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Autoimmune Hepatitis

 

Jaundice, or yellowing of the skin and sclera of eyes.
Jaundice, or yellowing of the skin and sclera of eyes, is a symptom of autoimmune hepatitis.

What Is Autoimmune Hepatitis?

Autoimmune hepatitis is an autoimmune attack against liver cells that is characterized by inflammation and results in chronic liver disease which includes low blood albumin and cirrhosis.

Autoimmune hepatitis is diagnosed by detection of autoantibodies in blood and liver biopsy.

Q: What is cirrhosis?

A: Cirrhosis is a degenerative process of the liver that can be fatal. Normal lobular liver structure is distorted and replaced with nodules of regenerating liver cells separated by bands of fibrous tissue that cannot properly carry out liver function and block the necessary flow of blood through the liver, ending in liver failure.

The liver is the largest organ within the body and lies mostly in the upper part of the abdomen on the right side just under the diaphragm. About 70% of liver tissue is made up of cube shaped cells called hepatocytes that do the main work of the liver. Other cells form structure and are arranged in single layers around blood vessels, sinusoids, and bile ducts.

Bile ducts carry bile, a greenish brown liquid made by the liver, to the gall bladder for storage until needed to aid in the digestion and absorption of fat from the small intestine. Bile emulsifies fat eaten in the diet so that the pancreatic enzyme called lipase can break it down into its fatty acid and glycerol components.

The liver is a very busy organ, carrying out over 500 metabolic processes! Nutritionally, it is the first to receive all the blood carrying nutrients freshly absorbed from the digestive tract. Hepatocytes then convert the nutrients to provide the body with energy, a host of amino acids as building blocks for numerous cell activities, and proteins such as albumin and fibrinogen. In fact, hepatocytes build the structural proteins for the liver itself. Imagine the array of nutrients the liver uses and keeps at its disposal for its metabolic functions. Included in liver storage are vital vitamins and minerals such as vitamin A and vitamin B12.

As a detoxifier, Kupffer cells located in the sinusoids act like amoebas to engulf and digest unwanted matter. As a blood cleanser, the liver removes waste products produced by normal metabolism and toxic substances and rids it by preparing these substances for elimination in urine, such as ammonia converted to urea, and/or excreting them in bile for eventual elimination in stool. Bile is continually made by the liver from phospholipids salt, cholesterol, aging blood cells it removes from circulation.

Autoimmune hepatitis is classified into several types. Type 1 autoimmune hepatitis is the most common form in North America. Type 1 can occur at any age; however, it most often starts in adolescence or young adulthood. People with type 1 autoimmune hepatitis commonly have other autoimmune disorders (see listed below).

Type 2 autoimmune hepatitis is less common and occurs more often in children than adults. People with type 2 can also have any of the autoimmune disorders (see listed below).

Both types of autoimmune hepatitis are treated with prednisone, a corticosteroid hormone to control inflammation and reduce the body’s immune activity against the liver.1

What Is Autoimmune Hepatitis In Celiac Disease and/or Gluten Sensitivity?

Sources:
  1. National Digestive Diseases Information Clearinghouse [↩]

Cutis Laxa, Acquired

Image on left shows how atherosclerosis impedes blood flow through coronary arteries while blood clots block blood flow. Courtesy Google.
Figure on right shows how atherosclerosis impedes blood flow through coronary arteries while blood clots block blood flow. Courtesy Google.

What Is Coronary Artery Disease (CAD)?

C oronary artery disease (CAD), also called ischemic heart disease, is a gradual narrowing of medium and large arteries of the heart by fatty buildups, called atherosclerotic plaques.

It is characterized by slowly developing interference with blood flow to heart tissue itself, resulting in oppressive chest pain called angina and, ultimately, thrombosis (clot) causing heart attack.  

The heart is a muscular organ that is working all the time, so it needs a constant supply of oxygen. Oxygen is brought to the working heart tissue by the coronary arteries with each beat of the heart. When heart muscle has to work harder, it needs more oxygen delivered to itself. Lack of oxygen causes pain.

