Morphology of Cell Injury

Transcript

1. Morphology of Cell Injury and Death Microscopy of reversible injury, necrosis and apoptosis Membrane failure
2. Morphology reflects injury mechanism The timing and type of insult shape the tissue pattern. Ultrastructural alterations may precede lightmicroscopic change. Reversible injury classically produces swelling, blebbing and fatty change. Necrosis combines protein denaturation, enzymatic digestion and cell membrane damage. Apoptosis produces isolated, condensed and fragmented cells.
3. What is visible at different scales? Level Typical early finding Later finding Electron microscopy ER and mitochondria swell Membrane disruption / dense deposits Light microscopy Swelling; vacuolation Nuclear loss and eosinophilia Gross morphology Often no visible change Organ-specific necrotic pattern Morphologic visibility lags behind the biochemical insult.
4. Reversible injury: ultrastructure Cellular organelles respond to impaired energy and ion homeostasis. Plasma membrane blebs and shortening or loss of microvilli. Mitochondrial swelling without destructive collapse. ER dilation with ribosome detachment and polysome disaggregation. Nuclear chromatin clumping and occasional myelin figures.
5. Cellular swelling under the microscope Also termed hydropic change. Pale expanded cytoplasm and enlarged cell outlines. Small clear vacuoles may represent distended or pinched-off ER. Commonly seen in renal tubular, hepatic and myocardial parenchymal cells. May regress if the injurious stimulus resolves promptly.
6. Fatty change is a different process Cytoplasmic clear vacuoles may reflect triglyceride storage. Predominantly observed in cells handling lipid metabolism. Large vacuoles may displace the nucleus to the periphery. Microvesicular patterns may be associated with mitochondrial metabolic defects. Routine H&E does not distinguish every cause of vacuolation.
7. The microscopic appearance of fatty change Recognize the vacuolar pattern Numerous optically empty hepatocytic vacuoles are consistent with steatosis. Nuclear displacement is common with large droplets. Correlate the pattern with biochemical and etiologic studies. H&E images from the supplied intracellular accumulations lecture.
8. Irreversible injury: ultrastructure Profound membrane and mitochondrial defects mark lethal damage. Severe mitochondrial swelling and electrondense deposits. Loss of cell membrane integrity with leakage of cytosolic components. Lysosomal disruption and autolytic digestion. Membrane failure Nuclear fragmentation or fading follows loss of viability.
9. Necrosis: working definition Pathologic tissue changes after cellular death. Cell membrane integrity is lost and intracellular components escape. Enzymes digest cell structures while proteins denature. The reaction often recruits inflammatory cells into surrounding viable tissue. Membrane failure The specific gross and microscopic pattern depends on tissue and cause.
10. Timing matters in tissue necrosis Biochemistry, microscopy and inflammation evolve at different rates. Immediately after ischemia, microscopic structure may remain deceptively normal. Cytoplasmic eosinophilia and nuclear change emerge after an interval. Inflammatory infiltrates require time to accumulate. Membrane failure Late lesions may show macrophages, granulation tissue and fibrosis.
11. Two processes in necrotic tissue 01 02 03 04 05 Cell death Protein denaturation Proteolysis Inflammation Removal / repair Irreversible molecular injury Structures become eosinophilic Hydrolytic enzymes digest cells Leukocytes respond to released contents Macrophages and fibrosis or regeneration Autolysis involves tissue enzymes; heterolysis involves enzymes from recruited leukocytes.
12. Cytoplasmic changes in necrosis Staining and texture change as macromolecules are lost. Eosinophilia increases due to protein denaturation and loss of basophilic RNA. Cells may appear smooth, glassy or homogeneously pink. Vacuoles and a moth-eaten pattern result from organelle digestion. Membrane failure Laminated phospholipid masses may appear as myelin figures.
13. Three nuclear patterns of necrosis 01 02 03 Pyknosis Karyorrhexis Karyolysis Nuclear condensation and shrinkage Nuclear fragmentation Progressive fading and dissolution These patterns do not necessarily form a fixed linear sequence in every cell.
14. Necrosis versus apoptosis in H&E Feature Necrosis Apoptosis Distribution Groups / contiguous areas Often individual cells Cytoplasm Swollen then eosinophilic Condensed, intensely eosinophilic Nucleus Pyknosis / fragmentation / lysis Dense condensed fragments Host response Inflammatory response common Usually no acute inflammation Both patterns can coexist after the same major insult.
15. Coagulative necrosis Protein denaturation preserves dead-cell outlines transiently. Typical of ischemic infarction in many solid organs except brain. Architecture persists as pale or eosinophilic anucleate “ghost” cells. Subsequent inflammatory infiltration removes dead material. Membrane failure Examples: myocardial, renal and splenic infarction.
