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Flashcards in GI Mod 4 Deck (134):
1

what divides R/L lobes of liver

Cantlie's line

2

top and bottom borders of liver

IVC
gallbladder

3

connective tissue of liver

1. falciform ligament
2. Glisson's capsule-surrounds liver, invaginates at hilum of the liver

4

what is the functional unit of the liver

1. hexagonal arrangement of hepatocytes and microvasculature
2. at center of the hexagon is the central vein
3. at each outer corner of hexagon is a portal triad
4. microvasculature consists of sinusoids and bile canaliculi

5

what does the portal triad of liver consist of

1. terminal branch of hepatic artery
2. terminal branch of portal vein
3. terminal bile duct

6

bile canaliculi drain into

terminal bile ducts

7

terminal bile ducts eventually drain into

R/L hepatic ducts

8

R/L hepatic ducts merge to form

common hepatic duct

9

common hepatic duct eventually divides into

1. cystic duct which connects to gallbladder
2. common bile duct which descends to merge with pancreatic duct and drain into duodenum

10

t/f hepatocytes have ability to regenerate

true

11

what are 3 signaling mechanisms for liver regeneration

TGF - transforming growth factor
HGF - hepatocyte growth factor
EGF - epidermal growth factor

12

there is a critical ratio bw _______ _________ mass and ________ mass

funcational hepatocyte mass and body mass

13

fluctuations in the ratio of functional hepatocyte mass vs body mass signal what

regeneration or apoptosis

14

what is the duration of liver regeneration if 50-60% of liver is damaged from 4 days of tylenol overdose

completely regenerates in 30 days

15

hepatic circulation

1. afferent pathways to liver
2. sinusoids
3. efferent pathway from liver
4. lymphatic circulation of lymph - large production of lymph

16

what are the afferent pathways to the liver

1. portal pathway - 75% from hepatic portal vein
2. arterial pathway - 25% from hepatic artery

17

what are sinusoids in liver

microvasculature within liver

18

what are the efferent pathway from liver

1. central veins drain into hepatic veins
2. hepatic veins eventually drain into IVC

19

avg weight of the liver

2-3 lbs

20

portal pathway - hepatic portal vein

1. receives blood from GI tract, spleen and pancreas
2. contains large amount of nutrients from GI tract
3. relatively small amount of oxygen
4. divides into R/L branches and then further divides until it finally delivers blood to portal vein

21

portal pathway - hepatic portal anastomosis
-4 veins

collateral venous circulation with numerous veins of abdominopelvic region
1. gastroesophageal vein
2. rectal vein
3. paraumbilical vein
4. portorenal vein

22

portal pathway - portal HTN

portal circulation congested and reverse portal blood flow towards portal anastomoses
-occurs when cirrhosis develops

23

liver arterial pathway - hepatic artery

delivers oxygenated blood to liver
accounts for approx 25% of blood flow to liver
originates from celiac trunk

24

arterial pathway of liver - hepatic artery and portal HTN

blood flow to liver from hepatic artery is not impaired
the relative high amount of O2 delivered to hepatocytes is synergistic with regeneration

25

sinusoids act as what for hepatocytes

capillary bed

26

sinusoids receive blood from

2 or 3 portal triad vessels
-terminal branches of hepatic portal veins and hepatic artery
-merges nutrient rich blood and O2 rich blood

27

sinusoids are lined with what

hepatocytes - expose hepatocytes to hepatic blood flow

28

sinsuoids drain into

central vein

29

structure of sinusoid/hepatocyte interface

1. Kupffer cells
2. fenestrated endothelium
3. space of Disse - stellate cells
4. pit cells
5. microvilli of hepatocytes

30

what are Kupffer cells

monocyte/macrophage origin
located along surface of endothelium
function: phagocytic removal immune complexes, cell debris, etc; and removal of damaged RBC
serves as early or front line defense against liver injury

31

what is fenestrated endothelium

-large holes in endothelial lining of sinusoid vessel
-allows nutrients/lipids to travel thru sinusoidal wall and flow to microvilli of hepatocyte
-endothelium also has pinocytosis function to active transport molecules to microvilli of hepatocyte

