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Dysbiosis (Intestinal)

What Is Intestinal Dysbiosis? [dropcap]I[/dropcap]ntestinal dysbiosis is an imbalance of the composition and quantity of microbe populations (called the microbiota), that naturally inhabit our human gut. Dysbiosis causes altered gut immunity, abnormal fermentation of undigested foodstuffs,… 

Osteoporosis

Woman with long standing osteoporosis. Courtesy of Wikimedia.
Woman with long standing osteoporosis. Courtesy of Wikimedia.

What Is Osteoporosis?

[dropcap]O[/dropcap]steoporosis is a metabolic bone disorder characterized by diminished bone mass (density) with normal cell appearance but fragile bone strength that prediposes to broken bones, and with high bone turnover.

This condition usually goes undetected until late when loss of height or a bone fracture occurs. In fact, each year  1.5 million fractures mainly of the hip, spine and wrist are attributed to osteoporosis. Compression fractures of vertebrae bones are the most common, accounting for 700,000 cases.

Bone is composed of specialized connective tissue called osseous tissue. Osseous tissue is made up of living bone cells (osteocytes) that are embedded in a hard matrix (framework) of calcified substance.

Bone matrix contains collagen fibers and the minerals calcium phosphate and calcium carbonate, which provide strength to bone. The copper enzyme, lysyl oxidase, is involved in the cross-linking of collagen in forming the framework for depositing calcium and other minerals to build and repair bone.

Q: How do osteocytes function in bone?

A: Osteocytes maintain the health of bone by their metabolic activity in regulating normal bone turnover. Bone turnover is the breaking down and removal of old or damaged bone and rebuilding or remodeling of healthy bone that is ongoing throughout life. The bone formation process takes about 3 months to complete.

Osteoporosis develops from failure of the body to maintain health and to provide bone tissue with adequate nutrition for proper function. Risk factors that can be modified include: low calcium intake, sedentary lifestyle, smoking, drinking alcohol excessively, eating a diet with excessive caffeine, protein, and phosphate, and taking certain medications over a long time such as steroids, thyroid preparations, the anti-convulsive drug phenytoin, aspirin, antacids, anticoagulants, some diuretics, and some chemotherapeutic drugs. See below for a fuller description.

In addition to celiac disease, osteoporosis is associated with advancing age, family history, nulliparity (no pregnancies) and post-menopause in females, certain disorders such as hyperthyroidism, hypogonadism, inflammatory bowel disease like Crohn’s disease, multiple myeloma, anorexia nervosa, and Cushing’s disease.

Bone strength is easily measured by testing bone mineral density (BMD). BMD is evaluated by DEXA scan (dual-energy X-ray absorptiometry).  DEXA at the femoral neck and lumbar spine is considered the gold standard to confirm the diagnosis of osteoporosis.  Results are expressed as T and Z scores. T scores compare the result with a 20 to 40 year old helathy person while  Z scores compare the result with persons in the same age group. Both are measured in standard deviations (SD).

According to WHO criteria (World Health Organization), a T-score of -1 SD or greater denotes normal bone, a T-score between −1 to −2.5 SD denotes osteopenia, and a T-score of −2.5 or more denotes osteoporosis.1

Treatment is aimed to preserve and increase bone density, minimize symptoms for better quality of life and reduce risk of bone fractures.

What Is Osteoporosis In Celiac Disease and/or Gluten Sensitivity?

The cumulative effects of gluten-induced inflammation, treatment delay, and malabsorption result in lower bone density and bone fragility.2

Sources:
  1. Pantaleoni S, Luchino M, Adriani A, Pellicano R, Stradella D, Ribaldone DG, Sapone N, Isaia GC, Di Stefano M, Astegiano M. Bone mineral density at diagnosis of celiac disease and after 1 year of gluten-free diet. ScientificWorldJournal. 2014;2014:173082. doi: 10.1155/2014/173082. []
  2. Grace-Farfaglia P. Bones of Contention: Bone Mineral Density Recovery in Celiac Disease-A Systematic Review. Nutrients. 2015 May 7;7(5):3347-3369. []

Non-Alcoholic Fatty Liver Disease

Smooth muscle. Courtesy pathguy.com
Smooth Muscle. Courtesy pathguy.com

What Are Anti-Endomysium Antibodies?

