Pathology of the Gastro Intestinal Tract part II
Objectives of: Pathology of the gastrointestinal tract part II1- identify diseases of the stomach, including: Congenital hypertrophic pyloric stenosis Acute gastritis its causes and pathogenesis Chronic gastritis, types and pathogenesis Peptic ulcer disease: pathogenesis, types, causes, pathological features and complications. Gastric tumors and tumor like conditions. 2- identify diseases of small and large bowel, including: Congenital anomalies Infectious conditions Mal-absorption syndrome
DISEASES OF THE STOMACH
Congenital hypertrophic pyloric stenosisAffect male infants four times more often than females. Persistent, projectile vomiting usually appears in the second or third week of life. There is visible peristalsis and a firm, ovoid palpable mass in the region of the pylorus. resulting from hypertrophy and hyperplasia of the muscularis propria of the pylorus.
Acquired pyloric stenosis in adults may complicate 1. Antral gastritis or peptic ulcers close to the pylorus. 2. Malignancy e.g. carcinomas of the pyloric region or adjacent panceas, or gastric lymphomas 3. Hypertrophic pyloric stenosis (rare) due to prolonged pyloric spasm
A 54 year old woman complains of burning pain in her epigastrium and vomiting a few days after she started taking medication for her rheumatoid arthritis. Which of the following forms of gastritis would most likely be found in this patient? a. Acute gastritis b. Chronic antral gastritis c. Chronic fundal gastritis d. Hypertrophic gastritis e. Lympocytic gastritis
Acute gastritis Usually transient in nature. The inflammation may be accompanied by hemorrhage into the mucosa (acute hemorrhagic gastritis) and sometimes by (mucosal erosions) Acute erosive gastritis is an important cause of acute upper gastrointestinal bleeding. Although a large number of cases have no obvious cause (idiopathic), acute gastritis is frequently associated with: 1. Heavy use of nonsteroidal anti-inflammatory drugs (NSAIDs) particularly aspirin, cancer chemotherapeutic drugs, 2. radiation 3. Excessive consumption of alcohol, 4. heavy smoking5. ingestion of strong acids or alkali as in suicidal attempts 6. Uremia 7. Severe stress (e.g., trauma, burns, surgery) 8. Mechanical trauma (e.g., nasogastric intubation) 9. Distal gastrectomy (reflux of duodenal contents).
Acute hemorrhagic & erosive gastritis
Diffuse hyperemia with punctate haemorrhages
Multiple generally small ulcers & erosions are present.
A 57 year old woman with anemia is found to have a decreased Vitamin B12 level. Antibodies to intrinsic factor are identified. Levels of all other vitamins are within normal limits. Which of the following is most likely to be associated with this condition? a. Duodenal ulcer b. Ulcerative colitis c. Dietary Vit. B12 deficiency d. Atrophic gastritis e. Angiodysplasia
Chronic Gastritis is defined as "chronic inflammation of the gastric mucosa that eventuates in mucosal atrophy and intestinal metaplasia". The epithelial changes may progress to dysplasia, which constitute a soil for the development of carcinoma. Pathogenesis Major etiologic associations of chronic gastritis are: 1. Chronic infection by H. pylori 2. autoimmune damage 3. Excessive alcohol consumption & heavy cigarette smoking 4. Post-antrectomy (due to reflux of bile-containing duodenal secretions) 5. Outlet obstruction, uremia, and other rare causes
Helicobacter pylori Infection and Chronic Gastritis Infection by H. pylori is the most important etiologic cause of chronic gastritis. Those with H. pylori-associated chronic gastritis are at increased risk for the development of: Peptic ulcer disease 2. Gastric carcinoma 3. Gastric non-Hodgkin’s lymphoma H. pylori are curvilinear, gram-negative rods. They have adapted to survive within the superficial mucus layer on the surface and within the gastric pits, which is lethal to most bacteria. They do not invade the mucosa. The specialized features that allow these bacteria to flourish include: 1. Motility (via flagella), allowing them to swim through the viscous mucus2. Urease production, which releases ammonia and CO2 from endogenous urea, thereby buffering the harmful gastric acid in the immediate vicinity of the bacteria3. Expression of adhesion molecules, which enhances binding of the bacteria to adjacent foveolar cells
The bacteria appear to cause gastritis by stimulating - production of pro-inflammatory cytokines - directly damaging epithelial cells by toxins e.g. vacuolating toxin (VacA), urease, proteases and phospholipases. After initial exposure to H. pylori, gastritis occurs in two patterns: 1. Antral-predominant gastritis with high acid production and elevated risk for duodenal ulcer 2. Pan gastritis with low acid secretion and higher risk for adenocarcinoma IL-1β is a potent pro-inflammatory cytokine and a powerful gastric acid inhibitor. Infected patients with higher IL-1β production pangastritis, lower IL-1β production antral-predominant gastritis.