32

what are stellate cells

location: Disse Space
function: store vit A, produce/secrete hepatic growth factors for liver regeneration

33

what happens if stellate cells are stimulated via pathology/disruption of environment homeostasis

transform into fibroblastic function (produce collagen) and myblastic function (contractile)
-role in fibrosis

34

what are pit cells

aka granular lymphocytes or NK cells (natural killer)
location: surface of endothelium
function: front line immune defense against tumor formation, viruses, etc (attacks tumor/virus)
also plays role in liver regeneration

35

lymph system of liver - hepatic lymphatics
-what % of total lymph fluid
-drain fluid from where
-function

-liver produces largest amount of lymph fluid in body
-approx 20% of total lymph fluid
-drain fluid from Disse space, glisson's capsule and other interstitial spaces of liver
-play critical defensive role in protecting against intestinal bacteria/antigens

36

what are the two regional zones of hepatocytes in the lobule zone circulation

periportal hepatocytes
centrilobular hepatocytes

37

what is the third regional zone sometimes described in the lobule zone circulation

mid way bw periportal and centrilobule zones

38

what are periportal hepatocytes

-first to receive blood
-O2 and nutrient rich
-functional: last to experience necrosis; first to regenerate

39

what are centrilobular hepatocytes

last to receive blood
less O2 and nutrient availability
functional: susceptible to ischemia/necrosis; region of drug metabolism (biotransformation)

40

liver metabolizes what macromolecules

carbs, fats, proteins

41

liver stores what

fat soluble and some water soluble vitamins
-vitA
-vitK (critical for clotting cascades)
-vitD (precuresor involved in conversion of inactive D to active D)
-vit B12 (water soluble)

42

liver as endocrine function

vit D conversion & T4 to T3 conversion

remove some circulating hormones: insulin, glucagon, GI hormones

43

liver role in drug metabolism/biotransformation

liver serves as intermediate step
drugs ingested in hydrophobic form
liver converts to hydrophilic form to allow excretion

44

function of liver in carb metabolism

regulate blood glucose
inital mechanism to reduce blood glucose - insulin mediated

45

synthesis of glycogen (glycogenesis)

liver stores glucose for future energy needs
glycogen is approx 10% of total liver weight
glycogen synthesized from glucose, amino acids, and pyruvate

46

gluconeogenesis

-production of glucose from non carb sources
-glucose can be produced from fatty acids, amino acids, and lactate (rate limiting step is the amount of available substrate NOT liver enzymes)
-important role to maintain blood glucose during fasting
-stimulated by glucagon and sympathetics (inhibited by insulin)

47

what removes FFA and lipoproteins from plasma

liver

48

what is the fasting state of fat metabolism with liver

released into plasma from adipose tissue
FFA are removed from plasma by liver
FFA in liver have two fates:
1. used in energy production - B oxidation, ketone body formation
2. used to synthesize VLDL

49

feeding state of fat metabolism with liver

chylomicron remnants are removed from plasma by liver
-TGs from chylomicron remnants can be used from energy production (FFA formation) or to synthesize VLDL
-cholesterol from chylomicron remnants used to synthesize VLDL

50

lipoprotein synthesis in liver

the liver plays impt role in synthesizing lipoproteins needed for lipid transport in plasma

51

classes of lipoproteins

1. chylomicrons
2. VLDL
3. LDL
4. HDL

52

what are chylomicrons

largest diameter, most lipid, least concentration of proteins
lipids - 99% lipids, TG rich
-synthesized in intestines, transport TGs (digested fats)

53

what is VLDL

very low density lipoprotein
smaller diameter than chylomicron
lipids-90%, TG rich not as much as chylomicron
-synthesized in liver (small amnt in intestines)
-transport TGs to periphery

54

what is LDL

low density lipoprotein
small diameter than VLDL
lipids - 80% lipids, cholesterol rich
-synthesized in plasma (small amnt in liver)
-transport cholesterol from liver to peripheral tissue

