occurs in the following variations:
Squamous cell carcinoma originates from stratified squamous epithelium; marked by production of keratin
Transitional cell carcinoma arises from transitional cell epithelium of urinary tract. Smoking is risk factor for
transitional cell carcinoma Which is usually cancer of the bladder. Think if you smoke with your penis youll get
cancer
Adenocarcinoma a carcinoma of glandular epithelium
Metastatic Carcinoma
Most common malignancy found in bone (NOT osteosarcoma, giant cell tumor, chondrosarcoma, multiple
myeloma) Wow... you wouldnt think that SCC is most common in bone, dont get clowned son!
Sarcoma: Think of osteosarcoma... Bone is a CT
Malignant tumor of mesenchymal origin
Usually metastasize via blood easy to remember... bc blood is also considered a CT!
EXs: osteosarcoma (bone), leiomyosarcoma (smooth muscle), & liposarcoma (adipose tissue)
Cancer Facts/Figures
Men
Most common =
Lung > Colorectal > Prostate

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Highest Mortality =
Lung > Colorectal > Prostate
Women
Most common =
Breast > Lung > Colorectal
Highest Mortality =
Lung > Breast > Colorectal
IN general
Cancer is the second leading cause of death in the US (Heart disease is 1st)
Lung cancer:
Most common cause of cancer in men think about all the rough and tough men more them smoke then women
Most common cause of cancer death in women and Men
Affects males 4x more than femalesoutdated????
But in the past 30 years, the mortality rate for women has increased
Most common types:
Adenocarcinoma
Most common primary malignancy of the lung
Epidermoid (SCC)
Most forms arise from lining epithelium of the tracheobronchial tree
SCC of lung associated endocrine effect of hyperparathyroidism; calcitonin
Small cell (oat cell) 25%
Most commonly associated with Paraneoplastic Syndrome
Large cell (anaplastic) 15%
Most arise from main bronchus & are therefore termed bronchogenic carcinomas
Primary malignant neoplasm of the lung, originating from transformed epithelium of bronchial tree walls
Most lung cancers arise from bronchiolar epithelium
Main symptom persistent cough (smokers cough)
Other signs & symptoms hoarseness, wheezing, dyspnea, hemoptysis, & chest pains
of the cancers are inoperable by the time pt is first seen in hospital
First signs of lung cancer are often related to metastatic spread, particularly to the brain
Other areas include to endocrine glands, skin, liver, & bones
Metastasis is through lymphatic channels
Most common cancer to metastasize!
Metastasis to lungs commonly from breast, colon, prostate, kidney, thyroid, stomach, cervix, rectum, testis, bone, &
skin
Etiologic agents in causation of lung cancer: cigarette smoking, industrial & air pollutants, familial susceptibility
Other diseases due to smoking:
Chronic obstructive pulmonary disease, which includes emphysema, chronic bronchitis
Carcinoma of the larynx and oral cavity
Dx for a pt with a hx of smoking, dysphonia, dysphagia, and weight loss
Increased incidence of carcinoma of the esophagus, pancreas, kidney, & bladder
Peptic ulcer disease
Low birth weight infants LOOK THIS UP PLEASE DR SHOFF!!!
NOT 5 things
STOMACH or COLON CANCER, CHRONIC GASTRITIS (Acute?), or Acute Respiratory Distress
Syndrome
Chronic gastritis is not due to smoking
Carcinogens
Most potent is Benzopyrene
Benzopyrene is a very potent carcinogen found in cigarette smoke mo money mo problems, want that BENZO, its a cancer
son!!!
Binds to existing DNA bases & causes frame-shift mutations
Breast Cancer:
Most common cancer affecting women
# 2 Killer of women ages 35-54 Second to Lung
Lifetime risk: 1 out of 11
Rare before age 25 & increasingly more common w/ age until menopause incidence then slows down
Almost always an adenocarcinoma makes sense breasts make milk, milk comes from glandular epithelium
Factors increasing risk: from Wikipedia
Age (40+)
Nulliparity
Family Hx
Strongest association family Hx, specifically breast cancer in 1st-degree relatives (mother, sister, daughter)
Early menarche
Late menopause

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Fibrocystic disease
Previous Hx of breast cancer
Obesity (but NOT Estrogen deficiency or silicone implants)
Younai says silicone implants for sure increased risk!! Faribas a fucking idiot
Wikipedia begs to differ with Fariba, search silicone implants and click on the risks link
Alcohol / Hormones both are debated
More common in left breast than right & more commonly in the outer upper quadrant Boys are right handed!!
Widespread metastasis can occur by way of lymphatic system & bloodstream, through right side of heart & lungs, eventually
to the other breast, chest wall, liver, bone, & brain
A women with metastastic carcinoma of the jaws most likely came from Breast cancer
Characterized by:
Painless mass is usually the initial sign or symptom
Retraction of skin or nipple Do matt and jimmy have breast cancer? LOL!?!?!?!?
Peau dorange (swollen pitted skin surface) along w/ Orange sized titties are about perfect!
Enlargement of axillary lymph nodes may also be present
Increased pigmentation of the nipple
NOT spontaneous acute redness, swelling, and tenderness of the breast
Lymph node involvement is most valuable prognostic predictor
With adjuvant therapy, 70-75% w/ negative nodes will survive 10+ years; only 20-25% of women w/ positive nodes
Growth is influenced by hormones (same as Prostatic carcinoma) emotional women
crazy hormones even fx
cancer growth
Fibrocystic disease:
Most common cause of a clinically palpable breast mass in women (28-44 y.o.)
Signs & symptoms lumpiness throughout both breasts
Pain is common, especially prior to menstruation
Non-malignant may lead to increased risk of developing carcinoma
Teratoma:
Tumor composed of multiple tissues (may contain elements of all 3 embryonic germ cell layers)
Includes tissues not normally found in the organ in which they arise
Occurs most frequently in the ovary here it is usually benign & forms dermoid cysts
Also occurs commonly in testes here it is usually malignant
Pancreatic Cancer
Tumors MORE common in the HEAD (because obstructive)
Carcinoma of the tail of the pancreas is the LEAST likely to cause acute pain
Pt with this malignancy have the WORST Px of any malignancy
Associated w/ serum concentration of carcinoembryonic antigen (CEA)
Colon & rectal cancer:
Malignant neoplasm of colonic or rectal mucosa
Almost always an adenocarcinoma
2nd most common cancer-causing death in men; 3rd most common cancer-causing death in women
Disease is entirely treatable if caught early
Greatest 5 yr survival Rate @ 60%
No single cause, but almost all begin as a polyp
Most colorectal carcinomas arise from Adenomatous polyps (NOT hemorrhoids, diverticula, etc)
Most associated cancer with villus adenoma
Associated w/ serum concentration of carcinoembryonic antigen (CEA) and Pancreas
Predisposing factors adenomatous polyps, inherited multiple polyposis syndromes, long-standing ulcerative colitis, genetic
factors, & low fiber, high animal fat diet, more common in industrialized nations
Why Gardners disease is associated w an increase cancer risk!
Rapidly increasing incidence w/ age, starting at age 40
Symptoms rectal bleeding w/ diarrhea, abdominal pain, & weight loss
Tumors on the left side are more likely to cause symptoms those shitty LEFT-wing ppl, more likely to be vocal, have
a rally/protest and stir things up!
Symptoms usually only occur in advanced states
Sigmoid colon most common site (NOT TRANSVERSE)
Sigmoidoscopy can disclose the majority of the tumors makes sense since the most common spot is in the sigmoid colon
Tumors of descending colon usually cause constipation & are generally dxd at an earlier stage than tumors ascending colon
Prostate cancer:
3rd most common cause of death from cancer in men of all ages
Most common cause of death from cancer in men >75 y.o., common in men > 50 y.o., rarely found in men <40 y.o.
Most are adenocarcinomas that arise in peripheral glands (posterior lobe)
Invade throughout prostate

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Most likely metastasize to Bone & other tissues (e.g., lungs)


Clinical findings of prostatic cancer are often the mestastasis to the vertebral column (bone)
Indication of in serum Acid Phosphatase & PSA (prostate-specific antigen)
Lab findings elevated levels of acid phosphatase & PSA
Most prostate cancers are now found before they cause symptoms due to PSA testing
Prostate cancer serum acid phosphatase with prostate cancer that metastisizes to bone
Unknown cause relationship between high fat intake & increased testosterone levels (may be hormonally dependent
same as breast cancer)
Benign prostatic hyperplasia = Benign prostatic hypertrophy = Nodular hyperplasia of prostate:
Very common in men over 50
May be due to an age-related increase in estradiol with possible sensitization of the prostate to the growth promoting effects
of DHT
Characterized by a nodular enlargement of the periurethral (lateral and middle lobes) of the prostate gland, compressing the
urethra into a vertical slit
Often presents with increased frequency of urination, nocturia, difficulty starting and stopping the stream of urine, dysuria
May lead to destruction and hypertrophy of the bladder, hydronephrosis, and UTIs
**NOTE: hypertrophy is a misnomer in this case, because the increase in size is due to hyperplasia
Benign enlargement of prostate gland due to hyperplastic nodules of stroma & glands distorting the prostate
Compresses urethra & causes urinary tract obstruction
Complications
Pyelonephritis, hydronephrosis, & painful or difficult urination (dysuria)
Chief complication is urinary obstructions
Not considered to be premalignant (LEAST possible complication)
Not malignant or inflammatory usually progressive & may lead to obstruction of the urethra
65 yr old male who cant void bladder and has urinary retention
Rhabdomyosarcoma:
Malignant neoplasm derived from skeletal (striated) muscle
NOTE: neoplasms of muscles are rare & usually malignant
Affects throat, bladder, prostate, or vagina in infants & large muscle groups of arm & leg in the elderly
Prognosis is poor
Rhabdomyoma
Benign tumor arising from voluntary muscle
Can arise in any skeletal muscle & produce a mass in the affected muscle
Leiomyoma (aka fibroid):
Benign tumor derived from smooth muscle
Occurs anywhere in body but most frequently in the myometrium of the uterus
Most common tumor of women 25% of women >30 y.o. (during the reproductive years)
Other areas (less frequent) stomach, esophagus, & small intestine
Prognosis is good
Cause of fibroid tumors of uterus is unknown
Suggested that fibroids may enlarge w/ estrogen therapy (such as oral contraceptives) or w/ pregnancy
Growth depends on regular estrogen stimulation rare before age 20 & shrinks after menopause
Fibroid will continue to grow as long as women menstruates, but growth is slow
Uterine fibroids most common pelvic tumor present in 15-20% of reproductive-age women, 30-40% of women > 30 y.o.
Endometrial Carcinoma/Uterine Cancer Increased Estrogen not good for Endometrium we learned this.
Risk factor is Hyperestrogenism (so early menarche, late menopause, nulliparity, anovulation) & obesity
Cervical Cancer
Predisposed by Multiple sex partners, Having Sex with Uncircumcized Males, Smoking, HIV, Chlamydia, Oral
Contraceptives, Lots of pregnancies, Early age of Intercourse, HPV
NOT Early Menarche
Early Menarche
Risk factor for,
The ones involved in the Menses Process Endometrial (uterine), Ovarian, Uterine Sarcoma, Breast
(sensitive during Menses)
Keratoacanthoma:
Relatively common low grade malignancy that originates in the pilosebaceous glands
Pathologically resembles SCC
Characterized by rapid growth over a few wks to months, followed by spontaneous resolution over 4-6 months in most cases
Etiologic factors sunlight, chemical carcinogens, trauma, HPV, genetic factors, immunocompromised status
Can (rarely) progress to invasive or metastatic carcinoma
Aggressive surgical Tx is advocated
Dermatofibromas:

