Malabsorption Syndrome

Mal absorption Syndrome and associated disorders

1. M alabsorption Syndrome

2. The Gastrointestinal (GI) Tract & Absorption

3. Malabsorption Syndrome Maldigestion: impaired breakdown of nutrients (carbohydrates, protein, fat) to absorbable split-products (mono-, di-, or oligosaccharides; amino acids; oligopeptides; fatty acids; monoglycerides) Malabsorption: defective mucosal uptake and transport of adequately digested nutrients including vitamins and trace elements .

4. Malabsorption Syndrome Malabsorption Syndrome is a clinical term that encompasses defects occurring during the digestion and absorption of food nutrients by the gastrointestinal tract

5. The digestion or absorption of a single nutrient component may be impaired, as in lactose intolerance due to lactase deficiency. However, when a diffusion disorder, such as celiac disease or Crohn's disease, affects the intestine, the absorption of almost all nutrients is impaired.

6. Pathophysiology (Mechanism) In general, the digestion and absorption of food materials can be divided into 3 major phases: Luminal Mucosal Post - absorptive.

7. The luminal phase is the phase in which dietary fats, proteins, and carbohydrates are hydrolyzed and solubilized by secreted digestive enzymes and bile. The mucosal phase relies on the integrity of the brush-border membrane of intestinal epithelial cells to transport digested products from the lumen into the cells.

8. In the post - absorptive phase, reassembled lipids and other key nutrients are transported via lymphatic and portal circulation from epithelial cells to other parts of the body.

9. Causes of Malabsorption Syndrome The best way to classify the numerous causes of malabsorption is to consider the 3 phases of digestion and absorption.

10. The Luminal Phase Impaired nutrient hydrolysis The most common cause for impaired nutrient hydrolysis is pancreatic insufficiency due to chronic pancreatitis, pancreatic resection, pancreatic cancer, or cystic fibrosis. The resultant deficiencies in lipase and proteases lead to lipid and protein malabsorption, respectively. Inactivation of pancreatic enzymes by gastric hypersecretion, as seen in Zollinger-Ellison syndrome, is another cause.

11. The Luminal Phase Inadequate mixing of nutrients, bile, and pancreatic enzymes, as seen in rapid intestinal transit, gastrojejunostomy, total and partial gastrectomy, or intestinal resection after mesenteric emboli or thrombosis, also causes impaired hydrolysis. Rarely, a failure to convert a proenzyme to active form, such as enterokinase and trypsinogen deficiencies, also can cause protein maldigestion and malabsorption.

12. Impaired micelle formation Impaired micelle formation causes a problem in fat solubilization and subsequent fat malabsorption. This impairment is due to different reasons, including (1) decreased bile salt synthesis from severe parenchymal liver disease (eg, cirrhosis); (2) impaired bile secretion from biliary obstruction or cholestatic jaundice (eg, primary biliary cirrhosis, primary sclerosing cholangitis ); (3) impaired enterohepatic bile circulation, as seen in small bowel resection or regional enteritis; or (4) bile salt deconjugation due to small bowel bacterial overgrowth.

13. Stasis of intestinal content caused by a motor abnormality (eg, scleroderma, diabetic neuropathy, intestinal obstruction), an anatomic abnormality (eg, small bowel syndrome, stricture, ischemia, blind loops), or small bowel contamination from enterocolonic fistulas can cause bacterial overgrowth.

14. Luminal availability and processing Luminal bacterial overgrowth can cause a decrease in the availability of substrates, including carbohydrates, proteins, and vitamins (eg, vitamin B-12, folate ). Vitamin B-12 deficiency due to pernicious anemia is caused by a lack of intrinsic factor and by pancreatic enzyme deficiency.

15. Mucosal phase Impaired brush-border hydrolase activity Disaccharidase deficiency can lead to disaccharide malabsorption. Lactase deficiency, either primary or secondary, is the most common form of disaccharidase deficiency. Genetic factors determine primary lactase deficiency. Secondary lactase deficiency can be due to acute gastroenteritis (rotavirus and giardia infection), chronic alcoholism, celiac sprue, radiation enteritis, regional enteritis, or AIDS enteropathy.

16. Mucosal phase Immunoglobulin A (IgA) deficiency (most common immunodeficiency) is due to decreased or absent serum and intestinal IgA, which clinically appears similar to celiac disease and is unresponsive to a gluten-free diet. Acrodermatitis enteropathica is an autosomal recessive disease with selective inability to absorb zinc, leading to villous atrophy and acral dermatitis.

17. Mucosal phase Autoimmune enteropathy primarily diagnosed in children presenting with intractable secretory diarrhea and villous atrophy. Autoimmune enteropathy is due to antibodies directed against intestinal epithelial and goblet cells. Additional cell types affected by auto antibodies include islet and parietal cells. Other carbohydrase deficiencies, such as sucrase-isomaltase deficiency, may be the cause.

18. Mucosal phase Impaired nutrient absorption Nutrient malabsorption is due to inherited or acquired defects. Inherited defects include glucose- galactose malabsorption, abetalipoproteinemia , cystinuria , and Hartnup disease.

