Reversible VS Irreversible Injury Necrosis & Apoptosis Flashcards
Describe the cell responses to injury depending on the cell type & injury.
- Adaptation (inc efficiency or productivity)
- Degen (diminished functional capacity)
- Death
Describe acute cell swelling.
-reversible
-early, sublethal manifestation of cell damage
-inc cell size & vol bc H2O overload
-most common expression of cell injury
FIRST Na/K ATPase THEN cell membrane damage
Describe the cells highly vulnerable to hypoxia & cell swelling.
-cardiomyocytes
-prox renal tubule epi
-hepatocytes
-endothelium
-CNS neurons
Describe the etiology of acute cell swelling.
-loss of ionic & fluid homeostasis
>failure of cell energy prod
>cell membrane damage
>injury to enzymes regulating ion channel of membrane (Na/K ATPase)
-EX: physical/mechanical injury, hypoxia, toxic agents, free radicals, viral organisms, bacterial organisms, immune mediated injury
Describe the pathogenesis of acute cell swelling.
Describe the gross appearance of acute cell swelling.
-swollen organ w rounded edges
-pallor (pale areas)
-cut surface: tissue bulge & cant be easily put in correct apposition
-heavy ‘wet’ organ
Describe the histologic appearance of cell swelling.
-H2O uptake dilute cytoplasm (pale)
-cell enlarged
-inc cytoplasmic eosinophilia
-nucleus in norm position w no morphological changes
Describe epidermis cell swelling.
‘Ballooning degen’
-hydropic degen variation
-ex: swine pox virus
Describe the morphological changes of cell swelling.
- PM alterations
-blebbing, blunting, loss of microvilli - Mitochondrial changes
-swelling
-sm amorphous densities - Dilation of ER
-detachment of polysomes
-intracytoplasmic myelin - Nuclear alterations
-disaggregation of granular & fibrillar elements
-change in chromatin
Describe what the increase in a size of a cell is due to.
- Hydropic change, fatty change = cell swelling
-bc high uptake of H2O & then diffuse disintegration of organelles & cytoplasmic proteins
-stressed & abnormal - Hypertrophy = cell enlargement
-bc inc of normal organelles
Describe the prognosis of cell swelling.
*depends # of cells affected & imp of cells:
1. Good = if O2 restored before point of no return
2. Poor = progression to irreversible cell injury
Describe fatty changes.
-reversible
-sublethal cell damage
-accumulation of lipids in cytoplasm
>TAG, cholesterol/esters, phospholipids, lipids & carbohydrates (lysosomal storage disease)
-may be preceded or accompanied by cell swelling
Describe lipidosis.
-accumulation of TAG & other lipid metabolites (neutral fats & chol) in parenchymal cells
>heart, skeletal, muscle, kidney, liver (most common)
-liver (hepatic lipidosis) = alter function bc most central organ to lipid metabolism
Describe the etiology of fatty change.
-hypoxia, toxicity, metabolic disorders
-seen in abnormalities of synthesis, utilization or mobilization of fat
Describe the pathogenesis of fatty change.
Impaired metabolism of FA -> accumulation of TAG -> formation of intracytoplasmic fat vacuoles
Describe the pathogenesis of fatty liver.
Hepatic lipid metabolism results in lipid accumulation if:
1. Excessive delivery of FFA from fat stores/diet
2. Dec oxidation or use of FFA
3. Impaired syn of apoprotein
4. Impaired combination of protein & TAG to make lipoprotein
5. Impaired release of lipoproteins from hepatocytes
Describe the gross appearance of fatty changes.
(Fatty liver, hepatic lipidosis/steatosis)
-diffuse yellow if all cells affected
-enhanced reticular pattern if specific zones of hepatocytes affected
-rounded edges & bulge
-soft tissue, friable, cuts easy, greasy
-severe condition = sm liver sections float in fixative/water
Describe the causes of hepatic lipidosis.
[reminder: ketones used as alt fuel, made in liver by mitochondria, conversion of acetylCoA from FFA = lipolysis]
1. Physiologic = esp ruminants
-late preg = preg toxemia
-heavy early lactation = ketosis
2. Nutritional disorders
-obesity (inc fat stores)
-protein cal malnutrition (impaired apolipoprotein syn)
-starvation (inc mobilization of TAG)
3. Endocrine disease
-diabetes mellitus (inc mobilization of TAG)
4. Genetic disorders
-niemann pick disease = lysosomal storage disease
Describe the histologic appearance of fatty change.
