Jaundice and Chronic Liver Disease Flashcards
What does the liver synthesise?
- Clotting factors
- Bile acids
- Carbohydrates
- Proteins
- Lipids
- Hormones
What relating to carbohydrates takes place in the liver?
- Gluconeogenesis
- Glycogenolysis
- Glycogenesis
What protein is synthesised in the liver?
Albumin
What lipids are synthesised in the liver?
- Cholesterol
- Lipoproteins
- TG
What hormones are synthesised in the liver?
- Angiotensinogen
- Insulin like growth factor
What are the detoxification functions of the liver?
- Urea production
- Detoxification of drugs
- Bilirubin metabolism
- Breakdown of insulin and hormones
What is the immune function of the liver?
- Combating infections
- Clearing the blood of particles and infections including bacteria
- Neutralising and destroying all drugs and toxins
What is the storage function of the liver?
- Stores glycogen
- Stores vitamin A, D,B12, K
- Stores copper and iron
What is bilirubin a by product of?
Haeme metabolism
What generates bilirubin?
Senescent RBCs in the spleen
Describe the conjugation of bilirubin.
- Unconjugated: initially bound to albumin
- Conjugated: liver helps to solubilise it
What can cause pre-hepatic elevate bilirubin?
Haemolysis
What can cause hepatic elevated bilirubin?
Parenchymal damage
What can cause post hepatic elevated bilirubin?
Obstruction
What are aminotranferases?
Enzymes present in hepatocytes
Which aminotransferase is more specific?
ALT
What can the AST/ALT ratio point towards?
ALD
What can the ST/ALT ration point towards?
Parenchymal involvement
What is alkaline phosphatase?
Enzyme present in bile ducts
What may elevated alkaline phosphatase suggest?
- Obstruction
- Liver infiltration
Other than the bile ducts, where is alkaline phosphatase also present?
- Bone
- Placenta
- Intestines
What is gamma GT?
Non-specific liver enzyme
When is gamma GT elevated?
Alcohol use
What is gamma GT useful for?
Confirm liver source of ALP
What can elevate gamma CT other than alcohol?
Drugs like NSAIDs
What is albumin an important test for?
Synthetic function of the liver
What can low levels of albumin suggest?
- Chronic liver disease
- Kidney disorders
- Malnutrition
What is an extremely important test for liver function?
Prothrombin time
What does the prothrombin time indicate?
Degree of liver dysfunction
What is prothrombin time used to calculate?
Scores to decide stage of liver disease, who needs a liver transplant and who gets a liver transplant
What is creatinine essentially?
Kidney function
What does creatinine determine?
Survival from liver disease
What is creatinine testing essential in?
Critical assessment for need for transplant
What is an important source of thrombopoietin?
Liver
What can splenomegaly be a result of?
Cirrhosis
Why are platelets low in cirrhotic subjects?
As a result of hypersplenism
What is the platelet count an indirect marker of?
Portal hypertension
What are 4 symptoms of liver failure?
- Jaundice
- Ascites
- Variceal bleeding
- Hepatic encephalopathy
Jaundice
Yellowing of the skin sclerae and other tissues caused by excess circulating bilirubin
When is jaundice detectable?
When total plasma bilirubin levels exceed 34umol/l
What is the differential diagnosis for jaundice?
Carotenemia
Describe the life of bilirubin.
-RBC release heme
-Heme acted on by heme oxygenase to form biliverdin
-Biliverdin acted on by biliverdin reductase to form bilirubin
-Bilirubin acted on by UGT to for bilirubin diglucuronide
Bilirubin diglucuronide excreted in stool or enter enterohepatic recirculation
What are the 3 classifications of jaundice?
- Pre hepatic: unconjugated
- Hepatic: conjugated
- Post hepatic: conjugated
What does human waste look like in pre hepatic jaundice?
Normal coloured urine
What does human waste look like in hepatic jaundice?
-Very yellow urine
What does human waste look like in post hepatic jaundice?
- Very yellow urine
- Pale stools
What is the pathology behind pre hepatic jaundice?