A number of diagnostic tests have been developed for the detection of H. pylori. 1. Noninvasive tests including a. Serologic test for antibodies b. Stool culture for bacterial detection c. Urea breath test: based on the generation of ammonia by bacterial urease. 2. Invasive tests: detection of H. pylori in gastric biopsy tissue samples including a. visualization of the bacteria in histologic sections with special stains b. bacterial culture of the biopsy c. bacterial DNA detection by the polymerase chain reaction
Helicobacter gastritis: Staining of the gastric biopsy shows the characteristic curved rods embedded in the mucin layer of the stomach. Helicobacter organisms may be tested for urease activity.
Rod-shaped organisms are present along the luminal surfaces of the epithelium and in the luminal mucus. They do not invade the mucosa. They are best seen on giemsa stain, where they stain bluish-purple.
H. pylori gastritis (Giemsa stain)
Autoimmune gastritis About 10% of chronic gastritis are autoimmune in nature. It results from the presence of autoantibodies to components of parietal cells, including the acid-producing enzyme H+/K+-ATPase, gastrin receptor, and intrinsic factor. Gland destruction and mucosal atrophy lead to loss of acid production (hypo- or achlorhydria). In the most severe cases, production of intrinsic factor is also impaired, leading to pernicious anemia. Affected patients have a significant risk for developing gastric carcinoma and endocrine tumors (carcinoid tumor).
Autoimmune chronic gastritis Anti-parietal cell antibody Immunofluorescence technique
Gross (endoscopic) features The mucosa of the affected regions is usually hyperemic and has coarser rugae than normal. With long-standing disease, the mucosa may become thinned and flattened because of atrophy. Autoimmune gastritis is characterized by diffuse mucosal damage of the body-fundic mucosa, with sparing of antral rgion (Corpus-predominant gastritis). Environmental gastritis i.e. due to environmental etiologies (including H. pylori infection) tends to affect antral mucosa (antral gastritis) or both antral and body-fundic mucosa (pangastritis).CHRONIC GASTRITIS Heavy mainly chronic inflammatory cell infiltration of the lamina propria with glandular destruction (mucosal atrophy)
Lt. heavy chronic inflammatory cell infiltration of the lamina propria with acute neutrophilic component; a collection of neutrophils is present within & outside one of the glands (arrows).
Rt. Heavy infiltration by plasma cells with glandular destruction.
CHRONIC GASTRITIS
Chronic atrophic gastritis with intestinal metaplasia and glandular atrophy
Several additional histologic features are characteristic; these include Intestinal metaplasia: the mucosa may become partially replaced by metaplastic columnar cells and goblet cells of intestinal morphology; these may display flat or villous arrangement. If columnar cells are absorptive (with ciliated border) the metaplasia is termed complete, otherwise it is incomplete. Atrophy: marked loss of the mucosal glands. Parietal cells, in particular, may be absent in the autoimmune form. Dysplasia: with long-standing chronic gastritis, the epithelium develops dysplastic changes. Dysplastic alterations may become so severe as to constitute in situ carcinoma. The development of dysplasia is thought to be a precursor lesion of gastric cancer. It occurs in both autoimmune and H. pylori- associated chronic gastritis.A 50yr old man who is on NSAIDs for his heart problem for last 4yrs and smokes 2 pack cigarette per day last 10-15yrs presents in OPD with the c/o recurrent epigastric pain 15-20 min after taking meal which is relieved by vomiting. What is the diagnosis? a. Coelic disease b. Peptic ulcer disease c. Gastric ca d. Gastro Esophageal Reflux Disease e. Cholecystitis
PEPTIC ULCER DISEASE An ulcer is "a breach in the mucosa of the alimentary tract that extends into the submucosa or deeper." Erosions are limited to the mucosa and do not extend into the submucosa.
