physiology and pharmacology of the liver Flashcards

1
Q

what are the metabolic functions of the liver

A

carbohydrate metabolism

fat metabolism

protein metabolism

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2
Q

what comprises of carbohydrate metabolism

A

*is hormonally regulated
>gluconeogenesis - to produce glucose from amino acids
>glycolysis - to form pyruvate thence lactate or ACh
>glycogenesis - to store polymerised glucose as glycogen
>glycogenolysis - to release glucose

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3
Q

what does fat metabolism consist of

A

processing of chylomicron remnants
synthesis of lipoproteins and cholesterol
ketogenesis (in starvation)

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4
Q

what does protein metabolism consist of

A

synthesis of plasma proteins
transamination and deamination of amino acids
conversion of ammonia to urea

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5
Q

what hormones are deactivated by the liver

A

insulin
glucagon
anti-diuretic hormone (vasopressin)
steroid hormone

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6
Q

what hormones are activated by the liver

A

conversion of thyroid hormone

conversion of vitamin D to 25-hydroxyvitamin D2

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7
Q

what are the major functions of the liver

A

storage
synthesis of proteins
protection
detoxification

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8
Q

what does the liver store

A
  • fat soluble vitamins A D E K in hepatocytes
  • water soluble vitamin B12
  • iron, copper
  • glycogen
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9
Q

what proteins does the liver synthesise for export

A
  • coagulation factors II VII IX and X
  • proteins C and S
  • albumin
  • complement proteins
  • apolipoproteins
  • carrier proteins
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10
Q

what is the role of Kupffer cells

A

> they are liver phagocytes that digest particulate matter and old erythrocytes

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11
Q

other than Kupffer cells what the protective function does the liver confer

A

the production of immune factors

-host defence proteins

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12
Q

how is the liver involved in detoxification

A

> it has many endogenous substances ie bilirubin as a metabolite of haemoglobin breakdown
and has many exogenous substances ie xenobiotics (drugs and alcohol)

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13
Q

what is bile

A

it participates in the digestion and absorption of fats and the excretion of products of metabolism
>produced continuously by hepatocytes and bile duct cells

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14
Q

secretion of bile with regards to food intake

A

> between meals bile is stored and concentrated in the gall bladder as the sphincter of Oddi is closed
during a meal chyme in the duodenum stimulates gall bladder smooth muscle to contract (via CCK and vagal impulses)
-the sphincter of Oddi opens via CCK
-bile spurts into the duodenum via cystic and common bile ducts

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15
Q

what does neutral / slightly alkaline bile assist with

A

micelle formation
neutralisation of chyme
pH adjustment for digestive enzyme action
protection of the mucosa

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16
Q

what do hepatocytes mainly secrete and where

A

primary juice into canaliculi which drain into biliary ductules and ducts

17
Q

what does the primary bile acid contains

A

> contain mainly cholic and chenodeoxycholic acids
- which can be dehydroxylated by bacteria to form the secondary bile acids, deoxycholic acid and lithocolic acid
water and electrolytes including sodium, chloride and bicarbonate
lipids and phospholipids
cholesterol
-excess cholesterol relative to bile acids may precipitate microcrystals the can become gall stones (cholelithiasis)
IgA
bilirubin
metabolic wastes and conjugated drug metabolites

18
Q

what is cholelithiasis

A

*most common pathology of the biliary tract

when there is excess cholesterol relative to bile salts and lecithin that may precipitate and form microcrytsals that may aggregate and form gall stones

19
Q

how to treat symptomatic stones

A

laparoscopic cholecystectomy

eg stones causing cholangitis and pancreatitis

20
Q

how to treat patients with unimpaired gall bladder function who have small/medium sized stones (CH stones)

A

ursodeoxycholic acid dissolves these stones

> may cause diarrhoea

21
Q

analgesia for biliary colic

A

morphine is contraindicated - the pain may worsen due to constriction of the sphincter of Oddi and increase intrabiliary pressure
»buprenorphine and pethidine are alternatives

22
Q

how may biliary spasms be relieved

A

atropine and GTN

23
Q

bile salts and enterohepatic recycling

A

only a small fraction of bile salts entering the duodenum is lost in the faeces
most is reabsorbed by active transport in the terminal ileum and undergoes enterohepatic recycling

> secondary bile acids upon returning to the liver are conjugated with glycine or taurine and recycle as bile salts

24
Q

what are resins

A

bile salt sequestrants
ie colveselam colestipol colestyramine

> they are neither digested not absorbed by the gut
act by binding to bile acids preventing their reabsorption

25
Q

how do resins lower plasma LDL-cholesterol indirectly ?

A

> they promote hepatic conversion of cholesterol to bile acids
increase cell surface expression of LDL-receptor in hepatocytes
increase clearance of LDL cholesterol from plasma

26
Q

what are the clinical uses of resins

A

for hyperlipidaemia
cholestatic jaundice (itch)
bile acid diarrhoea

27
Q

side effects and limitations resins

A

unpalatable, inconvenient
frequently cause diarrhoea
reduced absorption of fat-soluble vitamins and some drugs ie thiazide diuretics

28
Q

what are drugs

A

xenobiotics

29
Q

functions of drug metabolism

A
  • convert parent drugs to more polar metabolites that are not readily reabsorbed by the kidney facilitating excretion
  • convert drugs to metabolites that are usually pharmacological less active than the parent compound
30
Q

unusual actions of metabolites

A
  • can be converted from inactive prodrugs to active compounds or gain activity
  • have unchanged activity
  • possess a different type or spectrum of action
31
Q

what is the main organ of drug metabolism

A

the liver

32
Q

what is the function of haem proteins

A

-they are located in the endoplasmic reticule of the liver hepatocytes mediating oxidation reactions (phase 1) of many lipid soluble drugs

33
Q

what are the cytochrome P450 (CYP) family of monooxygenases ?

A

haem proteins

34
Q

CYP 3A4

A
3 = gene family 
A =  gene subfamily 
4 = individual gene
35
Q

what are the main families in human liver

A

CYP1
CYP2
CYP3

36
Q

what are phase 2 reactions involved in

A

conjugation of chemically reactive groups ie OH SH NH2 with glucuronyl, sulphate, methyl or acetyl groups

> > glucuronidation is a common reaction involving the transfer of glucuronic acid to electron-rich atoms of the substrate N O S forming amide ester or thiol bonds

> many endogenous substances are subject to glucuonidation ie bilirubin and adrenal corticosteroids

37
Q

what is hepatic encephalopathy HE

A

in severe hepatic failure - detoxification of ammonia via the urea cycle to urea fails

> blood ammonia levels rise (hyperammonemia) exerting a toxic effect upon the CNS that causes incoordination, drowsiness, coma and death due to cerebral oedema

38
Q

how to treat HE

A

> lactulose - a disaccharide of fructose and lactose

which:
- is not digested or absorbed in the small intestine
- when broken down in the colon acidifies the stool (reduces pH)
- converts ammonia to ammonium which is not absorbed

> antibiotics - neomycin rifamixin
-suppress colonic flora and this inhibit ammonia generation