GI problem III - Ow Flashcards
Give some signs that are stigmata of chronic liver disease
Yellowing of the sclera - Jaundice
Palmar erythema
Spider naevi - often in chest, upper arms and back
what are the two main patterns of liver test abnormality?
Cholestaysis: when the GGT and ALP together rise
Hepatitis or hepatocellular pattern: AST and ALT go up.
Mixed picture: both transaminases and GGT are up.
What are some causes of high GGT
If obstruction expect to see the ALP go up with it
What tests mark synthetic function of the liver?
Albumin and prothrombin
Causes that lead to a fall in albumin
Inflammation (dec)
Low albumin in the contest of liver disease suggests?
They’ve had liver dysfunction for some time (chronic)
what is a good indicator of acute liver failure?
Raised prothrombin ratio in the context of liver disease
GGT up alone
Usually indicates steatosis i.e fat deposited into liver cells (either from alcohol or non-alcoholic fatty liver disease)
GGT and ALP
Think of cholestasis i.e obstruction to biliary drainage e.g. bile duct obstruction
AST and ALT
Think of hepatitis i.e. hepatocellular drainage
Steatosis - causes
Alcohol Non-alcoholic fatty liver disease - metabolic syndrome i.e: diabetes Dyslipidaemia Hypertension Increased BMI
Hepatitis - causes of hepatocellular damage
- viral hepatitis
- Alcoholic hepatitis (separate to alcoholic steatosis)
- Non-alcoholic hepatitis (what you get from the inflammation caused by non-alcoholic steatosis)
- Autoimmune hepaitis
- Ischaemic hepatitis (e.g. in severe blood loss or dehydration)
- Haemochormatosis(iron overload)
- Drugs/ herbal or natural supplements
What do drugs do to the liver?
Cholestasis
Hepatitis
Mixed
Not just new drugs, sometimes drugs that people have been on for a long time can cause abnormal liver tests
Liver tumors
- can present with?
- Types?
Cholestasis
mixed pattern
primary: hepatocellular carcinoma (above) only really develops in people with cirrhosis or chronic liver diseases
Secondary: liver mets (right)
lets talk about alcoholic liver disease
spectrum between steatosis and hepatitis
As the normal liver becomes exposed to alcohol you get fatty change e.g. fatty deposits in the liver, this is reversible so if you abstain from alcohol steatosis can improve and may disappear.
If people are binge drinkers they may get episodes of hepatitis with sudden or large volume exposure e.g. binge drinking
If you have chronic progressive steatosis, the liver doesn’t like to have fat in it, so over time will contribute to hepatitis and you will get inflammation from that. similarly if you abstain the hepatitis will go away and you’ll be left with steatosis.
And over time (usually with episodes of binge drinking) get cirrhosis, irreversible scarring of the liver (when fibrosis isn’t given time to repair itself)
Lets talk about Non-alcoholic fatty liver disease
instead of alcohol the cause is metabolic syndrome (encompasses a number of conditions including insulin resistance and risk factors for that e.g. diabetes, obesity, high lipids, hypertension)
Normal liver –> steatosis –> fat cells –> fibrosis/cirrhosis
Diagnosis of ALD and NAFLD?
Usually clinically
Transmission Hep A, B and C
A: fecal oral, contaminated food or water
B: Body fluids and blood - sex, transfusion and IDU
C: Blood: IDU
Problems with blood transfusions in underdeveloped contruies
Hepatitis D can only cause infection of you have?
Hep B, co infection. or superinfection. Cant have D alone
Hep E
Very much like Hep A also fecal oral
EBV and CMV
mostly asymptomatic in healthy adults
EBV –> infectious mono / glandular fever
CMV –> similar mono like syndrome
autoimmune hepatitis
Chronic autoimmune disease
Unknown aetiology
Autoantibodies attack the liver causing inflammation and damage
Episodic (flares), recurrent
More common in females than males
bimodal age distribution: young groups: 10-20 years, older group 45-70 years
Diagnosis:
- Autoimmune screen for certain liver antibodies
- Liver biopsies
Islamic hepatitis
results form severe haemodynamic compromise
- cariogenic
- severe dehydration
- severe sepsis
- blood clot to hepatic artery
Haemochromatosis
Hereditary - Autosomal recessive - Mutation of HFE gene - Most common: homozygous for C282Y - Europeans at highest risk - Low hepcidin levels --> increased iron absorption in GI tract Secondary - blood disorders - repeated blood transfusions Diagnosis: ferritin and iron saturation
Drugs and what they can do to the liver?
Paracetamol overdose
- antidote is NAC (N-acetylcysteine)
- narrow window period to give antidote
- History: at risk of self harm?
- Paracetamol - need to know time of ingestion
- Or give empirically if high risk
many drugs can affect liver function tests and present as
- Cholestasis
- Mixed
- predominantly hepatitis
Risk factors for liver tumours?
for heptocellular carcinoma - underlying liver cirrhosis - chronic hepatitis B with or without cirrhosis --> oncogenic virus for liver mets - known cancer elsewhere
If AST and ALP are in the thousands, typically 3 possibilities
- viral
- Ischemia
- paracetamol
… if AST and ALP in the hundreds no so helpful as it can be anything
AST >2x ALT usually suggests alcoholic hepatitis
How to work up a patient with abnormal LFTs
Is there jaundice? - indicates severity of disease (bilirubin)
Is synthetic function impaired?
