Module 5 Part 1 - Hepatobiliary Disease

Question 1

Causes of Hepatocellular Damage

Answer 1

Infectious agents
- hepatitis A, B, C
Trauma
Ischaemic damage
- oxygen supply problem
- cardiac failure/myocardial infarction
- shock and acute hypotension
Toxins
- drugs
Others
- infiltration e.g. by tumor
- autoimmune and inflammatory conditions
- genetic causes

Question 2

Causes of Cholestasis

Answer 2

Cholestasis - impairment of the flow of bile, inflammation of bile ducts
Causes can be intrahepatic or extrahepatic
Intrahepatic
- some form of viral hepatitis
- primary biliary cholangitis
- space occupying lesions (e.g. malignancies)
- drugs
- cirrhosis
- biliary atresia
Extrahepatic
- gallstones
- tumors/malignancies (this and gallstones most common among this group)
- biliary atresia (absence of narrowing)
- cholangitis
- inflammation

Question 3

Progression of Liver Disease

Answer 3

Acute damage or chronic injury
- entry point for liver disease
- acute damage is usually recovered by can become chronic
Chronic injury then undergoes fibrosis
- always present as a healing adaptation to injury
Fibrosis followed by cirrhosis
- loss of functioning tissue mass
This can then lead to death and encephalopathy (brain disease)

Question 4

Liver Functions Tests

Answer 4

Test for:
Synthetic function - albumin, prothrombin time (measures coagulation factors 2, 7, 10. Vit K dependent)
Metabolic/excretory function - bilirubin
Tissue damage - ALT, AST, ALP, GGT

Question 5

Cholestasis vs Hepatocellular Damage

Answer 5

Cholestasis
- elevations in ALP
- elevations in bilirubin
- small rises in ALT/AST
- if GGT is normal, rise in ALP unlikely to be of hepatic origin
Hepatocellular Damage
- elevation in ALT
- elevation in GGT
- elevation in AST (not very specific)
- smaller rises in ALP
Bilirubin may be raised in either scenario

Question 6

Progression of Liver Disease - Enzyme Abnormalities

Answer 6

Acute damage - abnormal ALT/AST/GGT and/or ALP/Bil/GGT
In active phases may have increased ALT/AST, GGT, ALP, Bil
- active phases include chronic injury, fibrosis, cirrhosis
At cirrhosis - decreases in PTT and albumin, beta-gamma fusion
Encephalopathy - usually accompanied with elevated ammonia

Question 7

Fatty Liver Disease

Answer 7

In fatty liver disease, liver becomes
- enlarged
- pale
- filled with fat deposits
Caused by toxins
- e.g. alcohol
Can also be caused by metabolic disturbances
- metabolic syndrome
- diabetes
- obesity

Question 8

Non-Alcoholic Fatty Liver Disease (NAFLD)

Answer 8

Also known as liver steatosis or hepatosteatosis
Can range from mild liver steatosis (fat) to non-alcoholic steatohepatitis (NASH)
NASH: inflammation/fibrotic infiltration
- can lead to cirrhosis with irreversible scarring
- leads to increased cancer risk

Question 9

Fat Accumulation in Cells

Answer 9

Occurs in the cytoplasm of a cell
Multiple small droplets
Becomes larger and pushes the nucleus to one side

Question 10

When to Suspect NAFLD

Answer 10

Abnormal LFTs with no clear explanation
Obesity (raised BMI)
Type 2 diabetes mellitus or hyperlipidemia

Question 11

Pancreatic Functions - Endocrine and Exocrine

Answer 11

Endocrine
- islets of langerhans (a ~20-30%, b ~60-70%, g ~2-8%)
- glucagon secreted by alpha cells, insulin by b cells and somatostatin and gastrin by gamma cells
Exocrine functions
- makes ~1.5-2L of pancreatic juice/day
- this juice is rich in HCO3- (increased pH)
- rich in digestive enzymes such as:
- trypsinogen, chymotrypsinogen, carboxypeptidase and
- other proteases such as elastase and collagenase

Question 12

Pancreatitis

Answer 12

Inflammation of the pancreas
Types:
- acute
- relapsing/recurrent (acute/chronic)
- chronic (irreversible)

Question 13

Acute Pancreatitis - Pathological Changes

Answer 13

Characterised by autodigestion of the pancreas
Leads to:
- haemorrhage of pancreas
- pancreatic fat necrosis
There is a release of enzymes into the peritoneal cavity and bloodstream
Fluid accumulates in the peritoneal cavity resulting in a decrease of circulating volume
- severe abdominal pain
- hypotension and shock
Can also lead to the formation of pseudo-cysts (cysts formed from autodigestion of pancreatic tissue), abscess formation

Question 14

Causes/Risk Factors of Acute Pancreatitis

Answer 14

Commonly due to obstruction of the pancreatic duct
Predisposing factors
- alcoholism
- cholestasis (biliary tract disease): especially if due to gallstones
Can significantly increase the risk:
- hyperparathyroidism/hypercalcaemia
- hypertriglyceridemia
Additional risk factors for obstruction of the pancreatic duct:
- surgery involving or near the pancreas
- mumps
- drugs (diuretics, antibiotics, antimetabolites)

Question 15

Tests Related to Risk Factors for Pancreatitis

Answer 15

LFT - bilirubin, ALP, GGT may be raised, ALT/AST may also be raised
Calcium
Triglycerides

Question 16

Tests Related to the Consequences of an Attack from Pancreatitis

Answer 16

U & E - to check renal function

Blood gases - to check pulmonary function which could be compromised

Question 17

Amylase

Answer 17

Its a hydrolase
Catalyses hydrolysis of starch and glycogen
Major source: pancreas and salivary glands
Small amounts in skeletal muscle and fallopian tubes
Analysis is almost exclusively for investigation of acute pancreatitis
Typically rises 5x or more
Levels rise 5-12h after onset of attack, peak at 24h, return to normal by 2-3 days
Diseases associated with elevated levels:
- renal failure
- macroamylasemia
- salivary gland lesions
- perforated peptic ulcer
- intestinal obstruction
- acute appendicitis

Question 18

Pancreatic Lipase

Answer 18

Hydrolyses triglyceride to fatty acids and 2-monoglyceride
Acts on emulsified fats
Rises as quickly as amylase, but remains elevated for 3-5 days
More specific than amylase
- not influenced by salivary gland disorders
- however, may also be raised in some of the other intestinal disorders (perforated peptic ulcer, intestinal obstruction and acute appendicitis)

Question 19

Chronic Pancreatitis

Answer 19

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
- malabsorption
- greasy bulky stools
- weight loss
- vitamin deficiency
- may eventually develop diabetes mellitus
Amylase/lipase less often elevated, especially in between acute attacks
Decreased acinar cell mass due to chronic damage
Patients at increased risk of pancreatic cancer

Question 20

Pancreatic Insufficiency and Cystic Fibrosis

Answer 20

Cystic Fibrosis is an important cause of pancreatic insufficiency and malabsorption in children
Autosomal recessive disorder
Gene on chromosome 7 codes for protein forming a chloride conductance channel called the cystic fibrosis transmembrane regulator
Results in thickened secretions of the pancreas
The secretions block the exocrine movement of the digestive enzymes into the duodenum and result in irreversible damage to the pancreas often with painful inflammation (pancreatitis)

Question 21

Differences Between Cholestasis, Cholecystitis, and Cholilithiasis

Answer 21

Cholestasis - liver disease caused when the flow of bile from the liver is blocked
Cholecystitis - inflammation of the gall bladder
Cholilithiasis - formation of gallstones