Describe the physiology of the liver:
- Liver receives blood from the portal vein (where blood is carried from the intestine to the liver as well as from the hepatic artery)
- The liver regenerates itself (unlike the kidney) - Hence in liver transplants only a part of the liver is transplanted, and it can regenerate into a new liver
Describe the function of the liver:
- Liver is involved in cholesterol synthesis and triglyceride (fats)
- Important as it detoxifies the body as well as involved in drug metabolism
- Liver is also involved in glucose homeostasis; Gluconeogenesis (production of glucose from other sources), glycogenolysis (breakdown of glycogen) and glycogenesis (production of glycogen); It produces glucose by metabolising fat
- It also breaks down insulin and other hormones
- It also produces coagulation factors such as albumin
- Liver is also the storage organ for Vitamin K, D, A, E, iron and copper
- It breaks down haemoglobin (its metabolised in the bile)
- It breaks ammonia to urine (ammonia is toxic)
Why does jaundice occur?
- Jaundice happens when there is accumulation of bilirubin – means that liver is not functioning well; the test is done in babies to check the liver is fully formed and functioning
- Bilirubin is a component of red blood cells
What is the liver’s involvement with bile, and therefore what is the function of bile?
- Liver produces bile which is involved in fat breakdown in the stomach; Bile is stored in the gallbladder and is secreted when required
- Some of the bile is drained directly to the duodenum, and some is stored in the gallbladder .
What does the liver function test measure?
- Used to aid in differential diagnosis of liver diseases and injury
o Bilirubin
o Aminotranferase (AST and ALT)
o Alkaline phosphatase (ALP)
o Gamma Glutamyl transferase (GGT)
o Albumin
o Prothrombin time
Increase in albumin and prothrombin time indicate chronic liver damage and hence are not always tested - only if there is potential for long term damage
Bilirubin, AST and ALT, and ALP are present in acute liver damage (e.g., infection)
People without a spleen have a higher risk of infection and therefore are given penicillin V for life (and sickle cell disease)
Spleen metabolises haemoglobin but if not present then the liver does this
How does haemoglobin metabolism work?
- Spleen metabolises haemoglobin forming unconjugated bilirubin (albumin bound)
- When it enters the liver, it is metabolised into conjugated bilirubin (phase 2 metabolism)
- Then it is secreted into the bile duct
- Then it goes into the gut Where the bacteria converts it to stercobilinogen which is why stool is brown coloured
Bilirubin test information:
- The normal bilirubin concentration is <17 micromol/l; High value is due to:
- Haemolysis (can be in immature newborns and haemolytic anemia)
- Failure of conjugating mechanism within the hepatocytes which can be due to infection or by toxins e.g. paracetamol overdose
- Obstruction in the biliary system (cholestasis - where bile flow is decreased)
- Gilbert syndrome (hyperbilirubinemia)
o Jaundice appears at bilirubin concentration >50micromol/L
o In pregnancy, if a women experiences itchiness, this can be a sign of bilirubin levels increasing which can be damaging for the foetus
- This symptom is treated by antihistamines, skin emollients or colestyramine (it causes the elimination of bile acids from the body)
What are aminotransferases? (AST and ALT)
- AST (10-40 Units/L) and ALT (5-40 Units/L)
- ALT is mainly localised in the liver but is present in other tissue e.g. heart and kidney
- High enzyme levels indicate true liver damage, hepatitis or acute toxic injury (shows damage to liver where cells are leaked out)
- A small increase is seen in obstructive jaundice and cirrhosis (liver scarring)
- An AST:ALT ratio of more than 2:1 is characteristic in patients with alcoholic liver disease
o Alcoholics are depleted of vitamin B family especially (pyridoxine (B6)) which is required for the synthesis of these two enzymes
What are alkaline phosphatase?
- Normal range 30-300 Units/L
- It is a membrane associated enzyme
- Main indicator of cholestasis (block in bile flow)
- Again, this is not specific to the liver but also to other areas e.g. bones
- It is also raised in pregnancy
What is gamma glutamyl transpeptidase (GGT)?
