CROHN’S DISEASE (REGIONAL ENTERITIS)

Epidemiology

                       Most common in north america and northern europe, with incidence of 05 per 100,000. In the UK 56 per 100,000 is reported. It is slightly more common in women than men but most commonly diagnosed in the young patients between the age of 25 and 40 years.

Aetiology

Crohn’s disease has some features suggesting chronic infection, with no causative organism has ever been found. Focal ischaemia has also been postulated as a causative factor, possibly arising from vasculitis. Smoking increasing the risk three folds. Genetic factors are thought to play a part. About 10% of the patients have a first degree relatives with the disease. There is an association with ankylosing spondylitis. It mostly manifests in the ileum.

Pathogenesis

                      It is thought that an increase in the permeability of the mucous membrane. This leads to increase passage of antigen, which are thought to induce a cell mediated inflammatory response. This results in release of cytokine such as interleukine-2 and TNF which co-ordinate local and systemic response. It is thought that there is defect in supressor T-cells which usually act to prevent escalation of the inflamatory process.

Pathology

                 Ileal disease is the most common accounting for 60% of cases. 30% cases are limited to the large intestine and 10% are more proximal small intestine. Anal lesions are common. Resection  specimens show a fibrotic thickening of the intestinal wall with a narrow lumen. There is usually dilated gut just proximal to the stricture and in the strictured area there is  deep mucosal ulceration with linear or snake like pattern. The transmural inflamation leads to adhesions inflamatory masses with mesenteric abscess and fistula into the adjacent organs. The serosa is usually opaque. There is thickening in the mesentery and the mesenteric lymph nodes are enlarged. This condition is discontineous with inflamed areas seperated from normal intestine. So called skip lesion. Under the microscope there are focal areas of chronic inflamation involving all layers of the intestinal wall. There are non-caseating giant cell granuloma but these are found  in 60% of patients. They are most common in ano rectal disease. The earliest mucosal lesions are discrete aphthus ulcers.

Clinical features

                            Depends upon the area of involvement.

Acute crohn’s disease

                                   Acute crohn’s disease occurs in only 5% cases. Symptoms and signs resemble those of acute appendicitis but there is usually diarrhoea preceding the attack. Rarely there could be a free perforation of the small intestine resulting in a local or diffuse peritonitis. Acute colitis with or without mega colon can occur in crohn’s disease but less common than in ulcerative colitis.

Chronic crhohn’s disease

                                            Mild diarrhoea extending over many months occuring in bouts accompanied by intestinal colic. Patient may complain of pain, particularly in right iliac fossa a tender mass may be palpable. Intermittent fever, secondary anaemia and weight loss are common. A perianal abscess or fissure may be the first  presenting feature of crohn’s disease, the cause is often an infected anal crypt associated with concomittent diarrhoea.

   After months of repeated attack with acute inflamation, the affected area of the intestine begins to narrow with fibrosis causing obstructive symptoms.With progression of the disease, adhesions and transmural fissuring, intra-abdominal abscess and fistula tracts can develop.

1)           Entero-enteric fistula can occur with adjacent small gut loop or pelvic colon and entero-vesical fistula may cause repeated urinary tract infection and pneumaturia.

2)           Entero-cutaneous fistula- rarely occur spontaneously and usually follow previous surgery.

Anal disease

                     In presence of active disease, the perianal skin appears bluish. Superficial ulcer with undermined edges are relatively painless and can heal with bridging of epithelium. deep cavitating ulcers are usually found in upper anal canal, they are usually painful and can cause perianal abscess and fistula. The most distressing feature of anal disease is sepsis from secondary abscess and perianal fistula.

Investigations

                      Complete blood count to exclude anaemia, fall of albumin, magnesium, zinc, seleneum specially in active disease.

                    Endoscopy

                                       Sigmoidoscopy- Ulceration in anal canal is readily seen. AS a result of the dis contineous nature of CD, there will be area of normal colon or rectum. The earliest appearance are aphthoid like ulcers surrounded by a rim of erythematous mucosa. These become larger and deeper with increasing severity of disease.

                        Imaging

                                     Ba enema will show similar features to those of  colonoscopy in the colon. THe best investigation of the small intestine is small bowel enema.

