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Occipital Lobe Epilepsy With Cerebral Calcifications

Close-up Slice of a Small Intestinal Villus Showing How Enterocytes Appear Tightly Lining the Entire Outside Surface Of A Villus. Courtesy Cleo Libonati

What Is Increased Intestinal Permeability?

I ncreased intestinal permeability is characterized by dysfunctional intestinal permeability (leakiness) allowing for the penetration of harmful entities from the gut into the bloodstream such as undigested proteins and microbes. The popular name is “leaky gut.”

Q: Why does intestinal permeability increase?

A: Intestinal permeability is an essential function of the small intestinal mucosal lining by which wanted substances such as properly digested foodstuffs are allowed to permeate through the lining to enter the body via the bloodstream and lymphatics. At the same time unwanted substances are kept out.

The mucosal lining is one cell thick and makes up the surface between the digested foodstuffs inside the hollow of the intestine and the underlying tissues.

The mucosal lining is covered by millions of microscopic finger-like structures called villi that project toward the inside of the intestine giving the appearance of a shag rug.

Each one, called a villus, contains a capillary bringing blood to absorb nutrients, a vein to take away nutrients, and a lacteal to absorb and take away digested fat. Its wall is made up of a single layer of tightly connecting cells, called enterocytes.

This single layer of cells separates the contents of our small intestine from the lamina propria (underlying tissues of the small intestine) and the rest of our body. Breaching of this single layer of cells by leakiness can expose lymphocytes (immune cells) located in the lamina propria to a myriad of microorganisms and food antigens, leading to immune reactions.1

To protect the body from unwanted substances, a gatekeeping barrier system operates to regulate the passage of nutrients, or permeation, through the surface mucosal lining. This system acts to seal the inside body from the gut.

The integrity of intestinal permeability is determined by interactions among several barrier components including the unstirred water layer, mucosal surface hydrophobicity, the surface mucous coat, and cell factors (especially tight junctions).

Tight junctions hold cells tightly together side-by-side to prevent unwanted substances from passing through the lining. Tight junctions are complex structures comprising over 50 proteins, such as the claudin proteins which are considered to be the structural backbone of tight junctions.

Tight junctions include a series of special proteins forming fibrils (springy like proteins) that cross the plasma membrane and interact with proteins in the adjoining cells. Tight junctions are regulated by the protein zonulin.2

If zonulin deregulates from the action of substances such as gliadin (gluten in wheat) and bacteria, the tight junction barrier fails which results in increased intestinal permeability. Dysfunction of the barrier system allows unwanted substances to enter the body where they are damaging to many tissues.

Tight junction dysfunction has been shown to be a part of certain autoimmune diseases such as celiac disease, type I diabetes mellitus, multiple sclerosis, and rheumatoid arthritis. Other diseases associated are cancer, allergies, and infections.3

Important gastrointestinal infections that cause leaky gut include rotavirus, parasites, pathogenic bacteria (escherichia coli, clostridium difficile), and mycotoxins produced by fungi found in stored grain and dried fruit.4

Fortunately, the presence of some commensal (friendly intestinal bacteria) and probiotic strains leads to an increase in tight junctions  proteins at the cell boundaries and in some cases prevents or reverses the adverse effects of pathogens, food and stress. Various dietary components are also known to regulate epithelial permeability by modifying expression and localization of  tight junctions proteins.2

What Is Increased Intestinal Permeability In Celiac Disease and/or Gluten Sensitivity?

Sources:
  1. Fahardi A, Banan A, Fields J, Keshavarzian A. Intestinal barrier: an interface between health and disease. Journal of Gastroenterology and Hepatology. 2003; 18: 479-497. [↩]
  2. Ulluwishewa D, Anderson RC, McNabb WC, Moughan PJ, Wells JM, Roy NC. Regulation of tight junction permeability by intestinal bacteria and dietary components. J Nutr. 2011 May;141(5):769-76. doi: 10.3945/jn.110.135657. [↩] [↩]
  3. Fasano A. Zonulin and Its Regulation of Intestinal Barrier Function: The Biological Door to Inflammation, Autoimmunity, and Cancer. Physiological Reviews. January 2011Vol. 91no. 151-175DOI: 10.1152/physrev.00003.2008 [↩]
  4. Farhadi A, Banan A, Fields J, Keshavarzian A. Intestinal barrier: an interface between health and disease. Journal of Gastroenterology and Hepatology. 2003;18:479-91. [↩]

Cardiomegaly

Cardiomegaly-Heart-frontWhat Is Cardiomegaly?

