Block A - Medicine - GI Data interpretation Flashcards
Parameters of liver function test
Cellular integrity:
- ALT and AST
Protein synthesis:
- Albumin and PT
Excretory function:
- Bilirubin, ALP and GGT
Other parameters:
- Arterial ammonia for Hepatic encephalopathy
- LDH
- AFP (HCC)
Markers of hepatocellular injuries
Intrinsic functions of these markers
Sources of these markers
ALT and AST
Gluconeogenesis function
transfer of amino acid from alanine acid (ALT) or aspartic acid (AST) to Ketoglutaric acid to produce Oxaloacetic acid and pyruvic acid respectively
Sources:
ALT: Cytosolic enzyme, specific to liver*****
AST: Cytosolic and mitochondrial enzyme, found in liver, cardiomyocytes, skeletal muscles, kidneys, pancreases, blood cells
ALP
- sources
- confounding conditions that change ALP level
- Confirmation of source of ALP
Sources: Liver, bone, intestines, placenta
Conditions: Fracture, growth spurt, age, sex…etc
Confirm liver origin of ALP:
- ALP isoenzyme test
- Check GGT level (concomitant increase)
- 5’ nucleotidase
GGT
Intrinsic function
Causes of isolated GGT increase w/ normal ALP
Function: Microsomal enzyme which transfers gamma-glutamyl groups from gamma-glutamyl peptides to other proteins
Causes of isolated GGT increase
- Drug: Phenytoin, carbamazepine, barbituates
- Alcohol
- Fatty liver disease: a/w metabolic syndrome
Causes of increased unconjugated bilirubin
- Increase bilirubin production: Hemolysis, ineffective erythropoiesis, resorption of hematoma
- Decrease hepatic uptake: e.g. Rifampicin reaction
- Decrease conjugation (isolated hyperbilirubinemia) - Gilbert’s syndrome, Criggler-Najjar syndrome
Infective, autoimmune and metabolic markers of liver function
Infective:
- Viral hepatitis markers
Autoimmune: e.g. PBC, PBS
- ANF, AMA, Anti-Smooth muscle Ab
Metabolic:
- Iron: Total Fe, Ferritin, TIBC
- Copper: Total Cu, Ceruloplasmin
Define the units of alcohol and recommended consumption
1 unit = 10g of alcohol
e.g. 1 beer = 5% alcohol at 200mL = 10g of alcohol
Male: average 2-3 unit per day maximum
Female: average 1-2 unit per day maximum
Alcoholic cirrhosis: 9-10 units per day
40-year-old male with one week history of non-specific symptoms, with development of jaundice 2 days ago, and a relatively unremarkable P/E apart from jaundice
Ddx
o Pre-hepatic: hemolysis (CBC)
o Intrahepatic: viral hepatitis, drugs, cirrhosis, tumors (LFT)
o Post-hepatic: gallstones, cancers of the bile duct…
Investigations for viral hepatitis
Acute HAV:
- Anti-HAV IgM
Chronic HAV:
- Anti-HAV IgG
Acute HBV: - Anti-HBc IgM - HBsAg Recovered HBV: - Anti-HBs - Anti-HBc IgG
Acute HEV:
- Anti-HEV IgM
Acute HCV (no marker)
Recovered HCV:
- Anti-HCV
- HCV RNA
How to differentiate acute Hep. B vs Chronic Hep B with flare
Acute Hepatitis B or Chronic Hep B with flare BOTH give high Anti-HBc IgM
IgM does not distinguish between acute flare and acute infection
Differentiation by HBV DNA level and waiting 6 months for remeasurement of IgM and HBsAg clearance
HBV DNA > 640 million copies/ mL is acute Hep B
Describe the serological course of Acute Hep B infection with recovery
Immediate investigations for acute, markedly elevated ALT and AST
Flare or new onset of autoimmune hepatitis
- Check autoimmune antibodies e.g. ANA, anti-smooth muscle antibody, anti-LKM1
Acute viral hepatitis (by Hep ABCE)
- Anti- HAV IgM, HBsAg, Anti-HBc IgM, Anti-HCV, Anti-HEV
Drug-induced liver damage:
- Toxicology for paracetamol (+ Others)
Ultrasound
Differentiate the underlying causes:
- Only Anti-HBs Antibody
- Only Anti-HBc antibody
- Anti-HBc antibody and Anti-HBs antibody
- Anti- HBc and HBsAg
- Only Anti-HBs Antibody: Vaccinated against Hep B
- Only Anti-HBc antibody: Occult Hep B infection/ recovering from acute infection, distant resolved infection
- Anti-HBc antibody and Anti-HBs antibody: Past infection, resolved
- Anti- HBc and HBsAg: Active HBV infection (with anti-HBc IgM)
Role of Hep B - e antigen?
