Describe and discuss the aetiology of acute and chronic diarrhea including infectious and non- infectious causes with simple explanation in exam Pov extract content from robbins & microbiology & medicine textbook

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Aetiology of Acute and Chronic Diarrhoea - Exam Notes

Sources: Robbins & Kumar Basic Pathology | Robbins, Cotran & Kumar Pathologic Basis of Disease | Goldman-Cecil Medicine | Harrison's Principles of Internal Medicine | Medical Microbiology (Murray)

DEFINITION FIRST (Exam Tip)

Acute diarrhoea: Duration < 4 weeks (most resolve in < 2 weeks)
Chronic diarrhoea: Duration > 4-6 weeks
Normal: < 200 g stool/day and < 3 loose stools/day

MECHANISMS OF DIARRHOEA (Pathophysiology Framework)

Robbins classifies diarrhoea into 4 types - memorize this framework because every aetiology fits into it:

Type	Mechanism	Key Feature	Stops with Fasting?
Secretory	Abnormal ion transport - excess Cl⁻ secretion or impaired Na⁺ absorption	Large volume, watery, no osmotic gap	No
Osmotic	Non-absorbed solutes retain water in lumen	Osmotic gap present, bloating	Yes
Malabsorptive	Defective nutrient absorption - fat/carb/protein	Steatorrhoea, bulky greasy stools	Yes
Exudative/Inflammatory	Mucosal damage with blood, pus, protein loss	Bloody, fever, tenesmus	No

Robbins Basic Pathology: "Diarrhoea can be characterized as secretory, osmotic, malabsorptive, or exudative."

ACUTE DIARRHOEA - AETIOLOGY

A. INFECTIOUS CAUSES (Most Common)

Most acute diarrhoea is infectious and self-limiting.

1. BACTERIAL

Organism	Mechanism	Key Feature
Vibrio cholerae	Releases preformed toxin → massive Cl⁻ secretion → secretory diarrhoea	Rice-water stools, no blood, massive volume
E. coli (ETEC)	Heat-labile (LT) and heat-stable (ST) enterotoxins → secretory diarrhoea	Traveller's diarrhoea
E. coli O157:H7 (EHEC)	Shiga-like toxin → HUS (haemolytic uremic syndrome)	Bloody diarrhoea, no fever
Salmonella	Invasive → exudative/inflammatory diarrhoea	Food poisoning, S. typhi → typhoid
Shigella	Invasive → dysentery	Bloody diarrhoea + tenesmus + fever
Campylobacter jejuni	Most common bacterial enteric pathogen in high-resource countries	Also a frequent cause of traveller's diarrhoea
Staphylococcus aureus	Preformed enterotoxin in food (toxin-mediated)	Rapid onset (1-6 hrs), vomiting prominent
Bacillus cereus	Preformed toxin (emetic type) OR diarrhoeal toxin	Short incubation, rice-associated
Clostridium perfringens	Enterotoxin in cooked meat	8-16 hr incubation
Clostridioides difficile	Toxins A+B disrupt epithelial function → necrosis	Antibiotic-associated, pseudomembranous colitis
Yersinia	Invasive, ileocaecal region	Can mimic appendicitis

Robbins: "Salmonella and Shigella spp. are invasive and associated with exudative bloody diarrhoea (dysentery)." / "Pseudomembranous colitis is often triggered by antibiotic therapy that disrupts the normal microbiota and allows C. difficile to colonize and grow."

2. VIRAL (Very Common, Especially in Children)

Organism	Key Feature
Rotavirus	Most common severe diarrhoea in children worldwide; loss of mature enterocytes → malabsorption + increased fluid secretion; vaccine available
Norovirus (Calicivirus)	Most common epidemic acute gastroenteritis in adults and older children; cruise ships, schools
Adenovirus (types 40-42)	Second most common viral gastroenteritis in infants; rarely causes fever or respiratory symptoms
Astrovirus	Children and elderly

Robbins: "Rotavirus is a common cause of severe childhood diarrhoea worldwide. The diarrhoea is secondary to loss of mature enterocytes, resulting in malabsorption and increased fluid secretion."

