Acute Appendicitis And Tumors Of The Appendix.

                                       A normal appendix
  The Appendix is the normal diverticulum of the cecum and is prone for acute and chronic inflammation .
What is Acute Appendicitis?

•   Inflammation of the appendix .It is an emergency condition .
• Occurs in adolescents and young adults mostly.
• Males have a slightly higher risk .
• Should not be confused with mesentric lymphadenitis, acute salpingitis , ectopic pregnency, meckel's diverticulum.

Pathogenesis:

• Progressive increase in the intraluminal pressure which compromises the venous outflow.
• Normally associated with overt luminal obstruction, fecalith ,gall stone , tumours, and worm infestation .
• Ischemic injury and Stasis of blood favours the bacterial growth and hence forth leads to inflammation including tissue edema and neutrophil infiltrate of the lumen , muscular wall and the periappendiceal soft tissue.

Morphology:

• In Early Acute Appendicitis subserosal vessels are congested and there is modest perivascular infiltrate .
• The glisening serosa is hence forth turned dull , granular , and erythematous .
• Diagnosis involves neutrophil infiltrate into the lamina propria.
• Sometimes there is serosal fibrinopurulent reaction and hence this leads to focal abscess (Acute Suppurative Appendicitis)
• Further compromise leads to hemorragic ulceration and gangrenous necrosis (Acute Gangrenous Appendicitis) followed by rupture and suppurative peritonitis.

Clinical features:

• Periumbilical pain localised to lower right quadrant pain .
• Nausea ,vomiting .
• Low grade fever .
• Mildly elevated peripheral white cell count .
• Classical physical finding is McBurney's sign. deep tenderness located two thirds of the distance from the umbilicus to the right superior iliac spine (Mcburney's point).
• In a retro cecal appendix the pain may be to right flank or a pelvic pain.
• In a malrotated appendix the pain is in the left upper quadrant.
• Complications include pyelophlebitis, bacteremia, portal venous thrombosis, liver abscess.

The diagnosis of acute appendicitis in young adults is difficult as there are lots of other causes for abdominal emergencies. Even highly skilled surgeons remove normal appendices .This is preferred  to the delayed resection of a diseased appendix
Tumors of the Appendix:

• The most common one is the Carcinoid.
• Involves the distal tip of the appendix .
• Produces a solid bulbous swelling showning a intramural and transmural extension.
• Adenomas and non mucin producing Adenocarcinomas also occur leading to obstruction and enlargement.
• Mucocele,a dilated appendix that contains mucin and may be a complication of Mucinous cystadenoma or Mucinous cystadenocarcinoma.
• the above condition maylead to sesding in the pritonium and leads to the spred of the tumor although it is rare in the other conditions associated with the appendix.
• Psuedo myxoma peritonii,abdomen filled with tenacious semisolid mucin.This can be held in check by debulking but mostly it leads a fatal course.

CONGENITAL ABNORMALITIES OF THE GIT

What are the congenital abnormalities associated with the gastro intestinal tract?

       Depending upon the nature and timing of insult a large number of developmental abnormalities can affect the GI tract.Some of them are given here ..

Atresia,fistulae and duplications:

•      When present within the esophagus it is detected shortly after birth as it causes regurgitation.and they shoud be promptly corrected as the are incompatible for life.
• Agenesis refers to the total absence of the esophagus (rare)
• Atresia refers to the incomplete development .
• In esophageal atresia there is a thin non canalized cord replacing the segment of the esophagus and thereby causing mechanical obstruction .
• The proximal and distal parts of the esophagus are thus connected to the pharynx and the stomach respectively .
• Atresia commonly occurs near the bifurcation of the trachea and hence it can also cause fistula thus connecting the esophageal pouches to the parts of bronchus.
• Thus fistula formation causes aspiration ,perforation,suffocation , pneumonia and severe electrolyte imbalance.
• Esophageal atresia is associated with other congenital abnormalities like congenital cardiac abnormaliteis and neurologic defecits .
• Intestinal atresia is usally at the duodenum and ischaracterised by a segment of bowel lacking the lumen .
• Stenosis is an incomplete form of atresia which is charactrised by marked reduction in the caliber of the lumen and so it causes complete or the incomplete obstruction due to the fibrous thickening of the wall.
• Stenosis is most common in the esophagus and the small intestine .
• Imperforate anus is due to the failure od=f the cloacal diaphragm to involute.( most common intestinal atresia)
• Stenosis can also be caused by inflammatory scaring.
• Congenital duplication cysts may be saccular or elongated cystic masses containing smooth muscle layers  and may be found in the esophagus or small intestine.

