Goljan Day 1: Cell Injury

Hypoxia—Inadequate oxygenation of tissues. Inner mitochondrial membrane. O2 electron acceptor in

Electron Transport Chain…ATP generation. O2 content Hemoglobin X O2 Sats + PPArterial O2. Ferrous
iron +2. O2 in RBC attached to heme group measured with pulse Ox. PP of O2 is O2 dissolved in plasma.
Ischemia: decrease in arterial blood flow…most common cause is thrombus in muscular artery. Hypoxemia:
ppAO2—dissolved in arterial plasma. Respiratory acidosis: Nitrogen remains constant, retain CO2….pO2
must go down….to equal 760mm Hg. Respiratory alkalosis…O2 must go up.
Ventilation defect: Hyaline membrane disease. Adult respiratory distress syndrome. Ventilation defect.
Patient with hypoxemia. Give them 100%...if pO2 doesn’t increasevent defect (SHUNT). Pulmonary
Embolism=perfusion defect (decrease blood flow—stasis in deep veins during long flight)….produce increase
in dead space.
Diffusion defect: Sarcoidosis…. Fibrosisrestrictive lung disease. Fluid—heart failure: dyspnea, J
receptor, Cranial nerve X. Can’t take full breath.
Hemoglobin related problems: Anemia—O2 contentnormal gas exchange (hemoglobin decreased, O2
sats are normal, normal pO2…exercise intolerance.)
CO poisoning: “house fire”—CO and cyanide poisoning. O2 sats are decreased because CO is sitting
on heme group instead of O2. pO2 totally normal. Treat with 100% O2. Decrease in O2 sats….cyanosis.
Cherry red pigment masks decrease in pO2. Headache is first symptom of CO poisoning.
Methemoglobin poisoning: chocolate colored blood. pO2 normal, Sats are decreased. (B/c Iron is +3)
RBCs have methemoglobin reductase. “Patient who has been in Rocky mountains….cyanotic, oxygen therapy
doesn’t correct the cyanosis, water is loaded with nitrites and nitrates. Give O2 and it doesn’t help. Tx: IV
methalene blue, followed by vitamin C….sulfa and nitro drugs produce methemoglobin, cause hemolysis in
G6PD deficiency (dapsone, nitroglycerine, TMP-SMX—treatment of pnemocystis carinii and HIV patients.)
Right shifted curve: Hemoglobin wants to release O2 in tissue…2,3 BPG, fever, low pH, high altitude
(respiratory acidosis….hyperventilate)
Left shift: fetal hemoglobin, alkalosis, low 2,3 BPG, CO
Cytochrome oxidase: Cyanide and Carbon monoxide (inhibit)
Uncoupling: Inner mitochondrial membrane permeable to Hydrogen ions, can’t synthesize ATP.
Dinitrophenol, alcohol, aspirin—uncoupling agents. Reactions that make NADH, FADH….will rev reactions
up. Increase rate of chemical reactions…increase temp….hyperthermia. Salicylate toxicity.
Respiratory acidosis: O2 sats decrease. pO2 decreased
Anemia: only hemoglobin affected.
Decrease in ATP: go into anaerobic glycolysislactic acid, b/c of increase in NADH…get 2ATP….build up of
lactic acid in cell…metabolic acidosis. Increase in acid in cell will denature proteins, cell can’t even autodigest
itself. Coagulation necrosisinfarction—tissue hypoxia in a cell microscopically.
All ATPase pumps are screwed up. Na/K pump….Digitalis blocks to allow sodium to go into cardiac
cell and increase Ca++ intracellularly. Cell will be swollen in tissue hypoxia b/c sodium enters and water goes
with it…ATP can’t pump it out.
Cell without O2….irreversible changes… In hypoxia Calcium enters cells, if ATP is decreased, calcium
has access to cell…activates phospholipases, activates mitochondrial enzymes. Can get acute pancreatitis from
hypercalcemia. (ICM II story of kid with hemorrhagic pancreatitis) Cell membrane gets damaged. CK MB,
ALT, AST can be released when cell/tissue dies. Amylase released in pancreatitis.
Free radicals: Lipofuscin—wear and tear. Lipid that you can’t break down all the way. O2 can be a
free radical…50% or higher O2…reperfusion injury, into cardiac muscle involving O2 free radicals. Kids with
respiratory distress syndrome. Retinopathy prematurity.
Most common cancer in radiation…hydroxyl free radicals…leukemia.
Tylenol: #1 cause of fulminant hepatitis because of acetaminophen—free radical production. CytoP450 can
change drugs into active metabolite. Around central vein in liver. Treatment: N-acetyl cysteine. Glutathione:
generation of NADPH neutralizes hydrogen peroxide. Pentose Phosphate shunt…main function is to neutralize

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free radicals. Ace + Aspirin…say bye-bye to kidneys, aniliate renal medulla and aspirin knocks off PGE2
(vasodilator). AngII incharge of renal blood flow. Analgesic nephropathy.
Y chromosome: Mullerian inhibitory factor—signal for apoptosis…germinal ridges---uterus, upper 1/3 of
vagina, cervix inhibited….b/c of caspases.
X Chromosome: Absence of y chr causes germinal ridge to go ovarian route. Metanephric duct.
Thymus—involution in adult: larger in child, if absent….DiGeorge syndrome (midline defects, low set ears, no
philtrum) and tetany.
Councilman body—eosinophilic cell w/out nucleus—example of apoptosis in alcoholism…liver.
Neurons: pyknotic nucleus lost brain mass due to ischemia
Types of necrosis: tissue damage.
Coagulation necrosis infarction,
Pale vs. Hemorrhagic: consistency of tissue that determines result….if good consistency…will grossly look
pale= heart, kidney, liver, spleen…..Red testicles, lungs, intestines…red blood cells can trickle out and color
tissue. Pale coag necrosis, usually due to embolus. Infective endocarditis…mitral stenosis….group A strep.
Arrhythmia associated with embolus in systemic circ=atrial fib.
Dry gangrene: don’t see any pus…diabetic, popliteal artery…Small lumen + atherosclerotic plaque.
Ischemia….decrease in arterial blood flow. Due to atherosclerosis.
Piece of small bowel: hemorrhagic infarction, indirect inguinal hernia. Second most common casuse of
infarction to small bowel. MCC from adhesions of previous surgery.
Brain….exception to the rule…infarct the brain (bruit in carotid artery, platelet develops over
atherosclerotic plaque) TIA--motor or sensory abnormalities that go away in 24 hours. Analogous to fibroblast
in brain: Astrocyte, protoplasmic properties. Liquifactive necrosis in brain. Normally related to neutrophils…
phagocytose, acute infection producing abscess.
Staph; Gram positive cocci in clusters…coagulase (form abscesses with staph a) converts fibrillogen
into fibrin….localizes infection Strept; releases hyaluronidase?
Lung: high fever and productive cough….broncho pneumonia, MCC: strep pneumo…liquifactive necrosis.
“Patient with fever night sweats and weight loss” TB…granuloma…caseasous necrosis. Means you
have myco bacterial infection or systemic fungi infection causing cheesy appearance in granuloma.
Pancreas: Epigastric pain radiating to the back. Pancreatitis. Enzymatic fat necrosis. Dystrophic
calcification—bluish discoloration. Saponification. Due to lipase (more specific than amylase). Underlying
cause, alcohol. (think ICM II story of 16 yr old—from Iowa)
Traumatic fat necrosis…usually occurs in breast tissue or other adipose tissue, calcification in breast that
is painful. Differs from calcification in cancer….painless.
Fibrinoid necrosis: looks like….but its not…Necrosis of immunologic disease. Palpable purpura—
small vessel vasculitis. Type III hypersensitivity. Immune complex deposition. Activates complement
(alternative system…c5a activated…chemotatic to neutrophils—produce damage) Henoch Schonlein purpura
(Type III). Morning stiffness….rheumatoid arthritis.
Liver: fatty change. Three structures, portal vein, hepatic artery, bile duct. Liver has sinusoids…just
like spleen and bone marrow. Sinusoids have gaps btw endothelial cells, so that inflammatory cell and RBCs
can fit through. Taken up by central vein, becomes hepatic vein..inferior vena cava and right side of heart. If
right sided heart failure…sinusoids will fill with blood…nutmeg liver. If you block Portal vein...nothing
happens. If you block hepatic vein Budd Chiari syndrome. Zone 1, yellow fever hits zone 2. Zone 3 gets fatty
change. Around central vein gets least amount of O2. Most common cause of fatty change…alcohol. NADH
part of metabolism of alcohol. Increase in NADH in alcoholics. Lactic acidosis always seen in alcoholic
because NADH drives it in that direction. Fasting state….alcoholic will have hypoglycemia because pyruvate
is forced to lactate. Increase in synthesis in ketoacids, (Beta hydroxybutric acid.)
Forces to become glycerol 3 phosphate. Glycerol 3P Shuttle to get NADP. Carb backbone to form triglycerides.
Add three FA….you get triglycerides…VLDL. Endogenous triglycerides synthesized in liver. Restrict carbs
would decrease synthesis of VLDL because there is a glucose intermediate that it is made from.

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 Liver: Fatty change…Kwashiorkorapoproteins need to be placed around VLDL to get it out of liver.
Doesn’t solubilize in water. Protuberant abdoment….decreased protein…decreased oncotic pressure.
Types of calcification: Dystrophicabnormal calcification….damaged tissue that calcifies. Most
common cause of aortic stenosis.
Metastatic calcificationHigh phosphorous or high calcium deposition in bone.
Defect in cell membranespherocytosis: if you can’t see a central area of pallor…it’s a spherocyte. Need
spectrin to form a biconcave disk. Spherocytosis…think spectrin.
Ubiquitin: stress protein…Intermediate filaments=keratin, desmin, vimentin…when damaged…get
ubiquinated. Mallory bodies….keratin filaments that are damaged…alcoholic hepatitis.
Neurofibrillary tangles: Jakob Creutzfeld…tau protein…ubiquinated neurofilament
Substantia nigra: Parkinsons...Lewy body….shows up blue….dopamine
Types of cells: Labilecell that division is via stem cells…bone marrow, skin and base of crypts
in intestine. Affected by drugs that affect cell cycle. Bone marrow suppression…diarrhea, skin rashes.
Stabile cells in Go phase…will do division.
Smooth muscle can under go hypertrophy and hyperplasia. Most variable phase of cell cycle is G1…
Proliferative phase in menstrual cycle is analogous. If cancer cells have a longer cell cycle….would be due to
G1 phase. Check point G1 to S phase.
Cyclin Dependent Kinase: Phosphorylation. Usually activate something. Phosphorylates Rb and allows
S phase. Rb suppressor protein…blocks Rb gene from going into cell cycle. Human papilloma virus inactivate
Rb suppressor and p53 (Chr 17)….makes E6 (knocks off p53) and E7 (Rb suppressor) genes. Not only
retinoblastoma. Osteogenic sarcoma in child. If you knock off p53you will always go into S phase. In G2
phase you make tubulin. Blocked by bleomycin.
Vinalkaloids: work at mitotic spindle. Paclitaxil, griesofulvinM phase, ---“HIV positive person with
dyspnea and tachypnea and white out of the lung, put on a drug and ends up with cyanosisdapsone
Acute gouty arthritiscolchicine acts on M phase.
Different growth alterations: Atrophy, decreases in tissue mass. Hydronephrosisstone in ureter causeing
increased pressure on cortex and medulla. Could knock off the neurons in layers 3,5,6. Alzheimers,
degeneration in neurons….overall mass of brain is reduced. Beta amyloid protein.
Hypopituitarism…adrenal gland will be atrophy…fasculata (cortiso) and reticularis (androgens).
Because ACTH does nothing for z. glomerularis.
Biopsy of pancreas from a child with CF….atrophy….CFTR on chr 7. Mucus secretion problems. Ducts are
blocked…glands are atrophied b/c of backpressure. Malabsorption in all children with CF.
Hypertrophy: Of cardiac muscle…supposed block is before the G2 phase. 4N….after everything is doubled.
1N is a sperm…2N is normal diploid cell….3N is bad interms of cancer or triploidy
Hyperplasia: increase in number of cells. Hyperplasia left unchecked you run the risk of cancer.
Gravid uterus: after delivery…hyperplasia and hypertrophy.
Normally should have 3x as many WBCs as RBCs. If more RBCs—COPD—increase in EPO made in
endothelial cell of peritubular capillary.
Psoriasis: on ebow…example of hyperplasia. Squamous cell proliferation unregulation.
Prostate gland: Hyperplasia….hormone stimulated gland…wall of bladder undergoes hypertrophy b/c is it
muscular…related to afterload…what it is pushing against.
Metaplasia: replacement of one adult cell for another. Mucus secreting cells and glandular cells in lower
esophagus. Squamous cells should be there. Barretts esophagus. Adenocarcinoma of distal eso is number one
eso cancer. GERD #1 precursor for esophageal cancer.
Lining of mainstem bronchus…ciliated pseudostratified columnar…to squamous is metaplasia.
Goblet cells in stomach…would be glandular metaplasia caused by H. pylori. Precursor lesion for
adenocarcinoma.
Lung: Squamous dysplasia can go into squamous carcinoma.
Two parasites that are cancerous=clonorchis senisus&schistosoma.
Dysplasia; atypical hyperplasia.

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Precursor for squamous cell carcinoma of the skin: Actinic Keratosis, solar keratosis. UVB light damaged
skin…..farmer with sun exposure…scrapes it off and it comes back.
Bee Sting: Acute inflammation: Ruborredness…histamine dilates arterioles
Calorheat….histamine again from vasodilatation
Tumorincreased vessel permeability, in veinule due to histamine.
Dolorpain…bradykinin….hagemans factor 12 and 11. Intrinsic
pathway automatically activates kininogen system. Degraded by Angiotensin converting enzyme. Angio
edema with ACE inhibitor.
Neutrophils in small vessels get sticky…will marginate to endothelial cells…Type 4 collagenase
drill through…cancer cells also have type 4 collagenase to get through BM. Emigrate…directed chemotaxis…
C5a. LTB4
Opsonizers: C3b, IgG…..Sex linked recessive Bruton A-gammaglobulinemia. Mechanism is no IgG to
phagocytose bacteria. Neutrophils have receptors for opsonizers… Monocytes and macrophages for chronic
inflammation.
Molecular O2 converted by NADPH oxidases not in macrophages…commonly synthesized by
Glucose 6 phosphate dehydrogenase. Respiratory burst….O2 free radical that gives off energy. NBT dye test.
Will cause a blue color dye change if respiratory burst occurred. Can find Chronic granulomatous disease.
O2 dependent myeloperoxidase system…potent bactericidial mechanism…neutrophils and monocytes-----
macrophages don’t have the system.
Chronic Granulomatous disease….mother to son…mother is asymptomatic….Missing NADPH oxidase
Can’t kill staph, but can kill strep. Staph is cat and coag positive. Strep is catalase negative.
Myeloperoxidase deficiency…do have respiratory burst. Normal NBT dye test, but can’t make bleach.
Microbiocidal defects…MD & CGD.
Child whose umbilical cord doesn’t fall off….adhesion molecule defect. Histamine=vasodilates
arterioles.
NO made in endothelial cells….potent vasodilator. Big time role in septic shock.
IL-1 is pyrogen…stimulates hypothalamus…prostaglandins cause fever.
Cortical steroids inhibit phospholipase A2…supreme anti-inflammatory agent. Linoleic acids block
platelet aggregation.
LTC4, D4,E4….potent vasoconstrictors. Aspirin blocks cycloxygenases.
PGH2, PGI2vasodilator, inhibits platelet aggregation, opposite of Thromboxane A2. Dipiramidol blocks
thromboxane A2.
PGE2vasodilator in kidney…keeps patent ductus arteriosus patent. Makes mucus barrier in stomach, causes
dysmenorrhea in women. Abortofactant in pregnancy.
Cortical steroids: decrease adhesion molecule synthesis, Epi, NE. Decrease B cell count by apoptosis. Signal
for caspasases. Only thing increased is neutrophils. Lymphocytes and eosinophils decreased.
Addisons disease: no cortisol, so neutrophil count decreases and eosinophil count increases.
Electron microscopy of inflammatory cells: Neutrophils…many lobes. In Lung “type two pneumocytes &
alveolar macrophage”—little black dots. Monocyte, grayish nucleus—scavenges around can phagocytose
oxidized LDL. Form foam cells. Lymphcyte...all nucleus with very little cytoplasm-->Most likely T cell…
CD4 (2:1 vs. CD8)
Cell with Rough endoplasmic reticulum: makes proteins—plasma cell…derived from B cell….located in
germinal follicle.
Killing invasive helminthes: type II hypersensitivity, cell hooking into an antibody on a target cellcoated
with IgE antibodies. Major Basic Protein destroys helminth. Eosinophilsreddish color with crystals in the
granules (charcot-leiden crystals in sputum of an asthmatic). In type I hypersensitivity, mast cells are in charge
of eosinophil chemotaxis. Basophilsmore bluish.
Cluster Designations: Marker for t cells CD3
Marker for Histiocytes CD1
Marker for most common leukemia in children: CD 10 CALLA antigen.
Reed Sternberg cells CD15/30
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 CD 21...EBV hooks into on B cells.
CD 45 is on all leukocytes.
Fever: IL-1….PGE2. Right shifted O2 dissociation curve. When you give antipyretic for patient with
infection….not smart. B/c you stop mechanism for oxygen getting to the neutrophils to stop infection. Hot
temp in body are not good for reproduction of bacteria and viruses. Getting lots of O2 to tissue.
Types of Inflammation: Post partum woman with pus coming out of lactiferous duct. Staph A.
Bone in child with sepsis (metaphysis) Osteomyelitis---hematogenous spread Staph, If
child had Sickle cell...Salmonella
Hot over face spread out….cellulitis….Group A strep pyogenes (beta hemolytic).
Corynebacterium diphtheria…grey/white pseudomembrane developssimilar to Clostridium difficile. Toxin
damages membrane.
Most common organism in third degree burn: pseudomonas auerginosa—green pus due to pyocyanin.
Bread and butter pericarditis…fibrinous pericarditis. Friction rub in Lupus, also seen in coxsackie virus.
Basal cell layer on both sides of cut go underneath clot…By 48 hours the wound is sealed off. Granulation
tissue starts on day 3….fibronectinadhesion/chemotatic agent. Type 3 collagen responsible for initial stages
of wound repair. Max wound strength you can have in wound by 3 months—80%. Type 3 collagenases --- Zn
deficiency always causes problems with wound healing.
Ehlers Danlos syndrome—defective collagen, would have poor wound healing.
Patient with scurvy…defect in hydroxylation of proline and lysine….triple helix formed by cross bridging.
Lysyl oxidase. Weak abnormal collagen in scurvy b/c no cross bridges. Hemarthrosis (bleeding into joints)

Granulation tissue has a lot of blood vessels b/c of fibroblast growth factor.
Hypertrophic scar is excess of type 3 collagen….Relationship of squamous cell carcinoma and third degree
burns. Chronically draining sinus tracts predisposes to squamous cell carcinoma. Hyperplasia of epithelium.
Main component of Acute inflammation: IgMten antigen recognition sites, and it goes C1-9. IgG requires
two to activate complement…and it only goes to C3. Key cell is neutrophil. Viral infection cell is
lymphocytes.
Chronic inflammation: Strong IgG response. Plasma cells and lymphocytes…won’t see pus or exudate.
GranulomaCaseous necrosis in TB. Roundish and pink….multinucleated giant cells. Type 4
hypersensitivity. Cytotoxic T cells—DTH (poison ivy). Alveolar macrophage takes TB all around the body.
Processes antigen. Presents it to helper T cell. Will release cytokines. Activated by gamma interferon.
Epitheliod cells are activated macrophages. When they die…form multinucleated giant cells.
Subset I—Helper T cells: when macrophage secretes IL-12 it presents antigen to subset I helper T cells.
CD4 Tcells become memory cells of antigen experience. Most cases of TB are reactivation TB. Positive
PPD…injected into skin. Histiocyte of skin=Langerhans cells—CD1…birbeck granules (look like tennis
rackets) Hooks in by Class II sites. Helper T cells release cytokines to cause inflammation. “+ PPD” Person
with AIDS won’t get granuloma b/c they don’t have the helper T cell count.
Reaction to injury: Heartscar tissue. Ejection fraction will decrease b/c fibrous tissue doesn’t contract.
Kidneyscar. Medulla most succeptible to ischemia, Most succeptible part of
nephronstraight portion of proximal tubule…where most oxidative phophorylation occurs. Thick ascending
limb in medullary segment where lasix works. Na+/K+/2Cl cotransport pump generates free water. 20 ml for
every Na+, K+ and Cl+ that is excreted. Resorb Na/K and 2 Cl….80 ml resorbed.
Type II pneumocytes; repair cell of lung….synthesizes surfactant
Astrocyte: proliferation when CNS is injured.
Wallerian Degeneration: PNS…schwann cell can regenerate axons. (nerves can regenerate at 1mm/day under
optimal conditions.
(AD) Neurofibromatosis has genetic correlation to Schwannoma of 8th cranial nerve….acoustic neuroma.
Erythrocyte sedimentation rate: put whole blood into cylinder how many mm in hour it settles. Increased sed
rate is due to increased IgG--Inflammation. If they stick together in clumps….IgM. Cold agglutinins…