3. PARASITIC/PROTOZOAL

Organism	Key Feature
Giardia lamblia	Small bowel; profuse watery/fatty diarrhoea; cysts in faeces; common in travellers
Entamoeba histolytica	Large bowel; amoebic dysentery (bloody diarrhoea); can cause liver abscess
Cryptosporidium	Acid-fast oocysts; severe in immunocompromised (HIV); self-limiting in normal hosts
Strongyloides	Can persist decades; hyperinfection in immunosuppressed

Robbins: "Parasitic and protozoal infections affect over half of the world's population on a chronic or recurrent basis. Among the important agents causing human disease are roundworms (Ascaris and Strongyloides), hookworms (Necator and Ancylostoma), and protozoa (Giardia and Entamoeba)."

B. NON-INFECTIOUS CAUSES OF ACUTE DIARRHOEA

Medications/Drugs
- Antibiotics (direct mucosal injury or dysbiosis)
- Laxatives, antacids (Mg-containing), NSAIDs, colchicine, metformin, chemotherapy
- Sorbitol-containing foods/sugar-free products
Food toxins (distinct from infection - the toxin itself, not the organism)
- Staphylococcal preformed toxin, B. cereus toxin
Ischaemic colitis - sudden, usually in elderly with vascular disease
Acute onset of chronic diseases (diarrhoea as first presentation)
- Inflammatory bowel disease (IBD) - Crohn's, UC
- Coeliac disease
- Microscopic colitis
Stress/acute illness - hospital-acquired diarrhoea

CHRONIC DIARRHOEA - AETIOLOGY

Goldman-Cecil: "An estimated 5% of the U.S. population suffers from chronic diarrhoea... Causes include persistent infectious or inflammatory diarrheas, malabsorptive syndromes, and watery diarrheas."

A. PERSISTENT INFECTIOUS (Don't Forget These!)

Giardia lamblia - most commonly missed chronic cause
Cryptosporidium - especially HIV/AIDS
Tropical sprue (Brainerd diarrhoea) - chronic watery after travel
Intestinal tuberculosis - chronic granulomatous inflammation
Whipple disease - Tropheryma whipplei - lymphatic obstruction → malabsorption
HIV/AIDS-related diarrhoea - multiple opportunists (CMV, MAC, Cryptosporidium, Isospora)

B. MALABSORPTIVE CAUSES (Steatorrhoea/Fatty Stools)

Robbins describes 4 phases of nutrient absorption that can be disrupted:

Intraluminal digestion
Terminal digestion (brush border)
Transepithelial transport
Lymphatic transport

Disease	Defect Phase	Mechanism
Coeliac disease	Terminal + Transepithelial	Gluten-triggered immune response → villous atrophy → loss of brush border surface area
Chronic pancreatitis / Cystic fibrosis	Intraluminal	Pancreatic enzyme deficiency → undigested fat/protein → osmotic + malabsorptive diarrhoea
Crohn disease	Multiple	Transmural inflammation, skip lesions, can affect terminal ileum (bile salt malabsorption)
Lactase deficiency	Terminal digestion	Inability to break down lactose → osmotic diarrhoea, bloating, flatulence
Whipple disease / Mycobacterial infection	Lymphatic	Lymphatic blockage → fat malabsorption
Abetalipoproteinemia	Transepithelial	Cannot secrete triglyceride-rich lipoproteins
Bacterial overgrowth (SIBO)	Intraluminal + Transepithelial	Bile acid deconjugation, fat malabsorption, vitamin B12 deficiency
Radiation enteritis	Multiple	Post-radiation mucosal damage
Tropical sprue	Terminal + Transepithelial	Similar to coeliac but in tropical regions

Robbins: "The most common chronic malabsorptive disorders in Western countries are pancreatic insufficiency, celiac disease, and Crohn disease."

C. INFLAMMATORY CAUSES (Exudative)

Cause	Key Feature
Ulcerative colitis (UC)	Limited to colon + rectum; mucosal inflammation; bloody diarrhoea, tenesmus
Crohn disease	Anywhere in GI tract; transmural; skip lesions; perianal disease
Microscopic colitis (collagenous + lymphocytic)	Grossly normal colon but histological changes; chronic watery diarrhoea; middle-aged women
Radiation colitis/enteritis	Post-radiotherapy to pelvis/abdomen
Eosinophilic gastroenteritis	Eosinophilic infiltration; often with allergy history
Graft-versus-host disease (GVHD)	After bone marrow/stem cell transplant

Robbins: "Microscopic colitis takes two forms, collagenous colitis and lymphocytic colitis, that both cause chronic watery diarrhea. The intestines are grossly normal, and the diseases are identified by their histologic features."