Peptic Ulcers are chronic, most often solitary lesions and usually small. They occur in any portion of the GIT exposed to the aggressive action of acid-peptic juices. They are located, in descending order of frequency in: 1. Duodenum (first portion) 2. Stomach, (usually antral, along the lesser curve) 3. Gastro-esophageal junction (complicating GERD or Barrett esophagus) 4. Margins of a gastro-jejunostomy 5. Multiple in the duodenum, stomach, and/or jejunum (in Zollinger-Ellison syndrome) 6. Within or adjacent to a Meckel diverticulum (containing ectopic gastric mucosa) The male/female ratio for DU is 3:1, GU is 2:1. Women are most often affected at or after menopause.
Pathogenesis Peptic ulcers are produced by an imbalance between gastro-duodenal mucosal defenses and the damaging forces ( gastric acid and pepsin). Hyperacidity is not necessary; A minority of patients with DU have hyperacidity, It is even less common in those with GU
H. pylori infection is a major factor in the pathogenesis of peptic ulcer. It is present in virtually all patients with DU and in about 70% of those with GU.With present-day therapies aimed at inhibition of acid secretion (H2 receptor antagonists and parietal cell H+/K+-ATPase pump inhibitors), and eradication of H. pylori infection (with antibiotics), most ulcers heal within a few weeks.Antibiotic treatment of the H. pylori infection also prevents their recurrence. The possible mechanisms by which this tiny organism impairs mucosal defenses include: 1- H. pylori induce intense inflammatory and immune responses production of pro-inflammatory cytokines, (esp. IL-8) by the mucosal epithelial cells. Recruitment & activation of neutrophils with their damaging properties.
2- Several bacterial products (esp. vacuolating toxin called Vac A) cause epithelial cell injury; 3- H. pylori secrete urease, proteases & phospholipases which cause direct epithelial damage. 4- H. pylori enhance gastric acid secretion and impair duodenal bicarbonate production, thus reducing luminal pH in the duodenum with its damaging effects on the duodenal mucosa.5- Thrombotic occlusion of surface capillaries is provoked by a bacterial platelet-activating factor. ischemic mucosal damage. Most persons (80-90%) infected with H. pylori do not develop peptic ulcers. Perhaps there are unknown interactions between H. pylori and the mucosa that occur only in some individuals.
Other contributing factors to peptic ulceration 1. Gastric hyperacidity, when present, may be strongly ulcerogenic. The classic example is Zollinger-Ellison syndrome, in which there are multiple peptic ulcerations in the stomach, duodenum, and even jejunum. This is due to excess gastrin secretion by a gastrinoma and, hence, excess gastric acid production. 2. Chronic use of NSAIDs suppresses mucosal prostaglandin synthesis; aspirin also is a direct irritant. 3. Cigarette smoking impairs mucosal blood flow and healing of the ulcer. 4. Corticosteroids in high doses and with repeated use encourage ulcer formation.
5. In some patients with duodenal ulcers, there is rapid gastric emptying, exposing the duodenal mucosa to an excessive acid load. 6. Patients with alcoholic cirrhosis, chronic obstructive pulmonary disease, chronic renal failure hyperparathyroidism are more prone to develop duodenal ulcer. Chronic renal failure and hyperparathyroidism are associated with hypercalcemia, which stimulates gastrin production and acid secretion. 7. Personality and psychological stress are important contributing factors, even though data on cause and effect are lacking.
Causes and defense mechanisms against peptic ulceration
CHRONIC DU: Well-defined rounded ulcer with undermined edge. Note the hyperemia due to associated duodenitis.GU of small & large size on upper endoscopy. All gastric ulcers are biopsied to exclude malignancy. Smaller, more sharply demarcated ulcers with radiating mucosal folds are more likely to be benign.
Gross features The vast majority of peptic ulcers are located in the first portion of the duodenum or in the stomach, in a ratio of about 4:1. Gastric and duodenal ulcers may coexist in up to 20% of the cases. Gastric ulcers are predominantly located along the lesser curvature. Although over 50% of peptic ulcers have a diameter less than 2 cm but about 10% are greater than 4 cm. Ulcerated carcinomas (which tend to be large) may be less than 4 cm in diameter and may be located anywhere in the stomach. Thus, size and location do not differentiate a benign from a malignant ulcer.
