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Semester 4 > Case 5 > Flashcards

Case 5 Flashcards

1
Q

Contents within bile

A

Bile salts, electrolytes, bile pigments (bilirubin), cholesterol and lipids

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2
Q

What structures are present at the periphery of sinusoids / hexagon lobule?

A

Hepatic arteriole, portal venule, bile duct, lymph vessel

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3
Q

What are sinusoids?

A

Wide diameter, porous membranes that radiate out to the corners of a hexagon lobule

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4
Q

What and where is the space of Disse?

A

Between hepatocytes and sinusoids, they have leaky membranes so nutrients/toxins is absorbed into the space of Disse where metabolic exchange between blood and hepatocytes take place

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5
Q

What happens to some of the blood drained into hepatocytes that doesn’t drain back into sinusoids?

A

They form the lymph and gets drained into lymph vessels

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6
Q

What secretes bile

A

Hepatocytes

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7
Q

Where are the endothelial cells and kupffer cells?

A

In the sinusoidal lining

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8
Q

Name a structural advantage hepatocytes have for absorption and secretion

A

Microvilli increase surface area for absorption and secretion

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9
Q

Features of periportal cells

A

Most active in bile salts uptake from blood, Secrete bile into bile canaliculi, Oxidative metabolism, gluconeogenesis , Glycogen deposition

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10
Q

Features of peri venous cells

A

Active in bio transformation reactions, Secrete toxic metabolites, Glycolytic & ketogenic reactions, Fat deposition

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11
Q

Canaliculi have Microvilli that project into the lumen

A

large SA for secretion

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12
Q

Bile is likely to be pumped towards the bile ducts. How can it do this?

A

Actin filaments in the canaliculi Microvilli and Actin and myosin in the cytoplasm around canaliculus can contract

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13
Q

Bile consists of 2 secretions. Where are they from?

A
  1. hepatocytes, 2. cells lining bole duct
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14
Q

Bile Secretions from duct cells are

A

Alkaline fluid rich in HCO3-, Secretion has Na+,K+, Cl-, HCO3-

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15
Q

What does hormone secretin do?

A

In response to acid in duodenum, secretin is secreted from duodenal walls. It controls the secretion of alkaline from bile duct cells and pancreatic juice form Brunner’s glands in duodenum

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16
Q

Bile secretion from hepatocytes contains

A

Bile acids, lecithin (phospholipid), cholesterol, albumin, IgA, conjugated bilirubin

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17
Q

Name the primary bile acids

A

Cholic acid and chenodeoxycholic acid

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18
Q

How do primary bile acids convert to secondary?

A

Primary bile acids get dehydrolysed by bacteria in intestines

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19
Q

Name the secondary bile acids

A

Lithocholic acid and deoxycholic acid

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20
Q

Bile acids are conjugated in the hepatocytes with which amino acids?

A

Glycine/taurine

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21
Q

Where are the conjugated bile acids absorbed?

A

Ileum

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22
Q

What does phase 1 of bio transformation of anions in the hepatocytes to conjugate metabolites and drugs consist of?

A

Makes molecule more POLAR by oxidation by mixed function oxygenate system in the ER. Most important enzyme - p450

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23
Q

What does phase 2 of bio transformation of anions in the hepatocytes to conjugate metabolites and drugs consist of?

A

Conjugation of anion that gives it a -ve charge, production of glucaronides catalysed by UDP-glucaronyl transferase

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24
Q

Small organic anion molecular mass less than _(a)___ Da are excreted by kidneys and bigger anions by __(b)__

A

(A) 500 Da, (B) bile

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25
Q

Name the carrier that allows the transport of bilirubin, sulphonamides, etc into the hepatocytes

A

Organic anion transporter (OATP) - has a Cl- antiport system

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26
Q

Name the carrier which allows the transport of conjugated bilirubin, glucaronides, conjugates of xenobiotics into bile

A

Canalicular multiorganic anion transporter (cMOAT) - MRP2

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27
Q

Name the carrier which allows the transport of hydrophobic, neutral compounds and organic cations into bile

A

P-transporters - mdr-3

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28
Q

Name the different types of jaundice

A

Prehepatic, intrahepatic, post hepatic

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29
Q

What level of plasma bilirubin is obviously jaundice

A

> 34 umol/L

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30
Q

Prehaeptic jaundice: causes, diseases, type of bilirubin present

A

Causes: excess haemolysis of RBCs –> formation of bilirubin exceed capacity of liver to excrete it, Diseases: haemolytic anaemia, Bilirubin: unconjugated

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31
Q

Intrahepatic jaundice: causes, diseases, type of bilirubin present

A

Causes: hyperbilirubinaemia due to decreased uptake of bilirubin into hepatocytes, defective intracellular protein binding or conjugation, disturbed secretion into bile canaliculi, Diseases: acute hepatitis, Bilirubin: unconjugated or conjugated or mixed (depends where the defect is)

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32
Q

Posthepatic jaundice: causes, diseases, type of bilirubin present

A

Causes: blockage of intrahepatic or extra hepatic bile ducts causes jaundice as the bile is refluxed into blood, Diseases: gall stones, Bilirubin: conjugated

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33
Q

How many ATP molecules are produced by the glycolysis of 1 glucose molecule?

