Sandbox: malabsorption

Diarrhea

Abbreviations: GI: Gastrointestinal, CBC: Complete blood count, WBC: White blood cell, RBC: Red blood cell, Plt: Platelet, Hgb: Hemoglobin, ESR: Erythrocyte sedimentation rate, CRP: C–reactive protein, IgE: Immunoglobulin E, IgA: Immunoglobulin A, ETEC: Escherichia coli enteritis, EPEC: Enteropathogenic Escherichia coli, EIEC: Enteroinvasive Escherichia coli, EHEC: Enterohemorrhagic Escherichia coli, EAEC: Enteroaggregative Escherichia coli,

Categories		Cause		Clinical manifestation									Lab findings									Extra intestinal findings	Cause/Pathogenesis	Gold standard diagnosis
				Symptoms								GI signs
				Duration		Diarrhea			Fever	Abdominal pain	Weight loss
													Stool exam					CBC			Other lab findings
				Acute	Chronic	Watery	Bloody	Fatty					WBC	RBC	Ova/Parasite	Osmotic gap	Other	WBC	Hgb	Plt
Gastrointestinal		Crohns disease		–	+	+	+	+	±	+	+	Abdominal tenderness Mouth ulcer Tachycardia Hypotension	+	+	–	–	–	↑	↓	↑	Anti saccharomyces cerevisiae antibodies (ASCA) Vitamin B12 deficiency Elevated ESR Elevated CRP	Uveitis Arthritis Erythema nodosum Pyoderma gangrenosum Amyloidosis Venous and arterial thromboembolism Renal stones Bronchiectasis	Abnormal immune response to self antigens	Colonoscopy with biopsy
		Ulcerative colitis		–	+	+	+	+	+	+	+	Normal in mild cases Abdominal tenderness Tachycardia Hypotension Pallor Blood on rectal examination	+	+	–	–	–	↑	↓	↑	Anti–neutrophil cytoplasmic antibody (P–ANCA) Hypoalbuminemia Hypokalemia Hypomagnesemia Elevated ESR Elevated CRP	Skin rash Iritis Uveitis Seronegative arthritis Clubbing of the fingers Erythema nodosum	Abnormal immune response to self antigens	Colonoscopy with biopsy
		Celiac disease		–	+	±	–	±	–	+	+	Abdominal distention Increased bowel sounds Mouth ulcers Hepatosplenomegaly Ascites	–	–	–	–	Fat droplets on sudan stain	–	↓	–	IgA endomysial antibody Anti–tissue transglutaminase antibody Anti–gliadin antibody Fat soluble vitamins deficiency	Malabsorption Dementia Dermatitis herpetiformis	HLA–DQ2 HLA–DQ8 Innate responses to wheat proteins	IgA endomysial antibody Anti–tissue transglutaminase antibody
		Cystic fibrosis		–	+	–	–	+	±	+	+	Abdominal distention Hepatosplenomegaly Rectal prolapse	–	–	–	–	Fat droplets on sudan stain	–	↓	–	Positive DNA analysis for cystic fibrosis transmembrane conductance regulator (CFTR) Nasal transepithelial potential difference Fat soluble vitamins deficiency	Malabsorption Recurrent respiratory tract infection Bronchiectasis Diabetes mellitus Scoliosis Infertility	Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) protein	Positive genetic testing Elevated sweat chloride ≥60 mmol/L
		Chronic pancreatitis		–	+	+	–	+	–	+	+	Abdominal tenderness	–	–	–	–	Fat droplets on sudan stain Positive fecal elastase measurement	–	–	–	Slightly elevated amylase and lipase Abnormal pancreatic function test Secretin stimulation test	Malabsorption Diabetes mellitus Pancreatic pseudocyst	Toxins Repeated acute pancreatitis Genetic Autoimmune	Magnetic resonance cholangiopancreatography (MRCP)
