Glossary of Pathology - Cell Injury, Death and Adaptation
Other Decks By This User
- How do cells ADAPT to environmental stress?
- hypertrophy, hyperplasia, aplasia, hypoplasia, atrophy, metaplasia, dysplasia
- What is hypertrophy?
- Increase in organ/tissue size due to increase in SIZE OF CELLS, w/increased expression of genes and protein synth
- What causes hypertrophy?
- Adaption to...
increased workload (hypertension), increased endocrine stim (puberty, preg)
- What is hyperplasia
- Increase in size of organ/tissue due to increase in NUMBER OF CELLS, w/inc express of growth-promoting genes (proto-oncogenes), inc DNA synth, cell div; may occur with hypertrophy
- Physiologic causes of hyperplasia?
- -compensatory (after partial hepatectomy)
-hormonal stim (breast devel)
-antigenic stim (lymphoid hyperplasia)
- Pathologic causes of hyperplasia?
- -endometrial hyperplasia
-prostatic hyperplasia of aging
- What is aplasia?
- Failure of cell production
- Examples of aplasia?
- -fetal development, can result in AGENESIS (absence of organ)
-late in life, permanent loss of precursor cells in proliferative tissues (e.g. marrow)
- What is hypoplasia?
- Decrease in cell production, less extreme than aplasia
- When is hypoplasia seen?
- partial lack of growth and maturation of gonadal structures in TURNER SYNDROME and KLINEFELTER SYNDROME
- What is atrophy?
- Decrease in size and functional ability of organ/tissue due to dec. in mass of pre-existing cells
- Markers of atrophy?
- Lipofuscin granules, autophagosomes on EM, intracytoplasmic vacuoles w/debris
- What causes atrophy?
- Disuse, ischemia, malnut, lack of endocrine stim, aging, denervation
- 3 types of metaplasia?
- Squamous, osseous, and myeloid metaplasia
- What is metaplasia?
- Replacement of one differentiated tissue by another (usu. reversible)
- What is squamous metaplasia?
- When epithelial cells are replaced by squamous epith, often reversible
- Where does squamous metaplasia occur?
- -Replacement of columnar epith at squmocolumnar jn of cervix by squamous epith
-In resp epith of bronchus, endometrium, and panc ducts
- What causes squamous metaplasia?
- Chronic irritation (e.g. smoking), vit A deficiency
- What is osseus metaplasia?
- formation of new bone at sites of tissue injury (cartilaginous metaplasia may also occur)
- What is myeloid metaplasia?
aka. extramedullary hematopoiesis
- Prolif. of hematopoietic tissue in non-bone marrow sites (e.g. liver or spleen)
- What is dysplasia?
- Abnormal prolif of cells, characterized by changes in cell size, shape, loss of cellular organiz; premalignant
ex: cervical dysplasia
- What causes dysplasia?
- similar stimuli to those that produce cancer (HPV, esophageal reflux)
- Causes of hypoxic cell injury?
- Ischemia (most common), anemia, CO poisoning, decreased tissue perfusion (hypotens), dec oxygenation of blood (pulm disease)
- What happens during EARLY hypoxic cell injury? 3
- 1.AFFECTS MITOCHONDRIA -> dec oxidative phosphorylation and ATP synth, and failure of memb pump
2. disaggregation of ribosomes and dec prot synth
3. Stim of phosphofructokinase
- What happens when Na-K ATPase fails?
- 1. cellular SWELLING, aka hydropic change (large vacuoles in cytoplasm)
2. swelling of ER
3. swelling of mitochon
(Ca, H2O, Na influx, K efflux)
- What happens when phosphofructokinase activity increase?
- inc glycolysis, lactate accum, dec intracell pH (which causes reversible clumping of nuclear chromatin)
- What is a pathophysiological correlate of decreased protein synthesis?
- Lipid deposition (fatty change) --> apoproteins required for lipid mobilization
- What are the signs of reversible membrane damage?
- Myelin figures (whorl-like structures), cell blebs (cell surf deformity due to disrupted cytoskel)
- What happens during LATE hypoxic cell injury?
- MEMBRANE DAMAGE -> Ca influx into mitochondria, leakage of lysosomal enzymes
- When does the cell reach the POINT OF NO RETURN?
- massive Ca influx, irrevers damage to memb and oxidat phosphor, calcification of mitochon, intracellular activation of lysosomal hydrolases
- What are the cellular markers of the point of no return? (indicates necrosis)
- Myocardial enzymes in serum: AST (aspartate aminotransferase), LDH (lactate dehydrogenase), CK (creatine kinase), troponins, myoglobin
Liver enzymes in serum: ALT (alanine aminotransferase), AST, alkaline phosphatase, GGT (gamma-glutamyltransferase)
- How long does it take for hypoxic injury to become irreversible?