In fact, failure of diseased coronary arteries to deliver adequate oxygen to heart tissue is the most common cause of angina pectoris – substernal pain (under breastbone) or pressure brought on by exertion and relieved by rest. 

Thrombosis, or clot formation, occurs when blood cells within a narrowed artery can no longer get through. Trapped, blood cells pile up and block the artery thus triggering a cascade of events called heart attack. Coronary arteries that are narrowed by atherosclerotic plaques can rupture causing injury to the coronary blood vessel resulting in blood clotting which blocks the flow of blood to the heart muscle. Blood clots may form, partially dissolve, and later form again and angina can occur each time a clot blocks blood flow in an artery.1

Q: How does coronary artery disease develop?

A: Coronary artery disease slowly develops from this combination of events:

  • Dysfunction of epithelial cells that line the inside of arteries cause the vessels to stiffen, and subsequently

  • Accumulation of lipid (fat) in smooth muscle cells beneath the inside lining of arteries and in foam cells cause buildup of fatty deposits on the inside walls progressing to fibrous plaque formation.

Oxidized low-density lipoprotein (oxLDL), so-called bad cholesterol, and oxysterols play important roles in the development of  atherosclerosis. OxLDL triggers the immune system to produce autoantibodies against oxLDL that are detectable in serum. These antibodies are called anti-oxLDL. Anti-oxLDL antibody and oxysterol concentrations are associated with coronary artery stenosis. Oxidative stress may be greatly increased in unstable angina.2 and Chronic inflammation in the general population is a major risk factor for ischemic heart disease.

The pathophysiology of atherosclerosis is, clearly, different in women when compared to the men. The women have a higher risk of blood coagulability making them at high risk for the blood clot formation. In a large number of women endothelial dysfunction, small vessel size and diffuse atherosclerosis have been identified as causes of ischemia without evidence of blockade in the coronary arteries.3

Also, atherosclerotic plaque in women is less fibrotic and contains more lipid filled foam cells, implying greater potential for reversibility but also potentially greater vulnerability for plaque rupture and thrombosis.4

Who is Affected in the General Population?

  • Coronary artery disease remains the leading cause of death in developed countries despite significant progress in primary prevention and treatment strategies.

  • It is the leading cause of death in women, as well as an important cause of disability.

  • Older patients are at particularly high risk of poor outcomes following acute coronary syndrome.5

What Is Coronary Artery Disease In Celiac Disease and/or Gluten Sensitivity?

Ischemic heart disease is the leading cause of death in the United States, making cardiovascular risk assessments and potential interventions or treatments imperative for patients with celiac disease.6

Sources:
  1. http://www.heart.org/HEARTORG/Conditions/HeartAttack/SymptomsDiagnosisofHeartAttack/Unstable-Angina_UCM_437513_Article.jsp# [↩]
  2. Yasunobu Y, Hayashi K, Shingu T, Yamagata T, Kajiyama G, Kambe M. Coronary atherosclerosis and oxidative stress as reflected by autoantibodies against oxidized low-density lipoprotein and oxysterosis. Atherosclerosis. Apr 2001;155(2):445-53. [↩]
  3. Kunadian V, Ford GA, Bawamia B, Qiu W, Manson JE. Vitamin D deficiency and coronary artery disease: A review of the evidence. Am Heart J. 2014 Mar;167(3):283-291. doi: 10.1016/j.ahj.2013.11.012. Epub 2013 Dec 19. [↩]
  4. Kunadian V, Ford GA, Bawamia B, Qiu W, Manson JE. Vitamin D deficiency and coronary artery disease: A review of the evidence. Am Heart J. 2014 Mar;167(3):283-291. doi: 10.1016/j.ahj.2013.11.012. Epub 2013 Dec 19. [↩]
  5. Kunadian V, Ford GA, Bawamia B, Qiu W, Manson JE. Vitamin D deficiency and coronary artery disease: A review of the evidence. Am Heart J. 2014 Mar;167(3):283-291. doi: 10.1016/j.ahj.2013.11.012. [↩]
  6. Robinson BL, Davis SC, Vess J, Lebel, J. Primary care management of celiac disease. Nurse Practitioner. February 2015: Vol 40 – Issue 2; 28–34. [↩]

Ataxia, Gait

Normal Liver Lobule. Courtesy almostadoctor.com
Figure 1: Normal Liver Lobule. Courtesy almostadoctor.com

What Is Autoimmune Cholangitis?