		Bile acid malabsorption		–	+	+	–	+	–	–	+	Hypotension Tachycardia	–	–	–	–	Fat droplets on sudan stain	–	–	–	Reduced cholesterol level	Malabsorption	Genetic defects in SLC10A2	SeHCAT test
		Microscopic colitis		–	+	+	–	–	–	+	+	Abdominal tenderness Fecal incontinence	–	–	–	–	–	–	↓	–	Hypokalemia Elevated CRP Elevated autoantibodies include: RF ANA AMA ANCA	Arthritis Uveitis Idiopathic thrombocytopenic purpura Pleuro pericarditis Hypothyroidism Psoriasis	Mucosal immune responses to luminal factors in a genetically predisposed individual Drug–induced	Colonoscopy with mucosal biopsy with mononuclear infiltrates: Collagenous colitis is characterized by a colonic subepithelial collagen band >10 micrometers in diameter Lymphocytic colitis is characterized by ≥20 intraepithelial lymphocytes (IEL) per 100 surface epithelial cells
		Infective colitis		–	+	+	+	–	+	+	+	Rebound abdominal tenderness	+	+	+	–	Positive stool culture Positive fecal calprotectin Positive fecal lactoferrin	↑	↓	↑	Elevated CRP Elevated ESR	Arthritis Uveitis	Salmonella Shigella Campylobacter E. coli 0157:H7 Clostridium difficile Entamoeba histolytica Adenovirus Cytomegalovirus Herpes simplex virus	Stool culture Blood culture
		Ischemic colitis		+	+	+	+	–	+	+	+	Hyperactive then absent bowel sounds Abdominal tenderness	+	+	–	–		↑	↓	↑	Elevated CRP Elevated ESR Elevated serum lactate Elevated lactate dehydrogenase (LDH)  Elevated creatine phosphokinase (CPK) Elevated amylase Hypoalbuminemia	IgA vasculitis	Hypercoagulability  Nonocclusive colonic ischemia Embolic and thrombotic arterial occlusion Mesenteric vein thrombosis	Abdominal CT scan
		Lactose intolerance		+	+	+	–	–	–	+	–	Abdominal tenderness Hypotension Tachycardia Nausea and vomiting	–	–	–	↑		–	–	–	Hydrogen breath test	Bloating Flatulence Symptoms begin mainly after ingestion of lactose	Reduction of lactase enzyme activity or inability to produce persistent lactase Congenital lactase deficiency	Lactase activity assay
		Irritable bowel syndrome		–	+	±	–	±	–	±	–	Abdominal tenderness Flatulence Normal bowel sounds	–	–	–	–		–	–	–				Diagnosis of exclusion
Infection	Bacterial	Whipple's disease		–	+	+	–	+	±	+	+	Hepatosplenomegaly Ascites	–	–	–	–	Positive fecal fat	↓	↓	↓/↑	Hypoalbuminemia Fat soluble vitamins deficiency	Malabsorption Abnormal extraocular movement Lymphadenopathy Hyperpigmentation Uveitis Endocarditis Encephalitis Dementia Pleural effusion	Tropheryma whipplei	Small intestine biopsy for Tropheryma whipplei testing PCR testing
		Tropical sprue		+	+	+	–	+	+	+	+	Pallor Angular stomatitis Mouth ulcers Edema	+	–	–	–	Positive stool culture	–	↓	–	Fat soluble vitamins deficiency Vitamin B12 deficiency Folate deficiency Hypokalemia	Myalgia Neuropathy	Escherichia coli Klebsiella pneumoniae Enterobacter cloacae	Diagnosis of exclusion