19. Acquired disorders are far more common and are caused by the following: (1) decreased absorptive surface area, as seen in intestinal resection of intestinal bypass; (2) damaged absorbing surface, as seen in celiac sprue, tropical sprue, Crohn's disease, AIDS enteropathy, chemotherapy, or radiation therapy; (3) infiltrating disease of the intestinal wall, such as lymphoma and amyloidosis ; and (4) infections, including bacterial overgrowth, giardiasis, Whipple's disease, cryptosporidiosis, and microsporidiosis .

20. Post - absorptive Phase Obstruction of the lymphatic system, both congenital (eg, intestinal lymphangiectasia , Milroy disease) and acquired (eg, Whipple disease, neoplasm [including lymphoma], tuberculosis), impairs the absorption of chylomicrons and lipoproteins and may cause fat malabsorption or a protein-losing enteropathy.

21. External Causes Hyperthyroidism Hypothyroidism Addisons' disease Diabetes mellitus Hyperparathyroidism Hypoparathyroidism Carcinoid syndrome Widespread skin disease Malnutrition. Collagen diseases. Eating disorders.

22. Risk Factors Factors that may increase your chance of having malabsorption include: Medical conditions affecting the intestine Use of laxatives Excessive use of antibiotics Intestinal surgery Excessive use of alcohol Travel to countries with high incidence of intestinal parasites.

23. Symptoms of Malabsorption Syndrome The osmotic load resulting from the inability of the intestine to absorb certain nutrient elements causes the presenting symptoms. On occasion, the products of digestion produced by bacterial flora also result in a secretory reaction by the intestine.

24. Diarrhea Diarrhea is the most common symptomatic complaint. Diarrhea frequently is watery, reflecting the osmotic load received by the intestine. Bacterial action producing hydroxy fatty acids from undigested fat also can increase net fluid secretion from the intestine, further worsening the diarrhea.

25. Steatorrhea Steatorrhea is the result of fat malabsorption. The hallmark of steatorrhea is the passage of pale, bulky, and malodorous stools. Such stools often float on top of the toilet water and are difficult to flush. Also, patients find floating oil droplets in the toilet following defecation.

26. Weight loss and fatigue Weight loss is common and may be pronounced; however, patients may compensate by increasing their caloric consumption, masking weight loss from malabsorption. The chance of weight loss increases in diffusion diseases involving the intestine, such as celiac disease and Whipple disease.

27. Flatulence and abdominal distention Bacterial fermentation of unabsorbed food substances releases gaseous products, such as hydrogen and methane, causing flatulence. Flatulence often causes uncomfortable abdominal distention and cramps.

28. Edema Hypoalbuminemia from chronic protein malabsorption or from loss of protein into the intestinal lumen causes peripheral edema. Extensive obstruction of the lymphatic system, as seen in intestinal lymphangiectasia , can cause protein loss. With severe protein depletion, ascites may develop.

29. Anemia Depending on the cause, anemia resulting from malabsorption can be either microcytic (iron deficiency) or macrocytic (vitamin B-12 deficiency). Iron deficiency anemia often is a manifestation of celiac disease. Ileal involvement in Crohn disease or ileal resection can cause megaloblastic anemia due to vitamin B-12 deficiency.

30. Bleeding disorders Bleeding usually is a consequence of vitamin K malabsorption and subsequent hypoprothrombinemia . Ecchymosis usually is the manifesting symptom, although, occasionally, melena and hematuria occur.

31. Metabolic defects of bones Vitamin D deficiency can cause bone disorders, such as osteopenia or osteomalacia . Bone pain and pathologic fractures may be observed. Malabsorption of calcium can lead to secondary hyperparathyroidism.

32. Neurologic manifestations Electrolyte disturbances, such as hypocalcemia and hypomagnesemia , can lead to tetany , manifesting as the Trousseau sign and the Chvostek sign. Vitamin malabsorption can cause generalized motor weakness ( pantothenic acid, vitamin D) or peripheral neuropathy (thiamine), a sense of loss for vibration and position ( cobalamin ), night blindness (vitamin A), and seizures (biotin).

33. Physical Signs of Malabsorption General Manifestations Patients may have orthostatic hypotension. Patients may complain of fatigue. Signs of weight loss, muscle wasting, or both may be present. Patients may have signs of loss of subcutaneous fat.

34. Abdominal manifestations The abdomen may be distended, and bowel sounds may be hyperactive. Ascites may be present in severe hypoproteinemia . Dermatologic manifestations Pale skin may reveal anemia. Ecchymoses due to vitamin K deficiency may be present. Dermatitis herpetiformis , erythema nodosum , and pyoderma gangrenosum may be present. Pellagra, alopecia, or seborrheic dermatitis may be present.

35. Neurologic al manifestation Motor weakness, peripheral neuropathy, or ataxia may be present. The Chvostek sign or the Trousseau sign may be evident due to hypocalcemia or hypomagnesemia . Cheilosis , glossitis , or aphthous ulcers of the mouth Peripheral edema

36. Possible Complications Long-term malabsorption can result in: Anemia Gallstones Kidney stones Osteoporosis and bone disease Malnutrition and vitamin deficiencies

37. Celiac Disease

38. Celiac Disease Celiac disease is a digestive disorder. It is caused by an immune reaction to gluten. Celiac disease is also known as: Celiac sprue Non - tropical sprue gluten intolerance gluten-sensitive enteropathy