Diaphragmatic hernia ,Omphalocele ,and Gatroschisis:

• Diaphragmatic hernia occurs when there is incompete formation of the diaphragm . This leads to the herniation of the abdominal contents into the thoracic cavity and in severe cases it may also lead to pulmonary hypoplasia.
• Omphalocele incomplete closure of the abdominal musculature  and so there is herniation into the ventral membraneous sac and is associated with other congenital abnormalities .
• Gastroschisis similar to the omphalocele but this involves all the layers form the peritonium to the skin.

Ectopia:

         These are developmental rests.

• Ectopic gastric mucosa may be present in the upper third of the mucosa (inlet patch)and if it causes acid production it leads to severe complications like dysphagia, esophagitis, barret's esophagus ,and rarely adenocarcinoma may be caused .
• Ectopic pancretic tissue may be aymptomatic or if prsent in the pyloric part of the stomach they may cause inflammation ->scaring ->complete or incomplete obstruction.
• They also mimic invasive cancer.
• Gastric heteropia ectopic gastric mucosa in the small bowel and colon and may lead to occult blood lossdue to peptic ulceration of the adjacent mucosa.

Meckel diverticulum:

• A True diverticulum is a outpoching of the alimentary tract, lined by the mucosa, and communicates with the lumen  and is lined by all the three layers of the bowel wall ( it has mucosa , sub mucosa, and mucularis propria) .The frequent one is the meckel's diverticulum .
• The Meckel diverticulum is due to the failed involution of the vittiline duct (which connects the developing gut to the yolk sac).
• It is a solitary diverticulum extending from the antimesentric side of the bowel.
• It is present in 2%of the patients ,presents at the age of 2,it is 2 inches long ,present within 2 feet of the ileocaecal valve, and occurs as twice as in males than in females  ( rule of 2's)
• This may also contain ectopic tissue.
• This leads to peptic ulcertion and leads to bleeding and abdominal pain and mimica acute appendicitis or intestinal obstruction .
• Most common site for other diverticula is sigmoid colon.

Pyloric stenosis:

       Congenital Hypertropic Pyloric Stenosis occurs with high risk in males , monozygotic twins,

turners syndrome , trisomy 18 and is associated with polygenic inheritance.

• Onset:second or third week of life as new onset regurgitation and presistant , projectile , non bilious vomiting.
• Physical examination: hyperperistalsis, ovoid, firm mass due to hypertropy of the muscularis propria thus leading to obstruction
• Edema and inflammtory changes in the mucosa and submucosa
• As a curative measure surgical splitting of the muscularisis done .(myotomy)
• Acquired pyloric stenosis is due to peptic ulceration .
• Carcinoma also causes stenosis.

Hirschsprung disease:

            Occurs in association with other congenital abnormalitis or may be isolated.

Pathogenesis:

•           It is also known as congenital aganglionic megacolon.
• Normally the enteric plexus develops from the neural crests that migrate to the bowel wall during embryogenesis.
• Here the migration of the neural crest cells from cecum to the rectum is arrested or there is immature death of the ganglionic cells .
• Distal intestinal segment lacks the auerbach myentric plexus and meissner's plexus.(aganglionosis).
• Peristalsis is absent and so there is obstruction and the proximal segment is dilated .
• There is genetic prepondrance .simple mendelian inheritance .
• Heterozygous loss of function mutation in the receptor tyrosine kinase RET
• Mutations associted with ehteric neuronal development including endothelins tyrosine kinase RET ligand glial neuratropic factor...
• Environmental and sex linked factors are also included.

