Term
| What initiates normal cell replication? |
|
Definition
| GF binding to and activating its receptor => activation of signal-transduction proteins. |
|
|
Term
| What causes DNA transcription that promotes entrance to the cell cycle? |
|
Definition
| Signal tranduction thru the nucleus => activation of nuclear transcription regulatory factors. |
|
|
Term
|
Definition
| transient intracellular signal transduction |
|
|
Term
| How are Ras proteins activated? |
|
Definition
|
|
Term
| What does activated Ras stimulate? |
|
Definition
| MAP kinase cascade => nuclear signals for proliferation |
|
|
Term
| What binds to Ras to inactivate it & therefore terminate signal transduction? |
|
Definition
| GTPase-activating proteins (GAPs) (enhance GTP hydrolysis) |
|
|
Term
| Which GAP specifically is important in the termination of Ras protein signal transduction? |
|
Definition
|
|
Term
| Does Ras need GDP or GTP for activation? |
|
Definition
|
|
Term
| What does MYC encode for? |
|
Definition
| nuclear protein integral to both cell proliferation & apoptosis |
|
|
Term
| What are the 2 ways MYC can be activated? |
|
Definition
1) with GF binding GF receptor => mitogenic signal transduction to the nucleus
or
2) without GF stimulation |
|
|
Term
| What happens in MYC is activated without GF stimulation? |
|
Definition
|
|
Term
| How does MYC induce transcription activation? |
|
Definition
| MYC-MAX protein forms and binds to DNA |
|
|
Term
| What 2 things must be transcriptionally activated to enter the cell cycle? |
|
Definition
|
|
Term
| What are the 3 cell cycle regulators? |
|
Definition
cyclins
CDKs (cyclin-dependent kinases)
CDK inhibitors |
|
|
Term
| How do CDKs become phosphoylated & activated? |
|
Definition
| inactive CDK binds to cell cycle-specific cyclins |
|
|
Term
| How do activated CDKs promote progression through the cell cycle? |
|
Definition
| they phosphoylate key proteins necessary |
|
|
Term
| What is bound to the hypophosphorylated retinoblastoma (RB) protein to inhibit it's function in G0 & G1? |
|
Definition
| E2F transcription factor complex |
|
|
Term
| When in the cell cycle do organelles double in number? |
|
Definition
|
|
Term
| What leads to the phosphorylation of RB in G1? |
|
Definition
| synthesis of cyclin D & cyclin E => phosphorylated D/CDK & E/CDK |
|
|
Term
| What causes the dissociation of E2F from RB & transcriptional activation of E2F-targeted genes in G1? |
|
Definition
|
|
Term
| What happens in S phase of the cell cycle? |
|
Definition
| nuclear DNA is replicated |
|
|
Term
| What cyclin & therefore cyclin/CDK complex is formed in the S phase of the cell cycle? |
|
Definition
|
|
Term
| When in the cell cycle are new membrane formed in preparation for cell division? |
|
Definition
|
|
Term
| What is done in G2 to initiate mitosis? |
|
Definition
| cyclin B synthesis => B/CDK |
|
|
Term
| What are the 5 phases of mitosis? |
|
Definition
1)Prophase
2)Prometaphase
3)Metaphase
4)Anaphase
5)Telophase |
|
|
Term
| What characterizes completion of mitosis? |
|
Definition
| Removal of phosphate groups from RB which regenerates hypophosphorylated form |
|
|
Term
When is the restriction point in the cell cycle?
What regulates it? |
|
Definition
| in the middle of G1
regulated by GFs |
|
|
Term
| Where in the cell cycle are the checkpoints for DNA damage? |
|
Definition
|
|
Term
| When is RB phosphorylated in the cell cycle? |
|
Definition
|
|
Term
| What do CDK inhibitor respond to? |
|
Definition
| growth suppressing signals |
|
|
Term
| How do CDK inhibitors block progression of the cell cycle? |
|
Definition
| inactivating cyclin/CDK complexes or inhibiting their formation |
|
|
Term
|
Definition
| check for DNA defect prior to replication |
|
|
Term
| What happens if there's a DNA defect detected at the G1/S checkpoint? |
|
Definition
| increase levels & activation of p53 => up regulation of p21 => cell cycle arrest & stimulation of DNA repair |
|
|
Term
| What happens if there is a DNA defect detected in the G1/S checkpoint, and it's successfully repaired? |
|
Definition
| p53-induced transcriptional activation & formation of self-degrading protein => cell cycle resumed |
|
|
Term
| What happens if there is a DNA defect detected at G1/S checkpoint, but it's not repaired successfully? |
|
Definition
| p53-induced transcriptional activation of pro-apoptotic genes, repression of pro-proliferative & anti-apoptotic genes => apoptosis |
|
|
Term
|
Definition
| check for DNA defect after replication & before separation of the chromatids |
|
|
Term
| What happens if there is a DNA defect detected at the G2/M checkpoint? |
|
Definition
| cell cycle arrest via p53-dependent & independent processes. |
|
|
Term
|
Definition
| increased number of cells => increased tissue volume |
|
|
Term
| What 3 stimuli can cause hyperplasia? |
|
Definition
1) hormones
2) GF
3) cytokines |
|
|
Term
| What is the mechanism of cell proliferation in hyperplasia? |
|
Definition
| usually increased transcription of genes encoding GF & receptors and cell cycle promotors. Also, there's occasional recruitment of stem cells. |
|
|
Term
| What induces glandular epithelial cell proliferation in female breast in puberty & pregnancy? |
|
Definition
|
|
Term
| What induces smooth muscle cell proliferation in uterus in pregnancy? |
|
Definition
|
|
Term
| When might hyperplasia be compensatory? |
|
Definition
Partial hepatectomy (regeneration of liver needed)
unilateral nephrectomy (enlargement of contralateral kidney) |
|
|
Term
| What causes the endometrium in the uterus undergo hyperplasia? |
|
Definition
| prolonged unopposed estrogen stimulation |
|
|
Term
| Where is hyperplasia seen in wound healing & repair? |
|
Definition
|
|
Term
| Where does HPV cause hyperplasia? |
|
Definition
|
|
Term
|
Definition
| increased cell size due to increased synthesis of cellular components => increased tissue volume |
|
|
Term
| Can hypertrophy or hyperplasia been seen in non-mitotic cells? |
|
Definition
hypertrophy only.
hyperplasia can only been seen in cells with mitotic capability. |
|
|
Term
| What 2 stimuli can cause hypertrophy? |
|
Definition
1) hormones
2) increased workload |
|
|
Term
| Where is hypertrophy seen in pregnancy? |
|
Definition
| increased uterine smooth muscle cell size |
|
|
Term
| What causes hypertophy in skeletal muscle cells of weightlifters? |
|
Definition
|
|
Term
| When is hypertrophy seen in cardiac myocytes? |
|
Definition
| increased workload due to hypertension or stenotic outflow valve |
|
|
Term
| What 2 signals cause hypertrophy in cardiac myocytes? |
|
Definition
|
|
Term
| What does the heart do in response to increased workload? |
|
Definition
| increase transcription or re-express fetal genes to increase synthesis of proteins to increase cardiac function & decrease workload |
|
|
Term
|
Definition
| decreased cell size due to decreased cellular components => decreased tissue volume |
|
|
Term
| What 8 stimuli can cause atrophy? |
|
Definition
1) decreased workload
2) denervation
3) decreased vascular supply
4) malnutrition
5) decreased hormonal stimuli
6) aging
7) compression
8) cytokines
note: some of these can occur simulaneously |
|
|
Term
| Why do we not have some of our embryologic structures as adults? |
|
Definition
|
|
Term
| What in the postpartum mother atrophies? |
|
Definition
|
|
Term
| What in the postmenopausal female atrophies? |
|
Definition
|
|
Term
| What can atrophy after a spinal cord trauma? |
|
Definition
|
|
Term
| What can cause cerebral atrophy? |
|
Definition
| decreased blood flow & aging |
|
|
Term
| What atrophies due to starvation (malnutrition)? |
|
Definition
|
|
Term
|
Definition
| increased destruction of cellular components by lysosomes & proteasomes => incrased autophagic vacuoles |
|
|
Term
| What may atrophy be accompanying? |
|
Definition
| apoptosis/necrosis => fatty infiltration |
|
|
Term
|
Definition
| replacement of one mature cell type by another |
|
|
Term
| What stimuli initiates metaplasia? |
|
Definition
| chronic tissue trauma/irritation |
|
|
Term
| How does chronic tissue trauma/irritation cause metaplasia? |
|
Definition
| leads to signals by cytokines, GF & ECM components => transcriptional change => differentiation towards a new cell |
|
|
Term
| What epithelial metaplasia does cigarette smoke cause to the epithelium of the RT? |
|
Definition
| pseudostratified, ciliated, columnar epi => stratified squamous |
|
|
Term
| What epithelial metaplasia does gastroesophageal reflux cause to the epithelium of the lower esophagus? |
|
Definition
| stratified squamous => gastric & intestinal-type glandular epi. |
|
|
Term
| What CT metaplasia can be seen after trauma to skeletal muscle? |
|
Definition
myosis ossificans
(skeletal muscle => bone) |
|
|
Term
| What are the 2 normal functions of lysosomes? |
|
Definition
|
|
Term
| Which cells do most of the lysosomal heterophagy? |
|
Definition
| neutrophils & macrophages |
|
|
Term
|
Definition
| endocytosis of extracellular maerial => fusion of lysosome to form phagolysosome => enzymatic degradation |
|
|
Term
|
Definition
| collection of injured or unnecessary intracellular material to vacuoles => fusion with lysosomes to form autophagolysosomes => enzymatic digestion |
|
|
Term
| What happens when a lysosome is functioning abnormally? |
|
Definition
| enzymatic dysfunction => excess accumulation of lysosomal contents & potential cellular injury |
|
|
Term
| What can lead to enhanced smooth ER metabolism? |
|
Definition
| chronic exposure to certain agents metabolized by smooth ER => increased smooth ER synthesis => enhanced metabolism |
|
|
Term
| What alterations can cellular mitochondria see? |
|
Definition
Hypertrophy (increased #)
Atrophy (decreased #)
Genetic metabolic disease
Aquired disorder |
|
|
Term
| What 3 cellular components can have alterations in the cytoskeleton? |
|
Definition
Microtubules
Thin Filaments
Intermediate Filaments |
|
|
Term
| Which of the cytoskeleton cellular components that can have alterations, which can occur both genetically or aquired? |
|
Definition
Mirotubules & Intermediate filaments
(thin filament alterations are due to aquired alterations secondary to toxins) |
|
|
Term
| In what cellular reaction rate imbalances will there be an accumulation of normal endogenous substances? |
|
Definition
| if production/absorption rate > metabolic/removal rate |
|
|
Term
| In what cellular reaction defects will there be an accumulation of normal or abnormal endogenous substances? |
|
Definition
| alterted synthesis/metabolism/transport |
|
|
Term
| When what in the cell is lacking will there be an accumulation of abnormal exogenous substances? |
|
Definition
| lack of cellular metabolic/secretory pathways |
|
|
Term
|
Definition
|
|
Term
| What causes fatty deposits in the liver? |
|
Definition
| 1) stravation => fatty acid uptake from adipose 2) protein malnutrition & CCl4 toxicity => decreased apoprotein synthesis => decreased lipoprotein export
3) damage due to alcholism, DM, obesity, hypoxia => triglyceride production/removal alterations |
|
|
Term
| How are triglycerides removed from the liver? |
|
Definition
| Added to apoproteins to form lipoproteins |
|
|
Term
| How are trigylcerides formed in the liver? |
|
Definition
| from a fatty acid precursor |
|
|
Term
| What are the 2 fates of fatty acids in the liver? |
|
Definition
| become triglycerides or catabolism (to ketones, phospholipids, or cholesterol) |
|
|
Term
| What gross changes are seen in a fatty liver(steatosis)? |
|
Definition
| enlarged, greasy & yellow |
|
|
Term
| Microscopically, what is seen in a steatotic liver in an H&E stain? |
|
Definition
| clear vesicular cytoplasmic vacuoles in the parenchymal cells |
|
|
Term
| Microscopically, what is seen in a steatotic liver in an oil red-O stain? |
|
Definition
|
|
Term
| What gross change is seen in tissue with high cholesterol content? |
|
Definition
|
|
Term
| What microscopic change is seen in a tissue with excess cholesterol & cholesterol esters? |
|
Definition
| foam cells (round with clear bubbly cytoplasm) |
|
|
Term
| How do atherosclerotic plaques look microscopically? |
|
Definition
|
|
Term
| How do xanthomas due to hyperlipidemia look? |
|
Definition
| Masses that are often subcutaneous |
|
|
Term
| When is cholesterolosis in the subepithelium of the gallbladder seen? |
|
Definition
| with cholesterol-predominant gallstones |
|
|
Term
| How do protein deposits look microscopically? |
|
Definition
| variably-sized, pink, cytoplasmic globules |
|
|
Term
|
Definition
| increased protein reabsorption by the proximal renal tubular epithelial cells |
|
|
Term
| What causes Russell bodies is plasma? |
|
Definition
|
|
Term
| What causes α1-antitrypsin protein in ER of hepatocytes? |
|
Definition
| mutations in the α1-antitrypsin gene => abnormal protein => decreased intracellular transport & secretion |
|
|
Term
| How does glycogen accumulation look microscopically in an H&E stain? |
|
Definition
| small, clear, cytoplasmic vacuoles |
|
|
Term
| How does glycogen accumulation look microscopically in a PAS stain? |
|
Definition
|
|
Term
| Why does glycogen accumulate in DM? |
|
Definition
| abnormal glucose metabolism |
|
|
Term
| What inherited enzyme deficiencies can lead to glycogen accumulation? |
|
Definition
| glycogen storage diseases due to abnormal glycogen metabolism |
|
|
Term
| What type of pigments are unable to be degraded and persist in phagolysosomes? |
|
Definition
|
|
Term
| What 2 exogenous pigments can persist? |
|
Definition
|
|
Term
| What permanant pigment is seen due to carbon? |
|
Definition
| black granular pigment in the cytoplasm of macrophages |
|
|
Term
|
Definition
| black granular pigment caused by carbon in the cytoplasm of macrophages in lungs & hilar lymph nodes |
|
|
Term
| How can carbon cause anthracosis? |
|
Definition
| inhalation of carbon dust => phagocytosis of alveolar macrophages |
|
|
Term
| How does tattoo pigment become permanent? |
|
Definition
| phagocytosis by dermal macrophages |
|
|
Term
| What are the 4 endogenous pigments that can accumulate? |
|
Definition
lipofuscin
melanin
bilirubin
hemosiderin |
|
|
Term
|
Definition
"wear & tear pigment"
indigestible phospholipis/protein remnant within autophagolysosomes |
|
|
Term
|
Definition
| free radical injury => subcellular membrane lipid peroxidation |
|
|
Term
| What does lipofuscin look like microscopically? |
|
Definition
| perinuclear, finely granular, yellow-brown pigment with long-lived cells |
|
|
Term
| Where is lipofuscin especially prominent? |
|
Definition
|
|
Term
| What produces the brown-black pigment of melanin? |
|
Definition
|
|
Term
| How is bilirubin derived? |
|
Definition
| from the porphyrin ring of hemoglobin |
|
|
Term
| What are the 2 components that hemoglobin is broken down into? |
|
Definition
|
|
Term
| What are the 2 components that heme is broken down into? |
|
Definition
|
|
Term
| What does the porphyrin ring break down into? |
|
Definition
| biliverdin (open chain) => unconjugated bilirubin |
|
|
Term
| Where is unconjugated bilirubin found? |
|
Definition
| blood plasma - tightly bound to albumin |
|
|
Term
| How do hepatocytes remove unconjugated bilirubin? |
|
Definition
| conjugate it to bilirubin glucuronides |
|
|
Term
| Where is unconjugated bilirubin excreted from? |
|
Definition
|
|
Term
| Where is hemoglobin broken down into unconjugated bilirubin? |
|
Definition
|
|
Term
| What happens to the aa of globin? |
|
Definition
|
|
Term
| What happens to the Fe of heme? |
|
Definition
| transported to the bone marrow by transferrin & recycled |
|
|
Term
| Why must bilirubin be conjugated? |
|
Definition
| To become water-soluble for excretion |
|
|
Term
| How do serum unconjugated bilirubin levels increase? |
|
Definition
1) increased RBS destruction => increased production
2) hepatocyte dysfunction => decreased bilirubin conjugation |
|
|
Term
| How does hepatocyte dysfunction occur? |
|
Definition
|
|
Term
| How do serum conjugated bilirubin levels increase? |
|
Definition
1) hepatocyte dysfunction => decreased bilirubin secretion
2) cholestasis (biliary tract obstruction) => decrased excretion |
|
|
Term
| What can cause intrahepatic choestasis? |
|
Definition
| space-occupying leisons in the liver, destruction of intrahepatic bile ducts, cirrhosis, hepatic injury/swelling, medication |
|
|
Term
| What can cause extrahepatic cholestasis? |
|
Definition
| gallstones in biliary tract, internal compromise or external compression of common bile duct |
|
|
Term
| How do we test for cholestasis? |
|
Definition
| test for increased alkaline phosphatase (though conjugated bilirubin is also increased, it's a much less sensitive test) |
|
|
Term
| What does cholestasis look like mircoscopically? |
|
Definition
| smooth, green to golden-brown, globular pigment most commonly found in the liver |
|
|
Term
|
Definition
| intracellular, end-stage storage form of excess iron |
|
|
Term
| What are the 2 fates of intracellular iron? |
|
Definition
|
|
Term
| What does iron combine with prior to storage? |
|
Definition
|
|
Term
| What does iron combined with apoferritin form? |
|
Definition
|
|
Term
| How is hemosiderin formed? |
|
Definition
| Excess ferritin aggregates to form clusters & are engulfed by lysosomes & degraded |
|
|
Term
| What causes excess hemosiderin formation? |
|
Definition
1) increased absorption of dietary iron
2) increased degredation of hemoglobin
3) parenteral iron excess |
|
|
Term
| Where does increased absorption of dietary iron accumulate? |
|
Definition
| parenchymal cells (esp. pancreas, liver, and heart) |
|
|
Term
| Where does increased degradation of hemoglobin accumulate? |
|
Definition
| mononuclear phagocytes (macrophages) |
|
|
Term
| What can cause increased degradation of hemoglobin? |
|
Definition
localized breakdown of RBCs (hemorrhage)
systemic RBC destruction (hemolytic anemia) |
|
|
Term
| Where does parenteral iron excess accumulate? |
|
Definition
|
|
Term
| What is seen microscopically in hemosiderin accumulation in an H&E stain? |
|
Definition
| coarsely granular, rusty-orange/brown, refractile, sytoplasmic pigment |
|
|
Term
| What is seen microscopically in hemosiderin accumulation in a Prussian Blue stain? |
|
Definition
|
|
Term
| What 4 serum lab tests are there to assess iron status? |
|
Definition
1) ferritin
2) iron
3) transferrin - iron-bindind capacity
4) % transferrin saturation |
|
|
Term
| Where is transferrin synthesized? |
|
Definition
|
|
Term
|
Definition
| binds/transports all plasma iron |
|
|
Term
| How do you calculate % trasnferrin saturation? |
|
Definition
| serum iron/IBC (iron-binding capacity) |
|
|
Term
| What % of the transferrin iron-binding sites are normally filled? |
|
Definition
|
|
Term
|
Definition
| There is no physiological excretion mechanism |
|
|
Term
| Where does the majority (75%) of all iron absorbed per day go to? |
|
Definition
| bone marrow for RBC/hemoglobin synthesis |
|
|
Term
| What is seen microscopically with hyaline change? |
|
Definition
| smooth, pink tissue appearance with H&E stain |
|
|
Term
| What causes the smooth pink tissue appearance in H&E with hyaline change? |
|
Definition
| excessive protein deposition |
|
|
Term
| What are 2 examples of intracellular hyaline changes? |
|
Definition
Russell bodies in plasma cells
alcoholic hyalin in hepatocyes |
|
|
Term
|
Definition
|
|
Term
|
Definition
| aggregates of intermediate filaments (mostly keratin) |
|
|
Term
| What are 3 examples of extracellular hyaline change? |
|
Definition
collagen in long-standing injury
amyloid deposits
thickened basement membrane in DM |
|
|
Term
|
Definition
| any alteration within cells or in the extracellular spaces or structures that gives a homogeneous, glassy pink appearance in tissue sections stained with H&E |
|
|
Term
| What are the 2 ways ATP can be synthesized? |
|
Definition
Aerobic oxidative phosphorylation
Anaerobic glycolysis |
|
|
Term
def
Aerobic oxidative phosphorylation |
|
Definition
| efficient production of ATP via mitochondrial ETC |
|
|
Term
|
Definition
| inefficient production of ATP via the metabolism of glucose |
|
|
Term
| What is the most common causative mechanism of ATP depletion? |
|
Definition
| decreased O2 availability |
|
|
Term
| What are the 3 causes of decreased O2 availability? |
|
Definition
1) hypoxia
2) *ischemia
3) deleterious cellular rxns |
|
|
Term
|
Definition
| decreased systemic O2 due to any etiology |
|
|
Term
| What are the 3 etiologies of hypoxia? |
|
Definition
1) decreased oxygenation of the blood (decreased hemoglobin levels)
2) decreased oxygen-carrying capacity of the blood (decreased oxygenation of hemoglobin)
3) ischemia |
|
|
Term
| When will you see decreased oxygenation of the blood? |
|
Definition
| resp. disorders or heart failure |
|
|
Term
| When will you see decreased oxygen-carrying capacity of blood? |
|
Definition
| severe anemia or carbon monoxide poisoning |
|
|
Term
|
Definition
| decreased blood flow to a tissue/organ |
|
|
Term
| What are the 3 consequences of ischemia? |
|
Definition
1) Hypoxia
2) dcreased supply of nutrients
3) decreased removal of toxic metabolic end-products |
|
|
Term
| What are the 4 deleterious cellular rxns caused by decreased ATP? |
|
Definition
| 1) decreased function of Na+/K+ pump
2) increased anaerobic glycolysis
3) decreased function of membrane-associated Ca2+ pump
4) loss of integrity of the rER |
|
|
Term
| What does decreased function of plasma membrane N+/K+ pump cause? |
|
Definition
| increased intracellular Na+ & H2O |
|
|
Term
| What does increased anaerobic glycolysis cause? |
|
Definition
| increased production of lactic acid => decreased intracellular pH |
|
|
Term
| What does decreased function of the membrane of the membrane-associated Ca2+ pump cause? |
|
Definition
| influx of Ca2+ => activation of numerous intracellular enzymes |
|
|
Term
| What does decreased function of the membrane of the membrane-associated Ca2+ pump cause? |
|
Definition
| influx of Ca2+ => activation of numerous intracellular enzymes |
|
|
Term
| What does loss of integrity of rER cause? |
|
Definition
| decreased and abnormal protein synthesis |
|
|
Term
| What is the normal ratio of cytosolic:extracellular [Ca2+]? |
|
Definition
|
|
Term
| What can cause an increase in cytosolic Ca2+? |
|
Definition
| 1) decreased activity of membrane-associated Ca2+ pump
2) increased permeability of subcellular & plasma membranes |
|
|
Term
| What numerous intracellular enzymes can be activated by increased intracellular Ca2+? |
|
Definition
1) ATPases
2) phospholipases
3) proteases
4) endonucleases |
|
|
Term
|
Definition
|
|
Term
|
Definition
| increased subcellular and plasma membrane permeability |
|
|
Term
|
Definition
| degradation of stuctural proteins |
|
|
Term
|
Definition
|
|
Term
|
Definition
| highly reactive molecules with an unpaired e- |
|
|
Term
| What are the 4 common causes on free radicals? |
|
Definition
1) aerobic oxidation
2) exposure to ionizing radiation
3) drug/toxin metabolism
4) neutrophil activation |
|
|
Term
| What are the body's 4 protective mechanisms against free radicals? |
|
Definition
| 1) enzymatic inactivation of O2-·
2) enzymatic breakdown of H2O2
3) antioxidants
4) iron- & copper- binding proteins |
|
|
Term
| What 2 enzymes does the body have to catalyze breakdown of H2O2? |
|
Definition
1) catalase
2) glutathione peroxidase |
|
|
Term
| What are the 3 deleterious cellular rxns caused by free radicals? |
|
Definition
1) lipid peroxidation of plasma & subcellular membranes
2) protein alteration & degradation
3) DNA damage
*propagation of autocatalytic chain of rxns |
|
|
Term
| What can cause mitochondrial injury? |
|
Definition
| activation of Ca2+-dependent intracellular enzymes or free-radical damage |
|
|
Term
| What 3 deleterious cellular rxns are caused by mitochondrial injury? |
|
Definition
1) decreased ATP
2) loss of membrane potential => inability to produce ATP => necrosis
3) escape of cytochrome c into cytosol |
|
|
Term
| What happens when cytochrome c escapes to the cytosol? |
|
Definition
|
|
Term
| What can cause cellular & subcellular membrane damage? |
|
Definition
| 1) decrease synthesis due to mitochondrial injury
2) increased degradation dur to phospholipase activation by increased cytosolic Ca2+
3) accumulation of phospholipid breakdown products
4) lipid peroxidation due to ROS
5) loss of cytoskeletal framework due to protease activity
6) direct lysis |
|
|
Term
| What 3 deleterious cellular rxns can occur due to cellular & subcellular membrane damage? |
|
Definition
| 1) mitochondrial membrane injury =>
a) loss of membrane potential => necrosis
b) escape of cytochrome c => apoptosis
2) plasma membrane injury => influx of Ca2+ & H2O and leakage of cellular contents
3) lysosomal membrane injury => release & activation of lytic enzymes |
|
|
Term
| What are the 3 types of cellular death & injury? |
|
Definition
1) *Hypoxia
2) Ischemia
3) Chemical injury |
|
|
Term
| What can cause hypoxic ischemia? |
|
Definition
Arterial or venous obstruction
severe hypotension |
|
|
Term
| What does the everity of cellular consequences of hypoxia depend on? |
|
Definition
| duration & particular cell type vulnerability |
|
|
Term
| Why does hypoxia due to ischema cause a greater degree of cellular damage than other causes of hypoxia? |
|
Definition
| decreased availability of glycolytic substrates and decreased removal of metabolic byproducts. |
|
|
Term
| Why is atrophy seen in hypoxia? |
|
Definition
| response due to decreased metabolic requirements in order to balance the oxygen supply |
|
|
Term
| What cellular injury caused by hypoxia is reversible? |
|
Definition
| decreased phosphorylation & ATP formation => decreased protein synthesis & Na+/K+ pump function => influx of Na+ & H2O => swelling => decreased cell function |
|
|
Term
| What cellular injury caused by hypoxia is irreversible? |
|
Definition