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Raynauds phenomenon in cold weather. Get ischemic in distal limbs. Cryoglobulins….high association with
Hepatitis C and cryoglobulins.
CBC…complete blood cell count….if acute appendicitis…absolute neutrophil count increase. Toxic
granulation. See left shift. Myeloblast on left to segmented neutrophil on right….go back to immature
neutrophils. Greater than 10% band (left shifted neutrophils)
Oxygen dependent myeloperoxidase system…in azurophilic granules…lysosomes. Most potent system to kill
bugs.
Fluid and Hemodynamics: Edema Excess fluid in extracellular space. Pitting…fluid/transudate
right heart failure.
Transudate Starling’s forces: Forces that keep fluids in blood vessels….80% related to albumin…oncotic
pressure. Hydrostatic pressure tries to push fluid out. Anytime you have decreased albumin you would have
leakage of transudate (protein poor/cell poor).
Albumin: made in liver, chronic liver disease will lead to low albumin. Can lose via plasma in third degree
burns, excrete in urea and feces…nephrotic syndrome.
Alkaline tide: Cephalic phase of digestionevery H+ that goes into stomach before eating, you get a
bicarb that goes into the blood. Vagal nerveGastrin cells stimulated and PNS. Develop metabolic alkalosis.
Compensation is respiratory acidosis, PO2 is decreased….tissue hypoxia…tires you out.
Gastric phaseHCl…H+ ions in food will eventually be reunited with bicarb.
MI 24 hours ago….lung fluid…transudate…increased hydrostatic pressure….left heart failure back up into
lungs.
Exudates pus…doesn’t pit. Histamine..Type 1 hypersensitivity. 1st step in managementairway. 1:1000
aqueous epinephrine sub q for bee sting.
Cirrhosis…ascites, decreased albumin and blockage at portal vein. Decrease in oncotic pressure. If R
heart failure….decrease in hydrostatic pressure when fluid backs up.
Lymphedema: dermal lymphatics can plug with cancer, Peau d’ orange….dimpling on surface of breast. Post
radical mastectomy…can end up with sarcoma.
Renal: ECF: two compartments….vascular 2/3 ….interstitial How many liters of isotonic saline would you
have to infuse to get 1 liter in plasma….3.
ICF: 2/3 larger than ECF.
Height of squares is normal plasma osmolality…X axis is volume.
Osmolality: measure of solutes in fluid. Sodium, glucose and BUN.
Osmolality 2x sodium level + ten = measured osmolality. ECF compartment urea can equilibrate across
compartments, therefore urea doesn’t contribute to osmolarity. Sodium and glucose are limited to ECF
compartment. Diffusion goes from high to low but osmosis goes from low to high…Hyperosmolar solution
will draw water….ICF will be expanded in brain in hyponatremia. Hypernatremia (ratio of total body sodium
to total body water): water will move out of ICF and into ECF. Brain cells will be contracted. Mental status
abnormalities.
Diabetic ketoacidosis…1000mg/dl blood sugar. Glucose goes into cell with phosphorus. Water will move
from ICF to ECF. Cells shrink. Serum sodium concentration will decrease with hyperglycemia.
Urea doesn’t control water movements.
Tonicity: Isotonic: Loss of fluidlosing equal amounts of salt and water. Would be in ECF.
Serum sodium concentration would be normal. ECF would be contracted. Hemorrhage/Adult Diarrhea.
Isotonic gain too much normal saline. Serum sodium would be normal…Excess in ECF. No gradient for
water movement.
Hypotonic: Low osmolality…hyponatremia…lose more salt than water. Serum sodium
decreased. Kidneydiuretic: lose hypertonic fluid in urine. Water would more into ICF. If you gain pure
water but no salt. Inappropriate ADH syndrome. Small cell carcinoma of the lung. Concentrated urine. Gain
pure waterADH always present…into ECF compartment. ICF and ECF expanded. Tx: restrict water.
Lowest serum sodium that you will ever see is in SIADH. Serum sodium less than 120…SIADH. Type II
diabetic….all oral sulfonylureas (esp 1st generation) can cause SIADH. Edema states: Pitting edema, R heart

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failure, cirrhosis….total body sodium when increased always causes pitting edema. ECF: in interstitial fluid
compartment, you will end up with transudate b/c of increase in Na+ in ECF.
Hypertonic: Hypernatremia or hyperglycemia. Hypernatremia…ICF compartment is
shrunken. Lose pure water, diabetes insipidus. Osmotic diuresis-mixed, glucose in urine or mannitol, you lose
a hypotonic salt solution. Baby diarrhea is hypotonic loss. Rotovirus infection should have hypernatremia in
baby. Give baby Gatorade or Pedialyte. Needs glucose to resorb sodium in intestine. Cotransport pump.
Sweat is hypotonic. Should have hypernatremia when you cross finish line after a race.
Arterial Blood Volume: SV in CO. When CO decreases physiologic mechanisms to restore volume...
Baroreceptorslow pressure on venous, high on arterial side. High pressure innervated by CN 9/10. When you
have a decreased in SV or CO you underfill the arch vessel and the carotid….catecholamines released…
Sympathetic nerve response on low volume. Will constrict venules. Peripheral resistance Arterioles
constricted…maintains diastole…Angio II stimulates aldosterone release to resorb salt and water to get cardiac
output back up.
If you lose large amount of blood…give normal saline…hypovolemic shock…keep BP up with normal saline,
since it resembles plasma. 0.9% Normal saline stays in ECF compartment.
Peritubular capillary pressures. Proximal tubule…60-80% of sodium reabsorb. Peritubular oncotic pressure
increases when cardiac failure causes less flow to renal arteries, b/c hydrostatic pressure decreases.
If Stroke volume increased….baroreceptors (CN9/10) will be stretched…will get parasymp response. Fluid
overloaded…get rid of it. ANP released—from RA gets rid of salt. ADH release is decreased. Lose hypotonic
fluid in urine. Peritubular hydrostatic pressure is higher than oncotic pressure….can’t reabsorb salt into blood.
“Patient given 3% hypertonic saline….” Osmolality will increase. (pOsm) Serum ADH will increase.
Total body sodium in patient: look at dry tongue….decreased. Skin turgor says normal total body sodium.
Dependent Pitting edema in patient…total body sodium is increased.
Inappropriated ADH—gaining pure water…total sodium normal, serum sodium decreased.
R. heart failure: serum sodium will be low. Nonpharmacological treatment: restrict salt and water.
Shock: hypovoluemic shockcholera/diarrhea. Sweating. Patient with Diabetes insipidus is not
hypovoleumic there are losing pure water. Tilt test…if you stand up and BP drops but pulse goes up—means
they are volume depleted—due to catecholamine effect. Tx: Normal Saline.
Tonicity of sweat….hypotonic Tilt test: 100/80 lying down—normal pulse, 70/50 standing up—pulse
150….infuse with normal saline. Still have dry mouth after a couple liters….hang up hypotonic salt solution…
Diabetic ketoacidosis: 1st step for hypovolumia…normal saline…make them normotensive. Losing more water
than salt in urine, hang half normal saline with insulin.
SHOCK: Hypovolemic shock: blood loss, cold clammy skin (vasoconstriction of peripheral vessels),
diarrhea, anytime you lose salt, pulse increased.
Cardiogenic: BP decreased, cold clammy skin (vasoconstriction of peripheral vessels), pulse
increased.
Septic shock: most commonly due to Ecoli from indwelling urinary catheter. Endotoxins in cell
wall…LPS makes gram negative organisms. Alternative complement system activated. Anafilatoxins released
C3b C5b. If blood flow is increased through peripheral vessels. NO and PGI2 are vasodilators in peripheral
resistance vesselsblood is gushing through. TPR decreases as radius increases. Due to turbulence, tissue
can’t get Oxygen. Coming back to heart faster than normal b/c arterioles are dilated. CO is increased in septic
shock. Skin feels warm. High output failure.
TPR=viscosity of blood/radius to 4th power main factor in controlling, radius. Viscosity increased in
polycythemia, decreased in anemia.
Swanganz catheter: CO in Rside of heart,
Systemic vascular resistance, tells you what is going on in arterioleshypovolemic and
cardiogenic shock is increased….vasoconstriction
Mixed venous Oxygen content absolute best test for tissue hypoxia. What is actually
returning from tissue. Hypovolemic and cardiogenic shock MVOC is very low…no force behind blood
pushing it through. In septic shock, tissues can’t extract the O2 out, so MVOC is high.

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 Pulmonary capillary wedge pressure: Measure of left ventricular end diastolic volume
and pressure. Hypovolemic: low, Cardiogenic shock: high.
Of all organs in body: Kidney Medulla suffers most from decrease in CO. In brain, collateral circulation
of blood from Circle of Willis. Oliguria and increase in BUN…causes shivers in body because patient is going
into acute tubular necrosis. Give dobutamine to increase renal blood flow. Chances of survival in ATN is zip.
Sickle Cell trait: Young black woman, normal physical exam except microscopic hematuria…..first
step: sickle cell screen. Oyxgen tension in renal medulla is low enough to induce sickling and cause
microinfarctions ing the kidney.
Acid/Base: Acidosis…increase in hydrogen ions, pH decreased.
pH is equal to Bicarb / pCO2. If you increase Bicarb…increased pH, therefore metabolic alkalosis.
Compensation is body’s attempt to try to maintain normal pH. If respiratory acidosis is primary, need to raise
numerator…metabolic alkalosis. Hyperventilation…increasing respiratory rate, blow off more CO2—shift
equation to bicarb resp. alkalosis.
Respiratory Alkalosis: Anxiety-feeling paraesthesias.…ionizing calcium level gets lower...breathing too fast.
Treaussea’s sign—thumb adducting into palm. Tetany. Positive Chovstek sign. Pregnant women with high
estrogen…clear more CO2 per breath than normal woman. AV fistulas in lungs of pregnant woman.
Endotoxins overstimulate the system. All patients in shock--Anaerobic metabolismMetabolic acidosis.
Aspirin intoxicationadd acid to body, metabolic acidosis, but increased ventilation (so mixed disorder). “6
year old child with inspiratory stridor….swollen epiglottis, acute infection of H. influenza”. 3 month
old….Crouplaryngotracheal bronchitis…parainfluenza…obstruction is in trachea. Restrictive lung disease,
problem getting air in. Sarcoidosis, Pneumoconisis.
Resp Acidosis: Barbituates depress respiratory center, CNS injury to medulla. Chest bellows, Erb Duschenne
palsy…Diaphragm on right side is elevated…retain CO2. Amytropic Lateral sclerosis. Guillan Barre:
ascending paralysis in someone that had upper respiratory tract infection one week ago. Spinal fluid shows
increase in protein, slight increase in lymphocytes. Things that paralyze muscles of respiration can produce
resp. acidosis. Obstructive lung disease. Problem of getting air out…increased CO2.

Day 2:
For every 30/33ft you increase one atmosphere of pressure. Reverse is true in high altitude. Have to
hyperventilate at high altitude b/c as you lower PO2 you increase PCO2. Caisson’s disease—the bends.
Nitrogen comes out in tissue.
NUTRITION:
Eating disordersanorexia nervosadistorted body image difference btw bulimia nervosa. Lose 15%
of body weight, GnRH decrease, FSH and LH decrease, low estrogen levels, develop osteoperosis. Try to
convince person to gain enough weight to get periods back. “think cheap”…Usually die of cardiac disease.
Bulimia; no distorted body image, but they binge/purge. Enamel wears down and Dentin shows.
Metabolic abnormalityalkalosis, which left shifts your curve, compensation is respiratory acidosis…Tissue
hypoxia….Throw premature ventricular contractions/arrhythmias. Could vomit up blood…Mallory Weiss tears
in distal eso/proximal stomach. Or Borhoff syndrome…rupture or air into pleural cavity… “Hammond’s
crunch” by stethoscope.
Obesity: BMI…kg/m^2 magic number is 30…OBESE….over 40 morbidly obese. Main complication:
hypertension. Left ventricular hypertrophy, gall bladder disease. If a lot of adipose, run risk for estrogen
related cancers b/c of converting enzyme.
Marasmus….total calorie deprivation.
Kwashiorkor…poor cellular immunity levels, low albumin…ascites, cirrohsis. Copper deficiency…reddish
hair.
Fat Soluble: Taken up by chylomicrons. ADEK. More likely to be stored in fat. Toxicity is worse.
Water Soluble: Cofactors for biochemical reactions.

8
VIT A: Very important for growth in children. Normally prevents squamous metaplasia…Def: Area of
squamous metaplasia around eye. Failure to thrive with Vitamin A deficiency. Night blindness-Nictolopia.
Hypervitaminosis A: “Bear liver…big game hunter with headaches, cerebral edema with papilledema.”
Retinoic acid…can produce severe liver toxicity.
VIT D: Deficiency…most common source is sunlight. Starting from cholesterol, (cell membranes, bile salts,
etc) Gets reabsorbed in jejunum, two hydroxylations, first in liver (25 hydroxylation), then in kidney. PTH puts
it into proximal tubule. 1alpha hydroxlase—active Vit D. Reabsorbs Ca++ and phosphorus from jejunum…
mineralizes bone and cartilage.
PTH: Increased calcium reabsorption. Where thiazides block in distal tubule. Hypercalcemia is
potential side effect of thiazides. Most calcium stone formers, want to suck calcium OUT of urine.
Decreases reabsorption of PO4 in proximal tissue and decreases HCO3. Osteoblasts have receptor for Vit D.
Alpha1phosphatase activated. PTH breaks down bone, has receptors on osteoblasts too, and releases IL-1
(osteoclast activating factor). Sex hormone are check on IL-1. Calcitonin has receptors on osteoclasts.
Vit D more concentrated on mineralizing bone and cartilage. Deficiencylack of sunshine, poor diet, liver
disease “patient on phenytoin—patient had hypocalcemia” alcohol, rifampin, barbiturates (induces cyto p450
and revs up metabolism of ) metabolize Vit D.” “Woman on phenytoin and birth control and got
pregnant….SER gammaglutamyl transferase revved up by alcohol.
--Most common is renal disease (MCC of chronic renal disease in states diabetes mellitus), if second
hydroxylation can’t happen. Osteomalacia in adults…easy to fracture, Rickets in children, soft skulls,
“Craniotabes” …..Hypervitaminosis D…complication would be kidneystones.
Type I vitamin D dependent rickets missing 1alpha hydroxylase, Type 2 you are missing the receptor for Vit D.
VIT E: Maintain cell membranes…prevent lipid peroxidations, free radical damage. Also can neutralize
oxidized LDL-->the one that macrophages will phagocytose to produce foam cells. Can be deficient, CF
patients, malabsorption due to pancreatitis. Malabsorption of fat, give them fat soluble vitamins. Hemolytic
anemia when RBCs are succeptible to free radical damage. Toxicity more than 1100 units. Prevents
synthesis of vitamin K coagulation Factors II, VII, IX, X, protein C and protein S. You become
anticoagulated with excess Vit E. “patient with MI, take antioxidants, and aspirin”. Patient goes home on 3
months of warfarin after anterior MI…and takes Vit E….BAD NEWS. Over anticoagulation. Synergistic with
warfarin.
VIT K: most comes from anaerobes in gut. Give to infant, b/c it’s not in breast milk, and not in gut yet.
Usually get colonized after 5 days. K2 inactive and needs to be converted to K1. Epoxide reductase is the
enzyme that converts K2K1. K1 gamma carboxylates Vit K coag Factors, 2,7,9,10. Only coag factors that
are bound to clot by calcium. Glutamic acid residues get carboxylated and allows Ca++ to bind to the factors.
Warfarin blocks activation of K1(epoxide reductase). Deficiency: broad spectrum antibiotic. If def:
Hemorrhagic diaphesis—bleeding in brain/skin. Tx: with intramuscular vit K.
Water Soluble vitamins: “tea and toast” diet….malnourished…bleeding gums….vit C deficiency (scurvy—
golgi apparatus, weak collagen, can’t cross bridge it. Blood vessels are unstable. Type 1 collagen.
Hemarthrosisbleeding into joints
Perifollicular hemorrhage hair follicles will have ring of rupture around follicle. Get cork-screw hairs.
Tongue—glossitis,
Excess Vit C.= Renal stones, excess uric acid.
Vit C can be used as ancillary treatment for methemoglobinemia. Vit C required for catecholamine reactions.
Dehydrogenase reactions require thiamine: PDHT.L.C.F.N.
Pyruvate dehydrogenase….converts pyruvate to acetyl CoA. If thiamine deficit…can’t enter Krebs Cycle.
ATP depletion.
Wet Beri Beri/Dry Beri-BeriWernicke/Korsakoff…need a lot of ATP to make myelin….will get peripheral
neuropathies if you don’t have it. Foot drop, perineal nerve. Claw hand…ulnar nerve. Korsakoffs…memory
related. Most common cause is alcohol in US. Wet beri-beri is heart failure. Bi-ventricular enlargement.

9
“Patient in ER needs IV line….5% dextrose and normal saline…nystagmus & opthalmoplegia” Subclinical
thiamine deficiency. Hang thiamine before giving glucose in setting of an emergency room on patient that is
semi-comatose.
Niacin Deficiency: Pellagra…rash in sun exposed area. Diarrhea, dermatitis, dementia. “Kassels necklace”
NAD reactions…oxidation/reduction. Nicitinic acid. FH…drug of choice for hyperlipidemia.
Riboflavin: Flavin Adenine Mononucleotide. FAD/FMN reactions. Oxidized glutathione to
glutathioneriboflavin is cofactor for that reaction.
Periodoxine Succinyl CoA + glycine (ala synthase)…synthesis of Heme. Vit B6. Transaminases…SGOT.
B6 is important in synthesizing neurontransmitter….isoniazid most common cause of Vit. B6 deficiency.
Patient will develop neurologic problems.
Biotin: Pyruvate Carboxylaseforms oxaloacetate…would get deficient if you ate large amount of raw eggs
everyday.
Trace elements: chromium..glucose tolerance factor…helps insulin do its job. Good if you are a type II
diabetic.
Copper deficiencyLysyl oxidase; puts cross bridge between collagen fibrils and elastic tissue. Can
get dissecting aortic aneurysm.
Flourine: too muchget white chalky teeth, get calcification where ligaments go into bone.
Selenium: Pentose phosphate shunt. Necessary for Glutathione peroxidase reaction.
Zn: Older person with dysjucia, abnormal taste and smell. Metaloenzyme…breaks down type III
collagen so that you can make Type I collagen. Diabetics are all Zn deficient.
Dietary Fiber: Soluble fiber can lower cholesterol…will suck up water from colon, and cholic acid as
well…95% of bile acids are resorbed in terminal ileum. Lipocholic acid…which gets excreted.
Protein restriction diet: Restrict in renal failure…b/c protein will be broken down to ammonia and
kidneys will have to excrete more urea. Cirrhosis as well, defective urea cycle.
NEOPLASIA: Benignusually doesn’t metastasize, malignant has capacity.
Lyeomyoma: most common benign tumor in a woman is most commonly located in uterus. Tumor of
smooth muscle.
Most common benign tumor in male: Lipoma.
Benign tumors of glands: adenoma could be making cortisol…could suppress ACTH…would screw up
fasciulata and reticularis…undergoing atrophy. If it was secreting mineralocorticoids (Conn’s syndrome)
would cause atrophy of glomerulosa (aldosterone). Fasiculata (cortisol) reticularis (androgens) GFR=ACA
Tubular adenomastrawberry on a stick…precursor for colon cancer.
Carcinoma malignancy of epithelial tissue…squamous (red swirls--squamous pearls), glandular—round
with something in the middle, transitional cell carcinoma—bladder, urethra, renal pelvis.
Nevis is benign version, melanoma is malignant…neurosecretory granules of Amine Precursor Uptake
Decarboxylation (APUD—NC) origin. S100 antigen positive.
Sarcoma malignancy of mesenchymal tissue. Metaphysis is split upOsteogenic sarcoma—sunburst
appearance. Embryonal Rhabdomysarcoma…”necrotic mass coming out of vagina”….striations of
muscle….most common sarcoma in children. Lyeiomyosarcoma—smooth muscle, striated muscle—
Rhabdomyosarcoma. Mixed Tumor at angle of the jaw…Most common overall salivary gland tumor.
Teratoma: teeth and hair…derived from all three cell layers. “16 year old girl sudden onset of R lower
quandrant pain (DDX: appendicitis, Crohns, ectopic pregnancy, ovarian cyst) with calcifications….teratoma”
Tendency to stay in midline….pineal gland.
Leukemia: Auer rod…malignancy of stem cells in bone marrow. Hepatosplenomegaly.
Malignant lymphoma arise from LYMPH NODES. Extra-nodal lymphoma usually occurs in stomach. H.pylori
can produce them. Peyer’s patches (GI—terminal ileum) is second most common site. B cell lymphoma is
most common of all lymphomas.
Hydatidiform mole…looks like a bunch of grapes…1st trimester with signs of preeclampsia (hypertension,
proteinuria and edema in 1st tri). Uterus too large for gestational age. Complete mole—highest probability of
going into choriocarcinoma. Mole= Benign tumor of chorionic villus, lined by trophoblastic cells.

