Liver Failure, Liver Cirrhosis, Portal Hypertension Flashcards
Examination findings of liver cirrhosis
A. Hyperbilirubinaemia and impaired hepatic metabolism
1. Jaundice
2. Scratch marks - from pruritus
3. Fetor hepaticus
4. Finger clubbing
B. Hypoalbuminaemia
5. Leuconychia
6. Lower limb oedema
C. Altered sex hormones
7. Spider naevi
8. Palmar erythema
9. Gynaecomastia
10. Loss of axillary hair
11. Testicular atrophy
D. Platelet dysfunction and coagulopathy
12. Easy bruising, petechiae, ecchymoses
E. Portal hypertension
13. Caput medusae - recannalisation of umbilical vein due to portal hypertension
14. Ascites, assess volume status if present
15. Splenomegaly
G. Encephalopathy
16. Terminal asterixis - flapping tremor on outstretched dorsiflexed hands
(Flexion more rapid than extension)
H. Liver examination
17. Cirrhotic - small, shrunken
18. Alcoholic and NAFLD - +/- hepatomegaly due to fat deposition
19. Tender hepatomegaly - stretch of liver capsule
20. HCC - hard, irregular
21. Hepatic venous hum - collateral betwen portal and umbilical vein, murmur over epigastrium
What are the specific signs to elicit for the following cause of chronic liver disease?
- HCC
- Alcoholism
- Hepatitis B and C
- PBC
- Haemochromatosis
- Congestive heart failure
- Wilson’s disease
- AAT
- Budd-Chiari
HCC
- Hard and craggy hepatomegaly
- Constitutional symptoms
Alcoholism
- Duputyren’s contracture
- Parotid enlargement
Hep B/C infection
- Tattoos
- IV needle marks
- PCT
- Cryoglobulinaemia - palpable purpura, livedo reticularis
PBC
- Hyperpigmentation
- Xanthalesma and tendon xanthomata
- Excoriation marks - severe pruritus
Haemochromatosis
- Bronze pigmentation
- Arthtopathy
- Finger tip skin pricks - DM requiring BGM testing
Congestive cardiac failure
- Raised venous pressure
- S3
Wilson’s disease
- Kayser-Fleischer rings
- Akinetic-rigid syndrome
Alpha-1-antitrypsin deficiency
- Lower zone emphysema
Budd-Chiari syndrome
- Loss of hepatic jugular reflex (vena cava involvement)
What are the nail changes of hypoalbuminaemia?
- Leukonychia - nail bed opacification
- Muerkche’s lines - transverse white lines
What conditions may cause hepatic bruit?
- Alcoholic hepatitis
- Hepatocellular carcinoma
- Hepatic AVM
- Intestinal AVM
- Hepatic hemangioma
- TIPS
What is the definition of liver cirrhosis?
Defined pathologically - nodules of regenerating hepatocytes surrounded by scar tissues
- Diffuse fibrosis in portal tracts, central veins and space of Disse
- Chronic inflammation stimulates stellate cells transformation into myofibroblasts
- Extension of fibrosis from space of Disse to other parts of lobules causesp sinusoids to separate from hepatocytes
- Venulisation (sinusoids converted from fenestrated endothelial channels)
- Shunting of blood from portal to central veins, reduced detoxification of metabolites, hepatocytes deprived of nutrients - Nodule formation - regenerating hepatocytes
- Disrupted tissue architcture - bridging fibrosis and shunt formation
What is the pathogenesis of liver failure?
Large hepatic reserve - up to 80-90% hepatocytes before liver failure sets in
- Sudden massive destruction (fulminant hepatitis)
- Progression of hepatic insufficiency to hepatic encephalopathy within 2-3 weeks
- Subfulmiant - less rapid course within 3 months - Tipped into decompensation by triggers
What are the causes of cirrhosis?
1. Alcohol 2. Viral (hepatitis B, hepatitis C) 3. Autoimmune (primary biliary cirrhosis, primary sclerosing cholangitis, autoimmune hepatitis) 4. Metabolic (NAFLD, haemochromatosis, cystic fibrosis) 5. Drugs (methotrexate, isoniazid, amiodarone, phenytoin)
_Full List of Causes_
Toxins
1. Alcohol
2. Drugs (methotrexate, isoniazid, amiodarone, phenytoin, methyldopa)
3. Alfatoxins
Infective
4. Viral (hepatitis B, hepatitis C)
Vascular
5. Cardiac related cirrhosis - TR, right heart failure
6. Veno-occlusive disease
7. Budd-Chiari (malignancy, PRV, AI, OCPs, IBD, PNH)
8. Haemolytic disease
Autoimmune
9. Primary biliary cirrhosis (more in female)
10. Primary sclerosing cholangitis
11. Autoimmune hepatitis (more in female)
12. Secondary biliary cirrhosis - RPC, chronic CBD stones
Metabolic
13. NAFLD
14. Haemochromatosis, usually secondary in Singapore (HH gene is NOT found in Singapore)
15. Wilson’s disease
16. Alpha-1 antitrypsin deficiency
17. Galactosaemia
18. Type 4 glycogen storage disease
19. Cystic fibrosis
20. Idiopathic (cryptogenic)
What are the complications of cirrhosis?
