5.2 Liver and pancreatic disease Flashcards
What are the main functions of the liver?
- Bile production
- Carbohydrate, protein and lipid metabolism
- Protein synthesis
- Vitamin D synthesis
- Detoxification
- Vitamin and mineral storage
- Phagocytosis
What liver function tests would indicate hepatocellular damage? (2)
- Aminotransferases (ALT/AST)
* γ-Glutamyl transpeptidase (γ-GT)
What liver function tests would indicate cholestasis (bile ducts)? (2)
- Bilirubin
* Alkaline phosphatase
What liver function tests would indicate synthetic function? (3)
- Albumin
- Prothrombin time (clotting)
- Glucose
What is jaundice?
What is the main cause?
Yellow pigmentation of the skin and sclera caused by accumulation of bilirubin in tissue
Caused by the disruption of normal bilirubin metabolism eg. uptake, transport, conjugation and/or excretion
What are the normal levels of bilirubin?
What levels of bilirubin are indicative of jaundice?
Normal range <22 umol/L
Clinically detectable when bilirubin >40 umol/L
What are the 3 ways in which we can classify the type of jaundice?
1) Prehepatic (haemolytic)
2) Hepatic (hepatocellular)
3) Post hepatic (obstructive)
What are the products of haemoglobin breakdown?
How are these metabolised in the liver?
What are the 3 fates of the final product following oxidation by bacteria?
Haemoglobin breaks down to heme (hame➞biliverdin ➞biliruben) and globin (breaks into amino acids)
1) biliruben entering liver is unconjugated
2) In liver: bilirubin is conjugated to glucuronic
acid by UDP-glucuronosyltransferase
3) this forms the conjugated version (water soluble) which is released in bile into duodenum and small intestine
5) In the small intestine, it is oxidised by bacteria to urobilinogen
Urobilinogen can do 3 things:
1) some is reabsorbed
2) some is excreted via kidney as urobilin
3) remaining turned into stercobilinogen and furthur oxidised into stercobilin which is excreted in the feces
What give urine its yellow colour and faeces its brown colour?
urine: yellow because of urobilin
faeces: brown because of stercobilin
Explain the relationship between bilirubin and bile
Bile salts aid in digestion and Bilirubin is the main pigment in bile
How is the unconjugated bilirubin transported in the blood?
bound to albumin (it then reaches liver)
How is pre-hepatic jaundice (haemolytic) characterised?
Characterised by excessive haemolysis ➞ liver unable to cope with excess bilirubin
What 3 lab findings would indicate pre-hepatic jaundice and why?
1) Unconjugated hyperbilirubinaemia ➞ excess RBC break down, so increased unconjugated bilirubin entering liver
2) Reticulocytosis ➞ hemolysis results in increased production of reticulocytes by bone marrow (reticulocytes -= immature RBCs)
3) Anaemia ➞ due to excess haemolysis
Give 3 causes of pre-hepatic jaundice for the following:
Inherited
Aquired
Congenital hyperbilirubinaemias
Inherited: RBC membrane defects, haemoglobinopathies, metabolic defects
Aquired: Infection, drugs, mechanical
Congenital hyperbilirubinaemias (in order of most-least common)
1) Gilberts syndrome ➞ decreased activity of UGT
2) Crugler-Najjar syndrome ➞ absent UGT
3) Dubin-Johnson syndrome ➞ un-excretable bilirubin
How is hepatocellular jaundice (parenchymal) characterised?
Characterised by deranged hepatocyte function ➞ cell necrosis which causes inabilty to metabolise or excrete bilirubin
+ there is an element of cholestasis (reduction or stoppage of bile flow)
What 4 lab findings would indicate hepatocellular jaundice and why?
1) Mixed unconjugated and conjugated hyperbilirubinaemia ➞ some hepatocytes still normal
2) raised AST/ALT ➞ due to liver damage
3) normal or raised ALP ➞ indicates cholestasis due to swollen cells
4) Abnormal clotting ➞ some hepatocytes cant produce clotting factors
Give 4 causes of hepatocellular jaundice
1) Drugs (eg. paracetamol)
2) Cirrhosis
3) Hepatic tumours
4) congenital
How is post-hepatic jaundice (obstructive) characterised?
How can it be sub-classified and what does this mean?
Characterised by obstruction of the biliary system ➞ passage of conjugated bilirubin is blocked
Sub-classification:
Intrahepatic ➞ hepatocyte swelling
Extrahepatic ➞ obstruction distal to bile canaliculi
What 5 lab findings would indicate post-hepatic jaundice and why?
