Tubular necrosis

Renal Effects. Hemorrhage of the medullary layer of the kidneys was reported in three persons who died following ingeshon of endosulfan (Terziev et al. 1974). Acute renal failure was a major contributor to the deaths of two individuals who ingested unknown amounts of endosulfan (Blanco-Coronado et al. 1992 Loetal. 1995). In both cases, postmortem examination revealed extensive tubular necrosis. In contrast, no kidney lesions were found in a man who died 4 days after ingesting approximately 260 mg endosulfan/kg (Boereboom et al. 1998). 

ChanJ. 1995. Acute tubular necrosis following endosulfan insecticide poisoning Author s reply. Clin Toxicol 33(4) 377-378. 

Lo RSK, Chan JC, Cockram CS, etal. 1995. Acute tubular necrosis following endosulphan insecticide poisoning. J Toxicol Clin Toxicol 33(l) 67-69. 

Proximal tubule cells are exquisitely sensitive to vasculat disturbances and acute tubular necrosis (ATN) can occur naturally in areas of poor perfusion resulting from falling blood pressure, or vasospasm of renal vessels or arterioles. In other words hypoxia associated with partial ischaemia can cause severe damage. It is not then surprising that anoxia associated with iatrogenic, surgically induced total ischaemia produces irreversible damage within a short time unless steps are taken to prevent it. 

Loop diuretics (dose depends on severity of renal insufficiency) ° Not directly beneficial in established acute tubular necrosis. 

During phase I, each seizure causes a sharp increase in autonomic activity with increases in epinephrine, norepinephrine, and steroid plasma concentrations, resulting in hypertension, tachycardia, hyperglycemia, hyperthermia, sweating, and salivation. Cerebral blood flow is also increased to preserve the oxygen supply to the brain during this period of high metabolic demand. Increases in sympathetic and parasympathetic stimulation with muscle hypoxia can lead to ventricular arrhythmias, severe acidosis, and rhabdomyolysis. These, in turn, could lead to hypotension, shock, hyperkalemia, and acute tubular necrosis. 

Tubular and interstitial diseases (e.g., analgesic nephropathy, drug-induced nephritis, oxalate nephropathy, radiation nephritis, acute tubular necrosis, and sarcoidosis)... 

ADHD Attention-deficit hyperactivity disorder ATN Acute tubular necrosis... 

Acute tubular necrosis A form of acute renal failure that results from toxic or ischemic (insufficient oxygen) injury to the cells in the proximal tubule of the kidney. 

There is evidence that y-aminobutyric acid A receptors may be modified during SE and become less responsive to endogenous agonists and antagonists. Two phases of GCSE have been identified. During phase I, each seizure produces marked increases in plasma epinephrine, norepinephrine, and steroid concentrations that may cause hypertension, tachycardia, and cardiac arrhythmias. Muscle contractions and hypoxia can cause acidosis, and hypotension, shock, rhabdomyolysis, secondary hyperkalemia, and acute tubular necrosis may ensue. 

Acute tubular necrosis Ischemic Hypotension Vasoconstriction Exogenous toxins Contrast dye Heavy metals Drugs (amphotericin B, aminoglycosides, etc.) (continued)... 

Common laboratory tests are used to classify the cause of ARF. Functional ARF, which is not included in this table, would have laboratory values similar to those seen in prerenal azotemia. However, the urine osmolality-to-plasma osmolality ratios may not exceed 1.5, depending on the circulating levels of antidiuretic hormone. The laboratory results listed under acute intrinsic renal failure are those seen in acute tubular necrosis, the most common cause of acute intrinsic renal failure. 

Drug-induced allergic interstitial nephritis, renal transplant rejection Tubular necrosis... 

Tubular epithelial cell damage Acute tubular necrosis Pentamidine... 

Acute-, intermediate-, and chronic-duration oral exposures of male rats to doses of 10 mg/kg/day or greater were associated with renal tubular nephropathy (Gorzinski et al. 1985 NTP 1977, 1989 Weeks et al. 1979). Affected animals displayed tubular necrosis, hyaline droplets in tubular epithelial cells, regenerative tubular epithelium, interstitial nephritis, and fibrosis. The severity of the renal lesions varied with the dose and the duration of exposure. 

In adult male rats, after mercuric chloride injection, in addition to tubular necrosis and rise in tubular cell counts, transient elevation of urinary glutamic-oxaloacetic transaminase activity has been found [230]. 

Renal 4 F (tubular necrosis, hyalin and calcium containing casts, lipid peroxidation) ... 

Effects Noted in Study and Corresponding Doses Doses of 0.20 mg/kg/day and greater resulted in neurotoxicity evidenced by convulsions, tremors, and degenerative lesions in the brain and systemic toxicity which included renal tubular necrosis, respiratory distress and pulmonary edema, and diffuse degenerative lesions of the heart. One animal administered diet corresponding to 0.20-0.27 mg/kg/day died after 47 days of feeding. 

These results suggest acute renal failure (ARF) due to tubular necrosis caused by phenol. Plasma sodium is low due mainly to impaired reabsorption in the nephron, although the slightly low albumin suggests haemodilution possibly as a result of excessive i.v. fluids. Potassium is raised due to poor exchange with sodium in the distal tubule and the acidosis (low pH and low bicarbonate concentration) arises from defective acidification of the glomerular filtrate acidosis is often associated with hyperkalaemia (raised plasma... 

Renal tubular necrosis, protein casts, and papillary hemorrhage were not observed in rats treated with a single gavage dose of 120 mg/kg phenol in water, but were seen in 60% of animals examined at the next highest dose of 224 mg/kg (Berman et al. 1995). No histopathological changes in the kidney were observed after 14 daily doses of 12 mg/kg/day, but were observed in 3 of 8 animals given 14 daily doses of 40 mg/kg/day (Berman et al. 1995). 

Cell proliferation, predominantly in the proximal tubules, occurred in Wistar rats following a single oral dose of 100 mg/kg 1,2-dibromoethane in corn oil. Mitotic activity peaked at 30 hours. Lack of any histologic evidence of tubular necrosis between 8-48 hours after treatment indicates that such proliferation was not a regenerative response (Ledda-Columbano et al. 1987b). 

Tubular necrosis was observed in male mice after acute exposure to chloroform concentrations >246 ppm (Culliford and Hewitt 1957 Deringer et al. 1953). Tubular calcifications were observed in mice that survived the exposure and were terminated after a 12-month recovery period. 

---