Testing for HBeAg and anti-HBe is not part of the diagnostic panel for HBV
Phases of infection determines amount of E antigens
Amount of E antigens can indicate antiviral treatment and further investigations (e.g. liver biopsy)
Define the phases of Hep B infection and HepB- E Antigen levels
Role of liver fibroscan
Stages of fibrosis
noninvasive assessment of liver fibrosis (3 min) for staging fibrosis
Measures liver stiffness (kPa): correlates with underlying fibrosis
Controlled attenuation parameter (CAP): correlates with underlying steatosis
F0 = No fibrosis F1 = Portal fibrosis with no speta F2 = Portal fibrosis with infrequent septa F3 = Numerous septa but no cirrhosis F4 = Cirrhosis (asymptomatic unless decompensated)
Wilson’s disease
Genetic defect
Inheritance
Diagnostic tests
Genetic defect: ATP7B - Copper-transporting ATPase defect
Inheritance: AR
Diagnostic tests:
- Neurological S/S: Ceruloplasmin <20mg/dL + Kayser Fleischer rings
- Asymptomatic: Hepatic Cu concentration >250mg/g of dry weight + Low serum ceruloplasmin level
Ceruloplasmin level
- Causes of increase
- Causes of false negative
Increase: Inflammation, pregnancy, estrogen use
False positive: protein deficiency states (e.g. nephrotic syndrome, liver cirrhosis, malnutrition, malabsorption, protein-losing enteropathy…)
Overall not a very specific marker to Wilson’s disease
Clinical scenario:
Past IVDU, chronic alcoholism
2 weeks abdominal swelling with mild fever
Umbilical hernia with shifting dullness, scattered spider naevi on P/E
Overall picture: decompensated liver cirrhosis with development of ascites
Outline next investigations
Full blood tests: CBC with diff. MCV and Hb WCC Plt, PT, INR Electrolytes
LFT:
- ALT, AST, ALT:AST ratio
- ALP and GGT
- Albumin
- AFP (HCC or necro-inflammation in liver)
Viral hepatitis panel (Especially HCV for IVDU)
Ultrasound
OGD for variceal screening, Portal-hypertensive gastropathy
Diagnostic paracentesis (All ascites cases to r/o SBP)
Outline the spectrum of tests in Diagnostic paracentesis
Color and turbidity
Protein
RBC
WCC count with PMN count - SBP = >250 PMN/mm3 or positive culture with <250 PMN/mm3
Serum ascites albumin gradient (SAAG): serum albumin – ascites albumin
High SAAG > 11 – non-peritoneal cause
Low SAAG <11 – peritoneal cause
Causes of high vs low SAAG from Diagnostic paracentesis
High SAAG > 11 – non-peritoneal cause: Cirrhosis Acute liver failure Veno-occlusive disease Hepatic vein obstruction CHF Nephrotic syndrome Protein-losing enteropathy Malnutrition
Low SAAG <11 – peritoneal cause: Primary peritoneal mesothelioma Secondary peritoneal carcinoma TB Peritonitis
Assessment/ scoring systems of liver cirrhosis
Child Pugh score: A(5-6), B(7-9), C(>=10) or 3-15 Metrics: Bilirubin Albumin INR / prothrombin time Ascites Encephalopathy Decompensation indicates cirrhosis with a Child-Pugh score of 7 or more (class B)
MELD score Metrics: Serum Cr Serum bilirubin INR
Treatment of HCV infection in a previous IVDU and chronic alcoholic with ascites
o HCV – direct acting antivirals (now ~100% cure rate for Hep C)
o Alcoholic liver disease – abstinence