                           

Treatment

   Medical therapy:-

1)       Steroids-

Steroids are the mainstay of  treatment. These are effective in inducing remision in moderate to severe disease in 70-80% of cases. Steroids can also be used as topical agents in rectum with reduced systemic bio availability but long term uses can  cause  adrenal suppression. Patients suffering a relapse are treated with upto 40mg of prednisolone orally daily, supplemented by 5- ASA compounds in those patients with colonic involvement.

2)      Anti-biotics:

  Those who have symptoms and signs of a mass or an abscess are also treated with anti biotics. Metronidazole is used  especially in perianal disease.

Immunomodulary agent

    Azathioprine is used for its additive and steroid sparing effect and is now standard maintanance therapy. It is a purine analogue, which is metabolized to 6, mercaptopurine and works by inhibiting cell mediated events.  Cyclosporine acts by inhibiting cell mediated immunity.

Monoclonal antibody:-    Infliximab, the  murine chimeric monoclonal antibody directed towards TNF-alpha, target patients with severe, active disease who are refractory to conventional treatment and who are at high risk of surgical interventions.

Nutritional support 

Nutritional support is essential. Severely malnourished people way require intra venous feeding regimens. Anaemia, hypo proteinaemia  and electrolytes, vitamins, and metabolic bone problems must all be addressed.

Indication for surgery                                                  

·         Recurrent intestinal obstruction.

·         Bleeding

·         Perforation

·         Failure to medical therapy

·         Intestinal fistula

·         Fulminant colitis

·         Malignant changes

·         perianal disease

Surgery

·         Ileocaecal resection

·         Segment resection

·         Colectomy and ileo rectal anaestomosis

·         Emergency colectomy

·         Laparoscopic surgery

·         Temporary loop ileostomy

·         Procto colectomy

·         Strictureplasty

·         Anal disease is usually treated conservatively by simple drainage of abscess.

 

APPENDICITIS

Introduction – Appendix is a blind muscular tube with mucosal, submucosal, muscular  & serous layers. At birth the appendix is short & broad at its junction with caecum but differential growth of the caecum produces the typical tubular structure by about the age of two years. During childhood continued growth of the caecum commonly rotates the appendix into a retrocaecal but intraperitoneal position.

figure:Appendix

ABDOMINAL TUBERCULOSIS

Abdominal tuberculosis can be divided into

·         Tuberculous peritonitis and

·         Tuberculosis of the intestine.

TUBERCULOUS PERITONITIS

Acute tuberculous peritonitis

                                                  Tuberculous peritonitis sometimes has an onset that so closely resembles acute peritonitis that the abdomen is opened. Straw coloured fluid escapes and tubercles are seen scattered over the peritoneum and greater omentum. Early tubercles are greyish and translucent. They soon undergo caseation and appear white or yellow and are then less difficult to distinguish from carcinoma. On opening the abdomen and finding tuberculous peritonitis, the fluid is evacuated, some being retained for histological studies. A portion of diseased omentum is removed for histological confirmation of the diagnosis and the wound closed without drainage.

 

Chronic tuberculous peritonitis

                                                        The condition presents with abdominal pain (90% of cases), fever (60%),          weight loss (60%), ascites(60%), night sweats (37%) and abdominal mass (26%).

Origin of the infection

                                       Infection originate from:

·         tuberculous mesenteric lymph  nodes

·         tuberculosis of the ileocaecal region

·         a tuberculous pyosalphinx

·         blood borne infection from pulmonary tuberculosis usually the miliary.

Varieties of tuberculous peritonitis

 There are four varieties of tuberculous peritonitis:

ascitic, encysted, fibrous and purulent.

Ascitic form

                     The peritoneum is studded with tubercles and the peritoneal cavity becomes filled with pale, straw-coloured fluid. The onset is insidious. There is loss of  energy, facial pallor and some loss of weight. The patient is usually brought for advice because of the distension of the abdomen. Pain is often absent; in other cases there is considerable abdominal discomfort, which may be associated with constipation or diarrhoea. On inspection, dilated veins may be seen coursing beneath the skin of the abdominal wall. Signs of ascites can be elicited readily. Because of raised intra-abdominal pressure, an umbilical hernia commonly occurs. On abdominal palpation, a transverse solid mass can often be detected. This is rolled- up greater omentum infiltrated with tubercles.