(6+4 liver dysfunction)
- Portal hypertension (varices, ascites, hypersplenism)
- Liver dysfunction
- Coagulopathy (thrombocytopenia, reduced clotting factors)
–> Easy bruising, petechiae, mucocutaneous bleeding,
- Hepatic encephelopathy
- Hyperbilirubinaemia - jaundice, pruritus
- Hypoalbuminaemia - lower limb oedema - Hepatorenal syndrome - oliguria
- Hepatocellular carcinoma
- Sepsis and multiorgan failure
- Fluid, electrolyte, acid-base disturbances
What are the causes of decompensation in cirrhosis?
- Infection, inflammation, spontaneous bacterial peritonitis
- Hypokalaemia - from diuretics, high volume paracentesis
(or electrolyte imbalance from vomiting, diarrhoea) - GI bleeding (variceal bleeding)
- Constipation - accumulation of ammonia
- Increased protein/urea load - diet, BGIT, uraemia
- Drugs - alcohol binge, anti-depressants, narcotics, sedatives
- Trauma - surgery, portosystemic shunt
- Hepatocellular carcinoma
What are the signs of hepatic decompensation?
How do you assess the severity of cirrhosis?
Signs of Decompensation
1. Jaundice
2. Hepatic flap
3. Coagulopathy
4. Ascites
5. Lower limb oedema
Severity Assessment
Childs-Pugh score
- Prognostic score based on bilirubin, albumin, INR, ascites and encephalopathy
- Graded from A-C (A best prognosis)
What is the definition of hepatic encephalopathy?
How do you classify the severity of hepatic encephalopathy?
What are the triggers for hepatic encephalopathy?
(not discussed on this card - similar to causes of decompensated cirrhosis)
Definition: reversible neurological dysfunction or coma related to decompensated liver disease
- Reduced detoxification of ammonia from intrahepatic shunting.
-> High serum ammonia - impairs neuronal function and causes brain oedema
West Haven Classification
Graded from 1 to 4 depending on degree of impairment
Stage 1: depression, euphoria, sleep disturbance, personality change, slurred speech (normal EEG)
Stage 2: lethargy, moderate confusion, bradykinesia and asterixis (abnormal EEG)
Stage 3: marked confusion, arousable, marked asterixis (abnormal EEG)
Stage 4: coma (abnormal EEG)
Asterixis may be present at any stage
How would you investigate a patient for liver cirrhosis?
A. Confirm diagnosis
1. LFT - hyperbilirubinaemia, AST ALT ratio, ALP GGT, albumin
2. Abdominal US
3. CT AP
B. Identifying etiology
3. Hepatitis markers
4. Autoimmune screen
5. Tumour markers - AFP
6. CAGE questionnaires
7. Liver biopsy
C. Assess complications
6. FBC - IDA/B12/folate anaemia, alcoholism, SBP
7. Renal function
8. Coagulation panel - coagulopathy
9. OGD - TRO varices
10. Ascites fluid analysis
11. Surveillance for mitotic changes - AFP, ultrasound
12. EEG for hepatic encephalopathy
D. Evaluation for liver transplant
1. MELD score
2. Consider for those with refractory ascites, SBP or HRS
5 year survival rate for post-liver transplant 70-80%
(vs only 30-40% without)
How would you manage a patient with cirrhosis?
1. Involvement of multidisciplinary team 2. Slow or reverse liver disease (alcohol abstinence, antiviral therapy) 3. Preventing further liver damage (immunisations, abstinence) 4. Preventing complications (hepatoma surveillance, endoscopy, prophylaxis against variceal bleeds with propranolol) 5. Liver transplantation
_Full Answer_
A. Slows down progression
1. Alcohol abstinence and programmes - NAMS, AA
2. Antiviral therapy for hepatitis B, hepatitis C, immunomodulators for autoimmune causes
3. Regular follow up and surveillance
B. Prevention of decompensation
4. Low protein diet
5. Regular laxatives - prevents constipation/ammonia build up
6. Immunisation - hep B, pneumococcal, influenza
C. Preventing complications
7. HCC surveillance
8. Endoscopy
9. Propranolol
10. TIPSS
11. Ursodeoxycholic acid - reduces pruritus
12. Vitamin D, calcium supplement, Vit K supplement
D. Consideration for liver transplant
13. Based on clinical indications and MELD score
14. MARS dialysis (molecular adsorbent recirculating system) as interim before liver transplant
What are the complications of portal hypertension?
