Lab Investigation of Diarrhoea and Malabsorption Flashcards
Diarrhoea
> 200g/day
Acute = <2 weeks Persistent = 2-4 weeks Chronic = >4 weeks
Acute diarrhoea classification
Sudden alteration in frequency or liquidity of stool
90% infectious
Inflammatory
- damage to intestinal mucosal barrier by direct invasion or cytotoxins e.g. CHESS organisms, entamoeba, IBD
- cramps, urgency, +/- fever
- stool: bloody, small volume
- stool exam: leukocytes and RBC +++
Non-Inflammatory
- no disruption or damage to intestinal epithelium e.g. virus, enterotoxic bacteria, IBS, food intolerance
- no pain or fever
- stool: watery with no blood
- stool exam: leukocytes absent
Investigation of acute diarrhoea
Not routinely done due to self limiting nature of disease
Only indicated if:
- severe dehydration, recent antibiotic use, bloody stools, fever, severe pain etc.
- detect complications
Ix:
- stool: culture, microscopy for parasites, viral studies, C. difficile toxin
- colonoscopy with biopsy
Chronic diarrhoea classifications
Mostly non-infectious
Secretory, Osmotic, Steatorrhea, Dymotility, Inflammatory
Secretory: manifestation, cause, lab results
Derangement in fluid and electrolyte transport across mucosa
Painless watery large volume outputs
Persists with fasting
Causes
- stimulant laxative, cholera, bowel resection, VIPoma, carcinoid
Lab
- suppressed stool osmolal gap (290-2x{Na + K} <50 mOsm/kg)
Osmotic: manifestation, cause, lab results
Poorly absorbable, osmotically active solutes draw fluid into lumen exceeding reabsorptive capacity of colon
Ceases with fasting
Causes
- osmotic laxative, lactase/ disaccharidase deficiencies, non-absorbable carbohydrates e.g. sorbitol, lactulose, PEG
Lab
- elevated stool osmolal gap >100 mOsm/kg
Steatorrhea: manifestation, cause
Fat malabsorption
Greasy, foul-smelling, difficult to flush diarrhoea
a/w weight loss and nutritional deficiencies
(osmotic effects of fatty acids)
Causes
- intraluminal maldigestion e.g. exocrine pancreatic insufficiency, bacterial overgrowth
- mucosal malabsorption e.g. celiac disease, Whipple’s disease
Dysmotility: cause
Rapid transit of GI contents
Causes
- hyperthyroidism, IBS
Inflammatory: manifestation, cause, lab results
Exudation, disrupted fluid/electrolyte absorption, inflammatory mediators
Pain, fever, bleeding, other manifestations of inflammation
Causes
- IBD, GI malignancies
Lab
- fecal calprotectin increased (distinguish inflammatory and non-inflammatory causes)
Diagnostic approach for chronic diarrhoea
- Hx, P/E, basic tests (CBC, RLFT, thyroid function etc.)
- Studies for acute diarrhoea (microbiology)
- Specific tests
- endocrine e.g. hormone secreting tumours (urine 5-HIAA, fasting serum VIP/ gastrin)
- faecal occult blood
- faecal calprotectin
- urine laxative screen
- specific tests for malabsorption or steatorrhea e.g. faecal elastase, CT pancreas, small bowel biopsy
Normal physiology of absorption and specific requirements for absorption of certain substances
Normal digestion/absorption:
- speed of passage
- absorbable forms of nutrients
- intestinal mucosa
Specific requirements:
- lipid – bile, lipase
- carbohydrate – amylase, disaccharidase
- protein – pepsin, trypsin, chymotrypsin
- B12 - IF, intestinal flora (consume B12), lower ileum
Generalised malabsorption
Pancreatic dysfunction (digestion) - chronic pancreatitis, fibrocystic disease of pancreas, inactivation of lipase by Zollinger-Ellison syndrome
Intestinal disease (absorption)
- reduced absorptive surface/ impaired transport e.g. celiac disease, tropical sprue
- extensive infiltration or inflammation e.g. Crohn’s, amyloidosis
- increased rate of passage e.g. carcinoid syndrome, post-gastrectomy
Malabsorption of specific substances
Altered bacterial flora e.g. blind-loop syndrome (stasis causing overgrowth), diverticula, surgery
–> fat (bile salts deconjugated), B12
Biliary obstruction
–> fat and substances dependent on fat absorption e.g. fat-soluble vitamins
Local disease or surgery
–> B12 in terminal ileum resection/ Crohn’s
Gastric atrophy e.g. pernicious anaemia
–> B12
Disaccharidase deficiency e.g. congenital or acquired
–> carbohydrates
Protein-losing enteropathy
Isolated transport defects from IEM
Manifestations of generalised malabsorption: fat, vitamins, protein, carbohydrates
Fat
- steatorrhea, bulky/gray/soft/sticky/foul-smelling stools
- fat-soluble vitamin malabsorption
- lab: fractional fat excretion >6%
Fat-soluble vitamins and Ca
- hypovitaminosis D impairs Ca absorption –> hypoCa, secondary hyperPTH, high ALP
- hypovitaminosis K –> bleeding with prolonged PT
- hypovitaminosis A –> night blindness, dermatitis (rarely clinically evident)
Protein
- muscle atrophy
- oedema (less albumin)
- recurrent infection (less Ab)
Carbohydrate
- flat OGTT or imparted polysaccharide absorption (intestinal and pancreatic)
- osmotic diarrhoea, flatulence, high stool osmolar gap
- lab: increased H2 breath test
Manifestations of specific malabsorption: B12 and lactase deficiency
