Lecture 31: Pathophysiology of Diarrhea Flashcards
In a healthy subject, secretion and absorption of solutes is ____, if either one of the mechanisms is comprised it will result in diarrhea
Isosmotic
What 3 things are in excess in diarrhea
Water, electrolytes and fat
What type of diarrhea is caused by excess amounts of poorly absorbable, low molecular weight substances that remain in intestinal lumen
Osmotic diarrhea—> solutes will retain water in lumen
What are some causes of osmotic diarrhea
- Poorly absorbable substrates
- Excessive salt, laxatives
What type of diarrhea does exocrine pancreatic insufficiency cause and why
Malabsorption/ Maldigestion
Inadequate production of digestive enzymes from pancreatic Acinar cells
What are some potential causes of exocrine pancreatic insufficiency
- Immune mediated pancreatic Acinar atrophy
- Secondary to chronic pancreatitis
What type of diarrhea does lactose intolerance cause
Malabsorption/ Maldigestion
What causes lactose intolerance
Decreased lactase deficiency at brush border, typically decreases to 10% lactase activity after weaning
What type of diarrhea does lymphangiectasia cause
Maldigestion/ malabsorption
What causes lymphagiectasia
Increased venous/ lymphatic pressure due to malformation of lymphatic drainage or tumor causing obstruction
What disease that causes malabsorption/ Maldigestion diarrhea can be characterized by hypoproteinemia, lymphopenia, hypocalcemia, hypocholesterolemia, peripheral edema, ascites and hydrothorax
Lymphangiesctasia
What causes secretory diarrhea
Excessive/uncontrolled ion transport
What are some various causes of secretory diarrhea and what is the mechanism of action
MOA: all stimulate CFTR Cl- channel causing H20 and Na+ to follow
- Bacterial- cholera, E.coli
- Fatty acids malabsorption
- Bile acids (after ilial resection)
How does enterotoxic E. Coli cause secretory diarrhea
Binds GPCR—> increase cGMP—> increase cAMP—> phosphorylation of CFTR Cl- channel—> H20 and Na+ follow into intestinal lumen
The nutrient absorption in the small intestine is largely normal in secretory diarrhea, why?
The Na+ dependent nutrient absorption via SGLT-1 in SI is functional
Why does fasting not affect secretory diarrhea
CFTR is stimulated by toxins/other agents not by digesta
Explain how a gastrinoma can cause diarrhea
- Hyper secretion of HCl
- Acid inactivates pancreatic enzymes and bile salts resulting in Maldigestion/ malabsorption
- Histamine (activated by HCl) causes excessive fluid and electrolyte secretions
- Acid causes damage to mucosa causing malabsorption
- Gastrin increases motility
What signs are associated with a diarrhea associated with metabolic alkalosis and hypokalemia
Vomiting
Describe how gastrointestinal loss of H+, volume depletion, and decreased K+ play a role in metabolic alkalosis and hypokalemia
- alkalosis causes H+ to leave the cell to combat increase pH
- RAAS is activated during volume depletion which is going to promote Cl- and Na+ uptake primarily in PT, LOH, and DCT
- the uptake of Cl- in these sections leave little Cl- to make it to the collecting duct which results in decrease HCO3- secretion via Cl-/HCO3- exchanger resulting in alkalosis - Aldosterone is activated by RAAS which promotes Na+ reabsorption but K+ secretion resulting in hypokalemia
Does Secretory diarrhea, villous adenoma, illeostomy and jejunoileal bypass result in metabolic acidosis and hypokalemia OR metabolic alkalosis and hypokalemia
Metabolic acidosis and hypokalemia
Explain why secretory diarrhea, villous adenoma illeostomy, and jejunoileal bypass result in metabolic acidosis and hypokalemia
- Volume loss activates RAAS stimulating Na+ reabsorption
- Na/H+ and Cl-/HCO3- coupled transporter in LI will be affected by Cl- loss in diarrhea via CFTR which is going to stimulate HCO3/Cl exchanger and results in increased secretion of HCO3- to try and rescue Cl-, Na+ and H20 will follow
How does volume depletion affect tissue perfusion and how does that contribute to metabolic acidosis
Volume depletion results in decreased organ perfusion, lactic acid will start being produced which will contribute to the acidosis
