Steatorrhea pathophysiology

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sunny Kumar MD [2]

Overview

Stearorhea is loss of fatty undigested fecal material in stools. The processes invokes defect if the digestive tract. It may involve defect of synthesis or secretion or function of enzymes of GI tract which are needed to metabolize fatty content of food. It can also be due to defect in anatomical structures of GI tract.

Pathophysiology

Normal Fat malabsorption

To understanf the pathophysiology of fat malabsoption we need to understand follwoing points:.

• Normal fat absorption involves a complex mixture of digestive enzymes, bile salts, and an intact intestinal mucosa to enable uptake of these hydrophobic complexes.
• After ingestion, dietary lipids are initially emulsified in the stomach and then hydrolyzed by the action of gastric and pancreatic lipase and colipase.
• The hydrolyzed lipids are then aggregated into micelles or liposomes with the addition of bile salts in the duodenum and jejunum.
• These micelles are absorbed across the intact intestinal villi by both active and passive processes. Finally, they are packaged into chylomicrons within intestinal epithelial cells and transported to the circulation via the lymphatic system
• More than 90% of daily dietary fat is absorbed into the general circulation, but any defects in the processes can reduce this uptake and lead to fatty diarrhea/ steatorrhea.
• The bulk of dietary lipid is neutral fat or triglyceride, composed of a glycerol backbone with each carbon linked to a fatty acid.
• Foodstuffs typically also contain phospholipids, sterols like cholesterol and many minor lipids, including fat-soluble vitamins.
• Finally, small intestinal contents contain lipids from sloughed epithelial cells and considerable cholesterol delivered in bile.

Emulsification, Hydrolysis and Micelle Formation:

• Bile acids play their first critical role in lipid assimilation by promoting emulsification.
• As derivatives of cholesterol, bile acids have both hydrophilic and hydrophobic domains (i.e. they are amphipathic).
• On exposure to a large aggregate of triglyceride, the hydrophobic portions of bile acids intercalate into the lipid, with the hydrophilic domains remaining at the surface. 
• Such coating with bile acids aids in breakdown of large aggregates or droplets into smaller and smaller droplets.
• Hydrolysis of triglyceride into monoglyceride and free fatty acids is accomplished predominantly by pancreatic lipase.
• The activity of this enzyme is to clip the fatty acids at positions 1 and 3 of the triglyceride, leaving two free fatty acids and a 2-monoglyceride.
• The drug orlistat (Xenical) that is promoted for treatment of obesity works by inhibiting pancreatic lipase, thereby reducing the digestion and absorption of fat in the small intestine.
• Lipase is a water-soluble enzyme, and with a little imagination, it's easy to understand why emulsification is a necessary prelude to its efficient activity. 
• Shortly after a meal, lipase is present within the small intestine in rather huge quantities, but can act only on the surface of triglyeride droplets.
• For a given volume of lipid, the smaller the droplet size, the greater the surface area, which means more lipase molecules can get to work.
• As monoglycerides and fatty acids are liberated through the action of lipase, they retain their association with bile acids and complex with other lipids to form structures called micelles. 
• Micelles are essentially small aggregates (4-8 nm in diameter) of mixed lipids and bile acids suspended within the ingesta.
• As the ingesta is mixed, micelles bump into the brush border of small intestinal enterocytes, and the lipids, including monoglyceride and fatty acids, are taken up into the epithelial cells.

Absorption and Transport into Blood:

• The major products of lipid digestion - fatty acids and 2-monoglycerides - enter the enterocyte by simple diffusion across the plasma membrane.
• A considerable fraction of the fatty acids also enter the enterocyte via a specific fatty acid transporter protein in the membrane.
• Lipids are transported from the enterocyte into blood by a mechanism distinctly different from what we've seen for monosaccharides and amino acids.
• Once inside the enterocyte, fatty acids and monoglyceride are transported into the endoplasmic reticulum, where they are used to synthesize triglyeride.
• Beginning in the endoplasmic reticulum and continuing in the Golgi, triglyceride is packaged with cholesterol, lipoproteins and other lipids into particles called chylomicrons. Remember where this is occurring - in the absorptive enterocyte of the small intestine.
• Chylomicrons are extruded from the Golgi into exocytotic vesicles, which are transported to the basolateral aspect of the enterocyte.
• The vesicles fuse with the plasma membrane and undergo exocytosis, dumping the chylomicrons into the space outside the cells.
• Because chylomicrons are particles, virtually all steps in this pathway can be visualized using an electron microscope, as the montage of images to the right demonstrates.
• Transport of lipids into the circulation is also different from what occurs with sugars and amino acids.
• Instead of being absorbed directly into capillary blood, chylomicrons are transported first into the lymphatic vessel that penetrates into each villus. 
• Chylomicron-rich lymph then drains into the system lymphatic system, which rapidly flows into blood. Blood-borne chylomicrons are rapidly disassembled and their constitutent lipids utilized throughout the body.
• When large numbers of chylomicrons are being absorbed, the lymph draining from the small intestine appears milky and the lymphatics are easy to see.
• In the image below, of abdominal contents from a coyote, the fine white lines (arrows) are intestinal lymphatics packed with chylomicrons. That lymph passes through mesenteric lymph nodes (LN) and then into larger lymphatics.
• Another lipid of importance that is absorbed in the small intestine is cholesterol. 
• Cholesterol homeostatis results from a balance of cholestrol synthesis, absorption of dietary cholesterol, and elimination of cholesterol by excretion in bile. 
•  Years ago it was shown that cholesterol, but not plant sterols, is readily absorbed in the intestine. More recently, a specific transport protein (NPC1L1) has been identified that ferries cholesterol from the intestinal lumen into the enterocyte. 
• From there, a bulk of the cholesterol is esterified, incorporated into chylomicrons and shuttled into blood by the mechanisms described above.

Genetics:

Following are the causes of fat malabsorption which are have genetic defect. Patients having these defects are affected because of decreased production of enzymes required in that are required to digest the the fatty food.

• Cystic fibrosis
• Crohn’s disease
• Ulcerative colitis
• Abetalipoproteinemia 

Gross pathology

On Gross pathology the GIT looks normal in conditions which involves enzyme deficiencies. However in condition which involves obstruction of ducts involved in secretion of enzymes will look narrowed. The luminal causes which damage the luman of GIT and does not allow the absoption of faty products will also look ulcerated.

Microscopic pathology

On microscopy the GIT looks normal in conditions which involves enzyme deficiencies. However in condition which involves obstruction of ducts involved in secretion of enzymes will look narrowed. The luminal causes which damage the luman of GIT and does not allow the absoption of faty products will also look ulcerated.