Membrane blebbing leading to fragmentation - caused by cytoskeletal destruction
Swollen mitochondria and other organelles - mito deposits means death for sure
Reversible Cell Injury
Loss of Microvilli
mildly dilated mito
Irreversible Cell Death
Severely swollen Mito w dark deposits
Cell death resulting from severe damage cell's proteins, organelles, or membranes. Results in enzymatic destruction of contents and leakage into environment. ALWAYS causes inflammation.
Denaturation of structural and enzymatic proteins, leading to cell lysis
Observed in ischemic injuries - except CNS
Karyolysis - nuclear fading, Frayed PM, ghosted dead cell outlines
Complete digestion of cells, creates a gelatinous mass, could be supporative.
Seen with bacterial infection (toxins digest cells) or intense leukocyte response (cell enzymes digest). Indicative of CNS ischemia.
A form of coag - granulomatous inflammation. Cheesy and yellowish - friable.
Central necrosis surrounded by macros and lymphocytes (TH1 cells).
Mycobacterial and fungal infection.
Coag necrosis involving a large part of the body (usually a limb).
Dry - no infection. Wet - infected.
NOT gas gangrene from C perfringens
White a chalky deposits.
Lipase released from inflamed pancreas digests lipids. Fatty acids complex w Ca, creating the deposits.
3 Causes of liquefaction necrosis
Bacterial Infection with toxin release
Intense inflammatory response - leukocyte enzymes
Ischemia in CNS
2 Major causes of Caseating necrosis
Mycobacterium - mostly TB (NOT mycobacterium marinum or leprae)
Fungi is the other one
NOT Caseating - sarcoidosis, brucellosis, tatoos
The 5 mechanisms of cellular injury
Loss of Ca homeostasis
ATP Depletion - How it kills
Ischemia/Hypoxia reduce O2 available for ATP via Ox Phosph
Less ATP - NaKATPase pump stops - Cell potential fails - cell swells - membrane damage
Ca pump (2nd active trans) also fails. Extra Ca opens Mito pore
Ribosomes detach - misfolded protein resp
Mito Damage - how it kills
Mito pore in inner membrane opens under various stimuli. Open pore wrecks gradient - ends ATP production. Increased mito permeability releases cytochrome C - a pro apoptotic signal activating caspases. Mito damage - increases ROS (cant reduce O2)
Loss of Ca homeostasis - how it kills
Cyto Ca increases after injury - released from organelles and through PM.
3) Inflammation is amplified - hypoxic cells make cytokines to activate endothelium Damaged endothelium increases adhesins - both bring in more leukocytes
No modification needed.
Usually damages GI and Kidney
Chemical not biologically active - usually converted in SER of hepatocytes by cytochrome P450.
Cause liver damage
Depletes hepatocyte glutathione, resulting liver necrosis from mito damage
Extrinsinc Apoptosis Pathway
Stimuli - death receptor bound (Fas/FasL, TNF) - activates initiator caspases - activate executioner caspases: endonuclease, cytoskeleton breakdown, protein degradation. Breaks into apoptotic bodies for phagocytosis
Intrinsic Apoptotic Stimuli
GF withdrawl, DNA damage, Protein misfolding (ER stress)
Intrinsic Apoptosis Pathway
Stimuli removes BCL (antagonists) - allows Bax and bak (agonists) to bind. Bax & Bak open mito pore (increase permeability) - allow pro-apoptotics out (cytochrome C). Caspases activated due to pro-apoptotic shifted balance.
3 Promoters of Phagocytosis (for apoptosed cells)
PS on outer leaflet
Ab and complement
Local Deposition of Ca in non viable tissue despite normal blood Ca levels
deposition of Ca in normal tissue w high blood calcium
PTH imbalance - neoplasia
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