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PHAR 123 > Liver and Biliary System > Flashcards

Liver and Biliary System Flashcards

1
Q

What structures does the portal triad encapsulate? PBH

A

Portal Vein
Bile Duct
Hepatic Artery

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2
Q

What are the functions of the liver? (6)

A

Metabolism
Bile Production
Cholesterol Metabolism
Glucose storage
Iron Storage
Production of clotting factors, serum proteins, fat soluble vitamins, and proteins

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3
Q

What is the goal of the liver when it encounters drugs?

A

Elimination of foreign substances

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4
Q

What is the difference between phase 1 and phase 2 metabolism?

A

Phase 1 is the activation, while phase II is the conjugation, goal is to go from lipophilic to water solube

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5
Q

What is the function of Bile?

A

Digestion of fats in the duedenum,

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6
Q

What is Bile composed of? (3)

A

Acids, salts, phospholipids/surfactants (main ones)

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7
Q

How much bile does the liver excrete every day?

A

500-1000ml

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8
Q

What is the function of the gallbladder?

A

Used as a storage site for bile in the event the stomach needs more

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9
Q

What are the steps to normal Bilirubin metabolism (9)

A
  1. Hemoglobin release and breakdown (spleen, bone marrow)
  2. Heme enzymatically converted to bilirubin.
  3. Bilirubin enters the liver through the circulation
  4. Hepatocytes add additional functional groups to bilirubin to increase its solubility and excretion
  5. Most of the conjugated bilirubin is then excreted in the bile.
  6. Bile enters the GI tract
  7. A small fraction of the bilirubin is
    reabsorbed and sent back to the liver
  8. Most of the bilirubin (~90%) is excreted in
    the feces after being enzymatically
    reduced by colon bacteria.
  9. The break down products contribute to
    fecal colour.

Blood –> Heme –> Bilirubin –> Bile –> GI Tract –> limited reabsorption if bilirubin –> Bile is excreeted

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10
Q

What are the risk factors for liver disease?

A

Obesity/Diabetes
Exposure to chemcials/toxins
Alcohol abuse
Family history
Hep B/C

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11
Q

What are the symptoms of liver disease

A

Nausea, vomiting or loss of appetite
Abdominal swelling (ascites) or tenderness in the area of the liver
Chronic fatigue
Itchy skin (pruritus) *Dark coloured urine *Pale stool
Dementia-like confusion (if hepatic encephalopathy is present)
Ascites

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12
Q

How does Jaundice occur?

A

This is due to the livers inability to transform unconjugated bilirubin to the conjugated form, This free bilirubin escapes to the blood causing yellow colour.

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13
Q

What is Cirrhosis?

A

liver becomes fibrotic after some severe chronic injury, such that the liver becomes nodular with regenerating hepatocytes surrounded by scar tissue

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14
Q

What is NAFLD

A

Non-alcoholic fatty liver disease, which is associated with hypertension, diabetes, dyslipidemia,

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15
Q

Is NAFLD reversible? How?

A

Yes, weight loss and exercise

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16
Q

What is the main cause of posthepatic Jaundice Obstruction?

A

Intrahepatic cholestasis (bile not moving out of the liver through the ducts)

Extrahepatic obstruction of the biliary tract, which prevents bilirubin from moving into the intestines.

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17
Q

What is Intrahepatic cholestasis

A

bile not moving out of the liver through the ducts

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18
Q

What can Intrahepatic cholestasis caused by?

A

functional impairment of the hepatocytes in the secretion of bile and/or due to an obstruction at any level of the excretory pathway of bile.

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19
Q

What can Cholestatic jaundice be classified into?

A

Intrahepatic or extrahepatic cholestasis

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20
Q

What does cholestasis lead to?

A

Retention of the constituents of bile in the blood

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21
Q

Hepatocellular Causes (With respect to intrahepatic cholestasis)

A

Viral hepatitis, acute alcoholic hepatitis, parenteral nutrition

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22
Q

Canalicular Membrane Changes (With respect to intrahepatic cholestasis)

A

Drugs:oral contraceptives, antibiotics, antithyroid drugs, sulphonamides; cholestasis in pregnancy

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23
Q

Canalicular/Ductular Luminal Obstruction: (With respect to intrahepatic cholestasis)

A

Cholestasis due to sickle cell disease, bacterial infections, sepsis, cystic fibrosis

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24
Q

Ductopenia (With respect to intrahepatic cholestasis)

A

Familial, drug- induced, chronic allograft rejection, Hodgkin disease, sarcoidosis, primary sclerosing cholangitis, primary biliary cholangitis

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25
Q

How is intrahepatic cholestasis treated?

A

Surgical, but also symptom based

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26
Q

How is pruritis managed?

A

Cholestyramine (reduces cholesterol)

ursodeoxycholic acid in some cases, antihistamines (sleep), phenobarbitone or naloxone (investigational)

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27
Q

How are pigmentary stones formed? Cholelithiasis

A

Solubility of the cholesterol or bile pigments is exceeded in the bile

A nidus of precipitated salts forms

More precipitate is added and the “stone” grows larger

Symptoms only when they cause obstruction, irritation or infection results

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28
Q

What is Ursodiol?

A

Most common drug used. It solubilizes cholesterol in micelles and acts by dispersing cholesterol in aqueous media.

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29
Q

What are some complications of gallstones

A

Obstruction at the biliary cirrhosis or obstruction near the pancreas head

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30
Q

What are the main causes of Cirrhosis of the liver?

