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General Principles

General Definitions and Concepts + Biochemistry

Irreversible injury hypoxia membrane/ mitochondrial damage Increase cytosolic Ca2+ activates phospholipase, proteases, endonuclease
Mitochondrial damage release cytochrome c activates apoptosis
Free radicals unpaired electron in outer orbit damage cell membranes and DNA
What are some common free radicals? Superoxide, hydroxyl, peroxide, drugs (acetaminophen)
Superoxide dismutase neutralizes superoxide
Glutathione Neutralizes peroxide
Catalase Neutralizes peroxide
Lipofuscin Indigestible lipid of lipid peroxidation brown pigment increased in atrophy and FR damage
Reperfusion injury in heart Superoxide FRs + calcium
Mitochondrial injury cytochrome c in cytosol initiates apoptosis
What substances can cause SER hyperplasia? alcohol, barbiturates, and phenytoin
What are complications of SER hyperplasia? Increases drugs metabolism Low vitamin D
Chediak-Higashi membrane protein defect in transferring lysosomal enzymes to phagocytic vacuoles AR; giant lysosomes
I cell disease absent enzyme made in Golgi apparatus (mannose 6-phosphate) empty lysosomes
Rigor mortis stiff muscles after death due to ATP depletion
What is the MCC of Fatty Liver? Alcohol (increases NADH)
Fatty change in liver VLDL pushes nucleus to side DHAP ---> G3P -----> TG
What are causes of fatty change? Increase synthesis of TG/FAs, beta-oxidation of FAs, synthesis apoproteins/release VLDL
Fatty change in Kwashiorkor Decrese synthesis of apoproteins
Ferritin Primary iron storage protein soluble in blood; serum level reflects marrow storage iron
Hemosiderin Insoluble ferritin degradation product visible with Prussian blue stain
Atrophy Reduction in cell/tissue mass by either loss or cell shrinkage
Brain atrophy Ischemia
What neurological condition is associated with brain atrophy? Alzheimer's
Exocrine gland atrophy in CF duct obstruction by thick secretions
Labile cells stem cells Skin, bone marrow, GI tract
Stable cells in G0 phase Smooth muscle and hepatocytes
Permanent cells cannot replicate Cardiac/striated muscles; neurons
Hypertrophy increase in cell size
LVH - Increase preload (valve regurgitation), - Increase afterload (HTN, aortic stenosis)
RVH Pulmonary hypertension
Bladder smooth muscle hypertrophy Prostate hyperplasia constricts urethra
Removal the kidney causes Hypertrophy of remaining kidney
Hyperplasia Increase number of cells
Endometrial Hyperplasia Unopposed estrogen
What are some associated conditions with UNOPPOSED estrogen? Obesity, exogenous estrogen
RBC hyperplasia Increased EPO Blood loss, ectopic secretion, high altitude
Prostate hyperplasia increased DHEA
Gynecomastia Hyperplasia male breast tissue; normal in newborn, adolescent, elderly
Metaplasia one adult cell type replaces another cell type
Squamous metaplasia in bronchus smoking
Intestinal metaplasia in stomach is associated with? Paneth cells, Goblet cells H. pylori chronic atrophic gastritis
Squamous metaplasia bladder Schistosoma haematobium infection
Barrett's esophagus glandular metaplasia of distal esophagus; due to GERD
Dysplasia atypical hyperplasia and metaplasia are precursors for cancer
Squamous dysplasia in cervix Human papillomavirus
Squamous dysplasia in bronchus is mostly caused by ___________________. Smoking
Necrosis death of group of cells
Coagulation necrosis preservation of structural outline
What is the cause of coagulation necrosis? Increased to lactic acid
Infarction pale; hemorrhagic; dry gangrene
Liquefactive necrosis Brain infarct, bacterial infections wet gangrene
Caseous necrosis variant coagulation necrosis granulomas due to TB/systemic fungi
Granulomas activated macrophages (epithelioid cells) multinucleated giant cells
Granulomas are formed by ________ (+) ____cells. CD4 TH1 cells
Epithelioid cells Gamma-interferon released by CD4 T cells activates macrophages
Multinucleated giant cells fusion of epithelioid cells
Granulomas are associated with type ______ hypersensitivity. IV
Enzymatic fat necrosis associated with pancreatitis soap formation (Ca2+ fatty acids)
Fibrinoid necrosis necrosis of immune reactions
Example conditions that produce fibrinoid necrosis. Immune vasculitis and endocarditis
Postmortem necrosis autolysis; no inflammatory reaction
Dystrophic calcification calcification of damaged tissue with normal serum calcium Pancreatitis; atherosclerotic plaque
Metastatic calcification calcification of normal tissue increased serum calcium or phosphorus
Nephrocalcinosis Metastatic calcification of collecting tubule basement membranes
Signs and symptoms of Nephrocalcinosis Polyuria due to nephrogenic DI + renal failure
Apoptosis gene regulated individual cell death
Signals activating apoptosis Mullerian inhibitory factor (MIF), TNF, and hormone withdrawal
Signal modulator of apoptosis TP53 suppressor gene, BCL-2 genes
BCL-2 genes anti-apoptosis gene prevents cytochrome c from leaving mitochondria
Caspases responsible for enzymatic cell death in apoptosis proteases and endonucleases
Markers of apoptosis Eosinophilic cytoplasm, pyknotic (ink dot) nucleus
Apoptosis Loss Mullerian epithelium in male fetus Thymus involution; killing cancer cells
Histamine key chemical in acute inflammation mast cell; arterioles vasodilation; increase in venular permeability
Rubor acute inflammation rednes arteriole vasodilation (histamine)
Calor acute inflammation Heat; arteriole vasodilation (histamine)
Tumor acute inflammation swelling; Increase vessel permeability
Dolor acute inflammation Pain; bradykinin, PGE
Acute inflammation Neutrophil dominant Increased levels of IgM
Initial vessel evetns transient vasoconstriction --> arteriolar vasodilation --> Increase venular permeability
Neutrophil rolling acute inflammation due to selectins
Integrins neutrophil adhesion molecules C5a and leukotriene B, activate; neutrophil margination
CD11/CD18 markers for integrins
Endothelial cell adhesion molecules activated IL-1 and TNF
ICAM intercellular adhesion molecule
VCAM vascular cell adhesion molecule leukocyte adhesion molecule defect
Activation neutrophil adhesion molecules neutropenia; endotoxins Neutrophilic leukocytosis; corticosteroids
Chemotaxis directed moventem C5a and LTB4
Opsonizing agents IgG, C3b enhance phagocytosis
Neutrophils, monocytes, macrophages receptors for IgG, C3b
O2-dependent MPO system most potent microbicidal system neutrophils and monocytes
Production of superoxide from O2 NADPH oxidase with NADPH cofactor produces respiratory burst
Nitro blue tetrazolium (NBT) Test for respiratory burst
Superoxide dismutase converts superoxide to peroxide
Myeloperoxidase lysosomal enzyme that combines peroxide + Cl to form bleach (HOCl)
Microbicidal defects chronic granulomatous disease childhood (XR), myeloperoxidase deficiency (AR)
Chronic granulomatous disease absent NADPH oxidase No respiratory burst
Anaerobic glycolysis ATP synthesis in hypoxia Lactate decreases intracellular pH, and denatures proteins
Created by: rakomi



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