L15 - Hepatobiliary diseases

Question 1

Causes of Hepatocellular Damage

Answer 1

• Infectious agents
• Trauma
• Ischaemic damage
• Toxins
• Other

Question 2

Causes of Hepatocellular Damage (Infectious agents)

Answer 2

• Hepatitis A, B, C

- Infectious mononucleosis

Question 3

Causes of Hepatocellular Damage (Trauma)

Answer 3

• Surgery,

- crush injuries.

Question 4

Causes of Hepatocellular Damage (Ischaemic damage)

Answer 4

• Oxygen supply problem
• Cardiac failure/ myocardial infarction
• Shock and acute hypotension

Question 5

Causes of Hepatocellular Damage (Toxins)

Answer 5

• Drugs (alcohol, paracetamol)

- carbon tetrachloride

Question 6

Other causes of Hepatocellular Damage

Answer 6

• Infiltration e.g. by Tumour

- Autoimmune and Inflammatory conditions

Question 7

Intrahepatic causes of cholestasis

Answer 7

•   Some forms of viral hepatitis
•   Primary biliary cholangitis
•   Space occupying lesions e.g. malignancies
•   Drugs (steroids/chlorpromazin)
•   Cirrhosis
•   Biliary atresia

Question 8

Extrahepatic causes of cholostasis

Answer 8

•   Gallstones
•   Tumours/malignancies
•   Biliary atresia (absence or narrowing)
•   Cholangitis
•   inflammation

Question 9

Markers of tissue damage for liver

Answer 9

ALT/AST, ALP, GGT

Question 10

Marker of metabolic/excretory function

Answer 10

Bilirubin

Question 11

Marker of synthetic function

Answer 11

Albumin, Prothrombin time

Question 12

NAFLD

Answer 12

•   Common.
•   Association with diabetes and obesity.
•   Very common cause of abnormal liver function test, and can progress to more serious forms
•   Risk for the development of advanced fibrosis and cirrhosis
•   Has reached epidemic proportions; considered to be the most common cause of chronic liver disease in Western countries.
•   ~20 to 30% of adults in the West affected.
•   More than double this number in the obese and in diabetics.

Question 13

NAFLD in Children

Answer 13

•  More and more children are found to have the disorder

*  The development of cirrhosis from NASH in children as young as the early teens has also been described.

Question 14

When to suspect NAFLD

Answer 14

• Abnormal LFTs with no clear explanation (infections, evidence of clinically significant alcohol abuse etc) and especially in those with risk factors:
• Obesity (raised BMI)
• Type 2 diabetes mellitus, or hyperlipidaemia;

Question 15

Tissue Types in The Pancreas

Answer 15

•  Endocrine: Islets of Langerhans (α~20-30%, β~60-70%, δ~2-8%)

–  Islet cells: Insulin (β), glucagon (α), somatostatin( δ), gastrin(δ)

•  Exocrine functions

–  ~1.5 to 2 L of pancreatic juice/day

•  Rich in HCO3-, épH (up to pH 8.3) •  Rich in digestive enzymes

Question 16

Acute pancreatitis

Answer 16

•  Characterised by auto-digestion of the pancreas.
•  Losses of large volumes of fluid into tissues and peritoneal cavity
•  Mortality in severe attacks is high: 20-50%.
•  In mild forms, 1-5% mortality.
•  Recovery usually complete after 1st attack, but risk of subsequent attacks is increased

Question 17

Acute Pancreatitis - pathological changes

Answer 17

•  Auto-digestion.

• Haemorrhage of pancreas
• Pancreatic fat necrosis

•  Release of enzymes into peritoneal cavity and blood stream.

•  Fluid accumulates in the peritoneal cavity, results in lesscirculating volume.
- Severe abdominal pain - Hypotension & shock

Question 18

Acute Pancreatitis (most common predisposing factors)

Answer 18

• Alcoholism: Can be precipitated by heavy bout of drinking, e.g. 20-24h later
• Cholestasis (Biliary tract disease): Especially if due to gallstones: present in 30-50% Bilirubin may be raised.

Question 19

Acute Pancreatitis (high risk predisposing factors)

Answer 19

• Hyperparathyroidism/hypercalcaemia
• Hypertriglyceridaemia: ~20% of alcoholics with pancreatitis have hypertriglyceridemia
• Oestrogen use + high triglycerides

Question 20

Acute Pancreatitis (additional risk factors for obstuction of duct)

Answer 20

•   Surgery/procedures involving or near the pancreas
•   Mumps
•   Drugs (diuretics, antibiotics)

Question 21

Measurement of amylase & lipase

Answer 21

•   Pancreatic enzymes released are absorbed into the blood stream
•   Amylase
•   A hydrolase
•   Catalyzes hydrolysis of starch and glycogen.
•   Major sources: pancreas and salivary glands
•   Analysis is almost exclusively for investigation of acute pancreatitis.
•   Typically rises 5X or more

Question 22

Amylase

Answer 22

• Relatively low MW: 50-55 kDa; cleared by the kidney.

- Levels rise 5-12 h after onset of attack, peak at 24h, return to normal by 2-3 days.

Question 23

Other disorders associated with elevated levels of amylase

Answer 23

•   Renal failure
•   Macroamylasaemia (1-2% frequency; Ig-amylase complex)
•   Salivary gland lesions (mumps, parotitis).

Question 24

Pancreatic Lipase

Answer 24

•   Hydrolyzes triglyceride to fatty acids and 2-monoglyceride.
•   Acts on emulsified fats.
•   As for amylase, measurement of activity almost exclusively in context of acute pancreatitis.
•   Rises as quickly as amylase, but remains elevated for 3-5 days.
•   More specific than amylase.
•   Three isoenzyemes. L2 considered most specific/sensitive.

Question 25

Chronic Pancreatitis

Answer 25

• Chronic pancreatic inflammation; loss of functional tissue
• Symptoms develop over several years
• Most common cause is long-term alcohol abuse, or recurrent bouts of acute pancreatitis
• Complications arise from pancreatic insufficiency (Mal-absorption, Greasy bulky stools, Weight loss, Vitamin deficiencies)
• Amylase/lipase less often elevated, especially in between acute attacks. Also have a decreased acinar cell mass due to chronic damage.
• increased risk of pancreatic cancer

Question 26

Pancreatic Insufficiency and Cystic Fibrosis

Answer 26

• Cystic Fibrosis is an important cause of pancreatic insufficiency and malabsorption in children.
• Autosomal recessive disease.
• 1 in 22 Caucasians are carriers. Incidence is 1:2000 live births.
• Gene on chromosome 7 codes for protein forming a chloride conductance channel called the cystic fibrosis transmembrane regulator.
• When pancreatic ducts are blocked by thick secretions , this can cause progressive fibrosis and atrophy of exocrine glands