Renal medulla

While the osmotic concentration of renal cortical tissue is isotonic, interstitial solute concentration begins to rise at the border between renal cortex and renal medulla to... 

Cyclooxygenase (COX) activity is responsible for the formation of prostaglandins from their arachidonic acid precursor. Two COX isoforms have been identified, COX-1 and COX-2. While COX-1 is constitutively expressed in most tissues, COX-2 is typically only found after induction by proinflammatory stimuli. However, a constitutively expressed and highly regulated COX-2 is found in the kidney, both in the renal medulla and in the renal cortex. Renal cortical COX-2 is located in the area ofthe juxtaglomerular apparatus, and prostaglandins formed by COX-2 regulate the expression and secretion of renin in response to a reduction in NaCl concentration at the macula densa. 

This is true of skeletal muscle, particularly the white fibers, where the rate of work output—and therefore the need for ATP formation—may exceed the rate at which oxygen can be taken up and utilized. Glycolysis in erythrocytes, even under aerobic conditions, always terminates in lactate, because the subsequent reactions of pymvate are mitochondrial, and erythrocytes lack mitochondria. Other tissues that normally derive much of their energy from glycolysis and produce lactate include brain, gastrointestinal tract, renal medulla, retina, and skin. The liver, kidneys, and heart usually take up... 

The procedure for purification of Na,K-ATPase in membrane-bound form from the outer renal medulla of mammalian kidney offers the opportunity of exploring the structure of the Na,K-pump proteins in their native membrane environment. The protein remains embedded in the membrane bilayer throughout the purification procedure thus maintaining the asymmetric orientation of the protein in the baso-lateral membrane of the kidney cell in the purified preparation. This preparation has been particularly useful in studies of ultrastructure, protein conformation and for... 

In an ideal pure preparation of Na,K-ATPase from outer renal medulla, the al subunit forms 65 70% of the total protein and the molar ratio of a to is 1 1, corresponding to a mass ratio of about 3 1 [1,5]. Functionally the preparation should be fully active in the sense that each a/ unit binds ATP, Pj, cations and the inhibitors vanadate and ouabain. The molecular activity should be close to a maximum value of 7 000-8 000 Pj/min. The highest reported binding capacities for ATP and phosphate are in the range 5-6 nmol/mg protein and close to one ligand per otjS unit [29], when fractions with maximum specific activities of Na,K-ATPase [40 50 pmo Pj/min mg protein) are selected for assay. 

The kidneys lie outside the peritoneal cavity in the posterior abdominal wall, one on each side of the vertebral column, slightly above the waistline. In the adult human, each kidney is approximately 11 cm long, 6 cm wide, and 3 cm thick. These organs are divided into two regions the inner renal medulla and the outer renal cortex. The functional unit of the kidney is the nephron (see Figure 19.1 and Figure 19.2). Approximately 1 million nephrons are in each kidney. The nephron has two components ... 

Renal effects have been observed in both male and female rats in a chronic-duration oral study. Male Fischer 344 rats exposed to 1,4-dichlorobenzene at 150 and 300 mg/kg/day for 2 years exhibited nephropathy, epithelial hyperplasia of the renal pelvis, mineralization of the collecting tubules in the renal medulla, and focal hyperplasia of the tubular epithelium. Each of these effects was associated with hyalin droplet formation. There were also increased incidences of nephropathy in female Fischer 344 rats dosed with 1,4-dichlorobenzene at 300 and 600 mg/kg/day. Histopathologically, the nephropathy was characterized by degeneration and regeneration of the tubular epithelium, tubular dilatation with attenuation and atrophy of the epithelium, granular casts in the tubules of the outer stripe of the medulla, thickening of the basement membranes, and minimal accumulation of interstitial collagen (NTP 1987). 

The smallest functional unit of the kidney is the nephron. In the glomerular capillary loops, ultrafiltration of plasma fluid into Bowman s capsule (BC) yields primary urine. In the proximal tubules (pT), approx. 70% of the ultrafiltrate is retrieved by isoosmotic reabsorption of NaCl and water. In the thick portion of the ascending limb of Henle s loop (HL), NaCl is absorbed unaccompanied by water. This is the prerequisite for the hairpin countercurrent mechanism that allows build-up of a very high NaQ concentration in the renal medulla In the distal tubules (dT), NaCl and water are again jointly reabsorbed. At the end of the nephron, this process involves an aldosterone-controlled exchange of Na+ against 1C or H. In the collecting tubule (C), vasopressin (antidiuretic hormone, ADH) increases the epithelial permeability for water, which is drawn into the hyperosmolar milieu of the renal medulla and thus retained in the body. As a result, a concentrated urine enters the renal pelvis. 

