MICROBIOLOGY AND PATHOLOGY

Green is pre 2002

Yellow is post 2002
USC messed up the following questions:
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
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:

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

1

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 aulolyse 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 H 2O2

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 (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

Plasma cells:
The predominant cell in synthesis of Abs

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 That would be B-cells.

Responses to viral infections:

Production of lymphokines

Direct cell-mediated cytotoxicity

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 (So, reticuloendothelial
cells + B-cells).
Two classes of helper T cellsTh1 & Th2 cells
Distinguished by the types of cytokines they secrete
Th1: release IL-2 & IFN-gamma
Stimulate proliferation & cytotoxic responses
Th2: release Il-4, IL-5, IL-6, Il-10
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
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

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

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:

5

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

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)
thats why they dont stain.
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
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 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
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

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)
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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 wherein 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

Transfer of genetic material from one bacterial cell to another by viral infection

No cell-to-cell contact required

Least susceptible to DNAase

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

DNAs
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)

Capsule

Gelatinous (polysaccharide) coat often used 1) as an indicator of virulence (Enables them to

stick to other cells) & 2) to determine bacterial pathogenicity

10

**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 (except this is a yeast)
Pilus/Fimbria

Mediates adherence of bacteria to cell surface

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

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

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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 Nacetylmuramic 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-deoxyoctanoate!!!)
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
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

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 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
Sulfur granules

PHB (polyhydroxybutyric acid)

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

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
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Streptococcus Pnuemoniae
Haemophilus influenzae
Neisseria meningitides -BIodome
Klebsiella pneumoniae
Cryptococcus Neoformans Inside the Crypt - yeast

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

Endotoxin
Cell wall of most Gram ONLY
No (Just a breakdown product)
Lipopolysaccharide
Most bacterial endotoxins are
composed of lipoproteinpolysaccharide complexes
Plasmid or bacteriophage
Bacterial chromosome
High (fatal if dose on the order Low (fatal dose on the order of
of 1microg)
hundreds of micrograms)
Various
Fever, shock
Various
Includes TNF and IL-1
Induces high titer antibodies
Poorly antigenic thats why no
called antitoxins
vaccine to this.
Toxoids are used
No toxoids formed and no
vaccine avail.
Destroyed rapidly at 60 degrees Stable at 100 degrees C for 1
C (except Staph enterotoxin)
hour
(Heat Labile)
Tetanus, botulism, diphtheria,
Meningococcemia, sepsis by
anthrax
Gram- rods
High
Detoxified by formalin
Different from exotoxins in
Highly immunogenic
that they activate
complement via the alternate
pathway
Play a role in PD because the
role endotoxins play in
inciting an inflammatory
response

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
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 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
Botulism
Paralysis, blocks neural
(Gram +)
(A,B,E)
transmission
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
Tetanus
Spastic paralysis interferes w/
(Gram +)
(tetanospasmin)
motor neurons
Blocks release of inhibitor
glycine
Causes Lockjaw
Corynebacterium
Diphtheria toxin
Diphtheria
Blocks protein synthesis at
(Gram +)
*a lysogenic phage
level of translation
encodes it
Inactivated E2-F by ADP
ribosylation (similar to
Exotoxin A of Psuedomonas)
Causes
Pharyngitits/Psuedomembrane
Streptococcus Pyogenes Various hemolysis
Lysis of RBCs
(Group A Strep)
Streptolysin O
Rheuamtic fever Causes symptoms of rheumatic
(Gram +)
Streptolysin S
fever
Erythrogenic
Scarlet fever
Causes rash of scarlet fever
Staphylococcus aureus
Enterotoxin Very fast Food poisoning Intestinal inflammation
(Gram +)
food poisoning
Toxic Shock
Toxin is a superantigen that
Syndrome
binds to MHC II and T cell
receptor, inducing IL-1 and IL2 synthesis in toxic shock
syndrome
Bacillus anthracis
Anthrax
One toxin in the Tripartite toxin
(Gram +)
complex is an adenylate
cyclase
Gram Shigella dynsenteriae
Neurotoxin
Bacterial
Hemorrhage, paralysis
(bacillary)
dysentery
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Escherichia coli

Diarrrhea

Vibrio Cholerae

Rice-water
diarrhea

Bordetella pertussis

Whooping
Cough

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 Dont give Abx bc youll kill bact and rls more

exotoxin.
Cannot undo damage, but may slow/stop further physical & mental deterioration body can

heal itself over months

Diphtheria
ABCDEFG

16

ADP ribosylation
Beta-prophage (exotoxin is encoded by)

Club Shaped (Coryne means club shaped)

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

Gram + (purple/blue)

Rods

Clostridium (tetany, botulism, difficile psuedomemb. Colitis, Gas gangrene - perfringes)

SPORE FORMING
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 (optochin resistant)
Viridans Streptococci (i.e. S. mutans) (Endocarditis, caries, Brain
abscess)
Beta
Group A (Bacitracin Sensitive) -- according to carb found in cell wall

17

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)
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

18

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)
Pyocyanin 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 ulcernus, 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

19

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 The Haemophilus influenza POEM here it is.

haEMOPhilus causes Pneumonia, Otitis, Epiglottitis, Meningitis,

Large Capsule
Small gram coccobacillary coccoid rod
Aerosol transmission
Most invasive disease is caused by capsular type b
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 Now officially considered a
carcinogen.
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) Kevin Schaffer never liked to go
proselyting.

20

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
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)
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
Enterobacter
Vibrionaceae Vibrio cholerae

Pasteurellas Haemophilus, Gardnerella, Pasteurella

Gram - and PCN

21

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

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
RICKETTSIAE & CHLAMYDIAE Rickettsia, Coxiella, Chlamydia
Both rickettsia & chlamydia:

Can cause human disease

Posess both DNA & RNA Bacteria have Both.
Growth can be inhibited by antimicrobial drugs
Are inactivated by heat, drying, and chemical agents
NOT multiply in bacterial cells
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:

Small G- aerobic coccobacillary bacteria that are obligate intracellular parasites

Rickettsia and viruses have in Common they are both intracellular parasites

22

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
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.)

