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
 Glyoxysomes: common in fat-storing tissues of the germinating seeds of plants

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  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
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  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 cell’s 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

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  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 cells→Th1 & 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/MФs)
 Eosinophils
 Release histaminase & aryl sulfatase to help control allergic reactions
 Basophils
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 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 Function
T helper cells (Th) Help or assist other T cells and B cells to express their immune function
Cytotoxic T cells Kill target cells expressing foreign Ag/s (cells containing obligate intracellular
(Tc) parasistes & tumor cells)
T suppressor cells Suppress or inhibit the immune function of other lymphocytes
(Ts)
T memory cells Long-lived cells that recognize previously encountered T dependent antigens
B lymphocytes Differentiate into antibody-producing plasma cells and B memory cells in
response to an antigen
B memory cells Long lived cells that recognize a previously encounter antigen
Natural killer cells Kill and lyse target cells that express foreign antigens
(NK)
Plasma cells Actively secrete antibody

 Cells that maintain latent capacity for mitotic division:

 Blood (RBCs live for 120 days, WBCs only 2-5 hours), bone marrow, liver, and salivary glands
 Liver undergoes regeneration: occurs as adaptive mechanism for restoring a tissue or organ
 After removal of 70% of liver, numerous mitoses of hepatocytes occur reaching a peak at
33 hours
 By day 12 the mass of liver is totally restored
 Liver is the least common site for infarcts (than brain, heart, kidney, adrenals)
 NOTE: Bone cartilage & intestinal mucosa are also able to regenerate
 Cells that do not have ability to undergo mitosis:
 Nerve cells (least ability to regenerate) in the CNS, skeletal, cardiac, & smooth muscle cells,
lungs
 Striated muscle is harder to regenerate than smooth muscle
 Heart, brain, & lungs are very vulnerable to hypoxia & anoxia
 They die & are unable to regenerate
 The heart can undergo hypertrophy in response to injury

BACTERIA
 A quick note on organisms in general:
 Commensalism:
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  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) -
that’s why they don’t 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
 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. aeruginosaqo
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  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)
 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

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  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 CO 2 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 – don’t get clowned)
 3 types of RNA:
 1) rRNA – combines w/ proteins to form ribosomes
 2) mRNA – dictates sequence of aa assembly
 3) tRNA – transports aa’s 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

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  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 (inside→out):
 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
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 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
 **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
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  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 (inside→out):
 Inner Cell Membrane
 Cell Wall – components:
 Thick murein (peptidoglycan) layer
 The backbone biochemical of the bacterial cell wall (makes up ~90% of the cell wall)
 Peptidoglycan (murein):
 The rigid component of the cell wall in most bacteria – not found in archaebacteria or
any eukaryotic cell
 Two parts of molecule:
 Peptide portion: short, attached, cross-linked peptide chains containing unusual
amino acids
 Glycan portion: alternating units of amino sugars N-acetylglucosamine and N-
acetylmuramic acid
 The NAG-NAM backbone is attacked by the enzyme lysozyme
 Lipoteichoic acids
 Teichoic acids
 Unique to G+ bacteria
 Polysaccharides that serve as attachment sites for bacteriophages
 No outer membrance
 Capsule (sometimes)
 G- cell envelope (inside→out):
 Inner Cell Membrane
 Outer Membrane
 Cell Wall – components:
 More complex than G+ cell wall
 Thin murein layer (~10% of cell wall)
 Lipoproteins are an integral part of cell wall
 Lipopolysaccharide (LPS) layers (= endotoxin)
 Located in the outer MB of G- bacteria
 Basic chemical structure consists of:
 Somatic O Polysaccharide, Core Polysaccharide, and Lipid A (and Keto-deoxy-
octanoate!!!)
 NOT Teichoic acid (That is only in G+ cell wall !!!)
 Lipid A is the most responsible for the endotoxin’s toxic activity
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  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
 Don’t get clowned by “bacterial metabolites including enzymes” accumulating in the
crevice
 Shwartzman reaction
 In this reaction, endotoxin elicits the response
 Rabbit is injected intradermally with a small quantity of lipopolysaccharide (endotoxin)
followed by a second intravenous injection 24 hours later and will develop a
hemorrhagic and necrotic lesion at the site of the first injection
 Phospholipids
 Proteins
 Other Cell Contents:
 Granules (inclusion bodies) – storage areas for nutrients
 Volutin – reserve of high energy stored in the form of polymerized metaphosphate that can be
used in synthesis of ATP
 Commonly associated w/ Pseudomonas aeruginosa & Cornybacterium diphtheriae
 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
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  Determine traits not essential for the viability of the organism but that change the organism’s
ability to adapt
 Transposons –
 Consists of two insertion sequences flanking an ABX resistance gene
 Pieces of DNA that move readily from one site to another, either w/in or between the DNAs of
bacteria, plasmids, or bacteriophages
 Genes that often encode proteins necessary for ABX resistance and that can change
positions on a chromosome or “jump” from a plasmid to a chromosome
 Frequently associated w/ formation of multiple-drug resistance plasmids
 Encapuslated Bacteria
 Polysaccharide capsule is antiphagocytic virulence factor
 IgG2 necessary for immune response`
 Capsule serves as antigen in vaccines (Pneumovax, H. influenzae b., Meningococcal vaccines)
 Quellung Rxn = Caspsular “Swellung” rxn  capsule swells when specific anticapsular antisera
are added
 Streptococcus Pnuemoniae
 Haemophilus influenzae
 Neisseria meningitides -BIodome
 Klebsiella pneumoniae
 Cryptococcus Neoformans – Inside the Crypt - yeast

 Exotoxin Vs. Endotoxin

Property Exotoxin Endotoxin
Source Some Gram + and Gram - Cell wall of most Gram – ONLY
Secreted Yes (Diffuse out) No (Just a breakdown product)
Chemistry Polypeptide Lipopolysaccharide
 Most bacterial endotoxins are
composed of lipoprotein-
polysaccharide complexes
Location of genes Plasmid or bacteriophage Bacterial chromosome
Toxicity/Potency High (fatal if dose on the order Low (fatal dose on the order of
of 1microg) hundreds of micrograms)
Clinical effects Various Fever, shock
Mode of action Various Includes TNF and IL-1
Antigencity Induces high titer antibodies Poorly antigenic – that’s why no
called antitoxins vaccine to this.
Vaccines Toxoids are used No toxoids formed and no
vaccine avail.
Heat Stability Destroyed rapidly at 60 degrees Stable at 100 degrees C for 1
C (except Staph enterotoxin) hour
(Heat Labile)
Typical Diseases Tetanus, botulism, diphtheria, Meningococcemia, sepsis by
anthrax Gram- rods
Specificity High
Miscellaneous  Detoxified by formalin  Different from exotoxins in
 Highly immunogenic that they activate
13
 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
 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 Eaton’s
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

14
 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 IL-
2 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
Escherichia coli Diarrrhea Heat labile toxin stimulates
adenylate cyclase by ADP
ribosylation of G protein
Vibrio Cholerae Rice-water Stimulates adenylate cyclase by
diarrhea ADP ribosylation of G protein,
increasing pumping of Cl- and
H20 into the gut
Bordetella pertussis Whooping Stimulates adenylate cyclase by
Cough 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

15
  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 – Don’t give Abx bc you’ll 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
 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
16
  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
 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 MacConkey’s)
 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)
17
 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
(swimmer’s ear), UTI
 Motile by means of polar flagella
 Produce characteristic fluorescent pigments (P. aeruginosa), but others do not
 Has ability to adapt and thrive in many ecological niches, from water to soil to plants &
animals, including humans
 Exotoxin A
 Inhibits protein synthesis (not DNA synthesis)
 Inactivates E2-F
 Important nosocomial infection in immunocompromised & chronically ill patients
 People w/ cystic fibrosis, burn victims, individuals w/ cancer & pts requiring
extensive care in hospitals
 Nosocomial infections often caused by:
 Staph, Strep, E. coli, & P. aeruginosa are common bugs in hospital-acquired
infections
 Once established, produces a number of toxic proteins which cause not only extensive
tissue damage, but also interfere w/ the human immune defense mechanisms
 An infection followed a serious skin burn that is characterized by greenish pus and is
resistant to ABX is probably caused by P. aeruginosa (think P. aeru-green-osa)
 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
18
  Young Healthy person exposed to Legionella Pneumophilia, what happens 
 Initial symptoms are flu-like, including fever, chills, and dry cough. Advanced stages of
the disease cause problems with the gastrointestinal tract and the nervous system and
lead to diarrhea and nausea
 Causes Pontiac fever and Legionnaires’ disease and Atypical Pneumonia
 Treat w/ erythromycin
 Haemophilus Influenzae – 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.
 All ferment glucose and are oxidase negative
 Think COFFEe
19
  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
 DON’T 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 traveler’s 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
 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
20
  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
 The only bacteria that are IPs are Rickettsia and Chlamydia (they stay inside when
it’s Really Cold)
 This means they only survive by establishing residence inside animal cells and utilizing
the host’s 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
21
  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 words…what they have in common with fellow
bacteria):
 Have BOTH DNA and RNA (viruses only have one or the other)
 Synthesize their own proteins (viruses do not)
 Are sensitive to ABX (obviously viruses are not)
 Reproduce by a complex cycle w/ Binary Fission (Bacteria = Binary Fission; Viruses =
synthesis & assembly)
 Possess an energy yielding, autonomous enzyme metabolism (Rickettsia only)
 Divided into two groups:
 Spotted-Fever Group – Rash is inward (from palms inward)
 Rocky mountain spotted fever tick
 R. rickettsii (which accounts for 95% of rickettsial diseases in U.S.)
 Endemic in East Coast, that is why it’s 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 Brill’s 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
22
  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
 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
23
  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
 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) α-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)
24
  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 (that’s strep pyogenes – Scarlet fever/Rheumatic Fever)
 Treatment/Prevention:
 Vancomycin or erythromycin
 PCN resistance on the rise – due to transformation
 Vaccine: 23-valent vaccine available
 Viridans Streptococcus (optochin resistant)
 NOT afraid of the CHIN
 Normal flora of the oropharynx and cause dental caries and bacterial endocarditis
 S. sanguis – the major cause of subacute endocarditis in those w/ abnormal heart
valves
 Lots of Blood in heart
 S. mutans – causes dental caries
 Treat w/ PCN
 2) β-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 β-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
25
  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
 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
26
  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 β-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) γ-hemolytic Streptococcus
 Produce no hemolysis
 Enterococci
 Pen G resistant
 Major concern with enterococci in the hospital
 Cause UTI and Subacute endocarditis
 Part of normal fecal flora
 Lactic Acid bacteria
 General
 Use lactic acid fermentation pathway (pyruvate → lactic acid)
 Aciduric – can tolerate acid environment
 Acidogenic – acid-forming
 NOTE: lactic acid is the main cause of enamel decalcification
 Lactobacillus
 Labeled as cariogenic because of ability to produce acid
 Significant secondary invader of dental caries
 In coronal caries, causes progression of existing caries
 Found in deep dental caries and increases in the saliva during periods of caries
activity
 Regular, non-sporing, G+ bacteria
 Most likely to tolerate the lowest pH (lower than even Streptococci)
 Found in vagina, GI tract, mouth
 L. acidophilus – added to milk products to aid in digestion of milk products
 Bacterial enzymes convert milk sugars to digestible products
 Streptococcus
 Streptococci are the predominant bacteria found in saliva
 S. mutans – Know this.
 Smooth surface caries

27
  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 (they’re all G+)
 Actinomyces – root surface caries
 MYCOBACTERIA
 M. tuberculosis – Often resistant to multiple drugs
 M. kansasii – Pulmonary like TB symptoms
 M. scrofulaceum – Cervical lymphadenitis in kids
 M. avium-intracellulare – Causes disseminated disease in AIDS
 M. leprae – leprosy (M. leprae = Hansen’s 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

28
  Cord Factor  Glycolipid found in the cell wall of M. Tb and allows them to grow in
serpentine cords
 Slow-growing – 20-60 days before growth can be visualized
 NO exotoxins or endotoxins
 Tubercle (Ghon focus) –
 A small, rounded nodule produced by infection w/ M. tuberculosis
 Primary lung lesion in the periphery
 Usually in lower lobes
 Primary lung lesion of pulmonary TB
 Primary TB
 Nonimmune host (usually child)
  Ghon Focus  Ghon complex (from there it can go to below options)
 Heal by fibrosis  Immunity and Hypersensitivy  Tuberculin positive
 Progressive lung disease (HIV)  Death (rare)
 Severe bacteremia  Miliary TB  Death
 Preallergic lymphatic or hematogenous dissemination  Dormant tubercle bacilli in
several organs  Reactivation in adulthood  Extrapulmonary TB (See below)
 Secondary TB
 Partially immune hypersensitized host (usually adult)
 From either Reinfection or Reactivation tuberculosis in the lungs
 Causes fibrocasseous cavitary lesion in upper lobes
 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 = Hansen’s 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

29
  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 121°C for 20 min at 15 psi
 Most important endospore producers: Bacillus & Clostridium genera (perfingens and tetany)
 Difference between Clostridium and Bacillus is that Bacillus is aerobic (Nice Pets
Must BBBBreath)
 Clostridium
 C. Botulism
 Botulism is caused by C. botulinum
 From Bad Bottles of food or honey from Bees
 Floppy Baby
 C. Perfringens
 Gas gangrene is caused by C. perfringens
 Gas gangrene is produced by a G+, spore-forming anaerobic bacillus
 Perforates a gangrenous leg
 C. Difficile
 Produces a cytotoxin, an exotoxin that kills enterocytes, causing pseudomembranous
colitis
 Often secondary to ABX use, especially clindamycin or ampicillin
 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
30
 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 stream→bacteremia
 Viremia
 A viral infection of the bloodstream
 Major feature of disseminated infections
 The infecting virus is most susceptible to circulating antibodies
 Some enzymes:
 Streptodornase (DNAase) – depolymerizes DNA in exudates or necrotic tissue
 Hyaluronidase – degrades HA, which is the ground substance of subcutaneous tissue
 Produced by Streptococcus, Staphylococcus, Clostridium (Think Perfringens)
 The purposes of Hyaluronidase are
 Avoid the immune system
 Cause disease in host
 Disseminate
 NOT for Nutrition
 The spreading factor produced by some Strep

Some Extracellular Enzymes Involved in Microbial Virulence

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 Normal Microbiota

Oral cavity (saliva, tongue, plaque)
Gastrointestinal tract
Upper respiratory tract (nasal cavity and
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,
31
nasopharynx Neisseria, Haemophilus, Bacteroides, and
Fusobacterium
Lower respiratory tract None
Upper urinary tract (kidney and bladder) None
Genitourinary tract (urethra and vaginal tracks) Streptococcus, Lactobacillus, Bacteroides, and
Clostridium

 Predominant subgingival bacteria associated w/ gingival health:

 Streptococcus mitis & S. sanguis
 Actinomyces viscosus & A. naeslundii
 Rothia dentocariosus
 Staphylococcus epidermidis
 Small spirochetes
 Periodontal disease:
 IgG is found in the highest concentration in serum samples from pts w/ PD disease
 Prevotella melaninogenica and Prevotella intermedia (NEW NAMES)
 [Bacteroides melaninogenicus = OLD NAME]
 Anaerobic bug from gingival scrapings
 Forms a black pigmented colonies on hemin-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
32
  Campylobacter rectus
 Fusobacterium nucleatum
 Spirochetes
 **When T cells from people with chronic periodontitis react with certain plaque bacterial
antigens they produce:
 MIF & Lymphotoxin
 Lymphotoxin is synonymous with TNF-beta
 MIF = (macrophage) migration inhibitory factor
 Here’s 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

33
  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 2–10 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??
 Often occurs together w/ chlamydia and syphilis
 Ophthalmia neonatorum
 A very serious complication of an infant delivered of mother with gonorrhea
34
 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 Hutchinson’s triad – abnormal teeth, interstitial keratitis, 8th
nerve deafness
 Cannot be grown on artificial media (neither can M. leprae) -- armadillos
 Also disrupts the vasa vasorum of aorta with consequent dilation of aorta and valve ring, often
affects the aortic root and ascending aorta, Associated with tree bark appearance of the aorta,
Responsible also for some Aortic anuerysms
 3 stages of Syphillis:
 PRIMARY:
 Non-painful chancre – reddish lesion w/ raised border (appears in 3-6 wks at the site of
local contact)
 Lips are most common site for chancres to appear in 1° oral syphilis
 SECONDARY:
 Characterized by:
 Cutaneous lesions
 Positive VDRL test
 Mucous membrane lesions
 Presence of Spirochetes in the lesions
 NOT Development of a gumma (tertiary)
 Highly infectious stage – 6 wks after non-treatment of 1° syphilis
 Maculopapular rash
 Rash appears on palms of hands & soles of feet – just like in Rocky Mountain spotted
fever
 Condyloma latum/lata
 Flat-topped papules (mucous patches) appearing on moist skin/mucosal surfaces

