Block 3 Week 2

Front 1

describe the pathway of heme breakdown

Back 1

macrophage eats RBC > globin > broken down to heme > bilirubin (insoluble) > bound to albumin (soluble) > conjugated to glucaronic acid in the liver > secreted to bile > bacteria convert to urobilinogen

Front 2

explain how to measure bilirubin

Back 2

direct/indirect bilirubin

direct - conjugated
indirect - both direct and indirect

Front 3

four primary causes of jaundice

Back 3

1. physiological, 2. antibody against fetal RBC, 3. hereditary hemolytic disorder, 4. gilbert's

Front 4

what is kernicterus

Back 4

elevated unconjugated bilirubin, can penetrate immature fetal BBB to cause brain damage (binds to plasma membrane), treat with phototherapy

Front 5

describe heme synthesis pathway, and one pathology that can occur

Back 5

glycine + succinyl CoA with ALA synthase makes ALA, then converted to heme

lead poisoning inhibits pathway from ALA > heme, results in elevated ALA

Front 6

describe two types of porphyria and pathogenesis

Back 6

1. primary - hereditary, autosomal dominant; a) acute - early step defect (ALA build-up), b) cutaneous - late step, sunlight converts intermediate to toxic compounds
2. secondary/acquired - chemical effect (eg Pb poisoning)

Front 7

what cytoplasmic molecule binds iron

what plasma molecule binds iron

Back 7

apoferritin, forms ferritin after binding

transferrin

Front 8

explain how ferritin can be used as a diagnostic tool

Back 8

indicator of iron storage, except in inflammatory states where ferritin levels will be increased

Front 9

name three primary causes of anemia

Back 9

1. iron deficiency, 2. defective iron storage, 3. defective Fe utilization

Front 10

what is hepcidin, explain pathology associated with this

Back 10

binds to ferroportin and causes internalization/degradation of the protein, so cannot export iron into blood, causes iron deficiency

Front 11

explain sideroblastic anemia

Back 11

can be hereditary or acquired; inability to incorporate Fe into hemoglobin, leads to excess ferritin that accumulates into hemosiderin, this can cause organ damage

Front 12

explain pathology of hemochromatosis

Back 12

hereditary; excessive Fe absorption due to underactive hepcidin; caused by mutation in hepcidin or regulatory gene (HFE) [primary method]

Front 13

how does excretion of ammonia occur

Back 13

liver converts NH3 to urea, excreted by kidneys or intestine

Front 14

what is the important amino acid in urea formation

Back 14

ornithine

Front 15

where does urea cycle take place

Back 15

liver

Front 16

describe hereditary hyperammonia

Back 16

defect in enzymes of urea cycle, causes excretion of intermediates, but this exhausts ornithine since it is not regenerated

Front 17

describe treatment of hyperammonia

Back 17

low-protein diet, arginine (ornithine replacement), high carbohydrate diet

Front 18

describe acquired hyperammonia

Back 18

liver disease (caused by cirhossis, hepatitis), causes NH3 to accumulate in bloodstream

Front 19

describe some consequences of NH3 toxicity

Back 19

disruption of ion channels, decreased ATP generation (due to increased glutamate synthesis depleting alpha-ketoglutarate of the TCA)

Front 20

describe hepatic encephalopathy

Back 20

hepatic dysfunction causes accumulation of toxins, which reach brain and cause cognitive anomalies

Front 21

compare male vs female metabolism of alcohol

Back 21

most metabolism takes place in liver, but 15-20% metabolized in stomach, but this only true for males

Front 22

describe three metabolic pathways for ethanol

Back 22

1. alcohol dehydrogenase to acetaldehyde dehydrogenase to acetic acid; 2. microsomal alcohol oxidizing system (MAOS) -- EtOH activates CYP450 and affects drug metabolism; 3. catalase converts EtOH to acethaldehydes

Front 23

three consequences of liver exposure to EtOH

Back 23

steatosis (fatty liver), hepatitis, cirrhosis

Front 24

define primary and secondary hemostatis

Back 24

1. vasoconstriction and platelet seal; 2. coagulation to form blood clot

Front 25

describe platelet seal formation

Back 25

1. platlet binds to exposed collagen, 2. activation of platelet, 3a. shape change, pseudopodia form, enhanced adherence, 3b. secretion of ADP and thromboxane A2 to enhance activation/adherance

Front 26

name two drugs interfering with platelet function

Back 26

aspirin blocks thromboxane A2, plavix competitively inhibits ADP

Front 27

how do undamaged ECs keep platelets from aggregating

Back 27

secretion of prostagladin 2

Front 28

how is intrinsic clotting pathway initiated

Back 28

damage to endothelium activates kallikrein

Front 29

describe intrinsic pathway cascade down to common source

Back 29

damaged tissue components disturb factor XII to activate it > 11 > 9 > 10 -> IX is stabilized by XIII (stablized by vWF)

Front 30

describe common pathway

Back 30

activated factor X acts with factor V to get thrombin, then makes fibrin, and XIII act with fibrin to get clots and XB

Front 31

describe extrinsic pathway

Back 31

tissue trauma activates tissue trauma factor (III) to activate factor VII -- this activates factor X

Front 32

what does thrombin do

Back 32

activate fibrin, and factor V and factor VIII

Front 33

describe the function of thrombin

Back 33

1. activates fibronogen, 2. activates factor V and VIII, 3. cleaves/inactivates active forms V and VIII

Front 34

describe two methods of limiting clotting

Back 34

1. throbomodulin binds thrombin, activates protein C, and degrades V and VIII, 2. antithrombin degrades active proteases, activity enhanced by heparin, 3. thrombin resorbed into forming fibrin

Front 35

what is important ion in clotting cascade

Back 35

calcium is required

Front 36

what clotting things is vitamin K important in

Back 36

X, VII, IX, prothrombin, protein C

Front 37

how would vitamin K deficiency occur

Back 37

inability to resorb fats, liver disease, bile obstruction

Front 38

describe pathology of hemophilia

Back 38

deficient in factor VIII or IX, x-linked recessive

Front 39

what are the anticoagulant factors/proteins

Back 39

protein C, thrombomodulin, antithrombin, heparin, plasmin

Front 40

describe hereditary thrombophilia

Back 40

hypercoagulation caused by 1) mutated factor V, 2) elevated prothrombin expression, 3) decreased anticoagulant factors

Front 41

describe pathogenesis of DIC

Back 41

small clots form in blood vessels, depletes all platelets, then excessive bleeding in other parts

Front 42

describe structure of the hepatocyte functional unit

Back 42

central vein surrounded by portal vein/hepatic artery/bile duct (portal triad); central vein is area of low O2, bile duct is area of high O2

Front 43

what is th dual blood supply to the liver

Back 43

hepatic artery and portal vein

Front 44

what are four sites affected by portal hypertension

Back 44

1) rectal varices, 2) esophageal/gastric varices, 3) splenomegaly, 4) caput medusae (umbilical veins)

Front 45

describe bile production

Back 45

1) secretion of bile salts/cholesterol into bile canaliculi, 2) ducts/ductules add secretions (HCO3), 3) gallbladder can store/concentrate

Front 46

where is bile and fat-soluble vitamins resorbed

Back 46

terminal ileum

Front 47

what is primary component of bile

Back 47

bile salts

Front 48

what is precursor to bile

Back 48

cholesterol

Front 49

what are the only types of energy brain can use

Back 49

glucose and ketones (free fatty acids can be converted to ketones)

Front 50

what cell secretes intrinsic factor

Back 50

parietal cell