A

Hep B C D, NAFLD, Alcohol

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31
Q

Describe the things that can lead to liver failure? (5)

A

Liver cellular damage, Fibrosis, nodule formation, impaired blood flow, bile obstruction

32
Q

What is the leading cause of non-alcoholic fatty liver disease?

A

Obesity, Diabetes

33
Q

What is the treatment that is involved in treating cirrhosis?

A

Weight reduction, blood lipid management

34
Q

What are the stages of alcoholic liver disease?

A

Fatty Liver
Alcoholic hepatitis
Alcoholic Cirrhosis

35
Q

Disease progression of alcoholic hepatitis can be attributed?

A
  • lipid peroxidation
  • dysregulated lipid metabolism
  • acetaldehyde protein adduct formation
  • disruption of cytoskeletal and membrane function
36
Q

What occurs due to the inability of lipoprotein transport to occur?

A

Lipid Vacuoles form and develop

37
Q

How does liver dysfunction disrupt other parts of the body?

A

Edema, Muscle wasting, collateral veins, jaundice, hair thinning

38
Q

What are some systemic complications due to cirrhosis? (5)

A

Reduced clotting factor formation
Hematemesis and

Hepatic Encephalopathy
Hepatorenal syndrome
Steroid hormones deficiencies
Hematemesis and exsanguination

39
Q

What is Hematemesis?

A

Internal bleeding

40
Q

what is exsanguination?

A

Process of draining

41
Q

What are the liver function tests we focused on?

A

AST and ALT

42
Q

What are some other Liver function tests other then AST/ALT we test for? (3)

A

Albumin, Bilirubin, and prothrombin time

43
Q

What factors cause elevated AST or ALT values?

A

Autoimmune hepaptitis
Hep B/C
Drugs
Ethanol
Fatty liver
Growths
Hemodynamic disorders
Iron deficiency
Muscle injury

44
Q

Hepatocellular carcinoma is what?

A

tumor that is relatively uncommon in North America, although its incidence is rising, principally in relation to the spread of hepatitis C infection.

45
Q

What are the two types of benign liver tumors discussed?

A
  • Hemangioma
  • Hepatocellular adenoma
46
Q

What is intrahepatic Cholestasis?

A

Inability of the hepatic cells to not excrete bile. Can happen within the liver or biliary pathway

47
Q

What is the treatment for non-alcholic fatty liver disease?

A

Weight reduciton/Dietary improvement, blood lipid management

48
Q

What do reactive oxygen species do?

A

They can generate free radicals that react with membranes and proteins in the liver

49
Q

What does alcohol interfere with?

A

It is a hepatotoxin that interferes with mitochondrial and microsomal function in hepatocytes, leading to an accumulation of lipids in the liver

50
Q

What is ALT?

A

alanine aminotransferase, can be indicative of acute injury to the liver

51
Q

What is AST?

A

Aspartate aminotransferase, high value could mean acute liver injury

52
Q

What is the biggest risk factor of hepatocellular carcinoma?

A

Hep B/Hep C

53
Q

What is the definition of drug-induced liver injury?

A

Hepatic inflammation, necrosis or jaundice due to exposures to a medication or toxin

54
Q

Medications can cause DILI at what types of doses?

A

Therapeutic doses and overdose

55
Q

What is idiosyncratic drug metabolism/

A

Where normal therapeutic doses cause liver damage

56
Q

What are the 3 major drug classes that cause liver disease?

A

Antimicrobials,
Herbal and dietary supplements
Cardiovascular agents

57
Q

What is the #1 cause of acute liver failure?

A

Drugs

58
Q

What is the signs of DILI?

A

Wide range

Asymptomatic to liver enzymes elevation to liver failure

59
Q

What is Zonal hepatocellular necrosis?

A

This could be indicative of a DILI because the drug has caused necrosis around the central vein located near the middle of the liver lobule

60
Q

What is macro/microsteatosis?

A

Accumulation of fat droplets in the liver

Micro is most serious as it is associated with Reyes syndrome in children!

61
Q

What is the normal range of ALT?

A

12-37U/L

62
Q

What are ALT?

A

Found mainly in hepatocyte cytosol, and is more liver specific

63
Q

What is the normal range of AST

A

15-65

64
Q

What are AST?

A

Found in hepatocyte mitochondria, and will be more elevated then ALT during chronic alcohol use and cirrohisis

65
Q

What is total protein and albumin?

A

Major proteins produced by the liver

66
Q

What is the significance on Oncotic pressure?

A

Oncotic pressure draws fluids into the blood stream

67
Q

What is globulin?

A

Help with immune response

68
Q

What is direct bilirubin?

A

This is conjugated and water-soluble, a sign of normal funciton

69
Q

What is indirect bilirubin

A

This is an indirect measurement taken from total-direct and it can indicate whether hepatic function has decreased

70
Q

Is increased or decreased bilirubin an indicator for liver injury?

A

increased

71
Q

What does a prothrombin time tell us?

A

How long it takes the blood to clot

72
Q

GGT can also be elevated with

A

Alcohol toxicity

73
Q

Which zone does acetaminophen affect first?

A

closest to the central vein, Zone 3 or pericentral cells

74
Q

What is cholestasis?

A

marked reduction bile flow and secretion

75
Q

What is Cholelithiasis?

A

Gallstones

76
Q

What is cholecystitis?

A

Infection of ulcers

PHAR 123 (11 decks)

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