35
 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  MacConkey’s agar (PINK)
 Legionella pneumophila  Charcoal yeast extract agar buffered with increased iron and
cysteine
 Fungi  Sabouraud’s agar
 Stains
 Congo Red  Amyloid; apple-green birefringence in polarized light
 Giemsa’s  Borrelia, trypanosomes, Chlamydia
 PAS (Periodic Acid Schiff)  Stains glycogen, mucopolysaccharides, Dx Whipple’s disease
 Ziehl-Neelson  Acid-fast bacteria (military TB) – or Kinyoun’s acid-fast stain – Think
German Military
36
  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 DON’T know the ABCs of Breathing
 Actinomyces -- Sulcus Dwellers
 Bacteroides
 Clostridium – Spore forming that doesn’t breath
 Food Posioning Bugs
 Staph aureus  (Meats, mayonnaise, and custard) THE
FASTEST!!
 Vibrio parahaemolyticus and Vibrio vulnificus (Seafood)
 Bacillus cereus  (Reheated Rice)
 Clostridium perfringens (Reheated Meat dishes)
 Clostridium botulism (Canned foods)
 E. coli (Undercooked meat)
 Salmonella (Poultry, meat, eggs)
 Diarrhea Bugs
 E. coli  Ferments lactose No Fever Watery/Bloody
 Vibrio cholerae Comma-shaped organism No Fever Watery
 Salmonella No lactose fermentation, mobile Fever Bloody
 Shigella No lactose ferm, nonmobile, Fever Bloody
 Campylobacter jejuniComma or S shaped organism Fever Bloody
 Vibrio parahaemolyticus Transmitted by Seafood Fever
 Yersinia enterocolitica From Pet feces (puppies) Fever Bloody
 Cholera vs. Pertussis
 Vibrio cholera
 Toxin permanently 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
37
  Think pink colonies growing on MacConkey’s agar
 Think MacKonKEEs
 Klebsiella
 E. coli
 Enterobacter
 Zoonotic Bacteria
 Think Bugs From Your Pets
 Borrelia burgdorferi Lyme Disease Tick bites (living on deer and
mice)
 Brucella Brucellosis Fever Dairy products, contact with
animals
 Francisella tularensis Tularemia Tick bites; rabbits, deer
 Yersinia pestis Plaques Flea bite; rodents;
especially prairie dogs
 Pasteurella multocida Cellulitis Cat, Dog bites
 Normal Flora
 Skin S. epidermidis
 Nose S. aureus
 Oropharynx viridans Streptococcoi (S. mutans)
 Dental Plaque S. mutans
 Colon B. fragilis, and S. young
 Vagina Lactobacillus, colonized by E. coli, group B strep, J. Cragun

VIRUSES
 Virion: the complete infectious viral particle
 A viral nucleic acid (genome) is composed of DNA or RNA (NOT both) encased in a protein coat
called a capsid
 Capsid or Protein coat
 Composed of polypeptide units called capsomers
 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 it’s Really Cold)
 Not sensitive to antibiotics – but are sensitive to interferon, which inhibits their replication
 Depend on host cells for energy production
38
  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 cell’s metabolic activities
 The virus then uses the metabolic capacity of the host cell to reproduce new viruses
 Host cell provides the metabolic NZs, and the virus provides the genetic information
 Often the replication of these new viruses causes death of the host cell
 Viruses must first adsorb to the cell surface of the host cell
 This involves a specific interaction between a viral surface component and a specifice cell
receptor on the cell membrane
 Adsorption does NOT involve insertion of virally specified glycoproteins into the host cell
membrane
 Cellular tropism by viruses is dependent upon cell surface receptors (they interact with the spikes
on the viruses)
 For a retrovirus, what precedes integration into the host?
 Synthesis of complement DNA from RNA
 NOT synthesis of viral protein, capsid from nuclear membrane, or budding
 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:
39
  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
 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
40
  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
 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
41
  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
 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)
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 Hepatitis viruses
 Include DNA & RNA viruses
 Detailed info is found in the section on the Liver
RNA VIRUSES
 RNA ENVELOPED VIRUSES
 Orthomyxovirus
 ssRNA Segmented
 Influenza A, B, C
 Causes influenza, duh!
 Composed of unique segmented ssRNA genome, a helical nucleocapsid, and an outer
lipoprotein envelope
 Envelope is covered w/ two different types of spikes that contain either hemagglutinin
or neuraminidase
 Causes a fever, runny nose, cough, headache, malaise, muscle ache
 Fever distinguishes flu from common cold
 Classified as type A, B, or C depending on the nucleocapsid Ag
 Passed on via respiratory droplets
 Microorganism characteristic of requiring a specific receptor site to infect a host
 (incorrect options included anthrax, syphilis, dysentery, gas gangrene)
 Influenza A:
 Most common flu; causes the most severe disease
 Ability to cause epidemics depends on antigenic changes in the hemagglutinin &
neuraminidase
 Two types of changes:
 Antigenic shifts
 which are major changes based on reassortment of genome pieces
 This leads to new surface molecules (change in envelope)
 Antigenic drifts
 which are minor changes based on random mutations
 Amantadine/Rimantadine
 Inhibits replication of influenza A virus by interfering w/ viral attachment &
uncoating
 Effective in prophylaxis & Tx of influenza A
 Main mode of prevention is vaccine – consists of killed influenza A & B viruses
 Staph aureus is associated with fatalities post influenzal infection
 One serious complication associated w/ outbreaks of influenza is the development of
Reye’s 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 & Reye’s syndrome
 Reye’s 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

43
 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
 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/ Koplik’s spots in the oral cavity (BAD cops in
Mexico)

44
  Koplik’s spots – small, bluish-white lesions surrounded by a red ring; occur opposite
the molars
 So, Koplik spot = measles = paramyxovirus
 Pt can have:
 A cold and red & runny eyes
 Blotchy reddish rash behind ears and on the face
 3 Cs  Cough, Coryza, Conjunctivitis
 Transmitted by respiratory droplets
 what are features of measles except:
 koplik
 negri 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 Koplik’s spots  That’s 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
45
  The malformations are widespread & involve primarily:
 The heart (e.g., patent dutus arteriosus)
 The eyes (e.g., cataracts)
 The brain (e.g., deafness & mental retardation)
 Flavivirus (Flavi = Yellow)
 Yellow fever – a mosquito-borne flavivirus infection
 Has a monkey or human reservoir
 Symptoms: fever, black vomit, jaundice (yellow)
 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

46
  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:
 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)
47
 Fungal
 Candidiasis, Cryptococcus (meningitis), Histoplasmosis, Pneumocystic carinii
pneumonia (PCP)
 Most common cause of pneumonia in HIV pts is from PCP
 Protozoan
 Toxoplasmosis, Cryptosporidium Enterocolitis
 NOT Adenovirus conjunctivitis
 Strains
 New strains of HIV are the result of errors in transcription (remember, reverse
transcriptase!)
 In other words, by frequent errors induced by viral reverse transcriptase
 NOT the result of genomic recombination or errors in translation
 Dx
 Made with ELISA  High false positive rate, simply a Rule Out test
 Positive ELISA are then confirmed with Western blot assay, Rule In test
 HIV is NOT oncogenic
 AIDS
 Info available elsewhere in file
 RNA NON-ENVELOPED VIRUSES
 NAKED  CPR (Calicivirus, Picornavirus, Reovirus)
 PicoRNAvirus = picornavirus
 Very small, non-enveloped; composed of positive stranded, ssRNA genome
 NOT capable of causing cell transformation (naked DNA)
 Retrovirus, Herpes, Hepatitis B, and Human Papilloma are capable of causing cell
transformation
 Subdivision: Enteroviruses
 Poliovirus
 Causes poliomyelitis
 RNA is the Only nucleic acid present…duh
 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)

48
  Effective Polio Vaccine forms what kind of antibodies??  Membrane bound
IgG??? – I think
 This is why SABIN (OPV or live) is better because it ALSO induces sIgA
synthesis
 Vaccine for Polio would be most affective if directed at Intestinal Mucosa
 These immunize against polio in more than 90% of recipients
 Coxsackie A & B virus
 Most commonly isolated virus in the feces
 Incorrect options: Hep C, influenza, rubella, herpes simplex
 NOTE: you can get avian influenza from bird feces…just “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

49
 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
 All are large (120–200 nm diameter) – 2nd only to poxvirus in size
 Are medium-sized enveloped viruses w/ an icosahedral nucleocapsid containing linear,
dsDNA
 Replicate in the nucleus of the host cell and are the only viruses to obtain their
envelopes by budding from the nuclear membrane
 Cause acute (primary) infections
 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)
 Recurrent herpes most likely found on the labial mucosa

50
  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 don’t 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 infant’s CNS &/or eyes
 What causes cervicitis?
 HSV 2, syphilis, HPV, chlamydia
 Has been shown to have relationship to carcinoma of the cervix
 Candidate virus for the induction of cervical cancer (carcinoma)
 Varicella-zoster virus
 Member of the herpes virus group
 Causes 2 distinct diseases in different age groups
 Very contagious and may be spread by direct contact or respiratory droplets

51
  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
 Hodkin’s Lymphoma
 Associated w/ development of Burkitt’s 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 ID’d by
the hereophile test
 (aka: “mononucleosis spot test” or “monospot test”)
 Ab eventually appears in serum of > 80% of pts w/ IM, hence it is highly diagnostic
 Infectious Mononucleosis (IM):
 Viral infection causing high temperature, sore throat, & swollen lymph glands,
especially in the neck, necrotizing pharyngititis, and splenomegaly
 Typically caused by EBV – can also be cause by CMV
 EBV-caused IM is responsible for approximately 85% of IM cases
 Often transmitted by saliva
52
  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/ Burkitt’s lymphoma, nasopharyngeal carcinoma, & hairy
leukoplakia
 Cytomegalovirus
 Congenital abnormalities
 CMV is the major viral cause of birth defects in infants in developed countries
 C in TORCH
 HHV-6
 6th disease = roseola infection

Virus Usual site of latency Recurrent infection Route of transmission

HSV-1 Cranial sensory ganglion Herpes labialis, encephalitis, Via respiratory secretions
(CN V) keratitis and saliva
HSV-2 Lumbar or sacral sensory Herpes genitalis Sexual contact, perinatal
infection
Varicella Cranial/thoracic sensory Zoster Via respiratory secretions
zoster ganglia
Epstein-Barr B lymphocytes None Via respiratory secretions
and saliva
CMV Uncertain None Intrauterine infection,
transfusions, sexual contact,
via secretions (eg saliva and
urine)

 HepaDNAvirus
 Hepatitis B
 Blood borne virus
 Parenteral, sexual, maternal-fetal
 Long incubation period (3 months)
 Reverse transcription occurs?????
 Poxviruses
 DNA viruses – the largest & most complex animal viruses
 Brick shaped particles containing enveloped linear dsDNA genome
 Multiply in the cytoplasm of host cell & are usually associated w/ skin rashes
 Smallpox
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 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, that’s 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)
 NOT associated with HIV opportunistic infection
 Pharyngoconjunctival fever characterized by fever, pharyngitis, & conjunctivitis
 Parvovirus (PAR – V – Fifth’s disease)
 Erythema infectiosum (slapped-cheeks syndrome, 5th disease)
 Transient aplastic anemia crisis
 Fetal infections

Virus Disease Vaccine Treatment

available
RNA viruses
Influenza A Influenza Yes Amantadine/Rimantadine

54
Parainfluenza Croup No None
Respiratory Bronchiolitis and No Ribaviron
synctial pneumonia in infants
Rubella Rubella Yes None
Measles Measles Yes None
Mumps Parotitis, meningitis Yes None
Rhinovirus Common cold No None
Coronavirus Common cold No None
Coxsackie Herpangina, hand foot and No None
mouth
DNA viruses
Herpes simplex Gingivostomatitis No Acyclovir in
type1 immunodeficient pt
Epstein barr Infection mononucleuosis No None
Varicella Chickenpox, shingles No None
Adenovirus Pharyngitis, pneumonia No None

Portal of Entry Virus Disease

Respiratory tract Adenovirus Pneumonia
Cytomegalovirus Mononucleosis syndrome – most
common pneumonia in bone
marrow transplant pt
Epstein barr Infection mononucleosis
HSV type 1 Herpes labialis
Influenza Influenza
Measles Measles
Mumps Mumps
Respiratory synctial Bronchiolitis and pneumonia in
infants
Rhinovirus Common cold
Rubella virus Rubella
Varicella zoster Chickenpox
Gastrointestinal Hep A Hep A
Polio Poliomyelitis
Rota Diarrhea
Skin Rabies Rabies
HPV Papillomas (warts)
Genital HPV Papillomas (warts)
Hep B Hep B
HIV AIDS
HSV type II Herpes genitalis and neonatal
herpes
Blood Hep B Hep B
Hep C Hep C
HIV AIDS

55
 Cytomegalovirus 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

FUNGI
 Fungi:
 Eukaryotic, all are G+; contain both DNA & RNA
 Grow in Sabouraud’s 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

56
  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
 Cold = Mold/Mycelial (soil) Heat = Yeast (tissues)
 Characterized by the capability to produce both a yeast & a mycelial phase
 Exist as molds in the saprophytic, free-living state at ambient temperatures
 Exist as yeasts in host tissue at body temperature
 These fungi include the major pathogens – Blastomyces, Histoplasma, Coccidioides, and
Candida
 Reproduction
 Asexual:
 Most fungal spores are asexual
 Asexual spores (conidia) form through mitosis
 Differentiating conidia help to ID various fungi
 Sexual:
 They mate & form sexual spores
 Mechanism for disease is through type IV hypersensitivity reaction
 Fungal spores:
 Morphological characteristics (e.g., shape, color, & arrangement) of conidia help to ID fungi
 Conidium is an asexually formed fungal spore
 Fungal spores cause allergies in some people
 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
 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 pt’s 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 Tinea…from Dr. Christensen’s Path
course
57
  Infect only the skin, nails, and hairs
 Athlete’s 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
 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

58
 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 “Gilchrist’s disease” or “North American blastomycosis”)
 Caused by Blastomyces dermatidis – a dimorphic fungus that exists 1) as a mold in soil & 2) as a
yeast in tissue
 Causes necrotic skin and bone lesions – Blasted through my Skin to my Bone
 Think B for Big, Broad-Based Budding
 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
59
  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)
 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, don’t 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
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  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  Sabouraud’s agar, Stain with India ink – enCrypted message with India ink
 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

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  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 it’s a yeast
 Inhaled
 Most infections are asymptomatic, but due to AIDS, etc.
 Most common cause of pneumonia in HIV pts is PCP
 Tx when CD4 drop below 200 cells/mL in HIV pts

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
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  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
 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 cat’s 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:
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  Roundworms w/ a cylindrical body & a complete digestive tract
 Two categories based on primary location of body:
 Intestinal nematodes: enterobius (pinworm), trichuris (whipworm), ascaris (giant roundworm)
and Necator and Ancylostoma (the two hookworms)
 Tissue nematodes: Wuchereria, Onchocerca, and Lao are called “filarial worms”
 Bx of tongue mass – small, coiled, encysted larvae of nematode worms: Trichinae
 Infections caused by certain nematodes cause marked eosinophilia (abnormally large numbers of
eosiopnils in the blood)
 Eosinophils do not ingest the parasites – they attach to the surface of parasites via IgE &
secrete cytotoxic enzymes contained w/in their eosinophilic granules
 Cestodes
 Tapeworms
 Trematodes
 Flukes

ANTIMICROBIAL AGENTS
ANTIBIOTICS:
 Broad-spectrum antibiotics: Tetracycline, Chlormycetin, & Cephalosporins
 (NOT isoniazid, PCN, Dihydrostreptomy, or streptomycin)
 Prolonged use of streptomycin can result in damage to auditory nerve
 Steptomycin is an ABX which inhibits the process of transcription in prokaryotes
 The indiscriminate use of broad-spectrum ABX is contraindicated because…
 They interfere with indigenous bacteria (NOT produce dependency rxns – Susan Kinder
Haake would be pissed)
 Possible toxic effects of the antibiotics
 Allergic reactions induced in patients
 Development of drug resistance by an infectious agent
 Secondary effects experienced due to creation of an imbalance in the normal body flora
 Alteration of the immune response
 Mechanisms of Action:
 Cell wall inhibitors:
 ***Inhibit terminal step in peptidoglycan formation – NOT cell membrane
 ***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

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  50S – Chloramphenicol – Protein synthesis inhibition by inhibiting translocation by
binding to 50S subunit
 50S – Lincomycin
 50S – Erythromycin – ABX of choice for a dental pt w/ a heart valve abnormality AND a
PCN allergy
 If you have a bact sensitive to penicillin but pt is allergic what would u use instead
 Cephalosporin – NO: cross-allergenic
 Amoxicillin – NO, duh!
 erythromycin
 clindamycin would have been a better choice??? – 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)
 Don’t 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
β-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