[dropcap]A nti-endomysium antibodies (EmA) are connective tissue autoantibodies produced in persons who have inherited the genes for celiac disease, an autoimmune disease, and are reacting to gluten in their diet.

Autoantibodies are abnormal in that they attack the body’s own tissue.

Q: What is endomysium?

A: Endomysium is the delicate connective tissue that surrounds individual muscle fibers. The autoantigen, or target, that stimulates the autoimmune response is the naturally occuring enzyme in endomysium called tissue transglutaminase (tTG), or more specifically tranglutaminase-2 (TG2). Anti-tissue transglutaminase antibodies recognize the same antigen as EmA, from which they differ in terms of detection method.

Anti-endomysium antibodies (EmA) are tested by the indirect immunofluorescence method and directed against “reticulin-like” fibres in connective tissue around smooth muscle fibres in the esophagus, liver, stomach, and bladder of monkeys, in the sections of the jejunum and kidneys of rats and in sections of the human umbilical cord. In comparison, for the determination of anti-tissue transglutaminase IgA and IgG antibodies, ELISA with human extractive or recombinant transglutaminase is recommended.1

EmA‐binding patterns in serum samples from patients with celiac disease have proved to be exclusively TG2‐targeted and the correlation between EmA and TG2 antibodies is therefore good. Evidence shows that celiac autoantibodies are produced in the small‐bowel mucosa.2

What Are Anti-Endomysium Antibodies In Celiac Disease and/or Gluten Sensitivity?

Sources:
  1. Trigoni E, Tsirogianni A, Pipi E, Mantzaris G, Papasteriades C. Celiac disease in adult patients: specific autoantibodies in the diagnosis, monitoring, and screening. Autoimmune Dis. 2014;2014:623514. doi: 10.1155/2014/623514. []
  2. Salmi TT, Collin P, Korponay-Szabó IR, Laurila K, Partanen J, Huhtala H, Király R, Lorand L, Reunala T, Mäki M, Kaukinen K. Endomysial antibody‐negative coeliac disease: clinical characteristics and intestinal autoantibody deposits.Gut. 2006 Dec;55(12):1746-53. []

Gluten Sensitive Enteropathy (Active Celiac Disease)

canstockphoto17997339What Is Gluten Sensitive Enteropathy?

Gluten sensitive enteropathy is active celiac disease characterized by inflammation of the small intestinal mucosa that results from an inherited immunologic intolerance to ingested gluten.

Q: What does the inflammation do to the mucosa in the small intestine?

A: Inflammation is a cell level immune response to gluten that has these effects on the mucosa:

  • Damages the barely visible villi (multitudinous finger-like structures) by causing atrophy or loss.
  • Likely affects the structural support and microcirculation of the villus, leading to collapse of the villus.
  • Elongates the crypts between villi. The thickening of the crypt is not so much a response to loss of surface enterocytes but represents inflammation of the mucosa.1
  • Increases round cells in the lamina propria and surface epithelial cells leaving few, irregular microvilli (brush border) on the surface of villi.
  • Damage is most intense in the duodenum and decreases toward the large intestine.
  • The extent of the damage to the intestine determines the malabsorptive consequences of the disease. Both gastric and small intestinal permeability are disrupted in patients with celiac disease.2
  • Relationship between active celiac disease and intestinal permeability: There is a clear association between degree of mucosal damage and the intestinal-permeability ratio, and a normal ratio generally implies near-normal small intestinal structure. A raised intestinal permeability of the mucosal lining (leaky gut) could predispose to a high absorption of gluten and exacerbate an existing lesion and hence convert a latent to an overt enteropathy.3
  • Relationship between active celiac disease and tight junction proteins: A study of intestinal permeability showed that the expression of all junction proteins of the small intestinal lining (occludin, claudin 3, zonula occludens 1, and E-cadherin) was already decreased in early stage celiac disease when compared with non-celiac controls, showing leaky gut and confirming the above earlier study by Johnston et al. Junction protein expression correlated positively with mucosal villus structure and negatively with the number of intraepithelial lymphocytes (IELs), the intensity of small-intestinal autoantibody deposits, and serum autoantibodies. The expression of claudin 3 showed a negative correlation with diarrheal score.4
  • Relationship between active celiac disease and inflammation. In celiac disease there is an over production of inflammatory interleukin-15 (IL-15) which inhibits the correct removal of damaged intraepithelial lymphocytes caused by the reaction to gluten. Serum levels of IL-15 are directly correlated with the seriousness of tissue damage.5
  • Relationship between active celiac disease and gut microbiota. Results of a study investigating intestinal microbiota (normal bacterial residents) in patients with celiac disease suggest that with lower levels of the genus bifidobacteria, celiac patients have an imbalance in the intestinal microbiota even while on a gluten-free diet. This fact could favor the pathological process of the disorder. The concentration of bifidobacteria per gram of feces was significantly higher in healthy subjects (2.5 ± 1.5 x107 CFU/g) when compared to celiac patients (1.5 ± 0.63 x108 CFU/g).6

