Cellular Injury2 PDF

The cellular injury  Cell necrosis Morphological changes that follow cell death in a living tissue or organ. Death of groups of contiguous cells in tissue or organ Resulting from degrading action of enzymes on irreversibly damaged cells with denaturation of cellular pro...

The cellular injury  Cell necrosis Morphological changes that follow cell death in a living tissue or organ. Death of groups of contiguous cells in tissue or organ Resulting from degrading action of enzymes on irreversibly damaged cells with denaturation of cellular proteins. Morphological changes - cytoplasmic - nuclear Cytoplasmic changes in necrosis More eosinophilia - Loss of cytoplasmic RNA - Increased binding of eosin to the denatured proteins. More homogeneous appearance - loss of glycogen particles The cytoplasm becomes vacuolated when enzymes have digested the cytoplasmic organelles, Nuclear changes in necrosis Normal chromatin clumping Pyknosis karyorrhexis karyolysis Liver cell necrosis: Nuclear changes normal pyknosis karyorrhexis karyolysis  Types of cell necrosis 1. Coagulative necrosis. 2. Liquefactive necrosis. 3. Fat necrosis 4. Caseation (caseous) necrosis 5. Gangrenous necrosis.  Necrosis is a dynamic process H&E stained section is just a snapshot in time: what one sees depends on the following factors –Degree of enzyme release: (more favours liquefactive necrosis) From lysosomes in dying cells (autolysis) and/or Infiltrating inflammatory cells (heterolysis) Versus –Degree of protein denaturation (more favours coagulative necrosis) Versus –Extent to which necrotic debris have been cleared away enzymatic digestion (autolysis and heterolysis), fragmentation and phagocytosis  Define coagulative necrosis. Give examples  Coagulative necrosis Outlines of cells are still discernible, but Fine structural details lost. The nuclei are lost. The cytoplasm stains homogeneous deeply eosinophilic Sudden severe ischemia in organs cause denaturation not only of structural proteins but also of enzymes, which blocks proteolysis of the dead cells  Coagulative necrosis Alive Coagulative Protein denaturation > necrosis enzymatic digetsion Cells dead but basic shape and architecture of tissue endures Most common manifestation of necrosis in tissues. Affected tissue maintains solid consistency.  Coagulative necrosis-kidney Normal Infarct The renal cortex has undergone anoxic injury at the left so that the cells appear pale and ghost-like. There is a hemorrhagic zone in the middle where the cells are dying or have not quite died, and then normal renal parenchyma at the far right. This is an example of coagulative necrosis Within the area of necrosis (Lt) the outlines of tubules and glomeruli are still preserved but fine structural details are lost (inset)  Coagulative necrosis Kidney Microscopic view of the edge of the infarct, with normal kidney (N) and necrotic cells in the infarct (I). The necrotic cells show preserved outlines with loss of nuclei, and an inflammatory infiltrate is present  Coagulative necrosis myocardium The necrotic myocytes are intensely eosinophilic with loss of both cross striations & nuclei. The outlines of individual fibres are still maintained. There are inflammatory cells infiltration & RBCs in-between the necrotic fibers..Define liquefactive necrosis.Give examples  Liquefaction (liquefactive) necrosis Seen in two situations – Ischemic destruction of brain tissue – Bacterial infections e.g. abscesses complete digestion of dead cells by enzymes cyst filled with debris + fluid Lung abscess This is an example of liquefactive necrosis. There is confluent broncho- pneumonia (scattered pale areas) complicated by abscess formation, which is seen here as a cystic cavity (arrow). The contained pus poured off during the sectioning of the lung tissue. Brain infarction: This is an example of liquefactive necrosis; the affected area is wedge-shaped, pale, soft & cystic. Identify the organ? Describe the gross pathological changes?  Gangrene Gangrenous necrosis A term used in surgical practice: lower limb, intestine Gangrene = coagulative necrosis (ischemia) + liquefactive necrosis (bacterial infection) Two subtypes 1- Dry gangrene 2- Wet gangrene  Ganagrene of lower limb Dry gangrene Wet gangrene.Define caseous necrosis Give an example  Caseous necrosis Alive Caseous Necrosis Accumulation of amorphous (i.e. no structure) debris Tissue architecture is abolished Characteristically associated with certain infections especially tuberculosis.  CASEOUS NECROSIS B A A- A tuberculous lung with a large area of caseous necrosis containing yellow-white and cheesy debris. B- Caseous necrosis in a hilar lymph node infected with tuberculosis. The node has a cheesy yellow to white appearance. Caseating TB granuloma Caseous necrosis is characterized by amorphous (acellular), granular pink areas of necrosis, surrounded by a granulomatous inflammatory process.  