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  Methicillin, cloxacillin, dicloxacillin, nafcillin, oxacillin, amoxicillin/clavulonate
potassium (Augmentin), ampicillin/sulbactim (Unasyn), piperacillin/tazobactam (zosyn),
ticarcillin/clavulonate potassium (Timentin)
 Penicillin G:
 Used for growing Gram + bacteria
 Penicillin V:
 Methicillin:
 Prescribed primarily in the treatment of severe penicillinase-producing staphylococcal
infections
 Given IV
 Not frequently used due to:
 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
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  Pseudomembranous colitis is a major adverse effect of prolonged therapy with clindamycin
 Side effects are caused by overgrowth of Clostridium difficile (95% of Pseudo… cases
caused by C. difficile)
 Bacteriostatic & active against most G+ & many anaerobic organisms, including Bacteroides
fragilis (anaerobic G-)
 Is alternate antibiotic used in dentistry when:
 Amoxicillin cannot be used for bacterial endocarditis prophylaxis
 Tx of common oral-facial infections caused by aerobic G+ cocci & susceptible anaerobes
 For prophylaxis for dental patients w/ total joint replacement
 Can be given to patients allergic to penicillins since there is no cross allergencitiy
 AMINOGLYCOSIDES:
 TETRACYCLINES:
 Tetracycline
 No tetracycline for pregnant women or children under 9 years of age
 Causes pigmentation of developing teeth
 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
 Don’t get clowned by “increased mutation rate”
ANTIMYCOBACTERIAL AGENTS
 RIPE:  For TB
 Rifampin
 Isoniazid
 Pyrazinamide
 Ethambutol
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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

Summary of Some Antifungal Agents

Topical agent Use Mechanism on Form
fungal cell
Clotrimazole Oropharyngeal candidiasis Alters cell membrane Troche
Nystatin Oral cavity candidiasis Alters cell membrane Oral
suspension
Topical agents
(cream)
Amphotericin B Cutaneous & mucocutaneous Alters cell membrane Cream
Cand
Ketoconazole Cutaneous and muco Cand Alters cell membrane Cream

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 Nystatin Cutaneous and muco Cand Alters cell membrane Ointment
Systemic agents
Fluconazole Oral, esophageal, Alters cell membrane Tablets
oropharyngeal Cand
Ketoconazole Oral, esophageal, Alters cell membrane Tablets
oropharyngeal Cand
Amphotericin Systemic candidiasis 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 (Don’t 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
 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
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  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
 Freund’s Adjuvant:
 Common experimental adjuvant – consists of killed M. tuberculosis suspended in lanolin &
mineral oil
 Used to elicit stronger T- & B-cell mediated responses when Ag/s alone fail to evoke sufficient
response
 Human vaccines contain aluminum hydroxide or lipid adjuvants
 Alum-precipitated Ag/s:
 Formed from protein Ag/s mixed w/ aluminum compounds
 Serves as a local inflammatory stimulus

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  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 recom’d in us ‘cuz of low chance of
infectivity, ruins PPD test
 Unlike DPT, BCG vaccine consist of avirulent bacteria
 DPT – pertussis is killed whole bact,  in US now suggest DTaP (pertussis Ag/s, not killed bact);
diph / tetanus
 Rubeola (measles), pertussis, smallpox, poliomyelitis, mumps & tetanus are all prevented by
active immunization

INFECTION CONTROL

 The most effective means of preventing disease transmission in a dental office is based on the concept
of Universal Precautions
 Don’t get clowned by “sterilization”, “asepsis”, or “barrier techniques” – Universal precautions
encapsulates all of these
 FIND OUT  OSHA’s blood borne pathogen protocol is used to protect whom?????
 To protect the employees!!!

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  OSHA’s 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 cross-
contamination and cross-infection
 Bactericidal:
 Antibacterial solution w/ directly kills bacteria
 “Cidal” agents & processes are designed to ensure microbial inactivation
 EXs: Glutaraldehyde, betabropiolactone, ethylene oxide, formaldehyde are all 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: high→low
 Prions→Bacterial spores→Mycobacteria→Parasitic bacteria→Small, non-enveloped
viruses→Trophozoites→Non-sporulating G- bacteria→Fungi→Large non-enveloped
viruses→Non-sporulating G+ bacteria→Enveloped 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 μm
 This size will retain all bacteria and spores
 Filters work by physically trapping particles larger than the spore size
 Used for liquids that will be destroyed at temps over 90°C
 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

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  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
 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
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  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
 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
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 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 Touch mucous membrane but not
level disinfection penetrate; no blood, (mirrors,
burnishers, amalgam carriers,
etc.)
Non-Critical Intermediate Level Low Unbroken skin contact; no blood;
(masks, clothing. b.p. cuffs)
Environmental Low Level Minimal No direct patient contact, no
surfaces: Equipment disinfection; blood units, knobs, light floors,
housekeeping sanitation walls, counters

 Saturated steam sterilization (autoclave):

 Most practical & economical & most currently effective sporicide
 Most efficient method for destruction of viral & fungal microorganisms
 Moist heat destroys bacteria by denaturation of the high protein-containing bacteria via heat under
pressure
 121°C (250°F) at 15 psi for 20 min
 Used for wrapped instruments
 To positively destroy all living organisms, the minimum required temperature is 121°C
 So, a case with solder that melts at 175°C is OK
 134°C (270°F) at 30 psi for at least 3 minutes (flash cycle)
 Indicated for unwrapped instruments
 Usually only 10 min required to destroy all bacteria
 Additional time is allowed for penetration when the instruments are wrapped
 Spore forming pathogens provide the ultimate test for efficacy of sterilization
 Resist boiling at 100°C 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:
 320°F (160°C) for 2hrs at 15 psi
 340°F (171°C) for 1hr – also effective
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  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/177°C for Wrapped
 6 minutes at 350 °F/177°C 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
 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:
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  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
 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
 20–30% 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 pt’s
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

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  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 10–30% of exposed, susceptible HC workers
 Concentration of HBV in chronic carrier ranges between 106 & 109 virions per ml, it is
significantly lower for AIDS
 Viral concentration of HCV infected individuals is between HIV & HBV
 Transmission of Hep B – parenteral, dirty instruments, microabrasions, and blood, feces, saliva
 Hepatitis C – transmitted by accidental needle sticks, blood transfusions, drug addicts sharing
contaminated syringes
 Anionic surface acting substances (soaps/detergents):
 These substances alter the nature of interfaces to lower surface tension & increase cleaning
 Their primary value appears to be their ability to remove microorganisms mechanically from the
skin surface
 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
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  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:
 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
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  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 knows…why individuals do NOT have an immune response to
self proteins
 Clonal deletion:
 Immature lymphocytes that make self reactive receptors, are deleted before they are
released to do their thing
 In the medulla of the thymus
 1 of 3 current theories to explain why we don’t 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 costimulator…this is all part of
Congitive Recognition, which is the reason Frogs don’t snap at every black
particle, it must act like a fly…which is the same thing as why our body’s 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 Naïve 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 Naïve 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)

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  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:
 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. pneumoniae’s
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 person’s 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
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 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 mother’s milk)
 Acquired immunity:
 Develops in response to Ag exposure
 Comprised of Ab/s (IgG, IgA, etc) and sensitized lymphocytes (T cells & B cells)
 Specific
 Improves upon repeated exposure to the organism
 Long-term memory
 May have an anamnestic response – subsequent response is faster & bigger
 Due to memory T cells & B cells
 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 (That’s 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

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  Artificial Passive – injection of immune serum or γ-globulin
 If person were given tetanus antitoxin  NOTE Toxin = ANTItoxin
 NOTE: Hypersensitivity – an exaggerated immunological response upon re-exposure to a specific
antigen
 EX – positive skin test after having a disease
 See below for more info on the four types of hypersensitivity reactions
 Immunogens & Antigens:
 Antigen = any substance that can be specifically bound by Ab or a TCR
 Immunogen = an antigen that induces an immune response
 Include all proteins (they are the most antigenic), most polysaccharides, nucleoproteins, and
lipoproteins
 Epitope –
 ON the AntiGEN
 the 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 don’t 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

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  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)
 MHC I Ag loading occurs in rER (viral antigens)
 MHC II: (Think Public Health Inspector—Ate 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
 3rd—CD4 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)

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

 IL-3: T-cell product that stimulates the growth & differentiation of various blood cells in
bone marrow
(B in T-Bone)
Secreted by activated T cells

 IL-4: Secreted by activated helper T cells & mast cells

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

 IL-5: Secreted by activated helper T cells

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

 Acute Phase cytokines  IL-1, IL-6, and TNF alpha (secreted by macrophage to do a bunch of
stuff, 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”
 Binds to the Phagocytes, Mast cells, Basophils, Eosinophils, etc.

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  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 surface…which 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:
 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
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  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

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  Enterosalivary Pathway
(SEE PIC)
 We absorbed antigen in the
gut (via M cell of Peyer’s
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

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 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 don’t need Ab to work like Classical does
 This pathway protects the body in the absence of antibody
 Seems to be of major importance in host defense against bacterial infection
 Activated by invading microorganisms
 Ab independent
 Classical pathway:
 Activated by IgG and IgM (Think GM makes classic cars)
 Activated by Ab-Ag complexes (immune complexes)
 Activated by C1 – binds to a specific part of the Ab
 C1 – composed of three proteins (C1q, C1r, & C1s); Ca2+ is required for activation
 Ab dependent
 NOTE: both pathways lead to cell lysis by terminal components (C8 & C9); initiation differs
 NOTE: C1 esterase deficiency leads to angioedema (overactive complement)
 Membrane attack complex (MAC)
 End product of the activation
 Contains C5b, C6, C7, C8, & C9
 Makes holes in the MBs of G- bacteria & RBCs, resulting in cytolysis
 Biologically important C proteins:
 C2a, C4a = weak anaphylatoxins
 C3a, C5a = strong anaphlatoxins (bigger numbers, bigger response)
 C5a = potent chemotaxin
 C3b = potent opsonin (think C3b-O, like C3PO, O for opsonin)
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 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 donor’s 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
 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

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  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 C3a…1000x more effective than C4a
 Most important chemotactic factor from the complement pathway
 Chemotactic accumulation of inflammatory cells where immune complexes are
deposited is most probably due to the presence of C5a
 Produce smooth muscle contraction, mast cell histamine release, affect platelet aggregation, & act
as mediators of the local inflammatory process
 Anaphylaxis caused by complement components is less common that caused by Type 1 (IgE
mediated) hypersensitivity
 Sensitization
 All of the following require prior sensitization:
 Anaphylaxis (TYPE I), Arthus rxn (TYPE III), Erythroblastosis fetalis, and Contact Dermatitis
(TYPE IV)
 Anaphylactoid reactions do not require prior sensitization
 Uticaria = Hives
 Skin reaction characterized by wheals (small, smooth, slightly elevated areas that are redder or
paler than surrounding skin)
 Can be allergic reaction to food, medicine, or other substance
 1st symptom is usually itching – quickly followed by wheals
 Angioedema:
 Related to & sometimes coexistant w/ uticaria
 The swelling covers large areas & extends deep beneath skin
 Involve part or all of the hands, feet, eyelids, lips, genitals, or even oral mucosa, throat, & airways
(makes breathing difficult)

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 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
 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
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  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 ½ of the cases clear by 3 y.o.
 In adults – chronic or recurring condition
 A hypersensitivity reaction occurs in the skin, causing chronic inflammation
 Result: skin becomes itchy & scaly
 Rhinitis (hay fever & year-around symptoms):
 When the allergen interacts w/ sensitized cell of the upper respiratory tract
 Symptoms – coughing, sneezing, congestion, tearing eyes, & respiratory difficulties
 Histamine is the 1° mediator – released from sensitized mast cells & basophils
 Allergic asthma:
 Allergic reaction primarily affecting the lower respiratory tract
 Common in children
 Characterized by SOB & wheezing
 Specific IgE Ab/s & nonspecific inhaled irritants provoke mast cell degranulation
 Release of histamine & leukotrienes (SRS-As) cause bronchospasm & bronchial
mucus secretions
 Allergic desensitization is produced by competitive inhibition  Basis for allergy
shots
 FIND OUT  What kind of hypersensitivity is it if you take multiple doses of Pen G for
syphilis, and then the ABX seeps into the RBCs?????? – I think Type I

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 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
 Goodpasture’s 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
 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
Abs→Ag-Abs complex in skin
 Immediate type of reaction where Histamine does NOT play a major role

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  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 doesn’t
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 it’s a TYPE IV rxn, which would mean Allergic contact DERMATITIS, then go with
the following!!!
 Type IV reaction due to latex gloves, consists of Macrophages, Lymphokines, and T
lymphocytes
 Allograft rejection
 When a 1st rejected allograft is followed by a 2nd allograft from the same donor…the 2nd
rejection occurs more rapidly than the 1st
 Hence, a reminder that you need presensitization
 Primary tissue transplant, such as allogenic skin, kidney or heart, are most commonly
rejected due to
 Cell-mediated immune responses to cell-surface autoantigens
 Similarities between Type I and IV???
 Complement OR Response after 24 hours???
 Thymectomized and nude mice:
 Have reduced numbers of T-lymphocytes
 Can’t reject allografts
 Have reduced Ab production to most antigens – no helper Ts
 Have decreased or absent delayed type IV hypersensitivity

Classification of Hypersensitivity Reactions

Type Immunologic Mechanism Example
Type I (anaphylactic IgE antibody mediated – mast cell Hay fever, asthma, anaphylaxis,
type): Immediate activation & degranulation atopic dermatitis, eczema
hypersensitivity
Type II (cytotoxic type): Cytotoxic (IgG, IgM) antibodies Autoimmune hemolytic
Cytotoxic antibodies formed against cell surface antigens. anemias, antibody-dependent
Complement is usually involved cellular cytotoxicity (ADCC),
Goodpasture’s syndrome
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Type III (immune Antibodies (IgG, IgM, IgA) formed
complex type): Immune against exogenous or endogenous
complex disease antigens. Complement and leukocytes
(neutrophils, macrophages) are often
involved
Type IV (cell mediated Mononuclear cell (T lymphocytes,
type): Delayed type macrophage) w/ interleukin and
hypersensitivity lymphokine production
*Q answer: sensitized lymphocytes
SLE, rheumatoid arthritis, most
types of glomerulonephritis,
arthus rxn, serum sickness
Granulomatous disease
(Tuberculosis, Sarcoidosis,
Crohn’s, Fungus), contact
dermatitis, graft rejection

Blood Group Ag/s (agglutinogens) on Antibodies (agglutinins) in

erythrocytes plasma
O (universal donor) *none* Anti A & Anti B
A A Anti B
B B Anti A
AB (universal recipient) A & B (alloantigens – both A & *none*
B)

 Autoantibodies
 Anti-nuclear antibodies (ANA) Systemic Lupus
 Anti-dsDNA, anti-Smith Specific for Systemic Lupus
 Anti-histone Drug-induced Lupus
 Anti-IgG Rheumatoid arthritis
 Anti-neutrophil Vasculitis
 Anti-centromere Scleroderma (CREST)
 Anti-Scl-70 Sclerderma (diffuse)
 Anti-mitochondria 1ary biliary cirrhosis
 Anti-gliadin Celiac disease
 Anti-basement membrane Goodpasture’s syndrome
 Anti-epithelial cell Pemphigus vulgaris
 Anti-microsomal Hashimoto’s 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:

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  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
 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
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  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

