Cell Death 1- Necrosis Cellular Pathology 4 PDF

Cell Death 1- Necrosis Cellular Pathology 4 Michael M. Yakubovskyy, MD, PhD 1 Learning Objectives 1.List the types of cell death; define and differentiate necrosis and apoptosis. 2.Correlate between the causes and mechanisms of necrosis. 3.Describe and recognize the characteristic gross and micr...

Cell Death 1- Necrosis Cellular Pathology 4 Michael M. Yakubovskyy, MD, PhD 1 Learning Objectives 1.List the types of cell death; define and differentiate necrosis and apoptosis. 2.Correlate between the causes and mechanisms of necrosis. 3.Describe and recognize the characteristic gross and microscopic features of necrosis. 4.Discriminate between the most common morphologic patterns of necrosis. 2 Fate of Cells in Multicellular Organisms • Proliferation: cell division to maintain a pool of stem and progenitor cells, e.g., hematopoietic cells • Senescence: (synonyms: cell aging and replicative senescence) • Dormancy: a cell stays alive, but with significantly slowed down functions, e.g., quiet state of stem and progenitor cells after embryonic period • Death 3 • Necrosis • Apoptosis Types of Cell Death • Necroptosis • Pyroptosis • Ferroptosis • NETosis • Anoikis • etc. 4 Necrosis vs Apoptosis • Necrosis: morphologic changes that follow irreversible injury of cells in the living tissues o o o Cellular “homicide” that affects groups of cells Seen only in pathologic conditions Induces an acute inflammatory response (neutrophilic influx) • Apoptosis (Greek “apoptosis” – a falling off): morphologic changes that follow programmed cell death in living tissues o o o Cellular “suicide” that affects single cells Seen in both physiologic and pathologic conditions Apoptotic bodies (cellular remnants) are readily cleared and digested by macrophages 5 Causes and Mechanisms of Cell Injury and Necrosis (from the Previous Lecture) Causes 1 2 3 4 5 6 7 Mechanisms Hypoxia and ischemia Microorganisms Chemical agents and drugs Physical agents (heat, cold, radiation, mechanical trauma) Immunologic reactions Genetic derangements Nutritional imbalances 6 1 2 ATP depletion Mitochondrial damage 3 Generation of free radicals 4 5 6 7 Reperfusion injury Membrane damage Calcium influx DNA damage Necrosis: Three Types of Nuclear Changes • Karyolysis: nuclear dissolution • Pyknosis: (Greek “pyknos” – thick, crowded): nuclear shrinkage and increased basophilia o NB: apoptosis may also start with pyknosis • Karyorrhexis: (Greek “rrhexis” – a rupture): fragmentation of the pyknotic nucleus (formation of “nuclear dust”) 7 Karyolysis of Cardiomyocytes and PMN Infiltration, Myocardial Infarction: LM Control 8 Pyknosis on Neurons (Red Neurons), Cerebral Ischemia: LM Control 9 Necrosis: Clinico-Morphologic Patterns • Coagulative necrosis • Liquefactive necrosis • Gangrenous necrosis • Caseous necrosis • Fat necrosis o o Enzymatic fat necrosis Traumatic fat necrosis • Fibrinoid necrosis 10 Coagulative Necrosis • Definition: necrosis with preservation of cellular outlines and tissue architecture • Mechanism o Calcium influx o Denaturation (preservation) of structural proteins and enzymes o No proteolysis • The o most common cause: ischemia Infarction: ischemic necrosis 11 Coagulative Necrosis: Morphology • Histology: anuclear cells with eosinophilic cytoplasm and recognizable cellular outlines • Gross appearance o o Dead tissue is dense and dry. Cut surface is white-grey. • Outcome: an inflammatory response with enzymatic digestion by infiltrating neutrophils and following clearance by macrophages 12 Coagulative Necrosis, Myocardial Infarction: Gross and LM https://openi.nlm.nih.gov/imgs/512/251/1395330/PMC1395330_1476-7120-4-73.png?keywords=ventricular%20free%20wall%20rupture,myocardial%20infarction https://en.wikipedia.org/wiki/Contraction_band_necrosis#/media/File:M I_with_contraction_bands_very_high_mag.jpg 13 Coagulative Necrosis, Renal Infarct: Gross and LM Control 14 Liquefactive Necrosis • Definition: necrosis with loss of cell outlines and tissue architecture • Causes o o Liquefaction of an ischemic area, e.g., cerebral infarct Bacterial or fungal infections Mechanism: inflammatory response and lysis of structural proteins • Outcome: formation of a cavity • o If caused by infection: abscess filled with pus • Pus: a collection of necrotic debris, viable and dead leukocytes, bacteria, fibrin, and other plasma proteins 15 Liquefactive Necrosis, Brain Abscess: Gross and LM 16 Gangrenous Necrosis • Definition: gangrene is a clinical term to define necrosis of organs, which contact with environment (skin, lungs, and gut) o Necrotic changes can be coagulative or liquefactive in nature • Usually black in color due to accumulation of iron sulphide. 