Term
|
Definition
| Complete absence of an organ and its associated primordium. |
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Term
|
Definition
| Absence of an organ due to failure of development of the primordium. |
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Term
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Definition
| Incomplete development or decreased size of an organ with decreased number of cells. |
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Term
| Describe origins of word "diabetes." |
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Definition
| From Greek meaning "siphon" because pts passed water like a "siphon." |
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Term
| Describe origins of word "mellitus." |
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Definition
| From Latin meaning "honey-sweet" because pts' urine tasted sweet. |
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Term
| Describe where insulin is synthesized and how it is prepped for secretion. |
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Definition
| The insulin gene is expressed in B cells of the pancreatic islets; preproinsulin is synthesized in the RER and delivered to Golgi; proteolytic steps generate mature insulin and C-peptide; both are stored in secretory granules and secreted upon physiologic stimulation. |
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Term
| Describe how insulin is released in response to glucose in pancreas. |
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Definition
| Glucose uptake occurs in pancreatic B cells, facilitated by insulin-independent glucose-transporter (GLUT2). Glucose passes through glycolysis and creates ATP, which inhibits the activity of the ATP-sensitive K+ channel, leading to membrane depoartization and influx of extracellular Ca. Increase in Ca stimulates secretion of insulin. |
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Term
| What are the general effects of insulin in adipose tissue? |
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Definition
Increase glucose uptake
Increase lipogenesis
Decrease lipolysis |
|
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Term
| What are the general effects of insulin in striated muscle? |
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Definition
Increase glucose uptake
Increase glycogen synthesis
Increase protein synthesis |
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Term
| What are the general affects of insulin in liver? |
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Definition
Decrease gluconeogenesis
Increase glycogen synthesis
Increase lipogenesis |
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Term
| Describe the insulin receptor. |
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Definition
| Tetrameric protein composed of two alpha and two beta subunits. The beta subunits have tyrosine kinase activity. |
|
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Term
| Describe the insulin signaling pathway. |
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Definition
| Insulin binds to the insulin receptor, which activates the beta subunit tyrosine kinase resulting in autophosphorylation and phosphorylation of insulin receptor substrate (IRS) proteins; IRS-PI3K-PKB pathway activates trafficking of GLUT4 to the PM, which promotes glucose uptake. |
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Term
| What is the genetic basis for Type 1 DM? |
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Definition
| There are over a dozen susceptibility loci; the most important is the HLA locus on chromosome 6p21, which can contribute up to 50% of genetic susceptibility. |
|
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Term
| What are three mechanisms proposed to explain the role of viruses in induction of autoimmunity with Type 1 DM? |
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Definition
1) "Bydstander" damage where viral infections induce islet injury and inflammation.
2) Viruses produce proteins that mimic B-cell antigens.
3) "viral deja vu" where viral infections in early life might persist in tissue of interest and subsequent re-infection leads to immune response against the infected islet cell. |
|
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Term
| What is the fundamental abnormality in Type 1 DM? |
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Definition
| Failure of self-tolerance in T-cells, which are poised to respond to self-antigens thus, the presence of islet cell antibodies is used as a predictive marker for the disease. |
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Term
| What is the most likely genetic association with Type 2 DM? |
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Definition
| Transcription factor 7-like-2 on chromosome 10q, which is not involved in immune tolerance and regulation; it is not an autoimmune basis. |
|
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Term
| What are the two metabolic defects that characterize Type 2 DM? |
|
Definition
1) decreased response of peripheral tissues to insulin
2) B-cell dysfunction that is manifested as inadequate insulin secretion in the face of insulin resistance and hyperglycemia. |
|
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Term
| What are the effects of insulin resistance? |
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Definition
| Decreased uptake of glucose in muscle, reduced glycolysis and fatty acid oxidation in the liver, and an inability to suppress hepatic gluconeogenesis. |
|
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Term