- Portal gastropathy (watermelon stomach - strips of dark and light red)
- Varices (oesophagus, fundus)
- Caput medusae
- Haemorrhoids
- Ascites
- Splenomegaly
How would you manage variceal bleeding and portal hypertension?
Variceal bleeding
1. ABCDE approach
2. IV esomeprazole 80mg STAT, then infusion esomeprazole 8mg/hour for 72 hours
3. Sengstaken-Blakemore tube or Minnesota tube
4. Octreotide or terlipressin
5. OGD with variceal banding or sclerotherapy
6. Emergency surgery
Reducing portal hypertension
7. Propranolol 20mg BD (reduces HR by 25% to 55-60/min)
8. Contiuning octreotide or terlipressin
9. TIPSS
What is hepatorenal syndrome?
What is the pathogenesis of hepatorenal syndrome?
What are the clinical features of hepatorenal syndrome?
What is the prognosis?
Life threatening renal failure in patients with severe chronic liver disease without intrinsic renal causes
Renal function improves with correlation of underlying liver failure
Systemic vasodilation reduces circulating volume, causing activation of RAAS -> renal vascular vasoconstriction
–> Reduced renal perfusion pressure and reduced eGFR
Clinical features: oliguria, raised urea and creatinine, concentrating ability maintained (hyperosmolar urine, low urinary sodium)
Poor prognosis - mean survival 2 weeks to 6 months
Describe the anatomy of the portal system
- Superior mesenteric vein + splenic vein unite behind neck of pancreas = portal veins
- drains: small and large intestines, stomach, spleen, pancreas, gallbladder - Portal vein divides into 2 lobar veins
- right branch drains cystic vein
- left branch drains umbilical and paraumbilical veins - Coronary vein receives distal oesophageal veins, runs along lesser curvature of stomach
Portal hypertension is the increased pressure within portal system, with increased resistance to portal blood flow.
Portal pressure >5-10mmHg or pressure gradient > 12mmHg
What are the causes of portal hypertension?
Pre-hepatic
1. Portal vein compression or thrombosis
- malignancy, peritoneal sepsis, pancreatitis, LAD?
2. Splenic vein thrombosis
3. Splenic vein shunting - massive splenomegaly
Intrahepatic
4. Liver cirrhosis
Post-hepatic
5. Hepatic vein obstruction (Budd Chiari syndrome)
6. Veno-occlusive disease
7. IVC obstruction
8. Right heart failure
9. Constrictive pericarditis
What are causes of hepatic dysfunction without overt necrosis?
- Reye’s syndrome
- Tetracycline toxicity
- Acute fatty liver of pregnancy
Hepatocytes viable but unable to perform normal metabolic function
What are the causes of fulminant hepatitis
- Shock - ischaemic or hypoxic
- Infection - hepatitis B > hepatitis A, HSV
- Drug overdose - paracetamol, PTB drug, MAOIs, halothane, TCM
- Toxin - Amanita phalloides (mushroom)
- Wilson’s disease
- Leukaemia
- Idiopathic
What is Budd-Chiari syndrome?
What is the possible cause/pathogenesis?
Obstruction of 2 or more major veins
Pathogenesis/Causes:
1. Idiopathic fibrosis of hepatic vein
2. Thrombosis - PRV, OCP use
3. Tumour invasion - HCC, RCC
What are the causes of veno-occlusive disease?
- Toxic alkaloids (brush tea from Africa)
- Cytotoxic drugs
Results in endothelial injury to hepatic veins causing thrombosis and fibrosis
How do you determine the direction of abdominal wall collateral vessels?
What are the significance?
Occlude the vessels below umbilicus
Direction of flow away from umbilicus, towards the leg= caput medusae
Direction of flow towards the head = IVCO
What are the important considerations and indications for liver transplant?
- Specific conditions: intractable pruritus in PBC, recurrent cholangitis in PSC
Cirrhosis
Acute hepatic failure (paracetamol overdose, hepatitis)
Primary biliary cirrhosis
Haemochromatosis - Severity of condition balanced with comorbidity
- Alcohol abstinence at least 6 months (which also improves liver function)
- Age < 65 years old
What autoantibodies are implicated in liver disease?
Primary biliary cirrhosis - anti-mitochondrial antibodies
Primary sclerosing cholangitis - Anti-nuclear antibodies, anti-smooth muscle antibodies
Autoimmune hepatitis - anti-smooth muscle, anti-liver/kidney microsomal type 1
What are the signs of alcohol misuse?
- Cachexia
- Tremor
- Parotid enlargement
- Dupuytren’s contracture
- Cerebellar syndrome
- Peripheral neuropathy
- Myopathy