| decreased phospholipid synthesis & Ca2+ pump failure => influx of Ca2+ => Ca2+ damage => lysis of the lysosomes => irreparable damage to mitochondria => cell death (necrosis) |
|
|
Term
|
Definition
| exacerbation of ischemic cellular damage after restoration of blood flow to an area |
|
|
Term
| What are the 3 causes of reperfusion injury? |
|
Definition
1) *increased production of ROS
2) influx of leukocytes (mainly neutrophils)
3) activation of complement after Ab deposition |
|
|
Term
| How can chemical injury occur? |
|
Definition
Direct toxicity
Toxicity due to metabolic byproducts |
|
|
Term
| What metabolizes CCl4 to CCl3·? |
|
Definition
|
|
Term
|
Definition
| autocatalytic lipid peroxidation => rER damage & mitochondrial & plasma membrane damage |
|
|
Term
| What happens once CCl3· leads to rER damage? |
|
Definition
| decreased protein synthesis (including apoprotein) => decreased triglyceride export => fatty liver |
|
|
Term
| What happens once CCl3· leads to mitochondrial & plasma membrane damage? |
|
Definition
| increased membrane permeability & cytosolic Ca2+ => cell death |
|
|
Term
| When may cell injury not be apparent morphologically? |
|
Definition
|
|
Term
|
Definition
|
|
Term
| What can cause cellular swelling? |
|
Definition
| 1) plasma membrane damage => increased permeability => influx of Na+ & H2O
2) if ischemia
a) decreased blood flow => decreased O2 => decreased ATP => failure of Na+/K+ pump => influx of Na+ & H2O
b) increased cytosolic [osmotic] => influx of H2O |
|
|
Term
| What gross changes are seen in a organ with cellular swelling? |
|
Definition
|
|
Term
| What microscopic changes are seen in swollen cells? |
|
Definition
| enlarged cells with pale/clear cytoplasm |
|
|
Term
| What EM changes are seen in swollen cells? |
|
Definition
| cell surface blebs and distended mitochondria & ER |
|
|
Term
| What organ can have fatty change? |
|
Definition
|
|
Term
| What causes fatty deposits? |
|
Definition
| injury to ER => decreased protein synthesis => decreased lipid export => intracellular accumulation of fat |
|
|
Term
| What is seen microscopically in a fatty infiltration? |
|
Definition
| cytoplasmic lipid vacuoles. |
|
|
Term
| What are the 2 types of irreversible cell injury? |
|
Definition
|
|
Term
| Is necrosis or apoptosis always pathogenic? |
|
Definition
|
|
Term
|
Definition
| enzymatic digestion & leakage of cellular contents |
|
|
Term
| What is a key role in cellular & subcellular membrane damage due to Ca2+ influx? |
|
Definition
|
|
Term
| What are the 4 pathogenic causes of necrosis? |
|
Definition
1) plasma membrane: loss of cytosolic substrates
2) mitochondria: decreaed ATP
3) ER: decreased protein synthesis
4) lysosomes: release & activation of acid hydrolases => autolysis |
|
|
Term
| What cytoplasmic changes are seen in necrosis? |
|
Definition
1) increased eosinophilia
2) dense, clumped, irregular appearance |
|
|
Term
| What causes increased eosinophilia of cytoplasm in necrosis? |
|
Definition
1) decreased pH
2) decreased RNA
3) denatured proteins |
|
|
Term
| What causes the dense, clumped, irregular appearance of the cytoplasm in necrosis? |
|
Definition
1) decreased glycogen
2) disrupted cytoskeleton |
|
|
Term
| What causes nuclear changes in necrosis? |
|
Definition
| activated lysosomal enzymes & decreased pH (ultimately complete loss of nuclei) |
|
|
Term
| What are the 3 types of nuclear change that can be seen in necrosis? |
|
Definition
1) karyolysis
2) pyknosis
3) karyorrhexis |
|
|
Term
|
Definition
| fading of nuclear chromatin due to DNases |
|
|
Term
|
Definition
| nuclear condensation & shrinkage |
|
|
Term
|
Definition
|
|
Term
| Where does necrosis often surround? |
|
Definition
| host inflammatory response |
|
|
Term
| What ultrastructural changes are seen in necrosis? |
|
Definition
1) myelin figures
2) membrane disruption
3) amorphous intracellular debris |
|
|
Term
| What can help determine the etiology of necrosis? |
|
Definition
| specific morphologic patterns |
|
|
Term
| What ultimately happens to all areas of necrosis? |
|
Definition
| enzymatic degradation & phagocytosis by leukocytes |
|
|
Term
| What are the 5 types of necrosis? |
|
Definition
1) coagulative
2)liquefactive
3)caseous
4)fat
5)fibrinoid |
|
|
Term
| What are the 5 types of necrosis? |
|
Definition
1) coagulative
2)liquefactive
3)caseous
4)fat
5)fibrinoid |
|
|
Term
|
Definition
|
|
Term
| What causes coagulative necrosis? |
|
Definition
| hypoxia/ischemia (not in brain) => denaturation of enzymatic & structural proteins => delayed proteolysis |
|
|
Term
| What is seen in coagulative necrosis microscopically? |
|
Definition
| initial preservation of the tissue architecture (pink, ghost, cellular remnants with structural outlines intact) |
|
|
Term
| What are 3 examples of coagulative necrosis? |
|
Definition
1) MI
2) renal infarct
3) dry gangrene |
|
|
Term
| What causes liquefactive necrosis? |
|
Definition
hypoxia/ishemia (brain only)
usually pyogenic bacterial inf. => imflammation => WBC lysosomal enzyme release => enzymatic digestion & liquefaction of tissue |
|
|
Term
| What is seen microscopically in liquefactive necrosis? |
|
Definition
| focal loss of tissue architecture which is replaced by cellular debris & inflammatory cells |
|
|
Term
| What are 3 examples of liquefactive necrosis? |
|
Definition
1) abscess
2) cerebral infarct
3) wet gangrene |
|
|
Term
| What causes caseous necrosis? |
|
Definition
| mycobacterial and fungal inf. => activated macrophages & T cells => granulomatous inflammation with caseous (central) necrosis |
|
|
Term
| What is the gross appearance of caseous necrosis? |
|
Definition
| Caseous - crumbly, white & cheesy |
|
|
Term
| What is seen microscopically in caseous necrosis? |
|
Definition
| focal loss of cellular architecture & replacement by pink amorphous debris surrounded by a rim of plump epithelioid macrophages & lymphocytes |
|
|
Term
| What are 2 examples of caseous necrosis? |
|
Definition
|
|
Term
| What causes fat necrosis? |
|
Definition
| inappropriate release & activation of pancreatic lipases => breakdown of plasma membrane & intracellular triglycerides => saponification of calcium bound to the free fatty acids |
|
|
Term
| What is the gross appearance of fat necrosis? |
|
Definition
|
|
Term
| What is seen microscopically in fat necrosis? |
|
Definition
| hazy basophilic outlines of necrotic adipocytes with associated acute inflammation |
|
|
Term
| What's an example of fat necrosis? |
|
Definition
|
|
Term
| What causes fibrinoid necrosis? |
|
Definition
| vascular injury due to disorders => deposition of abundant fibrin |
|
|
Term
| What is seen microscopically in fibrinoid necrosis? |
|
Definition
| smudgy, hypereosinophilic appearance to the areas of necrosis typically involving small arteries, arterioles or capillaries |
|
|
Term
| What are 4 examples of fibrinoid necrosis? |
|
Definition
1) polyarteritis nodosa
2) malignant hypertension
3) hyperacute transplant rejection
4) rheumatoid nodules |
|
|
Term
| What are the 4 serum lab markers for necrosis? |
|
Definition
1) troponins
2) transaminases
3) lactate dehydrogenase
4) amylase & lipase |
|
|
Term
| What are the 3 subunits of troponins? |
|
Definition
|
|
Term
|
Definition
| components of an intracellular protein complex integral to striated muscle contraction |
|
|
Term
|
Definition
| regulate the calcium-mediated interaction b/w actin & myosin |
|
|
Term
| What can cause elevated serum levels of cardiac troponins? |
|
Definition
| cellular damage due to necrosis => increased permeability & leakage |
|
|
Term
| What are the 3 clinical uses of testing for serum troponins? |
|
Definition
1) sensitive & specific for early indication myocardial necrosis
2) persistant elevated levels => myocardial injury (up to 2 weeks)
3) prognostic |
|
|
Term
| What are the 2 transaminases tested for in the serum? |
|
Definition
|
|
Term
|
Definition
| catalyze removal & transfer of an amino group from an amino acid to an α-keto acid |
|
|
Term
| What do transaminases use as a co factor? |
|
Definition
|
|
Term
| What are transaminases important for in the liver? |
|
Definition
| energy production & nitrogen excretion |
|
|
Term
| What causes elevated serum ALT & AST? |
|
Definition
| hepatic membrane damage due to necrosis => increased permeability & leakage |
|
|
Term
Are ASTs or ALTs more specific for liver damage?
Why? |
|
Definition
| ALTs since AST is found in other tissues |
|
|
Term
| Are AST & ALT used for prognostic purposes? |
|
Definition
| No, since levels of elevation don't correlate with extent of liver damage or prognosis |
|
|
Term
| Where are lactate dehydrogenases (LDs) found? |
|
Definition
| widely distributed in various tissue |
|
|
Term
| How many tetrameric isoenzymes does LD have? |
|
Definition
|
|
Term
| *What are the 5 tetrameric isoenzymes of LD composed of? |
|
Definition
| various combination of H & M chains |
|
|
Term
| What are the 5 LD tetrameric isoenzymes? |
|
Definition
|
|
Term
| Which LD isoenzyme has 4 M chains? |
|
Definition
|
|
Term
| Which LD isoenzyme has 4 H chains? |
|
Definition
|
|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
|
Definition
| kidneys, pancreas, & placenta |
|
|
Term
|
Definition
|
|
Term
| *Which LD isoenzyme predominates in the serum? |
|
Definition
|
|
Term
Function
Lactate Dehydrogenase |
|
Definition
| catalyze conversion of pyruvate to lactate & vice versa |
|
|
Term
| What causes elevated serum levels of LD? |
|
Definition
| membrane damage in necrosis => increased permeability & leakage |
|
|
Term
| What are the 2 clinical uses of increased serum LD? |
|
Definition
nonspecific indication of necrosis
if LD-1>LD-2, indicated MI |
|
|
Term
|
Definition
| pancreas & saliva (salivary α-amylase) |
|
|
Term
|
Definition
|
|
Term
|
Definition
| catalyze hydrolysis of α(1-4) glycoside bonds in starch to form simple sugars |
|
|
Term
|
Definition
| catalyze hydrolysis of triglycerides into monoglycerides & free fatty acids |
|
|
Term
| What causes increased serum amylase & lipase? |
|
Definition
| pancreatic duct obstruction/acinar cell injury => inappropriate pancreatic enzyme release & activation => pancreatic lysis and increased serum amylase & lipase |
|
|
Term
| Is elevated lipase or amylase more sensitive for acute pancreatisis? |
|
Definition
|
|
Term
|
Definition
| highly regulated pattern of cell death occuring via cascade |
|
|
Term
| Can apoptosis coexist with necrosis? |
|
Definition
|
|
Term
| How is apoptosis used physiologically? |
|
Definition
| mechanism for removal of cells which become unecessary or deleterious to the individual |
|
|
Term
| What are 4 examples of physiological use of apoptosis? |
|
Definition
1) embryologic development
2) loss of hormonal/GF stimulation
3) cytotoxic T-cell response
4) deletion of lymphocytes that recognize self-Ag |
|
|
Term
| What are 3 examples of when might apoptosis be used pathologically? |
|
Definition
1) viral inf.
2) irreparable damage to DNA (radiation)
3) accumulation of lg. quantities of defective folded proteins |
|
|
Term
| What are the 4 key mechanisms to apoptosis initiation? |
|
Definition
1) extrinsic, death receptor-mediated
2) intrinsic, mitochondrial
3) p53
4) perforin/granzyme |
|
|
Term
| What is the extrinsic, death receptor-mediated pathway of apoptosis? |
|
Definition
| binding of Fas ligan to Fas receptor => cross-linking Fas receptors => binding cytoplasmic domains of receptors to FADD (Fas-associated death domain) adapter protein => activation of caspase cascade |
|
|
Term
| What is the intrinsic, mitochondrial pathway of apoptosis? |
|
Definition
| decreased hormonal/GF stimulation => replacement of anti-apoptotic proteins in mitochondrial membrane => increased mitochondrial permability => release of pro-apoptotic molecules to cytosol => activation of caspase cascade |
|
|
Term
| What is the p53 pathway of apoptosis? |
|
Definition
detection of DNA damage => increased levels & activation of p53 => cell-cycle arrest & attempted DNA repair
if unsuccessful repair => p53-induced transcriptional activation of pro-apoptotic genes => caspase activation |
|
|
Term
| What is the perforin/granzyme pathway of apoptosis? |
|
Definition
| cytotoxic T-cell (CTL) recognition of foreign Ag presented by MHC I => CTL secretion of perforin & subsequent release of granzyme B => activation of caspase cascade |
|
|
Term
| How is apoptosis executed? |
|
Definition
| caspase cascade (proteases activated by cleavage of inactive pro-enzyme) |
|
|
Term
| What degrades first in apoptosis? |
|
Definition
| cytoskeletal & nuclear matrix proteins |
|
|
Term
| What nust be activated prior to DNA cleavage in apoptosis? |
|
Definition
|
|
Term
| What 3 biochemical alterations occur in apoptotic cells? |
|
Definition
1) proteolysis
2) DNA fragmentation
3) cell membrane modification |
|
|
Term
|
Definition
| breakdown of nuclear structure & cytoskeleton |
|
|
Term
| What causes the DNA ladder pattern in electrophoresis (DNA fragmentation) in apoptosis? |
|
Definition
| DNase activation => enzymatic cleavage of nuclear DNA |
|
|
Term
| How are apoptotic cells removed without an inflammatory response? |
|
Definition
| expression of unique cell surface molecules & secretion of substances => enhanced macrophage recruitment, recognition, opsonization & phagocytosis |
|
|
Term
| Why are apoptotic cells frequently inapparent? |
|
Definition
1) targeting of single cells
2) rapidity
3) absence of inflammation |
|
|
Term
| What do apoptotic cells look like microscopically? |
|
Definition
| rounded, condense, hypereosinophilic cell with peripherally compacted nuclear chromatin (eventual nuclear/cytoplasmic fragmentation) => formation of dense apoptotic bodies |
|
|
Term
| What apoptotic disorders are there? |
|
Definition
1) decreased apoptosis (s.a autoimmune)
2) increased apoptosis (s.a. neurodegenerative) |
|
|
Term
| What influences cellular aging? |
|
Definition
| genetic & exogenous factors |
|
|
Term
|
Definition
| short, repetitive nucleotide sequences located at the ends of chromosomes which help protect replication of intervening DNA |
|
|
Term
|
Definition
| enzyme that helps restore telomeres are incomplete nucleotide duplication during cell divion |
|
|
Term
| Where are telomerases active? |
|
Definition
| Germ cells & lesser extent in stem cells (none in somatic cells) |
|
|
Term
| What helps germ cells retain cellular replicative capacity? |
|
Definition
| telomerase activity to maintain chromosomal telomeres |
|
|
Term
| What happens in somatic cells without telomerase activity? |
|
Definition
| gradual loss of telomere length => eventual damage to ends of intervening DNA => cellular senescence |
|
|
Term
|
Definition
| inabilit for further cell division |
|
|
Term
| What happens as somatic cells lose the length of their telomeres? |
|
Definition
| Gradual loss of functional abilities |
|
|
Term
| What affects cumulative nonlethal cell injury? |
|
Definition
| amount of cellular damage, accumulation of abnormal metabolic byproducts, & cellular reparative ability |
|
|
Term
| What 3 parts of the cell can see cumulative nonlethal cellular injury? |
|
Definition
1) membranes
2) chromosomes
3) organelles |
|
|
Term
| What are the 2 major types of calcification? |
|
Definition
|
|
Term
|
Definition
| normal serum levels & metabolism of calcium. It's site specific & disrupts function. |
|
|
Term
| What causes dystrophic calcification? |
|
Definition
| tissue injury/death => increased membrane permeability & formation of extracellular vesicles => influx of Ca2+ & blinding of Ca2+ to the vesicle membrane => addition of phosphate (PO4) groups => development & propagation of intra- & extra- cellular calcium phosphate crystals |
|
|
Term
| What are 3 examples of dystrophic calcification? |
|
Definition
1) atherosclerotic plaques
2) pulmonary nodule secondary to histoplasmosis
3) long-standing, congenital bicuspid aortic valve |
|
|
Term
|
Definition
| calcium deposits systemically, but doesn't disrupt function (initially) |
|
|
Term
| What causes metastatic calcification? |
|
Definition
| increased serum levels of Ca2+ => systemic deposition of Ca2+ salts |
|
|
Term
| What are 3 examples of metastatic calcification? |
|
Definition
1) increased PTH => bone resorption
2) lytic skeletal disorders => done destruction
3) inceased Vit D activity |
|
|
Term
| Where does dystrophic calcification occur? |
|
Definition
| focal sites of tissue damage & necrosis |
|
|
Term
| Where does metastatic calcification occur? |
|
Definition
| normal organ with relatively alkaline interstitium |
|
|
Term
| What does calcification look like grossly? |
|
Definition
| hard, white foci (if sufficient quantity) |
|
|
Term
| What does calcification look like microscopicly? |
|
Definition
| basophilic particulate matter |
|
|
Term
| What unique variants can be seen microscopicly in dystropic calcification? |
|
Definition
| psammoma bodies & ectopic bone |
|
|
Term
|
Definition
| circular concretions with concentric layering |
|
|
Term
| Does dystrophic or metastatic calcification cause tissue dysfunction? |
|
Definition
|
|
Term
|
Definition
| heterogeneous group of disorders characterize by the accumulation of diverse extracellular proteins |
|
|
Term
| What does amyloidosis look like in an H&E stain? |
|
Definition
| smooth, glassy, eosinophilic, homogeneous, extracellular material |
|
|
Term
| What does amyloidosis look like in a congo red stain in light microscopy? |
|
Definition
|
|
Term
| What does amyloidosis look like in a congo red stain in polarization microscopy? |
|
Definition
| apple green-yellow birefringence |
|
|
Term
| What is the structure of amyloidosis as seen my transmission electron microscopy? |
|
Definition
| straight, criss-crossing fibrils |
|
|
Term
| What is the conformation of amyloidosis as seen in x-ray crystallography? |
|
Definition
|
|
Term
|
Definition
overproduction of normal or synthesis of abnormal protein => protein misfolding
if there's insufficent degradation => aggregation into insoluble fibrils & accumulation in tissue |
|
|
Term
| *What is amyloid composed of? |
|
Definition
primarily fibrillary proteins
sm. contribution of glycoproteins
serum amyloid P component |
|
|
Term
| *How many biochemical types are there of amyloid? |
|
Definition
|
|
Term
| What are the 3 major biochemical types of amyloid? |
|
Definition
1) AL (amyloid light chain)
2) AA (amyloid-associated)
3) Aβ (β-amyloid) |
|
|
Term
|
Definition
| complete or partial Ig light chains, usually λ |
|
|
Term
|
Definition
| serum amyloid-associated (SAA) protein |
|
|
Term
|
Definition
| an acute phase reactant synthesized by hepatocytes |
|
|
Term
|
Definition
| cleaved fragment of amyloid precursor protein (APP) |
|
|
Term
|
Definition
| a neuronal cell surface molecule |
|
|
Term
| What are the 4 minor biochemical types of amyloid? |
|
Definition
| 1) ATTR (transthyretin amyloid)
2) Aβ2M (β2-microglobulin amyloid)
3) AE (endocrine amyloid)
4) PrP amyloid (prion protein amyloid) |
|
|
Term
| What is ATTR comprised of? |
|
Definition
| normal-sequence or variant-sequence transthyretin |
|
|
Term
|
Definition
| serum protein tht binds & transports thyroxine & retinol |
|
|
Term
| What is Aβ2M composed of? |
|
Definition
|
|
Term
|
Definition
| protein in the serum & on the surface of most nucleated cells as a component of MHC I |
|
|
Term
|
Definition
| protein hormones s.a. amylin, atrial natriuretic factor, calcitonin & insulin |
|
|
Term
| What are the 4 types of systemic amyloidosis? |
|
Definition
1) *Primary
2) Secondary/Reactive
3) Hemodialysis-associated
4) Senile systemic |
|
|
Term
| *What causes primary amyloidosis? |
|
Definition
plasma cell dyscrasia => overproduction of a monoclonal Ig/free light chains => protein misfolding
if there's insufficient degradation => amyloid accumulation |
|
|
Term
|
Definition
| an abnormal bodily condition |
|
|
Term
| What biochemical type of amyloid is associated with primary amyloidosis? |
|
Definition
|
|
Term
| What causes secondary/reactive amyloidosis? |
|
Definition
chronic inflammation => long-standing hepatic production of serum amyloid-associated protein (SAA) => protein misfolding
if there's insufficient degradation => amyloid accumulation |
|
|
Term
| What amyloid biochemical type is associated with secondary/reactive amyloidosis? |
|
Definition
|
|
Term
| What causes hemodialysis-associated amyloidosis? |
|
Definition
| long term hemodialysis => retention β2-microglobulin in serum => protein misfolding
if there's insufficient degradation => amyloid accumulation |
|
|
Term
| What biochemical type of amyloid is associated with hemodialysis-associated amyloidosis? |
|
Definition
|
|
Term
| What causes senile systemic amyloidosis? |
|
Definition
accumulation of normal-sequence transthyretin in elderly individuals
can be due to a genetic mutation resulting in abnormal transthyretin molecules that are amyloidogenic |
|
|
Term
| What biochemical type of amyloid is associated with senile systemic amyloidosis? |
|
Definition
|
|
Term
| What organ is primarily affected by senile systemic amyloidosis? |
|
Definition
|
|
Term
| What are the 3 types of localized amyloidosis? |
|
Definition
1) Cerebral
2) Endocrine
3) Other |
|
|
Term
| When is cerebral amyloidosis seen? |
|
Definition
| with Alzheimer's & cerebral amyloid angiopathy |
|
|
Term
| What biochemical type of amyloid is associated with cerebral amyloidosis? |
|
Definition
|
|
Term
| What are 3 forms of endocrine anyloidosis? |
|
Definition
1) Medullary Thyroid Carcinoma
2) Type 2 DM
3) Isolated atrial amyloidosis |
|
|
Term
| What biochemical type of amyloid is associated with endocrine amyloidosis? |
|
Definition
|
|
Term
def
Medullary thyroid carcinoma |
|
Definition
| malignancy of C cells (parathyroid cells) |
|
|
Term
| Where are associated amyloid deposits derived from in medullary thyroid carcinoma? |
|
Definition
|
|
Term
| Where is there amyloid accumulation in Type 2 DM? |
|
Definition
| in the pancreatic iselts of Langerhans |
|
|
Term
| Where are amyloid deposits derived from in isolated atrial amyloidosis? |
|
Definition
| atrial natriuretic factor |
|
|
Term
| What can cause Other localized amyloidosis? |
|
Definition
| nodular deposition of amyloid in a wide variety of organs |
|
|
Term
| What are the 2 herediary/familial amyloidosis? |
|
Definition
1) Familiar Mediterranean Fever
2) Familial Amyloidotic Neuropathies |
|
|
Term
| How common are hereditary/familial amyloidosis conditions? |
|
Definition
|
|
Term
| What causes familial mediterranean fever? |
|
Definition
| autosomal recessive disorder of pyrin => systemic accumulation of amyloid |
|
|
Term
| What biochemical type of amyloid is associated with familial mediterranean fever? |
|
Definition
|
|
Term
Sx
familial mediterranean fever |
|
Definition
recurrent fever
abdominal & joint pain
serositis (inflammation of serous tissue)
overproduction of IL-1 (chronic inflammation) |
|
|
Term
| What causes familial amyloidotic neuropathies? |
|
Definition
| autosomal dominant disorder of transthyretin => deposition of amyloid (esp. in peripheral & autonomic nerves) |
|
|
Term
| What biochemical type of amyloid is associated with familial amyloidotic neuropathies? |
|
Definition
|
|
Term
| What do is the gross characteristic s of organs with amyloidosis in general? |
|
Definition
|
|
Term
|
Definition
| initially nonspecific => depends on site & extent of organ involvement |
|
|
Term
| *Where does amyloid accumulate in kidney? |
|
Definition
| glomeruli, ateries, & interstitium |
|
|
Term
| *What happens due to amyloidosis in the kidney? |
|
Definition
| proteinuria & eventual renal failure |
|
|
Term
| Where does amyloid accumulate in the lover? |
|
Definition
| initially within the space of Disse => widespread involvement |
|
|
Term
| What leads to widespread amyloid accumulation in the liver? |
|
Definition
| pressure atrophy of hepatocytes |
|
|
Term
| What happens to liver function in amyloidosis? |
|
Definition
|
|
Term
| Where does amyloid accumulate in the spleen? |
|
Definition
| Either in the white pulp or red pulp |
|
|
Term
|
Definition
| white pulp accumulation of amyloid |
|
|
Term
|
Definition
| red pulp accumulation of amyloid |
|
|
Term
| What happens due to amyloidosis in the spleen? |
|
Definition
|
|
Term
| What do subendocardial amyloid deposits cause in the heart? |
|
Definition
| conduction disturbances & arrythmias |
|
|
Term
| What do myocardial amyloid deposits cause in the heart? |
|
Definition
| pressure atrophy of cardiac myocytes & restrictive cardiomyopathy => congestive heart failure |
|
|
Term
| What does amyloid deposition in endocrine organs cause? |
|
Definition
|
|
Term
| What does amyloid accumulation in the tongue cause? |
|
Definition
| macroglossia => speech & swallowing impairment |
|
|
Term
|
Definition
| hypertrophy of the tongue |
|
|
Term
| Where in the skin is especially prone to amyloid deposits? |
|
Definition
|
|
Term
| What happens due to amyloid deposits in the GI tract? |
|
Definition
| difficulties with digestion or absorption |
|
|
Term
| Where in the RT can amyloid accumulation occur? |
|
Definition
|
|
Term
| Which amyloid biochemical type is most frequently associated with joing & tendon amyloidosis? |
|
Definition
|
|
Term
| What does amyloidosis in joints & tendons cause? |
|
Definition
| carpal tunnel & arthropathy (arthritis) |
|
|
Term
| What amyloid biochemical type is found in blood vessels/senile plaques in the brain? |
|
Definition
|
|
Term
| When are amyloid deposits seen in peripheral & autonomic nerves? |
|
Definition
| Familial amyloidotic neuropathies |
|
|
Term
Gross appearance
Steatotic liver |
|
Definition
|
|
Term
| What are the 3 comonents of the portal triad? |
|
Definition
1) Hepatic artery
2) Bile duct
3) Portal vein |
|
|
Term
| How do you ID the 3 parts of the portal tiad? |
|
Definition
Portal v. - largest structure with think layer epi.
