GI And Liver Flashcards
What is ALP and when is ALP affected
Alkaline phosphatase - Role in dephosphorylating molecules particularly in the bone and biliary tree
…SO…
Increased in biliary tree damage + bone pathology
Not just specific to liver pathology but may be indicative of it
What is GGT and when is GGT affected
Gamma-glutamyl transferase - enzyme which has a role in glutathione synthesis (major antioxidant)… found everywhere in body but mainly the liver
…SO…
It’s increased in Acute liver disease
Shows a hepatic/bony cause for the change
REMEMBER… ALP suggests biliary tree damage
Not just specific to liver pathology but may be indicative of it
Define appendicitis
Inflamed appendix; usually due to luminal obstruction
Surgical emergency
Causes of appendicitis
Faecolith (hard solidified faeces)
Lymphoid hyperplasia (in teens, of peyer’s patches)
Worms
Blockage typically affected with ecoli and as pressure increases inside appendix you get increased risk of rupture (SBP)
Signs and Sx of appendicitis
Umbilical pain which localises to the McBurney’s point
Pyrexia + rebound tenderness & abdo gauging
Rosving’s - palpation of the left iliac fossa causes pain in the RIF).
Obturator sign - pain is worsened by flexing and internally rotating the hip.
Psoas sign - pain is worsened by extending the hip.
Complication of appendicitis
Rupture
Peri-appendiceal abscess
Investigation and Dx of appendicitis
CT Abdo + pelvis - gold standard
Rule out pregnancy in females of child-bearing age assume they are pregnant until proven otherwise - to rule out ectopic pregnancy (presents with right iliac fossa pain)
Tx for appendicitis
Antibiotics
- ensure the abcess is drained before giving ABx (they are walled off bacterial collection therefore systemic ABx aren’t useful; drain and give intra-abscess ABx)
Then appendectomy (laproscopic)
What is AST / ALT
Also useful markers that may help identify liver pathology (like GGT and ALP)
They are found in the liver, heart, kidney muscles
AST:ALT ratio ≈ 1 (so if the ratio is off then may suggest pathology)
> 2:1 ratio suggests alcoholic liver disease (esp with increased GGT)
> 4.5:1 ratio suggests Wilson’s (Copper accumulation) / hyperthyroidism
< 0.9:1 ratio suggests NAFLD
A 19-year-old woman is admitted to hospital having taken an overdose of over 200 paracetamol tablets at home. Despite treatment with n-acetylcysteine she develops jaundice, worsening coagulopathy on her clotting studies and is now confused. She is referred for liver transplant.
What condition does she have..?
Acute liver failure
Pathophysiology of acute liver failure
The rapid decline in hepatic function characterised by jaundice, coagulopathy and hepatic encephalopathy
Coagulopathy: INR > 1.5
Essentially liver loses ability to regenerate and repair -> irreversible damage (i.e. decompensated cirrhosis)
What is fulminant liver failure
Rare syndrome of massive hepatocyte necrosis (histological LH see multi-acinar necrosis too)
Onset………..
Hyperacute: within 7 days
Acute: between 8 and 28 days
Sub-acute: between 29 days and 12 weeks
Main cause of fulminant liver failure
paracetamol overdose - in 70% of cases
What is acute on chronic liver failure
Rapid decline in Px with chronic liver Sx
What is chronic liver failure
Px with progressive Hx of liver disease
Name 3 types of liver function tests we can measure
Bilirubin (conjugated/unconjugated) increases
Albumin decreases
Prothrombin time (PT/INR) increases
These 3 are directly relate to liver damage…v.specific
Remember the enzymes (AST,ALT,GGT,ALP) aren’t as specific as they can be altered by a lot of other things
Name 2 hepatocellular enzymes
Transaminases
AST
ALT
Name a Cholestatic enzyme
Alkaline phosphatase:
ALP
Give 5 causes of acute liver failure
Viral; Hep A, B, E / CMV / EBV
Autoimmune Hep
Drugs; Paracetamol / alcohol / ecstasy
HCC (hepatocellular carcinoma)
Budd-chiari syndrome (post hepatic vein blockage)
Signs and Sx of acute liver failure
Acute presentation of…
Jaundice, coagulopathy and
hepatic encephalopathy - Altered mood, sleep disturbance, inappropriate behaviour
What criteria is used for hepatic encephalopathy
West haven criteria grade 1-4:
1) altered mood / sleep disturbance
2) lethargy / mild confusion / Asterixis
3) marked confusion
4) comatose
Investigation and Dx of acute liver disease
Bloods:
LFTs - (increased bilirubin, decreased albumin, increased PT/INR)
Increased serum AST/ALT decreased glucose
Imaging:
USS to check for budd-chiari syndrome
Microbiology:
Rule out infections; blood culture, urine culture, ascites tap
Tx for acute liver disease
Acute: ABCDE; IV fluids, analgesia
Then treat underlying cause + complications;
Paracetamol overdose; give activated charcoal + N-acetyl cysteine.