10
Synctialtrophoblast: makes hormones: Beta HCG and Human placental lactogen.
All that ends in -oma is not necessarily benign. Melanoma, lymphoma. And is not necessarily a neoplasm…
Hammartomaovergrowth of tissue not normally present in that area—Bronchial hammartoma. Nonneoplastic
lesion polyp of Peutz Jagers syndrome.
Heterotopic rest: Tissue growing in location where another type of tissue predominates. Meckels Diverticulum
—common complication is bleeding.
CANCER: more chr than normal…atypical mitotic spindle. 30 doubling times and you get a tumor that you can
detect clinically. Lack adhesion…usually anaerobic metabolism…need collagenases and proteases.
Metastasis—Lymphatic Carcinomas usually mestastisize via local lymph nodes…subcapsular sinus.
HematogenousSarcoma…lungs and bone are common sites of metastasis for sarcomas.
Renal adenocarcinoma likes to invade the renal vein. Hepatocellular carcinoma always invades vessels.
SeedingOvarian cancers…malignant implants. Pouch of Douglass is comparable to prostate…
most dependant part of a womans pelvis—unclotted blood goes in ruptured ectopic, endometrial implant
in endometriosis. Glioblastoma multiformae…can seed in the spinal cord.
Most common cancer….IS METASTASIS MORE COMMON THAN THE PRIMARY CANCER? Lung…
most common is breast cancer….women are more likely to have mestastasis to lung.
Bone…Batson system, base of skull to sacrum…woman with breast cancer dislodges into vena cava…3 months
has lower back pain.
Most common bone to metastasize to is the vertebral column…2nd most commonFemoral head….
Most common organ metastasized to…lymph nodes
Most common cancer of liver…metastasis…lung.
Testicular cancer metastasizes to paraaortic lymph nodes, not inguinal lymph nodes. Seminoma…
Left supraclavicular node....Virchow’s node….stomach is primary. Weight loss and epigastric distress.
Lytic—break bone down…multiple myeloma has nice punched out lesions due to IL-1…pathologic fractures
and hypercalcemia. Collapsed vertebra. Absence of bone.
Blastic—dense response…alkaline phosphatase is elevated…most likely male with prostate cancer.
CT scan of the liver: if you see gross specimen with multiple lesions it is metastasis.
Most common cancer of the brain, metastasis, most common primary is lung.
Most common cancer of lung is metastasis from a breast primary
Adrenal gland; metastasis from lung.
Desmin…intermediate filaments. Muscle tumors. Most carcinomas have keratin. If you had histiocytoma
you’d see Birbeck granules…APUD tumor, you’d see neurosecretory filaments. If vascular malignancy, you’d
see Weibel Palade bodies that have Von Willebrands factor in them.
Oncogenesis: “Fraternities and Sororities”
First Step: Initiation…mutation.
Promotion…going through cell cycle.
Progression…different kinds of cancer cells have different functions--subspecializing
Two sets of genes involved in cancer; growth factorsneed to hook onto a receptor. EDGF, Ras protoncogene,
Abl-in cytosol, tyrosine kinasephosphorylation
suppression genes: Rb suppressor and p53, try to keep cell cycle in G1 phase.
Mutation mechanism…point mutation (p53, and ras oncogene knocked out by point mutation) amplification—
ErbB2. Translocation—chronic myelogenous leukemia Abl—tyrosine kinase activity (t: 9-22) Philadelphia
chromosome…fusion gene.
(t: 8-14) Burkitts lymphoma…EBVreceptor on all B cells CD21, causes B cells to become plasma cells and
make antibody, increasing mitotic rate…myc oncogene. (t14:18) Bcell lymphoma. (t15:17 Acute
progranulocytic leukemia)—can treat with retinoic acidmatures the blast…malignant cell becomes benign.
Suppressor genes: Adenomatosis polyposis, Wilms tumor, BRCA 1 &2 BRCA2 is totally associated with
breast cancer…most breast cancers are not genetic.
Chemicals, viruses and radiation. Chemicals is the most common cause of death. (Smoking)

11
Papillary tumor in bladder…most common cause is transitional cancer from smoking, unless you work in a dye
factory. Analine Dyes. If you were being treated with cyclophosphamide and had side effects, they could be
avoided by treatment with Mensa.
Non puritic raised lesions: kaposis sarcoma…Herpes 8.
Burkitts: EBV—Nasopharyngeal (Chinese)… Hepatitis B +cirrhosis+ Aflatoxin; increase risk for
hepatocellular carcinoma (asian countries)
HIV: primary CNS lymphoma…increase in cancer in US is related to increase in HIV rates.
HPV: anus in homos, cervix, vaginal, vulvar cancer. E6/ E7 protein products.
Radiation: Leukemia, Chronic myelogenous (ABL). Radiation in head and neck, non tender myelogenous
masses. Osteogenic sarcoma.
Basal cell carcinoma: derived from basal cell layer, multifocal. Non ionizing…UVB—radiation that causes
skin cancers. Thymidine dimers.
Actinic Keratosis: squamous cell carcinoma. Produces a dysplastic lesion. Arsenic predisposes…Bangladesh
—in water supply.
Retinoblastoma: Chr 13. Sporadic—two separate mutations and familial. White eye reflex. Drug that
predisposes to cataracts Glucocorticoids.
Xeroderma Pigmentosum—DNA repair enzymes—AR disease,
From upper lip up is basal cell, from lower lip down is squamous cell.
Helicobacter Pylori, low grade malignant lymphoma and adenocarcinoma.
Grade and Stage: Grade is what cancer looks like….if it is still well differentiatedlow grade
StageTNM system. Size of Tumor—2 sonometers…if over has a chance to metastasize. Nodes,
Metastasis. ---distant mets are most important prognostic indicator.
CD8 Cytotoxic t cell look for class I antigens that are altered…perforin signal for caspases to apoptotically kill.
Catchexia: TNFalpha—irreversible.
Most common anemia in malignancy: anemia of chronic disease. Most patients with disseminated cancer are
hypercoagulable. Tendency for forming clots. “patient with painless jaundice, light colored stool and DVTs
that jump around—Treauseau’s signCarcinoma of the head of the pancreas” Thrombocytosis—elevated
platelet count. Often related to colon cancer so do stool guiac for any normal physical exam.
Most common cause of fever in malignancy is gram neg organism. Ecoli for indwelling catheter.
Paraneoplastic symptoms: signs that say you may have an underlying cancer present. Hypercalcemialytic
lesions in bone or renal adenocarcinoma or squamous carcinoma of main stem bronchus that cause
Parathormone-like peptide.
Two black lesions in skin: Acanthosis nigricans, and subhorreic keratosis in sudden development: Lesser Trelat
SignPhenotypic marker for gastric adenocarcinoma
Clubbing: Hypertrophic osteoarthropathyprimary lung cancer.
Dermatomyositis: Raccoon eyes, inflammation of skin and muscleIncreased Serum CK, association with
leukemias, lymphomas, lung cancer.
Vegetations of mitral valve…myrantic endocarditis. Mucus secreting colon cancers.
Hyponatremia or Cushings…lung cancer, small cell carcinoma….ADH or ACTH. Apud tumors, NC
origin. S100 antigen
Hypercalcemia or 2ndary polycythemia: Renal adenocarcinoma..PTH like peptide.
Hypocalcemia or Cushings: medullary carcinoma of the thyroid…calcitonin can be converted into
amyeloid.
AFP marker for Yolk Sac tumor. Also assoc. with hepatocellular carcinoma.
Alpha feto protein; open neural tube defects is elevated…downs syndrome is decreased
Bence Jones Protein is the light chain of the immunoglobulin—monoclonal spike (IgG): Multiple myeloma
Prostate cancer tumor marker…Sensitive yes, specific no. PSA. It is not an enzyme. Will not increase with
rectal exam. Prostatic acid phosphatase will increase.
CEA—Carcinoma Embryonic Antigensmall cell carcinoma, colon cancercan produce Diffuse
Membranous Glomerulonephritis as it deposits in glomeruli.

12
Most common primary tumor of brain in kids: cerebellar cystic astrocytomaall astrocytoma are benign. Most
common primary cancer of brain in kids is medullary blastoma.
Most common childhood cancer: Acute lymphoblastic leukemia.
Cancer Incidence Women: Breast, lung, colon
Men: Prostate, Lung, colon
Cancer Killers Lung men and women…men prostate, Second most common cancer killer in men and women
combined is colon cancer.
GYN cancers: Most common cancer#1 Endometrial, #2 Ovarian, #3 Cervical….due to cancer.
Cancer Killer: #1Ovarian, #2 Cervical, #3 Endometrial
Only known existing tumor vaccine. Hep B: most common infection transmitted by accidental needle stick in
hospital: B…won’t get Hep D. Won’t get hepatocellular carcinoma.
Hematology: Big picture— microcytic anemia…MCV < 80 Iron deficiency most common: anemia of
chronic disease, Thalassemia, sideroblastic anemia.
Macrocytic anemia….MCV>100…B12, folate deficiency…alcoholic
Normocytic anemia: Low reticulocyte count corrected. Aplastic anemia, renal disease
High reticulocyte count corrected: Spherocytosis, G6PD Defic. Sickle cell,
autoimmune hemolytic anemia.
Reticulocyte: young RBCwill become mature RBC with biconcave disk. Count tells you where the problem
is. If bone marrow is problem, won’t be appropriate response. If nothing wrong, should have good reticulocyte
response. Correct reticulocyte count for degree of anemia: Hematocrit divided by 45 and multipled by
reticulocyte count given.
Reticulocyte: need special stain to see RNA filaments...still synthesizing hemoglobin.
Polychromasia younger RBCs that still have basophila (bluish color)…bone marrow is pushing really young
cells out. Make additional correction (divide by two)
Multiply Hemoglobin by 3 and should get hematocrit.
For every unit of packed RBC you introduce to a patient you raised the hemoglobin by 1 and hematocrit by 3%.
“patient got 5 gram hemoglobin, given 3 units of packed RBC…following day the heme is 6 and hematcrit is
18…Appropriate response? NO. should have been 8 for heme and 24 for hematocrit. Patient has a GI bleed…
obviously the patient is bleeding. Most common cause of iron deficiency is GI bleed.
MVC: Mean Corpuscular volume….how big is it….? Sizing of all RBC. Best way to classify anemia. Normal
is 80-100. If average is less than 80, by definition it is microcytic…most likely iron deficiency. Between 80-
100…Normocytic. If over 100: macrocytic…B12 or folate deficiency
Small cells and large cells….MCV would be normal. Fe absorbed in duodenum, folate in jejunum and B12 in
terminal ileum. Celiac Disease: malabsorption in duodenum and Jejunum (biopsy for celiac)—would lead to
multiple anemias.
RDW: RBC distribution widthall uniformly…small, normal, or macrocytic. Reported as number.
Microcytic anemia with RDW increased. Difference in size of small cells would lead to high RDW.
Spherocyte…Too little membrane levels. Target cell…..is an obese cell. Excess membrane, more hemoglobin
Target cell is marker for alcoholic because of increased cholesterol levels.
Central area of pallor is due to biconcave disk shape in RBC and more hemoglobin in periphery.
All microcytic anemias have decrease in hemoglobin synthesis…larger area of central pallor.
Spherocytes have no area of central pallor.
Hematology;
Anemia MCV best way to classify…Microcytic anemia. If polychromasia is present 3% or higher
good bone marrow response, 2 or lower, bad.
Physical signs—spoon nails, iron deficiency. Koilonicia. Pallor of conjunctiva—if pale, 6 gram of hemoglobin
or less. Palmar crease—no red, signifies anemia. Neuro exam is very important in B12 deficiency, knock off
posterior columns and lateral cortical spinal tract. Decreased vibratory sensation, Babinskis sign.
Microcytic: Iron studies—Serum Iron normally about 100
Ferritin: circulating form of iron stores. Represents amount stored in bone marrow.

13
 TIBC: = Transferrin is carrying enzyme for iron. Relationship of iron in bone marrow to
transferrin synthesized in liver. When iron in bone marrow is deficientSignal for liver to make more
tranferrin…therefore it is increased in iron deficiency (TIBC is increased when iron deficient). Low iron
stores(ferritin)increased TIBC(transferrin….greater capacity to bind iron) Decreased TIBC=adequate iron
stores
% SaturationSerum Iron divided by TIBC. TIBC is normally 300. % Sat is normally 33%.
Microproblem in making hemoglobin…RBC developing in marrow….heme conc. in marrow determines
number of cell divisions. DECREASE in Hemoglobin. Heme is iron + protoporphyrin + globin chains.
Anemia of chronic disease: when we have bugs in system…bugs reproduce with iron. Iron normally
stored in macrophages in bone marrow. Don’t want bacteria to have access so we lock it away but don’t have
the key. Serum iron is decreased, don’t have enough iron to make Heme.
Sideroblastic anemia: Most common cause is Alcohol. B/c it is a mitochondrial poison, uncoupled
oxidative phosphorylation. Damages the inner mitochondrial membrane. Iron gets caught in mitochondria.
RINGED Sideroblast. Will have excess iron.
B6 deficiency: Isoniazid will deplete. The first reaction of synthesis of heme (Succinyl CoA + Glycine
=Ala Synthaseheme has feedback mechanism with Ala synthase) won’t happen.
Lead poisoning: Produces a sideroblastic anemia. Denaturing of proteins. All heavy metals denature
proteins. Ferrochelatase gets denatured. Iron gets into mito again, but can bind to protoporphyrin. Microcytic
anemia. Ringed sideroblast.
Thalasemia: Genetic disease, AR. Alpha thal: seen in asian pop & black population. Hemoglobin
electrophoresis. Separate HbA(2 alpha 2 beta), HbF, HbA2. Alpha thal is a problem in making alpha chains.
Hemoglobin electrophoresis is normal because all hemoglobin is equally decreased. 2 gene deletionsmild
anemia, globin part is decreased…microcytic anemia. Three gene deletions HbH forms…4 beta chains form
hemeogloblin. 4 gene deletions rarely ever born. Higher spontaneous abortion rate in far east--Alpha thal.
ThereforeHigher rate of choriocarcinoma. TREATMENT of alpha thal=DON’T GIVE THEM IRON. Then
you iron overload…leave them alone. They most likely have alpha thalassemia.
Beta thal: Black, Greek and Italiansdeals with splicing defects and stop codons. Mild beta is
decreased, alpha is ok, delta and gamma are ok. Decreased hemoglobin A. Don’t do anything about it.
Beta/Delta thal: Heme electrophoresis would show hemoglobin F. Don’t have anemia.
MOST COMMON CAUSE OF IRON DEFICIENT ANEMIA by age/sex:
Prematurity infant: iron stores are decreased
Newborn: check stool…might be positive for blood. Usually blood that baby swallowed from mom. If it is
HbF most common cause is Meckels diverticulum.
Woman under 50: menorrhage…anovulatory cycles.
Men under 50: peptic ulcer disease, duodenal ulcer.
M&W over 50: colon cancer.
Anemia of chronic disease: Iron studiesserum iron low, TIBC low (high iron stores), serum ferritin low, %
sat high.
Sideroblastic anemia---get iron blood level.
Lead poisoning: Coarse basophilic stipiling—RBC with lots of blue spotsvery specific in persistent ribosome
for lead poisoning.
--Pb can deposit in Epiphysis of bone, won’t be able to grow properly. Severe abdominal colic,
convulsions, failure to thrive, cerebral edema (increased vessel permeability and related to buildup of delta
aminolevulinic acid). Guys who work in automobile factories with abdominal colic and diarrhea—battery
exposure. Moonshine is made in bathtub. Pottery painter…using lead based paints. Licking the tip of the
brush. Adults get foot slapping gait—peroneal palsy, lead lines in teeth/gums.
Iron overload: Serum iron is high, TIBC is low, % sat is high, Ferritin is high.
Porphyrin synthesis begins in bone marrow, mitochondrial. Succinyl CoA + glycine
ALA synthase is RLE of heme synthesis. Cofactor is pyridoxine phosphate. Ferochelatase…combines iron
with protoporphyrin.

14
B12 and folate: Macrocytic/Megaloblastic anemiasDNA synthesis inappropriate.
Won’t be able to make DNA if you are deficient. Cobalamin (B12)—cobalt…circulating form of folate
is methyltetrahydrofolate. Cobalamin takes methyl group off of methyltetrahydrofolate. = THF. If you don’t
get the methyl group off, you can’t make DNA. Cobalamin adds methyl group to homocysteine….it becomes
methionine (necessary aa for one Carbon transfer reactions) Serum homocysteine levels will be high if you are
B12 or folate deficient. Homocys…damages endothelial cells which predisposes them to MI. MCC Elevated
homocysteine: folate deficiency. THF is start of cycle for making DNA. Dihydrofolate reductase converts
oxidized DHF form back to THF. Drugs that block: Methotrexate, TMP-Sulfamethox…
****Vit B12: Odd chain fatty acid metabolism. Proprionate metabolism. Converts methylmalonyl CoA into
Succinyl CoA. Methylmalonic Acid levels build in B12 deficiency. Neurologic problems in B12 def because
can’t synthesize myelin. End up with Dementia and demyelination of dorsal columns and lateral cortical spinal
tract. Problems with proprioception, vibration, and upper motor neuron problems. Can correct the anemia with
high levels of folate, but can’t correct the neuro problems.
Normal metabolism of B12: animal products…Pure Vegan needs B12 supplement. Binds to R factor in
saliva...protects it from getting destroyed by stomach acid. Intrinsic factor made by parietal cells in the
body/fundus of the stomach. Cleave off R factor with functional pancreas. Take a long trip to terminal ileum
where intrinsic factor/B12 complex gets reabsorbed. Crohn’s disease is affected in same area…Crohn’s bile
salt deficiency, B12 deficiency. MCC: pernicious anemia….destruction of parietal cells in body/fundus.
Autoimmune response where everything is destroyed…atrophic gastritis of body and fundus. No acid, no
intrinsic factor. Predisposed to gastric adenocarcinoma. Could have chronic pancreatitis because you couldn’t
cleave off R factor in duodenum…could have fish tapeworm Diphyllobothrium latum….(Great Lakes)…can
have bacterial overgrowth too and it can reduce B12/intrinsic factor.
FOLATE: when you eat it, it needs to be converted to monoglutamate form. Intestinal Conjugase.
Phenytoin blocks intestinal conjugase…macrocytic anemia. Monoglu: BC pill and alcohol blocks reabsorbtion
of folate. MethytetrahydrofolatetetrahydrofolateDNA. Hypersegmented neutrophil because it has more
than 5 lobes. Means you have B12 or folate deficiency!!! If Neuro exam is normal: folate def. If abnormal:
B12. Rhomberg testfor proprioception…..hand drift with eyes closed.
Megaloblastic hematopoeic cells made outside the sinusoids in the bone marrow. Analogous to Cords of
Bilroth in spleen. Severe pancytopenia in B12/folate def…macrocytic anemia, neutrocytopenia,
thrombocytopenia…cells can’t get out of marrow.
Shilling’s test: Localizing B12 deficiency give them radioactive B12…collect urine…see a problem in
reabsorbing B12. Give Intrinsic factor too. Pernicious anemia…if corrected by antibioticbacterial
overgrowth. Pancreatic extract….Dx: chronic pancreatitis.
Normocytic Anemia: Correct reticulocyte count under 3%. See early iron deficiency and anemia of chronic
disease. Blood loss less than one week…won’t have increase in reticulocyte increase because you need more
than one week. Aplastic anemiano marrow….will see pancytopenia in peripheral blood. Find out what drugs
the patient is on: Indomethacin, phenylbutazone, thryroid related drugs. Hepatitis C is major second infection
cause for aplastic anemia. Chronic renal failure: decreased EPO….decreased RBC production.
Correct reticulocyte count over 3%--bone marrow isn’t responding appropriately. Can kill a RBC
outside a blood vessel (macrophage) Cords of Billroth. Macrophage has receptors for IgG or C3b. If RBC has
those on surface. Or could be spherical (spherocyte). Extravascular hemolytic anemia (autoimmune or have
abnormal shape and is removed by macrophages). Unconjugated bilirubin is end product of phagocytosing an
RBC. Enzyme splits Heme from Globin in macrophage…binds to albumin. Will see jaundice in patient in
extravascular hemolytic anemia…but won’t see any bilirubin in urine, cause it is bound to albumin.
Intravascular hemolytic anemia: if you bang into
something…if you had IgM on surface of RBC…potent activator of complement system. Protein made in
liver…haptoglobin…binds to hemoglobin during intravascular hemolysis and is broken down in macrophage to
save hemoglobin. Hemoglobinuria and low haptoglobin levels.
Hemolytic anemia that is intrinsic, no spectrin or no decay accelerating factor in cell membrane to neutralize
complement, no G6PD enzyme in HMP shunt in RBC.

