Liver and Pancreas Pathology

Question 1

Describe the process of bilirubin formation and excretion

Answer 1

• Breakdown of red cells occurs extravascularly in macrophages in the spleen and liver
• Bilirubin released by heme breakdown is hydrophobic and therefore bound to albumin before being carried to the liver
• In the liver, bilirubin is conjugated with glucuronic acid by UDP glucuronyl transferase
• Conjugated bilirubin is water soluble and is secreted by hepatocytes into the bile canaliculi
• Bile then enters the duodenum and converted to urobilinogen
• 10% of urobilinogen is reabsorbed into the blood and excreted from the kidneys as urobilin
  
  • Light yellow colour
• 90% of urobilinogen remains in the intestines and excreted as stercobilin in feces
  - Dark brown colour

Question 2

Outline the anabolic function of the liver

Answer 2

• Albumin - measured clinically
• Glycogen
• Numerous coagulation factors - measured clinically
• Haematopoiesis in fetus

Question 3

Outline the catabolic function of the liver

Answer 3

• Drugs - cytochrome P450
• Hormones
• Haemoglobin - measured clinically
• Poisons - cytochrome P450
• Can take over removal of aged red cells after splenectomy

Question 4

What tests can be conducted to measure liver function

Answer 4

• Hypoalbuminaemia reflects severe liver dysfunction
• Prolonged prothrombin time (INR) - failure to produce coagulation factors
• ALT
• ALP
• Gamma GT

Question 5

What does high ALT show

Answer 5

• Alanine aminotransferase (ALT)
• Released by inflamed or damaged hepatocytes into blood
• Raised in hepatitis

Question 6

What does high ALP show

Answer 6

• Alkaline phosphate (Alk Phos)
• Enzyme present in the liver canaliculi, bile ducts and bone
• Normally higher in growing bone - up to 20 years old
• Raised in liver disease with cholestasis
  
  • Biliary obstruction, cirrhosis, liver metastases
  • Drugs
• Raised in bone disease
  
  • Bone metastases, bone fractures - can compress bile duct
  • Osteomalacia, hyperparathyroidism
  • Paget’s disease of bone - failure to replace old bone with new bone

Question 7

What does high gamma GT show

Answer 7

• Enzyme present in bile duct cells and some in hepatocytes
• Raised in bile duct obstruction, cirrhosis, liver metastases, drugs
• Raised in alcoholism
  
  • Could be raised in alcoholism with no liver damage

Question 8

List potential causes of jaundice

Answer 8

• Hepatitis
• Common bile duct stones
• Carcinoma of the head of the pancreas
• Liver metastases
• Late stages of cirrhosis

Question 9

Describe pre-hepatic jaundice

Answer 9

• Too much bilirubin production
• Eg. Haemolytic anaemia (sickle cell anaemia) - breakdown lots of RBC
• Mild jaundice
• Urine colour normal but stools may be very dark
• No pruritis
• Blood test
  
  • Raised serum bilirubin
  • Increased urinary urobilinogen
  • No conjugated bilirubin in urine

Question 10

Describe intra-hepatic jaundice

Answer 10

• Failure of hepatocytes to conjugate and/or secrete most of the bilirubin presented to them
• Eg. Hepatitis, cirrhosis
• Partial conjugation - not all excreted into bile
• Stasis within the liver is called cholestasis - bile stuck in liver
• Moderate jaundice
• Stools normal but urine dark
• No pruritis usually
• Blood test
  
  • Raised serum bilirubin
  • Increase in unconjugated bilirubin levels
  • Normal urinary urobilinogen
    
    • Conjugated bilirubin present in urine

Question 11

Describe post-hepatic jaundice

Answer 11

• Failure of the biliary tree to convey the conjugated bilirubin to the duodenum
• Eg. Biliary tree obstruction
• Inability to secrete bile salts leads to itching (pruritis)
• Severe jaundice
• Stools pale and urine dark
• Blood test
  
  • Raised serum bilirubin
  • Decreased urinary urobilinogen - as bilirubin does not enter GI system
  • Conjugated bilirubin present in urine

Question 12

How is conjugated bilirubin seen in urine

Answer 12

• Conjugated bilirubin is water soluble - if levels are high in blood, then it will be excreted in urine
• Turns the urine a dark yellow colour
• Can be measured with a dipstick

Question 13

State causes of hepatitis

Answer 13

• Viral - hepatitis A, B, C
• Acute alcohol intake
• Fatty liver disease - obesity leading to fat deposition and cirrhosis
• Drugs/toxins

Question 14

Describe consequences of liver failure

Answer 14

• Increased susceptibility to infections - mostly bacterial
• Increased susceptibility to toxins and drugs
• Increased blood ammonia due to failure to clear ammonia via urea cycle
  
