Compare and contrast five etiologies for granuloma formation. Discuss clinical findings along with both gross and microscopic pathologic findings. (More than five are given below for comparison and for example.) (<250 words)

Granuloma formation results when an agent present in the body cannot be easily eliminated, with the result that macrophages are recruited into the inflammatory response to produce epithelioid cells and giant cells. Granulomas are typically localized and can persist for months to years.

Mycobacterium tuberculosis infects the lung and can produce "primary" infection of limited extent in children or "secondary" infection with more extensive cavitation in adults. With poor immune response, a "miliary" pattern of spread in lung or to other organs can occur. The granulomas grossly show caseous necrosis and microscopically have Langhans type giant cells with the nuclei lined up around the edge of the cell. Acid- fast bacilli are present.

Mycobacterium leprae (leprosy) typically involves the skin and peripheral nerves. There is a tuberculoid form with a good immune response and a lepromatous form with a poor response. Skin biopsy is needed to show the acid-fast bacilli.

Mycobacterium avium-intracellulare (MAI) is often a disseminated infection seen in immunocompromised patients, particularly those with AIDS. Sheets of acid-fast bacilli appear in macrophages. Liver, spleen, and lymph nodes are often enlarged.

The pathogenic fungi (H. capsulatum, C. immitis, C. neoformans, etc.) can produce granulomatous disease similar to tuberculosis in lung. Histoplasmosis is seen more in the Mississippi river region, whereas coccidioidomycosis is seen more in the southwestern U.S. Cryptococcosis has a propensity to produce a meningitis, particularly in patients with AIDS. The granulomas can be caseating.

Sarcoidosis is a granulomatous disease of unknown etiology that mostly affects lungs and lymph nodes. The granulomas are characteristically non-caseating and acid-fast bacilli or fungi are not present.

Inhaled dusts such as silica and asbestos can produce a granulomatous response that involves the lungs. The granulomas are progressive and reduce lung capacity. A fibrous to foreign body type response is seen.

Various foreign bodies (suture, wood splinters, breast implants, etc.) can produce a localized granulomatous response that contains so-called foreign body type giant cells in which the nuclei are scattered through the cytoplasm.

Syphilis can produce a peculiar type of granulomatous response in which gummatous necrosis is present, more often in the late (tertiary) stage.

Bacterial infections with Listeria monocytogenes, Nocardia braziliensis, and Actinomyces israeli may on occasion produce granulomatous inflammation with ill-defined foci that may have mixed inflammatory infiltrates but include epithelioid cells. Often these involve the respiratory tract. These infections can be persistent.

How does edema occur? (<250 words)

(Example 1)

Edema is an increase of extravascular fluid and can be caused by a number of factors. Inflammation can lead to edema because the inflammatory response involves vasodilation and increased vascular permeability, both of which contribute to edema by bringing more blood to a region and allowing filtration of blood (fluid and proteins) into the tissues. Increased hydrostatic pressure increases capillary filtration. This can occur in patients with congestive heart failure in which the backup of blood increases pressures, especially in extremities. Other causes for increased hydrostatic pressure may include venous thrombosis, portal hypertension, and pregnancy. Decreased oncotic pressure in the vasculature can lead to decreased reabsorption at the capillary, and thus edema. This can occur with liver disease and malnutrition since less serum proteins such as albumin are made in these states. It can also be caused by excessive loss of serum protein by renal disease or enteropathy. Increased sodium retention can increase total body water, and can occur with congestive heart failure and renal disease, or with hormonal alterations in the menstrual cycle or in pregnancy. Finally, lymphatic obstruction can lead to edema, because excess fluid cannot be drained by lymphatics. Decreased lymphatic flow can occur because of neoplasms, previous surgery, and inflammation (elephantiasis).