  Diagnosis is seldom difficult except when it occurs in an acute form or when it first appears in an adult, in which case it has to be differentiated from other forms of ascites, especially malignancy. Laparoscopy is useful by allowing inspection of the peritoneal cavity, where the appearance is often diagnostic. Areas of caseation an be biopsied for histopathology. The ascitic fluid is pale yellow, usually clear and rich in lymphocytes.

  Once the diagnosis of tuberculous peritonitis has been made, it is always important to look for tuberculous disease elsewhere. A chest radiograph should always be taken before laparoscopy or laparotomy is performed.

 Encysted form

                          The encysted form is similar to the ascitic form except that one part of the abdominal cavity alone is involved. Thus a localized intra-abdominal swelling is produced, which may give rise to difficulty in diagnosis. In the women above the age of puberty when the swelling is in the pelvis an ovarian cyst will probably be diagnosed. In the case of  a child it is sometimes difficult to distinguish the swelling from a mesenteric cyst. Late intestinal obstruction is a possible complication.

Fibrous form

                      The fibrous form is characterized by the production of widespread adhesions, which cause coils of intestine, specially the ileum, to become matted together and distended. This distended coils act as a ‘blind loop’ and give rise to steatorrhoea, wasting and attacks of abdominal pain. On examination the adherent intestine with omentum attached, together with the thickened mesentery, may give rise to palpable swelling. The first intimation of the disease may be sub-acute or acute intestinal obstruction. If the adhesions are accompanied by fibrous strictures of the ileum as well, it is best to excise the affected bowel, provided that not too much of the small intestine need to be sacrificed. Anti-tubercular therapy will often rapidly cure the condition without the need for surgery.

Purulent form

                        The purulent form is rare. When it occurs, usually it is secondary to tuberculous salphingitis. Amidst a mass of adherent intestine and omentum, tuberculous pus is present. Sizeable cold abscess often form and point on the surface, commonly near the umbilicus, or burst into the bowel. In addition to prolonged general treatment, operative treatment may be necessary for the evacuation of cold abscesses and possibly for intestinal obstruction. If a faecal fistula forms, it usually persists because of distal intestinal obstruction. Closure of the fistula must therefore be combined with some form of anaestomosis between the segment of intestine above the fistula and an unobstructed area below. The prognosis of this variety of tuberculous peritonitis is relatively poor.

Tuberculosis of the intestine

                                                        Tuberculosis can affect any part of the gastrointestinal tract from mouth to the anus. The sites affected most often are the ileum, proximal colon and peritoneum. There are two principal types.

 Ulcerative tuberculosis

                                          Ulcerative tuberculosis is secondary to pulmonary tuberculosis and arises as a result of swallowing tubercle bacilli. There are multiple ulcers in the terminal ileum, lying transversely and the overlying serosa is thickened, reddened and covered in tubercles

Clinical features

                             Diarrhoea and weight loss are the predominant symptoms, and the patient  will usually be receiving treatment for pulmonary tuberculosis.

Radiology

                 A barium meal and follow thorough or small bowel enema will show the absence of filling of the lower ileum, caecum and most of the ascending colon as a result of narrowing and hyper motility of the ulcerated segment.

Treatment

                  A course of chemotherapy is given. healing often occurs provided the pulmonary tuberculosis is adequately treated. An operation is only required in the rare event of a perforation or intestinal obstruction.

Hyperplastic tuberculosis

                                            This usually occurs in the ileo-caecal region, although solitary and multiple lesions in the lower ileum are sometimes seen. This is caused by ingestion of Mycobacterium tuberculosis by patients with a high resistance to the organism. The infection establishes itself in lymphoid follicles, and the resulting chronic inflamation causes thickening of the intestinal wall and narrowing of the lumen. There is early involvement of regional lymph nodes, which may caseate. Unlike CD with which it shares many similarities, abscess and fistula formation is rare.

Clinical features

                             Attacks of abdominal pain with intermittent diarrhoea are the usual symptoms. The ileum above the partial obstruction is distended, and the stasis and consequent infection lead to steatorrhoea, anaemia and loss of weight. Sometimes, the presenting picture is  of a mass in the right iliac fossa with vague ill health. The differential diagnosis is that of an appendix mass, carcinoma of the  caecum CD, tuberculosis or actinomycosis of the caecum.

Radiology

                 A barium follow thorough or small bowel enema will show a long narrow filling defect in the terminal ileum.