 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 (50–75%)
 Increase dramatically in response to infection/inflammation
 Fxns:
 Phagocytosis of bacteria
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  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
 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:
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  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
 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:
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 The initial response of tissue to injury, particularly bacterial infections, involving vascular and
cellular responses
 What is involved in the early phase of wound repair?
 Inflammatory  bacteria and debris are phagocytosed and removed, factors are released
that cause the migration and division of cells involved in proliferative stage
 Proliferative and Maturation are more in chronic
 Three major phenomena:
 1) Increased vascular permeability – tissue exudate forms
 Mean capillary pressure decrease and osmotic pressure decreases in acute
inflammation
 2) Leukocytic cellular infiltration – mainly PMNs via C5a & C3a
 3) Repair – regeneration or replacement
 Chemotactic accumulation of mononuclear cells which occurs at the sites where immune
complexes were deposited is probably the result of C3 (only if C5a is not an answer)
 Local signs:
 Redness = rubor, Heat = calor, Swelling = tumor, Pain = dolor, organ dysfunction
 Systemic effects:
 Fever, Tachycardia, Leukocytsosis (esp. PMNs)
 Vascular phase:
 Vasoconstriction (temporary) – seen as blanching of skin
 What happens before Vasodilation in inflammation???  Vasoconstriction
 Only transient
 Vasodilation – increased blood flow to infected area
 Happens immediately after vasoconstriction
 Done by Histamine, Bradykinin, and Serotonin
 The 1st vascular reaction (following transient vasoconstriction) to injury in the sequence of
events in inflammation
 Increased permeability – allows diffusible components to enter the site
 Congestion in the early stages of inflammation is caused by active hyperemia (NOT
ischemia, venous dilitation, venous constriction, lymphatic obstruction)
 Cells
 Basophils, Mast cells, Platelets – present in vascular phase – all release histamine
 Vasodilation and increased permeability lasting for several days in an area of inflammation
indicate
 Endothelial cell damage and dysfunction
 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:
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  Develops at a site of injury that persists longer than several days
 Cells: Lymphocytes, Macrophages, and Plasma Cells – not PMNs or Mast Cells
 Necrosis commonly occurs & recurs
 EXs: chronic hepatitis, pyelonephritis, and autoimmune diseases
 Granulomatous inflammation:
 A subtype of chronic inflammation characterized morphologically by granulomas
 Proliferative processes dominate (NOT exudation, transudation, and congestion)
 Characterized by a circumscribed collections of lymphocytes, macrophages, epitheliod
cells with a background of fibroblasts, capillaries, and delicate collagen fibers
 EXs: TB, sarcoidosis, & silicosis
 Vasodilation & ↑vasopermeability lasting several days in inflamed area indicate formation of
granulation tissue
 Initial vasodilation of inflammation is due to serotonin, histamine, bradykinin
 SIDENOTE
 Chronic Granulomatous Disease
 Hereditary disease where neutrophil granulocytes are unable to destroy ingested pathogens
 Neutrophils normally require a set of enzymes to a reactive oxygen species to destroy bacteria
after their phagocytosis
 These NZs are called phagocyte NADPH oxidase complex, which is responsible for
initiating the respiratory burst
 SO in CGD, PMNs ingest baceria but then cannot kill them
 MOST infections are caused by Staph Aureus, or CATALSE + bugs
 Hence bugs that destroy the respiratory burst are left behind to cause chronic GD
 Inflammatory Infiltrate
 Fluids, PMNs, and Macrophages
 Exudates:
 Principally water – also contains nutrients, oxygen, Ab/s & WBCs
 Characterized by being protein-rich, cell-rich, glucose-poor & has a high specific gravity (>
1.020)
 First role – flush away any foreign material from site of injury
 If fluid is cloudy/discolored – strong indication of infection
 Acts as a carrier to bring fibrin, etc., to the site of injury
 Acts as a carrier for leukocytes – provides oxygen/nutrients for ingestion of bacteria & debris
 Nutrients are used by the new tissue to help in the generation of granulation tissue
 Act as a lubricant, speeding up epithelial cell migration across wound surface to complete initial
repair
 Types of imflammatory exudates:
 Suppurative
 Purulent
 Fibrinous
 Pseudomembranous
 Serous
 NOT Fibrous
 Acute inflammatory exudates
 Includes Plasma fluid, plasma proteins and WBCs
 NOT Plasma cells

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 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
 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) – body’s 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

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  Girl with ulcerated lesion on tongue has Langerhans cells and granulomatosis, what is
the disease???
 Tuberculosis Granuloma???
 Fungal infections – blastomycosis, histoplasmosis, & coccidiomycosis
 Spirochetes: T. pallidum, which causes syphilis
 Cat scratch disease – caused by Bartonella henselae
 Foreign material – suture or talc
 Sarcoidosis – unknown etiology, NON-caseating, NON necrotizing (whereas tuberculosis
is caseation necrosis)!!!!!
 Crohn’s 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:
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 Growth of tissue that forms an abnormal mass
 Caused by abnormal regulation of cell division
 Generally provide no useful function & grow at the expense of healthy tissue
 Necrosis:
 Set of morphologic changes that accompany cell death w/in a living body
 Differs from autolysis – a process of cell death outside a living body
 May manifest in different ways, depending on the tissue or organs involved
 Coagulative necrosis is the most basic and most common type of necrosis
 When larger areas of tissues are dead, the tissue is called gangrene

Types Causes Most likely sites involved

Coagulation necrosis Ischemia (loss of blood supply) Heart & kidney (renal &
cardiac infarcts)
Liquefaction necrosis (infarct Suppuration, abscesses & ischemic Brain or spinal cord
to brain) CNS injury
Caseous necrosis (Caseation) Granulomatous inflammation Granulomatous inflammatory
(typical of TB) sites
Calcification and “Soapy” – Think
Cheesy TB Lesion
Gangrenous necrosis Putrefactive bacteria acting on Lower extremities or bowel
necrotic bowel or extremity
Fibrinoid necrosis Immune-mediated vascular damage Arterial walls (RA,
Scleroderma, RF)
Fat necrosis Injured pancreas, trauma to adipose Adipose tissue, pancreas
tissue
 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 artery…anticipated 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
 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
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  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
 Treponema, Bacteroides, Actinobacillus, and Fusobacterium
 NOT Mycobacteria
 Actinomyces naeslundii
 Branching, filamentous microorganism that is a normal inhabitant of the gingival
crevice and tonsilar crypts

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  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)
 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)

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  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):
 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)
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  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 –
 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

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  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): “Vincent’s 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
 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 it’s 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

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  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!!!!!
 Ludwig’s angina:
 Aka “submandibular space infection” or “sublingual space infection”
 Not often seen
 An extension of infection from the Mn molar teeth into the floor of mouth
 Characteristics:
 First – brawny induration that doesn’t 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
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  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”
 Behcet’s 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
 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
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  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
 Barrett’s esophagus: BARRett’s = 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 (Auerbach’s)
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
 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., Zenker’s diverticulum), Esophageal web/EtOH, Familial
 Most common malignant neoplasm of the esophagus is a squamous cell carcinoma – not
adenocarcinoma from Barrett’s
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??
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  NOT associated with Smoking????
 Chronic gastritis:
 Type A (fundal): (most superior part)
 Think 4 A’s  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 smoke…very 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
 Diet changes don’t 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
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  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 Brunner’s glands
 Tend to have clean “punched out” margins unlike the raised/irregular margins of carcinoma
 Not associated w/ corticosteroids and alcohol
 20% aren’t related to H. pylori (other source says that almost 100% are caused by H. pylori),
NSAIDs or elevated gastrin & are idiopathic
 Tx of H. pylori w/ triple therapy:
 metronidazole, bismuth salicylate, & amoxicillin or tetracycline
 Zollinger-Ellison syndrome (uncommon):
 Gastrin-producing tumor leading to increased HCl & multiple persistant ulcers
 Usually located in the pancreas
 May be associated with MEN Type I
 50% are malignant
 A decubital ulcer is an example of tissue destruction caused by ischemia – (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 doesn’t get into stomach.
 BUT…Smoking about doubles the risk of stomach cancer for smokers – American Cancer
Society
 Termed linitis plastica when diffusely infiltrative (thickened, rigid appearance)
 Associated:
 Virchow’s node: involvement of supraclavicular node by metastasis from stomach
 Krukenberg’s tumor: bilateral metastasis to ovaries. Abundant mucus, signet-ring cells
SMALL INTESTINE
 Meckel’s 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
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 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,
doesn’t 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
 Motility disorder: irritable bowel syndrome, surgical bypass
 Tx: treat underlying cause, opiates to slow peristalsis (except in acute infx), replace lost fluids
 Bismuth subsalicylate—inhibit 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 Crohn’s 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 Symptoms

Deficiency
Vitamin B1 Wet beriberi, dry beriberi High cardiac output; Pins and needles sensation,
(thiamine) peripheral neuropathy especially in feet
Vitamin B2 Cheilosis; glossitis Skin fissures at angle of Sore tongue and cracks at
(riboflavin) mouth; inflammation of edge of mouth
tongue
Vitamin B3 Pellagra Dementia, dermatitis, &
(niacin) diarrhea
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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 Anemia, pins and needles
B12 pernicious anemia) predominant # of sensation
(cobalamin Neurologic dysfunction megaloblasts & few
) normoblasts
Folic acid Megaloblastic anemia Anemia w/ a predominant Anemia
Neuroligic dysfunction is # of megaloblasts
not a feature (abnormally large
nucleated RBCs)
Vitamin C Scurvy, defective formation Swollen, bleeding gums, Weakness, bleeding gums
(ascorbic of mesenchymal tissue & muscle, joint, & bone
acid) osteoid matrix; defective pain, abnormal bleeding
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
 Whipple’s disease:
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  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:
 Disorder of children & young adults in which lymph vessels supplying the lining of small
intestines enlarges
 Main symptom = massive fluid retention
LARGE INTESTINE
 Hirschsprung’s disease:
 Think you bowels Have SPRUNG out of control (Parasympathetic)
 Congenital megacolon characterized by lack of enteric nervous plexus in segment (Auerbach’s
and Meissner’s 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
 Meckel’s 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
 Crohn’s disease & Ulcerative colitis
Crohn’s 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

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Microscopic Noncaseating granulomas Crypt abscesses and ulcers
morphology
Complications Strictures, fistulas, perianal disease, Severe stenosis, toxic
malabsorption—nutritional depletion megacolon, colorectal
carcinoma
Extraintestinal Migratory polyarthritis, erythema nodosum Pyoderma gangrenosum,
manifestation sclerosing cholangitis
 Crohn’s 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 Crohn’s, 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/ Gardner’s 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)
 Gardner’s syndrome:
 Type of hereditary polyposis
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  Autosomal Dominant
 Various types of noncancerous tumors occur in intestines & elsewhere in the body
 Characterized by polyposis of the colon
 Carries a high risk of colon cancer
 Peutz-Jehgers syndrome: (Polyps – Jejunum Syndrome)
 Condition in which many small lumps (juvenile polyps) appear in a variety of sites in the
GI tract
 Most common site = small intestine (esp. jejunum)
 Hereditary condition affecting males/females equally
 Characterized by melanin pigmentation of oral mucosa, especially of lips & gums
 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,
that’s 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, Meckel’s 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)
 BUT…Recent studies have shown that smokers are 30-40% more likely to die of colorectal
cancer than nonsmokers – American Cancer Society
 Intussusception: telescoping of one bowel segment into distal segment; can compromise blood supply
(Like a telescope)
 Volvulus: twisting of portion of bowel around its mesentery; can lead to obstruction
APPENDIX
 Appendicitis:
 Possible sequelae of acute appendicitis: general peritonitis, periappendiceal abscess formation,
pylephlebitis, hepatic abscess
 Sudden inflammation of the appendix
 One of the most common causes of emergency abdominal surgery in children
 More common in males – peak in the teens & early 20s
 Leukocytosis is a “Sign” of appendicitis
 Generally follows obstruction of the appendix by feces, a foreign body, or a tumor (rare)
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  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 “McBurnery’s 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:
 Crohn’s (Left)
 Meckel’s 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
 Hemmorrhage
 Inlammation
 Fat necrosis
 Parenchymal necrosis
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  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 pt’s 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’/Plummer’s
 Hypo (Myxedema/Cretinism) Hashimoto’s
 Adrenal
 Hyper Cushing’s
 Hypo Addison’s
HEAD / BRAIN PROBLEMS
 One out-of-place congenital problem:
 Neural tube defects:
 associated w/ high levels of alpha fetoprotein in the amniotic fluid and maternal serum.
Their incidenc is decreased w/ maternal folate ingesting during pregnancy
 Spina bifida occulta:
 failure of bony spinal canal to close, but no structural herniation. Usually seen in lower
vertebral levels in association w/ tuft of hair (associated with increased levels of AFP)
 Meningocele:
 meninges herniate through spinal defect
 Meningomyelocele:
 meninges and spinal cord herniate through spinal canal defect
 Anencephaly: no development
 Concussion:
 Transient paralysis of cerebral function immediately after head trauma
 Manifested by dizziness, cold perspiration, visual disturbance & loss of consciousness
 Most people recover completely w/in a few hours or days
 Contusion:
 Bruise of the brain parenchyma typically involving the subunit of the gyrus
 Brain Tumors
 Adult
 70% above Tentorium (i.e. cerebral hemispheres)
 Incidence: Metastases > Astrocytoma (including glioblastoma) > Meningioma
 Child
 70% below Tentorium (i.e. cerebellum)
 Incidence: Astrocytoma > Medulloblastoma > Ependymoma
 Subdural head injury:
 Traumatic subdural hematomas are among the most lethal of all head injuries, common
during abuse cases

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  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 trauma→dx:
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 Marfan’s
syndrome
 May result in cerebrovascular accident
 Parenchymal Hematoma
 Caused by HTN, amyloid angiopathy, DM, and Tumor
 Meningioma:
 Intracranial tumor arising from arachnoid, usually occurring in adults >30 y.o.
 Cerebral infarction (stroke):
 Infarction of cerebrum due to arterial occlusion by a thrombus or embolus from the heart or
carotid artery
 Common signs/symptoms – sudden paralysis & numbness on one side of body
 Encephalitis:
 An uncommon inflammation of the brain
 Most commonly caused by VIRAL infection –Like HSV
 Exposure to viruses via:
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  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
 Don’t 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
 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)
 Don’t 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
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  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:
 Alzheimer’s disease:
 Most common cause of dementia in the elderly
 Multi-infarct dementia is the 2nd most common cause
 Associated w/ senile plaques (beta amyloid core) & neurofibrillary tangles (abnormally
phospharylated tau protein)
 Gross cortical atrophy
 Familial form (10%) associated w/ specific genes
 Pick’s disease:
 Associated w/ Pick bodies (intracytoplasmic inclusion bodies) & is specific for the
frontal & temporal lobes
 Basal ganglia and brain stem:
 Huntington’s disease:
 Autosomal dominant inheritance, choréa, dementia
 Atrophy of caudate nucleus (loss of GABA neurons)
 Parkinson’s 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
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  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 Gehrig’s 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 Can’t 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 body’s own immune cells attack nervous system
 Inflammation destroys myelin sheath in that area, leaving multiple areas of scar tissue
(sclerosis) along the myelin
 Results in slower transmission of nerve impulse, leading to symptoms of MS
 Affects approximately 1/1000 – women more commonly affected
 Commonly begins between 20-40 y.o.
 Characterized by paresthesia, unsteadiness of gait, incontinence, paralysis, and plaques
of demyelination
 Plaques are evident in the white matter
 Large amounts of protein are found in CSF
 Injectable interferon reduces frequency of MS relapses
 Periventricular plaques, preservation of axons, loss of oligodendrocytes, reactive astrocytic
gliosis
 Patients present w/ sudden loss of vision
 Classic triad is: Think SIN  Scanning speech, Intention tremor, and Nystagmus
 Increase incident w/ increased distance from equator
 Progressive multifocal leukoencephalopathy:
 Associated w/ JC virus and seen in 2-4% of AIDS patients (reactivation of latent viral
infection)
 Postinfectious Encephalomyelitis
 Metachromatic Leukodystrophy
 Guillain Barre syndrome: (Guillen can’t 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
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  Facial diplegia in 50% of cases
 Autonomic function may be severly affected (eg., cardiac irregularities, hypertension)
 Findings include: elevated CSF protein w/ normal cell count (“albumino-cytologic
dissociation) and elevated proteinpapilledema
 Associated with C. jejuni or herpesvirus, but non definite link to pathology
 Seizures:
 Causes
 Children  Genetic, infection, trauma, congenital, metabolic
 Adults  Tumors, trauma, stroke, infection
 Elderly  Stroke, tumor, trauma, metabolic, infection
 Partial seizures: 1 area of the brain
 They can secondarily generalize
 Simple partial (awareness intact): motor, sensory, autonomic, psychic
 Complex partial (impaired awareness)
 Generalized seizures:
 Absence: blank stare (petit mal)
 Myoclonic: quick, repetitive jerks
 Tonic clonic: alternating stiffening and movements (grand mal)
 Tonic: stiffening
 Atonic: “drop” siezures
 Aphasia:
 Broca’s (expressive): nonfluent aphasia w/ intact comprehension: Broca’s area—inferior frontal
gyrus
 Think Broca for Broken speech
 Wernicke’s (receptive): fluent aphasia w/ impaired comprehension. Wernicke’s area—superior
temporal gyrus
 Wernicke’s 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
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  ~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 it’s 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
 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

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  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
 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 –Don’t 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)

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  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
 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
 Wilson’s disease
 (A hereditary accumulation of copper in the liver, kidney, brain, and cornea)

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  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)
 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)
 Reye’s 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
 Wilson’s 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
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 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
 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 pt’s 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:
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  Elevated transaminases, hyperbilirubinemia, elevated alkaline phosphatase
 Most patients recover fully
 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: Pt’s lab results show both the HBs and anti-HBs…means 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
 Most common reason for liver transplantation in the U.S.
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  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 can’t get down into the intestine where it is made
 (pt does NOT have aplastic anemia, hemolytic anemia, acute hepatitis, or alcoholic
cirrhosis)
 Types:
 Cholesterol stones (radiolucent w/ 10-20% opaque due to calicifications):

