High yield (cell injury)

Question 1

If the oxygen partial pressure (in the plasma) is decreased, the oxygen saturation (on Hb) MUST also decrease.

Answer 1

Thrombosis in a muscular artery is the most common cause of ischemia

Question 2

Hypoxemia (decrease oxygen partial pressure) is a cause of hypoxia

Answer 2

Respiratory acidosis => CO2 inc => pO2 dec (and vice versa).

Question 3

Hypoxemic patient that gets 100% oxygen and his pO2 didn’t increase => shunt => ventilation defect (ARDS, hyaline membrane disease).

Answer 3

Perfusion defect (PE) => inc dead space (100% O2 will get the pO2 up)

Question 4

Diffusion defect (sarcoidosis, pulmonary edema)

Answer 4

J reflex innervated by the Kent nerve, cause dyspnea (fluid in lung interstitium irritating the J receptors).

Question 5

Anemia (Hb related problem) => pO2 normal, saturation normal, Hb decreased => exertional dyspnea.

Answer 5

House fire produces tissue hypoxia in 2 ways: CO poisoning (saturation dec, give 100% oxygen) and CN poisoning. Both inhibit cytochrome oxidase.

Question 6

Cyanosis is the clinical evidence of decreased saturation. Red pigment hides the cyanosis in CO poisoning (most frequent symptom is headache).

Answer 6

MetHb => saturation decreased because the Hb is Fe3 and not Fe2 (chocolate color blood) => 100% oxygen doesn’t improve cyanosis. Treatment is IV methylene blue, vitmamin C (also but not main)

Question 7

Sulfa and nitro drugs (oxidizing agent): 1. produce MetHb. 2. Hemolytic anemia, G6PD deficiency.

Answer 7

MetHb common in HIV, because we use sulfa drugs to treat pneumocystis carinii

Question 8

Right shift curve: 2,3BPG inc, high altitude, acidosis, fever.

Answer 8

Left shift curve: CO, MetHb, HbF, 2,3BPG dec, alkalosis.

Question 9

Uncoupling agents (mitochondrial membrane permeable to protons): dinitrophenol (wood preserving), alcohol, salicylates. To compensate, NADH, FAD producing systems (which produce protons) increase => hyperthermia (alcoholics are more susceptible to heatstroke).

Answer 9

Respiratory acidodis = Hb normal, Saturation dec, pO2 dec

Anemia = Hb decrease, saturation normal, pO2 normal

CO + MetHb = Hb normal, saturation dec, pO2 normal

Question 10

Anaerobic glycolysis => lactate acidosis => denature proteins + enzymes (can’t even
auto digest itself) => coagulation necrosis => infarct.

Answer 10

Anaerobic glycolysis => ATP pump malfunction, decrease ATP => Na enters cells => water follows ! cellular swelling (reversible!).

Question 11

Irreversible cell damage: ATP decrease => Ca ATPase dec => intracellular Ca inc => activates nuclear enzymes ( => pyknosis), phosphlipase (=> cell membrane damage)
=> pancreatitis.

Answer 11

Cell death: CK, GOT, GLT, amylase increase.

Question 12

Lipofuscin (wear and tear pigment) is a brown pigment in atrophic organs in elderly. It cannot be digested. Hemosiderin or bilirubin can also produce a brown pigment.

Answer 12

Reperfusion injury (oxygen radicals) can be caused after giving TPA for coronary thrombosis, then oxygenated blood go to the injured cardiac muscle.

Question 13

IRDS: retinopathy of prematurity (oxygen radicals destroying the retina, blindness) and bronchopulmonary dysplasia (fibrosis)

Answer 13

Most common cancer of radiation is Leukemia

Question 14

Iron overload cause free radicals => cirrhosis, restrictive cardiomyopathy, pancreas failure => malabsorption + diabetes

Answer 14

Acetoaminaphen (Tylenol) is the #1 cause of drug induced fulminant hepatitis (damage around central vein). Treatment: N-acetyl cystein (inc glutathione)

Question 15

Neutralization of superoxide is by superoxide dismutase (turns into peroxide).

Answer 15

PPP generates Glutathione and NADPH.

Question 16

CCL4 can also be converted to a free radial (CCL3) ! fulminant hepatitis.

Answer 16

Acetoaminaphen (radicals) + Aspirin (dec PG) => kidney damage (renal medulla)

Question 17

Di-george syndrome: absence of thymus, cause tetany.

Answer 17

Councilman body in Hepatitis: apoptotic eosinophilic cell with no nucleus

Question 18

Coagulation necrosis - Pale infarct: Heart, kidney, spleen, liver

Hemorrhagic infarct: Bowel, testicle (torsion), lungs.

Answer 18

Vegetation of acute rheumatic fever rarely embolize. Infective endocarditis does.

Question 19

Mitral stenosis can cause thrombi in left atrium => atrial fibrillation

Answer 19

The arrhythmia most associated with systemic emboli is atrial fibrillation

Question 20

Most common cause of non traumatic amputation is diabetes (inc ATH of popliteal
artery)

Answer 20

Most common cause of bowel infarction: #1: adhesions of previous surgery, #2: piece of small bowel trapped in an indirect inguinal hernia.

Question 21

Liquefactive necrosis is related to an infection where neutrophils are involved (acute inflammation, lung/brain abscess, cellulites by strep.) and also related to brain infarct.

Answer 21

Granulmatose necrosis: caseous – mycobacteria or systemic fungal infection. Non caseous – sarcoidosis.

Question 22

Epigastric distress with pain radiating to the back => pancreatitis (retroperitonea

Answer 22

Enzymatic fat necrosis (pancreas) or traumatic fat necrosis (breast, adipose) ca both calcify (look like cancer on X-ray) but it’s painful unlike cancer.