The major characteristics of the renal response to mannitol diuresis include a fall in urine osmolality and a decrease in the osmolality of the interstitial fluid of the renal medulla. The quantity of urine formation and Na excretion is generally proportional to the amount of mannitol excreted. Although there is a significant inhibition of proximal water reabsorption, the effects of mannitol on proximal Na+ reabsorption are not marked. 

Renal eorrex Renal medulla Renal pelvis... 

Dousa TP Interaction of lithium with vasopressin-sensitive cyclic AMP system of human renal medulla. Endocrinology 95 1359-1366, 1974... 

A family of integral proteins discovered by Peter Agre, the aquaporins (AQPs), provide channels for rapid movement of water molecules across all plasma membranes (Table 11-6 lists a few examples). Ten aquaporins are known in humans, each with its specialized role. Erythrocytes, which swell or shrink rapidly in response to abrupt changes in extracellular os-molarity as blood travels through the renal medulla, have a high density of aqua-porin in their plasma membranes (2 X 105 copies of AQP-1 per cell). In the nephron (the functional unit of the kidney), the plasma membranes of proximal renal tubule cells have five different aquaporin types. 

Water Flow through an Aquaporin Each human erythrocyte has about 2 X 105 AQP-1 monomers. If water molecules flow through the plasma membrane at a rate of 5 X 10s per AQP-1 tetramer per second, and the volume of an erythrocyte is 5 x 10 n mL, how rapidly could an erythrocyte halve its volume as it encounters the high osmolar-ity (1 m) in the interstitial fluid of the renal medulla Assume that the erythrocyte consists entirely of water. 

In rabbits given a single intravenous dose of aluminum lactate, aluminum concentrations did not increase above controls in the cerebellum, white brain tissue, hippocampus, spinal cord, adrenal glands, bone, heart, testes, or thyroid (Yokel and McNamara 1989). Treated animals did have significant increases of aluminum in the liver, serum, bile, kidneys, lungs, and spleen. The liver of exposed rabbits had over 80% of the total body burden of aluminum. Persistence of aluminum in the various tissues, organs, and fluids varied. Estimated half-times of aluminum were 113, 74, 44, 42, 4.2, and 2.3 days in the spleen, liver, lungs, serum, renal cortex, and renal medulla, respectively. The kidneys of treated rabbits also demonstrated a second half-time which exceeded 100 days. 

Subcutaneous injection of rabbits with aluminum chloride daily for 28 days was associated with significant accumulation of aluminum in bone, followed in order by significantly increased aluminum concentrations in renal cortex, renal medulla, liver, testes, skeletal muscle, heart, brain white matter, hippocampus, and plasma (Du Val et al. 1986). Because the brain tissue of treated rabbits had the lowest aluminum concentrations of the tissues evaluated, the authors suggested that there was a partial blood-brain barrier to entry of aluminum. 

Brezis M, Rosen S. Hypoxia of the renal medulla—its implications for disease. N Engl J Med 1995 332 647-655. 

The mechanism of acetaminophen toxicity has been studied extensively in experimental animals. Oxidation of acetaminophen in the liver via cytochrome P450 results in the formation of a cytotoxic electrophile, N-acetyl-p-benzoquinoneimine (NAPQI), that binds to hepatic protein. In the kidney, the formation of a one-electron oxidation product, namely N-acetyl-benzosemiquinoneimine radical, occurs via prostaglandin H synthase. This free radical binds to renal proteins and damages the renal medulla. 

The renal medulla is the middle portion of the kidney and consists of the loops of Henle, vasa recta, and collecting ducts. Medullary blood flow (about 6% of total renal blood flow) is considerably lower than cortical flow. However, by virtue of its countercurrent arrangement between tubular and vascular components, the medulla may be exposed to high concentrations of toxicants within tubular and interstitial structures. 

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