39. Celiac disease (CD) is an immune-mediated disorder, the only one with a well-established origin, resulting from a permanent gluten intolerance, which primarily involves the gastrointestinal tract. It is characterized by the presence of chronic inflammation of the small bowel’s mucosa and submucosa, and is clinically characterized by the presence of diverse systemic manifestations. It may start at any age, both during childhood and adolescence, and is also relatively common in adulthood. It is being increasingly diagnosed even in elderly patients (up to 20% of patients are older than 60 years, at the time of diagnosis)

40. The causative agent, gluten, is well established; a mixture of proteins present exclusively in cereals –mainly wheat, barley, rye and oats- but not corn. It affects only predisposed individuals, whose most susceptible genetic features are related to human leukocytes antigens from class two (HLA-􁶘), predominantly HLA-DQ2 (90%), while much less frequency HLA-DQ8 (5%-10%). However, these genetic markers are a necessary, but not a sufficient condition, since a significant frequency of CD patients (5%-10%) are DQ2 and DQ8-negative. This means that other, still not well-established, genotypes may exist that probably correspond to the class one HLA system (HLA-􁶗), including MICA, MICB and others.

41. A strong genetic susceptibility is present with about 75% concordance rate, among monozygotic twins. Certain populations have an increased prevalence of CD. For instance, the first-degree relatives of individuals with biopsy-proven CD, have a prevalence between 4%-12% of those suffering from this disease. Second-degree relatives also appear to have an increased prevalence. Patients with type 1 diabetes mellitus (IDDM) have a prevalence of CD ranging to 3%-8%. In Down´s syndrome, the presence of CD is found between 5%-12%. Also, CD is associated with Turner’s and William’s syndromes, IgA deficiency and several autoimmune disorders.

42. Risk Factors for Celiac Disease People suffering from other immune diseases and certain genetic disorders are more likely to have celiac disease. Some disorders associated with celiac include: rheumatoid arthritis type 1 diabetes thyroid disease autoimmune liver disease Addison’s disease Sjogren’s disease lupus Down syndrome Turner syndrome lactose intolerance intestinal cancer intestinal lymphoma

43. Pathogenesis The triggers for CD are specific immunogenic peptides that are present only and exclusively in the dietary gluten proteins, from wheat and similar structural cereals such as rye and barley. These peptides are resistant to digestion by gastric and pancreatic enzymes and find their way into the lamina propria of the small bowel, presumably after some changes occur in the intercellular tight junctions with an increase in the intestinal permeability. One such peptide is a 33-amino acid sequence, which is a potent activator of specific T-cell lines from patients with CD.

44. The subsequent infiltration by CD4 (+) T Lymphocytes into the lamina propria and CD8 (+) into the intestinal epithelium, are a hallmark of active CD. The recognition of HLA-bound gluten peptides by T cells, leads to their activation and clonal expansion of B cells that produce antibodies. Other cytokines released by activated CD4 T cells that involve the adaptive immune response, promote various inflammatory mechanisms and produce the intestinal lesion.

45. Less information is available on the activation and mode of action of intraepithelial T cells, which are mediated by the innate immune system. The expression of the interleukin-15 cytokine appears to play a central role in driving various processes that lead to the increased number of intraepithelial lymphocytes (IELs) as well as in the destruction process of the epithelial cells and the mucosal damage

46. Tissue transglutaminase 2 (tTG), plays an important role in the immune response and is present in several tissues in the body. The cross-linking activity of tTG is involved in several functions, such as wound healing, formation of cell envelopes in apoptosis and Stabilization of the extra-cellular matrix. In addition, this enzyme can deaminate glutamine residues. Glutamine-rich gluten peptides are, therefore, excellent substrates for tTG. The resulting deaminated and thus, negatively-charged peptides, have much higher affinity for the HLA-DQ2 and DQ8 molecules, and have a key step in the immune response in CD.

47. Normal Pathology

48. Risk groups and associated disorders First degree relatives Down´s and turner´s syndromes IgA selective deficiency Endocrine diseases o Type 1 diabetes mellitus o Autoimmune thyroid diseases o Alopecia areata Neurologic diseases o Cerebellar ataxia o Epilepsy o Peripheral neuropathy o Multiple sclerosis

49. Liver diseases o Primary biliary cirrhosis o Autoimmune hepatitis o Autoimmune cholangitis o Idiopathic hypertransaminasemia Rheumatologic diseases o Rheumatoid arthritis o Sjögren´s syndrome Heart diseases o Idiopathic dilated cardiomyopathy o Autoimmune myocarditis

50. Cutaneous diseases o Dermatitis herpetiformis o Psoriasis o Vitiligo Others o Iron-deficiency anemia o Osteoporosis o Increased risk of fractures o Infertility o Amenorrhea o Dental enamel defects o Depression and anxiety o Chronic asthenia

51. Epidemiology Until the last decade, CD was considered to be a rare disease, but today it is known to be universally distributed, to involve all races, and it is one of the most commonly known genetic diseases, with a mean prevalence of 1%-2% in the general population, being clearly underestimated and under diagnosed worldwide.

52. Clinical Presentations The clinical presentation of CD varies greatly, ranging from asymptomatic to severely malnourished patients. The most common clinical manifestations of CD include abdominal cramping pain with moderate to severe abdominal distension, frequently associated with relapsing or permanent dyspepsia, presence of gastro- Esophageal reflux (GERD) and recurrent episodes of altered bowel habits (diarrhea and/or constipation), weight loss, bone disease, anemia and weakness.

