Session 7 - Liver And Pancreas Pathology Flashcards
What veins lead into the hepatic portal vein?
Superior mesenteric vein Inferior mesenteric vein Splenic vein Right gastric vein Left gastric vein
What arteries arise from the coeliac trunk?
Left gastric artery
Common hepatic artery
Splenic artery
Where does the break down of red blood cells occur?
Break down of red blood cells occurs extravascularly in macrophages in the spleen and liver.
How is bilirubin transported to the liver?
Bound to albumin (because bilirubin is hydrophobic) and transported in the blood stream.
What happens to the bilirubin once it reaches the liver?
It is conjugated with glucoronic acid by UDP glucuronyl transferase. Conjugated bilirubin is water soluble and is secreted by hepatocytes into bile canaliculi.
What molecules does the liver produce?
Albumin
Glycogen
Numerous coagulation factors
Also responsible to haematopoiesis in foetus (can be revived in adults if bone marrow is failing)
Give two examples of assay results which show decreased anabolism in the liver.
Hypoalbuminaemia - not enough albumin being produced.
Prolonged prothrombin time (INR) - not enough coagulation factors being produced.
Both reflect severe liver dysfunction
What molecules does the liver catabolise?
Drugs (cytochrome P450) Hormones Haemoglobin Poisons (cytochrome P450) Can take over the removal of red cells after a splenectomy
What is jaundice?
Yellowing of the skin and sclera due to build up of bilirubin in the blood and tissues.
What causes pre-hepatic jaundice?
Too much bilirubin, e.g. due to haemolytic anaemia
What causes intra-hepatic jaundice?
Failure of hepatocytes to conjugate and/or secrete most of the bilirubin presented to them. E.g. due to hepatitis, cirrhosis.
Cholestasis
What is cholestasis?
The reduction or stoppage of bile flow from the liver to the duodenum. Disorders of the liver, bile duct or pancreas can cause cholestasis.
What causes post-hepatic jaundice?
Failure of the biliary tree to convey conjugated bilirubin to the duodenum, e.g. biliary tree obstruction
Is conjugated bilirubin soluble?
Yes
What affect will high serum levels of conjugated bilirubin have on the urine?
Conjugated bilirubin is water soluble so if serum levels are high it will be excreted in the urine and turn the urine dark yellow (bilirubinuria).
The amount of bilirubin in urine can be measured with a dipstick.
Will excess urobilinogen noticeably colour the urine?
No, but it can be measured using a dipstick
In post-hepatic jaundice, the inability to secrete bile salts leads to what?
Pruritis (itching)
Describe what would be found in pre-hepatic jaundice.
Mild jaundice (lemon tinge)
Stools may be very dark
Urine colour normal
No pruritis
Raised serum bilirubin
Increased urinary urobiliogen
No conjugated bilirubin present in the urine
In the colon, urobilinogen is converted to what?
Urobilinogen is converted to stercobilin by bacteria in the colon. Stercobilin give stool a dark brown colour.
Describe what would be found in intra-hepatic jaundice.
Moderate jaundice
Stools normal
Urine dark
No pruritis usually
Raised serum bilirubin
Normal urinary urobiliogen
Conjugated bilirubin present in urine
Describe what would be found in post-hepatic jaundice.
Severe jaundice (green tinge)
Stools pale
Urine dark
Pruritis
Raised serum bilirubin
Decreased urinary urobiliogen
Conjugated bilirubin present in urine
What cells release alanine aminotransferase (ALT)?
Inflamed or damaged hepatocytes
Where is the enzyme alkaline phosphatase (Alk Phos) found?
Liver canaliculi
Bile ducts
Bone
What pathology can cause a raised Alk Phos?
Bone disease
Liver disease - particularly with cholestasis or biliary obstruction
When would a raised Alk Phos be normal?
When there is growing bone
The enzyme gamma-glutamyl transferase (Gamma GT) is present in what cells?
Bile duct cells and to a lesser extent in hepatocytes.
What can caused a raised Gamma GT level?
Bile duct obstruction
Also induced by alcohol - raised level may indicate alcoholism
What are the possible causes of a raised ALT?
Hepatitis:
- viral (hepatitis A, B, C, etc.)
