Live disease

Liver Anatomy

• Hepatocytes - hexagonal units called lobules and each lobule centred around central vein that drains blood into hepatic vein
  
• Hepatic portal vein and artery are branched from the lobules .
• Sinusoids are formed by the vessels branch among the hepatocytes
• 70% of SA of hepatocytes to max exchange between blood and cells
  
• 15% faces the bile canaliculi

Function

• Metabolism ( Vitamine D, fat protein, carbo, hormones, drug and toxins )
  
• Clearance
  
• synthesis
  
• storage
  
• excretion
  
• secretion
  
• homeostasis ( glucose)
  
• Defence ( Kupffer cells- hepatic macrophages)
  

Type of live injury

1. hepatocellular - alcohol,toxins or drugs or viruses
   
2. cholestatic - blockage of bile duct
   
3. Infiltrative - cancer

Liver disease classification

1. acute LD
   
2. Acute LF/ fulminant hepatic F
   
3. Chronic LF
   

Causes - Autoimmune, alcohol, drugs, chronic viral hepatitis Wilson's disease

Autoimmune

• auto-antibodies in the serum
  
• usually presents as chronic progressive disease
  
• affects the biliary tree
  

Wilson's disease

• Inherited metabolic disease
  
• characterised by copper overload
  
• excessive absorption and deposition of dietary
  copper in liver, brain, kidneys and other tissues
  

Gilbert syndrome - Benign condition - no active treatment

• Hyperbilirubinemia- >50umol/L
  
• symptoms: Hyperpyrexia, fatigue, nausea, abdominal discomfort.
  

Sign and symptoms of liver Disease

• spider naevi
  
• finger clubbing
  
• Gynaecomastia
  
• Loss of body hair
  
• jaundice
  
• Enlarged Liver
  
• Alopecia- hair loss
  
• White nails
  
• Ascities - abnormal accumulation of fluid in the abdomen
  
• Portal Hypertension
  
• Pruritis - itch

Chronic complication of liver disease

Jaundice

• can be both an acute and a chronic sign of liver disease.
  
• it occurs when serum bilirubin levels are high. ( Bilirubin is metabolised by the liver) Therefore, it will accumulate if the liver is not functioning to its full capacity.
  
• it is clinically detectable when plasma bilirubin is 35umol/L.
  
• Jaundice presents as yellowing of the skin, mucous membrane and iris

Portal Hypertension (PH)

• Usual portal venous pressure is 2-5mmHg. If this becomes chronically high, collateral veins can form. ( This can form throughout the body) but are found mainly in the GI tract.
  
• The presence of these veins allows portal blood to enter the systemic circulation directly bypassing the liver.
  
• if the portal venous pressure remains high, this may lead to bleeding varices ( bleeding of dilated veins caused by liver disease) and it is potentially life-threatening. The damage can cause disruption of blood flow and liver function- processes that take place in the liver. metabolism, protein synthesis, etc. Raise in Bilirubin levels.
  
• PH also contributes to hepatic encephalopathy and ascites.

Cirrhosis- Progressive replacement of normal hepatic cells by fibrous tissue.
* associated with high level of aldosterone.

Ascites
- is the accumulation of fluid in the abdominal cavity. In liver disease, there are 3 main causes of ascities.

• PH : altering capillary pressure and permeability, leading to the accumulation of fluid in the peritoneal cavity.
  
• low blood albumin following reduced synthesis in the liver leads to fluid seepage from blood vessels.
  
• Aldosterone : the hormone responsible for fluid retention) . Accumulation when the damaged liver cannot metabolise it adequately.
  

Hepatic Encephalopathy

• occurs in profound liver dysfunction.
  
• Neurotoxic substances enter directly into the brain, bypassing the damaged liver.
• Ammonia is one such substance and it alters the permeability of the blood-brain barrier.
  
• the patient presents with an altered mental state, euphoria and confusion.
  
• In severe cases, coma can be the end-result.
  

Gynaecomastia

• The damaged liver is unable to metabolise oestrogen which can lead to feminisation in males.
  
• in Women, it presents as irregular menstrual cycle and reduce fertility.

Investigations

Liver function test (LFTs)

• Bilirubin is raised in hepatocellular damage, cholestasis and haemolysis
  
• Transaminases :aspartate transaminase (AST) and Alanine transaminase ( ALT) released from the liver in hepatocellular damage.
  
• Alkaline phosphatase (ALP) is released in cholestasis ( damage of bile duct)
  
• Albumin is synthesised in the liver. Serum albumin indicates the extent of chronic liver disease as it has a long half life ( approx 20 days)
  
• Prothrombin time: Clotting factors synthesised in the liver. Good indicator of acute liver disease due to short half life ( 6 hours) .

Liver biopsy- diagnostic

Management

Ascites- is the excess fluid in between the tissue lining the abdomen and the abdominal organd ( the peritoneal cavity.

• Sodium intake should be restricted to 60-90mEq per day (hyperkalemia)
  
• Spironolactone( aldosterone antagonist) is the drug of choice. SF: hyperkalemia and gyneacomastia. ( 100mg daily increasing to 400mg daily)
  
• Paracentesis is a procedure involving a needle of drainage of fluid from the peritoneal cavity. It can relieve the abdominal pressure from ascites.
  
• TIPSS- is placed to provide portosystemic shunting to reduce portal pressure.
  
• Liver transplant
  
• Desired weight loss: 0.5-1kg per day. Water in versus Water out should be monitored.
  

Portal Hypertension

• Propranolol : the only beta-blocker licenised for portal hypertension. it is given to reduce portal venous pressure and prevent recurrent variceal bleeds. ( 10mg BD-TDS)
  
• SF: vivid dreams, bradycardia, coldness of extremities, fatigue and bronchospasm.
  
• should not stop taking unless advised by a doctor
  

Hepatic Encephalopathy

• dietary protein intake should be reduced to 20g per day
  
• Lactulous : an osmotic laxative. It can reduce the pH of colonic content thus reducing colonic ammonia absorption. The GI transit time will be decreased, so patient are monitored for 2 to 3 bowel motions a day.
• Metronidazole reduces ammonia production from GI bacteria
  
• Interaction with alcohol: a disulfiram type reaction ( like dizziness and vomiting) occurs if metronidazole is taken with alcohol.
• Alternative: Neomycin - reduces plasma ammonia. Max of 7 days 1g QDS ( ototoxicity & nephrotoxicity)

Pruitis

• Antihistamines are not very effective but if given, non-sedating antihistamines would be preferable ( e.g. Loratidine) , as sedating could mask the effect of hepatic encephalopathy
  
• Anion exchange resins ( Colestyramine) bind to the bile acids that cause itching and it is 1st line treatment. it can redice the absorption of other drugs taken at the same time. - taken 1 hour before or 4 hours after taking a dose of anion exchange resins.
• Topical preparations such as calamine lotion can be used.
  

Oesophageal varices

• Vasopressin: reduce portal blood flow and portal pressure; it is given IV to stop bleeding. ( 20units IV over 15-20mins)
  
• SF: angina, myocardial infarction and arrhythmia
• Should not be given to patients with ishaemic heart disease. GTN ( glyceryl trinitrate) can be given to overcome the cardiac SF ( vasoconstriction)
  
• Terlipressin : given IV, is the drug of choice ; it releases vasopressin over several hours without the cardiac effects ( 2mg then 1 -2mg ever 4-6hours until bleeding is controlled for upto 72 hours)
  
• Octreotide: A somatostatin, given IV, stops variceal bleeding and reduce portal venous pressure. it inhibits release of vasodilating hormones (e.g. glucogon)