ICP - IV MANNITOL
Hepatic encephalopathy - LACTULOSE; Increase NH3 excretion
Ascites - diuretics; spironolactone
Haemorrhage - Vitamin K
Sepsis - SEPSIS 6.
What type of complications are there in acute liver disease?
ICP
Hepatic encephalopathy
Ascites
Haemorrhage
Sepsis
Tx of acute liver disease complications
ICP - IV MANNITOL
Hepatic encephalopathy - LACTULOSE; Increase NH3 excretion
Ascites - diuretics; spironolactone
Haemorrhage - Vitamin K
Sepsis - SEPSIS 6
Define chronic liver failure
Progressive liver disease over 6 months due to repeated liver damage
Causes of chronic liver failure
Most common - alcoholic liver disease
Non-alcoholic fatty liver disease
Viral; Hep B,C (± D)
Drugs
Metabolic
Risk factor for chronic liver failure
Alcohol
Obesity
Diabetes mellitus type 2
Drugs
Metabolic disease - Wilson’s
Stages of liver failure
Hepatitis / cholestasis ———> Fibrosis (reversible damage) ———> Cirrhosis (irreversible) ———>
Compensated Some extent of liver function.
…OR…
Decompensated End stage liver failure.
———> HCC
Give 5 signs of decompensated liver failure
Jaundice
Hepatic encephalopathy
Coagulopathy
Ascites (portal HTN, oesophageal varices)
Serum albumin decreased
What score is used for assessing the progression of liver failure
Child Pugh score (A-C) based on a 1yr survival:
A… 100%
B… 80%
C… 45%
Decompensated liver cirrhosis has a huge risk of developing what
Hepatocellular carcinoma
Patients Sx with chronic liver failure
Jaundiced
Ascites
Hepatic encephalopathy
Capital medusae
Spider naevi
Palmar erythema
Gynecomastia
Investigation and Dx of chronic liver failure
Liver biopsy (gold standard) - used to determine extent of cirrhosis/fibrosis
LFTs + USS + ascetic tap culture
Tx of chronic liver disease
Prevent progression; lifestyle modification
Consider liver transplant (if decompensated liver failure)
Manage complications:
hepatic encephalopathy - lactulose
Ascites - diuretics
Define gallstones
Small solid stones that form within the gallbladder
3 types:
Cholesterol (80%) gallstones
Bilirubin / pigment gallstones
Mixed gallstones
What are gallstones made up of
Most common type: Cholesterol gallstones (80%) - due to increased cholesterol, reduced bile salts and biliary stasis
Can also get… Bilirubin (pigment) gallstones
Could have a mix of the 2 types… cholesterol and bilirubin
Define cholestasis
Blockage of bile flow
Define cholelithiasis
Gallstones
Define choledocholilithiasis
Gallstones that have moved into the bile duct
Define biliary colic
Still essentially gallstones…
intermittent right upper quadrant pain caused by the gallstones irritating bile ducts
Define cholecystitis
Inflammation of gallbladder
Define cholangitis
Inflammation of the bile ducts
Define gallbladder empyema
Pus build up in gallbladder
Difference between cholecystectomy and cholecystostomy
Cholecyst_ecto_my: surgical removal of the gallbladder
Cholecyst_osto_my: inserting a drain into the gallbladder
Role of gallbladder
It stores bile - a fluid produced by the liver that helps break down fatty foods
Risk factors for gallstones
Remember as 5F:
Fat
Female
Forties
Fertile
FHx of gallstones
+ DM / Crohns / haemolytic conditions (** haemolysis (e.g. sickle cell disease) causes excess circulating bilirubin resulting in pigment gallstones**)
Clinical features of gallstones
RUQ ‘biliary colic’ pain
Constant pain >30mins
Worse after fatty foods.