Bile duct - has a clear columnar epithelial border
Hepatic a. - smaller, thick wall structure |
|
|
Term
| What 3 substances stain clear on an H&E? |
|
Definition
|
|
Term
| How do you detect steatosis on a physical exam? |
|
Definition
|
|
Term
| Where do you find pseudostriated ciliated columnar epi? |
|
Definition
|
|
Term
| What metaplasia is seen in RT due to cigarette smoke? |
|
Definition
| eip => stratified squamous |
|
|
Term
|
Definition
| chronic tissue trauma/irritation => signals => transcription change => new cell differentiation |
|
|
Term
| Why do smoker's lungs turn black? |
|
Definition
|
|
Term
| Why does the black granular pigment of carbon inhalation remain permanent? |
|
Definition
| remain in the cytoplasm of macrophages |
|
|
Term
| Why might a person with multiple blood transfusions have an enlarged liver? |
|
Definition
|
|
Term
|
Definition
|
|
Term
| What pigment is caused by iron accumulation? |
|
Definition
|
|
Term
| What are the for possible pigment changes in the liver? |
|
Definition
lipofuscin - yellow/brown
melanin (cancerous) - brown/black
bilirubin - green/golden brown (bruise)
hemosiderin - rusty |
|
|
Term
| What causes the hemosiderin pigment? |
|
Definition
| ferritin (storage form of iron) broken down by lysosomes |
|
|
Term
| When can you see a localized accumulation of hemosiderin in tissue? |
|
Definition
|
|
Term
| What causes breat enlargement during pregnancy & lactation? |
|
Definition
|
|
Term
| What histological differences should be seen during pregnancy & lactation? |
|
Definition
1) uterine hyperplasia
2) uterine hypertrophy
3) glandular epitherial cell proliferation in breast |
|
|
Term
| What happens microscopically to breat tissue during lactation? |
|
Definition
| more clear cytoplasm, enlarged glands, enlarged ducts |
|
|
Term
| What causes increased breat size in lactating breast? |
|
Definition
|
|
Term
| What is the difference b/w dystrophic & metastatic calcification? |
|
Definition
D: focal with functional change
M: systemic with no functional change |
|
|
Term
What do you expect to happen to the heart due to an abnormal aortic valve?
Why? |
|
Definition
hypertrophy (esp. L ventricle)
increased workload |
|
|
Term
| Why is hypertrophy seen in the heart & not hyperplasia? |
|
Definition
| Not as capable of mitotic division |
|
|
Term
|
Definition
| free radical injury => lipid peroxidation => indigestible phospholipid/protein remnants |
|
|
Term
| What is seen microscopically in a patient with hypertrophy of the heart? |
|
Definition
| more dense muscle cells, striations aren't as clean, hyperchromatic (more condensed) & more basophilic nucleus |
|
|
Term
| How does hypertrophy increase the functional capacity of the cardiac muscle? |
|
Definition
| increased mitochondria => more energy => more work |
|
|
Term
| How do you tell the difference b/w a proximal & a distal convoluted tubule? |
|
Definition
Proximal: fuzzy, taller, darker pink
Distal: cleaner, shorter |
|
|
Term
| What causes swelling in the glomeruli & tubules? |
|
Definition
| decreased blood flow => decreased O2 => decreased ATP => Na+/K+ pump failure => increased H2O & Na+ intracellular (hydropic change) |
|
|
Term
| What cytoplasmic & nuclear changes are seen in coagulative necrosis? |
|
Definition
cytoplasm: more eosinophilic
nucleus: slowly disappears, stages of karyolysis, pyknosis, & karyorrhexis |
|
|
Term
| What causes coagulative necrosis? |
|
Definition
| hypoxia/ischemia => denaturation => delayed proteolysis |
|
|
Term
| What type of necrosis looks "cheesy"? |
|
Definition
|
|
Term
| How do you ID microscopically the 5 types of necrosis? |
|
Definition
coagulative: ghost structure remnants
liquefactive: infiltration of debris
caseous: hypereosinophilic center surrounded by macrophages
fat: hazy basophilic outline
fibrinoid: hypereosinophilic around blood vessels |
|
|
Term
| What are the giant cells that can surround caseous necrosis? |
|
Definition
|
|
Term
| What 2 infection types can cause caseous necrosis? |
|
Definition
|
|
Term
| What 3 things should all adequate diets provide? |
|
Definition
1) energy (carbs, fats, protein)
2) aa & FA (essential & non-essential)
3) vitamins/minerals |
|
|
Term
|
Definition
|
|
Term
def
secondary malnutrition |
|
Definition
| deficiency due to inadequate absorption, impaired usage/storage, excess loss, increased need |
|
|
Term
|
Definition
| deficiency or inadequacy of any or all nutrients needed in an adequate diet |
|
|
Term
|
Definition
| act as co-enzymes or hormones in vital metabolic pathways |
|
|
Term
| What are the 2 categories of vitamins? |
|
Definition
|
|
Term
| What are the fat soluble vitamins? |
|
Definition
|
|
Term
| What are the water soluble vitamins? |
|
Definition
|
|
Term
| What is required for dietary absorption of FS vitamins? |
|
Definition
| effective pancreatic & biliary function for dietary absorption |
|
|
Term
| What usually causes FS vitamin deficiency? |
|
Definition
| disturbances of fat absorption |
|
|
Term
| What causes WS vitamin deficiency? |
|
Definition
| primary or seconday malnutrition |
|
|
Term
| Are FS or WS vitamins found to have higher body stores? |
|
Definition
|
|
Term
|
Definition
| carotene family, retinal group |
|
|
Term
| What are the 4 normal functions of Vit A? |
|
Definition
1) component of visual pigment rhodopsin: retinal
2) maintain specialized epithelial differentiation (affects transcription of genes thru interation with DNA)
3) effects metabolism, inc. FA
4) resistance to infection & stimulation of immune system |
|
|
Term
| What are the dietary sources of Vit A? |
|
Definition
1) animal-derived products (fish, eggs, milk - retinol)
2) leafy green/yellow vegetables (carotenoids, β-carotene) |
|
|
Term
| Where is 90% of Vit A stored in the body? |
|
Definition
|
|
Term
| What is the storage form of Vit A? |
|
Definition
|
|
Term
| What is the visual pigment form of Vit A? |
|
Definition
|
|
Term
|
Definition
1) nyctalopia (night blindness)
2) squamous metaplasia & keratinization
a) eye: xerophtalmia (dry eye), keratomalacia (corneal ulceration), corneal clouding
b) skin & other epithelia: follicular hyperkeratosis
3) susceptibility to inf. (esp. measles)
4) predisposition to neoplasia (via squamous metaplasia) |
|
|
Term
| What causes nyctalopia in Vit A deficiency? |
|
Definition
| decreased rhodopsin in retinal rods & cones |
|
|
Term
|
Definition
|
|
Term
| What is the normal function of Vit D? |
|
Definition
| maintain plasma calcium & phasphate levels for adequate bone mineralization |
|
|
Term
| What are the sources of Vit D? |
|
Definition
| dietary: meat, dairy, additives (D2)
conversion: via UV light to D3 |
|
|
Term
| Where does Vit D travel to, once absorbed the gut or converted via UV? |
|
Definition
| Blood (has D-binding protein transporter) => liver |
|
|
Term
| What metabolism of Vit D occurs in the liver? |
|
Definition
| hydroxylation via 25-hydroxylase => 25-OH-D |
|
|
Term
| Where does 25-OH-D go once leaving the liver? |
|
Definition
|
|
Term
| What metabolism of 25-OH-D occurs in the kidney? |
|
Definition
| hydroxylation by 1-hydroxylase => 1,25(OH)2D |
|
|
Term
| What is the active form of Vit D? |
|
Definition
|
|
Term
| How does 1,25(OH)2D facilitate calcium & phosphate aborption in sm. bowel? |
|
Definition
| activating synthesis of calcium-binding proteins |
|
|
Term
| What are the possible Vit D deficency causes? |
|
Definition
1) malnutrition
2) malabsorption
3) chronic underexposure to sunlight
4) chronic liver diesaes
5) chronic renal disease
6) induction of CYP450
7) defective hydroxylase enzymes |
|
|
Term
| What diease is seen in Vit D deficiency in children? |
|
Definition
|
|
Term
| What disease is seen in adults with Vit D deficency? |
|
Definition
|
|
Term
|
Definition
- bowing deformities of wt-bearing long bones & spine
- overgrowth of cartilage at apiphyseal plates & ribs (rachitic rosary)
- other deformities |
|
|
Term
|
Definition
- decreaed bone density on radiographs
- osteoid excess
- minimal deformity
- susceptibility to microfractures |
|
|
Term
|
Definition
| bone is mineralized, but composed of thinner trabeculae |
|
|
Term
|
Definition
| bone density loss => wt-bearing areas brittle & susceptible to fracture (esp. hips & vertebral bodies) |
|
|
Term
|
Definition
|
|
Term
|
Definition
| cofactor for carboxylation rxns important in blood clotting |
|
|
Term
| What are the sources of Vit K? |
|
Definition
dietary: green, leafy vegetables
other: intestinal bacteria synthesis |
|
|
Term
Function
carboxylase Vit K is a cofactor for |
|
Definition
| converts glutamyl residues to γ-carboxyglutamates (provides calcium-binding sites) |
|
|
Term
Effect
carboxylase + Vit K cofactor |
|
Definition
| Allows interaction b/w clotting factors II, VII, IX, X (prothrombin family) & phospholipid surface necessary to generate thrombin |
|
|
Term
| What inactive form of Vit K is formed after use? |
|
Definition
|
|
Term
| How is Vit K epoxide recycled to active Vit K? |
|
Definition
|
|
Term
| How does Warfarin affect the Vit K cycle? |
|
Definition
| inhibits recycling of Vit K epoxide |
|
|
Term
| Why are Vit K deficencies rare? |
|
Definition
1) efficient recycling
2) interstinal flora provide ongoing source |
|
|
Term
|
Definition
| bleeding diathesis (=> hematoma, hematuria, melena, eccymoses, gingival bleeding, etc) |
|
|
Term
| What can cause Vit K deficency? |
|
Definition
1) neonates - absence of gut flora
2) diffuse liver disease - fat malabsorption
3) Abx - destruction of normal flora
4) warfarin therapy - inhibition of hepatic reductase |
|
|
Term
|
Definition
|
|
Term
| What is the dietary source of Vit E? |
|
Definition
|
|
Term
|
Definition
| anti-oxidant: inhibit formation of oxygen radicals |
|
|
Term
|
Definition
| phenol-like aromatic head attached to saturated hydrocarbon tail (allows molecule to "sit" in membrane lipid layers) |
|
|
Term
| How does Vit E protect from oxidation by free radicals? |
|
Definition
| Vit E is readily oxidized (takes lipid membrane place => protection) |
|
|
Term
| Why is it important to protect membranes from lipid peroxidation? |
|
Definition
| it's an autocatalytic charin rxn => single oxidation could propagate throughout the membrane |
|
|
Term
| Why is Vit E deficency rare? |
|
Definition
|
|
Term
| When can Vit E deficency occur? |
|
Definition
1) severe fat malabsorption
2) premature infants => low levels at birth combined with oxidative stress s.a. oxygen therapy |
|
|
Term
|
Definition
1) spinocerebellar degeneration
2) hemolytic anemia (esp. newborns)
3) increased susceptibility to ischemic heart disease |
|
|
Term
| What are the general properites of water soluble vitamins? |
|
Definition
1) sm. organic molecules
2) required in sm. amounts
3) used in universal energy utilization pathways
4) limited body stores easily depleted
5) deficency => systemic syndrome |
|
|
Term
|
Definition
|
|
Term
| What are the sources of thiamine? |
|
Definition
1) widely in nature (not in refined foods)
2) low intracellular reserves (muscle, heart & brain) |
|
|
Term
|
Definition
rxns where aldehyde groups are transferred
1) ATP sunthesis
2) pentose phosphate pathway
3) maintenance of normal nerve membranes/conduction |
|
|
Term
| Where in the world is thiamine primary malnutrition of thiamine common? |
|
Definition
| underdeveloped countries where diet consiss of processsed food |
|
|
Term
| What is the main source of thiamine defiency? |
|
Definition
| chronic alcoholism - inadequate diet or tansketolast abnormality |
|
|
Term
| What in thiamine deficiency affects cerebral function? |
|
Definition
| impiared glucose metabloism |
|
|
Term
| What in thiamine deficency impairs myocardial function? |
|
Definition
|
|
Term
| What 2 myocardial syndromes are seen in thiamine deficency? |
|
Definition
Dry Beri-beri
Wet Beri-beri |
|
|
Term
| What 2 cerebral syndromes are seen in thiamine deficency? |
|
Definition
| Wenicke & Korsakoff's syndromes |
|
|
Term
|
Definition
| myocardial failure with edema & vasodilation |
|
|
Term
|
Definition
peripheral neuropathy affecting lower extremities more than upper
affects motor, senory & reflex function |
|
|
Term
|
Definition
|
|
Term
Sx
Wernicke's encephalopathy |
|
Definition
eye movement abnormalities (nystagmus, ophthalmoplegia)
dysarthria
confusion
ataxia |
|
|
Term
|
Definition
retrograde amnesia
anterograde amnesia
confabulation |
|
|
Term
| What is the pathology of Wernicke & Korsakoff? |
|
Definition
| acute hemorrhagic necrosis of mammillary bodies & periventricular gray matter => atrophy |
|
|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
| Why are deficencies of riboflavin, pyridoxine, & niacin rare? |
|
Definition
| widely present in common food sources |
|
|
Term
|
Definition
| Co-factor in energy pathways (FMN, FAD) |
|
|
Term
|
Definition
cofactor in transamination/decarboxylation rxns
needed for neurotranmitter systhsis and other synthetic pathways |
|
|
Term
|
Definition
| Co-factor in energy pathways (NAD/NADP) |
|
|
Term
| How do B2, B3, & B6 deficiencies manifest? |
|
Definition
| In organs with rapid turnover/active metabolism => abnormalities |
|
|
Term
Sx
B2, B3, B6 Deficiencies |
|
Definition
Epithelium (dermatitis, glossitis)
Bone marrow (anemia)
neural tissues (neuropathy, dementia) |
|
|
Term
|
Definition
| clinical syndrome of dermatitis, diarrhea, dementia from niacin deficency |
|
|
Term
| What is the first & most chariacteristic Sx of riboflavin deficency? |
|
Definition
| cheilosis (cracks & fissures @ edge of mouth) |
|
|
Term
|
Definition
|
|
Term
| What are the sources of Vit C? |
|
Definition
dietary: fresh leafy vegetables, tomatoes, citrus fruit
body store: depleted in 30-40 d without intake |
|
|
Term
|
Definition
1) anti-oxidant/free radical scavenger
2) biosynthesis
3) immune function
4) collagen cross-linking |
|
|
Term
| What happens to excess Vit C intake? |
|
Definition
|
|
Term
| What disease is seen in Vit C deficency? |
|
Definition
|
|
Term
|
Definition
1) bleeding tendency
2) slow/inadequate wound healing
3) children: skeletal changes (Moeller-Barlow disease: compare to rickets)
4) dermatologic change & frequent gingival/periodontal inf. |
|
|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
Function
B12 as a cofactor |
|
Definition
| 1) help enzyme generate FH4 (THF) from it's methylated form
2) aids conversion of methylmalonyl CoA ro succinyl CoA |
|
|
Term
| What is THF a co-enzyme for? |
|
Definition
| thymidylate synthetase (required for DNA precursor generation) |
|
|
Term
| What happens to THF in B12 deficency? |
|
Definition
| trapped in methylated form => THF deficency |
|
|
Term
| What happens when the succinyl pathway is interrupted by B12 deficency? |
|
Definition
| accumulation of methylmalonate & propionate => abnormal FA formation => membrane damage |
|
|
Term
| What is the Vit B12 source |
|
Definition
|
|
Term
| Why are primary B12 decfiencies rare (except in vegans/macrobiotic diets)? |
|
Definition
| storage reserves last for years |
|
|
Term
| What is the main source of B12 defiency? |
|
Definition
| malabsorption since the B12 absorption pathway is complex |
|
|
Term
|
Definition
| autoimmune diease resulting from production of auto-Ab to IF or gastric parietal cells (they synthesize & secrete IF) |
|
|
Term
|
Definition
| chronic inflammation of gastric lining epithelium => gastric gland atrophy, achlorhydria & intential metaplasia w/ atrophic glossitis |
|
|
Term
| What is the source of folate? |
|
Definition
| green vegetables, fruit, animal proteins |
|
|
Term
What type of folate decifency is common?
Why? |
|
Definition
secondary due to increased requirement resulting from increased DNA synthesis
1) pregnancy
2) infancy
3) hemolytic anemias
(or B12 deficency => B9 deficency) |
|
|
Term
| What drugs can inhibit folate absorption? |
|
Definition
Oral contrsceptives
Phenytoin |
|
|
Term
| What drugs can inhibit folate metabolism? |
|
Definition
|
|
Term
| What causes megaloblastic anemia? |
|
Definition
| insufficent B12/folate due to impaired DNA synthesis |
|
|
Term
| What happens to hematopoiesis in megaloblastic anemia? |
|
Definition
| nuclear-cytoplasmic dystrophy wtih immature nuclei lagging behind maturation => clinically ineffective hematopieosis |
|
|
Term
| What happens to RBCs & neutrophils in megaloblastic anemia? |
|
Definition
1) enlarged ovioid RBCs
2) hypersegmented neutrophils |
|
|
Term
def
subacute combined degeneration |
|
Definition
| Severe B12 deficency where myelin degeneration develops in posterior & lateral funiculi of SC |
|
|
Term
Sx
Subacute combined degeneration |
|
Definition
spastic paraparesis
sensory loss
painful paresethsias (itching, burning) |
|
|
Term
| What can happen in severe B12 deficency when treated with folate? |
|
Definition
anemia response
no neurological response |
|
|
Term
|
Definition
| minerals occuring at concentration <1 mg/gm |
|
|
Term
| What 3 things in the body is iron essential to the function of? |
|
Definition
1) hemoglobin
2) myoglobin
3) enzymes
~ 75% of all body iron is in these processes |
|
|
Term
| Why is iron absorption & storage availability tightly regulated? |
|
Definition
1) potential cellular toxicity
2) sequestered from pathogenic orgs
3) limited ability to dispose of increased stores |
|
|
Term
| What is the storage form of iron that's immediately accessible? |
|
Definition
|
|
Term
|
Definition
| iron aggregates without protein shell stored in lysosomes |
|
|
Term
| Where is iron absorption controlled? |
|
Definition
|
|
Term
| What does the liver secrete to inhibit the transfer of iron from mucosal cells to the plasma? |
|
Definition
|
|
Term
| How much of dietary iron is actually absorbed per day? |
|
Definition
|
|
Term
| What mediates iron transport in the blood? |
|
Definition
| transferrin => delivers to RBC precursors |
|
|
Term
| What happens to unused iron stores not transferred to the blood? |
|
Definition
|
|
Term
def
total iron binding capacity |
|
Definition
| potential serum iron level if all transferrin binding sites are completely occupied (usually ~1/3 TIBC) |
|
|
Term
| What can cause iron deficency? |
|
Definition
1) inadequate diet
2) infants/children (increased need, low dietary content)
3) chronic blood loss
4) impaired absorption |
|
|
Term
| What happens in iron deficency due to decreased heme synthesis? |
|
Definition
| microcytic-hypochromatic anemia |
|
|
Term
| What occurs in iron deficency due to decreased iron containing enzymes? |
|
Definition
1) nail changes
2) atrophic glossitis
3) esophageal webs |
|
|
Term
| What is Plummer-Vinson syndrome in iron deficency? |
|
Definition
| atrophic glossitis + esophageal webs + anemia |
|
|
Term
|
Definition
1) decreased serum ferritin
2) decreased bone marrow hemosiderin on biopsy
3) increased TIBC (due to increased transferrin)
4) decreased transferrin saturation |
|
|
Term
|
Definition
|
|
Term
|
Definition
| anemia & collagen defects |
|
|
Term
|
Definition
| chronic pain, cardiac disease |
|
|
Term
|
Definition
| susceptibility to tooth decay |
|
|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
| How does iodine deficency cause goiter? |
|
Definition
| iodine deficency + inadequate production of thyroid hormone => TSH secretion => enlargement |
|
|
Term
|
Definition
impaired neurological development(cretinism)
myxedema (diffuse edema with slowing of mental/physical function) |
|
|
Term
| What can cause hypothyroidism besides iodine deficency? |
|
Definition
| disturbance in thyroid, pituitary, or hypothalamous |
|
|
Term
| What vitamins can be toxic? |
|
Definition
|
|
Term
|
Definition
1) teraogenesis
2) hepatic dysfunction
3) increased ICP (children)
4) if consume too many vegetables with β-carotene => non-toxic yellow skin |
|
|
Term
|
Definition
|
|
Term
|
Definition
| hypercalciruia => nephrolithiasis & metastatic calcifications |
|
|
Term
| What can cause iron toxicity? |
|
Definition
Diet
Increased RBS turnover
genetic disease
repeated blood transfusions |
|
|
Term
|
Definition
hemosiderosis (localized or systemic)
hemochromatosis (acquired or inherited) |
|
|
Term
| Where is protein-energy malnutrition seen? |
|
Definition
famine/war-torn areas
severely ill |
|
|
Term
| What are the 2 primary forms of protein-energy malnutrition? |
|
Definition
1) marasmus
2) kwashiorkor |
|
|
Term
| What are the 2 components of body protein? |
|
Definition
1) somatic (skeletal muscle)
2) visceral (organ stores) |
|
|
Term
What comparentment of preotein is depleted in marasmus?
kwashiorkor? |
|
Definition
|
|
Term
|
Definition
| deficency of protein AND energy (calories) |
|
|
Term
| What 2 mechanisms are used by the body to compensate for severe caloric restriction in marasmus? |
|
Definition
1) gradual metabolism of fat & muscle mass
2) dramatic reduction of energy utilization by reducing cellular ion pumps |
|
|
Term
| What is the main Sx in marasmus? |
|
Definition
|
|
Term
|
Definition
Atrophy of muscle mass & depletion of fat stores
Low metabolic activity
Growth rate decline
Mental & emotional impairment |
|
|
Term
| When is marasmus well compensated? |
|
Definition
|
|
Term
|
Definition
| Diet adequate in calories but deficent in protein => deficit in endogenous protein synthesis |
|
|
Term
|
Definition
edema
heptaomegaly
mental changes
hypermetabloic state
oxidative cellular damage
anemia
depigmentation of hair & skin (scaly/brittle) |
|
|
Term
| What causes edema in Kawshiorkor? |
|
Definition
| decreased plasma oncotic pressure |
|
|
Term
| What causes hepatomegaly? |
|
Definition
| fatty liver deposits due to inability to synthesize lipid carrier proteins |
|
|
Term
| Why is the hypermetabolic state of kwashiorkor maladaptive? |
|
Definition
| exacerbates already low fuel stores |
|
|
Term
| What causes oxidative cellular damage in kwashiorkor? |
|
Definition
imbalance in free radical producton/disposal exacerbated by:
1) inf.
