It refers to yellowish appearance of:Skin Sclerae Mucous membranes It results from an increased bilirubin concentration in the body fluids It become clinically detectable if serum bilirubin exceeds 50 μmol/l (3 mg/dl). Internal tissues & body fluids are colored yellow but not the brain, as bilirubin does not cross blood brain barrier except in the immediate period
Mechanisms producing jaundice
Increased production of bilirubin:Hemolysis Impaired excretion of bilirubin:Congenital non-hemolytic hyperbilirubinemia:Gilbert’s syndrome Crigler-Najjar type I & type IIDubin-Johnson syndrome Rotor’s syndrome Hepatocellular Jaundice:Acute paranchymal liver diseaseChronic paranchymal liver diseaseCholestasisPathway of bilirubin excretion
Sources of unconjugated bilirubinHemoglobin breakdown Catabolism of other hem-containing proteins e.g. myoglobin & cytochrome enzymes. Ineffective erythropoeisis
Hemolytic Jaundice
This results from increased destruction of RBCs or their precursors in the marrow, causing increased bilirubin production. It is usually mild because: Liver is capable to excrete bilirubin load 6 times greater than normal before unconjugated bilirubin accumulates in the plasma Clinical features: No stigmata of chronic liver disease other than jaundice Normal colored or dark stool Urine turn dark on standing Pallor due to anemia Splenomegaly due to excessive reticuloendothelial activityPlasma bilirubin is usually less than 100μmol/l (6 mg/dl). Liver function tests are otherwise normal No bilirubinuria Blood count & film may show evidence of hemolytic anemia. Hemolytic Jaundice-Investigations
Congenital non-hemolytic hyperbilirubinemia
Hepatocellular JaundiceIt results from inability of the liver to transport bilirubin into the bile It occurs as consequence of parenchymal liver disease In parenchymal liver disease: Impaired transport of bilirubin across the hepatocytes Swelling of cells and edema resulting in obstruction of biliary canaliculi The concentrations of both the conjugated and the unconjugated bilirubin will be increased
Cholestatic Jaundice
In unrelieved cholestasis, jaundice tends to become progressively more & more severe because: Conjugated bilirubin is unable to enter the bile canaliculi and passes back into the blood There is failure of clearance of unconjugated bilirubin arriving at the liver cells
Causes of cholestatic jaundice
Intrahepatic:Primary biliary cirrhosis Primary sclerosing cholangitis Alcohol Drugs Viral hepatitis Autoimmune hepatitis Severe bacterial infection Post-operativeHodgkin’s lymphoma Pregnancy Idiopathic recurrent cholestasisCauses of cholestatic jaundice
Extrahepatic: Choledocholithiasis Carcinoma: Ampullary Pancreatic Bile duct (cholangiocarcinoma) Secondary Cystic fibrosis Parasitic infection Traumatic biliary stricturesClinical features in cholestatic Jaundice
Cholestasis Early features: Jaundice Dark urine Pale stools Pruritus Late features: Xanthelasma & xanthomata Malabsorption: Weight loss Steatorrhea Osteomalacia Bleeding tendencyCholangitis Fever Rigors Pain Hepatic abscess
Scratch marks in cholestatic jaundice
XanthelasmaTendon xanthoma
Clinical features suggesting an underlying cause of cholestatic jaundice
Clinical feature
Causes
Jaundice Static or increasing Fluctuating
Carcinoma Stone Stricture Pancreatitis Choledochal cyst
Abdominal pain
Stone Pancreatitis Choledochal cyst
Clinical feature
CausesCholangitis
Stone Stricture Choledochal cyst
Abdominal scar
Stone Stricture
Irregular hepatomegaly
Hepatic carcinoma
Palpable gall bladder
Carcinoma below cystic duct (usually pancreas)
Clinical features suggesting an underlying cause of cholestatic jaundice
Clinical feature
Causes
Abdominal mass
Carcinoma Pancreatitis (cyst) Choledochal cyst
Occult blood in stools
Papillary tumor
Clinical features suggesting an underlying cause of cholestatic jaundice
HEPATIC ENCEPHALOPATHY
The term hepatic encephalopathy (HE) encompasses a wide array of transient and reversible neurologic and psychiatric manifestations usually found in patients with chronic liver disease and portal hypertension, but also seen in patients with acute liver failure. HE develops in 50% to 70% of patients with cirrhosis, and its occurrence is a poor prognostic indicator.Symptoms may range from mild neurologic disturbances to overt coma. HE is often triggered by an inciting event that results in a rise in the serum ammonia level.Clinical Stages of Hepatic Encephalopathy
0 : Normal 1 : Personality changes, attention deficits, irritability, depressed state. 2 : Changes in sleep-wake cycle, lethargy, Asterixis, ataxic gait, speech abnormalities (slow and slurred). 3 : Altered level of consciousness (somnolence), confusion, disorientation, and amnesia. 4 : Stupor and coma.HEPATIC (PORTOSYSTEMIC) ENCEPHALOPATHY
Hepatic encephalopathy is a neuropsychiatric syndrome caused by liver disease.Aetiology
It is a biochemical disturbance of brain function Liver failure and portosystemic shunting of blood are two important factors underlying hepatic encephalopathy. ‘Neurotoxins' causing the encephalopathy are thought to be mainly nitrogenous substances produced in the gut, (by bacterial action), which are normally metabolised by the healthy liver and therefore excluded from the systemic circulation. Some factors appear to precipitate hepatic encephalopathy by increasing the availability of these substances:Clinical assessment
Examination usually shows a flapping tremor, hyper-reflexia and bilateral extensor plantar responses.Management
The principles of management are to treat or remove precipitating causes and to suppress production of neurotoxins by bacteria in the bowel. Lactulose (15-30 ml 8-hourly) is a disaccharide which is taken orally and reaches the colon intact, to be metabolised by colonic bacteria. The dose is increased gradually until the bowels are moving twice daily. It produces an osmotic laxative effect, reduces the pH of the colonic content, thereby limiting colonic ammonia absorption.Neomycin (1-4 g 4-6-hourly) is an antibiotic which acts by reducing the bacterial content of the bowel. Neomycin is poorly absorbed from the bowel. It is less desirable than lactulose for long-term use; ototoxicity is the main deleterious effect.