23

 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)
Rash that spreads to lips and Buccal mucosa.
Typhus Group Rash is outward spread
Louse-borne typhus (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
**The Only rickettsia that is xmitted via aerosol (dust)
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)
Kaplan says they CAN occur in pairs & short chains

Facultative

Posess both superoxide dismutase & catalase

24

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 Know this.

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

25

Incubation period of 2-4 hours (quick) (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 affecting cell wall

synthesis
Lack catalase although they can live in conditions where O2 is present

1) -hemolytic Streptococcus Know this.

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
a yeast.)
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

26

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
Stapylokinase 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

27

Streptokinase, Streptodornase, deoxyribonuclease

Diseases of S. pyogenes:
Toxigenic
Scarlet Fever
Toxic Shock Syndrome
Suppurative
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
28

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 Know this.

Smooth surface caries

First stable organism to colonize oral cavity and remains in significant numbers???
LOOK-UP 2002 Q05
In the presence of sucrose, produces deposits of a gummy polysaccharide called glucan
Produces Glycosyltransferase from Sucrose
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

29

 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
30

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
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. Know

this
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 ay 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)

31

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
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 (or their toxins) 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

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

32

 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

Enzyme
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
Lecithinase
Destroys RBC and other tissue
Clostridium
cells
Collagenase
Breaks down collagen (CT fiber) Clostridium, Bacteroides,
Actinobacillus, AA, and Bacillus
(Think PD bugs)
Phospholipase
Lyses RBC
Staph. Aureus
Fibrinolysin, staphlokinase,
Dissolve blood clots
Staph and Strep
streptokinase
(Plasminogen Plasmin)
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
33

 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-containinng culture media

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:
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:
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

34

**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) Know this.
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)

Serotypes

A,B,C

Africa, Blindness, Chronic infection

35

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

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.

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? Look up.

Inclusion conjunctivitis

Ocular trachoma

LGV

Lymphadenopathy ??

Pruritus ??

Chlamydia trachomatis. Which is false?

Most women are Sx-atic, More men are Sx-atic than women, causes keratoconjunctivitis

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
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 POEM (hemophilus) 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??

36

Often occurs together w/ chlamydia and syphilis

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
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

37

Maculopapular rash
Rash appears on palms of hands & soles of feet just like in Rocky Mountain spotted
fever
Condyloma latum/lata
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
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)

38

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 (military 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
Brucella
Bordetella
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

39

Shigella
No lactose ferm, nonmobile,
Fever
Bloody
Campylobacter jejuniComma 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 activates 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
Enterobacter
Zoonotic Bacteria
Think Bugs From Your Pets

Lyme Disease
Tick bites (living on deer and
Borrelia burgdorferi
mice)
Brucellosis Fever
Dairy products, contact with
Brucella
animals
Tularemia
Tick bites; rabbits, deer
Francisella tularensis
Plaques
Flea bite; rodents;
Yersinia pestis
especially prairie dogs
Cellulitis
Cat, Dog bites
Pasteurella multocida
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
40

Capsid or Protein coat

Composed of polypeptide units called capsomers
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)

Only naked DNA viruses are Papovaviruses, Adenoviruses, and Parvoviruses (cause gotta be

naked for PAP smear).

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)

41

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

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 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 only
genetically similar bacteria within a species will be lysed by the same phage.
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

42

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)
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)

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

43

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 nonmutaed 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:
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

44

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

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

45

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

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
Surface spikes include hemagglutinin, neuraminidase, or fusion proteins
Disease resembles common cold in adults

46

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 Look up
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 (sarampion)
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

47

negri body 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)
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
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
Posterior auricular lymphadenopathy is characteristic
Milder, shorter disease than measles
A teratogen 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

48

Symptoms: fever, black vomit, jaundice (yellow)

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

California encephalitis virus

Hantavirus
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

Three groups:

49

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 complex
Viral
Herpes simplex, Varicella zoster, CMV, Progressive mulitfocal leukoencephalopathy
(PML), Hairy Leukoplakia
NOT Adenovirus (conjunctivitis)
Fungal
Candidiasis, Cryptococcus (meningitis), Histoplasmosis, Pneumocystic carinii
pneumonia (PCP)

50

 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

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
51

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
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

52

Replicate in cytoplasm
Produce minor respiratory tract infections & GI disease

Rotavirus

Segmented (BOAR)
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
nd
All are large (120200 nm diameter) 2 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
Produces a latent virus (ECHO, measles, smallpox, coxsackie all do NOT)
Latency in the 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
Associated with oral and ocular lesions
Pt may have acute symptoms
Affects the lips, face, skin, & oral mucosa (above the waist)

53

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
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
54

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 Look up
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

55

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 can also be cause by CMV
EBV-caused IM is responsible for approximately 85% of IM cases
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
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
th
6 disease = roseola infection

Virus
HSV-1
HSV-2

Usual site of latency

Cranial sensory ganglion
(CN V)
Lumbar or sacral sensory

Recurrent infection
Herpes labialis, encephalitis,
keratitis
Herpes genitalis

Varicella
Cranial/thoracic sensory
zoster
ganglia
Epstein-Barr B lymphocytes

Zoster

CMV

None

Uncertain

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

56

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

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)
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

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)

57

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

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

No

Infection mononucleuosis
Chickenpox, shingles
Pharyngitis, pneumonia

No
No
No

Acyclovir in
immunodeficient pt
None
None
None

Portal of Entry
Respiratory tract

Virus
Adenovirus
Cytomegalovirus
Epstein barr
HSV type 1
Influenza
Measles
Mumps
Respiratory synctial