2) sm. bowel bacterial overgrowth
3) selective deficency in antioxidant nutrients |
|
|
Term
| In which protein-energy malnutrition syndrome, which one do you see loss of appetite? |
|
Definition
|
|
Term
|
Definition
|
|
Term
| When can patients develop cachexia? |
|
Definition
| terminal condition of chronic disease |
|
|
Term
| When can patients develop a kwashiorkor-like condition? |
|
Definition
| "line-fed" patients with inadequate protein intake |
|
|
Term
|
Definition
| excess accumulation of fat representing an imbalance b/w energy intake & expenditure |
|
|
Term
|
Definition
| central/upper accumulation |
|
|
Term
|
Definition
| peripheral/lower accumulation |
|
|
Term
| What happens to fat in obesity? |
|
Definition
| hypertrophy & hyperplasia |
|
|
Term
| What accounts for energy expenditure? |
|
Definition
70% - basal metabolic rate (BMR)
15% - thermic effect of food
15% - physical activity |
|
|
Term
| What are some medical conditions linked to obesity? |
|
Definition
medical school (lmao jk)
HTN
T2DM
metabolic syndrome
CVD
cancer
others |
|
|
Term
|
Definition
| abberant eating practices leading to disease or disability |
|
|
Term
|
Definition
|
|
Term
|
Definition
| binging followed by excessive means to reduce caloric intake (purging, excessive exercise) |
|
|
Term
|
Definition
disordered eating
amenorrhea
loss of bone density |
|
|
Term
|
Definition
|
|
Term
|
Definition
| underfeeding children to prevent future obesity, CVD, etc |
|
|
Term
| What complications are seen in AN? |
|
Definition
protein-energy malnutrition
anemia
depression |
|
|
Term
| What complications are seen in BN? |
|
Definition
demineralization of teeth
electrolyte imbalance
esophagus/stomach damage |
|
|
Term
def
iatrogenic nutritional disease |
|
Definition
| physician-induced malnutrition induced by therapeutic drugs |
|
|
Term
| What patients in the hospital must nutrition be monitored? |
|
Definition
1) Certain medical diseases
a) with medically relavent nutritional aspects
b) with substantial excretory loss of nutrients
c) with therapeutic intervention that induces malnutrition
2) ill/surgical patients (due to increased metabolism) |
|
|
Term
|
Definition
| nonspecific cellu;ar & molecular rxn to injury of vascularized tissue, beneficial in intent, and also potentially damaging to the host |
|
|
Term
| What are the 2 types of inflammation? |
|
Definition
|
|
Term
When does acute inflammation occur as opposed to chronic?
How long do they persist for? |
|
Definition
acute: soon after injury & resolves relatively quickly
chronic: after prolonged injurous event & persists in the tissue |
|
|
Term
| When do leukocytes infiltrate in acute inflammation? |
|
Definition
| after initial vascular response |
|
|
Term
| How is leukocyte infiltration different in actue & chronic inflammation? |
|
Definition
acute: neutrophils first, then monocytes => macrophages
chronic: macrophages, lymphocytes & plasma cells |
|
|
Term
|
Definition
| rubor, tumor, calor, & dolor |
|
|
Term
| What happens to vasculature in acute inflammation? |
|
Definition
| dilation & increased permeability |
|
|
Term
| When does tissue repair occur? |
|
Definition
| With inflammation, but usually finishes after inflammation has gone |
|
|
Term
| What is included in tissue repair? |
|
Definition
1) regeneration of injured cells
2) formation of scar tissue |
|
|
Term
| What occurs as a result of vasodilation + increased vascular permeability in acute inflammation? |
|
Definition
| increased extravascular fluid with high protein content (edema) & intravascular stasis of blood (increased pressure) |
|
|
Term
| What mediates vasodilation in acute inflammation? |
|
Definition
| chemical mediators (histamine, NO) |
|
|
Term
| What are the 4 pathogenic mechaniss of increased vascular permeability in acute inflammation? |
|
Definition
1)*formation of gaps b/w endothelial cells of venules
2)injury to endothelium of microcirculation
3) increased endothelial transcytosis
4) secondary to angiogenesis (repair) |
|
|
Term
| How long can gap formation b/w endothelial cells of venules last? |
|
Definition
delayed, longer lasting response
immediate transient response |
|
|
Term
| What causes delayed, longer lasting response gap formation b/w venule endothelial cells? |
|
Definition
| cytoskeletal changes of endothelium resulting in retraction |
|
|
Term
| What causes immediate transient response gap formation b/w venule endothelial cells? |
|
Definition
| endothelial cell contraction (retraction) |
|
|
Term
| What can cause injury to endothelium of microcirculation? |
|
Definition
1) bacterial toxins, tissue necrosis, cell damage of some type, etc
2) activated leukocytes |
|
|
Term
| What causes increased edothelial transcytosis? |
|
Definition
| changes in the cytoplasmic vesiculovacuolar channels |
|
|
Term
| What is the most common cause of increased vascular permeability in acute inflammation? |
|
Definition
| retraction of endothelial cells |
|
|
Term
| What is the most common leukocyte response in acute inflammation? |
|
Definition
| neutrophils for 1st 2 days & then monocytes |
|
|
Term
| *What in acute inflammation leads to leukocyte margination, rolling, adhesion, diapedesis, chemotaxis, activsation, phagocytosis & release of toxic products? |
|
Definition
| intravascular stasis of blood |
|
|
Term
| How does stasis or blood promote margination of WBCs & leukocytes? |
|
Definition
| disrupts normal axial flow |
|
|
Term
|
Definition
| low-affinity, transient attachment of leukocytes to endothelium via interaction b/w selectins & their ligands |
|
|
Term
| What promotes/mediates rolling of leukocytes in inflammation? |
|
Definition
| chemical mediators released in response to injury promote increased expression of P- & E- selectins on endothelial cell surface => weakly bind to ligands on leukocyte, WBC cell membrane => transient attachement (rolling) |
|
|
Term
|
Definition
| high affinity, firm attachment of leukocytes to endothelium b/w integrins & lignads |
|
|
Term
| What promotes/mediates adhesion of leuokocytes in inflammation? |
|
Definition
on endothelium: various cytokines => increased integrin ligans on endothelial cell surface
and
on leukocytes: binding of chemokines to endothelial proteoglycans => activation of leukocyte transmembrane integrins to a high-affinity state |
|
|
Term
| What promotes diapedesis of leukocytes in inflammation after adhesion? |
|
Definition
| chemokine response => migration b/w endothelial cells thru basement membrane & into extravascular CT matrix |
|
|
Term
| What in the intracellular junctions of endothelial cells has a role in diapedesis? |
|
Definition
|
|
Term
| What is secreted to promote diapedesis thru the basement membrane of endothelial cells? |
|
Definition
|
|
Term
| When in diapedesis are leukocyte adhesion molecules required again? |
|
Definition
| in the extravascular CT matrix |
|
|
Term
|
Definition
| movement in response to a chemical gradient |
|
|
Term
| How do chemotactic agents (exogenous & endogenous) cause contraction of the filopodium (i.e. causing leukocytes to move)? |
|
Definition
| chemotactic agents bind leukocyte G protein coupled receptors => cellular activation => actin reoganization => regulated interaction b/w polymerized actin & myosin => contraction of filopodium |
|
|
Term
| What causes cellular activation? |
|
Definition
| binding of receptors to various ligands => cellular modifications |
|
|
Term
| What do TLRs (toll-like receptors) bind to cause cellular activation? |
|
Definition
| microbial products s.a. LPS |
|
|
Term
| What do G protein coupled receptors bind to cause cellular activation? |
|
Definition
| substances s.a bacterial peptides, chemokines, C5a, arachidonic acid metabolites |
|
|
Term
| What do receptors for cytokines bind to cause cellular activation? |
|
Definition
|
|
Term
| What do receptors for opsonins bind to cause cellular activation? |
|
Definition
| substances s.a. IgG, C3b, certain plasma lectins |
|
|
Term
| What are the 2 consequences of cellular activation? |
|
Definition
1) amplification of inflammatory response
2) initiation of phagocytosis with release of toxic products |
|
|
Term
| What increases phagocytosis? |
|
Definition
|
|
Term
| How are items recognized for phagocytosis? |
|
Definition
|
|
Term
| What needs to be modified in order for engulfment to occur? |
|
Definition
| cytoskeletal & cell membrane modifications |
|
|
Term
| How does engulfment occur? |
|
Definition
| cytoplasmic pseudopods surround particle => formation of phagosome => fusion with lysosome => degranulation into resultant phagolysosome |
|
|
Term
| What are the 2 mechanisms of cellular killing? |
|
Definition
*oxygen dependent
oxygen-independent |
|
|
Term
def
*oxygen-dependent killing mechanism |
|
Definition
activation of NADPH oxidase in phagolysosomal membrane => formation of surperoxide anion => formation of hydrogen peroxide =>
a) hydroxyl free radical
b) hypochlorite (when myeloperoxidase is combined with a halide) |
|
|
Term
def
oxygen independent killing |
|
Definition
| proteins in leukocyte granules s.a. bactericidal premeability increasing protein, enzymes, lactoferrin, etc |
|
|
Term
| How does degradation occur after killing? |
|
Definition
| lysosomal acid hydrolysis |
|
|
Term
| Where are 2 places toxic products can be released to? |
|
Definition
1) phagolysosome
2) extracellular tissue |
|
|
Term
| What are the 3 ways toxic products are released to the extracellular tissue? |
|
Definition
1)regurgiation during feeding
2)frustrated phagocytosis
3)cytotoxic release |
|
|
Term
| What causes termination of acute inflammation? |
|
Definition
| removal of initial stimulus, short-lived chemical mediators, apoptosis of neutrophils, & production/release of various agents (anti-inflammatories) |
|
|
Term
| What are the 5 sources of chemical mediators of acute inflammation? |
|
Definition
1) preformed cellular stores
2) plasma proteins
3) newly synthesized cellular products
4) phagolysosome components of activated leukocytes
5) other pro-inflammatory mediators |
|
|
Term
| What source of chemical mediation of acute inflammation are the early responders? |
|
Definition
| preformed cellular stores |
|
|
Term
| What do the preformed cellular stores chemical mediators of acute inflammation consist of? |
|
Definition
*vasoactive amines
a) histamine
b) serotonin |
|
|
Term
Function
vasoactive amines |
|
Definition
| vasodilation & increased vascular permeability via endothelial cell contraction |
|
|
Term
| What is the source of histamine as a chemical mediator of acute inflammation? |
|
Definition
| mast cell degranulation triggered via multiple stimuli |
|
|
Term
| What is the source of serotonin as a chemical mediator of acute inflammation? |
|
Definition
|
|
Term
| How are plasma proteins chemical mediators of acute inflammation? |
|
Definition
| they're inactive precursors |
|
|
Term
| What happens when plasma protein precursors of chemical mediators of acute inflammation are activated? |
|
Definition
| they regulate systems of enzymatic cascades to amplify the inflammatory response |
|
|
Term
| What are the 3 systems of plasma protein chemical mediators of acute inflammation (i.e. cascades that amplify acute inflammatory response)? |
|
Definition
1) complement system
2) kinin system
3) coagulation systems |
|
|
Term
| What are the 3 pathways of activation of the complement cascade? |
|
Definition
classical, alternative, or lectin pathways
(also C3 & C5 can be activated via proteolytic enzymes within inflammatory exudate) |
|
|
Term
| How is the classical complement system activation? |
|
Definition
| C1 fixation to Ag-Ab complex |
|
|
Term
| How is the alternative complement system activated? |
|
Definition
| direct activation by microbial products |
|
|
Term
| How is the lectin complement pathway activated? |
|
Definition
| C1 activation via plasma lectin binding to microbial sugars |
|
|
Term
| Where do all 3 complement pathways coverge? (i.e. what step is the same) |
|
Definition
| formation of C3 covertases to cleave C3 |
|
|
Term
| What happens when C3 is cleaved? |
|
Definition
| release of C3a & binding of C3b |
|
|
Term
| What is formed once C3b binds? |
|
Definition
| C5 convertases to cleave C5 |
|
|
Term
| What happens when C5 is cleaved? |
|
Definition
| release of C5a & binding of C5b |
|
|
Term
| What happens ince C5b binds? |
|
Definition
| C6-C9 follow the same formation => formation of membrane attack complex (MAC) to form pores |
|
|
Term
| What are the 4 major effects of the activated complement system? |
|
Definition
1) vasodilation & increased vascular permeability (via C3a & C5a => stimulate mast cell degranulations => histamine release)
2) leukocyte chemotaxis & activation (via C5a)
3) opsonization (via C3b) => phagocytosis
4) cell lysis (via MAC) |
|
|
Term
| What activated the kinin system? |
|
Definition
| contact of factor XII (hageman factor) |
|
|
Term
| What does activation of factor XII cause? |
|
Definition
| production of factor XIIa |
|
|
Term
| What does factor XIIa cause? |
|
Definition
| coversion of prekallikrein to kallikrein |
|
|
Term
| What does kallikrein cause? |
|
Definition
| proteolytic cleavage of high-molecular wt (HMW) kininogen |
|
|
Term
| What does proteolytic cleavage of HMW kininogen cause? |
|
Definition
|
|
Term
| What are the 3 major effects of activation of the kinin pathway? |
|
Definition
1) HMW kininogen & kallikrein => increased XII activation
2) kallikrein => chemotaxis & generation of plasmin
3) bradykinin => vasodilation, increased vascular permeability & pain |
|
|
Term
| What 2 systems are coagulations systems? |
|
Definition
1) clotting system
2) fibrinolytic system |
|
|
Term
| What 2 pathways converge in the clotting system? |
|
Definition
| interconnected intrinsic & extrinsic pathways |
|
|
Term
| What plays a key role in the clotting system? |
|
Definition
|
|
Term
| What is thrombin generated from? |
|
Definition
| prothrombin near the end of the coagulation cascade that results in fibrin formation |
|
|
Term
| What does thrombin bind to in the clotting system? |
|
Definition
| protease-activated receptors (g protein coupled receptors) on many cells |
|
|
Term
| What does thrombin binding cause in the clotting system? |
|
Definition
| increased inflammatory response |
|
|
Term
| What plays a key role in the fibrinolytic system? |
|
Definition
|
|
Term
|
Definition
| cleavage of plasminogen by plasminogen activator |
|
|
Term
| What does plasmin formation cause? |
|
Definition
| increased inflammatory response |
|
|
Term
| What are the 4 newly synthesized chemical mediators of acute inflammation? |
|
Definition
1) eicosanoids
2) PAF (platelet activating factor)
3) cytokines
4) NO |
|
|
Term
| What eicosanoids are chemical mediators of acute inflammation? |
|
Definition
| arachidonic acid metabolites |
|
|
Term
| What activates arachidonic acid production & release from the cell membrane? |
|
Definition
| mutiple stimuli => increased cytosolic Ca2+ & phospholipase A2 activation |
|
|
Term
| How does arachidonic acid mediate the acute inflammatory response? |
|
Definition
| => metabolic rxns by enzymes => production of mediators to amplify inflammatory response (via G protein coupled receptors) |
|
|
Term
| What arachidonic acid metabolites are synthesized by cyclooxygenases (COX 1 & COX 2) induction? |
|
Definition
| prostaglandins & thromboxane |
|
|
Term
| What is the effect of prostaglandins? |
|
Definition
1) vasodilation, increased vascular permeability, pain, & fever
2) inhibit platelet aggregation |
|
|
Term
| Where is thromobane mainly produced? |
|
Definition
|
|
Term
| What effect does thromboxane have? |
|
Definition
| vasoconstriction & platelet aggregation (opposite effect of prostaglandins) |
|
|
Term
| What arachidonic acid metabolite is synthesized by lipoxygenases? |
|
Definition
|
|
Term
| What happens to metabolite production due to the selective presence of various lipoxygenases in different cell types? |
|
Definition
| can only occur in thru the mutual interation of neutrophils & platelets |
|
|
Term
| What leukotriene is produced mostly by neutrophils? |
|
Definition
|
|
Term
|
Definition
| chemotactic & activated other neutrophils |
|
|
Term
| Function
Leukotrienes: LTC4, LTD4, LTE4 |
|
Definition
| vasoconstriction, bronchospasm & increased vascular permeability |
|
|
Term
|
Definition
| inhibt acute inflammatory leukocyte response |
|
|
Term
| What so anti-inflammatory drugs target? |
|
Definition
| newly-synthetic reactions |
|
|
Term
| What does aspirin & other NSAIDs inhibit? |
|
Definition
| COX (and therefore prostaglandins & thromboxane) |
|
|
Term
| What do steroids inhibit? |
|
Definition
| phospholipase (and therefore all arachidonic acid & it's metabolites) |
|
|
Term
| What is PAF synthesized from? |
|
Definition
|
|
Term
| What leads to PAF production? |
|
Definition
| stimulation of multiple cell types |
|
|
Term
| How does PAF mediate the acute inflammatory response? |
|
Definition
| binds to G protein coupled receptor => increased inflammatory response |
|
|
Term
|
Definition
| secreted proteins that alter the activity of other cell types |
|
|
Term
| What are the 3 cytokines? |
|
Definition
1) TNF (tumor necrosis factor)
2) Interleukins
3) chemokines |
|
|
Term
| What produces TNF & IL-1? |
|
Definition
| macrophages activated at inflammatory sites |
|
|
Term
| What 3 local effects are seen by TNF & IL-1? |
|
Definition
1) leukocyte stimulation (inflammation)
2) endothelial activation (inflammation)
3) stimulation of fibroblasts (repair) |
|
|
Term
| What acute systemic effects are seen by TNF & IL-1? |
|
Definition
| fever, anorexxia, fatigue, increased # circulating neutrophils, APP production, potential hemodynamic alterations |
|
|
Term
| What chronic systemic effects are seen by TNF & IL-1? |
|
Definition
| cachexia (altered metabolic state => wasting) |
|
|
Term
|
Definition
|
|
Term
| What cells secrete chemokines? |
|
Definition
| various cells activated by inflammation |
|
|
Term
| What happens when chemokines bind to their receptors? |
|
Definition
| leukocyte chemotaxis (can be selective) |
|
|
Term
| What increases NO production? |
|
Definition
|
|
Term
| *What 3 actions does NO have? |
|
Definition
1) vasodilation
2) inhibition of inflammation
3) antimicrobial activity |
|
|
Term
| How does NO cause vasodilation? |
|
Definition
| relaxation of vascular smooth muscle |
|
|
Term
| How does NO inhibit inflammation? |
|
Definition
| decrease WBC & platelet adhesion |
|
|
Term
| How does NO have antimicrobial activity? |
|
Definition
|
|
Term
| Why are phagolysosome components of activated leukocytes critical in host defense? |
|
Definition
1) killing &/or degradation of phagocytosed material
2) amplification of inflammatory response |
|
|
Term
What is present in the serum &/or tissue to counteract agents in phagolysosome?
Why are they necessary? |
|
Definition
| essential inactivators (s.a. antiproteases & antioxidants) to protect neiboring cells & ECM |
|
|
Term
| What are the 2 degradative components of phagolysosome of activated leukocytes that can regulate the acute inflammatory response? |
|
Definition
| lysosomal enzymes & oxygen-derived free radicals |
|
|
Term
| *What are the 3 key lysosomal enzymes? |
|
Definition
1) acid hydrolases
2) neutral proteases
3) phospholipase |
|
|
Term
| How are oxygen-derived free radicals formed in the phagolysosome? |
|
Definition
| secondary to NADPH oxidase activation |
|
|
Term
| What are the 3 "other" pro-inflammatory mediators? |
|
Definition
1) neuropeptides
2) hypoxia-induced factor 1α
3) uric acid |
|
|
Term
| Where are neuropeptides (s.a. substance P) produced? |
|
Definition
|
|
Term
| What cells generate hypoxia-induced factor 1α? |
|
Definition
| cells with inadequate oxygen |
|
|
Term
| What is uric acid the end product of? |
|
Definition
|
|
Term
| What is uric acid derived from? |
|
Definition
| breakdown of nucleic acids |
|
|
Term
*Function
thrombin & plasmin |
|
Definition
| amplify multiple steps in the acute inflammatory response |
|
|
Term
|
Definition
| anti-inflammatory function |
|
|
Term
| What 7 chemical mediators of acute inflammatory response are responsible for that vascular changes (vasodilation/increased vascular permeability)? |
|
Definition
| 1) vasoactive amines (preformed histamine & serotonin)
2) anaphylatoxins (C3a & C5a)
3) bradykinin
4) prostaglandins
5) NO (vasodilation only)
6) Leukotrienes (increased vascular permeability only) - except LTB4
7) PAF (increased vascular permeability only) |
|
|
Term
| What 7 chemical mediators of acute inflammatory response are responsible for leukocyte activation? |
|
Definition
| 1) C3b (opsinization)
2) C5a (chemotaxis)
3) LTB4
4) PAF
5) TNF & IL-1
6) chemokines (chemotaxis)
7) lysosomal enzymes & oxygen derived free radicals |
|
|
Term
| What 2 chemical mediators of acute inflammatory response are responsible for platelet activation? |
|
Definition
1) thromoxane (platelet aggregation)
2) PAF |
|
|
Term
| What 2 chemical mediators of acute inflammatory response are responsible for pain? |
|
Definition
1) bardykinin
2) prostaglandins |
|
|
Term
| What 2 chemical mediators of acute inflammatory response are responsible for tissue destruction? |
|
Definition
1) lysosomal enzymes
2) oxygen derived free radicals |
|
|
Term
| What 2 chemical mediators of acute inflammatory response cause systemic effects? |
|
Definition
1) prostaglandins (fever)
2) TNF & IL-1 |
|
|
Term
| *How do small lymphatics eventually drain into the systemic venous circulation? |
|
Definition
| Sm. peripheral thin-walled lyphatic capillaries => larger lyphatic vessels w/ one-way valves => filtration thru lymph nodes => eventual drainage |
|
|
Term
| Why are lymphatics important in acute inflammation? |
|
Definition
| it's a potential source for dissemination of initially local processes |
|
|
Term
| What 2 roles (besides potential dissemination route) does lymphatics have in acute inflammation? |
|
Definition
1) clearance of excess interstitial fluid (edema)
2) enhancement of host response by adaptive & mononuclear phagocytic systems |
|
|
Term
| How do lymphatics cause enhancement of hose response by adaptive imune & mononuclear phagocytic systems? |
|
Definition
| exposure of Ag, Ag processing cells & activated lymphocytes drained from injured site to lymph nodes |
|
|
Term
| *What are the consquences of acute inflammation dependent on? |
|
Definition
| severity, duration & site of inciting stimulus and effectiveness of host inflammatory response |
|
|
Term
| What are the 3 potential consequences of acute inflammation? |
|
Definition
1) complete resolution
2) healthing with fibrosis
3) persistent inflammation |
|
|
Term
|
Definition
| restoration of tissue back to normal morphology & function |
|
|
Term
| What causes healing with fibrosis? (scarring?) |
|
Definition
| more significant tissue damage, as well as sites with limited regeneration |
|
|
Term
| What are the 4 distinctive variations of acute inflammation? |
|
Definition
1) Serous inflammation
2) fibrinous inflammation
3) suppurative (purulent) inflammation
4) ulceration |
|
|
Term
|
Definition
| responsed to injury characterized predominately by an accumulation of sparsely cellular fluid (i.e. superficial burn, blister) |
|
|
Term
def
fibrinous inflammation |
|
Definition
| an acute inflammatory response process in which extravascular fibrin deposition plays a prominent role (esp. on tissue surfaces within body cavities) |
|
|
Term
def
suppurative (purulent) inflammation |
|
Definition
| dense collection of acture inflammatory cells with accomplanying proteinaceous edema fluid and necrotic cellular debris (exudate) |
|
|
Term
| What often causes suppurative (purulent) inflammation? |
|
Definition
|
|
Term
| What type of suppurative inflammation is in its own distinctive category? |
|
Definition
|
|
Term
|
Definition
| focal accumulation of suppurative inflammation within an organ that destroys the resident tissue => liquefactive necrosis |
|
|
Term
| What surround abcess if it's long lasting? |
|
Definition
|
|
Term
|
Definition
| erosion of an organ's epithelial surface & subjacent tissue dur to shedding of necrotic cells & debris, accompanied by an acute inflammatory exudate |
|
|
Term
| What happens in ulceration is long-standing? |
|
Definition
| chronic inflammation & fibrosis develop at the base |
|
|
Term
| What causes realease of acute inflammatory mediators? |
|
Definition
|
|
Term
| What do inflammatory mediators promote in the inflammatory response? |