55

what is HDL

high density lipoprotein
smallest diameter, least lipid, largest concentration of proteins
lipids - 40-60% lipids, cholesterol rich
-synthesized in plasma (small amount in liver)
-remove/transport cholesterol from periphery to liver

56

lipoprotein removal

liver plays important role in removal (catabolism) of lipoproteins

57

LDL removal

LDL receptors on the liver bind LDL and remove from circulation
ex. familial hypercholesterolemia = LDL receptor deficiency

58

hepatic cholesterol production

1. B oxidation of FFA in the liver creates acetyl CoA
2. acetyl CoA can be used for energy or can be used to synthesize cholesterol
3. rate limiting step in cholesterol synthesis is conversion HMG CoA to mevalonate
4. HMG CoA reductase is enzyme needed for rate limiting step

59

hepatic cholesterol has four possible fates

contribute to formation of VLDL
formation of bile acids
formation of cell membranes in liver
excreted from body

60

statins MOA

inhibit HMG-CoA reductase
-this is necessary for cholesterol formation
-this is the rate limiting step of cholesterol formation in the liver

61

result of statin use

decrease cholesterol synthesis by liver
increased production of LDL receptors on liver
increased uptake of LDL by liver
decreased plasma LDL cholesterol levels

62

protein metabolism in the liver

involved in many different pathways of amino acid metabolism
-synthesis of plasma proteins and tissue proteins
-utilized as fuel source (glucose, ketone bodies, acetyl CoA)
-pathway to remove nitrogenous wastes from body (urea cycle)

63

synthesis of plasma proteins - albumin

-synthesizes 9-12 grams/day
-critical role in maintaing fluid homeostasis
-pathology: ascites/edema

64

synthesis of plasma proteins - proteins of clotting cascade

prothrombin and fibrinogen

65

syntehsis of plasma proteins - a1 antitrypsin

protect against protein destruction

66

what 4 plasma proteins does the liver synthesize

1. albumin
2. blood clotting cascade factors
3. a1 antitrypsin
4. iron transport proteins

67

amino acids utilized as _____ source by liver

fuel

-formation of glucose
-formation of ketone bodies
-transamination of amino acids to form Acetyl CoA - substrate for Kreb's cycle

68

amino acids remove what from body

nitrogenous wastes

69

what is produced from amino acid/nucleic acid breakdown

ammonia
-highly toxic
-level is 10xs higher in liver vs plasma

70

ammonia is converted to what to be excreted

urea

71

urea cycle in liver

forms urea from ammonia by products
-liver accounts for 90% of nitrogenous waste excreted in urine

72

transamination of amino acids in liver for

glutamate/aspartate

73

two necessary enzymes needed for transamination of amino acids in liver

ALT - alkaline transaminase
AST - aspartate transaminase

74

which liver enzyme is more specific to liver than the other

AST more than ALT

75

bile fluid is composed of

1. bile acids
2. phospholipids
3. cholesterol

76

bile fluid contains/transports via what

micelle complex

77

what does bile fluid contain/transport

1. bile pigments - bilirubin
2. inorganic ions - NA+, K+, Ca++, Cl-, HCO3-
3. drug metabolites
4. fat soluble vitamines

78

bile function

1. assist in intestinal fat digestion - emulsfication of lipids in intestines
2. excretion of hydrophobic substances - cholesterol, bilirubin, hormones, drugs, fat soluble vitamins

79

bile is produced in and secreted from

hepatocytes

80

1. hepatocytes synthesize bile acids from

cholesterol

81

2. hepatocytes secrete bile into

canaliculi
(bile acids, phospholipids, cholesterol, bilirubin, drug metabolites all flow into canaliculi) - specific transporters required for each, flow transports componenets via micell comples

82

what stimulates bile production and secretion

CCK, secretin

83

bile pathway

secreted in bile canaliculi and flow thru biliary tree
1. during fasting - 75% flows into gall bladder - gallbladder will concentrate bile; 25% continue on and flow into duodenum
2. during feeding - gall bladder contract via CCK and vagal stimuli
-bile reaches duodenum and enters enterohepatic circulation

