Chapter 1 Flashcards
hypertrophy
increase cell size
gene activation, protein synth, organelle production
hyperplasia
increase cell #
stimulate stem cells
permanent tissues
cardiac muscle, skeletal muscle, nerve, blood
only undergo hypertrophy (cardiac myocytes hypertrophy in response to HTN)
pathologic hyperplasia
progress to dysplasia and eventually cancer
*except benign prostate hyperplasia (BPH) - pathologic but not cancerous
atrophy
decrease stress - decrease cell size and #;
decrease # via apoptosis;
decrease size via ubiquitin-proteosome degradation and autophagy
ubiquitin
tags intermediate filaments of cytoskeleton for degradation by proteosomes
autophagy
autophagic vacuoles combine with lysosomes, enzymes break down cell components
metaplasia
change in stress leads to change in cell type better able to handle new stress;
usually of the surface epithelium;
reprogramming of stem cells;
reversible if stress removed
Barrett esophagus
change from squamous to columnar epithelium to handle acid reflux (metaplasia)
persistent metaplasia
progress to dysplasia and cancer
*except apocrine metaplasia of breast
Vitamin A deficiency
leads to metaplasia;
Vit. A needed for cell differentiation of specialized epithelial cells
keratomalacia
Vit. A deficiency (metaplasia);
change from goblet/columnar cells of conjunctiva to keratinized squamous cells;
causes dry eyes, cornea destruction, blindness
myositis ossificans
metaplasia of connective tissue (muscle changes to bone following trauma)
dysplasia
disordered cell growth;
usually after prolonged hyperplasia or metaplasia;
reversible with removal of stress;
progress to carcinoma (irreversible)
cervical intraepithelial neoplasia (CIN)
dysplasia and precursor to cervical cancer
aplasia
failed cell production during embryogenesis;
unilateral renal agenesis
hypoplasia
decreased cell production during embryogenesis;
streak ovary in Turner syndrome
cell injury
stress exceeds cell’s ability to adapt;
depends on type of stress, severity, and type of affected cell;
common causes of cell injury
inflammation; nutritional deficiency or excess; hypoxia; trauma; gene mutations
hypoxia
low oxygen delivery to tissue;
oxygen is final electron acceptor in oxidative phosphorylation;
leads to decreased ATP;
lack of ATP causes cell injury
causes of hypoxia
ischemia;
hypoxemia;
decreased carrying capacity
ischemia
decreased blood flow through organ;
decreased arterial perfusion (atherosclerosis);
decreased venous drainage ( Budd-Chiari syndrome)
shock (generalized hypotension)
hypoxemia
low partial pressure of oxygen in blood (PaO2 < 60mmHg, SaO2 < 90%)
causes of hypoxemia
high altitude - decreased PAO2;
hypoventilation - increased PACO2, decreased PAO2 (COPD);
diffusion defect - thicker diffusion barrier prevents O2 to pass into blood (interstitial pulmonary fibrosis);
V/Q mismatch - blood bypasses oxygenated lungs (right-to-left shunt: cyanotic) or ventilation problem (atelectasis)
decreased O2 carrying capacity
hemoglobin loss or dysfunction
causes of decreased O2 carrying capacity
anemia - PaO2, SaO2 normal
CO poisoning - PaO2 normal, SaO2 decreased
methemoglobinemia - PaO2 normal, SaO2 decreased
CO poisoning
causes decreased O2 carrying capacity;
classic finding is cherry-red skin;
early sign is headache
methemoglobinemia
causes decreased O2 carrying capacity;
iron oxidized to Fe3+, unable to bind O2;
oxidant stress (sulfa and nitrate drugs) or in newborns;
cyanosis with chocolate colored blood;
tx with IV methylene blue (reduces Fe3+ to Fe2+)
low ATP effects on cell
disrupt sodium/potassium pump - sodium and water build up in cell;
disrupt calcium pump - calcium buildup in cytosol;
switch to anaerobic glycolysis - lactic acid buildup, low pH denatures proteins/precipitates DNA
reversible cell injury
cellular swelling - causes loss of microvilli, membrane blebbing;
RER swelling - ribosome dissociation, decreased protein synth
irreversible cell injury
membrane damage:
plasma membrane - enzymes leak into serum (cardiac troponins), calcium buildup in cell;
mitochondrial membrane - loss of ETC (inner membrane), cytochrome c leak activates apoptosis;
lysosome membrane - hydrolytic enzymes activated by high calcium
cell death
loss of nucleus via condensation (pyknosis), fragmentation (karyorrhexis), and dissolution (karyolysis);
necrosis and apoptosis
necrosis
large groups of cell death followed by acute inflammation;
pathological process, never physiologic
coagulative necrosis
necrotic tissues remain firm, shape and structure preserved;
