liver system and diseases

What are the key characteristics and structure of the liver?

• Largest gland and largest internal organ

• Makes up 2-3% of body mass and consumes 20-30% of total oxygen.

• Highly vascularised with 4 lobes: 2 major (Left & Right) and 2 minor (Caudate & Quadrate).

What is the basic functional unit of the liver and what are its components?

• The liver lobule is the basic functional unit.

• It consists of a central terminal hepatic venule

• interconnecting plates of hepatocytes,

• and a peripheral portal triad (hepatic artery, portal vein, bile duct).

What are the major functions of the liver?

• Xenobiotic detoxification and metabolism

• Decomposition of erythrocytes and bilirubin excretion

• Bile production

• Cholesterol synthesis, lipogenesis, and carbohydrate metabolism

• Protein synthesis (albumin, coagulation factors)

• Hormone production (thrombopoietin, angiotensin)

• Storage of glycogen, vitamins (A, D, E, K, B12), iron, and copper

What is thrombopoiten and angiotensin?

• • Thrombopoietin =regulates platelet production by bone marrow)

• • Angiotensin =raises blood pressure following renin activation

What are Transaminase Enzymes?

• ALT

• AST

• Transaminases are enzymes that help in the process of amino acid metabolism by transferring amino groups from one molecule to another.

What are the cholestaic enzymes ?

• ALP 

• GGT

• Cholestatic enzymes are enzymes that increase in the blood when there is damage or blockage in the bile ducts or problems with bile flow

What does an increase in (ALT) indicate?

• ALT increases when liver cells are inflamed or undergoing cell death;

• it rises dramatically in acute liver damage like viral hepatitis.

What is the significance of elevated (AST)?

• AST is raised in acute liver damage but is less specific for liver disease compared to ALT.

When is Alkaline Phosphatase (ALP) typically raised?

• ALP is raised in biliary tract damage and inflammation.

What is Gamma-Glutamyl Transferase (GGT) and what does its elevation indicate?

• GGT is produced by the bile duct and is a sensitive marker for cholestatic damage;

• it is raised in alcohol toxicity.

What bilirubin and related tests are used to assess liver function?

• Plasma total bilirubin

• Plasma direct (conjugated) bilirubin

• Urine urobilinogen

• Urine bilirubin

What is jaundice and how is it identified?

• A symptom of underlying disease or physiological dysfunction.

• Elevated serum bilirubin above normal limit (normal: 3-17 mmol/L).

• Clinically visible jaundice appears at about 35 mmol/L or higher.

What happens to bilirubin during its metabolism in circulation?

• Erythrocytes break down, releasing hemoglobin.

• 90% of hemoglobin is removed by macrophages in the liver, spleen, and lymph nodes.

• 10% hemolyse directly in circulation.

• Globin is metabolized; amino acids are recycled.

• Iron binds to transferrin and returns to liver stores.

• Hem is converted to bilirubin, which binds to albumin (making it insoluble).

What happens to bilirubin during metabolism in the liver?

• Bilirubin dissociates from albumin and enters hepatocytes.

• It is conjugated with two glucuronic acids by UDP-glucuronyl transferase.

• Conjugated bilirubin is water-soluble and secreted into bile canaliculi and bile.

• This is an energy-dependent process.

• Bile is secreted into the duodenum to aid digestion.

• Intestinal bacteria degrade bilirubin to urobilinogen:

  • 80% oxidized to stercobilin and excreted in feces.

  • 20% enters circulation and is excreted in urine.

Why does bilirubin accumulate in neonatal jaundice?

• Because bilirubin glucuronyl transferase is low at birth, especially in premature babies.

When does bilirubin glucuronyl transferase reach adult levels in newborns?

• Around 4 weeks after birth.

What type of bilirubin is increased in neonatal jaundice?

Unconjugated bilirubin.

What serious complication can result from elevated unconjugated bilirubin exceeding albumin’s binding capacity?

• It can diffuse into the basal ganglia causing toxic encephalopathy.

How is neonatal jaundice treated?

• By exposing the newborn’s skin to blue fluorescent light, which converts bilirubin into more polar and water-soluble isomers that can be excreted into bile without conjugation to glucuronic acid

What causes haemolytic jaundice?

• Excessive red blood cell (RBC) lysis producing bilirubin faster than the liver can conjugate it.

What happens to bilirubin levels in the blood during haemolytic jaundice?

• Increased unconjugated (indirect) bilirubin.

What changes occur in urine during haemolytic jaundice?

• Increased urobilinogen,

• no bilirubin in urine, 

• urine color remains normal.

How is the stool affected in haemolytic jaundice?

• Stool color remains normal.

What causes hepatocellular jaundice?

• Liver damage (e.g., hepatitis) leading to low conjugation efficiency and poor secretion of conjugated bilirubin into bile.

What bilirubin changes occur in the blood with hepatocellular jaundice?

• : Increased levels of both unconjugated (indirect) and conjugated (direct) bilirubin.

• ALT and AST levels are elevated

What are the urine findings in hepatocellular jaundice?

Bilirubin is present in urine, causing yellowish-brown urine color.

