tbl 3 pathology reading Flashcards
Intussusception occurs when a segment of the intestine, constricted by a wave of ____________, telescopes into the immediately distal segment . Once trapped, the invaginated segment is propelled by peristalsis and pulls the mesentery along.
Untreated intussusception may progress to _________, compression of mesenteric vessels, and infarction.
Intussusception is the most common cause of intestinal obstruction in children younger than 2 years of age. There usually is no underlying anatomic defect and the child is otherwise healthy. Other cases are associated with viral infection and rotavirus vaccines and may be related to reactive hyperplasia of Peyer patches, which can act as the leading edge of the intussusception.
_______________ are diagnostically useful and also are effective in correcting idiopathic intussusception in infants and young children. However, surgical intervention is necessary when an intraluminal mass or tumor serves as the initiating point of traction, as is typical in older children and in adults.
peristalsis; intestinal obstruction; Contrast enemas
Hirschsprung Disease
The enteric neuronal plexus develops from __________ that migrate into the bowel wall during embryogenesis. Hirschsprung disease, also known as ____________________, results when the normal migration of neural crest cells from cecum to rectum is disrupted. This produces a distal intestinal segment that lacks both the Meissner submucosal plexus and the Auerbach myenteric plexus (“aganglionosis”), and thus fails to develop coordinated peristaltic contractions. Mutations in the __________ account for a majority of familial cases and approximately 15% of sporadic cases. Mutations in other genes, including disease-modifying genes, as well as environmental factors must also be involved.
Hirschsprung disease always affects the rectum, but the length of the additional involved segments varies. Most cases are limited to the ___________, but severe disease can involve the entire colon. The aganglionic region may have a grossly normal or contracted appearance, while the normally innervated proximal colon may undergo ____________ as a result of functional distal obstruction. Diagnosis is made by demonstrating the absence of ganglion cells in the affected segment.
neural crest cells; congenital aganglionic megacolon; receptor tyrosine kinase RET
rectum and sigmoid colon; progressive dilation
Any weakness or defect in the wall of the peritoneal cavity may permit protrusion of a serosa-lined pouch of peritoneum called a hernia sac. Acquired hernias most commonly occur anteriorly, through the inguinal and femoral canals or umbilicus, or at sites of surgical scars. These are of concern because of ____________. This is particularly true of inguinal hernias, which tend to have narrow orifices and large sacs. Small bowel loops herniate most often, but portions of omentum or large bowel also protrude, and any of these may become entrapped. Pressure at the neck of the pouch may impair venous drainage, leading to __________________. These changes increase the bulk of the herniated loop, leading to permanent entrapment, or incarceration, and over time, arterial and venous compromise, or strangulation, can result in infarction.
visceral protrusion (external herniation); stasis and edema
Diarrhea is defined as an increase in stool mass, frequency, or fluidity, typically to amounts greater than 200 grams per day. In severe cases, stool volume can exceed 14 L per day and, without fluid resuscitation, result in death. Worldwide, diarrheal diseases account for greater than 700,000 deaths of children under 5 years of age, making them the second leading cause of death in this age group. Painful, bloody, small-volume diarrhea is known as __________. Diarrhea is a common symptom of many intestinal diseases, including those due to infection, inflammation, ischemia, malabsorption, and nutritional deficiency. It can be classified into four major categories:
- Secretory diarrhea is characterized by __________ and persists during fasting.
- Osmotic diarrhea, such as that occurring with lactase deficiency, is due to osmotic forces exerted by unabsorbed luminal solutes. The diarrheal fluid is at least 50 mOsm more concentrated than plasma, and the condition abates with fasting.
- ________________ caused by inadequate nutrient absorption is associated with steatorrhea and is relieved by fasting.
- Exudative diarrhea is due to inflammatory disease and characterized by ______________ that continue during fasting.
dysentery; isotonic stool; Malabsorptive diarrhea; purulent bloody stools
Malabsorption results from disturbance in at least one of the four phases of nutrient absorption:
1) ____________, in which proteins, carbohydrates, and fats are broken down into absorbable forms
2) ____________, which involves the hydrolysis of carbohydrates and peptides by disaccharidases and peptidases, respectively, in the brush border of the small-intestinal mucosa
3) _____________, in which nutrients, fluid, and electrolytes are transported across and processed within the small-intestinal epithelium
4) Lymphatic transport of absorbed lipids
Intraluminal digestion; Terminal digestion; Transepithelial transport
[Celiac disease pathogenesis]
Celiac disease is an intestinal immune reaction to gluten, the major storage protein of wheat and similar grains. Gluten is digested by luminal and brush border enzymes into amino acids and peptides, including a 33–amino acid ___________ that is resistant to degradation by gastric, pancreatic, and small-intestinal.