|
Definition
| vasodilation & increased vascular permeability => influx & activation of acute inflammatory cells (neutrophils & macrophages) |
|
|
Term
| What does activation of inflammatory cells lead to? |
|
Definition
| dilution/phagocytosis of initiating insult & amplification of the inflammatory response (via formation of additional mediators) => 1 of 3 consequences of acute inflammation |
|
|
Term
| What are the 7 vascular mediators in acute inflammation? |
|
Definition
1) Prostaglandins
2) Leukotrienes (C,D,E)
3) Anaphlatoxins (C3a, C5a)
4) NO
5) Bradykinin
6) PAF
7) Vasoactive amines (serotonin & histamine)
(PLAN BP Vasodilation - and every other letter starting with L does NOT do BOTH vasodilation & increase permeability)
Leukotrienes C,D,E (C=vasoConstrict therefore vascular permeability)
NO (vasodilation only)
PAF (vascular permeability) |
|
|
Term
| What are the 7 leukocyte mediators of acute inflammation? |
|
Definition
1) Chemokines (chemotactant)
2) C5a (chemotactant)
3) C3b (Obsonization)
4) Leukotriene B
5) Lysosomal enzymes/Oxygen free radicals
6) IL-1/TNP
7) PAF
(CCCLLIP - you clip things on)
*notice PAF is the past P for both PLAN BP Vasodilation & CCCLLIP |
|
|
Term
| What are the 2 causes of chronic inflammation? |
|
Definition
1) *persistent tissue injury
2) certain infection types |
|
|
Term
| How does persistent tirrue injury cause chronic inflammation? |
|
Definition
| inability to eliminate intial damaging stimulus in a few days => predominance of activated marcophages at site => chemical mediator & oxygen free radical production/release => ongoning tissue damage & cytokines => recruitment of extra monocytes & lymphocytes and growth factors => fibroblast proliferation & development of adaptive immune system => chronic inflammatory cell infiltrate, continuing tissue destruction & fibrosis |
|
|
Term
| What is host defense dependent upon in intracellular pathogens that chronic inflammation? |
|
Definition
|
|
Term
| What infiltrate is associated with tissue damage? |
|
Definition
| mononuclear inflammatory cell infiltrate ± fibrosis |
|
|
Term
| What are teh components of inflammatory cell infiltrate? |
|
Definition
| lymphocytes, marcophages, plasma cells |
|
|
Term
| What does fibrosis associated with tissue damage depend on? |
|
Definition
| nature, site, & severity of injury |
|
|
Term
| How do cytokines & GFs increases fibrosis in tissue damage? |
|
Definition
GF => proliferation of fibroblasts & fibrogenic cells => increased collagen synthesis
cytokines => increased collagen synthesis |
|
|
Term
| What are the 2 unique inflammatory responses? |
|
Definition
Granulomatous Inflammaton
Eosinophilic-Predominant Inflammation |
|
|
Term
def
granulomatous inflammation |
|
Definition
| chronic inflammation characterized by distinct aggregates of activated macrophages in addition to the other signs of chronic inflammation (tissue injury & fibrosis) |
|
|
Term
| What 2 agents can cause granulomatous inflammation? |
|
Definition
1) organisms resistant to killing => delayed-type hypersensitivity (i.e. mycobacteria, fungus)
2) particulate matter resistant to degradation => foreign body granulomas |
|
|
Term
| How are granulomas formed? |
|
Definition
| persistent stimulation by resistant agents => enlargement, adherence & coalescence of macrophages => activation to T cells => production of IFN-γ & IL-2 (further macrophage activation & augments T-cell response) |
|
|
Term
| What cells form the granuloma? |
|
Definition
| clusters of activated macrophages (some may be fused to giant cells) & is frequently surrounded by a rim of lymphocytes |
|
|
Term
| When can central caseous necrosis be within a granuloma? |
|
Definition
| if due to infectious causes (esp. TB) |
|
|
Term
| What 2 agents can cause eosinophilic-predominant inflammation? |
|
Definition
1) IgE-mediated type 1 hypersensitivity rxn
2) parasitic inf. |
|
|
Term
| *What is produced by inflammatory cell infiltrate to cause Systemic Inflammatory Response Syndrome (SIRS)? |
|
Definition
| cytokines (esp. TNF & IL-1) |
|
|
Term
| *With what type of infections is SIRS most prominent? |
|
Definition
|
|
Term
|
Definition
| nonspecific: fatigue, myalgias, & decreased appetite |
|
|
Term
| What causes fever in SIRS? |
|
Definition
| COX synthesis stimulation in hypothalamus => prostaglandin formation => increased body temp mediated by various neurotransmitters |
|
|
Term
|
Definition
|
|
Term
| What happens to peripheral WBC count in SIRS? |
|
Definition
|
|
Term
| *How is WBC count reported? |
|
Definition
| in CBC per unit volume, with % of different WBC types |
|
|
Term
| What causes reactive leukocytosis? |
|
Definition
| initial increase reserve leukocytes from bone marrow + later increased production of colony stimulating factors => increassed bone marroe leukocyte formation |
|
|
Term
|
Definition
| increased peripheral neutrophil count |
|
|
Term
| *What causes reactive neutrophilia? |
|
Definition
| many types of tissue injury (esp. bacterial inf) |
|
|
Term
| *When is left shift neutrophilia seen? |
|
Definition
| significant release of neutrophils from bone marrow |
|
|
Term
def
left shift neutropehilia |
|
Definition
| immature neutrophils seen frequently in the peripheral blood |
|
|
Term
| *What can be stimulated by a marked left shift of neutrophilia? |
|
Definition
|
|
Term
|
Definition
| marked left shift of neutrophilia |
|
|
Term
| *What 3 abnormal things can be seen in neutrophils in neutrophilia? |
|
Definition
1) Dohle bodies
2) toxic granulation
3) vacuolization |
|
|
Term
|
Definition
| increased peripheral lymphocyte count |
|
|
Term
| What infections tend to produce reactive lymphocytosis? |
|
Definition
|
|
Term
def
polyclonal population of lymphocytes |
|
Definition
| each clone with unique surface Ag receptors |
|
|
Term
| Besides polyclonal populations of lymphocytes, what other lymphocytes are seen in reactive lymphocytosis? |
|
Definition
| atypical lymphocytes (usually activated CD8+ T cells) |
|
|
Term
|
Definition
| increased peripheral monoctye count |
|
|
Term
| When in reactive monocytosis seen? |
|
Definition
| chronic inflammatory conditions (s.a. TB) |
|
|
Term
|
Definition
| increased peripheral eosinophil count |
|
|
Term
| What is reactive eosinophilia often found associated with? |
|
Definition
| IgE mediated allergic rxns & parasitic inf. |
|
|
Term
|
Definition
| increased peripheral basophil count |
|
|
Term
| When is reactive basophilia seen? |
|
Definition
|
|
Term
| What is the acute phase response seen in SIRS caused by inflammation? |
|
Definition
| increased or decreased synthesis of APP (mostly by liver) |
|
|
Term
| *What does the acute phase response do to the inflammatory process in the short-term? |
|
Definition
| aids in inflammatory process |
|
|
Term
| What does inflammation do to +APP? |
|
Definition
| increased plasma concentrations |
|
|
Term
| What 8 +APP are increased in inflammation? |
|
Definition
| 1) CRP (C reactive protein)
2) SAA (serum amyloid A protein)
3) fibrinogen
4) α1-antitrypsin
5) haptoglobin & ferritin
6) ceruloplasmin
7) factor VIII & von Willeband factor
8) complement proteins |
|
|
Term
| What are the anti-inflammatory cytokines? |
|
Definition
|
|
Term
| What is produced by the liver in response to anti-inflammatory cytokines? |
|
Definition
|
|
Term
| What +APP is a fairly sensitive marker of inflammation? |
|
Definition
|
|
Term
|
Definition
1)opsonization of damaged cells & some microorganisms
2)activation of complement (via C1 binding - classical)
3)amplification of inflammatory response |
|
|
Term
| When do SAA levels rapidly rise? |
|
Definition
|
|
Term
| When can AA amyloidosis form? |
|
Definition
| chronic formation of SAA with insufficient degradation |
|
|
Term
| What +APP causes increased erythrocyte sedimentation rate (ESR)? |
|
Definition
|
|
Term
|
Definition
| distance that RBCs settle in a verticle column of anticoagulated blood in 1 hr. |
|
|
Term
| Why test for increased fibrinogen & ESR? |
|
Definition
1) nonspecific marker for inflammation
2) increased risk of thrombosis |
|
|
Term
|
Definition
1) inhibit serine proteases
2) anti-inflammatory
=> protection of tissue |
|
|
Term
Function
haptoglobin & ferritin |
|
Definition
| bind free Hb & iron => inability for microorganisms to utilize iron |
|
|
Term
|
Definition
| scavenges free radicals & facilitates iron binding to ferritin |
|
|
Term
| What does inflammation do to -APP? |
|
Definition
| decrease plasma concentrations |
|
|
Term
| What 3 -APP decreased levels => increased availability of substrates & energy for synthesis of +APP? |
|
Definition
1) albumin
2) transferrin
3) retinol-binding protein |
|
|
Term
| Whaat 2 -APP decreased levels lead to temporarily increased bioactive hormone availability? |
|
Definition
1) transthyretin
2) cortisol-binding globulin |
|
|
Term
|
Definition
| potential multisystem organ failure |
|
|
Term
| What does SIRS lead to septic shock? |
|
Definition
| an overwhelming microbial inf. |
|
|
Term
| *What maintains tissue homeostasis? |
|
Definition
| closely regulated rates of cellular expansion, differentiation, & apoptosis |
|
|
Term
| What are the 3 classifications of tissues based on proliferative capacity? |
|
Definition
1) labile tissues
2) quiescent (stable) tissues
3) permanent tissues |
|
|
Term
| *What determines what proliferative capacity each organ will have? |
|
Definition
| The tisse's proliferative capacity, but most organs have a mixture |
|
|
Term
|
Definition
cells are continuously being replaced (generally from stem cells)
s.a. hematopoietic cells, mucosal epithelial cells, epidermis |
|
|
Term
def
quiescent (stable) tissue |
|
Definition
cells are usually resting, but can be stimulated to proliferate
s.a. hepatocytes, fibroblasts, endothelial cells, smooth muscle cells |
|
|
Term
|
Definition
cells with very limited regenerative capability
s.a. neurons, cardiac myocytes, skeletal muscle cells |
|
|
Term
| What 2 cells types serve as reservoirs for cellular expansion? |
|
Definition
1) parenchymal cells
2) adult stem cells |
|
|
Term
| *What does the relative contribution of parenchymal cells & adult stem cells in cellular expasion depend on? |
|
Definition
| tissue's proliferative capacity & state of health |
|
|
Term
| What is the main cellular replacement source for quiescent tissues? |
|
Definition
|
|
Term
|
Definition
| capacity for both self-renewal & differentiation |
|
|
Term
| What are adult stem cells the replacement source for? |
|
Definition
| labile tissues & injured permanent tissues |
|
|
Term
| What are the 2 types of adult stem cells? |
|
Definition
1) multipotent adult progenitor cells
2) tissue stem cells |
|
|
Term
| What type of adult stem cells are closely related to embryonic stem cells? |
|
Definition
| multipotent adult progenitor (due to broad differentiation capacity) |
|
|
Term
| Which tissues have multipotent adult progenitor cells? |
|
Definition
| many tissues, including bone marrow |
|
|
Term
| Where are tissue stem cells located? |
|
Definition
| outside of the bone marrow |
|
|
Term
| how does tissue stem cells differ from multipotent adult progenitor cells in terms of differentiation capacity? |
|
Definition
| tissue stem cells have restricted differentiation capacity |
|
|
Term
| What initiated normal cell replication? |
|
Definition
| appropriate stimulus binds receptor => activation od signal transducing proteins => activation of nuclear regulatory proteins => DNA transcription of pre-genes |
|
|
Term
| *What 2 cells (predominately) produce growth factors? |
|
Definition
| mesenchymal & inflammatory cells (fibroblasts, activated macrophages, etc) |
|
|
Term
|
Definition
| repair in tissue regeneration & healing by fibrosis |
|
|
Term
| *What 6 GFs have a key role in stimulation of replication? |
|
Definition
1) EGF (epidermal)
2) HGF (hepatocyte)
3) VEGF (vascular endothelial)
4) PDGF (platelet derived)
5) FGF (fibroblast)
6) TBF-β (transforming) |
|
|
Term
|
Definition
| stimulate proliferation of epithelial cells & fibroblasts |
|
|
Term
|
Definition
| promote replication & motility of most epithelial cells |
|
|
Term
|
Definition
| stimulus for growth of new vlood vessels (angiogenesis) |
|
|
Term
|
Definition
| induce migration & replication of fibroblasts, smooth muscle cells & monocytes |
|
|
Term
|
Definition
| promotes angiogenesis & influx of multiple cells needed for tissue regeneration |
|
|
Term
|
Definition
| stimulus for fibrosis & inhibit inflammation |
|
|
Term
| What are the 3 routes of stimulation of repair? |
|
Definition
1) autocrine
2) paracrine
3) endocrine |
|
|
Term
| *What is the most common route of stimulation in tissue regeneration & healing by fibrosis? |
|
Definition
|
|
Term
|
Definition
| cell secretes & is the target of stimulus |
|
|
Term
|
Definition
| target cell's close to the cell producing signaling molecule |
|
|
Term
|
Definition
| secreting sell acts on its target from a distance (usually via the bloodstream) |
|
|
Term
| What 4 receptors are stimulated in cellular proliferation? |
|
Definition
1) *tyrosine kinase receptors
2) w/o tyrosine kinase receptors
3) GPCR (g protein coupled receptors)
4) steroid homone receptors |
|
|
Term
| Which receptor is most frequently utilizaed during tissue repair? |
|
Definition
| receptors with intrinsic TK activity |
|
|
Term
| What occurs prior to TK activation after binding of receptor? |
|
Definition
|
|
Term
| What does TK activate in repair? |
|
Definition
| mutliple signal transduction pathways |
|
|
Term
Function
receptors without intrinsic TK activity in tissue repair |
|
Definition
| route for cytokine signaling |
|
|
Term
Function
GPCRs in tissue repair |
|
Definition
| diversified rxns activated by multiple ligands |
|
|
Term
Function
seroid hormone receptors in tissue repair |
|
Definition
| transcription factors (localized to nucleus) |
|
|
Term
|
Definition
| genes s.a. GFs, GFRs, & proteins promoting cell cycle advancement |
|
|
Term
| *What are the critical cell-cycle regulators? |
|
Definition
cyclins
CDKs
CDK inhibitors |
|
|
Term
| What causes CDK phosphorylation & activation? |
|
Definition
| CDK binds to cell-cycle-specific cyclins |
|
|
Term
|
Definition
| phosphorylation of key proteins for progression thru the cell cycle |
|
|
Term
| What are the 5 phases of the cell cycle? |
|
Definition
| G0 => G1 => S phase => G2 => M phase (=> G0 or G 1) |
|
|
Term
|
Definition
| synthesis of cyclin D & cyclin E => production of phosphorylated D/CDK & E/CDK => posphorylation of RB protein => trancriptional activation of genes promoting progression thru G1/S check point |
|
|
Term
|
Definition
| synthesis of cyclin A => formation of phosphorylated A/CDK |
|
|
Term
|
Definition
| synthesis of cyclin B => production of phosphorylated B/CDK => initiation of M phase |
|
|
Term
| What is the completion of M phase characterized by? |
|
Definition
| removal of phosphate groups from RB protein |
|
|
Term
| What do CDK inhibitors respond to? |
|
Definition
| growth suppressing signals |
|
|
Term
|
Definition
| block progression of the cell cycle by inactivating the cyclin/CDK complexes or inhibiting their formation |
|
|
Term
| Where are the 2 cell cycle check points? |
|
Definition
|
|
Term
|
Definition
| check for DNA defects prior to replication |
|
|
Term
| What happens if DNA damage is detected at G1/S checkpoint? |
|
Definition
=> p53 activation => cell-cycle arrect => attempt at DNA repair
if successful: continuation thru cell cycle
if unsuccessful: activation of apoptosis |
|
|
Term
|
Definition
| check for DNA defects after replication |
|
|
Term
| what happens if DNA damage is dected at the G2/M checkpoint? |
|
Definition
| cell-cycle arrest via p53 dependent & independent processes to allow DNA repair |
|
|
Term
def
true tissue regeneration |
|
Definition
| complete restoration back to the original state |
|
|
Term
| When can true tissue regeneration occur? |
|
Definition
| injury to labile & quiescent tissues when ECM framework remains intact |
|
|
Term
def
compensatory hyperplasia |
|
Definition
| restoration of the functional mass, but not the original anatomy |
|
|
Term
| *When might the liver undergo compensatory hyperplasia? |
|
Definition
| after partial liver removal |
|
|
Term
| What causes compensatory hyperplasia of the liver? |
|
Definition
| paracrine signaling of cytokines & GFs produced by nonparenchymal cells of residual liver => priming & ultimately proliferation of remaining hepatocytes => replication of hepatic nonparenchymal cells |
|
|
Term
| When after tissue injury is there attempt to neutralize the injurous agent & remove the damaged tissue? |
|
Definition
| after onset of acute inflammatory response |
|
|
Term
| What type of injury can result in complete tissue restoration? |
|
Definition
|
|
Term
| What type of healing occurs if the injury is sever, persistent or involves permanent cells? |
|
Definition
| healing with fibrosis & partial reconstitution of cells capable of regeneration |
|
|
Term
| What are the 2 sequential phases of tissue repair? |
|
Definition
1) granulation tissue
2) scar development |
|
|
Term
| What causes residual inflammation in granulation tissue? |
|
Definition
| neutrophils & macrophages still present in an acute injury |
|
|
Term
| *Why is there exudative edema in granulation tissue? |
|
Definition
| angiogenesis is occuring, and the immature vessels are leaky |
|
|
Term
| What stimulates angiogenesis in granulation tissue? |
|
Definition
| production of VEGF & FGF => migration, proliferation & differentiation of endothelial cells |
|
|
Term
| What causes capillary formation in granulation tissue? |
|
Definition
| bone marrow endothelial precursor cells & pre-existing local blood vessels |
|
|
Term
| What causes capillary maturation & stabilization in graulation tissue? |
|
Definition
| vessel remodeling, recruitment of surrounding pericytes & smooth muscle cells, and deposition of ECM proteins |
|
|
Term
| What elicits migration & proliferation of fibroblasts in granulation tissue? |
|
Definition
| mutiple GFs & inflammatory cytokines supported by extravascular plasma protein framework |
|
|
Term
| What GF is key to all phases of scar formation? |
|
Definition
|
|
Term
| What are the 3 steps to scar formation? |
|
Definition
1) decrease # of proliferating endothelial cells & fibroblasts
2) increase deposition of ECM
3) CT remodeling |
|
|
Term
| What balances ECM synthesis & degradation in CT remodeling? |
|
Definition
| closely regulated matrix metalloproteinases |
|
|
Term
| What are the 5 functions of macrophages in wound healing? |
|
Definition
1) removal of injured tissue/debris
2) antimicrobial activity
3) chemotaxis & proliferation of fibroblasts
4) angiogenesis
5) deposition & remodeling of ECM |
|
|
Term
| What are the 2 patterns of woound healing? |
|
Definition
Healing by first intention
Healing by second intention |
|
|
Term
| What wounds heal by first intention? |
|
Definition
| narrow skin wound with minimal tissue damage |
|
|
Term
| What wounds heal by second intention? |
|
Definition
| larger skin defect with more extensive tissue damage |
|
|
Term
Generation of a Fibrin Clot & Acute Inflammatory response
Healing by first intention |
|
Definition
days 1-3: gap filled with a blood clot
influx of neutrophils & then macrophages
beginning epidermal re-epithelialization |
|
|
Term
Generation of a Fibrin Clot & Acute Inflammatory response
Healing by second intention |
|
Definition
formation of a larger fibrin clot
more extensive tissue destruction w/ a prolonged & more intense acute inflammatory response |
|
|
Term
Grandulation Tissue Formation & Reconstitution of the Epidermis
Healing by first intention |
|
Definition
days 4-6: residual acute inflammatory cells, esp. macrophages
maximal angiogenesis w/ exudative edema
migration & proliferation of fibroblastsepidermal regeneration |
|
|
Term
Grandulation Tissue Formation & Reconstitution of the Epidermis
Healing by second intention |
|
Definition
| generation and persistence of much larger amounts of granulation tissue; delayed epidermal re-epithelialization |
|
|
Term
Development of a Scar
Healing by first intention |
|
Definition
over the following several weeks to months
gradual reduction in the number of WBCs, vessels, and fibroblasts
accumulation of collagen
ECM remodeling with increasing tensile wound stength (never completely back to pre-wound strength) |
|
|
Term
Development of a Scar
Healing by second intention |
|
Definition
| more extensive scar formation with significant wound contraction (role of myofibroblasts) |
|
|
Term
| What 5 factors can impede wound healing? |
|
Definition
1) *infection (local or systemic)
2) inadequate circulatory status via decreased blood supply or decreased drainage (impaired venous or lymphatic systems)
3) decreaed immune response
4) malnutrition
5) wound disruption |
|
|
Term
| What are 2 complications of wound healing? |
|
Definition
1) insufficient scar formation
2) excessive scar development |
|
|
Term
| What complications occur due to insifficient scar formation? |
|
Definition
| persistent ulceration or wound dehiscence |
|
|
Term
|
Definition
|
|
Term
| What 4 complication arise in excessive scar development? |
|
Definition
1) overabundant granulation tissue
2) hypertrophic scar
3) keloid
4) contracture |
|
|
Term
| Why is overabundant granulation tissue inhibitory to wound healing? |
|
Definition
| prevention of reconstitution of epidermis |
|
|
Term
|
Definition
| inordinate accumulation of collagen - results in raised scar |
|
|
Term
|
Definition
| deposition of extreme quantities of thick, aberrant collagen bands => extensive scar formation |
|
|
Term
|
Definition
| significant wound contraction => tissue deformaties |
|
|
Term
| What is the purpose of the lab & clinical pathology? |
|
Definition
1) Confirm/reject Dx
2) Guide patient management
3) Eastablish prognosis/stage
4) Detect occult disease
5) Monitor therapy
6) Estimate disease activity
7) Prevent irreparable damage |
|
|
Term
| What lab protocols must implicitly be followed in order to provide quality lab values? |
|
Definition
1) specimen collection
2) handling
3) processing |
|
|
Term
| What are the 3 settings lab results can be generated from? |
|
Definition
1) Clinical lab
2) POC (point of care)
3) physician's office |
|
|
Term
| When is POC testing appropriate? |
|
Definition
| actue condition in which changes are rapid s.a. ER or OR |
|
|
Term
| What is the advantage to POC testing? |
|
Definition
| provides "real time" results |
|
|
Term
| Who provides the guidance and training for POC testing? |
|
Definition
| clinical lab (they're also responsible to maintain quality control & quality improvement) |
|
|
Term
| What are the tests able to be performed at the physician's office? |
|
Definition
The "waived tests" - easy to perform technically s.a.:
-pregnancy
-rapid flu
-rapid strep
-mono-spot |
|
|
Term
| Why can't physician's offices perform tests beyond the "waived" scope? |
|
Definition
| CLIA 88 = amendment issued by Congress to closely regulate lab testing |
|
|
Term
|
Definition
| physician (written or direct order) |
|
|
Term
| What does the physician's order of test generate a list for? |
|
Definition
|
|
Term
| What must be contained on the order for testing? |
|
Definition
Patient's demographics:
-name
-sex
-age
-DOB
-date of admission
-date of test request
-hospital number
-ordering physician |
|
|
Term
| What 6 things must be considered that the patient can do that may influence lab determinations? |
|
Definition
1) Diurnal variations
2) Physical activity
3) Fasting Status
4) Chronic EtOH
5) Postural changes
6) Drug regimen |
|
|
Term
|
Definition
| variations that occur every day |
|
|
Term
| What 2 daily serum infiltrates have diurnal variation? |
|
Definition
1) Cortisol
2) Neutrophil count |
|
|
Term
| What is the nature of the diurnal variation of cortisol? |
|
Definition
| Highest in morning & lowest around midnigh for ppl w/ normal sleep pattern |
|
|
Term
| What causes the diurnal variation of cortisol? |
|
Definition
|
|
Term
| What is the nature of the diurnal variation of neutrophils? |
|
Definition
highest around 4 pm in ambulatory patients, lowest in the morning @ rest.
There is significant individual variation (some who display NO dinural variation) |
|
|
Term
| How does physical activity affect lab values? |
|
Definition
1) Transient increase in some enzymes (CK, AST, LD)
2) Long lasting effect on some lipoproteins |
|
|
Term
What serum values may change at a 48 hr fast?