- Male <50 Units/L vs. Female <32 Units/L
- GGT is a microsomal enzyme, found in tissue such as liver and renal tubules
- High GGT with no other LFT abnormalities is induced by alcohol or enzyme inducing drugs e.g. phenytoin, carbamazepine
- In cholestasis, rise in GGT is parallel with serum alkaline phosphotase (ALP)
- In acute hepatic damage changes in GGT IS PARALLEL TO aminotransferases
What is albumin?
It is a factor for coagulation
- Normal range of 35-48g/L
- T1/2 of 3 weeks in the plasma hence a good marker of chronic liver damage
- Hypoalbuminaemia is often associated with ascites
- Sodium controls osmolarity (need to know how to calculate osmolarity)
- Albumin controls oncotic pressure (plasma protein levels)
- Ascites – term describing excessive fluid in the peritoneal cavity caused by:
o Sodium water retention (due to low oncotic pressure)
o Hypotension (RAAS system kicks in, therefore water and sodium retention)
- Therefore more water is retained in peritoneal cavity (positive feedback); we can add furosemide as a diuretic and a part of treatment is low salt diet
o Here, spironolactone can be used which antagonises aldosterone and hence prevents water retention activated by RAAS
o Portal hypertension which can cause oesophageal varices (obstructed blood flow)- blood leaking – first line is B BLOCKERS
What is the prothrombin time?
Evaluates blood-clotting in the body
- PT indicator for hepatic synthesis function
- Does not become abnormal until more than 80% of liver synthetic capacity is lost
- Elevated PT can result from vit K deficiency, parental administration of Vit K will reverse abnormality
Alfa-fetoprotein test:
o Synthesised by foetal liver
o Normal value for adults <20mg/l
o Can be increased in
- Neural tube defects
- Tumours of the testis and ovaryWhat is hepatic encephalopathy?
- Reversible state of altered mental function associated with liver impairment
- Can go from drowsiness to coma
- Main neurotoxin is thought to be ammonia
- Management: The principal aim in the management of encephalopathy is to remove the precipitating factors and reduce the absorption of nitrogenous substances from the gut
What is spider naevus?
Spider Naevus (a vascular lesion characterized by anomalous dilatation of end vasculature found just beneath the skin surface. The lesion contains a central, red spot and reddish extensions which radiate outward like a spider’s web.) - Accumulating of oestrogen causes this
Drugs prescribed for liver disease can include:
- Impaired drug metabolism (following drugs are excreted via bile unchanged and hence if there is a blockage they will be accumulated)
o Rifampicin
o Fusidic acid - Hypoalbuminaemia (be careful with drugs which are protein bound as they usually bind to t)
o Phenytoin
o Prednisolone - Reduce clotting
o Oral anticoagulants - Hepatic encephalopathy (severe nervous system disorder from liver disease)
o Sedative drugs
o Opioids
o Diuretic (as potassium is eliminated by most of them)
o Drugs that cause constipation antimuscarinics - Ascites (some drugs can cause water retention)
o NSAIDS
o Corticosteroid - Hepatotoxic drugs
What is the treatment for hepatic encephalopathy?
o Lactulose (30-45ml QDS)
- Lactose gets converted in the body to lactic acid, formic acid, and acetic acid
- Ammonia in an acidic environment gets converted to an ammonium ion
- As its ionised it is easier to be excreted
- Increase in acidity means GI bacteria is killed (bacteria produces ammonia)
- Note do not give classes of drugs that cause constipation e.g. don’t give opioids as pain killers
o Neomycin
- Aminoglycocide antibiotic
- Is given commonly parentally
- However in this case its given orally as we want to kill the bacteria in the gut
o Pabrinex (vit b and c) os also indicated in adults and children for severe depletion of water soluble vit C and B (found in alcoholism) o Also thiamine (B1) is given acutely and long term as well
