GI Problems 1 (Clinical) (Ow) Flashcards
What medications can upset the liver?
Antibiotics
Anti-inflammatories
What are the (clinical signs) Stigmata of chronic liver disease (3)
Stigmata of chronic liver disease - presence of these signs often suggests that someone has chronic liver disease
- Top left: scleral jaundice
- Scleral jaundice can also occur in acute liver conditions
- Top right: palmar erythema
- Redness of the palm, typically in the thenar and hypothenar eminences
- Bottom left: Spider nevus
- Vascular lesions that occur typically on the anterior chest, sometimes the upper limbs and back
58-year-old chef
2-weeks unwell. Nausea, off food. Yellow eyes
Past medical history includes type 2 diabetes, dyslipidaemia, gallstones on ultrasound
Medications include glipizide, aspirin, simvastatin, no new medications
Was a heavy drinker for 25 years (45 standard units/week)
- Now only binge drinks
- Last weekend had a dozen cans of beer
Lives alone. Smokes 1 pack/day
Family history:
- Both parents with diabetes
- Father has fatty liver
- No cancer
See Blood test results below
What does the Blood test indicate?
- Bilirubin is high, the patient is Jaundiced
- In this patient AST and ALT are both elevated which indicates the inflammation of the liver
- Hepatitis/hepatocellular pattern - AST and ALT go up
-
GGT up alone
- Usually indicates steatosis (fat deposited into liver cells)
- Most common cause is alcohol or non-alcoholic fatty liver disease
- Cholestasis - GGT and ALP elevated
- Most common cause is alcohol or non-alcoholic fatty liver disease
- Usually indicates steatosis (fat deposited into liver cells)
-
Albumin and prothrombin ratio are what we call, “markers of synthetic functions of the liver”
- There are other causes of decrease in albumin levels e.g. inflammation (acute phase reaction)
- Low albumin level indicates a chronic dysfunction, whereas acute liver dysfunction is characterized in a prolonged PR
*
What are the 2 main patterns of Liver Function Test abnormality?
- Cholestasis - GGT and ALP elevated
- Hepatitis/hepatocellular pattern - AST and ALT go up
What are the markers of the synthetic functions of the liver?
-
Albumin and prothrombin ratio are what we call, “markers of synthetic functions of the liver”
- There are other causes of decrease in albumin levels e.g. inflammation (acute phase reaction)
- Low albumin level indicates a _chronic dysfunctio_n,
- Whereas _acute liver dysfunctio_n is characterized in a prolonged PR
What do the following indicate?
Breaking down the LFT
- GGT up alone
- GGT and ALP
- AST and ALT
Breaking down the LFT
- GGT up alone
- Usually indicates steatosis (fat deposited into liver cells)
- Most common cause is alcohol or non-alcoholic fatty liver disease
- Usually indicates steatosis (fat deposited into liver cells)
- GGT and ALP
- Think of cholestasis (obstruction to biliary drainage)
- AST and ALT
- Think of hepatitis (hepatocellular damage)
Describe the cause of Steatosis
What indicates Steatosis?
- Alcohol - someone who has a heavy consumption of alcohol normally have a background of elevated GGT
-
Non-alcoholic fatty liver disease
- Metabolic syndrome
- Diabetes
- Dyslipidaemia
- Hypertension
- Increased BMI
- Metabolic syndrome
- Diagnosis is due to history
- GGT up alone
- Usually indicates steatosis (fat deposited into liver cells)
What are the causes of hepatitis?
How does this show on Blood Tests?
- Causes of hepatocellular damage
- Viral hepatitis
- Alcoholic hepatitis
- Often due to a sudden binge
- Non-alcoholic hepatitis
- Often a complication of long durations of non-alcoholic fatty liver disease
- Autoimmune hepatitis
- Ischaemic hepatitis
- Acute ischaemic insult usually due to a catastropic even that leads to profound loss of blood to the liver that induces massive inflammation
- Haemochromatosis
- Iron overload
- Drugs/herbal or natural supplements
- Can present as cholestasis, hepatitis, mixed
- Always take a drug history to identify any new drugs or supplements that they started as they could cause any type of liver test abnormality
- Can present as cholestasis, hepatitis, mixed
- AST and ALT
- Think of hepatitis (hepatocellular damage)
Describe Liver Tumours
1) What it can present with
2) Types of Liver Tumours
- Can present with
- Cholestasis
- GGT & ALP
- Mixed pattern
- Cholestasis
- Primary: hepatocellular carcinoma
- Secondary: liver metastases
How do you work up a patient with abnormal LFTs? (Part 1)
How do you know what caused his abnormal LFTs?
