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.

2

- 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)

3

- 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.

4

- 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.