The digestive system breaks food into molecules small enough to cross cell membranes — and then absorbs those molecules into the blood for distribution to the body’s cells. It is a long tube (approximately 9 meters from mouth to anus) with specialized regions, each performing a distinct function in the sequence of digestion, absorption, and elimination.
Anatomy
Mouth — mechanical digestion begins here. Teeth break food into smaller pieces (increasing surface area for enzymes). Salivary glands produce saliva containing amylase, which begins starch digestion. The tongue forms the chewed food into a bolus and pushes it into the pharynx.
Esophagus — a muscular tube connecting the pharynx to the stomach. Peristalsis — coordinated waves of smooth muscle contraction — moves the bolus downward. The lower esophageal sphincter prevents stomach acid from refluxing into the esophagus; when it fails, the result is gastroesophageal reflux disease (GERD).
Stomach — a muscular sac that churns food with gastric juice (hydrochloric acid and pepsin). The acid kills most ingested bacteria and denatures proteins; pepsin begins protein digestion. The stomach lining is protected from its own acid by a mucus layer. NSAIDs (discussed in pharmacology) inhibit prostaglandin production — and prostaglandins maintain this protective mucus layer. This is why chronic NSAID use causes gastric ulcers: the drug’s therapeutic effect (reducing inflammation) and its major side effect (gastric damage) both follow from the same mechanism.
Small intestine — the primary site of digestion and absorption. It is approximately 6 meters long, divided into three segments:
- Duodenum — receives chyme (partially digested food) from the stomach, bile from the liver/gallbladder, and pancreatic juice from the pancreas. Pancreatic enzymes digest proteins (trypsin, chymotrypsin), fats (lipase), and carbohydrates (amylase). Bile emulsifies fats — breaking large fat droplets into smaller ones that lipase can access.
- Jejunum — the main absorptive segment. The intestinal wall is covered in villi (finger-like projections) and microvilli (microscopic projections on each villus), creating an enormous surface area (approximately 250 square meters — the size of a tennis court, similar to the alveolar surface area) for nutrient absorption.
- Ileum — absorbs bile salts (recycling them to the liver) and vitamin B12. Contains Peyer’s patches — aggregates of lymphoid tissue that are part of the gut-associated immune system.
Large intestine (colon) — absorbs water and electrolytes from the remaining material, converting liquid chyme into solid stool. The colon houses the gut microbiome — trillions of bacteria that ferment undigested fiber, produce vitamins (K, B12, biotin), and play a critical role in immune regulation. Disruption of the gut microbiome (by antibiotics, diet, or disease) is increasingly recognized as a factor in conditions far beyond the gut, including mood disorders, autoimmune disease, and chronic pain.
Rectum and anus — store and eliminate feces. Defecation is controlled by both involuntary (internal anal sphincter, smooth muscle) and voluntary (external anal sphincter, skeletal muscle) mechanisms.
The liver
The liver is the body’s central metabolic organ — and the primary site of drug metabolism. Its functions include:
- Bile production — bile is made in the liver, stored in the gallbladder, and released into the duodenum to emulsify fats
- Nutrient processing — absorbed nutrients pass from the intestine to the liver via the portal vein (the hepatic portal system). The liver converts glucose to glycogen for storage, synthesizes proteins (including albumin and clotting factors), and processes amino acids
- Detoxification — the liver metabolizes drugs, alcohol, and metabolic waste products. Most drugs undergo hepatic metabolism — they are chemically modified by liver enzymes (primarily the cytochrome P450 system) into forms that can be excreted by the kidneys. This is why liver disease profoundly affects pharmacokinetics — a damaged liver cannot metabolize drugs at the normal rate, leading to drug accumulation and toxicity
- First-pass metabolism — drugs taken orally are absorbed from the gut into the portal vein and pass through the liver before reaching the systemic circulation. The liver metabolizes a significant fraction of many drugs during this first pass, reducing their bioavailability. This is why some drugs must be given intravenously or sublingually — to bypass first-pass metabolism
The pancreas
The pancreas has two distinct functions:
- Exocrine — produces digestive enzymes (amylase, lipase, trypsin) and bicarbonate (to neutralize stomach acid in the duodenum)
- Endocrine — produces hormones that regulate blood glucose: insulin (lowers blood glucose by promoting cellular uptake) and glucagon (raises blood glucose by promoting glycogen breakdown in the liver). The balance between insulin and glucagon is a homeostatic system: rising glucose triggers insulin release; falling glucose triggers glucagon release. Diabetes mellitus is the failure of this system — either because the pancreas cannot produce enough insulin (Type 1) or because cells become resistant to insulin’s effects (Type 2).
Digestion and the autonomic nervous system
Digestion is controlled by the parasympathetic division of the autonomic nervous system (“rest and digest”). Parasympathetic activation (via the vagus nerve) increases gut motility, increases digestive enzyme secretion, and promotes blood flow to the gut. Sympathetic activation (“fight or flight”) does the opposite — it inhibits digestion and diverts blood away from the gut to the muscles.
This is why chronic stress disrupts digestion: sustained sympathetic activation suppresses gut function. Irritable bowel syndrome (IBS), functional dyspepsia, and other functional gastrointestinal disorders often involve autonomic dysregulation — the gut is structurally normal but functionally impaired because the nervous system is not supporting digestive function.
The gut also has its own intrinsic nervous system — the enteric nervous system — containing approximately 500 million neurons. This “second brain” can coordinate basic digestive functions (peristalsis, enzyme secretion) independently of the central nervous system, though it is modulated by both sympathetic and parasympathetic input.