Elevated homocysteine in blood, called hyperhomocysteinemia, indicates an abnormal blood level of this transient amino acid.
Q: How does the level of homocysteine become abnormal?
A: In metabolism, homocysteine is briefly formed in the breakdown of the amino acid methionine. It is normally converted to cystathione and then to the amino acid cysteine by means of an enzyme that requires vitamin B6.
In the reverse, conversion of homocysteine to methionine requires an enzyme dependent on adequate folic acid and vitamin B12 levels.
Insufficient methionine levels and/or inefficiency in this process results in elevated homocysteine plasma levels that are toxic to blood vessels.
Folic acid, vitamin B12 and vitamin B6 are involved in the metabolic removal of homocysteine, but folic acid deficit occurs the most often.1
What Is Elevated Homocysteine In Celiac Disease and/or Gluten Sensitivity?
Sources:
Lim PO, Tzemos N, Farquharson CA, et al. Reversible hypertension following coeliac disease treatment: the role of moderate hyperhomocysteinaemia and vascular endothelial dysfunction. Journal of Human Hypertension. Jun 2002;16(6):411-5. [↩]
Microscopic View of a Liver Granuloma. Courtesy pathology.med.umich.edu/greensonlab.
What Is Hepatic Granulomatous Disease?
H epatic granulomatous disease is an infiltrative chronic liver disorder characterized by growth of small granulomas.
Rather than being a final diagnosis, the presence of hepatic granulomas entails the need for further investigations towards identifying the underlying etiology, with a pathologist being at the center of the diagnostic process.1
Q: What are hepatic granulomas?
A: Hepatic granulomas are unique inflammatory formations that require liver biopsy for diagnosis.2
Hepatic granulomas develop through the interactions of T lymphocytes and macrophages, with the integral involvement of T-helper (T(H)) 1 or T(H)2 pathways or both, depending on the specific granulomatous disease.
Hepatic granulomas may be detected clinically by elevated levels of serum alkaline phosphatase and g-glutamyltransferase enzymes, damage to specific structures (e.g., intrahepatic bile ducts in primary biliary cirrhosis), or infrequently, progressive liver disease with portal hypertension and cirrhosis (e.g., sarcoidosis).
Systemic immunologic disorders, infectious diseases, drug hepatotoxicity, and reaction to neoplastic disease are the major causative factors responsible for granulomas in the liver.3
What Is Hepatic Granulomatous Disease In Celiac Disease and/or Gluten Sensitivity?
Sources:
Turhan N, Kurt M, Ozderin YO, Kurt OK. Hepatic granulomas: a clinicopathologic analysis of 86 cases. Pathol Res Pract. 2011 Jun 15;207(6):359-65. doi: 10.1016/j.prp.2011.03.003. Epub 2011 Apr 30. [↩]
Lots of Pyridoxine In This Pie…Chicken, Cheese,Spinach, Tomato
What Is Vitamin B6 (Pyridoxine)?
Pyridoxine is an essential vitamin that is required for the health of nerves, bones, blood, arteries, blood sugar, the immune system and metabolism of proteins.
Two important functions of pyridoxine involve coenzymes that are involved in regulating the metabolism of proteins like methionine and tryptophan and their intermediate amino acid building blocks.
In total, the coenzymic form of vitamin B-6, pyridoxal phosphate (PLP), serves as a coenzyme for over 140 enzymes in human metabolism.1 Functions are more fully described below.
Magnesium is required for pyridoxine to actually attach to enzymes dependent on it.
Because pyridoxine is excreted from the body by the kidneys, urinary excretion of it cannot be detected when vitamin intake is below the required levels. On the other hand, when intake exceeds saturation in the body, the vitamin and/or its metabolites are actively excreted into urine to prevent excessive toxicity of the vitamins.2
Smoking blocks use of pyridoxine.
What Is Pyridoxine Deficiency In Celiac Disease and/or Gluten Sensitivity?
Sources:
Gregory JF 3rd1, Park Y, Lamers Y, Bandyopadhyay N, Chi YY, Lee K, Kim S, da Silva V, Hove N, Ranka S, Kahveci T, Muller KE, Stevens RD, Newgard CB, Stacpoole PW, Jones DP. Metabolomic analysis reveals extended metabolic consequences of marginal vitamin B-6 deficiency in healthy human subjects. PLoS One. 2013 Jun 11;8(6):e63544. doi: 10.1371/journal.pone.0063544. [↩]
Shibata K, Hirose J, Fukuwatari T. Relationship Between Urinary Concentrations of Nine Water-soluble Vitamins and their Vitamin Intakes in Japanese Adult Males. Nutr Metab Insights. 2014 Aug 5;7:61-75. doi: 10.4137/NMI.S17245. [↩]
Folate, also called folic acid or vitamin B9, is a family group of essential water-soluble B vitamins needed to produce healthy blood cells and other tissue cells.
