4 morphological patterns of tissue necrosis
***ELICITS INFLAMMATION = Neutrophils
Structures maintained, tissue intact. Scarring. Characteristic of ischemia (MI). Common in organs with high metabolic demands (Q) - BRAIN IS EXCEPTION = LIQUEFACTIVE. Denaturation of proteins, eosinophilic cells & anucleate ghost cells.
Complete dissolution of tissue. Abscess formation, CNS infarcts. Massive neutrophil infiltration. Release of ROS.
Amorphous obliterated architecture, characteristic of granulomatous inflammation of mycobacterial infection (TB and MAI). Cheesy white areas, nodular caseating granulomas at ghon focus.
ONLY in adipose tissue, common with acute pancreatitis (lipase enzyme release). Free FA complex with Ca and undergo saponification.
Patterns of apoptosis
Cell shrinkage, pyknosis, karyorrhexis/lysis, apoptotic bodies (lipid vacuoles in cytoplasm), phagocytosis of apoptotic bodies, DOES NOT ELICIT INFLAMMATION!
Intrinsic caspase cascade (Cyt. C and procaspase 9)
DNA damage. p53 activates Bax/Bak to replace Bcl-2 (anti-apoptotic) in the mitochondrial membrane. Bax (pro-apoptotic) increases mytochondrial permeability and Cyt.C is released. Cyt.C binds Apaf1 and the Cyt.C-Apaf1 complex activates procaspase 9 --> caspase 9. Caspase 9 activates procaspase 3 --> caspase 3 which induces apoptosis.
Extrinsic caspace cascade (TNF, FAS, procaspase 8)
FAS: upregulates T lymphocyte apoptosis
FasR binds FasL & facilitates R polymerization. Once >3 R together, recruits FADD (Fas activated death domain) and FADD activates PC8 --> C8, C8 activates PC3 --> C3, apoptosis.
Extrinsic caspase cascade (TNF, FAS, procaspase 8)
TNF: upregulates apoptosis of hepatocytes during septic shock
TNF (cytokine) binds TNFR, TNFR interacts w/ TRADD (TNFR activated death domain). TRADD is adapter protein b/w TNFR and FADD --> apoptosis via C8/C3.
Apoptosis examples in:
1. Tissue development
2. Cell turnover
3. Viral infection
4. Tumor growth.
1. Tissue development - HoxA/D, 11/13
2. Normal cell turnover - GI, endometrium, prostatic atrophy after castration
3. Viral infection - HepC in liver
4. Tumor growth - XRT, chemo, endometrium at menopause, small cell lung ca
True/False: Cell death comes in two patterns: necrosis is ALWAYS pathologic while apoptosis can be EITHER physiologic or pathologic?
True/False: Coagulative necrosis results from ischemic necrosis of most tissues with liquefacive necrosis occurs in CNS infarcts/abscesses?
True/False: Caseous necrosis is limited to mycobacterial infections while fat necrosis can be seen in pancreatitis and trauma to adipose tissues?
True/False: Unlike necrosis, apoptosis can be either physiologic or pathologic, requires ATP & does NOT incite inflammatory response?
True/False: Apoptosis proceeds through 2 phases, initiation phase with activation of caspase enzymes and then execution phase with caspase degradation of DNA/proteins?
True/False: There are 2 pathways to initiate apoptosis?
True/False: Apoptosis can be initiated via intrinsic pathway which uses Bax/Bak, Bcl2, Cyt.C?
True/False: Apoptosis can be initiated via extrinsic pathway by instruction from a cell surface receptor using TNF/TRADD or FAS/FADD?
1. Active or passive
2. Physiologic or pathologic
3. Causes inflammation
4. Causes slow changes
5. Has pathways which are NOT conseverved among species
4. False - changes occur quickly. Degradation of nucleus and formation of apoptotic bodies, which are then rapidly engulfed by macrophages.
5. False - highly conserved, reproducible
True/False: Apoptosis & necrosis cannot coexist?
False - these processes can occur together.
True/False: Thrombospondin is an adhesive glycoprotein that is recognized by phagocytes and macrophages released by apoptotic cells, marking them for degradation?
True/False: Myelin figures are derived from degenerating cellular membranes are are found in the plamsa?
False - Myelin figures are derived from degenerating cell membranes and are found in the CYTOPLASM!
True/False: Distrophic calcification occurs in areas of necrosis, whether they are coagulative, caseous, liquefactive & in foci of enzymatic necrosis of fat.
True/False: Metastatic calcification may occur in normal tissues whenever there is hypercalcemia; it also accentuates dystrophic calcification.
True - there are for main causes:
1. Increased TPH secretion and bone resorption
2. Increased destruction of bone secondary to bone tumors
3. Vitamin D disorder
4. Renal failure and retention of phosphate leading to secondary hyperparathyroidism