lect 3 cell injury.pptx

Sequence of Events in Cell Injury and Cell Death Dr. Fawaz Almutairi Prof. Layla S. Abdullah Pathology Department Faculty of Medicine KAU Patterns of Acute Cell Injury Reversible Injury: • Two microscopic patterns of reversible injury : 1. Cellular swelling 2. Fatty change Patterns of Acute Ce...

Sequence of Events in Cell Injury and Cell Death Dr. Fawaz Almutairi Prof. Layla S. Abdullah Pathology Department Faculty of Medicine KAU Patterns of Acute Cell Injury Reversible Injury: • Two microscopic patterns of reversible injury : 1. Cellular swelling 2. Fatty change Patterns of Acute Cell Injury • Reversible Injury: 1. Cellular swelling (hydropic change, vacuolar degeneration): • May result from –hypoxia or –chemical poisoining • The changes are reversible • If the injurious cause persisted the changes may be irreversible Reversible Injury • Grossly: – Organ pallor, increased weight • Microscopically: – Cytoplasm becomes pale and swollen with small, clear cytoplasmic vacuoles – due to accumulation of fluids (earliest change of injured cells) Reversible Injury • Intracellular changes – plasma membrane blebbing, blunting and distortion of microvilli and loosing of intercellular attachments. – mitochondrial swelling, phospholipid-rich amorphous densities – dilation of endoplasmic reticulum with detachment of ribosomes and dissociation of polysomes – nuclear alterations, such as clumping of chromatin Reversible Injury 2. Fatty change: – Vacuolation of cells due to accumulation of lipid droplets (triglyceride) – Results due to disturbance of ribosomal function and uncoupling of lipid from protein metabolism Reversible Injury Fatty change: – The liver (steatosis) is commonly affected – Occurs in hypoxic injury, toxic (alcohol), metabolic (diabetes mellitus) – Moderate fatty changes are reversible, but sever changes may not be Irreversible injury: Irreversible change occurs when: 1. 2. 3. 4. severe mitochondrial dysfunction Plasma membrane damage Lysosomal rupture loss of DNA and chromatin structural integrity. Patterns of Cell Death: 1. Necrosis 2. Apoptosis • 1. Necrosis: – Definition: sequence of morphologic changes that follow cell death in living tissue – The morphologic appearance of necrosis is due to: • Enzymatic digestion of cell: – Autolysis: hydrolytic enzymes are derived from the dead cells themselves (ruptured lysosome) – Heterolysis: hydrolytic enzymes are derived from invading inflammatory cells (inflammation) • Denaturation of proteins Microscopic appearance of dead cells: – A: Cytoplasmic changes 1. Eosinophilia (pink) increased: – Due to eosin binding to denatured proteins 2. Decreased basophilia (blue): – Partly to loss of basophilic ribonucleic acid (RNA) in the cytoplasm 3. Glassy homogenous cytoplasm: – due to loss of glycogen Eosinophilia Glassy homogenous cytoplasm Microscopic appearance of dead cells: • B: Nuclear changes  due to break down of DNA • Karyolysis: decrease basophilia of chromatin • Pyknosis: nuclear shrinkage and increased basophilia • Karyorrhexis: fragmentation of pyknotic nucleus ,By electron microscopy Discontinuities in plasma and • organelle membranes Marked dilation of mitochondria • Appearance of large amorphous • intramitrochondrial densities Disruption of lysosomes • Kidney, necrosis of tubular cells Patterns of Acute Cell Injury • Specific Morphologic Patterns of Necrosis – Coagulative necrosis – Liquefactive necrosis – Gangrenous necrosis – Caseous necrosis – Fat necrosis – Others (fibrinoid necrosis) 1. Coagulative Necrosis Definition • Preservation of the structural outline of the dead (coagulated) cell for days • The most common form of necrosis (particularly in myocardium, liver, kidney) • Characteristic of hypoxic cell death in all tissues except in the brain Coagulative Necrosis E.g. – Myocardial infarction Mechanism: • Denaturation of proteins and enzymes  blocking cellular proteolysis  preserve cell outline Morphology of Coagulative Necrosis: Gross: • pale color, • normal firm texture at the beginning  become soft later due to digestion by macrophages (may lead to rupture of infarcted myocardium) Microscopic: • first few hours  no abnormalities • later  progressive loss of nuclear staining, with preservation of cell boundaries • finally  damaged cells are removed by macrophages (the presencjmke of necrotic tissue usually evokes inflammatory response followed by repair) Coagulative Necrosis Kidney Normal Kidney Coagulation necrosis Heart, Normal Heart, coagulation necrosis Patterns of Acute Cell Injury • Specific Morphologic Patterns of Necrosis – Coagulative necrosis – Liquefactive necrosis – Gangrenous necrosis – Caseous necrosis – Fat necrosis – Others (fibrinoid necrosis) Liquefactive Necrosis • complete digestion of the dead cells with rapid dissolution – characteristic of bacterial and some fungal infection  accumulation of white blood cells e,g. Abscess – also seen in hypoxic cell death in the central nervous system (brain lacks supporting stroma) • There is NO cell structure remains The necrotic area is soft and filled with fluid Brain, normal Brain, liquefaction necrosis Patterns of Acute Cell Injury • Specific Morphologic Patterns of Necrosis – Coagulative necrosis – Liquefactive necrosis – Gangrenous necrosis – Caseous necrosis – Fat necrosis – Others (fibrinoid necrosis) Gangrenous Necrosis • It is not a distinctive type of cell death • The term is commonly used in surgical practice • It refers to ischemic coagulative necrosis (frequently of limb) with superimposed infection and putrefaction (liquefaction) of tissue  Wet gangrene Gangrenous Necrosis • Wet gangrene – Certain bacteria notably clostridia may result in gangrene – Clostridia is common in the bowel  intestinal necrosis is liable to proceed to gangrene (e.g. gangrenous appendicitis) • Dry gangrene – usually seen in the toes as a result of arterial obstruction in » atherosclerosis or » D.M. Patterns of Acute Cell Injury • Specific Morphologic Patterns of Necrosis – Coagulative necrosis – Liquefactive necrosis – Gangrenous necrosis – Caseous necrosis – Fat necrosis – Others (fibrinoid necrosis) Caseous Necrosis • A distinctive form of necrosis • Dead tissue architecture is completely obliterated (no structure) • Characteristic of tuberculous infection Caseous Necrosis • Gross: • “Caseous” = Cheesy, white gross appearance of the central necrotic area • Microscopic: • Structureless amorphous granular debris in a ring of granulomatous inflammation Kidney, caseous necrosis Patterns of Acute Cell Injury • Specific Morphologic Patterns of Necrosis – Coagulative necrosis – Liquefactive necrosis – Gangrenous necrosis – Caseous necrosis – Fat necrosis – Others (fibrinoid necrosis) Fat necrosis • Definition: – Does not denote a specific pattern of necrosis – It describes focal areas of fat destruction • Caused: – Commonly seen with direct trauma to adipose tissue: • Grossly:  white, chalky areas • Microscopic:  shadowy outlines of necrotic fat cells with basophilic calcium deposits Fat necrosis • Examples: • Breast trauma: • release intracellular fat  • inflammatory response  • polymorphs and macrophages phagocytose fat • palpable mass in superficial sites (e.g. breast) • Acute Pancreatitis • release of pancreatic lipases  • liquefy fat cells & hydrolyze triglyceride esters  • released fatty acids + calcium  • Fat saponification Patterns of Acute Cell Injury • Specific Morphologic Patterns of Necrosis – Coagulative necrosis – Liquefactive necrosis – Gangrenous necrosis – Caseous necrosis – Fat necrosis – Others (fibrinoid necrosis) Fibrinoid Necrosis • Describes the histological appearance of arteries in cases of vasculitis and hypertension • Necrosis of smooth muscle in arterioles wall  leakage of plasma into media  Fibrin deposition in the damaged necrotic vessel wall (hence the name fibrinoid) Fate of Necrosis • Most of necrotic tissue is removed by leukocyte (Phagocytosis) combined with extracellular enzyme digestion • If necrotic tissue is not eliminated  it attracts Ca++ salts  dystrophic calcification Clinically useful markers of tissue damage • Leakage of intracellular proteins through the damaged cell membrane and ultimately into the circulation • Myocardial infarction: creatine kinase and contractile protein troponin. • Bile duct disease: alkaline phosphatase • Liver disease: transaminases.