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  Associated w/ obesity, Crohn’s 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 (don’t get clowned by angiotensin)
 Does not directly invoke vasodilation
 Proteolytic enzyme formed in kidney & released into bloodstream where it has an important role
in activating angiotensin
 Produced by & stored in the juxtaglomerular apparatus that surrounds each arteriole as it enters a
glomerulus
 Release is controlled by activity of sympathetic nerves to kidney & renal arterial BP (if ↓ pressure,
renin secretion ↑)
 Acts on angiotensinogen (manufactured by the liver & present in the blood)
 Converts angiotensinogen to angiotensin I
 In turn AT I is converted to AT II by ACE – associated w/ capillary walls, particularly in the
lungs
 AT II stimulates aldosterone release from the zona glomerulosa of the adrenal cortex
 Aldosterone causes Na+ retention by enhancing Na+ reabsorption by distal convoluted
tubules & collecting ducts
 Nephrolithiasis (Kidney Stones)
 Presence of renal calculi (kidney stones) w/in renal pelvis or calyces
 Calcium stones are the most commonly occurring form of nephrolithiasis
 Most likely the result from Hyperparathyroidism
 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

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  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:
 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:
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  UTI
 Dysuria, Frequency, suprapubic pain
 Most common causing bugs are E. Coli and Proteus
 Staph saprophyticus is 2nd common cause in young ambulatory women
 Think 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
 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
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  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
 Goodpasture’s syndrome  Type II Hypersensitivity, Linear pattern, anti GBM
antibodies
 Membranoproliferative glomerlonephritis  Subendothelial humps, tram track
 IgA Nephropathy (Berger’s disease)  Mesangial deposits of IgA
 Glomerluar inflammation resulting in sudden appearance of hematuria w/ clumps of RBCs
(casts) & variable proteinuria
 Most common in 3-7 y.o. boys
 Starts suddenly and usually resolves quickly
 Associated with destruction of basement membranes via PMNs (NOT lymphokines,
eosinophils, or IgE Ab/s)
 Elevated antistreptolysin O (ASLO) titers
 Low serum complement
 3) Chronic nephrotic syndrome
 Aka chronic glomerulonephritis
 Slowly progressive disease characterized by glomerular inflammation resulting in sclerosis,
scarring & renal failure
 Conditions that can lead to chronic GN – SLE, Goodpastures’ syndrome, & acute GN
 4) Rapidly progressive glomerulonephritis (RPGN)
 Aka ‘rapidly progressive nephritic syndrome’ or ‘crescentic GN’
 May be idiopathic or associated w/ a proliferative glomerular disease such as acute GN
 Uncommon disorder in which most of the glomeruli are partly destroyed, resulting in kidney
failure
 Starts suddenly & worsens rapidly
 Occurs most commonly in 50-60 y.o. people
 Glomerular diseases:
 Damage to glomeruli caused by antibodies directed against glomerular basement membrane
or antibody-antigen complex deposition in which complement helps or hurts condition
 Hematuria, proteinuria, and renal insufficiency are hallmarks and renal biopsy is needed to
establish diagnosis
 Renal Insufficiency
 May produce Parathyroid Hyperplasia
 I think it has to do with lacking the Vitamin D formation, so PTH has to work harder to
increase serum Ca
 May have a hemorrhagic tendency
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 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 (BUN—normal 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
 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
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  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:
 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 Gierke’s disease: Think VON GlyKe’s
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  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
 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)

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  Hemorrhagic (red) infarcts most commonly found in the LUNG (NOT brain, spleen, or
kidney)
 Even if there’s 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
 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
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  Elevated cold agglutinins
 Bronchopneumonia:
 Affects infants & elderly
 Inflammation of the walls of the smaller bronchial tubes
 Also spread of inflammation into alveoli & alveolar ducts
 Patchy distribution of lobular inflammation; not just the bronchus itself
 B for Bacteria
 S. aureus, H. flu, Klebsiella, S. Pyogenes
 Lobar pneumonia:
 Diffuse distribution of inflammation
 Pneumococcus most frequent (Strep pneumoniae)
 Affects middle-aged people
 Marked by fever, chest pains, cough & blood-stained sputum
 Rusty sputum
 Inflammation & consolidation of one or more lobes of the lunugs
 Chest pain associated w/ lobar pneumonia attributable to coexistent pleurisy
(inflammation of pleura)
 Diplococcus pneumoniae
 The essential antigen which determines both its virulence & its specific type is the distinct
capsular polysaccharide
 Common Causes of Pneumonia
 Children (6 wk – 18 y) Viruses (RSV), Mycoplasma, Chlamydia pneumoniae, S. pneumoniae
 Adults (18 y – 40 y)  Mycoplasma #1 in Young Adults (THEY WALK a LOT), Chalymdia
pneumoniae, S. pneumoniae
 Adults (41 y – 65 y)  S. pneumoniae, H. influenzae, Anaerobes, Viruses, Mycoplasma
 Elderly (65+)  S. pnuemoniae, Viruses, Anaerobes, H. influenzae, Gram – rods
 Special Types of Pneumonia
 Nosocomial Staph, Gram – rods
 Immunocompromised Staph, Gram – rods, Fungi, Viruses, PCP
 Aspiration Anaerobes
 Alcoholic/IV drug user S. pneumoniae, Klebsiella, Staph
 Postviral Staph, H. influenzae
 Neonate Group B Strep, E. coli
 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
It’s 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
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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:
 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
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 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
Chronic bronchitis Productive cough characterized by hypersecretion of mucus
Emphysema (pulmonary Often coexists w/ chronic bronchitis, labored breathing, and
emphysema) an increased susceptibility to infection
Bronchiecstasis 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 (that’s 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
 Here’s 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
 ½ 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 – ½ 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 β2-agonist (terbutaline, albuterol)
 Status asthmaticus
 Particularly severe episode of asthma
 Usually requires hospitalization
 Does not respond adequately to ordinary therapeutic measures
 Emphysema: (pink puffer)
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  Form of COPD that involves damage to the air sacs (alveoli)
 Air sacs are unable to completely deflate (hyperinflation) – unable to fill w/ fresh air to ensure
adequate O2 supply to body
 Characterized by normal or increased lung capacity
 Lack of elastic recoil in the lungs
 Generally bilateral
 More common in males
 May lead to cardiac failure
 Is a significant public health problem
 Does NOT show hemoptysis
 A tissue change, rather than mucous production (seen in asthma & chronic bronchitis)
 Cigarette smoker with gradual onset of progressive, labored breathing, with prolonged expiratory
effort
 Labored breathing
 Show Pursed Lips
 Dyspnea, decrease in breathing sounds, tachycardia and decreased I/E ration
 Increased susceptibility to infection
 May be fatal, results from degenerative atrophy; and may be secondary to bronchial
inflammatory disease
 Two problems:
 1) Lungs are fixed in inspiration
 2) Respiratory surfaces of lungs have deteriorated so much that they no longer adequately
exchange gases
 Complete blood count likely shows polycythemia
 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
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  Strong association w/ smoking
 Common results of chronic bronchitis:
 Cor pulmonale (enlargement of the right ventricle) – from working too hard to push blood
through pulmonary system
 Airway narrowing
 Obstruction of the bronchial tree along w/ squamous metaplasia
 Squamous metaplasia is most commonly encountered in the bronchial mucosa (NOT
stomach, oral mucosa, etc.)
 Characteristic pathologic change:
 Hyperplasia of bronchial submucosal glands & bronchial smooth muscle hypertrophy
 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 can’t blow as fast, so less than
80% of the volume is out at 1 second
 Types:
 Poor breathing mechanics (extrapulmonary): poor musclar effort—polio, myasthnia gravis;
poor apparatus—scoliosis
 Interstitial lung disease (pulmonary): adult respiratory distress syndrome, neonatal respiratory
distress syndrome, pneumoconiosis, Sarcoidosis, Goodpasture’s
 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 macrophages…creates intensly pigmented areas
 Silicosis:
 Aka Stone Mason’s 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 Worker’s 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 pt’s lungs
 Goodpasture’s syndrome:
 Anti-glomerular basement membrane antibodies produce linear staining on
immunofluorescence
 Findings: pulmonary hemorrhage leading to hemoptysis; renal lesions lead glomerulonephritis w/
hematuria
 This is a type II hypersensitivity
 Think GP  Good Pasture, Glomerular and Pulmonary
 Most common in men between ages 20-40
 Cystic Fibrosis
 Autonomic recessive disorder – heterozygotes unaffected
 Generalized dysfunction of the exocrine glands affecting multiple organ systems
 Inherited disease caused by a defective gene, chromosome 7q
 The gene encodes a MB-associated protein called “cystic fibrosis transmembrane regulator
(CFTR)”
 Is thought to regulate Cl– & Na+ across epithelial MBs
 Results in defective Cl- channels, leading to very thick mucous secretions
 Has elevation of Na+ and Cl- secretions
 Affects mucus & sweat glands & Na+ channels
 Causes respiratory & digestive problems
 Thick mucus forms in breathing passages of lungs & predisposes pt to chronic lung infections
 Effects males & females – life expectancy = 28 yrs
 Present usually in 1st year of life w/ steatorrhea
 Most common fatal genetic disease in white children
 Dx with Sweat Chloride test (elevated Cl- in sweat)
 Complications include:
 Pulmonary disease, pancreatic insufficiency, & meconium ileus (form of intestinal obstruction
in newborns)
 Lung abscess:
 Pus-filled cavity in the lung surrounded by inflamed tissue & caused by infection
 Most common cause is aspiration – often in the settings of altered consciousness
 Associated with aspiration of material from caries teeth
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  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 – You’re 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
 Kartagener’s syndrome:
 Think Can’t 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
 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.

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  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 – can’t 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
 Pancoast’s tumor:
 May result from intrathoracic spread of bronchogenic cancer
 Carcinoma that occurs in apex of lung and may affect cervical sympathetic plexus,
causing Horner’s 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
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 Horner’s syndrome

HEART DISORDERS
 CONGENITAL HEART DEFECTS:
 Infective endocardititis
 The following are predisposers:

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  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 T’s  Tetralogy, Transposition, Truncus
 Eisenmenger’s
 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
 Eisenmenger’s syndrome:
 Uncorrected ventricular septal defect, arterial septal defect & patent ductus arteriosus leads
to progressively pulmonary HTN
 As pulmonary resistance increases, the shunt changes from left to right to right to left, which
causes late cyanosis (clubbing and polycythemia)
 Coarctation of aorta:
 Infantile type (preductal): aortic stenosis proximal to insertion of ductus arteriousus. Male to
female 3:1
 INfantile: IN close to the heart (associated w/ Turner syndrome)
 Adult type (postductal): stenosis distal to ductus arteriosus, associated w/ notching of the ribs,
hypertension in upper extremities, weak pulses in lower extremities
 aDult: Distal to Ductus
 PERICARDITIS:
 Causes  infection, ischemic heart disease, chronic renal failure, CT diseases
 Effusions are usually serious; hemorrhagic effusion are associated with TB and malignancy
 Findings  Pericardial pain, friction rub, EKG changes, Pulsus paradoxus
 Can resolve w/o scarring or lead to chronic adhesive or chronic constrictive pericarditis
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  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:
 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
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  Contributing factors include chronic HTN and high levels of LDLs
 NOT Usually results from complete occlusion of one or more coronary arteries
 Doesn’t 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
 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 2-
7 days post-MI
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  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:
 Cardiac arrhythmia (90%), highest rise 2 days postinfarct
 LV failure and pulmonary edema (60%)
 Thromboembolism—mural 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 infarct—highest risk of mortality)
 Rupture of ventricular free wall, interventricular septum, papillary muscle (4 – 10 days
post MI), cardiac tamponade
 Fibrinous pericarditis—friction rub (3-5 days post MI)
 Dressler syndrome—autoimmune 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, β-hemolytic streptococcus
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 Secondary infection from Group A strep, due to autoimmune, not from bacteria
 Can be a sequelae to Scarlet Fever
 Most common in children 5-15 y.o.
 Onset is usually sudden
 Occurs 1-5 symptom-free wks following recovery from sore throat or scarlet fever
 Mild cases may last 3-4 wks, severe cases may last 2-3 months
 Treatment – penicillin & rest
 Although RF may follow a streptococcal infection, it is not an infection
 It is an inflammatory reaction to an infection
 Heart is damaged because of a hypersensitivity rxn to group A, Beta Hemolytic streptococci
 Clinical Dx – requires 2 major criteria or 1 major + 2 minor (the Jones criteria)
 Major – carditis, arthritis, chorea, erythema marginatum & subcutaneous nodules
 Minor – fever, arthralgias (joint pain w/o inflammation), Hx of RF, EKG changes & lab
tests
 Heart inflammation
 A pt with rheumatic heart disease would most likely develop congestive heart failure due to
valvular insufficiency
 Disappears gradually, usually w/in 5 months
 May permanently damage heart valves – resulting in rheumatic heart disease
 Mitral valve (between left atrium & ventricle) is most commonly damaged
 Valve may become leaky (mitral valve regurgitation) abnormally narrow (mitral valve
stenosis) or both
 Classic lesion of rheumatic fever is the Aschoff body – FEVER Causes ASHES
 An area of focal interstitial myocardial inflammation
 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
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 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
 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
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  Retention of H2O and NaCl
 Decreased GFR
 Cells of Heart Failure:
 Hemosiderin-laden macrophage in alveoli, aka siderophore
 Hemosiderin in the lungs is caused by…Heart 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 – α-hemolytic strep causes ~½ of cases
 Most common cause from a dental procedure  S. viridans
 Other common organisms: Staph, Group D Strep
 Less common organisms: Pseudomonas, Serratia, Candida
 Can cause growths on heart valves, lining of heart or lining of the BVs
 Fused platelets, fibrin, bugs are found in vegetation due to bacterial endocarditis
 Growths may be dislodged & send clots to brain, lungs, kidneys or spleen
 Health care provider may hear changing murmurs & detect enlarged spleen & mild anemia
 Murmurs result from changes in valvular blood flow when clumps of bacteria, fibrin & cellular
debris collect on valves
 Self-infection (esp. by IV drug users) w/ S. aureus causes most severe damage (acute
endocarditis)
 Endocarditis on right side of the heart suggests IV drug abuse
 Symptoms:
 Fever is hallmark – may be present daily for months before other symptoms appear
 Fatigue, headache, malaise, night sweats
 Janeway lesions (small red lesions on palm/sole) – Roth’s spots (round white spots on retina
surrounded by hemorrhage)
 Nail bed (splinter) hemorrhages – Osler’s nodes (tender raised lesions on finger or toe pads)
 Fever – Anemia – Murmur – Emboli
 Think JR = NO FAME  Janeway Lesions, Roth’s spots, Nail-bed hemorrhage, Osler
nodes, Fever, Anemia, Murmur, Emboli
 TYPES OF ENDOCARDITIS:
 Acute bacterial endocarditis: HIGH VIRULENCE
 STAPHylococcus aureus
 Large vegetations on previously normal valves, rapid onset
 Subacute bacterial endocarditis: LOW VIRULENCE
 STREPtococcus viridans
 The most common organism producing subacute bacterial endocarditis is alpha-
hemolytic streptococcus
 (S. sanguis, which is a Viridans Streptococcus)
 Smaller vegetations on congenitally abnormal or diseased valves
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  Sequela of dental procedures
 More insidious onset than Acute
 Tetralogy of Fallot, Congenital aortic stenosis; Patent ductus arteriosus; & Ventricular
septal defect are all at risk of developing secondary endocartitis
 MYOCARDITIS = Cardiomyopathy:
 Disease of myocardium w/ unknown etiology
 Dilated (congestive) cardiomyopathies: heart dilates and looks like a balloon on chest X ray
 Systolic dysfunction ensues
 most common 90% of casts
 Think ABCsDs  Alcohol, Beriberi, Coxsackie B, Cocaine, Chagas’ disease,
Doxorubicin, Diastolic Dysfunction
 Hypertrophic cardiomyopathy (formerly IHSS):
 Diastolic dysfunction ensues
 often asymmetric and involving the intraventricular septum.
 50% of cases are familial and are inheritied as an autosomal-dominant trait
 Cause of sudden death in young athletes
 Walls of LV are thickened and chamber becomes banana shaped on echocardiogram
 Restrictive/obliterative cardiomyopathy:
 major causes include sacroidosis, amyloidosis, scleroderma, hemochromatoisis, endcardial
fibroelastosis, and endomyocaridal fibrosis (Loffler’s)
 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
 Buerger’s Disease
 Known as smoker’s disease and thromboangitis obliterans
 Idiopathic, segmental, thrombosing vasculitis of intermediate and small peripheral arteries
and veins
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  Findings  Intermittent claudication, superficial nodular phlebitis, cold sensitivity, severe pain in
affected part, may lead to gangrene
 Tx with Cessation of Smoking
 Don’t smoke in Burger King
 VS. Raynaud’s Disease
 Symmetric asphyxia (impaired oxygen exchange); idiopathic paroxysmal bilateral
cyanosis of the digits due to arterial and arteriolar contraction
 Caused by cold or emotion
 Takayasu’s Arteritis
 “Pulseless Disease”
 Thickening of aortic arch and/or proximal great vessels, causing weak pulse in upper extremeities
and ocular disturbances
 Associated with elevated ESR
 Think FAN My Skin  Fever, Arthralgia, Night sweats, MYalgia, SKIN nodules