- Increased quantity of bilirubin (haemolysis)
- Impaired transport
What is the pathology behind hepatic jaundice?
- Defective uptake of bilirubin
- Defective conjugation
- Defective excretion
What is the pathology behind post hepatic jaundice?
Defective transport of bilirubin by the biliary ducts
What are the clues in the history of patients with pre hepatic jaundice?
- History of anaemia (fatigue, dyspnoea, chest pain)
- Acholuric jaundice
What are the clues in the history of patients with hepatic jaundice?
- Risk factors for liver disease (IVDU, drug intake)
- Decompensation (ascites, varieal bleed, encephalopathy)
What are the clues in the history of patients with post hepatic jaundice?
- Abdominal pain
- Cholestasis (pruritus, pale stools, high coloured urine)
What are the clues on clinical examination of someone with pre hepatic jaundice?
- Pallor
- Splenomegaly
What are the clues on clinical examination of hepatic jaundice?
- Stigmata of CLD (spider naevi, gynaecomastia)
- Ascites
- Aterixis
What are the clues on clinical examination of someone with post hepatic jaundice?
Palpable gall bladder (Courvoiser’s sign)
What are the investigations carried out for a patient who is jaundiced?
- Liver screen
- Abdominal ultrasound
- CT/MRI
- ERCP
- MRCP
What is included in a liver screen?
- Hepatitis B and C serology
- Autoantibody profile, serum immunoglobulins
- Caeruloplasmin and copper
- Ferritin and transferrin saturation
- Alpha 1 anti-trypsin
- Fasting glucose and lipid profile
Why is an abdominal ultrasound the most important test?
- Differentiates extrahepatic and intrahepatic obstruction
- Delineates site of obstruction
- Delineates cause of obstruction
- Documents evidence of portal hypertension
- Preliminary staging of extent of disease e.g cancer spread
What are the features of an ultrasound scan?
- Cheap
- No radiation
- Portable, widely available
- Good for gallstones
- High specificity
- Lower sensitivity
- Examines organs as well as biliary system
What are the feature of a CT/MRI scan?
- Expensive
- Radiation (CT only)
- Requires CT/MRI scanner
- Better for pancreas
- High specificity
- High sensitivity
- Examines organs and biliary system
What are the features of MRCP?
- No radiation
- No complications
- 5% claustrophobic
- Can image outwith the ducts
What are the features of ERCP?
- Radiation
- Sedation
- Complications
- Failure
- Only image ducts
- Therapeutic option
What can therapeutic ERCP be used for?
- Dilated biliary tree with visible stones or tumour
- Acute gallstone pancreatitis
- Stenting of biliary tract obstruction
- Post operative biliary complications
What sedation related complications can arise from ERCP?
- Respiratory
- Cardiovascular
What procedure related complications can arise from ERCO?
- Pancreatitis
- Cholangitis
- Sphincterotomy (bleeding/perforation)
When is percutaneous transhepatic cholangiogram used?
- ERCP not possible due to duodenal obstruction or previous surgery
- Hilar stenting
What is a disadvantage of percutaneous transhepatic cholangiogram?
More invasive than ERCP
What is possible to collect using endoscopic ultrasound?
Biopsy
What is endoscopic ultrasound used for?
- Characterising pancreatic masses
- Staging tumours
- Fine needle aspiration of tumours and cysts
- Excluding biliary microcalculi
Chronic liver disease
Liver disease that persist beyond 6 months
Give examples of liver diseases which are chronic.
- Chronic hepatitis
- Chronic cholestasis
- Fibrosis and cirrhosis
- Others like steatosis
- Liver tumours
What is the main cause of cirrhosis?
Alcohol
Other than alcohol, what else can cause cirrhosis?
- Autoimmune
- Hemochromatosis
- Chronic viral hepatitis
- NAFLD
- Drugs
- Cystic fibrosis, a1 anti-trypsin deficiency, Wilson’s disease
- Vascular problems
- Cryptogenic
- Other
What are the pathological changes which take place with cirrhosis?
