Lipid malabsorption

Rati tails often present with chronic fat-containing diarrhea due to dietary lipid malabsorption. 

Normally more than 95% of ingested lipid is absorbed. When a large fraction is excreted in the feces, it is called steatorrhea. Measurement of fecal lipid with adequate lipid intake is a sensitive indicator of lipid malabsorption. Malabsorption can result from impairment in lipolysis (Table 12-6), micelle formation (Table 12-7), absorption, chylomicron formation, or transport of chylomicrons via the lymph to blood. 

The fat-soluble vitamins share many properties despite their limited chemical similarity. They are absorbed into the intestinal lymphatics, along with other dietary lipids, after emulsification by bile salts. Lipid malabsorption accompanied by steatorrhea usually results in poor uptake of all the fat-soluble vitamins. Deficiency disease (except in the case of vitamin K) is difficult to produce in adults because large amounts of most fat-soluble vitamins are stored in the liver and in adipose tissue. The fat-soluble vitamins are assembled from isoprenoid units this fact is apparent from examination of the structures of vitamins A, E, and K cholesterol, the precursor of vitamin D, is derived from six isoprenoid units (Chapter 18). Specific biochemical functions for vitamins A, D, and K are known, but a role for vitamin E, other than as a relatively nonspecific antioxidant, remains elusive. 

The symptoms of abetalipoproteinemia include lipid malabsorption (and its accompanying symptoms, such as steatorrhea and vomiting), which can result in caloric deficiencies and weight loss. Because lipid-soluble vitamin distribution occurs through chylomicron circulation, signs and symptoms of deficiencies in the lipid-soluble vitamins may be seen in these patients. 

The vitamin is absorbed through the intestine by a mechanism similar to that involved in the absorption of other liposoluble vitamins consequently, intestinal disorders leading to lipid malabsorption are associated with malabsorption of vitamin E. Humans with such malabsorption syndromes have reduced levels of vitamin E in their tissues. They do not show classical symptoms of muscular dystrophy, although a certain degree of muscular fatigue may be observed. 

Toxicants that effect pancreatic iipase action (e.g., aflatoxin) may cause lipid malabsorption. 

Vitamin E deficiency is seen rarely in humans. However, there may be a risk of vitamin E deficiency in premature infants because the placenta does not transfer a-tocopherol to the fetus in adequate amounts. When it occurs in older children and adults, it is usually a result of lipoprotein deficiencies or a lipid malabsorption syndrome. These include patients with abetalipoproteinemia or homozygous hypobeta-lipoproteinemia, those with cholestatic disease, and patients receiving total parenteral nutrition. There is also an extremely rare disorder in which primary vitamin E deficiency occurs in the absence of lipid malabsorption. This disorder is a rare autosomal recessive neurodegenerative disease caused by mutations in the gene for a-TTP. This disorder is known as ataxia with vitamin E deficiency (AVED). Patients with AVED have extraordinary low plasma vitamin E concentrations (<5pgml ) and have an onset between 4 and 18 years, with progressive development of peripheral neuropathy,... 

Hypolipoproteinemias Abetaiipoproteinemia No chylomicrons, VLDL, or LDL are formed because of defect in the loading of apo B with lipid. Rare blood acylglycerols low intestine and liver accumulate acylglycerols. Intestinal malabsorption. Early death avoidable by administration of large doses of fat-soluble vitamins, particularly vitamin E. 

As patients lose exocrine function of the pancreas, they have decreased ability to absorb lipids and protein ingested with normal dietary intake. Weight loss from nutritional malabsorption is a common symptom of chronic pancreatitis not often seen in acute pancreatitis. Fatty- or protein-containing stools are also common carbohydrate absorption is usually unaffected. Even though patients with chronic pancreatitis have decreased ability to absorb lipid from the gastrointestinal tract, there does not appear to be an increased incidence of fat-soluble vitamin deficiency in these patients.34... 