Pain may radiate to the right shoulder or interscapular region
Murphy’s sign negative: On palpation of the right upper quadrant there is no arrest of inspiration
Pain is often reproduced after eating, but not on palpation
In which condition might u feel pain on eating fatty foods and why
Gallstones
Fat entering the digestive system causes cholecystokinin (CCK) secretion from the duodenum. CCK triggers contraction of the gallbladder, which leads to biliary colic.
Patients with gallstones and biliary colic are advised to avoid fatty foods to prevent CCK release and gallbladder contraction.
Give 4 complications of gallstones
Acute cholecystitis
Ascending cholangitis
Obstructive jaundice - stone blocks the ducts
Pancreatitis
Gallbladder cancer
Investigation / diagnosis of gallstones
1st line: Abdo USS
Could do LFTs
Consider: Magnetic resonance cholangiopancreatography (MRCP): if no common bile duct stones are seen on abdominal ultrasound, but…The common bile duct is dilated on abdominal ultrasound and/or Liver function tests are abnormal
Tx for gallstones
Elective laparoscopic cholecystectomy - for all symptomatic px
Until then…….
For mild pain: oral NSAIDs (Diclofenac) / paracetamol
For severe pain: IM NSAIDs (IM Diclofenac)
+ Lifestyle ∆: avoid fatty foods and increase fibre intake
Other than gallstones which 2 other conditions can come under biliary tract diseases
Acute cholecystitis
Ascending cholangitis
Define acute cholecystitis
Acute inflammation of the gallbladder - 90% of acute cholecystitis is caused by inflammation impacted at the neck of the gallbladder or cystic duct, resulting in inflammation of the gallbladder wall.
Bacterial overgrowth, usually involving gram-negative rods or anaerobes. This is known as calculous cholecystitis
What colours are the gallstones
cholesterol stones (yellow)
pigmented stones (black or brown) which are made up of calcium salts.
Risk factors for acute cholecystitis
Same as gallstones:
5 ‘Fs’ -fat, female, fertile, forties, FHx
Signs and Sx of cholecystitis
Should not be jaundiced
RUQ pain (>30 mins) + fever, tender gallbladder
Pain might be referred to right shoulder tip
Murphy’s sign positive: palpating the RUQ whilst the patient breathes in deeply causes pain
Investigation and dx of cholecystitis
1st line: abdo USS - Thickened gallbladder wall (≥3mm)
LFTs are normal
FBCs - Leukocytosis & neutrophilia
Tx for cholecystitis
1st line:
Iv fluids + analgesia (diclofenac)
+ IV broad spec ABx - cefuroxamine (for gram-negative and anaerobic cover)
Early laparoscopic cholecystectomy
2nd line:
Urgent cholecystostomy
38-year-old overweight female presents to the emergency department with persistent right upper quadrant pain, with severe pain on inspiration when the doctor palpates the right subcostal region. She has a temperature of 38.9°C.
What condition might she have
Acute cholecystitis
Define cholangitis
Infection of the biliary tree / bile ducts
- surgical emergency - high mortality due to sepsis
Pathophysiology of cholangitis
Commonly caused by gallstones (cholelithiasis)
which move into the common bile duct (choledocholithiasis). Obstruction causes cholestasis and promotes the growth of bacteria, most commonly gram-negative, which then cause an ascending infection.