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 Intrinsic: Corrected reticulocyte count greater than 3%. MAD: Membrane defect (spherocytosis,
paroxysmal nocturnal hemoglobinuria) Abnormal hemoglobin (sickle cell disease and trait), Deficient enzyme
(G6PD deficiency)…don’t see central area of pallor….it will be removed extravascularly (unconjugated
bilirubin) Defect in spectrin (AD disease), splenomegally, gall bladder disease commonly—more unconjugated
bili coming to liver—can get gallstone disease. Diagnostic test: Osmotic fragility…put in test tubes with
different quantities of saline. Treatment, spleenectomy.
Paroxysmal nocturnal hemoglobinuria Mild respiratory acidosis/obstructive sleep apnea…acidosic
predisposes complement coming in and sitting on cells. If you are missing DAF: complement will start
breaking down red blood cells. Pancytopenia.
Sickle cell: Oxygen tension in blood can determine sickling. Autosomal recessive. Sickle cell trait: Do
sickle cell screen for trait in black person with microscopic hemoglobinuria. Vasoocclusive crisis b/c of
sickling, ischemia produces pain. Splenomegally—trapped RBCs, first 10 years of life…autosplenectomy after
about 18 years of life. Howell Jolly body…pieces of nucleus in peripheral blood shows that spleen is not
working. Strep pneumonia sepsis is MCC of death in young person with sickle cell. HbF inhibits
sickling….for 1st 6 months they are OK. By 6- 9months first vasoocclusive crisis. Dactylitis…infarction of
bone…..Pb poisoning will accumulate in epiphysis of bones. Patient are succeptible to Salmonella infections
due to dysfunctional spleenosteomyelitis. Hydroxyurea increases HbF synthesis and decreases vasoocclusive
crisis.
G6PD deficiency: Sex linked recessive (lesch nyhan too—HGPRT def) Make glutathione and ribose
5 carbon sugars. Make NADPH. NADPH will reduce glutathione so that H2O2 can be reduced to water.
Heinz bodies….clumped up hemoglobin because of excessive H2O2. Primaquinecan get hemoglobinuria,
chills. Dapsone: used in treating leprosy, has same effects. Greeks, blacks, Italians. Bite cells…just a small
bit taken off by macrophages…characteristic finding in peripheral vasculature. Favism can precipitate it as
well.
Autoimmune hemolytic anemia: WAHA IgG &C3b on surface of RBC—removed via macrophages
—extrinsic hemolytic anemia (Direct Coombs detect directly)…MCC is Lupus. When looking for Antibody in
SERUMIndirect Coombs test)
Drug induced hemolytic anemia: PenicillinBPO group of penicillin attaches to RBC. If you develop
IgG antibody against it (type II hypersensitivity) and clumping—can be taken to spleen and broken down.
Methyl Dopa: Antihypertensive (can be given to pregnant woman along with Hydralazine---can
precipitate drug induced lupus. Methyl dopa screws around with Rh antigens on RBC so that you form IgG
antibodies against them. Macrophages break them down.
Quinidine: Act as a hapten. IgM antibody attached to drug and circulates in body. Activates
complement—haptoglobin is decreased and hemoglobin is present in urine.
Microangiopathic hemolytic anemiaSchistocytes: Split RBCs—have hit something in circulation:
AORTIC STENOSIS—systolic ejection murmur, right second intercostal space, S4, prominent
PMI….intravascular hemolysis. Haptoglobin levels go down, potentially get iron deficiency anemia b/c it is a
chronic hemolysis. See low MCV. DIC can also lead to it. Runningmight see hemoglobin after a race.
Superinfection of malariafalciparum…produces a hemolytic anemia.
Extrinsic: RBC happens to be at wrong place at wrong time.
WBC: Benign changes that occuracute inflammation…left shift, increased neutrophils. Leukomoid
reaction—overexaggerated response to infection….children get it. Pertussis….big time lyphocytosis. No
anemia, no thrombocytopenia. Atypical lymphocyte responds to antigen by getting bigger. “Mono”,CMV,
any cause of Hepatitis, phenytoin. EBV-CD21 receptor on B cells. Exudative tonsillitis, no jaundice,
transaminases are very high. Spleen that has the tendency to rupture…DON’T play sports for awhile.
Atypical lymphocyte: Lots of cytoplasm. Monowhich test do you order? “Heterophile antibodies” Anti-
horse antibodies. “Don’t look for Mono spot test” Monocytosis, patients with chronic infection….RA, SLE,
crohn’s, malignancy. Eosinophilia: hayfever, rash in patient with penicillinno protozoa produces
eosinophilia (giardia, amebiasis)…only invasive helminthes (stronglyloides). Type I hypersensitivity YES.

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 Polycythemia: increased RBC, hemoglobin and hematocrit. Difference btw RBC mass and count…
Masstotal number of RBC in body/kg. Count is number in certain volume of blood. If you are volume
depleted (sweating) you would be hemoconcentrated. RBC mass would be normal. Relative Poly, decreased
plasma level, increase in RBC count, but normal mass. Appropriate increase is due to tissue hypoxia--COPD,
high altitude.
Inappropriate increase: tumor increasing EPO or Polycythemia Ruba vera…myeloproliferative disease (CML,
essential thrombocytopenia)--stem cell disease, neoplastic, no longer respond to checks and balances.
Polycythemia Ruba Vera: 4H’s Hyperviscositythrombosis, blood sludging around, create iron deficiency
with phlebotomy…will take longer time to get more RBCs. Hypervolemiaincrease in plasma volume that
matches increase in RBC volume. Histaminemia Mast cells and basophils increased in polycythemia:
“when I take a shower, I itch all over my body…temperatures cause mast cell degranulation. Increased
histamine release. Face that is ruddy…vasodilatation….headaches. Hyperuricemia….purines from nuclei
that die. Cancer cells patients need to be put on allopurinol to block xanthine oxidase so that tubules don’t
get filled up by purines.
Leukemia: malignancy of stem cells in marrow, abnormal cells in peripheral blood, BLASTS. Will
always have anemia (normocytic). Usually will have thrombocytopenia and increase in white blood cell count.
Acute from Chronic….count blasts in peripheral marrow…<30%=Chronic, over 30% Acute.
Age brackets0-14= ALL CD 10+, CALLA antigen positive
15-39=AML (myeloblasts with Auer rod)
40-59=AML (greater than 30% blasts) & CML (less than
30% blasts…Philadelphia Chr (t9:22) Abl protooncogene, leukocyte alkaline phosphatase score (which should
be low ….zero) 60 and above=CLL….most common leukemia and most cc
of generalized nontender lymphadenopathy in someone over 60—metastasizes to lymph nodes.
(CLLmarkers CD19 & CD20 + CD5 as well. CLL is CD23 positive and CD10 negative)
Hepatosplenomegally. Hypogammaglobulinemia: neoplastic cells can’t transform into plasma cells. TRAP
stainHairy cell leukemia: Indolent disease of older men. Tartrate resistant acid phosphatase.
Teardrop RBC: worming its way through strands of fibrous tissue in bone marrow…got hemapoeitic
cells to move to spleen. Extramedullary hematopoesis. Huge spleen. Adenogenic myeloid metaplasia.
Megakaryocytes lay down collagen in bone marrow. Some RBCs stay in fibrous tissue in marrow.
AML: (t15:17 translocation, Auer rods, treat with retinoic acid—causes blasts to mature into benign
cells) DIC!!
Lymph nodes: painful lymphadenopathy is not malignant—means inflammation. Nontender
lymphadenopathy….metastasis or primary lymphoma. Generalized painful lymphopathy…systemic disease.
EBV, SLE, HIV. Lymphoma…avoids the elastic arteries and cartilage.
Follicular lymphoma: (t14:18), most common non-Hodgkins lymphoma…apoptosis gene gets knocked off.
EBVBurkitts, myc 8:14 translocation. Myc oncogene. Starry sky appearance. In US most often found in
children in peyer’s patches…African children in jaw.
Sezary cell: Mycosis fungoides—malignant helper T cells in peripheral blood
Histiocytosis X: Birbeck granules in histiocytes…CD1 positive…Clostridium tetany terminal end spores also
look like tennis rackets.
Hodgkin Disease: nontender lymphadenopathy. Fever, night sweat, weight loss, Reed Sternberg (owl eye)
cells…Neoplastic cell. The less you have, the better prognosis.
Day 3: HematologyLymph nodes: Most common cancer of a lymph node—malignancy.
Hodgkin’s disease: Nodular sclerosing Hodgkinsmost common…and more common in women than men.
Collagen deposition, hard, nonpainful node. Usually a woman and lymph node involvement in two places.
Nodes in anterior mediastium and somewhere above diaphragm. Malignant cell is Reed Sternberg cell.
Polyclonalmany clones of plasma cells. Benign. GAMMA—G, A, M…most abundant immunoglobulins.
Chronic inflammation…diffuse elevation of gamma globulin peak.
Monoclonal gammopathy: one clone…others are suppressed. Usually means malignancy of a plasma cell.

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 Multiple Myeloma. Usually see in people over 50, most common is IgK. Osteoclast activating factor.
IL-1 produces lytic areas in bone. Sharp borders to lytic areas. Pathologic fractures. Bence Jones protein.
“Elderly woman who coughs and then develops severe pain…point tenderness…see lytic lesion on X-ray=MM”
Amyloidosis: Many different kinds of proteins can be converted into amyloid. Prealbumin, calcitonin-
thryroid cancer, light chains…Beta amyloid protein on Chr 21. Toxic to neurons. Downs Syndrome. Patients
die of endocardial cushion defect or Alz.
Lysosomal storage diseases: macrophage with wrinkled paper appearance….Gauchers—AR--
glucocerebrosides build up.
Patient with severe mental retardation: Tay Sachs—GM2, gangliosides. & Niemann Pickbubbly
cytoplasm…cherry red macula. Sphingomyelin builds.
Pompe—only glycogen storage disease that is lysosomal storage. Cardiac problems.
Hemostasis: Arterioles, venules, capillaries. Have heparin (GAG-mucopolysaccaride) enhances antithrombin
3. PGI2 endothelial cells, vasodilator. Protein C&S (Vit K dependent factors) inactivate factors 5&8 to
reduce clotting. Tissue plasminogen activator (tPA)—produces plasmin to eat up little clots. BC pill is
thrombogenic because it increases the synthesis of 5&8, inhibits Antithrombin III. BC pill antagonizes heparin.
Smoking is thrombogenic because it damages endothelial cells.
When you cut small vesselsBleeding time: used to evaluate platelet function. If you have hemophilia A and
have 0 factor VIII has nothing to do with bleeding time. BT: Should be about 7-9 minutes. Tissue
thromboplastin will be released. Collagen will be exposed, Hagemanns factor (12—intrinsic) will be activated.
Von Willebrands factor (by endothelial cells, and megakaryocytes) is made to stick to platelets. Platelets have
receptors for VWF. “platelet adhesion”—ADP released****Potent aggregating agent. Platelets stick together.
Thromboxane A2 madepotent vasoconstrictor—makes it easier for platelets to stick with slower flow,
bronchoconstrictor, and platelet aggregator.
One cause of increased bleeding time; thrombocytopenia (less than 90,000 platelets , von Willebrands
disease (most common genetic hereditary diseaseautosomal dominant defect—1/250), aspirinblocks COX
irreversible.
Thrombin converts Fibrinogenfibrin…makes stable platelet plug. Plasminogen will remove platelet plug.
Platelet problem, bleeding time will be increased, Petechia and ecchymosis and nose bleeds with platelet
problem. Molar tooth removed? If no problem after extracting wisdom tooth…no problem with coagulation
system. Late rebleeding, GI bleeds, hemarthrosis seen in coagulation deficiency.
For platelet deficiencies, platelet count, bleeding time is test for platelet function. Ristocetin cofactor assay
(VWF—). “Patient with chronic headaches and osteoarthritis that goes into surgery…Bleeding after surgery”
Coagulation: If patient is on aspirin or nonsteroidal, get a normal platelet transfusion…not blood transfusion.
Extrinisic system: Factor 7—PT deficiency…
Intrinisic: 12, 11, 9, 8. Both systems share final common pathway: 10—5(thrombin)—2(prothrombin)—1
(fibrin)
PTT—partial thromboplastin time—intrinsic pathwaymost likely Factor 8 (hemophilia A) if PT is normal.
Warfarin blocked epoxide reductase…blocks Gamma carboxylation (coagulation) of 2…7...9…10 Patient on
warfarin will have prolonged PTT, and PT. Follow heparin therapy with PTT. PT does a better job at
following Warfarin.
Antithrombin III knocks off 12, 7, 11, 10….elevated PT and PTT.
Plasmin: breaks down fibrinogen and coagulation factors. Fibrin degradation products.
D-dimers—absolute best test for DIC. Detects a fibrin clot.
Vessel abnormalities: Senile purpura…vessels get unstable. Age dependent finding. Present in places that
normally hit things, shins and back of the hands.
Osler Weber Rondu: most common vascular genetic diseasehereditary telengiectasia, see throughout GI
tract. Chronic iron deficiency b/c telengietasias rupture.
Platelet disorder: petechia (won’t blanch when you press on it) and eccymosis, epistaxis=nosebleeds.
Idiopathic thrombocytopenia purpura—macrophages in spleen remove platelets, cause they are
tagged with IgG. Platelet count prolonged, BT low, PT, PTT normal. “Kid who had respiratory infection 1 wk

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ago presents with epistaxis, lesions that don’t blanch when you press on them—platelet count is 20,000” Type
II hypersensitivity.
TTP-HUS: NOT DICPT and PTT are normal. Not consuming coag factors. Strong platelet
plug….in small vessels damaged throughout your body. Thrombocytopenia and bleeding. Red blood cells will
get smashed and will have schistocytes…microangiopathic hemolytic anemia. HUSE.coli 0157:H7….acute
renal failure in children. Shigella toxin can also cause HUS. LOW platelet, prolonged BT. PT and PTT should
be fine, cause you are only consuming platelets.
Hemartrosis: Hemophila AFactor 8=Increased PTT. Difference btw Hem A and vWF disease:
Von=platelet adhesion defect and coagulation defect therefore BT increased. Menorragia, easy bruisability.
Hemo A=sex linked recessive, 8 coagulant is deficient, normal 8 antigen levels and normal vWF.
Von=Autosomal Dominant, 8 antigen, 8 coag and vWF are all deficient. Ristocetin cofactor assay….
Desmopressin (ADH) can cause synthesis of all Factor 8 blood components. Will help treat mild Hemophilia
A, as does estrogen from BC pill….relief from bleeding disorder.
Antiphospholipid syndrome includes lupus anticoag, and cardiolipin antibodies.
DIC: clotting thoughout the body in small vesselsfibrinogen, prothrombin, thrombin, platelets, 5 and 8
consumed. Thrombi in vessels and anticoagulated at same time because you’ve consumed all the factors.
Patient in shock, bleeding from any orifice=DIC. E coli, most common cause of septic shock. Amniotic fluid
embolism—contains thromboplastin…precipitates DIC—look for D dimer.
Factor 5 Leiden: protein C&S can’t break it down…Will always have increased Factor 5….will lead you to
thrombose.
“patient with DVT, give them the heparin, PTT is normal….antithrombin III deficiency”
Blood Bank:
O—anti A IgM, anti B IgM, anti AB IgG—universal donor, most common type—O assoc. with duodenal ulcer
A—anti B IgM—A assoc with gastric cancer
B—anti A IgM
AB—nothing---universal recipient
Newborn doesn’t have IgM antibodies floating around. Older people have hardly any either….lower levels of
antibodies. “Old person with Blood Group A, and received group B….no reaction, b/c low antibody levels”
Duffy antigen: missing in black population, therefore less likely to get P. vivox malariacan’t get into RBC.
Most common antibody in the US=CMV….everyone is exposed to it.
CMV is the most common infection transmitted by blood. Most common Hep post blood transfusion is Hep C.
Hep B is the most common infection from accidental needle stick.
1:300 chance from someone who is HIV positive after an accidental needle stick. Go on triple therapy.
Transfusion reactions; allergicType I, itching, hives,
Febrile reaction: due to HLA antibodies against donor unit leukocytes. Pyrogens released from
neutrophil. If you have never been transfused, you shouldn’t have HLA antibodys against anything.
Hemolytic transfusion reactions: “clerical error…”—transfuse A into B blood. Other thing that
can happen is for patient to have antibodies against blood that was transfused. Anti Kell antibodies. Memory B
cells would attack the Kell antigen….from previous transfusion. Anti Kell IgG antibodies. Can occur within a
few hours or within a week. Delayed hemolytic transfusion reaction. “woman postpartum gets transfused…
week later, jaundice, and hemoglobin less than when she left the hospital.” Coombs test proves it. Type II
hypersensitivity reaction.
ABO/Rh incompatibility:
O- woman with baby A-: baby will be born with mild anemia and mild jaundice (most common cause of
jaundice in a newborn is ABO incompatibility) UVB lightConverts bilirubin in skin to dipyrole which is
water soluble. Anemia is very mild. Can be the first pregnancy.
Rh incompatibility: Mom is O- baby is O+….fetal maternal bleed on first pregnancy. Now is sensitized
(anti D) Second time baby is O+ again. IgG will cross placenta, baby will be more severely anemic. Give
mother Anti D (Rh immunoglobulin) around 28 weeks. ABO incompatibility will have protective factor
against Rh sensitization.

