Protein Loosing Enteropathy (PLE)

What is PLE?

PLE describes a diverse group of disorders characterised by an excessive loss of serum proteins into the gastrointestinal tract resulting in hypoproteinemia and edema. PLE should be suspected in pts with unexplained hypoproteinemia in the absence of renal disease, liver disease and malnutrition.

Hypoproteinemia occurs when the extent of net enteral protein loss is greater than the capacity of liver to synthesise particular proteins. Hepatic protein synthesis in PLE is usually normal or slightly increased. Thus proteins with slow catabolic rate (long half life) will be reduced mostly like albumin and immunoglobulins (IgG, IgA, IgM); whereas there is little change in the serum concentrations of proteins with a rapid turnover rate like insulin, clotting factors and IgE.

Discuss the pathogenesis/causes of PLE?

  • Increased permeability due to mucosal disease without erosions/ulcerations E.g.-Coeliac disease, Giant hypertrophic gastritis (menetrier’s disease), Lymphocytic gastritis, amyloidosis, microscopic colitis, autoimmune diseases (RA, SLE, MCTD), infections (bacterial overgrowth, Whipple’s disease, viral/parasitic infections), eosinophilic gastroenteritis
  • Inflammatory exudations due to mucosal erosions/ulcerations IBD, GI cancers, bacterial gastroenteritis, H. Pylori infection, NSAID enteropathy
  • Lymphatic obstruction or increased lymphatic hydrostatic pressure, resulting in direct leakage of lymph containing plasma proteins. Intestinal lymphagiectasia (congenital or acquired), Rt sided heart failure (increased CVP causes increased lymphatic pressure), lymphoma, portal hypertension

What are the clinical manifestations of PLE?

  • Symptoms and signs
  • Edema, diarrhoea,
    Hypoproteinemia can also be associated with fat and carbohydrate malabsorption and fat soluble vitamin deficiencies due to small bowel involvement by the primary disease.
    Laboratory abnormalities

  • Hypoalbuminemia, decreased serum gamma globulins (IgG, IgA, IgM), decreased serum proteins (ceruloplasmin, AIAT, fibrinogen, transferrin, hormone binding proteins), decreased serum lipoproteins. Significant lymphocytopenia (due to loss of lymphocytes in the gut) can occur, leading to detectable alterations in cellular immunity. Increased susceptibility to infections is uncommon due to low immunoglobulins.

How do you confirm the diagnosis of PLE?

  • Alpha-I antitrypsin (AIAT) is excreted intact in stool because it is resistant to degradation in the gut lumen. Further it is not secreted or absorbed. Faecal excretion of AIAT is thus used as an indirect measure of enteric albumin loss.

    • There is poor correlation between random stool concentrations of AIAT and clearance measurements. A 24 hour stool specimen is thus preferred, since it produces a more reliable estimate of AIAT excretion than a spot sample. Alternatively a more reliable estimate of protein loss can be obtained by measuring the concentration in stool with simultaneous plasma measurement from which an estimate of intestinal protein loss can be derived.
    • Diarrhoea can increase AIAT clearance. A1AT clearance greater than 24ml/day (4.8mg/g of stool) in patients without diarrhoea and greater than 56ml/day (11.2mg/g of stool) in pts with diarrhoea is considered abnormal.
    • There is an inverse correlation between AIAT plasma clearance and the serum albumin concentration; as serum albumin levels fall below 3 g/dl, the clearance of AIAT exceeds 180 ml/day.
    • AIAT is degraded at a gastric pH below 3 and thus cannot be used to measure gastric protein loss. PPI can be used to avoid this.
    • Intestinal bleeding can also significantly increase the clearance rates. Thus positive OBT make the reading unreliable.
  • Technetium 99m-labelled human serum albumin (Tc HSA) scintigraphy is a less sensitive test than AIAT to detect and monitor enteric protein loss. An additional advantage is that it can localise the specific site of gastric or enteric protein loss. It can also be used like AIAT to monitor response to therapy. Also it has a higher sensitivity in pts with low serum albumin, reflecting a higher degree of enteric protein leakage
  • Technetium 99m-labelled dextran scintigraphy is another method to identify and monitor enteric protein loss.

How do you evaluate suspected PLE?

Step 1- Confirm by increase AIAT clearance, in the absence of confounding variables.
In addition Tc HAS scintigraphy can confirm and quantitate the extent of the disorder, directing the work up to a specific organ (stomach or small bowel)

Step 2- Check for steatorrhea

  • If steatorrhea absent- Endoscopy/biopsy. Endoscopy may reveal scattered white spots in a snow flake like appearance. Histology may reveal markedly dilated lymphatics.
  • Presence of steatorrhea indicate small bowel disease- barium meal follow through will help. If abnormal- consider biopsy. If however normal consider CT scan, cardiac evaluation, laparoscopy or lymphagiogram, if available.

How do you manage PLE?

  • Treat the underlying disorder
  • Pts should be given a diet low in saturated fat and high in protein. In PLE, the protein requirements may increase to 1.5-3.0g/kg/day. Protein supplements may be needed to achieve positive nitrogen balance. Low fat MCT enriched diet is useful in selected patients as they do not require lymphatic transport and therefore do not stimulate lymph flow.
  • Supportive care- diuretic to reduce edema

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