Essential fatty acid deficiency is rare but can occur with prolonged lipid-free parenteral nutrition, very low fat enteral formulas, severe fat malabsorption, or severe malnutrition. The body can synthesize all fatty acids except for linoleic and linolenic acid, which should constitute approximately 2% to 4% of total calorie intake. 

Steatorrhea, the clinical result of insufficient intraluminal lipid hydrolysis, is the most important digestive malfunction in pancreatic exocrine insufficiency. As a rule, concomitant malabsorption of the lipid-soluble vitamins A, D, E, and K must be suspected in these patients. Naturally, potential differential diagnoses have to be considered in patients who present with steatorrhea (Table 26-1). The pivotal role of fat malabsorption in chronic pancreatitis is due to several interacting mechanisms ... 

The coefficient of fat absorption is defined as the amount of fat absorbed as a percentage of the ingested amount. This coefficient normally exceeds 93% and is used (rather than crude fecal fat excretion) to indicate efficacy of luminal fat digestion following different dietary lipid intakes. By contrast, fecal carbohydrate measurements do not fully reflect the extent of starch malabsorption because carbohydrates are metabolized by the intracolonic microbial flora. Since intracolonic metabolism of carbohydrates... 

In ABL, fat malabsorption is responsible for the diarrhea and flatus. Symptoms are prominent in affected newborns with the severity coupled to their lipid-rich diets. Chronic diarrhea results in nutrient wasting and, in some cases, failure to thrive. Since fat malabsorption is responsible for the initial gastrointestinal symptoms, it is not uncommon for affected individuals to restrict dietary fat independent of medical advice, alleviating the frequency of diarrhea and flatus. Occasional exacerbations still occur, but not serious enough to provoke a clinical visit. As a result, affected individuals often develop normally, unaware of their disease, until a gross secondary neuropathy becomes symptomatic toward the third decade of life or even earlier. 

Endoscopic analysis and intestinal biopsies are useful to rule out other diseases of the intestine and to confirm ABL. In ABL, the intestinal lumen has a gelee blanche or white frothy appearance from massive accumulation of lipids within the mucosa, which persists even in the setting of a low-fat diet. On microscopic evaluation of a biopsy sample taken from this region, inflammation commonly observed in other malabsorption syndromes is usually ab-... 

Chronic malabsorption does not fully explain the different extents of fat-soluble vitamin deficiencies associated with ABL. More specifically, why are plasma vitamin E levels more severely affected than those of vitamins A or K The answer for this can be traced to apoB lipoprotein biosynthesis and catabolism (Fig. 27-2). Just as observed for lipids, hydrophobic, fat-soluble vitamins require apoB lipoproteins as vehicles for plasma transport. The reliance of each fat-soluble vitamin on apoB lipoproteins varies, and this variable dependency is directly related to the severity of symptoms observed in ABL. 

To treat the malabsorption and subsequent diarrhea, lipid-poor diets (<5 g/day) should be implemented with a restriction of triglycerides containing long-chain fatty acids. Medium-chain fatty acids rely on other protein carriers besides apoB (i.e., albumin) for plasma transport, making them an ideal lipid substitute. However, long-term supplementation should be cautioned as associated hepatic fibrosis could occur. Diets should also contain increased protein and carbohydrate content to compensate for caloric loss from fat restriction. 

PhyUoquinone is vitamin Ki, menaquinones are vitamin K2, and the synthetic compounds menadione and menadiol are vitamin K3. In addition to menadione itself, menadiol diacetate (acetomenaphthone) is used in pharmaceutical preparations, and two water-soluble derivatives, menadione sodium bisulfite and menadiol sodium phosphate, have been used for administration of the vitamin by injection and in patients with malabsorption syndromes that would impair the absorption of menadione, phylloquinone, and menaquinones, which are lipid soluble. 

Abetalipoproteinemia is a rare lEM involving lipid dysfunction. Also called Bassen-Komzweig syndrome, it is characterized by extremely low cholesterol due to deficient or absent beta lipoproteins, which are an important component of the cholesterol molecular complex. Symptoms include growth retardation, neurological dysfunction, retinal pigment degeneration, and upper intestinal malabsorption. 

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