Benign peptic ulcer is a round to oval, sharply demarcated crater. The margins are usually level with the surrounding mucosa or only slightly elevated. Heaping-up of these margins is rare in the benign ulcer but is characteristic of the malignant ones. converging folds of mucosa (due to underlying fibrosis) gives benign peptic ulcers a spoke- or star-like appearance.
Sharply delimited chronic peptic ulcer with converging folds of mucosa in the upper half. The ulcer bed is covered by fibrinopurulent exudate.
Peptic ulcers penetrate the wall to a variable extent. When the entire wall is penetrated, the base of the ulcer may be formed by adherent pancreas, omental fat, or liver. The base of a peptic ulcer is smooth and clean, owing to peptic digestion of any exudate that may form. Sometimes, thrombosed or patent blood vessels (the source of life threatening hemorrhage) are evident at the base of the ulcer. Ulcer-related scarring may involve the entire thickness of the gastric wall; puckering of the surrounding mucosa creates mucosal folds that radiate from the crater in spoke-like fashion. This is different from malignant ulcers where there is flattening of the mucosal folds (because of malignant infiltration) in the immediately surrounding of the ulcerative
Chronic peptic ulcer: The external muscle layer has been totally destroyed. Note the overhanging mucosa on one edge and the sloping mucosa on the other.
Chronic peptic ulcer shows four layers The base and walls have a superficial thin layer of fibrinoid necrosis. Beneath this layer is a zone of predominantly neutrophilic inflammatory infiltrate. Deeper still, there is granulation tissue infiltrated with inflammatory cells. This rests on Fibrous or collagenous scar.
The complications of peptic ulcer disease are 1. Bleeding is the most frequent complication (20%). It may be life-threatening; fatal in 25% of the affected patients. It may be the first warning of an ulcer. 2. Perforation is much less frequent (5% of patients) but much more serious being fatal in 60% of patients. 3. Obstruction (from edema or scarring) occurs in 2%, most often due to pyloric channel ulcers but may occur with duodenal ulcers. Total obstruction with intractable vomiting is rare. 4. Malignant transformation does not occur with duodenal ulcers and is extremely rare with gastric ulcers. When it occurs, it is always possible that a seemingly benign gastric ulcer was, from the outset an ulcerative gastric carcinoma.
"Hourglass" stomach Due to chronic peptic ulceration there is fibrosis and contracture of the stomach leading to an hourglass shape as well as altered mobility.
There are multiple, small (less than 1 cm) and circular defects that occur anywhere in the stomach and sometimes in duodenum. The ulcer base is frequently stained a dark brown by the acid digestion of blood. The margins and base of the ulcers are not indurated The related mucosal folds (rugae) are normal (cf. chronic peptic ulcer, which show convergence on the ulcer)
Acute gastric ulcers
Microscopically Acute ulcers range in depth from mere shedding of the superficial epithelium (erosions) to deeper lesions that involve the entire mucosal thickness and deeper (ulceration). Unlike chronic peptic ulcers, there is no chronic gastritis or scarring. Healing with complete re-epithelialization occurs after the causative factor is removed. Acute ulcers are not precursors of chronic peptic ulcers Bleeding from superficial gastric erosions or ulcers sufficient to require transfusion develops in up to 5% of these patients. If the underlying cause is corrected recovery is complete.
GASTRIC TUMORS & TUMORS-LIKE CONDITIONSDivided into 1. Epithelial (++) 2. mesenchymal/stroma ___________________________________________________A. Benign B. malignantBENIGN TUMORSGastric polyps •A polyp is “any nodule or mass projecting above surrounding mucosa.” Mucosal polyps classified 1. Non-neoplastic Hyperplastic polypi, fundic gland polyps, hamartomatous Peutz-Jeghers polyps, juvenile polyps, and inflammatory fibroid polyp 2. Neoplastic. (adenomatous) polypi
Hyperplastic polyps (the most frequent; 90%) They’re small, sessile and multiple in about 25% of cases. Many of the lesions show central umbilication. There is hyperplasia of the surface epithelium and cystically dilated glandular tissue.
