Gastro Flashcards
Which LFTs suggest hepatocellular injury?
ALT/AST
what are causes of hepatocullular injury ?
Hepatitis (viral, alcoholic, ischaemic)
Liver cirrhosis
Drug / toxin-induced liver injury (e.g. paracetamol overdose)
Malignancy (hepatocellular carcinoma)
what in the ALT/AST suggest alcoholic liver disease
The AST:ALT ratio can help determine the aetiology of hepatocellular injury, with a >2:1 ratio classical of alcoholic liver disease.2
where is ALP released from?
Serum alkaline phosphatase (ALP) is derived from biliary epithelial cells (cells lining the biliary tract) and bones.3 Raised ALP levels can therefore be caused by cholestasis or bone disease.
Where is GGT released from?
Gamma-glutamyltransferase (GGT) is found in hepatocytes and also biliary epithelial cells.2 It is a non-specific but highly sensitive marker of liver damage and cholestasis.
ALP with normal GGT
An ALP rise with normal GGT suggests bone disease (e.g. Paget’s disease, vitamin D deficiency, bony metastases)
ALP with a rise GGT rise?
An ALP rise with associated GGT rise is more suggestive of cholestasis
Isolated GGT
An isolated GGT rise is classically associated with alcohol excess.
Bilirubin metabolism
When red blood cells are broken down, unconjugated (insoluble) bilirubin is created as a waste product and binds to albumin in the bloodstream
Hepatocytes take up unconjugated bilirubin and metabolise it to form conjugated (soluble) bilirubin
Hepatocytes excrete conjugated bilirubin into the biliary tract, where it flows into the bowel lumen as bile
Gut bacteria further metabolise bilirubin in bile to form urobilinogen, which is eventually excreted in the stools as stercobilinogen
A small amount of urobilinogen is reabsorbed from the intestine into the portal venous system, and as urobilinogen is water-soluble, the kidney is able to excrete some of this into the urine.
Pre-hepatic jaundice?
Pre-hepatic jaundice occurs when increased red blood cell breakdown produces excess bilirubin. This can overwhelm metabolism/excretion pathways, leading to jaundice.
The most common cause of increased red blood cell breakdown is haemolysis. Bilirubin is unconjugated in the blood, as the hepatocytes have not yet metabolised it. The remainder of LFTs are generally normal, as the liver is otherwise working well.
Hint: In pre-hepatic jaundice, patients are often anaemic due to excess red blood cell breakdown. The diagnosis may be Gilbert’s syndrome if no anaemia is present.
Gilbert’s syndrome?
Gilbert’s syndrome is a congenital disorder present in up to 5% of the population. It results from a deficiency of glucosyltransferase, the enzyme responsible for the conjugation of bilirubin within hepatocytes.
Gilbert’s syndrome classically presents following viral infection with raised bilirubin but normal LFTs/ full blood count. The disease is benign and requires no specific management.
Hepatocellular jaundice
Hepatocellular jaundice occurs when hepatocytes are damaged and dysfunctional, leading to an inability to metabolise unconjugated bilirubin from the bloodstream. This leads to high levels of unconjugated bilirubin in the blood. There will generally also be very high ALT / AST levels, marking hepatocyte damage.
Hint: Common causes of hepatocellular injury are covered above (hepatitis, cirrhosis, malignancy, drug or toxin insult). When liver injury is severe, there are not enough functioning hepatocytes to metabolise bilirubin, and jaundice will develop.
Cholestatic jaundice
Cholestasis is an interruption in bile flow from hepatocytes to the gut. When this interruption is severe, bilirubin levels will build up in the blood. The bilirubin has been metabolised in the liver, and thus the bilirubin in the blood is predominantly conjugated bilirubin. There will generally also be high ALP levels with associated high GGT, marking dysfunction of the biliary system.
Obstructive jaundice will classically lead to dark urine and pale stools. Bilirubin cannot enter the gastrointestinal tract due to cholestasis, leading to low stercobilinogen excretion in stools.
The bilirubin in the blood is conjugated and can be filtered by the kidneys. The presence of conjugated bilirubin gives the urine a very dark colour.
