Cirrhosis and Liver fibrosis Flashcards
Histologically, how can we see irreversible liver damage
Loss of normal hepatic architecture with bridging fibrosis and nodular regeneration
Main causes of irreversible liver damage
- Chronic alcohol abuse
- Non-alcoholic fatty liver disease
- Hep B + D
- Hep C
What is Wilson’s disease
Copper build up in the body - causes liver disease
What diseases can cause liver damage
- Autoimmune hep
- Alpha-antitryspin deficiency
- Hereditary haemochromatosis
Risk factors for liver damage
Alcohol use
How does liver injury result in irreversible liver damage
- Chronic injury causes inflammation, matrix deposition, necrosis and angiogenesis -> fibrosis
- Liver injury causes necrosis + apoptosis releasing cell contents and ROS
- Activates hepatic stellate cells + kupffer cells
- Kupffer cells phagocytose necrotic and apoptotic cells + secrete inflammatory mediators
- Increased myofibroblasts leads to progressive collagen matrix deposition resulting in fibrosis and scar accumulation in the liver
- Severe reduction liver function
Name two inflammatory mediators
TGF-beta
PDGF
Role of TGF-beta
Transdifferentiation of stellate cells to myofibroblasts
Role of PDGF
Stimulates myofibroblast proliferation
What happens to the liver if fibrosis is eliminated
Liver can recover
In cirrhosis, can regression occur
Yes
What are characteristic features of cirrhosis
Regenerating nodules separated by fibrous septa + loss of lobular architecture within nodules
What two types of cirrhosis are there
Micro nodular
Macro nodular
What is micro nodular cirrhosis
Regenerating nodules are less than 3mm in size
What is micro nodular cirrhosis caused by
Alcohol + biliary treat disease
What is macro nodular cirrhosis
Nodules are of varying size and normal acini may be seen within the larger nodules
What is macro nodular cirrhosis caused by
Chronic viral hepatitis
Clinical presentation of cirrhosis
- Leuconychia
- Clubbing
- Palmar erythema
- Dupuytren’s contracture
- Spider nave
- Xanthelasma
- Hepatomegaly
- Bruising
- Ankle swelling + oedema
- Abdominal pain due to ascites
What is Xanthelasma
Yellow fat deposits under the skin usually around the eyelids
What is leuconychia
White discolourations on nails due to hypoalbuminaemia
How is cirrhosis diagnosed
- Ascites, encephalopathy
- HIGH bilirubin
- LOW albumin
- LONG PTT (1-3 and added up to give score)
- Liver biopsy (main way - confirms diagnosis + severity)
- Raised AST and ALT
- Low Na
- Raised serum creatine
What child-pugs classification is gives best prognosis
<7
What child-pughs classification is a sign of BAD prognosis
> 10
What is the risk at >8
Risk of vatical bleeding
Presence of alpha-fetoprotein indicates what
HEPATOCELLULAR CARCINOMA
How does an Ultrasound help in cirrhosis diagnosis
- Shows change in size + shape of the liver - hepatomegaly
- Shows modularity of liver and distortion of arterial vascular architecture
HEPATOCELLULAR CARCINOMA
What can a CT show for cirrhosis
- Hepatosplenomegaly
2. HEPATOCELLULAR CARCINOMA
What can an MRI show for cirrhosis
Detects tumours
What can an endoscopy show for cirrhosis
Detection of varies and portal hypertensive gastropathy
Complications of cirrhossi
- Fall in clotting factors
- Encephalopathy + confusion
- Hypoalbuminaemia (oedema)
- Portal hypertension
How is cirrhosis treated
- Good nutrition
- Alcohol absintence
- 6 month ultrasound screening for early development of hepatocellular carcinoma
- Treat underlying cause
- Hep A and B vaccination
- reduce salt intake
Why should we avoid NSAIDs in treating cirrhosis
Can precipitate gastro-intestinal bleeding or renal impairment
What forms the portal veins
Union of superior mesenteric and splenic veins
normal pressure of portal veins
5-8mmHg
Main pre-hepatic cause of portal hypertension
Portal vein thrombosis
Main intra-hepatic cause of portal hypertension
- CIRRHOSIS
- Schistosomiasis
- Sarcoidosis
Main post-hepatic cause of portal hypertension
- RHF
- Constrictive Pericarditis
- IVC obstruction
How does portal hypertension cocur
Liver injury + fibrogenesis the contraction of myofibroblasts contributes to increased resistance to blood flow
How is portal hypertension initially compensated
Splanchnic vasodilatation from portal hypertension causes drop in BP/ increased CO and formation of collaterals between portal and systemic systems
Where are collaterals forms
- Gastro-oesophageal junction
- Rectum