1) Conjugated hyperbilirubinaemia ➞ conjugation still occurs in liver
2) Dark urine (bilirubin in urine) ➞ obstruction causes conjugated bilirubin in liver to be excreted in kidney in that form (not oxidised to urobilin), giving the dark colour
3) Pale stools/”clay stools” ➞ obstruction means bilirubin cant flow into small intestine and be converted in stercobilinogen, so no brown in faeces
4) raised canalicular enzymes (ALP)
5) normal or raised liver enzymes (ALT and AST)
Give 4 causes of post-hepatic jaundice for Intrahepatic AND Extrahepatic
Intrahepatic:
1) Hepatitis
2) Drugs
3) Cirrhosis
4) Primary biliary cirrhosis
Extrahepatic:
1) Gallstones
2) Biliary stricture
3) Carcinoma
4) Pancreatitis
5) Sclerosing cholangitis
Give 4 types of Carcinoma that can lead to post-hepatic jaundice (include locations)
- Head of pancreas
- Ampulla
- Cholangiocarcinoma (bile duct)
- Porta hepatis lymph nodes
- Liver metastases
What is Courvoisier’s law in reference to post-hepatic jaundice
States that: ‘in the presence of a non-tender palpable
gallbladder, painless jaundice is unlikely to be caused by gallstones’.
Why is a non-tender palpable gallbladder unlikely to be gallstones? (Courvoisier’s law)
Give an example
As gallstones are formed over a long period of time it would result in a shrunken fibrotic gallbladder.
An enlarged gallbladder is more indicative of pathologies causing biliary obstruction which occurs over shorter periods of time
Eg. a tender gallbladder may be seen with acute cholecystitis or a tender and distended gallbladder may be seen with a mucocele or empyema related to gallstones
What is hepatitis?
List 3 causes
inflammation of the liver
Causes:
1) Infections- viral
2) Toxins (Alcohol, drugs, wilsons, haemochromatosis)
3) Autoimmune
List 2 findings that would be indicative of ACUTE hepatocyte breakdown
1) Aminotransferase release (AST/ALT)
2) Jaundice
List 3 findings that would be indicative of prolonged/ chronic hepatocyte damage
1) Synthetic failure
2) decreased albumin
3) decreased clotting factors
What are the 3 types of viral hepatitis?
List how each is spread and whether it is acute or chronic
1) Hepatitis A
• Faecal-oral (shellfish)
• Usually acute
2) Hepatitis B
• Blood/Body fluids/vertical spread
• Acute and chronic ➞ may progress to cirrhosis
3) Hepatitis C
• Blood spread
• 50% chronic liver disease, 30% cirrhosis, 5% hepatocellular carcinoma
What are the 3 stages of Alcoholic liver disease
1) Fatty liver
2) Alcoholic hepatitis
3) Cirrhosis
List 6 complications of Alcoholic liver disease
1) Hepatocellular carcinoma
2) Liver failure
3) Wernicke-Korsakoff syndrome
4) Encephalopathy
5) Dementia
6) Epilepsy
What is seen in liver cirrhosis and give 2 ways this effects function
What is the difficulty with diagnosis?
Liver cell necrosis which leads to nodular regeneration and fibrosis
Results in increased resistance to blood flow and deranged liver function. Final outcome is often liver diseases
Early diagnosis is difficult as clinical signs are usually only seen after 80-90% of liver parenchyma has already been destroyed
Give 3 causes of liver cirrhosis
1) Alchol
2) Hepatitis B or C
3) Non-alcoholic fatty liver disease
4) Primary biliary cirrhosis
Give 4 signs/symptoms of liver dysfunction + 2 other clinical features
- Jaundice
- Anaemia
- Bruising
- Palmar erythema
- Dupuytren’s contracture
+ Portal hypertension and spontaneous bacterial peritonitis
List 6 lab findings that would indicate liver cirrhosis
1) normal to raised ALT/AST
2) increased ALP
3) increased bilirubin
4) decreased albumin
5) deranged clotting
6) decreased Na
list 3 main principals of treatment/management of liver cirrhosis
1) Stop drinking alcohol
2) Treat complications
3) Transplantation
What defines portal hypertension and what is this a result of?
Give the 2 main causes of this
Portal venous pressure >12 mmHg, due to intrahepatic or extrahepatic portal venous compression or occlusion
Causes:
1) Obstruction of portal vein
2) Obstruction of flow within liver (eg. cirrhosis)
What are the visible clinical signs of portal hypertension? (5)
1) splenomegaly
2) ascites
3) spider naevi
4) caput medusa
5) oesophageal/rectal varices
Give 4 pathological processes that may cause diseases of the gallbladder and/or biliary tree
What is the main consequence of this
1) obstruction
2) Infection
3) Inflammation
4) neoplasia
We cannot store or and deliver bile from liver to duodenum, which is necessary for the absorption of fats
What is the clinical name for gallstones?