  • Relationship between active celiac disease and endoscopy technique. The most severe degree of villous atrophy was detected when distal duodenal biopsy specimens were taken in addition to a duodenal bulb biopsy specimen from either the 9- or 12-o’clock position (96.4% sensitivity; 95% CI, 79.7%-100%). The difference between the 12-o’clock position biopsy and the 3-o’clock position biopsy in detecting the most severe villous atrophy was 92% (24/26 patients) versus 65% (17/26 patients).7
  • Relationship between active celiac disease and diet adherence. Patients with consistent gluten free diet adherence experience symptomatic responses to dietary gluten (SRDG) faster and more severe in comparison to their prior gluten exposure possibly demonstrating an adept immunological response. Anxiety and depression also enhance the speed of symptom onset and co-existing visceral hypersensitivity is a risk factor for severe reactions to dietary gluten.8
  • Relationship between active celiac disease and atrial fibrillation: Patients with celiac disease, verified by intestinal biopsy, are at increased risk of atrial fibrillation. This observation is consistent with previous findings that elevation of inflammatory markers predicts atrial fibrillation.9

How Prevalent Is Gluten Sensitive Enteropathy?

Sources:
  1. Murray JA, the widening spectrum of celiac disease. American Journal of Clinical Nutrition. Mar 1999; 69(3):354-365. []
  2. Murray JA, the widening spectrum of celiac disease. American Journal of Clinical Nutrition. Mar 1999; 69(3):354-365. []
  3. Johnston SD, Smye M, Watson RGP. Intestinal permeability and morphometric recovery in coeliac disease. Lancet. Jul 28, 2001;358(9278):259, 2p. []
  4. Rauhavirta T, Lindfors K, Koskinen O, Laurila K, Kurppa K, Saavalainen P, Mäki M, Collin P, Kaukinen K. Impaired epithelial integrity in the duodenal mucosa in early stages of celiac disease. Transl Res. 2014 Sep;164(3):223-31. doi: 10.1016/j.trsl.2014.02.006 []
  5. Stazi AV, Trinti B. Selenium status and over-expression of interleukin-15 in celiac disease and autoimmune thyroid diseases. Ann Ist Super Sanita. 2010;46(4):389-99.DOI: 10.4415/ANN_10_04_06. []
  6. Golfetto L, de Senna FD, Hermes J, Beserra BT, França Fda S, Martinello F. Lower bifidobacteria counts in adult patients with celiac disease on a gluten-free diet. Arq Gastroenterol. 2014 Apr-Jun;51(2):139-43. []
  7. Kurien M, Evans KE, Hopper AD, Hale MF, Cross SS, Sanders DS. Duodenal bulb biopsies for diagnosing adult celiac disease: is there an optimal biopsy site? Gastrointest Endosc. 2012 Jun;75(6):1190-6. doi: 10.1016/j.gie.2012.02.025. []
  8. Barratt SM, Leeds JS, Sanders DS. Factors influencing the type, timing and severity of symptomatic responses to dietary gluten in patients with biopsy-proven coeliac disease. J Gastrointestin Liver Dis. 2013 Dec;22(4):391-6. []
  9. Emilsson L, Smith JG, West J, Melander O, Ludvigsson JF. Increased risk of atrial fibrillation in patients with coeliac disease: a nationwide cohort study. Eur Heart J. 2011 Oct;32(19):2430-7. doi: 10.1093/eurheartj/ehr167. []