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Benign neoplasms that appear as small, red-to-brown nodules that result from fibroblast accumumlation
Acrochordon (aka skin tag):
Extremely common lesion most often found on neck, in armpit, or groin
Actinic keratosis:
Premalignant epidermal lesion caused by excessive chronic sunlight exposure
NOTE: dont get clowned by verrucus vulgaris as an option for What is generally considered precancerous?
Common in light-skinned elderly people
Seborrheic keratosis (aka seborrheic warts):
Extremely common benign neoplasm of older people
Flesh-colored, brown, gray, or black growths that can appear anywhere on skin
Think gray, scaly, & greasy (typical appearance)
Acanthosis nigricans:
Cutaneous disorder marked by hyperkeratosis & pigmentation of axilla, neck, flexures, & anogenital region
More than of these pts have cancer (GI carcinomas, particularly of the stomach)
More skin disorders (while were here):
Dermatitis:
Group of inflammatory pruritic skin disorders
Etiology: allergy (usually type IV hypersensitivity), chemic injury, or infection
Psoriasis:
Nonpruritic chronic inflammation of the skin, particularly on the knees and elbows
Associated w/ HLA-B27, HLA-13, etc
Auspitz sign: seen when removal of scale results in pinpoint areas of bleeding
Treat w/ topical steroids & UV irradiation
Bullous pemphigoid:
Autoimmune disorder w/ IgG antibody against epidural basement membrane (linear immunofluorescence). Similar to
but less severe than pemphigus vulgarisaffects skin but spares oral mucosa
Pemphigus vulgaris:
Potentially fat autoimmune skin disorder. Intrdermal bullae involving the oral mucosa and skin. Findings: acantholysis
(breakdown of epithelial cell-to-cell junctions), IgG antibody against epidermal cell surface.
Impetigo:
Highly infectious skin infection most common in pre-school aged children during warm weather
Results from epidermal invasion by Staph. aureus or Strep. pyogenes
Similar to cellulitis, but more superficial
Begins as an itchy, red sore that blisters, oozes & finally becomes covered w/ a tightly adherent crust
Tends to grow & spread
Impetigo sores heal slowly & seldom scar
Impetigo is contagious infection is carried in the fluid that oozes from the blister
Rarely, impetigo may form deep skin ulcers
Tx mild infection typically treated w/ Rx antibacterial cream (Bactroban)
Oral Abx (erythromycin or dicloxacillin) frequently prescribed rapid clearing of lesions
Cure rate is extremely high but often recurs in young children
Acute glomerulonephritis one of the more common renal diseases in children an occasional complication of impetigo
Erythema multiforme (EM):
Type of hypersensitivity (allergic) IgM reaction occurring in response to medication, infections, or illness
Medications sulfonamides, penicillin, barbiturates, & phenytoin
Infections HSV & mycoplasma
Exact cause is unknown
Believed to involve damage to BVs of skin w/ subsequent damage to skin tissues
Fairly common, w/ a peak incidence in 2nd & 3rd decades of life
May present w/ classic skin lesions over dorsal aspect of hands/forearms w/ or w/o systemic symptoms
Classic lesion a central lesion surrounded by concentric rings of pallor & redness (target, bulls eye shape)
Stevens-Johnson syndrome:
Severe systemic symptoms & extensive lesions involving multiple body areas (especially mucous MBs)
Toxic epidermal necrolysis (TEN syndrome, or Lyells syndrome)
Involves multiple large blisters (bullae) that coalesce, followed by sloughing of all or most of the skin & mucous
MBs
Lymphadenitis
Inflammation of a lymph node or nodes
Lymphadenopathy Any pathy of a lymph node
Any disease process affecting a lymph node or nodes
The Q reads: Enlarged, tender, & inflamed lymph nodes are one form of.Lymphadenitis or Lymphadenopathy??? 2000 Q86
Hodgkins lymphoma = Hodgkins disease (Ryan Hodges is nice not as malignant)

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Malignancy characterized by painless progressive enlargement of lymphoid tissue


1st sign often an enlarged lymph node that appears w/o a known cause
Can spread to adjacent lymph nodes & later may spread outside lymph nodes - to lungs, liver, bones, or bone marrow
Unknown cause
BIMODAL (Also Think also HOMOzygous Histo)
Affects 2x as many males as females; usually develops between ages 15-35
Splenomegaly is common
Most important presence of Reed-Sternberg cells (Ryan Hodges looks like a Reed) the actual neoplastic cells (Reed S.
cells are CD30+ & CD15+)
Heterozygous Histology is NOT characteristic of Hodgkins
Symptoms anorexia, weight loss, generalized pruritus, low-grade fever, night sweats, anemia, & leukocytosis
Prognosis most favorable w/ early Dx & limited involvement & with lymphocytic predominance
Believed to start as an inflammatory/infectious process & then become a neoplasm
Some believe it is an immune disorder
50% of cases are associated with EBV
Non-Hodgkins lymphomas = malignant lymphomas = lymphosarcomas
Heterogenous group of malignant diseases originating in lymphoid tissue
Associated with HIV and immunosuppression
Most involve B cells
Cause is unknown some suggest a viral source
Occur in all age groups; 2-3x more common in males
More common than Hodgkins disease
Present as solid tumors composed of cells that appear primitive or resemble lymphocytes, plasma cells, histiocytes
Small lymphocytic lymphoma: adult B cells, that clinically presents like CLL, low grade.
Follicular lymphoma: (small cleaved cell): Adult B cells with t(14;18) chromosome, bcl-2 expression. It is difficult to
cure; indolent course; bcl-2 is involved in apoptosis
Diffuse large cell: usually older adules, but 20% are children w/ 80% B cell and 20% T cells (mature). It is aggressive
but 50% are curable
Lymphobalstic lymphoma: children most often affected, T cells are immature. Commonly presents w/ ALL and
mediastinal mass; very aggressive T cell lymphoma
Burkitts lymphoma:
High-grade B-cell lymphoma (lymph gland tumor) classified as a non-Hodgkins type of lymphoma
EBV may be the cause of this lymphoma
The 1st human cancer that has been strongly linked to a virus
Undifferentiated malignant lymphoma that usually begins as:
African form: (ENDEMIC FORM)
95% of cases associated w/ EBV
Affects children of middle African regions
Usually begins as a large mass in the jaw
American form:
Less closely associated w/ EBV
Usually begins as an abdominal mass Think americans are Fatter (abdominal), and we are cleaner (less
virus association)
Jaw tumors are rare
Both types are caused by defective B-cells
Children affected most, their B cells: t(18;14) c myc gene moves next to heavy chain Ig gene 14.
Starry sky appearance (sheets of lymphocytes w/ interspersed macrophages, associated w/ EBV; jaw lesions in
endemic form in Africa, pelvis or abdomen in sporadic form
Mycoisis fungoides:
Rare, persistent, slow-growing type of non-Hodgkins lymphoma originating from a mature T-cell
Affects the skin; may progress to lymph nodes & internal organs
1st indication swollen lymph glands (lymphadenopathy), enlarged tonsils & adenoids; painless, rubbery nodes in cervical
supraclavicular areas (all lymph shit)
Pt develops symptoms specific to involved area & systemic complains fatigue, malaise, weight loss, fever, & night sweats
Pathophysiologically similar to Hodgkins disease, but:
Reed-Sternberg cells are not present
Specific mechanism of lymph node destruction is different
Biopsy differentiates Non-Hodgkins from Hodgkins
Hodgkins
Presence of Reed-Sternberg cells

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Non-Hodgkins
Non-Hodgkins associated w/ HIV and immunosuppression

Localized, single group of nodes, extranodal rare; contiguous


spread
Constitutional signs/symptomslow-grade fever, night sweats,
weight loss
Mediastinal lymphadenopathy
50% of cases associated w/ EB; bimodal distribution: young
and old; more common in men except nodular sclerosis type
Good prognosis = increase lymphocytes, low number of Reed
Sternberg cells

Multiple, peripheral nodes;extranodal involvement common;


noncontinguous spread
Majority involve B cells (except lymphoblastic T cell origin)
No hypergammaglobulinemia (cf., multiple, where excess B cells
are in resting stage)
Fewer constitutional symptoms
Peak incidence 20 -40 years old

Ann Arbor staging of Hodgkins: HENCE Extranodal a definite possibility


I: single lymph node or single extralymph organ
II: 2 or more sites, on same side of diaphragm
III: 2 or more sites; on both sides of diaphragm
IV: Disseminated
Which type of Hodkins is dx at Stage IV??
A: without constitutional symptoms
B: with constitutional symptoms (fever, night sweats, weight loss)
Multiple Myeloma:
A cancer of plasma (clear) cells arising in bone marrow (a monoclonal plasma cell w/ fried-egg appearance) or older adults
Disease associated with proliferation of plasma cells showing punched out lesions
Another question: Called them Lytic Lesions
Most common bone tumor arising from w/in the bone in adults
Characterized by excessive growth & malfunction of plasma cells in bone marrow
Hyperglobulinemia
Produces large amounts of IgG (55%) or IgA (25%)
Growth of these extra plasma cells interferes w/ the production of RBC, WBC, & platelets
Causes anemia & susceptibility to infection
Clinical features:
Anemia, pathologic bone fractures, increased susceptibility to infection (most common cause of death), increased
bleeding tendencies, anemia, hypercalcemia, renal failure, & amyloidosis
Cancer cells produce osteolytic lesions throughout skeleton (flat bones, vertebrae, skull, pelvis, ribs)
Renal failure is frequent complication caused by excess calcium in blood from bone destruction
This increases the susceptibility of pt to infection & anemia
Accounts for 1% of all cancers mostly found in men >40 y.o.
Earliest indication severe, constant back & rib pain increasing w/ exercise may be worse at night
The pain arises from pressure created by malignant plasma cells on nerves in the periosteum
Radiographs punched-out appearance & primary amyloidosis
Bence Jones protein in urine & hypercalciuria
Result of light-chain dimers in urine
Absence does not rule out multiple myeloma
Has monoclonal Ig spike (M-protein, also found in Waldenstroms macroglobulinemia)
SIDENOTE on Waldenstroms:
Neoplasms of lymphocytoid plasma cells that produce monoclonal IgM
Lacks the lytic bone lesions of multiple myeloma
Blood smear shows RBC stacked like poker chips (rouleau formation)
SKIN CANCER:
General info:
Most common malignancy in U.S.
Most to least common: Basal cell carcinoma SCC Malignant melanoma
Basal cell carcinoma (BCC):
Most common skin malignancy in man
75% of all skin cancers most common of all cancers in U.S.
Derived from epidermal basal cells
>90% occur on areas of skin regularly exposed to sunglight/UV radiation
Most common site is the upper face
Invasive, ulcerative, often indurated, slow-growing & locally destructive does NOT metastasize
53-yr-old pt with chronic, indurated lesion near the inner canthus
Prognosis is good usually cured by excision; radiosensitive (if necessary)
Prognosis is Better than multiple myeloma, osteosarcoma, carcinoma of breast or esophagus
Characterized by clusters of darkly staining cells w/ typical palisade arrangement of cell nuclei at periphery of cell cluster

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Also has pearly papules in gross pathology


Usually occurs in persons > 40
More prevalent in blond, fair-skinned males on skin exposed to regular sunlight/UV radiant
Similar to SCC in that BOTH are:
Invasive
Exhibit mitotic figures
Cured by early excision
Incorrect: readily metastasize, commonly occur in the oral cavity
LEAST likely to metastasize (among neuroblastoma, chondrosarcoma, epidermoid carcinoma, or mucinous adenocarcinoma)
Squamous Cell Carcinoma (SCC):
Involves cancerous changes to keratinocytes middle portion of epidermal skin layer
Usually painless initially may become painful w/ development of non-healing ulcers
May begin on normal skin; skin of a burn, injury, or scar; or site of chronic inflammation
Commonly found on hands & face
Most often originates from sun-damaged skin areas, such as actinic keratosis
Actinic keratosis is a precursor to SCC
Usually begins > age 50
Usually metastasizes via lymphatics
Malignant & more aggressive than basal cell carcinoma, but still may grow slowly
Q reads: Which is not commonly mistaken for SCC? Candida
TB, histoblastosis, & blastomycosis are mistaken for SCC
Most often locally invasive but SCC can infiltrate underlying tissue or metastasize in lymphatic channels
Oral Cancer (squamous cell) most commonly resembles the most common form of cervical cancer in histology &
behavior think that mouth and vagina are kinda the same as far as I am concerned HAHA!
Adenocarcinoma is the most common primary malignant neoplasm of the lung
Histopathologically contains squamous / epithelial / keratin pearls and intercellular bridges
Resemble prickle cells & form keratin pearls
Malignant epithelial cells have # of laminin receptors
Laminin (a glycoprotein) = major component of basement MBs???????True pg 100 in path book
Has as numerous biological activities including promotion of cell adhesion, migration, growth & differentiation
IS in the ECM, where as tubulin is NOT, remember laminins in the lamina lucida!!
Malignant melanoma:
Involves the melanocytes produce melanin responsible for skin & hair color
Can spread very rapidly
Most severe & most deadly skin cancer leading cause of death from skin disease
May appear on normal skin OR may begin at a mole (nevus) or other area that has changed appearance
Relevance to prognosis of pt:
Depth of invasion has the GREATEST relevance to Px
Vertical invasion or growth is related to Px of Melanoma
Degree of pigmentation has the LEAST relevance to Px
Multiple biopsies
Sex of the pt
Palpable lymphadenopathy
Some moles that are present at birth may develop into melanomas
Development is related to sun exposure, particularly to sunburns during childhood
Most common among people w/ fair skin, blue or green eyes, & red or blonde hair
Depth of tumor correlates w/ risk of metastasis
Four Types:
Superficial spreading melanoma (most common):
Usually flat & irregular in shape & color, w/ varying shades of black & brown
May occur at any age or site
Most common in Caucasions
Nodular melanoma:
Usually starts as a raised area dark blackish-blue or bluish-red (although some lack color)
Poorest prognosis
Lentigo maligna melanoma:
Usually occurs in the elderly
Most common in sun-damaged skin on face, neck, & arms
Abnormal skin areas are usually large, flat, & tan w/ intermixed areas of brown
Develops from preexisting lentigo maligna (Hutchinson freckle)
Acral lentiginous melanoma:

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Least common form of melanoma.