Question 23

• Calcium bound to fatty acid = saponification (chalky white areas on X-ray).
• Bluish discoloration on histologic sections is calcium (dystrophic calcification).
• Fibrinoid necrosis (looks like fibrin but isn’t): immunological diseases (rhematic fever,
  rheumatic arthritis, glomerulonephritis, SLE, vasculitis).
• Palpable purpura: small vessel vasculitis, hypersensitivity type 3. Conditions that present with palpable purpura include: Henoch-Schönlein purpura, subacute bacterial endocarditis and Rocky Mountain spotted fever.

Answer 23

• Immune complex => activate alternative complement system=>! C5a => chemotaxis of neutrophils that cause the actual damage.
• Yellow fever (Arbovirus) damages the liver zone 2 (mid-zone necrosis)

Question 24

• Alcoholics have fasting hypoglycemia, lactic acidosis (inc NADH shift pyruvate to lactate so there is no substrate for GNG), keto-acidosis (B-hydroxybutyrate).
• Restriciting CH will reduce the synthesis of VLDL (Glycolysis provides glycerol 3 phosphate, which is the backbone of TAG which is incorporated into VLDL).
• Kwashiorkor: reduce protein intake => no apo-proteins => huge fatty liver: Reduce protein intake => no oncotic pressure => Ascites.
• Ferritin (soluble iron storage) is a marker for diagnosing iron deficiency anemia or hemosiderosis, hemochromatosis: Hemosiderin (insoluble iron storage), stored in MP and BM. Stained with Prussian blue.

Answer 24

• Dystrophic calcification: damaged tissue gets calcified (fat necrosis, ATH, aortic
  stenosis, hemolytic anemia), normal serum calcium.
• Metastatic calcification: hypercalcemia or hyperphosphatemia => calcium deposits in
  normal tissue.
• Congenital bicuspid aortic valve is the most common cause of aortic stenosis.
• Spectrin is needed to keep a bi-concave disc, if it’s defective => spherocytosis.
• Ubiquination - Mallory bodies = alcoholic hepatitis
• Neurofibrillaty tangles (tau protein) = Alzheimer, Creutzfeldt-Jakov disease.
• Lewy body = Parkinson (substantia nigra, dopamine)

Question 25

- Labile cells = division is via stem cells (BM, skin, intestinal crypts), in cell cycle. - Cell cycle specific or non specific drugs => BM suppression, diarrhea, rash. - Stable cells = mostly in G0, but can be stimulated to divide (liver, spleen, kidney, smooth muscle, endometrium) - Permanent cells = can’t get into the cell cycle (striated and cardiac muscles, neurons), can go through hypertrophy. - Hyperplasia = increase in number, hypertrophy = increase in size. - The length of the cell cycle is decided by the length of the G1 stage. - Glucagon is a phosphorylator, insulin is a dephosphorylator.

Answer 25

- Rb (chr.13) prevents the cell from going into S phase. When phosphorylated by CDK, it’s inactive. p53 (chr.19) induces a CDK inhibitor, gives time to detect and correct defects before entry to S phase. - HPV E6 suppresses p53, HPV E8 suppresses Rb. - No Rb protein => Retinoblastoma, osteogenic sarcoma, breast cancer. - Codman’s triangle seen in: osteosarcoma, Ewing sarcoma, subperiosteal abscess. - Vinca Alkaloids (periwinkle plant), Paclitaxel (chemotherapy, yew tree), Colchicine, Griseofulvin (M phase), Etoposide (G2 phase), MTX, Bleomycin (S phase) - MTX, used in rheumatoid arthritis, inhibits DHF reductase => can cause macrocytic anemia.

Question 26

- Atrophy = decrease in tissue mass, decrease cell size, less mitochondria. - Hydronephrosis is mostly caused by renal stones => increase pressure => ischemia => atrophy of renal tubules. - ATH, Alzheimer (B-amyloid protein, layers 3,5,6 destroyed), ALS => brain atrophy, neuron degeneration. - Hypopituitarism => adrenal gland atrophy (zona reticularis and fasiculata ONLY) - Oral thyroid => thyroid atrophy. - CF (Chr.7) => block lumen => pancreas atrophy - Renal vascular hypertension => kidney atrophy, other kidney hypertrophy (inc renin) - If you block G2 phase, you have 4n chromosomes (no mitosis) - Hyperplasia left unchecked is predisposing for cancer (EXCEPT prostate) - Unopposed estrogen (no progesterone) causes endometrial hyperplasia => atypical hyperplasia => cancer. - Gravid uterus (after delivery): 50% hypertrophy, 50% hyperplasia. - RBC hyperplasia in BM may be caused by COPD

Answer 26

- Erythropoetin is made in the endothelial cells of the peri-tubular capillary. - Psoriasis is an unregulated proliferation of squamus cells in the skin (hyperplasia). Treatment: MTX (works on the basal cells). - All hormone stimulated glands go through hyperplasia, not hypertrophy. - Urinary bladder goes through hypertrophy of smooth muscle cells related to afterload caused by urethra narrowing. - H. Pylori is the most common cause of adenocarcinoma of the stomach. - Clonorchis Sinensis (Chinese liver fluke) is associated with cholangiocarcinoma - Schistosome Haematubium causes squamus metaplasia (instead of transitional) in the urinary bladder => SCC. - Dysplasia = atypical hyperplasia, precursor for cancer. - Actinic (solar) keratosis is premalignant to SCC of the skin, related to chronic sun exposure and excess keratin. If off, it grows back. - No premalignant lesion to basal cell carcinoma. It is more common.