		Small bowel bacterial overgrowth		–	+	+	–	+	–	+	+	Muscle atrophy Abdominal distention	+	–	–	–	Positive stool culture Positive fecal fat	–	↓	–	Hypoalbuminemia Abnormal hydrogen breath test Lactic acidosis	Malabsorption Rosacea	Excess bacteria in the small intestine Alterations in intestinal anatomy or GI motility	Diagnosis of exclusion
		Pseudomembranous enterocolitis		+	–	+	±	–	+	+	±	Generalized abdominal tenderness Abdominal distention Rebound abdominal tenderness Lethargy	+	+	–	–	enzyme–linked immunoabsorbant assay (ELISA) Polymerase chain reaction (PCR) assay or C. difficile antigen	↑	↓	↓	Elevated serum creatinine Hypoalbuminemia Elevated lactic acid	Dehydration Acute kidney injury Bacteremia Reactive arthritis Necrotizing fasciitis	Clostridium difficile Recent antibiotics use Recent surgery	Stool exam Pseudomembranes on colonoscopy
		Campylobacteriosis		+	–	+	+	–	+	+	–	Dehydration Diffuse abdominal tenderness	+	+	–	–	Positive stool culture	↑	–	–		Toxic megacolon Sepsis Arthritis Endocarditis  Guillain–Barré syndrome	Campylobacter jejuni	Stool culture
		Salmonellosis		+	+	+	+	–	+	+	–	Hypotension  Tachycardia Abdominal distention Diffuse abdominal tenderness Hepatosplenomegaly	+	+	–	–	Positive stool culture Positive serologic testing	↑	–	↑	Hypokalemia Hypernatremia Hyponatremia Hypercalciuria Hypocitraturia	Post–infectious arthritis Obtundation Bacteremia Pericarditis Pyelonephritis Brain abscess	Salmonella	Stool culture
		Shigellosis		+	–	+	+	–	+	+	–	Abdominal distention Hyperactive bowel sounds Diffuse abdominal tenderness	+	+	–	–	Positive stool culture	↑/↓	↓	↓	Elevated CRP Elevated ESR Hyponatremia Hypoglycemia Azotemia	Headache Lethargy Seizures Delirium Post–infectious arthritis Myocarditis	Shigella	Stool culture
		Escherichia coli enteritis	ETEC (Traveler's diarrhea)	+	–	+	–	–	+	–	–	Dehydration Diffuse abdominal tenderness	+	–	–	–	Positive stool culture	↑	–	–			Enterotoxigenic escherichia coli Enterotoxins: Heat–labile enterotoxin (LT) Heat–stable enterotoxin (ST)	Stool culture
			EPEC	+	+	+	+	–	+	+	+	Dehydration Diffuse abdominal tenderness	+	+	–	–	Positive stool culture	↑	–	–			Enteropathogenic E. coli	DNA probe or polymerase chain reaction (PCR) of the EPEC adherence factor Stool culture
			EIEC	+	–	+	+	–	+	+	–	Dehydration Diffuse abdominal tenderness	+	+	–	–	Positive stool culture	↑	–	–			Enteroinvasive E. coli	DNA probe Stool culture
			EHEC	+	–	+	+	–	–	+	–	Dehydration Diffuse abdominal tenderness			–	–		↑	↓	↓	Azotemia	Hemolytic uremic syndrome (HUS) Renal failure	Enterohemorrhagic E. coli  Shiga toxins
			EAEC	+	+	+	–	–	–	+	–				–	–
		Yersinia enterocolitica		+	–	+	+	–	+	+	–				–	–
		Vibrio cholera		+	–	+	–	–	–	+	–	Dehydration			–	–
		Aeromonas		+	+	+	+	-	+	+	-	Abdominal distention Hyperactive bowel sounds Diffuse abdominal tenderness	+	+	–	–		↑	-	-		Wound infection Bacteremia Opportunistic infections in immunocompromised patients	Aeromonas virulence factors including endotoxins, hemolysins, enterotoxins, and adherence factors	Blood culture Wound culture
		Plesiomonas		+											–	–
		Mycobacterium avium complex		+	+		+		±	+	–		+/–	+	–	–		↓	–	–	Immune system analysis may show defects