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Erythroblastosis fetalis: baby dies of heart failure.
Kernicterus: Unconjugated bilirubinlipid soluble. Rh incompatibility blood brain barrier is immature…
yellowish color.
CARDIO:
JVPusually on right side
A wave: right atrial contraction in late diastole
C wave: tricuspid closes in systole and bulges out into right atrium
X wave: negative pressure in pulmonary artery pulls tricuspid down
V wave: RA needs to fill up again, corresponds to beginning of diastole. S2 heart sound.
Irregular Irregular pulse: Mitral stenosis…a wave disappears. Atrial fib, will lose S4
Tricuspid stenosis—giant a wave….doesn’t want to close.
Regurgitation—giant c/v wave
Turbidity of plasma: only due to triglyceride…chylomicrons (exogenously—diet derived)
VLDL: Glycerol 3 Phosphate pushed from Alcoholism NADH. Type IV hyperlipidemia.
Exanthelasma: cholesterol by the eyelid…get lipid profile
Achilles tendon xanthoma: FH type 2 Autosomal dominant disease. No LDL receptors.
SCIDAdenine deaminase gene therapy…stuck it into adenovirus, and cured child.
Atherosclerosis: reaction to injurysomething injures vascular arteries and muscular arteries…poisons,
cigarette smoking, viral infections, Chlamydia pneumonia, homocysteine. PDGF causes smooth muscle cells to
migrate into intima of blood vessels. Macrophages cause fatty streak.
Atherosclerosis: primary factor for coronary artery disease, stroke, AAA.
Arterioles—Hyaline arteriolosclerosis in diabetes non enzymatic glycoslyation…Hb A1c. Glucose attaching
to aa and protein. Osmotic damage, aldose reductase….glucose into sorbitol. Microaneurysm in eyeretinal
vessels are damaged. Peripheral neuropathies b/c schwann cells are destroyed. Membranes are rendered
permeable to proteinto glomerular BM=microalbuminuria=1st change of diabetic nephropathy.
Hypertensive arteriolar sclerosis…vessel disease seen in hypertension
Aneurysm: area of outpouching of vessel due to weakening of vessel wall. Bronchiectasis would be
the analogous lesion in lung. Diverticular disease is analogous in GI tract. Law of Laplacewall stress
increases as radius increases. As you dilate it, wall stress increases. All aneurysms will rupture….just a matter
of when…AAA=sudden onset of left flank pain, hypotension, and pulsatile mass on palpation.
Syphillis: vasculitis of arterioles…painless chancre—ischemic necrosis. In arch of aorta, endarteritis
obliterans. Syphilitic aortitis. Stretch aortic ring=Aortic regurgitation: should be closing in diastole…pump
blood out, some drips back in….more volume of blood in LV. Increased contraction. 200ml, get out 100, .50
ejection fraction. Increased SV, Waterhammer pulse.
Key factor to cause tear in aorta is hypertension…must be weakening….elastic tissue
fragmentation+cystic medial necrosis. Wherever area of weakness is, the blood will dissect. Will have
diminished pulse on left compared to right. Will have a tearing pain that goes into the back. Widening of
proximal aortic nob. Marfans (AD) can predispose. Fibrillin is defective—elastic tissue is weak. Mitral valve
prolapse.
Smoker that develops primary lung cancer….superior vena caval syndrome. Headaches & blurry vision.
Sturge Weber syndrome: vascular malformation in facetrigeminal nerve distribution…AV malformation on
same side of brain. Slightly mentally retarded.
Osler Weber Rondu: small telengiectasia in GI tract. Spider angioma—AV fistula (blanches) increased
estrogen level predisposesnormal in pregnant women. In cirrohsis, can’t metabolism estrogen.
Kid with red lesion on face: Capillary angiomas leave it alone…by 8 years of age it will disappear.
AIDS Patients….lesion that looks like kaposi’s but is due to (Vasilary angiomatosis) Bartonella henslae.
Angiosarcoma of the liver. Vinyl choride and arsenic.
Vasculitis: small vessel vasculitis…usually Type III hypersensitivity. Palpable purpura. Antigen antibody
complexes.
Kawasaki’s in children: complication is coronary artery vasculitis. Erythematous palms and soles.

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Knock off an elastic artery: Takayashu’s Arteritis. Loss of a pulse…young far east lady with absent pulse.
Temporal arteritis smokers, aches and pains, painful chewing, granulomatous vasculitis digital vessel
thrombosis.
14 year old boy upper respiratory infection one week ago, presents with polyarteritis, hematuria, RBC casts and
palpable purpura in buttocks & legs. Henloch scholein purpura. Anti IgA immune complex.
Wegner’s granulomatosis: (3 issues….sinusitis, bilateral pneumonitis, focal segmental
glomerulosclerosis) Saddle nose deformitylung problems, rip-roaring glomerulosclerosis. C-
ANCA...antineutrophil cytoplasic antibody. Treat with: Cyclophosphamide—hemorrhagic cystis consequence
—prevent with Mesna.
Polyarteritis nodosa—p-anca antibody, association with Hepatitis B. “IV drug abuser with chronic
hepatitis B who has nodular inflamed mass on lower extremity and hematuria.” Glomerular problems.
Rocky Mountain spotted Fever: infect endothelial cellspetechia, Ricketsia starts on extremities and goes to
trunk.
Spirochetes: Leptospira, Borrellia and Treponema
Patient with Diabetic Ketoacidosis…frontal sinuses w/extra sinus they invade the frontal lobes…mucor mycosis
(& rhizopus)…infarction of frontal lobes.
Raynauds Phenomenon: some involve cold reacting antibodies. CREST syndrome (anti centromere antibodies)
C-Calcinosis, and centromere antibody
R-Raynauds
E-sophogeal dysmobility
S-Sclerodactyly
T-Telangiectasia
Ergot derivatives…vaso constriction can cause Raynauds.
Hypertension—Essential (blacks)…multifactorial inheritance. (gout, type II diabetes)
Genetics—can’t get rid of salt in urine…salt stays in ECF…plasma volume will increaseStroke
volume will increase. Systolic hypertension. When sodium enters smooth muscle…calcium comes in too and
causes contraction or smooth muscle arterioles. Retain more blood in arterial system. Low renin hypertension.
Left ventricular hypertrophyhas to contract against an increased resistance. Hydrochlothiazide is treatment of
choice in hypertensive patients. Complications: MI, strokeblood in globus pallidus/putamen…where most
hypertensive bleeds occur in the brain. Lenticulo striate vessels that form Charcot-Buchard aneurysms.
Concentric hypertrophy is afterload problem. Dilatation and hypertrophy is preload problem. If
increased preload in heart need to work at increasing the force of contraction.
In systole S1—tricuspid and mitral valves close. In Diastole Pulmonary and Aortic valves close=S2variation
on inspiration. An S3 heart sound can be normal in anyone younger than 35 years. Occurs due to blood going
into overloaded chamber in diastole. Only hear S3 heart sound in volume overloaded chamber. S4 heart sound
is in late diastole, when atrium contracts to get last volume of blood out into the ventricles. Problem with
compliance…filling term. LA encounters problem putting blood into LV in late diastole. All right sided heart
murmurs increased in intensity during inspiration. Left Side murmurs increase on expiration.
Murmurs: Stenosis—problem in opening….Regurgitation—problem in closing
Stenosis--Systole: Aortic and pulmonic valves MR ASS. Aortic stenosis (R 2nd intercostals space—ejection
type of murmur radiating into carotids, increasing on expiration, hear S4)
Stenosis--Diastole: Mitral and tricuspid under-filling ventricles won’t have hypertrophy. Atria have to do the
work. Opening snap with mid diastolic rumble.
Regurgitation—Systole: Mitral and tricuspid valves—close. Pansystolic murmur…that may obliterate S1&S2.
“IV drug abuser with murmur. S3/S4 heart sound. What is most likely diagnosis…? Infective endocarditis of
tricuspid valve.”
Regurgitation—Diastole: Aortic and Pulmonic—close: Blood trickles back to Ventricles. Volume overloaded
chamber. EDV of 200 mls. Hear murmur after second heart sound. S3 &S4 heart sound….with bounding
pulses. Austin Flynt murmur…anterior chamber of aortic valve.

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HEART FAILURE: Leftforward failure…having to push against an afterload. Alveolar macrophages that
have broken down red blood cells, increase hydrostatic pressure….pulmonary edema. Main symptom is
dyspnea. Pillow orthopnea, feel the need to sit up in bed. Paroxsysmal nocturnal dyspnea.
Right heart failure blood builds up behind RA…neck vein distension. Hepatomegaly…
nutmeg liver (mottled appearance) hepatic vein transmits pressure to central vein. Pitting edema. Ascites. Best
non pharmacological treatment…restrict water and salt…ACE inhibitor needed to reduce preload. ACE
inhibitor + Spirinolactone better increase in prognosis. High output failureEndotoxic shockincrease flow
to heart. Thiamine deficiency, ATP deficiencyvasodilatation of peripheral resistance blood vessels. Graves
disease, thyroid hormone….systole pressures are higher…high output failure. AV fistula.
Congenital heart disease: fetal circ…pulmonary vessels in fetus look like they have hypertension. All
O2 comes from chorionic villus. Need high affinity Hemoglobin. HbF. Kids have polycythemia. O2 goes
through umbilical vein…highest O2 content. Into liver—hepatic vein—ductus venosis. IVCinto patent
foramen ovale and into LA and to body. Superior vena cava….into tricuspid and into RV. Out pulmonary
arterytremendous pressure…goes into patent ductus arteriosis. PGE2 keeps it open—vasodilator. RL
shunt into aorta. Baby breathes…pulmonary vessels open in a millisecond. Gas exchange occurs in lungs.
Oxygen levels go up in baby.
Step up and step downLeft to right shunt….oxygenated blood into unoxygenated blood…step up.
VSD step up of oxygenated blood into RV and pulmonary artery. Uncorrected left to right
shuntpulmonary hypertensionEisenmengers syndrome=tendency to reverse the shunt.
ASD LR shunt….step up of O2 in RA. Volume overloaded right side of heart. If you have DVT
that ends up in arteries…need to have patent foramen ovale. Teratogen assoc: fetal alcohol syndrome
Patent ductus arteriosisnormal in fetus…connection btw aorta and PA. Oxygenated blood going into
pulmonary artery. Shimi murmur heard btw the shoulder blades. Can get unoxygenated blood going into
Aorta once shunt reverses from RV hypertrophypulmonary hypertension…baby will be pink on top and blue
on bottom. Distal to subclavian artery. Teratogen—congenital rubella. Indomethacin will close PDA.
Tetralogy of Fallotoverriding aorta, septal defect, pulmonic stenosis, RV hypertrophy. Degree of
pulmonic stenosis determines degree of cyanosis. “Which groups of shunts is protective in Tetralogy of
Fallot….patent ductus arteriosis and atrial septal defect.” ASD—blood goes left to right…steps up O2 in RA.
Patent ductus arteriosis—unoxygenated blood into pulmonary artery to lungs…to pulmonary
vein….oxygenated. In R-L shunting will get polycythemia. Infective endocarditis.

Transposition of the Great Vessels: Atria are fine…Ventricles/Aorta and pulmonary artery are
transposedIncompatible with life without shunts: Patent ductus arteriosis—blood from aorta into Pulmonary
artery. To lungs and getting oxygenated. With Kartageners Syndrome you have a normal heart on the right
side.
Coarctation: preductal and postductalpreductal occurs in Turner’s syndrome. Post ductals aren’t
present at birth. Come on as an adult. Stenosis in aorta…proximally, problem getting blood through, (systolic
murmur heard at shoulder blades). Hypertension would make Berry Aneurysms a realistic thing. Stretch aortic
ring and get a murmur of aortic regurg. Pressure on aortic wall could get dissecting aortic aneurysm. Problem
with coarctation is hypertension: High renin hypertension. Problem with getting collaterals…superficial
epigastric artery with internal mammillary arteries. Intercostals…on undersurface of ribs produce notching…
as they get more blood flow.
Risk factor for females and coronary artery disease is HDL…due to estrogen levels. HDL levels
decrease after menopause if they aren’t taking estrogen. Smoking is a major risk factor.
Angina: Exertionalchest pain that goes away with resting…ST depression (sub endocardial ischemia)
with stress test (treadmill)
Prinz Metalusually in women and in morning…vasospasm of coronary artery. Transmural
ischemia…ST elevation.
Unstable angina while resting…put them in hospital…usually get angioplasty

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 Sudden Cardiac death syndrome: Death within one hour. Won’t see coronary thrombus…but do have
severe coronary artery disease. Die of ventricular arrthymia.
Chronic ischemic heart disease: Subendocardial infarctions that get replaced by fibrous tissue. Fibrous
tissue has no contractility.
Internal mammilary artery—can use for vessel bypass. Use Saphenous vein, has tendency towards fibrosis over
time as it gets arteriolized.
LAD supplies entire anterior part of heart and anterior 2/3rds of septum. If complete heartblock, LAD
was most likely knocked out.
RCA-Posterior part of heart, posterior 1/3 and entire RV. Posterio-medial papillary muscle. Patient
with mitral regurg type murmur. Knock off AV node=sinus bradycardia. Knock off SA node, and atypical chest
pain. Stimulates Gastro Esophageal Reflux Disease. Older person complaining of severe epigastric
pain….careful on workup.
Heart is softest and has tendency to rupture at 3-7 days post MI. First see gross manifestations @ 24
hours. Coag necrosis @ 4-6 hours.
On Day 3 someone goes into heart failure with S3/4 heart sounds…massive volume overload that goes to lungs.
Mural thrombus: wall of artery…LAD almost always. Anterior MI…prevent infarction with aspirin,
and warfarin/heparin. Anticoagulant. Mural thrombi are mixed clots.
Fibrinous Pericarditis: chest pain, worse when leaning back
“Person with transmural infarct three component syndrome. 6 weeks later…autoimmune
symptomsDressler’s syndrome.” Autoimmune pericarditis.
Dextrocardia—ventricular aneurysm. Systolic bulge. Aneurysm lined by scar tissue, therefore, you
won’t rupture…most common cause of death is heart failure.
Ejection fraction is best diagnostic indicator for how you are going to do after infarct. CK-MB is gold standard
for diagnosing MI. MB isoenzyme is primarily in cardiac muscle. Usually after 6 hours and is gone in 3 days.
If present after 3 days…defines reinfarction. Troponin I comes in and peaks around 24 and lasts 7 days.
Replaces LDH isoenzymes for infarction studies. Normally LDH II is higher than I …but after infarction LDH
I is higher than II. “I / II flip”
Valvular diseases: Mitral valve prolapse. Too much valve extending into LA. Makes a click and
followed by short murmur. “Click-murmur”. Pathology: Myxomatous degenerationexcess of dermitan
sulfate in valve. Too floppyblood goes underneath and pushes it upward.
Mitral valve prolapse: deals with preload. If you increase preload—volume of blood in LV….comes
closer to S2. When laying down…comes closer to S2. What happens to clic and murmur in anxiety…heart rate
increases…less time to fill ventricles (less preload therefore closer to S1)
Aortic Stenosis: syncope with exercise and angina with exercise. Coronary arteries fill during diastole.
Ejection type of murmur, Rsecond intercostals space. Increase intensity of murmur…increase amount of blood
in LV. Most common valvular lesion causing angina.
Mitral stenosis: Murmur occurs in diastole. Snap and rumble. Apex…increase intensity on inspiration.
Rheumatic feveracute due to Group A beta Strep infection. Antistreptolysin O titer. M protein is pathogenic
factor. Mimicryantibody against own tissue. Jones criteria: young person with exudative tonsillitis that
now has joint pain, pansystolic murmur. Pancarditis. Migratory Polyarthritis in young person has very limited
differential. Skin rash, sub cutan nodules. Sydenham chorea.
LA is most posteriorly located chamber in heart. Often compresses esophagus and can result in dysphagia of
solids but not liquids. Irregular regular pulse….atrial fibrillation.
“Marfans->patient had sudden death, mitral valve prolapse and conduction defects” Dissection aortic
aneurysms won’t lead to sudden death.
Tricuspid Regurg: IVDA with infective endocarditis. Pansystolic, increases on inspiration.
Carcinoid Syndrome: need metastasis to liver from carcinoid tumor of the heart. Sertonin from tumor
gets into venous blood…produces fibrous tissue response of valves. TIPStricuspid insufficiency, pulmonic
stenosis. Diarrhea, cramping, bronchial spasm, teleangiectasia.

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 Infective endocarditis: Mitral valve…vegetations. Scattered….destroying valve. Most common
organismstrep viridans (sub acute)—usually colonize a previously damaged valve. Staph A can infect a
previously damaged valve or normal valve. Most commonly affected valve is mitral valve followed by aortic
valve. IVDAmost common is tricuspid followed by aortic valve. UCcolon cancer---strept bovis (group D
strept) Aortic valve…close relation to membranous portion of septum “patient had septal defect that wasn’t
picked up” Roth spots, (retinal emboli), Osler nodes (painful fingers and toes), Janeway lesions (palms and
soles) All are Type III hypersensitivity. Immune complex vasculitits.
Lebmann Sachs endocarditis—lupus relation
Myrantic vegetations: someone with mucus secreting colon cancer.
Coxsackie: most common cause of myocarditis and pericarditis, hand/foot/mouth disease, herpangina. Need to
do a biopsy of sub endocardial tissue. Patient in heart failure….lymphocytes on heart tissue.
Cardiomyopathies:
Dilated cardiomyopathy—“congested”…post partum 6 weeks, cardio-toxic drugs (tricyclics,
donorubicin), alcoholic with big heart (thiamine deficiency). Progressive CHF.
Hypertrophic cardiomyopathy—AD “idiopathic hypertrophic subaortic stenosis”…MCC of sudden
death in a young athelete. Asymmetrical cardiac hypertrophy most prominent in ventricular septum.
Abnormal conduction system. Ventricular outflow is obstructed. When things go through narrow opening
there is a negative pressure behind it. Anterior leaflet sucked behind blood flow. Things that increase preload
will decrease intensity of murmur.
Endocardiofibroelastosis: restrictive cardiomyopathy. Something is preventing the ventricle from
filling.
Cardiac myxoma: Left atrium (most)….MC primary benign tumors of heart in adults. Can move over
and block the orifice of mitral valve. Very soft, and can embolize….can get strange symptoms…fever, neuro
deficits, etc.
Cardiac rhabdomyoma: associated with Tuberous Sclerosis (AD)…child with tumor.
Water bottle configuration: patient has muffled heart sounds, whenever patient breathes in the neck veins
distend. Pulseon inspiration the pulse decreases. 10 mm Hg drop on inspiration. Pericardial effusion
(Beck’s triad…kussmal sign…pulsus peridoxis) Effusion in pericardial sac. RA can’t expand due to pressure
on heart, so neck veins distend. Left side of heart can’t pump blood out on inspirationdrop in pulse.
Echocardiogram is first step in workup on patient. Pericarditis: due usually to coxsackie…but young woman
with positive serum ANA & pericarditis…SLE until proven otherwise. Pleural effusion that you can’t
explain=lupus.
Pericardial knock—constrictive pericarditis….some filling of blood.
RESPIRATORY:
A-a gradient: Alveolar O and arteriolar PO2 are never the same. Ventilation and perfusion are not
evenly matched in the lungs. Perfusion is greater than ventilation in the lower lobe. Reactivation TB in apex,
pulmonary infarcts in lower lobe.
Normally Alveolar O is 100 and arteriolar PO2 is 95. If you have Aa gradient greater than 30mm of Hg you
have a problem. High specificity=high PPV.
Ventilation defects would cause a greater difference. Diffusion defect, perfusion defect. In patients with
hypoxemia tells you whether the hypoxemia is due to something in lungs or something outside the lungs.
Anything that produces respiratory acidosisparalyze muscles of respiration Guillian Barre, Amyotrophic
Lateral sclerosis…lung related, and if outside the lungs…Aa gradient will be normal.
21% O2 (.21 x 713) — PCO2/respiratory quotient(.8) 150-50=100 Alveolar O2 now subtract the
arteriolar PO2=Aa gradient.
Nasal polyps—never think polyp in nose of child that is allergic as allergic polyp. Alllergic polyps
develop in adults that have long chronic allergies. (If in child: CF—give them sweat test) Triad
asthmaaspirin or nonsteroidal, they have asthma and they get nasal polyp. Aspirin is responsible. Always a
woman (b/c pain in women is more common in women than men), some chronic pain condition, and asthma.
Will block COX but whole lipoxygenase pathway is still open. LTC, D, E4….potent vasoconstrictors.

