3. Thrombotic microangiopathy (TMA)

Definition: TMA is a collective name for diseases which primarily affect the endothelium, followed by intravascular coagulation and repair mechanisms. TMA may affect the whole renal vascular tree.

A plethora of diseases of varying etiology and pathogenesis are to be found under the title “Thrombotic Microangiopathy (TMA).  The common, final pathogenetic route is endothelial damage, accompanied and followed by intra-vascular coagulation. Just as variable as the etiology and pathogenesis is the resulting kidney disease. In principle, any vascular region, from the small arteries to the arterioles up to the glomeruli, may be involved. Although the various disease entities possess preferences – HUS: glomeruli and arterioles; malignant hypertension: arterioles and arteries, just to mention the extremes – in individual cases no reliable statements concerning the underlying disease can be made from the morphology alone. In addition, as a rule of thumb, younger patients are more likely to reveal glomerular, older patients arterial  changes.

This wide spectrum of morphological manifestations is complicated by changes in morphology as the lesion progresses: acute, subacute, chonic. As a rule, this results from a single event, not from superimposed, repeated injuries. However, the various stages of evolution of the lesions are frequently seen side by side. In the entire arterial region three different stages of TMA can be found.

1. Endothelial Injury and intra-vascular coagulation.

In the early stages the glomeruli are swamped with fibrin thrombi which may also be seen in the arterioles and small arteries. At the same time, individual glomeruli or glomerular tuft segments are collapsed or show massive dilation and are filled with blood. As a result of fibrin thrombi formation. mesangiolysis is seen with aneurismatic expansion of individual tufts. In the arterioles and arteries, so called fibrinoid vessel wall necroses are seen instead. The endothelium is, if still visible at all, detached from the vessel wall and severely damaged.

2.  Fibrin degradation and its effects accompanied by endothelial regeneration

Fibrin deposits are rapidly degraded and can no longer be detected. Immune histology does, however, allow fibrin to be detected in the affected structures for a long time. Together with removal of fibrin a characteristic lobulisation of the glomeruli is often present. The peripheral capillary loops are massively thickened and duplicated; regenerated endothelium forms a new basement membrane on the inner side, which results in severe constriction of the capillary lumen. A similar process occurs in the arterioles and arteries. So called mucoid material (acid glycosaminoglycans) accumulates beneath the regenerated endothelium. As in cultured cells, the small number of proliferating myofibroblasts expand within the thickened mucoid intima. Necroses in the vessel walls are repaired by the myofibroblasts.

 3. Repair phenomena up to restitutio ad integrum

During late stages, loop thickening in the glomeruli can revert to normal, then residual signs of damage to the basement membrane can only be visualised by electron microscopy. In the arterioles and arteries, an onion-skin type transformation of the vessel wall, due to reconstruction of the media, is seen. This is accompanied (by cell poor) intimal fibrosis without elastosis, which results in varying degrees of persisting constriction of the vessel lumens.

The accompanying changes in the tubulo-interstitial space are manifold ranging from extensive necroses to discrete lesions, e.g. protein storage in individual nephrons.