E. coli is the most common pathogen.
Most common causative pathogen of cholangitis
E. Coli
Signs and Sx of cholangitis
RUQ pain, fever, jaundice (obstructive; dark urine + pale stool)
Charcot’s triad
What condition is reynauds Pentad seen in
Ascending cholangitis
Charcot’s triad + altered mental state + hypotension
Investigation and Dx of cholangitis
1st line: abdo USS (Common.BD dilation + gallstones)
LFTs: hyperbilirubinuraemia
Gold standard: MRCP
Tx of cholangitis
ERCP
Then
Laproscopic cholecystectomy
Consider risk of sepsis - biliary obstruction increases back flow of ‘biliary sludge; stasis is the basis
Bacteria (e.coli) from intestines can climb up through Ampulla of V and colonise biliary tree
Give 7 roles of the liver
Carbohydrate metabolism
Oestrogen regulation
Detoxification
Bilirubin regulation
Immunity
Albumin production
Clotting factor production
remember as Call Of Duty; BIAC instead of Call of duty; blac..ops
What happens if things go wrong with the liver
Carbohydrate metabolism - Hypoglycaemia
Oestrogen regulation - Gynecomastia, spider naevi, palmar erythema
Detoxification - Hepatic encephalopathy
Bilirubin regulation - Jaundice, pruritus
Immunity - Bacterial infection
Albumin production - Oedema, Ascites, leukonychia
Clotting factor production - Easy bruising and bleeding
What is the best indicator for liver function
Serum albumin and PT
Define viral hepatitis
Inflammation of liver as a result of viral replication within hepatocytes
How long does hepatitis have to persist to be considered as chronic
6 months
Give 4 causes of acute hepatitis
Hep A-E infection
EBV
CMV
Toxoplasmosis
Give 3 non-infective causes of acute and chronic hepatitis
Autoimmune
Alcohol
Non alcoholic fatty liver disease
Drugs induced
Toxins
Give Sx of acute hepatitis
Abdo pain
General malaise
Myalgia
GI upset
Raised AST & ALT
± jaundice
Which Hep viruses are causes of chronic hepatitis
Hep B (± D)
Hep C
Hep E
Give potential complications of chronic hepatitis
Uncontrolled inflammation —> fibrosis —> cirrhosis —> HCC
Is hep A RNA / DNA virus
RNA
How is hep A transmitted
Faeco-oral transmission
- shellfish / contaminated water+food
Who’s might be at risk of hep A infection
Travellers
Food handlers
Is hep A acute or chronic
Acute
100% immunity after infection
How would you Dx someone with a viral infection
Viral serology:
Anti-HAV IgM and anti-HAV IgG
Describe management of HAV infection
Supportive; monitor liver function to prevent fulminant hepatic failure
Manage close contacts
What 1º prevention is there for HAV
Vaccination
Is HEV an RNA and DNA virus
Small RNA virus
How is HEV transmitted
Faecal oral
Is HEV acute or chronic
Acute; only will progress on to chronic if immunocompromised
True / false: Hepatitis is a notifiable disease and Public Health need to be notified of all cases.
True
What does HAV present with
N&V
Anorexia
Jaundice - it can cause cholestasis (slowing of bile flow through the biliary system) with dark urine and pale stools and moderate hepatomegaly
Is HBV a RNA or DNA virus
DNA
How is HBV transmitted
Blood-borne / bodily fluids
Like IVDU, sexual intercourse…
Which hepatitis has vertical transmission
passed from mother to child during pregnancy and delivery
Hepatitis B
What are the viral markers presented for viral infection
Surface antigen (HBsAg): active infection
E antigen (HBeAg): Viral replication: High infectivity
Core antibodies (HBcAb): implies past & current infection
Surface antibody (HBsAb): Vaccination
Hepatitis B virus DNA (HBV DNA): this is a direct count of the viral load
What types of core antibodies are there…
IgM
IgG
Explain how viral serology for hep B would work???
HBsAb suggests at some point the body interacted with HBsAg via interaction with the virus / vaccination
So how do we tell if the Px has the actual virus or a past interaction…
HBcAb can help differentiate between acute, chronic and past infection.
IgM implies active infection - low titre in chronic
IgG implies a longer interaction with the virus.
So to tell the difference between chronic infection and past… check HBsAg.
When IgG is high and theres a +ve for HBsAg = chronic
When IgG is high and theres a -ve for HBsAg = past infection
What does the viral marker HBeAg suggest
Released during replication
I.E. acute phase of the infection
The higher the E antigen, the higher the infectivity…
Primary prevention of hep B
Vaccination
Hep B is now included as part of the UK routine vaccination schedule (as part of the 6 in 1 vaccine).