How is stool affected in hepatocellular jaundice?

• Stool color is normal to pale due to low stercobilin.

What causes obstructive (post-hepatic) jaundice and what happens to conjugated bilirubin levels in the blood?

• Caused by bile duct obstruction preventing conjugated bilirubin from passing into the intestine.

• This leads to increased conjugated (direct) bilirubin circulating in the blood.

Which enzymes are elevated in obstructive jaundice? blood

• (GGT) and (ALP) are markedly elevated;

• ALT is normal or mildly elevated.

• Increased conjugated (direct) bilirubin.

What are the urine findings in obstructive jaundice?

• Bilirubin is present in urine; urobilinogen is reduced or absent in complete obstruction; urine is yellowish-brown.

How is stool affected in obstructive jaundice?

• Stool is pale due to low stercobilin.

What is hepatitis?

• Inflammation of the liver.

What characterizes acute hepatitis?

• Mild or transient changes in liver function with quick onset inflammation lasting a short time; patients usually recover.

What is chronic hepatitis?

• Liver damage developing over years without acute symptoms, potentially leading to fibrosis and cirrhosis.

What types of liver injury can viral hepatitis cause?

Both acute and chronic liver injury.

Name some common viral causes of hepatitis.

• Hepatitis A

• Hepatitis B

• Hepatitis C

• Hepatitis D

• Hepatitis E

• Epstein-Barr virus

• Yellow fever virus

• Herpes Simplex virus

• Cytomegalovirus

How is Hepatitis A transmitted?

• Enterically via faecal-oral spread.

What are key features of Hepatitis A?

• RNA virus

• Short incubation period

• Sporadic or endemic

• Acute, self-limiting hepatitis

• No chronic or carrier state

• Largely asymptomatic with virus-specific immunity

• Mild illness with usually full recovery

Does Hepatitis A progress to chronic liver disease?

No, it does not.

What is the treatment and prevention for Hepatitis A?

• No specific treatment

• Prophylactic anti-HAV immunisation for:
  • Travellers
  • High-risk groups
  • Chronic Hepatitis C patients

What are the key features of Hepatitis E? SAC CLIP

• Similar to Hepatitis A

• Acute, self-limited illness

• No progression to chronic liver disease

• More severe liver damage than Hep A

• Can be complicated by cholestasis

• Person-to-person spread is low

• Mainly transmitted via infected water supplies

• Possible zoonotic transmission (pigs and sheep)

• High fatality rate in pregnant women, especially in 3rd trimester

• Immunity is not lifelong (unlike Hep A)

What treatments are available for Hepatitis E?

• No specific treatment

• Antiviral Ribavirin used in major liver disease

• Vaccine currently in clinical trials

How is Hepatitis B transmitted and detected?

• Transmitted via blood, blood products, sexual contact, and vertically (in utero)

• Detected by hepatitis B surface antigen (HBsAg) in serum

What is the nature and outcome of Hepatitis B infection?

• DNA virus with long incubation (1–6 months)

• Liver damage caused by antiviral immune response

• carries exist

• Variable outcome: most adults recover with immunity; chronic infection if HBsAg persists ≥ 6 months

Treatment : How does Interferon alpha treat chronic Hepatitis B?

• Mimics interferons produced naturally by virus-infected cells.

• Binds to cell surface receptors on infected cells.

• Stimulates proteins that inhibit viral mRNA translation.

• Inhibits viral replication inside hepatocytes.

• Enhances clearance of the virus from hepatocytes

When are nucleoside analogues used in treating chronic Hepatitis B?

• Used if interferon alpha is unsuccessful

• poorly tolerated

• is contraindicated

How is Hepatitis C transmitted and what type of virus is it?

• Spread by blood and blood products

• Possibly sexually transmitted

• RNA virus

• Known as non-A, non-B hepatitis

What are key features and outcomes of Hepatitis C infection?

• Short incubation period

• Often asymptomatic

• Disease course waxes and wanes

• 75–85% develop chronic infection

• 5–15% of chronic cases develop cirrhosis within 20 years

• No vaccine available

What treatments are used for Hepatitis C?

• Treatment duration: 24 to 48 weeks depending on strain and disease stage

• Sofosbuvir: uridine nucleotide analogue that inhibits HCV polymerase and viral replication

• Sofosbuvir used with peg-interferon alfa and ribavirin, or ribavirin alone

What are the key characteristics of Hepatitis D?

• Most severe form of viral hepatitis

• Defective RNA virus

• Requires Hepatitis B surface antigen (HBsAg) to replicate

• Infects only those already infected with Hepatitis B virus (HBV)

How is Hepatitis D transmitted and how common is co-infection?

• Spread through blood-to-blood or sexual contact

• Can co-infect simultaneously with HBV or superinfect chronic HBV patients

• About 5% of chronic HBV patients (~12 million people) have HDV antibodies

What are the outcomes of Hepatitis D infection?

• Approximately 50% develop chronic HDV infection (>6 months)

• More aggressive than other viral hepatitis types

• Acute infection can cause acute liver failure

• Persistent infection often leads to cirrhosis, hepatocellular carcinoma, or liver failure