53. While diarrhea was almost considered a persistent symptom, this is not the case in adults, and up to 50% of patients predominantly have constipation, which on many occasions becomes refractory to all types of therapy. It should be noted, that up to 30% of celiac patients have increased body mass index (BMI) and obvious obesity at diagnosis.

54. CD is sometimes divided into clinical subtypes. The terms “symptomatic or classic” apply to cases that meet the typical features described above. By contrast, in the “atypical forms” of the disease, the Gastrointestinal symptoms may be absent or less pronounced, and in this case the extra-intestinal features predominate, such as chronic iron deficiency anemia, osteoporosis, short stature or failure to thrive, infertility and increased number of abortions. Since atypical presentations are found more frequently in later decades, CD is now considered to be a multisystemic disorder, rather than a sole gastrointestinal process

55. Gastrointestinal Symptoms Diarrhea is the most common symptom in untreated celiac sprue and present in 45-85% of all patients. Diarrhea caused by celiac sprue is due to maldigestion and malabsorption of nutrients. The stools might be watery or semiformed , light tan or gray, and oily or frothy. The stools have a characteristic foul odor. In infants and young children, extensive diarrhea can lead to severe dehydration, electrolyte depletion, and metabolic acidosis.

56. Gastrointestinal Symptoms Malabsorption of ingested fat (steatorrhea) results in the delivery of excessive dietary fat to the large bowel. This results in the production of hydroxy fatty acids by bacteria, which causes secretion of fluids into the intestine. Flatulence (28% of patients) and borborygmus (35-72% of patients) results from the release of intestinal gas by the bacterial florae feasting on undigested and unabsorbed food materials and often becomes excessive or even explosive.

57. Gastrointestinal Symptoms Weight loss (present in 45% of all patients) is variable because some patients might compensate for the malabsorption by increasing dietary intake. In infants and young children with untreated celiac sprue, failure to thrive and growth retardation are common. Weakness and fatigue (prevalence 78-80%) are usually related to general poor nutrition. In some patients, severe anemia can contribute to fatigue. Occasionally, severe hypokalemia due to the loss of potassium in the stool can cause muscle weakness. Severe abdominal pain (prevalence 34-64%) is unusual in patients with uncomplicated celiac sprue. However, abdominal bloating or cramps with excessive malodorous flatus is a common complaint.

58. Extra - Intestinal Symptoms Anemia (10-15% of patients) is usually due to impaired absorption of iron or folate from the proximal small intestine. In severe celiac disease with ileal involvement, absorption of vitamin B-12 might be impaired. A bleeding diathesis is usually caused by prothrombin deficiency due to impaired absorption of fat-soluble vitamin K.

59. Extra - Intestinal Symptoms Osteopenia and osteoporosis (prevalence 1-34%) might cause bone pain for several reasons, including defective calcium transport by the diseased small intestine, vitamin D deficiency, and binding of luminal calcium and magnesium to unabsorbed dietary fatty acids. Neurologic symptoms (frequency 8-14%) that result from hypocalcaemia include motor weakness, paresthesias with sensory loss, and ataxia. Seizures might develop because of cerebral calcifications. [3]

60. Extra - Intestinal Symptoms Skin disorders, including dermatitis herpetiformis (a pruritic papulovesicular skin lesion involving the extensor surfaces of the extremities, trunk, buttocks, scalp, and neck), is associated in 10-20% of patients with celiac disease. Hormonal disorders, such as amenorrhea, delayed menarche, and infertility in women and impotence and infertility in men, have been described.

61. Physical Abdominal examination shows a protuberant and tympanic abdomen due to distention of intestinal loops with fluids and gas. Ascites occasionally can be detected in patients with severe hypoproteinemia . Evidence of weight loss, including muscle wasting or loose skin folds Orthostatic hypotension

62. Physical Peripheral edema Ecchymoses Hyperkeratosis or dermatitis herpetiformis Cheilosis and glossitis Evidence of peripheral neuropathy Chvostek sign or Trousseau sign

63. Associated conditions Malignant disease Malignant diseases are more frequent in patients with long-term untreated classical CD. Small-bowel adenocarcinoma , esophageal and oropharyngeal squamous -cell carcinoma, and non-Hodgkin’s lymphoma occur more often in CD patients than in healthy control individuals.

64. Osteoporosis Measurement of bone mineral density is recommended when CD has been diagnosed, as reduced bone density is common in both adults and children with CD. The reduction in bone density is more severe in symptomatic CD than in the silent form and is associated with an increased risk of fracture.

65. Autoimmune disorders Autoimmune disorders occur ten times more frequently in adult patients with celiac disease than in the general population. Such disorders include: • Insulin-dependent type 1 diabetes • Thyroid disease • Sjögren’s syndrome • Addison’s disease • Autoimmune liver disease • Cardiomyopathy • Neurological disorders

66. Dermatitis herpetiformis Dermatitis herpetiformis is considered to be a cutaneous manifestation of gluten sensitivity in patients with CD. Dermatitis herpetiformis (DH) is a severe, itchy, blistering skin disease. The rash usually occurs on the elbows, knees, and buttocks. Although people with DH do not usually have digestive-tract symptoms, they usually have the intestinal damage characteristic of CD.