-well delineated, lipid filled vacuoles in cytoplasm
-vacuoles single to multiple, sm or lg, & displace cell nucleus to periphery
Describe prognosis of fatty change.
- Initially reversible
-can lead to hepatocyte death (irreversible) - Hepatic lipidosis
-rare in dogs but seen in cats, ruminants, donkeys
-ID & treat predisposing diseases
-nutritional support
-seen in obese cats or secondary to anorexia
-mortality high w/o treatment
-oral appetite stim
-(-) energy balance = take from energy reserves
Describe irreversible injury.
-swelling of mitochondria & lysosomes
-damage to PM = myelin figures
-myocardium infarcts - 30 to 40 min after ischemia
-cell death: necrosis or apoptosis
-necrotic change seen:
>ultrastructurally <6h
>histo 6-12h
>grossly 1-2d
Describe necrosis.
-cell death after irreversible cell injury by:
>hypoxia
>ischemia
>direct cell membrane injury
-morphologic due to:
>denature of protein
>enzymatic digestion of cell
—endogenous enzymes from lysosomes of dying cells (autolysis = self digestion)
—release of lysosome content from WBCs (commonly seen w inflammation!)
Describe necrosis light microscopy changes.
- Nucleus
- Cytoplasm
A) cause
-denature protein
-loss of RNA & glycogen
-enzyme digested cytoplasm organelles
B) appearance
-inc binding of eosin pink
-lose basophilia
-glassy
-vacuolation/moth eaten
-calcification
Describe necrosis gross appearance.
-description: multiple soft, friable, slightly depressed foci w sharply demarcated from viable tissue
-MDx: hepatitis, mutifocal to coalescing, subacute, severe, necrotizing
Describe the types of oncotic necrosis.
- Coagulative necrosis
- Caseous necrosis
- Liquefactive necrosis
- Gangrenous necrosis
- Fat necrosis
- Fibrinoid necrosis
Describe coagulative necrosis.
-early response to hypoxia, ischaemia, toxic injury
-denaturation of cell proteins
>structural proteins (maintain cell shape)
>lysosomal protein enzyme (auto digestion delay)
-nucleus show features of necrosis still (pyknosis, karyorrexhis, karyolysis)
>cell outline visible & tissue architecture
-commonly seen in liver, kidney, heart, skeletal muscle
*necrotic cells removed by phagocytes by WBCs & digestion via lysosomal enzymes of WBC
Describe an example of coagulative necrosis.
Describe liquefactive necrosis.
-dead cells digested -> transform tissue into liquid
-occurs in:
>tissue w high lipid content (CNS)
>tissue w high neutrophil & enzymatic release w digestion of tissue (abscess)
>focal bacteria & fungal infections
—microbes stim WBC & enzymes
Describe liquefactive necrosis examples.
Describe liquefactive necrosis in sheep.
-MDx = bilateral symmetrical encephalomalacia
-Aetiology = toxin from cl. Perfringens (same bacteria from pulpy kidney disease)
-Pathogenesis = overgrowth of intestinal cl perfringens bacteria type D -> release & absorption of epsilon toxin that target endothelial cell in brain & lung -> endothelial necrosis & anoxia/edema of neural parenchyma -> liquefactive necrosis (enterotoxaemia)
Describe liquefactive necrosis in horses.
‘Leukoencephalomalacia’
-pathogenesis: eat moldy corn containing toxin producing fumonisin B1 (fusarium verticilioides) -> inhibit sphingolipid syn -> accumulation of toxic sphingosine -> direct cell toxicity
-necrosis of white matter of cerebral hemispheres, brain stem, cerebellum
Describe gangrenous necrosis.
-begins as coagulative necrosis due to ischemia (ex. Frost bite)
-distal extremities (toes, ear, udder, pinna)
-multiple planes of tissue
-dry gangrene = no bacterial superinfection
-wet gangrene = bacterial superinfection, looks liquefactive bc degradative enzymes in bacteria & WBCs
Describe caseous necrosis.
