fluid and electrolytes

Question 1

1. Identify the sites of electrolyte and water absorption/secretion in the intestines.

Answer 1

• Small intestine:
  o Absorption of: sodium, potassium, chloride, and water.
  o Secretion of: bicarb.
• Large intestine:
  o Absorption of: sodium, chloride, and water.
  o Secretion of: bicarb and potassium.

Question 2

2. Identify and describe the key proteins and processes important for electrolyte and water absorption/secretion in the intestines.

Answer 2

• Sodium:
  o Movement into cell through luminal membrane: sodium channel (facilitated diffusion), sodium-hydrogen exchanger, sodium-glucose transporter-1 (SGLT1), amino acid transporter B.
  o Movement out of cell through basal membrane: sodium-potassium pump (important for maintaining gradient between lumen and cell to facilitate sodium absorption from GI lumen).
• Chloride and bicarb:
  o Absorption:
   Movement of chloride into cell (and bicarb out of cell) through luminal membrane: chloride/bicarb exchanger.
   Movement of chloride out of cell through basal membrane: chloride is dragged out through basal membrane to facilitate pulling Na+ out of cell too (sodium follows chloride everywhere it goes).
  o Secretion:
   Movement of chloride out of cell through luminal membrane: activation of cystic fibrosis transporter (CFTR): opening of this channel allows chloride to be secreted into lumen.
   Note: sodium follows chloride, and water follows sodium. Net result: water retained in lumen.
• Potassium:
  o Absorption:
   Movement out of lumen (through tight junctions): dragged along with water through weak tight junctions between cells as sodium is pulled out of lumen.
  o Secretion:
   Large amount of bicarb secretion in intestines  net negative charge of lumen  potassium dragged back into lumen through from within the cell.
   Note: sodium does not also leave cell for negatively charged lumen as it is being actively pumped out of the basal side by the Na+/K+-ATPase.
• Water:
  o Follows sodium.
  o Regulation:
   CFTR is stimulated by and sodium-hydrogen ion exchanger is inhibited by secondary messenger pathways (cAMP, cGMP, Ca2+)  chloride pushed out of cell, Na+ can’t get into cell  retention of water in lumen of GI tract.
   Steroids: regulate transcription of surface proteins (ex: sodium-hydrogen exchanger, sodium-potassium pump, etc.)  increased sodium uptake  increased water uptake  water absorbed.

Question 3

3. Describe how CFTR and the sodium-hydrogen ion exchanger are regulated by multiple stimuli including: bacterial toxins, immune cell secretions (prostaglandins, histamine), and neurotransmitters (Ach, serotonin, VIP).

Answer 3

• Action: stimulate CFTR, inhibit Na+/H+ exchanger.
• Mechanism: second messenger generation.
• Result: fluid secretion (diarrhea).
• Note: steroids, somatostatin, and NE: upregulate Na+ channels and/or Na+/K+ ATPase and/or Na+/H+ exchanger  fluid absorption. Note that everywhere else in the GI system, somatostatin acts as an “off button”. However, in terms of fluid absorption, it acts as an “on” button (and is thus used for treating diarrhea caused by cholera).

Question 4

4. Define and list the causes of the following symptoms of GI pathophysiology: osmotic diarrhea, secretory diarrhea, and constipation.

Answer 4

• Osmotic diarrhea:
  o Causes: nonabsorbable nutrient in lumen of GI tract  water retention in lumen (ex: disaccharidase deficiency, pancreatic enzyme deficiency, nutrient-binding substances, loss of enterocytes, bacterial overgrowth, antacids).
• Secretory diarrhea:
  o Causes: intestinal cells secrete fluid and electrolytes through secretion of chloride ions (ex: inflammatory cytokines, cholera toxin, tumors that secrete VIP and serotonin, etc.)
• Note: process that can cause both osmotic or secretory diarrhea: inflammatory conditions, infectious diseases.
• Constipation:
  o Causes: diet/lifestyle (decreased activity, decreased fluid intake, decreased fiber intake), GI (cancer, stricture, hernia, inflammation, adhesions), pharmacological (narcotics, anticholinergics, antacids, antipsychotics, laxative abuse, lead poisoning), endocrine (diabetes, hypothyroidism, hyperthyroidism), neurogenic (neuropathy, Parkinsons disease, paraplegia, cerebral palsy).
  o Note: inflammation can cause both diarrhea OR constipation.