HEMODYNAMIC DYSFUNCTION
 Edema
 Abnormal accumulation of fluid in the interstitial spaces or body cavities
 Edema due to hemodynamic dysfunction may result in the brain, lung, subcutaneous tissue,
peritoneal cavity
 NOT the pancreas
 May result from:
 Increased capillary permeability (principal factor)
 Elevated capillary pressure
 Increased interstitial fluid colloid osmotic pressure
 Decreased plasma colloid osmotic pressure
 Increased sodium retention
 Increased venule blood pressure
 Lymphatic obstruction
 Types of edema:
 Anasarca – Can’t see your Sarcs (Muscles because you’re 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:

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  1) Pitting edema – press against swollen area for 5 sec, then quickly remove it – indentation
left that fills slowly
 2) Nonpitting edema – press against swollen area for 5 sec, then quickly remove it – no
indentation left in skin
 Thrombus:
 Solid mass of clotted blood that develops in & is attached to a BV wall
 Formation enhanced by endothelial injury, alteration in blood flow (turbulence), &
hypercoagulability
 Arterial thrombi show alternating red & white laminations (lines of Zahn)
 Venous thrombi are more uniformly red w/ distinct lines
 Conditions predisposing to venous thrombosis:
 Heart failure, extensive tissue damage, bed rest, pregnancy, oral contraceptives, age,
obesity, & smoking, Just had surgery, bound to wheelchair, cirrhosis/Increased Portal
HTN
 Except COPD
 A whole thrombus may detach to form a large embolus or fragments may break off to generate
small emboli
 Different types of Thrombi:
 Agonal – forms in heart during the dying process after prolonged heart failure
 Mural –
 forms as a result of damage to ventricular endocardium (usually left ventricle,
following myocardial infarct)
 A major complication is a cerebral embolism
 It complicates myocardial infarctions, atrial fibrillation, & atherosclerosis of the aorta
 White – composed chiefly of blood platelets
 Red – rapidly forms by coagulation of stagnating blood – composed of RBCs rather than
platelets
 Fibrin – formed by repeated deposits of fibrin from circulating blood – usually does not
completely occlude the vessels
 Ten days after hospitalization for a large, incapacitating myocardial infarct, a 50-year-old man
suddenly develops paralysis of the right side of his body. The best explanation for his brain
damage is…detachment 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 Virchow’s 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:

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  Blood clot that moves through the bloodstream until it lodges in a narrowed vessel and blocks
circulation
 Mass of solid, liquid, or gas that moves w/in a BV to lodge at a site distant from its origin
 Most emboli are thromboemboli
 Can lodge in the vascular beds of vital organs, occluding blood flow & possibly causing infarction
 Splenic infarcts most commonly result from emboli originating in the left side of the heart
 56-yr-old with atrial fibrillation and hx of MI 2 yrs ago, experiences a right flank pain and
hematuria, paralysis of the right side of the body and ischemia to the left foot
 DUE to arterial emboli (NOT septicemia, venous thrombi or venous emboli)
 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, here’s 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
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  The most common cause of a TIA is an embolus, which most frequently arises from an
atherosclerotic plaque OR from a thrombus
 Phlebitis:
 Inflammation of a vein
 Pylephlebitis:
 Inflammation of portal vein or any branches
 Congestion:
 Accumulation of excessive blood w/in BVs
 Shock:
 Set of hemodynamic changes reducing blood flow below a level providing adequate O2 for
metabolic needs of organs/ tissues
 Requires immediate medical Tx – can worsen very rapidly
 Clinical signs:
 Reduced cardiac output is the main factor in all types of shock
 Tachycardia, hypotension, pallor, diminished urinary output, & muscular weakness
 Anoxia most severly affects brain & heart
 The body produces excess acid in the advanced stages of shock, when lactic acid is formed
through the metabolism of sugar
 Major classes of shock:
 Hypovolemic
 Produced by a reduction of blood volume
 Causes include hemorrhage, dehydration, vomiting, diarrhea, & fluid loss from burns
 Cardiogenic
 Due to the sudden reduction of cardiac output
 Main cause is myocardial infarction
 Septic
 Due to severe infection
 Most frequently caused by endotoxins from G- bacteria!!!!!
 Minor classes of shock:
 Neurogenic
 Results from injury to the CNS
 Anaphylactic
 Shock that occurs w/ severe allergic reactions
 Stages of shock:
 1) Non-progressive (early)
 Compensatory mechanisms maintain perfusion of vital organs (↑ HR & ↑ peripheral
resistance)
 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

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  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 (Werlhof’s 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
 NOT in serum
 Fibrin:
 Stringy, insoluble protein responsible for the semisolid character of blood clot
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  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 body’s nonspecific disease mechanism
 Lysozyme, complement, interferon & properdin ARE components of the body’s
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 don’t 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
 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 don’t change because they measure FACTORS, not platelets
 **Von Willebrand’s disease:
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 Characterized by spontaneous bleeding from mucous MBs & excessive bleeding following
trauma
 Deficiency of vWf resulting in impaired platelet adhesion (although there’s 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
 **Glanzmann’s 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 (Rosenthal’s 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
 HYPERTENSION:
 Usually has no symptoms at all (called the silent killer) – millions of people w/ high BP don’t
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

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  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, Cushing’s syndrome
 Even more other causes: Drugs, Diet, Excess erythropoietin, Endocrine disorders

Findings in HTN
Findings Basis of findings
Cardiovascular
BP persistently >140/90 Constricted arterioles – cause abnormal resistance
to blood flow
Angina pain Insufficient blood flow to coronary vasculature
Dyspnea on exertion Left-sided heart failure
Edema of extremities Right-sided heart failure
Intermittent claudication Decrease in blood supply from peripheral vessels
to legs
Neurologic
Severe occipital headaches w/ nausea & Vessel damage w/in brain, characteristic of severe
vomiting; drowsiness, giddiness; HTN
anxiety; mental impairment
Renal
Polyuria; nocturin; diminished ability to Arteriolar nephrosclerosis (hardening of
concentrate urine; protein & RBCs in arterioles w/in kidney) 25% die of renal failure
urine
Ocular
Retinal hemorrhage & exudates Damage to arterioles that supply retina

 Preeclampsia (Pregnancy-Induced HTN)

 Triad  HTN, proteinuria, and Edema
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  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
 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:

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  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
 Antibodies cross placenta into fetus’ circulation, where they attach to & destroy the fetus’
RBC – leads to anemia
 Can also result from blood type incompatibilities (i.e., mother may be type O & fetus may
be type A or B)
 2) Sickle Cell anemia:
 Caused by Hemoglobin S – an abnormal type of hemoglobin
 Autosomal recessive
 Heterozygous get the trait
 Homozygous get the disease (You know Homos are bad)
 So if pt homozygous, bad
 Globin portion of Hb S is abnormal – valine is substituted for glutamic acid in the 6th
position of Hb molecule
 Valine replacing glutamic acid is a MISSENSE mutation – base substitution
leading to different AA

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  When Hb molecules are exposed to low [O2], 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:
 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)
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  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 they’re 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
 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
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  Fatty material (atherosclerotic plaque) accumulates under inner lining of arterial wall
 Eventually the fatty tissue erodes arterial wall, diminishing elasticity (stretchiness) & interfere
w/ blood flow
 Plaques can also rupture, causing debris to migrate downstream w/in an artery
 Signs & symptoms – Angina, claudication, changes in skin color & temperature, headache,
dizziness, & memory defects
 Consequences of atherosclerosis:
 Ischemic heart disease (coronary artery disease) & heart attack (myocardial infarct)
 Stroke or aneurysm formation
 Described as degenerative changes in the walls of the arteries
 Microscopically:
 Fibrous cap of smooth muscle cells, collagen, CT matrix, leukocytes
 Cellular zone of necrotic cells, lipid-filled foam cells, plasma proteins
 Proliferating capillaries in advanced lesions
 Location  Abdominal aorta > Coronary artery > Popliteal artery > Carotid artery
 More common in men in all age groups & in post-menopausal women
 In very advanced cases, atherosclerotic plaques can become calcified & ulcerated
 Risks – smoking, HTN, heredity, nephrosclerosis, diabetes, & hyperlipidemia – NOT
alcoholism
 Glass of wine a day
 Arteriolosclerosis:
 Diffuse thickening of the arterioles & small arteries
 The kidney is particularly vulnerable to arteriolosclerosis
 Carbon monoxide poisoning:
 Very dangerous, colorless, odorless gas, generally associated w/ fumes from a car or a home
heating system
 Attaches to hemoglobin & blocks their ability to carry O2
 Severe CO poisoning can cause a coma or irreversible brain damage because of 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

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  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
 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 Buerger’s  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
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  Pelvic vein thrombophlebitis
 Congestion (hyperemia):
 Localized increase in the volume of blood in the capillaries & small vessels
 Active congestion – results from localized arteriolar dilation (e.g., inflammation, blushing)
 Passive congestion – results from obstructive venous return or increased back pressure from
CHF
 Occurs secondary to venous obstruction
 1) Acute – occurs in shock or right sided heart failure
 2) Chronic –
 a) of the lung (mostly caused by left-sided failure)
 b) of the liver (mostly caused by right-sided failure)  Leads to “Nutmeg Liver”
 Myeloproliferative disorders:
 Conditions in which myeloid stem cells develop & reproduce abnormally
 Characteristics – peak incidence in middle-aged persons, ↑ in blood basophils, serum uric acid, &
prominent splenomegaly
 Polycythemia vera:
 Aka primary polycythemia or erythemia
 A myeloproliferative syndrome characterized by a marked increase in erythrocyte mass
 Rare disorder of blood precursors – results in excess of RBCs (opposite of anemia)
 Pts may later develop anemia or acute leukemia due to “bone marrow burn out”
 Folate deficiency may also develop for the same reason
 Characteristics –
 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 (Osker’s
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
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  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: 5k–10k/mm3 blood
 Leukemoid reaction – when circulating levels of leukocytes reach very high levels (up to
100k/mm3)
 Sometimes difficult to differentiate from leukemia
 Parasitic infections cause an increase in eosinophil # in peripheral blood
 Pyemia: septicemia due to pyogenic organisms causing multiple abscesses

BONE & JOINT DISORDERS

BONE
 Long bones
 May be affected by Rickets, osteopetrosis, chondrodystrophy, fibrous dysplasia, osteogenesis
imperfecta
 Fracture:
 A break in the bone, usually accompanied by injury to surrounding tissues
 Occurs when force against bone exceeds bone strength
 Described as:
 Complete – bone breaks into two pieces
 Greenstick – bone cracks on one side only (not all the way through )
 Single – bone breaks into 2 pieces
 Comminuted – bone breaks into 3+ two pieces (or is crushed)
 Bending – bone bends but doesn’t 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
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  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
 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
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  Malabsorption of vitamin D by intestines
 Hereditary or acquired disorders of Vit D metabolism
 Kidney failure & acidosis
 Phosphate depletion associated w/ low dietary intake of phosphates
 Kidney disease or cancer (rare)
 Side effects of mediations used to treat seizures
 Characterized radiographically by diffuse radiolucency – can mimic osteoporosis
 Bone biospsy is often only way to differentiate between osteoporosis & osteomalacia
 Symptoms: diffuse bone pain (esp. in hips), muscle weakness, & bone fractures w/ minimal
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 (Albright’s syndrome)
 NOTE: Albright’s syndrome is a disease where two of the following three are present:
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  Café-au-lait spots
 Fibrous dysplasia
 Endocrine hyperfunction (includes precocious puberty)
 Pathologic fractures are often presenting complaint
 Paget’s 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 Recklinghasuen’s 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
 Affects different parts of body – categorized by one of three locations:

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  1) Physeal:
 Aka Scheuermann’s disease
 Occurs in the spine at intervertebral joints (physes), esp. in thoracic region
 2) Articular:
 Occurs at the joints (articulations)
 Legg-Calvé-Perthes disease – occurs at the hip
 Kohlers disease – foot
 Freiberg’s disease – 2nd toe
 The only type of osteochondrosis more common in females – all others affect sexes
equally
 Panner’s 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 skin…that 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
 Still’s disease = type of RA occurring in young people
 Gradual onset – fatigue, weakness, morning stiffness (lasting >1hr), diffuse muscular aches, loss
of appetite
 Joint pain eventually appears w/ warmth, swelling, tenderness, & stiffness of joint after inactivity
 NOTE: RA, SLE, polyarteritis nodosa, dermatomyositis & scleroderma are all classified as
collagen diseases
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  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
 Heberden’s 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
 Bouchard’s nodes
 Same as Heberden’s, but…
 Found in the proximal IP joint
 Characteristic morphologic changes in OA (in addition to Heberden’s & Bouchard’s nodes):
 Eburnation of bone – polished ivory like appearance of bone
 Osteophyte formation – bony spur formation
 They fracture & float into synovial fluid along w/ fragments of separated cartilage & are
called joint mice
 Gout
 Inherited disorder of purine metabolism occurring predominantly in men
 Marked by uric acid deposits in the joints
 There is hyperuricemia, too
 Can be characterized by acute arthritis of big toe
 Asymmetric
 Caused by a metabolic defect resulting in either:
 1) Overproduction of uric acid (monosodium urate crystals) OR
 Uric acid – end-product of purine metabolism, specifically xanthine metabolism
 Overproduction due to hyperuricemia (caused by Lesch-Nyhan syndrome, decreased uric
acid excretion, or G6P Deficiency)
 2) Reduced ability of the kidney to eliminate uric acid
 Almost 25% of all people who have gout develop kidney stones
 Exact cause of the metabolic defect is unknown
 May also develop in people w/ diabetes, obesity, sickle cell anemia, & kidney disease, or it may
follow drug therapy (Thiazide Diuretics inhibit the secretion of uric acid)

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  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
 Reiter’s 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  Can’t see (conjunctivitis), can’t pee (urethritis), can’t climb a tree (arthritis)
 Common in post GI or Chlamydia infections

NEOPLASMS
 Changes in Cell Growth
 Atrophy:
 Decrease in organ or tissue size resulting from a pathological decrease in mass of preexisting
cells
 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
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 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 tumor’s resemblance to normal
tissue)
 When malignant cells resemble more primitive undifferentiated cells
 Metaplasia:
 Process whereby one cell type changes to another cell type in response to stress
 Change of a more specialized cell type to a less specialized cell type
 Generally assists the host to adapt to the stress
 Does NOT change the number of cells involved only type of cell
 Examples:
 The most common type of epithelial metaplasia involves replacement of columnar cells by
stratified squamous epithelium (respiratory tract – smokers)
 Early bronchial mucosal alteration most likely seen in cigarette smokers
 Bone production in scar tissue
 Transformation of mucous secreting bronchial epithelium to a squamous epithelium
 Dysplasia (reversible):
 Type of nonmalignant cellular growth – it may precede malignant changes (preneoplastic)
 Epithelial change most predictive of cancer
 Associated w/ chronic tissue irritation by:
 1) chemical agents (e.g., cigarette smoke) OR
 2) chronic inflammatory irritation (e.g., chronic cervitis)
 Tissue appears somewhat structureless/disorganized & may consist of atypical cells w/o
invasion
 Abnormal tissue development
 Epithelium exhibitis acanthosis (abnormal thickening of the prickle cell layer)
 Changes in epithelial dysplasia: hyperchromatic nuclei, mitosis near the surface,
pleomorphism of cells

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  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
 What’s 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 Burkitt’s lymphoma
 Bcl-2 Follicular and undifferentiated lymphomas (inhibits apoptosis) – Think Blood Cell
Lesion -2
 Erb-B2 Breast, ovarian, and gastric carcinomas
 Ras Colon carcinoma – It’s 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:

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 1) Base substitutions – one base is inserted in place of another – results in either a missense or
nonsense mutation
 Missense mutation:
 Results in substitution of one aa for another
 Example  Val to glut in Sickle Cell
 Nonsense mutation:
 When base substitution generates a termination codon that prematurely stops protein
synthesis
 These mutations almost always destroy protein function
 Transverse mutation:
 Point mutation involving base substitutions in which the orientation of purine and
pyrimidine is reversed
 A purine is replaced by a pyrimidine or vice versa
 Transition mutation:
 Point mutation involving substitution of one base pair for another by replacing one
purine by another purine & one pyrimidine by another pyrimidine – no change in the
purine-pyrimidine orientation.
 Caused by base analogues
 2) Frame shift mutation –
 occurs when 1+ base pairs are added or deleted
 3) Transposons
 (insertion sequence) or deletions are integrated into DNA
 Caused by:
 Chemicals – nitrous oxide & alkylating agents alter the existing base
 Ionizing radiation (gamma & x-rays) – produce free radicals that attack DNA bases
 UV radiation – has lower energy than x-rays, causes cross-linking of adjacent pyrimidine
bases to form dimers
 Nucleic acids in bacteria and viruses are most sensitive to UV radiation (versus
protein, lipid, CHOs)
 Thymine dimers result in inability of the DNA to replicate properly
 THINK UV STERILIZATION
 Viruses – bacterial virus Mu (mutator bacteriophage) causes either frame-shift mutations or
deletions
 Bacterial mutation leading to the requirement for a single amino acid is due to absence of a
single NZ activity
 Radiosensitivity
 High radiosensitivity cells: lymphocytes > blood-forming cells >reproductive cells >
epithelial cells of GI tract
 Low radiosensitivity (radioresistant) – nerve cells, mature bone cells, muscle cells
 Most to least radiosensitive: spermatogonium > intestinal mucosa > endothelial > skeletal
muscle > osteocytes
 Most closely related to mitotic rate
 X-radiation
 Repeated exposure of low dose x-radiation can cause:
 Genetic mutations
 Carcinogenesis
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  Basic effect on living tissues is ionization (NOT denaturation, etc)
 Benign tumor:
 Localized, has a fibrous capsule, limited potential for growth, a regular shape, & well
differentiated cells
 Does not invade surrounding tissue or metastasize to distant sites
 Grow by expansion
 Causes harm only by:
 Pressure, hormone overproduction, or hemorrhage following ulcerations of overlying
mucosal surface
 Usually do not recur after surgical excision
 BENIGN neoplasms:
 Adenoma, Fibroma, Hemangioma, Lipoma
 Malignant tumors spread by local invasion and metastasis
 MALIGNANT neoplasms:
 Hepatoma, Lymphoma, Melanoma, Myeloma, Seminoma
 Metastasis occurs via bloodstream or lymph system
 Lymphatic – tumor 1st spreads to local & regional lymph nodes – then disseminates via
blood
 Hematogenous – 2° tumor nodules develop in liver, lung, brain, bone marrow, &
sometimes spleen & soft tissue

Benign 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
etc.) differentiated)
Slow growth Rapid growth
Encapsulated; well circumscribed Invasion
Localized Metastasis – most important distinguishing
characteristic
Movable 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:

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  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

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
Effects of tumors Effect
ACTH or ACTH-like peptide Cushing’s syndrome
ADH or ANP SIADH
PTH-related peptide, TGF- Hypercalcemia
alpha, TNF-alpha, IL-2
Erythropoietin Polycythemia
Antiboides against presynaptic Lambert-Eaton syndrome
Ca channels at neuromuscular (muscle weakness)
junction
Hyperuricemia due to excesss Gout
nuclei acid turnover (cytotoxic
therapy)

Cell type Benign Malignant

Epithelium Adenoma, papilloma Adenocarcinoma, papillary
carcinoma
Mesenchyme
Blood cells Leukemia, lymphoma
Blood vessels Hemangioma Angiosarcoma
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 Smooth muscle Leiomyoma (uterus) Leiomyosarcoma
Skeletal muscle (voluntary m) Rhabdomyoma Rhabdomyosarcoma
Bone Osteoma Osteosarcoma
Fat Lipoma Liposarcoma
>1 cell type Mature teratoma Immature teratoma

 Predisposers of cancer:
 Abestosis - mesothelioma
 Hepatitis C – hepatocellular carcinoma
 Gardner’s syndrome – multiple polyps  100% malignant change
 Ulcerative colitis – colonic adenocarcinoma.
 NOT Anthracosis – Coal miners (black lung) – doesn’t  CA
 Histological features of malignancy:
 Anaplasia
 Absence of differentiation (which is a measure of tumor’s resemblance to normal tissue)
 When malignant cells resemble more primitive undifferentiated cells
 Invasion
 Hyperchromatism
 Pleomorphism
 Abnormal mitosis

Diseases associated w/ neoplasms

Condition Neoplasm
Down syndrome Acute lymphoblastic leukemia –ALL We DOWN
Xeroderma pigmentosum Squamous cell and basal cell carcinoma of the
skin
Chronic atrophic gastritis, pernicious anemia Gastric adenocarcinoma
Tuberous sclerosis (facial angiofibroma, seizures, Astrocytoma and cardia rhabdomyoma
mental retardation)
Actinic keratosis Squamous cell carcinoma of skin
Barrett’s esophagus (chronic GI reflux) Esophageal adenocarcinoma
Plummer-Vinson syndrome (atrophic glossitis, Squamous cell carcinoma of esophagus (most
esophageal webs, anemia; all due to iron common CA of esophagus – more so than
deficiency) adenocarcinoma)
Cirrhosis (alcoholic, hepatitis B or C) Hepatocellular carcinoma
Ulcerative colitis Colonic adenocarcinoma
Paget’s disease of bone Secondary osteosarcoma and fibrosarcoma
Immunodeficiency states Malignant lymphomas
AIDS Aggressive malignant lymphomas (non-Hodgkin’s
& Kaposi’s)
Autoimmune disease (e.g., Hashimoto’s Benign and malignant thymomas
thyroiditis, myasthenia gravis)
Acanthosis nigricans (hyperpigmentation and Visceral malignancy (stomach, lung, breast,
epidermal thickening) uterus)
Dysplastic nevus Malignant melanoma

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 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,
Paget’s 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
leukemia—a B cell neoplasm

Oncogenic Virus Associated Cancer

HTLV-1 Adult T-cell leukemia
HBV, HCV Hepatocellular carcinoma
EBV Burkitt’s lymphoma, nasopharyngeal carcinoma
HPV Cervical carcinoma (16,18) penile/anal carcinoma
HHV-8 (Kaposi’s sarcoma associated herpes Kaposi’s sarcoma, body cavity fluid B cell
virus) lymphoma

Chemical Carcinogens Associated Cancer

Aflatoxins, vinyl chloride Liver
Nitrosamines Esophagus, stomach
Asbestos Lung (mesothelioma and bronchogenic
carcinoma)
Arsenic Skin (squamous cell)
CCl4 Liver (centrilobular necrosis, fatty change)
Naphthalene (aniline dyes) Bladder (transitional cell carcinoma)

 Carcinoma in situ:
 Pleomorphism
 Disorderly maturation
 Hyperchromatic nuclei
 BUT Basement membrane remains intact
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 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
 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 females—outdated????
 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 (smoker’s cough)
 Other signs & symptoms – hoarseness, wheezing, dyspnea, hemoptysis, & chest pains
 ½ 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

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  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
 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 ¾
 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
 Strongest association – family Hx, specifically breast cancer in 1st-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

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  Characterized by:
 Painless mass is usually the initial sign or symptom
 Retraction of skin or nipple
 Peau d’orange (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
 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 dx’d at an earlier stage
than tumors ascending colon
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 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
 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 can’t 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
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  Most common tumor of women – 25% of women >30 y.o. (during the reproductive years)
 Other areas (less frequent) – stomach, esophagus, & small intestine
 Prognosis is good
 Cause of fibroid tumors of uterus is unknown
 Suggested that fibroids may enlarge w/ estrogen therapy (such as oral contraceptives) or w/
pregnancy
 Growth depends on regular estrogen stimulation – rare before age 20 & shrinks after
menopause
 Fibroid will continue to grow as long as women menstruates, but growth is slow
 Uterine fibroids – most common pelvic tumor – present in 15-20% of reproductive-age women,
30-40% of women > 30 y.o.
 Endometrial Carcinoma/Uterine Cancer
 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: don’t 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
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  More than ½ of these pts have cancer (GI carcinomas, particularly of the stomach)
 More skin disorders (while we’re here):
 Dermatitis:
 Group of inflammatory pruritic skin disorders
 Etiology: allergy (usually type IV hypersensitivity), chemic injury, or infection
 Psoriasis:
 Nonpruritic chronic inflammation of the skin, particularly on the knees and elbows
 Associated w/ HLA-B27, HLA-13, etc
 Auspitz sign: seen when removal of scale results in pinpoint areas of bleeding
 Treat w/ topical steroids & UV irradiation
 Bullous pemphigoid:
 Autoimmune disorder w/ IgG antibody against epidural basement membrane (linear
immunofluorescence). Similar to but less severe than pemphigus vulgaris—affects 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”, “bull’s eye” shape)

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  Stevens-Johnson syndrome:
 Severe systemic symptoms & extensive lesions involving multiple body areas (especially
mucous MBs)
 Toxic epidermal necrolysis (TEN syndrome, or Lyell’s 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
 Hodgkin’s lymphoma = Hodgkin’s 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 Hodgkin’s
 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-Hodgkin’s 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 Hodgkin’s 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
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  Burkitt’s lymphoma:
 High-grade B-cell lymphoma (lymph gland tumor) classified as a non-Hodgkin’s type
of lymphoma
 EBV may be the cause of this lymphoma
 The 1st human cancer that has been strongly linked to a virus
 Undifferentiated malignant lymphoma that usually begins as:
 African form: (ENDEMIC FORM)
 95% of cases associated w/ EBV
 Affects children of middle African regions
 Usually begins as a large mass in the jaw
 American form:
 Less closely associated w/ EBV
 Usually begins as an abdominal mass
 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-Hodgkin’s lymphoma originating from a mature
T-cell
 Affects the skin; may progress to lymph nodes & internal organs
 1st indication – swollen lymph glands (lymphadenopathy), enlarged tonsils & adenoids; painless,
rubbery nodes in cervical supraclavicular areas
 Pt develops symptoms specific to involved area & systemic complains – fatigue, malaise, weight
loss, fever, & night sweats
 Pathophysiologically similar to Hodgkin’s disease, but:
 Reed-Sternberg cells are not present
 Specific mechanism of lymph node destruction is different
 Biopsy differentiates Non-Hodgkin’s from Hodgkin’s

Hodgkin’s
Presence of Reed-Sternberg cells
Localized, single group of nodes, extranodal rare;
contiguous spread
Constitutional signs/symptoms—low-grade fever,
night sweats, weight loss
Mediastinal lymphadenopathy
50% of cases associated w/ EB; bimodal
distribution: young and old; more common in
men except nodular sclerosis type
Good prognosis = increase lymphocytes, low
number of Reed Sternberg cells
Non-Hodgkin’s
Non-Hodgkin’s 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
Peak incidence 20 -40 years old
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 Ann Arbor staging of Hodgkin’s:  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 Hodkin’s 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 Waldenstrom’s macroglobulinemia)
 SIDENOTE on Waldenstrom’s:
 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:
 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

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  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
 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
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  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

 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 P’s—Pressure (elevated BP); Pain (headache),
Perspiration; Palpitations; Pallor/diaphoresis
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  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 Recklinghausen’s 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 Adam’s apple or THYROID
 MEN type I (Wermer’s syndrome):
 three P organs, pancreas, pituitary, and parathyroid. Presents w/ kidney stones and stomach
ulcers.
 MEN type II (Sipple’s syndrome): -- Sipping get to your thyroid
 medullary carcinoma of the thyroid, pheochromacytoma, parathyroid tumor, or adenoma
 MEN type III (Formerly MEN IIb):
 medullary carcinoma of the thyroid, pheochromocytoma, and oral and intestinal
ganglioneuromatosis
 Increased incidence of medullary carcinoma of the thyroid with pts suffereing from MEN type
III
 Von Hippel-Lindau disease (neurofibromatosis II):
 Characterized by hemangiomas of the retina, medulla, & the cerebellum
 Associated w/ cysts of liver, kidney (bilateral renal cell carcinomas), adrenal glands, & pancreas
 Autosomal dominant associated w/ VHL gene (tumor suppressor on chromosome 3 (3p)
 Bone tumors:
 Most are secondary (caused by seeding from a primary site) – From Stomach, Ovary, and Colon
 Primary tumors are more common in males, usually children & adolescents – some types occur in
persons ages 35-60
 They may originate in osseous or nonosseous tissue
 Osseous bone tumors arise from bony structure itself
 Non-osseous tumors arise from hematopoietic, vascular, or neural tissue
 Primary malignant bone tumors (aka sarcomas of bone)
 Rare, constituting less than 1% of all 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
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 In children, the most common types of bone tumors are Osteogenic & Ewings’s 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: Paget’s disease, bone infarcts, radiation, and familial
retinoblastoma – think Rb gene
 Periosteal osteogenic sarcoma:
 Usually in females ages 30-40
 Occurs most often in distal femur, may also be in humerus, tibia, & ulna
 Develops on bone surface (instead of interior) & progresses slowly
 Chondrosarcoma:
 Usually in males ages 30-50
 Occurs most often in pelvis, proximal femur, ribs, & shoulder girdle
 Develops from cartilage & grows slowly
 Usually painless; locally recurrent & invasive
 May be from primary origin or from osteochondroma
 Malignant giant cell tumor:
 Usually in females ages 18-50
 Arises from benign giant cell tumor
 Found most often in long bones, more so in knee area (epiphysis)
 Locally aggressive tumore found around the distal femur, proximal tubial region
 Characteristic “double bubble” or soap bubble appearance on x-ray; spindle-shaped
cells w/ multinucleated giant cells
 Bone pain is the most common indication of 1° malignant bone tumors
 Bone pain has greater intensity at night, is associated w/ movement & is dull & usually localized
 Bone tumors of nonosseous origin:
 Ewing’s 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 (Mark’s
Dad).
 Characteristic of kids and Teens???  Ewing’s 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
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  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 they’re derived from):
 Leiomyoma – from smooth muscle – includes the uterine leiomyoma or fibroid tumor – most
common neoplasm of women
 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:

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  Become poor infection fighters
 Multiply excessively & do not die off
 Increased number of circulating leukocytes in the blood
 Leukemic cells accumulate & reduce production of RBCs, platelets & normal leukocytes
 Prolongation of bleeding time in leukemia is a result of thrombocytopenia (reduced #s of
platelets)
 If untreated, surplus leukemic cells overwhelm the bone marrow, enter the bloodstream, & invade
other parts of the body:
 Lymph nodes, spleen, liver & CNS
 Behavior is different from other cancers, which usually begin in major organs & ultimately spread
to bone marrow
 Classified by the dominant cell type & by the duration from onset to death
 Incidence evenly split (50:50) between acute & chronic leukemias
 Can modify the inflammatory reaction
 Chemotherapy for leukemia predisposes for oral infections by C. albicans

 Risk factors for leukemias:

 Familial tendency
 Congenital disorders (Down syndrome [higher incidence of acute leukemias]; presence of
Philadelphia chromosome [CML])
 Leukemic pts have high Ab titer to EBV
 Ionizing radiation & exposure to benzene & cytotoxins (such as alkylating agents), some anti-
cancer drugs
 Acute leukemias:
 Rapid onset & progression: (few months)
 Sudden high fever, weakness, malaise, severe anemia, generalized lymphadenopathy, bone & joint
pain
 Common in children
 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
 Wth intensive therapy (chemo, radiation, & bone marrow transplants), remissions may last up
to 5 years
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  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)

Major Types of Leukemias

Type Progression WBC affected % of Leukemias Age group
ALL Rapid Lymphocytes 20 3-5 y.o.
AML Rapid Myelocytes 27 Mostly adults
CLL Slow Lymphocytes 31 > 60 y.o.
CML Slow Myelocytes 22 Any age

 Quick Notes on Several Leukemias:

 ALL:
 Children/lymphoblasts
 Down’s
 AML:
 Myeloblasts
 Auer rods
 CLL:
 Elderly
 Very similar to SLL (small lymphocytic lymphoma)
 CML:
 Massive splenomegaly
 Philadelphia chromosome (9,22)
 Acute Lymphoblastic Leukemia (ALL):
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  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 RARα 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 (It’s 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 untx’d can → death w/in 40 to 100 days from time of Dx
 Most common acute leukemia in adults
 Etiological factors (possible) include: ionizing radiation, chemicals such as benzene and
chemotherapeutic agents
 Symptoms & Signs: Petechiae, sternal tenderness, sometimes adenopathy, splenomegaly and
hepatomegaly may be found, testicular, cutaneous, and meningeal involvement as well
 Chronic Lymphoid Leukemia (CLL):
 Least malignant type – L for Least and NODES
 Older adults (average age = 60 y.o.)
 Characterized by abnormal small lymphocytes in lymphoid tissue
 Affects men 2-3x more than women

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  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
 “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):
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  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 doesn’t 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
 Causes  Ectopic ADH (small cell lung cancer), CNS disorder/head trauma, Pulmonary
disease, Drugs

ADRENAL GLANDS
 Addison’s 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)
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  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 Addison’s 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?  Addison’s - bc aldosterone
can’t do it’s 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 (Cushing’s syndrome) or not enough (Addison’s) is
being produced
 ACTH levels are high in Addison’s 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
 Cushing’s disease:
 Hyperfunction of the adrenal cortex
 Excess ACTH production (Also High IN addison’s, 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