16. Coagulative necrosis: diagnostic logic Ask what happened to the outline, nucleus and tissue framework. Preserved tissue scaffold with absent viable nuclei favors coagulative necrosis. Early lesions may show hypereosinophilia before complete nuclear loss. Time since insult changes the amount of neutrophilic infiltration. Membrane failure Coagulative necrosis is a morphologic pattern, not a specific disease.
17. Liquefactive necrosis Digestion predominates over preservation of the tissue framework. Common in bacterial or fungal infections that form abscesses. Characteristic for infarcts of the central nervous system. Dead tissue becomes viscous or liquid; cavities may form after clearance. Microscopy shows loss of architecture and abundant cellular debris.
18. Coagulative versus liquefactive necrosis Property Coagulative Liquefactive Predominant process Protein denaturation Hydrolytic digestion Tissue architecture Temporarily retained Lost Typical example Myocardial infarct Brain infarct / abscess Late outcome Fibrotic scar common Cystic cavity possible Both undergo inflammatory clearance and tissue remodeling.
19. Caseous necrosis A friable granular necrotic center within granulomatous inflammation. Classic setting: tuberculosis and some fungal infections. Grossly soft, white-yellow, cheese-like material. Microscopy: amorphous eosinophilic granular debris with loss of cell outlines. Membrane failure Often surrounded by epithelioid histiocytes and multinucleated giant cells.
20. Fat necrosis Destruction of adipocytes has distinct patterns. Enzymatic fat necrosis occurs in acute pancreatitis when lipases hydrolyze triglycerides. Released fatty acids bind calcium, producing chalky soap-like deposits (saponification). Traumatic fat necrosis may follow blunt injury, including in the breast. Foamy macrophages, inflammation and fibrosis develop during resolution.
21. Fibrinoid necrosis An injury pattern centered on vessel walls. Brightly eosinophilic amorphous material accumulates within damaged vascular walls. Typically reflects plasma protein leakage with immune injury and vascular damage. May be seen in vasculitis and selected severe hypertensive vascular lesions. Membrane failure Despite the name, it is not synonymous with ordinary fibrin deposition.
22. How to interpret fibrinoid vessel-wall injury The location is often more informative than the stain color. Evaluate whether eosinophilic material lies within a damaged arterial wall. Seek associated inflammation, vascular narrowing or thrombosis. Vessel-wall damage in immune-mediated disease can allow plasma proteins to enter the wall. Membrane failure Anatomic pattern and clinical tests are needed for etiologic classification.
23. Gangrene is a clinical designation A gross pattern, not a unique microscopic necrosis mechanism. Dry gangrene is usually ischemic with predominant coagulative necrosis. Wet gangrene involves infection and prominent tissue liquefaction. Gas gangrene involves infection by gas-forming organisms, often clostridia. Membrane failure Extent and clinical features determine urgent management.
24. Recognize necrosis patterns by site Heart, kidney, spleen Brain Pancreatic fat Ischemic infarction commonly gives coagulative necrosis. Ischemic infarction usually becomes liquefactive. Lipase-mediated fat necrosis and calcified soaps. Granuloma Vessel wall Limb Caseous necrosis supports— but does not prove—certain infections. Fibrinoid change suggests severe vascular injury. Gangrene describes clinically devitalized tissue.
25. Apoptosis in routine sections Single cells undergo controlled structural collapse. Smaller dense eosinophilic cell bodies in otherwise viable tissue. Nuclear chromatin condensation with fragmentation. Membrane-bound fragments are engulfed by local phagocytes. The inflammatory reaction is usually absent or limited.
26. Diagnostic pitfalls in cell death Avoid drawing conclusions from appearance alone. Autolysis after tissue removal can mimic or obscure cell injury. Nuclear pyknosis occurs in several contexts and is not by itself diagnostic of apoptosis. Dense inflammatory infiltrates may obscure the original necrosis pattern. Serial sections, organ context and suitable ancillary tests improve confidence.
27. Spot diagnosis: renal infarct A wedge-shaped renal cortical lesion shows preserved tubular outlines but no intact epithelial nuclei. Which morphologic type of necrosis is most likely?
28. Spot diagnosis: cerebral infarct Weeks after an ischemic stroke, a brain lesion has lost recognizable parenchymal architecture and contains macrophages and fluid-filled spaces. Which morphologic process explains the cavitation?
29. Rapid morphology review Pattern Useful signature Reversible injury Swollen cells, ER dilation, membrane blebs Apoptosis Cell shrinkage, condensed fragments, silent clearance Coagulative necrosis Ghost architecture and eosinophilia Liquefactive necrosis Digested tissue and absent architecture Caseous necrosis Granular amorphous debris in granulomas Fat necrosis Dead adipocytes, saponification
30. Suggested reading Robbins, Cotran & Kumar Pathologic Basis of Disease · Chapter: Cell Injury, Cell Death, and Adaptations For further study: correlate the molecular mechanisms with gross and microscopic pathology. Illustrative pathways are original schematics; selected histology images are retained from the supplied teaching material.