Cardiomegaly is a non-inflammatory disorder of the myocardium (heart muscle) causing the heart to enlarge.

Q: What happens when the heart enlarges?

A:The heart enlarges because excessive growth of muscle tissue (hypertrophy) thickens the heart walls which in turn reduces the size of the lower chambers (ventricles) and impairs the filling of the heart chambers with blood. In consequence, the heartbeat quickens.

Also, the enlarging heart encroaches on lung space which impairs their ability to expand with inspiration of air.

Cardiomegaly can result in heart failure because of inability to pump sufficient blood for the needs of the body and ventricular arrhythmias (irregular or missed beats) that can stop the heart. An echocardiogram, which is a test that uses sound waves to produce a picture of the heart, is used to detect and diagnose cardiomegaly.

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

Cachexia

Cachexia with Wasted Muscles, Weakness, and That Developed over 3 Years Time.
Cachexia with Wasted Muscles, Weakness, Weight Loss, Anemia, Skin Hemorrhages, Anorexia. GFW

What Is Cachexia?

Cachexia is a state of ill health involving deteriorating body composition that is characterized by general malnutrition and loss of lean tissue such as muscle.

Q: What are typical findings in cachexia?

A: Arm muscle triceps (the muscles at the back of the upper arm), skin folds, subscapular skin folds, fat area index, and bone mineral content are significantly lower than normal.

Cachexia may develop in protein-losing enteropathy such as celiac disease, chronic or severe infection such as pneumonia, tuberculosis, malaria, or many chronic diseases such as heart failure and cancer.

Cachexia can develop in persons of any age.

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

Vitality, Loss of

loss of vitalityWhat Is Loss of Vitality?

Loss of vitality is a state of diminished power to live or go on living, interfering with normal functioning and survival.

As weakness and fatigue worsen, the affected person increasingly loses interest in surroundings, activites, and the ability to care for self.

Q: Does loss of vitality affect only older individuals?

A: No. Loss of vitality can affect all ages.

What Is Loss of Vitality In Celiac Disease and/or Gluten Sensitivity?

Nosebleeds, Unexplained (Epistaxis)

Epistaxis1[1]What Is Epistaxis?

Epistaxis, or nosebleed, is a feature of secondary hemostasis (blood clotting) characterized by fragility of a plexus of blood vessels in the antero-inferior septum (just inside nostril) and/or abnormal blood coagulation.

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

Bruising, Easy (Ecchymosis)

Photo showing resolving deep bruise on the thigh.
Photo showing resolving deep bruise on the thigh.

What Is Easy Bruising?

Ecchymosis, or easy bruising, is a feature of impaired secondary hemostasis (blood clotting) characterized by subcutaneous bleeding (under the skin) in response to light trauma.

Q: What causes easy bruising?

A: Easy bruising is the direct result of vitamin K deficiency that develops from inadequate diet, malabsorption, dysbiosis, and vitamin K depleting medications.

What Is Easy Bruising In Celiac Disease and/or Gluten Sensitivity?

Atherosclerosis

ahterosclerosis celiac disease complication symtpomWhat Is Atherosclerosis?

Atherosclerosis is a disease of arteries involving the buildup of fatty material called plaque along the walls of medium and large arteries characterized by patchy subintimal thickening, hardening, and loss of elasticity of blood vessels.

The intima is the innermost layer of an artery, having contact with blood. The subintima is beneath it.

Q: What happens when arteries become narrowed and less flexible?

A: Narrowing of the inside diameter of blood vessels and hardening of their walls reduce or obstruct blood flow through them which impairs their ability to supply tissues of the body with oxygen and nourishment.

When tissues are deprived of oxygen, pain and dysfunction results such as angina pectoris involving heart muscle because the heart continually needs oxygen never being able to rest.

It is thought that atherosclerosis develops from 1) epithelial cell dysfunction of the intima, and 2) lipid (fat) accumulation in smooth muscle cells and in foam cells, causing buildup of fatty deposits on the inside walls progressing to fibrous plaque formation. That is, intimal smooth muscle cells are surrounded by connective tissue and intracellular and extracellular lipids (fat build-up inside and outside of these cells).

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

Hypoprothrombinemia (Low Prothrombin Level)

bruiseWhat Is Hypoprothrombinemia?

Hypoprothrombinemia is a deficiency of prothrombin (clotting factor II) in the blood that is characterized by impaired hemostasis in response to trauma or a laceration.

Q: What is hemostasis and how is it altered by a deficiency of prothrombin?

