Module 5 Part 1 - Hepatobiliary Disease Flashcards
Causes of Hepatocellular Damage
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
Causes of Cholestasis
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
Progression of Liver Disease
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)
Liver Functions Tests
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
Cholestasis vs Hepatocellular Damage
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
Progression of Liver Disease - Enzyme Abnormalities
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
Fatty Liver Disease
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
Non-Alcoholic Fatty Liver Disease (NAFLD)
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
Fat Accumulation in Cells
Occurs in the cytoplasm of a cell
Multiple small droplets
Becomes larger and pushes the nucleus to one side
When to Suspect NAFLD
Abnormal LFTs with no clear explanation
Obesity (raised BMI)
Type 2 diabetes mellitus or hyperlipidemia
Pancreatic Functions - Endocrine and Exocrine
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
Pancreatitis
Inflammation of the pancreas Types: - acute - relapsing/recurrent (acute/chronic) - chronic (irreversible)
Acute Pancreatitis - Pathological Changes
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
Causes/Risk Factors of Acute Pancreatitis
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)
Tests Related to Risk Factors for Pancreatitis
LFT - bilirubin, ALP, GGT may be raised, ALT/AST may also be raised
Calcium
Triglycerides
Tests Related to the Consequences of an Attack from Pancreatitis
U & E - to check renal function
Blood gases - to check pulmonary function which could be compromised
Amylase
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
Pancreatic Lipase
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)
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
- 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
Pancreatic Insufficiency and Cystic Fibrosis
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)
Differences Between Cholestasis, Cholecystitis, and Cholilithiasis
Cholestasis - liver disease caused when the flow of bile from the liver is blocked
Cholecystitis - inflammation of the gall bladder
Cholilithiasis - formation of gallstones