		Other infections aaaa bbbb			+		+		–	+	±		+	+	–	–	Stool culture may be positive for responsible organism	↑	–	–
	Virus	Rotavirus		+	–	+	–	–	+	–	–				–	–
		Echovirus		–											–	–
		Adenovirus		+	–	+	–	–	–	+	–				–	–
		Norovirus		+	–	+	–	–	+	+	–				–	–
		CMV colitis		+	+		+		±	+	–		+/–	+	–	–		↓	–	–	CD 4 level decreased as it is maily associated with HIV
		HIV		–	+	+									–	–
		Hepatitis	Hepatitis A	+											–	–
			Hepatitis E	+											–	–
	Parasite	Entamoeba histolytica		+	+	+	–								+	–
		Giardia		–											+	–
		Cryptosporidium		–											+	–
		Microsporidia		–											+	–
		Isospora			+		+			+	–		+	+	+	–		↑	–
		Other Parasitic diarrhea aaaa bbbb		+	+		+		–	+	±		+	+	+	–		↑	–	–
Tumors		Carcinoid tumor		–	+	+	+	–	–	+	+	Abdominal distention Tachycardia Hypertension	–	+	–	↓		–	–	–	Elevated urinary 5–hydroxyindoleacetic acid (5–HIAA) level High chromogranin A	Facial flushing Jaundice Edema Valvular heart disease Right–sided heart failure	Well–differentiated neuroendocrine tumor	Blood chromogranin A level
		VIPoma		+	+	+	–	+	–	+	+	Tachycardia Abdominal distention Abdominal RUQ tenderness Nausea Vomiting	–	–	–	↓		–	–	–	Elevated VIP level Hypokalemia Hypochlorhydria or achlorhydria Low osmotic gap (<50 mOsm/kg)	Rash Facial flushing Dehydration Lethargy Muscle weakness	Primary secretory tumor	Blood VIP levels Followed by imaging
		Zollinger–Ellison syndrome		–	+	+	+	+	–	+	+	Epigastric tenderness	–	–	–	↓		–	↓	–	Positive secretin stimulation test Elevated serum chromogranin A	Jaundice	Gastrin producing tumor mainly in duodenum	Secretin stimulation test
		Somatostatinoma		–	+	+	–	–	–	+	+	Epigastric tenderness	–	–	–	↓		–	–	–	Elevated fasting plasma somatostatin	Diabetes mellitus Cholelithiasis Jaundice	Neuroendocrine tumors of D–cell origin	Plasma somatostatin level Followed by imaging
		Lymphoma		–	+	+	+	–	+	+	+	Diffuse abdominal tenderness Hepatosplenomegaly	–	+	–	–		–	↓	–	Paraproteinemia	Malabsorption Lactose intolerance Ascites	Primary tumor of GI tract	Colonoscopy with biopsy
		Colorectal cancer		–	+	+	+	+	–	+	+	Diffuse abdominal tenderness	–	+	–	–		–	↓	–	Positive carcinoembryonic antigen	Metastasis	FAP gene HNPCC gene	Colonoscopy and biopsy
Medication/Toxicity		Medications ACE inhibitors Digoxin Cephalosporins Statins Thiazide diuretics Triptans Lactulose Anti retroviral agents Chemotherapeutic agents Antifungals Magnesium		+	+	+	–	±	±	+	+	Abdominal distention Dehydration	–	–	–	↑/↓		↑	–	–	Elevated plasma level of drug		Inflammation Pseudomembranous colitis	Clinical evaluation after discontinuation of the drgs
		Factitious diarrhea		+	+	+	–	–	–	+	+	Abdominal distention Dehydration	–	–	–	↑/↓		–	–	–	Hypokalemia  Metabolic alkalosis Hypermagnesemia	Malabsorption Lethargy Generalized weakness Acute renal failure	Medications	Clinical evaluation after discontinuation of the drgs