Gastrointestinal

Rhinovirus
Rubella virus
Varicella zoster
Hep A
Polio

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
58

Skin
Genital

Blood

Rota
Rabies
HPV
HPV
Hep B
HIV
HSV type II
Hep B
Hep C
HIV
Cytomegalovirus

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
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
59

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

Heat = Yeast (tissues)
Cold = Mold/Mycelial (soil)
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

Most fungal spores are completely killed when heated at 80 for 30 min (unlike bacterial spores)

Examples of asexual spores (conidia)

Arthrospores: formed by fragementation of the ends of hyphae; are the mode of transmission of

Coccidioides immitis
Chlamydospores: thick walled & quite resistant; characteristic of 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

60

 Example of sexual spores:

Zygospores: single large spores w/ thick walls

Ascospores: formed in sacs which are called an ascus

Basidiospores: formed externally on the tip of a pedestal called a basidium

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)

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,
Lesions, combs, toilet articles,
Trichophyton
headrests
Tinea corporis (ringworm of body) Epidermophyton,
Lesions, floors, shower stals,
Microsporum,
clothing
Trichophyton
Tinea pedis (ringworm of feet
Epidermophyton,
Lesions, floors, shoes & socks,
(athletes foot)
Trichophyton
shower stalls
Tinea unguium (ringworm of
Trichophyton
Lesions
nails)
Tinea cruris (ringworm of groin
Trichophyton,
Lesions, athletic supports
[jock itch])
Epidermophyton
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

61

 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

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)
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 (squamous cell carcinoma)

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

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 & itraconazole are also used to treat various fungal infections

BLASTOMYCOSIS: (aka Gilchrists disease or North American blastomycosis)

62

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

Fungus is endemic in North & Central America

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
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

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
Pseudomembrane (false MB) = desquamative and necrotic epithelial cells and matted and
tangled mycelia
Tx = Ketoconazole or Fluconazole (not Nystatin)

63

 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 enCrypted message with India ink

64

 ASPERGILLUS:
Species exist only as molds and are not dimorphic

Septate hyphae that branch at V-shaped 45 degree angle

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)
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)

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

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
65

 Tx when CD4 drop below 200 cells/mL in HIV pts

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.: giordio, 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

66

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 milde 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.

LEISHMANIA:
Transmitted by the sandfly

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)

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
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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

***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!
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 erythromycin
clindamycin would have been a better choice??? except for
pseudomembranous colitis only use when have to.
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 bacteriocidal 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:

69

Prescribed primarily in the treatment of severe penicillinase-producing staphylococcal

infections
Given IV

Not frequently used due to:

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+ & G

There 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)

70

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

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

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

71

ANTIVIRALS
For herpesviruses:
Acyclovir

Vidarabine

Ganciclovir

Foscarnet

For respiratory viral infections:

Amantadine & Rimantadine Influenza viruses.

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

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

Clotrimazole
Nystatin

Summary of Some Antifungal Agents

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

Topical agents
(cream)
Amphotericin B

Cutaneous & mucocutaneous

Topical agent

Alters cell membrane

Form
Troche
Oral
suspension
Cream
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Ketoconazole
Nystatin
Systemic agents
Fluconazole
Ketoconazole
Amphotericin

Cand
Cutaneous and muco Cand
Cutaneous and muco Cand
Oral, esophageal,
oropharyngeal Cand
Oral, esophageal,
oropharyngeal Cand
Systemic candidiasis

Alters cell membrane

Alters cell membrane

Cream
Ointment

Alters cell membrane

Tablets

Alters cell membrane

Tablets

Alters cell membrane

IV injection

VACCINES
Toxoids
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, 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)
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

Salmonella typhi vaccine fever

Typhoid Fever
Asymptomatic carriers are a major hazard Typhoid Mary
Vibrio cholerae vaccine cholera

Live attenuated bacterial vaccines:

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

73

 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)

SOME CURRENT VIRAL VACCINES

Disease
Type of Vaccine
Smallpox
Attenuated live virus
Yellow fever (viral hepatitis)
Attenuated live virus
Hepatitis B
Purified HBsAg: recombinants HBsAG
Measles
Attenuated live virus
Mumps
Attenuated live virus
Rubella
Attenuated live virus
Polio
Attenuated live virus (Sabin)oral
Polio
Inactivated virus (Salk vaccine)injection
Influenza
Inactivated virus
Rabies
Inactivated virus
Varicella (chickenpox)
Attenuated live virus
Hepatitis A
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
74

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:

DPT shot - 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
75

 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
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 crosscontamination 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 bacterio cidal
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
76

 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:
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
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
77

 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:
Evaproates 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
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 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
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

Level

Risk

Objects

Critical

Heat Sterilization

Very high

Touch bone or penetrate tissue;

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

Semi-Critical

Sterilization, High- Moderate

level disinfection

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

No direct patient contact, no

blood units, knobs, light floors,
walls, counters

Minimal

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

79

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

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

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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)

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

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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
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

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

82

Their primary value appears to be their ability to remove microorganisms mechanically from the
skin surface
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

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 - These both mark bacteria for phagocytosis.

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

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:

83

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

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:

84

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

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
via IL-2 Activates Cytotoxic T cell (CD8)
Humoral Immunity

(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

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:

85

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 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

Opsonization may occur as a component of the humoral immune system in response to

virulent Strep pneumoniae (Because you have to opsonize the S. pneumoniaes

antiphagocytic capsule before you can kill it)
If B cells were eliminated, how would you achieve humoral immunity???

Injections of gamma (G) globulin (Ig)???

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)

86

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

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 preformed 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
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:

87

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 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:
Small molecules that act as an Ab epitope, but will not induce immune responses since they

are not recognized as T-cell 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

A collection of polymorphic genes encoding for proteins that regulate immune responses

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

HLA Class I = HLA-A, HLA-B, HLA-C

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)

88

MHC I Ag loading occurs in rER (viral antigens)

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

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)

th
4 With 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 (as well as cytotoxic T cells)
89

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, like suppress viral replication)
IL-6, 7, 8, 10, 12: see Kaplan, p. 101 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
Fc (Cell)

The Stem of the Y

90

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

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.)