o Ascites – large vol paracentesis (7L removed), diuretics
Clinical scenario:
62-year-old man admitted to ED with acute onset of central abdomen pain, radiating to back, with associated nausea and vomiting for 12 hours, with fever
Tender epigastrium with guarding, no rebound, Scant bowel sounds on P/E
Preliminary investigations reveal lymphocytosis, cholestatic liver enzyme pattern
Ddx and investigations
Ddx: post-hepatic causes of liver enzyme elevation: acute cholecystitis, cholangitis, pancreatitis
Investigations: Full bloods For Ranson's criteria: - Serum Amylase - WBC - Glucose - LDH, Hct - AST - Ca, HCO3, BUN - PaO2
Imaging:
AXR
US abdomen
ERCP if gallstones
Clinical scenario:
20-year-old female presented with 3-week history of diarrhoea, with blood and mucus over the last 5 days with increasing abdominal pain and mild fever
No other significant Hx
Soft, diffuse tenderness on abdomen with fever, dehydration
Ddx and next investigations
Ddx:
o Infectious gastroenteritis – Campylobacter, Shigella, rotavirus
o Inflammatory bowel disease
o Less common – vasculitis, Behcets, C. difficile colitis, malabsorption
Investigations:
- CBC
- RFT and LFT
- Inflammatory marker CRP and ESR
- AXR
- Stool: Culture, microscopy, cell counts, C.diffile toxins, Fecal calprotectin
- Colonoscopy
Fecal Calprotectin
Intrinsic function
Test function
Calprotectin = small calcium-binding protein, 60% of content of cytosol in neutrophils
Distinguishes between functional (e.g. irritable bowel syndrome) and organic diarrhea (e.g. inflammatory bowel disease):
neutrophils migrate to intestinal mucosa in active intestinal inflammation, inflammatory disturbance to mucosa leads to leakage of calprotectin
Calprotectin <50μg/g = IBS likely
Calprotectin 50-150μg/g: Exclude other possible causes of GI tract inflammation, e.g. infection, NSAIDs etc.
Calprotectin >150μg/g = organic disease likely (IBD, colorectal cancer)
Clinical scenario: 58 year old man with increasing weight loss and RUQ pain Chronic Hep B carrier with no Tx Slight hepatomegaly on P/E Slightly high AST, ALT; High GGT, ALP
Most useful investigations?
Hep B status: active and chronic
AFP
Triphasic CT scan if positive AFP
High AFP is diagnostic of HCC
True or False, why?
False
AFP high in many conditions: Pregnancy HCC Acute hepatitis, active hepatocyte regeneration and necro-inflammation Germ cell tumour Lymphoma
Must do triphasic CT scan for supporting radiological Dx of HCC
Ddx the following profile:
65 year old woman with Hypochromic Microcytic anaemia
CEA 12 (2x normal limit)
FOB 1/3 positive
Most useful next investigation
GI bleeding, likely malignant due to elevated CEA (only very advanced)
Insidious bleed causing iron deficiency anaemia
Colonoscopy and CT abdomen
Factors of high CEA
Colon, lung, breast, stomach cancer
Chronic smoking
Peutz-Jeghers Syndrome
Genetic Defect and inheritance
Manifestations
STK11 (LKB1) mutation
Autosomal dominant
Manifestations:
- Benign hamartomatous polyps in GIT
- Hyperpigmented macules on lips and oral mucosa
- Intestinal obstruction due to intussusception (teenage)
- High risk GI cancer (adulthood)