58-year-old chef
2-weeks unwell. Nausea, off food. Yellow eyes
Past medical history includes type 2 diabetes, dyslipidaemia, gallstones on ultrasound
Medications include glipizide, aspirin, simvastatin, no new medications
Was a heavy drinker for 25 years (45 standard units/week)
- Now only binge drinks
- Last weekend had a dozen cans of beer
Lives alone. Smokes 1 pack/day
Family history:
- Both parents with diabetes
- Father has fatty liver
- No cancer
- Is the pattern of abnormality hepatocellular or cholestatic or mixed?
- Elevated GGT indicates steatosis
- Elevated AST and ALT indicates hepatitis
- Test result is possibly due to
-
Alcoholic hepatitis with a background of long term drinking
- Ask the patient to abstain from drinking for a period of time. If the disease is due to alcohol, the symptoms should subside.
-
Inflammation from non-alcoholic fatty liver due to increased BMI, diabetes, high lipids
- Can ask the patient to lose weight.
- Or can be a mixture of the 2
-
Alcoholic hepatitis with a background of long term drinking
What is Alcoholic liver disease (ALD)?
Describe it
- ALD is defined by multiple processes that can occur
- A combination of steatosis and hepatitis
- Normal liver may develop into steatosis from long term alcohol exposure
- Sudden binge drinking can cause hepatitis (severe exposure)
- Both s_teatosis and hepatitis are reversible through abstinence_
- However, chronic or repeated exposure can lead to cirrhosis (irreversible)
- = irreversible scarring (fibrosis)
Describe Non-alcoholic fatty liver disease (NAFLD)
- Main difference from ALD is the causative agent
- Rather than alcohol, the cause is metabolic syndrome
- Metabolic syndrome is a term that encompasses a number of conditions that are driven by insulin resistance e.g. diabetes, obesity, hyperlipidaemia
- Fat cells in hepatocytes can cause inflammation -> steatohepatitis -> fibrosis -> cirrhosis
- Rather than alcohol, the cause is metabolic syndrome
Compare and Contrast Alcoholic and non-alcoholic hepatitis
Same
- Both diseases related to excessive fat (i.e. steatosis/fatty liver) and inflammation
- Diagnosis of ALD and NAFLD usually clinical
Different
- Related to excessive alcohol (ALD)
- Not related to alcohol (NAFLD)
Describe the types of Viral Hepatitis
1) Transmission
2) Can cause Chronic Liver Disease?
- 2 routes of transmission - either through parenteral (body fluids, blood) or faecal-oral (contaminated food or water)
- Hepatitis A is transmitted through ingestion of contaminated food and water
- Hepatitis B and C have fairly similar risk factors
- Hepatitis B is transmitted through contaminated blood or other body fluids
- e.g. injective drug use, sexual transmission
- The most common route of transmission for Hepatitis C is injective drug use
- Hepatitis D can only cause infection if you have hepatitis B (co-infection)
- Hepatitis E is also faecal oral
- Both hepatitis E and A are acute hepatitis infections (they do not develop into chronic infections)
What viruses can cause CHRONIC hep
B and C
D co-exist with B
Besides Hep A, B, C, D, E what can cause hepatitis?
EBV and CMV
Descibre EBV and CMV
- Most EBV and CMV infections in healthy adults are asymptomatic
- EBV (Epstein-Barr virus) causes classic infectious mononucleosis (glandular fever)
- CMV may cause similar mononucleosis-like syndrome
Can cause hepatitis- ACUTE
Describe Autoimmune hepatitis
Autoimmune hepatitis
- Chronic autoimmune disease
- Unknown aetiology
- Autoantibodies attack the liver causing inflammation and damage
- Episodic, recurrent
- More common in females than males
- Bimodal age distribution: young group 10-20 years, older group 45-70 years
- Diagnosis
- Autoimmune screen for certain liver autoantibodies
- Conclusive diagnosis requires Liver biopsy
Describe Ischaemic Hepatitis
- Ischaemic hepatitis results from severe haemodynamic compromise i.e. shock
- Cardiogenic
- Severe dehydration/blood loss (hypovolemic shock)
- Severe sepsis
- Blood clot to hepatic artery (obstructive shock)
Describe Haemochromatosis
1) Cause
2) Diagnosis
-
Hereditary
- Autosomal recessive
- Mutation of HFE gene
- Most common: homozygous for C282Y
- Europeans at highest risk
- Low hepcidin levels -> increased iron absorption in the gut -> increased iron deposition in organs including the liver
- e.g. skin deposition -> bronze skin
- Heart deposition -> cardiomyopathy
- Joint -> arthritis
- Pancreas -> diabetes
- Brain -> memory loss
- Often deposits in the liver first
- Secondary
- Blood disorders
- Repeated blood transfusions
-
Diagnosis: iron study
- Ferritin and iron saturation
- Iron saturation would be elevated
-
Ferritin elevated
- __ferritin can also be elevated in inflammation. This can be seperated by looking at the iron saturation
- Ferritin and iron saturation
How can you diganose Haemochromatosis?