B12
- megaloblastic anaemia, peripheral neuropathy, glossitis
- lab: increased MCV, serum homocysteine and MMA increased, decreased B12
Lactase deficiency
- severe diarrhoea with typically acid stools
Biochemical tests
(in addition to stool culture/ microscopy to rule out infective causes)
Possible findings (not always present in mild cases):
- CBC – anaemia
- LFT - biliary cholestasis
- low vitamin B12/ folate/ iron
- low Ca/ PO4
- high ALP
- low total proteins/ albumin
- prolonged PT
- abnormal thyroid function
Specific biochemical tests for fat absorption
- Qualitative stool exam
- fat-soluble stain e.g. Sudan III
- false positives e.g. orlistat, mineral oils - Faecal fat quantitation
- 3-5 days collection required for reliable results
- compliance, collection and storage issues
==> steatorrhea generally a circumstantial Dx (most labs no longer do testing)
Specific biochemical tests for carbohydrate absorption
- Oral sugar tolerance test
- administer test sugar and measure blood glucose concentrations over time
- no rise = malabsorption
- MUCOSAL dysfunction because none of the sugars depend on pancreatic enzymes or bile for absorption - Hydrogen breath test
- fasting patients given sugar solution –> not absorbed in small intestine –> fermented by colonic bacteria which produces hydrogen –> absorbed in bloodstream and exhaled in breath
- take breath samples Q30min for 2.5 hrs
- diagnostic if positive; POCT/ lab
Disaccharidase deficiency: Sx, Dx and Tx
Symptoms
- diarrhoea (osmotic), failure to thrive, abdominal distension and pain (flatulence due to bacteria fermentation)
Diagnosis
- dietary exclusion
- endoscopy with biopsy and measurement of enzymes
- hydrogen breath test
Treatment
- avoid foods containing specific disaccharide
Specific biochemical tests for small intestine bacterial overgrowth
- Hydrogen breath test
- bolus of glucose ingested and measure breath hydrogen concentrations sequentially
- presence of bacteria in the small intestine = glucose fermented before it is absorbed and hydrogen produced
- non-specific (can only confirm SIBO if symptoms disappear after treating and eradicating bacteria) - Quantitative culture of jejunal aspirate
- gold standard but more dangerous and complex
Disorders a/w bacterial overgrowth
Small intestinal stasis
- anatomic abnormalities e.g. diverticulosis, surgically created blind-loops, strictures
- abnormal motility e.g. DM, scleroderma
Abnormal communication between proximal and distal GI tract
- gastrocolic and jejunocolic fistula
A/w multifactorial causes
- immunodeficiency, chronic pancreatitis, cirrhosis, ESRD
Specific biochemical tests for B12 absorption
- Serum B12 & folate; plasma homocysteine and methymalonic acid as second line Ix
- Anti-parietal cell and anti-IF Ab; high serum gastrin levels; Schilling test
- Dx of pernicious anaemia (need parenteral or IM B12 to treat!)
Vitamin B12 deficiency causes and symptoms/signs
Possible causes:
- lack of IF (pernicious anaemia)
- gastrectomy
- chronic pancreatitis
- bacterial overgrowth in jejunum
- ileum resection/ Crohn’s disease
Suspect if:
- macrocytic anaemia, hypersegmented neutrophils, pancytopenia
- peripheral neuropathy/ unexplained neurological signs
- elderly/ alcoholic/ strict vegan/ malnutrition
- previous bariatric surgery
Schilling test (no longer used now)
Part I: radioactive B12 PO and IM flushing dose of non-radioactive B12 within 2 hrs (saturate body stores)
–> 24 hr urine collection and radioactivity measured (normal body should absorb radioactive B12 and excrete it)
Part II: radioactive B12 + IF PO, flushing dose of non-radioactive B12
–> measure urine radioactivity
Results:
- Part I and II low = intestinal malabsorption at terminal ileum
- Part I low and II normal = pernicious anaemia
(modified schilling - part III repeat after antibiotics to Dx SIBO)
- assume adequate renal function, pancreatic exocrine function and no bacterial overgrowth of gut
Other tests
Radiological studies to aid diagnosis e.g. pancreas
Endoscopy with biopsy
- mucosal biopsy for panmalabsorption to identify or exclude diffuse mucosal disease
- aspirate jejunal contents
Celiac disease: cause, Sx, Dx, Tx
Rare in Chinese
Gluten sensitive enteropathy
- autoimmune, inflammatory disorder triggered by ingestion of gluten
- diarrhoea, steatorrhea, weight loss, abdominal pain, flatulence, fatigue, failure to thrive
Ix:
- anti-tissue transglutaminase Ab
- HLA-DQ2 or DQ8
- small bowel biopsy is gold standard
Dx confirmed if Sx relieved after gluten free diet
Tx: gluten free diet
Cystic fibrosis: cause, Sx, Dx, Tx
Congenital metabolic disorder with abnormal exocrine gland secretions
Sx
- failure to thrive, chronic respiratory infections, malabsorption
Dx
- newborn screening: immunoreactive trypsinogen
- CFTR gene test
- sweat test
- faecal trypsin, chymotrypsin or elastase (assess pancreatic exocrine insufficiency)
Tx
- antibiotics, enzyme replacement, physiotherapy