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

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
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:

91

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
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

92

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

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 immuntiy & inflammation

Participates in lysis of foreign cells, inflammation, & phagocytosis

Acts in a cascade w/ one protein activating another

93

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 forgein 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
2+
is required for activation
C1 composed of three proteins (C1q, C1r, & C1s); Ca
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:

C2a, C4a = weak anaphylatoxins

94

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
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

95

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

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)

96

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

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)

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
st
1 symptoms anxiety, weakness, sweating, SOB, & generalized urticaria

97

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
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 (pollen, 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

98

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) C in ACID.
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 cell-mediated 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
TYPE III: (Immune complex, Serum Sickess, Lupus, and Arthus Rxn)
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
99

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:

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 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
Serum Sickness is a type of an systemic Arthus rxn, so says an old Q, but Kaplan doesnt
mention it
TYPE IV: (Delayed, cell-mediated)
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

st
nd
nd
When a 1 rejected allograft is followed by a 2 allograft from the same donorthe 2
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

100

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

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

Blood Group
O (universal donor)
A
B
AB (universal recipient)

Classification of Hypersensitivity Reactions

Immunologic Mechanism
Example
IgE antibody mediated mast cell
Hay fever, asthma, anaphylaxis,
activation & degranulation
atopic dermatitis, eczema
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
Ag/s (agglutinogens) on
erythrocytes
*none*
A
B
A & B (alloantigens both A &
B)

Autoantibodies
Anti-nuclear antibodies (ANA)
Anti-dsDNA, anti-Smith
Anti-histone
Anti-IgG
Anti-neutrophil
Anti-centromere
Anti-Scl-70

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)
101

Anti-mitochondria
Anti-gliadin
Anti-basement membrane
Anti-epithelial cell
Anti-microsomal

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, E-selectin, 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 of glycopeptides

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

102

 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):

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, Hot T-Bone stEAk

IL-1:
A macrophage-derived factor (mmmm)

Stimulates activites of T-cells, B-cells, & macrophages

Stimulates IL-2 secretion
Pyrogenic (HOT)

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
103

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. 101 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 site

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

104

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) rls by platelets.

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

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

105

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)

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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
st
The 1 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
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

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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:
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

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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
Abscess:
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

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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):
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

Occur in the dermis & adjacent subcutaneous tissue, usually after trauma, surgery, a burn, or

severe cutaneous disease such as cystic acne, and is more common in blacks
Tumor:
Growth of tissue that forms an abnormal mass

Caused by abnormal regulation of cell division

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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

When larger areas of tissues are dead, the tissue is called gangrene

Types
Coagulation necrosis

Causes
Ischemia (loss of blood supply)

Liquefaction necrosis (infarct

to brain)
Caseous necrosis (Caseation)

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

Gangrenous necrosis
Fibrinoid necrosis
Fat necrosis

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
Arterial walls (RA,
Scleroderma, RF)
Adipose tissue, pancreas

Basic Types of Necrosis

Two types of necrosis are recognised 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
Karyopyknosis = pyknosis shrinkage of the cell nuclei & condensation of the chromatin
Another Q reads: condensation & shrinking of the cell nucleus w/ chromatin clumping
Karyorrhexis fragmentation of the cell nucleus & chromatin
Karyorrhexis follows karyopyknosis during the process of apoptosis
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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

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)

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

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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)

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 these should not

normally be in the mouth)

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

Gingival sulcus (Periodontal Pocket):

Principal oral site for growth of Spirochetes, Fusobacteria, & other G- anaerobes

Endotoxin (LPS) accumulates in the gingival crevice in the absence of gingival hygiene

Inhabitants

Normally G- anaerobic Rods and Fusobacteria

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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 contains gram POSitive bugs

Most of the the bugs in the dental operatory come from the pts mouth

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)

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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 aciodogenic

Bacteria that initiate caries must have ability to produce extracellular insoluble glucans

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):

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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 +
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

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

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

In pts with chronic PD, when the T cells react with certain plaque bacterial antigens, they

produce:
IL-2, TNF-alpha, IFN-gamma (looks like here, they want you to know what cytokines are)
NOT Immunoglobulin
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)
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

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 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
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

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 spreading 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

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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

BOTH 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
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

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

Invovles 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

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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

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
Heatburn most common sign, also accompanied 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 that is lined 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):
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

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Atrophic glossitis, esophageal webs, dysphagia

Associated w/ iron deficiency anemia

Mallory-Weiss syndrome:
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 (Mallory (mallard))

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

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??

NOT associated with Smoking????

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)

Think B for Bug

Caused by H. pylori infections

Both increase risk of gastric carcinoma

Not caused by Cigarette Smoke (why should it be affected by cigarette smokevery little

smoke gets into stomach.)

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, 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

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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)

DO NOT become malignant.

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 secretion or decrease in mucosal protection. (gastric ulcers tend

to have less acid secretion than normal).

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

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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 (Same thing as bed

sores??)
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

Esophagus is SCC - esoph has no glands so SCC. (Except w/Barrets where epithel has

changed to columnar just like stomach, so now, just like stomach Adenocarcinoma)
LUNG is Adenocarcinoma

Early aggressive local spread and node/liver metastasis

It is associated w/ dietary nitrosamines, achlorhydra, chronic gastritis

Is NOT etiologically associated w/ smoking smoke doesnt get into stomach.

