Malignancy pathophysiology

Cachexia is more difficult to treat, although it may resolve following treatment of the underlying malignancy. Nutritional consultation may be of aid, although cachexia is thought to be more attributable to internal pathophysiologic processes than malnutrition. 

FIGURE 96-4. Pathophysiology of the hypercalcemia of malignancy. PTHrP, parathyroid hormone-related protein TGF-P, transforming growth factor P TNF-a, tumor necrosis factor alpha Ca2+, calcium IL-1, interleukin 1 IL-2, interleukin 2. 

Pathophysiologically, this arises in three ways. First, output may be ineffective as occurs with deficiencies of folate and vitamin B12, or in the myelodys-plastic syndromes. Second, extensive infiltration by malignant disease or fibrous is to blame. Third, the blood-forming tissue is deleted - usually reversible... 

I 99 Fareed D, Bick R, Bacher P et al, Blood levels of nitric oxide, C-reactive protein and TNF-a are upregulated in patients with malignancy-associated hypercoagulable state pathophysiologic implications. Pathophysiol Haemost Thromb 2003 33(suppl I ) 69—76. 

Britt BA. 1979. Etiology and pathophysiology of malignant hyperthermia. Fed Proc 38 44-48. 

As early as 1964 and in later publications, it was possible to demonstrate the significance of glycoproteins (hexosamine, fucose, sialic acid [34], etc.) and cholinesterase for the detection of non-inflammatory, inflammatory or malignant disease and their follow-up as well as for the distinction between transudate and exudate in a so-called phlogogram (E. Kuntz, 1964). (see footnote p.298) Because of the significance and pathophysiological features of the mucopolysaccharides, appropriate biochemical parameters are likely to be of further interest. In addition, elevated values of hyaluronic acid have been found in the ascitic fluid of cirrhotic patients. 

Gallium nitrate has been used as an alternative to bisphosphonates in hypercalcemia of malignancy (11), in which it is effective but associated with a higher frequency of renal toxicity (10%) and of nausea and vomiting (14%) than the bisphosphonates. The pathophysiology and treatment of hypercalcemia of malignancy has been reviewed and the role of gallium nitrate considered (12,13). 

Calcium overload as a pathogenic mechanism of cell injury has been incriminated in various disorders of cardiac and skeletal muscle including catecholamine-induced cardiac necrosis (8, 13), myocardial ischemia (8, 13), myopathies (9, 17), and malignant hyperthermia (18). Of interest is that in the majority of these pathophysiological entities calcium antagonists effectively suppress calcium accumulation and cell necrosis (8, 13, 18). 

Thouennon E, Elkahloun A, Guillemot J, et al. Insights into the pathophysiology of pheochromocytoma malignancy. J Clin Endocrinol Metab. 2007 92 4865-4487. 

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