67. Lactose Intolerance

68. Lactose Intolerance Lactose intolerance is the inability to break down a type of natural sugar called lactose . Lactose is commonly found in dairy products, such as milk and yogurt.

69. Lactose Intolerance A person becomes lactose intolerant when his or her small intestine stops making enough of the enzyme lactase to digest and break down the lactose. When this happens, the undigested lactose moves into the large intestine. The bacteria that are normally present in the large intestine interacts with the undigested lactose. The condition may also be called lactase deficiency .

70. Pathophysiology Lactose, a disaccharide, is present in milk and processed foods. Dietary lactose must be hydrolyzed to a monosaccharide in order to be absorbed by the small intestinal mucosa. A deficiency of intestinal lactase prevents hydrolysis of ingested lactose. The osmotic load of the unabsorbed lactose causes secretion of fluid and electrolytes until osmotic equilibrium is reached. Dilation of the intestine caused by the osmosis induces an acceleration of small intestinal transit, which increases the degree of maldigestion. Within the large intestine, free lactose is fermented by colonic bacteria to yield short-chain fatty acids and hydrogen gas. The combined increase in fecal water, intestinal transit, and generated hydrogen gas accounts for the wide range of gastrointestinal symptoms.

71. Types of Lactose Intolerance There are three main types of lactose intolerance, each with different causes: Primary Lactose Intolerance Secondary Lactose Intolerance Congenital or Developmental Lactose Intolerance

72. Primary Lactose Intolerance This is the most common type of lactose intolerance. Most people are born with enough lactase. Babies need the enzyme in order to digest their mother’s milk. However, the amount of lactase a person makes may decrease over time. This is because as people age, they eat a more diverse diet and rely less on milk. The decline in lactase is gradual. This type of lactose intolerance is more common in people with Asian, African, Native American, or Mediterranean ancestry.

73. Secondary Lactose Intolerance Intestinal diseases such as celiac disease and inflammatory bowel disease or a surgery or injury to your small intestine can also cause lactose intolerance. Lactase levels may be restored if the underlying disorder is treated

74. Congenital or Developmental Lactose Intolerance In very rare cases, lactose intolerance is inherited. A defective gene can be passed from the parents to a child, resulting in the complete absence of lactase in the child. This is referred to as congenital lactose intolerance. The baby will be intolerant of his or her mother’s milk. He or she will have diarrhea as soon as human milk or a formula containing lactose is introduced. If it is not recognized and treated early on, the condition can be life threatening

75. Developmental Lactose Intolerance Occasionally, a type of lactose intolerance called developmental lactose intolerance occurs when a baby is born prematurely. This is because lactase production in the fetus begins later in the pregnancy, after at least 34 weeks.

76. Epidemiology Primary lactase deficiency - 70% of the world's population. Prevalence varies with ethnicity - eg , 2% in Northern Europeans and up to 80% in Hispanic populations. Age of presentation also varies - eg , Hispanic, Asian and Afro-Caribbean children present before the age of 5 years, whereas Northern Europeans usually present after the age of 5. Lactose intolerance in adults is very common and lactose may be found in many unexpected sources. These include saccharine processed meats, bread, cake mixes, soft drinks, and lagers. This may account for unexplained symptoms, including some cases of irritable bowel disease.

77. Causes Congenital lactose intolerance is inherited as an autosomal recessive trait and is very rare. Primary lactose intolerance is due to low levels of lactase, which develop after childhood.

78. Causes Secondary, or acquired, lactase deficiency may develop in a person with a healthy small intestine during episodes of acute illness. This occurs because of mucosal damage or from medications. Some causes of secondary lactase deficiency are as follows: Acute gastroenteritis Giardiasis Crohn disease Celiac sprue Tropical sprue Radiation enteritis Diabetic gastropathy Carcinoid syndrome Whipple syndrome HIV enteropathy Chemotherapy Gastrinoma

79. Risk factors Symptoms are caused only by the ingestion of lactose, found in milk and other dairy products. They are affected by the amount of lactose ingested and how fast the small intestine is presented with the lactose load. They will be more marked if the lactose reaches the intestinal mucosa fast but less so if gastric emptying is delayed as by being ingested with a large meal. Degree of symptoms is also affected by individual sensitivity and colonic flora.

80. Presentation Symptoms result from reduced absorption of lactose which is then broken down by intestinal bacteria leading to gas and short-chain fatty acids. Gas build up causes: Bloating. Flatulence. Abdominal discomfort.

81. The acidic and osmotic effects of undigested lactose may cause: Loose watery stool - with a degree of urgency an hour or two after ingestion of milk. Perianal itching due to acidic stools. Symptoms occur from one to several hours after ingestion of milk or dairy products. These symptoms are very nonspecific and occur with other disorders such as milk-protein sensitivity, allergic-type reactions to other substances in the meal, or intolerance of other saccharides .

82. Whipple Disease

83. Whipple’s Disease Whipple's disease is a rare bacterial infection that most often affects your gastrointestinal system. Whipple's disease interferes with normal digestion by impairing the breakdown of foods, such as fats and carbohydrates, and hampering your body's ability to absorb nutrients. Whipple's disease also can infect other organs, including your brain, heart, joints and eyes.