84

enterohepatic circulation of bile - duodenum

-bile acids secreted into duodenum
-bile acids emulsify intestinal fats and form micelles to assist in fat digestion/absorption

85

enterohepatic circulation of bile - jejunum/ileum

some of the bile acids interact with intestinal bacteria
form secondary bile acids

86

enterohepatic circulation of bile - terminal ileum

99% of intestinal bile acids (primary and secondary) are reabsorbed in the terminal ileum
1% excreted in feces

87

enterohepatic circulation of bile - liver

reabsorbed bile acids return to liver (recycled)

88

RBC degredation

lifespan 120 days
breakdown in spleen, liver (Kupffer cells) and thruout vascular system

89

bilirubin is a by product of what

RBC breakdown

90

pathophys of bilirubin from RBC

RBC broken down and hemoglobin is further divided
-globin: broken down into amino acids
-heme: broken down into iron and biliverdin
-iron is stored in liver and recycled into RBC formation in the bone marrow
-biliverdin is broken down into bilirubin and released in the plasma

91

bilirubin released into plasma is _____soluble

fat

92

because bilirubin is fat soluble, it needs a what for transport?

protein carrier

93

what does plasma bilirubin attach to

albumin

94

the plasma bilirubin is ______ and travels to the liver

unconjugated - can't be excreted in this form

95

bilirubin in the liver

plasma unconjugated bilirubin flows into hepatic circulation
becomes conjugated in hepatocytes = water soluble and can be excreted
the newly formed conjugated bilirubin mixes with the bile in the canaliculi
bile is secreted into intestines

96

bilirubin in the intestines

conjugated bilirbuin secreted into the duodenum
bacteria in the intestines convert the bilirubin into urobilinogen

97

intestinal urobilinogen will do one of two things

1. remain in colon and be excreted in stool (darker color) 80% of urobilinogen is excreted in feces
2. be reabsorbed into blood stream - 20% is reabsorbed
-the reabosrbed urobilinogen is recycled in liver or excreted in urine

98

what is jaundice

hyperbilirubinemia
aka icterus
bilirubin pigment causes yellowing (eyes, bruising)
-yellowing of skin and conjunctival membranes d/t excessive bilirubin in blood stream

99

jaundice is a s/s of what

dz/pathology that affects bilirubin metabolism/excretion pathways
-not specific to one dz

100

jaundice can be classified as what

pre hepatic or post hepatic

101

lab measurements of hyperbilirubinemia

1. total bili - measured directly in blood (if elevated = hyperbilirubinemia)
2. direct bili - measure directly in blood (if elevated = consistent with post hepatic pathology that impairs conjugated bilirubin secretion into GI
3. indirect bili - calculated from total and direct measurements (if elevated, consistent with pre hepatic pathology that impairs hepatocyte conversion of unconjugated bilirubin to conjugated bilirubin or increases amount of circulating unconjugated bilirubin

102

urobilinogen in urine

nl:0-4mg/24hrs
increased values = pre hepatic jaundice
nl or decreased values = post hepatic jaundice (if normal is 0, hard to have decreased)

103

what does pale stool indicate

decreased urobilinogen in intestines

104

what does dark urine mean

increased conjugated bilirubin excreted by kidney

105

classification of hyperbilirubinemia described by what

location of pathology that disrupts bilirbuin metabolism

106

what is pre hepatic jaundice

pathology before bilirubin is conjugated by the hepatocytes
ex. RBC breakdown, genetic dz (GIlbert's syndrome, sickle cell anemia, thalassemia), kidney dz
-sometimes referred to as hemolytic jaundice

107

what is post hepatic jaundice

pathology located after bilirubin is conjugated by hepatocyte and secreted (impaired transport of conjugated bilirubin to GI tract)
decreased secretion or transport of conjugated bilirubin from liver
-can occur anywhere from within canaliculi to sphincter of Oddi
-ex gallstones or pancreatic pathology that blocks the bile ducts
-sometimes referred to as obstructive jaundice

108

what is the result of hemolysis of RBCs

increased production of unconjugated bilirubin

109

labs for prehepatic jaundice pathology

total bili - elevated
indirect bili - elecated
direct bili - nml/potential elevated (d/t increased production of elevated conjugated bili)
urine - elevated urobilinogen
urine and stool color - nml