| What are the 4 ways obesity impacts insulin sensitivity? |
|
Definition
1) Excess intracellular nonesterified fatty acids (NEFAs) overwhelm the fatty acid oxidation pathways leading to decreased insulin sensitivity
2) Adiponectin levels are decreased in obesity, which decreases the activity of the AMP-activated protein kinase (AMPK) hence, lowering insulin sensitivity
3) Adipose tissue secretes pro-inflammatory cytokines which increase cellular "stress" causing insulin resistance
4) Adipose tissue secretes PPAR-gamma which shifts deposition of NEFAs to adipose tissue |
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Term
| Describe B-cell activity in the obese for progression of Type 2 DM. |
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Definition
| Insulin resistance is caused by increased adipokines, free fatty acids and chronic inflammation in adipose tissue; pancreatic B cells compensate with increased insulin secretion ultimately leading to B-cell failure. |
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Term
| What is the key mediator of long-term DM complications? |
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Definition
| Persistant hyperglycemia (glucotoxicity) |
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Term
| Define HbA1C and its importance in DM. |
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Definition
| HbA1C is glycosylated hemoglobin which is formed by nonenzymatic covalent addition of glucose moieties to hemoglobin in red cells. It provides a measure of glycemic control over the lifespan of a red cell and is not affected by day-to-day variations. Should be below 7% in diabetics. |
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Term
| What are the three metabolic pathways causing deleterious effects of persistent hyperglycemia on peripheral tissues? |
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Definition
1) Formation of advanced glycation end products (AGEs)
2) Activation of intracellular protein kinase C (PKC) and second messenger DAG
3) Intracellular hyperglycemia |
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Term
| What is the principle metabolic function of insulin? |
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Definition
| To increase the rate of glucose transport into the striated muscle cells and adipocytes, thus providing an increased source of energy. |
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Term
| Once glucose is taken up by striated muscle cells or adipocytes via insulin action, what is its fate? |
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Definition
| In muscle, the glucose is either stored as glycogen or oxidized to generate ATP. In adipocytes, it is stored as lipid while inhibiting lipid degradation. |
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Term
| What kind of hormone is insulin and what happens when it is deficient? |
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Definition
| Anabolic hormone; deficiency results in a catabolic state that affects glucose, fat and protein metabolism. |
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Term
| What are the long-term effects of both types of DM? |
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Definition
| Macrovascular complications such as MI, renal vascular insufficiency; diabetic nephropathy; visual impairment; diabetic neuropathy; enhanced susceptibility to infections |
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Term
| How does insulin deficiency cause ketoacidosis? |
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Definition
| Decreased insulin stimulates lipoprotein lipase, which breaks down adipose stores and FFA levels are increased. At the liver, FFA are esterified to fatty acyl CoA; the oxidation of fatty acyl CoA by hepatic mit produces ketone bodies. High rate of formation causes ketoacidosis. |
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Term
| What is the effect of epinephrine on Type 1 diabetics? |
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Definition
| This catecholamine hormone blocks any residual insulin action and stimulates secretion of glucagon, leading to severe hyperglycemia. |
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Term
| What are the four mechanisms of intracellular accumulations? |
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Definition
1) abnormal metabolism
2) defects in protein folding and transport; inability to degrade abnormal protein
3) defects in enzymes required for metabolism of substance
4) ingestion of indigestible materials |
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Term
| What are resulting conditions from accumulation of cholesterol in intracellular vacuoles? |
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Definition
| atherosclerosis, xanthomas, cholesterolosis, niemann-pick disease |
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Term
| What causes excess accumulation of triglycerides within the liver and what is this condition called? |
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Definition
| Caused by excessive entry or defective metabolism and export of lipids. It is called steatosis or fatty change. |
|
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Term
| How does alcohol cause steatosis? |
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Definition
| Alcohol is a hepatotoxin that alters mitochondrial and microsomal functions, leading to increased synthesis and reduced breakdown of lipids. |
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Term
| What is the morphology of steatosis in the liver and heart? |
|
Definition
Both show clear vacuoles within parenchymal cells.
