necrosis and apoptosis
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DESCRIPTION(Foundation Block, pathology). Lecturer name: Dr. Maha Arafah Lecture Date: 17-9-2012. Necrosis and apoptosis. Cell injury L2. Objectives. List causes of cell injury List mechanisms of cell injury Understand the changes in reversible and irreversible cell injury - PowerPoint PPT Presentation
Necrosis and apoptosis
Necrosis and apoptosis Cell injury L2Lecturer name: Dr. Maha ArafahLecture Date: 17-9-2012
(Foundation Block, pathology)
ObjectivesList causes of cell injuryList mechanisms of cell injuryUnderstand the changes in reversible and irreversible cell injury Define necrosis and apoptosisList the different conditions associated with apoptosis, its morphology and its mechanismList the different types of necrosis, examples of each and its featuresKnow the difference between apoptosis and necrosis
Etiologic agentsDEFICIENCY OF OXYGEN Ischemia vs. HypoxiaPHYSICAL AGENTSCHEMICAL AGENTSINFECTIONIMUNOLOGICAL REACTIONSGENETIC DERANGEMENTSNUTRITIONAL IMBALANCEAGING
Brain massive haemorrhagic focus (ischemia) in the cortex
This is a lesion caused by DEFICIENCY OF OXYGENAbscess of the brain (bacterial)
This is a lesion caused by infectious agent
This is a lesion caused by chemical agentHepatic necrosis (patient poisoned by carbon tetrachloride)Pulmonary caseous necrosis (coccidioidomycosis)
This is a lesion caused by infectious agentGangrenous necrosis of fingers secondary to freezing
This is a lesion caused by physical agent
The boutonnire (buttonhole) deformityThis is a lesion caused by intrinsic factors(autoimmune disease)Liver: macronudular cirrhosis (HBV)
This is a lesion caused by infectious agent:Viral hepatitis(chemical:alcohol, genetic:a1-AT deficiency)morphology of cells in reversible and irreversible injury
myocadial cells: loss of function after 1-2 min of ischemiaHowever do not die until 20 to 30 min of ischemia EM: 2-3 hours, LM 6-12 hours12
13Morphologic changes in Reversible InjuryEarly changes:(1) Cloudy swelling or hydropic changes: Cytoplasmic swelling and vacuolar degeneration due to intracellular accumulation of water and electrolytes secondary to failure of energy-dependent sodium pump.
(2) Mitochondrial and endoplasmic reticulum swelling due to loss of osmotic regulation.(3) Clumping of nuclear chromatin.
Vacuolar (hydropic) change in cells lining the proximal tubules of the kidney Reversible changesMorphologic changes in irreversible injury: 1. Severe vacuolization of the mitochondria, with accumulation of calcium-rich densities.
2. Extensive damage to plasma membranes.
3. Massive calcium influx activate phospholipase, proteases, ATPase and endonucleases with break down of cell component.
4. Leak of proteins, ribonucleic acid and metabolite.
5. Breakdown of lysosomes with autolysis.
6. Nuclear changes: Pyknosis, karyolysis, karyorrhexis.
IRREVERSIBLE CELL INJURY- NECROSIS19
21Morphologic changes in irreversible injury- Dead cell are either collapsed and form a whorled phospholipid masses or degraded into fatty acid with calcification.- Cellular enzymes are released into circula- tion. This provides important clinical parameter of cell deathe.g. increased level of creatinin kinase in blood after myocardial infarctionMyocardial infarct
This is a lesion caused by oxygen deprivationCell PathologyMechanisms of cell injuryDepletion of ATPDamage to MitochondriaInflux of CalciumFree radicals productionDisruption of cell membrane and chromatin
Mechanisms of cell injury
Death of cells occurs in two ways:
Necrosis--changes produced by enzymatic digestion ofcells after irreversible injuryApoptosis--vital process that helps eliminate unwanted cells--an internally programmed series of events effected by dedicated gene products
AutolysisAutolysis is the death of individual cells and tissues after the death of the whole organism. The cells are degraded by the post-mortem release of digestive enzymes from the cytoplasmic lysosomes.Autophagy:Self eating in starvation
NecrosisNecrosis is defined as the morphological changes that result from cell death within living tissues. In necrosis, death of a large number of cells in one area occurs.These changes occur because of digestion and denaturation of cellular proteins.Patterns of Necrosis: In Tissues or Organs
As a result of cell death the tissues or organs display one of these six macroscopic changes:
Coagulative necrosisLiquifactive necrosisCaseous necrosisFat necrosisGangrenous necrosisFibrinoid necrosis
Patterns of Necrosis In Tissues or OrgansCoagulative necrosis:Denaturation of intracellular protein leads to the pale firm nature of the tissues affected. The cells show the microscopic features of cell death but the general architecture of the tissue and cell ghosts remain discernible for a short time.
