What is the pathophysiology of lipid absorption?

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From the Guidelines

Fat absorption is a complex process that involves the breakdown of triglycerides into fatty acids and monoglycerides, which are then absorbed into enterocytes and re-esterified into triglycerides to form chylomicrons. This process begins in the stomach, where gastric lipase breaks down some triglycerides into fatty acids and diglycerides 1. The majority of fat digestion occurs in the small intestine, where bile salts from the liver emulsify large fat globules into smaller droplets, increasing the surface area for pancreatic lipase to act. Pancreatic lipase, along with colipase, hydrolyzes triglycerides into monoglycerides and free fatty acids, which then form mixed micelles with bile salts and approach the brush border of intestinal enterocytes.

Some key points about fat absorption include:

  • Short and medium-chain fatty acids can be absorbed directly into enterocytes and enter the portal circulation
  • Long-chain fatty acids and monoglycerides enter enterocytes through passive diffusion or specific transporters like CD36
  • Inside enterocytes, these components are re-esterified in the endoplasmic reticulum to form triglycerides, which combine with phospholipids, cholesterol, and apolipoproteins to form chylomicrons
  • Chylomicrons are then released into the lymphatic system via lacteals, eventually entering the bloodstream through the thoracic duct

Disorders affecting any step in this process, such as pancreatic insufficiency, bile salt deficiency, or genetic mutations in key transporters, can lead to fat malabsorption and steatorrhea, as seen in conditions like chronic pancreatitis 1. In such cases, pancreatic enzyme replacement therapy (PERT) may be necessary to alleviate symptoms and prevent malnutrition. The formation of chylomicrons and their subsequent transport into the lymphatic system is a critical step in fat absorption, and any disruption in this process can lead to significant morbidity and mortality.

From the Research

Pathophysiology of Fat Absorption

The pathophysiology of fat absorption is a complex process that involves multiple stages and components.

  • The initial stage of fat digestion occurs in the stomach, where gastric lipase begins the hydrolysis of triglycerides 2.
  • Most fat digestion takes place in the small intestine via pancreatic enzymes and bile salts, with emulsification of fat by bile acids facilitating enzymatic action 2, 3.
  • The products of lipolysis, monoglycerides and fatty acids, are removed from the emulsion surface by bile salts in the form of mixed micelles, which transport lipid digestive products across the unstirred water layer to the epithelial cell 3, 4.
  • Within the intestinal epithelial cell, a series of synthetic events occur, resulting in the formation of chylomicrons and very low-density lipoprotein (VLDL) 4.
  • Chylomicrons consist of an oily core of triglyceride surrounded by a membrane of phospholipids, free cholesterol, and apoproteins, which maintain the solubility of the particle in plasma 4.

Fat Malabsorption

Fat malabsorption can result from various underlying conditions, such as:

  • Exocrine pancreatic insufficiency 2
  • Bile acid disorders 2
  • Intestinal diseases 2
  • The clinical manifestations of fat malabsorption include steatorrhea, malnutrition, and deficiencies of fat-soluble vitamins 2.

Diagnostic Approaches

Diagnostic approaches for fat malabsorption involve:

  • Assessing fecal fat levels 2
  • Imaging studies 2
  • Various functional tests to identify the specific etiology 2

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Fat digestion and absorption: Normal physiology and pathophysiology of malabsorption, including diagnostic testing.

Nutrition in clinical practice : official publication of the American Society for Parenteral and Enteral Nutrition, 2024

Research

Mechanisms of intestinal fat absorption.

The American journal of physiology, 1981

Research

Lipid absorption and intestinal lipoprotein formation.

Australian and New Zealand journal of medicine, 1981

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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