Medulla interstitial cells

EPO in the human adult is synthesized almost exclusively by specialized kidney cells (peritubular interstitial cells of the kidney cortex and upper medulla). Minor quantities are also synthesized in the liver, which represents the primary EPO-producing organ of the foetus. 

Both the medulla and the cortex of the kidney synthesize prostaglandins, the medulla substantially more than the cortex. COX-1 is expressed mainly in cortical and medullary collecting ducts and mesangial cells, arteriolar endothelium, and epithelial cells of Bowman s capsule. COX-2 is restricted to the renal medullary interstitial cells, the macula densa, and the cortical thick ascending limb. 

The papilla is the smallest anatomical portion of the kidney. Papillary tissue consists primarily of terminal portions of the collecting duct system and the vasa recta. Papillary blood flow is low relative to cortex and medulla less than 1% of total renal blood flow reaches the papilla. However, tubular fluid is maximally concentrated and the volume of luminal fluid is maximally reduced within the papilla. Potential toxicants trapped in tubular lumens may attain extremely high concentrations within the papilla during the process of urinary concentration. High intraluminal concentrations of potential toxicants may result in diffusion of these chemicals into papillary tubular epithelial and/or interstitial cells, leading to cellular injury. 

The source of the renal medullary antihypertensive substances appears to be the interstitial cells located primarily in the papilla. Granulation of these cells and presumably secretion has been demonstrated to reflect changes in blood pressure of animals subjected to experimental hypertension . Recently, rabbit interstitial cells have been grovm in tissue culture . Hie cells were obtained from autotransplants of renal medulla which prevented renovascular and renoprlval types of hypertension. Extracts of the cultured cells were shown to contain the three renal medullary prostaglandins PGE, PGA and PGF jy. 

Because the transport of sodium is an active process, it is used to accumulate NaCl in the interstitial fluid of the medulla. In fact, this activity is involved in the initial establishment of the vertical osmotic gradient. Furthermore, sodium is actively transported out of the tubular epithelial cells up its concentration gradient until the filtrate is 200 mOsm/1 less concentrated than the surrounding interstitial fluid. This difference between the filtrate and the interstitial fluid is referred to as the horizontal osmotic gradient. Because the filtrate at the end of the Loop of Henle has an osmolarity of 100 mOsm/1, the kidneys have the ability to produce urine that is significantly more dilute than the plasma. 

Chronic exposure of both rats and mice resulted in tubular nephropathy in both males and females. In rats, lesions were present in 45-66% of the males when they were sacrificed at 110 weeks after receiving 212 and 423 mg/kg/day hexachloroethane for 66 weeks of a 78-week exposure period (NTP 1977 Weisburger 1977). The renal lesions were characterized by hyperchromic regenerative epithelium, necrosis, interstitial nephritis, fibrosis, focal pyelonephritis, tubular ectasis, and hyaline casts. Lesions were also present in females but had a lower incidence (18% and 59%) for the two dose groups. Two-year exposures of male rats to much lower doses (10 and 20 mg/kg/day) resulted in similar effects on the kidneys (NTP 1989). Minimal to mild nephropathy was present in females for doses of 80 and 160 mg/kg/day. Over 90% of the male and female mice exposed to 590 and 1,179 mg/kg/day hexachloroethane for 78 weeks displayed tubular nephropathy when sacrificed at 90 weeks (NTP 1977 Weisburger 1977). Regenerative tubular epithelium was visible and degeneration of the tubular epithelium occurred at the junction of the cortex and the medulla. Hyaline casts were present in the tubules, and fibrosis, calcium deposition, and inflammatory cells were noted in the kidney tissues. 

Blood flow to the two kidneys is approximately 22-25% of the cardiac output. The kidneys are supplied by the renal artery which enters the kidneys through the hilum and then branches progressively to form the interlobar arteries, arcuate arteries, interlobular arteries (also called radial arteries), and afferent arterioles, which lead to the glomerular capillaries. The distal ends of each glomerulus coalesce to form the efferent arteriole, which leads to a secondary capillary network, the peritubular capillaries which surround the renal tubules. The cortex receives approximately 90% of the blood flow compared to the medulla or papillae so blood-borne toxic molecules reaching the kidneys have a more toxic effect on the cortex, as compared to the medulla or renal papillae. The interstitial space is occupied by the fenestrated peritubular capillaries and a small number of fibroblast-like cells. Increase in thickness of interstitial space in pathological conditions is due to edema, proliferation of fibrous tissue, or infiltration of inflammatory cells (Guyton and Hall, 2006). 

Arginine vasopressin (AVP) is a potent vasoconstrictor that preferentially reduces renal medullary blood flow through the stimulation of the vasopressin Via receptor (VlaR). Studies have also shown that the vasopressin V2 receptor (V2R) may modulate AVP-mediated vasoconstriction. The transcriptional and translational sites of the VlaR and V2R in micro-dissected intrarenal vascular segments from both the cortex and medulla was studied [154]. The results indicate that VlaR mRNA and proteins are present in the isolated cortical or medullary vasculature, but the V2R mRNA and proteins were not found. This study suggests that the vasoconstrictor action of AVP within the renal medulla is mediated through the VlaR and that the modulatory V2R- mediated vasodilation is probably through the release of paracrine hormones found within the renal interstitial or tubular cells. 

IMLFG interstitial nucleus of medial longitudinal fasciculus, greater part 40-45,81,101-103 IMM intermediomedial cell column 117a,b imvc intermedioventral thalamic commissure 33,103 In intercalated nucleus of the medulla 70-71, 80, 94-95 InCo intercollicular nucleus 49-52, 82-84,107-110 Inf infracerebellar nucleus 64-65 InfS infundibular stem 34-36, 79... 

These diseases involve the renal tubules and their surrounding interstitial tissue. The presentation may be acute and reversible with interstitial inflammatory cell infiltrates, rapid loss of renal function, and systemic symptoms or chronic and irreversible with interstitial fibrosis, slow loss of renal function, and no systemic symptoms. Papillary necrosis, a variant of chronic interstitial nephritis, originates deep in the renal medulla and papillae. 

To understand the mechanism of urine concentration, one must retrace the fate of the fluid in the various segments of the kidney. In the glomerulus, the membranes of the Bowman s capsule cells allow passage of all plasma components except protein. The ultrafiltrate is markedly reduced in volume as it passes through the proximal tubule. In fact, only 20% of the original volume reaches the distal portion of the proximal convoluted tube. The volume of the ultrafiltrate is reduced due to passive water reabsorption. Passive means that no known molecular mechanism exists for the transport of water from the lumen of the proximal tubule to the interstitial tissue. However, the movement of water follows that of sodium. In the proximal tubule, sodium is excreted actively into the interstitial tissue, and as a result, the osmotic pressure of the interstitial tissues increases. This draws water from the lumen of the tubule into the interstitial environment of the medulla because the tubule is highly permeable to water. 

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