24
 Any male that is “well built is on anabolic steroids”….intraperitoneal hemorrhage. Football player or
wrestler…anabolic steroids produce benign liver cell adenomas which have a tendency to rupture.
False vocal cord: lined by squamous epithelium. True vocal cord lined by pseudostratified columnar
epithelium.
Laryngeal carcinoma: #1 smoking, #2 alcohol (synergism=alcoholic who smokes)
Inspiratory stridor….tracheal inflammatoryparainfluenza (Croup). H. influenza
Hyaline membrane disease: Respiratory distress syndrome. Degeneration of Type II pneumocytes.
Lamellar bodies contain surfactant. Collapsed alveoli. Atelectasisdeficiency of surfactant. Massive
ventilation defect, pulmonary shunting. Give them PEEP therapy. On expiration airways should stay open due
to surfactant. (decreases surface tension) L:S ratio should be 2:1.
--prematurity (before 36 weeks…give mom glucocorticoids to stimulate surfactant production in
newborn). Thyroxine increases surfactant…don’t give it to mom.
--Diabetes: if mom has hyperglycemia, so does child, so insulin levels are high….and insulin limits
surfactant production.
--C-section: STRESS on newborn is missing. Therefore ACTH and cortisol are not being
activatednot making surfactant.
Babies of women who have poor glycemic control are larger….insulin increases fat storage centrally,
increases muscle mass due to aa uptake. Often times are hypoglycemic at birth.
Respiratory Distress…mechanism is hypoxemiamassive intrapulmonary shunting.
Most common cause of ARDS is septic shock. Neutrophils will get into lung in septic shock. Get
massive collapse…neutrophils destroy type II pneumocytes producing hyaline membrane “leaky capillary
syndrome”.
Pneumothorax: Spontaneous—due to rupture of subpleura blebs. When yo have a hole in the pleura
there is no pressure to hold it open. Diaphragm shifts upward to take up space and trachea deviates to side
of collapse.
Tension—shift of thoracic organs across midline….most commonly due to knife injuries to
lung. Tear of pleural causing a flap. Similar to putting air in your tires…. On inspiration it opens, air stays in
pleural cavity. Air pushes lung and mediastinum to other side…causes compression. (Three Kings…
gunshot wound that was relieved as air was released) Diaphragm will be pushed down.
Pneumonia: TypicalStrep pneumonia—gram positive diplococcus—Penicillin G.
AtypicalMycoplasma pneumonia, Chlamydia pneumonia
NosocomialEcoli, Pseudomonas, Staph a.
Typical: signs of consolidation in lung leading to pus in alveoli/productive cough. Decreased
percussion, increased tactile fremitus=consolidation, EA sign listening to patient (says “E” and you hear
“A”), whispered pectorilioquy.
Atypical pneumonia: No exudates. Don’t have productive cough and not as high of fever. Slow
onset.
Rhinovirus: acid labile….common cold.
RSV: bronchiolitis….small airways…wheezing.
Influenza: antigenic shiftlarge change….anti drift, minor mutations year to year (doesn’t require new
vaccine) Vaccine against Influenza A.
Chlamydia psitticia: bird handlers
Chlamydia trachomatis: 1 wk old infant wheezing with increased AP diameter, no fever, conjunctivitis…
staccato cough. Got it from infected cervix on the way out.
Pseudomonas: ICU and CCU patients on respiratory. Patient with productive cough and green discolored
sputum.
Klebsiella pneumonia: Alcohol high spiking fevers, mucoid appearing sputum—thick capsule. Can cavitate
to upper lobe.
Legionella: non productive cough, “patient with classic atypical pneumonia & hyponatremia” legionella
can infect kidney and knock off JG apparatus, therefore, low renin levels, low aldosterone levels, will lose salt
in urine. Treat with Erythromycin.
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 Fungi: Systemic fungi Candida; normally from indwelling catheters
Midwest/Ohio River Valley: Histoplasmosis=Starlings, and bats…cave explorers in midwest
Pidgeon=Cryptococcus, Tx: Amphotericin**(note following day).
Southeastern: Blastomycosis, skin infections and lung infections.
Southwestern US: Coccidiodomycosis. Spheriole…endospores. “Indian artifact collector in
Arizona desert”

Goljan Day 4:
Rheumatic Fever---looks similar to myrantic vegetation
Fibrinoid Necrosis
Alveolar macrophage phagocytizing yeast—only systemic fungus with yeast forms specific to macrophages—
unique to Histoplasmosis
Pidgeons—cryptococcus
Spelunkering---Histoplasmosis
Blasto—broad based buds
Aspergilis
Inhabits abandoned TB cavities, R/L upper lobe lesion
Vessel invader in lung—hemorrhagic infarctions
Allergies to molds
Corona—septate
Mucormycocis—nonseptate
AIDS defining lesion…
Toxoplasmosis is most common space occupying lesion in brain of someone with AIDS
Pneumocystis Carinii can only see with silver stain…patients have incredible dyspnea, kypnea
Upper lobe of lung—cavitary lesion….reactivation TB primary TB has Ghon complex and Ghon focus.
(most people recover from primary….which may reactivate in apex)
-Histoplasmosis can also cavitate
-Klebsiella can also cavitate
AspirationStanding or sitting up: posterior-basal segment of right lower lobe
If lying down and aspirate---superior segment of right lower lobe
If lying on R side—upper lobe—lesion in posterior segment
Aspirations in Lung: Drunk who falls down
PE: embolus to lung….most originate from femoral vein…venous clots propagate to heart.
DVT of lower leg where they begin as thrombosis
Small embolus will infarct with preexisting lung disease
Saddle embolus—blocks pulmonary arteries…..very quick death with no infarction, acute R heart strain.
Screening test of choice: Ventilation/Perfusion scan for PE….radionuclei
Confirmatory test: pulmonary angiogram
Restrictive Lung Disease
Compliance—filling term
Elasticity—recoil of lung
HOT WATER BOTTLE—rubbery….can’t blow it up (compliance decreased….by interstitial
fibrosis
Elasticity increased though if you were to fill it up.
Can inhale, but can get it out fast. All volume and capacity is equally decreased
FEV 1 sec decreased (norm 4 liters…but in Restrictive….3 liters) /FVC is often the same: therefore Ratio is
HIGH
#1 cause of restrictive lung disease: Pneumoconiosis big cities, dust borne disease
Co-workers, anthrocotic pigment

26
 Silicosis, get graffiti off things, work in rock or quarries….big nodules in lung….quartz in lung
increase incidence in TB but not cancer
Asbestos: fibers look like dumbbells. Ferruginous bodies (Fe coating)
Caplan syndrome: Rheumatoid nodules in lung…with fibrosis (pneumoconisosis).
Most common pulmonary lesion associated with Asbestos: benign fibrous plaque not a precursor for
mesothelioma….most common cancer associated primary lung, second mesothelioma. If you smoke
and asbestos exposure….synergism for primary lung cancer.
“Roofer for 25 years”…(insulation used to have asbestos) ….most likely going to get=> PRIMARY
LUNG CANCER
Mesothelioma has long exposure. “worker in Naval shipyard”
Second most common cause of restrictive lung diseaseSarcoidosis…granulomatous disease…
noncaseating. Lungs are always involve, “more common in Blacks” uveitis…blurry vision or salivary glands,
lacrimal glands.
Vit D increases reabsorbtion of Ca and PO4
Pneumonitidies:
Silo fillers disease: put things in silos, ferments, gas…nitrogen dioxide….farmer went into room barn and
developed dyspnea.
Farmers lung: Thermophilic actinomycetes
Byssenosis: Worker in textile factory. “Monday morning blues”---feel better on the weekend…sick all week.

Obstructive lung disease: no problem getting it in…trouble getting it out

Compliance no problem
Elasticity residual volume increased…can’t get all air out….TLC increased…Depressed
diaphragms….increased A/P diameter in chest
VC decreased
Tidal volume decreases
FEV1sec very low (1L) / FVC Ratio is VERY LOW
Four Diseases of OBSTRUCTIVE: Bronchitis—smoking (purely clinical diagnosis…productive cough for
three months out of the year for two years) most small airway diseases in terminal bronchiole
Asthma—mucus plug in terminal bronchiole….ventilation perfusion ratio
Emphysema—smoking….not in terminal bronchioles…In respiratory bronchiole--- -
Central lobular….most often assoc. with smoking--upper lobules….more neutrophile in lungs (all smokers)
alpha 1 antitrypsin anti elastase produced by neutophils.
-Panacinar entire respiratory unit is destroyed. Genetic disease auto recessive. Early age
destroy lower lobes of lungs. Breathe in can’t breathe it out.
Bronchietasis bronchi extend to pleura. Mechanism: infection destruction of elastic support.
Fills up with pus “cup-fulls of pus” CF most common cause in US. TB in other countries.
--Kartageners syndrome….immotile cilia syndrome---dynein arm malfunction….males
and females are infertile.

Cromolyn Sodium for exertional asthma

Centrally located cancer in lung: Small cell and squamous cell
Peripheral cancer: Adenocarcinoma
Papaliconal stain….stains KERATIN bright red

Horners’ or pancoast tumor of lung….lower trunk of brachial plexus and knock off symp activity. Anhidrosis,
miosis…Mydriasis (D-Dialate pupils)
Pleural fluid: Transudate< 3 grams MCC: Heart failure
Exudate> 3 grams w/cells

27
GI: Herpes simplex Primary Herpes is a systemic infection, fever and generalized lymphadenopathy…then it
goes away stays latent in sensory ganglia. No more fever with recurrent herpes.
Tzanck Prep….will see inclusions on herpes. “TZANCK GOD I DON’T HAVE HERPES”
Hairy Leukoplakia infection due to EBV on tongue can be treated with acyclovir
Thrush IC patient….Candida, but newborns don’t have to be IC
Exudative tonsillitis; 30% Group A beta hemolytic Strep --70% VIRUS….DON’T immediately give penicillin.
Most pus tonsils are not bacteria…adenovirus…EBV
Hyperpigmentation: Addisons disease Increased ACTH—melanocyte stimulating properties. Low cortisol
levels buccal mucosa
Peutz Jeggers: polyps in small intestine. Hamartomas not neoplastic
Mixed Tumor: most common salivary gland tumor: Paramyxovirus. MUMPS amylase elevated. Not often
orchitis and infertility b/c unilateral.
Dysphagia and odynophagia Patient has problem swallowing foods; solid but not liquids---obstructive--
cancer, Plummer Vincent syndrome
If liquids and solids: peristalsis problem (myasthenia gravis—striated muscle—upper 1/3 of esophagus,
lower 1/3….sclerodermaCREST syndrome or achalasia)
Odynophagia—painful swallowing: candida in esophagus AIDS defining. Thrush (in mouth isn’t AIDS
defining)
TE fistula Most common…blindly ending esophagus, but distal esophagus arises from trachea.
Distended stomach
Mommy would have polyhydramnios
Duodenal atresia (bile stained at birth—double bubble sign…stomach and proximal duodenum) and
down syndrome
Zenker Diverticulum: tendency to regurgitate things….might come out nose.
Achalasia: LES-problem with ganglion cells missing VIP gone….function to relax LES. Constant constriction
of LES. Birds beak type of esophagus. Proximal portion is dilated. Peristalsis problem.
Chagas: Kissing bug (s. America)….one of the more common causes of heart disease in S.A.
Barretts esophagus…adenocarcinoma precursor
Esophageal varices…cirrotic who was alcoholic with portal hypertension….left gastric vein.

Diverticulosis---erode and bleed

Mallory Weiss tear…..bulimia/retching….in esophagus
Squamous cancer in middle esophagus…problem swallowing food but not liquids. Smoking and alcohol
synergism.
Congenital pyloric stenosis…3 wk old…non bile stained vomit.
NSAID ulcers…block PGE2 responsible for mucus barrier of stomach therefore…get ulcers..punched out
Helicobacter pylorisilver stain, comma shaped organism. Make urease and cytokines…convert urea to
ammonia. Pylorus/antrum…..atrophic gastritis. Lesser curvature. Site of gastric ulcers and stomach cancer.
The most common cause of stomach cancer!
Gastric; biopsy to R/0 cancer
Duodenal; never malignant ulcer
Melana with Upper GI bleed black stool…acid acts on hemoglobin and converts it to hematin (black pigment)
Usually gastric ulcer over duodenal ulcer
Patient….Executive under great stress…diaphragm referred pain to shoulder. Do flat plate of abdomen to
check for air under diaphragm.

“52 year old woman with weight loss and GI distress” Gastric adenocarcinoma: Linitus plastica….signet ring
cells invading walls of stomach….nucleus pushed to periphery….
Krukenberg Tumor: Hematogenous spread to ovaries. “biopsy of the ovary with signet rings”…no primary
cancer of ovaries with signet rings….therefore, metastasis from stomach.

28
Gastric cancer primary cancer in Japan….smoked fish/meats
Nasopharyngeal cancer: China
Left supraclavicular node drains abdomen. Lung cancers usually drain to R. supraclavicular node

Malabsorption: inability to reabsorb fats is usually the way to diagnose. Steatorrhea

Need lipases to breakdown fats: need functional pancreas
Need functional villi in small intestine: for absorptive purposes
Need something to emulsify fats and break them down to micelles: bile salts

Bile salts: made in liver from cholesterol…liver diseases can produce bile salt deficiency, crohns’, blockage in
bile duct.
Overall on fatty stool: small bowel wins. Celiac disease (most common cause of malabsorption in country)/
dermatitis herpetiformins (autoimmune vesicular lesion) if you have antibodies against glutin will destroy
villi.
Whipples disease; infection of small intestine by organism that you can’t gram stain. Can only see it by EM.
Will see flat blunt villi. ---whipple like syndrome (mycobacterium avium intracellularae in HIV+ person)
Alcoholic with malabsorption: chronic pancreatitis, and cirrohsis, and bile salt deficiency.
Diarrhea: ---get fecal smear for leukocytes… Subdivided Invasive: low volume. Campylobacter
jejuni. Comma shaped / S shaped organism.
Secretory: High volume. Enterotoxigenic ETEC: travelers—guanyl
cyclase activated…not invasive. Stimulates a pump. Cholera…adenyl cyclase.
Osmotic: High volume. lactase deficiency. Some osmotically active
substance sucking water out of lumen. Creates hypotonic fluid. “Disaccaridase/brush border deficiency.” Any
dairy product can’t be digested. Acidy stool.
Giardia: “Owl eye that moves”… METROdiazole.
Cryptosporidium parvum: most common organism assoc. with AIDS diarrhea. Partially acid fast
organism.
Pseudomembranous colitisClostridium diff: Ampicillin long term. Doesn’t invade, but toxins do.
Management: Toxin assay of stool. Metro as Tx. Analogous to Cornybacteria dip.
Small bowel obstructionHollow viscous that peristalsis….colicy pain…total obstruction of small bowel.
Patient can’t peristalis. Obstipation…can’t pass gas and can’t pass stool.
Down’s: Robertsonian Translocation with 46 Chr. One chr 21 would have another one attached to it.
Nondisjunction only for abnormal number of Chr. Look for Brushfield Spots on pupil of someone with Downs.
Do fecal smear: look for neutrophils,
Most common cause of obstruction: adhesions from previous surgery. OR bowel is entrapped in indirect
inguinal hernia.
Hirshsprungs Disease: Ganglion cells are missing. Can’t get stool through area in colon with no ganglion cells
because no peristalsis. Newborn child won’t pass myconium in first 24hrs.
Intusseseption: colicy pain, and compromised blood flow. 2 year old kid.
Gall stone ilieus: Air in biliary tree with colicy pain—flat plate of the abdomen.
Myconeom ilieus: CF
Vascular lesion: Hemorrhagic infarction. Small bowel usually infarcts more than large bowel. Supply—SMA.
Small bowel infarct vs. ischemic colitis…can pinpoint pain in ischemic….both with have bloody diarrhea.
Cecum with cystic spaces.
Meckels Diverticulum: 2 ft (from ilieo/cecal bowel) 2 inches 2 percent of population. Hematemesis and
Melana. “Newborn with Umbilicus draining feces”: persistence of vitelline duct….with urine come out
persistence of uracus.
Most common location for cancer in entire GI tract: Sigmoid colon
Most common location for polyps, diverticuli: Sigmoid colon
Area of weakness, where blood vessels penetrate the bowel.

29
Diverticulosis: complicationsdiverticulitis…left sided appendicitis. (fever, acute pain)
Fistula: cholovesical fistula pneumoturia—peeing air. Btw colon and bladder.
IBD: Crohn’s: terminal ileum 80% of the time. Cobblestone appearance. Transmural. Likes the anus,
fissures. “colicy R lower quandrant pain with diarrhea in young person.” Noncaseating granuloma
characteristic of Crohns.
UC produces bloody diarrhea, involves mucosa and submucosa. Always begins in the rectum. Never
involves the terminal ileum. Residual mucosa that is inflamed. HLA 27 positive anklosing spondilitis.
Polyps: hyperplastic polyp. Hamartomas, no neoplasm involved.
Strawberry on a stick: tubular adenoma, precursor lesion for colon cancer.
Juvenile polyp in rectum. No precancerous ability
Internal hemmorhoidbleed “adult with something reddish sticking out of butt”
External hemmorhoidsthrombos
Villus adenoma: greatest malignant potential of all polyps. Lots of mucus coating stool.
Familial adnenomatous polypsis: cancer btw 35-40 years. Variable expressivity. Autosomal dominant….late
manifestations. APC suppressor gene. Concept of penetrance.
Turcic syndrome (think turban): brain tumors/ auto recessive. Multiple lesions in soft tissue.

All Carcinoid tumors are malignant…MAKE Serotonin. Often in APPENDIX—bright yellow color.
Most common location that can be bigger…..In terminal ileum carcinoid syndrome b/c greater than 2
sonometers. Serotonin….vasodilator cause of diarrhea. If you metastasize to liver…will go to right side of
heart. Flushing is most common symptom. Diarrhea is second most common. Tryptophan could be
deficient…NIACIN therefore deficient….THEREFORE….could have pellagra. Low grade potential.

Colon cancer….left side obstructs, right side bleeds. In R colon greater diameter, better chance to go out and
form a polyp. Right sided lesion more likely to have iron deficiency.
Appendicitis: obstruction along the wall. Fecalith is most common cause in adults. Ischemia along with wall,
ecoli, inflammation. Measles and or an adeno infection in children. B/c of lymphoid tissue in appendix.

LIVER: Bilirubin metabolism most is unconjugated bili from RBC that were destroyed, bound to albumin,
taken to liver.
Gets conjugated (cyto p450) renders it water soluble. “Direct Bili”….shouldn’t have access to blood
stream. Stored in gall bladder goes into small intestine through common bile duct. Down to colon. Bacteria
break it down back into unconjugated bili. Urobilinogen gets oxidized to urobilin. A little gets taken up and
brought to kidney. Exactly the same pigment in stool and urine.
Total bili: percent that is conjugated
Jaundice: conjugated<20%
Conjugated 20-50%
Greater than 50% you have an obstruction of bile. Intrahepatic cholestasis, and extra (bile
duct…stone from gall bladder) Carcinoma of head of pancreas. Obstruction. Light colored stool. Dark urine.
Crigler Najjar Syndrome: deficiency of conjugating enzymes
Unconjugated Bili when liver is sick….builds up in blood.
Gilberts Syndrome: AD. Benign. Wwill have jaundice if don’t eat for 24 hours. Problem in taking up bili and
conjugating bili. Get total bilirubin when they aren’t jaundiced. Tell them not to eat for 24 hours if bilirubin
level doubles, they’ve got it. 2nd most common cause of jaundice in US. Hep B is most common.

