Physiology and pharmacology of the liver Flashcards by Amy Ireland

What are the 10 main functions of the liver?

Metabolic processing 
Detoxification and degradation
Synthesis of plasma proteins
Storage 
Activation of vitamin D
Removal of bacteria and old erythrocytes
Secretion of hormones
Production of acute phase proteins
Excretion of cholesterol and bilirubin
Production of hepatic bile

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What is the blood supply to the liver?

Dual blood supply
75% of the total blood in the liver comes from the portal vein
25% comes from the hepatic artery

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Where does arterial and venous blood mix in the liver?

In liver sinusoids

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What are sinusoids?

Fenestrated (leaky) capillaries

allow direct access between hepatocytes and the blood

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What is the passage of blood through the liver?

Hepatic artery & portal vein –> arterioles & venules–> sinusoids –> central vein of liver lobule –> branches of hepatic vein –> hepatic vein

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What are liver lobules?

Functional units of the liver

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How are hepatocytes arranged?

Hepatocytes are arranged in plates lining the blood-filled sinusoids

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What does the basolateral membrane of hepatocytes face?

Pericellular space/space of Disse

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What is the space of Disse?

The space between the hepatocytes and a sinusoid
Contain blood plasma
Microvilli of hepatocytes extend into this space, allowing proteins and other plasma components fro the sinusoids to be absorbed by the hepatocytes

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What do the apical membrane of adjacent hepatocytes form?

Canaliculi

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What does the sinusoidal space contain?

Endothelial cells
Kuppfer cells
Stellate cells

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What do the endothelial cells form?

A fenestrated structure that allows for free movement of solutes but not cells

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What are Kupffer cells and where are they found?

Kuppfer cells are macrophages resident to sinusoidal vascular space (found on the sinusoidal endothelaial wall)
They remove particulate matter and are involved in the breakdown of red blood cells

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What are stellate cells?

Within the space of Disse
Important for storage of vitamin A
May play a role in fibrosis in liver injury

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What is the intrahepatic bile system, in sequence (starting small)?

Canaliculi, terminal bile ductules, perilobular ducts, interlobular ducts, septal ducts, lobar ducts, two hepatic ducts and the common bile duct

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What is the name of the sphincter that controls the entrance of bile to the duodenum?

Sphincter of Oddi

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How much bile is produced per day?

0.6-1.2 liters

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Where is bile stored and concentrated?

Gallbladder

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What triggers the sphincter of Oddi to open?

Chyme is the duodenum stimulates gallbladder smooth muscle to contract

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What impulses cause the gallblader smooth muscle to contract?

CCK and vagal impulses

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What secretions is bile made up of?

Secretion of hepatocytes and secretion of bile duct cells (25%) that mixes in the ducts

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What are bile duct cells called?

Cholangiocytes

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What process is bile important for?

Emulsification of lipids

What is the secretion from cholangiocytes composed of?

Aqueous, alkaline, Na+, K+, Cl- and HCO3- rich

What substance triggers secretion from bile duct cells?

Secretin is released from duodenal S cells. Exchange occurs across the duct cells apical membrane = HCO3- moves out of the cell and Cl- move in This makes the gut lumen more alkali

What is the benefit of alkanisation in the gut lumen?

Enhances the pancreatic solution to neutralise chyme coming form the stomach - optimum pH for the pancreatic enzyme and helps protect the mucosa from erosion

Where do hepatocytes secrete their primary juice?

Into canaliculi which drain into terminal biliary ductules

What is hepatic bile composed of?

Primary bile acids, water, electrolytes, lipids, phospholipids, bilirubin and IgA

What are the two main bile acids?

Cholic and chenodeoxycholic acid

How are bile salts formed?

Binding of the bile acids to Na+ and K+

How are gallstones formed?

If there is excess cholesterol relative to bile acids it may precipitate and form microcrystals that aggregate into gallstones

What is the proper medical term for gallstones?

Cholelithiasis

What can be given to dissolve non-calcified cholesterol gallstones?

Ursodeoxycholic acid

What is bilirubin?

Breakdown product of porphyry a component of haemoglobin | Pigmented (gives urine and faces their colour)

What tissue does un-metabolised bilirubin that has not been excreted, often built up in?

Fatty tissue

What happens to the majority of bile salts that enter the duodenum?

The majority is reabsorbed by active transport in the terminal ileum and undergoes enterohepatic recycling

What happens do faeces if there is an absence of bile salts?

Steatorrhoea

What happens to bile salts that are reabsorbed by the liver?

Used again or made into cholesterol for the production of more bile

How is bile salt synthesised?

Series of 14 reactions starting with cholesterol

What controls the rate of synthesis of bile salts?

The hepatic portal blood concentration of bile salts | low concentration stimulates synthesis

By what type of transport does bile salt move across the apical membrane for secretion?

Active transport

How is the rate of secretion of bile salts controlled?

Most powerful stimulus is the bile salt returning to the liver by enterohepatic recirculation during and shorty after a meal - matched rate of secretion to need

What is the effect of cholecystokinin (CCK) on the gallbladder and the sphincter of Oddi?

Causes the gallbladder to contract and sphincter of Oddi to relax

What does secretin trigger?

Causes aqueous alkaline bile secretion

What treatment can be given fro cholelithiasis?

Ursodeoxycholic acid (non-calcified) or surgery

What medication can be given to patients with cholelithiasis for analgesia?

Morphine (but constricts sphincter of Oddi) Buprenorphine Pethidine

What medication can be given for relief of biliary spasm?

Atropine or glyceryltrinitrate (GTN)

How does GTN relieve pain?

Nitrates cause muscle relaxation

What is a xenobiotic substance?

A substance (usually a synthetic chemical) that is foreign to the body

What is the liver's role in drug metabolism?

Convert parent drug --> more polar metabolites to facilitate excretion by the kidney Convert drug --> metabolites

How can drug metabolites differ from the parent drug that entered the liver?

Usually pharmacologically less active than parent May convert inactive prodrugs to active compounds Gain activity Have unchanged activity Posses a different type/spectrum of action

Give an example of a drug that is activated in by metabolism

Enalapril --> enalaprilate

Give an example of a drug that has greater activity after metabolism

Codine --> morphine

What is the difference in the action of aspirin and it's metabolites?

Aspirin - anti-inflammatory and anti-platelet activity | Metabolite (salicylic acid) - anti-inflammatory not anti-platlet activity

What happens in phase I of metabolism?

Drug is made more polar, chemical reactive ('handle') group is added - oxidation, reduction and hydrolysis

What happens in phase II of metabolism?

Conjugation - endogenous compound is added increasing polarity (usually results in inactive products)