- acute alcohol intake
- fatty liver disease
- drugs/toxins
What are the possible causes of a raised Alk Phos?
Bile duct/liver disease with cholestasis:
- biliary obstruction, cirrhosis, liver metastases
- drugs
Bone disease:
- bone metastases, bone fracture
- osteomalacia, hyperparathyroidism
- Paget’s disease of bone
What are the possible causes of a raised Gamma GT?
Biliary duct obstruction/cholestasis Cirrhosis Liver metastases Drugs Alcoholism
Why is ultrasound a key investigation when looking at liver disease?
It can detect:
- biliary obstruction
- hepatic fibrosis (cirrhosis)
- fatty infiltration of the liver
- portal hypertension
- ascites
- gallstones in the gallbladder
- liver metastases
What is hepatitis?
The presence of inflamed and/or necrotic hepatocytes that cannot function normally.
What are the causes of hepatitis?
Viral (hepatitis A, B, C, etc.)
Acute alcohol intake
Fatty liver disease
Drugs/toxins
What are the consequences of liver failure?
Increased susceptibility to infections
Increased susceptibility to toxins and drugs
Increased blood ammonia due to failure to clear ammonia via the respiratory cycle. Increased ammonia causes hepatic encephalopathy.
What is hepatic encephalopathy?
A syndrome observed in patients with cirrhosis. It is a spectrum of neuropsychiatric abnormalities in patients with liver dysfunction, characterised by personality changes, intellectual impairment, and a depressed level of consciousness.
What are the symptoms of hepatitis?
Feels generally unwell, particularly if viraemic Anorexia Fever Right upper quadrant pain Dark urine Jaundice
What are the typical blood test findings in acute hepatitis?
Normal albumin and INR High serum bilirubin Conjugated bilirubin present in the urine VERY HIGH SERUM ALT Normal or very slightly raised Alk Phos Normal or very slightly raised Gamma GT
What is liver cirrhosis?
Liver fibrosis producing a shrunken hard modular liver
How does fibrosis lead to portal hypertension?
Fibrosis of the liver creates pressure and therefore occlusion of hepatic sinusoids. This causes portal hypertension which leads to portosystemic shunting.
What is portosystemic shunting?
Bypassing of the liver by the circulatory system. Can be either congenital or acquired. Acquired by cirrhosis leading to portal hypertension, which then leads to portosystemic shunting.
Portosystemic shunting diverts nutrient carrying blood away from the liver and causes oesophageal varices.
What are oesophageal varices?
Extremely dilated sub-mucosal veins in the lower third of the oesophagus, most often caused by portal hypertension due to cirrhosis.
What are the consequences of fibrosis in the liver?
Portal hypertension
Reduced ability to excrete toxins, bilirubin, etc (due to increased pressure on bile canaliculi)
Reduced albumin and clotting factor production (due to replacement of hepatocytes with fibrous tissue)
What are the main causes of cirrhosis?
Alcohol
Viral hepatitis
Fatty liver disease
Idiopathic
What are the common sites for portosystemic anastomoses?
Anorectal junction
Ligamentum teres of falciform ligament
Oesophagogastric junction
What are portosystemic anastomoses?
Type of anastomoses that occurs between the veins of the portal circulation and those of systemic circulation.
What happens to portosystemic anastomoses in portal hypertension?
The anastomoses become congested and form venous dilatations. Examples of such dilatations are oesophageal varices, rectal haemorrhoids and capturing medusaes.
What are the symptoms of liver cirrhosis?
Fatigue/weakness Bleeding and bruising easily Swollen abdomen (ascites) Swollen legs (hypoproteinaemia) Weight loss Jaundice Haematemesis (vomiting blood) and/or melaena (black bloody stools) Confusion, drowsiness and slurred speech (hepatic encephalopathy)
What are the typical blood test findings in liver cirrhosis?
MAY BE NORMAL
May show:
- low albumin or prolonged INR
- raised bilirubin
- slight rise in ALT (if there is ongoing inflammation)
- Alk Phos usually normal or very mildly raised if there’s some cholestasis
- Gamma Gt may be raised (if underlying problem is alcohol)
How is liver cirrhosis treated?
