Liver Cirrhosis and Metabolism Flashcards
how does does the liver respond to injury
- it responds in a stereotypical way
- if you damage the liver over time inflammation and fibrosis results which leads to cirrhosis
name the causes of cirrhosis
• Alcohol • Fat / Metabolic Syndrome • Viral Hepatitis – HBV / HCV • Biliary Disease – PBC / PSC • Autoimmune • Metabolic – HC / Wilson’s / A1AT deficiency / amyloid
describe how liver disease progresses
- Primary Injury
- Inflammation – associated with ongoing liver cell injury and death
- Liver cell injury / death
- Fibrosis – liver ability to regenerate liver cells is impaired then you end up with fibrosis
what drives the progression of liver disease
Degree / number of insults Genetics Microbiome Environment Diet Drugs Methotrexate and NAFLD
How can you quantify how much cirrhosis is present
- do a liver biopsy
- use a stain for car tissue then categories it on how much scarring they have
is cirrhosis reversible
- yes
what are the functions of the liver
Protein synthesis & metabolism
- Clotting factors
- Urea breakdown
Bile production
- Elimination of bilirubin
- Hormone metabolism
- Drug metabolism
- Carbohydrate metabolism
- Lipid metabolism
- Immunological function
what is simple definition of liver disease
- this is loss of function of the liver
what do you use to diagnose cirrhosis
- History
- Symptoms and signs
- Blood
- Imaging
- Histology
what are the symptoms of liver cirrhosis
• None • Systemic – Weight loss – Tiredness – fatigue and impaired quality of life can be in chronic liver disease • Cholestatic – Pruritis – Pale stools/dark urine dark urine due to bilirubin increased production • Complications of underlying disease
what would you look for in a history of liver cirrhosis
- Alcohol history
- Travel – healthcare intervention over seas
- Illicit drug use
- Sexual
- Medication
- Professional
- Family history
- Co-morbidity
what are the signs of chronic liver disease
- Clubbing
- Gynaesmatic - failure to breakdown oestrogen
- Leuchonychia - pale nails
- Palmar erythema
- Spider naevi
- Hair loss
- Proximal wasting
- Scratch marks
- Xanthelasma
what two things from signs of chronic liver disease can make you more sure that liver disease is happening
palmar erythema and spider naevi
what two factors that assess liver function
- Albumin – low albumin
- INR (prothrombin time) – blood doesn’t clot as well as it should, liver makes Vitmain K clotting factors,
what are the factors that assess the stage of disease of the liver
- Platelet count
- ALT/AST
what is an important factor in assessing the stage of disease in the liver
- As liver disease progressive and the spleen gets bigger the platelet count drops – platelet count is an important test – can get a rough idea of who is at risk of having a more advance disease
name some liver tests that can be used
- bilirubin
- aspirate aminotransferae (AST)
- Alanine aminotransferase (ALT)
- alkaline phosphatase
- gamma glumly transpeptidase
describe the liver tests that can be used and the things that can cause them to rise independent to the liver
• Bilirubin – Unconjugated vs conjugated • Aspartate aminotransferase (AST) – hepatocyte release – Mitochondrial enzyme – Heart/muscle/kidney – hepatitis
• Alanine aminotransferae (ALT) – hepatocyte release – involved in moving amino groups to make new amino acids from keotacids
– Liver specific
• Alkaline phosphatase
– Bile cannalicular + sinusoidal membranes
– Bone/placenta it is also present in here, can be high in pregnancy
– Cholestasis – intra/extrahepatic
• Gamma glutamyl transpeptidase (GGT) – Hepatocellular – Cholestasis – Alcohol often associated – Made in liver and biliary cells
If is AST/ALT are high this indicates
hepatic damage
if Alkaline phosphate and gamma GT is high this indicates
cholestatic
if
- AST > ALT
ALT > AST
AST > ALT – alcohol
ALT > AST – eg viruses / NAFLD
alcohol does not put …
– Alcohol doesn’t put ALT > 500
- 500-1500 prephaps due to an autoimmune hepatitis
- If greater than 1500 acute hepatitis virus/drugs/ischemia
what imaging do you use on the liver
• Ultrasound – Biliary tree – Liver lesions – Ascites – Spleen – Veins – Other pathology • CT • MRI • ERCP / MRCP – looks at the bile ducts and pancreas