Dubin Johnson—inability to get rid of conjugated bili in bile ducts. conjugated type of bili, black livers.
Liver function tests: Transamineases indices of liver cell necrosis. Viral Hepatitis. ALT is specific for liver.
SGOT is found other places. ALT will be elevated in liver cell necrosis. AST in alcoholics (AST higher than
ALT) Fatty change, cirrhosis. And an increase in serum gammaglutamyl transferase—acute/recently drinking
binge.
Alkaline phosphatase is not of liver origin.
30
Albumin made in liver therefore with cirrhosis, decreased albumin, edema. Prothrombin time is slightly better
than albumin—most coagulation factors made in liver.
Alpha feto protein increased in hepatocellular carcinoma.
Most common Hepatitis: A
D requires B
Daycare centers: A
Jails: A
IV drug abusers: B
Most common infection from accidental needle stick: B
Anti HAV IgG antibodies. Hep B surface antigen comes up first. Core Antibody IgM comes.
E antigen and HBV DNA infective:
90% of people with HBV recover. Last of the antigens that goes away; surface antigen. Impossible to be E
antigen positive and surface antigen negative.
Marker for window as to recovery from HBV: Core antibody IgM….not infective, without E antigen
Chronic Hep: how long have you had surface antigen….more than 6 months…then you have chronic hep.
HBV DNA and E antigen as chronic hepinfective. Bad news. ***Alpha interferon therapy***
Acute Hep B: Markers; surface antigen, core antibody, HBV DNA.
Recovered from Hep, surface antibody, and core IgG
Entamoeba histolytica: Resistant to acid. Excysts in cecum. tx; Metrodiazole, Can phagocytose RBCs---no
other amoeba can phagocytose. Can start dissolving liver. “ANCHOVY PASTE”
Definitive host: can mate and lay eggs. Intermediate host; only has larval form
Sheepherder’s disease: don’t want to rupture cysts..if fluid gets into abdominal cavity you can go into
anaphylactic shock.
Taenia Solium: Pig tapeworm. Pig meat has larva, will develop into adult in you…you become definitive host,
pig was intermediate host. Can form cysts that travel to brain…Cystercercosis. Calcified cyst—leads to seizure
activity.
Nutmeg liver—right heart failure: Thrombus in portal vein…will have ascites, but liver is not big and
congested.
Budd Chairi syndrome: Most common cause of polycythemia ruba vera. Thrombus in hepatic vein. Huge liver,
surgical emergency. Post hepatic (hepatic vein)
Alcoholic liver disease: Fatty change. b/c of alcohol metabolism, lots of NADH, acetyl coA, liver converts it
to triglycerides. Totally reversible if they stop drinking.
Alc. Hepatitis: fever, AST higher than ALT. Will die if you don’t stop drinking. Mallory Bodies—
ubiquinated keratin filaments. Acetaldehyde bound to a protein. Ito cell normally stores Vit. A.
Acetaldehyde tells Ito cell to start making collagen. Responsible for cirrhosis.
Cholestasis: cholesterol stone in common bile duct. Liver is deep green. Block bile with conjugated bilirubin
into sinusoids in liver. Lots of bilirubin in stool. Gammaglutamyl transferase elevated & alkaline phosphatase.
Bile salts in skin…..itching.
Bile duct radical: UC left lower quadrant pain…cholangial carcinoma most common cause in US, in other
countries Clonorchis sinitis (Chinese liver fluke)
Woman with generalized itching, enlarged liver, not jaundiced, alk phos and transaminases are high primary
biliary cirrhosis. Autoimmune distruction of bile ducts in portal triad. Antimitochondial: Biliary cirrhosis
Antimicrosomal antibodiesHashimotos
Birth control pill and anabolic steroids: both produce intrahepatic cholesystitis… “weightlifter” that develops
cirrhosis. High alk phos levels. One of the most common causes of jaundice in pregnancy, benign intrahepatic
cholecystasis. Liver cell adenoma, benign, but likes to rupture. Could produce intra-peritoneal
hemorrhage….weightlifter, becomes hypotensive and collapses. Blood in peritoneal cavity. Rupture of Benign
liver cell adenoma.

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“adult who is diffusely hyperpigmented and has Type I diabetes—‘bronze diabetes’” Hemochromatosis…iron
overload disease. Hemosiderosis is acquired iron overload—alcohol. Contraindicated to take iron supplements
in older female. Resorb more iron from diet everyday. Target organ for hemochromatosis…liver. Free
radicals, will lead to cirrhosis. Screen: serum ferritin. Excess iron stores…TIBC is decreased. Treatment is
phlebotomy. One of most common Autosomal recessive diseases. Iron can go into a number of organs.
Kaiser Fleischer ring: Wilsons’ disease. hepatolenticular degeneration….abnormal movement,
dementia, cirrhosis. AR disorder…can’t get rid of copper in bile. Copper builds up and accumulates in liver.
Most (95%) of total copper level is copper bound to ceruloplasm. Total copper level is actually decreased (b/c
ceruloplasm levels are decreased), but free copper level is high. Tx: penicillamine—copper binder.
Cirrhosis: never focal…always diffuse. Regenerative nodules. Liver tissue is stable (usually Go phase)
Can’t regenerate a basement membrane/sinusoid/portal triad.

Portal hypertension…pitting edema, ascites, can’t metabolize estrogen Gynecomastia. “13 year old boy has
unilateral subalveloar mass”…leave it alone. Normal.
Palmar erythema….related to estrogen
Dupytren contracture: fibromatosis. Increase fibrin tissue around tendon sheaths.
A complication of ascites: spontaneous peritonititis…E. coli (adults) but in kids Streptococcus pneumonia
Hepatocellular carcinoma: Nodularity. Almost always develops in backdrop of cirrhosis. Ectopic
hormones…secondary polycythemia. Suddenly ascites gets worse and patient starts losing weight. Tests: look
for alpha feto protein.
Metastasis: colon to liver. (if non-smoker)
Gall Bladder disease: pathogenesis of stones….too much cholesterol in bile and too little bile salts.
Congenital spherocytosis…supersaturated bile with bilirubin….and calcium bilirubinate stones.
Ultrasound, screening test of choice.
CT is screening test of choice for pancreas.
Atrophy of exocrine ducts, malabsorption, CF kids often get type I diabetes.
Chr 7 3 nucleotide deletion…phenylalanine…real problem is posttranslational at Golgi apparatus. No
CFtransmembrane regulator. Would normally reabsorb Na and Cl-…inspisated mucus…CFTR in lungs…need
to have salt in lumen secretions to have them flow. Na is being sucked out and Cl is being pumped in.
Females can get pregnant, but only about 30% chance of being fertile….cervical mucus is too thick.
Acute Pancreatitis: most commonly due to alcohol. Epigastric pain with radiations to back.
R. upper quadrant…dystrophic calcifications. Wouldn’t have bile salt deficiency.
Carcinoma of the head of the pancreas….most often will be a smoker, or chronic pancreatitis. Palpable gall
bladder. Jaundiced…conjugated bilirubin. C-sign…duodenum.
Peristalsis of duodenum will stop. Sentinal sign. Due to inflammation. Localized ileus. Will get distension.
Segment of bowel distended in right lower quadrant, could be appendicitis producing sentinel sign.
KIDNEY:
Urinalysis----- Castmold of whatever is going on in nephron. Passed in urine, can see what is going on in
tubules. Glomerularnephritis. RBC casts…
Renal tubular necrosis…renal tubular casts
Renal failure….kidney loses ability to concentrate urine. Take urine at morning void, specific gravity of urine.
If greater than 1.023 patient is concentrating urine. Kidneys normal. If 1.010 patient can’t concentrate
urine….in renal failure.
Benign cast: hyaline cast of protein, usually from spilling protein. Generally means nothing.
Uric acid crystal. pH of urine has to be acidic. CA inhibitor to treat.
Horseshoe kidney: Inferior mesenteric artery traps movement.
Cystic diseases of kidney: Infantile polycystic kidney disease (AR) present at birth…oligohydramnios. Very
little amniotic fluid…Potter’s facies…due to pressure in womb. Cysts in liver and pancreas….incompatible
with life

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Adult polycystic KD: Autosomal dominant disease. No cysts present at birth. Will always develop
hypertension. Berry Aneurysm…Blood in subarachnoid space “worse headache you’ve ever had”. History of
hypertension click murmur. Mitral valve prolapse. Diverticulosis. Suddenly loss of blood, anally
Hematochesia.
Marfans: Incomplete penetrance…can have the disease and not express the disorder.
If it ends in -itis it is Type III hypersensitivity.
Focal segmental glomerulosclerosis:
__________________________________________________________________________________________
Renal: Endothelial cells of capillary and then BM and then podocytes on visceral epithelial side. Slit
pores/fenestra. Visceral epithelial cells synthesize the BM. Strong negative charge in BM. Glycosaminoglycan
Heparan sulfate…will spill protein if BM gets damaged.
Immunoflourescent stain; linear or granular (lumpy bumpy). Immune complexes. Goodpasteurs anti
IgG basement membrane antibodies. Will see it everywhere. Linear staining. Type II
Immune complexes, depending on size and charge will deposit where they can. Post streptococcal
glomerulonephritis. Can deposit underneath epithelial side. Won’t have nice smooth pattern. Any immune
complex disease. Type III disease.
Nephritic: unique cast…red. Biconcave disk. Inflammation of glomerulus, will spill mild protein. (<3
g per 24 hours) Will have oliguria. Retain sodium leading to hypertension.
Nephrotic: Fatty cast…greater than 3.5 g of protein in 24 urine cycle. Will have pitting edema.

Scarlet fever two weeks ago….periorbital edema…Acute Poststreptococcol glomerularnephritis.

Subepithelial deposits.
“woman 35, positive serum ANA…lupus. Diffuse proliferative glomerulonephritis.”

Crescent Glomerulonephritis: worst one to have b/c will go into acute renal failure in 3 months. Goodpasteurs
syndrome presents with crescents…bad diagnosis.

Nephrotic: Maltese crosses. Pathognomnic cast of Nephrotic syndrome. Pitting edema all over the body…
anasarca. Fusion of podocytes always seen in nephrotic. Albumin levels go down and liver makes more
cholesterol. Minimal change disease/Lipoid nephrosis. Albumin can get through and go into urine. Treat with
cortical steroids. Most common cause of nephrotic syndrome in kids.
Focal Segmental glomerulosclerosis…most common glomerular lesion in AIDS patients. And IV drug
users. Hepatitis B can produce Diffuse Membranous Glomerularnephritis. Nonsteroidals as well. Captopril—
for heartfailure treatment. Membranoproliferative Type 1 Hep C relationship

Lowest complement levels: Dense deposit disease. Entire basement membrane is immune complex.
TramTrack: endothelial cell, mesangial cell processes extend in BM and endothelial cell.
Christmas Ball disease; Diabetic renal disease. Hyaline arteriolarsclerosis efferent arteriole. Hyperfiltration
damage. Increased creatinine clearance. Nonenzymatic glycosylating. Makes BM permeable to protein.
Microalbuminuria. Give Diabetic patient ACE inhibitor afferent arteriole and its caliber controlled by PGE2.
Efferent arteriole controlled by angiotensin II (constricts it). Takes pressure off glomerulus. Get glycosylated
hemoglobin under 6%. Type IV collagen in mesangium forms big circles in diabetic glomerulosclerosis. Bad
news. (Kimmel Stiel Wilson disease) Nodular glomerulosclerosis.
Ameloid: Apple green bi-refringence. Polarized after Congo Red stain. Assoc. with Nephrotic syndrome.
IgA (Berger’s) Glomerulonephritis. Type III. Episodic bouts of gross hematuria in children…mild
hematuria in adults. Most common of all glomerulonephritis.

BUN/Creatinine ratio:
Blood urea nitrogen—urea can be filtered and reabsorbed in PCT. BUN normally 10. Creatinine norm 1

33
Prerenal azotemia: nothing wrong with kidney but CO is decreased. B/c GFR decreases, less filtered…PCT
more time to reabsorb more urea than it normally would. Creatinine not reabsorbed, but will be backup b/c of
decreased GFR. Slight increase in creatinine…Greater than 15: 1 BUN/Creat. = prerenal azotemia
With renal failure…oliguria, casts in urineacute…urea and creatinine will be affected equally. Both increase
proportionally. BUN 80 : 8 Creatin….if maintain the ratio but both are elevated Acute renal failure…
ischemic acute tubular necrosis. Patients CO decreases and they develop oliguria. Renal tubular casts.
Basement membrane gets damaged as well. Two parts of nephron most succeptible to ischemia….straight
portion of PT and thick ascending limb of medullary segment.
Nephrotoxic drugs….gentamycin, aminoglycosides. PCT. Basement membrane remains intact.
Older people GFR decreases….if you give a drug that has no nephrotoxicity, and you give it in same dosage as
a younger person….you are killing them. Body weight and serum creatinine. Pharmacy will calculate correct
dose.
Acute pyelonephritis: infection of kidney, not all people have normal vesico-ureteral junction…reflux.
Mechanism of all UTI….ascending infection. Ecoli in introitus up urethral and into bladder.
Fever, flank pain, white blood cell casts…acute pyelonephritis. New born girls. Abscesses in kidney.
Recurrent attacks can lead to chronic condition: risk hypertension.
Chronic: Scarred kidney, blunting of calyces.
Reaction to Drugs will have fever and will develop a rash…..oliguria, eosinophiluria, Acute drug induced
interstitial nephritis. Lasex, Penicillins, methicillin.
Renal medulla: discoloration…ring signAnalgesic Nephropathy…acetaminophen (free radical
damage) + aspirin. Aspirin blocks PGE2. Angiotensin II is vasoconstrictor of efferent arteriole. Produces
ischemia—renal papillary necrosis. Diabetic nephropathy can also cause.
Chronic renal failure: BUN of 10 : 1 for more than 3 months. Both kidneys fail: won’t excrete salt,
won’t make EPO normocytic anemia…Metabolic acidosis...Proximal tubules screwed 1 alpha hydroxylase…
will develop bone disease. Hypovitaminosis D. Parathyroids will develop Secondary hyperparathyroidism.
Essential hypertension: With 10 years of poor control…nephrosclerosis. Papilla edema w/ flame
hemorrhages. Malignant hypertension. BUN:Creatinine 80/8. Petechia visible on surface of kidney.
Treatment: IV nitroprusside. CNS edema. Will stroke out if you don’t resolve hypertension.
Pale, depressed looking areas on kidney irregular irregular pulse…Atrial Fib…Pale infarct with coag
necrosis. Most dangerous for embolization, emboli go to kidney.
Atrophy, hydronephrosis. Similar to CF ducts that are filled with mucous. Thin cortex and medulla.
Most common cause is stone.
Staghorn calculus: urine smells like ammonia….Proteus species, urease producing organism. Don’t
pass the stone. Will have to do surgery to correct. Alkaline urine pH.

Tumors of kidney: Renal adeno carcinoma—Adult, but in child--Wilms tumor. Derive from proximal tubule,
MCC=smoking. Ectopic hormone production, PTH. EPO. May invade the renal vein.
Flank mass + hypertension in child….wilms tumor is making renin. Chr 11. About 4th most common
tumor in kids. Duplicate embryogenesis of kidney. Likes to metastasize to lung. Anoridia—absent iris,
hemihypertrophy of an appendage.
Most common urinary abnormality. Ecoli=> Positive dipstick for blood. Hemorrhagic cystitis.
Dysuria, increased frequency, superpubic pain. Leukocyte esterase +, Nitrate positive. UTI. If patient has
fever, white blood cell casts, flank pain…..upper UTI. If not, lower UTI. Chlamydia (Most common sexually
transmitted disease) and TB (miliary TB—infects kidney) can cause.
Transitional cell carcinoma of the bladder….Smoking. Tx: cyclophosphamide prevent complications with
MESNA.
Hypospadias: below head of penis, Epispadias…defect in genital tubercle. Priapism=permanent
erectionsee in SC disease b/c red blood cells get trapped in vasculature. Lack of circumcision…poor hygiene
may develop squamous cell carcinoma of head of penis.
Testicle: Cryptorchidtransabdominal migration: Mullerian inhibitory factor….2nd part of trip is androgen
dependent.  Risk of seminomas (PLAP is marker) if not down in scrotum by two years of age.
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Turners: Menapause before menarche. Ovary without any follicles….streaked gonad….called dysgerminomas.
Remove surgically both ovaries.
Varicocele: spermatic vein on left is connected to left renal vein. Spermatic vein on right is connected to IVC.
One of most common causes of male infertility. “block left renal vein, will develop varicocele”
Torsion: spermatic cord twisting shortens it, testicle will go up a little…lose cremasteric reflex.
Hydrocele: persistence of tunica vaginalis. Transilluminate…if it doesn’t its cancer. Painless enlargement of
testicle…CANCER.
Seminoma: lymphocyctic infiltrate. Usually will melt with radiation. Most common. Will go to paraaortic
lymph nodes.
Most common in kid: Yolk sac—alpha feto protein as marker.
Worst one: choriocarcinoma. “25 year old man has unilateral gynecomastia”, primary is in
testicle….beta hcG stimulates progesterone…similar to LH.
Older male: malignant lymphoma…metastasis.
Prostate: hyperplasia—periurethral portion of prostate. Prostate cancer in periphery of prostate gland. “75 yr
old man with urinary retention—prostate hyperplasia….Dihydrotestosterone…in charge of prostate.
5 alpha reductase inhibitor…finasteride. Would increase testosterone.

Day 5--------Female
Hirsutism: excessive of hair in normal hair growing areas. Free testosterone is predominantly synthesized in
ovary. Dihydro sulfate in adrenals ….if DHA sulfate elevated…coming from adrenals
Virilization…masculinization, clitorialmegaly
Polycystic ovarian syndrome…common cause of hirsutism. FSH suppressed and LH increased. LH
responsible for hormone synthesis in theca interna…. Synthesis of 17ketosteroids in ovary. DHA and
androstenedione. Converted into testosterone. Aromatase converts Test in to estradiol. Often found with
obesity. Aromatase in adipose tissue. Woman with signs of excess testosterone, yet have excess estrogen too…
b/c converted by aromatase. Constantly enhancing LH and inhibiting FSH. Break cycle with birth control pill.
Cysts develop because of FSH suppression. Cystic space where follicle used to be. Can feel by pelvic
exam.
Menstrual dysfunction: dysmenorrheal…primary too much PGF. Secondary cause is endometriosis.
Dyfunctional uterine bleeding DUB. Hormone imbalance causing bleeding change.
Anovulatory cycles—young lady….persistent estrogen stimulation on mucosa, without effect of
progesterone
Inadequate luteal phase, irregular shedding
Primary amenorrhea: hypothalamus/pituitary problem?
Ovarian problem?
End Organ Problem? Cervical stenosis? DES exposure?
1st step in work up of amenorrhea—pregnancy test
Turner’s syndrome….XO…no Barr body. Can make diagnosis at birth. Swelling of the hand of feet on
newborn female…lymphadema. Nuckle Nuckle dimple knuckle. 4th metacarpal. Cystic Hydromas….in neck
area, stretches skin, looks like webbing. Preductal coarctation. Can be fertile if mosaic. Menopause before
menarche. Streaked gonad. Succeptible to dysgerminomas.
Adenomyosis; glands and stroma within myometrium….very common, doesn’t predispose to cancer.
Endometriosis: gland and stroma outside confines of uterus. Produces bleeding in ovary, can be in
pouch of douglass. “Does it hurt when you have your period when you defecate…but not when you don’t have
your period?”
Unapposed estrogen…run risk for endometrial cancer
Pouch of Douglass…could collect pus, blood,
Endometrial hyperplasia….Unopposed estrogen. Risks: Early menarche…late menopause…obesity(associated
with Type II diabetes) ….(estrogen factory in fat stores)
55 post menopausal is usually when you see endometrial cancer. 45 yrs cervical, 65 yrs ovarian.

35
Leiomyoma: most common benign tumor in woman.
Lower abdominal pain…beta hCG to rule out ectopic pregnancy
Female Tumors;
Surface derived….from lining of ovary.
Germ cell types-teratoma and dysgerminoma
Sex cord stromal tumors-can make estrogens, granulosa cell tumors, sertoli leydig cell tumor will make
virilization/hirsutism.
Most common cause of ovarian mass in young woman….afollicular mass.
Serrous cyst adenocarcinoma—malignant---Psommoma bodies—apoptosis of tumor cell and replacement by
dystrophic calcification.
Serrous cyst adenoma--benign
55 yr old woman bilateral ovarian enlargement---cancer til proven otherwise….ovaries shouldn’t be palpable.
Fibromas--benign, Meig syndrome—right sided pleural effusion.
Signet ring cells….metastasis from another site….stomach. Krukenburg tumor. CLEARLY.
Chorionic villusoutside layer is synctial trophoblast. BetaHcG& human placental lactogen (growth hormone
of pregnancy. )
Hyadidaform mole: Complete 46 XX both from Dad. Partial is triploid, 69 chrs and can have fetus present.
…..complete has better chance to move onto choriocarcinoma—maligancy of trophoblast tissue.
BREAST LESIONS: Nipple….Paget’s disease of breast
Most common cause of bloody nipple discharge in woman under 50…lactiferous ductal cancer in older woman.
Lobular carcinoma--BILATERAL
Most common cause of a mass in the breast of a woman under 50…fibrocystic changeover 50…infiltrating
ductal cancer.
Woman 35 movable mass in breast…fibroadenoma. Neoplastic component is stroma. As it grows and
compresses has slit like spaces.
Fibrocystic change…lumpy bumpy worse as cycle goes on.
Epithelial cells lining the ducts are estrogen sensitive.
Woman over 50 with painless papable mass…..cancer. Outer quadrant of breast…most common location for
cancer. Nipple sucked in, stellate appearing mass….on mammography, fine calcification.
FINE NEEDLE ASPIRATION: 1st step in management of mass in breast. Can get diagnosis and can tell if
solid or cystic.
Commedo carcinoma—pus like substance that comes out: Erb2 oncogene. Aggressive.
PAGET’s Disease: older woman cancer of duct underneath that has spread onto skin above. Rash around
Nipple.
Inflammatory carcinoma: BAD! Dimple skin because lymphatics are filled with cancer and lymph fluid is
leaking out. Lymphatic tumor.
Terminal lobules….famous for bilaterality.
Winged scapula on radical mastectomy…long thoracic nerve…C5,6,7.
ERA PRA; Estrogen receptor….relationship btw presence of estrogen and receptor synthesis. Tamoxifen is
weak estrogen. Blocks receptor. Menopausal type symptoms with risk of endometrial cancer. ERA PRA
positive is responding to the tumor.
Endocrinology:
Hashimotos with hypothryroidism—primary
Adenoma on thryroid gland—primary
Hypocalcemia—Vit D deficiency—2nd parathyroidism
Stimulation test: on underactive gland to see if we can get it working again.
Tumors in pituitary gland: prolactinoma—bromocriptine: dopamine analogue, dopa inhibiting prolactin. Can
use it in treating parkinson’s disease too.
Pituitary Cushings: can suppress with high dose of dexamethasone.
Hypocortisolism: ACTH stimulation test.