Folate is required for healthy blood cells, the metabolism of at least 5 amino acids, the production of DNA, RNA and tRNA (genetic material), the normal development of a baby in the womb, male and female fertility, and regulation of homocysteine (amino acid) by reduction of harmful blood levels in conjunction with vitamin B6 and vitamin B12.
Urinary excretion of folate cannot be detected when vitamin intake is below the required levels. On the other hand, when intake exceeds saturation in the body, the vitamins and/or their metabolites are actively excreted into urine to prevent excessive toxicity of the vitamins.1
What Is Folate Deficiency In Celiac Disease and/or Gluten Sensitivity?
Sources:
Shibata K, Hirose J, Fukuwatari T. Relationship Between Urinary Concentrations of Nine Water-soluble Vitamins and their Vitamin Intakes in Japanese Adult Males. Nutr Metab Insights. 2014 Aug 5;7:61-75. doi: 10.4137/NMI.S17245. eCollection 2014. [↩]
Vitamin B12, also called cobalamin, is a highly complex vitamin that functions in two coenzyme forms: adenosylcobalamin and methylcobalamin.
These forms of the vitamin play important roles in the physical and chemical processes by which amino acids become proprionate, proprionate that becomes acetate, and single carbons.
Q: Why are these steps important?
A: These steps are essential for normal function in the workings of all cells, especially for those of the digestive tract, bone marrow and nervous tissue.
Vitamin B12 is mainly excreted through bile into the duodenum (first part of the small intestine) for excretion in stool.1 However, if vitamin B12 is needed, it is reabsorbed in the ileum (end of the small intestine) while excess is excreted in stool and very little in urine.2
The blood level of vitamin B12 in healthy people ranges between 140 and 750 pg/ml.
What Is Vitamin B12 Deficiency In Celiac Disease and/or Gluten Sensitivity?
Sources:
Shibata K, Hirose J, Fukuwatari T. Relationship Between Urinary Concentrations of Nine Water-soluble Vitamins and their Vitamin Intakes in Japanese Adult Males. Nutr Metab Insights. 2014 Aug 5;7:61-75. doi: 10.4137/NMI.S17245. [↩]
Shinton N K. Vitamin B 12 and folate metabolism. Br Med J. Feb 26, 1972; 1(5799): 556–559. [↩]
Microscopic View of Gastric Biopsy Showing a Collagen Band Stained Pink Under the Surface Mucosal Cells. Courtesy Gastrolab.com
What Is Collagenous Gastritis?
C ollagenous gastritis is a rarely reported stomach disorder characterized by the deposition of a subepithelial collagen band and accompanying inflammatory infiltrate in the stomach wall.
A subepithelial collagen band means that collagen, a tough fibrous protein, has abnormally accumulated under the surface layer of epithelial cells which form the mucosa lining the stomach.
The surface mucosa may remain intact and not show lymphocytosis and/or gastritis on endoscopic examination or it may become stripped off and bleed from entrapped capillaries. Biopsy is necessary to diagnose collagenous gastritis.1
Q: Why does collagen become deposited under the surface lining of the stomach?
A: It is thought that collagen deposition is preceded by inflammation and tissue damage. However, the natural history and pathogenesis of collagenous gastritis remain unclear.2
What Is Collagenous Gastritis In Celiac Disease and/or Gluten Sensitivity?
Sources:
Jain R, Chetty R. Collagenous gastritis. Int J Surg Pathol. 2010 Dec;18(6):534-6. doi: 10.1177/1066896908329588. Epub 2008 Dec 22. [↩]
Leung ST, Chandan VS, Murray JA, Wu TT. Collagenous gastritis: histopathologic features and association with other gastrointestinal diseases. Am J Surg Pathol. 2009 May;33(5):788-98. doi: 10.1097/PAS.0b013e318196a67f. [↩]
D iabetic instability, also called brittle diabetes, is poor control of blood sugar characterized by frequent rise (hyperglycemia) and fall (hypoglycemia). These fluctuations can be life-threatening and cause unnecessary complications.
Q: What are complications in diabetes?
A: Complications of diabetes include any/all of the following:
Peripheral neuropathy that causes burning, numbness, or tingling in the extremities.
Skin infections and ulcers that do not heal and can lead to amputation of toes, feet or legs.
Damage to retina that can progress to blindness.
Cataracts and glaucoma that impair vision and can cause blindness.
Increased susceptibility to serious infections of the genitourinary tract, lung and upper respiratory tract that can become systemic and life-threatening.
