Chapter17: INTESTINES:Malabsorption and Diarrhea Flashcards

Question

What is involved in transepithelial transport?

Answer 1

in which **nutrients, fluid, and electrolyte**s are transported across and processed within the small intestinal epithelium

Answer 2

of absorbed lipids

Answer 3

In many malabsorptive disorders a **defect in one of these processes** **predominates**, but **more than one usually contributes.** As a result, malabsorption syndromes resemble each other more than they differ.

Answer 4

General symptoms include: * diarrhea (from nutrient malabsorption and excessive intestinal secretion), * flatus, * abdominal pain, and * weight loss. * Inadequate absorption of vitamins and minerals can result in anemia and mucositis due to pyridoxine, folate, or vitamin B12 deficiency; bleeding, due to vitamin K deficiency; osteopenia and tetany due to calcium, magnesium, or vitamin D deficiencies; or peripheral neuropathy due to vitamin A or B12 deficiencies. A variety of endocrine and skin disturbances may also occur

Answer 5

Diarrhea is **defined as an increase in stool mass, frequency, or fluidity,** typically **greater than 200 g pe**r **day**.

Answer 6

14 L per day and, without fluid resuscitation, result in death.

Answer 7

Painful, bloody, small-volume diarrhea is known as dysentery.

Answer 8

* **Secretory diarrhea** * **• Osmotic diarrhea** * **• Malabsorptive diarrhea** * **• Exudative diarrhea**

Answer 9

is **characterized by isotonic stool** and **persists during fasting**

Answer 10

Osmotic diarrhea, such as that **which occurs with lactase deficiency, is due to the excessive osmotic forces exerted by unabsorbed luminal solutes.** The diarrhea fluid is over 50 mOsm more concentrated than plasma and abates with fasting.

Answer 11

follows **generalized failures of nutrient absorption** and is associated with ***_steatorrhea and is relieved by fasting_***

Answer 12

Exudative diarrhea is due to **inflammatory disease** and **characterized by purulent, bloody stools that continue during fasting**

Answer 13

Due to the **absence of the epithelial cystic** * *fibrosis transmembrane conductance regulator (CFTR),** individuals with cystic fibrosis have * *defects in intestinal chloride ion secretion.** This **interferes with bicarbonate, sodium, and water secretion,**ultimately r**esulting in defective luminal hydration.** Formation of intraductal concretions can begin in utero, leading to **duct obstruction, low-grade chronic autodigestion of** the pancreas, and eventual exocrine pancreatic insufficiency in more than 80% of patients . The result is failure of the intraluminal phase of nutrient absorption, which can be effectively treated in most patients with oral enzyme supplementation.

Answer 14

Celiac disease is also known as **celiac sprue** or **gluten-sensitive enteropathy**. It is an *_immunemediated enteropathy triggered by the ingestion of gluten-containing cereals, such as wheat, rye, or barley, in genetically predisposed individuals_*. In countries where most people are **Caucasians of European ancestry, celiac disease i**s a common disorder, with an estimated prevalence of 0.5% to 1%.

Answer 15

because the e**nvironmental precipitant, gluten**, is known.

Answer 16

Gluten is the **major storage protein of wheat** and **similar grains, and the alcohol-soluble fraction** of **gluten, gliadin,** contains most of the disease-producing components.

Answer 17

Gluten is digested **by luminal and brush-border** enzymes **into amino acids and peptides,** including a **33–amino acid α-gliadin peptide** that is **resistant to degradation by gastric,** **pancreatic, and small intestinal proteases** ( Fig. 17-25 ).

Answer 18

The **network of immune reactions** to **gliadin that are thought to result in celiac disease** is illustrated below. Some **gliadin peptides induce epithelial cells** to **express IL-15**, which in **turn triggers activation** and **proliferation of CD8+ intraepithelial lymphocytes** that are induced to express NKG2D, a natural killer cell marker. ``` These **lymphocytes become cytotoxic and kill enterocytes with surface MIC-A, an HLA class I–like protein** expressed in response to stress. ``` NKG2D is the receptor for MIC-A. Thus, unlike the CD4+ T cells, these NKG2D+ CD8+ T cells do not recognize gliadin. The resulting epithelial damage may contribute to the process by which other gliadin peptides cross the epithelium to be deamidated by tissue transglutaminase. Deamidated gliadin peptides are then able to interact with HLA-DQ2 or HLA-DQ8 on antigen-presenting cells and be presented to CD4+ T cells. These T cells produce cytokines that contribute to tissue damage and the characteristic mucosal pathology.

Answer 19

FIGURE 17-25 The left panel illustrates the morphologic alterations that may be present celiac disease, including villous atrophy, increased numbers of intraepithelial lymphocytes (IELs), and epithelial proliferation with crypt elongation (compare to Fig. 17-26 ). The right panel depicts a model for the pathogenesis of celiac disease. Note that both innate and adaptive immune mechanisms are involved in the tissue responses to gliadin.

