Cell injury:

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

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

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

- Respiratory acidosis ! CO2" ! pO2# ALWAYS (and vice versa).

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

- Perfusion defect (PE) ! "dead space (100% O2 will get the pO2 up)

- Diffusion defect (sarcoidosis, pulmonary edema)

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

- Anemia (Hb related problem) ! pO2 normal, saturation normal, Hb decreased exertional dyspnea.

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

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

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

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

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



- Right shift curve: 2,3BPG", high altitude, acidosis, fever. Left shift curve: CO, MetHb, HbF, 2,3BPG#, alkalosis.
- 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).
- Respiratory acidodis = Hb normal, Saturation#, pO2# Anemia = Hb decrease, saturation normal, pO2 normal CO + MetHb = Hb normal, saturation#, pO2 normal
- Anaerobic glycolysis ! lactate acidosis ! denature proteins + enzymes (can’t even auto digest itself) ! coagulation necrosis ! infarct. Anaerobic glycolysis ! ATP pump malfunction, decrease ATP ! Na enters cells ! water follows ! cellular swelling (reversible!).
- Irreversible cell damage: ATP decrease ! Ca ATPase# ! intracellular Ca" ! activates nuclear enzymes (! pyknosis), phosphlipase (! cell membrane damage) ! pancreatitis.
- Cell death: CK, GOT, GLT, amylase increase.
- 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.
- Reperfusion injury (oxygen radicals) can be caused after giving TPA for coronary thrombosis, then oxygenated blood go to the injured cardiac muscle.
- IRDS: retinopathy of prematurity (oxygen radicals destroying the retina, blindness) and bronchopulmonary dysplasia (fibrosis)
- Most common cancer of radiation is Leukemia
- Iron overload cause free radicals ! cirrhosis, restrictive cardiomyopathy, pancreas failure ! malabsorption + diabetes.
- Acetoaminaphen (Tylenol) is the #1 cause of drug induced fulminant hepatitis (damage around central vein). Treatment: N-acetyl cystein ("glutathione)
- Neutralization of superoxide is by superoxide dismutase (turns into peroxide).
- PPP generates Glutathione and NADPH.
- CCL4 can also be converted to a free radial (CCL3) ! fulminant hepatitis.
- Acetoaminaphen (radicals) + Aspirin (#PG) ! kidney damage (renal medulla)
- Di-George syndrome: absence of thymus, cause tetany.
- Councilman body in Hepatitis: apoptotic eosinophilic cell with no nucleus.
- Coagulation necrosis - Pale infarct: Heart, kidney, spleen, liver Hemorrhagic infarct: Bowel, testicle (torsion), lungs.
- Vegetation of acute rheumatic fever rarely embolize. Infective endocarditis does.
- Mitral stenosis can cause thrombi in left atrium ! atrial fibrillation.
- The arrhythmia most associated with systemic emboli is atrial fibrillation.
- Dry gangrene: no pus
- Most common cause of non traumatic amputation is diabetes ("ATH of popliteal artery)
- Most common cause of bowel infarction: #1: adhesions of previous surgery, #2: piece of small bowel trapped in an indirect inguinal hernia.
- 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.
- Granulmatose necrosis: caseous – mycobacteria or systemic fungal infection.
Non caseous – sarcoidosis.
- Epigastric distress with pain radiating to the back ! pancreatitis (retroperitoneal)
- Enzymatic fat necrosis (pancreas) or traumatic fat necrosis (breast, adipose) can both calcify (look like cancer on X-ray) but it’s painful unlike cancer.
- 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.
- 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)
- Alcoholics have fasting hypoglycemia, lactic acidosis ("NADH shift pyruvate to lactate so there is no substrate for GNG), keto-acidosis (& 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.
- 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)
- 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.
- 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 & 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.
- 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 (& 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 ("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
- 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 scraped off, it grows back.
- No premalignant lesion to basal cell carcinoma. It is more common.