A utoimmune cholangitis is a rare inflammatory self-targeted disease of the biliary tract produced by high levels of immunoglobulin G (IgG) antibodies and antinuclear antibodies (ANA).

Autoimmune cholangitis is characterized by progressive inflammation and scarring that leads to narrowing and destruction of the bile ducts and development of biliary cirrhosis of the liver.

Autoimmune cholangitis is also termed anti-mitochondrial antibody-negative primary biliary cirrhosis because there is no production of anti-mitochondrial antibodies.

Q: What happens when bile ducts can no longer transport bile out of the liver?

A: Bile that cannot be removed from the liver by the biliary tract backs up and damages the liver, causing cirrhosis. In Figure 1, bile back up would directly damage the hepatic (liver) cells seen here as grey “blocks.” 

Bile is a greenish brown liquid continually made by the liver cells (hepatocytes) from phospholipids salt, cholesterol, and aging blood cells that it removes from circulation. 

Bile also carries away waste products produced by normal metabolism and toxic substances that are removed by the liver for eventual elimination in stool. As such, bile must continually flow out of the liver to prevent build-up in the liver. 

Bile from the hepatic cells drains into small tubes called canniculi and then into larger bile ducts to be carried out of the liver to the gall bladder for storage until needed to aid in the digestion and absorption of fat from the small intestine.   Bile emulsifies fat eaten in the diet so that the pancreatic enzyme called lypase can break it down into its fatty acid and glycerol components. 

Unfortunately, autoimmune cholangitis is difficult to diagnose because it mimics many other diseases such as primary sclerosing cholangitis, sarcoidosis, cancer and lymphoma.

What Is Autoimmune Cholangitis In Celiac Disease and/or Gluten Sensitivity?

Liver or Hepatic Granulomatous Disease 

This is a model of Immunoglobulin-G Antibody (IgG)
This is a model of Immunoglobulin-G Antibody (IgG)

What Are Anti-Gliadin Antibodies?

A nti-gliadin antibodies (AGA) are produced by the body as an immune response against partially digested gliadin peptides (fragments) that have abnormally entered the body from the intestinal tract. Gliadin is a protein in wheat grain.

Anti-gliadin antibodies circulating in blood are measured by laboratory testing on blood that is drawn. The antibodies are both immunoglobulin A (IgA) and immunoglobulin G (IgG) types, which are termed AGA-IgA and AGA-IgG.

The presence of anti-gliadin antibodies in blood is an abnormal laboratory finding. That is, when the intestinal lining is healthy and able to keep out undigested matter from the body, there are no molecules of gliadin present to trigger the immune system for defense.

Q: Who produces anti-gliadin antibodies?

A: Persons, with or without celiac disease, can produce anti-gliadin antibodies if and when leaky gut (increased intestinal permeability) develops that then allow gliadin peptides to get into the bloodstream.

Gliadin itself causes leaky gut, but there are other causes such as various foods, intestinal infections, medications, and other diseases of the gastrointestinal tract. Whatever the cause of leaky gut, if poorly digested gliadin is present, it can slip through the leaky lining and enter the bloodstream where it can trigger an antibody response by anti-gliadin antibodies.

What Are Anti-Gliadin Antibodies In Celiac Disease and/or Gluten Sensitivity Or Non-Celiac Gluten Sensitivity?

Edema

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?

C achexia 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?

Ataxia, Gluten

This photo taken during laparoscopy shows the gall bladder (small white organ in middle) surrounded by yellow fat. Liver (dark red organ) is overlying.
This photo taken during laparoscopy shows the gall bladder (small white organ in middle) surrounded by yellow fat. Liver (dark red organ) is overlying.