Hint: Stools may also be pale in hepatocellular jaundice, as there is decreased bilirubin metabolism/excretion, however as the bilirubin in the blood is unconjugated, it will not be able to pass into the urine. Therefore, the urine should remain a normal colour.
causes of cholestasis??
Causes of intrahepatic obstruction (obstruction of the hepatic bile canaliculi):
Hepatitis
Cirrhosis
Malignancy
Drugs (e.g. antibiotics, oral contraceptive pills, anabolic steroids)
Pregnancy
Causes of extrahepatic obstruction (obstruction of hepatic ducts, or distal biliary tree):
Gallstones
Primary sclerosing cholangitis
Intraluminal malignancy: cholangiocarcinoma
Extraluminal malignancy causing duct compression: head of pancreas tumours
comparing the pattern of ALT and ALP res
A greater than 10-fold increase in ALT and a less than 3-fold increase in ALP suggests a predominantly hepatocellular injury
A less than 10-fold increase in ALT and a more than 3-fold increase in ALP suggests cholestasis
It is possible to have a mixed picture involving both hepatocellular injury and cholestasis
An isolated ALP rise without a GGT rise should raise your suspicion of bony pathology.
Liver Screen
Hepatitis serology (A/B/C)
Epstein-Barr Virus (EBV)
Cytomegalovirus (CMV)
Anti-mitochondrial antibody (AMA)
Anti-smooth muscle antibody (ASMA)
Anti-liver/kidney microsomal antibodies (Anti-LKM)
Anti-nuclear antibody (ANA)
p-ANCA
Immunoglobulins – IgM/IgG
Alpha-1 Antitrypsin (to rule out alpha-1 antitrypsin deficiency)
Serum Copper (to rule out Wilson’s disease)
Ceruloplasmin (to rule out Wilson’s disease)
Ferritin (to rule out haemochromatosis)
causes of acute liver failure?
paracetamol overdose
alcohol
viral hepatitis (usually A or B)
acute fatty liver of pregnancy
Clinical features of acute liver failure?
Features*
jaundice
coagulopathy: raised prothrombin time
hypoalbuminaemia
hepatic encephalopathy
renal failure is common (‘hepatorenal syndrome’)
*remember that ‘liver function tests’ do not always accurately reflect the synthetic function of the liver. This is best assessed by looking at the prothrombin time and albumin level.
what is the definition of acute liver failure?
Acute liver failure (ALF) is a rare, life-threatening, potentially reversible condition with a rapid decline in hepatic function characterised by jaundice, coagulopathy (INR >1.5), and hepatic encephalopathy in patients with no evidence of prior liver disease
How is liver failure classified?
ALF may be classified as hyperacute, acute, or subacute, depending on the interval from the onset of jaundice to the development of encephalopathy
When should acute liver failure be discussed with transplant centre?
All cases of acute liver failure should be discussed with a transplant centre for consideration of transfer; however, robust supportive management prior to transfer is crucial.
For any acute liver injury with significant or worsening (liver-related) coagulopathy, rapid recognition and evaluation of severity should be followed by prompt discussion with a liver transplant centre, facilitating early provision of advice and transfer where appropriate.
.
what is acute liver injury?
Acute liver injury (ALI) is defined as an acute derangement in liver function tests associated with liver-related coagulopathy, in the absence of underlying chronic liver disease (CLD)1. A subset progress to acute liver failure (ALF), a relatively rare syndrome characterised by altered consciousness due to hepatic encephalopathy (HE) in the setting of an ALI.
what is acute on chronic liver failure?
cute-on-chronic liver failure (ACLF) is a distinct phenomenon, involving rapidly progressive organ failure in the context of established cirrhosis, triggered by superimposed liver injury or extrahepatic precipitants such as infection
How is acute liver failure subcategorised?
ALF can be subcategorised by time elapsed between onset of jaundice and development of encephalopathy, into “hyperacute” (< 7 days), “acute” (7-28 days), and “subacute” (4-24 weeks) liver failure
Assessment and initial investigations for acute liver failure?
Stabilise the patient through robust supportive care
Determine aetiology
Acquire baseline investigations and establish severity
Exclude CLD and causes of secondary liver dysfunction (e.g. ischaemic hepatitis/malignant hepatic infiltration1)
Ensure timely liaison with an LT centre.