- low albumin suggests possible cirrhosis
- Normal prothrombin ratio suggests no acute liver failure
Investigations
US - Gallstones, normal looking gall bladder - Bile ducts not obstructed - check echogenicity of liver, nodules? Hep A, B and C serology Iron studies Auto antibodies
Treatment of portal hypertension
Started on diuretics to treat ascites
Protein supplements to improved nutrition and albumin
Advised must stop alcohol
How canyon have no alcohol for years but liver failure?
brought on by infection
How can you treat hepatic encepalopthy?
Lactulose and fleet enema
What happens after decompensation
cant fix, liver gets worse medical emergency Code red for large volume haematemesis BP low, HR inc Peripheries cold IV fluid started for ressus Urgent full blood count Blood transfusion commenced
Spontaneous bacterial peritonitis
A complication that can occur in patients with cirrhosis and ascites
- Translocation of bacteria and endotoxins from the gastrointestinal tract to peritoneal fluid
Facilitated by: impaired defensive mechanisms in cirrhotic patients.
Spontaneous infection in peritoneal cavity i.e. peritonitis
Diagnosis: ascitic tap - neutrophils 250x10^6/L
Treatment:
- identify organism on culture
- treat with appropriate antibiotic
Acute versus chronic hepatitis B, the different types of transmission
Acute hep B
- adult transmission
- Parenteral (IV drug use/ contaminated blood transfusion) and sexual
Because your immune system will clear hep B as an adult
Chronic Hep B
- Neonate or childhood transmission
- perinatal / vertical and horizontal (child to child) comm
The different stages of HBV infections and the antigens / antibodies present
HBsAg - when initially infected
Shortly after this you develop symptoms
Start to develop immune response
Core antibodies: IgM is initial immune response to virus, when these rise the surface antigen levels start to fall. This is an acute antibody that doesnt stay in the system forever.
Over time the IgM core antibodies are replaced by the more permanent anti HB surface antibodies
Window period
if you do a blood test at a particular point in time it may not show you that the person has actually been exposed e.g. time between when the surface antigen disappears and when the surface antigen appears, so you need to request a core IgM antibody
if you’ve been successfully vaccinated, but not exposed to HBV what will show up on the antigen / antibody test?
Anti-HBs
The stages of chronic Hep B from childhood onwards
Phase 1: when baby / child infected, because their immune system is underdeveloped they are tolerant to the hep B so they don’t develop an immune response and therefore don’t have inflammation, typically they have very high levels of virus and the ALT is usually normal
Phase 2: as the child matures and enters adulthood in their 20’s and 30’s, the body tries to clear the virus, in this phase you’re most at risk of inflammation and fibrosis caused by the immune system attacking infected hepatocytes. Viral load will start to drop, get fluctuating levels of ALT, from inflam. Chronic Hep B is one of the leading causes of cirrhosis.
Phase 3: The body controls the virus, inflammation gone. this can last for many years
Phase 4: in some people the virus escapes from the immune regulation and reactivates –> ongoing liver damage
So chronic Hep B patients need regular blood tests to check for immune activation and inflammation.
briefly describe the progression of symptoms of hepatic encephalopathy
- mild confusion, limited attention span, irritability, inverted sleep, incoordination, tremor, impaired handwriting
- drowsiness, personality changes, intermittent dterioirdation, asterixis, ataxia, dysarthria
- somnolent, gross disporietaiton, marked confusion, slurred speech, hyperreflexia, muscle rigidity, babinski sign
- coma, no response to pain, decrebarte posture
Liver functions summary
- removes toxins
- metabolises glucose, produces energy
- removes bacteria from blood, helps body fight infection
- produces bile so we can absorb fats
- stores vitamins, minerals and sugar
- Produces most of the proteins needed by the body
- Produces most of the substances that regulate blood clotting
What is the Child-pugh score?
classifies the severity of cirrhosis and predicts mortality without transplantation (uses, billlirubin, albumin, PR ratio, degree of ascites and encephalopathy)
Complication of cirrhosis result from?
portal hypertension (variceal haemorrhage, ascites) of liver insufficiency (jaundice) both give encephalopathy
Manifestations of portal hypertension
arteriovenous shunting and or mechanical obstruction
hypersplenisim
- moderate anaemia
- neutropenia
- thrombocytopenia
oesophageal varices
caput medusae
Haemorrhoids
Pathogenesis of ascites
cirrhosis Inc resistance to portal flow Portal hypertension Two pathways: 1. Inc hydrostatic pressure + decreased albumin 2. Splanchnic vasodilation systemic arterial underfilling Activation of ADH and RAAs Renal Na and H20 retention
What is hepatic encephalopathy
the inability to get rid of the ammonia in the circulation, which we all form through breakdown of proteins in the gut.
It passes through the BBB
Mechanism of action of lactulose
- a non-absorbable daiassachride
produces osmosis of water - Diarrhoea
Reduces pH of colonic content and thereby prevents absorption of NH3
Converts NH3-NH4 that can be excreted
Some causes of portal hypertension other than cirrhosis
Right heart failure
Portal vein thrombosis
Budd chiari syndrome
how does portal hypertension lead to ascites?
PH splanchnic vasodilation Decreased effective circulatory volume Activation of RAAs 1. Renal sodium retention --> ascites 2. Renal vasoconstriction --> heptorenal syndrome
Definition of hepatorenal syndrome: types 1 and 2
Type 1:
doubling of serine creatinine over 24 hours
frequently follows a precipitating event such as infection
Survival without treatment in the order of weeks
Type 2:
less rapid renal functional deterioration than type 1
Mainly presents with refractory ascites
Survival without treatment in order of months
HCC treatment
if detected early can be cured
all patients with cirrhosis need HCC surveillance
- liver ultrasound and alpha fetoprotein every 6 months