Ascites refers to the accumulation of free fluid in the peritoneal cavity.
Abdominal swelling in ascitesAscites is the presence of fluid within the peritoneal cavity and is a common complication of chronic liver failure. The pathogenesis of the development of ascites in liver disease is controversial, but is probably secondary to renal sodium and water retention, portal hypertension, splanchnic vasodilatation, and low serum albumin.
CAUSES OF ASCITES Common causes Malignant disease Hepatic Peritoneal Cardiac failure Hepatic cirrhosis
Investigations
Ultrasonography is the best means of confirming ascites, particularly in the obese and those with small volumes of fluid. Paracentesis can also be used to confirm the presence of ascites but is most useful for obtaining ascitic fluid for analysis.The appearance of the ascitic fluid may point to the underlying cause Cirrhosis: clear, straw-coloured or light greenMalignant disease: bloodyInfection: cloudyBiliary communication: heavy bile stainingLymphatic obstruction: milky-white (chylous)
Useful ascitic fluid investigations
1- Ascites protein concentration and the serum-ascites albumin gradient used to distinguish ascites due to transudation from ascites due to exudation. Cirrhotic patients typically develop a transudate with a total protein concentration below 25 g/l and relatively few cells. More specific is calculation of the serum-ascites albumin gradient (by subtracting the concentration of the ascites fluid albumin from the serum albumin). A gradient of more than 11 g/l is strongly suggestive of portal hypertension and cirrhosis.Exudative ascites (ascites protein concentration above 25 g/l or a serum-ascites albumin gradient of less than 11 g/l) raises the possibility of infection (especially tuberculosis), malignancy, hepatic venous obstruction, pancreatic ascites or, rarely, hypothyroidism.
Management
Successful treatment of ascites relieves discomfort but does not prolong life, and if over-vigorous, can produce serious disorders of fluid and electrolyte balance and precipitate hepatic encephalopathy. The rate of loss of sodium and water is most easily measured by regular weighing. The body weight should not fall by more than 1 kg daily if fluid depletion in the rest of the body is to be avoided.1) Sodium and water restriction Restriction of dietary sodium intake is essential to achieving negative sodium balance in patients with ascites. Drugs containing relatively large amounts of sodium (e.g Antacids, Sodium valproate), and those promoting sodium retention, such as NSAID, must be avoided. Restriction of water intake to 0.5-1.0 litre/day is necessary only if the plasma sodium falls below 125 mmol/l.
2) Diuretic drugs Most patients require diuretic drugs in addition to sodium restriction. Spironolactone (100-400 mg/day) is the drug of choice for long-term therapy because it is a powerful aldosterone antagonist. Some patients will also require powerful loop diuretics, e.g. furosemide, although these can cause fluid, electrolyte and renal function disorders. Patients who do not respond to doses of 400 mg spironolactone and 160 mg furosemide are considered to have refractory or diuretic-resistant ascites and should be treated by other therapeutic measures.
3) Paracentesis The first-line treatment of refractory ascites is large-volume paracentesis with intravenous albumin. Paracentesis to dryness or the removal of 3-5 litres daily is safe, provided the circulation is supported by giving intravenous colloid such as human albumin or another plasma expander.
4) shunt Peritoneo-venous (LeVeen) shunt allows ascitic fluid to pass directly into the systemic circulation. It is effective in ascites resistant to conventional treatment but complications limit its use and insertion of these stents is now rare. Transjugular intrahepatic portosystemic stent shunt (TIPSS) TIPSS can relieve resistant ascites but does not prolong life. It can be used where liver function is reasonable, but should not be used in the terminally ill.