In-Depth Notes on the Pathogenesis of Diarrhea

By the end of this session, students will be able to:

• List the targets for microbial colonization and/or destruction of intestinal mucosae

  • Understand the role of specific pathogens in the colonization and destruction process, including bacteria, viruses, and parasites.

  • Identify key areas of the intestinal mucosa most affected by these microbes, and discuss how they disrupt normal gut function.

• Define diarrhea

  • Explore the clinical definition of diarrhea as an increase in stool frequency, fluidity, or volume, and differentiate between acute and chronic diarrhea.

  • Identify the thresholds used to define diarrhea in various species including humans, and the implications of differing definitions.

• Analyze the basic pathological process that explains the development of diarrhea

  • Discuss the interrelated factors of fluid secretion, absorption, and motility that lead to diarrhea.

  • Examine the involvement of the gut's microbiome and its balance in maintaining intestinal health versus the development of diarrhea.

• Describe the most common combinations of diarrhea pathological processes using clinically relevant examples

  • Explore mixed types of diarrhea, providing case studies of conditions where multiple mechanisms are at play, such as infections coupled with malabsorption.

  • Include differential diagnoses and the importance of recognizing signs that indicate which processes are predominantly involved.

• Identify the most common clinical signs of diarrhea from the small bowel and large bowel

  • Discuss abdominal pain, changes in bowel habits, and accompanying symptoms such as fever and vomiting.

  • Understand the implications of these signs for diagnosing underlying causes.

• Describe the consequences of diarrhea

  • Expound on short-term and long-term health implications, including how chronic diarrhea can lead to nutritional deficiencies and chronic diseases.

  • Analyze the social and economic impacts of diarrhea in both developed and developing countries, emphasizing prevention and treatment strategies, including rehydration therapies.

Dysfunction/Responses to Injury

• Types of Responses:

  • Inflammation

  • Necrotizing Processes

  • Lymphangiectasia

  • Disorders of Innervation

  • Diarrhea:

    • Small bowel diarrhea

    • Large bowel diarrhea

Inflammation

• Chronic Injury of the lamina propria:

  • Results in dense cellular infiltration leading to diarrhea through various overlapping mechanisms.

  • Mechanisms include:

    • Physical impairment of mucosal diffusion → disruption of the overlying epithelium leading to increased permeability

    • Swelling of the lamina propria → blunting and fusion of intestinal villi → reduced absorptive surface area

  • Examples:

    • Canine histiocytic ulcerative colitis as a case study highlighting chronic inflammation in canines.

    • Johne’s disease of ruminants highlighting prolonged inflammation due to persistent infection.

    • Amyloidosis resulting from protein deposits disrupting normal function.

    • Lymphoma presenting as a malignant cause of enteritis and diarrhea.

Necrotizing Processes

• Mechanisms:

  • Primary necrosis of the Gut Associated Lymphoid Tissue (GALT) can compromise intestinal immunity and extend to the overlying epithelium, exacerbating diarrhea.

  • Examples:

    • Bovine viral diarrhea (BVD) in cattle reduces physiological homeostasis.

    • Rhodococcus equi infection in horses leading to severe enteritis.

    • Endotoxemia possibly causing vascular damage and disseminated intravascular coagulation (DIC), complicating recovery efforts.

Lymphangiectasia

• Causes:

  • Secondary to obstruction or idiopathic origins (common in small-breed dogs) including limited lymphatic drainage, which can lead to protein-losing enteropathy.

  • Obstruction can also occur due to space-occupying lesions (SOLs) in the lamina propria, including:

    • Johne’s disease (ruminants) causing persistent diarrhea due to chronic infection.

    • Granulomatous lymphangitis and lymphadenitis affecting absorption and fluid balance.

Disorders of Innervation

• Agangliosis and Dysautonomia:

  • Malfunction of cranial nerves, spinal nerves, ganglia, and/or the autonomic nervous system (ANS) can severely disrupt intestinal motility and contribute to chronic diarrhea.

  • Neurohormonal Interchange:

    • Interaction between intestinal microbiota and the brain affects gut function through mechanisms such as the gut-brain axis, implicating conditions like:

    • Irritable bowel syndrome (IBS) as a chronic condition affected by psychological factors.

    • Crohn’s disease being exacerbated by stress-related gut responses.

    • Psychiatric disorders linked to gut health indicating a significant connection to overall health and disease outcomes.

Diarrhea Classification

• Small Bowel Diarrhea:

  • Conditions affecting digestion, absorption, or motility often result in significant nutritional repercussions.

  • Common Causes:

    • Infections such as viral, bacterial or protozoal invaders disrupting normal processes.

    • Malabsorption syndromes due to anatomical or functional anomalies.

    • Inflammatory disorders such as celiac disease.

  • Signs:

    • Watery, large-volume stools indicating significant fluid loss.

    • Nocturnal diarrhea suggesting underlying systemic issues.

    • Weight loss, dehydration, and malabsorption leading to nutrient deficits.

• Large Bowel Diarrhea:

  • Usually related to the colon's limited capacity to absorb water.

  • Common Causes:

    • Infectious colitis challenging the colonic mucosa, leading to symptoms.

    • Inflammatory bowel disease (IBD) presenting as chronic inflammation.

    • Food intolerances triggering inflammatory responses.

  • Signs:

    • Frequent small-volume diarrhea indicating urgency.

    • Increased mucus production, potentially with blood in stools; abdominal cramping as an additional symptom.

Pathogenesis of Diarrhea

• Definition:

  • Characterized by increased fecal fluidity, reflecting an imbalance between water absorption and secretion, leading to increased frequency and volume.

  • According to Pathogen:

    • Differentiation between disease states caused by various classifications of pathogens:

    • Enterotoxigenic (e.g., E. coli) producing toxins.

    • Inflammatory agents (e.g., Salmonella) causing epithelial injury.

    • Invasive organisms (e.g., Lawsonia) with the ability to breach mucosal barriers.

  • Pathophysiological Mechanisms:

    • Involves malabsorption, osmotic imbalance, hypersecretory states, exudative processes, and hypermotility leading to differential presentations of diarrhea.

Consequences of Diarrhea

• Fluid Loss: Normal feces contain approximately 75% water, whereas diarrheal feces can contain over 85% water, emphasizing the importance of rapid assessment and intervention.

• Consequences include:

  • Dehydration, which can lead to hypotension and critical metabolic acidosis, highlighting the urgency of treatment, especially in vulnerable populations.

  • Electolyte imbalances that may result in significant physiological disturbances, including cardiac issues and renal failure.

  • Identify the broader impacts of diarrhea, such as economic burdens related to healthcare costs and loss of productivity in affected communities.

Summary of Key Points

• Classifying diarrhea based on location (small vs. large bowel) and physiological mechanisms enhances diagnostic accuracy.

• Recognizing main responses to intestinal injury and understanding the roles of various pathogens provides a framework for effective treatment strategies.

• Identifying the importance of inflammation and neurohormonal interactions in gut health and implications for developing interventions aimed at restoring gastrointestinal wellbeing.