Usually occurs on palms, soles & under nails
More common in African Americans
Tumor growth patterns w/in skin:
Initial radial growth (do not metastasize) characteristic of spreading types
Vertical growth (metastasis may occur) characteristic of nodular melanoma
Tumors of the adrenal medulla:
1) Pheochromocytoma:
Chronic chromaffin-cell tumor of the adrenal medulla that secretes an excess of epinephrine & norepinephrine
Results in severe HTN, increased metabolism, & hyperglycemia
Endocrine effect of HTN
Common between ages 30-60 most common tumor of adrenal medulla in adults
If tumor is derived from extra-adrenal chromaffin cells, it is called a paraganglia (metastasis is more common in this
tumor)
Episodic hyperadrenergic symptoms: 5 PsPressure (elevated BP); Pain (headache), Perspiration; Palpitations;
Pallor/diaphoresis
Rule of 10s 10% are malignant, bilateral, extraadrenal, calcify, kids, familial
Tx with alpha antagonists, especially pheoxybenzamine, a nonselective irreversible alpha blocker
May be a part of or associated w/ MEN II and III(multiple endocrine neoplasia), neurofibromatosis (von
Recklinghausens disease) or von Hipple-Lindau disease (multiple hemangiomas)
2) Neuroblastoma:
Highly malignant tumor of early childhood most common malignant tumor of childhood & infancy
Think NEUW and BLASTIC
Usually originates in the adrenal medulla, but it can go anywhere on the sympathetic chain
Complications invasion of abdominal organs by direct spread & metastasis to liver, lung or bones
First symptoms in many children large abdomen, sensation of fullness, & abdominal pain
These are followed by an abdominal mass
~90% of neuroblastomas produce hormones, such as epinephrine, which can HR & cause anxiety
I think it has highest incidence in Causcasians
NOT schwannoma, Wilms tumor, carcinoid tumor
Multiple endocrine neoplasm: all have auto dom characteristic, II, and II have ret gene association
Think MEN have large Adams apple or THYROID
MEN type I (Wermers syndrome):
three P organs, pancreas, pituitary, and parathyroid. Presents w/ kidney stones and stomach ulcers.
MEN type II (Sipples syndrome): -- Sipping get to your thyroid
medullary carcinoma of the thyroid, pheochromacytoma, parathyroid tumor, or adenoma
MEN type III (Formerly MEN IIb):
medullary carcinoma of the thyroid, pheochromocytoma, and oral and intestinal ganglioneuromatosis
Increased incidence of medullary carcinoma of the thyroid with pts suffereing from MEN type III
Von Hippel-Lindau disease (neurofibromatosis II):
Characterized by hemangiomas of the retina, medulla, & the cerebellum
Associated w/ cysts of liver, kidney (bilateral renal cell carcinomas), adrenal glands, & pancreas
Autosomal dominant associated w/ VHL gene (tumor suppressor on chromosome 3 (3p)
Bone tumors:
Most are secondary (caused by seeding from a primary site) From Stomach, Ovary, and Colon
Primary tumors are more common in males, usually children & adolescents some types occur in persons ages 35-60
They may originate in osseous or nonosseous tissue
Osseous bone tumors arise from bony structure itself
Non-osseous tumors arise from hematopoietic, vascular, or neural tissue
Primary malignant bone tumors (aka sarcomas of bone)
Rare, constituting less than 1% of all malignat tumors
Metastatic bone tumors
Have spread to bone from original site elsewhere in the body
Cancers most likely spread to bone breast (30%), lung (20%), prostate (5%), kidney (15%), & thyroid cancers (5%)
NOTE: The percentages above and below are from Sapps book and are metastases to Jaws
Cancer least likely to spread to bone? Options are:
Thyroid, melanoma, breast, prostate BULLSHIT! According to Sapp text, breast is 30%, then prostate,
thyroid and melanoma are all at 5%. There had to have been another option
In children, the most common types of bone tumors are Osteogenic & Ewingss sarcomas
Most common malignancy in bone is metastatic carcinoma

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Bone tumors of osseous origin:


Osteogenic sarcoma: (aka Osteosarcoma)
Most common
Usually in males ages 10-30
Which is the least likely location for a primary osteosarcoma?
Occurs most often in femur, but also tibia & humerus; less often, in fibula, ileum, vertebra, or Mn
Tumor arises from bone-forming osteoblasts and bone-digesting osteoclast
Most often in metaphysic of long bones
Bone lesion w/ radiopaque structures radiating from the periphery
Predisposing factors include: Pagets disease, bone infarcts, radiation, and familial retinoblastoma think Rb gene
Periosteal osteogenic sarcoma:
Usually in females ages 30-40
Occurs most often in distal femur, may also be in humerus, tibia, & ulna
Develops on bone surface (instead of interior) & progresses slowly
Chondrosarcoma:
Usually in males ages 30-50
Occurs most often in pelvis, proximal femur, ribs, & shoulder girdle
Develops from cartilage & grows slowly
Usually painless; locally recurrent & invasive
May be from primary origin or from osteochondroma
Malignant giant cell tumor:
Usually in females ages 18-50
Arises from benign giant cell tumor
Found most often in long bones, more so in knee area (epiphysis)
Locally aggressive tumore found around the distal femur, proximal tubial region
Characteristic double bubble or soap bubble appearance on x-ray; spindle-shaped cells w/ multinucleated giant
cells
Bone pain is the most common indication of 1 malignant bone tumors
Bone pain has greater intensity at night, is associated w/ movement & is dull & usually localized
Bone tumors of nonosseous origin:
Ewings Sarcoma:
Malignant tumor that can occur any time during childhood usually develops during puberty during rapid bone growth
NOTE: osteogenic sarcoma is another malignant tumor in kids myeloma is not
Characteristic of kids and Teens??? Ewings Sarcoma (I watched Patrick Ewing when I was in my teens)
Usually in males ages 10-20
Usually originates in bone marrow & invades diaphyses of long & flat bones
Usually affects lower extremeties, most often in femur, innominate bones, ribs, tibia, humerus, vertebra, & fibula
Often metastasizes to lungs & other bones
Metastasis in ~ 1/3 of children at time of Dx
From anaplastic small blue cell malignant tumor
Extrememly aggressive w/ early metastisis
Few symptoms most common is pain
Pain is increasingly severe & persistent
Occasionally swelling at tumor site
Fever may also be present
Children may also have a pathologic fracture
Very radiosensitive tumor
Also exhibits characteristic onion skin
Often difficult to distinguish histologically from a neuroblastoma or reticulum cell sarcoma
Fibrosarcoma:
Usually in males ages 30-40
Originates in fibrous tissues of bone
Invades long or flat bones femur, tibia, & Mn
Also involves periosteum & overlying muscle
Chordoma: Chord noto-CHORD!
Usually in males ages 50-60
Derived from embryonic remnants of notochord
Progresses slowly
Usually found at end of spinal column & in spheno-occipital, sacrococcygeal, & vertebral areas
Characterized by constipation & visual disturbances
Benign tumors of mesenchymal origin (& where theyre derived from):
Leiomyoma from smooth muscle includes the uterine leiomyoma or fibroid tumor most common neoplasm of women

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Rhabdomyoma skeletal muscle


Lipoma adipose tissue most common soft tissue tumor
Chondroma cartilage
Papilloma surface epithelium (e.g., squamous epithelium of skin or tongue)
Adenoma glandular epithelium
Myxoma connective tissue
Angioma neoplasm of either blood or lymph vessels
Choristoma:
Small, benign mass of normal tissue misplaced w/in another organ, such as liver tissue w/in intestinal wall
Hamartoma:
Benign tumor-like overgrowth of cell types; regularly found w/in affected organ, such as a hemangioma
Glioblastoma Multiforme: ?????
Most common type of astrocytoma
FIND OUT
Malignant Myoepithelia is associated with cigarettes, asbestos, polyaromatic hydrocarbons?????
LEUKEMIAS
Leukemia:f
Form of cancer that begins in blood-forming cells of bone marrow
Damaged leukocytes remain in immature form:
Become poor infection fighters
Multiply excessively & do not die off
Increased number of circulating leukocytes in the blood
Leukemic cells accumulate & reduce production of RBCs, platelets & normal leukocytes
Prolongation of bleeding time in leukemia is a result of thrombocytopenia (reduced #s of platelets)
If untreated, surplus leukemic cells overwhelm the bone marrow, enter the bloodstream, & invade other parts of the body:
Lymph nodes, spleen, liver & CNS
Behavior is different from other cancers, which usually begin in major organs & ultimately spread to bone marrow
Classified by the dominant cell type & by the duration from onset to death
Incidence evenly split (50:50) between acute & chronic leukemias
Can modify the inflammatory reaction
Chemotherapy for leukemia predisposes for oral infections by C. albicans

Risk factors for leukemias:


Familial tendency
Congenital disorders (Down syndrome [higher incidence of acute leukemias]; presence of Philadelphia chromosome [CML])
Leukemic pts have high Ab titer to EBV
Ionizing radiation & exposure to benzene & cytotoxins (such as alkylating agents), some anti-cancer drugs
Acute leukemias:
Rapid onset & progression: (few months)
Sudden high fever, weakness, malaise, severe anemia, generalized lymphadenopathy, bone & joint pain
Common in children

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Most often seen in the under 20-yr-old age group


Principal organ involved: bone marrow (along w/ liver & spleen)
Characterized by immature, abnormal cells in bone marrow & peripheral blood
Frequently in the liver, spleen, lymph nodes, & other parencymatous organs
Fatal, unless treated quickly
Petechiae & ecchymosis on skin & mucous MBs, hemorrhage from various sites; bacterial infections common
Clinical picture is marked by:
Effects of severe anemia (fatigue, malaise) & thrombocytopenia
Absence of functioning granulocytes (prone to infection/inflammation)
Spleen & liver usually moderately enlarged
Enlarged lymph nodes seen mainly in ALL
Lab findings: leukocytosis 30k-100k/mm3; immature forms (myeloblasts & lymphoblasts) predominate
In 75% of cases of ALL, the lymphocytes are neither B- nor T-cells (they are called null cells)
Untreated pts die w/in 6 months
Wth intensive therapy (chemo, radiation, & bone marrow transplants), remissions may last up to 5 years
Death usually due to hemorrhage (brain) or a superimposed bacterial infection
Shorter, more devastating clinical course than chronic leukemias
Are characterized by proliferations of lymphoid or hematopeoietic cells that are less mature than those of the chronic
leukemias
Chronic leukemias:
Slower onset & progression: w/ weakness and weight loss, disease may be detected during examination for some other
condition (e.g., anemia, unexplained hemorrhages, or recurrent intractable infection)
Longer, less devastating clinical course than acute leukemias
Develop in more mature cells can perform some duties, but not well
More difficult to treat in many cases
Characterized by proliferations of lymphoid or hematopoeitic cells (more mature than those of acute leukemias)
Organ involvement
Massive splenomegaly is characteristic of CML
Lymph node enlargement in CLL
Petechiae & ecchymosis, recurrent hemorrhages, baceterial infections
Lymphocytic anemia may be complicated by autoimmune hemolytic anemia
Lab findings: leukocytosis >100k/mm3; mature forms (granulocytes and lymphocytes) predominate
Philadelphia chromosome & low levels of leukocyte ALP alkaline phosphatase common in CML
Median survival time:
CML 4 years w/ death due to hemorrhage or infection
CLL runs a variable course (older pt may survive years even w/o Tx)

Type
ALL
AML
CLL
CML

Progression
Rapid
Rapid
Slow
Slow

Major Types of Leukemias


WBC affected
% of Leukemias
Lymphocytes
20
Myelocytes
27
Lymphocytes
31
Myelocytes
22

Age group
3-5 y.o.
Mostly adults
> 60 y.o.
Any age

Quick Notes on Several Leukemias:


ALL:
Children/lymphoblasts
Downs
AML:
Myeloblasts
Auer rods
CLL:
Elderly
Very similar to SLL (small lymphocytic lymphoma)
CML:
Massive splenomegaly
Philadelphia chromosome (9,22)
Acute Lymphoblastic Leukemia (ALL):
Most common type in children
Peak age 4 y.o.
Characteristics: found in children, is most responsive to theraby and is associated w/ Down syndrome
biologically distinct