- Left renal vein
- Diaphragm
- Retroperitoneum
What happens to the microvasculature of the gut during portal hypertension
Becomes congested
Causes hypertensive gastropathies and colopathies
Symptoms of portal hypertension
Often asymptomatic
Clinical sign of portal hypertension
Splenomegaly
How does chronic liver disease clinically present in conjunction with portal hypertension
- Haematemesis and Malena from ruptured gastro-oesophageal varice OR portal hypertensive gastropathy
- Clubbing
- Palmar erythema
- Dupuytren’s contracture
- Spider Naevi
What will most patients with cirrhosis develop over the next 10 years
Gastro-oesophageal varices
How many of those with gastro-oesophageal varies will bleed
1/3
When will bleeding occur in gastro-oesophageal varices
Those with large varies or those with red signs at endoscopy and severe liver disease
How is bleeding from portal hypertension maanged
- Resuscitate until haemodynamically stable
- Blood transfusion if anaemic
- Correct clotting abnormalities
Why is vasopressin given during portal hypertension
Cause vasoconstriction
What vasopressin do we give for portal hypertension
IV TERLIPRESSIN (SOMATOSTATIN if contraindicated IHD)
What antibiotic is given to people with is given to treat infection and why in portal hypertension
CEPHALOSPORIN
Why is cephalosporin given in portal hypertension
Reduce early rebleeding and mortality
What is vatical banding
Band is put around avarice using an endoscope (after a few days, banded vary degenerate and falls off)
What other surgical methods are there for treating portal hypertension
- Ballon tamponade to reduce bleeding by placing pressure on avarice if banding fails
- Transjugular intrahepatic portoclavical shunt
When is TIPS done
When bleeding can’t be controlled whether acutely or following rebreeding (shunts between systemic and portal system to reduce portal vein pressure)
How is portal hypertension prevented
Non-selective B-blocker (PROPRANOLOL) - reduces portal pressure
VARICEAL BANDING repeatedly
Liver transplant
What is Primary Biliary Cirrhosis
Chronic disorder with progressive destruction of small bile ducts = cirrhosis
What people does primary biliary cirrhosis effect
Women aged 40-50
What gender does primary biliary cirrhosis effect
Females
Risk factors for primary biliary cirrhosis
- Positive family history
- Many UTIs
- Smoking
- Past pregnancy
- Other autoimmune disease
- Use of nail polish
Pathophysiology of primary biliary cirrhosis
Interlobar bile ducts are DAMAGED by chronic autoimmune inflammation resulting in cholestasis which may lead to fibrosis, cirrhosis and portal hypertension
What is cholestasis
Bile can’t flow from the liver to the duodenum (caused by a gallstone usually)
What is found in all patients’ blood with primary biliary cirrhosis
Anti-mitochondrial antibodies
Clinical presentation of patients with primary biliary cirrhosis
- Hepatomegaly
- Raised serum alkaline phosphate
- AMA
- Pruritus (itching)
- Lethargy and fatigue accompanying itching
- Eventually jaundice due to hepatomegaly
- Pigmented xanthelasma
What is pigmented xanthelasma
Yellow fat deposits under the skin usually around the eyelids
Complications of primary biliary cirrhosis
Cirrhosis
Osteoporosis
Malabsorption of fat-soluble vitamins due to cholestasis
Decreased bilirubin in gut lumen = osteomalacia and coagulopathy
What is osetomalacia
Softening of the bone due to a loss of phosphates and calcium
Differential diagnosis of Primary biliary cirrhosis
- Autoimmune cholangitis
Extahepatic biliary obstruction
How is extra hepatic biliary obstruction excluded
Ultrasound
Blood test for primary biliary cirrhosis
- Increased alkaline phosphate
- Raised serum cholesterol
- AMAs
- Raised IgM
What can an ultrasound show for primary biliary cirrhosis
Diffuse altering in liver architecture + excludes extra hepatic cholestasis
How can a liver biopsy help in diagnosis of primary biliary cirrhosis
- Portal tract infiltrate
- Granulomas (40% have them)
- Damage to and loss of small bile ducts + ductur=lar proliferation
- Portal tract fibrosis and eventually cirrhosis
How is primary biliary cirrhosis treated
- URSODEOXYCHOLIC ACID
- BISPHOSPHONATES
- Supplements of vit A,D,E,K
Why is URSODEOXYCHOLIX ACID given
Improves bilirubin and aminotransferase
Why are bisphosphonates given
Osteoporosis
How is pruritus treated
COLESTYRAMINE
NALOXONE and NALTREXONE
Problem with COLESTYRAMINE
Unpalatable