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GIGU > Hepatobiliary Fxn > Flashcards

Hepatobiliary Fxn Flashcards

1
Q

What capillary beds does the hepatic portal system connect?

A

1) hepatic sinusoidal capillaries

2) portal vein (abd organs from lower esophagus to anal canal)

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2
Q

What organs are drained via portal vein to liver?

A 
Pancreas
Gallbladder
Spleen
SI and LI--> anal canal
Lower esophagus
Stomach
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3
Q

What is the function of the liver in carb metabolism?

A

Makes glucose
Stores glucose as glycogen
Releases glucose

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4
Q

What is the function of the liver in protein metabolism?

A
  • Synthesizes non-essential AA
  • Modifies aa so it can feed into glucose metabolism
  • Synthesizes plasma proteins
  • Converts ammonia–>urea
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5
Q

What results in liver failure?

A

Hypoalbuminemia

–>low albumin because liver can’t make it–>EDEMA

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6
Q

What is the function of the liver in lipid metabolism?

A
  • fatty acid oxidation

- synthesis of lipoproteins, CHOLESTEROL, phospholipids

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7
Q

How does impaired liver fxn results in hepatic encephalopathy?

A

Decreased urea cycle metabolism in liver (d/t cirrhosis or shunting)—> accumulation of AMMONIA

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8
Q

How does impaired liver fxn results in ascites?

A

can’t make plasma proteins, decreased osmotic pressure and portal HTN–>fluid flows out of blood into tissue

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9
Q

Describe cirrhosis

A

Chronic liver disease–> normal liver cells damaged and replaced by SCAR TISSUE

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10
Q

What is the most common cause of cirrhosis?

A

excessive alcohol

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11
Q

How does impaired liver fxn results in bruising?

A

can’t make coagulation proteins–>increased bruising d/t easy bleeding

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12
Q

What is steatohepatitis?

A

fatty liver with inflammation–> leads to scarring of liver (cirrhosis)

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13
Q

What can cause portal HTN?

A

cirrhosis

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14
Q

Why does portal HTN develop?

A

there is resistance to portal blood flow d/t scarring

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15
Q

What changes in venous circulation are associated with portal HTN?

A

Esophageal varices

Caput medusae

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16
Q

What are examples of portosystemic shunting d/t portal HTN?

A

esophageal varices

caput medusae

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17
Q

How does ammonia cause hepatic encephalopathy?

A

increased ammonia (d/t impaired urea cycle in liver) crosses blood-brain barrier and alters brain fxn (toxic)

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18
Q

How does ammonia cause hepatic encephalopathy?

A

increased ammonia (d/t impaired urea cycle in liver) crosses blood-brain barrier and alters brain fxn (toxic)

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19
Q

What composes bile?

A 
bile salts (50%)
bilirubin
cholesterol
phospholipids (40%)
ions
water
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20
Q

What is the fxn of bile?

A

solubilizes lipids in intestines

vehicle for elimination of substances from body

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21
Q

Where is bile produced and secreted?

A

liver

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22
Q

Examples of primary bile acids

A

cholic acid

chenodeoxycholic acid

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23
Q

Examples of secondary bile acids

A

deoxycholic acid

lithocholic acid

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24
Q

Examples of bile salts

A

acids + glycine or taurine (lower pKA)