How does edema occur? (<250 words)

(Example 2)

Edema is a common medical problem that can occur as a result of the complex interactions of cytokines and chemical mediators or from simpler processes such as obstruction of lymphatic vessels. With inflammation, the first step in the sequence of events is vasodilation, primarily of the venules. Prostaglandin, histamine, and leukotrienes are examples of chemical mediators for this process and/or for increased vascular permeability. Contributing to production of edema is a decrease in intravascular oncotic pressure from a relative decrease in plasma albumin compared to the extravascular tissues into which it is leaked. The vasodilation also allows vascular stasis with increased intravascular hydrostatic pressure. Vascular stasis can also be positional. Patients immobilized in bed can exhibit edema in the sacral region. Patients with congestive heart failure can exhibit lower extremity edema following prolonged standing or sitting. Congestive heart failure can also compound the problem by causing sodium retention, drawing fluid into the cells and interstitium. Renal failure can also cause sodium retention. Finally, edema can be caused by obstructive problems as well. Surgical resection or trauma can block flow in lymphatics, leading to upper extremity edema, for example, following radical mastectomy. Neoplasms can also physically obstruct lymphatics.

Discuss the process of wound healing in a patient who has undergone a coronary artery bypass grafting operation. (<250 words)

(Example 1)

Following the coronary bypass operation, the chest wall incision will be closed. As is the usual case with surgical incisions, the edges are brought close together with sutures. In such a case, the wound healing is by first intention. A blood clot forms initially and then is replaced over the next few days by inflammatory cells. By the end of the first week there is a minimal amount of granulation tissue with capillaries and fibroblasts. The fibroblasts direct deposition of type III collagen, which eventually is replaced by stronger type I collagen. Re-epithelialization occurs over the surface by 1 to 2 weeks. After 3 months, the wound has achieved 70 to 80% of the strength of the original skin, but will not achieve much more. If there is wound dehiscense or infection, then there will be a larger skin and soft tissue defect. This will heal by second intention, with more time needed for granulation tissue to fill in the defect and wound contraction to occur. Poor tissue perfusion in patients with heart failure and poor wound healing in patients with diabetes mellitus will delay wound closure. Corticosteroid therapy also inhibits wound healing. Foreign bodies can produce a granulomatous reaction and impede healing, but sutures produce a minimal reaction.

Discuss the process of wound healing in a patient who has undergone a coronary artery bypass grafting operation. (<250 words)

(Example 2)

At sites of surgical anastomosis, endothelial damage will result in activation of coagulation mechanisms to form thrombus that fills the gaps left by incisions. Both intrinsic and extrinsic coagulation pathways participate in conversion of prothrombin to thrombin and then fibrinogen to fibrin. Platelets are activated by exposed collagen to elongate and aggregate. Platelets can release factors such as ADP to form a "primary plug" and thromboxane to further promote aggregation and "secondary plug" formation along with thrombin. The platelets are enmeshed in fibrin to form a clot. As neutrophils and macrophages arrive, they remove necrotic cells and promote angiogenesis and fibroblast proliferation to produce granulation tissue that eventually resolves to a small collagenous scar at the site of the surgical anastomosis. Thrombus is removed by the fibrinolytic system, with activation of substances such as plasminogen to produce plasmin that lyses fibrin to maintain an open lumen in the vessels. In places where anastomoses of the saphenous vein graft to the distal coronary artery beyond the stenosis caused by atherosclerosis have been made, there is re-endothelialization of the vascular lumens. Unfortunately, the vein grafts can re-accumulate atheromas faster than the original artery if dietary and lifestyle factors promoting atherosclerosis are not changed.

Discuss the process of wound healing in a patient who has undergone a coronary artery bypass grafting operation. (<250 words)

(Example 3)

A coronary artery bypass graft procedure is usually done when the patient has had a myocardial infarction. The MI results from atherosclerosis and coronary artery narrowing with ischemia involving an area of myocardium. If blood flow to the ischemic area can be re-established quickly, then damage can be limited. In areas with more ischemic injury, reperfusion of the damaged muscle can promote formation of free radicals that cause further damage. The ischemic damage that causes the death of myocardial cells results in an infarct, which is an area of coagulative necrosis. To heal the infarct, there are neutrophils that are attracted to the necrotic muscle that help to cause cell lysis so that macrophages may then come into the infarct and phagocytize the dead cells. Granulation tissue in the form of fibroblasts and capillaries forms under the influence of mediators such as fibroblast growth factor and vascular endothelial growth factor. The granulation tissue is eventually replaced by more and more collagen that is laid down until a scar remains where the heart muscle once was. Myocardial fibers cannot regenerate. Larger areas of infarction can lead to the formation of an aneurysm. Large infarcts reduce the function of the heart and make heart failure more likely.