Hyperplastic polyp Polyps are due to proliferation of foveolar cells
Adenomatous polyp (adenoma) (10% of gastric polypi). They contain proliferative dysplastic epithelium & have malignant potential. They are usually single, and may grow up to 4 cm in size.CANCERS OF THE STOMACH - Gastric adenocarcinoma (90%)- Commonest- Gastric Non-Hodgkin’s Lymphomas (5%)- Carcinoids (3%)- Mesenchymal tumors (2%): gastrointestinal stromal tumors (GISTs), leiomyosarcoma, and schwannoma.
Epidemiology Of Gastric CarcinomaA common tumor in the worldMarked geographical variation in incidence - ↑↑ Japan, Chile, China, Russia- less common in USA, UK, Canada, Australia, France >> lower socioeconomic groups♂/♀: 2/1 Steady ↓ in incidence over past 60 yr/Still the leading cause of cancer death worldwide The advent of endoscopy (1960s)improvement in 5 yr survival rate/remain poor (20% in USA)
Gastric CA are morphologically of two main subtypes1. Intestinal type: bulky tumors, morphology: Forms glands2. Diffuse type: infiltrative tumors; Poorly differentiated discohesive malignant cells; no attempt of glandular formation •These two types have different pathogenesis1. Intestinal type predominates in high-risk areas & develops from precursor lesions Vs Diffuse type: incidence relatively constant/ no precursor lesions 2. Intestinal type: mean age of incidence of 55 yr; ♂/♀: 2/1 Vs Diffuse: younger patients; with equal gender incidence3. Drop in incidence occurred only for intestinal type; incidence of both is now the same
Pathogenesis •The major risk factors apply more to intestinal type1. Chronic Helicobacter pylori Infection- ↑ risk X5.- HP chronic gastritis atrophy/intestinal metaplasia dysplasiacarcinomaBacterial proteins/host immune response (genetic background) – Ch. mucosal inflam ↓HCl/pepsin secretion↑Bacterial growthchronic inflammationEpith cell damage &proliferation ↑risk of genomic mutation ↑oxidative stress
2- Environmental factors Diet suspected to be a primary factor, supported by migration studies. common in high risk areas are - Nitrites derived from nitrate (preserved food/water) - consumption of preserved/smoked/salted foods - lack of fresh fruit and vegetables - low socio-economic status - Smoking The intake of green, leafy vegetables and citrus fruits, which contain antioxidants such as vitamin C, vitamin E and beta-carotene, seems to play a protective role
3. Adenomas (harbor ca in 40%) (adjacent ca 30%)4. Autoimmune gastritis: due to chronic inflam. & intestinal metaplasia. 5. Genetic factors- Germ-line gene mutations (familial cases) of gastric canceri. family historyii. HNPCC syndrome: colonic ca/gastric caiii. E-cadherin gene mutations - early diffuse type adenocarcinoma/breast cancer- Blood group A (slight ↑)6. Partial gastrectomy for PUD (bile reflux)7. Menetrier's disease
Gross features of gastric carcinoma The most common location of gastric carcinomas is the pyloric antrum (50%). A favored location is the lesser curvature. Although less common, an ulcerative lesion on the greater curvature is more likely to be malignant.
Depth of invasion is the most important determinant of prognosis.
In early gastric carcinoma (A), the tumor is confined to the mucosa and submucosa and may exhibit an exophytic, flat or depressed, or excavated conformation. Advanced gastric carcinoma (B) extends into the muscularis propria and beyond. Linitis plastica is an extreme form of flat or depressed advanced gastric carcinoma.Early
Advanced
d
Polypoid (Fungating, exophytic) adenocarcinoma of the stomach (readily identified by radiography and endoscopy)
Adenocarcinoma-ulcerative (excavating)
Ulcerative carcinoma may closely mimic chronic peptic ulcers. However, in advanced cases, there are heaped-up, beaded margins and necrotic bases. The neoplastic tissue extends into the surrounding mucosa and wall; this leads to flattening of the mucosa surrounding the ulcer.The wall of the stomach is thickened & rubbery hard due to an extensive infiltration with diffuse type adenocarcinoma of signet ring cells.
