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The glomeruli ofjuxtamedullary nephrons are located deeper in the cortex (by198Renal PhysiologyA. Anterior surface of right kidneySuperior extremityFibrous capsuleincised andpeeled offHilusLateral marginRenal arteryRenal veinRenal pelvisUreterInferior extremityB. Right kidney sectioned in several planes, exposingparenchyma and renal sinusFibrous capsuleCortexMinor calycesBlood vesselsentering renalparenchymaMedulla (pyramid)Papilla of pyramidRenal sinusMajor calycesRenal column (of Bertin)Renal pelvisFat in renal sinusMedullary raysMinor calycesUreterFigure 16.1 Anatomy of the Kidney The kidneys are bilateral organs with arterial blood supply fromthe abdominal aorta through the renal arteries (A). The plasma is filtered at the glomeruli, which are locatedin the cortex. About 20% of the cardiac output enters the kidney (∼1 L/min), and excess fluid and solutesare excreted as urine.
The urine collects in the renal sinuses and exits the kidney via the ureter (B), whichleads to the bladder for storage until elimination.the medullary junction) and have long loops of Henle, extending deep into the inner medulla, forming the papillae.As stated, all nephrons have the same basic structures, but thelocation of the nephrons and the length of specific segmentsvary, with important consequences.
The primary nephronsegments are listed in sequential order in Table 16.1 withfunctions and distinctive characteristics.Blood FlowBlood flow to the kidneys (renal blood flow, RBF) is about 1liter per minute (L/min), or ∼20% of the cardiac output. Theblood enters the kidneys via the renal arteries and follows thepath shown:→→→→→→→interlobar arteriesarcuate arteries (at corticomedullary junction)interlobar/cortical radial arteriesafferent arteriole (site of regulation)glomerular capillariesefferent arteriolecortical peritubular capillaries (or vasa recta in deepnephrons)→ venule→ veinsThe plasma fraction of the blood is filtered at the glomerulus.Blood enters the capillary from the afferent arteriole and exitsthe capillary by the efferent arteriole. Efferent arterioles associated with cortical nephrons, lead to the peritubular capillar-Overview, Glomerular Filtration, and Renal ClearanceCapsuleCortexcorticisProximal convolutionProximalconvolutionDistalconvolutionJuxtamedullarynephrons concentrate anddilute the urineOuter zoneOuterInnerstripestripeCortexJuxtamedullaryglomerulusCorticalglomerulusDistal convolutionCortical nephronsdilute the urinebut do not concentrate the urineHenle’s loopHenle’sloopTHE NEPRHON:KEYGlomerulusAfferent andefferent arteriolesInner zoneMedulla (pyramid)199Proximal tubuleConvoluted segmentStraight segmentThin descending and ascendinglimbs of Henle’s loopDistal segmentsThick ascending limb ofHenle’s loopDistal convoluted tubuleMacula densaCollecting ductRenal blood flowGlomerular filtrationrateUrine flow rate1–1.2 L/min100–125 mL/min140–180 L/day0.5–18 L/dayNumber of nerphonsCorticalJuxtamedullary2.5 million2.1 million0.4 millionFigure 16.2 Nephron Structure The nephron is the functional unit of the kidney, and the structurediffers depending on the location of the glomerulus.
The glomeruli of cortical (superficial) nephrons arelocated in the upper cortical zone of the kidney and have loops of Henle that extend only to the outer zoneof the medulla. The glomeruli of the juxtamedullary (deep) nephrons are located at the cortico-medullaryjunction and have loops of Henle that extend deep into the inner medulla. There are ∼5 times more corticalthan juxtamedullary nephrons in the human kidney.ies, which collect material reabsorbed from the nephrons;efferent arterioles of the juxtaglomerular nephrons lead to thevasa recta (straight vessels), which collect material reabsorbedfrom medullary tubules.The GlomerulusThe glomerulus is a capillary system, from which an ultrafiltrate of plasma enters into Bowman’s space (Fig. 16.3).
Theglomerular capillary has a fenestrated endothelium and basement membrane, which prevent filtration of blood cells,proteins, and most macromolecules into the glomerular ultrafiltrate. The glomerulus is surrounded by epithelial cells(podocytes) a single layer thick, which contribute to the filtration barrier.
Filtration by the glomerulus occurs according tosize and charge—because the basement membrane and podocytes are negatively charged, most proteins (also negativelycharged) cannot be filtered. There are also mesangial cells that200Renal PhysiologyTable 16.1Nephron Segments: General Functions and Differences between Segments in Cortical vs.Juxtamedullary NephronsSegmentsDescription and GeneralFunctions of SegmentCharacteristics in CorticalNephronsCharacteristics inJuxtamedullary NephronsGlomerulusThe capillary net that filtersplasma, making ultrafiltrate.Upon entering the proximaltubule, ultrafiltrate is calledtubular fluid.Located superficially, in theouter and mid-cortex; theirefferent arterioles give rise tothe peritubular capillaries.Located deep in the cortex, by themedullary junction; efferent arteriolesgive rise to the vasa recta, whichare adjacent to deep nephrons andaid in concentration of urine.Proximal ConvolutedTubuleHas brush border villusmembrane and is main site ofreabsorption of solutes andwater.Shorter than proximalconvoluted tubules injuxtamedullary nephrons.Longer than in cortical nephrons,allowing relatively more reabsorptionof solutes.Proximal Straight TubuleAdditional reabsorption.Much longer than in deepnephrons.Shorter than in cortical nephrons.Thin descending loop ofHenle (tDLH)Impermeable to solutes butpermeable to water; thus, itconcentrates tubular fluid aswater diffuses out.Much shorter than in deepnephrons.Very long, forming pyramids, crucialfor concentrating tubular fluid.Thick ascending loop ofHenle (TALH)Impermeable to water, but hasNa+-K+-2Cl− transporters thatreabsorb more solutes anddilute the tubular fluid.