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has a t(15;17) that juxtaposes the RAR gene on chromosome 17 w/ the PML gene on chromosome 15
associated w/ frequent DIC
responds to All-trans-retinoic acid
In the monoblastic type of leukemia (FAB M5) leukemic cells often infiltrate:
Skin
Gums, perianal area
CNS
Treatment: Chemotherapy bone marrow transplant
Allogeneic form causes graft vs. host disease
But graft vs. leukemia can be beneficial
Prognosis
depends on:
age of patient
cytogenetic pattern of leukemic cells
previous exposure to radiation, benzene or chemotherapy (worse)
aggressiveness of post remission therapy
Overall about 70% of adults enter complete remission
10 yr old with ALL, has clinical features:
CNS infiltration related to headaches, vomiting, and palsies
Bone pain secondary to leukemia infiltration of the marrow and periosteum
Symptoms related to bone marrow suppression, including anemia and thrombocytopenia
NOT multiple, acutely tender lymph nodes due to the central node ischemic necrosis
Same pt, white cell count reveals no neutrophils, Why?
Bone marrow has been replaced by leukemic cells
Acute Myeloid Leukemia (AML):
Think AMbuLance labs (Its the Worst)
Most malignant type
Characteristics include: 9 FAB subtypes along myelocytic, monocytic, erythrocytic and megakaryocytic lines
Among the most aggressive malignancies of humans
If left untxd can death w/in 40 to 100 days from time of Dx
Most common acute leukemia in adults
Etiological factors (possible) include: ionizing radiation, chemicals such as benzene and chemotherapeutic agents
Symptoms & Signs: Petechiae, sternal tenderness, sometimes adenopathy, splenomegaly and hepatomegaly may be
found, testicular, cutaneous, and meningeal involvement as well
Chronic Lymphoid Leukemia (CLL):
Least malignant type L for Least and NODES
Older adults (average age = 60 y.o.)
Characterized by abnormal small lymphocytes in lymphoid tissue
Affects men 2-3x more than women
Presents w/ lymphadenopathy, hepatospenomegally and few symptoms
Takes an indolent course
Increase in smudge cells in peripheral blood smear
Warm Ab autoimmune hemolytic anemia
Very similar to SLL (small lymphocytic lymphoma)
Q reads: On the basis of histo and transitions observed clinically, there appears to be a relationship between
lymphocytic lymphoma and.. Lymphocytic Leukemia
Chronic Myeloid Leukemia (CML):
Think M for Massive Spleen, cMl, and Ph chroMMMMosome
Invariably fatal
Most common in young & middle-aged adults (slightly more common in men); rare in children
90% of pt have Philadelphia, or Ph1 chromosome the long arm of chromosome 22 is translocated, usually to
chromosome 9
Induced by radiation, carcinogenic chemicals
Characterized by abnormal overgrowth of granulocytic precursors (myeloblasts & promyelocytes) in bone marrow,
peripheral blood & body tissues
Characterized by massive splenomegaly
Low-to-absent leukocyte alkaline phosphatase
Cells resemble nearly normal granulocytes
Two distinct phases of clinical course:
1) Insidious chronic phase anemia & bleeding disorders
2) Blastic crisis or acute phase rapid proliferation of myeloblasts, the most primitive granulocyte precursors
ENDOCRINE PATHOLOGY

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HYPOTHALAMUS/PITUITARY
Gigantism:
Oversecretion of GH in childhood before fusion of growth plates leads to bone growth & abnormal height
Acromegaly:
Chronic metabolic disorder caused by excessive amounts growth hormone (GH)
Endocrine etiology
Occurs after closure of the growth plates
Cause of GH secretion usually a benign tumor of pituitary gland
Somatotroph adenoma of the pituitary gland in 30 yr old pt results in acromegaly
Think GH = somatotropin
Results in gradual enlargement of the body tissues bones of face, jaw, hands, feet, & skull
Usually begins between ages 35-55
Growth plates have closed, so bone becomes deformed rather than elongated
Common findings:
Gradual marked enlargement of the head, face, hands, feet, & chest
Excessive perspiration & offensive body odor
Prognathism
Enlarged tongue
Deep voice
Dwarfism (pituitary dwarfs):
Characterized by arrested growth
Frequently pts have improperly formed or proportioned limbs & features
Caused by undersecretion of GH
Diabetes insipidus (central):
Rare condition caused by damage to hypothalamus (specifically, the supraoptic nuclei) or pituitary gland (posterior)
Due to lack of ADH (vasopressin) produced in supraoptic nuclei (produced in the hypothalamus) & secreted by
posterior pituitary
Damage may be related to surgery, infection, inflammation, tumor, or head injury
Very rarely caused by a genetic defect
Body fluid volumes remain pretty close to normal so long as the pt drinks enough water to make up for increased clearance
Think of girl on house drinking all that water!
Polyuria, Polydipsia
Large volumes of dilute urine
High serum osmolarity
Hypernatremia Remeber ADH just allows water to leave and doesnt mess with Na/K pump so relatively more Na
left Since soo much water out and no Na out get relatively high concentration of Na within.
Marked by extreme thirst & excessive urine output caused by ADH deficiency normally limit amount of urine made
Responds to exogenous ADH therapy
Nephrogenic diabetes insipidus:
Rare disorder characterized by passage of large volumes of urine due to a defect of kidney tubules Makes sense due to name
of disease diabetes insipidus (have to pee and drink a lot) but due to kidneys!
Specific kidney defect usually a partial or complete failure of receptors on kidney tubules that respond to ADH
Excessive amounts of water are excreted w/ the urine, producing a large quantity of very dilute urine
May be present at birth as a result of a sex-linked defect (congenital nephrogenic DI)
Usually affects men (women can pass on the gene)
SIADH (Syndrome of Inappropriate ADH)
Excessive water secretion
Hyponatremia
Serum hypo-osmolarity with urine osmolarity>serum osmolarity
Causes Ectopic ADH (small cell lung cancer), CNS disorder/head trauma, Pulmonary disease, Drugs
ADRENAL GLANDS
Addisons disease:
Adrenal insufficiency
Chronic adrenal disorder characterized by anorexia, hypoglycemia, hypotension, and hypovolemia, and skin
hyperpigmentation (increased MSH) & perioral lesions
Primary deficiency of aldosterone and cortisol due to adrenal atrophy
Hormone deficiency caused by damage to the adrenal cortex
Aka primary adrenal hypofunction or adrenal insufficiency
Life-threatening condition caused by partial or complete failure of adrenocortical function
May be the result of autimmune processes, infection, neoplasm, or hemorrhage in the gland

140

> 90% of cortex must be destroyed before obvious symptoms occur, but it does involve all 3 cortical divisions (GFR)
Characterized by
Nausea, vomiting, hypotension, and asthenia feeling of being weak, but not really
Insidious onset of weakness, fatigue, depression hypotension & bronzing of the entire skin
Think of the weakness, anorexia and hypotension all from the hypoglycemia. Hypovolemia and hypotension both from
the increased secretion of Na!!!
Oral signs:
Consist of diffuse pigmentation of the gingiva, tongue, hard palate, & buccal mucosa = melanosis
The most common oral manifestation of Addisons is melanosis
Pigmentation of oral tissues tends to persist cutaneous pigmentation most likely disappears following therapy
Lab tests low BP, low cortisol level, low serum Na + & perhaps high serum K+
What disease is associated with Na+ secretion in the urine?
Addisons
ACTH test: (aka corticotropin test)
Measures pituitary gland function
*Pituitary releases ACTH which stimulates outer layer of adrenal cortex
*ACTH causes release of hydrocortisone, aldosterone, & androgen. cortisol is most important
Used to determine if too much cortisol (Cushings syndrome) or not enough (Addisons) is being produced
ACTH levels are high in Addisons disease
Tx cortisol administration
Distinguished by secondary insufficiency, which has no skin hyperpigmentation
Waterhouse-Friderichsen syndrome:
Catastrophic adrenal insufficiency & vascular collapse due to hemorrhagic necrosis of the adrenal cortex
Rapidly progressing infection caused by N. meningitidis
Most often found in association w/ meningococcal meningitis
Characterized by coagulopathy, hypotension, adrenal cortical necrosis, and sepsis (usually fatal)
Produces severe diarrhea, vomiting, seizures
Cushings disease:
Hyperfunction of the adrenal cortex
Excess ACTH production (Also High IN addisons, trying to compensate)
From pituitary adenomas, higher CNS stimulation CRH
Or from tumors like small cell carcinoma of lung Just remember it SMALL CELL TUMOR IN LUNG, for some
freaking reason, PRODUCES ACTH which will lead to CUSHINGS!!!!
Excess due to pituitary gland hyperplasa, adenoma, or carcinoma
Unknown cause, Iatrogenic excess, is most common
From Cushing disease (primary pituitary adenoma); increased ACTH
Primary adrenal hyperplasia/neoplasm; decreased ACTH
Ectopic ACTH production (small cell lung cancer); increase ACTH
Pulmonary neoplasm most likely to produce ACTH
Iatrogenic; decrease ACTH
Signs:
Think IRENE
Typical habitus, moon faces, buffalo hump, truncal obesity, striae(From collagen problems), and osteoporosisexcess gluccocorticoids leads to bone breakdown
Increased body weight, edema, hypertension, osteoporosis and pathologic fractures, fatigabiliy, weakness, hirsutism,
amenorrhea, ecchymosis, personality change, hyperglycemia (from insulin resistance), hyopkalemia
Dx: test urinary free Cortisol of suppression test w/ dexamethasone
Tx: aims at source if from pituitarysurgery, radiation (gamma knife), drugs, iatrogenictaper carefully
Hyperaldosteronism:
Primary (Conns syndrome):
Caused by an aldosterone-secreting tumor, resulting in HTN, hypokalemia, metabolic alkalosis, & low plasma renin
Secondary:
Due to renal artery stenosis, chronic renal failure, CHF, cirrhosis, and nephritic syndrome. Kidney perception of low
intravascular volume results in an overactive renin-angiotensin system. Therefore it is associated w/ high plasma renin
THYROID
Thyroid Gland:
Secretion of T3 (triiodothyronin) & T4 (thyroxin) controlled by pituitary gland & hypothalamus
Thyroid disorders may result from defects in thyroid gland itself, & also from abnormalities of the pituitary or hypothalamus
Hyperthyroidism (thyrotoxicosis): -- Jared Corbridge
Imbalance of metabolism caused by overproduction of thyroid hormone
Characterized by exophthalmos, tachycardia, heat intolerance, and fine tremor, warm moist skin, and fine hair
Caused by excessive production of T4 (thyroxin)
Thyroxin stimulates cellular metabolism, growth, & differentiation of all tissues

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Excess leads to high basal metabolism, fatigue, weight loss, excitability, temperature, & generalized osteoporosis
Premature eruption of teeth & loss of deciduous dentition
Findings Increased TSH if primary, increased total T4, increased T4, and increased T3 uptake
Graves disease (most common form):
Hyperthyroidism with thyroid-stimulating/TSH receptor antibodies
Autoimmune disease occuring most frequently in women between ages 20-40
Arises following an infection or physical/emotional stress
Symptoms:
Diffuse Goiter from overactive thyroid?
Range from anxiety & restlessness to insomnia & weight loss
Eyeballs may begin to protrude (exophthalmos) causing irritation & tearing
Plummers disease (toxic nodular goiter):
Arises from long-standing simple/Nodular goiter & occurs most often in the elderly
Symptoms same as Graves disease BUT no protruded eyeballs Nadia would never be a plummer!
Risk factors: female > 60 y.o.
Never seen in children a plummer is no job for a child!
Hypothyroidism:
Characterized by weight gain, cold intolerance, lowered pitch of voice, mental/physical slowness, constipation, dry skin,
coarse hair, edema, positive nitrogen balance???Hypothyroid pts are bigger so they keep it in, decrease in plasma
bound iodine, decrease in iodine uptake by thyroid, and increased blood cholesterol
NOT Increased oxygen consumption Would increase O2 consumption if under heavy metabolism (HYPERthryoidsism)
Another Q: Congenital hypothyroidism most likely causes delayed eruption of teeth BUT Jareds kid has HYPO
Underactivity of the thyroid gland
May cause a variety of symptoms and may affect all body functions
Normal rate of functioning slows down causes mental & physical sluggishness
Considerably more common in women
Extreme hypothyroidism in adults = Myxedema
Symptoms fatigue, slowed speech, cold intolerance, dry skin, coarse, brittle hair, puffy face
Characterized by puffiness of face & eyelids, and swelling of tongue & larynx
Skin becomes dry & rough, and hair becomes sparse
Affected individuals also have poor muscle tone, low strength, & get tired very easily
Findings Increased TSH (sensitive test for Primary Hypothyroidism, decresed Total T4, Decreased T4, Decreased
T3 uptake
Alleviated by administering thyroid hormones
Risk factors age >50, female, obesity, thyroid surgery, & exposure of the neck to x-ray or radiation Tx
Hashimotos Disease:
Most common cause of hypothyroidism
Caused by an autoimmune reaction against the thyroid gland (Thyroiditis)
Common thyroid gland disorder
Production of Ab/s in response to thyroid Ag/s & the replacement of normal thyroid structures w/ lymphocytes &
lymphoid germinal centers
Onset is slow may take months or years for condition to be detected
Most common in middle-aged women & individuals w/ family Hx of thyroid disease
Estimated to affect 0.1-5% of all adults in Western countries
Less common cause failure of pituitary gland to secrete TSH (secondary hypothyroidism)
Severe hypothyroidism in children leads to Cretinism:
Endemic cretinism occurs wherever endemic goiter is prevalent (lack of dietary iodine)
(Dont get confused with the goiters of Graves and Plummers)
Sporadic cretinism is caused by defect in T4 formation or developmental faiulure in thyroid formation
Retardation of growth & abnormal bone development due to lack of thyroid hormone
Mental retardation is caused by improper development of the CNS
If recognized early, it can be markedly improved by use of thyroid hormones
Findings Pot-bellied, puffy faced child with protruding umbilicus and protuberant tongue
Dental findings in child underdeveloped Mn w/ an overdeveloped Mx, delayed eruption & retained deciduous teeth
Mental retardation, delayed growth, and delayed tooth eruption NOT caused by lack of GH (dont get clowned)
PARATHYROID GLANDS
1 Hyperparathyroidism
Common; major cause is an adenoma (benign tumor of glandular epithelium)
Lab findings hypercalcemia, serum phosphate (because of diuresis), & serum ALP & serum PTH
Clinical characteristics cystic bone lesions (osteitis fibrosa cystica or von Recklinghausens bone disease), nephrocalcinosis,
kidney stone & peptic duodenal ulcers