Linitis plastic/diffuse type carcinoma
Intestinal type 0f gastric adenocarcinoma is characterized by the formation of infiltrative malignant glands
Diffuse-type carcinoma showing malignat signet ring cells
Gastric adenocarcinoma A, Intestinal type demonstrating gland formation by malignant cells, which are invading the muscular wall of the stomach. B, Diffuse type demonstrating signet-ring carcinoma cells.A
B
13- A 65 year old man presents to a physician because of a palpable mass immediately above the left clavicle. Biopsy of the mass demonstrates metastatic adenocarcinoma in a lymph node. Which of the following organs should be most strongly suspected as containing the primary tumor? a. Bladder b. Large bowel c. Liver d. Stomach e. Pancreas
Local extension of gastric Ca occur into the duodenum, pancreas & retroperitoneum Metastasis of gastric CaOccur to regional and distant LN.sHematogenous to liver (especially) and to lungSeeding of the peritoneum Virchow’s NodeMetastases from gastric carcinoma to the left supraclavicular area. Virchow’s node
Gastric Ca can also metastasize to the periumbilical region to form a subcutaneous nodule. This nodule is called a Sister Mary Joseph nodule after the nun who noted this lesion as a marker of metastatic carcinoma.
Typical gross appearance of Krukenberg tumors of ovary. The involvement is bilateral and the tumors are characterized by a multinodular outer appearance.
Although uncommon, metastatic adenocarcinoma to the ovaries (from stomach, breast, pancreas, and even gallbladder) is distinctive & designated Krukenberg tumor
Prognosis of gastric carcinoma This depends primarily on 1. The depth of invasion and 2. The extent of nodal and distant metastasis The histologic type (intestinal or diffuse) has minimal independent prognostic significance. The five-year survival rate of surgically treated early gastric cancer is 90%; This drops to below 15% for advanced gastric cancer.
Gastric Lymphomas represent 5% of all gastric malignancies. The stomach is the most common site for extra-nodal lymphoma (20%). Nearly all primary gastric lymphomas are B-cell type and of mucosa-associated lymphoid tissue (MALT lymphomas). The majority of gastric lymphomas (>80%) are associated with chronic gastritis and H. pylori infection. The role of H. pylori infection as an important etiologic factor for gastric lymphoma is supported by the elimination of about 50% of gastric lymphomas with antibiotic treatment for H. pylori. Generally, the prognosis of gastric lymphoma is better than carcinoma.
SMALL & LARGE INTESTINE
SMALL & LARGE INTESTINECONGENITAL ANOMALIES Anomalies of the intestine are rarely encountered; these include Duplication of the small intestine or colon; Malrotation of the entire bowel; Omphalocele (birth of an infant with herniation of abdominal contents into a ventral membranous sac related to umbilicus); Heterotopia of pancreatic tissue or gastric mucosa; Atresia and stenosis; imperforate anus (due to failure of the cloacal diaphragm to rupture).
A 10 year old boy complains of intermittent abdominal pain. Endoscopy fails to demonstrate peptic ulcer or chronic gastritis. The clinician suspects that the patient may have a heterotopic rest of gastric mucosa that is producing enough acid to cause ulceration of adjacent mucosa. Which of the following is the most likely diagnosis?a. Ectopic pancreatic tissueb. Meckel’s diverticulumc. False diverticulumd. Appendicitise. Cancer of the cecum
Meckel diverticulum Results from failure of involution of the vitelline duct, which embryologically connects the lumen of developing gut to the yolk sac. The small pouch lies on the antimesenteric side of the bowel, usually 30 cm proximal to the ileo-cecal valve. It consists of mucosa, submucosa, and muscularis propria. The mucosal lining may be that of normal small intestine, but heterotopic gastric mucosa or pancreatic tissue are frequently found. Meckel diverticula are present in 2% of the normal population, but most remain asymptomatic. When peptic ulceration occurs in the small intestinal mucosa adjacent to the heterotopic gastric mucosa, intestinal bleeding or symptoms simulating those of an acute appendicitis may result. Other complications include intussusception, incarceration, or perforation.
A to D, Meckel’s diverticulum that has undergone intussusception, as seen from the serosal side (A, B) and the mucosal side (C, D). Meckel's diverticulum
This is a Meckel's diverticulum from an adult that was excised because of blood loss from ulceration (a small red ulcer is seen. Meckel's diverticula may contain ectopic gastric mucosa (which can ulcerate surrounding mucosa with pain and bleeding) or ectopic pancreas (which is of no consequence unless it forms a mass large enough to predispose to intussusception). .