Kidney disease that can lead to kidney failure.
Heart disease that can lead to heart failure.
Vascular disease that can lead to stroke.
Impaired motility in digestive tract that can lead to dyspepsia and constipation.
Pregnancy complications.
Shortened life expectancy.
The main causes of brittleness include malabsorption, certain drugs (alcohol, antipsychotics), defective insulin absorption or degradation, defect of hyperglycemic hormones especially glucocorticoid and glucagon, and above all delayed gastric emptying as a result of autonomic neuropathy.1
What Is Diabetic Instability In Celiac Disease and/or Gluten Sensitivity?
Sources:
Vantyghem MC, Press M. Management strategies for brittle diabetes. Ann Endocrinol (Paris). 2006 Sep;67(4):287-96. [↩]
Microscopic Slide of Biopsy Sample Showing Lymphocytic Colitis. Courtesy Quizlet.com
What Is Lymphocytic Colitis?
L ymphocytic colitis is a microscopic inflammation of the large intestinal mucosa with infiltration of lymphocytes (IELs) that is characterized by non-bloody secretory diarrhea.
Secretory diarrhea describes bowel movements that consist of a large volume of liquid stool.
Q: What are IELs?
A: IELs is an abbreviation for intraepithelial lymphocytes, which are white blood cells that infiltrate within epithelial cells or between them. Epithelial cells form the surface mucosa of the large intestine also called the colon.
The histopathological criteria (biopsy) for lymphocytic colitis are a density of at least 20 IELs per 100 surface epithelial cells; chronic inflammatory infiltrate of mononuclear cells in the lamina propria; epithelial damage; and a subepithelial collagen layer of less than 10 µm. The increased collagen band consists basically of collagen type I and III, which are the subtypes produced by repair functions, indicating a reactive origin.1That is, the mucosa is reacting to some irritative substance.
Up to 10% of adults undergoing colonoscopy for investigation of chronic diarrhea and having visibily normal appearing mucosa may have lymphocytic colitis.2
Bile acid malabsorption has been shown to coexist in 60% of patients with lymphocytic colitis.1
Lymphocytic colitis (LC) is categorized as primary or secondary. Primary LC is a clinical and histopathological disease of unknown cause. Secondary LC may develop as the result of iritating factors acting on the colon such as smoking or many medications. In one study, the most common drug treatments as a percentage of the study group were corticosteroids (32.1%), proton pump inhibitors (26.0%), antidepressant drugs, specifically selective serotonin reuptake inhibitors (21.4%), angiotensin-converting enzyme inhibitors or angiotensin II receptor antagonists (18.3%), statins (17.6%), thyroid hormones (17.6%), and beta-blockers (16.0%).3
Secondary lymphocytic colitis is associated with several concomitant diseases including celiac disease. This is why lymphocytic changes must be interpreted with caution before considering them as a separate entity of autoimmune origin, instead of secondary reactions to ischemia and toxic stimulants. Efforts must be made to better classify and diagnose patients with real, primary lymphocytic colitis to avoid over-prescription of corticosteroids for treatment.3
What Is Lymphocytic Colitis In Celiac Disease and/or Gluten Sensitivity?
Sources:
Ohlsson B. New insights and challenges in microscopic colitis. Therap Adv Gastroenterol. 2015 Jan;8(1):37-47. doi: 10.1177/1756283X14550134. [↩] [↩]
Abdo AA, Urbanski SJ, Beck PL. Lymphotcytic and collagenous colitis: the emerging entity of microscopic colitis. An update on pathophysiology, diagnosis and management. Canadian Journal of Gastroenterology. Jul 2003;17(7):425-32. [↩]
Roth B, Manjer J, Ohlsson B. Drug Target Insights. 2013 Aug 11;7:19-25. doi: 10.4137/DTI.S12109. [↩] [↩]
Malignant lymphoma high grade B-cell. Courtesy Wikimedia
What Is B-Cell Non-Hodgkin’s Lymphoma?
B cell non-Hodgkin’s lymphoma is a malignant, monoclonal (arising from a single cell) proliferation of lymphocytes that is preceded by lymphadenopathy and characterized by varying, less predictable spread than Hodgkin’s disease.
Lymphadenopathy is enlargement of lymph nodes greater than 1.5 cm caused by activation and increased production of lymphocytes and phagocytes (type of white blood cell that engulfs pathogens during infection) or invasion by a tumor.
Q: How does this type of lymphoma develop?
A: 80% to 85% of non-Hodgkin’s lymphoma arise from B-lymphocytes (B-cells).
What Is B Cell Non-Hodgkin’s Lymphoma In Celiac Disease and/or Gluten Sensitivity?
