Pathogenetic Considerations

The basic lesion in Gaucher s disease has not yet been elucidated. The storage of cerebrosides, and their identification as glucocerebrosides have stimulated intensive studies on a possible abnormality of cerebroside metabolism. These have 

Consideration of a primary defect in cerebroside metabolism calls for answers to the following questions 1) is there only a quantitative disturbance, i.e. a balance problem between cerebroside synthesis and breakdown, or 2) is there a qualitative abnormahty of cerebroside metabolism, evidenced by a) the finding of an abnormal cerebroside and/or b) an abnormal relation between various cerebrosides which are defined by their sugar and fatty acid moieties respectively, and 3) is the presumed metabolic error limited to certain cells, i.e. cells which are to become GC, or is it a general feature of all cells with the ability to synthesize and metabolize cerebrosides. 

From evidence available it seems most likely that the basic disturbance in GD is located at some enzymatic step in cerebroside biosynthesis or breakdown (see figure 7). According to present knowledge, cerebrosides are normally formed from larger glycosphingolipids, the majority of which may originate in red cells. Increased formation from these precursors may result from deletion of normal feedback control on the other hand accumulation of cerebrosides may result from a decreased rate of catabolism. 

There are several studies supporting the latter possibility. Brady s (1963) proposal that an enzymatic defect resulted in impairment of cleavage of the ceramide-glucose bond of the cerebrosides, was supported by studies on cerebrosides 

The finding of a normal ceramide content of the Gaucher spleen may also be interpreted to result from interference in GD with cerebroside catabolism before this stage. 

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Awad lA, Robinson JR, Mohanty S, Estes ML (1993) Mixed vascular malformations of the brain clinical and pathogenetic considerations. Neurosurgery 33 179-188 Barr RM, Dillon WP, Wilson CB (1996) Slow-flow vascular malformations of the pons capillary telangiectasias AJNR Am J Neuroradiol 17 71-78 Baumann CR, Schuknecht B, Lo Russo G, Cossu M, Citterio A, Andermann F, Siegel AM (2006) Seizure outcome after resection of cavernous malformations is better when surrounding hemosiderin-stained brain also is removed. Epilepsia 47(3) 563-566... 

Fisher, E.R., Reidbord, H. Gaucher s disease Pathogenetic considerations based on electron microscopic and histochemical observations. Amer. J. Path. 41, 679-692 (1962)... 

Shin MS, Young KR, Ho KJ. Wegener s granulomatosis upper respiratory tract and pulmonary radiographic manifestations in 30 cases with pathogenetic consideration. Clin Imaging 1998 22(2) 99-104. 

Zollner G, Marschall HU, Wagner M, et al. Role of nuclear receptors in the adaptive response to bile acids and cholestasis pathogenetic and therapeutic considerations. Mol Pharmacol 2006 3 231-251. 

Although, in many species, the adult scolex does little damage to the mucosa, some species (e.g. D. latum, H. microstoma, Multiceps sp.) can produce marked pathogenetic effects. Consideration of these is beyond the scope of this book. The literature in this field has been reviewed by Arme et al. (25). 

The considerably increased (20-40-fold) excretion of acid mucopolysaccharides suggests that Marfan s syndrome also represents a defect in the metabolism of connective tissues (B4). The major mucopolysaccharides excreted were indistinguishable in their electrophoretic mobilities from hyaluronic acid and chondroitin 4- or 6-sulfate. Examination of the levels of mucoproteins and acid mucopolysaccharides in the serum of cases of Marfan s syndrome revealed an increase in the latter, while the former is decreased. Bacchus (B1) considers that this pattern might be of clinical and pathogenetic significance. 

The numerous biochemical substances that may be considered with regard to hepatic encephalopathy or ascites have been outlined in detail, (s. tabs. 15.2 16.5) Similarly, an extensive synopsis of pathogenetically effective biochemical factors can be drawn up for HRS as well. All of them ultimately interfere — directly or indirectly - with the renal retention or excretion of sodium and/ or the balance between vasodilation and vasoconstriction. RAAS is markedly activated. (5, 28, 33, 41, 62, 64, 65) (s. tab. 17.1) Vasodilative factors under discussion include bilirubin, bile acids, nitrogen monoxide (NO), false neurotransmitters, calcitonin peptide (25) as well as platelet-activating factor (RAF). In more recent studies, considerably higher plasma values of the vasoconstrictor leukotrienes (C4 and D4) (41) and endothehn 1 and 3 (42) were detected. 

This is an autosomal recessive condition which can appear in a sporadic or familial form. Ductal plate malformation of interlobular bile ducts has been suggested as a pathogenetic mechanism of this disease (H.E. Mac-Mahon, 1929 R.G.F. Parker, 1956). Histologically, congenital hepatic fibrosis is characterized by dense mature fibrous tissue of the considerably enlarged and restructured portal fields subsequently, broad bands of connective tissue surround normal lobules and connect the portal fields with each other. These fibrous bands contain partly obliterated, partly dilated bile ducts, the latter often in the form of microcysts, (s. fig. 32.17)... 

The primary pathogenetic mechanism of Bartter s syndrome is still unresolved. There is considerable evidence in support of the hypothesis that an overproduction of renal prostaglandins is the underlying abnormality Treatment with inhibitors of prostaglandin synthesis has... 

To understand the pathogenetic mechanism of progressive alkalosis in the case of intractable vomiting, one must keep in mind (1) that the vomitus contains, in addition to, considerable amounts of Na, , ... 

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