What are the 5 MAIN risk factors + 2 others (hint 5F’s)
Gallstones = Cholelithiasis
Risk factors: ‘Fair, fat, fertile, female and forty’
Others incl: Increasing age, FHx, diabetes, OCP
Give the 3 main types of gallstones + their composition and appearance
1) Mixed 80% (most common) ➞ cholesterol with calcium and bile pigment
2) Pure cholesterol 10% ➞ usually solitary and upto 5cm
3) Pigment stones (bilirubin stones) 10% ➞ calcium bilirubinate, usually multiple that are small and black
What are 3 major complications of gallstones?
List 2 others
1) Billary colic
2) Cholecystitis
3) Ascending cholangitis
Others:
• obstructive jaundice
• acute pancreatitis
What is Billary colic?
Describe the pain a patient would present with and list 2 associated symptoms
How would you treat?
Occurs when a gall stone blocks the cystic duct (recurrent acute attacks may become chronic)
Presentation: when gallbladder contracts patient feels sudden onset severe epigastric/RUQ pain that radiates to the back and lasts 15 minutes - 24 hours
Associated symptoms: nausea and vomiting
Treatment: usually resolves spontaneously but If it doesn’t analgesics can be used
What is Cholecystitis and how would this present?
How would you treat and what are 2 serious consequences if untreated?
Inflammation of the gallbladder (often followed by infection) due to Irritation of the biliary tract by stone
Presentation: RUQ pain and fever
Treatment: analgesia, IV antibiotics + fluids, laparoscopic cholecystectomy
If untreated can progress to: sepsis, local peritonism, raised WCC, gallbladder mass
What is Ascending cholangitis?
Describe the pain a patient would present with
Why Is this a medical emergency and how would you treat?
Inflammation/infection of the CBD due to bacteria ascending from duodenum
Presentation: Charcot’s triad (RUQ pain, Jaundice, Fever)
Infection can become life threatening because the CBD is already partially obstructed by gallstones
Treatment: resuscitate, IV broad spectrum antibiotics, endoscopic drainage of CBD
What are the endocrine and exocrine functions of the pancreas?
Endocrine: Insulin, glucagon, somatostatin
Exocrine: HCO3 and enzymes (protease, amylase, lipase etc…)
List the 4 close anatomical relations of the pancreas
1) duodenum
2) common bile duct
3) portal vein
4) coeliac trunk
What is pancreatitis and what causes it?
Inflammation of the pancreas ➞ caused by effects of
enzymes released from pancreatic acini
What is seen in acute vs chronic pancreatitis?
Acute: oedema, haemorrhage, necrosis
Chronic: fibrosis, calcification
Give the 2 MAIN causes of pancreatitis + 4 other causes
GET SMASHED
Main: 80% of cases
1) gallstones
2) ethanol
Other: trauma, steroids, mumps, autoimmune, scorpion bite, hyperlipidaemia, ERCP/Iatrogenic, drugs
What is the Pathogenesis of pancreatitis? (why does it develop) (5)
1) Duct obstruction ➞ juice and bile reflux
2) Acinar damage ➞ from reflux or drugs
3) Protease ➞ tissue destruction
4) Lipase ➞ fat necrosis
5) Elastase ➞blood vessel destruction
Enzymes digest pancreatic tissue!!
What is the clinical presentation of ACUTE pancreatitis?
What are the biochemical changes (lab findings)?
How would you treat
Presentation: sudden severe epigastric pain that penetrates to the back a/w with vomiting (steadily decreases over 72 hours)
Biochemical changes (lab findings) ↑Amylase ↓Ca2+ ↑Glucose ↑ALP/Bilirubin
Treatment: supportive - fluid balance
What does CHRONIC pancreatitis result in? (4)
Give 4 causes
What Is the clinical presentation?
Results in: parenchymal destruction, fibrosis, loss of acini and duct stenosis
Causes: chronic alcoholism, cystic fibrosis, inherited conditions, biliary disease
Clinical presentation:
• pain
• malabsorption ➞ steatorrhoea and weight loss
• diabetes mellitus ➞ damage to endocrine pancreas
• jaundice
What is the prognosis of Pancreatic carcinoma and why?
Which is the most common type and what is the most location
Give 6 risk factors
Poor survival rates b/c of late presentation and early metastases (5th cause of cancer death in UK)
90% ductal adenocarcinoma and 70% in head of pancreas
Risk factors: smoking and alcohol, over 60, high fat diet, chronic pancreatitis, diabetes, FHx
Describe the progression that would be seen in Pancreatic carcinomas
1) Initially symptomless/vague
2) painless progressive obstructive jaundice
3) nausea and vomiting
4) severe progression to: pain, weight loss, carcinomatosis (multiple carcinomas), malabsorption
How do you treat Pancreatic carcinomas?
- Surgery (only 10-20%)
- Chemotherapy
- Palliative