110

examples of what would cause post hepatic jaundice pathology
-impaired secretion from hepatocytes vs biliary duct system

1. impaired secretion from hepatocytes: pregnancy, cancer, hepatitis, cirrhosis, infiltrative dz (amyloidosis, sarcoidosis, TB), meds
2. biliary duct system: gallstones, strictures, pancreatitis,cancer/tumor

111

labs for post hepatic pathology

total bili - elevated
direct bili - elevated (d/t congestive back up)
indirect bili - nml
urine - elevated conjugated bili = dark color, decreased urobilinogen
stool - loss of dark color due to decrease in urobilinogen in feces

112

direct bili vs indirect bili

direct bili measures conjugated bili

indirect bili - measures unconjugated bili

113

neonatal jaundice onset and duration

onset- 1-2 days after birth
duration - 1-3 weeks

114

neonatal jaundice - result of neonatal physiology

increased rate of fetal RBC breakdown
low capacity of liver (hepatocytes) to conjugate bilirubin
decreased GGT and ligandin which impairs conjugation of bilirubin

115

treatment of neonatal jaundice

phototherapy - light creates isomers of bilirubin that are water soluble and can be excreted

severe: blood transfusion

116

complications of neonatal jaundice

1. hyperbilirubinemia neurotoxicity
2. monitor neuro

117

what is viruses cause hepatitis

viral - Hep A, B, C, D, E, G

118

what is the pathology of hepatitis

1. hepatic cell death/scarring
2. kupffer cell hyperplasia
3. inflammation may disrupt canaliculi

119

hepatic cell damage is more severe with what viruses

hepatic cell damage more severe in hepatitis B and C

120

what is fulminating hepatitis

rare complication in which massive hepatic cell death and liver failure

121

what is cirrhosis of the liver

irreversible inflammatory condition
-considered one of the leading causes of death in US
-many different disorders cause cirrhosis

122

what is the pathology of cirrhosis of the liver

hepatic tissue becomes nodular and fibrotic
size of liver may expand or shrink

123

initial phase of alcoholic cirrhosis

fatty accumulation develops within hepatocytes

124

chronic alcohol metabolism and alcoholic cirrhosis

-metabolism of alcohol produces acetaldehyde which disrupts hepatocyte function/metabolism
-cell damage initiates an inflammatory response and necrosis
-promotes excessive collagen synthesis and fibrotic accumulation/scarring

125

alcoholic cirrhosis - fibrosis eventually alters what

biliary and vascular drainage

-effects: liver functino declines, portal HTN, GI bleeding, caricose veins, ascities, hepatomegaly, splenomegaly

126

which stages of alcoholic cirrhosis are reversible and irreversible
-fatty liver
-fibrosis
-cirrhosis

fatty: reversible
fibrosis: reversible with scarring
cirrhosis: irreversible

127

2 types of biliary cirrhosis

primary and secondary

128

what is primary biliary cirrhosis

autoimmune dz that attacks small intrahepatic bile ducts (canaliculi)
inflammation of duct system leads to fibrotic changes

129

what is secondary biliary cirrhosis

develops as a result of chronic obstruction of biliary flow
obstruction leads to inflammation which leads to fibrotic changes
tx: address the cause of obstruction

130

2 types of gallstones

cholesterol stones
pigment stones

131

what are cholesterol stones

1. most common
80% of cases
yellowish/green

132

what are pigment stones

15%+ of cases
subtypes
black pigment (bili + calcium and other componenets
brown pigment (bilirubin + bacteria)

133

gall bladder and storage of bile

concentrates bile that is stored in gallbladder
-5x increase in concentration
-absorbs water and small electrolytes
leaves behind all of the organic substances in bile (cholesterol, bile salts, bilirubin, lecithin)
-stores approx 1-2 oz of concentrated bile

134

cholesterol stone formation

supersaturation of cholesterol in gallbladder
incomplete emptying of gallbladder, excess cholesterol formation