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43-year-old with radiolucencies (not associated with apices), and radiolucencies in humerus. Lab tests indicate elevated
calcium, but serum phosphorus and alkaline phosphatase are normal. She also has giant cells in her bone lesion
Dx: hyperparathyroidism Pagets doesnt have Giant Cell lesions
Signs/Symptoms
Urolithiasis/Nephrolithiasis
Elevated serum Calcium
Central Giant-cell bone lesions
Loss of lamina dura surrounding multiple teeth
NOT tetany
NOTE: Osteoporosis, giant cell granulomas, & metastatic calcification are manifestations of hyperparathyroidism
How does Hypercalcemia affect muscle contraction? causes weakness & fatigue
2 Hyperparathyroidism
Caused by hypocalcemia of chronic renal disease
Excessive urinary Ca2+ loss stimulates PT glands to undergo hyperplasia due to feedback mechanism
Low calcium, high phosphate
Resulting metabolic effects are identical to those w/ 1 Hyperparathyroidism
REMBER PTH-related Peptide
3 Hyperparathyroidism
Hyperparathyroidism that persists after definitive therapy for secondary
Hypoparathyroidism
Most commonly caused by accidental surgery excision during thyroidectomy
May result in tetany (from low Ca)
Pseudoparathyroidism
Defective end-organ responsiveness to PTH
***SIDENOTE on Tetany:***
Clinical neurological syndrome characterized by muscle twitches, cramps & carpopedal spasm
When severe, larygnospasm & seizures develop
Usually associated w/ Ca2+ deficiency, Vit D deficiency or alkalosis
Associated with Parathyroid Hypofunction
Kills patient before other effects can develop
Normally occurs when blood [Ca2+] reaches approximately 6 mg% (normal is ~10 mg%) lethal at 4 mg%
Chvosteks sign: tapped with Chop stick
Tap the facial neve above mandibular angle, adjacent to earloble
Facial muscle spasm causing upper lip to twitch confirms tetany
Trousseaus sign: swordfighter
Apply a BP cuff to the pts arm
A carpopedal spasm causing thumb adduction & phalangeal extension confirms tetany
PANCREAS
Diabetes Mellitus:
Recessive Inheritance
Metabolic disease involving mostly CHOs & lipids
Most common pancreatic endocrine disorder
Caused by absolute insulin deficiency (type 1) or resistance to insulin action in peripheral tissues (type 2)
Causes decrease in liver glycogen, hyperglycemia, glucosuria, and polyuria
Classic traid of symptoms = Polydipsia, Polyuria, & Polyphagia
Usually leads to Dehydration or Acidosis Coma, death
Only of pts are ever diagnosed
More common in blacks, especially females; American Indians
Characterized by:
Hyperglycemia, glycosuria, Hyperlipemia, and Ketonuria
Increased susceptibility to infection, increased fatigability, recessive inheritance, and polyuria
Signs & symptoms:
Non-specificfatigue, weakness, polydipsia, polyuria, skin lesions-including fungal infections of skin & mucous MBs
Chronic Manifestations
Small vessel disease thickening of BM, retinopathy, nephropathy
Large vessel atherosclerosis, coronary artery disease, peripheral vascular occlusive disease, gangrene, CV disease
Neuropathy
Cataracts, glaucoma
Susceptibility to infections, neuropathies, impotence, ketoacidosis, lipid metabolism abnormalities including
atherosclerosis
Long term complications of poorly controlled type I diabetes:
Hyaline arteriosclerosis, Proliferative retinopathy, Nodular glomerulosclerosis, peripheral symmetry neuropathy

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NOT Pancreatic Carcinoma


Hyperglycemia increase intercellular sorbitol, which is in turn associated with depletion of intracellular myoinositol levels
Diabetics are a high-risk group for the following infections:
Klebsiella pneumonia
Sinus mucormycosis
Malignant otitis externa (P. aeruginosa)
Chronic osteomyelitis
Sudden onset of a seizure in a non-compliant type I diabetic would be most likely due to hypoglycemia also from
hypocalcemia
Pt takes insulin in the am, goes jogging, then comes into the dental office with symptoms of anxiety and is just not his
usual self Pt is Hypoglycemic He forgot to eat.
Hb A1c plays role in long-term glucose control Used for long term monitor a diabetics compliance to controlling glucose
Dx:
Fasting serum glucose, glucose tolerance, HbA1c Glycosylated hemoglobin (amount of glucose) Diabetes
impaired fasting glucose is over 100 after 8 hrs of fasting and oral glucose load is over 200 after 2 hours
Tx: diet, oral hypoglycemics, insulin, weigth loss, transplantation, and vigilance for complications
Type 1 DM:
Usually diagnosed in childhood
Diminished beta-cell mass
Body makes little to no insulin
Daily injections of insulin are required to sustain life
Three etiologic mechanisms:
Viral infection, genetic predisposition, autoimmune response

Characteristic
Level of insulin secretion
Typical age of onset
Percentage of diabetics
Basic defect
Associated w/ obesisty
Speed of development of symptoms
Development of ketosis
Treatment
Concordance in identical twins
Genetic predisposition
Association with HLA system
Beta cell numbers in islets
Classic symptoms of 3 Polys

Type 1 vs. Type 2 Diabetes Mellitus


Type 1 Diabetes
Type 2 Diabetes
None or almost none
May be normal or exceed normal
Childhood <30
Adulthood >40
1020%
8090%
Destruction of B-cells
Reduced sensitivity of insulins target cells
No
Usually
Slow
Rapid
Rare
Common if untreated
Insulin injections, dietary management
Dietary control & weight reduction;
occasionally oral hypoglycemic drugs
50%
100%
Weak, polygenic
Strong, polygenic
Yes (HLA DR 3 and 4)
No
Reduced
Variable
Common
Sometimes

Diabetic Ketoacidosis
One of the most complications of DM Type I
Not a type II complication!
Usually due to an increase in insulin requirements from an increase in stress (i.e. infection)
Excess fat breakdown and increased ketogenesis from the increase in free FAs, which are then made into ketone bodies
Signs
Kussmaul Respirations (Rapid/deep breathing), hyperthermia, nausea/vomiting, abdominal pain, psychosis/dementia,
dehydration, Fuity breath odor
Labs
Hyperglycemia, Increased H+, Decreased HCO3-, Increased blood ketone levels, leukocytosis
Complications
Life-threatening mucormycosis, Rhizopus infection, cerebral edema, cardiac arrhythmias, heart failure
Tx
Fluids, insulin, and potassium, glucose is necessary to prevent hypoglycemia
EYES
Ocular trachoma:
Eye infection caused by Chlamydia trachomatis
Incubation period of 5-12 days begins slowly as conjunctivitis (pink eye)

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If untreated, may become chronic & lead to scarring


Pinkeye is transmitted person to person
If eyelids are severly irritated, eyelashes may turn in & rub against cornea
This can cause eye ulcers, further scarring, visual loss, & even blindness
Occurs worldwide primarily in rural settings in developing countries (rare in U.S.)
Leading cause of blindness in developing countries
Frequently affects children, although the consequences of scarring may not be evident until later in life
Inclusion conjunctivitis:
Conjunctivitis caused by Chlamydia trachomatis
Often affecting newborns also contracted by adults in swimming pools or during sexual contact
I wonder what happens if someone has sexual contact in a swimming pool?
Characterized by enlarged papilla on inner eyelids & a purulent discharge
Chronic inflammation/hypertrophy of conjuctiva forms grayish, yellowish translucent granules
Pinkeye:
Aka acute contagious conjunctivitis
Acute, contagious form of conjunctivitis caused by Hemophilius aegyptius
Characterized by inflammation of eyelids & eyeballs w/ a mucopurulent discharge
Keratoconjunctivitis Sicca:
Long-standing dryness of both eyes, leading to dehydration of conjunctiva & cornea
NOTE: dry eyes may be a symptom RA, SLE or Sjogrens syndrome
Herpes conjunctivitis
Specific chemotherapy is used to tx it (NOT used to tx measles, smallpox, hepatitis, IM)
IMMUNO DISEASES
Sarcoidosis:
Characterized by immune-mediated, widespread noncaseating, non-necrotizing granulomas where TB is Caseating and
elevated serum ACE levels
TBCaseating, Necrotizing
Crohns disease NON-caseating, NON-necrosis, granulomatous inflammation of the gut wall
Common in black females
GRAIN: gammaglobulinemia, rheumatoid arthritis, ACE increase, Interstitial fibrosis, Noncaseating granuloma
Associated w/ restrictive lung disease, bilateral hilar lymphadenopathy, erythema nodosum, Bells palsy, etc
IMMUNODEFICIENCIES (as outlined in Kaplan)
PRIMARY IMMUNODEFICIENCY DISEASES
Selective IgA deficiency:
The most common immunodeficient state
Low levels of IgA
Common variable (B lymphocyte hypogammaglobulinemia:
B cells normal, but fail to differentiate into plasma cells
Low circulating Ab levels
X-linked (Brutons) agammaglobulinemia:
Rare, sex-linked, & results in decreased production of Ab/s
Tx involves repeated administration of IgG to maintain adequate Ab levels in blood
IgM, IgG, IgA, IgD, IgE, & circulating B-cells are absent or deficient (T-cells are intact)
Almost exclusively affects males
Causes severe, recurrent bacterial infections during infancy (mostly pyogengic bacteria)
Results from failure of B-cells to mature & differentiate into plasma cells (which produce Ab/s)
Think B for Brutons, B-cell deficient, and Bacteria infections
Pre-B cells are normal B cells are absent
Failure to mature is caused by a mutation in the B-cell protein tyrosine kinase
Tx with Giving Gamma Globulins
Normal cell-mediated immunity
Adequate host defense mechanisms exist for resistance tovirus infections (NOT bacterial or fungal)
Remember viruses are in the cell, so usually T-cell mediated
Viruses enter, start production, then MHC I is made in rER!!!!!!
MHC II, deals more with cells eating Bad bugs of bacteria
***The pt is just missing gamma globulins
DiGeorge Syndrome: T-- George
Think T for Thymic aplasia, T-cell deficiency, Tetany due to hypocalcemia You need Vitamin D-George!!!!
Thymic hypoplasia or aplasia Remember youre BORN with it
Rare immunodeficiency disorder characterized by various congenital abnormalities arising late in fetal development
The causative defects occur in areas known as the 3rd & 4th pharyngeal pouches

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These pouches develop into the thymus & parathyroid glands (which may be missing or underdeveloped)
Development abnormalities may also occur in the 4th branchial arch
Primary problem is the repeated occurrence of various infections due to a diminished immune system
Prone to viral & fungal infections T cell GUYS!!!
Absence of thymus results in T-cell deficiency
These children have normal B-cells & form antibodies
They have decreased or absent delayed-type hypersensitivity
Absence of parathyroids causes hypocalcemia leads to development of tetany
Severe Combined Immunodeficiency Disease (SCID):
Most dangerous type of congenital (inherited) immunodefieicency
Defects in lymphoid stem cells (results from failure of stem cells to differentiate properly)
Pts have neither B-cells nor T-cells Without T or B cells, your life will come SCIDing to a hault!
Pts are incapable of any immunological response
Children usually die before 2 y.o.
ACQUIRED IMMUNODEFICIENCY DISEASES
AIDS = acquired immunodeficiency syndrome
See HIV in virus section for more info
Caused by HIV (a lentivirus)
The viral MB contains a transMB protein, gp160
gp160 is usually detected by Western blot analysis as 2 fragments gp41 & gp120
Characterized by a profound loss of CD4+ T cells
The virus can also infect CD4+ cells (macrophages & astrocytes)
Cellular consequences:
T cells: loss of CD4+ T cells AND decrease in response of T cells to Ag AND impaired cytokine production
B cells: steadily lose ability to mount an effective Ab response to new Ag/s
Diagnosis:
ELISA detects Ab/s to HIV
Western blot confirmatory tests
Associated with:
Loss of cellular immunity defenses
Alteration of Helper T/Suppressor T ratio
Increased susceptibility to opportunistic infections
Results in Opportunistic infections, i.e.:
Pneumocystis carinii
Most common cause of pneumonia in AIDS pts
Mycobacterium avium intracellulari
Malignant neoplasms:
Kaposis sarcoma
Non-Hodgkins lymphoma
NOT Bronchogenic or Testicular Carcinomas, Neuroblastoma, Rhabdomyosarcoma, or Mycosis fungoides
PHAGOCYTIC CELL DISORDERS
Neutropenias
Cyclic, Hereditary, or Acquired
Opsonic defects
Chemotactic defects
AUTOIMMUNE DISEASES
Autoimmune disorders
Mechanism or cause of autoimmune diseases is not fully known
Arise by way of:
Release of sequestered antigen
Cross rxn between exogenous and self-antigens
Loss of T-suppressor activity against autoreactive (forbidden) clones
NOT from persistant depression of the immune system In fact, exact opposite of this!
Systemic Lupus Erythematosus (SLE):
Chronic, inflammatory autoimmune disorder that may affect many organ systems (skin, joints, kidneys, heart, blood, & CNS)
Results in episodes of inflammation in joints, tendons, & other CT & organs
Appears most often between ages 10-50
90% of SLE cases are in women in late teens to 30s
May be caused by certain drugs (drug-induced lupus erythematosus) usually reversible when medication is stopped
Disease course varies from mild episodic illness to a severe fatal disease
Symptoms vary widely in a particular pt over time:

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Fever, fatigue, weight loss, arthritis, malar rash, photosensitivity, pleuritis, pericarditis, or non-bacterial endocarditis,
Raynauds, Wire LUP (loop) lesions in kidney with immune complex deposition
NOT clubbing or cyanotic digits (Polycythemia, congenital heart disease, congestive heart failure, chronic
pulmonary disease DO) Remember Raynauds is just from Cold, emotion
SLE causes LSE (Libman-Sacks Endocarditis) Valvular vegetations found on both sides of mitral valve, No
embolizations
Characterized by periods of remission & exacerbation
At onset, perhaps only one organ system involved
Renal failure commonly occurs & is the usual cause of death
Severe CNS involvement may appear
Acrocyanosis (Raynauds phenomenon) often associated w/ SLE
Immunosuppressive therapy and corticosteroids medication allow prolonged survival
Characteristic auto-antibodies:
Positive ANA
Anti-dsDNA & Anti-Sm Ab/s appear to be specific for SLE
Butterfly rash over cheeks & bridge of nose affects ~ SLE rash worsenes w/ sunlight
Scleroderma (progressive systemic sclerosis-PSS)
Excessive fibrosis & collagen deposition throughout the body
Damage is done to small BVs
75% female
Commonly sclerosis of skin but also of cardiovascular and GI systems & kidney
NOTE: Most common characteristic lesion of rheumatic fever, scleroderma and RA is Fibrinoid degeneration
2 categories:
Diffuse scleroderma:
Associated with anti-Scl-70 antibody
Widespread skin involvement, rapid progression, early visceral invovlement
CREST: (Remember the Teradactyl)
Calcinosis, Raynauds phenomenon, Esophageal dysmotility, Sclerodactyly, and Telangiectasia
Limited skin involvement, confined to fingers and face.
More benign clinical course
Assoicated w/ anticentromere Ab/s pathognomonic for CREST
Sjogrens syndrome:
2nd most common autoimmune rheumatic disorder after RA
Occurs mainly in women (90% of patients) mean age is 50
Characterized by diminished lacrimal & salivary gland secretion (sicca complex)
These glands have chronic inflammation caused by WBC infiltration
Usually progresses to fibrosis & atrophy of these glands
Triad of findings:
1) Associated CT disorders (e.g., rheumatoid arthritis)
Chronic arthritis
2) Xerostomia (dry mouth)
May cause rampant caries reminiscent of radiation caries (due to shift toward more acidogenic microflora)
Parotid enlargement
3) Keratoconjunctivitis Sicca (dry eyes)
All three rarely occur in one patient
Definite Dx made only when at least two symptoms are present
Occasionally the lymphocytic infiltration is massive, causing enlargement of the glands (called Mikuliczs syndrome)
Increased risk for B-cell lymphoma
Sicca syndrome: dry eyes, dry mouth, nasal and vaginal dryness, chronic bronchitis, reflex esophagus
AMYLOIDOSIS
Amyloidosis:
Rare, chronic condition related to abnormal production of Ig by plasma cells
Characterized by deposition of amyloid protein in the extracellular space of various organs & tissues
Results in accumulation of an abnormal fibrillar scleroprotein (amyloid) which infiltrates body organs and soft tissues
In the tongue
Amyloid deposits are primarily in the stromal CT
Usually affects adults middle-aged & older
Renal disease is often the 1st manifestation
Displays apple-green birefringence under polarized light w/ Congo red stain
Forms:
Primary:

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Cause unknown
Associated w/ abnormalities of plasma cells (as is multiple myeloma, which may be associated w/ amyloidosis)
Typical sites of amyloid buildup heart, lungs, skin, tongue, thyroid gland, intestines, liver, kidney, & BVs
Secondary:
Amyloidosis is secondary to another disease such as TB, RA, or familial Mediterranean fever
Amyloid buildup spleen, liver, kidneys, adrenal glands, & lymph nodes (heart rarely involved)
Hereditary:
Affects nerves & certain organs; has been noted in people form Portugal, Sweden, & Japan
NOTE: Alzheimers disease, Type 2 DM, & Familial Mediterranean fever are amyloid associated conditions
Amyloid deposits characterize all of them (EX Type 2 DM: amyloid deposits in islet cells)
TRANSPLANTATION & TUMOR IMMUNOLOGY
Graft types
Autograft:
Surgical transplantation of any tissue from one location to another in the same individual
Type of maxillofacial bone graft with best success
Aka autogenic graft, autologous graft, autoplastic graft or auto transplant
Isograft: I for Identical twins
Composed of tissues taken from an individual of the same species who is genetically identical (e.g., identical twins)
Allograft: All for we all get along and share tissues with people we dont know!
Tissue taken from a genetically unrelated individual of the same species
Aka allogenic graft, homologous graft, or homoplastic graft
Xenograft: X for X me out of taking skin from a pig or a turtle or a dog.
Tissue from another species used as a temporary graft in certain cases, as in treating a severely burned patient
Quickly rejected but provides a cover for the burn for the first few days
In skin graft rejection, the major host response is a cell-mediated immune response (delayed type IV
hypersensitivity)
Reaction Types
Hyperacute rejection
Antibody mediated due to the presence of preformed anti-donor antibodies in the transplant recipient
Occurs within minutes after transplantation
Acute rejection
Cell mediated due to cytotoxic T lymphos reacting against foreign MHCs
Occurs week after implantation
Reversible with immunosuppressants such as cyclosporine and OKT3
Primary tissue transplants, such as allogenic skin, kidney or heart, are most commonly rejected due to:
Cell-mediated immune responses to cell-surface autoantigens
Chronic rejection
Antibody-mediated vascular damage (fibrinoid necrosis)
Occurs months to years after transplantation
Irreversible
Graft vs. Host Disease
Grafted immunocompetent T cells proliferate in the irradiated immunocomprmised host and reject cells with foreign
proteins, resulting in severe organ dysfunction
Major symptoms include a maculopapular rash, jaundice, hepatosplenomegaly, and diarrhea
Most feared consequence of graft therapy in immunodeficient pts is graft vs. host reaction
Usually occurs when graft contains its own viable lymphoid cells
Cyclosporin A has been used to control these adverse transplant events (T cell suppressor)
When a graft is rejected once & a graft from the same donor is tried, it will be rejected more rapidly the 2nd time
CONGENITAL PATHOLOGY / GENETIC DISORDERS
Penetrance:
The frequency, expressed as a fraction or percentage, of individuals who are phenotypically affected, among persons
of an appropriate genotype (i.e., homozygous or hemizygous for recessives, heterozygotes or homozygotes for dominants);
factors affecting expression may be environmental, or due to purely random variation; contrasted with hypostasis where the
condition has a genetic origin and therefore tends to cause correlation in relatives.
Example: Autosomal dominant trait showing 50% penetrance, will be phenotypically present in what percent of the
offspring?
25%, because if (Aa x aa) gives 50% Aa & 50% aa, then 50% of the offspring have the right allele; but, with 50%
penetrance, only 25% of all the offspring will phenotypically express the gene
Codominance
Phenotypic of BOTH alleles in a gene pair
Pink flower instead of white and red

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Teratogens:
Teratology is the study of developmental anomalies
Chemical, physical, & biological agents that cause developmental anomalies
Susceptibility to teratogens is variable
Susceptibility to teratogens is specific for each development state
Mechanism is specific for each teratogen
Teratogens are dose dependent
Produce growth retardation, malformation, functional impairment, or death
Teratogenic agents:
Misc Ach inhibitors, cocaine, DES, Iodide, Thalidomide
Physical agents radiation, hypoxia, excessive CO2, & mechanical trauma
Maternal infection (TORCH): Toxoplasmosis, Other agents, Rubella, CMV, and HSV
Rubella and Toxoplasmosis Both are teratogenic Be careful Rubeola is not a teratogen
Rubella
Greatest incidence of rubella associated w/ cardiac anomalies occurs during 1st trimester
CMV
The major viral cause of birth defects in infants in developing countries
Hormones sex hormones & corticosteroids
Vitamin deficiencies riboflavin, niacin, folic acid, and vitamin E
Chemotherapy used for treating malignancies
Antibiotics mitomycin, dactinomycin, puromycin (used as chemotherapy agents)
AUTOSOMAL-DOMINANT DISEASES:
Familial hypercholesterolemia:
Genetic defect characterized by abnormalities of LDL receptors so LDL receptor deficiency!!!***
Elevated LDL owing to defective or absent LDL receptors.
LDL carries cholesterol from periphery to liver
Homozygotes, very rare, have cholesterol of 700 mg/dL
Severe atherosclerotic disease early in life, and tendon xanthomas (classically in the Achilles tendon), pg 1189 path
book myocardial infarcts may develop before age 20
Marfans syndrome:
Fibrillin gene mutation leading to a CT disorder:
Uncommon hereditary CT disorder resulting in abnormalities of the eyes, bones, heart, & BV
Pts are tall & thin w/ abnormally long legs & arms & spider-like fingers
Skeletal abnormalities: tall w/ long extremities, hyperextensive joints, and long tapering fingers and toes
Cardiovascular: cystic medial necrosis or aorta leading to aortic incompetence and dissecting aortic aneyrysms. Floppy
mitral valve
NOT Mental Retardation
Ocular: subluxation of lenses
Familial adenomatous polyposis = familial polyposis coli
Think FAP Familal Adenomatous Polyposis, chromosome 5, Autosomal dom, Positively will get colon cancer
Adenomatous Polyps predispose for Colon Cancer
Info found in GI tract section
Adult polycystic kidney disease:
Always bilateral, massive enlargement of kidneys due to multiple large cysts
Patients present w/ pain, hematuria, hypertension, progressive renal failure
90% of cases are due to mutation in APKD1
Associated w/ polycystic liver disease, berry aneurysms, mitral valve prolapse
Adult form is Autosomal Dominant (renal adenoma, glomerulonephritis, and 2 amyloidosis are NOT)
Juvenile form is recessive
Huntingtons disease:
Progressive neurologic disorder
Depression, progressive dementia, choreiform movments, caudate atrophy, & decreased levels of GABA & Ach in
brain
Symptoms manifest affected individuals between the ages of 30 and 50death follow 15-20 years later
Gene located on chromosome 4, (Hunting 4 Sexy Triplets), triplet repeat disorder
Wilms tumor = nephroblastoma
Embryonal tumor
Most common renal malignancy of childhood
Dont Get Clowned Neuroblastoma is most common PLAIN malignancy in children and infants
Involves one or both kidneys
Often reaches enormous size palpable abdominal mass

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Can be part of WAGR complex Wilms tumor, Aniridia, Genitourinary malformation, mental-motor
Retardation
Retinoblastoma
Associated with Rb gene
Embryonal tumor affecting one or both eyes
Osteosarcoma is associated w/ familial forms
Neurofibromatosis I: (von Recklinghausens disease)
Characterized by multiple pigmented macules of the skin
TOO reckless with you Coffee and Punch Holes in the Walls (Bone)
Has > 6 caf au lait spots, neural tumors, Lisch nodules (pigmented iris hamartomas)
Also marked by skeletal disorders (dg. Scoliosis) and increased tumor susceptibility
On long arm of chromosome 17, 17 letters in von Recklinghausen
Heriditary spherocytosis:
Intrinsic, extravascular hemolysis due to spectrin or ankyrin defect
RBCs are small and round w/ no central pallorless MB leading to increase MCHC
Osmotic fragility test used to confirm
Associated w/ gallstones, splenomegaly, anemia, and jaundice
Distinguish from warm antibody hemolysis by direct Coombs test. Hereditary spherocytosis is Coombs negative
Spheroid erythrocytes; hemolytic anemia, increased MCHC. Splenectomy is curative
AUTOSOMAL RECESSIVE DISEASES:
Cystic fibrosis:
Autosomal recessive defect in CFTR gene on chromosome 7
Defective Cl- channels leads to secretion of abnormally thick mucus that plugs lungs, pancreas, and liver which leads to
recurrent pulmonary infections (Pseduomonas species and S. aureus)
Chronic bronchitis, bronchiectasis, pancreatic insufficiency (malabsorption & steatorrhea), meconium ileus in
newborns
Increased concentration of Na+ and Cl- ion in sweat test diagnostic
Infertile in males due to absent vas deferens
Fat soluble vitamin deficiencies (ADEK)
Can present as failure to thrive in infancy
Most common lethal genetic disease in Caucasions
Treatment: N-acetylcystein to loosen mucous plugs
Glycogen storage diseases
Type IType VI, including von Gierkes disease (found elsewhere in file)
Lysosomal storage diseases
Mucopolysaccaridoses
NOTE: Hunters is not an autosomal recessive disease
Hurler syndrome Cant stop GAGGING, so you HURL
Caused by a deficiency of the enzyme alpha L-iduronidase, which results in the accumulation of the
mucopolysaccharides, heparin sulfate and dermatan sulfate in the heart, brain, liver, and other organs
It is characterized by dwarfism and mental retardation
Death occurs by age 10
NOTE: mucopolysaccharide is an old term for glycosaminoglycan (GAG)
Hurler syndrome is an example of the mucopolysaccharidoses, a group of inherited metabolic diseases caused
by the lack of certain enzymes necessary to break down GAGs
Mucopolysaccharidoses are hereditary disorders characterized by the accumulation of GAGs in various
tissues due to deficiency of one of the lysosomal hydrolytic enzymes
Sphingolipidoses = Lipid storage diseases:
***AN APPROPRIATE SIDENOTE (youll see)***
Reticuloendothelial system (mononuclear phagocyte system):
Composed of monocytes & macrophages located in reticular connective tissue (e.g., spleen)
Functional, rather than an anatomical system involved in defense against infection & disposal of breakdown
products
Constitutes all phagocytic cells of body (except granulocytes) including the cells present in bone marrow,
spleen, & liver
EXs:
Microglia = macrophages of the CNS
Kupffer cells = phagocytic cells found within the sinusoids of the liver Kupffers come from monocytes
Alvoelar macrophage (dust cells) = macrophages fixed in alveolar lining of lungs (aka: reticulum cells of
the lungs)
Histiocytes = fixed macrophages in CT