Meckel's diverticulum
After four days, a neonate has not passed meconium, and begins vomiting. Physical examination reveals abdominal distension. Which one of the following is the correct diagnosis? A. Hirchsprung's disease B. Meckel's diverticulum C. Omphalocele D. Renal agenesis E. Tracheoesophageal fistula
Hirschsprung’s disease colon
Hirschsprung’s disease colon In this congenital disorder there is absence of ganglia of the submucosal and myenteric neural plexuses, within a portion of the intestinal tract. The outcome is contraction and functional obstruction of the aganglionic segment (arrows) with secondary proximal dilation.Enterobius vermicularis (pinworms) These do not invade host tissue and live their entire life within the intestinal lumen. Adult worms living in the intestine migrate to the anal orifice at night, where the female deposits eggs on the perirectal mucosa. As the eggs are quite irritative, rectal and perineal pruritus ensues. Diagnosis is easily made by applying cellophane tape to the perianal skin and examining the tape for eggs under the microscope. Amebiasis is caused by the protozoan Entamoeba histolytica. The parasite infects approximately 500 million persons in developing countries resulting in approximately 40 million cases of dysentery and liver abscesses. The presence in stool of trophozoites containing ingested red blood cells is diagnostic. The patient may present with abdominal pain & bloody diarrhea.
Pathologic features Amebiasis most frequently involves the cecum and ascending colon. In severe cases, however, the entire colon is involved (pancolitis). Amebae invade through the crypt epithelium and burrow into the mucosa and submucosa, eliciting a neutrophilic reaction. They are stopped by the muscularis propria thus forced to spread out laterally to create a flask-shaped ulcer with a narrow neck and broad base. The mucosa between ulcers is often normal.
Characteristic rounded, slightly elevated areas of the mucosa with irregular yellow necrotic centers surrounded by edematous hyperemic tissue. Some times Hgic centres The intervening mucosal folds have a mostly normal appearance, although one segment is congested and edematous.
Amebic colitis
Amebic colitis
There is characteristic flask shaped ulcer extending into the submucosaAmebic colitis
Numerous ameba trophs causing lysis (histolytica) of the mucosa. Trophs are pale stained; Inflammatory cells dark stainedAmebic colitis
Amebae are round PAS positive organisms. Stain PASGiardiasis Giardia lamblia is the most common pathogenic parasitic infection in humans. Infection may cause acute or chronic diarrhea, steatorrhea, or constipation. Trophozoites multiply in the intestinal lumen. The flagellated trophozoite has two nuclei & resides in the duodenum, adhering to, but do not invade the intestinal epithelial cells. Tight contact between the parasite and the epithelial cell is made by a sucker-like disc. It also contains surface protein that resembles diarrhea-causing toxins secreted by certain snakes. The physical presence of rapidly proliferating trophozoites and their toxic proteins damages the microvillus brush border, causing a malabsorption.
Pathological features In stool smears, G. Iamblia trophozoites are pear shaped and binucleate. Duodenal biopsy specimens are often packed with sickle-shaped trophozoites, which are tightly bound to the surface of the small intestinal villi. As Giardia does not invade the mucosa, small intestinal morphology is often normal. Infected patients exhibit a malabsorptive diarrhea, owing to mucosal epithelial cell injury. Diagnosis Examination of stool for cysts Small intestinal biopsy or examination of a small intestinal aspirate that permit identification of the trophozoite.
Giardia lamblia
Giardia lamblia infection of the small intestine. The small pear-shaped trophozoites live in the duodenum and become infective cysts that are excreted. They produce a watery diarrhea. A useful test for diagnosis of infectious diarrheas is stool examination for ova and parasites.NECROTIZING ENTEROCOLITIS (NEC) This acute, necrotizing inflammation of the small and large intestines may progress to transmural necrosis of intestinal segments. It is the most common acquired gastrointestinal emergency of neonates, particularly those who are premature or of low birth weight. COLLAGENOUS AND LYMPHOCYTIC COLITIS These distinctive disorders of the colon are characterized by chronic watery diarrhea (no blood) Collagenous colitis is characterized by band-like collagen deposits directly under the surface epithelium, whereas lymphocytic colitis is characterized by prominent intraepithelial infiltrate of lymphocytes. Collagenous colitis occurs primarily in middle-aged and older women; lymphocytic colitis affects males and females equally. Radiographic studies are unremarkable, and endoscopy characteristically reveals normal mucosa. The pathogenesis of these conditions remains unclear. While collagenous colitis and lymphocytic colitis are uncommon, they must be considered in every adult patient who presents with a noninflammatory, watery diarrhea.