Treatment

                  When the diagnosis is certain and the patient has not yet developed obstructive symptoms, treatment with chemotherapy is advised and may cure the condition. When obstruction is present, operative treatment is required and ileocaecal resection is best.

ORGAN TRANSPLANTATION

Transfer of tissue or organ from one place to another is called organ transplantation.

Types of graft

·       Autograft – one site to another site in the same body.

·       Allograft – From one person to another person in same species.

·       Isograft – Transplantation between identical twin.

·       Xenograft – Graft performed between different species.

 Graft rejection-

        Occur due to immune response. Later study demonstrated that T-lymphocyte play an essential role in orchestrating the graft rejection response. Cyto-toxic T- cells in the delayed type hypersensitivity and antibody dependent effector mechanisms all play a role.

Allograft rejection response is directed against a group of cell surface molecule called human leukocyte antigen (HLA). HLA is highly polymorphic and play a special role in immune response.

Two types of HLA molecules-

·       HLA class-1

·       HLA class-2

HLA class-1 antigen present on all nucleated cells while HLA class-2 antigen have a more restricted distribution and are expressed strongly on antigen presenting cell such as dendritic cell, macrophage, and  B – lymphocyte.

T- lymphocyte recognize peptide antigen bound to HLA molecule through their T-cell receptor and T-cell expresses a unique TCR that bind to a particular HLA peptide complex.

Types of graft rejection

·       Hyper acute graft rejection- occurs immediately.

·       Acute graft rejection- occurs within o6 months.

·       Chronic graft rejection- occurs within months or years after transplantation.

    

Hyper acute graft rejection

Occur due to presence of pre-formed antibody against HLA class-1 antigen expressed by the donar. They may occur from blood transfusion, failed transplant or previous pregnancy. This typeof rejection also occur if an ABO group incompatible organ graft is performed. Kidney transplants are particularly vulnerable to hyper acute graft rejection.

Acute graft rejection

It is mediated predominantly by T-lymphocyte but allo-antibody also play an important role. It is characterized by infiltration of mononuclear cells of the graft and includes cyto-toxic T cell, B cell, NK cell and macrophages. All types of grafts are susceptible to this form of rejection is about 25-50% cases.

Chronic graft rejection

Occur due to antibody mediated effector mechanism. All types of grafts are susceptible to chronic rejection and it is the major cause of allograft failure.

Risk factors of chronic graft rejection

·       Previous episodes of acute graft rejection

·       Degree of HLA mismatch

·       Long cold ischaemia time

·       Cyto megalo-virus infection

·       Raised blood lipid

·       Inadequate immuno suppression.

Immuno suppression agents

Commonly used agents are-

·       Azathioprine

·       Cyclosporine

·       Tacrolimus

·       Rapamycin

·       Cortico-steroids

·       Anti CD-25 monoclonal antibody.

Complications of immuno-suppression

·       Infection 

Bacterial

    Viral

    Protozoal

    Fungal.

·       Malignancy

Skin malignancy

NHL

Squamous cell carcinoma

Basal cell 

Malignant melanoma.

SKIN GRAFTING

Graft of the skin can be used to reconstruct wound having been harvested as a split (leaving some epidermal components) or full thickness graft. The process by which a skin graft adheres to and heals a wound is a unique and unnatural process in which normal wound healing at the recipient site is altered by the presence of the graft. The survival of the skin graft is largely dependent on how fast the graft derives a new blood supply from the wound on which it is placed. Until the graft establishes a new blood supply, nutrition is derived by diffusion through the fibrin layer formed between it and the wound bed. After 48-72 hours a fine capillary network grows into the graft and anaestomosis with the native vasculature of the graft. Factors that inhibit the process (formation of haematoma, seroma or bacterial exudates between graft and wound bed) will decrease the likelihood that the graft will successfully.

Grafts are tissues that are transferred with their blood supply which therefore have to re-vascularise once they are in a new site.

Split thickness skin graft – These are sometimes called Thiersch graft.

Full thickness skin graft (wolfe graft) - Epidermis + dermis.

Composite skin graft - Skin & fat or skin & cartilage.

Nerve graft – Sural nerve, but smaller cutaneous nerve may be used.

Tendon graft – usually from palmaris longus or planteris tendon are used for injury loss or nerve damage correction