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Hypopituitarism: Pituitary adenoma—sella turcica—sphenoid bone--usually non functioning and destroy
pituitary.
Pregnant woman—Sheehans post partum necrosis. If breast milk stops. Infarcted pituitary.
Coagulation necrosis. Pregnant women have 2x normal size pituitary.
Cranial pharyngeoma—Tumor of Rathkes pouch—NC cells, suprasella. Goes down and destroys pituitary…
Bitemporal hemianopsia b/c of damage to optic chiasm.
Gonadotropins get damaged. Males will get impotence/women amenorrhea.
Growth hormone stimulated liver, activates Insulin like Growth Factor I…somatomedins.
In child….pituitary dwarfism…incompletely developed child. GH released in early morning Arginine/histidine
essential for normal growth of a child—stimulate GH. Arginine stimulation test.
TSH, low, T4 low…brittle hair, fatigue, delayed reflexes.
ACTH—will be fatigued with low cortisol level. Will have fasting hypoglycemia.
Diabetes insipidus: Central—sever stalk to pituitary…ADH will be one of the first things to go. Deficient all
releasing factors that come from hypothalamus. Peeing all the time…tremendous thirst. Car accident.
Nephrogenic: Losing pure water…constantly diluting (opposite of inappropriate ADH
release) Serum sodium will go up…Increase in plasma osmolality. Diagnose by restriction of water. Look at
urine osmolality. Give them vasopressin/ADH…look at response of osmolarity.
Diabetes mellitus; polydipsia, hypercalcemia,
Acromegaly: look at old picture of patient. Giantism if kid whose kidney’s haven’t fused….
--Die of cardiomyopathy. Increase GH. Hat size increases. Feet/organs get bigger.
Galactorrhea: Men don’t get it. Don’t have enough terminal lobules…..Women—find out what drugs they are
on to stimulate prolactin. Hydralazine, Calcium channel blockers. Always get TSH. TRH actually used as
stimulation test for prolactin. R/O hypothyroidism.
Thyroid studies: T4, TSH, and I131 uptake…if TSH is normal then thryroid is normal.
Binding protein for calcium: albumin---BP for iron; ferritin.
Measure total T4, free (metabolically active)
Women: if on birth control pill…..increased syn. of thyroidbinding globulin. Total T4 is elevated. Same thing
true for cortisol. Transcortin increased….free cortisol levels still normal.
Anabolics: break down proteins normally used for other things. Thyroidbinding globulin decreased.

Low T4 with normal TSH---Anabolic steroids

Woman with Low T4 but normal TSH….estrogen
Person with High T4 but low TSH…..hyperthyroidism
Person with Low T4 and increased TSH…primary hypothyroidism
I131 uptake…Gave person radioactive iodine….will have increased I131 uptake (graves disease too) ….If
taking thyroid hormones to lose weight…TSH level will be suppressed…glands will atrophy….I131 will be
decreased.

Midline cyst…thyroglossal duct cyst

Thyroiditis….hashimotos…
Graves…Exopthalmos unique…excess glycosaminoglycans being deposited in orbital fat.
Old people with Graves…apathetic graves. George Bush Sr. Heart problems with atrial fibrillation. Must
get TSH to R/O Graves. Will be suppressed.
Hyperthyroidism: Systolic hypertension, heat intolerance, diarrhea, sinus tachycardia. Potentially could have
hypercalcemia…increased bone turnover….catecholamine effects. Phenylalanine to tyrosine to dopamine to
dopa to norepi and Epi. T4 increased synthesis of beta receptors. Initial treatment of graves…beta blocker…
block all adrenergic response. Can stop all the symptoms except sweating. T4 high, TSH low, I131 uptake is
low. Puffyness in periorbital area…..glycosaminoglycans

Pretibial myxedema….increase in deposition…hoarse throats same thing. GAGs. Water follows.

37
Mitral valve prolapse: increase in dermatan sulfate
Hashimotos (IgG against receptor that inhibits gland) and Graves (IgG antibody against TSH receptor—Type
II) autoimmune diseases.
Decrease in GAGs metabolismlysosomal storage diseases (Hurlers and Hunters)
Hypothyroidism muscle weakness….proximal muscle myopathy, brittle hair, coarse skin, periobital
puffyness, diastolic hypertension. Low T4, High TSH. Low 131 uptake.
Estrogen: TSH normal, increase T4.
Rule out cretinism or hypothyroidism in newborn for normal development.
Graves: T4 high, TSH low, I131 high
Goiter: thyroid big….Most common cause of a goiter is iodine deficiency. Either hypothyroidism or borderline
hypothyroidism. TSH stimulates in cycles…thyroxine is proper tx. Sometime will have a nodule. Sudden
increase may be due to ruptured cyst.
Cold Nodule: whether nodule is taking up I131 or not. Cold—doesn’t. Chance that a cold nodule is malignant
in woman15-20%....IN MAN…cold nodule in man is cancer until proven otherwise. Papillary cancer of
thyroid.
Papillary: Psomomma bodies. Will metastasize to cervical lymph nodes.
Follicular cancer: invades vessels. Hemotogenously to lungs and bone.
Medullary carcinoma: Ret protooncogene. Mulitple Endocrine Neoplasm: MEN I—pituitary tumor,
Zollinger Ellison, IIA, IIB (pheochromocytomas…)
“Where would the cancer in body be where the tumor marker (calcitonin) is converted to amyloid?” Thyroid—
medullary carcinoma.
Calcium Bound—metabolically inactive. About 40% is ionized…metabolically active….hypoalbuminemia…
most common cause of hypocalcium.
Alkalosis: low H+ ions. Acidic amino acids, glutamate, aspartate. Albumin…good binder of calcium b/c most
negative aa (acidic) of any protein in body. Can bind more calcium. Has decreased the ionized calcium level…
tetanymechanism: threshold of AP before nerve is stimulated. Decreased ionized Calcium lowers
threshold…partially depolarized.
Parathyroid hormone: If serum calcium is low and PTH is low….primary hypoparathyroidism.
MCCprevious thryroid surgery. DiGeorge syndrome also a cause…midline defects, no thymic shadow.
Ca: Low calcium and High PTH is secondary parathyroidism. Hypovitaminosis D with renal failure.
Hypercalcium: Increased PTH? Gland is not obeying negative feedback…primary hyperparathyroidism.
Cushings…purple stria…thin extremities and obese trunk. MCC: long term steroids. Pituitary account
for 2/3rds of cases. Adrenal Cushingslow ACTH levels. Ectopic cushingshighest ACTH levels, small cell
carcinoma. –Screening Tests. 24 hour urine for free cortisol. Cortisol in urine not attached to any protein.
Best test for Cushings. USMLE will ask about suppression tests. Dexamethasone suppression tests. Cortisol
analogue…Should suppress ACTH. In a patient with Cushings you see a lack of suppression.
Look at HIGH dose Dex suppression test. Can suppress adrenal production of cortisol
Hypercortisolism….gluconeogenic…main substrate is aa….breakdown of muscles in extremities. Thin arms
and legs. Glucose will be high, insulin will be high, fat storage will be increased. Purple striacortisol
decreases collagen syntheis.
Trousseau sign,(thumb and fist)hypertension, hyponatremia hypokalemia, tetany…primary aldosteronism
alkalosis, number of negative charges on albumin, decreases, more bound. Conn’s syndrome.
Pheochromocytoma: benign, more common in adults, adrenal medulla, Neuroblastoma, malignant
more common in kids….hypertension…person with unstable hypertension…sweat a lot, anxious. 24 hour urine
for metanephrins or VanillicMandelicAcid….breakdown products of Norepi and Epi. Assoc. with MEN II A/B.
Gram negative diplococcus…neisseria menigitidis. Child with high fever and nuchal rigidity…petechial
lesions. Waterhouse Friedrichson syndrome…. Most common cause of meningitis from 1 months of age to 18
yrs. Only meningitis w/ petechial lesions all over the body…Hypotensive shock…hemorrhaged adrenals.
Addisons disease….autoimmune destruction of the glanddestroy entire adrenal cortex...ACTH is
high...will see hyperpigmentation in skin (mouth) will have hyponatremia, hyperkalemia (peaked T waves)…
metabolic acidosis.
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Ambiguous genitalia: get karyotype. 21 hydroxylase deficiency. 17 hydroxys are decreased….losing salt.
ACTH is high as cortisol is decreased….children are hyperpigmented.
17 hydroxylases are responsible for 17 ketosteroidsDHEA and androstenedione (can be converted into
testosterone)
17 hydroxy deficient: males—no testosterone, increase in mineralocorticoidshypertension, girls will have
underdeveloped genitalia.
Islet Cell tumors: Zollinger Ellison syndrome—making to much gastrin, have peptic ulcers.
Insulinoma….injecting or do you have insulinoma....look at C-peptide b/c released when you released insulin.
Will be suppressed if you are injecting insulin, but increased if you have insulinoma.
Diabetes: Type Iabsolute insulin deficiency, ketoacidosis, HLA relationship (+ certain environmental
factor----Coxsackie, mumps, EBV)
Type IIameloid destruction, obesity.
Osmotic damage….tissue must have aldose reductase in it. Pericytes in retinal vessels. Can rupture and
produce blindness. Nonenzymatic glycosylization. Hemoglobin A1c…long term glycemic control. Diabetic
nephropathy…hyaline arteriolarsclerosis. Dry gangrene. Proliferative retinopathy.
50 years old. Blurry vision…new glasses…constant change in refraction…coverting glucose to sorbitol
and changing refraction of lens. Get fasting blood glucose. Greater than 126 mg/dl on two separate
occasions….diabetes.
Increases Sensitivity…when numbers were changed from 140 mg/dl to 126….will pick up more people
with diabetes early on.
Risk of gestational diabetes…Respiratory distress syndrome.

Musculoskeletal: Crystals in synovial fluid…TophusGOUT: Yellow and parallel to analyzer, usually big toe
first one to develop gout. Indolmethacin usually used. Overproduction (allopurinal…blocks xanthine synthase)
or underexcretion of uric acid. 90% of cases are underexcretion. Probenacid or sulfinpurasolas uricosuric
agents. Multifactorial inheritance. Wouldn’t want to eat red meats/ red wine/alcohol…metabolic acidosis.
Lactic acidosis and beta hydroxyl acidosis compete in kidney for excretion.
PSEUDOGOUT: 2 types of crystals, Blue and parallel to analyzer
Rhematoid Arthritis: Swelling of MCP joints. Rheumatoid factor…IgM antibody against IgG…immune
complexes form, and damage joint. Pannus formation. Synovial tissue that is hyperplastic. Ulnar deviation
symmetrical. Dry eyes dry tongue…Sjorgen’s syndrome Lacrimal gland destruction. Methotrexate.
Macrocytic anemia develops. Interstitial fibrosis in lung.
Osteo: wearing down of articular cartilage. Reaction to injury that occurs…osteocyte or spur. Haverdean’s
node. Knuckles..metacarpal interphalangeal joints.
Inflammation of aorta, blurry vision, arthritic changes.
Degenerative disease in vertebral column + Black urine = Alkaptonuria….
HLA-27 postive….chlamydia can push you over to develop Reiters’ syndrome. Pathognomonic for Reiters…
Achilles tendon inflammatory reaction.
Hot joint, pustule on palm that has aspirated…disseminated gonoccemia….rhematoid arthritis in adults. C5-C9
final common pathway of complement. Most common cause of septic arthritis….Gono…will be in the knee.
--Erythema chronicum migrans, Concentric circles. Borrelia burgdorferi, Ixodes tick. Lymes disease… Tx
with tetracycline. ANY PATIENT WITH: bilateral bells palsy….lymes diseases until proven otherwise.
Chronic lymes: affects 7th cranial nerve.
Hemolytic anemia: babesia (white tailed deer….also in Ixodes tick) 20% of people with lymes have
babesiosis as well. Ceftriaxone.
Bluish discoloration to sclera…osteogenesis imperfecta. Defect: type 1 collagen. Mechanism of blue
sclera reflection of choroidal veins.
Osteopetrosis: can’t break bone down…severe anemia.
Osteoperosis: mechanism, break more bone down than you are putting in. Mineral and organic content is low.
Collapse in vertebral column. Colles fracture of distal radius. Is swimming a good exercise for preventing
osteoperosis…NO….walking/weight training is better…you need the stress on bones.
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 Two most common cartilaginous bone tumors: Osteochondroma: cartilage capped by bone on surface.
Osteogenic sarcoma: adolescent, bone pain. Develops in metaphysic of bone. Lifting of periosteum. Sun burst
appearance. Codman’s triangle…Rb suppressor, Chr 13.
Pseudohypertrophy of calves: Duschennes muscular dystrophy---don’t have dystrophy. Beckers:
mechanism (sex linked recessive) make defective dystrophy.
Panacinar emphysema: don’t make alpha 1 antitrypsin.
Myotonic Dystrophy: Most Common Adult dystrophy—Triplet repeat disease. Huntingtons’, fragile
X….anticipation disease. Genetic councilor telling couple that if they had children, disease would be fatal…
couple didn’t listen and child died after one month.
Muscle weakness in face: “couldn’t release hand from golf club” Diabetes and cardio defect.
Myasthenia gravis: Autoantibody against Ach receptor. Type II. Ach can’t get to receptor..get double vision,
dysphagia for solids and liquids…striated muscle affected. Give ach esterase inhibitor. B cell hyperplasia
(antibody being made in thymus)
Butterfly distribution of rash on face: Lupus…positive ANA. Order two antibodies, anti Smith
antibody (100% specificity), anti double stranded DNA. Morning stiffness, photophobia, pericardititis.
Tight face, dysphagia for solids and liquids, CREST or progressive systemic sclerosis.
Sjorgens syndrome: dry eyes, dry mouth, biopsy of lower lip…confirmatory diagnosis. Anti SSA and SSB.
Skin pimples: basal cell carcinoma, squamous cell, actinic (rub it off and it comes back) Psoriasisrash
on elbow. Atopic dermatitis…eczema. Contact dermatitis: type 4 hypersensitivity question.
Subhorreic dermatitis: Malesszia furfur…worry about IC condition if it is diffuse.
Tinea capitis—Trycophyton. All other superficial dermatophyte infections due to trycophyton
rubrim….red outer edge, hyphae and yeast forms.
Molluscum contagiousum; pox virus…dna virus.
Non-pruritic rash—pale in middle, oblong looking, do KOH prep. Rash in Lines of Langer, Christmas tree
distribution on trunk. Pedoriasis rosea
Precursor lesion for malignant melanoma: more than 100 nevi….dysplastic nevus syndrome.
Excision first step in management. Superficial spreading malignant melanoma. Lentigo malignant least likely
to metastasize. “Black individual with malignant melanoma…look at under the nails, palms, soles of feet for
primary lesion.” -- depth of invasion is key prognostic sign.
Poisonous spiders Black Widow: Red hour glass on undersurface….Neurotoxin…spasm in abdomen.
“Violin spider”Brown Recluse…bite doesn’t hurt, but it is a necrotoxin….most
potent of all venoms in world ounce for ounce.
Structure responsible for piloerection, receptor for androgens in skin…sebaceous glands. More
testosterone, more acne…proprionium bacteria.
Spironolactone: prevent Hirsutism, can produce gynecomastia in male
CNS: choroid plexus—develops cerebrospinal fluid.
Spinal fluid=Cloride is way higher in spinal fluid than serum. Cribriform plate breaks…hit by baseball
in eye…fluid leaking out.
Aqueduct of sylvius, build up in 3rd . Foramen of Luska and Magendia in 4th. Dura is tightly adherent to
skull. Epidural hemotoma….arterial pressure can split periosteum. Middle meningeal artery.
Get rid of fluid through arachnoid granulations….into dura sinuses. Valsalva to see if entire
arachnoid space is patent.
Hydrocephalus: Communicating benign tumor of choroids plexus, making more spinal fluid.
Noncommunicating( more common) something is preventing spinal fluid from
ventricles from getting into subarachnoid space. Stenosis of aqueduct of sylvius. Ependymoma. Meningitis in
base of brain
Arnold Chiari Syndrome: Medulla into cervical region.
Herniation: If you have cerebral edema and there is no where else for it to go. Cerebellum squeezed into
tentorium cerebelli
Uncal herniation, oculomotor nerve palsy…down and out.

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 Parasympathetic nervous system, normally constrict the pupil…If messed up, you get mydriasis…first
sign of uncal herniation, mydriasis.
Papillaedema, don’t see sharp margins to the disk…vitamin A toxicity could cause, as well as any
increase in intracranial pressure.
Tublerous Sclerosis: hammartoma…nonneoplastic proliferation.
Anencephaly; absent brain…
Spinobifida occulta….vertebral arches don’t quite touch. Alpha feto protein levels increased in
mother….DECREASED in mother in downs syndrome.
Café au lait: neurofibromatosis…autosomal dominant diseases—late manifestations, penetrance,
variable expressivity.
Sphyringomyelia: person works in factory, “you’re burning your hand” loss of musculature in internal
muscles of hand. Lack of pain response. Sensory and motor.
ALS is pure motor disease….not about pain and temp. No bladder problems.
Infections: Meningitis: NUCAL rigidity. Cerebral abscess, deafness as complication. Group B Strep is
most common cause in newborn. Premature rupture of uterine membrane…then ecoli then listeria
monocytogenes…SOFT CHEESES bad…gram positive with tumbling motility…after 1 month its Neisseria
menigitidis, until 18 year then Strep pneumonia (Gram positive diplococcus)
Encephalitis: Sleeping sickness…trypanosome…mental status changes.
Rabies: most common cause skunks in US. Dogs in third world countries. Raccoons in jersey. Negri bodies.
Child with congenital infections—periventricular calcification…CMV due to encephalitis. CMV most
common congenital infection in kids…urine is most productive to culture.

Narrow based buds: Cryptococcus. IC patients. Most common aquired immuno def in US. Crypto is common
cause of meningitis in AIDS patients.
AIDS patient: Toxoplasma—space occupying lesion
“Pig herder…long time problem with seizure…cystacercosis…taenia solium
JC disease—prions, neuropathologists, neurosurgeons…beef, Lettuce from Arizona, cow manure for fertilizer.

Epidural hematoma: Whacked in head in temporal parietal lobe…bone must be fractured. 50 mls of blood.
Unconscious for a little while and then lucid…into coma.
Subdural hematoma: rupture bridging veins between subdura and arachnoid. Fluctuating levels of dementia.
Stroke: patient would have big cystic space…liquifactive necrosis where hemorrhage was.
Wedge shaped appearance….embolic infarct. Will go into MCA.
Hypertension: pressures cause lenticulostriate vessels to aneurysm…Bouchard aneurysm. Rupture and big
infarct occurs.
Subarachnoid hemorrhage: Berry aneurysm
AV malformation; Sturge Webber. On side of face.
Lacunar infarcts: Internal capsule, can have pure motor or pure sensory damage….most commonly due to
hypertension.
Most common demyelinating disease in US. Autoimmune. Plaques of Multiple Sclerosis. Oligodendrocytes in
CNS, schwann in PNS. Nystagmus…ataxia, optic neuritis. Intranuclear opthalmoplegia….Eye on side of
direction of movement moves, other doesn’t….(right eye looks right, left stays straight ahead)
Senile Plaque; beta ameloid protein. Toxic to neurons. More dementia…more plaques. Downs all have
Alzheimers by 35/40 years old.

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