Liver: organ enlarges and becomes yellow, nucleus is displaced to periphery of cell, fatty cysts
Heart: small droplets of lipid, bands of yellowed myocardium |
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Term
| What is the appearance of intracellular accumulations of protein? |
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Definition
| Rounded, eosinophilic droplets, vacuoles, or aggregates in the cytoplasm. |
|
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Term
| What are some causes of protein excess within cells? |
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Definition
| reabsorption droplets in proximal renal tubules, Russell bodies, defective intracellular transport and secretion of critical proteins, accumulation of cytoskeletal proteins, aggregation of abnormal proteins |
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Term
| What does 'hyalin' refer to? |
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Definition
| An alteration within cells or in the extracellular space that gives a homogenous, glassy, pink appearance in routine histologic sections stained with H&E; caused by various accumulations. |
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Term
| What is the intracellular accumulation of glycogen called and how does it appear? |
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Definition
| Glycogenoses; appear as clear vacuoles within the cytoplasm. |
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Term
| Describe the accumulation of exogenous pigment such as carbon. |
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Definition
| Blackens the tissues of the lungs (anthracosis) and involved lymph nodes. |
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Term
| Describe the accumulation of the endogenous pigment lipofuscin. |
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Definition
| Sign of free radical injury and lipid peroxidation; appears as yellow-brown, finely granular cytoplasmic, often perinuclear, pigment. |
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Term
| Describe the accumulation of the endogenous pigment melanin. |
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Definition
| Non-hemoglobin-derived, brown-black pigment formed when the enzyme tyrosinase catalyzes the oxidation of tyrosine to dihydroxyphenylalanine in melanocytes. |
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Term
| What causes the accumulation of the endogenous pigment hemosiderin? How does it look like? |
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Definition
| When there is a local or systemic excess of iron, ferritin forms hemosiderin granules. golden yellow-to-brown, granular or crystalline pigment. |
|
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Term
| What are the 3 main causes of hemosiderosis? |
|
Definition
1) increased absorption of dietary iron
2) hemolytic anemias
3) repeated blood transfusions |
|
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Term
| What is the normal major pigment found in bile? |
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Definition
| Bilirubin--derived from Hb but contains no iron. |
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Term
| What is pathologic calcification? |
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Definition
| Abnormal tissue deposition of Ca salts, together with smaller amounts of Fe, Mg, and other mineral salts. |
|
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Term
| What is the site for dystrophic calcification? |
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Definition
| Areas of necrosis, commonly in aging or damaged heart valves. |
|
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Term
| What is the pathogenic process (4) of calcium concentration in membrane-bound vesicles in cells for dystrophic calcification? |
|
Definition
1) Ca binds to phospholipids present in vesicle membrane
2) Phosphatases associated with the membrane generate P groups
3) Cycle of Ca and P binding is repeated
4) Structural change occurs in the arrangement of Ca and P groups, generating a microcrystal |
|
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Term
| What is the morphology of dystrophic calcification? |
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Definition
| Ca salts appear as fine, white granules or clumps, often felt as gritty deposits. Heterotopic bone may be formed; layering can lead to psammoma bodies. |
|
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Term
| What are the 4 principal causes of hypercalcemia? |
|
Definition
1) increased secretion of PTH with subsequent bone resorption
2) destruction of bone tissue
3) vitamin D-related disorders
4) renal failure |
|
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Term
| Where does metastatic calcification occur? |
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Definition
