HyperplasiaMetaplasiaDysplasia Increase in cell number Change in cell type due to reprogramming of stem cell Proliferation of pre cancerous cells Reversible Reversible Reversible Pathologic hyperplasia can progress to cancer Can progress to dysplasia and cancer Can progress to cancer BPH don't increase risk of cancer Apocrine metaplasia don't increase risk of breast cancer Physiologic (ex pregnancy) Pathologic (ex Etiology: Vit A deficiency (keratomalacia, myositis ossificans) Cellular stress (barret's esophagus) Etiology: Long standing pathologic hyperplasia or metaplaisa Etiology: ProcessesProperties Hyperplasia and HypertrophyUsually, hyperplasia and hypertrophy occur together Permanent cell undergro hypertrophy only cardiac myocytes, skeletal cells, and nerves. Pathologic hyperplasia (not physiologic ex pregnancy)can progress to dysplasia and cancer. Exception is benign prostatic hyperplasia (is pathologic but does not increase risk of cancer). Atrophycan occur by decrease in cell number (apoptosis) or decrease in cell size. Decrease in cell size occurs by ubiquitin proteosome degradation of cytoskeleton and autophagy of cellular components Metaplasiachange in cell type. Mostly affects surface epithelium. Ex (change from squamous to columnar) MOA: occurs by reporgramming of stem cells Reversible Can progress to dysplasia and cancer. Ex Apocrine metaplasia metaplasia seen when fibrocystic changes in breast occur. Vitamin A deficiency can result in metaplasia. Ex keratomalacia and myositis ossificans. Mesenchymal tissue can undergo metaplasia (ex bone, blood vessel, fat etc). ex myositis ossificans inflammation of skeletal muscle reads to metaplasia to bony tissue. Growth adaptations
Fig myositis ossificans Dysplasiadisordered cell growth; proliferation of precancerous cells. Ex Cervical intraepithelial neoplasia Arises from longstanding pathologic hyperplasia or metaplasia Reversible If dysplasia persists, it can progress to cancer. Aplasia Failure of cell production during embryogenesis. Ex unilateral renal agenesis (failure to make 1 kidney) Hypoplasiadecrease in cell production in embryogenesis. Results in relatively small organ. Ex streak ovary in Turner syndrome. Vitamin A is necessary for maintainence of special epithelial tissue in body ex conjucitva of eye. Conjuctiva is a thin delicate membrane that covers eye. Deficiency of vit A can result in metaplasia of cells in conjucitva where cells thicken which is called keratomalacia. Fig keratomalacia. Extras Vitamin A is necessary for maturation of immune system. 15 17 translocation in pt genome causes acute promyelocytic leukemia. The translocation causes mutation in vit A receptor retinoic acid receptor. Mutation of receptors cause immune cells to be trapped in blast stage. Treatment for Promyelocytic leukemia is all trans retinoic acid (drug) which can bind to mutated receptor. Cells can mature and be neutrophil.
What is cellular injury?1. If cellular stress overcomes cell's ability to adapt, then cell gets injured. What does cellular injury depend on?2. Type of stress Severity Type of cell neurons can withstand hypoxia only for 3 5mins. Skeletal muscle can withstand for a very long time. What are causes of hypoxia(low O2 delivery to tissue)? 3. ischemia, hypoxemia (PaO2<60 mm Hg), low O2 carrying capacity (ex anaemia, CO poisoning, methmeglobinemia) What is shock? What are it's causes?4. Shock is a generalized decreased perfusion of a vital organ. Can occur by hypovolemia, cardiogenic, spetic, neurogenic, anaphylactic causes What is Budd chiari syndrome?5. Blockade of hepatic vein can result in hepatic infraction, aka budd chiari syndrome. Most common cause of budd chiari syndrome is polycythemia vera. Polycythemia vera is a disease with too much RBC which leads to clot formation. Another cause is lupus. What will PaO2 and O2 sat be in anaemia?6. PaO2 and O2 sat will be normal in anaemia What will PaO2 and O2 sat be in CO poisoning?7. PaO2 will be the same and O2 sat will reduce. CO binds to Hb 100 times stronger than O2. What are signs/symptoms of CO poisoning?8. Early sign is headache (ask a pt if he has headache if you suspect CO poisoning). Pt may have cherry red color skin. What is methemoglobinemia?9. Normally, Fe in hemoglobin is in 2+ state and can bind to O2. If it gets oxidized to 3+, it can't bind to O2 and this is methemoglobinemia. What will PaO2 and O2 sat be in methemoglobinemia?10. PaO2 will be the same and O2 sat will reduce. What are causes of methemoglobinemia?11. Oxidative stress sulfa drugs, nitrate drugs. Also seen in newborns because their machinery to reduce Fe 3+ isn't good. What are signs/symptoms of methemoglobinemia?12. Cyanosis with chocolate colored blood. What is treatment of methemoglobinemia?13. Cellular injury
Fig right is normal glomerulus and left is coagulative necrosis of glomerulus. Note cellular and organization structure is preserved with loss of nucleus. Area of infracted tissue is often wedge shaped and pale. Wedge points to the blocked blood vessel. When does red infraction (hemorrhagic infraction) occur?5. Red infraction occurs when blood reenters a loosely organized tissue. Ex ischemia of testis, lungs. (is red infraction a type of coagulative necrosis?) Describe liquefactive necrosis6. Necrosis in which enzymatic lysis of cells and proteins result in liquefaction Characteristic of brain (microglial cells destroy the tissue), abscess (neutrophils contain hydrolytic enzyme that destroy the tissue), and pancreatitis (pancreatic enzyme digest the pancreas and liquify; however surrounding fat will have fat necrosis) Describe gangrenous necrosis7. It is coagulative necrosis that resembles mummified tissue (dry gangrene). If infection occurs on dry gangrene, liquifactive necrosis occurs and is called wet gangrene. Characterstic of ischemia of lower limb and GI tract Describe caseous necrosis8. It is soft, friable necrosis with 'cottage cheese' like appearance It's liquefactive necrosis with debris that thickens the soup to make it cheese like Characteristic of granulomatous inflammation of TB or fungal infection (fungal cell wall and micobacterium thickens the soup).