Answer 20

While **nearly all people eat grain and are exposed to gluten and gliadi**n**, most do not develop celiac disease.** ***_Thus, host factors determine whether disease develops_***

Answer 21

. Among these, **HLA proteins** seem to be critical, since almost **all people with celiac disease carry the class II HLADQ2** **or HLA-DQ8 allele.** However, the HLA locus accounts for less than half of the genetic component of celiac disease. Remaining genetic factors may include polymorphisms of immuneregulatory genes, such as those **encoding IL-2, IL-21, CCR3, and SH2B3,** [46] and genes that determine epithelial polarity. [47,] [48]

Answer 22

* type 1 diabetes, * thyroiditis, and * Sjögren syndrome, as well as * ataxia, * autism, * depression, * some forms of epilepsy, * IgA nephropathy, * Down syndrome, and * Turner syndrome.

Answer 23

**Biopsy specimens** from the **second portion of the duodenum or proximal jejunum,** which are ***_exposed to the highest concentrations of dietary gluten,_*** are generally diagnostic in celiac disease.

Answer 24

The histopathology is characterized by **increased numbers of intraepithelial CD8+ T lymphocytes *_(intraepithelial lymphocytosis)_***, ***_crypt hyperplasia,_*** and ***_villous atrophy_* (** Fig. 17-26 ). This loss of mucosal and brush-border surface area probably accounts for the malabsorption. In addition, increased rates of epithelial turnover reflected in increased crypt mitotic activity, may limit the ability of absorptive enterocytes to fully differentiate and contribute to defects in terminal digestion and transepithelial transport.

Answer 25

* increased numbers of plasma cells, * mast cells, * and eosinophils, especially within the upper part of the lamina propria.

Answer 26

. With increased frequency of serologic screening and early detection of disease-associated antibodies, it is now appreciated that an ***_increase in the number of intraepithelial lymphocytes_***, particularly ***_within the villus_***, is a marker of less advanced celiac disease. [49 However, intraepithelial lymphocytosis and villous atrophy are **not specific for celiac disease** and can be **present in other diseases, including viral enteritis.** ****The combination of histology and serology is most specific for diagnosis of celiac disease

Answer 27

The **combination of histology and serology** is most specific for diagnosis of celiac disease

Answer 28

FIGURE 17-26 Celiac disease. * A, Advanced cases of celiac disease show complete loss of villi, or total villous atrophy. Note the dense plasma cell infiltrates in the lamina propria. * B, Infiltration of the surface epithelium by T lymphocytes, which can be recognized by their densely stained nuclei (labelled T). Compare to elongated, pale-staining epithelial nuclei (labelled E).

Answer 29

**of 30 and 60**. However, many cases escape clinical attention for extended periods **because of atypical presentations.**

Answer 30

Some patients **may have silent celiac disease**, defined as **positive serology and villous atrophy** **without symptoms.**

Answer 31

in which **positive serology** is *_**not accompanied by villous atrophy.**_*

Answer 32

* anemia, * chronic diarrhea, * bloating, or * chronic fatigue.

Answer 33

women, perhaps **because monthly menstrual bleeding increases the demand for iron and vitamins****and accentuates the effects of impaired absorption.**

Answer 34

malabsorption or atypical symptoms affecting almost any organ. [50]

Answer 35

In those with classic symptoms, disease typically **begins between ages of 6 and 24 months,** after introduction of gluten to the diet, and includes: * irritability, * abdominal distention, * anorexia, * chronic diarrhea, * failure to thrive, * weight loss, or * muscle wasting. [50]

Answer 36

Children with nonclassic symptoms tend to present at **older ages with complaints of abdominal pain, nausea, vomiting, bloating, or** **constipation.** Common extra-intestinal complaints include arthritis or joint pain, seizure disorders, aphthous stomatitis, iron deficiency anemia, pubertal delay, and short stature.

Answer 37

A characteristic itchy, blistering skin lesion, dermatitis herpetiformis, can be present in as many as 10% of patients, and the incidence of lymphocytic gastritis and lymphocytic colitis is also increased.

Answer 38

a glutenfree diet, but, despite the challenges of adhering to this diet, it does result in symptomatic improvement for most patients. A gluten-free diet may also reduce the risk of long-term complications including anemia, female infertility, osteoporosis, and cancer

Answer 39

Noninvasive serologic tests are generally performed prior to biopsy. [51]

Answer 40

* **presence of IgA antibodie**s to tissue transglutaminase * **or IgA or IgG antibodies to** **deamidated gliadin**.

Answer 41

**Anti-endomysial antibodies a**re highly specific but less sensitive than other antibodies.

Answer 42

In cases with negative IgA tests, IgA deficiency, which is more common in celiac patients, should be ruled out. If IgA deficiency is present, titers of IgG antibodies to tissue transglutaminase and deamidated gliadin should be measured. The absence of HLA-DQ2 or HLA-DQ8 is useful for its high negative predictive value, but the presence of these alleles is not helpful in confirming the diagnosis.