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 supraclavicular 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. Atresia = absence

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

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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
Vitam
Physiologic function
Result of deficiency
in
A
Helps maintain normal body growth & health
Night blindness, skin lesions,
of specialized tissues (esp. retina); production xerophthalmia (keratinization &
of rhodopsin (photopigment)
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

Deficiency Leads To

Characteristic of
Deficiency
Vitamin B1 Wet beriberi, dry beriberi
High cardiac output;
(thiamine)
peripheral neuropathy
Vitamin B2 Cheilosis; glossitis
Skin fissures at angle of
(riboflavin)
mouth; inflammation of
tongue
Vitamin B3 Pellagra
Dementia, dermatitis, &
(niacin)
diarrhea
Vitamin B6 Cheilosis; glossitis, anemia Skin fissures at angles of
(pyridoxine
mouth; inflammation of
)
tongue; # of RBCs is
below normal
Vitamin
Megaloblastic anemia (i.e., Anemia in which there is a
B12
pernicious anemia)
predominant # of
(cobalamin Neurologic dysfunction
megaloblasts & few
)
normoblasts
Folic acid
Megaloblastic anemia
Anemia w/ a predominant
Neuroligic dysfunction is
# of megaloblasts
not a feature
(abnormally large

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

Anemia, pins and needles

sensation
Anemia

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nucleated RBCs)
Swollen, bleeding gums,
muscle, joint, & bone
pain, abnormal bleeding

Vitamin C
Scurvy, defective formation
Weakness, bleeding gums
(ascorbic
of mesenchymal tissue &
acid)
osteoid matrix; defective
Essential
wound healing
in bone
Impaired collagen
formation 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

Typical symptoms steatorrhea, diarrhea, weight loss, & a sore tongue from Vit B deficiency

Disaccharidase deficiency:

Most common is lactase deficiency

Whipples disease:

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 lymphangiectasia:

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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 you 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:

Inflammation of diverticula classically causing lower left quadrant pain (Sigmoid area)

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

Inflammatory bowel diseases

Crohns disease & Ulcerative colitis

Crohns Disease
Ulcerative colitis
Possible etiology
Infectious
Autoimmune
Location
May involve any portion of the GI tract,
Colitis = colon inflammation.
usually the terminal ileum, small
Continuous lesion w/ rectal
intestines, and colon. Skip lesions, rectal
involvement
sparing
Gross morphology
Transmural inflammation. Cobblestone
Mucosal inflammation. Friable
mucosa, creeping fat, bowel wall
mucosal pseudopolyps w/ freely
thickening (string sign on x ray) linear
hanging mesentery
ulcers, fissures
Microscopic
Noncaseating granulomas
Crypt abscesses and ulcers
morphology
Complications
Strictures, fistulas, perianal disease,
Severe stenosis, toxic
malabsorptionnutritional depletion
megacolon, colorectal
carcinoma

126

Extraintestinal
Migratory polyarthritis, erythema nodosum Pyoderma gangrenosum,
manifestation
sclerosing cholangitis
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 scratching his

anal fissures.
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

127

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

Polyps are hamartomas not true neoplasms

They do not increase risk of cancer in intestinal tract

Pts are at increased risk for cancer of pancreas, breast, lung, ovary, & uterus (Wow,
thats tricky!! Intestinal related dsz that d.n. increase intestinal CA risk, but does
increase it for all these other things).
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)

Colon Cancer:
Adenocarcinoma is the most common type of colon cancer

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). Again, smoke

d.n. get to these areas.

(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

128

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)

Meckels diverticulitis (Duodenum)

Pelvic Inflammatory Disease

Gastroenteritis with mesenteric adenitis

NOT Duodenal Peptic Ulcer (heart burn) relieved pain with eating
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

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

Associated w/ alcoholism & biliary disease

Manifestations/consequences

Enzymatic hemorrhagic fat necrosis w/ calcium soap formation & resultant hypocalcemia

129

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)

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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

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
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
Parenchymal Hematoma

Caused by HTN, amyloid angiopathy, DM, and Tumor

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 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
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 think 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 (elderly)

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

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Most common in adults Neisseria meningitidis & S. pneumoniae

Most common in the elderly S. pneumoniae

NOTE all 3 of the most common have Capules

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
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

The #1 cause of congenital malformations in the U.S.

NERVOUS SYSTEM
Degenerative disease:
Cerebral cortex:

Alzheimers disease:

Most common cause of dementia in the elderly

nd
Multi-infarct dementia is the 2 most common cause

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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:

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

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

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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 proteinpapilledema

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

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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
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 Ab/s that attack ACh receptors that lie on the muscle side of the

neuromuscular 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

Portal hypertension:
High BP in the portal vein

Portal vein receives blood drained from entire intestines, spleen, pancreas, & gallbladder

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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 (deposition of pigments in gray matter
permanent damage to certain areas of the brain of newborns)
This can cause a characteristic form of crippling athetoid cerebral palsy
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

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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

Hemolysis of any cause usually results in unconjugated bilirubin predomination

NOT Causes:

Aplastic anemia Dont have the cells

Fibrosis of the liver

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:
These things can be Attributed to hepatic failure:

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

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

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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

Esophageal varices are most common source of massive hematemesis in alcoholics

Hematemesis Vomiting blood

Hemoptysis (coughing up blood) 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)

Other inborn metabolism errors: galactosemia, glycogen storage disease, or alpha 1-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)

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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

High morbidity, low mortality

Highly contagious infectious disease involving liver

Usually transmitted by the fecal-oral route

Also transmitted parenterally or sexually

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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

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Some develop chronic persistent hepatitis or chronic active hepatitis

Markers:

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)

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

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Most common reason for liver transplantation in the U.S.

Extrahepatic manifestations: rash, arthritis, glomerulonephris, 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

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

143

(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

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Most likely the result from Hyperparathyroidism

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
Painless hematuria as a common early clinical sign in acute diffuse glomerulonephritis, carcinoma of
the bladder, focal glomerulonephritis, and renal cell carcinoma so, if you see urinary disease, think
hematuria.

