21. Hepatobiliary Function Flashcards

1
Q

Main functions of the liver

A

Bile production and secretion

Metabolism of carbs, proteins, and lipids

Bilirubin production and excretion

Detoxification of substances

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2
Q

Chronic liver disease in which normal liver cells are damaged and replaced by scar tissue (fibrosis)

A

Cirrhosis

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3
Q

Most common cause of cirrhosis

A

Excessive alcohol intake

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4
Q

How does excess alcohol intake lead to cirrhosis?

A

Initial accumulation of fat within hepatocytes leads to steatohepatitis (fatty liver + inflammation) which leads to liver scarring and cirrhosis

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5
Q

Chronic disease that causes bile ducts in liver to become inflamed, damaged, and are eventually lost

A

Primary biliary cirrhosis

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6
Q

Most common cause of portal HTN

A

Cirrhosis

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7
Q

Portal HTN develops when there is increased _____ to portal blood flow, which most often occurs in the liver

A

Resistance

[this increase in resistance is because of loss of connections in parallel]

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8
Q

Complications of portal HTN in the setting of cirrhosis

A

Hepatic encephalopathy
Esophageal varices
Splenomegaly
Ascites

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9
Q

What changes in the starling forces cause ascites in the setting of cirrhosis?

A

Cirrhotic liver produces less albumin, thus reducing oncotic pressure

Increased portal pressure leads to increased hydrostatic pressure

Fluid begins leaving mesenteric capillaries into interstitial spaces

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10
Q

Bile is produced and secreted by the ___

A

Liver

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11
Q

Composition of bile

A
Bile salts (50%)
Bile pigments like bilirubin (2%)
Cholesterol (4%)
Phospholipids, such as lecithin (40%)
Ions
Water
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12
Q

Primary function of bile

A

Solubilizes lipids that are naturally insoluble by forming micelles; vehicle for elimination of substances from the body

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13
Q

Formation of bile salts begins with primary bile acids, then secondary bile acids, then bile salts.

There are relative amounts of bile acids, which ones are most common?

A

Cholic acid > chenodeoxycholic acid > deoxycholic acid > lithocholic acid

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14
Q

Where are primary bile acids synthesized?

A

Hepatocytes

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15
Q

Where are secondary bile acids synthesized

A

Small intestine

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16
Q

Primary bile acids are synthesized in the liver from ________, catalyzed by the ______ enzyme to become cholic or chenodeoxycholic acid

A

Cholesterol; 7-alpha hydroxylase

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17
Q

Where are bile salts conjugated?

A

Liver

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18
Q

What is the primary hormonal mediator of bile secretion? What does it cause?

A

CCK

Causes contraction of gallbladder and relaxation of the sphincter of Oddi

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19
Q

Action of CCK is mediated through extrinsic _____ and intrinsic _____ nerves

_____ may antagonize CCKs actions

A

Vagal; cholinergic

Secretin

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20
Q

What effect do pancreatic polypeptide and somatostatin have on gallbladder contractility?

A

Decrease it

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21
Q

How does the parasympathetic nervous system affect bile secretion?

A

Stimulation via vagus nerve:
Increases bile flow
Induces contraction of gallbladder

[sympathetic system opposes these things]

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22
Q

What is the role of secretin in bile secretion from the liver?

A

After bile is secreted from the liver, secretin stimulates addition of ions and water, thus diluting the bile

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23
Q

After bile is released from the liver, where does it go? What does it do there?

A

Gallbladder, which concentrates the bile

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24
Q

CCK stimulates contraction of the gallbladder and relaxation of the sphincter of Oddi. Where does the bile that is released go from there?

A

Enters duodenum, travels through to ileum, and gets reabsorbed via portal circulation for recycling back to the liver

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25
Q

________ bile is secreted by ductule cells in response to the osmotic effects of anion transport

Newly synthesized and returning bile acids are secreted into the _________ as conjugated bili

A

Canalicular

Bile canaliculi

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26
Q

Although most bile transported through the small intestine is recycled, some is excreted in ______. The more that is lost, the _____ gets synthesized

A

Feces; more

[so fecal loss should equal hepatic synthesis of bile]

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27
Q

What transporters in the basolateral membrane of hepatocytes are responsible for bile reuptake/recylcing back into hepatocytes from enterohepatic circulation?