what are the complications of chronic liver disease
- Liver failure – if the liver is damaged it might not work well so we look at function tests of the liver
- Cirrhosis – leads to portal hypertension
- Malignancy
What happens f you have raised portal hypertension
- the blood builds up and you end up with pressure in the portal system
can result in three things - dilated abdominal veins - caput medusa
- ascites
- splenomegaly
what does a child-turocotte -pugh score determine
- this is a measure of how badly cirrhosis you liver is, helps work out if the liver is compensated or decompensated
what re the 5 points on the child -turoctte- Pugh score
- bilirubin - as the amount of bilirubin increases the score increases
- albumin - as the amount of albumin increases the score increases
- prothrombin score as the prothrombin time increases the score increases
- hepatic encephopahty symptom grade - as this gets more controlled the points increase
- asicites - as this gets worse the points increase
- each of the 5 points can be given a mark of 1 to 3 depending on severity
- the lowest score you can get is 5
- 5-6 is class A where your. liver is compensated and works normally
- 7-9 class B and 10-15 class C this is when the liver is decompensated and does not work properly
what are the three things that should you have hepatic decompensation
encephalopathy
portal hypertension
bleeding
describe how ascites happens
1, portal hyperntesion increases this causes the back up of blood in the splenic vein
2, leads to splanchnic vasodilation
3, this decreases the effectiveness of the circulatory volume
4, this activates the renin-angiontesin-aldosterone system
5, leads to renal sodium remaining in the body
6, this leads to ascites due to an increase in onoctic pressure
or
when the renin angiotensin aldosterone system is activated you could have renal vasoconstriction and this leads to hepatorenal syndrome
what are the treatments of ascites
– Low salt diet
– Diuretics
– 50% 2 year mortality
• transplantation
what are varcies
- these can form in the oesophagus and rectum
- they are big baggy veins that have dilated
- these can bleed and can cause haemorrhage
how do you treat variceal bleeding
Resuscitation
Terlipressin and Antibiotics
Banding or injection sclerotherapy
TIPSS
what are the primary and secondary prophylaxis for variceal bleeding
Propranolol / Carvedilol
Banding
what is an hepatic encephalopathy caused by
- sepsis
- bleeding
- drugs
- deteriorating liver function
how do you diagnose a hepatic encephalopathy
Hepatic flap
Clinical
EEG/MRI changes
what are the treatments for hepatic encephalopathy
Lactulose
transplantation
- L ornithine and L arginine can be used in acute liver failure to treat this
what are the signs of hepatic encephalopathy
- disorientation
- confusion
- comma
what drives hepatic encephalopathy
ammonia
describe how hepatic encephalopathy is caused
- usually glutamine is converted to glutamate and ammonia - ammonia then goes to the liver where it is transformed and converted to urea and passed out through the kidney
- but when the liver is not working ammonia goes to the muscles where it combines back with glutamate and is converted to glutamine this then goes to the brain
what are the causes or decompensation of the liver
SEPSIS - Ascitic Tap Bleeding Drugs - NSAIDs Venous occlusion Hepatocellular carcinoma
what are the risk factors for hepatocellular carcinoma
– Chronic viral hepatitis – Cirrhosis – Male – Ethnicity (African + Asian) – Smoking – Family history
name a biomarker for hepatocellular carcinoma
raised alpha fetoprotein
How do you treat hepatocellular carcinoma
– Ethanol injection) – Radiofrequency ablation – Transarterial chemoembolisation – Antiangiogenic drugs – Surgical resection
Liver transplantation
- Criteria depends upon size
what is non alcoholic fatty liver (steatosis)
- this is liver caused by the presence of excess fat
- there is no secondary cause for steatosis
how much fat in the liver is too much and what happens if the fat in the liver increases by too much
• Small amount of fat is physiological (2-3%) • Increased hepatic fat (>5-10%) – Steatosis – Inflammation – Fibrosis – Insulin resistance