  • Produced by colonic bacteria and deamination of amino acids
  • Causes hepatic encephalopathy - neuropsychiatric abnormalities due to liver disease

Question 15

What would be see on a blood test for hepatitis

Answer 15

• Very high serum ALT
• High serum bilirubin
• Normal albumin and INR

Question 16

Describe the consequences and progression of alcoholic liver disease

Answer 16

• Alcoholic fatty liver disease -> alcoholic hepatitis -> cirrhosis
• Damage to liver greater than its ability to regenerate
• Can lead to internal bleeding, build up of toxins in the brain (encephalopathy), ascites, liver cancer

Question 17

Describe the consequences of liver cirrhosis

Answer 17

• Pressure and occlusion of the hepatic sinusoids
  
  • Leads to portal hypertension which leads to portosystemic shunting (bypass liver in circulation)
• Pressure on the bile canaliculi and therefore reduced ability to excrete toxins, bilirubin
• Replacement of hepatocytes by fibrous tissue which leads to reduced albumin and clotting factor production

Question 18

What are symptoms of liver cirrhosis

Answer 18

• Fatigue/weakness
• Bleeding and bruising easily
• Ascites
• Swollen legs - hypoproteinaemia
• Weight loss
• Jaundice
• Haematemesis and or melaena
• Confusion, drowsiness, slurred speech - hepatic encephalopathy

Question 19

Outline how liver diseases may lead to portal hypertension and appreciate the associated pathology these may lead to

Answer 19

• Hepatic sinusoids are a low pressure system
  
  • Inflammation due to hepatitis can block sinusoids or bile ducts, thus increasing pressure
  • Hepatic arteries have high pressure so not normally compromised
• Increase in pressure in the hepatic sinusoids causes increase in portal vein pressure
• Leads to ascites due to increased hydrostatic pressure within the portal veins

Question 20

Describe the blood test seen on gallstones

Answer 20

• Serum bilirubin very high

- Raised Alk Phos and gamma GT

Question 21

Why do gallstones form

Answer 21

• Gallstones develop in the gallbladder as a result of chemical imbalances in the bile
• 80% due to excess cholesterol crystallizing and growing to form stones
• 20% due to gallstones forming from excess levels of bilirubin

Question 22

Describe what a biliary colic is

Answer 22

• Pain in the right upper quadrant that radiates to the tip of the right scapula/right shoulder
• Due to lodged gall stone in the cystic duct
• Often precipitated by eating a fatty meal
• Lasts up to 6 hours
• Not a true colic - colic is intermittent pain due to muscular contractions attempting to move past an obstruction

Question 23

What is acute cholecystitis

Answer 23

• Inflammation of the gall bladder
• If a gallstone obstructs the cystic duct, then there is stasis of the gallbladder contents - infection risk
• E. Coli normally infecting organism
• Presents with severe gall bladder pain and also is systemically unwell

Question 24

What would be seen on a blood test for liver metastases

Answer 24

• Raised Alk Phos
• Raised serum bilirubin
• Conjugated bilirubin present in urine

Question 25

Describe the causes of acute pancreatitis

Answer 25

• Alcohol - increases zymogen secretion from acinar cells and decreases bicarbonate and fluid from the ducts
  
  • Pancreatic juices become thick, which can form a plug and block the duct
  • Leads to auto-digestions and cell destruction
• Gallstones - gallstone at the sphincter of oddi can block pancreatic secretions and activates zymogens

Question 26

Describe the pathogenesis of acute pancreatitis

Answer 26

• Acute pancreatitis due to premature activation of pancreatic proteases in the pancreas
• Proteases auto-digest the pancreas and the retroperitoneum

Question 27

Describe the blood test for acute pancreatitis

Answer 27

• Raised serum amylase or serum lipase

- CT scan may be used in moderate/severe cases to look for pancreatic necrosis/pseudocyst

Question 28

Describe the treatment for acute pancreatitis

Answer 28

• No specific treatment

- Analgesia (pain relief) - fluid resuscitation needed as patients lose many litres of fluid in their retroperitoneum

Question 29

Describe the causes and consequences of chronic pancreatitis

Answer 29

• Chronic pancreatitis due to repeated low grade pancreatitis that causes pancreatic fibrosis
• Due to alcohol abuse, cystic fibrosis, tumours
  
  • Cystic fibrosis - pancreatic secretions become thick and sticky
• Pancreas becomes calcified and patients suffer severe epigastric and back pain that leads to opiate addiction
• Both exocrine and endocrine gland fail due to fibrosis

Question 30

Describe the presentation of carcinoma of the pancreas

Answer 30

• Anorexia, malaise, fatigue
• Significant weight loss
• Epigastric and/or back pain
• Dark urine, pale stools, pruritis - can be due to bile duct obstruction