The outline of the dead cells are maintained and the tissue is somewhat firm. Example: kidney and heart injury caused by ischaemia.
Kidney: ischemia and infarction (loss of blood supply and resultant tissue anoxia). Coagulative necrosisRemoval of the dead tissue leaves behind a scar
Acute renal tubular necrosis (ischemia) :increased eosinophilia and pyknosis in necrotic cellsNormalNecroticCoagulative necrosis:
Remember: True coagulation necrosis involves groups of cells, and is almost always accompanied, by acute inflammation (infiltrate)Patterns of Necrosis In Tissues or Organs2. Liquefactive necrosis:The dead cells undergo disintegration and affected tissue is liquefied.This results from release of hydrolytic lysosomal enzymes and leads to an accumulation of semi-fluid tissue. Example: cerebral infarction.Abscess
Liquefactive necrosis in brain leads to resolution with cystic spaces.
Liquefactive necrosis of the brain: macrophages cleaning up the necrotic cellular debrisRemoval of the dead tissue leaves behind a cavity
Liquefactive necrosis: two lung abscessesRemoval of the dead tissue leaves behind a cavity or scar
Localized liquefactive necrosis liver abscessRemoval of the dead tissue leaves behind a scarPatterns of Necrosis In Tissues or Organs3. Caseous necrosis: A form of coagulative necrosis but appear cheese-like.The creamy white appearance of the dead tissue is probably a result of the accumulation of partly digested waxy lipid cell wall components of the TB organisms. The tissue architecture is completely destroyed.Example: tuberculosis lesionsfungal infectionsCoccidioidomycosisblastomycosis histoplasmosis
Caseous necrosis in a hilar pulmonary lymp node infected with tuberculosis.
Pulmonary tuberculosis:tubercle contains amorphous finely granular, caseous ('cheesy') material typical of caseous necrosis. Removal of the dead tissue leaves behind a scar
Caseous necrosis is characterized by acellular pink areas of necrosis, surrounded by a granulomatous inflammatory process.
NPatterns of Necrosis In Tissues or Organs4. Fat necrosis: This can result from direct trauma or enzyme released from the diseased pancreas. Example: Necrosis of fat by pancreatic enzymes.Traumatic fat necrosis in breastAdipocytes rupture and the released fat undergoes lipolysis catalyzed by lipases. Macrophages ingest the oily material and a giant cell inflammatory reaction may follow. Another consequence is the combination of calcium with the released fatty acids.
Fat necrosis secondary to acute pancreatitis
Fat NecrosisSpecific to adipose tissue with triglycerides.With enzymatic destruction(lipases) of cells, fatty acids are precipitated as calcium soaps.
Grossly- chalky white deposits in the tissue.Microscopically amorphous, basohilic /purple deposits at the periphery of necrotic adipocytes.
Patterns of Necrosis In Tissues or Organs5. Gangrenous necrosis:This life-threatening condition occurs when coagulative necrosis of tissue is associated with superadded infection by putrefactive bacteria. These are usually anaerobic gram-positive Clostridia spp. Derived from the gut or soil which thrive in conditions of low oxygen tension. Patterns of Necrosis In Tissues or Organs5. Gangrenous necrosis:Gangrenous tissue is foul smelling and black.The bacteria produce toxins which destroy collagen and enable the infection to spread rapidly. If fermentation occurs, gas gangrene ensues.Infection can become systemic (i.e. reach the bloodstream, septicaemia). The commonest clinical situation is gangrene of the lower limb caused by poor blood supply and superimposed bacterial infection. This is a life-threatening emergency and the limb should be amputated.
Example: necrosis of distal limbs, usually foot and toes in diabetes.
Wet" gangrene of the lower extremity in patient with diabetes mellitus:
liquefactive component from superimposed infection
coagulative necrosis from loss of blood supply.
Patterns of Necrosis In Tissues or Organs6. Fibrinoid necrosis: typically seen in vasculitis and glomerular autoimmune diseases
Fibrinoid necrosis: afferent arteriole and part of the glomerulus are infiltrated with fibrin, (bright red amorphous material)
Depending on circumstances: necrotic tissue may be walled off by scar tissue, totally converted to scar tissue, get destroyed (producing a cavity or cyst), get infected (producing an abscess or "wet gangrene"), or calcify.
If the supporting tissue framework does not die, and the dead cells are of a type capable of regeneration, you may have complete healing.
Outcome of necrosisCell Death
Vital process.Programmed cell death.Can occurs in physiological or pathological conditions.
Physiologic process to die
This process helps to eliminate unwanted cells by an internally programmed series of events effected by dedicated gene products. It serves several vital functions and is seen under various settings.Remember: apoptosis require energy to die