Keywords
Water handlingIntestinal electrolyte transportNa + transportK+ transportDiarrheaBiliary FistulaPancreatic fistulasVillous adenomaCholestyramineMajor acid–base disorders of GI origin
Hyperchloremic metabolic acidosis | Metabolic alkalosis |
|---|---|
Diarrhea Biliary fistula Pancreatic fistula Villous adenoma Ureterosigmoidostomy Ureterojejunostomy Ureteroileostomy Laxatives Cholestyramine Short bowel syndrome (D-lactic acidosis) | Vomiting Nasogastric suction Psychogenic vomiting Gastrostomy drainage Congenital chloridorrhea Ulcerative colitis Crohn’s disease Villous adenoma Calcium (milk)-alkali syndrome Antacids |
Before we discuss the pathophysiology of hyperchloremic metabolic acidosis, it is essential to understand water and electrolyte handling by the GI tract.
Water Handling
Daily intake of water from diet and drinking amounts to 2 L.
Secretions from the saliva, stomach, bile, pancreas, and small intestine amount to 7 L.
Thus, the daily total handling of water by the GI tract is 9 L.
Of these 9 L, 4 L are absorbed by the duodenum and jejunum, 3.5 L by the ileum, and 1.4 L by the colon, leaving 100–200 mL in the stool.
Water handling by the normal gastrointestinal tract
Intestinal Electrolyte Transport
Na+ and Cl− Transport in the Small Intestine
The epithelial cells lining the small intestine and colon absorb most of the delivered electrolytes and water in isoosmolar concentrations. Thus, the fluid that is absorbed is always isosmotic . The absorption of Na+ and Cl− in the small intestine is similar to that of the proximal tubule; however, a Cl/HCO3 exchanger is localized which transports Cl− into the cell in exchange for HCO3 −. This chloride anion exchanger is also called downregulated in adenoma (DRA). Thus, NaCl absorption occurs along the small intestine. The following transport mechanisms are responsible for NaCl entry into the cell (Fig. 9.2):
- 1.
Na+ transport alone via water channels
- 2.
Na/H-ATPase with generation and absorption of HCO3 −
- 3.
Na/Cl cotransporter
- 4.
Na+ transport coupled with solutes (glucose, amino acids, etc.)
- 5.
Cl/HCO3 exchanger
- 6.
Na+ and Cl− exit via Na/K-ATPase and K/Cl cotransporter, respectively
- 1.
NaCl transport in the epithelium of small intestine. Solute refers to glucose and amino acids
Na+ and K+ Transport in Colon
The colon has both absorptive and secretory functions.
Like principal cells, the epithelial cells of the colon contain Na+ (epithelial Na+ channel or ENaC) and K+ channels separately (Fig. 9.3).
Absorption of Na+ and secretion of K+ occur via their respective channels.
Aldosterone regulates both Na+ and K+ transport.
Na+ reabsorption and K+ and Cl− secretion in colon. ENaC epithelial sodium channel, CFTR cystic fibrosis transmembrane conductance regulator
Intestinal Secretion of Cl−
The epithelial cells lining the intestinal crypts secrete both electrolytes and water.
The apical membrane of crypt cells contains Cl− channels, and the basolateral membrane contains Na/K-ATPase, Na/K/2Cl cotransporter, and a K+ channel. Na+, K+, and Cl− enter the cells from blood via these transporters. Cl− is secreted into the lumen via Cl− channel, whereas Na+ enters the lumen passively via the paracellular pathway. Subsequently, water moves into the lumen following NaCl secretion.
Usually, Cl− channels are closed but remain open following activating substances. These substances bind to their receptor at the basolateral membrane, leading to the stimulation of adenylate cyclase and production of cAMP in crypt cells. cAMP then keeps Cl− channel open, facilitating its secretion into the lumen.
Cystic fibrosis transmembrane conductance regulator (CFTR) was identified as the Cl− channel that is located in the apical membrane of epithelial cells. It mediates efflux of Cl− into the lumen, thus involved in secretory function of the colon. CFTR is defective in cystic fibrosis, resulting in less Cl− efflux (Fig. 9.3).
HCO3 − Handling in the Colon
Although HCO3 − is secreted in the colon, all of it is not excreted in the stool. Most of this HCO3 − is used up for the production of organic acids such as propionic acid, butyric acid, acetic acid, and lactic acid. These acids are the products of unabsorbed carbohydrates that are fermented by bacteria.
Titration of these acids by NaHCO3 generates sodium propionate, sodium butyrate, and other organic acids, which enter the liver for regeneration of HCO3 −. Therefore, the stool contains low HCO3 −.
Volume and Electrolyte Concentrations of GI Fluids
Table 9.2 shows the normal values of electrolytes in various fluids of the GI tract. The information is useful in assessing the acid–base disturbances due to GI disorders.
It is evident from Table 9.2 that the GI tract as a whole absorbs all the secreted Na+ and Cl−, leaving very few milliequivalents in the stool.
More specifically, the jejunum absorbs about 100 mEq of Na+ and 3 L of water, whereas the ileum absorbs 400 mEq each of Na+ and Cl− as well as 3.5 L of water.
Finally, the colon is the most efficient segment of the intestine, absorbing >90% of 200 mEq of Na+, 100 mEq of Cl−, and 1.4 L of water delivered to it. Because of this tremendous absorptive capacity of the colon, the stool contains <100–200 mL of water and low quantities of Na+, Cl−, and HCO3 −; however, K+ concentration in stool is more than the other electrolytes because of its secretion in the colon.
Volume and concentrations of electrolytes in fluids of normal GI tract
Source | Volume (L/day) | Na+ (mEq/L) | K+ (mEq/L) | Cl− (mEq/L) | HCO3 − (mEq/L) |
|---|---|---|---|---|---|
Saliva (meal stimulated) | 1 | 50–88 | 20 | 50 | 60 |
Gastric fluid (stimulated) | 2 | 10–20 | 5–14 | 130–160 | 0 |
Bile | 1 | 135–155 | 5–10 | 80–110 | 20 |
Pancreatic fluid | 2 | 120–160 | 5–10 | 30–76 | 70–120 |
Small intestinal fluid | 1 | 75–120 | 5–10 | 70–120 | 30 |
Stool | 0.1–0.2 | 20–30 | 55–75 | 15–25 | 30 |
Diarrhea
Water and Electrolyte Loss
Diarrhea is defined when stool weight exceeds >200 g/day or >200 mL/day, when secretions of fluids exceed their absorption.
Diarrhea is the most common nonrenal cause of hyperchloremic metabolic acidosis.
Unlike renal acidoses where hyperchloremic metabolic acidosis is due to defects in transport mechanisms, diarrhea or GI disorders-induced hyperchloremic metabolic acidosis is due to loss of HCO3 − and other electrolytes in the stool.
The composition of the diarrheal fluid varies depending on the etiology of diarrhea (Table 9.3).
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