Lecture 31: Pathophysiology of Diarrhea

Question 1

In a healthy subject, secretion and absorption of solutes is ____, if either one of the mechanisms is comprised it will result in diarrhea

Answer 1

Isosmotic

Question 2

What 3 things are in excess in diarrhea

Answer 2

Water, electrolytes and fat

Question 3

What type of diarrhea is caused by excess amounts of poorly absorbable, low molecular weight substances that remain in intestinal lumen

Answer 3

Osmotic diarrhea—> solutes will retain water in lumen

Question 4

What are some causes of osmotic diarrhea

Answer 4

1. Poorly absorbable substrates
2. Excessive salt, laxatives

Question 5

What type of diarrhea does exocrine pancreatic insufficiency cause and why

Answer 5

Malabsorption/ Maldigestion

Inadequate production of digestive enzymes from pancreatic Acinar cells

Question 6

What are some potential causes of exocrine pancreatic insufficiency

Answer 6

1. Immune mediated pancreatic Acinar atrophy
2. Secondary to chronic pancreatitis

Question 7

What type of diarrhea does lactose intolerance cause

Answer 7

Malabsorption/ Maldigestion

Question 8

What causes lactose intolerance

Answer 8

Decreased lactase deficiency at brush border, typically decreases to 10% lactase activity after weaning

Question 9

What type of diarrhea does lymphangiectasia cause

Answer 9

Maldigestion/ malabsorption

Question 10

What causes lymphagiectasia

Answer 10

Increased venous/ lymphatic pressure due to malformation of lymphatic drainage or tumor causing obstruction

Question 11

What disease that causes malabsorption/ Maldigestion diarrhea can be characterized by hypoproteinemia, lymphopenia, hypocalcemia, hypocholesterolemia, peripheral edema, ascites and hydrothorax

Answer 11

Lymphangiesctasia

Question 12

What causes secretory diarrhea

Answer 12

Excessive/uncontrolled ion transport

Question 13

What are some various causes of secretory diarrhea and what is the mechanism of action

Answer 13

MOA: all stimulate CFTR Cl- channel causing H20 and Na+ to follow

1. Bacterial- cholera, E.coli
2. Fatty acids malabsorption
3. Bile acids (after ilial resection)

Question 14

How does enterotoxic E. Coli cause secretory diarrhea

Answer 14

Binds GPCR—> increase cGMP—> increase cAMP—> phosphorylation of CFTR Cl- channel—> H20 and Na+ follow into intestinal lumen

Question 15

The nutrient absorption in the small intestine is largely normal in secretory diarrhea, why?

Answer 15

The Na+ dependent nutrient absorption via SGLT-1 in SI is functional

Question 16

Why does fasting not affect secretory diarrhea

Answer 16

CFTR is stimulated by toxins/other agents not by digesta

Question 17

Explain how a gastrinoma can cause diarrhea

Answer 17

1. Hyper secretion of HCl
2. Acid inactivates pancreatic enzymes and bile salts resulting in Maldigestion/ malabsorption
3. Histamine (activated by HCl) causes excessive fluid and electrolyte secretions
4. Acid causes damage to mucosa causing malabsorption
5. Gastrin increases motility

Question 18

What signs are associated with a diarrhea associated with metabolic alkalosis and hypokalemia

Answer 18

Vomiting

Question 19

Describe how gastrointestinal loss of H+, volume depletion, and decreased K+ play a role in metabolic alkalosis and hypokalemia

Answer 19

1. alkalosis causes H+ to leave the cell to combat increase pH
2. 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
3. Aldosterone is activated by RAAS which promotes Na+ reabsorption but K+ secretion resulting in hypokalemia

Question 20

Does Secretory diarrhea, villous adenoma, illeostomy and jejunoileal bypass result in metabolic acidosis and hypokalemia OR metabolic alkalosis and hypokalemia

Answer 20

Metabolic acidosis and hypokalemia

Question 21

Explain why secretory diarrhea, villous adenoma illeostomy, and jejunoileal bypass result in metabolic acidosis and hypokalemia

Answer 21

1. Volume loss activates RAAS stimulating Na+ reabsorption
2. 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

Question 22

How does volume depletion affect tissue perfusion and how does that contribute to metabolic acidosis

Answer 22

Volume depletion results in decreased organ perfusion, lactic acid will start being produced which will contribute to the acidosis