84. Causes The cause of Whipple's disease is infection with the bacterium Tropheryma whipplei . This bacterium initially affects the mucosal lining of your small intestine, forming small lesions within the intestinal wall. The bacterium also damages the fine, hair-like projections (villi) that line the small intestine. With time, the infection can spread to other parts of your body.

85. The bacteria will lead to the development of internal sores and cause body tissue to thicken. When the villi (finger-like tissues that absorb nutrients in the small intestine) begin to thicken, their natural shape begins to change. This damages the villi and prevents them from effectively absorbing nutrients. This, in turn, leads to many of the symptoms connected with Whipple’s.

86. Whipple's Disease: showing macrophages in the small intestine

87. Risk factors Because so little is known about the bacterium that causes Whipple's disease, risk factors for the disease haven't been clearly identified. Based on available reports, it appears more likely to affect: Middle-age and older individuals. Males more than females. Caucasian patients. Family clusters (suggesting an immunogenetic component). HLA-B27 antigen; HLA-DRB1*13 and DQB1*06 alleles. Sewage plant workers, farmers and agricultural workers.

88. Symptoms Associated With Whipple’s Disease Because it causes your body to be unable to properly absorb nutrients, Whipple’s disease affects many different parts of the body and is associated with a variety of symptoms. In advanced disease, the infection may spread from the intestines to other organs such as the heart, lungs, brain, joints, and eyes.

89. Common signs and symptoms Gastrointestinal signs and symptoms are common in Whipple's disease and may include: Diarrhea Abdominal cramping and pain, which may worsen after meals Weight loss, associated with the malabsorption of nutrients

90. Other frequent signs and symptoms associated with Whipple's disease include: Inflamed joints, particularly your ankles, knees and wrists Fatigue Weakness Anemia

91. Less common signs and symptoms In some cases, signs and symptoms of Whipple's disease may include: Fever Cough Enlarged lymph nodes Skin darkening ( hyperpigmentation ) in areas exposed to the sun and in scars Chest pain Enlarged spleen

92. Neurological signs and symptoms may include: Difficulty walking Visual impairment, including lack of control of eye movements Seizures Confusion Memory loss

93. Complications The lining of your small intestine has fine, hair-like projections (villi) that help your body absorb nutrients. Whipple's disease damages the villi, impairing nutrient absorption. Nutritional deficiencies are common in people with Whipple's disease and can lead to fatigue, weakness, weight loss and joint pain. Whipple's disease is a progressive and potentially fatal disease. Although the infection is rare, associated deaths continue to be reported, due in large part to late diagnoses and delayed treatment. Death often is caused by the spread of the infection to the central nervous system, which can cause irreversible damage.

94. Tropical Sprue

95. Tropical Sprue Tropical sprue is caused by inflammation of your intestines. This swelling makes it more difficult for you to absorb nutrients from food. People with tropical sprue do not absorb nutrients properly, especially vitamin B12 and folic acid. Normal small intestines have fingerlike projections called villi that provide more surface area for nutrients to be absorbed. In people with tropical sprue, these villi are flattened, making absorption difficult.

96. Pathophysiology The exact role of microbial agents in the initiation and propagation of the disease is poorly understood. One theory is that an acute intestinal infection leads to jejunal and ileal mucosa injury; then intestinal bacterial overgrowth and increased plasma enteroglucagon results in retardation of small-intestinal transit. Central to this process is folate deficiency, which probably contributes to further mucosal injury.

97. Hormone enteroglucagon and motilin levels are elevated in patients with tropical sprue. Enterocyte injury can cause these elevations. Enteroglucagon causes intestinal stasis, but the role of motilin is not clear. The upper small intestine is predominantly affected; however, because it is a progressive and contiguous disease, the distal small intestine up to the terminal ileum may be involved. Pathological changes are rarely demonstrated in the stomach and colon. Coliform bacteria, such as Klebsiella , E coli and Enterobacter species are isolated and are the usual organisms associated with tropical sprue.

98. What Causes Tropical Sprue? Tropical sprue is rare unless you live in or visit tropical areas. Researchers believe the condition is caused by an overgrowth of bacteria in your intestines. The specific bacteria that cause tropical sprue are unknown. You may be at risk for tropical sprue if you: live in a tropical area have traveled through a tropical area for a long period of time

99. Epidemiology Tropical sprue usually occurs in residents of tropical or subtropical, usually in developing countries. The incidence varies considerably with geography. It occurs mostly in South East Asia and the Caribbean. There is no predilection for race or gender. It tends to affect adults but can also occur in children. The condition may present in natives or travellers and may not present until after they have left the area.

100. What Are the Symptoms of Tropical Sprue? Symptoms of tropical sprue may include any of the following: abdominal cramps diarrhea, which may get worse on a high-fat diet excessive gas indigestion irritability muscle cramps numbness paleness weight loss

101. Short Bowel Syndrome

102. Short Bowel Syndrome Short bowel syndrome is a complication that can occur in people who have a large part or all of their small intestine removed. Short bowel syndrome (SBS), a disorder characterized by diarrhea, malabsorption, fluid and electrolyte disturbances, and eventually malnutrition. Short bowel syndrome may be present at birth due to a congenital anomaly or may develop in older infants and children as a result of disease or trauma, occurring later in life.