Normal A B Identify the organ? Describe the gross pathological changes in B?  Fat necrosis of acute pancreatitis Injury to the pancreatic acini leads to release of powerful enzymes which damage fat through lipases; these liberate fatty acids which complex with calcium leading to the production of soaps, and these appear grossly as the soft, chalky white areas seen here on the cut surfaces.  Fat necrosis Involves adipose tissue Mediated through lipases Seen in 1. acute pancreatitis 2. breast trauma (traumatic fat necrosis) Grossly chalky white Microscopically: - shadowy outlines of necrotic cells - surrounding inflammatory cells - calcium soaps: bluish deposits Acute pancreatitis A, The microscopic field shows a region of fat necrosis (right), and focal pancreatic parenchymal necrosis (center). B, The pancreas has been sectioned longitudinally to reveal dark areas of hemorrhage in the pancreatic substance and a focal area of pale fat necrosis in the peripancreatic fat (arrow).  Fat necrosis in acute pancreatitis. The areas of white chalky deposits represent foci of fat necrosis with calcium soap formation (saponification) at sites of lipid breakdown in the mesentery.  Acute pancreatitis The fat necrosis consists of fat cells that have lost their nuclei and whose cytoplasm has a granular pink appearance. Some hemorrhage is seen at the left in this case.  Fibrinoid necrosis of an artery in polyarteritis nodosa. The wall of the artery shows a circumferential bright pink area of necrosis with protein deposition and inflammation (dark nuclei of neutrophils).  Infarction Like gangrene, also not a specific pattern of necrosis Term refers to the CAUSE: when necrosis is due ischaemia i.e. infarct = ischaemic necrosis  Infarction Infarction (ischaemic necrosis) can be –coagulative e.g. myocardial infarct –liquefactive e.g. brain infarct Two further ways of describing infarcts –White ;Occlusion of end artery –the usual arrangement in an organ and therefore commonest pattern –Red/haemorrhagic: may occur in the following situations Venous occlusion; Dual blood supply; Loose tissues; Previously congested tissues Infarction  White infarct  Red infarct  Apoptosis This form of cell death is a regulated suicide program in which the relevant cells activate enzymes (CASPASES) capable of degrading the cells' own nuclear DNA and other nuclear and cytoplasmic proteins. Apoptotic cells may appear as round or oval masses with intensely eosinophilic cytoplasm. Nuclei show chromatin condensation and aggregation and, ultimately fragmentation (karyorrhexis). The cells rapidly shrink, form cytoplasmic buds, and fragment into apoptotic bodies composed of membrane-bound vesicles of cytoplasm and organelles. Fragments of the apoptotic cells then break off (apoptosis = "falling off"). These fragments are quickly extruded and phagocytosed without eliciting an inflammatory response. Even substantial apoptosis may be histologically undetectable  Apoptosis -basics Single-cell death. An active process -energy consumed Derived from Greek "falling off" (as for autumn leaves) May be physiological or pathological  APOPTOSIS vsNECROSIS HISTOLOGICAL FEATURES Apoptosis Necrosis Patterns of death Single cells Groups cells Shrinkage; Cell size Fragmentatio Swelling n Plasma membrane Preserved continuity Early lysis Increased membrane permeabilityCytochr Mitochondria omec release; Swelling; Disordered structure Contracted; Organelle shape "Apoptotic Swelling; Disruption bodies" Clumped Chromatin: Pyknosis; Nuclei & Fragmented karryhexis; karyolysis Internucleosom DNA degradation al cleavage; Diffuse & Random Phagocytosis Inflammation; Cell degradation ; No inflammation Macrophage invasion  Apoptosis -triggers Intrinsic –Withdrawal of growth stimuli, e.g. growth factors –DNA damage, e.g. p53-induced apoptosis Extrinsic –Death signals, e.g. TRAIL and Fas ligand  Apoptosis -mechanisms Intrinsic Extrinsic (Viral Hepatitis) The cell is reduced in size and contains brightly eosinophilic cytoplasm and a condensed nucleus. The cytoplasm is intensely esoniphilic (pinkish) and the nucleus condensed (pyknotic)  INTRAcellular ACCUMULATIONS Lipids Neutral Fat Cholesterol– Hyaline” = any “proteinaceous” pink“ “glassy” substance Glycogen Pigments (EX-ogenous, END-ogenous) Calcium  LIPID LAW ALL Lipids are YELLOW grossly and WASHED out (CLEAR) microscopically FATTY LIVER FATTY LIVER  PIGMENTS EX-ogenous--- (tattoo, Anthracosis) END-ogenous--- they all look the same, (e.g., hemosiderin, melanin, lipofucsin, bile), in that hey are all golden yellowish brown on “routine” Hematoxylin & Eosin (H&E) stains TATTOO, MICROSCOPIC ANTHRACOSIS Hemosiderin/Melanin/etc.  CALCIFICATION DYSTROPHIC (LOCAL CAUSES) (often with FIBROSIS) METASTATIC (SYSTEMIC CAUSES) – HYPERPARATHYROIDISM – “METASTATIC” Disease