What type of virus is hep C
SsRNA
How do you Tx hep C
DAA
Direct Acting Antivirals
Is hep C acute / chronic
1 in 4 fights off the virus and makes a full recovery
3 in 4 it becomes chronic
What are the complications of chronic hep
Fibrosis —> compensated cirrhosis —> decompensated cirrhosis —> HCC
What type of virus is hep D
Defective RNA virus - dependant on HBsAg to survive so hep D only exists with Hep B
Tx for hep D
No proper Tx
How to test hep C
Hepatitis C antibody (HCsAb) is the screening test
Hepatitis C RNA testing is used to confirm the diagnosis of hepatitis C, calculate viral load and identify the genotype
Tx for hep C
DAA
Ribavarin + N55Ai / N55Bi - needed for viral replication
Define autoimmune hepatitis
Rare cause of chronic hepatitis.
T cell-mediated response against the liver cells. This is where the T cells of the immune system recognise the liver cells as being harmful and alert the rest of the immune system to attack these cells.
Causes lupus like rash -
Types of autoimmune hepatitis
Type 1: adults females (80%)
Type 2: children / young females
Risk factor for autoimmune hepatitis
Females
Autoimmune disease
HLADR3 / DR4
What type of autoantibodies are found in autoimmune hep
Type 1 -
Anti-nuclear antibodies (ANA)
Anti-smooth muscle antibodies (ASMA)
Type 2 -
Anti-liver kidney microsomes-1 (anti-LKM1)
Anti-liver cytosol antibody-1 (anti-LC1)
Investigation and Dx of autoimmune hep
Serology
Confirm with liver biopsy
Tx of autoimmune hep
Corticosteroid (prednisolone)
Azathioprine (immunosuppressant)
End-of-life liver: liver transplant
Physiology of jaundice
Spleen
RBC —> (globin) + haem —> (fe3+) + bilirubin —> unconjugated bilirubin - transported in blood using albumin - not water soluble
Liver
UGT (UDP glucuronosyl transferase) + glucuronic acid —> conjugated bilirubin
Small intestine
Conjugated bilirubin travels to S.I via common bile duct with opening Ampulla of Vater —> modified to Urobiligen using colonic flora
—> Stercobilin (90%) - makes faeces brown
—> Urobilin (5%) - makes urine yellow
—> Enterohepatic recycling (5%)
Define jaundice
AKA icterus
Yellowing of the skin and eyes due to bilirubin accumulation of unconjugated and conjugated bilirubin
Causes of jaundice
Pre-hepatic
Haemolytic anaemias
Sickle cell anaemia
G6PDH deficiency
Hereditary spherocytosis
AHA
Gilbert’s syndrome
Intra-hepatic
Parenchymal disease
HCC
ALD/NAFLD
Hepatitis
Post-hepatic
Biliary tree obstruction
Choledocholelithiasis
Pancreatic cancer
Cholangiocarcinoma
When do you get pale stools and dark urine
When Px has conjugated hyperbilirubinaemia, it moves into bloodstream via osmosis
So the bilirubin is filtered in the kidney giving darker pee
And paler stools.
Define Gilbert’s syndrome
Autosomal recessive mutation of the UDP1A1 gene which increases the under-activity of the enzyme UGT
UGT converts unconjugated —> conjugated bilirubin in liver - so reduced production of conjugated bilirubin
Typical Px for Gilbert’s: Young male (≈20y/o) with Painless jaundice + sudden onset
When is Reynolds Pentad seen….
Ascending cholangitis
- Fever, RUQ pain, jaundice, confusion, hypotension
Charcot’s triad + confusion, hypotension
the jaundice is obstructive jaundice
When is Murphy’s sign positive
Cholecystitis
Dx of jaundice
Bloods and LFTs: liver markers will be altered
Urine bilirubin compared to urine urobilinogen will also be changed…
Normal: -ve urine bilirubin … +ve urine urobilinogen
Haemolysis (prehepatic): -ve urine bilirubin … raised urine urobilinogen
Hepatic disease (intra-hepatic): +ve urine bilirubin … decreased urine urobilinogen
Biliary obstruct (post-hepatic): +ve urine bilirubin … decreased urine urobilinogen
What is the progression of alcoholic liver disease
Alcohol related fatty liver (Steatosis)
Build-up of fat in the liver. If drinking stops this process reverses in around 2 weeks
Alcoholic hepatitis (with Mallory bodies)
Drinking alcohol over a long period causes inflammation in the liver sites. Binge drinking is associated with the same effect. Mild alcoholic hepatitis is usually reversible with permanent abstinence.
