in which disease is defective ubiquination thought to be the cause of illness?
neurodegenerative diseases like parkinsons, also storage diseases and aging
what is the function of chaperones?
they maintain correct protein folding and degrade misfolded proteins
what are 3 examples of chaperonopathies?
retinitis pigmentosa, hereditary spastic paraplegia, von Hippel-Lindau disease (VHL)
What is the pathology behind von Hippel-Lindau disease (VHL)?
genetic mutation in the gene encoding for chaperone proteins = chaperonopathy. protein misfolding inactivates tumor supressors, leading to tumors of kidney, adrenals and brain.
what are 5 examples of channelopathies?
cardiac arrythmias, myotonias, familial periodic paralysis, epilepsy and some Diabetes M
where is the defect in the diabetes mellitus?
it is a channelopathy, mutation of the K+ channels that regulate insulin secretion
what are the steps of necrosis?
1. injury causes cytoplasm to become eosinophilic, nucleus becomes dense and pyknotic
2. karyorrhexis - nuclear fragmentation *** histological sign of necrosis
3. karyolysis - dead cell, nucleus dissolves, still eosinophilic cyto.
4. cell ruptures, releasing enzymes (which you can measure - useful clinically)
what are two types of "patterns" seen under light microscopy in reversible injury
1. hydropic change/ vacuolar degeneration - caused by extracellular water getting into the cell. cell swells and compresses surrounding microvasculature.
2. fatty change (steatosis) - abnormal accumulation of fat within parenchymal cells "signet cell ring"
what findings might you see in a male with alcoholic steatosis
shrunken testicles! fatty liver steatosis causes increases in estrogen = small testes.
what would the liver look like in an autopsy of someone with alcoholic steatosis? heart?
liver would be large, yellow and greasy. heart is tigered - brown and yellow stripes (this is prolonged moderate hypoxia.
what is the cause of coagulative necrosis?
hypoxic cell death EXCEPT THE BRAIN! this causes cell proteins to denature and coagulate
where else can liquefactive necrosis be found?
in abscesses, bacterial infections liquefy cells and leave an abscess with leukocytes.
what is the primary disease associated with caseous necrosis? what do these lesions look like?
tuberculosis - they are white, cheesy lesions.
what is the mechanism behind enzymatic fat necrosis
fats get digested by lipases and the FFas combine with calcium to make a chalky precip.
in what condition do you see enzymatic fat necrosis?
acute pancreatitis... lipases escape into the tissue and break up fats, FFAs combine with calcium to make a chalky precip.
what is the difference between gangrene and necrosis?
gangrene = everything is dead (muscle, CT, bone, etc). necrosis is just one small part.
major difference between dry and wet gangrene
wet gangrene is with an infection, dry is due to ischemia
what types of necrosis accompany
1. dry gangrene
2. wet gangrene
1. dry gangrene usually goes along with coagulative necrosis
2. wet gangrene usually goes along with liquefactive necrosis.
which genes and which mutated genes (2) inhibit apoptosis, thereby causing cancer?
BCL2 suppresses apoptosis
mutation in p53 and bax suppresses apoptosis (usually it enhances apoptosis)
what are 4 diseases that are caused by excessive apoptosis?
why is the BCL-2 gene a problem
bcl-2 gene suppresses apoptosis. if apoptosis is suppressed, more effed up cells survive = more mutations --> can lead to cancer
what is the relationship between p53 and bax genes and why do we care
p53 normally enhances bax gene expression --> stimulates apoptosis. if p53 is mutated, bax is suppressed and so is apoptosis.
what are heat shock proteins and why do we care?
heat shock proteins are chaperones (ubiquitin) and rescue proteins of injured cells.
in the heart, what do you see in moderate prolonged hypoxia versus severe hypoxia?
moderate hypoxia is the tigered effect - striations of fatty yellow myocardium (fatty steatosis) with bands of healthy myocardium.
severe hypoxia is more uniform and yellow (fatty)
what are foam cells?
foam cells are macrophages with intracellular accumulations of lipids (trig and chl) in atherosclerosis. their multiple lipid filled vacuoles make them look foamy
what are the two types of calcium deposits? what are they caused by?
dystrophic calcification or metastatic calcification
in which type of calcification are serum calcium levels normal? in which are they elevated?
serum calcium levels are normal in dystrophic calcification and are elevated in metastatic calcification.
what type of calcification only affects arteries, damaged heart valves, around worms or necrotic tissue?
dystrophic calcification- normal serum calcium levels
what is the definition of metastatic calcification?
calcium deposits in normal tissue because of fked up calcium metabolism
what is the mnemonic for metastatic calcification?
Malignancy (mult myeloma)
Hyperparathyroid/hyper vit D
where does metastatic calcification primarily happen?
walls of arteries, kidneys, gastric mucosa and lungs
what is pressure atrophy and what is an example?
pressure atrophy is atrophy that occurs due to prolonged pressure as in an aortic aneurysm on the sternum or spine
what is senile atrophy?
atrophy that is due to the aging process, organs have fewer cells and are smaller but usually retain their shape.
what types of cells undergo hypertrophy? hyperplasia?
permanent cells like heart, brain undergo hypertrophy because they cannot reenter mitosis.
labile cells can undergo hyperplasia (skin, bone marrow)
what are some examples of hypertrophy?
weight lifters and skeletal muscle, cardiac hypertrophy in distance runners, L ventricular hypertrophy in aortic stenosis or high BP, growth of uterus during pregnancy
what is an ex of endocrine hyperplasia
estrogen producing endometrial tumor causing prolif of endometrium
what are some causes of metaplasia?
chronic irritation or infection, vitamin A deficiency, renal and cholecystic calculi causes change from more specialized cells to less specialized.
what happens with connective tissue metaplasia?
after injury, fibroblasts --> osteoblasts. it is associated with repair.
what is myositis ossificans?
it is a type of CT metaplasia - damage to muscle produces bone at the hamstrings also called riders bone.
what is the difference between dysplasia and metaplasia?
metaplasia is the replacement of one type of cell with another, ie: intestinal metaplasia when acid secreting cells turn into colonic type (columnar) due to repeated irritation or infection.
dysplasia is abnormal cells, all different sizes, shapes and orientations.
what is hyperchromasia?
hyperchromasia is abnormal chromatin that forms clumps with an irregular and thickened nuclear mbn.