D. SECRETORY (Watery, Large-Volume, No Osmotic Gap, Persists with Fasting)

Cause	Mechanism
VIPoma (Verner-Morrison syndrome)	Vasoactive intestinal polypeptide → secretory diarrhoea (WDHA: watery diarrhoea, hypokalaemia, achlorhydria)
Carcinoid tumour	Serotonin, prostaglandins → secretory diarrhoea + flushing
Gastrinoma (Zollinger-Ellison)	Acid inactivates pancreatic enzymes → diarrhoea + peptic ulcers
Medullary thyroid carcinoma	Calcitonin → secretory diarrhoea
Bile acid malabsorption	After ileal resection/disease → bile acids stimulate colonic secretion
Microscopic colitis	Already listed above

E. OSMOTIC CAUSES (Stop with Fasting, Osmotic Gap Present)

Cause	Mechanism
Lactase deficiency	Most common disaccharidase deficiency; lactose not absorbed → osmotic effect
Mg-containing antacids/laxatives	Non-absorbed osmotic load
Sorbitol/fructose (diet foods, sugar-free gum)	Non-absorbed carbohydrates
Coeliac disease	Damaged brush border → carbohydrate malabsorption

F. MOTILITY DISORDERS

Cause	Mechanism
Irritable Bowel Syndrome (IBS)	Altered intestinal motility + visceral hypersensitivity; no structural pathology; most common cause of chronic diarrhoea in young adults
Hyperthyroidism	Accelerated transit
Diabetic autonomic neuropathy	Loss of motility control
Post-surgical (vagotomy, gastrectomy, colectomy)	Rapid gastric emptying, dumping syndrome
Scleroderma / systemic sclerosis	Intestinal dysmotility

G. DRUG-INDUCED CHRONIC DIARRHOEA

Commonly tested drugs:

Metformin (very common)
Colchicine
Misoprostol
Orlistat (fat malabsorption mechanism)
SSRIs
Magnesium-containing drugs
Chemotherapy agents
Olsalazine

EXAM SUMMARY TABLE

Feature	Acute Diarrhoea	Chronic Diarrhoea
Duration	< 4 weeks	> 4-6 weeks
Common causes	Infection (viral > bacterial)	IBS, IBD, malabsorption, infection
Most common overall	Viral gastroenteritis (Norovirus/Rotavirus)	IBS
Most common in children	Rotavirus	Coeliac disease
Bloody + fever	Shigella, Salmonella, Campylobacter, C. diff	UC, Crohn, CMV colitis
Watery, no fever	Cholera, ETEC, viruses	VIPoma, microscopic colitis, bile acid malabsorption
Antibiotic-associated	C. difficile	C. difficile relapse
Travel-related	ETEC, Salmonella, Campylobacter	Giardia, tropical sprue
HIV/immunocompromised	Cryptosporidium, CMV, Salmonella	Cryptosporidium, MAC, Isospora
Steatorrhoea	-	Coeliac, chronic pancreatitis, Crohn, SIBO

EXAM MEMORY AID: "IMFOSM" for Chronic Diarrhoea Causes

I - Infection (persistent: Giardia, Cryptosporidium, TB)
M - Malabsorption (Coeliac, Pancreatic insufficiency, Crohn)
F - Functional (IBS)
O - Osmotic (Lactase deficiency, Mg, Sorbitol)
S - Secretory (VIPoma, Carcinoid, Bile acids)
M - Motility/Medications (Thyroid, DM neuropathy, Metformin)

Sources:

Robbins & Kumar Basic Pathology - Malabsorptive Diarrhea section, Table 13.3
Robbins, Cotran & Kumar Pathologic Basis of Disease - Malabsorption and Diarrhea section, Table 17.6
Goldman-Cecil Medicine - Chapter 126: Diarrhea, Tables 126-2 and 126-3
Harrison's Principles of Internal Medicine 22e - Chapter 333: Diarrhea
Medical Microbiology (Murray) - Gastroenteritis and Diarrhea section

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