- Infiltrating lymphocytes
- Extracellular matric proteins
- Apoptotic hepatocytes
- Activated Kupffer cells
- Sinusoid lumen with increased resistance to blood flow
What is the clinical presentation of cirrhosis?
- Compensated chronic liver disease picked up by screening test or abnormal LFTs
- Decompensated chronic liver disease presents with ascites, variceal bleeding and hepatic encephalopathy
- Hepatocellular carcinoma
What is found on physical examination of ascite?
Dullness in flanks and shifting dullness
How can ascites be confirmed?
Ultrasound
What is the corroborating evidence for ascites?
- Spider naevi
- Palmar erythema
- Abdominal veins
- Fetor hepaticus
- Umbilical nodule
- JVP elevation
- Flank haematoma
What should all patients with new onset ascites have?
Diagnostic paracentesis
What initial investigations are required for ascites?
- Protein and albumin concentration
- Cell count and differential
- SAAG
What is routinely done as part of ascetic fluid analysis?
- Cell count
- Protein
- Albumin
What is optionally done as part of ascetic fluid analysis?
- Culture
- Glucose
- LDH
- Amylase
- Gram stain
What can be done but is unusual as part of ascetic fluid analysis?
- TB culture
- Cytology
- Triglyceride
- Bilirubin
What is unhelpful in ascetic fluid analysis?
- pH
- Lactate
- Cholesterol
- Fibronectin
- ADA
- CEA
SAAG
Serum ascites albumin gradient
What does a SAAG of >1.1g/dl point to?
- Portal hypertension
- CHF
- Constrictive pericarditis
- Budd Chiarri
- Myxedema
- Massive liver metastases
What does a SAAG of<1.1g/dl point to?
- Malignancy
- Tuberculosis
- Chylous ascites
- Pancreatic
- Biliary ascites
- Nephrotic syndrome
- Serositis
What are the treatment options for ascites?
- Diuretics
- Large volume paracentesis
- TIPS
- Aquaretics
- Liver transplantation
What are varices due to?
Portal hypertension
Where can varices occur?
- Skin
- Oesophageal and gastric
- Rectal
- Posterior abdominal wall
- Stomal
What is the immediate management for varices?
- Resuscitate patient
- Good IV access
- Blood transfusion as required
- emergency endoscopy
Why are varices treated as medical emergencies?
Prone to rupture
How are varices treated?
- Endoscopic band ligation
- Add Terlipressin for control
- Sengstaken-Blakemore tube for uncontrolled bleeding
- TIPSS for rebleeding after banding
Hepatic encephalopathy
Confusion due to liver disease
How is hepatic encephalopathy graded?
1-4
What are the precipitants fro hepatic encephalopathy?
- GI bleed
- Infection
- constipation
- Dehydration
- Medication
- Sedation
How is hepatic encephalopathy reversed?
Treat underlying cause
What is the treatment usually fro hepatic encephalopathy?
- Laxatives (phosphate enemas and lactulose)
- Broad spectrum non absorbed antibiotic such as neomycin or rifaximin
What is repeated admissions with hepatic encephalopathy an indicator for?
Liver transplant
What does hepatocellular carcinoma occur in the background of?
Cirrhosis
What does hepatocellular carcinoma associated with?
Chronic hepatitis B and C
What is the presentation of hepatocellular carcinoma?
- Decompensation of liver disease
- Abdominal mass
- Abdominal pain
- Weight loss
- Bleeding from tumour
How is hepatocellular carcinoma diagnosed?
- Tumour markers: AFP
- Ultrasound
- CT
- MRI
- Liver biopsy (rare)
What are the treatment options for hepatocellular carcinoma?
- Hepatic resection
- Liver transplantation
- Chemotherapy
- Locally ablative treatments
- Sorafenib (tyrosinase kinase inhibitor)
- Hormonal therapy (tamoxifen)
What chemotherapy can be used with hepatocellular carcinoma?
- Locally delivered TACE: trans catheter arterial chemo-embolization
- Systemic chemotherapy
What locally ablative treatments are there for hepatocellular carcinoma?
- Alcohol injection
- Radiofrequency ablation