Alcoholic Cirrhosis (micronodular)
Liver is made up of scar tissue rather than healthy liver tissue. This is irreversible. Stopping drinking can prevent further damage. Continued drinking has a very poor prognosis.
What’s the recommended alcohol consumption
< 14 units of alcohol
**If drinking 14 units in a week, this should be spread evenly over 3 or more days and not more than 5 units in a day
Units calculation = (strength (ABV) x Vol/mL) / 1000
1 unit = 8g
Give 5 complications of alcohol
Alcoholic liver disease
Cirrhosis
Alcohol dependence and withdrawal
Wernicke-korsakoff syndrome (WKS)
Pancreatitis
Alcoholic cardiomyopathy
Signs of liver disease
Jaundice
Hepatomegaly
Spider naevi
Palmar erythema
Gynaecomastia
Asterixis - “flapping tremor” in decompensated liver disease
What is the functions of the liver
Oestrogen level regulation
Albumin production
Clotting factors
Storage (vits/Fe/Cu/fat)
Immunity
Detoxification
Bilirubin metabolism
Signs on liver disease are dependant on its function, so what are the signs of liver disease?
Oestrogen level regulation ——— gynaecomastia, palmar erythema, spider naevi
Albumin production ——— ascites, oedema
Clotting factors ——— bleeding disorder
Storage (vits/Fe/Cu/fat) ——— haemochromatosis, Wilson’s
Immunity
Detoxification ——— hepatic encephalopathy
Bilirubin metabolism ——— jaundice
What is the main cause of liver failure (decompensated cirrhosis)
Alcoholic liver disease
Risk factors for alcoholic liver disease
Chronic alcohol abuse
Obesity
Smoking
How do you calculate units of alcohol drank
Units calculation = (strength (ABV) x Vol/mL) / 1000
1 unit = 8g
Signs and Sx of alcoholic liver disease
Early stages:
V.little signs and Sx
Later more severe stages:
Sx of chronic liver failure + alcohol dependency
Jaundice, hepatic encephalopathy, spider naevi, easy bruising
What questionnaires can be used for alcohol dependancy
CAGE
Cut down, Annoyed, Guilty, Eye opening
≥ 2 dependant
AUDIT
10 questions, its an alcohol use disorder ID test
Used 1st line but longer
Investigation and Dx of alcoholic liver disease
LFTs
*AST : ALT > 2
Increased GGT, decreased Albumin
FBC
Macrocytic non-megloblastic anaemia
Biopsy
Needed to confirm extent of cirrhosis / hepatitis
Mallory cytoplasmic inclusion bodies
Tx for alcoholic liver disease
Conservative Tx:
stop alcohol
Pharmacological Tx:
Give Chlordiazepoxide // diazepam (for delirium tremons - withdrawal symptoms.)
Consider b1 + folate supplements
Surgical Tx:
Consider liver transplant for ESLF - only if abstained from alcohol for atleast 3 months
Complications of alcoholic liver disease
Pancreatitis (GET SMASHED) - Ethanol
Hepatic encephalopathy
Wernicke korsakoff syndrome
Define Wernicke korsakoff syndrome
A complication of alcoholic liver disease
Combined B1 deficiency and alcohol withdrawal Sx ———
Ataxia, nystagmus, encephalopathy
Px may also be confabulational - make up stories to fill gaps in their memory; amnesia; disproportional memory loss
Tx: IV THIAMINE
Define non alcoholic fatty liver disease
Chronic liver disease not due to alcoholism
Risk factor for non alcoholic fatty liver disease
Obesity
Htn
T2DM
Drugs - NSAIDs / Amiodarone
someone with T2DM/obesity and deranged LFTs, think NAFLD as a common condition
What is the progression of NAFLD
Hepatosteatosis (non alcoholic fatty liver) —> non-alcoholic steatohepatitis (inflammation) —> fibrosis —> cirrhosis
And signs or sx of NAFLD
ASx
May be an incidental finding
Investigation and Dx of NAFLD
1st line:
Abdominal USS
Assess severity of fibrosis using FIB-4 (>2.67 is advanced)
Tx for NAFLD
Lose weight
Control risk factors (statins, ACEi, metformin)
Vitamin E (good to improve the histological steatoric / fibrotic liver appearance)
