Tubulo proximal upch

Notas del editor

• #28: S1 has a tall brush border and a well-developed vacuolar-lysosomal system. Basolateral plasma membrane forms extensive lateral invaginations, and lateral cell processes extending from the apical to the basal surface interdigitate with similar processes from adjacent cells. Elongated mitochondria are located in the lateral cell processes in proximity to the plasma membrane.
• #29: S2 is similar to S1; the brush border is shorter, the basolateral invaginations are less prominent, and the mitochondria are smaller. Numerous small lateral processes are located close to the base of the cell. The endocytic compartment is less prominent than in the S1. The number and size of the lysosomes vary among species and between males and females, and numerous large lysosomes are often observed in the S2 segment of the male rat
• #30: S3, lateral cell processes and invaginations are essentially absent, mitochondria are small and randomly distributed. The length of the brush border in the S3 segment varies among species. Tall in the rat, short in the rabbit, and intermediate in human. Variation is observed in the vacuolar-lysosomal compartment. In rat and human, endocytic vacuoles and lysosomes are small and sparse, in the rabbit, large endocytic vacuoles and numerous small lysosomes are present. Peroxisomes are present throughout the proximal tubule. They increase in number along the length of the proximal tubule and are most prominent in the S3 segment.
• #36: COMPLEJOS RELATIVAMENTE PERMEABLES, APARIENCIA DE CORDONES. TUBULO PROXIMAL TIENE UN SOLO CORDON FRENTE A 8 DE DISTAL.
• #41: Ammonia transport along the various renal epithelial segments. Ammonia is primarily produced in the proximal tubule. It is preferentially secreted into the luminal fluid through mechanisms which involve NHE-3-mediated Na+/NH4+ exchange, NH4+ transport through Ba2+-inhibitable K+ channels, and an uncharacterized NH3 transport pathway. Ammonia is reabsorbed by the TAL through a process primarily involving Na+-K+-2Cl− cotransporter (NKCC2)-mediated NH4+ reabsorption. Recycling of ammonia through secretion in the DTL results in ammonia delivery to the turn of the loop of Henle that exceeds total excreted ammonia. NH4+ reabsorption in the TAL, however, results in total ammonia delivery to distal nephron segments that accounts for only a minority of total excreted ammonia. Ammonia secretion in the collecting duct involves parallel H+ and NH3 secretion. Numbers in blue reflect proportion of total urinary ammonia delivered to indicated sites. Specific details of ammonia secretion in each of these nephron segments are provided in the text.
• #42: Ammonia transport in the proximal tubule. Ammonia is produced in the proximal tubule primarily from metabolism of glutamine and occurs primarily in the mitochondria. The enzymatic details of ammoniagenesis are not shown. Three transport mechanisms appear to mediate preferential apical ammonia secretion. These include Na+/NH4+ exchange via NHE-3, parallel NH3 secretion and NHE-3-mediated Na+/H+ exchange, and a Ba2+-sensitive NH4+ conductance likely mediated by apical K+ channels. HCO3− is produced in equimolar amounts as NH4+ in the process of ammoniagenesis and is primarily transported across the basolateral plasma membrane by NBCe1. Minor components of basolateral NH4+ uptake via Na+-K+-ATPase and by basolateral K+ channels are not shown.
• #44: EL ENLACE PARECE SER EL ATP QUE INHIBE LOS CANALES DE POTASIO BASOLATERALES. SI AUMENTA LA REABSRCION DE SODIO SE CONSUME ATP Y SE PIERDE EL EFECTO INHIBITORIO AUMENTANDO EL NUMERO DE CANALES DE POTASIO BASOLATERALES ABIERTOS
• #62: PROBLEMA CON ESTA TEORIA, DISMINUYENDO LA PRESION ONCOTICA EN LOS CAPILARES PERITUBULARES, SE REDUCE LA ABSORCION DE NACL PERO NO LA DE GLUCOSA O BICARBONATO, NO EXPLICABLE POR LA MAYOR PERMEABILIDAD DE LOS COMPLEJOS DE UNION AL CLORO PORQUE ES LA REABSORCION ACTIVA LA QUE ESTA DISMINUIDA
• #70: There must be a parallel increase in proximal tubule transport with the maturational increase in glomerular filtration rate. If this did not occur the neonate would die of dehydration when the glomerular filtration rate increased after birth. The surface nephrons are relatively immature compared to the juxtamedullary nephrons.