Diagnosis: iron study Ferritin and iron saturation
- Iron saturation would be elevated
-
Ferritin elevated
- ferritin can also be elevated in inflammation. This can be seperated by looking at the iron saturation
DNA test: common gmutation: homozygous for C282Y
Describe Drugs that can cause hepatitis
- Always thing of drugs
-
Paracetamol overdose
- Antidote is NAC (N-acetylcysteine)
- Narrow window period to give antidote (needs to administer NAC relatively soon after overdose)
- History: at risk of self-harm?
- Paracetamol level
- Need to know time of ingestion
- Or give empirically if high risk
- Many drugs can affect LFTs and present as:
- Cholestasis
- Mixed
- Predominantly hepatitis
What are the risk factors for hepatocellular carcinoma
Liver tumours
- You really only see liver tumours in people with risk factors for hepatocellular carcinoma
- Underlying liver cirrhosis
-
Chronic hepatitis B with or without cirrhosis
- Hepatitis B is an oncogenic virus - formation of cancer even in the absence of cirrhosis
- If AST and ALT are in the thousands it means….
- If AST and ALT are in the hundreds it means….
- AST > 2x ALT usually suggests…..
- If AST and ALT are in the thousands , typically 3 possibilities
- Viral
- Ischemic
- Paracetamol overdose
- On the other hand, if AST and ALT are in the hundreds, not so helpful as it can be anything
-
AST > 2x ALT usually suggests alcoholic hepatitis
- This is known as AST/ALT ratio reversal
What sort of investigations would you do if someone came in with
1) Jaundice
2) High alcohol intake
3) High BMI
1) Ultrasound
2) Viral serology (A, B, C)
3) Iron studies
4) Liver autoantibodies
Describe Hep A, B and C serology
Hep A serology
- HAV IgM (current infection)
- HAV IgG (past infection)
Hep B serology
- HBsAg (current infection)
- HBsAb (previous infection or vaccination)
- If they also have HB core Ab, they’ve been previously infected, if not, it was a vaccination
- HB core Ab (previous infection)
Hep C
- anti-HCV ab (past or current infection)
- Seperated by PCR
What is the diagnosis and plan for this patient?
58-year-old chef
2-weeks unwell. Nausea, off food. Yellow eyes
Past medical history includes type 2 diabetes, dyslipidaemia, gallstones on ultrasound
Medications include glipizide, aspirin, simvastatin, no new medications
Was a heavy drinker for 25 years (45 standard units/week)
- Now only binge drinks
- Last weekend had a dozen cans of beer
Lives alone. Smokes 1 pack/day
Family history:
- Both parents with diabetes
- Father has fatty liver
- No cancer
Diagnosis and plan
- Alcoholic hepatitis, with possible underlying cirrhosis
- Significant alcohol history
- AST/ALT reversal
- Low albumin with clinical signs of chronic liver disease
- Advised complete abstinence
- Lose weight
- Long-term control of diabetes and dyslipidaemia
- He stops drinking
- Joins the gym and lost 5kg in weight with exercise
- Liver tests returned to normal
- A year later he returns with 3 weeks of increasing abdominal distension
- Loss of appetite
- Drinking 3 cans of beer every night for 3 months
Discuss the findings
- The l_ow albumin suggests poor synthetic function_ by the liver i.e. the liver is failing from cirrhosis
- The ascites is a sign of portal hypertension
- The l_ow platelet count (thrombocytopenia) is a sign of hypersplenism_ i.e. due to portal hypertension
- Blood from the spleen drains into the liver via the portal vein
- In portal hypertension, back pressure causes congestion of the spleen -> excessive destruction of platelets
- The slightly high bilirubin (jaundice) is due to ongoing alcohol exposure causing hepatic inflammation and necrosis
Describe the treatment of this patient
- He stops drinking
- Joins the gym and lost 5kg in weight with exercise
- Liver tests returned to normal
- A year later he returns with 3 weeks of increasing abdominal distension
- Loss of appetite
- Drinking 3 cans of beer every night for 3 months
Treatment of portal hypertension
- Started on diuretics to treat ascites
- Protein supplements to improve nutrition and albumin
- Advise MUST stop alcohol!!!