Fig caseous necrosis Describe fat necrosis9. Necrotic fat with Chalky white appearance due to deposition of Ca. MOA When fat cells die by trauma or when fat is broken down by lipase, fatty acids are released. In presence of Ca, saponification occurs which gives it the chalky white apperance. Ca accumulation happens by dystropic calcification. Characteristic cases trauma to fat (ex as in car accident trauma in breast), pancreatitis mediated damage of peripancreatic fat Fig fat necrosis around pancreas What is fibrinoid necrosis10. Necrotic damage to blood vessel Proteins leak into vessel wall which results in bright pink staining of vessel wall in H&E Characteristic of malignant hypertension and vasculitis. Pre eclampsia can cause fibrinoid necrosis of placenta. (benign HTN is chronic low increase in BP that cause slow damage. Malignant hypertension is sudden super elevated BP that is a medical emergency findings such as headache, renal failure, papilledema). Super high BP in malignant HTN can kill vessel wall cells. What are mechanism by which calcium can deposit in human tissue?11. Dystropic calcification Metastatic calcification What is dystropic calcification?12. It's a mechanism by which Ca deposits in a human body (it's abnormal as calcium is not supposed to just randomly accumulate). Mechanism when there's a dead tissue, calcium can accumulate even if serum Ca is normal. Ex in fat necrosis,in tumor as center of tumor might not get enough blood supply and die. What is metastatic calcification?13.
What is metastatic calcification?13. Serum Ca or PO4 is elevated. This elevated stuff can force Ca to accumulate on tissue. It doesn't mean that pt has metastatic cancer. Apoptosis Explain apoptosis. (apoptosis means falling of leaves)14. It is purposeful, energy dependent killing of small group of cells Examples Endometrial shredding during menstruation, removal of cells in embryogenesis, CD8 cell mediated killing of virally infected cells What is mechanism of apoptosis?15. Cell shrinks (and becomes eosinophilicdue to concentration of cytoplasm) and nucleus also shrinks and fragments. Apoptotic bodies fall from cell like leaves fall from tree. Then they are eaten by macrophage. No inflammation occurs Fig compare the pink apoptotic cell to it's surrounding neighbors What is biochemical pathway leading to apoptosis?16. Caspases activate proteases that break down cytoskeleton. Caspases also activate endonucleases that break down nucleus. Caspase activation is the key step. What 3 pathways lead to caspase activation? (HY)17. Intrinsic mitochondrial pathway Bcl2 is a protein whose function is to stabilize mitochondrial membrane so that cytochrome C from mitochondria can't leak out. Due to membrane damage (cellular injury), DNA damage, or decreased hormonal stimulation of cell (ex endometrial cells in lack of estrogen), Bcl2 can be inactivated. Leakage of cytochrome C will then activate caspase. Example FAS ligand binds to FAS death receptor(CD95) on target cell and target cell dies via activation of caspases. Case report new CD8+ T cells from bone marrow undergo positive selection (I.e., if they can bind to self antigen on MHC I molecule, they get to live) and negative selection (i.e., if they bind to self antigen on MHC I molecule very strongly, they die) in thymus. The killing of these young T cells in negative selection happens by binding of FAS ligand to FAS death receptor on T cells. Another example TNF binds to TNF receptor on target cell and cell dies. Extrinsic receptor ligand pathway Cytotoxic CD8+ T cell pathway When CD8+ cells recognize foreign antigen on MHC I receptors, they release perforins that make holes on target cell. Then, they release granzyme that enter target cell and activate caspases.