Liver Disease Flashcards
what does hepatitis mean
means inflammation of the liver
describe the blood flow of the liver
- Hepatic artery 25% of total blood flow
- Portal vein is 75% drains the GI tract and spleen
define the acinus
this is the functional unit of the liver
how many zones are there of the acinus
3
- zone 1
- zone 2
- zone 3
describe the oxygen supply to zones of the acinus
- Zone 1 – well oxygenated closet to the arterial part,
- zone 2 – less oxygenated
- zone 3 – least oxygenated part of the liver
list some of the functions of the liver
- Protein metabolism - synthesis/degradation,
- Coagulation factors
- Carbohydrate metabolism - glycogen
- Lipid metabolism – lipoproteins/cholesterol
- Formation of bile
- Hormone and drug inactivation
- Immunological function – a sieve
Name the liver function tests
Liver function - protein synthesis - albumin - coagulation cascade - prothrombin time (INR) Liver biochemistry - AST ALT – cells in trouble - Alkaline phosphatase (ALP) – bile ducts function - Gamma GT – likewise to ALP Bilirubin high - Jaundiced
what is AST and ALT a marker for
– hepatocytes in trouble – hepatocellular pattern, they go up and they tell you that the cells are in trouble
- ALT is more specific to the liver whereas the AST can rise in heart problems
what is alkaline phophatase (ALP) and gamma GT a marker for
- bile ducts are effected - these can be due to obstruction, alkaline phosphatase is secreted in the bile duct, it can also come from bone and various other places so need to make ALP is due to liver and not bone
- Gamma GT – likewise to ALP
what are the types of hepatitis virus
A B C D E
what hepatitis viruses are acute
A and E
these are acute – get cured or rarely get killed – do not go on for chronic liver disease – most without getting jaundice – get a faecal oral transmission,
- in pregnant women there is a high mortality in E
what are the most common hepatitis viruses
B C D
if you have hepatitis D you must also have..
hepatitis B
- you have to have hepatitis B in order to get hepatitis D
what happens with liver cirrhosis
- If you damage the liver with virus, alcohol or drug you get fibrosis but because it regenerates itself you lose the good architecture of the liver, blockages all back up,
what do you get with liver cirrhosis
- get portal hypertension
name the complications of cirrhosis
- porto-systemic encephalopathy
- haematemesis
- ascites
describe the complications of cirrhosis
- Porto-systemic encephalopathy – cant clear everything things go into the brain and make you a bit foggy
- Haematemesis – oesophageal varices- this is because the porto systemic pressures are higher in the portal system, develop veins and you bleed from them
- Ascites – all of these have a reason of why they are there – fluid in the peritoneal cavity, this is a symptom of chronic liver disease
what is the difference between liver failure, portal hypertension, and cirrhosis
Liver failure
- Liver failure is the inability of the liver to perform its normal synthetic and metabolic function as part of normal physiology.
portal hypertension
- Portal hypertension is an increase in the blood pressure within a system of veins called the portal venous system
cirrhosis
- a chronic disease of the liver marked by degeneration of cells, inflammation, and fibrous thickening of tissue. I
what can cause liver cirrhosis
- Hep B
- Hep C
- Alcoholic liver disease
- Diseases affecting bile ducts
- Non-alcoholic fatty liver disease
- Genetic disorders – excess amount of copper in your body, haemochromatosis – iron overload
- Paracetamol overdose
- Hepatocellular carcinoma
what is the most common cause of liver cirrhosis in UK
Hep B and Hep C
what are the types of organ transplant for the liver
- Deceased organ donation – when the liver has taken from someone who has died
- Living donor liver transplant – section taken and it can grow a back to normal
- Split donation – liver is split and given to two patients
what is the process for being chosen for a liver transplant
- Assessment- initial tests and investigations
- Model for end-stage liver disease (MELD) – looks at bilirubin, INR, and something
- Patient on waiting list
- Match found
- Surgery
- Treatment for life – immunosuppressants
what is the complications of liver transplants
- Liver rejection – usually happens in the first few weeks to months
- Infections – weakened immune system due to immunosuppressants – course of antibiotics, antivirals
- Biliary problems – 1 in 10 can get a biliary problem, like having a bile leak, obstruction and put a stent in
- Kidney failure – happens in 1 to 3 patients – side effect of taking the immunosuppressed
- Graft failure – when the transplanted liver doesn’t work as it should be, most common cause is reduce blood supply, only solution has to have another transplant
- Cancer
what causes dark urine
- bilirubin being excreted by the kidneys
what cause pale stools
– bile salts excreted by the kidney
what causes coughing up blood
- this is when the blood does not clot properly
what are the symptoms of liver cirrhosis
- dark urine
- pale stools
- coughing up blood
describe autoimmune hepatitis
- Uncommon – most common form is viral, autoimmune diseases effect women more then men,
- More likely in middle age women 4x
- 30-50% of people with autoimmune hepatits have another autoimmune disease
describe the mechanism that can cause autoimmune hepatitis
Molecular Mimicry
- Can have a virus or pathogen or food
- Acts as an stimulus
- Makes T cells
- Clonally expand
- These cause the hepatocyte to produce antibodies that are complementary in shape
- Similar shape to liver
- So immune system and antibodies produced by the liver attack the liver
how can you diagnose liver autoimmune hepatitis
- blood tests
- CY2PD6
what is the treatment of autoimmune hepatitis