SOLITARY RECTAL ULCER SYNDROME This is an inflammatory condition of the rectum resulting from motor dysfunction of the anorectal musculature, in particular impaired relaxation of the anorectal sling. The latter may create sharp angulation of the anterior rectal wall. Abrasion of the overlying rectal mucosa creates an oval ulcer and surrounding mucosal inflammation. Associated partial prolapse of the rectal mucosa is common. Patients experience rectal bleeding & mucus discharge.
THE MALABSORPTION SYNDROMES Malabsorption is characterized by defective absorption of fats, fat-soluble and other vitamins, proteins, carbohydrates, electrolytes and minerals, and water. The most common clinical presentation is chronic diarrhea, and the hallmark of malabsorption is steatorrhea (excessive fecal fat content). Although many causes of malabsorption can be established clinically, small intestinal mucosal biopsy may be required to satisfactorily identify or exclude celiac disease.
Celiac Disease Celiac disease (gluten-sensitive enteropathy, GSE) is a chronic disease, in which there is a characteristic mucosal lesion of the small intestine and impaired nutrient absorption, which improves on withdrawal of wheat gluten from the diet.PathogenesisThe fundamental disorder in celiac disease is sensitivity to gluten component called gliadin, which is a protein present in wheat and closely related grains (e.g. oat). There is a T-cell mediated chronic inflammatory reaction, which develops as a consequence of a loss of tolerance to gluten. Interplay between genetic predisposing factors, the host immune response, and environmental factors, is central to disease pathogenesis. The small intestinal mucosa, when exposed to gluten, accumulates intraepithelial CD8+ T cells and large numbers of lamina propria CD4+ T cells, which are sensitized to gliadin.Gliadin is deamidated by the enzyme transglutaminase; the resultant peptides are recognized by CD4+ T cells. This leads to secretion of interferon γ, which damages enterocytes.
Pathological features By endoscopy, the duodenal mucosa appears flat (normally shows mucosal folds). Biopsies demonstrate enteritis with partial or total loss of villi (partial villous atrophy or completely flat mucosa respectively) The surface epithelium shows degeneration, loss of the microvillus brush border, and an increased number of intraepithelial lymphocytes. The crypts exhibit increased mitotic activity and are hyperplastic, so that, despite villous atrophy, the overall mucosal thickness remains the same. The lamina propria has an overall increase in plasma cells and lymphocytes. Although the above changes are characteristic of celiac disease, they can be mimicked by other diseases, most notably tropical sprue. Mucosal histology usually reverts to normal or near-normal following gluten exclusion from the diet. A characteristic skin-blistering lesion, dermatitis herpetiformis (DH), can occur in patients with celiac disease. Detection of serum anti-gliadin or "anti-endomysial" antibodies strongly favors the diagnosis of celiac disease.
Normal small intestinal mucosa is seen at the left, and mucosa involved by celiac sprue at the right. There is loss of villi with flattening of the mucosa*.
Comparison between normal mucosa and that of celiac disease
The small intestinal mucosa at high magnification shows marked chronic inflammation in celiac sprue. The enteropathy shown here has loss of crypts, increased mitotic activity, loss of brush border, and infiltration with lymphocytes and plasma cells.
Celiac disease small intestine mic
Jejunal mucosa in celiac disease. It is totally flat and devoid of villi, but its height is not decreased.Definitive diagnosis of celiac disease rests on clinical documentation of malabsorption demonstration of the intestinal lesions by small bowel biopsy and Definite improvement in both symptoms and mucosal histology on gluten withdrawal from the diet. If there is doubt about the diagnosis, gluten challenge (reintroduction of gluten to the diet) followed by rebiopsy has been advocated. Serologic tests, mentioned above, are used for screening or treatment follow-up. Most patients with celiac disease who adhere to a gluten-free diet remain well indefinitely and ultimately die of unrelated causes. However, there is a long-term risk of malignant disease, which includes small intestinal non-Hodgkin lymphoma (moderate risk), small intestinal adenocarcinoma, and esophageal squamous cell carcinoma (50- to 100-fold higher risk than the general population).