Miscarriage (Spontaneous Abortion)

Pitting edema. Right photo shows that indent remains from pressing. Courtesy wikimedia.
Pitting edema. Right photo shows that indent remains from pressing. Courtesy wikimedia.

What Is Edema?

[dropcap]E dema is an abnormal swollen condition of the skin characterized by excess extracellular fluid volume, meaning there is an increase of the fluid that normally surrounds cells. Edema may be hardly noticeable or it can become extensive.

Edema can have various appearances and can develop from various causes.

Q: What are the appearances and causes of edema?

A: Here are the appearances of edema:

  • Pitting edema. It is called pitting edema if when the skin is pressed with a finger, the indent remains. This edema results from fluid leaking out of the bloodstream into the surrounding tissues. Pitting edema can be a feature of many disorders including heart disease, kidney disease, vascular disease, cancer, and malnutrition.
  • Myxedema is a firm swelling or thickening of subcutaneous skin that does not pit, as seen in thyroid disease.

Here are causes of edema:

  • Local edema as a response to trauma or infection.
  • Lower extremity edema from poor circulation and malnutrition.
  • Edema in the lungs from right sided heart disease.
  • Abdominal edema from liver disease, intestinal disease.
  • Body wide edema from heart disease, kidney disease, thyroid disease.

What Is Edema In Celiac Disease and/or Gluten Sensitivity?

Muscle Pain and Tenderness, Chronic 

Reproduction of a lithograph plate showing inside of the stomach from Gray's Anatomy. Courtesy Wikipedia Commons.
Reproduction of a lithograph plate showing inside of the stomach from Gray’s Anatomy. Courtesy Wikipedia Commons.

What Is Delayed Gastric Emptying?

[dropcap]D elayed gastric emptying is a stomach motility or movement disorder characterized by abnormally slow movement of gastric contents from the stomach through the pyloric sphincter into the duodenum, causing dyspepsia.

Q: What determines how fast the stomach empties?

A: How fast the stomach empties depends on the pressure of strong coordinated muscle contractions in the top region of the stomach propelling chyme against resistance at the pylorus (base region of the stomach).

Chyme is food that has been dissolved and thoroughly mixed with stomach secretions.

In the digestion of carbohydrate, protein and fat, protein leaves the stomach first (1 hour), then carbohydrates (1 1/2 to 2 hours), and fat takes longest to digest (2-4 hours). Plain water is able to pass through the pylorus within 5 minutes.

What Is Delayed Gastric Emptying In Celiac Disease and/or Gluten Sensitivity?

Weight Loss, Unexpected/ Inability To Gain Weight

unexpected weight loss celiac disease symptomWhat Is Unexpected Weight Loss?

[dropcap]U[/dropcap]nexpected weight loss is unintentional loss of body mass composition or inability to gain weight marked by decreased serum proteins and increased stool fat.1

What Is Unexpected Weight Loss In Celiac Disease and/or Gluten Sensitivity?

Sources:
  1. Krause’s Food, Nutrition, & Diet Therapy. 10th Edition. Kathleen Mahan, Sylvia Escott-Stump. 2000. W.B. Saunders Company. []

Bone Fractures 

Proptosis and lid retraction are features of  Grave's disease, or hyperthyroidism. Courtesy of Wikimedia.
Proptosis and Lid Retraction are Features of Grave’s Disease, or Hyperthyroidism.

What Is Grave’s Disease (Hyperthyroidism)?

[dropcap]G rave’s disease, or hyperthyroidism, is an autoimmune thyroid disease characterized by diffuse nontender goiter, elevated thyroxine hormone levels (T4, T3), suppressed thyroid stimulating hormone (TSH), and presence of thyroid receptor antibodies in the blood.