72 hours? |
|
Definition
48 hrs:
biliribun increase slightly
72 hrs:
hypoglycemia
increase triglycerides
increase fatty acids |
|
|
Term
| How long should a person fast prior to lab tests to provide an evaluation of the basal rate? |
|
Definition
|
|
Term
| What happens if a patient chooses not to fast & has a small meal prior to lab tests? |
|
Definition
| may affect several parameters including fat, protein, & serotonin |
|
|
Term
| What serum parameters are affected by chronic EtOH use? |
|
Definition
incrase HDL, cholesterol, & some liver enzymes
incease in MCV (mean corpuscular volume) |
|
|
Term
| How can postural changes affect lab values? |
|
Definition
| proplonged standing or sitting can cause loss of intravascular fluid due to increased hydrostatic pressure. |
|
|
Term
| What serum levels may be affected by postural changes? |
|
Definition
increased albumin & total protein
increased sm. moleculed bound to serum proteins
increased Hb, Hct & PMNs |
|
|
Term
| What drugs do we expect to see adjusted lab values with? |
|
Definition
| 1) Cholesterol lowering drugs to affect LDL
2) heparin to prolong aPTT
3) several drugs affect K+ values (up or down)
4) some drugs may have intrinsic properties that affect the assay itself adjusting the numbers |
|
|
Term
| What do the colors of the blood collection tubes mean? |
|
Definition
What is contained in the tube:
Anticoaglulant? Which one? |
|
|
Term
| What color means there's NO additive to the blood collection tube? |
|
Definition
|
|
Term
| Why would an anticoagulant be used? |
|
Definition
| to test whole blood or plasma after reparation from the red cells |
|
|
Term
|
Definition
| coagulated blood (plasma with no clotting factors) |
|
|
Term
|
Definition
| no coagulation (to assess cellular or coagulation factors) |
|
|
Term
| Why wouldn't an anticoagulant be used in blood collection? |
|
Definition
| allow the blood to clot & serum to separate |
|
|
Term
| Why must serum or plasma be separated from RBCs? |
|
Definition
| prevent an increase in chemicals & enzymes found intracellular |
|
|
Term
| Why is it important to know if blood was collected from a vein or an artery? |
|
Definition
| v. & a. differ in oxygen content, pH, CO2, hematocrit |
|
|
Term
| What is the source of most blood collection? |
|
Definition
|
|
Term
| What are the steps for proper collection of a venous puncture? |
|
Definition
1) patient ID
2) cleanse area
3) application/removal of tourniquet
4) invert tubes containing anticoagulant for mixing
5) proper disposal of sharps
6) check on patient status after draw
7) label tubes |
|
|
Term
| How many times should you attempt a draw before asking for help? |
|
Definition
|
|
Term
| What are the possible complication of venipuncture? |
|
Definition
hematoma
excessive bleeding
thrombosis of vein
infection (rare) |
|
|
Term
| Why is it important to remove the tourniquet at the appropriate time? |
|
Definition
| prolonged application can cause hemocencentration => higher Hb & hematocrit |
|
|
Term
| When might a skin punture be used as opposed to a venipuncture? |
|
Definition
| pediatric patients (infants) |
|
|
Term
|
Definition
| heel prick is made following 5-10 min exposure to warm water |
|
|
Term
| What values cannot be obtained in a skin puncture? |
|
Definition
|
|
Term
|
Definition
| catheter into vein or artery eliminating need for multiple draws |
|
|
Term
|
Definition
drug & fluid administration
drawing blood |
|
|
Term
Function
Arterial catheter |
|
Definition
| allow continuous, real time monitoring of blood gases & acid base balance |
|
|
Term
| What artery is usually used in arterial catheters? |
|
Definition
|
|
Term
| Hore catheters kept open? |
|
Definition
| heparin, therefore there is need to draw 3-6 mL of blood PRIOR to your actual blood collection if needing cogaulation values |
|
|
Term
| What are the 4 problems associated with blood collection? |
|
Definition
1) short draw
2) hemolysis of blood sample
3) oxylate & citrate can inhibit amylase, lactic dehydrogenase, & acid phosphatase activity
4) sodium & potassium salts in anticoagulant can give false sodium or potassium values |
|
|
Term
|
Definition
| dilution due to increased ratio of anticoagulant |
|
|
Term
| When drawing multiple tubes, is there an order to the draw? |
|
Definition
| Yes, draw the non-additive tubes first (unless blood cluture draw- which should be first) |
|
|
Term
| Why accounts for 1/3 of sample processing time? |
|
Definition
|
|
Term
| Why shouldn't blood samples be agitated during tansportation? |
|
Definition
|
|
Term
| Why shouldn't blood samples be exposed to light? |
|
Definition
| to avoid breakdown of analytes (i.e bilirubin) |
|
|
Term
| How are unstable constituents of the blood sample transported? |
|
Definition
|
|
Term
| What lab processes must be done prior to sample analysis? |
|
Definition
| centrifugation, aliquoting & distribution (50% of lab time) |
|
|
Term
| How are patient's IDed in the lab? |
|
Definition
|
|
Term
| How are lab results released? |
|
Definition
| technician checks the results and the automated system interface releases the analysis to the hospital computer system |
|
|
Term
|
Definition
|
|
Term
| How quickly are routine testing results available? |
|
Definition
|
|
Term
| When can lab results take days to weeks? |
|
Definition
| if samples need to be sent out for testing |
|
|
Term
| How is the reference range of a metabolite determined? |
|
Definition
testing a large number of "normal" subjects (not known to have disease) grouped by age & sex
The range is determined by ± 2 standard deviations from the mean |
|
|
Term
|
Definition
| lab results indicitive of need from prompt clinical intervention |
|
|
Term
| What is the protocol when a critical lab value is noticed by the lab technician? |
|
Definition
1) verify value by repeating test
2) immediately notify ordering physician/nurse
3) document notification |
|
|
Term
|
Definition
| true positive will test positive |
|
|
Term
|
Definition
true positive/ (true positive + false negative)
(B/c TP + FN = patients with disease) |
|
|
Term
|
Definition
| true negatives will test negative |
|
|
Term
|
Definition
true negative/ (true negative + false positive)
TN + FP = patients w/o disease |
|
|
Term
| When should sensitivity be maximized? |
|
Definition
| serious but curable disease |
|
|
Term
| When should specificity be maximized? |
|
Definition
| serious, but incurable (since if false negative, it won't change your outcome) |
|
|
Term
Function
positive predictive value |
|
Definition
| determines the likelihood that someone with a positive test has the disease |
|
|
Term
Equation
postivie predictive value |
|
Definition
= true positive/ (true positive + false positive)
TP + FP = total positives |
|
|
Term
| What is the purpose of tests? |
|
Definition
| to reduce clinical uncertainty |
|
|
Term
| What type of test is needed to rule out a disorder? |
|
Definition
| very sensitive therefore negative = negative |
|
|
Term
| What type of test should be used to confirm a Dx? |
|
Definition
| specific therefore positive = positive |
|
|
Term
| Does a single test lead to a Dx? |
|
Definition
| No, at least 1 more test should be done to confirm any Dx |
|
|
Term
| When is an abnormal result more likely to indicate an actual abnormal result? |
|
Definition
| the further it is from the normal range |
|
|
Term
| When can a result in the normal range be considered abnormal? |
|
Definition
| when different from the patient's baseline |
|
|
Term
| When should lab tests be ordered? |
|
Definition
only if likely to help in:
Dx
management
prognosis |
|
|
Term
| How often should tests be done to follow progress of a disorder? |
|
Definition
| depends on the dynamics of the analyte you're testing and the treatment |
|
|
Term
| What is the most common source of errors in results? |
|
Definition
pre-analytical errors:
incorrect draw
incorrect patient
mislabeling of specimen |
|
|
Term
| What happens if the lab instruments give an erroneous result? |
|
Definition
1) try to correct
2) obvious there was an issue with the smear |
|
|
Term
|
Definition
automatic comparison of a sample to the patient's previous samples to avoid random analytical errors
if delta check fails, test automatically re-ran |
|
|
Term
| What is the concern when multiple lab tests are repeatedly requested? |
|
Definition
|
|
Term
| What are the 3 types of thermal injury? |
|
Definition
1) Thermal burns
2) hyperthermia
3) hypothermia |
|
|
Term
| *Why are the number of thermal burn deaths decreasing? |
|
Definition
| smoke detectors, hot water temp regulators, imoprovements in burn care, flame-retardent sleepwear |
|
|
Term
| What can cause thermal burns? |
|
Definition
1) flame/flash
2) scalding from hot liquids
3) contact with hot object (iron, cigarette)
4) steam/gas
5) electricity |
|
|
Term
| What are the 3 classifications of thermal burns? |
|
Definition
1) superficial
2) partial-thickness
3) full-thickness |
|
|
Term
|
Definition
| injury limited to epidermis (i.e. sunburn) |
|
|
Term
def
partial-thickness burn |
|
Definition
1) damage extends to the dermis (blisters frequent)
2) adnexal (appendage) structures injured, but can regrow |
|
|
Term
|
Definition
deeper injury with destruction of the epidermis, dermis, & subcutaneous tissue.
Can extend to tendons, skeletal muscle & bone |
|
|
Term
| What type of necrosis affects thermal burns? |
|
Definition
|
|
Term
| What is the pathology of superficial & partial-thickness burns? |
|
Definition
| typical acute inflammatory response (hyperemia, exudative edema, infiltration by neutrophils & macrophages, pain) |
|
|
Term
| What is the pathology of full-thickness burns? |
|
Definition
| extensive damage to superficial blood vessels, never endings & adnexal structures => white or black dry, lethery, insensate wounds |
|
|
Term
| *does morbidity & mortality of thermal burns depend on? |
|
Definition
| extent & depth of burns, inhalation &/or coexistent traumatic injuries, age, pre-existent medical conditions, & adequacy of Tx |
|
|
Term
| What 6 complications can arise in thermal burns? |
|
Definition
1) hypovolemic shock
2) hyperkalemia
3) sepsis
4) resp. failure
5) gastric ulcers
6) chronic complications |
|
|
Term
| How is % of body covered in burns estimated clinically? |
|
Definition
| Rule of 9's (don't need to know now) |
|
|
Term
| When is hypovolemic shock a concern in burn victims? |
|
Definition
|
|
Term
| Why are fluids lost in thermal burns => hypovolemic shock? |
|
Definition
1) increased vasular permeability => loss of fluid into interstitum
2) evaporation due to loss of skin |
|
|
Term
| What causes hyperkalemia in thermal burns? |
|
Definition
| cellular disruption from the heat |
|
|
Term
| What causes spesis in thermal burns? |
|
Definition
| loss of skin barrier & decreased inflammatory response => wound infections => bacteremia => septic shock with multisystem organ failure |
|
|
Term
| What can cause resp. failure in thermal burns? |
|
Definition
inhalation injury
pneumonia
diffuse alveolar damage |
|
|
Term
| Why are gastric ulcers a concern in patients with thermal burns? |
|
Definition
| can lead to upper GI bleeding |
|
|
Term
| What 2 chronic complications can arise from thermal burns? |
|
Definition
1) excessive scar formation
2) contractures (esp. in children) |
|
|
Term
| What are the effects of hyperthermia dependent on? |
|
Definition
| duration of exposure , humitidy of the air, adequacy of fluid/electrolyte replacement, age, level or exertion, current medical conditions |
|
|
Term
| What are the 3 effects of hyperthermia? |
|
Definition
1) Heat cramps
2) heat exhaustion
3) heat stroke |
|
|
Term
|
Definition
| intermittent, involuntary, painful muscle spasms during or after strenuous exercise - often in hot environments |
|
|
Term
|
Definition
| electrolyte abnormalities |
|
|
Term
|
Definition
relatively sudden onset of dizziness, neausea, headache, profuse sweating, & fatigue associated with hypotension, tachycardia & low-grade fever
skin usually pale, cool, & moist |
|
|
Term
| What causes heat exhaustion? |
|
Definition
| inadqeuate compensation for hypovolemia & elevated body temp |
|
|
Term
| *What's the most severe form of hyperthermia? |
|
Definition
| heat stroke - potentially like-threatening |
|
|
Term
|
Definition
extremely high core body temp associated with hot, dry, flushed skin
tachycardia
difficulty breathing
neurological Sx
may progress to multi-organ failure & rhabdomyolysis |
|
|
Term
| What are the differences between heat stroke & heat exhaustion seen in a patient? |
|
Definition
Heat stroke: dry, hot skin. high body temp
heat exhaustion: moist clammy skin, normal/subnormal temp |
|
|
Term
|
Definition
| inability for heat dissipation fast enough => markedly elevated body temp => denaturation of proteins/cell membranes, alteration in HSP (heat shock protein) expression, amplified acute phase response => thermoregulatory failure |
|
|
Term
| What do the effects of hypothermia depend on? |
|
Definition
| duration of exposure, wind, moisture, age, weight, current medical conditions |
|
|
Term
|
Definition
| shivering, loss of motor coordination, slurred speech, confusion, drowsiness, apathy, irrational behavior, progressive loss of consciousness, focal tissue injury => cardiorespiratory failure & death |
|
|
Term
| *What 4 places on the body are likely to see focal tissue injury due to hypothermia? |
|
Definition
1) ears
2) nose
3) fingers
4) toes |
|
|
Term
| What is the pathogenesis of focal tissue injury in hypothermia? |
|
Definition
| peripheral vasoconstriction, interstitial fluid crystalization w/ cellular dehydration & protein denaturation, increased vascular permiability, & thrombosis |
|
|
Term
| What are the 4 consequences of focal tissue injury due to hypothermia? |
|
Definition
1) frostbite => 2) gangrene
3) trench (immersion) foot
4) chilblains (perniosis) |
|
|
Term
|
Definition
initially affected areas appear pale & have associated burning & clear blisters.
increasing severity: leisons become discolored (red => purple => black), swollen, firm, & ulcerated with eventual loss of sensation |
|
|
Term
| What causes trench (immersion) foot? |
|
Definition
| prolonged exposure to cold, damp, unsanitary conditions with constrictive footware => vascular, soft tissue & nerve injury with secondary infections |
|
|
Term
def
chilblains (perniosis) |
|
Definition
| abnormal vascular reaction to cold |
|
|
Term
|
Definition
| small, prutitic, swollen, painful skin leisons (red => blue) that develop upon re-warming |
|
|
Term
| What are the 3 ways radiation can be measured? |
|
Definition
1) emitted radiation
2) absorbed radiation
3) biological effect of radiation (equivalent doses) |
|
|
Term
|
Definition
| decay of a radionuclide per second |
|
|
Term
|
Definition
| energy absorbed per tissue mass |
|
|
Term
def
biological effect of radiation |
|
Definition
| product of the absorbed dose & the Quality Factor (depends on the type of radiation) |
|
|
Term
| What are the units of emitted radiation (conventional & SI)? |
|
Definition
c: curie [Ci]
SI: becquerel [Bq] |
|
|
Term
| What are the units of absorbed radiation (conventional & SI)? |
|
Definition
|
|
Term
| What are the units of biological effect of radiation (conventional & SI)? |
|
Definition
|
|
Term
| What are the 3 additional factors that determine radiation's biologic effects? |
|
Definition
1) Rate of delivery
2) extent of exposure
3) tissue vulnerability |
|
|
Term
| Why does rate of delivery of radiation affect the biological effect? |
|
Definition
| there may be time for cellular dependent depending on how fractioned the doses are |
|
|
Term
def
extent of radiation exposure |
|
Definition
|
|
Term
| What 3 factors affect tissue vulnerability to radiation? |
|
Definition
1) rate of cellular proliferation
2) availability of oxygen
3) extent of vascular injury |
|
|
Term
| Are tissues with high cellular turnover more or less susceptible to radiation damage? |
|
Definition
|
|
Term
Are well oxygenated tissues more or less vulnerable to radiation injury?
Why? |
|
Definition
| more b/c oxygen-derived free radicals exert the greatest damage to DNA |
|
|
Term
| Are acute or chronic effects of radition seen in vessels? |
|
Definition
|
|
Term
| What are the areas of the cell that are affected by radiation? |
|
Definition
|
|
Term
| What happens in the nucleus when exposed to ionizing ration & resultant free-radical formation? |
|
Definition
DNA damage & attampted repair =>
1) DNA recovery
2) persistant DNA abnormalities => apoptosis or perpetual alterations |
|
|
Term
| What happens in the cytoplasm when exposed to ionizing ration & resultant free-radical formation? |
|
Definition
| cellular swelling, injury to plasma & organelle membranes |
|
|
Term
| What is the pathology of early radiation complication? |
|
Definition
1) reversible & irreversible parenchymal cell injury, particularly in susceptible tissues
2) endothelial damage => hyperemia, increased vascular permeability, hemmorhage & thrombosis |
|
|
Term
| What is the pathology of late radiation complication? |
|
Definition
1) vascular & intestinal fibrosis w/ associated tissue atrophy & telangiectasia => secondary complications
2) cataracts
3) malignancies
4) CV disease
5) teratogenic effects |
|
|
Term
|
Definition
|
|
Term
| *What malignancies are seen due to radiation therapy? |
|
Definition
| laukemias, breask carcinoma, papillary thyroid carcinoma (esp. exposed children) |
|
|
Term
| What teratogenic effects can be seen in radiation injury? |
|
Definition
| impaired physical & mental development |
|
|
Term
| What is the pathology of early & late radiation complication? |
|
Definition
radiation-induced cytologic atypia (inc. enlarged, hyperchromatic, pleomorphic nuclei)
abnormal mitotic figures
bizarre giant cells |
|
|
Term
What are the singular circular cross sections in a lung?
What are the paired circular cross sections seen in a lung? |
|
Definition
singular: veins
paired: arteries & bronchioles |
|
|
Term
| What epithelium is seen in a bhronchiole? |
|
Definition
| pseduostratified ciliated |
|
|
Term
| How do you distinguish a bronchus? |
|
Definition
| bronchus is associated with cartillege & glands |
|
|
Term
A 73 yr old woman developed SOB, lethargy, fever, & productive cough of greenish-yellow sputum. WBC count was found to be high, with 93% neutrophils.
What do you think might be going on? |
|
Definition
pneumonia
(clues: age, productive cough, neurophils => acute bacterial pneumonia) |
|
|
Term
| What causes pale, firm areas in a pneumonic lung? |
|
Definition
| possibly microabcesses, purulent inflammation |
|
|
Term
| What infiltrates a pneumonic lung? |
|
Definition
| PMNs & RBCs, proteinous excudate |
|
|
Term
What type of inflammation is seen in a pneumonic lung?
How do you know? |
|
Definition
| suppurative b/c more PMNs (as opposed to lymphocytes) |
|
|
Term
| How does the pale pink exudate infiltrate the pneumonic lung? |
|
Definition
| protein leakage from the vasculature |
|
|
Term
|
Definition
| focal accumulation of supprative inflammation destroying resident tissue => liquefactive necrosis |
|
|
Term
| What are you looking for in an abcess? |
|
Definition
| sea of purple surrounded by pink |
|
|
Term
| What cellular mediators are the cause of liquefactive necrosis seen in an abcess? |
|
Definition
| lysosomal enzymes & O2-derived free radicals |
|
|
Term
| Why do pneumonia patients have SOB? |
|
Definition
| alveoli are almost non-existant due to infiltrate |
|
|
Term
| What inflammatory mediators cause fever, lethargy, & high peripheral neutrophil count (neutrophilia)? |
|
Definition
|
|
Term
| What inflammatory cells are residents of the normal colon? |
|
Definition
eosinophils
plasma cells
lymphocytes |
|
|
Term
| What is the name of the outermost layer of the colonic wall? |
|
Definition
|
|
Term
| Why in a colonic biopsy do gastroenterologists not want to sample the full thickness of the colon? |
|
Definition
| you don't want to perforate the colon |
|
|
Term
| In a chronically damaged colon, what chronic inflammatory cells could be seen? |
|
Definition
primarily: plasma cells
macrophage
eosinophil
lymphocyte
PMNs |
|
|
Term
| In chronic colinic damage where are PMNs primarily found? |
|
Definition
|
|
Term
|
Definition
| break in epithelium with infiltration of inflammatory cells & necrotic debris |
|
|
Term
In chronic inflammation of the colon where is chromic inflammation seen?
Where is acute inflammation seen? |
|
Definition
acute: in crypts (PMNs)
chronic: in lamina propria (lymphocytes/plasma cells) |
|
|
Term
| What is the difference b/w proximal & distal convoluted tubules? |
|
Definition
distal: clear & circular lumen
proximal: fizzy & star shaped lumen |
|
|
Term
| Where in the kidney are the glomeruli found? |
|
Definition
|
|
Term
| What is contained in the medulla of the kidney? |
|
Definition
| tubules & collecting ducts |
|
|
Term
|
Definition
|
|
Term
| What inflammatory cells are expected in a typical chronic inflammatory cell infiltrate? |
|
Definition
primarily: lymphocytes
macrophages |
|
|
Term
| What type of necrosis is seen when there are ghost remnants of old structures? |
|
Definition
|
|
Term
| What cells should be seen in fibrosis or scarring? |
|
Definition
macrophages
plasma cells
lymphocytes
fibroblasts |
|
|
Term
| What causes tissue fibrosis? |
|
Definition
1) decreased # proliferating endothelial cells
2) increased deposition of ECM (fibrillar collagens)
3) CT remodeling |
|
|
Term
| When will chronic inflammatory cell infiltrate predominate? |
|
Definition
| persistent infection or certain types of infection or recurrent infections |
|
|
Term
| In a recurrent infection, when might you see both acute & chronic inflammatory cell infiltrates? |
|
Definition
the first couple recurrent infections
the beginning of each infection |
|
|
Term
| What type of necrosis is seen in TB? |
|
Definition
|
|
Term
| Where are B cells found in lymph nodes? |
|
Definition
| primary follicle & gernminal center of secondary follicle. |
|
|
Term
| Where are T cells found in lymph nodes? |
|
Definition
| paracortex (b/w follicles) |
|
|
Term
| What is the subcapsular sinus on the edge of the lymph node? |
|
Definition
|
|
Term
| Why is granulomatous inflammation important to recognize? |
|
Definition
| latent infections that are difficult to irradicate |
|
|
Term
| What is expected in granulomatous inflammation? |
|
Definition
| macrophages clustered w/ fibrosis surrounded by lymphocyte rim |
|
|
Term
| What is the pathogenomonic cell of a granuloma? |
|
Definition
| macrophages (tho giant cells are NOT needed for Dx) |
|
|
Term
| How do you identify necrosis in a granuloma? |
|
Definition
|
|
Term
| How do you distinguish between necrosis & fibrosis in granulomatous inflammation? |
|
Definition
| fibrosis occurs outside a granuloma, necrosis is inside |
|
|
Term
| What inflammatory mediators are responsible for fever, night sweats & weight loss associated with TB? |
|
Definition
TNFα
IL-1
prostaglandins
(produced by macrophages & lymphocytes) |
|
|
Term
| What cells would be expected at one day after a skin injury? |
|
Definition
|
|
Term
| What cells would be expected at 3 days after a skin injury? |
|
Definition
PMNs
macrophages begin entry |
|
|
Term
| What cells would be expected at one week after a skin injury? |
|
Definition
| macrophages & lymphocytes |
|
|
Term
| What is the wound appearance that can mean healing? |
|
Definition
|
|
Term
| What are the 3 components of granulation tissue? |
|
Definition
1) residual inflammatory cells
2) newly formed, leaky capillaries
3) proliferating fibroblasts |
|
|
Term
| What residual inflammatory cells should be found in granulation tissue? |
|
Definition
primarily macrophages
PMNs
lymphocytes |
|
|
Term
| What suggests that capillaries are leaky in granulation tissue? |
|
Definition
|
|
Term
| Why is it a good thing that the capillaries are in repair in granulation tissue? |
|
Definition
| allows easier access to tissue for inflammatory cells & other "helpers" |
|
|
Term
| What growth factors are needed for capillary repair? |
|
Definition
|
|
Term
| What cells predominate below the epidermis in a wound several weeks old? |
|
Definition
|
|
Term
| How does the area beneath the dermis differ from the area beneath the epidermis in a skin wound several weeks old? |
|
Definition
| no lymphocytes, more fibroblasts |
|
|
Term
| How does a skin wound several weeks old differ from a granulation skin wound? |
|
Definition
| no macrophages, complete blood vessels |
|
|
Term
| How does a late scar compare to an early scar? |
|
Definition
| late scar has less fibroblasts & is mostly collagen |
|
|
Term
| What inflammatory cells should be seen in inflammation caused by an IgE-mediated allergic reaction? |
|
Definition
|
|
Term
How much of the body's water is contained in the intracellular fluid?
extracellular fluid? |
|
Definition
|
|
Term
| What is considered part of the ECF: |
|
Definition
*interstitial fluid
intravascular fluid (plasma)
third space fluid (w/in body cavities) |
|
|
Term
| What type of equlibrium are ICF & ECF in? |
|
Definition
|
|
Term
| What is considered intravascular vs. extravascular fluid? |
|
Definition
intravascular = plasma
extravascular = rest of total body water |
|
|
Term
| Where does fluid exchange occur b/w intravascular & extravascular compartments? |
|
Definition
|
|
Term
| What has free movement b/w IVF & EVF at the capillary beds? |
|
Definition
water
electrolytes
small molecules |
|
|
Term
|
Definition
| measure of number of dissolved particles in a solution |
|
|
Term
| Does osmolality of electrolytes & small molecules affect water flow across the capillary wall? |
|
Definition
|
|
Term
| What equation defines the determinants of transcapillary fluid dynamics? |
|
Definition
|
|
Term
| What are the Starline equation variables? |
|
Definition
hydrostatic pressure
oncotic pressure gradient
capillary permeability |
|
|
Term
Function
hydrostatic pressure |
|
Definition
| normally drives fluid out of the vasculature into the interstitium at the arterial end of the capillary bed |
|
|
Term
| What determines the oncotic (colloid osmotic) pressure gradient? |
|
Definition
1) concentration of large molecular wt. particles, mainly protein (esp. albumin)
2) capillary permeability |
|
|
Term
|
Definition
| normally favors fluid reabsorption into the vasculature at the venous end of the capillary bed |
|
|
Term
| How do lymphatics participate fluid balance? |
|
Definition
| when filtration out of the microcirculation at the arterial end of the capillary bed exceeds reabsorption at the venous end, the lymphatics drain the excess fluid |
|
|
Term
|
Definition
| increased fluid within the interstitium |
|
|
Term
|
Definition
|
|
Term
|
Definition
| edema fluid within the thoracic cavity |
|
|
Term
|
Definition
| edema within the peritoneal cavity (looks pregnant) |
|
|
Term
| What are the 3 types if edema? |
|
Definition
trandudative
exudative
due to lymphatic obstruction |
|
|
Term
| What characterizes transudative edema? |
|
Definition
1) low protein
2) low specific gravity
3) few cells |
|
|
Term
| What causes tranudative edema? |
|
Definition
NORMAL vascular permeability & either:
1)increased intravascular hydrostatic pressure
2) decreased plasma oncotic pressure |
|
|
Term
| What can cause increased intravacular hydrostatic pressure? |
|
Definition
1) venous obstruction
2) heart failure |
|
|
Term
What does left ventricular failure lead to?
right ventricular failure? |
|
Definition
LVF: pulmonary edema
RVF: generalized systemic edema |
|
|
Term
| What can cause decreased plasma oncotic pressure? |
|
Definition
1) decreased synthesis of protein (albumin)
2) increased loss of protein (albumin) |
|
|
Term
| What complication is seen in transudative edema? |
|
Definition
|
|
Term
| What causes the Na+ & H2O retention in transudative edema? |
|
Definition
| decreased renal perfustion => activation of renin-angiotensin-aldosterone system => increased reabsorption of Na+ & H2O |
|
|
Term
| What characterizes exudative edema? |
|
Definition
1) high protein
2) high specific gravity
3) many cells |
|
|
Term
| What causes exudative edema? |
|
Definition
| INCREASED vascular permeability |
|
|
Term
| What can cause an lymphatic obstruction => edema? |
|
Definition
1) infection - filariasis
2) malignancy ± Tx |
|
|
Term
| What can severe subcutaneous soft tissue edema lead to? |
|
Definition
|
|
Term
| When is subcutaneous soft tissue edema seen in the periorbital area? |
|
Definition
|
|
Term
| What does subcutameous soft tissue edema interfere with? |
|
Definition
|
|
Term
| How do the lungs look grossly when they have edema? |
|
Definition
|
|
Term
| Where in the lungs does fluid accumulation in edema? |
|
Definition
|
|
Term
| How does edema in the lungs look microscopically? |
|
Definition
| pale pink, proteinaceous fluid ± inflammatory cells |
|
|
Term
| Why is lung edema important clinically? |
|
Definition
1) impairs ventillation
2) predisposes to infection |
|
|
Term
| What does the brain look like grossly when it has edema? |
|
Definition
| heavy & swollen with flattening of the gyri & compression of the sulci |
|
|
Term
| Why is brain edema important clinically? |
|
Definition
1) herniation
2) vascular compression |
|
|
Term
| *How does the lab determine b/w transudative & exudative edema? |
|
Definition
| specific gravity of the fluid, protein, LD, & cholesterol content (compared to levels in serum) |
|
|
Term
|
Definition
PASSIVE increased intravascular blood due to impaired venous outflow
(blue-red) |
|
|
Term
|
Definition
ACTIVE increased blood due to expanded arterial inflow
(red) |
|
|
Term
How does congestion in the lungs look when it's acute?
chronic? |
|
Definition
acute: heavy & wet, blue/red
chronicL heavy & dry, rusty brown |
|
|
Term
| Hows does acute congestion in the lungs look microscopically? |
|
Definition
1) pulmonary capillaries distended with RBCs
2) ± transudative edema, microhemorrhages |
|
|
Term
| Hows does chronic congestion in the lungs look microscopically? |
|
Definition
| alveolar spetal fibrosis with intra-alveolar, hemosiderin-laden macrophages (heart failure cells) |
|
|
Term
| What does liver congestion look like grossly? |
|
Definition
|
|
Term
| What does a congestion liver look like microscopically - acute & chronic? |
|
Definition
1) centrilobular sinusoids expanded with blood (acute)
2) hepatocytes
a) centrilobular necrosis or atrophy (chronic)
b) periportal normal or fatty
3) centrilobular fibrosis & hemosiderin-laden macrophages (chronic) |
|
|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
|
Definition
| small punctate hemorrhages within skin, mucosa or serosa |
|
|
Term
|
Definition
| decreased or abnormal platelets & increased intravascular pressure focally |
|
|
Term
|
Definition
| slightly larger hemorrhages frequently due to vascular pathology |
|
|
Term
|
Definition
| bruises - hemorrhages in subcutaneous tissue |
|
|
Term
| What are the 4 hemorrages into body cavities? |
|
Definition
1) hemothorax
2) hemopericardium
3) hemoperitoneum
4) hemarthrosis |
|
|
Term
| What causes transient arteriolar vasoconstriction? |
|
Definition
1) reflex neurogenic
2) endothelin (secreted by endothelial cells) |
|
|
Term
|
Definition
| platelets - adhesion, activation, aggregation |
|
|
Term
|
Definition
| addition of coagulation cascade activation via tissue factor & platelet phospholipids => thrombin & fibrin |
|
|
Term
| What are the 4 normal antithrombotic mediators? |
|
Definition
1) plasma membrane
2) antiplatelet
3) anticoagulant
4) fibrinolytic t-PA (tissue-type plasminogen activator) |
|
|
Term
Function
plasma membrane as a antithrombotic mediator |
|
Definition
|
|
Term
| What are the 3 antiplatelet antithrombotic mediators? |
|
Definition
| 1) prostacyclin (PGI2)
2) NO
3) ADPase |
|
|
Term
| What are the 3 anticoagulant antithrombotic mediators? |
|
Definition
1) heparin-like molecules
2) thrombomodulin
3) TFPI (tissue factor pathway inhibitor) |
|
|
Term
Function
heparin-like molecules |
|
Definition
| bind & amplify action of antithrombin III => inhibition of thrombin & other activated coagulation factors |
|
|
Term
|
Definition
| binds thrombin => activation of protein C & protein S => degradation of Va & VIIIa |
|
|
Term
|
Definition
| inhibits tissue factor-mediated coagulation (Xa & VIIa complex) |
|
|
Term
| What are the 3 prothrombotic mediators in an endothelial injury or activation? |
|
Definition
1) proplatelet
2) procoagulant
3) anti-fibrinolytic |
|
|
Term
What is the proplatelet mediator?