Sets upand maintains interstitialconcentration gradient.Longer than deep nephrons,dilutes tubular fluid.Dilutes tubular fluid and is critical inproducing the large concentrationgradient in the inner medulla.Distal convoluted tubuleElectrolyte modifications;aldosterone acts on late distalsegments.Similar in cortical and deepnephrons.Similar in cortical and deepnephrons.Collecting ducts (CD)Site of free water reabsorptionthrough water channels(aquaporins) controlled byADH.
CDs are also importantfor acid–base balance: the aintercalated cells allow H+secretion; b-intercalated cellshave HCO3−/Cl− exchangers,which allow HCO3− secretion,when necessary.The cortical collecting ducts(CCD) reabsorb some Na+and Cl− and secrete K+ (fromaldosterone-sensitive principalcells).
Less effect on urineconcentration compared withdeep nephrons because theducts do not extend far intomedulla. CCDs also have aand b-intercalated cells foracid–base regulation.Because they extend deep into themedulla, the final concentration ofurine occurs here. The innermedullary collecting ducts (IMCD)have principal cells (withaldosterone-sensitive Na+ and K+channels), as well as intercalatedcells (as seen in CCDs). MedullaryCDs are a key site of ADHdependent urea reabsorption, whichcontributes to the high medullaryinterstitial fluid osmolarity.ADH, antidiuretic hormone.support the glomerulus but can also contract, decreasingsurface area for filtration.The Juxtaglomerular ApparatusAnother important structural and functional aspect is the juxtaglomerular apparatus—this is the area where the distal convoluted tubule returns to its “parent” glomerulus.
At this site,specialized macula densa cells are in contact with the distalconvoluted tubule and afferent arteriole, forming the juxta-glomerular apparatus (see Fig. 16.3). The macula densa cellsof the juxtaglomerular apparatus are important in sensingtubular fluid flow and sodium delivery to the distal nephron,and because of their proximity to the afferent arteriole, maculadensa cells can regulate renal plasma flow and glomerular filtration rate (GFR) (autoregulation).
Macula densa cells alsoparticipate in the regulation of the release of the enzyme reninfrom juxtaglomerular cells adjacent to the afferent arterioles.The renin secretion aids in fluid and electrolyte homeostasis(see Chapter 19). Macula densa cells also receive input fromadrenergic nerves through β1-receptors.Overview, Glomerular Filtration, and Renal ClearanceCLINICAL CORRELATEGlomerulonephritisThe glomerulus is a key site for renal damage.
Diseases and drugsthat damage the glomerular basement membrane reduce the negative charge and allow large proteins (especially albumin) tobe filtered. Because there is no mechanism for reabsorbing largeproteins in the nephron, the protein is excreted in the urine (proteinuria). In addition, diseases (such as diabetes) that increasemesangial matrix deposition increase rigidity and decrease area offiltration of the glomerulus, reducing renal function.Acute glomerulonephritis is usually caused by different factors inchildren and adults. In children, a common cause is streptococcalinfection. In adults, acute glomerulonephritis can arise as a complication from drug reactions, pneumonia, immune disorders,and mumps.
Acute glomerulonephritis can be asymptomatic(about 50% of cases) or can be associated with edema, low urinevolume, headaches, nausea, and joint pain. Treatment is aimed atreducing the inflammation, usually with steroids or immunosuppressive drugs, while determining and addressing the cause, whenpossible. In most cases patients recover completely.201In contrast, chronic glomerulonephritis is associated with longterm inflammation of glomerular capillaries, resulting in thickened basement membranes, swollen epithelial cells, and narrowingof the capillary lumen.
Major causes of chronic glomerulonephritis are diabetes, lupus nephritis, focal segmental glomerulosclerosis, and IgA nephropathy. The rate of progression of kidneydamage to chronic renal failure (GFR less than 10 to 15 mL/min)is widely variable and can take as few as 5 years or more than 30years, depending on the overall cause of the inflammatory process.Chronic glomerulonephritis can lead to other major systemiccomplications including hypertension, heart failure, uremia, andanemia. Treatment is dependent on the cause of the damage, andin the case of diabetes-induced disease, angiotensin II receptorblockers or angiotensin-converting enzyme inhibitors are beneficial in slowing the renal damage. As the damage progresses towardend-stage renal failure, the GFR is insufficient to rid the body ofwaste, and uremia is one of the results.
Patients usually start hemodialysis when their GFR is less than 20 mL/min. Dialysis can beused for years, although many patients opt for renal transplantation, which is a common procedure.Chronic glomerulonephritis: Electron microscopic findingsEpithelial cell swollenBasement membrane thickenedElectron-dense deposits may be present subendotheliallyCapillary lumen narrowedEndothelial cell swollenFoot processes may or may not be fusedExtensive deposits of mesangial matrix in lobular stalkOnly slight proliferation of mesangial cellsLate stage of chronic glomerulonephritisContracted, pale,coarsely granular kidneyGlomeruli in various stages of obsolescence.
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