| In normal tissues wherever there is hypercalcemia; principally in tissues that have an internal alkaline compartment that predisposes them to metastatic calcification. |
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Term
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Definition
| Result of a progressive decline in cellular function and viability caused by genetic abnormalities and the accumulation of cellular and molecular damage due to the effects of exposure to exogenous influences. |
|
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Term
| What are the principal changes that contribute to cellular aging? |
|
Definition
1) decreased cellular replication
2) accumulation of metabolic and genetic damage |
|
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Term
| What is the mechanism for progressive senescence of cells? |
|
Definition
| With each cell division there is incomplete replication of chromosome ends (telomere shortening), which ultimately results in cell cycle arrest. |
|
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Term
| What is a protective response to counterbalance progressive damage in cells? |
|
Definition
| Recognition and repair of damaged DNA by DNA helicase. |
|
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Term
| How do sirtuins help prolong life? |
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Definition
| Calorie restriction and red wine helps longevity through sirtuins, which have histone deacetylase activity. This promotes the expression of certain genes whose products increase longevity. |
|
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Term
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Definition
| Increase in number of cells, resulting in increased mass of organ or tissue—occurs in cells capable of dividing. |
|
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Term
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Definition
| Increase in size of cells, resulting in increase in size of organs—occurs in nondividing and dividing cells; most common stimulus is increased demand. |
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Term
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Definition
| Reduced size of an organ or tissue resulting from a decrease in cell size and number; causes include disuse, loss of innervation, diminished blood supply, inadequate nutrition, loss of endocrine stimulation, pressure. |
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Term
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Definition
| Reversible change in which one differentiated cell type (epithelial or mesenchymal) is replaced by another cell type; most common is columnar to squamous. |
|
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Term
| What is the characteristic microscopic features of HSV? |
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Definition
| large, pink to purple intranuclear inclusions consisting of intact and disrupted virions with stained host cell chromatin pushed to edges of nucleus; also produces inclusion-bearing multinucleated syncytia. |
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Term
|
Definition
| Pathway of cell death induced by tightly regulated pathway in which cells destined to die activate enzymes that degrade the cells’ own nuclear DNA and nuclear/cytoplasmic proteins, which are packaged into apoptotic bodies. No inflammation. |
|
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Term
| Give ex of physiologic situations for apoptosis. |
|
Definition
- Programmed destruction of cells during embryogenesis
- Involution of hormone-dependent tissues upon hormone withdrawal
- Cell loss in proliferating cell populations
- Elimination of potentially harmful self-reactive lymphocytes
- Death of host cells that have served its useful purpose such as neutrophils in acute inflammatory response |
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Term
| Give ex of pathologic situations for apoptosis. |
|
Definition
- DNA damage (ie radiation)
- Accumulation of misfolded proteins
- Cell death in certain infections
- Pathologic atrophy in parenchymal organs after duct obstruction |
|
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Term
| What does VINDICATE stand for wrt cell injury? |
|
Definition
Vascular
Infections
Neoplastic
Drugs/Toxins
Iatrogenic/Idiopathic
Congenital/Developmental/Genetic
Autoimmune/Immune
Trauma
Endocrine/Metabolic/Nutritional |
|
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Term
|
Definition
| When a cell can't divide anymore. |
|
|
Term
| What is the appearance of coagulative necrosis? |
|
Definition
| eosinophilic, anucleate cells, firm texture on tissue, inflammatory infiltrate, yellow |
|
|
Term
| What causes coagulative necrosis? |
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Definition
| Ischemia and other injury which denature structural proteins and enzymes, blocks proteolysis of dead cells. |
|
|
Term
| What is the appearance of liquefactive necrosis? |
|
Definition