ischemic infarction in all organs except brain;
often wedge-shaped and pale;
red infarction if blood reenters tissue
liquefactive necrosis
enzymatic lysis of cells and proteins causes liquefaction;
brain infarction - proteolytic enzymes of microglial cells
abcess - proteolytic enzymes of neutrophils
pancreatitis - proteolytic enzymes of pancreas
gangrenous necrosis
coagulative necrosis resembles mummified tissues;
ischemia of lower limb or GI tract;
superimposed infection leads to liquefactive necrosis (wet gangrene)
caseous necrosis
soft and friable necrosis (cheese-like);
combination of coagulative and liquefactive necrosis;
granulomatous inflammation of tuberculosis or fungal infections
fat necrosis
adipose tissue with chalky white appearance due to calcium deposits;
giant cells, fat, and calcium histologically;
trauma to fat (breast) and pancreatitis to peripancreatic fat;
fat + calcium = saponification
dystrophic calcification
calcium deposits on dead tissue;
normal serum calcium and phosphate levels
metastatic calcification
calcium deposits in normal tissue;
high serum calcium and phosphate levels;
not always from cancer
fibrinoid necrosis
necrosis of blood vessel walls;
proteins (fibrin) leak causing pink histological staining;
malignant hypertension and vasculitis
apoptosis
ATP dependent cell death of single cells;
not followed by inflammation;
mediated by caspaces - activate proteases (cytoskeleton) and endonucleases (DNA)
caspace activation pathways
intrinsic mitochondrial - inactivation of Bcl2 (mitoch. membrane stabilizer) causes cytochrome c leakage;
extrinsic receptor-ligand - FAS ligand binding FAS (CD95) or TNF binding TNF receptor;
CD8+ T cell mediated - perforins from CD8+ T cells create pores, allowing granzymes to enter cells
physiologic free radicals
oxidative phosphorylation - cytochrome c oxidase transfers electrons to oxygen, yields superoxide, hydrogen peroxide, and hydroxyl radical
pathologic free radicals
ionizing radiation - water to hydroxyl radical (most damaging);
inflammation - NADPH oxidase makes superoxide from killing neutrophils;
metals (copper, iron) - Fe2+ makes hydroxyl (Fenton rxn);
drugs/chemicals - P450 system in liver metabolizes drugs, making free radicals
how do free radicals cause damage?
peroxidation of lipids;
oxidation of DNA and proteins
free radical elimination
antioxidants;
metal carrier proteins (transferrin);
enzymes:
superoxide dismutase (mitochondria) - superoxide to peroxide
glutathione peroxidase (mitochondria) - free radicals to water
catalase (peroxisomes) - peroxide to O2 and water
carbon tetrachloride (CCl4)
P450 (liver) converts to CCl3;
RER swelling, ribosome dissociation, decreased protein synth;
decreased apolipoproteins - fatty change in liver
reperfusion injury
blood return to ischemic tissues causes O2 derived free radicals leading to more damage;
rise in cardiac enzymes (troponin) after reperfusion of infarcted myocardial tissue
amyloidosis
misfolded protein deposits either systemically or locally;
many proteins can deposit as amyloid;
beta-pleated sheet configuration, congo red staining, green birefringence under polarized light
systemic amyloidosis
either primary or secondary;
almost any tissue can be involved;
kidney most commonly involved (nephrotic syndrome);
restrictive cardiomyopathy or arrhythmia;
tongue enlargement, malabsorption, hepatosplenomegaly;
biopsy required to diagnose;
organ transplant, amyloid cannot be removed
primary amyloidosis
systemic deposits of AL amyloid, derived from immunoglobin light chain
secondary amyloidosis
systemic deposits of AA amyloid, derived from serum amyloid-associated protien (SAA);
acute reactant that increases in chronic inflammatory states, malignancy, and Familial Mediterranean fever (FMF);
FMF - dysfuntion of neutrophils, episodes of fever and acute serosal inflammation (mimics appendicitis, arthritis, or MI)
localized amyloidosis
localized to single organ
senile cardiac amyloidosis
non-mutated serum transthyretin in heart;
usually asymptomatic
familial amyloid cardiomyopathy
mutated serum transthyretin in heart cause restrictive cardiomyopathy
amyloidosis with type II DM
amylin from insulin deposits on islets of pancreas
amyloidosis with Alzheimer disease
A-beta amyloid in brain causes amyloid plaques;
gene on chromosome 21 - most trisomy 21 have early onset Alzheimer disease
amyloidosis with dialysis
beta2-microglobulin deposits in joints
amyloidosis with medullary thyroid carcinoma
calcitonin deposits in tumor - tumor cells in amyloid background
