Physiology and pharmacology of the liver Flashcards
What is the metabolic hub of the body?
The Liver
What metabolism does the liver regulate?
Carbohydrate
Lipid
Amino Acid
What are the 4 steps of carbohydrate metabolism?
Glucogenesis
Glycolysis
Glycogenesis
Glycogenolysis
What are the steps for fat metabolism?
Processing of chylomicron remnants
Synthesis of lipoproteins and cholesterol
Ketogenesis
What are the steps of protein metabolism?
Synthesis of plasma proteins
Transamination and deamination of amino acid
conversion of ammonia to urea
Many important hormones are de/activated by the liver True/false?
True
What is deactivated by the liver?
Insulin
Glucagon
Anti-diuretic hormone (ADH)
Steroid hormone
What is activated by the liver?
Conversion of thyroid hormone to triiodothyronine
Conversion of vitamin D to 25-hydroxyvitamin D2
What does the liver store?
Fat soluble vitamins (ADEK) Water soluble vitamin B12 Iron Copper Glycogen
Where is vitamin A stored?
In ito cells
Where is vitamin K stored?
Hepatocytes
What proteins does the liver synthesize?
Coagulation factors 2,7,9 and 10 Proteins C+S Albumin Complement proteins Apolipoproteins Carrier proteins - a protein which combine to other molecules and carry them round the body
What are factors that protect the liver?
Kupffer cells
Production of immune factors: Acute phase proteins
What are Kupffer cells and what is their role?
Liver Phagocytes
Digest and destroy cellular debris and invading bacteria
What is the liver involved in the detoxification of?
Endogenous (Bilirubin) and exogenous substances (Drugs/alcohol)
What is the role of bile?
Participation in the digestion and absorption of fatzs and the exretion of products of metabolism
How much bile is produced each day?
0.6-1.2L
What are the two types of bile?
Hepatic (Hepatocytes)
Secretory (Cholangiocytes)
Between meals where does bile reside?
Stored in the gall bladder due to the sphincter of oddi being closed
What does the gallbladder do to bile?
Removes water
Can cause solids to precipitate out (cholesterol) leading to gall stones
What happens to bile during a meal?
Chyme in duodenum stimulates gall bladder smooth muscle to contract (via CCK and Vagal impulses)
Sphincter of oddi opens (Via CCK)
Bile spurts into duodenum via cystic and common bile ducts
What is gallbladder secretion high in?
Bicarbonate
What does slightly alkaline bile assist in?
Protection of the gastric mucosa
What does bile contain?
Secretion of hepatocytes Secretion of bile ducts (cholangiocytes) Bile acids (cholic and chenodeoxycholic) Water and electrocytes Lipids and phospholipids Cholesterol IgA Bilirubiin
What is bilirubin?
Breakdown product of porphyrin component of haemoglobin
Pigment rendering urine yellow and faeces brown
When present in excess causes jaundice
What is the process of bile secretion through the duodenum?
The hepatocytes produce two primary bile acids, these appear in the bile, during feeding they enter the duodenum with the rest of the bile, as it moves along the intestine, bacteria is encountered, bacteria then attacks the primary bile acids and converts them to the secondary bile acids. Both secondary and primary acids are reabsorbed where they return to the liver through the portal system where the process can begin again
What does the liver do when low in salt?
It uses Cholesterol
What is the most common pathology of the biliary tract?
Cholelithiasis
What is the best treatment for large, hard, calcified symptomatic gall stones?
Laparoscopic cholecystectomy
What is the treatment for non-calcified gall stones?
Ursodeoxycholic acid
When may potent analgesia be required?
Biliary colic
What drug relieves biliary spasm?
Atropine
GTN
What percentage of the bile salts that enter the duodenum are lost in faeces?
5%
What occurs to the majority of the bile?
Most is reabsorbed by active transport in the terminal ileum and undergoes enterohepatic recycling
What are three bile acid sequestrants (resins)?
Colvesam
Colestipol
Colestyramine
Are the bile acid sequestrants (resins) absorbed or digested?
Neither, they bind to bile acids to prevent their reabsorption
What do the resins do?
Lower plasma LDL cholesterol indirectly
Treating hyperlipidemia and cholestatic jaundice
Bile acid diarrhoea
What are the disadvantages of resins?
Unpalatable and inconvinient
GI side effects - frequently cause diarrhoea
Deficiency of fat soluble vitamins
What occurs in phase I of drug metabolism in the liver?
Oxidation (Mediated by cytochrome P450’s)
Reduction
Hydrolysis
Adds a polar group to the compound to causes one of these reactions to occur
What does it mean when a drug is Lipiphyllic?
Difficult for the kidney to excrete
Stay in the body for a long time
What is phase 2 of drug metabolism in the liver?
Conjugation
Adds an endogenous compound increasing the polarity of a drug with glucaronyl, sulphate, methyl, acetyl, glycyl etc. Makes them more readily excretable for the body