Gliadin is deamidated by tissue transglutaminase and is then able to interact with _______________ on antigen-presenting cells and be presented to CD4+ T cells. These T cells in ____________ produce cytokines that likely contribute to the tissue damage and characteristic mucosal histopathology.
An antibody response follows: This includes production of antibodies against tissue transglutaminase, deamidated gliadin, and, perhaps as a result of cross-reactive epitopes, anti-endomysial antibodies, which can be diagnostically useful. In addition to CD4+ cells, there is an accumulation of CD8+ cells that are not specific for gliadin but may play an ancillary role in causing tissue damage. It is thought that deamidated gliadin peptides induce epithelial cells to produce the ____, which in turn triggers activation and proliferation of CD8+ intraepithelial lymphocytes that become cytotoxic and kill enterocytes that have been induced by various stressors to express surface MIC-A. This molecule is recognized by the NKG2D receptor on activated CD8+ T cells. The damage caused by these immune mechanisms may increase the movement of gliadin peptides across the epithelium, which are then deamidated by tissue transglutaminase, thus perpetuating the cycle of disease.
While nearly all individuals eat grain and are exposed to gluten and gliadin, most do not develop celiac disease. Thus, host factors determine whether disease develops. Among these, HLA proteins seem to be critical, since almost all individuals with celiac disease carry the class II HLA-DQ2 or HLA-DQ8 alleles. There is also an association of celiac disease with other immune diseases including type 1 diabetes, thyroiditis, and _________________.
gliadin peptide; HLA-DQ2 or HLA-DQ8; lamina propria; cytokine IL-15; Sjögren syndrome
[celiac disease morphology]
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. The histopathology is characterized by increased numbers of T lymphocytes, with _____________, crypt hyperplasia , and villous atrophy . This loss of mucosal and brush-border surface area due to villous atrophy probably accounts for the malabsorption.
In addition, increased rates of epithelial turnover, reflected in increased ________, may limit the ability of absorptive enterocytes to fully differentiate and express proteins necessary for terminal digestion and transepithelial transport. Other histologic features of celiac disease can include increased numbers of plasma cells, mast cells, and eosinophils, especially within the _____________. It should be noted that intraepithelial lymphocytosis and villous atrophy can be present in other disorders, including viral enteritis. The combination of histologic and serologic findings is, therefore, most specific for diagnosis of celiac disease.
intraepithelial lymphocytosis;
crypt mitotic activity;
upper part of the lamina propria
[celiac disease clinical features]
Pediatric celiac disease, which affects male and female children equally, may manifest with classic symptoms, typically between 6 and 24 months of age (after introduction of gluten to the diet) with irritability, abdominal distention, anorexia, diarrhea, failure to thrive, weight loss, or muscle wasting. Children with nonclassic symptoms tend to present at older ages with complaints of abdominal pain, nausea, vomiting, bloating, or constipation. A characteristic pruritic, blistering skin lesion,____________, is also present in as many as 10% of patients, and the incidence of lymphocytic gastritis and lymphocytic colitis is increased as well.
In adults, celiac disease manifests most commonly between 30 and 60 years of age. However, many cases escape clinical attention for extended periods because of atypical presentations. Some patients have silent celiac disease, defined as positive serology and villous atrophy without symptoms, or latent celiac disease, in which positive serology is accompanied neither by villous atrophy nor symptoms. Symptomatic adult celiac disease is often associated with __________(due to iron deficiency and, less commonly, B 12 and folate deficiency), diarrhea, bloating, and fatigue.
Noninvasive serologic tests are generally performed before biopsy. The most sensitive tests are the presence of IgA antibodies to ___________ or IgA or IgG antibodies to _____________. Anti-endomysial antibodies are highly specific but less sensitive than other antibodies.
Patients with celiac disease exhibit a higher than normal rate of malignancy. The most common celiac disease–associated cancer is ______________, an aggressive tumor of intraepithelial T lymphocytes. Small-intestinal adenocarcinoma also is 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 recognize that failure to adhere to a gluten-free diet is the most common cause of recurrent symptoms, and that most individuals with celiac disease do well with dietary restrictions and die of unrelated causes.
dermatitis herpetiformis; anemia; tissue transglutaminase ; deamidated gliadin;
enteropathy-associated T cell lymphoma