103. Etiology of Short Bowel Syndrome Short bowel syndrome may be a congenital or acquired condition. Infants may be born with congenital jejunal or ileal atresia . Otherwise, short bowel syndrome results from surgical resection of bowel. This is usually related to multiple resections for recurrent Crohn’s disease, massive enterectomy made necessary because of a catastrophic vascular event such as mesenteric arterial embolism, venous thrombosis, volvulus , trauma, or tumor resection in adults, and, in children, gastroschisis , necrotizing enterocolitis (NEC), and volvulus .

104. Risk Factors   Factors that may increase your risk of short bowel syndrome include: Crohn's disease, which is the most common reason for the removal of the small intestine Vascular problems Premature birth or very low birth weight Necrotizing enterocolitis Intestinal atresias Gastroschesis

105. Symptoms   Symptoms of short bowel syndrome may include: Diarrhea Cramping Bloating Heartburn Malnourishment Poor growth Dehydration Weakness Fatigue Depression Weight loss Food sensitivities

106. Complications

107. Inflammatory Bowel Disease

108. Inflammatory Bowel Disease Inflammatory Bowel Diseases (IBD) is a broad term that describes conditions with chronic or recurring immune response and inflammation of the gastrointestinal tract. The two most common inflammatory bowel diseases are ulcerative colitis and Crohn’s disease.

109. Both illnesses have one strong feature in common. They are marked by an abnormal response by the body’s immune system. Normally, the immune cells protect the body from infection. In people with IBD, however, the immune system mistakes food, bacteria, and other materials in the intestine for foreign substances and it attacks the cells of the intestines. In the process, the body sends white blood cells into the lining of the intestines where they produce chronic inflammation. When this happens, the patient experiences the symptoms of IBD.

110. Signs and Symptoms Symptoms (Intestinal) include: Diarrhea: Possible presence of mucus/blood in stool; occurs at night Constipation: May be the primary symptom in UC and limited to rectum; obstipation may occur; may proceed to bowel obstruction Bowel movement abnormalities: Possible presence of pain or rectal bleeding, severe urgency, tenesmus Abdominal cramping and pain: Commonly present in the right lower quadrant in CD. Nausea and vomiting: More often in CD than in UC

111. Signs and Symptoms Systemic symptoms include: Cramping Irregular bowel habits, passage of mucus without blood or pus Weight loss Fever, sweats Fatigue Arthralgias Growth Grossly bloody stools Perianal disease (e.g., fistulas, abscesses)

112. Pathophysiology In several studies, genetic factors appeared to influence the risk of inflammatory bowel disease (IBD) by causing a disruption of epithelial barrier integrity, deficits in autophagy,deficiencies in innate pattern recognition receptors, and problems with lymphocyte differentiation. The immune response disrupts the intestinal mucosa and leads to a chronic inflammatory process.

113. Etiology Three characteristics define the etiology of inflammatory bowel disease (IBD): Genetic predisposition; An altered, dysregulated immune response; An altered response to gut microorganisms.

114. Epidemiology of the IBD The peak age of onset for IBD is 15 to 30 years old, although it may occur at any age. About 10% of cases occur in individuals younger than 18 years. Ulcerative colitis is slightly more common in males, whereas Crohn’s disease is marginally more frequent in women. IBD occurs more in people of Caucasian and Ashkenazic Jewish origin than in other racial and ethnic subgroups.

115. Complications of IBD disease Intestinal complications IBD can be associated with several gastrointestinal complications, including risk of hemorrhage, perforation, strictures, and fistulas—as well as perianal disease and related complications, such as perianal or pelvic abscesses, toxic megacolon, and malignancy (colorectal cancer, cholangiocarcinoma).

116. Complications of IBD disease Extra intestinal complications Extra intestinal complications include : Osteoporosis Hypercoagulability Anemia Gallstones Aphthous ulcers Iritis ( uveitis ) Episcleritis Skin complications

117. Extra intestinal manifestations of inflammatory diseases of intestine

118. Ulcerative Colitis

119. Ulcerative Colitis (UC) Ulcerative colitis is an inflammatory bowel disease (IBD) that causes long-lasting inflammation in part of your digestive tract. ulcerative colitis can be debilitating and sometimes can lead to life-threatening complications. Because ulcerative colitis is a chronic condition, symptoms usually develop over time, rather than suddenly.

120. Ulcerative colitis usually affects only the innermost lining of your large intestine (colon) and rectum. It occurs only through continuous stretches of your colon, unlike Crohn's disease, which occurs anywhere in the digestive tract and often spreads deeply into the affected tissues. There's no known cure for ulcerative colitis, but therapies are available that may dramatically reduce the signs and symptoms of ulcerative colitis.

121. Symptoms Ulcerative colitis symptoms can vary, depending on the severity of inflammation and where it occurs. For these reasons, doctors often classify ulcerative colitis according to its location.

122. Symptoms Here are the signs and symptoms that may accompany ulcerative colitis, depending on its classification: Ulcerative proctitis . In this form of ulcerative colitis, inflammation is confined to the area closest to the anus (rectum), and for some people, rectal bleeding may be the only sign of the disease. Others may have rectal pain and a feeling of urgency. This form of ulcerative colitis tends to be the mildest.

123. Proctosigmoiditis . This form involves the rectum and the lower end of the colon, known as the sigmoid colon. Bloody diarrhea, abdominal cramps and pain, and an inability to move the bowels in spite of the urge to do so (tenesmus) are common problems associated with this form of the disease. Left-sided colitis. As the name suggests, inflammation extends from the rectum up through the sigmoid and descending colon, which are located in the upper left part of the abdomen. Signs and symptoms include bloody diarrhea, abdominal cramping and pain on the left side, and unintended weight loss.