Morphology:

• Done by examination of suction biopsy specimens and documenting the aganlionosis.
• Also by H&E stains and immunochemical stains .
• Rectum and sigmoid colon are affected .
• Aganglionic region is normal or contracted .
• The normal region is progressively dilated .and the proximal portionis massively distended .(megacolon)
• May even lead to rupture of the thin colonic wall.
• Intraoperative frozen section Transmural analysis gives the diagnosis.

Clinical features:

• Failure to pass meconium in the early years.and hence obstructive constipation  is caused.
• Serious complications include enterolitis,perforation , peritonitis, fluid and electrolyte imbalance .
• Treatment includes surgical resection of the distal portion and anastamosis .

Acquired megacolon is associated with chagas disease, neoplasms, ulcerative colitis ,visceral myopathy or functional diorders.

ACUTE GASTRITIS

what is acute gastritis?

• Transient mucosal inflammatory process.
• Asymptomatic to symptoms like epigastric pain, nausea ,vomiting.
• Complicated to erosions,ulceration,hematoma,malena(blood stained stools)hemorrhage and also massive chronic blood loss 

normal histology of stomach:

Pathogenesis:
        The gastric lumen is highly acidic and it helps in digestion yet it can also cause damage to the mucosa .The mucosal damge is protected by lots of mechanisms . Some are

• Mucin secreted by foveolar cells.
• Mucus forms an unstirred layer of fluid over the epihtelium and also forms a neutral pH.
• The rich vascular supply provides oxygen and nutrients and also washes away the acid the has back diffused into the lamina propria of the layer. 

Acute or Chronic gastritis can be caused by the following mechanisms

• Reduced synthesis of mucin.
• NSAID's through reduced secretion of prostaglandins.
• Through secretion of urease by the helicobacter pylori infection.
• Ingestion of harsh chemicals like acid as a suicidal attempt or accidentally.
• Direct cellular injury through drugs chemotherpy ,alcohol,etc..including those which are mitotic inhibitors.
• Those substances which cause decreased oxygen supply.

Morphology:

The fiure shows the neutrophilic infiltretes during the acute inflammation process

•  Lamina propria shows only mild edema and vascular congestion .
• THE SURFACE EPITHELIUM IS INTACT.
• These both occur in mild acute gastritis.
• If the neutrophils and lymphocytes are present in large numbers above the basement membrane in contact with the epithelial cell. then it indicates ACTIVE INFLAMMATION.
• Complicated to erosions* and hemorrhage*.
• Concurrent erosion and hemorrhage leads to ACUTE EROSIVE HEMORRHAGIC GASTRITIS.
• It should be superficial if it extends deep then it leads to ulceration.

*erosion:loss of superficial epithelium with a defect in the mucosa limited to the lamina propria.neutrophil infiltrate within the mucosa and fibrin containing purulent exudate in the lumen .
*hemorrhage:they cause dark punctae and lead to hyperemic mucosa.


Acute gastric ulceration: what is it?

It usually occurs after NSAID's and severe physiological stress .and so differnt names are given to it . they are :

• Stress ulcers with shock and severe trauma.
• Curling ulcers in the proximal duodenum associated with burns or trauma .
• Cushing ulcers with intracranial disease and they carry a high risk of perforation.

Pathogenesis?

• Associated with NSAID's: due to inhibition of cyclooxygenase ->which prvents the production of prostaglandins->prevents the production of mucus -> ersion of the layer and on the long run it causes ulcer .
• Association with intracranial injury: direct vagal stimulation-> hypersecretion of the acid.
• Systemic acidosis.
• Hypoxia and educed blood flow.

Morphology:

• Shallow lesions to deeper erosions.
• They are round and the base is usually brown to black .This is due to the acid digestionof the extravasated blood and causes transmural inflammation and local serositis.
• Found anywhere in the stomach.
• Mutiple ulcers occur.
• They are sharply demarcated .
• Duration of the ulceration is the dependence factor.
• Scarring and thickening of the blood vessels are absent .
• Healing by re-epithelialisation occurs soon after the factors are removed . It takes weeks to months to heal.

Clinical features :

• Bleeding from superficial gastric erosions or ulcers. They may require transfusion.
• Perforation can occur.

        Treatment:

• Prophylactic H2 receptor antagonists(rantidine, cemetidine).
• Proton pump inhibitors(omeprazole).