what are the 5 things that happen when you are insulin resistance
• Increased glucose (activates ChREBP)
– De novo lipogenesis (SREBP1)
– Activates PKCe (inhibits IR tyrosine kinase)
• Inappropriate gluconeogenesis
– FOXO1-mediated
• Impaired glycogen synthesis (muscle and liver)
– Akt2-mediated
• Impaired suppression of lipolysis in adipocytes
– Glycerol and FFA
Induction of PPAR-γ (lipogenic)
how does hepatic fat accumulation happen
1, increased delivery of long chain fatty acids to the liver
– Adipocytokines (adiponectin & resistin)
– ↑ fatty acid translocase
– Central obesity
2, impaired clearance via VLDL formation
– ↓transport into mitochondria (CPT1 saturation)
– Fewer mitochondria for β-oxidation
describe the mechanism of injury for hepatic fat accumulation
Multiple hit hypothesis • Hepatic Fat Accumulation • Oxidative Stress (lioptoxicity) • Inflammation • Innate immune activation
how many units a week should you have
14 units a week
how many units a week can cause cirrhosis of the liver
-41 u/wk 12 years
• 3%men 4%women
– >42 u/wk
• 6-8%
describe what is an alcohol dependence
- Consistent high intake
- Less able to abstain
- Increased tolerance
- Physiological dependence
- Subjective insight
how do you treat alcoholic liver disease
• Community support • Detox / rehab programmes • Outpatient appointments – Blood tests / scans / biopsies • Emergency admissions – Bleeding / fluid retention / kidney failure – Expensive treatment – intensive care • Transplantation
what can result in alcoholic liver disease
You can get nutritional deficiencies these can lead to
- Possible re-feeding risk
- Thiamine and vitamin deficiencies
- Replace thiamine early or you will get
Wericke’s encephalopathy
Korsakoff’s syndrome
what are the causes of chronic liver disease
• Hepatitis B – Major problem worldwide – Drugs to control • Primary biliary cholangitis • Primary sclerosing cholangitis • Haemochromatosis • Wilson’s
describe how HBV can cause liver cirrhosis
causes inflammation of the liver this leads to cirrhosis which can cause liver failure and this leads to cancer
how do you prevent HBV
screening and vaccination
- do it in pregnancy
describe Hep B treatment
Pegylated interferon
Nucloside + nucleotide analogues
what does Hep B treatment do
Progression to cirrhosis can be halted
Fibrosis reduced
Reduce risk of HCC
what is haemochromatosis
iron overload
what is the mutation caused in haemochromatosis
90% - C282T mutation of HFE gene (Chr 6
how do you diagnose haemochromatosis
Serum iron > 30
Transferrin saturation >60% / TIBC
Liver biopsy
Genetic analysis
what is the treatment for haemochromatosis
venesection
what are the complications for haemochromatosis
Diabetes Cardiomyopathy Impotence Pigmentation Arthritis - chondrocalcinosis 30% develop hepatocellular carcinoma
what are the types of autoimmune hepatitis
Types
Childhood – a-LKM
Adult – a-SMA
Raised globulins (IgG
how do you treat autoimmune hepatitis
Treat with prednisolone and azathioprine
what is primary sclerosing cholangitis
Primary sclerosing cholangitis (PSC) is a long-term progressive disease of the liver and gallbladder characterized by inflammation and scarring of the bile ducts which normally allow bile to drain from the gallbladde
what are the symptoms of primary sclerosing cholangitis
Pruritis
Cholangitis
Dominant strictures leading to jaundice
what are the complications of primary sclerosing cholagnitis
Increased risk of:
Cholangiocarcinoma
Hepatocellular carcinoma
how do you diagnose primary sclerosing cholangitis
Positive pANCA / ANA / SMA
what are the treatments of primary sclerosing cholangitis
Beads on a string at ERCP
Ursodeoxycholic acid
Transplant
describe primary biliary cholangitis
Symptoms - CLD, pruritis, xanthelasma
Middle aged female
IgM; 96% AMA+ve
Ursodeoxycholic acid and vitamin replacement
Role for fibrates and obeticholic acid
what is Wilsons disease
Increased copper accumulation:
what are the symptoms of Wilson disease
Liver – cirrhosis / liver failure
Basal Ganglia – neuropsychiatric
Kidneys – Fanconi’s syndrome
Eyes – Keyser-Fleischer rings
how do you diagnose Wilsons disease
↑ 24hr[Cu]Ur, ↑ free Cu,
↓ total Cu, ↓ caeruloplasmin
how do you treat Wilsons disease
Penicillamine
Trientine
Zinc