A few years later…
- He is rushed to hospital
- Confused and drowsy for 3 days
- Been coughing brown sputum for 2 weeks
- Feverish, sweaty
- BP95/40, pulse 125/min, JVP -1cm
- Tachypnoeic with accessory muscle use
- Not responding to verbal commands
- Chest dull right base and crackles
- No ascites or jaundice
- Hepatic flap +ve
- Sister says he has been abstinent since last presentation a few years ago
Diagnose and Treatment
- Elevated PR indicates acute live failure on top of the cirrhosis, which goes with the decompensation of cirrhosis
Putting it together…
- Pneumonia and sepsis
- Dehydration due to pneumonia and sepsis
- Acute liver failure on background of cirrhosis with high PR
- PR is an acute measure of liver function
- Albumin is a more chronic measure of liver function
- Hepatic encephalopathy due to acute liver failure
- No alcohol for years, but liver decompensation has been brought on by infection
Treatment
- IV antibiotics for pneumonia
- IV fluids for dehydration
- Lactulose and fleet enema for hepatic encephalopathy
- NG feeding to maintain nutrition
Describe Spontaneous bacterial peritonitis
- SBP is a complication that can occur in patients with cirrhosis and ascites
- Spontaneous infection in peritoneal cavity i.e. peritonitis
- Diagnosis: ascitic tap - neutrophils elevated (>250x106/L)
-
Treatment
- Identify organism on culture
- Treat with appropriate antibiotic
25 year old man presents with 2 weeks of flu like illness, vomiting, anorexia and tiredness
His occupation is painting cars, but he has had minimal exposure to toxins at work
His usual alcohol intake is 4-5 beers, 2-3 times a week (approx. 15 standard units per week)
There is no history of IV drug use
He is on no regular medications
1) Diagnose
2) What are the possible causes?
- ALT and AST in the thousands
- Ischemia
- Viral
- Paracetamol
- Albumin low, PR elevated
- Acute severe hepatitis, with long-term impaired liver function
- What is the diagnosis in general terms at this point?
- Acute severe hepatitis with jaundice
- Does the history of a “flu-like illness” give any clues to the nature of the illness?
- When you have severe hepatitis, often you can have non-specific symptoms
- Therefore no it doesn’t, because when you get severe inflammation of the liver, you often have other symptoms that accompanies it
- Is there any evidence of a significant problem with liver synthetic function? Explain which tests may help determine hepatic function
- Yes
- PR prolonged - acute inflammation
- Albumin low, which suggests an underlying possibly chronic condition
- However, only marginally low -> could just be a result of severe inflammation
- What are the possible causes?
- Ischaemia
- Viral hepatitis
- Paracetamol overdose
Diagnose
Hepatitis B (RECENT due to lack of positive HB core Ab IgM)
This is important because it helps with outcome
Describe Hep B serology
- sAg -> current infection
- HBcAb IgM -> positive = acute, negative = chronic
Describe the The 4 phases of chronic hepatitis B
- In the beginning when the baby/child is infected, because their immune system is underdeveloped, they are tolerant to the Hep B (they don’t develop an immune reaction)
- High levels of Hep B and no inflammation of the liver (normal ALT)
- As the person matures, they then develop immune responses to Hep B
- During this phase is when you are most susceptible to inflammation and fibrosis
- Viral load starts to drop
- Fluctuating levels of ALT due to inflammation
- This immune clearance phase is the reason why chronic hepatitis B is the most common cause of liver fibrosis
- Successful suppression of hepatitis B
- Does not mean elimination - people with chronic Hep B will never get rid of the infection but instead, can only control and suppress the virus
- In some people during some stage in life, the virus may escape the immune regulation and cause inflammation again
- Rise in virus level
- ALT fluctuation
- He is admitted to hospital. He continues to deteriorate over the subsequent 2 weeks
- He is sleepy during the day and becomes muddled in his thinking, then eventually he becomes very drowsy
- Albumin continues to fall and PR continues to elevate -> progressive liver failure
- Decreased glucose level suggests severe liver failure
Stages of hepatic encephalopathy (don’t need to memorize, just know that there are stages)
What are the causes of symptoms associated with Cirrhosis?
Describe Portal Hypertension
Portal hypertension is hypertension (high blood pressure) in the hepatic portal system – made up of the portal vein and its branches, that drain from most of the intestine to the liver. Portal hypertension is defined as a hepatic venous pressure gradient.[2]Cirrhosis (a form of chronic liver failure) is the most common cause of portal hypertension; other, less frequent causes are therefore grouped as non-cirrhotic portal hypertension.
Describe the Pathogenesis of ascites
Describe Hepatorenal syndrome
- Hepatorenal syndrome is a form of renal failure that can occur in people with liver cirrhosis
- There are two types of hepatorenal syndromes and can occur in people with progressive liver disease