-cheese like, friable (crumble) white area of necrosis (dead WBCs)
-cause: bacterial infections where bacteria replicate in phagosome
>mycobacterium
>corynebacterium
>fusobacterium
>fungal infections
-compared w coagulation (early stage), caseous is chronic (lytic)
-poorly degradable lipids
Describe caseous necrosis gross appearance.
Describe caseous necrosis histology.
-eosinophilic granular cell debris w rim of inflam cells like macrophages
-karyorrhectic basophilic debris & cytoplasmic eosinophilic debris (lytic necrosis)
-dystrophic calcification in center of lesion
Describe fat necrosis.
- Enzymatic necrosis
-activated pancreatic lipases
-neutral fat (lipase -> TAG)
-FFA + Ca = saponification (chalky, gritty, white)
-inflammation - Traumatic necrosis (compression)
-dystocia
-SQ in inter muscular fat @ sternum - recumbent cattle - Necrosis of abdominal fat
-unknown cause
-mesentery, omentum, retroperitoneum
-intestinal stenosis
Describe fibrinoid necrosis.
-immune reactions w blood vessels
-Ag-Ab complex (type III hypersensitivity) deposited in walls of arteries
-deposit of immune complex + fibrin = fibrinoid (bright pink)
Describe apoptosis.
-programmed cell death (suicide)
-activate intrinsic enzymes that degrade cell DNA & nuclear & cytoplasmic proteins
-fragments = apoptotic bodies (portion of cytoplasm & nucleus)
-PM & receptors remain intact -> targets for phagocytes
Describe apoptosis physiologic VS pathological process.
- Physiologic (most common)
-during embryogenesis
-hormone dependent involution of organs in adult
-cell deletion in proliferating cell pop
-delete auto reactive T cell in thymus
-death of cells after served useful function - Pathologic
-elim cell injured beyond repair
-DNA damage
-misfolded proteins
-cell death in infections (viral) & neoplastic
-pathologic atrophy in parenchymal organs after duct obstruction
Describe apoptosis morphology.
-cell shrink w inc cytoplasmic density
-chromatin condensation (pyknosis)
-cytoplasmic blebs & apoptotic bodies (fragments)
-phagocytosis of apoptotic cell
Describe apoptosis mechanisms.
-activation of capases:
>initiator 9 & 8
>executioner 3 & 6
-Function:
>induce, regulate, execute apoptosis to form apoptotic bodies
(Intrinsic = mitochondria & extrinsic = death receptor)
Describe intrinsic VS extrinsic pathway.
INTRINSIC
-major mech in mammalian cell
-inc mitochondria permeability & release of pro apoptotic mol into cytoplasm
-cytochrome C = released into cytoplasm & initiate apoptosis
-controlled release by pro & anti apoptotic proteins
>pro: Bak, Bax
>anti: BCL
*BH3 proteins = sense damage/stress
EXTRINSIC
-initiated by death receptors: FasL expressed on self Ag T cells & CD8 cytotoxic T cell
-form binding site w death domain
-FAD -> binds inactive caspase 8 -> active -> apoptosis
Describe the removal of apoptotic cells.
- Apoptotic bodies
-edible for phagocytes
-expressed phospholipid in outer membrane to be ID by macrophage receptors
-coated w Ab & protein of complement (C1q) - Apoptotic cells
-secrete soluble factors that recruit phagocytes
-express thrombospondin (adhesive glycoprotein ID by phagocytes)
-macrophage make protein that bind to apoptotic cell for engulf
Describe disorders associated w dysregulated apoptosis.
- Defective apoptosis & inc cell survival
-abnormal cell survive
-cells w mutation in p53 (tumor suppressive gene) subjected to DNA damage & fail to die = mutations -> neoplasia defective DNA repair
-lymphocytes react against self ag = autoimmune
-fail to elim dead cells - Inc apoptosis & excessive cell death
-neurodegenerative = loss of neurons
-ischemic injury = stroke
-death of virus infected cell
Describe necrosis VS apoptosis.
Describe reversible VS irreversible cell injury morphologic.
Describe the other types of cell death.
- Necroptosis (programmed necrosis)
-inflam reaction - Pyroptosis
-fever inducing cytokine IL1