A: Hemostasis encompasses the tightly regulated processes of blood clotting, platelet activation, and blood vessel repair.1

Prothrombin is a protein clotting factor present in blood that is involved in the first part of hemostasis, which is blood clotting or coagulation. Vitamin K is required for prothrombin production.

When a laceration or wound is sustained, prothrombin is converted to the enzyme thrombin. Thrombin in turn acts on fibrinogen to convert it to fibrin which then forms the framework of a clot to stop bleeding. Deficiency of prothrombin prevents this series of events and bleeding is not properly stopped.

After the clotting process of hemostasis would come the second part, platelet activation. Eventually, coagulation and platelet activation are switched off by blood-borne inhibitors.

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

Sources:
  1. Versteeg HH, Heemskerk JWM, Levi M,  Reitsma PH. New Fundamentals in Hemostasis. Physiological Reviews Published 1 January 2013Vol. 93no. 327-358DOI: 10.1152/physrev.00016.2011 [↩]

Immune Thrombocytopenic Purpura

Photo of Skin Rash in ITP Courtesy Wikipedia.
Photo of Skin Rash in ITP Courtesy Wikipedia.

What Is Immune Thrombocytopenic Purpura?

Immune thrombocytopenia purpura (ITP), formerly called idiopathic, is an immune mediated bleeding disorder characterized by destruction of circulating platelets (thrombocytes) by autoantibodies in the presence of normal bone marrow and without other conditions that cause bleeding problems including many medications.

Q: How do autoantibodies destroy platelets?

A: Autoantibodies bind to normal platelet surface antigens (targets) which forms a complex that is cleared from blood by the reticuloendothelial system. Consequently, this condition results in an abnormal decrease in the number of platelets circulating in blood plasma.

Platelets are cells that are needed to stop bleeding. A normal platelet count is in the range of 150,000 to 450,000. With ITP, the platelet count is less than 100,000. By the time significant bleeding occurs, the patient may have a platelet count of less than 10,000. The lower the platelet count, the greater the risk of bleeding. 

Because of inability of blood to properly clot due to lack of sufficient platelets, a distinctive purplish rash develops under the skin from blood leakage and an appearance of many small red spots of varying size can cover the skin. Depending on the number of platelets, there may be minimal to extensive bleeding in various parts of the body.  Bleeding in the brain is the worst complication, causing death in approximately 1% of affected children and 5% of affected adults.

Immune thrombocytopenic purpura is common in childhood, on average 50 cases per 1,000,000 per year with same incidence in boys as girls. It may follow a viral infection or immunization and is caused by an inappropriate response of the immune system to cross react against the body’s platelets.1

The incidence of immune thrombocytopenic purpura in adults is approximately 66 cases per 1,000,000 per year.  Older persons and persons with a previous history of hemorrhage are at increased risk of severe bleeding in adult ITP.  

Spontaneous remission occurs in most children (80%).  Remission in adults usually requires treatment. 

What Is Immune Thrombocytopenic Purpura In Celiac Disease and/or Gluten Sensitivity?

Sources:
  1. Dogan M, Sal E, Akbayram S, Peker E, Cesur Y, Oner AF. Concurrent celiac disease, idiopathic thrombocytopenic purpura and autoimmune thyroiditis. Clin Appl Thromb Hemost. 2011 Nov-Dec;17(6):E13-6. doi: 10.1177/1076029610378502. Epub 2010 Aug 3. [↩]

Neutropenia 

neutrophilWhat Is Neutropenia?

Neutropenia  is a blood disorder characterized by presence of an abnormally low number of neutrophils.

Neutrophils are white blood cells (leukocytes) that serves as the primary defense against infections by destroying bacteria in the blood. 

Specfically, neutrophils are a type of granulocyte that contain granules filled with potent chemicals to break down the microbes they ingest. Some of these chemicals, such as histamine, also contribute to inflammation and allergy.

The process of eating and digesting microbes is called phagocytosis. Neutrophils are phagocytes.1

Q: How do neutrophils eat microbes?

A: Segmented neutrophils  are the mature phagocytes that migrate through tissues to destroy microbes and respond to inflammatory stimuli. Segmented neutrophils comprise 40-75 % of the peripheral leukocytes. They are usually 9 to 16 µm in diameter. The nuclear lobes, normally numbering from 2 to 5, may be spread out so that the connecting filaments are clearly visible, or the lobes may overlap or twist. The chromatin pattern is coarse and clumped. The cytoplasm is abundant with a few nonspecific granules and a full complement of rose-violet specific granules.1

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

Sources:
  1. http://www.wadsworth.org/chemheme/heme/microscope/seg.htm [↩] [↩]