A

NTCP

OATP

28
Q

Increased bile secretion should increase the rate of its return via enterohepatic circulation, this will lead to negative feedback on bile synthesis once enough is produced. Thus, the ______ enzyme is inhibited by bile salts

A

Cholesterol 7-alpha hydroxylase

29
Q

Interruption of enterohepatic circulation can ______ bile synthesis to values >10x normal

A

Increase

30
Q

What is the difference between bile acid-dependent secretion, and bile acid-independent secretion?

A

Acid-dependent = driven by bile acids

Acid-independent = driven by secretin (small portion of bile)

31
Q

Secretin stimulates HCO3 and water secretion from ______ cells, which increases volume, ______ pH, and ______ bile salt concentration

A

Ductile; increases; decreases

32
Q

______ bile is plasma ultrafiltrate

A

Cannalicular

33
Q

Describe bile acid secretion between meals (aka the interdigestion period)

A

Gallbladder fills with bile
Gallbladder is relaxed
Sphincter of Oddi is closed

34
Q

Describe bile acid secretion upon ingestion of food

A

CCK is released from I cells in duodenum
Contraction of gallbladder
Relaxation of sphincter of Oddi

35
Q

Bilirubin is initially produced from the breakdown of RBCs via the ________ system, forming bilirubin-albumin which travels to the ______ where it is conjugated. Some of the conjugated is excreted in the urine, but some is secreted in the _______ which travels to the small intestine and colon. Conjugated bilirubin that takes the latter route is converted to _______, then either _____ or ______ which are excreted in feces and give stools their darker color

A

Reticuloendothelial; liver; bile; urobilinogen; urobilin; stercobilin

36
Q

What enzyme, responsible for the conjugation of bilirubin, is synthesized slowly in newborns, thus explaining the relatively common incidence of neonatal jaundice?

A

UDP-gucuronyl transferase

[forms bilirubin glucuronide which is yellow]

37
Q

What are the steps of bilirubin formation from RBCs via the reticuloendothelial system?

A

RBCs —> hemoglobin released —> broken down to biliverdin —> bilirubin —> leaves via bloodstream as bilirubin-albumin

38
Q

______ = icturus

A

Jaundice

39
Q

Jaundice is a sign of what SPECIFIC medical condition

A

Hyperbilirubinemia

40
Q

What are the 5 known hereditary defects in bilirubin metabolism

A
Gilbert’s syndrome
Dubin-Johnson syndrome
Rotor syndrome
Crigler-najjar syndrome type 1
Crigler najjar syndrome type 2
41
Q

Is the following condition associated with conjugated or unconjugated bilirubin?

Biliary tree obstruction

A

Conjugated

42
Q

Is the following condition associated with conjugated or unconjugated bilirubin?

Dubin Johnson syndrome

A

Conjugated

43
Q

Is the following condition associated with conjugated or unconjugated bilirubin?

Gilbert’s syndrome

A

Unconjugated

44
Q

Is the following condition associated with conjugated or unconjugated bilirubin?

Rotor syndrome

A

Conjugated

45
Q

Is the following condition associated with conjugated or unconjugated bilirubin?

Crigler najjar syndrome

A

Unconjugated

46
Q

Is the following condition associated with conjugated or unconjugated bilirubin?

Hemolytic anemia

A

Unconjugated

47
Q

Is the following condition associated with conjugated or unconjugated bilirubin?

Heart failure

A

Unconjugated (decreased delivery of bilirubin for conjugation)

48
Q

Why does hemolytic anemia lead to increased unconjugated bilirubin leading to jaundice?

