Wednesday, January 18, 2017
Mast cell, leaky gut and body inflammation: A short primer.
Mast cells are cells that are fairly ubiquitous in the body. They contain a myriad of chemical mediators of inflammation including a large amount of histamine. Upon stimulus particularly real or perceived threat to the body mast cells undergo degranulation the releases these inflammatory mediators to defend the body against attack. There a times when the body is tricked by foreign proteins and/or ineffective barrier defense allows proteins to reach cells especially mast cells within the body triggering mast cell activation. An example of the latter is when the gut permeability is increased, i.e. a leaky gut condition exists. Proteins from foods, medications and/or microbes can get past the gut barrier and come in contact with cells, including mast cells triggering an inflammatory response. Mediators released by cells can act locally to cause pain and diarrhea or the mediators can circulate in the blood causing symptoms distant to the gut, such as in the brain, musculoskeletal system or skin. Intolerance to certain foods may manifest as symptoms as result of mediators released by intestinal infection fighting cells especially mast cells. An increase in the normal number of mast cells in intestinal lining can result in ongoing symptoms in the digestive system and the body systemically. Normally there are somewhere between 4-8 mast cells per high power field in the intestine. When the cells number greater than 20 per high power field as determined by special stains symptoms can arise that may respond to mast cell stabilizing medications ketotifen and sodium cromolyn. Blocking of histamine by type 1 (e.g. cetirizine/zyrtec) and type 2 antihistamines (e.g. ranitidine/zantac) can reduce symptoms as mast cells have abundant histamine. Leukotriene blockers (e.g. montelukast/singulair) also may help as mast cells secreted that inflammatory mediator as well. Ursodiol (Actigall) a hydrophilic bile acid also appears to reduce inflammation associated with mast cells. Mastocytic enterocolitis (MCE) is an increasingly recognized variant of irritable bowel syndrome (IBS) defined by increased mast cells in the intestine that may respond to such treatment regimen as outlined as well as elimination of foods that trigger reactions of food intolerance. I prefer to refer his condition in a broader term Mastocytic Inflammatory Bowel Disease (MIBD) to emphasize its inflammatory nature and response to mast cell specific anti-inflammatory medications. Interestingly mast cells have receptors for corticotrophin releasing hormone (CRH) also known as corticotrophin releasing factor (CRF) secreted by the pituitary gland in response to stress to simulate the adrenal glands for the “fight or flight” response. Therefore stress is also a potent trigger of intestinal mast cell activation supporting the brain gut connection to stress and gastrointestinal symptoms.