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25
What are the relative amounts of bile acids?
cholic acid> chenodeoxycholic acid> deoxycholic acid> lithocholic acid
26
What are the relative amounts of bile acids?
cholic acid> chenodeoxycholic acid> deoxycholic acid> lithocholic acid
27
Where are primary bile acids synthesized?
hepatocytes
28
Where are secondary bile acids found?
lumen of SI
29
Where are bile salts conjugated?
liver
30
What form micelles with products of lipid digestion?
bile salts
31
What are the biliary system organs?
``` Liver GB Bile duct Duodenum Ileum Portal circulation ```
32
What are the biliary system organs?
``` Liver GB Bile duct Duodenum Ileum Portal circulation ```
33
What agent activates ion and water addition to bile in the bile duct?
secretin
34
Where are ions and water absorbed to concentrate bile salt?
Gallbladder
35
What agent stimulates the contraction of the gallbladder AND relaxation of the sphincter of Oddi (pancreas)?
CCK
36
What happens to the bile salts after release into duodenum?
Form micelles--> absorbed into PORTAL circulation--> back to liver
37
What happens to bile salts when they are returned to the liver via portal circulation?
secreted into bile canaliculi along with newly formed bile acid--> ductule cells in response to anion transport (osmotic effects)
38
What drives bile-acid dependent bile formation?
Bile acids
39
What stimulates bile acid-independent/ ductular bile secretion?
secretin
40
What accompanies the secretion of bile acids into canaliculi?
passive movement of cations
41
What is the fxn of secretin in bile secretion?
Stimulates: - secretion of bicarb and water from ductile cells - sig increase in bile volume and pH - decrease in concentration of bile salts
42
When is CCK activated?
when eating
43
When is the GB relaxed and sphincter of Oddi closed?
between digestion/eating
44
How are bile salts recirculated to liver?
enterohepatic circulation --> ileum-portal blood- liver- synthesize what was lost
45
What mediates uptake of bile salts via basolateral membrane of hepatocytes?
- NTCP= sodium taurocholate cotransporting polypeptide (Na+ dependent transport protein) - OATPs= organic anion transport proteins (Na+-independent transport protein
46
What is cholesterol 7 alpha-hydroxylase inhibited by?
bile salts
47
What increases synthesis of bile acids 10 fold higher than normal?
interruption of the enterohepatic circulation
48
What does bile secretion normally increase?
increases rate of return of bile acids to liver via portal blood --> negative feedback synthesis==== inhibits 7alpha hydroxylase
49
Why do some infants have jaundice?
UDP glucuronyl transferase (conjugates bilirun) slowly synthesized after birth
50
What gives stool dark color?
urobilin | stercobilin
51
Where is bilirubin conjugated?
liver via UDP glucuronyl transferase
52
What happens to urobilinogen in terminal ileum?
Urobilinogen from conjugated bilirubin either: - converted to urobilin and stercobilin-->feces - back to liver via enterohepatic circulation-->urine
53
What are the characteristics (makeup) of saliva?
High bicarb and K+ hypotonic alpha amylase and lingual lipase
54
What factors increase secretion of saliva?
PNS (predominant) and SNS
55
What factors decrease secretion of saliva?
sleep dehydration atropine
56
What are characteristics (makeup) of gastric secretions?
HCL Pepsinogen Intrinsic factor
57
What factors increase gastric secretions?
Gastrin ACh Histamine PNS
58
What factors decrease gastric secretions?
H+ in stomach Chyme in duodenum Somatostatin Atropine Cimetidine Omeprazole
59
What are characteristics (makeup) of pancreatic secretions?
High bicarb Isotonic Pancreatic lipase, amylase, proteases
60
What factors increase pancreatic secretions?
Secretin CCK (potentiates secretin) PNS
61
What factors decrease pancreatic secretions?
N/A
62
What are characteristics (makeup) of bile?
Bile salts Bilirubin Phospholipids Cholesterol
63
What factors increase bile secretions?
CCK (contract GB, relax sphincter of oddi) PNS
64
What factors decrease bile secretions?
ileal resection
65
What is a sign of hyperbilirubinemia?
Icterus/Jaudice
66
What is icterus?
Yellow discoloration of the sclera, skin and mucous membranes
67
What shows in a quantitative jaundice test (bilirubin test)?
Direct (conjugated) Indirect (unconjugated) Total bilirubin
68
Describe the pathway of RBC breakdown to passage of bile
``` RBC Breakdown--> Unconjugated bilirubin-> Uptake to liver--> Conjugated bilirubin--> Secretion to bile--> Passage of bile ```
69
What stages of RBC breakdown can be involved in unconjugated jaundice?
RBC breakdown--> Unconjugated bilirubin-> Uptake to liver--> Conjugated bilirubin
70
What can cause increased bilirubin?
hemolytic anemia
71
What can cause decreased delivery of bilirubin to liver for conjugation?
Heart failure
72
What parts of the RBC breakdown pathway does Gilber's syndrome affect?
