GI Mod 4 Flashcards
1
Q
what divides R/L lobes of liver
A
Cantlie’s line
2
Q
top and bottom borders of liver
A
IVC
gallbladder
3
Q
connective tissue of liver
A
- falciform ligament
2. Glisson’s capsule-surrounds liver, invaginates at hilum of the liver
4
Q
what is the functional unit of the liver
A
- hexagonal arrangement of hepatocytes and microvasculature
- at center of the hexagon is the central vein
- at each outer corner of hexagon is a portal triad
- microvasculature consists of sinusoids and bile canaliculi
5
Q
what does the portal triad of liver consist of
A
- terminal branch of hepatic artery
- terminal branch of portal vein
- terminal bile duct
6
Q
bile canaliculi drain into
A
terminal bile ducts
7
Q
terminal bile ducts eventually drain into
A
R/L hepatic ducts
8
Q
R/L hepatic ducts merge to form
A
common hepatic duct
9
Q
common hepatic duct eventually divides into
A
- cystic duct which connects to gallbladder
2. common bile duct which descends to merge with pancreatic duct and drain into duodenum
10
Q
t/f hepatocytes have ability to regenerate
A
true
11
Q
what are 3 signaling mechanisms for liver regeneration
A
TGF - transforming growth factor
HGF - hepatocyte growth factor
EGF - epidermal growth factor
12
Q
there is a critical ratio bw _______ _________ mass and ________ mass
A
funcational hepatocyte mass and body mass
13
Q
fluctuations in the ratio of functional hepatocyte mass vs body mass signal what
A
regeneration or apoptosis
14
Q
what is the duration of liver regeneration if 50-60% of liver is damaged from 4 days of tylenol overdose
A
completely regenerates in 30 days
15
Q
hepatic circulation
A
- afferent pathways to liver
- sinusoids
- efferent pathway from liver
- lymphatic circulation of lymph - large production of lymph
16
Q
what are the afferent pathways to the liver
A
- portal pathway - 75% from hepatic portal vein
2. arterial pathway - 25% from hepatic artery
17
Q
what are sinusoids in liver
A
microvasculature within liver
18
Q
what are the efferent pathway from liver
A
- central veins drain into hepatic veins
2. hepatic veins eventually drain into IVC
19
Q
avg weight of the liver
A
2-3 lbs
20
Q
portal pathway - hepatic portal vein
A
- receives blood from GI tract, spleen and pancreas
- contains large amount of nutrients from GI tract
- relatively small amount of oxygen
- divides into R/L branches and then further divides until it finally delivers blood to portal vein
21
Q
portal pathway - hepatic portal anastomosis
-4 veins
A
collateral venous circulation with numerous veins of abdominopelvic region
- gastroesophageal vein
- rectal vein
- paraumbilical vein
- portorenal vein
22
Q
portal pathway - portal HTN
A
portal circulation congested and reverse portal blood flow towards portal anastomoses
-occurs when cirrhosis develops
23
Q
liver arterial pathway - hepatic artery
A
delivers oxygenated blood to liver
accounts for approx 25% of blood flow to liver
originates from celiac trunk
24
Q
arterial pathway of liver - hepatic artery and portal HTN
A
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