What Is Impaired Gall Bladder Motility?

I mpaired gall bladder motility means the gall bladder is slow to empty or is dysfunctional.

The functional disorder of the gallbladder is caused initially either by metabolic abnormalities or by an alteration in its muscular ability to contract (motility dysfunction).

The diagnostic criteria based on symptoms of motility dysfunction of the gallbladder are episodes of moderate to severe steady pain located in the epigastrium and right upper abdominal quadrant that last at least 30 minutes.

Gallbladder motility disorder is suspected after gallstones and other structural abnormalities have been excluded.1

Q: What does the gallbladder do?

A: The gallbladder is a small pouch-like organ about the size of a pear that receives bile produced by the liver and stores it until needed during digestion. It lies just under the liver.

Bile is a complex fluid containing water, electrolytes and many organic molecules including bile acids, cholesterol, phospholipids and bilirubin. Bile  acids are critical for digestion and absorption of fats and fat-soluble vitamins in the small intestine.  Many waste products, including bilirubin, are eliminated from the body by secretion into bile and elimination in feces.2

Before a meal, the gallbladder is usually full of bile. In response to fat in the diet, the gallbladder squeezes stored bile into the small intestine through a series of ducts. When emptied after meals, the gallbladder is flat.

What Is Impaired Gall Bladder Motility In Celiac Disease and/or Gluten Sensitivity?

Sources:
  1. Behar J, Corazziari E, Guelrud M, Hogan W, Sherman S, Toouli J. Functional gallbladder and sphincter of oddi disorders. Gastroenterology. 2006 Apr;130(5):1498-509. [↩]
  2. http://www.vivo.colostate.edu/hbooks/pathphys/digestion/liver/bile.html [↩]

Diabetes Mellitus, Type I

Image depicts tissue transglutaminase (tTg).
Image Depicts Tissue Transglutaminase (tTG).

What Are Anti-tissue Transglutaminase Antibodies?

A nti-tissue transglutaminase antibodies (anti-tTG) are connective tissue autoantibodies and can be detected in blood samples from affected persons who are reacting to gluten in the diet.

Autoantibodies are abnormal because they attack the body’s own tissue, which in the case of these antibodies is tissue transglutaminase 2 (TG2).

Q: What is tissue transglutaminase 2 (TG2)?

A: Tissue transglutaminase 2 (TG2) is an enzyme that appears in many cell locations and is particularly abundant in endothelial cells that line the small intestine. It has been implicated in a variety of cellular processes, such as differentiation, cell death, inflammation, cell migration and wound healing.

The cell appears to adapt the dynamics of this enzyme to meet specific sub-cellular needs or to respond to stress or other stimuli. Substantial evidence indicates that the location of TG2 within cells is critical for the regulation of its various biochemical activities, which subsequently trigger diverse downstream events,1

Although initially studied as an enzyme within cells, TG2 is now known to be secreted also into the extracellular space (between cells) or onto the cell surface.1

Abnormal activation of TG2 or deregulation of its function(s) is involved in a variety of human diseases, such as celiac disease, diabetes, neurodegenerative diseases, multiple sclerosis and rheumatoid arthritis. A role in inflammatory disorders and septic shock has also been shown. Moreover, multiple studies have revealed elevated TG2 expression in many types of cancer cells.1

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

Sources:
  1. Piacentini M, D’Eletto M, Farrace MG, Rodolfo C, Del Nonno F, Ippolito G, Falasca L. Characterization of distinct sub-cellular location of transglutaminase type II: changes in intracellular distribution in physiological and pathological states. Cell Tissue Res. 2014 Dec;358(3):793-805. doi: 10.1007/s00441-014-1990-x. [↩] [↩] [↩]

Macroamylasemia

Depiction of pancreatic amylase molecule.
Depiction of pancreatic amylase molecule.

What Is Macroamylasemia?

