The overall process of fat digestion and absorption consists of four distinct phases, related to the respective functions of the pancreas, liver, intestinal mucosa and lymphatics (Figure 8). Physiologically, these involve (1) lipolysis of dietary triglyceride (TG) to fatty acid (FA) and ß-monoglyceride (MG); (2) micellar solubilization with bile acid; (3) uptake into the mucosal cell, with re-esterification of the MG with FA to form TG, and chylomicron formation in the presence of cholesterol, cholesterol esters, phospholipids and protein; and (4) delivery of chylomicrons in lymphatics to the body for utilization of fat.

The average North American diet contains 60-100 g of fat each day, mostly in the form of neutral fat or triglycerides. In the proximal intestine, TG comes under hydrolytic attack by lipases, producing glycerol, FA and MG. These products of lipolysis first form an emulsion and later a micellar solution.

Following the entry of food and particularly fat into the duodenum, cholecystokinin (CCK) is released from mucosal cells, causing gallbladder contraction. Bile acids, along with other biliary constituents, are released into the proximal small intestine. Bile acids chemically resemble detergent molecules, in that a portion of the molecule is polar and water-soluble, while another portion of the molecule is nonpolar and fat-soluble. When the bile acids are present in sufficient amounts, known as the critical micellar concentration (CMC), they form negatively charged spheres, called simple micelles. Incorporation of FA and MG forms a larger, polymolecular aggregate, a mixed micelle. All this is necessary to solubilize fat and disperse it in small packets more effectively, setting the stage for further digestion by pancreatic lipase. This enzyme acts only at oil-water interfaces and requires a large surface area. Pancreatic lipase is secreted into the duodenunal lumen where it acts on ingested food.

Adequate concentrations of bile acid must be present within the jejunal lumen for effective micellar solubilization and lipolysis by pancreatic lipase, a preliminary to esterification and uptake. Such adequate concentrations of bile acids are maintained by the constant reutilization of a relatively small pool of bile acid. In the liver, about 0.6 g of new bile acid is produced daily from cholesterol. This is added to the total bile acid pool of 3.0 g, which cycles 6 to 10 times daily from passive absorption in the jejunum and active absorption in the ileum. Approximately 96% of the bile acid is absorbed through these mechanisms with each cycle; the remainder is lost in the stool. Bile acids return to the liver via the portal vein and are excreted once more. This recirculation of bile acid between the intestine and the liver is called the enterohepatic circulation.

The principal role of the bile salt micelle is to facilitate lipid absorption by maintaining the lipid in a water-soluble form, overcoming the resistance of the unstirred water layer and maintaining a high concentration of a local source of fatty acid and cholesterol, which leave the micelle and enter the mucosal cell.

The lipid-containing bile acid micelle is now ready for mucosal uptake. Two important events occur within the mucosal cell: re-esterification and chylomicron formation. The fatty acids are first reattached to the monoglycerides through re-esterification, and the resultant triglyceride is then combined with small amounts of cholesterol and coated with phospholipids and proteins to form a specific class of lipoproteins known as chylomicrons. The chylomicrons are then released from the basal portion of the columnar epithelial cell and find their way into the central lacteal of the intestinal villus. From there, chylomicrons travel in lymph up the thoracic duct and eventually reach the general circulation. Chylomicrons are then transported in the blood to the sites of disposal and utilization in the periphery (e.g., liver, muscle and adipose tissue).

From these physiological considerations, malabsorption of fat due to impaired lipolysis or micellar solubilization would be expected to occur in the following circumstances: (1) rapid gastric emptying and improper mixing - e.g., following vagotomy or postgastrectomy; (2) altered duodenal pH - e.g., the Zollinger-Ellison syndrome, where excessive duodenal acidification inhibits the action of lipase; (3) pancreatic insufficiency; (4) cholestasis - e.g., biliary obstruction, liver disease; and (5) an interrupted enterohepatic circulation - e.g., ileal disease or loss, and bile salt deconjugation due to the bacterial overgrowth syndrome.

Fat malabsorption due to impaired mucosal uptake, assembly or delivery would be expected to occur following (1) generalized impaired enterocyte function - e.g., celiac disease, Whipple's disease; (2) failure of the packaging process - e.g., abetalipoproteinemia, which represents a genetic defect of lipoprotein B synthesis with consequent impairment of chylomicron formation; (3) disorders of lymphatics - e.g., intestinal lymphangiectasia, retroperitoneal fibrosis or lymphoma; and (4) loss of mucosal surface area - e.g., the short bowel syndrome.