Cell Injury Flashcards
Oxygen Content
= Hgb x O2Sat + PaO2; Oxygen in RBC attached to Heme group is Oxygen SATuration (PULSE Oximeter). PaO2 = oxygen dissolved in plasma. If ppO2 dec, O2Sat has to decrease b/c heme gets oxygen from blood.
Ischemia
Decrease in arterial blood flow (e.g. thrombus, cardiogenic shock)
Hypoxia vs. Hypoxemia
Hypoxemia is a cause of hypoxia. Hypoxemia is low partial pressure of oxygen in arterial plasma. Dalton’s law…O2, Co2, N (remains constant). Retains Co2 (Any RESP acidosis) —> PaO2 MUST go down (Dalton’s). ANY resp acidosis -> hypoxemia.
Respiratory distress syndrome
Ventilation defect. Hyaline membrane disease. No ventilation but perfusion = intrapulmonary shunt. Patient with hypoxemia, gave 100% O2 but PO2 DIDN’T INCREASE
Perfusion defects
Dead space defect. e.g. PE. 100% O2 will help!
Diffusion defect
e.g. Fibrosis (sarcoidosis), pulmonary edema
Hypoxia 2/2 by hgb related problems
Anemia - PaO2 NORMAL, so OXSat normal, but HGB decreases. CO - heater in winter-time, auto exhaust, house-fire, high affinity for hgb—> meaning that O2Sat DECREASES. Tx = 100% O2. Cyanide (polyurethane products in house fire!).
Methemoglobinemia
Hb w/ Fe3+. “Chocolate covered blood.” PaO2, Hgb normal. But OxygenSat NOT. Still cyanotic after 100%. NItrates/nitrites in mountains oxidize hgb –> Fe3+ (mountain guy comes down w/ cyanosis). IV METHYLENE BLUE. Vitamin C (reducing agent) is side. Dapsone (treated for leprosy) = sulfa drug. Sulfa and Nitro drugs produce methhemoglobin + could produce G6PD hemolytic. Common in HIV b/c of ppx for PCP w/ TMP-SMX.
What will right shift HgB?
2,3-BPG, fever, low pH, high altitude (respiratory alkalosis, hyperventilate). Lower oxygen affinity = good!
Left shift hgb?
Hb F, CO, methhemoglobin, high pH; can’t release O2
Cytochrome oxidase - last enzyme before Oxygen acceptor
3 C’s - cytochrome oxidase, cyanide, co; all inhibit cytochrome oxidase.
Uncoupling
When intramembrane is permeable to H+. Dinitrophenol (preserving wood), alcohol, salicyclates. Increased NADH and FADH2, temperature increases. Hyperthermia
Anaerobic glycolysis used for tissue hypoxia
End product is lactate. Every cell can do. Surviving on 2 ATP per glucose with tissue hypoxia. Build-up of lactic acid in cell and outside. (Inc. AG-graph metabolic acidosis).
Inc acid in cell
Denature structures and enzymes. COAGULATION necrosis. Can’t even apoptosis itself.
W/o ATP, all ATPase pumps problem
Na/K (digoxin). Na+ gets into the cell –> water inside –> cellular swelling. Reversible.
Calcium in tissue hypoxia
It enter cells. Ca-ATPase pump generally keeps it out. ATP decreased, Ca+ has easy access. Activates phospholipases (membrane dog), nuclear pyknosis, mitochondria. Irreversible change. CELL membrane damage.
Free radicals
Lipofuscin is an end-product. Lipids are not digestible all the way = lipofuscin. Free radical has unpaired e- in outer orbit = unstable. Retinopathy of prematurity, bronchopulmonary. H2O -> OH-. Ionizing radiation produces hydroxyl free radicals -> mutations (leukemia is most common). Fe makes hydroxyl free radicals.
Acetaminophen
Free radical damage to liver (and kidney). Occurs right around CENTRAL vein b/c farthest away from hepatic artery. Tx = N-acetylcysteine —> replenishes glutathione. Fulminant liver disease. Damages renal medulla. (ASA gets rid of PGE2 - vasodilator - leaves A-II in charge –> vasoconstriction + renal medulla w/ free radicals –> renal tubules —> renal papilla).
Superoxide free radical neutralizer
Superoxide mutase (SOD)
Glutathione
Pentose phosphate shunt. F(x) = neutralizes free radicals, esp. drug and any peroxide ones.
Carbon tetrachloride
Dry cleaning industry –> free radical (liver). CCl3 -> fulminant liver failure.
Apoptosis
Embryology - lumens for solid organs, MIF (uterus, cervix, upper 1/3 vagina). Caspases —> apoptotic bodies to be phagocytosed. Lipofuscin is left-over. Women (Wollfian duct structure - epididymis, seminal vesicles, vas deferens). Thymic involution. Cancer-killing. Atrophy (reduced tissue mass). Liver w/ hepatitis - Councilman body, red neuron.
Coagulation necrosis
Pale on gross. Pale vs. hemorrhaghic infarct. Good consistency = pale (heart, kidney, spleen ok, liver…). Hemorrhagic - GI, testicle, lung. Vague outlines of normal tissue.
Dry gangrene
NO PUS. e.g. Diabetic. Popliteal artery.
Bowel infarction
Most common is adhesions from pervious surgery. Second is incarcerated in inguinal hernia.
Only place where infarction does NOT lead to coagulation necrosis
CNS - liquefactive necrosis. Brain has little structure –> liquify. NETUROPHILS. MOST of the time, liquefactive is actually an infectious picture.
Coagulase -> coagulation (Fibrin) strands –> ABSCESS
Strep releases hydrouranidase breaks down surrounding tissues -> cellulitis
Caseous necrosis
Systemic fungal or mycoplasma; The lipid of the cell wall –> Cheesy appearance. Caseation is ONLY for fungal or mycobacterial. Granuloma-type necrosis can also be sarcoid, etc.
Pancreas is retroperitoneal
Therefore pain gets referred to the pain (epigastric -> refer to back)
Fatty necrosis
Enzymatic fat necrosis. Also in breasts - but that’s traumatic (calcify) - and PAINFUL while cancer is usually not painful. Enzymatic fat necrosis is UNIQUE to the pancreas. FA + Ca -> chalky areas.
Calcium stains blue on H&E
Dystrophic calcification. Like atherosclerotic plaque.
Fibrinoid necrosis
Necrosis of IMMUNOLOGIC disease. IC-deposition.
Palpable purpura
T-III, small vessel disease. IC deposition in small vessel, glomerulus. Activates complement (alternative) –> C5a –> chemotactic factor for Neutrophils. Neutrophils ACTUALLY do the damage.
Sinusoids vs fenestrated epithelium
RBCs go through vs. filtration (e.g. kidney)
Fatty change
EtOh is most common cause. Acetyl-CoA and NADH required in EtOH metabolism. Alcoholics always have lactic acidosis b/c increase in NADH —> drive pyruvate to lactate. In fasting state, alcoholic won’t be able to gluconeogenesis –> fasting hypoglycemia. Increased synthesis w/ acetyl-CoA with beta-hydroxybutyric acid high. Ketoacidosis.
Fatty change pathogenesis
Glycerol-3-P shuttle. Also carbohydrate backbone for TG’s. VLDL in liver (endogenous production from glycolysis -> G3P -> TG’s).