A

2

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34
Q

Product of glycolysis in aerobic conditions

A

Pyruvate

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35
Q

Product of glycolysis in anaerobic conditions

A

Lactate

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36
Q

Lactate form skeletal muscle can be reoxidised to pyruvate. What is the name of this liver-muscle cycle?

A

Cori cycle

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37
Q

Products of triacylglycerol metabolism

A

Glycerol and fatty acids

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38
Q

Product of amino acid metabolism

A

Alpha-ketoacids e.g. Oxaloacetate

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39
Q

Which hormone is the main regulator of gluconeogenesis?

A

Glucagon

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40
Q

Where does glycolysis typically take place within mammalian cells?

A

Cytosol

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41
Q

Ammonia produced from protein catabolism is converted to a less toxic substance by

A

Urea cycle

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42
Q

Which amino acid plays a central role in nitrogen flow and disposal of excess waste nitrogen in mammals?

A

Glutamate

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43
Q

Conversion of ammonia to a less toxic substance primarily takes place in

A

Hepatocytes of the liver

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44
Q

Where in the mammalian cell does the citric acid cycle (kerbs cycle) take place?

A

Mitochondria

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45
Q

What does the citric acid cycle do?

A

Full oxidation of acetyl-CoA to 2 CO2

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46
Q

Upon oxidation in the mitochondrial electron transport chain, how many ATP molecules are produced for every glucose molecule?

A

38

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47
Q

In peripheral tissues, excess ammonia is converted to ____ and transported to liver

A

Glutamine

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48
Q

Glutamine –(a)–> glutamate –(b)–> a-ketoglutarate

A

(A) glutaminase

(B) glutamate dehydrogenase

49
Q

In the liver, two molecules of NH3 can be released from glutamine by the above metabolism of glutamine

A

…

50
Q

Ammonia van be transferred to oxaloacetate by

A

aspartate transaminase (AST)

51
Q

Resulting aspartate feeds into which cycle?

A

Urea cycle

52
Q

Alanine from muscle delivers NH3 to liver via

A

ALT (alanine transaminase)

53
Q

Resulting pyruvate goes into gluconeogenesis,

Glucose returned to muscle

A

…

54
Q

NADPH is necessary to make fatty acids

A

…

55
Q

During prolonged fasting, ketone bodies are formed in the liver as emergency fuel

A

…

56
Q

Which hepatitis viruses are acute?

A

HAV, HEV

57
Q

Which hepatitis viruses are chronic?

A

HBV, HCV

58
Q

Which HV is the only one with DNA as its nucleic acid rather than RNA?

A

HBV

59
Q

Transmission route of HAV

A

Faecal/oral

60
Q

Transmission route of HBV

A

Parenteral (IV)/sexual/vertical (mother to baby)

61
Q

Transmission route of HCV

A

Parenteral /(sexual)

62
Q

Transmission route of HDV

A

Parenteral/sexual

63
Q

Transmission route of HEV

A

Faecal/oral

64
Q

Chronic hepatitis–> cirrhosis –> hepatocellular carcinoma

A

…

65
Q

Pathogenesis of hepatitis

A

Hepatitis viruses noncytopathic (not degenerative) Hepatocyte damage immune-mediated antigen recognition by CTLs - apoptosis
chemokine driven recruitment of Ag-nonspecific cells

66
Q

Symptoms of viral hepatitis

A

•jaundice (icterus) •itching •right upper quadrant pain •fatigue •(rash)

67
Q

When does Alkaline phosphatase rise?

A

In cholestasis

68
Q

ALT and AST are raised in

A

Acute hepatic injury

69
Q

ASymptomatic and anicteric (no jaundice) in which hepatitis viruses?

A

HAV & HBV in children, and HCV

70
Q

Hep A prevalence

A

High prevalence: Africa, Asia, Central & S. America

Most children infected early -Rarely symptomatic

71
Q

HAV risk factors

A

Travel to endemic areas -Household contact

-Contaminated food •Salads •Berries •Tomatoes - sundried -Sex risk - especially male homosexuals -Intravenous drug users

72
Q

Incubation period of HAV

A

2-6 wks

73
Q

Which of the hep viruses are the most common cause of hepatitis worldwide

A

HEV

74
Q

HEV

A

Incubation period - 15-60 days
High death rate in pregnant women (15-25%)
High prevalence in India, Pakistan, Nepal, China, Central Asia Mexico

75
Q

HBV replication cycle key steps

A
  1. Generation of HBV ccc DNA from genomic DNA and its subsequent processing by host enzymes to produce viral RNA;
  2. Reverse transcription of the pregenomic (pg) RNA within the viral nucleocapsid to form HBV DNA
76
Q

What is HBsAg in serum suggestive of?

