7- Jaundice And Liver Failure

Question 1

What is the structure of the bilary tree

Answer 1

the biliary tree starts in millions of bile canaliculi adjacent to the hepatocytes, These drain into small ductules, then small bile ducts and larger bile ducts for each liver segment. These merge to form the right and left hepatic ducts, which converge to form the common hepatic duct. Connected to this duct is the cystic duct, which connects the gall bladder (a small muscular storage organ) to the biliary tree. The merging of the common hepatic duct and the cystic duct forms the common bile duct, which extends towards the duodenum. At its distal end the pancreatic duct joins and the vessel is then called the ampulla of Vater, which opens up into the medial wall of the duodenum at the duodenal papilla

Question 2

Characteristics of haemolytic jaundice

Answer 2

Haemolytic anaemias eg sickle cell disease.
↑ breakdown of red blood cells → ↑ production of bilirubin → jaundice.
Remember this is unconjugated bilirubin, which is not water soluble, therefore does not pass into the urine.
↑ serum urobilinogen but otherwise normal liver biochemistry.

Question 3

Characteristics of congenital jaundice

Answer 3

Impaired conjugation of bilirubin with glucuronic acid or bilirubin handling by the liver. Raised bilirubin but liver biochemistry otherwise normal.

Gilbert’s syndrome is the commonest congenital hyperbilirubinaemia.

Autosomal dominant
Mutation in gene coding for UDP-glucuronyl transferase → ↓ enzyme activity → ↓ conjugation of bilirubin
2-7% of the population.
Asymptomatic.
It is usually picked up as an incidental finding of slightly raised serum bilirubin (17-102µmol).
Triggers that lead to jaundice are dehydration, fasting, viral illness.
Diagnosis

Raised unconjugated hyperbilirubin .

Otherwise normal liver biochemistry.

Normal full blood count, smear and reticulocyte count (thus excluding haemolysis)

Absence of signs of liver disease

Management

Reassure the patient that no further investigation or treatment is necessary.

Question 4

Characteristics of cholestatic jaundice

Answer 4

Cholestatic jaundice is caused by the failure of bile secretion by the liver or bile duct obstruction. This is divided into intrahepatic and extrahepatic cholestasis.

Intrahepatic cholestasis is caused by hepatocellular swelling or abnormalities at cellular lever of bile excretion.

Extrahepatic cholestasis results from the obstruction of bile flow at any point distal to the bile canaliculi.

Characterised by:

Conjugated bilirubin.
Pale stool.
Dark Urine.
Abnormal liver biochemistry.

Question 5

How does liver control synthesis and metabolism of protein

Answer 5

Albumin which maintains intravascular oncotic pressure and transports water-insoluble substances such as bilirubin and some drugs in the plasma.
Transport and carrier proteins such as transferrin
All factors involved in coagulation and components of the complement system.
The liver eliminates nitrogenous waste by degradation of amino acids, conversion to urea and renal excretion.

Question 6

How does liver control lipid metabolism

Answer 6

The liver manufactures most of the body’s cholesterol; the rest comes from food.
Cholesterol is used to make bile salts and is also needed to make certain hormones, including oestrogen, testosterone and the adrenal hormones.
The liver also synthesizes lipoproteins and triglycerides (most are of dietary origin).

Question 7

How does liver produce bilirubin and bile salts

Answer 7

Bile acids are formed from cholesterol and excreted into bile and pass into the duodenum via the common bile duct (CBD), where they solubilize lipid for digestion and absorption.
Bilirubin is formed from the breakdown of mature red cells and eventually excreted in urine and faeces.

Question 8

What are the main causes of liver disease

Answer 8

Alcohol and non-alcoholic fatty liver disease are the commonest causes in the developed world, chronic viral hepatitis B or C in the developing world. Alcohol excess results in fatty change, alcoholic hepatitis, alcoholic cirrhosis.

Question 9

5 symptoms of early liver disease

Answer 9

Lethargy
Anorexia
Malaise
Pruritus – itchy skin
Right upper quadrant pain

Question 10

5 symptoms as liver disease progresses

Answer 10

Peripheral swelling
Abdominal bloating
Bruising
Vomiting of blood 
Confusion and somnolence

Question 11

6 signs of liver disease

Answer 11

Jaundice - bilirubin levels exceeds 40 µmol/l. spider naevi – a central arteriole with radiating small vessels, found in the distribution of the superior vena cava.

loss of body hair
gynaecomastia
testicular atrophy
palmar erythema - ‘liver palms’ - reddening of palms at the thenar and hypothenar eminences – a non-specific change of hyperdynamic circulation