• #71: As the delivered load increases to the tubule either by an increase in the serum concentration or an increase in glomerular filtration rate, the amount of solute absorbed increases. At some point, the renal tubular absorption reaches a maximum, called the threshold for that solute, and any further increase in the filtered load is excreted.
• #82: The high capacity–low affinity sodium dependent glucose transporter on the apical membrane is designated as SGLT-2 (332). This removes the bulk of the glucose from the glomerular ultrafiltrate. Some patients with familial glucosuria, a benign condition, have a mutation in SGLT2 (63, 184).
• #83: The low capacity–high affinity transporter is designated SGLT-1 (130, 143). The glucose that is transported by the tubule exits across the basolateral membrane by facilitative diffusion. A defect in SGLT-1 causes glucose-galactose malabsorption as this transporter is also present in the intestine.
• #85: Tm DE 375 mg/min , NO GLUCOSURIA HASTA Q LA CARGA FILTRADA SEA MAYOR. PARA UNA TFG 125ml/min NO GLUCOSURIA HASTA GLUCOSA > 300 mg/dl. GLUCOSURIA CON 180 A 200 mg/dl: APLANAMIENTO. HETEROGENEIDAD ENTRE TAMAÑO GLOMERULAR Y LONGITUD TUBULAR PROXIMAL EN NEFRONAS INDIVIDUALES
• #89: Schematic of calcium balance in a young adult who ingested 1000 mg/d dietary calcium. In the schematic, the calcium balance is neutral (zero). The dermal (skin) calcium loss, which rarely is measured, is not included in the numbers. The amount of calcium involved in bone formation and resorption rate is shown to be 200 to 500 mg/d (42,132,133), but it also has been shown that the amount of calcium that is involved in bone formation and resorption is much smaller than the total exchangeable calcium bone pool, which has been shown by radioisotope studies to be 3 to 6 g/d (42,132–134). Also shown in the inset is that whereas the bone balance of calcium (influx versus efflux) is neutral in a young adult, the influx of calcium is greater than the efflux of calcium in the young child and adolescent. Conversely, in the old adult, the influx of calcium to bone is less than the efflux of calcium from bone. Calcium balance also is affected by calcium intake. Greater calcium intake will improve calcium balance in all four groups, but the difference between young and old still is maintained. The mg values in the figure represents per day; Ca, calcium.
• #91: Regulation of serum calcium homeostasis. Serum calcium homeostasis is regulated by a rapid negative feedback hormonal pathway involving the concentration of ionized calcium in serum (Ca, green arrows) and the secretion of parathyroid hormone (PTH, blue arrows) from the parathyroid. A fall in serum calcium (↓ Ca) inactivates the calcium receptor in the parathyroid cell (CaR; green circle) and increases PTH secretion (↑ PTH), which restores serum calcium (↑ Ca) by activating the parathyroid receptor (PTHR; blue circles) in bone, to increase calcium resorption, and in kidney, to increase tubular calcium reabsorption. In kidney, the increased PTH secretion augments its calcium-restorative effect by increasing secretion of 1,25-dihydroxyvitamin D (1,25D; red arrows), which, acting on the vitamin D receptor (VDR, red circles) in gut, increases active calcium absorption and increases calcium resorption in bone.
• #99: Intrarenal localization and roles of the calcium-sensing receptor (CaSR). Cellular polarity of the CaSR is apical [in the proximal tubule and outer/inner medullary collecting duct (OMCD/IMCD)] and basolateral [in the thick ascending limb (TAL) and, occasionally, in the cortical collecting duct (CCD)]. Species differences exist in the distal convoluted tubule (DCT)/connecting segment (CNT), where receptor expression can be detected apically and/or basolaterally/intracellularly. PCT/PST, proximal convoluted/straight tubule; tDL/tAL, thin discending/ascending limb; MTAL/CTAL, medullary/cortical thick ascending limb; JGA: juxtaglomerular apparatus; TRPV5, transient receptor potential vanilloid 5; PMCA, plasma membrane Ca2+-ATPase; VitD, vitamin D; VDR, vitamin D receptor; NKCC2, Na+-K+-2Cl− cotransporter 2; ROMK, renal outer medullary potassium K+ channel; PTH, parathyroid hormone; AQP2, aquaporin 2.