A

Current infection (acute or chronic)

77
Q

anti-HBs+ and anti-HBc+

A

Past infection

78
Q

Anti-HBc+

A

Infection at sometime (current or past)

79
Q

Acute HBV infection

A

HBsAg + and anti-HBc IgM +

80
Q

How infectious the patient is to their contacts

A

positive for e antigen (HBeAg) and/or high levels of HBV DNA

81
Q

Whether the person is immune to hepatitis B

A

Usually indicated by being positive for antibody to HBsAg (anti-HBs). If not known, or low levels, complete vaccination course.

82
Q

Markers in a HBV carrier with low infectivity

A

Anti-HBc, HBsAg, anti-HBe

83
Q

Markers in a HBV carrier with high infectivity

A

Anti-HBc, HBsAg, HBeAg

84
Q

Markers in a recovered HBV patient

A

Anti-HBc, anti-HBs, ~anti-HBe

85
Q

Markers in an immune person after vaccination

A

Anti-HBs

86
Q

What are the 4 phases of chronic HBV

A

Immune tolerance
Immune clearance
Low replication inactive carrier
Reactivation

87
Q

Which hep virus requires presence of HBV to occur?

A

HDV

88
Q

2 forms of HDV infection

A

Coinfection with HBV -HDV acquired at same time as HBV
- increase in fulminant hepatitis (acute liver failure)

Superinfection- HDV acquired by hepatitis B carrier

  • high risk of progression to cirrhosis (70%)
  • high risk of hepatocellular carcinoma (16%)
89
Q

Incubation period of HDV

A

Average 6-7 weeks

Range 2-26 weeks

90
Q

HCV PCR

A

Appears early,
Marker of infectivity and active infection
Monitor HCV RNA viral load for treatment response

91
Q

HCV antibody

A

Total antibody
Slow response: 8-12 weeks
No IgM assay

92
Q

Cholangiocytes

A

Epithelial cells of bile duct - secrete 30-50% of hepatic bile, rich in HCO3-

93
Q

Bile secretion by cholngiocytes is stimulated by which hormones?

A

Glucagon, secretin, VIP

94
Q

Bile secretion by cholngiocytes is inhibited by which hormone?

A

Somatostatin

95
Q

Brussel sprouts ____ metabolism

A

increases

96
Q

Grape fruit _____ metabolism

A

decreases

97
Q

How does pregnancy affect drug metabolism?

A

⬆️ hepatic metabolism

98
Q

CYP polymorphisms: inheritance of a poor metaboliser

A

Homozygous for defective gene

99
Q

CYP polymorphisms: inheritance of an intermediate metaboliser

A

Heterozygous for defective gene

100
Q

CYP polymorphisms: inheritance of an extensive metaboliser

A

Homozygous for functional gene

101
Q

CYP polymorphisms: inheritance of an ultra-rapid metaboliser

A

Extra copies of functional gene

102
Q

Which enzyme converts alcohol to acetaldehyde

A

Alcohol dehydrogenase

103
Q

Which enzyme converts acetaldehyde to acetate

A

Aldehyde dehydrogenase

104
Q

Acetaldehyde is converted ton CO2 and excreted in citric acid cycle. Which cytochrome is involved?

A

Cytochrome P4502E1

105
Q

What is ALP

A

Alkaline phosphatase

106
Q

High ALP suggests

A

Obstructive jaundice

107
Q

High transaminases and GGT (gamma-glutamyl transferase) suggest

A

Hepatocellular jaundice

108
Q

What causes pruritus (itching) and how can it be treated?

A

Bilirubin buildup - by antihistamines

109
Q

Characteristic sign of acute liver failure

A

Encephalopathy

110
Q

What is the commonest cause of acute liver failure in UK

A

Paracetamol overdose

111
Q

What is the commonest cause of acute liver failure worldwide

A

Viral hepatitis

112
Q

How many grades of encephalopathy

A

I - IV

113
Q

Lamivudine

A

Treatment for hep B, a reverse transcription inhibitor that reduces viral load and serum ALT

114
Q

Adefovir

A

Treatment for hep B Pts with lamivudine resistance

115
Q

How many ATP produced in glycolysis?

A

2

116
Q

How many ATP produced in link reaction

A

0

117
Q

How many ATP produced in krebs cycle

A

2

118
Q

How many ATP produced in electron transport chain

A

34

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