Question 12

Signs of chronic liver dysfunction

Answer 12

Xanthelasma - sharply demarcated yellowish deposit of cholesterol underneath the skin, usually on or around the eyes
Finger clubbing
Pruritus - itchy skin causes scratch marks.
Dupuytren’s contracture may be a sign of alcoholic liver disease
Ascites and dilated veins of the abdomen
Hepatomegaly
Hepoatosplenomegaly
Caput medusa indicates severe portal hypertension.: distended and engorged paraumbilical veins, which are seen radiating from the umbilicus across the abdomen to join the systemic veins.
Oedema
Weight loss
Bruising

Question 13

What is liver cirrhosis

Answer 13

necrosis of liver cells, followed by progressive fibrosis and nodule formation which leads to the impairment of liver cell function and gross distortion of the liver architecture leading to portal hypertension and deterioration of liver function.

Question 14

What are 2 types of liver cirrhosis

Answer 14

Micronodular cirrhosis: uniform, small nodules up to 3 mm in diameter. This type is often caused by ongoing alcohol damage or biliary tract disease.

Macronodular cirrhosis: nodules of variable size. This type is often seen following chronic viral hepatitis.

Question 15

Define acute liver failure

Answer 15

severe hepatic dysfunction occuring within 6 months of the onset of symptoms of liver disease, with a clinical manifestation of hepatic encephalopathy or coagulopathy.

Question 16

3 classifications of acute liver failure

Answer 16

Hyperacute liver failure is when encephalopathy occurs within seven days of the onset of jaundice.

Acute liver failure is when encephalopathy occurs after 8-28 days of jaundice.

Subacute liver failure is when encephalopathy occurs 5-12 weeks after the onset of jaundice.

Question 17

How does liver failure effects the CNS

Answer 17

Accumulation of toxins, primarily derived from the gut, is thought to induce cerebral oedema and changes in the level of consciousness and eventually coma.

Question 18

What causes renal failure in liver failure

Answer 18

The kidneys are morphologically normal and, when transplanted into patients with chronic renal failure, function normally.

Renal failure is thought to be due to reduced renal blood flow - more marked in the cortex than the medulla - due to cortical vasoconstriction. The basis for the reduced perfusion is uncertain but may result from the accumulation of a vasoactive substance, thought to be endotoxin, which is usually cleared in the liver.

Question 19

What role does the liver play in coagulation

Answer 19

synthesis of coagulation factors I, II, V, VII, IX, X. Vitamin K dependent factors - II, VII, IX and X - and Factor V are affected first in disease. Factor VII is the earliest of all to decline because of its short half-life (6 hours). Fibrinogen (factor I) synthesis is affected only in severe disease.

inhibition of fibrinolysis / coagulation - the liver is responsible for synthesising plasma anticoagulant proteins, e.g. protein C, protein S and antithrombin III.
clearance of activated coagulation factors - fibrin and tissue plasminogen activator (tPA) are removed from the circulation by the liver’s reticuloendothelial system
absorption of vitamin K - malabsorption occurs in disease

Question 20

How is sepsis related to liver failure

Answer 20

In liver failure will have bacterial infection occurs 90% of cases and fungal infection in 32% of cases.

Infection most commonly presents within 3 days of hospital admission. Often the normal clinical features of fever and leucocytosis (high white cell count) are absent.

Question 21

What are the cardiovascular effects of liver failure

Answer 21

A common complication of acute hepatic failure is a reduction in peripheral resistance which requires a reflex increase in cardiac output to maintain blood pressure. Cardiac failure and hypotension may result if there is pre-existing heart disease.

Question 22

2 metabolic effects of liver failure

Answer 22

Hypoglycaemia and hypoxia

Question 23

When does chronic liver failure occur

Answer 23

deterioration in liver function superimposed on chronic liver disease

Question 24

What is the enterohepatic circulation

Answer 24

Bile salts take part in a loop that recycles them between liver, where they are excreted into the biliary tree and the gastrointestinal tract, where they are absorbed. Bile salts are reabsorbed from the portal circulation into the liver from the blood by an active transport mechanism. Bile salts may be recycled up to 10 times per day with loss of only 5% into the faeces

Question 25

Describe bilirubin metabolism

Answer 25

Bilirubin is derived from haemoglobin breakdown in the spleen and carried in the blood, bound to albumin. Unconjugated bilirubin is conjugated in the liver by glucuronyl transferase to bilirubin glucuronide.
Conjugation makes bile water soluble. This is then excreted into the duodenum in bile. In the gut, bilirubin glucoronides are degraded by bacteria and converted into a mixture of compounds, urobilinogen or stercobilinogen
Some urobilinogen is reabsorbed and excreted by the kidneys in urine. Urobilinogen is also converted by bacteria in the gut to stercobilinogen