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NnD > Liver and LFTs > Flashcards

Liver and LFTs Flashcards

1
Q

What are the two blood supplies of liver

A

portal vein and hepatic arter
75% portal vein

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2
Q

Where is bile formed from and what is its passage out of the liver

A

Bile is formed from the hepatocytes, flows through bile canaliculi to bile duct (⇒ flow is opposite to blood)

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3
Q

Where does blood in central veins go to

A

Blood collected in central veins goes to sublobular veins, then to collecting veins, and then hepatic veins leaving the liver

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4
Q

What maintain pressure within common bile duct

A

Ampulla of vater/ sphincter body
Pressure there should usually be higher than that of gallbladder

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5
Q

What causes gallbladder contraction (what hormone is involved)

A

Cholecystokinin release from mucosa in duodenum during feeding causes gallbladder contraction, reduced sphincter pressure on bile and allows bile to flow from gall bladder to duodenum

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6
Q

What are cholangiocytes

A

Bile duct epethelia, contribute to cell function

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7
Q

What forms the sieve plate in liver

A

Endothelial cells

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8
Q

Sinusoidal vs lateral faces in hepatocytes

A
  • Microvilli are present on sinusoidal face to project sparsely into bile canaliculi
  • A portion of the lateral faces of hepatocytes is modified to form bile canaliculi
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9
Q

Where are glycogen granules stored in hepatocytes

A

In association with SER

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10
Q

Difference between periportal and perivenous/pericentral zone in liver acinus

A

Periportal has good o2 supply and nutrient rich, involved in gluconeogenesis, glycogenolysis and bile salt formation, perivenous involved in glycolysis, lipolysis, glucuronidation, glycogenesis and cytochrome p450 reaction. Low in nutrients and relatively hypoxic

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11
Q

Three phases of biotransformation

A

I - oxidation, reduction and hydrolysis by CYP450
II- Conjuation in cytoplasm with endogenous substances like glucuronic acid to form inactive conjugates
III- secretion into bile, excretion mediated by ATP

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12
Q

What can conjugate with drugs in phase II metabolism

A

Gluthatione for oxidated species
or sulfur, acetyl or glucuronide for hydrolysed species

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13
Q

Glutathione conjugation in paracetamol metabolism??

A

Bonds with NAPQI to form non-toxic conjugates

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14
Q

What does N-acetyl cysteine do

A

Increases Glutathione to mop up NAPQI

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15
Q

What causes alcohol flush response

A

Deficiency in ALDH-2 ( Aldehyde dehydrogenase) that results in increased acetylaldehyde and catecholamine release

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16
Q

What happens to insulin and glucagon after feeding and main actions in liver

A

Increased insulin and decreased glucagon
- Hepatic glucose uptake
- Glycogen deposition in hepatocytes
- Glucose converted into glycerol and fatty acids

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17
Q

What happens to insulin and glucagon in fasting and main actions in liver

A

Reduced insulin and increased glucagon
- Glycogen breakdown in periportal hepatocytes
- Gluconeogenesis from lactate, pyruvate, AA, glycerol

18
Q

Synthesis of lipids in liver

A

Liver also synthesizes VLDL and HDL
Also synthesises cholesterol and phospholipids, some of which is secreted into bile and some is converted into bile acids

19
Q

What transport proteins are synthesised in liver

A

ceruloplasmin to transport copper and transferrin which transports iron

20
Q

Which enzymes synthesized in liver require vitamin K

A

II, VII, IX, X are post-translational modified by Vitamin K dependent enzymes ⇒ synthesis impaired by VItamin K deficiency

21
Q

How is unconjugated bilirubin formed

A

from breakdown of heme in spleen

22
Q

Where does bilirubin get conjugated and by what

A

By glucuronyl billirubin transferase in liver

23
Q

What does direct bilirubin get converted to and where

A

To urobilinogen in duodenum by microbiome, then to stercobilin

24
Q

What vitamins stored in large amounts in liver

A

A, D, B12

25
Q

What does an isolated rise in bilirubin suggest
What does rise suggest

A

Gilbert’s syndrome ⇒ problems with processing of bilirubin
Haemolysis
Rise - Biliary problems

26
Q

What is prothrombin time an indicator of

A

Synthetic function

27
Q

How is PT in ALF and cirrhosis

A

usually very good, also rarely abnormal in cirrhosis

28
Q

PT in paracetamol overdose

A

Very high, 100 instead of 10 or 12

29
Q

What do ALT and AST show

A

Increases when hepatocytes die ⇒ Leak out and give indication of how many died the previous day

30
Q

ALT in Hep C vs NAFLD

A

150 in Hep C vs75-100 in NAFLD

31
Q

Is ALT or AST usually higher and what does the ratio so

A
  • ALT usually higher than AST
    • In ALD, AST is higher
    • In NAFLD, AST goes up relative to ALT due to mitochondrial dysfunction as a result of scarring ( as AST leaks from Mito.)
      • Indicator of advancing fibrosis
32
Q

What does high Alkaline Phosphatase mean

A

Need to chek GGT if ALP is high, to see if ALP is from liver, if it is, suggests irritation of bile ducts => assess cholestasis ) stoppage of bile flow)

Biliary disease eg. stones, pancreatic cancer , PBC (Cholestatic LFTs, liver biopsy with granulomas, +ve AMA)

33
Q

What does high GGT suggest

A
  • Increases by induction,not damage
    • i.e. Enzyme induction by drugs
      • Alcohol, phenytoin, carbamazipine
    • Obesity, NAFLD cirrhosis
34
Q

What can affect albumin levels

A

Dehydration raises it, dilution or reduced synthesis reduces it . Can be low in pregnancy due to increased volume in circulation

35
Q

When are albumin levels often low in liver disease and why

A
  • In liver disease, retains salt and water and also dilutes albumin down.
    • Often normal in cirrhosis until liver is failing
36
Q

Mild ALT vs high ALT

A

Mild ALT
- NASH ⇒ Inflammation and scarring, cirrhosis
- AFLD ⇒ Fatty liver (umbrella term)
- HepC
- ALD, including ALcoholic Hep
High ALT⇒ Hepatitis including drug damage
- Inflammation of liver

37
Q

What does isolated high GGT suggest

A

Usually high GGT suggests alcoholism or drugs, or inactive cirrhosis (NAFLD)

38
Q

Serum markers of liver function include?

A

ALbumin, Pt, Bilirubin

39
Q

does space of disse have a basal lamina

A

no

40
Q

Is bilirubin high in cirrhosis

A

yes

41
Q

What vitamins and minerals are stored in the liver

A
  • Vit- A, D, B12, some K
  • Folate
  • Metabolises Vit D3 to 25-OH…
  • Iron in ferritin and haemosiderin
  • copper

NnD (10 decks)

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