124. Pancolitis . Affecting more than the left colon and often the entire colon, pancolitis causes bouts of bloody diarrhea that may be severe, abdominal cramps and pain, fatigue, and significant weight loss. Fulminant colitis. This rare, life-threatening form of colitis affects the entire colon and causes severe pain, profuse diarrhea and, sometimes, dehydration and shock. People with fulminant colitis are at risk of serious complications, including colon rupture and toxic megacolon, a condition that causes the colon to rapidly expand.

125. Pathophysiology Inflammation begins in the rectum and extends proximally in an uninterrupted fashion to the proximal colon and could eventually involve the entire length of the large intestine. The rectum is always involved in ulcerative colitis; and unlike in Crohn disease, there are no "skip areas. Even with less than total colonic involvement, the disease is strikingly and uniformly continuous. As ulcerative colitis becomes chronic, the colon becomes a rigid foreshortened tube, leading to the lead-pipe appearance.

126. Causes No one is quite sure what triggers ulcerative colitis, but there's a consensus as to what doesn't. Researchers no longer believe that stress is the main cause, although stress can often aggravate symptoms. Instead, current thinking focuses on the following possibilities:

127. Immune system. Some scientists think a virus or bacterium may trigger ulcerative colitis. The digestive tract becomes inflamed when your immune system tries to fight off the invading microorganism (pathogen). It's also possible that inflammation may stem from an autoimmune reaction in which your body mounts an immune response even though no pathogen is present. Heredity. Because you're more likely to develop ulcerative colitis if you have a parent or sibling with the disease, scientists suspect that genetic makeup may play a contributing role. However, most people who have ulcerative colitis don't have a family history of this disorder.

128. Risk factors Ulcerative colitis affects about the same number of women and men. Risk factors may include: Age. Ulcerative colitis usually begins before the age of 30. But, it can occur at any age, and some people may not develop the disease until their 50s or 60s. Race or ethnicity. Although whites have the highest risk of the disease, it can occur in any race. If you're of Ashkenazi Jewish descent, your risk is even higher. Family history. You're at higher risk if you have a close relative, such as a parent, sibling or child, with the disease.

129. Complications Possible complications of ulcerative colitis include: Severe bleeding A hole in the colon (perforated colon) Severe dehydration Liver disease (rare) Kidney stones Osteoporosis Inflammation of your skin, joints and eyes An increased risk of colon cancer A rapidly swelling colon (toxic megacolon)

130. Crohn’s Disease

131. Crohn’s Disease Crohn’s disease is a condition of chronic inflammation potentially involving any location of the gastrointestinal tract, but it frequently affects the end of the small bowel and the beginning of the large bowel.

132. Signs and Symptoms Symptoms include: Persistent diarrhea Cramping Abdominal pain Fever Rectal bleeding Loss of appetite weight loss Fatigue However, the disease is not always limited to the gastrointestinal tract; it can also affect the joints, eyes, skin, and liver.

133. Pathophysiology Crohn disease can affect any portion of the gastrointestinal tract, from the mouth to the anus, and causes 3 patterns of involvement: inflammatory disease, strictures, and fistulas. The most important pathologic feature of Crohn disease is that it is transmural, involving all layers of the bowel, not just the mucosa and the submucosa, which is characteristic of ulcerative colitis. Furthermore, Crohn disease is discontinuous, with skip areas interspersed between 2 or more involved areas.

134. Late in the disease, the mucosa develops a cobblestone appearance, which results from deep, longitudinal ulcerations interlaced with intervening normal mucosa . Rectal sparing is a typical but not constant feature of Crohn disease. However, anorectal complications (e.g., fistulas, abscesses) are common. Much less commonly, Crohn disease involves the more proximal parts of the GI tract, including the mouth, tongue, esophagus, stomach, and duodenum.

135. Complications The most common complication of Crohn’s disease is blockage of the intestine due to swelling and scar tissue. Symptoms of blockage include cramping pain, vomiting, and bloating. Another complication is sores or ulcers within the intestinal tract. Sometimes these deep ulcers turn into tracts—called fistulas. Patients may also develop a shortage of proteins, calories, or vitamins.

136. Cholelithiasis and Nephrolithiasis The incidence of gallstones and kidney stones is increased in Crohn disease because of malabsorption of fat and bile salts. Gallstones are formed because of increased cholesterol concentration in the bile, which is caused by a reduced bile salt pool. Patients who have Crohn disease with ileal disease or resection are also likely to form calcium oxalate kidney stones. With the fat malabsorption, unabsorbed long-chain fatty acids bind calcium in the lumen. Oxalate in the lumen is normally bound to calcium. Calcium oxalate is poorly soluble and poorly absorbed; however, if calcium is bound to malabsorbed fatty acids, oxalate combines with sodium to form sodium oxalate, which is soluble and is absorbed in the colon.

137. Crohn’s Disease & Ulcerative Colitis

138. Localization of damage Ulcerative Colitis Crohn’s Disease

139. Volume of damage Ulcerative Colitis Crohn’s Disease

140. Depth of damage Ulcerative Colitis Crohn’s Disease