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Disorders of the Reticuloendothelial system:


ALSO LIPID STORAGE DISEASES
Gauchers disease caused by deficiency of glucocerebrosidase
Niemann Pick disease caused by a deficiency of sphingomyelinase (die w/in a few years)
Tay-Sachs disease caused by deficiency of hexosaminidase A (rapidly fatal)
All are considered Lipid Storage Diseases
Liposes
Diseases (lipid storage disease) caused by abnormalities in the enzymes that break down (metabolize fats)
They result in a toxic accumulation of fat-by-products in tissues:
Series of disorders due to inborn errors in lipid metabolism result in abnormal accumulation of lipids
The 4 diseases discussed here are most common in people of Eastern European Jewish (Ashkenazi) ancestory
Tay-Sachs disease:
Tay SaX lacks heXosamididase A (YOU HAVE SACHs of GANGLIOSIDES)
Deficiency of hexosaminidase A leads to accumulation of gangliosides in brain & nerve tissue
This abnormality of fat metabolism in nerve cells causes CNS degeneration
Is an Autosomal recessive hereditary disorder in which the deficiency of the enzyme hexosaminidase A results
in the accumulation of gangliosides especially in neurons
Is associated with an inborn error of metabolism involving a specific enzyme which normally degrades
gangliosides in the gray matter
Characterized by progressive mental retardation, blindness, convulsions, & ultimately death by age 4
Niemann-Pick disease:
No MAN PICKs his nose with his SPHINGer
Caused by a genetic defect in sphingomyelinase
Deficiency leads to accumulation of sphingomyelin in brain, spleen, & liver
Also causes mental retardation & early death by age two
Fabrys disease:
The only sphingolipidosis that is not autosomal recessive (X LINKED)
Very rare, inherited & extremely painful systemic disorder related to deficiency of -galactosidase
Characterized by glycolipid accumulation in body tissues
Gauchers disease:
Rare, inherited, potentially fatal disorder
Deficiency of glucocerebrosidase leading to accumulation of glucosylceramide in lysosomes of certain cells
Others: Albinism, alpha-1-antitrypsin deficiency, phenylketonuria (PKU), thalassemias, sickle cell anemias, infant polycystic
kidney disease, hemochromatosis
PKU
Occurs because pt cannot convert Phenylalanine to Tyrosine
(Due to deficiency of Phenylalanine Hydroxylase)
X LINKED RECESSIVE:
Female carriers of X-linked recessive disorders rarely affected due to random inactivation of X chromosomes in each cell
Type of disease inherited through the mom while she is not affected
X linked recessive
Fragile X syndrome:
2nd most common cause of genetic mental retardation (most common is Down syndrome)
associated w/ macro-orchidism (enlarged testis), long face w/ a large jaw, large everted ears, and autism
Duchennes muscular dystrophy:
Frame shift mutation causes deletion of dystrophin gene and accelerated muscle breakdown
Onset occurs before 5 years of age
Dystrophin protein is absent (Think D for Duchennes, Deleted Dystrophin, and muscle Decrease)
Usually presesnt in muscle cell MBs (but its coded for on the X chromosome)
Weakness begins in pelvic girdle muscles and progresses superiorly
Pseudohypertophy of calf muscles due to fibrofatty replacement of muscle; cardiac muscle
Others: Hemophilia A is x-linked recessive & B, Fabrys, G6PD deficiency, Hunters, Ocular albinism, Lesch Nyhan (Gout
hyperuricemia), Brutons agammaglobulineia, Wiskott-Aldrick syndrome
DISORDERS OF CHROMOSOME NUMBER OR STRUCTURE:
Down syndrome (Trisomy 21):
Most common chromosomal disorder and cause of congenital mental retardation.
Flat facial profile, simian crease(hands), congential heart disease, prominent epicanthal fold, Duodenal atresia,
Alzheimers disease for people > than 35, increase risk for acute lymphoid leukemia (we ALL go DOWN)
Think D for Drinking age (21) and Downs, and Decreased AFP DOWNs
Pt w/ down syndrome comes in and you cant pull out their lower lip why? Due to hyperactive mentalis muscle
Causes:
95% due to meiotic nondisjunction of homologous chromosomes, associated w/ advanced maternal age (from
1:1500 in women < than 20 to 1:25 in women > than 45)

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Can also cause ear infections; sleep apnea, & thyroid disfunctions
Edwards syndrome: (Trisomy 18)
Mental retardation, rocker bottom feet, low-set ears, micrognathia, congenital heart disease, clenched hands (flexion of
fingers), prominent occiput
Death usually occurs w/in 1st year
Think E for Election age (18)
Pataus syndrome: (Trisomy 13)
Severe mental retardation, microphthalmia, microcephaly, cleft lip/palate, abnormal forebrain structures, polydactyly,
congenital heart disease
Death occurs w/in 1 year
Think P for Puberty age (13)
Cri-du-chat syndrome: congenital deletion of short arm of 5 (46, XX or XY, 5p)
Microcephaly, severe mental retardation, high pitched crying/mewing, cardiac abnormalities
Think Cry of the Chat (high pitched crying)
DiGeorges syndrome
More info elsewhere in file
Results from a deletion of chromosome 22q11
TRISOMY DISORDERS
Disorder
Incidence
Abnormality
Description
Prognosis
Trisomy 21
1/700 births
Extra chromosome 21 Delayed physical & mental
Affected people
Down syndrome
development; many physical
generally live until
abnormatlties. Small head w/ broad &
their 30s or 40s
flat face, slanting eyes & a short nose.
Enlarged tongue, small & low-set ears.
Heart defects are common
Trisomy 18
1/3000 births Extra chromosome 18 Facial abnormalities combine to give
Survival > a few
Edwards syndrome
the face a pinched appearance. Small
months is rare; severe
head & malformed, low-set ears
mental retardation
Trisomy 13
1/5000 births Extra chromosome 13 Severe brain & eye defects are common > 20% survive
Pataus syndrome
beyond 1 year; severe
mental retardation
Think Johnny DEP
D Trisomy 21 (21 Jump Street)
E Trisomy 18 (Edward Scissorhands)
P Patau Pan (Finding Neverland) uhTrisomy 13
DISORDERS OF SEX CHROMOSOMES:
Sex-linked Dominance
Male with x-linked dominant condition has daughters with an unaffected partner, what percentage of the daughters will
be affected = 100%
Klinefelters syndrome (male XXY): He FELT-HER, and then realized, She, was a HE!!!
Infant appears normal at birth the defect usually becomes apparent in puberty when 2 sex characteristic fail to develop
Hypogonadism, eunuchoid body shape, tall, long extremities, gynecomastia, female pubic hair distribution
Common cause of hypogonadism seen in infertility workups
Boys tend to be tall w/ long legs
Disorder is associated w/ advanced maternal & paternal age
Person frequently has mild retardation
Diagnosed by presence of inactivated X chromosome (Barr body)
Normal Females and Klinefelter Males Have 1
Turner syndrome (female XO):
Birth defect caused by the absence or defect of an X chromosome (sex chromosome)
Chromosome just looks like 45,X, and NOT 45.Y
Short stature, webbing of neck skin, absent or retarded development of 2 sex characteristics at puberty, absence of
menstruation, coarctation of the aorta, and bone & eye abnormalities
Inhibits sexual development & usually causes infertility
Most common cause of amenorrhea
No Barr body (XO) Think Hugs and Kisses XO from Tina Turner
The embryo develops into a female, because to become a male, a Y chromosome is necessary
A condition of just a Y with no X would be incompatible with life
Diagnosed
Either at birth (due to associated anomalies) or puberty (absent or delayed menses & delayed sexual development)
Know differences between this and FAS

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With Karyotyping
Double Y male (male XYY)
Phenotypical normal, very tall, severe acne, antisocial behavior
Seen in 1-2% of XYY males
Observed in higher frequency among inmates of penal institutions
Pseudohermaphroditism:
disagreement between the phenotypic (external genitalia) and gonadal (testes vs. ovaries) sex
Female (XX): ovaries present, but external genitalia are virilized or ambiguous
Due to excessive and inappropriate exposure to androgenic steroids during early gestation
Male (XY): testes present, but external genitalia are female or ambiguous
Most common form is testicular feminization which results from maturation in androgen receptor gene, blind end
vagina
True hermaphrodite:
46 XX, 47 XXY: both ovary and testicular tissue present; ambiguous genitalia
5-alpha deficiency: unable to convert testosterone to DHT. Ambigous genitalia until puberty, when increased testosterone
causes masculinzation of genitalia. Testosterone/estrogen levels are normal; LH is normal or increase
RANDOM STUFF
Causes black urine?
????? alkaptonuria or something like that
Kid comes in and all of a sudden resp rate goes to 40/min and HR to 100/min whats going on?
Asthma??????????? FIND OUT
NEXT Q: What is the most likely reason for this pts increased HR
Increased NE? (epi and Ach were also choices)
Ankyloglossia
Extra large lingual frenum attachment pt cannot move tongue very well
Associated with Mental retardation, downs syndrome, macroglossia NOT kidney problems
Infection terminology:
Contagious highly communicable
Subclinical unapparent; only detected by demonstrating a rise in Ab titer (rising is the most reliable finding) or isolating
the organism common in herpes
Latent state absence of symptoms until a reactivation occurs
Chronic carrier organisms continue to grow w/ or w/out producing symptoms in the host
Pandemic worldwide distribution
Endemic constantly present at low levels in a specific population and with low incidence of infection
Epidemic occurs much more frequently than usual
Swelling
In an autopsy, cellular swelling (a commonly observed tissue change, is of little practical diagnostic imporance
Cloudy swelling:
Early degenerative change characterized by increase cytoplamsic granularity & increased size
Swelling of cells due to injury to MBs affecting ionic transfer; causes an accumulation of intracellular water
Shy-drager syndrome (multiple system atrophy)
Rare degenerative condition w/ symptoms similar to Parkinsons pt may move slowly, be tremulous, & have shuffling gait
Wiskott-Aldrich syndrome (aka immunodeficiency w/ eczema & thrombocytopenia):
Affects only boys
Characterized by defective B-cell & T-cell functions, Just like SCID mouse
Clinical features thrombocytopenia w/ severe bleeding, eczema, recurrent infection, & increased risk of lymphoid cancers
Ataxia-telangiectasia:
Inherited disorder that affects many tissues & body systems
Multiple symptoms telangiectasis (dilation of capillaries), ataxic (uncoordinated) gait, infection prone, defective humoral &
cellular immunity, & incrased risk of malignancies
Most obvious symptoms multiple easily visible telangiectases in the sclera & skin areas such as ear & nose, graying of the
hair, & irregular pigmentation of areas exposed to sunlight
Decreased coordination of movement (ataxia) in late childhood
Hyper-IgE syndrome (Job syndrome): -- JOB even got ALLERGIES
Immunodeficiency disorder characterized by very high levels of IgE Ab/s & repeated infections (commonly w/ S. aureus)
Tx continual administration of Abx
Calcification abnormalities:

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Metastatic calcification:
Calcification occurring in nonosseous, viable tissue stomach, lungs, & kidneys
Cells of these organs secrete acid materials & under certain conditions in instances of hypercalcemia, the alteration in pH
seems to cause precipitation of calcium salts at these sites
Occurs particularly in hypercalcemia, hyperparathyroidism & hypervitaminosis D, NOT hypoparathyroidism
Pathologic calcification:
Calcification occurring in excretory or secretory passages as calculi (in tissues other than bone & teeth)
Eggshell calcification:
Thin layer of calcification around an intrathoracic lymph node, usually silicosis, seen on a chest radiograph
Dystrophic calcification:
Deposition of calcium in dying or dead tissues
Occurs in degenerated or necrotic tissue, as in hyalinized scars, degenerated foci in leiomyomas, & caseous nodules
Secondary to disease of affected tissue
NOT associated w/ high blood calcium levels
Unlike Metastatic Calcification
Calcinosis:
Presence of calcification in or under skin often associated w/ scleroderma & sometimes dermatomyositis
Staghorn stones:
Occupy renal pelvis & calyces big stones!
Hematuria:
Blood in urine should never be ignored!!
Usually caused by kidney & urinary tract disease
Exceptions:
Women blood may appear to be in urine when it is actually from the va-jay-jay
Men blood mistaken for urinary bleeding is sometimes a bloody ejaculation due to prostate problems
Children coagulation disorders (e.g., hemophilia) or other hematologic problems (e.g., sickle cell disease, renal vein
thrombosis, or thrombocytopenias) can be underlying reasons for newly discovered blood in urine
Kidney disease following strep throat is a classic cause of hematuria
Hematemesis:
Vomiting of bright red blood indication rapid upper GI bleding
Commonly associated w/ esophageal varices (common in alcoholics) or peptic ulcers
Hemoptysis:
Coughing up blood from respiratory tract
Blood-streaked sputum often occurs in minor upper respiratory infections or in bronchitis
Can also be seen in pts suffering from tuberculosis, lobar pneumonia (Diffuse, rusty sputum, S. pneumoniae), or
bronchogenic carcinoma (NOT emphysema)
Also can be seen in pts w/ a pulmonary embolism
Hemoptysis is the main symptom of idiopathic pulmonary hemosiderosis (iron in the lungs)
Glucosuria:
Presence of glucose in urine common in diabetes
Ketonuria:
Presence of ketones in urine produced by starvation, uncontrolled diabetes, usually Type I, & occasionally alcohol
intoxication
Proteinuria:
Presence of protein in urine usually a sign of kidney disease
Accumulation of endogenous pigments:
Bilirubin
Hemosiderin
Iron containing protein derived from ferritin, which is an iron storage protein
Melanin formed from tyrosine, synthesized in melanocytes
Increased melanin pigmentation seen in Addisons disease
Decrease melanin pigmentation seen in albinism & vitiligo, and PKU
Histiocytosis X (aka Langerhans Cell Histiocytosis & Differentiated Histiocytosis)
FIXED macrophages
Group of disorders in which histiocytes (scavenger cells) proliferate, esp. in bones & lung, often causing scars to form
Characterized by abnormal increase in # of histiocytes includes monocytes, macrophages, & dendritic cells
Eosinophilic granuloma:
Most benign form
More common in males ~20 y.o.
May be totally asymptomatic there may be local pain or swelling

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In the mouth, Mn is most likely affected loose teeth on affected side w/ signs of gingivitis
Letterer-Siwe disease:
Affects infants (< 2 y.o.) fatal
Child develops a skin rash w/ persistent fever & malaise
Anemia, hemorrhage, splenomegaly, lymphadenopathy, & localized tumefaction over bones are usually present
Oral lesions are uncommon
Hand-Schuller-Christian disease:
Occurs early in life, usually before 5 y.o. more common in boys
Triad of symptoms 1) exophthalmos, 1) diabetes insipidus, 3) bone destruction (skull & jaws are affected)
Oral signs bad breath, sore mouth, & loose teeth
Treatment radiation & chemotherapy (poor prognosis)
Habermanns disease:
Is not an example of Histiocytosis X
Sudden onset of a polymorphous skin eruption of macules, papules, & occasionally vesicles w/ hemorrhage
Polymyalgia rheumatica:
Condition causing severe pain & stiffness in muscles of neck, shoulders, & hips
Hydatidiform Mole
A pathologic ovum (empty egg ovum with no DNA) resulting in cystic swelling of chorionic villi and proliferation of
chorionic epithelium (trophoblasts)
Most common precursor of choriocarcinoma
High beta HCG (Human Chorionin Gonadotropin)
Honeycombed uterus, cluster of grapes appearance
Genotype of a complete mole is 46, XX and is purely paternal in origin (no maternal chromosomes); no associated fetus
Partial mole is commonloy triploid or tetraploid
Uterine Pathology
Endometriosis
Non-neoplastic endometrial glands/stroma in abnormal locations outside the uterus
Characterized by cyclic bleeding from ectopic endometrial tissue resulting in blood-filled, chocolate cysts
Ovary is most common site
Clinically is manifest by severe menstrual related pain
Often results in infertility
Endometrial Hyperplasia
Abnormal endometrial gland proliferation usually caused by excess estrogen stimulation
Increased risk for endometrial carcinoma
Most commonly mandifest clinically by vaginal bleeding
Endometrial Carcinoma
Most common gynecologic malignancy
Peak age is 55-65
Clinically presents with vaginal bleeding
Typically preceded by endometrial hyperplasia
Risk factors prolonged estrogen use, obesity, DM, and HTN
Polycystic Ovarian syndrome
Increased LH due to peripheral estrogen production leads to anovulation
Manifest clinically by amenorrhea, infertility, obesity, and hirsutism
Tx with weight loss, OCPs, gonadotropin analogs, or surgery
Leiomyoma (See Neoplasm section)
Leiomyosarcoma (See Neoplasm section)
Breast Disease
Fibrocystic Disease
Presents with diffuse breast pain and multiple lesions, often bilateral
Bx shows fibrocystic elements
Usually does not indicate increased risk for CA, although it is a risk factor
Histological types
Cystic fluid filled
Epithelial Hyperplasia Increase in number of epithlelial cell layers in terminal duct lobule, Increase risk for CA
Fibrosis Hyperplasia of breast stroma
Sclerosing Increased acini and intralobular fibrosis
Benign Tumors
Cystosarcoma phyllodes large, bulky mass of CT and cysts, breast surface has leaflike appearance (I love Fall)
Fibroadenoma most common tumor <25 yrs, small, mobile, firm mass with sharp edges, increases with pregnancy
Malignant Tumors
Comon Postmenopause

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Arise from mammary duct epithelium or lobular glands


Histologic types
Comedocarcinoma Cheesy consistency of tumor tissue due to central necrosis
Infiltrating ductal most common carcinoma, Firm, fibrous mass
Inflammatory lymphatic involvement, poor Px
Pagets disease Eczematous patches on nipple
Risk Factors Gender, age, early menarche, delayed first pregnancy, late menopause, family history of 1 st-degree relative
with breast cancer at a young age, but NOT fibroadenoma or nonhypplastic cysts
Wegeners Granulomatosis
Characterized by focal necrotizing vasculitis and necrotizing granulomas in the lung and upper airway and by necrotizing
glomerulonephritis
Symptoms Perforation of nasal septum, chronic sinusitis, otitis media, mastoiditis, cough, dyspnea, hemoptysis
Findings C-ANCA is strong marker of disease, CXR may reveal large nodular densities, hematuria and red cell casts
Tx corticosteroids and methotrexate
Alcoholism
Physiologic tolerance and dependence with symptoms of withdrawal (tremor, tachycardia, HTN, malaise, nausea, delirium
tremens) when intake is interrupted
Continued drinking despite medical and social contraindications and life disruptions
Ethanol via Alcohol Dehydrogenase and MEOS Acetaldehyde Acetate Acetyl-CoA Increased FAs Fat
Liver
Alcohol Dehydrogenase
Increases NADH/NAD+ ratio, which in turn:
Basically tricks your body into thinking you have energy
Increases Lactate/pyruvate
Inhibitis gluconeogenesis
Inhibits FA Oxidation
Inhibits Glycerophosphate dehydrogenase, leading to elevated glycerophosphate
Complications of Alcoholism
Alcoholic Cirrhosis
Long term alcohol use leads to micronodular cirrhosis with accompanying symptoms of jaundice,
hypoalbuminemia, coagulation factor deficiencies, and portal hypertension, leading to peripheral edema,
ascites, encephalopathy, and neurologic manifestations
Wernicke-Korsakoff Syndrome
Caused by Vitamin B1 (thiamine) deficiency in alcoholics
Classically may present with triad of psychosis, ophthalmoplegia, and ataxia
May progress to memory loss, confabulation, confusion (Irreversible)
Associated with periventricular hemorrhage/necrosis, especially in mamillary bodies
Tx with IV Vitamin B1
Mallory-Weiss Syndrome
DRUNK DUCKS
Longitudinal lacerations at the gastroesophageal junction caused by excessive vomiting with failure of LES
relaxation that could lead to fatal hematemesis
A Quick Review on Pathology Findings
Argyll-Robertson Pupils
Constricts with accommodation but is not reactive to light, pathognomonic for Tertiary syphilis
Think ARP Argyll-Robertson Pupil, Accommodation Response Present
Amyloidosis
Primary seen with multiple myeloma or Wadenstroms macroglobulinemia
Secondary can cause nephrotic syndrome in kidney, Apple-green birefringement on Congo Red stain
Alzheimers disease associated with Beta-amyloid deposition in the cerebral cortex
Islet cell amyloid deposition characterisitic of DM Type II
Aschoff Body
= Granuloma with Giant cells are also found with Anitschkows cells (activated histiocytes) in Rheumatic Heart
Disease
Think 2 RHussians Rheumatic
Auer bodies
Cytoplasmic inclusions in granulocytes and myeloblasts
Primarily seen in Acute Myelocytic Leukemia -- Ambulance
Casts (in Urine)
RBC glomerular inflammation, ischemia, or malignant HTN, Bladder Cancer
WBC casts inflammation in renal interstitium, tubules and glomeruli, Acute cystitis

156

Hyaline casts often seen in normal urine


Waxy casts Seen in chronic renal failure
ESR (Sed Rate)
Nonspecific test that measures acute-phase reactants
Dramatically increased with infection, malignancy, CT disease, with pregnancy, inflammatory disease, anemia
Decreased with Sickle cell anemia, polycythemia, CHF
Hyperlipidemia signs
Atheromata Plaques in blood vessel walls
Xantheloma Plaques or Nodules composed of lipid-laden histiocytes in the skin, especially the eyelids
Tendinous Xanthoma
Lipid deposit in the tendon, especially Achilles,
Familial Hypercholesterolemia
Corneal arcus Lipid deposit in cornea, nonspecific (arcus senilis)
Psammoma bodies
Laminated, concentric, calcific spherules seen in
Think PSaMMoma
Papillary adenocarcinoma of thyroid, Serous papillary cystadenocarcinoma of ovary,
Meningioma, Malignant Mesothelioma
RBC Forms
Biconcave
Normal
Spherocytes
Hereditary Spherocytosis, Autoimmune hemolysis
Elliptocyte
Hereditary Elliptocytosis
Macro-ovalocyte
Megaloblastic anemia, marrow failure
Helmet cell, Schistocyte
DIC, traumatic hemolysis
Sickle cell
Sickle cell anemia
Teardrop cell
Myeloid metaplasia with myelofibrosis
Acanthocyte
Spiny appearance in abetalipopreteinemia
Target cell
Thalassemia, liver disease, HbC
Poikilocytes
Nonuniform shapes in TTP/HUS, microvascular damage, DIC
Burr cell
TTP/HUS
HLA-B27
Think PAIR Psoriasis, Ankylosing spondylitis, Inflammatory bowel disease, Reiters syndrome
Virschows (sentinel) node
Firm Supraclavicular lymph node, often on left side, easily palpable, also known as jugular gland
Presumptive evidence of malignant visceral neoplasm (usually stomach)
Random Qs All of the following should be HIGHLIGHTED YELLOW
Bacteria surviving in CO2
Capnophiles or Anaerobics -- think???? I thought capnophiles love CO2 they do
Tran has another Q stating Anaerobics need CO2 to grow
Retrovirus causes what in infants????
Pneumonia, T-cell leukemia????
Mushroom Toxins
The recent answer was some Alpha-amanitin Toxin
Ehler-Danlos Syndrome
a group of inherited generalized connective tissue diseases characterized by overelasticity and friability of the skin,
hypermobility of the joints, and fragility of the cutaneous blood vessels and sometimes large arteries, due to deficient
quality or quantity of collagen;
the most common is inherited as an autosomal dominant trait; some recessive cases have hydroxylysine-deficient
collagen due to deficiency of collagen lysyl hydroxylase, and two tentatively ascribed to X-linked inheritance.
Also associated with Berry Aneurysms
What does CD stand for??
Not compact disc, but Cluster of Differentiation
They are surface molecules that are recognized by specific types of antibodies
CD 4 and CD 8--- Ring a bell?
Respiratory Burst
The rapid release of SUPEROXIDE anion when PMNs come in contact with bacteria
Throat Cancer
Most are squamous cell carcinomas Just like Skin and Esophagus
Oral Cancer
Occurs on the side of the tongue
Tracheomalacia
Trachea collapsing
Noma

157

Gangrenous disese of the mouth and cheeks


What is not confused with SCC? Look on page 136
Candida
TB I think its this one???????
Histoplasmosis
Blastomycosis
Arteriovenous Shunts (aka AV Fistulas):
Congenital or acquired
Most common in arms and legs
Most commonly seen in skin (not liver, bone, kidney)

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