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Semester 4 > Case 5 > Flashcards

Case 5 Flashcards

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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
Name the carrier that allows the transport of bilirubin, sulphonamides, etc into the hepatocytes
Organic anion transporter (OATP) - has a Cl- antiport system
26
Name the carrier which allows the transport of conjugated bilirubin, glucaronides, conjugates of xenobiotics into bile
Canalicular multiorganic anion transporter (cMOAT) - MRP2
27
Name the carrier which allows the transport of hydrophobic, neutral compounds and organic cations into bile
P-transporters - mdr-3
28
Name the different types of jaundice
Prehepatic, intrahepatic, post hepatic
29
What level of plasma bilirubin is obviously jaundice
>34 umol/L
30
Prehaeptic jaundice: causes, diseases, type of bilirubin present
Causes: excess haemolysis of RBCs --> formation of bilirubin exceed capacity of liver to excrete it, Diseases: haemolytic anaemia, Bilirubin: unconjugated
31
Intrahepatic jaundice: causes, diseases, type of bilirubin present
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)
32
Posthepatic jaundice: causes, diseases, type of bilirubin present
Causes: blockage of intrahepatic or extra hepatic bile ducts causes jaundice as the bile is refluxed into blood, Diseases: gall stones, Bilirubin: conjugated
33
How many ATP molecules are produced by the glycolysis of 1 glucose molecule?
2
34
Product of glycolysis in aerobic conditions
Pyruvate
35
Product of glycolysis in anaerobic conditions
Lactate
36
Lactate form skeletal muscle can be reoxidised to pyruvate. What is the name of this liver-muscle cycle?
Cori cycle
37
Products of triacylglycerol metabolism
Glycerol and fatty acids
38
Product of amino acid metabolism
Alpha-ketoacids e.g. Oxaloacetate
39
Which hormone is the main regulator of gluconeogenesis?
Glucagon
40
Where does glycolysis typically take place within mammalian cells?
Cytosol
41
Ammonia produced from protein catabolism is converted to a less toxic substance by
Urea cycle
42
Which amino acid plays a central role in nitrogen flow and disposal of excess waste nitrogen in mammals?
Glutamate
43
Conversion of ammonia to a less toxic substance primarily takes place in
Hepatocytes of the liver
44
Where in the mammalian cell does the citric acid cycle (kerbs cycle) take place?
Mitochondria
45
What does the citric acid cycle do?
Full oxidation of acetyl-CoA to 2 CO2
46
Upon oxidation in the mitochondrial electron transport chain, how many ATP molecules are produced for every glucose molecule?
38
47
In peripheral tissues, excess ammonia is converted to ____ and transported to liver
Glutamine
48
Glutamine --(a)--> glutamate --(b)--> a-ketoglutarate
(A) glutaminase | (B) glutamate dehydrogenase
49
In the liver, two molecules of NH3 can be released from glutamine by the above metabolism of glutamine
...
50
Ammonia van be transferred to oxaloacetate by
aspartate transaminase (AST)
51
Resulting aspartate feeds into which cycle?
Urea cycle
52
Alanine from muscle delivers NH3 to liver via
ALT (alanine transaminase)
53
Resulting pyruvate goes into gluconeogenesis, | Glucose returned to muscle
...
54
NADPH is necessary to make fatty acids
...
55
During prolonged fasting, ketone bodies are formed in the liver as emergency fuel
...
56
Which hepatitis viruses are acute?
HAV, HEV
57
Which hepatitis viruses are chronic?
HBV, HCV
58
Which HV is the only one with DNA as its nucleic acid rather than RNA?
HBV
59
Transmission route of HAV
Faecal/oral
60
Transmission route of HBV
Parenteral (IV)/sexual/vertical (mother to baby)
61
Transmission route of HCV
Parenteral /(sexual)
62
Transmission route of HDV
Parenteral/sexual
63
Transmission route of HEV
Faecal/oral
64
Chronic hepatitis--> cirrhosis --> hepatocellular carcinoma
...
65
Pathogenesis of hepatitis
Hepatitis viruses noncytopathic (not degenerative) Hepatocyte damage immune-mediated antigen recognition by CTLs - apoptosis chemokine driven recruitment of Ag-nonspecific cells
66
Symptoms of viral hepatitis
•jaundice (icterus) •itching •right upper quadrant pain •fatigue •(rash)
67