Specific questions in history in a patient with acute liver failure?
Presentation - time from onset of jaundice to encephalopathy
last time patient was clinically well
PMH
co-morbidities, previous abdominal surgery, performance status, exercise tolerance
Drug history - paracetamol, over the counter, herbal remedies, recent abx
SH - travel, smoking alcohol, drugs, high risk sexual behaviour
mental health
FH - Wilsons disease, IHD
Investigations for ALF?
Bloods
FBC, U&E’s
LFT including split bilirubin
Coagulation screen
group and save
Ammonia
ABG
Non invasive liver screen - Viral, autoanibody screen, metabolic
Paracetamol level
Septic screen
CT head, chest, abdominal, pelvis with triple phase liver imaging to assess vasculature
Echo
ECG
Management of acute liver failure
ALF patients are usually intravascularly deplete, so hypotension mandates aggressive initial fluid resuscitation; where response is inadequate, inotropes (including Noradrenaline and Vasopressin) are utilised to maintain adequate mean arterial pressure (MAP)1.
Endotracheal intubation to ensure airway protection is indicated in Grade 3-4 HE. Patients risk raised intracranial pressure from cerebral oedema driven by hyperammonaemia11. Neuroprotection is mandated (including nursing at 30º, Sodium control targeting 145-150mmol/L, high-volume CVVHF to lower ammonia levels, and avoidance of hypercapnia)
ALF patients are vulnerable to bacterial and fungal infections, which can preclude LT or increase post-LT mortality11. Prophylactic broad spectrum antibiotics and anti-fungals are indicated.
Prothrombin time/INR is a key marker of hepatic function, informing prognosis and guiding the need for LT3. Parenteral Vitamin K (10mg) should be administered, but coagulopathy should not be corrected without clear rationale (i.e. if bleeding)1,3, or following discussion with the LT centre.
Hepatological: N-acetylcysteine is indicated for all ALF patients, irrespective of aetiology1,3,12.
Enteral feeding with laxatives and enemea
Monitor for AKI
Patients are at risk of hypoglycaemia, and blood glucose should be checked hourly. Phosphate may fall rapidly, requiring aggressive replacement.
Decompensated Cirrhosis care bundle?
Investigations
Bloods, blood cultures, USS abdomen
Ascitic tap irrespective of clotting parameters and send to lab
If high alcohol intake - prescribe pabrinex and commence treatment for alcohol withdrawal if needed.
Treat with abx
SBP with abx and HAS
Manage AKI and hyponatramia
Suspend diuretics and nephrotoxic drugs
Fluid resuscitation - HAS or NaCL
Fluid balance
Map > 80
Esceleta to higher care
Manage GI bleeding
Fluid resuscitation
IV terlipressin
Prophylactic abx
PT prolonged - give IV VK, If > 20 seconds give FFP
If pets < 50 give IV pets
Transfer if Hb < 70
Lactulose 20-30mg TDS and phosphate enema
How to differentiate ascites ?
SAAG can differentiate ascites resulting from portal hypertension and from other causes. It is more useful than the protein based exudate / transudate concept. Calculate SAAG by:
SAAG = (serum albumin) – (ascites albumin)
If SAAG >11g/L then ascites very likely the result of portal hypertension (97% accuracy).
what would lead to SAAG < 11g/L
diffuse peritoneal mets
TB peritonitis
pancreatic ascites
Nephrotic syndrome
what would cause a SAAG > 11g/L
Cirrhosis
alcohol hepatitis
Cardiac ascites
massive liver mets
what should VTE prophylaxis be held in liver disease?
when Platelet count is < 50
Differential diagnosis for abdominal pain?
Peptic ulcer
appendicits
pancreatitis
Biliary colic
acute cholecystitis
diverticulitis
AAA
Intestinal obstruction
Unusual causes :
acute coronary syndrome
diabetic ketoacidosis
pneumonia
acute intermittent porphyria
lead poisoning
Clinial features of acute upper GI bleeding?
Haematemesis
Melena
rise in urea
Differentials for UGIB?
oesophageal varicose
Oesophagitis
Cancer
Mallory weiss tear
Gastric ulcer
Diffuse erosive gastritis
Dieulafor lesion (arteriovenous malformation)
Aortic enteric fistula