The autoantibodies involved are anti-thyroid peroxidase and anti-thyroglobulin antibodies. They bind to the thyroid stimulating hormone receptors, causing thyroid stimulation. These antibodies are detected by blood tests.

Q: What happens to the thyroid gland in Grave’s disease?

A: The thyroid gland is located in the front of the neck. This butterfly shaped gland consists of a large number of closed vesicles that contain a homogenous substance called colloid, which contains the thyroglobulin. Thyroglobulin is an iodine-containing protein secreted by the thyroid gland and stored within its colloid, from which the thyroid hormones thyroxine (T4) and triiodothyroinine (T3) are derived.1

Thyroxine molecule, chemical structure. Thyroid gland hormone that plays a role in energy metabolism regulation. It is a iodine containing derivative of thyrosine. Atoms are represented as spheres with conventional color coding: hydrogen (white), carbon (grey), oxygen (red), nitrogen (blue), iodine (purple).
Thyroxine molecule. Atoms are represented as spheres with conventional color coding: hydrogen (white), carbon (grey), oxygen (red), nitrogen (blue), iodine (purple).

T3 is the active hormone and is made from T4. Thyroid hormones are released into the bloodstream as needed to control metabolism, brain development, breathing, heart and nervous system functions, body temperature, muscle strength, skin dryness, menstrual cycles, weight, and cholesterol levels.

Thyroid hormone production is regulated by thyroid-stimulating hormone (TSH), which is made by the pituitary gland in the brain. Normally, when thyroid hormone levels in the blood are low, the pituitary releases more TSH in response to stimulation by the nearby hypothalamus which is continually monitoring levels of thyroxin. When thyroid hormone levels are high, the pituitary decreases TSH production. So in Grave’s disease, release of TSH by the pituitary gland is suppressed by the hypothalamus because thyroid hormone is elevated. Goiter develops from growth stimulation by thyroid stimulating autoantibodies.

What Is Grave’s Disease In Celiac Disease and/or Gluten Sensitivity?

Sources:
  1. Taber’s Cyclopedic Medical Dictionary. 19th ed. F.A. Davis Company. Philadelphia, PA. []

Abnormal Blood Values in Childhood

canstockphoto18551453
Illustration Showing Skin Anatomy.

What Is Pruritic Skin?

[dropcap]P ruritic skin is a symptom of a primary disease that may involve only the skin or a systemic disorder with other features and is characterized by chronic itching.

Q: What part of skin is affected by itchiness?

A: Itching may arise from any layer of skin, depending on the cause.

In the image to the right, the outermost protective surface layer, or stratum cornem, is shown as a thin tan line. It is the top dead layer of the epidermis that normally sloughs off as new cells move up to replace it. The epidermis is shown as a dark pink layer. It is composed of five layers of keratinocytes that flatten as they move upward.

The pink layer under the epidermis is the dermis, or true skin, which is composed of collagen and elastin tissue. It contains oil glands that lubricate skin, sweat glands, blood vessels, nerve endings, lymphatics, and hair follicles. Under the dermis is subcutaneous tissue containing fat cells here colored yellow on the bottom of the image.

What Is Pruritic Skin In Celiac Disease and/or Gluten Sensitivity?

Prolonged Prothrombin Time

bloodvialWhat Is Prolonged Prothrombin Time?

[dropcap]P[/dropcap]rolonged prothrombin time (PT) is a laboratory blood test result showing that blood clots too slowly which makes the patient subject to abnormal bleeding.

Q: What does the prothrombin time (PT) test measure?

A: The prothrombin test measures the clotting ability of blood protein factors I, II (prothrombin), V, VII, and X. If any of these factors are too low, it takes longer than normal for the blood to clot. Prothrombin is a vitamin K dependent factor meaning a deficiency of vitamin K will cause low prothrombin.

Blood is drawn into a blood collection tube with a light blue stopper which has a buffering additive. Tubes must be completely filled.

What Is Prolonged Prothrombin Time In Celiac Disease and/or Gluten Sensitivity?