Cirrhosis Flashcards
what is cirrhosis
the result of chronic inflammation and damage to liver cells
also known as end stage liver failure
damaged liver cells are replaced by scar tissue
what is portal hypertension
fibrosis affects the structure and blood flow through the liver which causes increased resistance in the vessels leading into the liver
causes of portal hypertension
prehepatic - portal vein thrombosis
Intrahepatic - schistosomiasis, cirrhosis.
Posthepatic - right sided heart failure
Describe the process of portal hypertension
- hepatocyte injury
- secretion of paracrine factors activate stellate cells
- stellate cells proliferate and release TGF-B
- produces collagen which is fibrotic
- extra fibrotic mass compresses sinusoids and central vein
- increases pressure which causes portal hypertension
What is the result of portal hypertension
collateral blood shunting to gastroesophageal veins or towards systemic circulation
Symptoms of portal hypertension
- mostly asymptomatic
- present when oesophageal varices rupture
complications of portal HTN
Ascites
bleeding varices
How does ascites lead to portal htn
fluid is more likely to get pushed into tissues and across into peritoneal cavity
most common causes of liver cirrhosis 4
alcoholic liver disease
non alcoholic fatty liver disease
hep B +D
hep c
What does chronic liver injury result in?
inflammation, matrix deposition, necrosis and angiogenesis all of which lead to FIBROSIS
What does liver injury cause
necrosis and apoptosis, releasing cell contents and reactive oxygen species (ROS)
This activates hepatic stellate cells and tissue macrophages (Kupffer cells)
What do hepatic stellate cells do?
release cytokines that attract neutrophils and macrophages to the liver which results in further inflammation and thus necrosis and eventual fibrosis
What do Kuppfer cells do? Macrophages
phagocytose necrotic and apoptotic cells and secrete pro- inflammatory mediators
What are the pr inflammatory mediators secreted by Kuppfer cells?
- Transforming growth factor-beta (TGF-beta) which leads to the transdifferentiation of stellate cells to myofibroblasts
- Platelet derived growth factor (PDGF) which stimulates myofibroblast proliferation
What does increased myofibroblasts do?
leads to progressive collagen matrix deposition resulting in fibrosis and scar accumulation in the liver
Characteristic features of cirrhosis
regenerating nodules separated by fibrous septa and loss of lobular architecture within the nodules
What are the two types of Cirrhosis?
Decompensated - the liver is no longer able to perform any of its functions
Compensated - the liver can still form majority of its functions and patient may be asymptomatic
Definitive diagnostic test
liver biopsy
Bloods and LFTs for liver cirrhosis
low albumin,
raised prothrombin time
high: AST, ALT, ALP, GGT, bilirubin,
low platelets,
low WCC
raised serum creatinine
What do MRIs show for liver cirrhosis
- Increased claudate lobe size,
- smaller islands of regenerative nodules
- presence of right posterior hepatic notch
Definitive treatment for liver cirrhosis
liver transplant
conservative management of liver cirrhosis
fluids
analgesia
alcohol abstinence
good nutrition
define hypoalbuminemia ?
reduced plasma oncotic pressure
renal water retention treatment ?
peripheral arterial vasodilation by NO
what is ascites
fluid in the peritoneal cavity
causes of ascites
- local inflammation = peritonitis
- low protein = nephrotic syndrome
- flow stasis = cirrhosis
how does cirrhosis cause ascites
Peritonitis - more leaky
Raised capillary hydrostatic pressure
Reduced colloid oncotic pressure
Peritoneal lymphatic draining
What is SAAG
The serum ascites albumin gradient (SAAG), which is based on the difference between the albumin level of serum and of ascitic fluid,
What are the values for high and low SAAG
High = more than or equal to 1.1
Low= lower than 1.1
Causes of high SAAG
- cirrhosis
- portal htn
- portal vein thrombosis
presentation of ascites
SHIFTING DULLNESS, gained weight, abdo distension.
Signs of liver disease.
Respiratory distress (pleural effusion).
investigations of ascites
diagnostic aspiration
Imaging- x ray
ultrasound scan
1st line treatment of ascites
salt restriction
diuretics- furosemide/ spironolactone
complications of ascites
Spontaneous bacterial peritonitis- an infection of ascitic fluid, most common causes are e coli
what are bleeding varices
GI bleeds on a background of chronic liver disease
GS investigation for bleeding varices
UPPER GI endoscopy
symptoms of bleeding varices
melaena
haematemesis
treatment for an active bleeding varice
Urgent gastroscopy/endoscopy
Fluid resuscitation, remember can be massive
1-Terlipressin (ADH analogue) or Octreotide
2-Balloon tamponade
Gold std - endoscopic therapy: band ligation or
sclerotherapy.
DD of varices
mallory wesis tear retching, abdo pressure
oesophageal varices - long history of alcohol abuse
How to prevent a bleed
- bb ( non selective) + nitrates
- repeat variceal banding
- last resort= liver transplant