When does Alkaline phosphatase rise?
In cholestasis
68
ALT and AST are raised in
Acute hepatic injury
69
ASymptomatic and anicteric (no jaundice) in which hepatitis viruses?
HAV & HBV in children, and HCV
70
Hep A prevalence
High prevalence: Africa, Asia, Central & S. America | Most children infected early -Rarely symptomatic
71
HAV risk factors
Travel to endemic areas -Household contact | -Contaminated food •Salads •Berries •Tomatoes - sundried -Sex risk - especially male homosexuals -Intravenous drug users
72
Incubation period of HAV
2-6 wks
73
Which of the hep viruses are the most common cause of hepatitis worldwide
HEV
74
HEV
Incubation period - 15-60 days High death rate in pregnant women (15-25%) High prevalence in India, Pakistan, Nepal, China, Central Asia Mexico
75
HBV replication cycle key steps
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
What is HBsAg in serum suggestive of?
Current infection (acute or chronic)
77
anti-HBs+ and anti-HBc+
Past infection
78
Anti-HBc+
Infection at sometime (current or past)
79
Acute HBV infection
HBsAg + and anti-HBc IgM +
80
How infectious the patient is to their contacts
positive for e antigen (HBeAg) and/or high levels of HBV DNA
81
Whether the person is immune to hepatitis B
Usually indicated by being positive for antibody to HBsAg (anti-HBs). If not known, or low levels, complete vaccination course.
82
Markers in a HBV carrier with low infectivity
Anti-HBc, HBsAg, anti-HBe
83
Markers in a HBV carrier with high infectivity
Anti-HBc, HBsAg, HBeAg
84
Markers in a recovered HBV patient
Anti-HBc, anti-HBs, ~anti-HBe
85
Markers in an immune person after vaccination
Anti-HBs
86
What are the 4 phases of chronic HBV
Immune tolerance Immune clearance Low replication inactive carrier Reactivation
87
Which hep virus requires presence of HBV to occur?
HDV
88
2 forms of HDV infection
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
Incubation period of HDV
Average 6-7 weeks | Range 2-26 weeks
90
HCV PCR
Appears early, Marker of infectivity and active infection Monitor HCV RNA viral load for treatment response
91
HCV antibody
Total antibody Slow response: 8-12 weeks No IgM assay
92
Cholangiocytes
Epithelial cells of bile duct - secrete 30-50% of hepatic bile, rich in HCO3-
93
Bile secretion by cholngiocytes is stimulated by which hormones?
Glucagon, secretin, VIP
94
Bile secretion by cholngiocytes is inhibited by which hormone?
Somatostatin
95
Brussel sprouts ____ metabolism
increases
96
Grape fruit _____ metabolism
decreases
97
How does pregnancy affect drug metabolism?
⬆️ hepatic metabolism
98
CYP polymorphisms: inheritance of a poor metaboliser
Homozygous for defective gene
99
CYP polymorphisms: inheritance of an intermediate metaboliser
Heterozygous for defective gene
100
CYP polymorphisms: inheritance of an extensive metaboliser
Homozygous for functional gene
101
CYP polymorphisms: inheritance of an ultra-rapid metaboliser
Extra copies of functional gene
102
Which enzyme converts alcohol to acetaldehyde
Alcohol dehydrogenase
103
Which enzyme converts acetaldehyde to acetate
Aldehyde dehydrogenase
104
Acetaldehyde is converted ton CO2 and excreted in citric acid cycle. Which cytochrome is involved?
Cytochrome P4502E1
105
What is ALP
Alkaline phosphatase
106
High ALP suggests
Obstructive jaundice
107
High transaminases and GGT (gamma-glutamyl transferase) suggest
Hepatocellular jaundice
108
What causes pruritus (itching) and how can it be treated?
Bilirubin buildup - by antihistamines
109
Characteristic sign of acute liver failure
Encephalopathy
110
What is the commonest cause of acute liver failure in UK
Paracetamol overdose
111
What is the commonest cause of acute liver failure worldwide
Viral hepatitis
112
How many grades of encephalopathy
I - IV
113
Lamivudine
Treatment for hep B, a reverse transcription inhibitor that reduces viral load and serum ALT
114
Adefovir
Treatment for hep B Pts with lamivudine resistance
115
How many ATP produced in glycolysis?
2
116
How many ATP produced in link reaction
0
117
How many ATP produced in krebs cycle
2
118
How many ATP produced in electron transport chain
34

Semester 4 (5 decks)

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