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  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 pituitary—surgery, radiation (gamma knife), drugs, iatrogenic—taper
carefully
 Hyperaldosteronism:
 Primary (Conn’s 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
 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
 Plummer’s 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
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  NOT Increased oxygen consumption
 Another Q: Congenital hypothyroidism most likely causes delayed eruption of teeth –
BUT Jared’s 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
 Hashimoto’s Disease:
 Most common cause of hypothyroidism
 Caused by an autoimmune reaction against the thyroid gland (Thyroiditis)
 Common thyroid gland disorder
 Production of Ab/s in response to thyroid Ag/s & the replacement of normal thyroid structures
w/ lymphocytes & lymphoid germinal centers
 Onset is slow – may take months or years for condition to be detected
 Most common in middle-aged women & individuals w/ family Hx of thyroid disease
 Estimated to affect 0.1-5% of all adults in Western countries
 Less common cause – failure of pituitary gland to secrete TSH (secondary hypothyroidism)
 Severe hypothyroidism in children leads to Cretinism:
 Endemic cretinism occurs wherever endemic goiter is prevalent (lack of dietary iodine)
 (Don’t get confused with the goiters of Grave’s 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 (don’t 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 Recklinghausen’s
bone disease), nephrocalcinosis, kidney stone & peptic duodenal ulcers
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  43-year-old with radiolucencies (not associated with apices), and radiolucencies in humerus. Lab
tests indicate elevated calcium, but serum phosphorus and alkaline phosphatase are normal. She
also has giant cells in her bone lesion
 Dx: hyperparathyroidism – Paget’s doesn’t 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
 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%
 Chvostek’s 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
 Trousseau’s sign: swordfighter
 Apply a BP cuff to the pt’s 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)
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 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 ½ 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-specific—fatigue, weakness, polydipsia, polyuria, skin lesions-including fungal infections
of skin & mucous MBs
 Chronic Manifestations
 Small vessel disease  thickening of BM, retinopathy, nephropathy
 Large vessel atherosclerosis, coronary artery disease, peripheral vascular occlusive disease,
gangrene, CV disease
 Neuropathy
 Cataracts, glaucoma
 Susceptibility to infections, neuropathies, impotence, ketoacidosis, lipid metabolism
abnormalities including atherosclerosis
 Long term complications of poorly controlled type I diabetes:
 Hyaline arteriosclerosis, Proliferative retinopathy, Nodular glomerulosclerosis, peripheral
symmetry neuropathy
 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:

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  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 10–20% 80–90%
Basic defect Destruction of B-cells Reduced sensitivity of insulin’s
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
Concordance in identical 50% 100%
twins
Genetic predisposition Weak, polygenic Strong, polygenic
Association with HLA Yes (HLA DR 3 and 4) No
system
Beta cell numbers in islets Reduced Variable
Classic symptoms of 3 Common Sometimes
Polys

 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
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  If eyelids are severly irritated, eyelashes may turn in & rub against cornea
 This can cause eye ulcers, further scarring, visual loss, & even blindness
 Occurs worldwide – primarily in rural settings in developing countries (rare in U.S.)
 Leading cause of blindness in developing countries
 Frequently affects children, although the consequences of scarring may not be evident until later
in life
 Inclusion conjunctivitis:
 Conjunctivitis caused by Chlamydia trachomatis
 Often affecting newborns – also contracted by adults in swimming pools or during sexual contact
 I wonder what happens if someone has sexual contact in a swimming pool…?
 Characterized by enlarged papilla on inner eyelids & a purulent discharge
 Chronic inflammation/hypertrophy of conjuctiva – forms grayish, yellowish translucent granules
 Pinkeye:
 Aka “acute contagious conjunctivitis”
 Acute, contagious form of conjunctivitis caused by Hemophilius aegyptius
 Characterized by inflammation of eyelids & eyeballs w/ a mucopurulent discharge
 Keratoconjunctivitis Sicca:
 Long-standing dryness of both eyes, leading to dehydration of conjunctiva & cornea
 NOTE: dry eyes may be a symptom RA, SLE or Sjogren’s 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
 TB–Caseating, Necrotizing
 Crohn’s 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, Bell’s
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 (Bruton’s) 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
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 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 Bruton’s, 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 to…virus infections (NOT bacterial
or fungal)
 Remember viruses are in the cell, so usually T-cell mediated
 Viruses enter, start production, then MHC I is made in rER!!!!!!
 MHC II, deals more with cells eating Bad bugs of bacteria
 ***The pt is just missing gamma globulins
 DiGeorge Syndrome: T-- George
 Think T for Thymic aplasia, T-cell deficiency, Tetany due to hypocalcemia – You need
Vitamin D-George!!!!
 Thymic hypoplasia or aplasia  Remember you’re BORN with it
 Rare immunodeficiency disorder characterized by various congenital abnormalities arising
late in fetal development
 The causative defects occur in areas known as the 3rd & 4th pharyngeal pouches
 These pouches develop into the thymus & parathyroid glands (which may be missing or
underdeveloped)
 Development abnormalities may also occur in the 4th branchial arch
 Primary problem is the repeated occurrence of various infections due to a diminished immune
system
 Prone to viral & fungal infections – T cell GUYS!!!
 Absence of thymus results in T-cell deficiency
 These children have normal B-cells & form antibodies
 They have decreased or absent delayed-type hypersensitivity
 Absence of parathyroids causes hypocalcemia – leads to development of tetany
 Severe Combined Immunodeficiency Disease (SCID):
 Most dangerous type of congenital (inherited) immunodefieicency
 Defects in lymphoid stem cells (results from failure of stem cells to differentiate properly)
 Pts have neither B-cells nor T-cells
 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)

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  Cellular consequences:
 T cells: loss of CD4+ T cells AND decrease in response of T cells to Ag AND impaired
cytokine production
 B cells: steadily lose ability to mount an effective Ab response to new Ag/s
 Diagnosis:
 ELISA – detects Ab/s to HIV
 Western blot – confirmatory tests
 Associated with:
 Loss of cellular immunity defenses
 Alteration of Helper T/Suppressor T ratio
 Increased susceptibility to opportunistic infections
 Results in Opportunistic infections, i.e.:
 Pneumocystis carinii
 Most common cause of pneumonia in AIDS pts
 Mycobacterium avium intracellulari
 Malignant neoplasms:
 Kaposi’s sarcoma
 Non-Hodgkin’s 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, Raynaud’s, Wire LUP (loop) lesions in kidney with immune
complex deposition
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  NOT clubbing or cyanotic digits (Polycythemia, congenital heart disease, congestive heart
failure, chronic pulmonary disease DO) – Remember Raynaud’s is just from Cold,
emotion
 SLE causes LSE (Libman-Sacks Endocarditis)  Valvular vegetations found on both sides of
mitral valve, No embolizations
 Characterized by periods of remission & exacerbation
 At onset, perhaps only one organ system involved
 Renal failure commonly occurs & is the usual cause of death
 Severe CNS involvement may appear
 Acrocyanosis (Raynaud’s 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 ~ ½ 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, Raynaud’s 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
 Sjogren’s 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)

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  May cause rampant caries reminiscent of radiation caries (due to shift toward more
acidogenic microflora)
 Parotid enlargement
 3) Keratoconjunctivitis Sicca (dry eyes)
 All three rarely occur in one patient
 Definite Dx made only when at least two symptoms are present
 Occasionally the lymphocytic infiltration is massive, causing enlargement of the glands (called
Mikulicz’s 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: Alzheimer’s 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
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  Isograft:
 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.
 Example: Autosomal dominant trait showing 50% penetance, will be phenotypically present
in what percent of the offspring?
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  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
 Greatest incidence of rubella associated w/ cardiac anomalies occurs during 1 st
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
 Marfan’s syndrome:
 Fibrillin gene mutation leading to a CT disorder:
 Uncommon hereditary CT disorder resulting in abnormalities of the eyes, bones, heart, & BV
 Pts are tall & thin w/ abnormally long legs & arms & spider-like fingers
 Skeletal abnormalities: tall w/ long extremities, hyperextensive joints, and long tapering
fingers and toes
 Cardiovascular: cystic medial necrosis or aorta leading to aortic incompetence and dissecting
aortic aneyrysms. Floppy mitral valve
 NOT Mental Retardation
 Ocular: subluxation of lenses

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 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
 Huntington’s 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 50…death 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
 Don’t 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 Recklinghausen’s disease)
 Characterized by multiple pigmented macules of the skin
 TOO reckless with you Coffee and Punch Holes in the Walls (Bone)
 Has café au lait spots, neural tumors, Lisch nodules (pigmented iris hamartomas)
 Also marked by skeletal disorders (dg. Scoliosis) and increased tumor susceptibility
 On long arm of chromosome 17, 17 letters in von Recklinghausen
 Heriditary spherocytosis:
 Intrinsic, extravascular hemolysis due to spectrin or ankyrin defect
 RBCs are small and round w/ no central pallor→less 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

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  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 I→Type VI, including von Gierke’s disease (found elsewhere in file)
 Lysosomal storage diseases
 Mucopolysaccaridoses
 NOTE: Hunter’s is not an autosomal recessive disease
 Hurler syndrome –Can’t 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 (you’ll see)***
 Reticuloendothelial system (mononuclear phagocyte system):
 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)
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  Histiocytes = fixed macrophages in CT
 Disorders of the Reticuloendothelial system:  ALSO LIPID STORAGE
DISEASES
 Gaucher’s 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
 Fabry’s disease:
 The only sphingolipidosis that is not autosomal recessive (No, I don’t know which
category it fall under)
 Very rare, inherited & extremely painful systemic disorder related to deficiency of α-
galactosidase
 Characterized by glycolipid accumulation in body tissues
 Gaucher’s 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

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  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
 Duchenne’s 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 Duchenne’s, Deleted Dystrophin, and muscle
Decrease)
 Usually presesnt in muscle cell MBs (but it’s 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, Fabry’s, G6PD deficiency, Hunter’s, Ocular albinism, Lesch Nyhan
(Gout – hyperuricemia), Bruton’s 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, Alzheimer’s disease for people > than 35, increase risk for acute lymphoid
leukemia (we ALL go DOWN)
 Think D for Drinking age (21) and Down’s, and Decreased AFP – DOWN’s
 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)
 Patau’s 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–)

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  Microcephaly, severe mental retardation, high pitched crying/mewing, cardiac abnormalities
 Think Cry of the Chat (high pitched crying)
 DiGeorge’s 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
Edward’s 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
Patau’s 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) – uh…Trisomy 13…
 DISORDERS OF SEX CHROMOSOMES:
 Sex-linked Dominance
 Male with x-linked dominant condition has daughters with an unaffected partner, what
percentage of the daughters will be affected = 100%
 Klinefelter’s 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
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  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

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

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 Shy-drager syndrome (multiple system atrophy)
 Rare degenerative condition w/ symptoms similar to Parkinson’s – 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:
 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!

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 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
 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 Addison’s 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
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  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)
 Habermann’s disease:
 Is not an example of Histiocytosis X
 Sudden onset of a polymorphous skin eruption of macules, papules, & occasionally vesicles w/
hemorrhage
 Polymyalgia rheumatica:
 Condition causing severe pain & stiffness in muscles of neck, shoulders, & hips
 Hydatidiform Mole
 A pathologic ovum (“empty egg” – ovum with no DNA) resulting in cystic swelling of chorionic
villi and proliferation of chorionic epithelium (trophoblasts)
 Most common precursor of choriocarcinoma
 High beta HCG
 “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
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  Manifest clinically by amenorrhea, infertility, obesity, and hirsutism
 Tx with weight loss, OCPs, gonadotropin analogs, or surgery
 Leiomyoma (See “Neoplasm’ section)
 Leiomyosarcoma (See “Neoplasm’ section)
 Breast Disease
 Fibrocystic Disease
 Presents with diffuse breast pain and multiple lesions, often bilateral
 Bx shows fibrocystic elements
 Usually does not indicate increased risk for CA, although it is a risk factor
 Histological types
 Cystic – fluid filled
 Epithelial Hyperplasia – Increase in number of epithlelial cell layers in terminal duct
lobule, Increase risk for CA
 Fibrosis – Hyperplasia of breast stroma
 Sclerosing – Increased acini and intralobular fibrosis
 Benign Tumors
 Cystosarcoma phyllodes – large, bulky mass of CT and cysts, breast surface has “leaflike”
appearance (“I love Fall”)
 Fibroadenoma – most common tumor <25 yrs, small, mobile, firm mass with sharp edges,
increases with pregnancy
 Malignant Tumors
 Comon Postmenopause
 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
 Paget’s disease – Eczematous patches on nipple
 Risk Factors  Gender, age, early menarche, delayed first pregnancy, late menopause, family
st
history of 1 -degree relative with breast cancer at a young age, but NOT fibroadenoma or
nonhypplastic cysts
 Wegener’s 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
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  Increases NADH/NAD+ ratio, which in turn:
 Basically tricks your body into thinking you have energy
 Increases Lactate/pyruvate
 Inhibitis gluconeogenesis
 Inhibits FA Oxidation
 Inhibits Glycerophosphate dehydrogenase, leading to elevated glycerophosphate
 Complications of Alcoholism
 Alcoholic Cirrhosis
 Long term alcohol use leads to micronodular cirrhosis with accompanying symptoms
of jaundice, hypoalbuminemia, coagulation factor deficiencies, and portal
hypertension, leading to peripheral edema, ascites, encephalopathy, and neurologic
manifestations
 Wernicke-Korsakoff Syndrome
 Caused by Vitamin B1 (thiamine) deficiency in alcoholics
 Classically may present with triad of psychosis, ophthalmoplegia, and ataxia
 May progress to memory loss, confabulation, confusion (Irreversible)
 Associated with periventricular hemorrhage/necrosis, especially in mamillary bodies
 Tx with IV Vitamin B1
 Mallory-Weiss Syndrome
 DRUNK DUCKS
 Longitudinal lacerations at the gastroesophageal junction caused by excessive
vomiting with failure of LES relaxation that could lead to fatal hematemesis
 A Quick Review on Pathology Findings
 Argyll-Robertson Pupils
 Constricts with accommodation but is not reactive to light, pathognomonic for Tertiary
syphilis
 Think ARP  Argyll-Robertson Pupil, Accommodation Response Present
 Amyloidosis
 Primary seen with multiple myeloma or Wadenstrom’s macroglobulinemia
 Secondary can cause nephrotic syndrome in kidney, Apple-green birefringement on
Congo Red stain
 Alzheimer’s 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 Anitschkow’s 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)
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  Nonspecific test that measures acute-phase reactants
 Dramatically increased with infection, malignancy, CT disease, with pregnancy,
inflammatory disease, anemia
 Decreased with Sickle cell anemia, polycythemia, CHF
 Hyperlipidemia signs
 Atheromata  Plaques in blood vessel walls
 Xantheloma  Plaques or Nodules composed of lipid-laden histiocytes in the skin, especially
the eyelids
 Tendinous Xanthoma  Lipid deposit in the tendon, especially Achilles,
 Familial Hypercholesterolemia
 Corneal arcus  Lipid deposit in cornea, nonspecific (arcus senilis)
 Psammoma bodies
 Laminated, concentric, calcific spherules seen in
 Think PSaMMoma  Papillary adenocarcinoma of thyroid, Serous papillary
cystadenocarcinoma of ovary, Meningioma, Malignant Mesothelioma
 RBC Forms
 Biconcave Normal
 Spherocytes Hereditary Spherocytosis, Autoimmune hemolysis
 Elliptocyte Hereditary Elliptocytosis
 Macro-ovalocyte Megaloblastic anemia, marrow failure
 Helmet cell, Schistocyte DIC, traumatic hemolysis
 Sickle cell Sickle cell anemia
 Teardrop cell Myeloid metaplasia with myelofibrosis
 Acanthocyte Spiny appearance in abetalipopreteinemia
 Target cell Thalassemia, liver disease, HbC
 Poikilocytes Nonuniform shapes in TTP/HUS, microvascular damage, DIC
 Burr cell TTP/HUS
 HLA-B27
 Think PAIR  Psoriasis, Ankylosing spondylitis, Inflammatory bowel disease, Reiter’s
syndrome
 Virschow’s (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;
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  the most common is inherited as an autosomal dominant trait; some recessive cases have
hydroxylysine-deficient collagen due to deficiency of collagen lysyl hydroxylase, and two
tentatively ascribed to X-linked inheritance.
 Also associated with Berry Aneurysms
 What does CD stand for??
 Not compact disc, but Cluster of Differentiation
 They are surface molecules that are recognized by specific types of antibodies
 CD 4 and CD 8--- Ring a bell?
 Respiratory Burst
 The rapid release of SUPEROXIDE anion when PMNs come in contact with bacteria
 Throat Cancer
 Most are squamous cell carcinomas – Just like Skin and Esophagus
 Oral Cancer
 Occurs on the side of the tongue
 Tracheomalacia
 Trachea collapsing
 Noma
 Gangrenous disese of the mouth and cheeks

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