A

With more hemolysis, more bilirubin gets produced which at that point is unconjugated

49
Q

2 main causes of neonatal jaundice

A

Elevated bilirubin production d/t breakdown of fetal erythrocytes

Low activity of UDP glucuronyl transferase

50
Q

What condition is characerized by increased levels of unconjugated bilirubin in the blood due to a mutation in the gene that codes for UDP glucoronyltransferase, is often asymptomatic and episodes of jaundice are typically brought on by physiologic stress?

A

Gilbert’s syndrome

51
Q

What is Crigler Najjar syndrome? What is the difference between the 2 types?

A

Increased levels of unconjugated bilirubin in the blood due to mutation in the gene that codes for glucuronyltransferase

Type 1 = severe
Type 2 = less severe

52
Q

Form of brain damage caused by neural accumulation of unconjugated bilirubin, leading to permanent neurologic sequelae of bilirubin-induced neurologic dysfunction

A

Kernicterus

53
Q

Which type of crigler-najjar syndrome starts earlier in life, is associated with kernicterus, and does not respond to phenobarbitol?

A

Type 1

54
Q

Which type of Crigler Najjar starts later in life, has less than 20% function of UDP glucuronyltransferase, is less likely to develop kernicterus and can be treated with phenobarbitol?

A

Type 2

55
Q

Dubin Johnson syndrome is associated with ________ bilirubin in the serum without elevation of liver enzymes. This condition results from a mutation in _____ which affects the ability of hepatocytes to secrete conjugated bilirubin into bile. Another characteristic sign is _____ pigmentation in the liver

A

Conjugated; MRP2; black

56
Q

Rotor syndrome is associated with both unconjugated and conjugated bilirubin in the blood but the majority is ______, due to mutations in _____ and _______. It is similar to Dubin Johnson, except that ____ cells are not pigmented

A

Conjugated; OATP1B1; OATP1B3; liver

57
Q

What is the primary treatment in neonates with unconjugated hyperbilirubinemia? How does this work?

A

Phototherapy

Process of isomerization that changes trans bili to cis bili

58
Q

4 primary causes of gallstones

A
  1. Too much absorption of water from bile
  2. Too much absorption of bile acids from bile
  3. Too much cholesterol in bile
  4. Inflammation of epithelium
59
Q

Which of the following is the most common?

A. Small gallstones impacted in cystic duct; causing acute cholecystitis
B. Small stones intermittently blocking cystic duct; causing intermittent biliary pain
C. Large gallstones that stay in the gallbladder; usually asymptomatic
D. Small stones impacted in distal bile duct; causing jaundice, biliary type pain, and risk of cholangitis and pancreatitis
E. Cannot be determined

A

C. Large gallstones that stay in the gallbladder; usually asymptomatic

(Followed by B, A, then D]

60
Q

The liver modifies drugs or toxic substances through the “____ _____ metabolism”

A

First pass

61
Q

Liver enzymes can modify both drugs, endogenous, and exogenous toxins to render them water soluble, which allows the excretion of these substances through bile or urine

What are the 2 possible phases of metabolism?

A

Phase 1 = drugs are processed via cytochrome p450 enzymes

Phase 2 = conjugation with glucuronide, sulfate, amino acids, or glutathione for further detox of drug

62
Q

One type of LFT is liver enzymes tests, which are commonly measured in the serum. What are these tests and what might they indicate?

A

Serum aminotransferase (ALT and AST) - when elevated, indicates hepatocyte injury

Alkaline phosphatase - when elevated indicates cholestasis

63
Q

Abnormal serum levels of what compounds might indicate impaired hepatic synthetic function?

A

Bilirubin
Albumin
Prothrombin time

64
Q

Why is albumin used as a liver indicator?

A

Severe impairment in liver function/hepatocyte function reduces albumin levels (i.e., liver failure)

Albumin is exclusively synthesized in the liver and levels will fall with worsening cirrhosis

65
Q

What LFT reflects the degree of hepatic synthetic dysfunction based on its increase as the ability of cirrhotic liver to synthesize clotting factors diminishes?

A

Prothrombin time (PT)

[also known as INR]