BUT NOT Nephrolithiasis (because that mofo just plain hurts)

Hydronephrosis:
Abnormal dilation of the renal pelvis & calyces

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:
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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 refux), 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

nd
Staph saprophyticus is 2 common cause in young ambulatory women
Think SSEEK 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
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

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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:

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

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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:

Often due to HTN and DM

GFR decreased by 25% and leads to uremia. It is most likely casued 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

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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

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

Benign Essential HTN:

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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 Nephroscerosis 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

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 Glyogneolysis
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

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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

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

Collapse of alveoli

May be secondary to:

Blockage of bronchus to aspirated foreign body

Blockage fo bronchus by mucous

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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

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

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

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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

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
S. pneumoniae
Intra-alveolar exudate consolidation, may
(Pneumococcus)
involve entire lung
Its got a big capsule, to go
everywhere
Bronchopneumonia
S. aureus, H. influenza,
Acute inflammatory infiltrates from
Klebsiella, S. Pyogenes
bronchioles into adjacent alveoli; patchy
distribution involving > 1 lobes
Interstitial (atypical)
Viruses (RSV, adenoviruses), Diffuse patchy inflammation localized to
pneumonia
M. pneumoniae, Legionella,
interstitial areas at alveolar walls;
Chlamydia psittaci (Birds)
distribution involving primary lobes

Inflammatory exudates in pneumonia

Definitely present in lobar pneumonia, lobular 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:

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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
Bronchial asthma
Dyspnea and wheezing expiration

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Chronic bronchitis
Emphysema (pulmonary
emphysema)
Bronchiecstasis

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

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, hypoxia, & 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

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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

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

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:

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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

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 intensly 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:

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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

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:

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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

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.
Surfactant = dipalmitoyl phosphatidylcholine

Tx with maternal steroids before birth, artificial surfactant for infant

Kartageners syndrome:
Think Cant move you 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

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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 no cytoplasm
Associated w/ ectopic hormone production (ADH, ACTH)
May lead to Lambert Eaton syndrome (muscle weakness due to Ag against motor
nerve cant rls ACh)
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%

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)
3 neuron oclusosympathetic pathway above projects from the hypothalamus to

intermediolateral column of the spinal cord, then to the superior cervical (sympathetic

160

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
HEART DISORDERS

CONGENITAL HEART DEFECTS:

Infective endocardititis

The following are predisposers:

Tetraology of Fallot
Congenital aortic stenosis
Patent ductus arteriosus
Ventricular septal defect
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:

1) Pulmonary stenosis
2) Right ventricular hypertrophy
3) Overriding aorta (overrides the ventricular septal defect)
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:

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:

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:
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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

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:

162

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 due 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 that would be a heart attack.
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

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Pain from an MI is NOT relieved by vasodilators such as nitroglycerin only angina is

relieved by this.
Thrombolytic agents such as streptokinase often limit the size of infarction
Myocardial necrosis usually begins 20-30 min after coronary artery occlusion
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 27 days post-MI
Creatine Kinase (CK), or CK-MB test test of choice in 1st 24 hours post- MI
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 infact), ST depression (subendocardial infarct), & Q waves
(transmural infarct)
Complications of myocardial infarctions:

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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
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

165

An area of focal interstitial myocardial inflammation

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

Paroxysmal nocturnal dyspnea (pt wakes up up grasping for air)

Other signs:

Peripheral edema (ankle edema), cyanosis, high venous pressure, passive congestion of the

liver, and orthopnea (sitting or standing in order to breath comfortably)

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

166

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
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

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)

Renal hypoxia
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

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

167

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 alphahemolytic streptococcus
(S. sanguis, which is a Viridans Streptococcus)
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

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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

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
Pulseless Disease

169

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
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

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
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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
Stoke following MI is caused by arterial thrombi (not venous)

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

171

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)

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

More info found elsewhere in file

Air Pulmonary thromboembolus = pulmonary embolus

Very common occurrence

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
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

Atheroslcerotic 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:

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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)
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

173

This means Amox reacts with IgE and activates cytotoxic T cells that release
lymphokines
BLOOD DISORDERS

Purpura spots:
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 DISRODERS:
Laboratory values:

PT = prothrombin time

Measures Factors I, II, V, VII, X

PTT = partial thromboplastin time

Measures Factor XII, prekallikren, 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
174

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
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
Prothrobmin 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

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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 (bc thrombin and
thromboplastin and all the factors they measure (1,2,5,7,10) are unaffected)
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, epistaxis, hematomas, & hemarthroses

Classifications of hemophilia:

A classical 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)
Normal bleeding time

176

 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
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 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 kidney thinks blood volume is low, so
tries to compensate and you get 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 &

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
177

vomiting; drowsiness, giddiness;

anxiety; mental impairment
Renal
Polyuria; nocturin; diminished ability to
concentrate urine; protein & RBCs in
urine
Ocular
Retinal hemorrhage & exudates

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

Increased 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:

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 (shorthness of breath), 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
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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
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 Erythrblastosis fetalis, the mother has very high levels of serum
complement and anti-Rh IgE

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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
th
Globin portion of Hb S is abnormal valine is substituted for glutamic acid in the 6
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 [O 2], they form fibrous precipitates w/ the
erythrocytes
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
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:

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Due to gene deletion

No compensatory increase of any other chain. Some forms result in hydrops fetalis and
intrauterine fetal death
Beta Thalassemias:
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)
Hemoglobinopathies (eg., sickle cell disease)
Autoimmune hemolytic anemia

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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.