Macroamylasemia is an acquired enzyme disorder that causes elevated levels of the enzyme amylase (hyperamylasaemia) in the bloodstream. It is characterized by altered amylase molecules that have become abnormally bound with plasma proteins in the bloodstream, commonly IgG (immunoglobulin G) and/or IgA (immunoglobulin A).

The resulting molecule is too large to be properly filtered by the kidneys and excreted in the urine as would be normal unbound amylase, causing sustained elevation of amylase levels in the plasma.

With normal kidney function, a hyperamylasemia without an increase in urine amylase suggests the diagnosis of macroamylasemia, and is confirmed by identifying the macromolecular components.1

Amylase is a an enzyme produced by the pancreas and the parotid glands to digest starch in the diet. Comparatively small amounts are also produced by other organs.

Q: How do the pancreas and parotid glands deliver their amylase for digestion of starch?

A: The parotid glands deliver their amylase into the mouth. The action of amylase in the mouth starts the breakdown of starch as it is chewed and moistened with saliva.

After the starchy food is liquified in the stomach, the mass empties into the duodenum. Here pancreatic amylase is delivered through the common bile duct into the duodenum where it turns starch into maltose sugar. The next step to final digestion of starch is carried out by enzymes in the small intestinal lining that split maltose into its component sugar which is glucose.

Glucose is a simple sugar that can be absorbed into the bloodstream for use in the body. Humans cannot live without adequate glucose.

Distinquishing macroamylasemia from hyperamylasemia due to pancreatic disease is necessary to prevent needless treatment and investigation for pancreatitis.2

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

Sources:
  1. Torrent Vernetta A, Segarra Cantón O, Soler Palacín P, Segura Cardona RM, Infante Pina D. Macroamylasaemia in paediatrics. An Pediatr (Barc). 2008 Nov;69(5):439-41. [↩]
  2. Isham CA, Ridgeway NA, Hedrick R, Cate JC 4th. Screening for macroamylase in a community hospital. Clin Chem. 1984 May;30(5):741-2. [↩]

Geographic Tongue

Geographic Tongue Due to Riboflavin Deficiency.
Geographic Tongue Due to Riboflavin Deficiency.

 What Is Geographic Tongue?

Geographic tongue is a painful alteration in tongue tissue that is characteristic of riboflavin (vitamin B2) deficiency.1

Q: How does the tongue surface appear?

A: Areas of inflamed tissue with flattened papillae develop among areas of normal tissue, giving a map-like appearance to the tongue surface. There are often swollen papillae that hurt or sting, such as is seen in the photo to the left.

A diet that does not provide adequate amounts of riboflavin and any condition that 1) interferes with riboflavin absorption from the gut, 2) depletes the vitamin from the body, 3) overuses the vitamin in the body, or 4) adversely affects its use in the body will result in riboflavin deficiency causing geographic tongue.

Riboflavin is essential for converting foodstuffs into energy, maintaining the normal lifespan of red blood cells and maintaining healthy skin, eyes, hair, and nervous system. Riboflavin is converted into its active forms, flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN). These enzymes are primarily involved as co-factors in oxidation reduction reactions that are essential for cellular energy production and respiration.

Riboflavin is required for the conversion of pyridoxine (vitamin B6) to its functional form and the production of niacin (vitamin B3) from the amino acid tryptophan. Riboflavin has a role in antioxidant status by activating glutathione reductase, which regenerates used glutathione, a powerful antioxidant.

Respiratory infection, exercise, certain diseases, drugs and hormones can adversely influence riboflavin status.2 Stress is a major depleter of riboflavin.

What Is Geographic Tongue 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. [↩]
  2. Lakshmi AV. Riboflavin metabolism–relevance to human nutrition. Indian J Med Res. 1998 Nov;108:182-90. [↩]

Carbohydrate Malabsorption

What Is Carbohydrate Malabsorption? Carbohydrate malabsorption is a digestive disorder characterized by the inability to properly digest and absorb carbohydrates within the small intestine to supply needed energy to the body. Q: What carbohydrates should be normally…