- 3-5mins for neurons
1-2hrs of myocardium and hepatocytes
many hours for skel muscle
- How are free radicals generated?
- -Normal metabolism
-oxygen toxicity (alveolar damage/ARDS, retrolental fibroplasia)
-drugs and chemicals (promote prolif of SER and P-450 system)
-reperfusion after ischemic injury
- What are our protective factors against free radicals?
- 1. Intracellular enzymes (glutathione peroxidase, catalase, superoxide dismutase)
2. Exogenous and enogenous antioxidants (vit A, C, E, cysteine, etc)
3. Spontaneous decay
- What is a good example of chemical injury to the liver?
- CCl4 -> *CCl3 by P-450 system in the SER
*CCl3 causes free radical injury:
1. disaggreg of ribosomes, dec protein synth, results in FATTY CHANGE
2. Memb damage, cell swelling, Ca influx, mitoch damage, protein denat, cell death
- What is necrosis?
- Sum of degradative and inflammatory reactions occuring AFTER TISSUE DEATH IS CAUSED BY INJURY; must be in a living organism though
- What is autolysis?
- degradative rxn in cells, caused by intracell enzymes indigenous to the cell
**postmortem autolysis occurs after organismal death but IS NOT NECROTIC**
- What is heterolysis?
- cellular degradation by enzymes derived from sources extrinsic to the cell
- What is coagulative necrosis?
- most common, results from sudden cutoff of blood supply, causes protein denaturation, usu occurs in heart, kidney
- Characteristic pathologic changes seen in coagulative necrosis?
- preservation of tissue architecture in early stages, increased eosinophilia, nuclear changes
- What is the morphologic hallmark of irreversible cell injury and necrosis?
- NUCLEAR CHANGES: pyknosis, karyorrhexis, karyolysis, disappearance of stainable nuclei
- What is pyknosis?
- chromatin clumping and shrinking with inc basophilia
- What is karyorrhexis?
- fragmentation of chromatin
- What is karyolysis?
- fading of chromatin material
- What is liquefactive necrosis?
- enzymatic liquefaction of necrotic tissues that results from interruption of blood supply (via autolytic mechs), usu in CNS, caused by ischemia (abscesses, brain infarcts, etc); also occurs in areas of bacterial infection (suppurative infections) via heterolytic mechs
- Where does liquefactive necrosis usually occur?
- usu in CNS (via autolytic mechs); also occurs in areas of bacterial infection (suppurative infections) via heterolytic mechs
- Characteristic pathologic changes seen in liquefactive necrosis?
- necrotic tissue soft and liquefied
- What is caseous necrosis?
- combination of coagulative and liquefactive necrosis; occurs as part of granulomatous inflammation, and is a manifestation of partial immunity caused by immune cells
- Characteristic pathologic changes seen in caseous necrosis?
- architecture not preserved, but tissue not liquefied, gross: cheese-like consistency
histologic: amorphous eosinophilic appearance
- In what disease is caseous necrosis most commonly seen?
- What are the common sites of gangrenous necrosis?
- usu. seen w/interruption of blood supply to: lower limbs, GI tract, gallbladder, testes
- What is wet gangrene?
- when complicated by infective heterolysis and consequent liquefactive necr
- What is dry gangrene?
- when characterized by coagulative necr w/o liquefaction
- What is fibrinoid necrosis?
- assoc w/immune-mediated vascular damage, characterized by deposition of fibrin-like proteinaceous material in arterial walls
- Characteristic pathologic changes of fibrinoid necrosis?
- smudgy pink appearance in vascular walls, eosinophilc homogeneous appearance
- What is fat necrosis?
- caused by the action of lipases on fatty tissue (e.g. w/pancreatic damage)
- What is traumatic fat necrosis?
- occurs after severe injury to tissue w/high fat content (eg breast)
- What is enzymatic fat necrosis?
- complication of acute hemorrhagic pancreatitis -> panc enzymes diffuse into tissue and digest parenchyma, liberated fatty acids form calcium salts (saponification), vessels are eroded, hemorrhage
- Characteristic pathologic changes of fat necrosis?
- necrotic fat cells, acute inflam, hemorrhage, calcium soap formation, clustering of lipid-laden macrophages (in panc)
- What is apoptosis?
- programmed cell death; active process under genetic control, mediated by cascade of capases (digest nuclear cytoskeleton proteins and activate endonucleases); impt mech for removal of cells; involves single cells or small clusters
- Morphologic changes associated with apoptosis?