| Transformation of tissue into liquid viscous mass, creamy yellow pus. |
|
|
Term
| What causes liquefactive necrosis? |
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Definition
| Digestion of dead cells, microbes stimulate accumulation of leukocytes and liberation of enzymes from cells, hypoxic death of cells |
|
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Term
| What is the appearance of gangrenous necrosis? |
|
Definition
| no specific pattern of cell death, looks like coagulative necrosis in lower limbs |
|
|
Term
| What is the cause of gangrenous necrosis? |
|
Definition
| loss of blood supply, action of degradative enzymes in bacteria and attracted leukocytes |
|
|
Term
| What is the appearance of enzymatic fat necrosis? |
|
Definition
| focal areas of fat destruction, chalky-white areas, shadowy outlines of necrotic fat cells w/ basophilic Ca soap formation at sites of lipid breakdown |
|
|
Term
| What is the cause of enzymatic fat necrosis? |
|
Definition
| release of activated pancreatic lipases into substance of pancrease and peritoneal cavity, pancreatic enzymes leak out of acinar cells and liquefy membranes of fat cells in peritoneum |
|
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Term
| What is the appearance of gas gangrene? |
|
Definition
| large, bullous vesicles that rupture, gas bubbles from bacterial fermentation, soft blue-black friable and semi-fluid |
|
|
Term
| What is the cause of gas gangrene? |
|
Definition
| massive protelytic action of released bacterial enzymes, extensive hemolysis, marked vascular injury w/ thrombosis, marked edema and enzymatic necrosis, severe myonecrosis |
|
|
Term
| What is the appearance of caseous necrosis? |
|
Definition
| "cheeselike", friable yellow-white appearance, collection of fragmented or lysed cells, amorphous granular debris enclosed within distinctive inflammatory border |
|
|
Term
| What is the cause of caseous necrosis? |
|
Definition
|
|
Term
| Where does tinea versicolor occur on the body and what layer of the skin? |
|
Definition
| upper trunk and present in the anucleate cornified layer of lesional skin, hair, or nails. |
|
|
Term
| Define autophagy and its effects upon cellular organelles. |
|
Definition
| Process in which a cell eats its own contents; organelles and cytosol are sequestered from cytoplasm in autophagic vacuoles which fuse with lysosomes to form an autophagolysosome where it is digested |
|
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Term
|
Definition
| Digestion by lysosomes of extracellular material that have entered the cell via phagocytosis or pinocytosis. |
|
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Term
|
Definition
| aka glycogen storage disease: results from hereditary deficiency of one of the enzymes involved in the synthesis or sequential degradation of glycogen |
|
|
Term
| What is the enzyme deficiency of the hepatic glycogenoses? |
|
Definition
|
|
Term
| What is the enzyme deficiency in myopathic glycogenoses? |
|
Definition
|
|
Term
| What deficiencies in glycogenoses did not fit into hepatic or myopathic categories? |
|
Definition
1) deficiency of alpha-glucosidase (acid maltase)
2) lack of branching enzyme |
|
|
Term
| What are morphologic changes from hepatic glycogenoses? |
|
Definition
| hepatomegaly and renomegaly from intracytoplasmic accumulations of glycogen |
|
|
Term
| What are morphologic changes of myopathic glycogenoses? |
|
Definition
| accumulations of glycogen in subsarcolemmal of skeletal muscle |
|
|
Term
| What are morphologic changes in miscellaneous glycogenoses? |
|
Definition
| mild hepatomegaly, cardiomegaly |
|
|
Term
| What are the clinical features of hepatic glycogenoses? |
|
Definition
| hepatomegaly, hypoglycemia, hyperlipidemia, bleeding tendency, failure to thrive, stunted growth |
|
|
Term
| What are the clinical features of myopathic glycogenoses? |
|
Definition
| painful cramps with exercise, myoglobinuria |
|
|
Term
| What are clinical features of miscellaneous glycogenoses? |
|
Definition
| massive cardiomegaly, muscle hypotonia |
|
|
Term
| What are two properties of hydrolytic enzymes such as those found in lysosomes? |
|
Definition
1) function in acidic milieu of lysosomes
2) enzymes constitute a special category of secretory proteins destined for intracellular organelles |
|
|
Term
| Where are lysosomal enzymes synthesized and transported? |
|
Definition
| synthesized in ER and transported to Golgi |
|
|
Term
| What specific post-translational modification do lysosomal enzymes undergo? |
|
Definition
| attachment of terminal mannose-6-phosphate groups to some of oligosaccharide side chains, serving as recognition sites by receptors |
|
|
Term
| What major process remains incomplete with an inherited deficiency of a functional lysosomal enzyme? |
|
Definition
| Catabolism of substrated from stophagy and heterophagy leading to accumulation of partially degraded insoluble metabolite within lysosomes |
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