17 Liquefactive Necrosis: Morphology • Histology o o Structureless tissue debris (no cellular outlines) Neutrophils (polymorphonuclears, PMNs) • Gross o o appearance Soft and wet tissue Color depends on presence of blood. • Pale (grey), red, brown, or black 18 Gangrene: Clinical Variants • Dry gangrene: ischemic/coagulative necrosis of the limbs (usually lower) o May progress to wet gangrene • Wet gangrene: necrosis with secondary bacterial infection and digestion of already dead tissue (liquefaction) o Gas gangrene: a subtype of wet gangrene, directly caused by bacteria without preceding tissue necrosis 19 Dry (1) and Wet (2) Gangrene: Gross 20 Caseous Necrosis • Definition: a distinct form of necrosis with loss of tissue architecture and cellular outlines, but firm in consistency • Etiology: M. tuberculosis, Histoplasma, etc. • Mechanism: accumulation and following death of macrophages laden with microorganisms • Gross appearance: white (yellow), granular and friable = “cheese-like” (Latin “case” – cheese) • Histology: eosinophilic structureless material 21 Caseous Necrosis, Pulmonary TB: Gross and LM By Yale Rosen from USA - Tuberculosis - Sub-pleural primary (Ghon) focusUploaded by CFCF, CC BY-SA 2.0, https://commons.wikimedia.org/w/index.php?curid=31127299 https://commons.wikimedia.org/wiki/File:Pulmonary_tuberculosis__Necrotizing_granuloma_(6545184743).jpg Yale Rosen from USA, CC BY-SA 2.0 <https://creativecommons.org/licenses/by-sa/2.0>, via 22 Wikimedia Commons Enzymatic Fat Necrosis • Definition: a focal areas of fat destruction resulting from an abnormal release of activated pancreatic enzymes into the substance of the pancreas and the peritoneal cavity • Etiology: acute pancreatitis • Mechanism: injury of acinar cells —> release of lipase —> release of fatty acids from neutral fat —> binding of fatty acids with calcium (saponification) 23 Traumatic Fat Necrosis • Organ affected: female breast • Causes o o Blunt breast trauma Needling procedures: fine needle aspiration and needle core biopsy • Mechanism: mechanical trauma —> cell injury and necrosis of adipose tissue —> inflammation —> calcification and scarring • Significance: mimics breast carcinoma 24 Fat Necrosis: Presentation • • • CT: enlarged pancreas with areas of heterogeneous density Gross appearance: chalky-white calcium deposits Histology o o Necrotic (anucleated) adipocytes Basophilic (blue) amorphous calcium deposits 25 https://commons.wikimedia.org/wiki/File:Fat_necrosis_-_high_mag.jpg Nephron, CC BY-SA 3.0 <https://creativecommons.org/licenses/by-sa/3.0>, via Wikimedia Commons Fibrinoid Necrosis: Definition • Definition: extracellular (not intracellular) degeneration with accumulation of fibrinoid within the injured/necrotic vascular wall o o Fibrinoid: a new protein containing fibrin, collagen, and vessel wall components Loses water and converts to hyaline (not a cartilage! See Accumulations!) • Usually indicates a severe vascular injury 26 Fibrinoid Necrosis: Presentation • Causes o o Severe arterial hypertension (hypertensive emergency) Immune-mediated vasculitides • Gross appearance: not changed • Histology: accumulation of deeply eosinophilic amorphous material within the vascular wall • Significance: irreversible process —> progresses to hyalinization with inhibition of metabolite transport 27 Fibrinoid Necrosis, Pulmonary Arteriole: LM Control https://commons.wikimedia.org/wiki/File:Blutgef%C3%A4%C3%9Fe_(1).jpg Rollroboter, CC BY-SA 3.0 <https://creativecommons.org/licenses/by-sa/3.0>, via Wikimedia Commons https://commons.wikimedia.org/wiki/File:Pulmonary_hypertensionassociated_vasculitis_(4348170903).jpg 28 via Yale Rosen from USA, CC BY-SA 2.0 <https://creativecommons.org/licenses/by-sa/2.0>, Wikimedia Commons The End 29