- cytoplasmic and cell shrinking, increased eosinophilic staining, nuclear chromatin condenses and fragments, blebbing, cell fragments are phagocytosed, NO INFLAMMATORY REACTION
- Stimuli for apoptosis?
- -cell injury and DNA damage
-lack of horm/cytoki/growth factors
-receptor-ligand signals (Fas binding to Fas ligand, TNF binding to TNFR1)
- Biochemical changes in apoptosis?
- cytochrome-c and bcl-2 activate capases (digest nuclear cytoskeleton proteins and activate endonucleases); REGULAR DNA fragmentation at nucleosomal boundaries ("laddered" gel pattern)
- What genes regulate apoptosis?
- bcl-2 inhibits
p53 stimulates by decreasing transcription of bcl-2 and increasing transcrip of bax
- Physiologic examples of apoptosis?
- embryogenesis, hormone-dependent apop (menstruation), selective death of lymphocytes in thymus
- Pathologic examples of apoptosis?
- viral hep (Councilman body), graft vs host disease, CF (duct obstruction and panc atrophy)
- Possible causes of fatty change (steatosis)?
- 1. inc transport of triglyc or fatty acids to cells
2. dec mobilization of fat from cells (usu. due to dec apoproteins required for transport -> **thus fatty change is linked to disagg of ribo and dec prot synth**)
3. dec use of fat by cells
4. overproduction of fat in cells
usu in heart, liver, kidney
- What is hyaline change?
- protein accumulations in cells; appear homogeneous, glassy, eosinophilic
- Commonly accumulated exogenous pigments?
- carbon/silica/dust (pulmonary), plumbism (lead), argyria (silver)
- Commonly accumulated endogenous pigments?
- Melanin, bilirubin, hemosiderin, lipofuscin
- What are changes in melanin pigmentation indicative of?
- Increased pig: tanning, wide variety of disease conditions
Decreased pig: albinism, vitiligo
- Breakdown of what forms bilirubin?
- bilirubin is catabolic product of heme moiety of hemoglobin (and to small extent myoglobin)
- Types of jaundice?
- Hemolytic (destruc of RBCs)
Hepatocellular (assoc w/parenchymal liver damage)
Obstructive (assoc w/intra or extrahepatic obstruction of biliary tract)
- What is hemosiderin?
- iron-containing pigment, consists of golden-brown amorphous ferritin aggregates in tissues, stains blue w/Prussian blue dye
- What is local hemosiderosis?
- local deposition of hemosiderin (derived from breakdown of hemoglobin), usu results from hemorrhage
- What is systemic hemosiderosis?
- generalized hemosiderin deposition W/O tissue/organ damage; may result from hemorr, mult transfusions, hemolysis, excessive dietary iron, often w/EtOH consumption
- What is hemochromatosis?
- extensive accum of hemosiderin w/tissue damage, scarring, organ dysfn
- Characteristics of hereditary hemochromatosis?
- mutation in Hfe gene; causes TRIAD of micronodular cirrhosis, diabetes mellitus, skin pigmentation (= "bronze diabetes"); causes inc serum iron and dec total iron binding capac (TIBC)
- Common cause of secondary hemochromatosis?
- usu caused by mult blood transfusions administered to pts w/hereditary hemolytic anemias (eg beta thalassemia major)
- What is lipofuscin?
- yellowish, fat-soluble pigment, end product of memb lipid peroxidation, aka "wear and tear pigment"
- Where is lipofuscin most often seen?
- elderly pts, w/in hepatocyes and at poles of nuclei of myocardial cells
- What is "brown atrophy"?
- Combination of lipofuscin accum and atrophy of organs
- What is "bronze diabetes"?
- occus in hereditary hemochromatosis; caused by TRIAD of micronodular cirrhosis, diabetes mellitus, skin pigmentation
- Causes of metastatic calcification?
- hypercalcemia (usu resulting from hyperparathyroidism), osteolytic tumors, hypervitaminosis D, excess Ca intake
- Causes of dystrophic calcification?
- occurs in previously damaged tissues (eg old trauma, TB lesions, scarred valves, atherosclerotic lesions); NOT caused by hypercalcemia (normal serum Ca conc.)
- What is causal mechanism of abnormal protein folding?
- failure of structural stabilization or degradation by chaperones (e.g. ubiquitin, a heat shock protein)
- What are 2 major consequences of abnormal protein folding?
- abnormal protein aggregation, abnormal prot transport/secretion
- What diseases are characterized by abnormal protein aggregation?
- amyloidosis, Alzheimers, Huntingtons, Parkinsons, and perhaps prion diseases (eg mad cow)
- What diseases are characterized by abnormal protein transport and secretion?
- CF, alpha-1-antitrypsin deficiency
You must Login or Register to add cards