Can’t: Uptake of bilirubin to liver conguated bilirubin
73
What part of the RBC breakdown pathway does Crigler-Najjar syndrome affect?
Can’t: | Conjugate bilirubin in liver
74
What part of the RBC breakdown pathway does Dubin-Johnson syndrome affect?
Can’t: | Secrete conjugated bilirubin to bile
75
What part of the RBC breakdown pathway does Rotor syndrome affect?
Can’t secrete conjugated bilirubin to bile
76
What part of the RBC breakdown pathway does a biliary tree obstruction affect?
Can’t pass bile
77
What parts of the RBC breakdown pathway correspond to conugated jaundice?
Secretion of bilirubin to bile and passage of bile
78
What are the 5 known hereditary defects in bilirubin metabolism?
Crigler-Najjar syndromes (1 and 2) Gilber's syndrome Dubin-Johnson syndrome Rotor syndrome
79
How does hemolytic anemia lead to increased unconjugated bilirubin?
Increased bilirubin level overwhelmes liver's capacity to produce conjugated bilirubin
80
What are 2 causes of physiological neonatal jaundice?
- elevated bilirubin production d/t increased breakdown of fetal RBCs - low activity of UDP glucuronyl transferase
81
What syndrome is implicated in a mutation of UDP glucuronyltransferase (UGT1A1)?
Gilbert syndrome
82
Describe Gilbert Syndrome
- increased unconjugated bilirubin - mild, adolescence. mild cases of hyperbilirubinemia in times of stress - 30% no sx
83
Is Type 1 or 2 Crigler-Najjar syndrome more severe?
Type 1
84
What syndrome causes increased levels of unconjugated bilirubin d/t nonhemolytic jaundice?
Crigler-Najjar syndrome -->also d/t mutation in UDP gene
85
Describe Type 1 Crigler-Najjar syndrome
- earlier in life with jaundice at birth/infancy - NO FXN of UDP glucuronyltransferase - TMT using phototherapy (most did not survive before this) - Kernicterus form of this
86
Is Kernicterus d/t type 1 or 2 Crigler-Najjar syndrome?
Type 1
87
Define Kernicterus
Permanent brain damage d/t accumulation of unconjugated bilirubin in brain and nerves --> CP, sensorineural hearing loss, gaze abn
88
Define Type 2 Crigler-Najjar syndrome
later in life, most survive into adulthood less than 20% fxn of UDP -not likely to develop kernicterus
89
What are the possible treatments for Crigler-Najjar Syndrome?
- phototherapy throughout life (doesn't work well after age 4 d/t thick skin) - blood transfusions - oral calcium phosphate and carbonate to form complexes with bilirubin in gut - liver transplant - phenobarbitol to treat TYPE 2 (conjugates bilirubin)
90
Define Dubin-Johnson syndrome
- increased conjugated bilirumin without elevation of liver enzymes ---> defect of ability to secrete into bile - mild jaundice after puberty or adulthood - liver is black but fxn normal
91
What is the function of multidrug resistance-associated protein 2?
transports bilirubin out of liver cells into bile --> MUTATED in Dubin-Johnson syndrome
92
What worsens jaudice in Dubin-Johnson syndrome?
alcohol, birth control pills, infection, pregnancy
93
Define Rotor syndrome
Buildup of both conj and unconj bilirubin in blood, but majority is conjugated -->similar to Dubin-Johnson, except mutations lead to nonfxnl OATP1B1 and OATP1B3 proteins -liver not pigmented
94
What are the fxns of OATP1B1 and OATP1B3 proteins?
transport bilirubin from the blood into liver to be cleared from body -->MUTATED in Rotor syndrome
95
How does phototherapy work on bilirubin?
Isomerization: trans bilirubin to water-soluble cis bilirubin isomer
96
What is cholecystitis?
Inflammation of GB d/t obstruction of cystic duct from cholelithiasis
97
What is choledocholithiasis?
Gallstones occlude common bile duct--> jaundice, conjugated hyperbilirubinemia
98
What is cholangitis?
Infection of the distal bile duct
99
Are liver function tests direct measures of liver fxn?
no, vary and can be abnl in patietns with nml liver fxn
100
Elevated plasma aminotransferases are primarily the result of ?
Hepatocyte injury
101
Elevated alkaline phosphatase in plasma are primarily the result of?
bile duct injury (cholestasis)
102
What are liver enzymes measured in serum?
Aminotransferases (alanine and aspartate: ALT and AST) Alkaline phosphatase
103
What are abnml function tests seen in impaired hepatic synthetic fxn?
serum bilirubin, albumin, prothrombin time
104
What does bilirubin function test measure r/t liver?
liver's ability to detoxify metabolites, transport organic anions into bile
105
Severe impairment of hepatocyte fxn likely to _______ level of albumin in plasma
reduce
106
Is hypoalbuminemia specific for liver disease?
No, can be seen in kidney glomerular disease
107
What does the prothrombin time function test reflect?
degree of hepatic synthetic dysfunction --> increases as liver decreases clotting factor synthesis --> worsening coagulation= severity of hepatic dysfunction

GIGU (37 decks)

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