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

182

 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 O 2 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)

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

183

 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

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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

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:
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

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
185

 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

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:
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

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The Abscess deprives 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 tinssue & 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 due 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

Drop in testosterone in men
Corticosteroids

Prolonged immobilization

Chronic malnutrition

Advanced age

NOT hypervitaminosis D
Women, especially > 50 get it more often than men

Can result from prolonged corticosteroid administration

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

187

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

trauma
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

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

Hereditary disorder (aka brittle bones)

Rare but demonstrates the effect of inadequate osteoid production

Defect in synthesis of type I collagen

Chris Kaman

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)

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:

Monostatic = 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

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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:
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

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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
nd
Freibergs disease 2 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

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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)

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

191

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

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
192

Atrophy:
Decrease in organ or tissue size resulting from a pathological decrease in mass of preexisting

cells
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
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
193

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:

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

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

194

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

195

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
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

st
Lymphatic tumor 1 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
Malignant
Well-differentiated (neoplastic cells
Less well differentiated (anaplastic: loss of
resemble comparable normal cells
structural difference)
meaning blasts are still making it to cytes, **Can be either (Can either be well or poorly
196

etc.)
Slow growth
Encapsulated; well circumscribed
Localized
Movable

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

Metastatic bone tumors are far more common than 1 bone tumors

MOST common organ receiving metastasis Adrenal Glands (Rich blood supply)
Usually first in medulla and then rest of gland

MOST common organ sending metastasis LUNG>Breast>Stomach

Paraneoplastic effects of tumors
197

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

Effects of tumors
ACTH or ACTH-like peptide

Effect
Cushings syndrome

ADH or ANP

SIADH

PTH-related peptide, TGFalpha, 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

Hemangioma
Leiomyoma (uterus)
Rhabdomyoma
Osteoma
Lipoma
Mature teratoma

Malignant
Adenocarcinoma, papillary
carcinoma
Leukemia, lymphoma
Angiosarcoma
Leiomyosarcoma
Rhabdomyosarcoma
Osteosarcoma
Liposarcoma
Immature teratoma

Predisposers of cancer:
Abestosis - mesothelioma

Hepatitis C hepatocellular carcinoma

Gardners syndrome multiple polyps 100% malignant change

Ulcerative colitis colonic adenocarcinoma.

NOT Anthracosis Coal miners (black lung) doesnt CA

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

198

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
Autoimmune disease (e.g., Hashimotos
thyroiditis, myasthenia gravis)
Acanthosis nigricans (hyperpigmentation and
epidermal thickening)
Dysplastic nevus

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 (most
common CA of esophagus more so than
adenocarcinoma)
Hepatocellular carcinoma
Colonic adenocarcinoma
Secondary osteosarcoma and fibrosarcoma
Malignant lymphomas
Aggressive malignant lymphomas (non-Hodgkins
& Kaposis)
Benign and malignant thymomas
Visceral malignancy (stomach, lung, breast,
uterus)
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
Carcinoembryoonic antigen (CEA)
Carcinoembryonic antigen. Very nonspecific but
produced by 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 extending outside prostate capsule
(Stage C or D)
Bombesin
Neuroblastoma, lung and gastric cancer
TRAP
Tartate-resistant acid phosphatase. Hairy cell
199

leukemiaa B cell neoplasm

Oncogenic Virus
HTLV-1
HBV, HCV
EBV
HPV
HHV-8 (Kaposis sarcoma associated herpes
virus)
Chemical Carcinogens
Aflatoxins, vinyl chloride
Nitrosamines
Asbestos
Arsenic
CCl4
Naphthalene (aniline dyes)

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
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 think squamous cells 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

Adenocarcinoma a carcinoma of glandular epithelium

Metastatic Carcinoma

Most common malignancy found in bone (NOT osteosarcoma, giant cell tumor,

chondrosarcoma, multiple myeloma) - Most bone CA came from somewhere else.

Sarcoma:
Malignant tumor of mesenchymal origin. Think liposarcoma.

Usually metastasize via blood

EXs: osteosarcoma (bone), leiomyosarcoma (smooth muscle), & liposarcoma (adipose tissue)

Cancer Facts/Figures
Men

Most common =
Lung > Colorectal > Prostate

Highest Mortality =
Lung > Colorectal > Prostate

Women

200

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

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
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

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

NOT 5 things

STOMACH or COLON CANCER, CHRONIC GASTRITIS (Acute?), or Acute

Respiratory Distress Syndrome - smoking has nothing to do with GI tract beyond the
esophagus.
Carcinogens

201

Most potent is Benzopyrene

Benzopyrene is a very potent carcinogen found in cigarette smoke

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

Factors increasing risk: from Wikipedia

Age (40+)

Nulliparity

Family Hx

st
Strongest association family Hx, specifically breast cancer in 1 -degree relatives
(mother, sister, daughter)
Early menarche

Late menopause

Fibrocystic disease

Previous Hx of breast cancer

Obesity (but NOT Estrogen deficiency or silicone implants)

Younai says silicone implants for sure increased risk!!

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

Peau dorange (swollen pitted skin surface) along w/

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)

Fibrocystic disease:
Most common cause of a clinically palpable breast mass in women (28-44 y.o.)

Signs & symptoms lumpiness throughout both breasts

202

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)
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
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

Symptoms usually only occur in advanced states

Sigmoid colon most common site (NOT TRANSVERSE)

Sigmoidoscopy can disclose the majority of the tumors

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

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

203

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

204

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
Risk factor is Hyperestrogenism

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:
Benign neoplasms that appear as small, red-to-brown nodules that result from fibroblast

accumumlation
Acrochordon (aka skin tag):
Extremmly 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 (wart) 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

205

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)
206

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 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)
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

207

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
st
The 1 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
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
st
1 indication swollen lymph glands (lymphadenopathy), enlarged tonsils & adenoids; painless,
rubbery nodes in cervical supraclavicular areas
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
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

Non-Hodgkins
Non-Hodgkins associated w/ HIV and
immunosuppression
Multiple, peripheral nodes;extranodal involvement
common; noncontinguous spread
Majority involve B cells (except lymphoblastic T
cell origin)
No hypergammaglobulinemia (cf., multiple
myeloma, where excess B cells are in resting stage)
Fewer constitutional symptoms

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Good prognosis = increase lymphocytes, low

number of Reed Sternberg cells

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 cells arising in bone marrow (a monoclonal plasma cell w/ fried-egg

appearance) or older aged adults

Disease associated with proliferation of plasma cells showing punched out 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 (rouleaux formation)

SKIN CANCER:
General info:
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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)

Px 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

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

Also associated w/ chemical carcinogens (e.g., arsenic) & radiation

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

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

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Malignant epithelial cells have # of laminin receptors

Laminin (a glycoprotein) = major component of basement MBs???????