How does it work? |
|
Definition
| von Willebrand factor (vWF) => mediation of platelet adhesion to the ECM |
|
|
Term
What is the procoagulant?
How does it work? |
|
Definition
| tissue factor => activation of extrinsic pathway of the coagulation cascade |
|
|
Term
| What is the anti-fibrinolytic? |
|
Definition
| PAIs (plasminogen activator inhibitors) |
|
|
Term
| What does the primary hemostatic plug consist of? |
|
Definition
|
|
Term
| What allows for platelet adhesion? |
|
Definition
| platelet GpIb - vWF - ECM |
|
|
Term
| How do α granules encourage platelet secretion/activation? |
|
Definition
| => multiple proteins inc. vWF, V, VII, fibrinogen, fibronectin, & platelet factor 4 |
|
|
Term
| How do δ granules (dense bodies) encourage platelet secretion/activation? |
|
Definition
| => substrates s.a. Ca2+ & ADP (for coagulation cascade & platelet activation/aggregation respectively) |
|
|
Term
| What are translocated to platelet surfaces for the coagulation cascade? |
|
Definition
|
|
Term
| What is synthesized by arachidonic acid to encourage platelet secretion/activation? |
|
Definition
|
|
Term
| What 4 things enhance platelet aggregation? |
|
Definition
| 1) ADP
2) TxA2
3) thrombin
4) fibrinogen |
|
|
Term
| What does fibrinogen bind to enhance platelet aggregation? |
|
Definition
| GpIIb-IIIa receptors (exposed during platelet activation) |
|
|
Term
| What 3 endothelial factors inhibit platelet aggregation? |
|
Definition
| 1) prostacyclin (PGI2)
2) NO
3) ADPase |
|
|
Term
|
Definition
| amplifying series of circulating, inactive proenzymes which are subsequently cleaved to form activated enzymes at sites of endothelial injury. |
|
|
Term
| *What are the 5 components of reaction complexes in the coagulation cascade? |
|
Definition
| 1) inactive coagulation factor (substrate)
2) previously activated coagulation factor in cascade
3) Ca2+
4) phospholipid surface (provided by platlets)
5) cofactor |
|
|
Term
| What is formed by the common pathway connecting extrinsic & intrinsic pathway of the coagulation cascade? |
|
Definition
|
|
Term
Function
Thrombin (IIa) in the coagulation cascade |
|
Definition
1) proteolytically cleaves soluble fibrinogen => insoluble fibrin (Ia)
2) activates XIII => XIIIa & other coagulation factors |
|
|
Term
| What does thrombin do to platelets? |
|
Definition
| enhances platelet activation & aggregation |
|
|
Term
Function
Thrombin (IIa) on endothelial cells |
|
Definition
1) stimulates leukocyte adhesion
2) modulates procoagulant & anticoagulant functions |
|
|
Term
| What are the 4 anticoagulants? |
|
Definition
1) antithrombin III
2) protein C
3) protein S
4) TFPI |
|
|
Term
|
Definition
| inhibits thrombin & other activated coagulation factors |
|
|
Term
| What markedly enhances AT III function? |
|
Definition
|
|
Term
|
Definition
|
|
Term
| What activates proteins C & S? |
|
Definition
| activated by thrombomodulin-thrombin complex |
|
|
Term
|
Definition
| inhibits tissue factor-mediated coagulation |
|
|
Term
| What is the enzyme of the fibrolytic system? |
|
Definition
|
|
Term
|
Definition
| degrades fibrin => fibrin split products |
|
|
Term
| What is plasmin generated from? |
|
Definition
|
|
Term
| How is plasmin generated from plasminogen? |
|
Definition
1) *t-PA
2) u-PA (urokinase-like plasminogen activator)
3) streptokinase |
|
|
Term
| *What produces t-PA (tissue-type plasminogen activator) |
|
Definition
|
|
Term
| *When is t-PA most effective? |
|
Definition
|
|
Term
| What counteracts the activity of plasmin? |
|
Definition
| inhibitors of plasmin & plasminogen activators |
|
|
Term
| In blood collection, what is whole blood? |
|
Definition
|
|
Term
| What blood collection tube is used in whole blood collection? |
|
Definition
|
|
Term
| Why would whole blood blood need to be collected? |
|
Definition
|
|
Term
|
Definition
| liquid component of blood (virtually cell-free supernatant of anticoagulated blood obtained after centrifugation) |
|
|
Term
| What blood collection tube is used for plasma collection? |
|
Definition
| light blue top with sodium citrate |
|
|
Term
| Why would plasma need to be collected? |
|
Definition
|
|
Term
|
Definition
| liquid (extracellular) portion of blood after coagulation is complete (plasma without clotting factor) |
|
|
Term
| What blood collection tube is used for serum? |
|
Definition
| red top w/ no additive (or one with clot activators) |
|
|
Term
| Why would serum need tobe collected? |
|
Definition
| routine chemistry & serology |
|
|
Term
| What are the 3 ways to evaluate platelets? |
|
Definition
1) platelet count
2) examination of peripheral blood smear ± bone marrow
3) platelet function assays |
|
|
Term
| What is examination of the peripheral blood smear ± bone marrow looking for with platelets? |
|
Definition
| evidence of abnormalities in destruction/production |
|
|
Term
Function
platelet function assays |
|
Definition
1) test for abnormalities in platlet adhesion & aggregation (primary hemostasis
2) differentiate b/w platelet abnormalities due to aspirin or other causes |
|
|
Term
| What have platelet function assays replaced? |
|
Definition
|
|
Term
*def
intrinsic & extrinsic pathways of blood coagulation |
|
Definition
| interconnected, self-amplifying pathways by which activation of the coagulation cascade can be initiated |
|
|
Term
| *Is the intrinsic or extrinsic pathway of blood coagulation more important in vivo? |
|
Definition
|
|
Term
| *What do both the intrinsic & extrinsic pathways of blood coagulation lead to? |
|
Definition
| common pathway of the coagulation cascade & activation of fibrinolytic system |
|
|
Term
Which of the intrinsic and extrinsic pathways of blood coagulation is the contact activation pathway?
tissue factor pathway? |
|
Definition
I: contact activation
E: tissue factor |
|
|
Term
| What is required for the intrinsic (contact activation) pathway? |
|
Definition
| substances found within the vasculature |
|
|
Term
| What is required for the extrinsic (tissue factor) pathway? |
|
Definition
| tissue factor (which is extrinsic to the vasculature) for initiation |
|
|
Term
Blood Coagulation Pathways
[image] |
|
Definition
1) intrinsic pathway
2) extrinsic pathway
3) final common pathway |
|
|
Term
|
Definition
| measurement of the integrit of the extrinsic & common pathways of coagulation (VII, X, V, II, & I) |
|
|
Term
| What are the factors contributing to the time it takes for a fibrin clot to form in a PT test? |
|
Definition
| 1) citrated, platelet poor plasma
2) tissue factor
3) phospholipid (sub for platelet membrane)
4) excess Ca2+ (toreverse effects or citrate) |
|
|
Term
| What are the 3 frequent causes of PT prolongation? |
|
Definition
1) deficiency of Vit K
2) decreased synthesis of coagulation factors
3) increased consumption of coagulation factors |
|
|
Term
| Why would Vit K deficiency lead to PT prolongation? |
|
Definition
| it's a cofactor for the γ-carboxylation of glutamate in synthesis of factors II, VII, IX, & X (& other proteins) |
|
|
Term
| Who are at risk for Vit K deficiency? |
|
Definition
1) infants
2) use of coumarin-derived anticoagulants (s.a. warfarin)
3) fat malabsorption |
|
|
Term
def
international normalized ration (INR) |
|
Definition
| calculation used to standardize the PT b/w various laboratories |
|
|
Term
def
aPTT (activated partial thrombin time) |
|
Definition
| measurement of the integrity of the intrinsic & common pathways of coagulation (XII, XI, IX, VIII, X, V, II, I) |
|
|
Term
| What are the factors contributing to the time it takes for a fibrin clot to form in an aPTT test? |
|
Definition
| 1) citrated, platelet-poor plasma
2) particulate contact activator
3) phospholipid (sub for platelet membrane)
4) excess Ca2+ (to reverse effects of citrate) |
|
|
Term
| What are the 6 frequent causes of aPTT prolongation? |
|
Definition
1) hereditary deficiency of any of the clotting factors (except VII & XIII)
2) acquired inhibitors to the above coagulation factors
3) antiphospholipid (anticardiolipin) Ab
4) heparin therapy (or contamination)
5) liver disease and/or Vit K deficiency
6) increased consumption of coagulation factors |
|
|
Term
What is deficient in hemophilia A?
hemophilia B? |
|
Definition
|
|
Term
| What factor is most likely to acquire an inhibitor to cause prolonged aPTT? |
|
Definition
|
|
Term
| What does thrombin activate in the intrinsic pathway? |
|
Definition
|
|
Term
| What does thrombin activate in the extrinsic pathway? |
|
Definition
|
|
Term
| What does thrombin act on in the combined pathway? |
|
Definition
|
|
Term
Which test is used to monitor heparin therapy?
coumadin therapy? |
|
Definition
heparin: aPTT
coumadin: PT |
|
|
Term
| What are the factors contributing to the time it takes for a fibrin clot to form in a TT (thrombin time) test |
|
Definition
1) citrated, platelet-poor plasma
2) thrombin |
|
|
Term
| What are the 2 frequent causes of prolongation of thrombin time? |
|
Definition
1) deficiencies/defects in fibrinogen (inherited or acquired)
2) inhibitors of thrombin |
|
|
Term
Function
fibrinogen assays |
|
Definition
| determine qualitative & functional abnormalities of fibrinogen |
|
|
Term
| What are the 3 causes of thrombosis? |
|
Definition
1) *endothelial injury or dysfunction
2) abnormal blood flow (stasis & turbulence)
3) hypercoagulability |
|
|
Term
| How does abnormal blood flow (stasis & turbulence) cause thrombosis? |
|
Definition
| => disruption of laminar flow => endothelial injury/dysfunction, platelet adhesion, & accumulation of activated coagulation |
|
|
Term
| *What causes a venous thrombi? |
|
Definition
|
|
Term
| What are the 2 types of hypercoagulability? |
|
Definition
1) primary (hereditary)
2) secondary (acquired) |
|
|
Term
| What are the 4 causes of primary hypercoagulability? |
|
Definition
1) factor V (Leiden) mutation
2) prothrombin mutation
3) increased homocysteine (inherited enzyme abnormalities)
4) anticoagulant deficiencies (AT II, proteins C & S) |
|
|
Term
| Why does factor V mutation cause hypercoagulability? |
|
Definition
| it's unable to be lysed by protein C |
|
|
Term
Sx
anticoagulant deficiencies |
|
Definition
| recurrent venous thrombi & pumlonary thromboemboli in young adulthood |
|
|
Term
| What are the 5 causes of secondary hyercoagulability? |
|
Definition
1) malignant neoplasms
2) oral contraceptive use/pregnancy
3) smoking
4) heparin-induced thrombocytopenia syndrome type 2 (HIT)
4) antiphospholipid (anticardiolipin) Ab syndrome (kupus anticoagulant syndrome) |
|
|
Term
| What do malignant neoplasms lead to cause hypercoagulability? |
|
Definition
| procoagulants (i.e. Trousseau syndrome) |
|
|
Term
|
Definition
| migratory thrombophelbitis |
|
|
Term
| Why do pregnancy/oral contraceptives cause hypercoagulability? |
|
Definition
|
|
Term
|
Definition
| serious limb & life threatening complication of heparin therapy occuring 5-10 days post exposure |
|
|
Term
| How does HIT syndrome cause hypercoagulability? |
|
Definition
| Ab complexes form b/w heparin & platelet factor IV => activation platelets by complexes binding their Fc receptors => amplification of the process, as well as endothelial cells => increased risk of thrombosis involving large blood vessels & decreased platelet count (due to condumption & increased splenic clearance) |
|
|
Term
| What is the pathogenesis of antiphospholipid (anticardiolipin) Ab syndrome? |
|
Definition
| Ab formed against phospholipids of certain plasma protein epitopes exposed by phospholipid binding (some coagulation factors & anticoagulants) |
|
|
Term
Effect
antiphospholipid (anticardiolipin) Ab syndrome in vitro |
|
Definition
|
|
Term
Effect
antiphospholipid (anticardiolipin) Ab syndrome in vivo |
|
Definition
|
|
Term
| What are the 2 classifications of antiphospholipid (anticardiolipin) Ab syndrome? |
|
Definition
1) primary (de novo)
2) secondary (in associated with an autoimmune diease i.e. SLE) |
|
|
Term
Sx
antiphospholipid (anticardiolipin) Ab syndrome |
|
Definition
recurrent thromboembolic episodes
pregnancy complication
thrombocytopenia |
|
|
Term
| How does a medical examiner tell the difference b/w a thrombi & a postmortem clot? |
|
Definition
post mortem clot:
1) gelatinous
2) not attached to the vascular wall
3) evidence of blood settling - dark red layer at bottom, yellow "chicken fat" layer at top
thrombi:
1) firm
2) attached to vascular wall
3) evidence of blood flow - alternating layers of platelets/fibrin (pale pink) with RBCs (dark red) |
|
|
Term
| Are thrombi more conspicuous in arterial or venous circulation? |
|
Definition
|
|
Term
| What are the 2 subtypes of thrombi? |
|
Definition
1) mural thrombi
2) vegetations |
|
|
Term
|
Definition
| thrombi adherent to the walls of large chambers |
|
|
Term
|
Definition
| thrombi formed on the heart valves |
|
|
Term
| Where are the common arterial sites of thrombi? |
|
Definition
| coronary, cerebral, & femoral arteries |
|
|
Term
| *What are the common sites for venous thrombi? |
|
Definition
| deep leg & pelvic veins (phlebothrombosis) |
|
|
Term
| What are the 4 possible outcomes of a thrombus? |
|
Definition
1) dissolution (resolution)
2) propagation
3) embolization
4) organization |
|
|
Term
def
dissolution of a thrombus |
|
Definition
| complete degradation by the fibrinolytic system |
|
|
Term
def
propagation of a thrombus |
|
Definition
| enlargement of the thrombus |
|
|
Term
def
emboliation of a thrombus |
|
Definition
| detatchment or fragmentation & travel to a distant site |
|
|
Term
def
organization of a thrombus |
|
Definition
| inflammation & repair process where inflammation occurs then ingrowth of granulation tissue => focal thickening of the vascular intima & recanalization |
|
|
Term
|
Definition
| capillaries of the granulation tissue anastamose & reestablish blood flow thru the thrombus |
|
|
Term
| What are the 2 consequences of a thrombus? |
|
Definition
1) Vascular obstruction
2) embolism |
|
|
Term
| What does a venous thrombus vascular obstruction cause? |
|
Definition
|
|
Term
| What does a venous thrombus arterial obstruction cause? |
|
Definition
| infarction (ischemic necrosis) |
|
|
Term
| Where does a venous thrombus embolism go? |
|
Definition
| lungs (esp. from deep leg veins) |
|
|
Term
| Where does an arterial thrombus embolism go? |
|
Definition
| kidneys, spleen, brain, extremities |
|
|
Term
| What causes disseminated intravascular coagulation (DIC)? |
|
Definition
| massive systemic activation of coagulation => multiple widespread microthrombi => consumption of platelets & coagulation factors, plus activation of fibrinolysis => hemorrhagic diathesis |
|
|
Term
| What are the frequent lab findings in a DIC? |
|
Definition
decreased platelet count
prolinged PT & aPTT
increased fibrin degradation products |
|
|
Term
|
Definition
| intravascular mass that travels to a site distinct from its point of origin |
|
|
Term
|
Definition
| embolus composed of thrombotic material |
|
|
Term
| What are the 2 types of thromboemboli? |
|
Definition
|
|
Term
| What is the most common source of thromboemboli in the lungs? |
|
Definition
|
|
Term
| What are the 5 consequences of pulmonary thromboemboli? |
|
Definition
1) *subclinical event
2) pulmonary hemorrhage
3) pulmonary infarction
4) sudden death
5) pulmonary hypertension |
|
|
Term
| *When will a pulmonary thromboemboli have a subclinical event? |
|
Definition
| small embolus with either complete dissolution or organized into a small intimal scar or fibrous web |
|
|
Term
| When will pulmonary thromboemboli cause pulmonary hemorrhage? |
|
Definition
| medium-sized embolus in an individual with a good bronchial circulation |
|
|
Term
| When can pulmonary thromboemboli cause pulmonary infarction? |
|
Definition
| small to medium-sized embolus in a patient with poor bronchial circulation |
|
|
Term
| When can pulmonary thromboemboli cause sudden death? |
|
Definition
| either one large embolus or many small simultaneous emboli |
|
|
Term
| When can pulmonary thromboemboli cause pulmonary hypertension? |
|
Definition
| multiple organized emboli which increase pulmonary vascular resistance |
|
|
Term
| What is the most common consequence of pulmonary thromboemboli? |
|
Definition
|
|
Term
| What are the 4 most common sources of systemic thromboemboli? |
|
Definition
1) *cardiac mural thrombi (L atrium or ventricle)
2) aortic atherosclerosis w/ superimposed thrombosis (± aneurysm)
3) vegetations (L sided valves)
4) deep leg vein thrombosis => atrial or ventricular septal defect (paradoxical embolus) |
|
|
Term
| What is the consequence of systemic thromboemboli? |
|
Definition
|
|
Term
| What are the 6 special types of emboli? |
|
Definition
1) fat
2) air
3) amniotic fluid
4) cholesterol
5) tumor
6) bone marrow |
|
|
Term
| What are the 2 risk factors of a fat emboli? |
|
Definition
1) *long bone fractures
2) soft tissue injury |
|
|
Term
| What are the 2 consequences of fat emboli? |
|
Definition
1) *subclinical (vast majority)
2) fat embolism syndrome |
|
|
Term
| What causes fat embolism syndrome? |
|
Definition
| vascular obstruction & endothelial damage |
|
|
Term
|
Definition
resp. diffuculty
neurologic impairment
thrombocytopenia => petechiae
anemia |
|
|
Term
|
Definition
| frozen sections & special stains |
|
|
Term
| What are the 4 common causes of air emboli? |
|
Definition
1) sudden decrease in atmospheric pressure (decompression sickness)
2) chest trauma
3) obstetric complication
4) surgical procedures |
|
|
Term
| What causes decompression sickness? |
|
Definition
| greater quantity of nitrogen dissolved at high pressures, then with rapid depressurization, gas bubbles may form |
|
|
Term
def
bends (acute decompression sickness) |
|
Definition
| air emboli within skeletal muscle & around large joints |
|
|
Term
def
chokes (acute decompression sickness) |
|
Definition
|
|
Term
Sx
chronic decompression sickness (caisson disease) |
|
Definition
| persistent air emboli => long bone infarction |
|
|
Term
| How often is amniotic fluid emboli seen? |
|
Definition
| not common, but it does have a high mortality rate |
|
|
Term
| How does an amniotic fluid emboli occur? |
|
Definition
| amniotic fluid => uterine veins => lungs => diffuse alveolar damage & DIC |
|
|
Term
|
Definition
| squamous cells & keratin in the maternal pulmonary microvasculature |
|
|
Term
|
Definition
shock
resp. insufficiency
neurologic abnormalities |
|
|
Term
| Wherer does cholesterol emboli come from? |
|
Definition
| ulcerated atherosclerotic plaques |
|
|
Term
|
Definition
| focal region of ischemic (coagulative) necrosis |
|
|
Term
| What are the 4 causes of vascular obstruction => infarction? |
|
Definition
1) thrombosis
2) embolism
3) torsion of vessels (twisting)
4) extrinsic vascular compression |
|
|
Term
| What are the 2 major types of infarcts? |
|
Definition
|
|
Term
| What causes a pale infarct? |
|
Definition
| arterial occlusion within an end-artery system in a solid organ |
|
|
Term
| What does a pale infarct look like grossly? |
|
Definition
| soft, pale, often pyramidal-shaped region with hyperemic margin |
|
|
Term
| What does a pale infarct look like microscopically? |
|
Definition
| coagulative necrosis => acute inflammatory cell infiltrate => reparative process => scar |
|
|
Term
| What are the 3 causes of hemorrhagic infarct? |
|
Definition
1) venous obstruction
2) tissues with a dual blood supply or with numerous anastomoses
3) reperfusion of a pale infarct |
|
|
Term
| What does a hemorrhagic infarct look like grossly? |
|
Definition
| firm, red, often pyramidal-shaped region => rust-brown |
|
|
Term
| What does a hemorrhagic infarct look like microscopically? |
|
Definition
| coagulative necrosis with extensive hemorrhage => inflammation & repair, along with numerous hemosiderin-laden macrophages |
|
|
Term
| What are the 2 special types of infarcts? |
|
Definition
|
|
Term
| What is caused by cerebral infarct? |
|
Definition
|
|
Term
| What is caused by septic infacrt? |
|
Definition
|
|
Term
| What 4 things determine the likelihood of infarction? |
|
Definition
1) vascular supply
2) rate of development of the vascular occlusion
3) tissue susceptibility to hypoxia
4) adequacy of blood oxygenation |
|
|
Term
|
Definition
| systemic hypoperfusion => widespread tissue hypoxia |
|
|
Term
| What are the 5 types of shock? |
|
Definition
1) cardiogenic shock
2) hypovolemic shock
3) septic shock
4) neurogenic shock
5) anaphylactic shock |
|
|
Term
| What causes cardiogenic shock? |
|
Definition
| "forward" heart failure => decreased cardiac output |
|
|
Term
| What causes hypovolemic shock? |
|
Definition
| loss of blood or plasma volume |
|
|
Term
| What causes septic shock? |
|
Definition
| overwhelming microbial infection |
|
|
Term
| What are the 2 etiological factors of septic shock? |
|
Definition
1) microbial products
2) host immune response |
|
|
Term
| What of the host immune response contributes to the etiology of septic shock? |
|
Definition
1) inflammatory cells (esp. neutrophils & macrophages): produce cytokines & ROS
2) Complement activation: C3a/C5a (vasodilation, increased vascular permeability, chemotactic, opsonin) |
|
|
Term
| What are the 3 effects of septic shock that lead to multi-organ failure? |
|
Definition
1) widespread endothelial cell injury/activation
2) metabolic derangements
3) decreased myocardial contractility |
|
|
Term
| What widespread endothelial cell injury/activation is seen in septic shock? |
|
Definition
1) prothrombotic phenotype => DIC
2) peripheral vasodilation & increased vascular permeability => systemic hypotension & potentiation of procoagulant tendency
3) diffuse alveolar damage (ARDS-adult resp. distress syndrome) |
|
|
Term
| What metabolic derangements are seen in septic shock? |
|
Definition
1) Acute phase responses
2) increased gluconeogenesis, decreased insulin production & increased insulin resistance => hyperglycemia
3) abnormal glucocorticoid production (initial increase => eventual decrease) |
|
|
Term
| What causes neurogenic shock? |
|
Definition
| loss of vascular tone => peripheral pooling of blood |
|
|
Term
| What causes anaphylactic shock? |
|
Definition
| generalized type I hypersensitivity rxn => systemic vasodilation & increased vascular permeability |
|
|
Term
| What are the 3 stages of shock? |
|
Definition
1) nonprogressive
2) progressive
3) irreversible |
|
|
Term
| When are the stages of shock most prominently seen? |
|
Definition
| hypovolemic & cardiogenic shock |
|
|
Term
def
nonprogressive phase of shock |
|
Definition
| compensation by neuronal & hormonal mechanisms |
|
|
Term
| What occurs in the nonprogressive phase of shock to induce tacycardia & fluid retention? |
|
Definition
1) SS response/catecholamines => peripheral VC => cool clammy pale skin, tachycardia, tachypnea
2) renin-angiotensin-aldosterone system/ADH => fluid retention |
|
|
Term
def
progressive phase of shock |
|
Definition
| widespread tissue hypoperfusion/hypoxia |
|
|
Term
| What occurs in progressive phase of shock? |
|
Definition
1) anaerobic glycolysis => lactic acidosis => peripheral vasodilation => drop in cardiac output => hypotension
2) endothelial injury => DIC
3) renal hypoperfusion => oliguria & electrolyte abnormalities
4) cerebral hypoxia => confusion |
|
|
Term
def
irreversible phase of shock |
|
Definition
| system, irreversible cell injury |
|
|
Term
| What 4 organs undergo ischemic/hypoxic cell injury in shock? |
|
Definition
1) brain (red, dead neurons)
2) heart (contraction band necrosis)
3) kidneys (acute tubular necrosis)
4) intestine (=> bacteremia) |
|
|
Term
| What happens to the adrenal glands in shock? |
|
Definition
| stress rxn => decrease lipid in the cortex |
|
|
Term
| What alveolar damage is seen with septic shock? |
|
Definition
|
|
Term
| What manifestations of DIC (disseminated intravascular coagulation) are seen in shock? |
|
Definition
| microthrombi, petechiaw, hemorrhagic diathesis, etc. |
|
|
Term
| What is the most common disease affecting blood vessels? |
|
Definition
|
|
Term
|
Definition
| a form of arteriosclerosis (hardening of the arteries) - thickening & loss of elasticity of the vessel wall |
|
|
Term
| What causes atherosclerosis? |
|
Definition
| formation of atheromas (lipid plaques) |
|
|
Term
| What are the consequences of atherosclerosis? |
|
Definition
| stenosis, occlusion of vessel lumen, or aneurysm => damage to organs by altering blood flow |
|
|
Term
| What are the 4 important clinical manifestations of atherosclerosis? |
|
Definition
1) IHD (ischemic heart disease)
2) MI
3) PVD (peripheral vascular disease)
4) cerebrovascular disease (inc. stroke) |
|
|
Term
|
Definition
usually subclinical until complications of late-stage leisons lead to overt disease s.a.