Prednisone – 1st line, can add azathioprine
Prednisolone – diabetes, high blood pressure, weight gain
Azathioprine – increased susceptibility to infection
Liver transplant – last resort not really used
what are the complications of autoimmune hepatitis
- Moon face
- Osteoporosis
- Truncal obesity
- Muscle wasting – weakness and thin extremities
- Increased facial hair
- Easily bruising
- Cardiac hypotrophy
describe the diagnosis of liver autoimmune hepatitis
Blood tests
- Anti-smooth muscle antibody
- Anti-liver kdney microsome type I antibody
- Anti-nucualr antibody
- There is an increase in IgG antibodies
- Liver biopsy – shows inflammation
CYP2D6
- 2 enzymes
- One is cytochrome P60 and one is cytochrome 2D6
- Involved in drug deactivation, fatty acid meabtolism, steroid metabolism, catabolism of exogenous compounds
what is the progression of autoimmune hepatitis
Prognosis – depends on degree of inflammation
Without treat – 50% die within 5-10 years
With treatment – remission rate of 80-94%
Treatment is life long
Complications – Cirrhosis
how much is 1 unit of alcohol
10 ml of pure alcohol
how do you work out units of alcohol
- Units – strength x volume /1000
what is the recommended unit intake
- Recommended unit intake this is less than or equal to 14 units a week
what are the two pathways of alcoholic metabolism in the liver
- cytoplasmic system - uses alcohol dehydrogenase
- microsome - uses enzymes such as CYP2E1
How is alcohol metabolised in the liver
- Ethanol is converted to acetyaldehyde this happens by alcohol dehydrogenase (produces NADH), catalase (produces water) microsomal ethanol oxidising system[produces P450] (produces NADP and water)
- Acetaldehyde and oxidised NAD is turned into acetate and NADH this reaction is catalysed by acetylaldehyde dehydrogenase
- ATP and acetate and CoA goes to AMP and PPi and acetyl-CoA
- Acetaldehyde and oxidised NAD is turned into acetate and NADH this reaction is catalysed by acetylaldehyde dehydrogenase
what are the three main stages of alcoholic liver disease
- Fatty liver (steatosis)
- Alcoholic hepatitis
- Alcoholic liver cirrhosis
describe fatty liver
- these are fatty deposits in hepatocytes
- asymptomatic
- liver enzymes are raised/normal liver
- reversible with alcohol abstinence
- AST or ALT are raised or normal
what does a fatty liver look like on an ultrasound
- In the fatty liver – reflects greater number of ultrasound waves therefore looks lighter on an ultrasound
what are the features of alcoholic hepatitis
- Fever
- Abdominal pain
- Hepatomegaly
- Jaundice (severe cases)
- Hepatocyte ballooning – sign of hepatocyte degradation when they accumulate with water and then lysis
- Fatty inclusions as well – especially those of zone 3
describe the biochemistry marker changes in alcoholic hepatitis
- AST is increased and ALT is increased
- AST;ALT ratio is greater than 2
- GGT is rasied – sensitive to alcohol liver disease but not specific
- Reduction in albumin this can lead to ascites
how do you manage alcohol liver disease
- abstain from alcohol
- Vitamin B1 thiamine deficient – IV pabrinex – beware of Wernicke Korsakoff can lead to this due to b1 deficiency – get ataxia, get confusion, can lead onto a more severe system called Korsakoff syndrome, best to give supplementation in the form of pabrinex – contains B1 B2 B6 and vitamin C
- Corticosteroids such as prednisolone severe cases
what causes hepatitis C
- Transfusion before 1991
- Injection drug use - large portion due to this
- Occupational
- Sexual
describe Hep C viral structure
- Member of flavivirdae family
- Small envlopemd single RNA virus
- Two viral envelope glycoproteins E1 and E2 shields the virus from the immune system
- E2 is also the most genetically variable so because of that one individual can have loads of species of hep C as the virus replicates therefore it is called quasispecies
describe the progression of Hep C
- 85% won’t have any symptoms and don’t know they have been infected with it
- 25% resolve infection, chronic infection 75%
- Stay asymptomatic for a long time, usually realise when they progress onto cirrhosis which 20% do, and then some develop carcinoma from the cirrhosis
what is the presentation acute of HCV
- Actue
- Vague and non syspepcifc
- Fatigue
- Loss of appetide
- Low grade fever
- Abdo pain
- Jaundice
what is the presentation of chronic HCV
- Fatigue
- Jaundice
- Nausea
- Loss of appetite
- Abdominal swelling – ascites
- Muddled thinking – cognitive dysfunction PSE
- Bleeding veins in oesophagus
describe the histological appearance of someone with HCV (Hep C) and how is it different from cirrhosis
- there is a lot of inflammation that happens around the portal triad which is different from cirrhosis
- in cirrhosis there are nodules that tend to be around the portal tracts and surrounded by fibrous tissue
how do you diagnose Hep C
- Blood tests – looking for antibodies
- PCR
- Liver biopsy and imaging
how do you treat HCV
- HCV infection is now potentially curable, in the past INF lpha and ribavirin
- New drugs – DAA (direct acting antiviral) – simeprevir, sofosbuvir, and daclatasvir
what is the major cause of hepatocellular carcinoma
Hep B
what are the causes of hepatocellular caricinoma
- Cirrhosis most of the time
- Alcohol
- Hep B and C
- Hemochromatosis
- Aflatoxins (aspergillus flavus toxins)
what are the symptoms of hepatocellular carcinoma
- Upper abdo pain
- Weight loss
- Palpable mass in upper abdomen
- Fever
- Jaundice
how do you investigate hepatocellular carcinoma
- Raised serum alpha fetoprotein in 50%
- Ultrasound
- CT and MRI with contrast
how to you treat hepatocellular carcinoma
- Only 20-40% are considered for surgical resection non operative therapy TACE – trans arterial chemoembolization PEI – percutaneous ethanol injection Brachytherapy Chemotherapy
Surgical
- Resection
- Transplantation