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:

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

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 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, increasd 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

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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 malignant tumors

Metastatic bone tumors

Have spread to bone from original site elsewhere in the body

Cancers most likely spread to bone breast, lung, prostate, kidney, & thyroid cancers

In children, the most common types of bone tumors are Osteogenic & Ewingss sarcomas

Most common malignancy in bone is metastatic carcinoma

Bone tumors of osseous origin:

Osteogenic sarcoma: (aka Osteosarcoma)

Most common

Usually in males ages 10-30

Occurs most often in femur, but also tibia & humerus; occasionally, in fibula, ileum, vertebra,

or Mn
Tumor arises from bone-forming osteoblasts and bone-digesting osteoclast

Most often in metaphysis 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

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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 (Marks
Dad).
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:

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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Rhabdomyom 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:
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

215

 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

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 parenchymatous 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

216

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

217

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 therapy and is associated w/ Down

syndrome
biologically distinct

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

218

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, hepatospenomegaly 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
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

219

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

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

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

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

220

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)

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

> 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

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 - bc aldosterone

cant do its job.

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

221

 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

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, and osteoporosis
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

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

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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
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

Risk factors: female > 60 y.o.

Never seen in children

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

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

223

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 foramtion 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

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
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

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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

225

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
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 NOT from ketoacidosis

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

Dx:

Fasting serum glucose, glucose tolerance, HbA1c

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

Type 1 vs. Type 2 Diabetes Mellitus
Characteristic
Type 1 Diabetes
Type 2 Diabetes
Level of insulin secretion
None or almost none
May be normal or exceed normal
Typical age of onset
Childhood <30
Adulthood >40
Percentage of diabetics
1020%
8090%
Basic defect
Destruction of B-cells
Reduced sensitivity of insulins
target cells
Associated w/ obesisty
No
Usually
Speed of development of
Rapid
Slow
symptoms
Development of ketosis
Common if untreated
Rare
Treatment
Insulin injections, dietary
Dietary control & weight
management
reduction; occasionally oral
hypoglycemic drugs

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Concordance in identical
twins
Genetic predisposition
Association with HLA
system
Beta cell numbers in islets
Classic symptoms of 3
Polys

50%

100%

Weak, polygenic
Yes (HLA DR 3 and 4)

Strong, polygenic
No

Reduced
Common

Variable
Sometimes

Diabetic Ketoacidosis
One of the most complications of DM Type I

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)

If untreated, may become chronic & lead to scarring

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:
227

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)
228

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

rd
th
The causative defects occur in areas known as the 3 & 4 pharyngeal pouches
These pouches develop into the thymus & parathyroid glands (which may be missing or
underdeveloped)
th
Development abnormalities may also occur in the 4 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

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:

229

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

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:

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

230

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 ~ of pts w/ SLE rash worsenes w/

sunlight
A more difuse rash may appear on other body parts exposed to sunlight

False positives on syphilis tests (RPR/VDRL)

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

231

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:

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:

232

Composed of tissues taken from an individual of the same species who is genetically identical
(e.g., identical twins)
Allograft:

Tissue taken from a genetically unrelated individual of the same species

Aka allogenic graft, homologous graft, or homoplastic graft

Xenograft:

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.
233

Example: Autosomal dominant trait showing 50% penetance, 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 expression of BOTH alleles in a gene pair

Pink flower instead of white and red

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

Rubella
st
Greatest incidence of rubella associated w/ cardiac anomalies occurs during 1
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

Elevated LDL owing to defective or absent LDL receptors.

Heterozygotes have cholesterol = 300 mg/dL

Homozygotes, very rare, have cholesterol of 700 mg/dL

Severe atherosclerotic disease early in life, and tendon xanthomas (classically in the Achilles

tendon), 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

234

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

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 caf au lait spots, neural tumors, Lisch nodules (pigmented iris hamartomas)

Also marked by skeletal disorders (dg. Scoliosis) and increased tumor susceptibility

235

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):

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Composed of monocytes & macrophages located in reticular conntect 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
Alvoelar macrophage (dust cells) = macrophages fixed in alveolar lining of lungs
(aka: reticulum cells of the lungs)
Histiocytes = fixed macrophages in CT
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

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Fabrys disease:
The only sphingolipidosis that is not autosomal recessive (No, I dont know which
category it fall under)
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:

X linked defect affecting the methylation and expression of the FMR1

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

Use of Gowers maneuver, requiring assistance of the upper extremities to stand up, is

characteristic (indicates proximal lower limb weakness)

Others: Hemophilia A & 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, 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

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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)
4% due to rebersonina translocation
1% due to down mosaicism (no maternal association)
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
Extra
Delayed physical & mental
Affected people
Down
births
chromosome 21 development; many physical
generally live
syndrome
abnormatlties. Small head w/ until their 30s or
broad & flat face, slanting
40s
eyes & a short nose. Enlarged
tongue, small & low-set ears.
Heart defects are common
Trisomy 18
1/3000
Extra
Facial abnormalities combine Survival > a few
Edwards
births
chromosome 18 to give the face a pinched
months is rare;
syndrome
appearance. Small head &
severe mental
malformed, low-set ears
retardation
Trisomy 13
1/5000
Extra
Severe brain & eye defects are > 20% survive
Pataus
births
chromosome 13 common
beyond 1 year;
syndrome
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

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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):
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)
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 gonaldal (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

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RANDOM STUFF
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

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, & increased 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:
Metastatic calcification:

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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 bleeding

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

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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 & Differntiated 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

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:
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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

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 commonly 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 manifest 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

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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

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 1st-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 nad 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

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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

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

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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????

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.
247

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
Gangrenous disese of the mouth and cheeks

248