• #114: Regulation of serum phosphate (P) homeostasis: interface with serum calcium (Ca) homeostasis at the kidney. Serum phosphate homeostasis is regulated by a negative feedback hormonal pathway (black arrows) involving the concentration of phosphate in serum (P, blue square) and the secretion of fibroblast growth factor 23 (FGF-23; blue circles) from bone cells. A fall in serum P (↓) decreases secretion of FGF-23 (↓), which restores serum P by acting on the type 2 sodium-phosphate renal tubular transporters (NaPi-II) to increase (↑) phosphate reabsorption (TmP; red squares) and by increasing secretion (↑) of renal 1,25-dihydroxyvitamin D (1,25D; purple hexagons) to increase phosphate gut absorption. A rise (↑) in serum P increases (↑) FGF-23 secretion, which restores serum P by lowering (↓) phosphate reabsorption (TmP; red squares) and by lowering secretion (↓) of renal 1,25-dihydroxyvitamin D (1,25D; purple hexagons) to decrease phosphate gut absorption. Changes in the Ca–PTH homeostatic system also have major effects on serum P, but not through a negative feedback pathway, because serum P does not directly regulate PTH secretion. Ca-induced changes in PTH secretion (green circles) induce changes in serum P by regulating tubular phosphate reabsorption (TmP; red squares) through the activity of the NaPi-ll renal tubular transporters. It should be noted that, although both FGF-23 and PTH have the same action on renal tubular reabsorption (TmP; red squares), these hormones have opposing effects on renal 1,25-dihydroxyvitamin D (1,25D; purple hexagons) secretion; the P-FGF23 homeostatic system is more slowly acting than the Ca-PTH homeostatic system; and the receptor for serum P remains to be discovered.
• #115: After being filtered at the glomerulus, phosphate is almost exclusively reabsorbed in the proximal tubule. Phosphate uptake at the apical (urinary) domain of the proximal tubular cell is a process that requires energy. The phosphate carriers use the gradient of sodium between the intracellular and extracellular space to transport phosphate into cells. Three main types of sodium−phosphate cotransporters are expressed at the apical domain: NPT2a, NPT2c, and PiT2. The bulk of phosphate is transported by NPT2a. The amount of phosphate reabsorbed depends on the number of sodium−phosphate cotransporter units expressed at the membrane. Two hormones reduce the expression of sodium−phosphate cotransporters: parathyroid hormone (PTH), which stimulates cyclic AMP (cAMP) and activates protein kinase A, and fibroblast growth factor (FGF) 23 (FGF-23). The multifunctional protein sodium− hydrogen exchanger regulatory factor 1 (NHERF1) can bind to the PTH type 1 receptor (PTH1R) and to NPT2a. The binding of NHERF1 to PTHR1 modifies cAMP produced by PTH in proximal tubular cells. FGF-23 binds to its coreceptor (klotho) and to an FGF receptor (probably FGFR1). KLOTHO is expressed not in the proximal tubule but in the distal tubule, suggesting an indirect action of FGF-23 on the functions of the proximal tubule. PHEX (phosphateregulating gene with homologies to endopeptidase on the X chromosome) and DMP1 (dentin matrix protein 1) are expressed in bone cells. Mutations of these proteins result in an increase in FGF-23 production. RXXR is the sequence in the FGF-23 protein where FGF-23 is cleared and inactivated. Mutations in this site make FGF-23 resistant to enzymatic cleavage.
• #120: autosomal recessive disorder of variable expression, characterized by a pellagralike rash, cerebellar ataxia, psychological and neurological disturbances
• #121: autosomal recessive disorder of variable expression, characterized by a pellagralike rash, cerebellar ataxia, psychological and neurological disturbances
• #122: autosomal recessive disorder of variable expression, characterized by a pellagralike rash, cerebellar ataxia, psychological and neurological disturbances