Tissue breakdown

Morbidity and mortality may be reduced by replacing amino acids lost from tissue breakdown (eg, renal failure)... 

Internal tissue breakdown in melons such as Galia and Cantaloupe occurs around the seedbed and eventually results in collapse of the seed bed into a mixture of liquid, seeds and tissue pieces. Unfortunately this disorder does not affect the skin or hardness of the outer layers so cannot be detected by visual inspection. Preliminary reports from the Volcani Center in Israel have shown that the tissue breakdown results in a small increase in T2 from, typically, 35 to 45 ms and a corresponding increase in signal intensity in spin-echo projection images acquired with a 4.7 T (200 MHz) imaging magnet. There is therefore a reasonable possibility of being able to detect this disorder by on-line projection MRI. 

Nyvad B and Fejerskov O (1990) An ultrastructural study of bacterial invasion and tissue breakdown in human experimental root-surface caries. J Dent Res 69, 1118-1125. 

Allopurinol, a xanthine-oxidase inhibitor, may decrease tissue urate deposits in patients who are overproducers of uric acid, i.e. patients with primary hypemricaemia, in myeloproliferative neoplastic diseases and in hyperuricaemia resulting from tissue breakdown after cancer chemotherapy or radiation therapy. Allopurinol may also be recommended, in certain circumstances, in undersecre-tors of uric acid. 

L. Wright, and A. Churg. Acute cigarette smoke-induced connective tissue breakdown is mediated by neutrophils and prevented by alphal-antitrypsin. Am J Respir Cell Mol Biol 2000 22(2) 244-252. 

Degenerative (pathology from age-related tissue breakdown)... 

The cascade of biochemical events described above enhances the cellular necrosis and tissue breakdown, leading to what meat scientists and food technologist call meat-tenderization. Since muscle is primarily protein in nature and since hydrolytic, and specifically proteolytic, activity increases during postmortem aging, muscle represents a remarkable pool of material for the production of flavor peptides and amino acids as well as other precursors for flavor development (2). 

The disease of bum is characterized by an overwhelming inflammation, with invasion of leucocytes within the whole tissue without any modulation of tissue breakdown, and an ulceration of the neCTOtic tissues. 

Sporadic elevations of tryptophan metabolites, particularly kynurenine and 3-hydroxykynurenine, in H subjects with neoplastic hematological disorders were also observed (M2), confirming the observation of Musajo and co-workers (M20). The fact that these patients were afebrile and yet excreted increased quantities of urinary tryptophan metabolites before and after loading argues against Dalgliesh s hypothesis (D3) that increased tissue breakdown associated with fever was responsible for this phenomenon. 

Patients taking diuretics and ciclosporin may be at higher risk of hyperuricemia and gouty complications, perhaps because of tissue breakdown caused by ciclosporin (44). 

Cawston, T.E. (1996) Metalloproteinase inhibitors and the prevention of connective tissue breakdown. Pharmacol. Then. 70.163-182. 

Preeclamptic Toxemia. This condition is associated with increasing plasma uric acid concentration, probably caused by uteroplacental tissue breakdown and decreased kidney perfusion. Plasma urate measurement can be used as an indicator of the severity of preeclampsia. Redman et al noted that concentrations in excess of 6.0mg/dL (0.36mmol/L) at 32 weeks gestation are associated with a high perinatal mortality rate. 

Non-Malignant Systems for the Study of Cell Invasion - The significance of protease activity during the invasive events of metastasis is further supported by the results from studies of the role of proteases in certain non-malignant biological processes. In vivo and in vitro analyses of inflammatory reactions and normal invasive or remodeling events and their hormonal and/or temporal controls have underlined the correlation between protease secretion and the local breakdown of tissue organization. In all such instances, the event and also the associated proteolysis and tissue breakdown have been found to be coordinately controlled. We devote the remainder of this review to a discussion of some of these studies, since they have not been summarized elsewhere. 

The answer is b. (Murray, pp 238-249. Scriver, pp 2165-2194. Sack, pp 121—144. Wilson, pp 287—324.) In treating inborn errors of metabolism that present acutely in the newborn period, aggressive fluid and electrolyte therapy and caloric supplementation are important to correct the imbalances caused by the disorder. Calories spare tissue breakdown that can increase toxic metabolites. Since many of the metabolites that build up in inborn errors ol metabolism are toxic to the central nervous system, hemodialysis is recommended for any patient in stage II coma (poor muscle tone, few spontaneous movements, responsive to painful stimuli) or worse. Dietary therapy should minimize substances that cannot be metabolized—in this case fatty acids, since the oxidation of branched-chain fatty acids results in propionate. Antibiotics are frequently useful because meta-bolically compromised children are more susceptible to infection. 

Cannabinoids have been recendy shown to reduce fhe number of metastatic nodes produced by paw injection of Lewis lung carcinoma cells in rats (Portella et al. 2003). Moreover, cannabinoid administration to glioma-bearing mice also decreases fhe activity and expression of matrix metalloproteinase-2 (MMP2), a proteolytic enzyme fhat allows tissue breakdown and remodelling during angiogenesis and metastasis (Blazquez et al. 2003). Hence it is conceivable that cannabinoids may also control tumour invasiveness. 

Pseudo-renal failure occurs when either the blood urea nitrogen (BUN) or creatinine concentration rises suggesting a decrease in renal function, despite maintenance of the GFR. The BUN concentration commonly increases without an increase in creatinine concentration during corticosteroid or tetracycline therapy. These drugs cause protein catabolism and thereby increase ureagenesis and the BUN concentration as the result of tissue breakdown. The GFR is unchanged and accurately reflected by the creatinine clearance and creatinine concentration. 

Golub LM, Lee HM, Ryan ME, et al. Tetracyclines inhibit connective tissue breakdown by multiple non-antimicrobial mechanisms. Adv Dent... 

Hyperkalemia is observed frequently in ARF secondary to protein catabolism and intracellular potassium release. Hyperkalemia also results from the impaired secretion and excretion of potassium by the kidney and the endogenous release secondary to tissue breakdown. If this is severe, emergent dialysis may be indicated. Patients on CRRT, however, usually will require potassium replacement to avoid hypokalemia due to dialytic potassium losses. 

Because phosphorus is excreted renally, hyperphosphatemia is common in ARF. Like potassium, large amounts of phosphorus are released into the circulation secondary to tissue breakdown during ARF. Control of hyperphosphatemia is important because as the calcium-phosphorus product (serum calcium in milligrams per deciliter multiplied by serum phosphorus in milligrams per deciliter) exceeds 55, the risk of developing metastatic calcification increases (see Chap. 44). Conversely, with initiation of dialysis, particularly CRRT, patients must be monitored for dialysis-induced hypophosphatemia. 

Hypermagnesemia is common in ARF secondary to impaired excretion and endogenous release from tissue breakdown. Both magnesium and calcium losses via CRRT have been quantified recently ... 

It would appear that lysosomes take little or no part in the tissue reaction to injury even after the most extreme tissue breakdown. This finding is not in agreement with the original hypothesis of de Duve (D6, D7) that rupture of lysosomes could initiate cell injury, but it is consistent with the findings of Slater and Greenbaum (Sll, S12). 

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