It is not possible to reverse the fibrosis.
Treatment aimed at dealing with the complications.
Only ‘cure’ is liver transplant.
What are the two main causes of biliary duct obstruction?
Gallstones migrating from gallbladder into the common bile duct.
Carcinoma of the head of the pancreas.
What would the laboratory findings for post-hepatic (obstructive) jaundice show?
Tests of hepatocyte anabolism (serum albumin and INR) normal
Tests of hepatocyte inflammation/necrosis (serum ALT) normal or very slightly raised
Serum bilirubin very high
Conjugated bilirubin present in the urine
Tests for bile duct dysfunction raised (Alk Phos and Gamma GT)
What is cholangitis?
Infection in the bile ducts, life-threatening complication of bile duct obstruction. Commonest bacteria is E.Coli.
What are the causes of gallstones?
Excess cholesterol crystallises and grows to form stones
Excess levels of bilirubin
What is biliary colic?
Pain in the right upper quadrant that radiates to the tip of the right scapula/right shoulder. Not a true colic (pain is constant, not intermittent). Lasts up to 6 hours, often precipitated by eating a fatty meal.
What is cholecystitis?
Infection of the gallbladder. Caused by obstruction of the cystic duct by a gallstone leading to stasis of gallbladder contents. Usually E.Coli.
What is the difference between cholecystitis and cholangitis?
Cholecystitis - infection of gallbladder
Cholangitis - infection of bile ducts
What are the symptoms of cholecystitis?
Severe gallbladder pain
Systemically unwell and ‘toxic’
Pyrexial
Very tender over the gallbladder
Why is the liver a common site for metastases?
Blood from many organs drains into the vein via the portal vein (intestines, spleen, stomach) and the hepatic artery (breast, lung, etc.)
What are the laboratory findings in liver metastases?
Raised serum bilirubin Conjugated bilirubin present in urine Raised Alk Phos ALT and Gamma GT may be slightly raised Serum albumin and INR usually normal
What is pancreatitis?
Inflammation of the pancreas, can be acute or chronic.
What are the causes of acute and chronic pancreatitis?
Acute pancreatitis - premature activation of pancreatic proteases in the pancreas itself. These proteases autodigest the pancreas and retroperitoneum.
Chronic pancreatitis - repeated low grade pancreatitis that causes pancreatic fibrosis, due to alcohol abuse.
What happens in chronic pancreatitis?
Pancreas becomes calcified and patients suffer severe epigastric and back pain. Can lead to opiate addiction and even suicide. Both the exocrine and endocrine pancreas fail due to fibrosis.
What is erythema ab igne?
Skin reaction caused by repeated exposure to heat, e.g. repeated application of hot water bottle or heat pads to treat chronic pain.
What is a pancreatic psuedocyst?
A circumcised collection of fluid rich in pancreatic enzymes, blood and necrotic tissue typically located in the lesser sac of the abdomen.
Usually a complication of pancreatitis, although can occur in children following abdominal trauma.
Explain the aetiology of acute pancreatitis.
Alcohol - alcohol enters the balance between proteolytic enzymes and protease inhibitors, thus triggering enzyme activation, autodigestion and cell destruction.
Gallstones - in biliary acute pancreatitis, outflow obstruction with pancreatic hypertension and a toxic effect of bile salts contribute to activation of pancreatic proteases.
What are the symptoms of acute pancreatitis?
Epigastric pain that goes through to the back
Vomiting
How can acute pancreatitis be diagnosed?
Raised serum amylase and serum lipase.
CT scan may be used in moderate/sever cases to look for pancreatic necrosis/pseudocyst.
History.
How is acute pancreatitis treated?
There is no treatment, can only manage the symptoms:
- analgesia
- fluid resuscitation (patients can sequester many litres of fluid in their peritoneum)
How does pancreatic cancer present clinically?
Anorexia Malaise Fatigue Significant weight loss Epigastric and/or back pain Dark urine Pale stools Pruritis
What are the common causes of jaundice?
Hepatitis (viral, drugs, acute alcohol intake) Common bile duct stones Carcinoma of the head of the pancreas Liver metastases Late stages of cirrhosis
