Tubules obstruction

Tubule obstruction. Given certain physicochemical conditions, crystals can deposit within the tubular lumen. Methotrexate, for example, is relatively insoluble at low pH and can precipitate in the distal nephron when the urine is acid. Similarly the uric acid produced by the metabolism of nucleic acids released during rapid tumour cell lysis can cause a fatal urate nephropathy. This was a particular problem with the introduction of chemotherapy for leukaemias until the introduction of allopurinol it is now routinely given before the start of chemotherapy to block xanthine oxidase so that the much more soluble uric acid precursor, hypoxanthine, is excreted instead. Crystal-nephropathy is also a... 

Additional studies of decalin exposure in rats have characterized the specific sequence of renal alterations first the variable occurrence of light-microscopically evident proximal convoluted tubule epithelial cell necrosis, presumably a reflection of cellular injury associated with excessive protein accumulation (hyaline droplets) then the occurrence of granular casts at the junction of the inner and outer bands of the outer zone of the medulla and finally, chronic nephrosis, occurring secondary to tubular obstruction by granular casts. It is not... 

As the glomerular filtrate proceeds down the tubule, the filtrate becomes increasingly concentrated and the pH of the filtrate becomes more acidic. Therefore chemicals with pH-dependent solubility have the potential to precipitate and cause tubular obstruction, resulting in local interstitial inflammation, granuloma formation, and fibrosis. Indinavir is a protease inhibitor used in the treatment of immunodeficiency virus that has been reported to cause renal toxicity. The solubility of indinavir is pH- and flow-dependent, and some patients treated with indinavir form urinary crystals that obstruct tubules, leading to inflammation or granuloma formation, resulting in renal failure [23]. 

Rabbit Glycerol 7.5g/kg Tubular obstruction Proximal tubules [196]... 

Rat Gentamycin 40-120 mg/kg/day Decreased ultrafiltration coefficient Tubular obstruction Proximal convoluted tubule [197-199]... 

The mechanism of the acute kidney injury is thought to be multifactorial and similar to other cases of myoglobinuric renal failure [118, 121-126]. These factors include obstruction of tubules, toxic effects of the pigment or iron on renal tubular cells and altered hemodynamics in association with inhibition of the vasodilator nitric oxide by myoglobin. Experimental animals exposed to heme pigment have increases in the renal synthesis of both heme oxidase and ferritin [125]. This allows for more rapid heme degradation and greater sequestration of potentially toxic iron by the tubular cells [125]. Whether narcotics or the hypotensive, hypoxic environment associated with rhabdomyolysis interfere with these protective effects of the kidney is unknown. 

Mannitol Osmotic diuretic Increases effective circulating volume and RBF May increase GFR May help to flush away debris that may obstruct the tubules May scavenge oxygen radicals Constant i.v. infusion required May induce hyperosmolality High doses may precipitate acute renal failure... 

Renal Tubular Acidoses, Types I and II These syndromes are predominantly characterized by loss of bicarbonate because of decreased tubular secretion of (distal or type I RTA) or decreased reabsorption of HCO3 (proximal or type II RTA). Because the major urine-acidifying power of the kidneys rests in the distal tubules, the proximal and distal RTAs may be differentiated by measurement of urine pH. In proximal RTA, urine pH becomes <5.5, whereas in distal RTA the distal tubules are compromised and urine pH is >5.5. When distal RTA is associated with obstructive nephropathy, sickle cell disease, or systemic lupus erythematosus, hyperkalemia may... 

Henderson-Hasselbalch equation, Chapter 1). It may result from central depression of respiration (e.g., narcotic or barbiturate overdose, trauma, infection, cerebrovascular accident) or from pulmonary disease (e.g., asthma, obstructive lung disease, infection). Increased [H+] is in part buffered by cellular uptake of H+ with corresponding loss of intracellular K" ". In acute hypercapnia, the primary compensatory mechanism is tissue buffering. In chronic hypercapnia, the kidneys respond to elevated plasma Pcoj increasing the amount of HCO formed by carbonic an-hydrase in the tubules and by excreting more H+. 

Obstructive nephropathy is the result of mechanical obstruction to urine flow following glomerular filtration. This may be due to intratubular obstruction from crystal precipitation within the tubules of the kidney or extrarenal obstruction of the ureters or bladder. Pain, hematuria, and infection may precede a significant rise in serum creatinine. 

Hyperkalemic distal (type IV) RTA resulting from generalized distal tubule defects is less common than hyporeninemic hypoaldosteronism, but is more common than classic distal (type I) RTA. Patients with this defect have impaired tubular potassium secretion in addition to impaired urinary acidification (urine pH >5.5 despite acidemia or acid loading). Urinary obstruction is the most frequent cause of this disorder, which may also be associated with sickle-cell nephropathy, systemic lupus erythematosus, HIV nephropathy, analgesic abuse nephropathy, amyloidosis, renal transplant rejection, and chronic cyclosporine nephrotoxicity. 

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