L15 - Hepatobiliary diseases Flashcards
Causes of Hepatocellular Damage
- Infectious agents
- Trauma
- Ischaemic damage
- Toxins
- Other
Causes of Hepatocellular Damage (Infectious agents)
- Hepatitis A, B, C
- Infectious mononucleosis
Causes of Hepatocellular Damage (Trauma)
- Surgery,
- crush injuries.
Causes of Hepatocellular Damage (Ischaemic damage)
- Oxygen supply problem
- Cardiac failure/ myocardial infarction
- Shock and acute hypotension
Causes of Hepatocellular Damage (Toxins)
- Drugs (alcohol, paracetamol)
- carbon tetrachloride
Other causes of Hepatocellular Damage
- Infiltration e.g. by Tumour
- Autoimmune and Inflammatory conditions
Intrahepatic causes of cholestasis
- Some forms of viral hepatitis
- Primary biliary cholangitis
- Space occupying lesions e.g. malignancies
- Drugs (steroids/chlorpromazin)
- Cirrhosis
- Biliary atresia
Extrahepatic causes of cholostasis
- Gallstones
- Tumours/malignancies
- Biliary atresia (absence or narrowing)
- Cholangitis
- inflammation
Markers of tissue damage for liver
ALT/AST, ALP, GGT
Marker of metabolic/excretory function
Bilirubin
Marker of synthetic function
Albumin, Prothrombin time
NAFLD
- 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.
NAFLD in Children
- 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.
When to suspect NAFLD
- 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;
Tissue Types in The Pancreas
• 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
Acute pancreatitis
- 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
Acute Pancreatitis - pathological changes
• 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
Acute Pancreatitis (most common predisposing factors)
- 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.
Acute Pancreatitis (high risk predisposing factors)
- Hyperparathyroidism/hypercalcaemia
- Hypertriglyceridaemia: ~20% of alcoholics with pancreatitis have hypertriglyceridemia
- Oestrogen use + high triglycerides
Acute Pancreatitis (additional risk factors for obstuction of duct)
- Surgery/procedures involving or near the pancreas
- Mumps
- Drugs (diuretics, antibiotics)
Measurement of amylase & lipase
- 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
Amylase
- 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.
Other disorders associated with elevated levels of amylase
- Renal failure
- Macroamylasaemia (1-2% frequency; Ig-amylase complex)
- Salivary gland lesions (mumps, parotitis).
Pancreatic Lipase
- 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.
Chronic Pancreatitis
- 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
Pancreatic Insufficiency and Cystic Fibrosis
- 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
