DESARROLLO GERENCIAL

preformed circulating antibodies which becom e fixed to the graft immediately the blood of the recipient begins to circulate through it. This form of rejection does not often pose a problem for the pathologist. The transplant surgeon frequently recognizes its occurrence before the operation is completed.

Type 2, 3 and 4 of Porter's classification correspond approximately with cellular, vascular and glomerular changes which are usually used to describe the alterations occurring in rejection. Although cellular rejection occurs characteristically in the early stages of the life of a transplant, varying degrees of rejection may be found throughout the life of any transplant. Vascular rejection may occur as an early manifestation of rejection, or as a late phenom eno in a transplant which has functioned for many years. In the more acute form of vascular rejection, the changes consist of the deposition of fibrin in the walls and lumina of arteries and arterioles, sometimes associated with inflammatory changes. In the more chronic form of vascular rejection, there is intimai proliferation which produces narrowing of the vessels concerned. Althought the more acute form is usually seen early in the life of the graft, it may be found at any time. Similarly, the intimai proliferatve changes are more characteristic of

a transplant which has survived for som e years, but they may also be found within weeks or months.

Types of rejection

1 - Hyperacute rejection

It occurs rapidly, often within minutes of establishing blood flow, and is characterized by heavy platelet deposition, endothelial dam age in both large and small vessels, prominent polymorphonuclear leukocyte infiltrate, relatively poor lymphocyte infiltrate (258, 259). Antibodies have been shown to be deposited within the rejected kidneys, and this type of rejection is generally thought to be due to preformed humoral antibodies directed against donor alloantigens (209, 260). It is often apparent to the surgeon who performs the transplant when, after an initial period of normal tone and colour, the kidney becom es soft and cyanotic. If urine formation has com m enced, this then ceases abruptly. The morphological appearances of this hyperacute form of rejection are dependent upon the time which lapses between the establishment of the blood supply and taking of the biopsy.

If the homograft is left in situ, further changes will take place. Thrombosis of arterioles and glomerular capillaries occurs with necrosis of their walls, accom pained by interstitial aedem a and h aem onh age, and tubular necrosis. Within a few days, the histological ficture is one of patchy cortical necrosis leading to complete infarction.

Immediate or hyperacute rejection is usually seen were there is a major ABO blood group incompatibility between donor and recipient, or when the recipient has been presensitized.

2 - Acute rejection

Acute rejection can be of cellular or vascular type.

When rejection occurs early in the course of the renal transplant, it is usually manifested histologically by focal infiltrates of m ononuclear cells. These cells consist of small lymphocytes, plasma cells, and larger cells, many of which have a round or indented vesicular nucleus with 1 or more nucleoli, and abundant basophilic cytoplasm; these large mononuclear cells have been called activated T lymphocytes.

The infiltrating cells tend to be perivascular and periglomerular in their distribution.

The close proximity of the large mononuclear cells to the endotelium of the intertubular capillaries has been observed. It is believed that these cells damage the endothelial cells of the capillaries allowing the escape of red cells and plasma into the interstial tissues (261, 262) (Fig. 1 1).

Progressive damage with disruption of the walls of the peritubular capillaries follows, allowing more fluid and cells to accumulate in the

Outflux W.-10 t- 7 Pro<if<?mUoo \ Antibody

0

Fig. 11 - Main cellular and molecular cascades of acute renal allograft rejection.

interstitial tissues in the areas previously occupied by the intertubular capillaries. This leads to an inadequate tubular perfusion, with resultant tubular necrosis and oliguria. The very early stages of cellular rejection are

not often seen in the human allograft, because a biopsy may not be taken until the changes have progressed sufficiently to cause clinical evidence of rejection. As cellular rejection develops, varying degrees of separation of the tubules by cells and fluid occur, and there may be interstitial haemorrhages. Usually the cellular infiltrate is focal in nature, but may som etim es appear diffuse. The maximum concentration of cells is usually around small blood vessels. These arterioles and small intertubular arteries frequently show swelling and eosinophilia of the muscle layer and are lined by swollen endothelial cells, which often project into the lumen.

If cellular rejection is treated adequately the cellular infiltrates and interstitial oed em a disappear. Tubular epithelium regenerates and it is comm on, in biopsies taken during rejection, to see varying number of mitotic figures in the tubules.

It is not uncommon to see minor abnormalities involving small arteries and arterioles in rejection occurring early in the post-transplant period. T hese changes occur mainly in vessels which are in the area of the graft affected by the cellular infiltration, but may also be seen in areas where this is absent. The muscle fibres of the media are swollen, poorly defined, and often exhibit a patchy eosinophilia. A cospicuous vacuolation of the muscle fibres may often be present. The endothelial cells instead of forming a flat lining are swollen, rounded, and rather prominent. Since

vessels away from the areas of cellular infiltration may be affected, it is possible that som e of the changes are merely a reflection of non specific ischaemic damage. The principal histopathological changes seen during vascular rejection are:

1) Fibrin deposition in arterial and arteriolar walls, sometimes associated with inflammatory changes.

2) Intimai changes producing varying degrees of narrowing of the lumina of involved vessels.

These 2 pathological manifestations of rejection may also be