E11 Digestion and absorption

Topic

Digestion transforms food macronutrients into molecules small enough to be absorbed. Enzymes from saliva, the stomach, the pancreas, and the surface of intestinal cells participate in this process. Concurrently, peristalsis propels chyme through the digestive tract. The transit speed determines how long food remains in contact with the intestinal mucosa and, consequently, directly influences nutrient absorption.

Gastric emptying is a key stage. Liquids leave the stomach relatively quickly, whereas solids are initially retained to be broken down before passing into the small intestine. Emptying slows down as particle size or the meal's caloric content increases. Certain medications, including metformin and GLP-1 analogs, delay gastric emptying, thereby slowing the arrival of glucose in the intestine and blunting the postprandial rise in blood glucose levels.

Once in the small intestine, fat-soluble nutrients can passively cross the lipid membrane of intestinal cells. The rate of this diffusion depends on the concentration gradient between the intestinal contents and the cell, the substance's solubility in membrane lipids, and the mucosal surface area available for exchange. This mechanism does not require the direct expenditure of energy.

Substances with low fat solubility, such as glucose and amino acids, rely instead on specific intestinal membrane transporters. These utilize the sodium gradient maintained by the cells to take up the nutrients. Since there is a finite number of transporters, this mechanism is saturable: at low concentrations, absorption increases almost in proportion to the available amount, but as maximum transport capacity is approached, the rate of increase progressively diminishes.

Intestinal absorption also determines the uptake of orally administered medications. The fraction that ultimately reaches the systemic circulation intact constitutes the drug's oral bioavailability. After crossing the mucosa, a portion of the drug may be metabolized within the intestinal wall itself; subsequently, blood draining from the intestine passes through the liver, where another fraction may be eliminated before reaching the systemic circulation. This first-pass metabolism reduces bioavailability. Drugs such as nitroglycerin, morphine, or lidocaine can undergo significant hepatic extraction; consequently, their oral availability may be low and can vary depending on hepatic blood flow and the activity of metabolizing enzymes.

When the movement of solutes and water across the mucosa is disrupted, various forms of diarrhea can occur. In osmotic diarrhea, substances that cannot be absorbed—such as certain sugars or magnesium salts—remain within the intestine. These particles retain water via osmosis, increasing the intestinal fluid content; the greater the amount of unabsorbed solute, the greater the water retention.

Secretory diarrhea involves a different mechanism. Certain bacterial toxins, such as the cholera toxin, trigger intracellular signals within intestinal cells that stimulate the active secretion of chloride into the intestinal lumen. Water follows the secreted ion, resulting in profuse fluid loss. Thus, whereas in osmotic diarrhea water is retained by unabsorbed substances, in secretory diarrhea the mucosa itself drives the secretion of electrolytes and water.

Collectively, digestion, motility, and absorption determine the entry of nutrients and medications into the body. Gastric emptying controls the rate at which they reach the intestine; passive diffusion and saturable transporters enable passage across the mucosa; intestinal and hepatic metabolism determine drug bioavailability; and alterations in water and solute transport account for different forms of diarrhea. These mechanisms provide insight into how clinical conditions modify nutrient absorption, influence the choice of drug administration routes, and help distinguish between intestinal disorders requiring different treatments.

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