		Heavy metal ingestion		–	+	+	–	–	–	+	+	Abdominal distention Dehydration	–	–	–	–		–	–	–	Elevated plasma heavy metal level	Headache Numbness Alopecia Vertigo	Heavy metal ingestion	Plasma level of heavy metal
		Organophosphate poisoning		+	+	+	–	–	–	+	–	Salivation Emesis	–	–	–	–		–	–	–	Reduced RBC acetylcholinesterase Plasma cholinesterase activity	Autonomic dysfunction Motor deficit Sensory deficit Bronchospasm Urination Miosis Bradycardia Lacrimation Sweating Cardiac arrhythmias Acute renal injury	Neurotoxins bind to acetylcholinesterase (AChE)	Clinical diagnosis
		Opium withdrawal		+	+	+	–	–	–	+	–	Hyperactive bowel sounds Tachycardia	–	–	–	–		–	–	–	Azotemia Hypokalemia Metabolic alkalosis	Dysphoria  Restlessness Sweating Rhinorrhea Lacrimation Myalgia Arthralgia		Clinical diagnosis following opium withdrawal
Iatrogenic		Short bowel syndrome		+	+	+	–	+	–	–	+	Abdominal distention Abdominal tenderness	–	–	–	–	Positive fecal fat	–	↓	↑	Hypoalbuminemia High level of acute phase reactant Abnormal liver function tests	Prior intestinal surgery Malabsorption Crohn's disease Malignancy Peripheral edema Muscle atrophy	Surgical bowel resection	Clinical diagnosis following bowel resection
		Radiation enteritis		+	+	+	+	+	–	+	+	Abdominal tenderness	+	+	–	–	Positive fecal fat	–	↓	–	Vitamin B12 deficiency Hypoalbuminemia	Prior history of malignancy and radiation therapy Malabsorption Telangiectasias	Radiation	Segmental bowel inflammation on endoscopy or colonoscopy
		Dumping syndrome		–	+	+	–	+	–	–	+	Hyperactive bowel sound	–	–	–	–	–	–	–	–	Hypoglycemia Hydrogen breath test	Malnutrition Fat soluble vitamin deficiency	Postgastrectomy	Clinical diagnosis following gastrectomy
Others		Abetalipoproteinemia		–	+	+	–	+	–	+	+	Abdominal distension	–	–	–	–		–	–	–	Low triglyceride Low total cholesterol levels  Acanthocytes Low vitamin E levels	Ataxia Visual field defect Dysarthria	Autosomal recessive disorder caused by mutations encoding the microsomal triglyceride transfer protein (MTP)	Clinical findings and low triglyceride and cholesterol level
		Hyperthyroidism		–	+	+	–	–	±	+	+	Tachycardia	–	–	–	–	Positive fecal fat	–	–	–	Elevated T4 Elevated T3 Decreased TSH High serum alkaline phosphatase	Lump in the neck Lid lag Malabsorption Sweating Hyperpigmentation Proptosis Tremor Increased DTR	Graves' disease Hashimoto's thyroiditis Toxic adenoma	TSH
		Diabetic neuropathy		–	+	+	–	+	–	+	+	Fecal incontinence	–	–	–	–	Positive fecal fat	–	↓	–	Hyperglycemia Azotemia Hypokalemia	Malabsorption	Unclear Disordered motility Increased intestinal secretion Small intestinal bacterial overgrowth	Clinical diagnosis in a patient with long lasting diabetes mellitus
		Systemic sclerosis		–	+	+	±	+	–	+	+	Epigastric tenderness Fecal incontinence	–	+	–	–	Positive fecal fat	–	↓	–	Anti–topoisomerase I (Scl‑70) antibodies Antinuclear antibodies (ANA) Anti–centromere antibodies Anti-RNA polymerase III antibody	Malabsorption Skin changes Raynaud phenomenon Pulmonary hypertension Arthritis Telangiectasia Chronic renal failure	Autoimmune reaction	Clinical diagnosis Followed by serologic tests