Intro to Pathology Flashcards
general mechanisms of cell injury
-disruption of metabolism
-inflammatory processes
-infectious diseases
-diseases of immunity
-environmental injury
-neoplasia
-genetic disorders
adaptations as a cellular response are reversible, and include:
-atrophy
-hypertrophy
-hyperplasia
-metaplasia
hypertrophy
increased size of an organ/tissue caused by an increase in size of cells
pathogenesis of hypertrophy
increased synthesis of cellular components
example of physiologic hypertrophy
uterus enlarging during pregnancy
example of pathologic hypertrophy
left ventricular hypertrophy and cardiomyopathy
clinical correlation: compromises cardiac function
hyperplasia
increased size of an organ/tissue caused by an increased NUMBER of cells
pathogenesis of hyperplasia
increased mitotic activity/cell division
example of physiologic hyperplasia
female breast exhibits hyperplasia during lactation for increased functional capacity
example 2 of physiologic hyperplasia
compensatory hyperplasia of the liver as a result of liver damage (increased mass following damage or loss)
examples of pathologic hyperplasia
-benign prostatic hyperplasia
-endometrial hyperplasia
-gynecomastia (breast growth in males)
-verruca plantaris (plantar warts)
dysplasia
disordered hyperplasia (can result from hyperplasia and can turn into neoplasia)
atrophy
decreased size of an organ/tissue caused by a decrease in mass of cells (size AND number)
pathogenesis of atrophy
- reduction of cellular components
- loss of cells (apoptosis)
example of pathologic atrophy
alzheimers (results in loss of parenchyma)
cachexia (loss of adipose)
atrophic gastritis (antibodies attacking cells that make intrinsic factor - parietal cells)
metaplasia
replacement of one differentiated tissue by another (reprogramming of a cell to make a diff type of cell)
pathogenesis of metaplasia
reprogrammed stem cells (persistent influences leading to metaplasia may induce neoplasia)
example of pathologic metaplasia
Barrett’s esophagus (making goblet cells in esophagus to protect from chronic acid reflux)
principles of cell injury
- injury depends on cause (duration, dose, type)
- injury depends on the cell’s specific response (cells respond differently to different things)
- injury results from functional abnormalities in one or more interconnected cellular components
top etiologies of cell injury
oxygen deprivation (hypoxia or ischemia) and chemicals
roles/functions of mitochondria in cell injury
decreased ATP production, high conductance channels, and leakage of cytochrome c into cytoplasm
roles/functions of ATP depletion in cell injury
- reduced plasma membrane energy-dependent pumps (loss of Na+/K+ ATPase leads to cell swelling and ER dilation)
- altered cell metabolism (reliance on glycolysis and increased lactic acid)
- reduced protein synthesis
- unfolded protein responses
- mitochondrial membrane damage
roles/functions of calcium in cell injury
important mediator of cell injury (cell injury leads to influx of calcium); increased calcium in the cell causes enzymes to function when they shouldn’t be working
roles/functions of free radicals in cell injury
molecules with unpaired electrons that, pathologically, disrupt macromolecules
free radical generation physiologically
red-ox reactions and fenton reactions
free radical generation pathologically
radiant energy, inflammatory oxidative bursts, enzymatic metabolism of exogenous chemicals/drugs, nitric oxide
antioxidants
block initiation and scavenge free radicals
ex. vitamins E and A; ascorbic acid; glutathione
enzymatic inactivation of ROS
superoxide dismutase
catalase
glutathione peroxidase
superoxide dismutase
converts superoxide and H to oxygen and hydrogen peroxide
catalase
converts hydrogen peroxide (H2O2) to oxygen and water
glutathione peroxidase
converts hydroxy radical and GSH to water and GSSG
oxidative stress
when a free radical gets inside a particular system and damages those molecules
oxidative stress on lipid membrane
-plasma and organelle membrane damage by hydroxyl radical
-lipid-free radical interaction yields autocatalytic processes
oxidative stress and proteins
induces conformational changes, leading to:
-altered enzyme activity and membrane potential
-protein-protein cross-links, fragmentation
-protein fragmentation
oxidative stress and DNA
-thymine reactions result in single-strand DNA breaks
-aging and malignant transformation
ischemia
reduced blood flow
-causes include thrombosis, shock, hypotension, etc
hypoxia
reduced oxygen availability
-glycolysis can continue (causing lactic acid buildup)
-causes include pulmonary disease, anemia, carbon monoxide poisoning
morphology of hypoxia cell injury
1) mitochondria first affected so decreased ATP production
2) leads to failed Na+/K+ ATPase and Ca2+ pump, causing cell to swell (hydropic change), plasma membrane changes, ER swelling, and mitochondrial swelling
3) failure of protein synthesis and disaggregation of ribosomes
4) increased glycolysis (pH change, more lactic acid) leads to clumped DNA
lipid accumulations (steatosis)
fatty change of liver or heart muscle
-accumulated triglycerides within parenchymal cells (alcohol abuse, toxins, diabetes, obesity)
-may be reversible or progressive
cholesterol accumulations in cells
-atherosclerosis
-inflammation and necrosis
-cholesterolosis
-xanthomas
causes of protein accumulations
-protein reabsorption (renal disease or glomerulonephritis)
-excess synthesis
-protein folding defects
protein folding defects
- defective intracellular transport
- ER stress induced by abnormally folded proteins
- aggregation of abnormal proteins
glycogen accumulation
excessive intracellular stores
-abnormal glycogen metabolism (diabetes, glycogen storage diseases)
pigment accumulation
colored substances accumulate within the cell (may be normal cellular constituent or abnormal)
lipofuscin
intracytoplasmic brown pigment, results from protein degradation over time; seen in cells undergoing slow, regressive changes (liver, heart)
bilirubin
derived from hemoglobin breakdown, gets processed in liver, normally excreted in urine
-excess could result from hemolytic disorders
-elevated bilirubin can cause jaundice
-can result from liver dysfunction or biliary obstruction
hemosiderin
derived from hemoglobin breakdown (the iron part)
-golden, yellow-brown crystalline pigment
-appears in bruises or can cause hemosiderosis (systemic overload)
exogenous pigment - carbon
accumulation usually due to inhalation
-can lead to anthracosis (black lung)
-tattoos also allow carbon accumulation that persists in macrophages
senescence
progressive decline in cellular function/viability caused by accumulation of genetic mutations, progressively decreased replication, and defective protein homeostasis
intrinsic clock and senescence
progressive declining proliferative and replicative activity
-telomeres ensure complete replication of chromosomal end
-telomerase adds telomeres (active in germ cells/stem cells, but NOT somatic cells)
extrinsic clock
progressive accumulation of cellular and molecular damage (DNA damage, etc)