Answer 43

**enteropathy-associated T-cell lymphoma** , -is an aggressive lymphoma of intraepithelial T lymphocytes. Small intestinal adenocarcinoma is also more frequent in individuals with celiac disease. Thus, **when symptoms such as abdominal pain,** **diarrhea, and weight loss develop despite a strict gluten-free diet,** *_cancer or refractory sprue,_* in which the response to a gluten-free diet is lost, must be considered. It is, however, important to remember that **failure to adhere to a gluten-free diet** is the **most common cause of recurrent symptoms,**and that most people with celiac disease do well with dietary restrictions and die of unrelated causes.

Answer 44

**response to a gluten-free diet is lost, must be considered.**

Answer 45

is a **malabsorption syndrome** that occurs **almost exclusively in people living in or visiting the tropics,**including *_**Puerto Rico, the Caribbean, northern South America, West Africa, India, and Southeast Asia.**_* Inexplicably, it is uncommon in Jamaica. The disease is generally endemic, although epidemics have occurred.

Answer 46

are **similar to celiac disease**, bu**t total villous atrophy is uncommon,**and**tropical sprue tends to involve the distal small bowel.** The latter probably **explains the frequency of folate or vitamin B12 deficiencies with enlarged (megaloblastic) nuclei within epithelial cells** that are reminiscent of those seen in pernicious anemia

Answer 47

**tropical sprue tends to involve the distal small bowel.**

Answer 48

Malabsorption usually becomes apparent within days or a few weeks of an acute diarrheal enteric infection in visitors. Although no definite causal organism has been identified, **overgrowth of aerobic enteric bacteria has been documented,** and **broad-spectrum antibiotics usually effect rapid recovery.** Various infections, including Cyclospora or enterotoxigenic bacteria, have been suggested as etiologic factors.

Answer 49

is an ***_X-linked disorder_* characterized** by ***_severe persistent diarrhea_*** and **autoimmune disease that occurs most often in *_young children_***.

Answer 50

A particularly *_**severe familial form, termed IPEX**_*, an acronym denoting**immune*****_dysregulation, polyendocrinopathyenteropathy, and X-linkage,_*** is due to a germline mutation in the**FOXP3**gene, which is located on the ***_X chromosome._***

Answer 51

is a **transcription factor** expressed in CD4+ regulatory T cells, [53] and individuals with IPEX and FOXP3 mutations have **defective T-regulatory function.** Other defects in regulatory T cell function have also been linked to less severe forms of autoimmune enteropathy. Autoantibodies to enterocytes and goblet cells are common, andsome patients may have antibodies to parietal or islet cells. Within the small intestine intraepithelial lymphocytes may be increased, but not to the extent seen in celiac disease, and neutrophils are often present. **Therapy includes immunosuppressive drug**s such as cyclosporine and, in rare cases, bone marrow transplantation.

Answer 52

* *apical brush-border membrane** of the * *villus absorptive epithelial cells.**

Answer 53

1. Congenital lactase deficiency 2. Acquired lactase deficiency

Answer 54

caused by a **mutation in the gene encoding lactase,** [55] is an autosomal recessive disorder. The disease is **rare** and presents as *_**explosive diarrhea with watery**_*, ***_frothy stools_*** and ***_abdominal distention upon milk ingestion._*** Symptoms abate when exposure to milk and milk products is terminated, thus removing the osmotically active but unabsorbable lactose from the lumen.

Answer 55

is caused by **down-regulation of lactase gene** expression and is particularly common among **Native Americans, African-Americans, and Chinese populations.**

Answer 56

Disease presents after childhood, perhaps reflecting the fact that, before farming of dairy animals**, lactase was unnecessary after children stopped drinking mothers' milk.**

Answer 57

is s**ometimes associated with enteric viral or bacterial infections.**

Answer 58

Symptoms, including *_**abdominal fullness, diarrhea, and flatulence**_*, due to ***_fermentation of the unabsorbed sugars_*** by colonic bacteria, are triggered by ingestion of lactose-containing dairy products.

Answer 59

**rare autosomal recessive disease** characterized by an **inability to secrete triglyceride-rich lipoprotein**s.

Answer 60

It is caused by a **mutation in the microsomal triglyceride transfer protein (MTP)** that catalyzes transport of triglycerides, cholesterol esters, and phospholipids. MTP-deficient enterocytes are **unable to export lipoproteins and free fatty acids.** *_**As a result, monoglycerides cannot be assembled into chylomicrons and triglycerides accumulate within the epithelial cells**_*. The malabsorption of abetalipoproteinemia is therefore a ***_failure of transepithelial transport._*** Lipid vacuolization of small intestinal epithelial cells is evident under the light microscope and **can be highlighted by special stains, such as oil red-O, particularly after a fatty meal.**

Answer 61

Abetalipoproteinemia **presents in infancy** and the clinical picture is ***_dominated by failure to thrive, diarrhea, and steatorrhea_***. Patients also have a *_**complete absence of all plasma lipoproteins containing apolipoprotein B,**_***although the gene that encodes apolipoprotein B itself is not affected.** Failure to absorb essential fatty acids leads to deficiencies of fat-soluble vitamins as well as lipid membrane defects that can be recognized by the **presence of acanthocytic red cells (burr cells) in peripheral blood smears.**

Answer 62

**Failure to absorb essential fatty acids** leads to **deficiencies of fat-soluble vitamins** as well as **lipid membrane defects**