The fraction of a drug that the liver can act on depends on how much of the drug is delivered to the liver. Often, this initial metabolism is called "first pass metabolism," and serves to determine the initial dose of each drug when it is taken orally. Decreasing blood flow, increasing binding of a drug to plasma proteins, liver disease (hepatocyte death), and genetic mutations that decrease the activity of the liver metabolism enzymes will all reduce the amount of drug available for the liver to act upon, leading to a decrease in drug extraction.

The functions of the liver are many and varied. The liver is responsible for gluconeogenesis (making new glucose), beta-oxidation of fats, detoxification of drugs and toxins via the cytochrome P450 system, removal of dead red blood cells from circulation, and the creation of blood proteins, including albumin and clotting factors.

The bone marrow is responsible for generating new red blood cells.

Bile is the substance released from the liver that digests fats through detergent-like mechanisms. This is not to be confused with the pancreas which secretes digestive enzymes, such as trypsin.

Bile is made in the liver and stored in the gallbaldder. People can survive without a gallbladder, but having a gallbladder helps release a large amount of bile into the small intestine when it is needed most. This helps make digestion of fats much more effective.

The liver utilizes the hepatic portal system, while the hypothalamus and anterior pituitary use the hypopheseal portal system. The kidneys, spleen, and stomach all use normal circulation, by which blood passes from arterioles to capillaries and immediately back to venules for transport back to the heart.

Digestion in the mouth involves the mechanical chewing of food and the action of salivary amylase, which breaks down starch. Proteins do not start getting digested until they are in the stomach, where pepsin breaks them down. Fats and carbohydrates are broken down in the small intestne by lipases and other enzymes like lactase.

A layer of mucous forms between the epithelial cells of the stomach and the acid within the stomach. This mucous is secreted by mucous cells lining the stomach. When the mucous layer is broken down, certain complications can take place (e.g. stomach ulcers).

D cells in the antrum of the stomach are neuroendocrine cells that secrete somatostatin, a neuropeptide that increases stomach pH by decreasing gastric acid secretion from fundal parietal cells. In a negative feedback mechanism, when the stomach pH falls too low, hydrogen ions (H⁺) will stimulate D cells to secrete somatostatin. This somatostatin blocks histamine release from enterochromaffin-like (ECL) cells in the stomach, preventing the stimulation of parietal cells to release hydrochloric acid.

Histamine is released by ECL cells, stimulating acid secretion from parietal cells. Gastrin is released by G cells, also stimulating acid secretion from parietal cells. Ghrelin is a neurohormone that stimulates hunger.

Iron, usually ingested in the Fe³⁺ form (ferric iron), must be reduced to Fe²⁺ (ferrous form) in order to be absorbed in the duodenum of the small intestine. The iron undergoes an oxidation-reduction reaction in the stomach, facilitated by the low pH of the stomach lumen.

The pyloric sphincter, between the antrum of the stomach and the duodenum of the small intestine, regulates the passage of chyme from the stomach to the small intestine. The antrum has rhythmic contractions that force chyme against the pyloric sphincter, allowing approximately five milliliters to flow through every contraction; thus, the pyloric sphincter allows for the gradual but continual digestion of gastric contents.

The upper and lower esophageal sphincters are involved in the process of swallowing, while the ileocolic sphincter joins the small intestine and large intestine.