transient vascular insufficiency
infarct
acute hemorrhage from ruptured aneurysm |
|
|
Term
| What vessels are affected by atherosclerosis? |
|
Definition
| elastic large to medium sized muscular arteries |
|
|
Term
| Where in vessels does atherosclerosis tend to affect? |
|
Definition
| branch points & origins of exiting vessels |
|
|
Term
| What are the 3 classical divisions of atherosclerosis? |
|
Definition
1) fatty streaks
2) atherosclerotic plaques (fibrous or fibroatheromatous)
3) complicated plaques |
|
|
Term
| What is the earliest atherosclerotic leison? |
|
Definition
|
|
Term
|
Definition
| subendothelial lipid deposits |
|
|
Term
| In fatty streaks, where does lipid accumulate? |
|
Definition
| "foam cells" (monocytes, macrophages, smooth muscle cells) |
|
|
Term
| What are the predominant cells in fatty streaks? |
|
Definition
|
|
Term
| What is the hallmark of atherosclerotic disease? |
|
Definition
|
|
Term
| How do atherosclerotic plaques form? |
|
Definition
| evolve from fatty streaks by progressive accumulation of lipid & smooth muscle cells |
|
|
Term
| What is at the core or atherosclerotic plaques? |
|
Definition
| necrotic center with cellular debris, lipids, & plasma proteins |
|
|
Term
| What covers the atherosclerotic plaque on the luminal surface? |
|
Definition
|
|
Term
| Where does neovascularization occur in an atherosclerotic plaque? |
|
Definition
|
|
Term
| Where in an atherosclerotic plaque are inflammatory cells found? |
|
Definition
| base & sides of the plaque |
|
|
Term
| What are the cells in plaques embedded into in an atherosclerotic plaque? |
|
Definition
| CT matrix produced by smooth muscle cells (SMCs) |
|
|
Term
| What are the 3 essential components of the atherosclerotic plaque? |
|
Definition
1) cells (SMCs, monocytes/macrophages, T cells)
2) CT (ECM, collagen, elastic, & proteoglycans)
3) lipids (intracellular & extracellular including cholesterol & cholesterol crystals) |
|
|
Term
| What is the primary cell type in an atherosclerotic plaque? |
|
Definition
|
|
Term
|
Definition
|
|
Term
|
Definition
| have prominent lipid core |
|
|
Term
| What are the 3 critical features of the atherosclerotic plaque that is responsible for expasion of the leisons => clinically overt disease? |
|
Definition
1) proliferation of intimal SMCs
2) accumulation of lipid & ECM in intima
3) on-going inflammation & collagen deposition |
|
|
Term
| What is the advanced leison in atherosclerosis? |
|
Definition
|
|
Term
| What does it mean that complicated leisons are "advanced"? |
|
Definition
plaques have undergone one of the following alterations:
1) calcification
2) ulceration (focal rupture)
3) thrombosis
4) hemorrhage into the plaque
5) aneurysmal dilation of the vessel wall |
|
|
Term
Effect
calcification of plaque |
|
Definition
| reduce flexibility of vessel wall |
|
|
Term
Effect
ulceration of plaque |
|
Definition
| embolization of plaque contents |
|
|
Term
Effect
thrombosis of plaque |
|
Definition
| partial or complete occlusion |
|
|
Term
Effect
hemorrhage into plaque |
|
Definition
| acute expansion or rupture of plaque |
|
|
Term
Effect
aneurysm dilation of vessel wall due to plaque |
|
Definition
| erosion of plaque into media => loss of elastic tirrue & smooth muscle due to: pressure, ischemic atrophy, or inflammatory damage => focal ballooning out of vessel wall |
|
|
Term
| What determines the clinical significance of advanced atherosclerosis? |
|
Definition
| vascular occlusion or rupture |
|
|
Term
| When will atherosclerosis remain subclinical until? |
|
Definition
1) acute occlusion => infarction
2) chronically diminished arterial flow => progressive organ dysfunction
or
3) hemorrhage occurs |
|
|
Term
| When does progressive stenosis reach a critical phase? |
|
Definition
|
|
Term
| When does acute arterial occlusion usually occur? |
|
Definition
| setting of plaque ulceration/rupture or hemorrhage into plaque with thrombosis |
|
|
Term
| Which plaques are particularly vulnerable to acute arterial occlusion? |
|
Definition
high lipid content
thin fibrous cap |
|
|
Term
|
Definition
| progressive damage to vessel wall with loss of elastic fibers & SMCs => impinge on adjacent structures or rupture acutely |
|
|
Term
| Where are atherosclerotic aneurysms most common? |
|
Definition
|
|
Term
| What are the 6 subclassification of atherosclerotic leisons as detailed by the AHA? |
|
Definition
I: initial leison (1st decade - silent)
II: fatty streak
III: intermediate leison (3rd decade)
IV: atheroma ( - silent or overt)
V: fibroatheroma (4th decade)
VI: complicated leison |
|
|
Term
| What are the major NON-modifiable risk factors for atherosclerosis (AS)? |
|
Definition
Age: increasing
Sex: M>F (Estrogen = premenopausal protecton)
Family Hx (inherited genetic abnormalities) |
|
|
Term
| Whata are the major modifiable risk factors for AS? |
|
Definition
Hyperlipidemia
DM
HTN
Smoking
Increased C-reactive protein level |
|
|
Term
| What are the minor, uncertain, or non-quantified risk factors for AS? |
|
Definition
obesity
physical inactivity
stress
diet: high CHO or trans fat intake
increased lipoprotein
chronic inflammatory diseasea (chlamydia)
increased homocysteine level
EtOH |
|
|
Term
| Where in the world is AS more prevalent? |
|
Definition
|
|
Term
| Why is there multiplicative effect of risk factors for AS? |
|
Definition
| Risk factors of AS are shared among other diseases s.a. ICD, HTN, DM, MI, stroke, renal disease, neurodegenerative diseases. |
|
|
Term
| What lipids play a role in AS? |
|
Definition
| cholesterol & other steroids, fatty acids, triglycerides |
|
|
Term
| What protein is used to transport lipids? |
|
Definition
|
|
Term
| What proteins synthesized in the liver form lipoproteins? |
|
Definition
|
|
Term
| How are lipoproteins classified? |
|
Definition
|
|
Term
| What are the 5 lipoproteins? |
|
Definition
1) chylomicrons
2) VLDL
3) IDL
4) LDL
5) HDL |
|
|
Term
| What 4 lipoprotein abnormalities were found in MI survivors? |
|
Definition
1) increased LDL
2) increased chylomicron remnant & IDL
3) increased abnormal lipoproteins
4) decreased HDL |
|
|
Term
|
Definition
1) chylomicron
2) chylomicron remnant
3) VLDL
4) IDL
5) LDL
6) HDL |
|
|
Term
| What happens to cholesterol when it's metabolized in the liver? |
|
Definition
Becomes free cholesterol =>
1) storage
2) synthesizing membranes
3) inhibits lipoprotein synthesis
4) inhibits synthesis of more cholesterol |
|
|
Term
| What types of lipoproteins are associated with high rish AS? |
|
Definition
LDL, VLDL, & IDL
IIa (LDL) - β
IIb (LDL & VLDL) - β & pre-β
III (IDL) - broad β |
|
|
Term
| What does high levels of LDL, VLDL, & IDL imply about blood cholesterol & triglyceride levels? |
|
Definition
|
|
Term
| What causes hypercholeseremia? |
|
Definition
| Genetic or acquired abnormalities in synthesis or degradation of plasma lipoproteins |
|
|
Term
| What implicates cholesterol as a risk factor for AS? |
|
Definition
1) increased dietary intake of cholesterol => increased risk
2) lipoprotein abnormalities seen in CVD
3) lipid genetic syndromes are associated with increased incidence AS
4) lab models derived from these observations |
|
|
Term
| What autosomal type is familial hypercholesterolemia? |
|
Definition
|
|
Term
| What abnormality is caused by familial hypercholesterolemia? |
|
Definition
| defect in LDL receptor protein or apoproteins (deficiency or functional impairment) |
|
|
Term
Sx
familial hypercholesterolemia |
|
Definition
1) early onset AS
2) deposits of lipid-laden macrophages in skin (xanthomas)
3) elevated cholesterol & LDL
4) Lipid profiles IIa (LDL) & IIb (vLDL & LDL) |
|
|
Term
| What other genetic mutation => increased risk for AS? |
|
Definition
| plasma lipoprotein mutations |
|
|
Term
| What does high HDL (or more specifically low total cholesterol/HDL ratio) correlate with? |
|
Definition
|
|
Term
| What results in intracellular deposition of lipoprotein-derived cholesterol? |
|
Definition
| oxidative modification of LDL (lipid peroxidation) => enhanced clearance by subendothelial macrophages (foam cells) |
|
|
Term
| What is one of the end products of lipid peroxidation? |
|
Definition
|
|
Term
| What are the 7 ways LDL peroxidation => increased AS leison? |
|
Definition
1) readily ingested by scavenger cells => foam cell formation
2) chemotactic for circulating blood monocytes
3) increased monocyte adhesion
4) inhibiting migration of foam cells
5) stimulating release of GFs & cytokines
6) toxic to EC & SMCs
7) serve as Ag => Ab formation |
|
|
Term
| What increased in dietary intake can reduce risk of AS? |
|
Definition
omega-3 PUFAs
antioxidants |
|
|
Term
| How does omega-3 PUFAs decrease AS risk? |
|
Definition
| inhibits EC synthesis of PDGF |
|
|
Term
| What drugs lower cholesterol? |
|
Definition
|
|
Term
Function
macrophages/monocytes in AS plaque |
|
Definition
1) phagocytose lipid to become foam cell
2) release mediators to interact with other cells |
|
|
Term
Function
SMCs in AS plaque |
|
Definition
1) migrate from media & proliferate
2) imbibe lipid to become foam cells
3) release mediators to interact with other cells |
|
|
Term
Function
T cells in AS plaque |
|
Definition
| release mediators to interact with other cells |
|
|
Term
| What is a key component of AS plaque formation that occurs early? |
|
Definition
|
|
Term
| What accounts for the progressive growth of AS leisons? |
|
Definition
| SMC proliferation & ECM deposition in intima |
|
|
Term
| Why happens when SMCs take up lipid in AS plaque? |
|
Definition
|
|
Term
| What stimulatory GFs are secreted in an AS plaque? |
|
Definition
PDGF via ECs, SMCs, monocytes/macrophages, platelets
bFGF via macrophages, ECs, & lymphocytes |
|
|
Term
| What inhibitory GFs are have decreased secretion in an AS plaque? |
|
Definition
| heparin-like compounds via EC |
|
|
Term
| How may SMC determine it's own proliferation? |
|
Definition
1)ability to proliferate changes with age
2)altered SMC kinetics may predispose to myointimal hyperplasia following endothelial injury |
|
|
Term
| What is considered the key event in the pathogenesis of AS? |
|
Definition
|
|
Term
| What role does endothelial injury play in AS? |
|
Definition
1) endothelial injury + high lipid diet => atheroma
2) most leisons develop under "normal" endothelium |
|
|
Term
| What is the relationship b/w endothelium & monocytes in early AS & late AS? |
|
Definition
early: recruitment of monocytes => protective
late: accumulated macrophages => recruitment of more inflammatory cells/produce toxic oxygen radicals |
|
|
Term
| What is the relationship b/w macrophages & T cells in AS? |
|
Definition
| => chronic inflammatory state & fibrosis |
|
|
Term
| Why is high levels of CRP indicative of increased AS risk? |
|
Definition
| biomarker of inflammation |
|
|
Term
| Why is it hypothesized that chlamydia can lead to increased AS risk? |
|
Definition
| produces local endothelial injury + chronic inflammation |
|
|
Term
| What 5 central questions should be addressed by any AS pathogenesis hypothesis? |
|
Definition
1) What is the basis for SMC proliferation?
2) By what mech. does lipid enter the plaque?
3) What are the characteristics and/or functions of the cells involved in AS
4) What is the role of AS risk factors?
5) What accounts for the anatomic location of the AS leisons? |
|
|
Term
| What is the earliest hypothesis of AS pathogenesis? |
|
Definition
|
|
Term
|
Definition
LDL enters endothelium via receptor-mediated uptake or non-specific uptake via pinocytosis.
(provides hypothesis for how lipid is accumulated, but not SMC proliferation. studies have concluded that lipids are engulfed by macropahges & then transported across vascular wall) |
|
|
Term
def
encrustation hypothesis |
|
Definition
small mural thrombi represent the initial event & organization of these thrombi => plaque formation.
Thus SMC proliferation is a reaction to the passage of lipids & proteins from blood to vessel wall.
(studied have concluded mural thrombosis is not an initial event) |
|
|
Term
|
Definition
an alteration in growth control of one a few SMC underlies the pathogenesis of AS. This alteration can be caused by some unknown factor s.a. mutagen, virus, etc.
(studies have shown many AS plaques are monoclonal) |
|
|
Term
def
response-to-injury hypothesis |
|
Definition
| the def. of endothelium injury was changed to include changes s.a. alteration in cell surface constituents, increased permeability, & increased endothelial turnover since endothelium is retained & remains intact in most AS plaques |
|
|
Term
def
oxidative-modification hypothesis |
|
Definition
reduced severity of AS is a result of the production of LDL resistant to oxidation.
(studies have shown that cellular antioxidants protect against AS damage, esp. endothelial dysfunction) |
|
|
Term
def
hemodynamic hypothesis |
|
Definition
hemodynamics plays a role since there is increased AS occurance at sites of prominent hemodynamic fluctuations & prominence of HTN as a risk factor.
hemodynamic forces can induce gene expression in EC (but can also induce gene expression of anti-atherogenic agents) |
|
|
Term
| What are the 3 stages of a unifying hypothesis of AS? |
|
Definition
1) initiation & formation
2) adaptation
3) clinical |
|
|
Term
| What occurs in the initiation & formation stage of a unifying hypthesis? |
|
Definition
1) initial intimal leison
2) lipid accumulation due to EC or SMC disruption
3) monocyte/macrophage response to injury
4) local mural thrombus incorporated into leisons
5) necrosis in deeper portions of thickened intima
6) fibroinflammatory lipid plaque |
|
|
Term
| What occurs in the adaptation stage of a unifyong hypothesis? |
|
Definition
| Luminal encroachment => hemodynamic changes & changes in vascular caliber |
|
|
Term
| What occurs in the clinical stage of a unifying hypothesis? |
|
Definition
1) plaque progression
2) complications |
|
|
Term
def
primary prevention of AS |
|
Definition
delaying formation of atheroma
(adjusting all modifiable risk factors) |
|
|
Term
def
secondary prevention of AS |
|
Definition
| preventing recurrance of symptomatic events |
|
|
Term
| What are the 4 aims of interventions at plaque regression? |
|
Definition
1) interfere with initiation of plaque formation (statins)
2) interfere with plaque progression (statins)
3) enhance plaque stability & thromboresistance => reduced likelihood of rupture, vasoreactivity or thrombosis (anticoagulants)
4) removal of plaque constituents (lipids, fibrin, collagen) (endarterectomy, angioplasty) |
|
|
Term
Increased CT matrix in fibrous plaques is:
A) of blood-borne origin
B) synthesized by smooth muscle cells
C) secreted by lipid-laden macrophages
D) not subject to proteinase activity |
|
Definition
|
|
Term
Characteristic features of fatty streaks include all of the following EXCEPT:
A) lipid-laden smooth muscle cells
B) thrombosis
C) lipid-laden macrophages
D) thickened intima
E) insignificant narrowing of the lumen |
|
Definition
|
|
Term
Which of the following processes converts a fibrous plaque into a complicated plaque?
A) cholesterol condenses into crystals
B) foam cells accumulate
C) neovascularization at the periphery of the leison
D) endothelial surface ulcerates
E) smooth muscle cells proliferate |
|
Definition
|
|
Term
Which of the following is most likely to be associated with an increased incidence of myocardial infarction due to coronary artery atherosclerosis?
A) an elevated HDL
B) a diet rich in omega-3 PUFAs
C) program of exercise & moderate EtOH consumption
D) elevated blood homocysteine level
E) normal blood level of lipoprotein Lp(a) |
|
Definition
|
|
Term
| Why is a person having an MI hypotensive, tachycardic & tachypneic? |
|
Definition
hypotensive: heart not working at full capacity
tachycardic: compensation for sm. stroke volume & to try to increase BP
tachypneic: due to decreased oxygen |
|
|
Term
| Why does someone having an MI have cool & clammy skin? |
|
Definition
| increased sympathetics to compenstate for decreased BP |
|
|
Term
|
Definition
| sound of turbulant blood flow |
|
|
Term
| What does a femoral bruit most likely indicate? |
|
Definition
| tubulant blood flow due to blockage of femoral a. |
|
|
Term
| What lab values are most indicative of cardiomyocyte damage? |
|
Definition
primarily: increased troponin
increased creatine kinase |
|
|
Term
| What does peripheral nerve look like microscopically? |
|
Definition
|
|
Term
| What risk factors does a 52 yr old male with diabetes & a smoking history have for MI? |
|
Definition
|
|
Term
| Why would someone be given a regimen of aspirin, heparin, & t-PA post-MI? |
|
Definition
| aspirin: inhibits COX1 => inhibits TXA2 => decreased platelet aggregation => decreased clotting
heparin: activated AT III => prevents thrombin (factor II) activation => decreased clotting
t-PA: thrombolytic activation of plasminogen to plasmin to break up clots |
|
|
Term
| Microscopically, how do you distinguish between a post-mortem clot & a thrombus? |
|
Definition
| thrombus has lines of Zhan |
|
|
Term
| What are the possible complications of an atheromatous plaque? |
|
Definition
1) calcification
2) ulceration
3) thrombus
4) hemorrhage
5) aneurysmal dilation |
|
|
Term
| What does calcification of an atherosclerotic plaque look like microscopically? |
|
Definition
|
|
Term
| Why is a pale infarct white? |
|
Definition
|
|
Term
| What coronary artery is sucspected of occlusion when the anterior L ventricle & anterior interventricular septum are involved in an MI? |
|
Definition
|
|
Term
| What happens when a pale infarct becomes reperfused? |
|
Definition
| becomes a hemorrhagic infarct |
|
|
Term
| How can reperfusion further damage cadiac myoctyes beyond initial injury? |
|
Definition
| formation of oxygen free radicals |
|
|
Term
| What microscopic features are characteristic of coagulative necrosis of the cardiac muscle? |
|
Definition
remnants of myocardiocytes with no nucleus/pyknotic nuclei
very eosinophilic
contraction band necrosis |
|
|
Term
| How can you distinguish a recent infarct <1 day old? |
|
Definition
some pyknotic nuclei
no neutrophils |
|
|
Term
| What happens to the subendocardium in a recent infarct? |
|
Definition
become fibrotic & have hydropic degeneration (swelling).
it's reversible cell injury, as opposed to necrosis, because there is some diffusion from the lumen |
|
|
Term
| What can cause a fever & increased WBC count in a MI recovering patient 3 days post-MI? |
|
Definition
| state of chronic inflammation => proinflammatory state via cytokines |
|
|
Term
| What cells predominate 3 days post MI? |
|
Definition
|
|
Term
| How do PMNs get to the MI site 3 days post-MI? |
|
Definition
| chemotactic: C5a, leukotrienes, other neutrophils, platelet activating factors |
|
|
Term
| Why is there so much clear space b/w muscle cells in area of infarction? |
|
Definition
|
|
Term
| How do you tell how old an infarct it? |
|
Definition
< 24 hr: no neutrophils
1-3d: neutrophils
3-7d: macrophages
5-7d: granulation tissue formation
weeks: new scar fibrosis
years: fibrosis, little fibroblasts |
|
|
Term
| Why do WBC count normalize 5d post-MI? |
|
Definition
| normalization due to decreased inflammatory response due to TGF-β & liopoxins |
|
|
Term
| What do you expect to see microscopically 5d post-MI? |
|
Definition
| macrophages, little neutrophils, granulation tissue formation |
|
|
Term
| What do the viable cariac myocytes look like 1 year post-MI? |
|
Definition
|
|
Term
| Why does fibrosis occur in subendothelial regions post-MI? |
|
Definition
| furthest area from coronary a. still perfused by them therefore less blood flow to them when occluded |
|
|
Term
|
Definition
| small clicking, bubbling, or rattling noises of the lungs |
|
|
Term
| What can cause rales in a person with heart issues? |
|
Definition
|
|
Term
| What causes pulmonary edema? |
|
Definition
|
|
Term
| What is the process that causes pulmonary edema due to L ventricular failure? |
|
Definition
|
|
Term
| What type of pulmonary edema is caused by L ventricular failure? |
|
Definition
| trsudate (little cells, little protein) |
|
|
Term
|
Definition
| increased intravascular blood due to impaired venous outflow |
|
|
Term
| Why would a person with previous heart failure have an enlarged liver & peripheral edema? |
|
Definition
|
|
Term
| Why would a person with R ventricular falure have an enlarged liver? |
|
Definition
| congestion on central v. due to decreased flow to IVC |
|
|
Term
| What happens to the liver in acute congestion? |
|
Definition
| centrilobular sinusoids expanded with blood |
|
|
Term
| What happens to the liver in chronic congestion? |
|
Definition
| centrilobular necrosis/atrophy, fibrosis & hemosiderin-laden macrophages |
|
|
Term
| Why are the portal triads spared from congestion in R ventricular failure? |
|
Definition
| triads flow into the portal veins => IVC. The back up starts at the IVC & works it's way backwards. The triad is just far enough back to not be affected |
|
|
Term
| What pigment in Kupffer cells indicates chronic liver congestion? |
|
Definition
|
|
Term
| What causes the hemosiderin pigment accumulates in a chronically congested liver? |
|
Definition
| abundance of blood => increased [iron] at that site |
|
|
Term
| What risk factors does a 52 yr old male with diabetes, a smoking history, and a previous MI have for thrombus formation? |
|
Definition
endothelial injury (atherosclerosis)
smoking
stasis of blood flow due to previous MI |
|
|
Term
| What are the components of granulation tissue? |
|
Definition
neovascularication
fibroblasts
inflammatory cells (mostly macrophages) |
|
|
Term
| Why would you see granulation tissue on scarred areas from old infarct? |
|
Definition
| New injury on old area of infarct |
|
|
Term
| What produces the lines of Zhan |
|
Definition
|
|
Term
| Are liens of Zhan more prominent in arteries or veins? |
|
Definition
|
|
Term
| What are the possible complications of a mural thrombus? |
|
Definition
vascular obstruction
embolism |
|
|
Term
| Why is a person with a thrombus likely to die from a stroke? |
|
Definition
| embolism to brain can cause stroke |
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