1625915643-5d53d156c9525bd62bd0d3434ecdc231 (843955), страница 56
Текст из файла (страница 56)
It is notbroken down in the blood, is freely filtered, and is not reabsorbed or secreted by the kidney. To measure inulin clearance(and thereby determine GFR), inulin is infused intravenously,and when a stable plasma level is achieved, timed urineThe RPF feeds the glomerular capillaries, but not all ofthe plasma presented to the capillaries is filtered. Thefiltration fraction (FF) is the proportion of the RPF that becomesglomerular filtrate:FF = GFR/RPFIn the normal adult, FF = (125 mL/min ÷ 600 mL/min) × 100= ∼20%, so ∼20% of the plasma entering the kidneys is filtered.At the individual nephrons, the unfiltered plasma exits theefferent arteriole to the peritubular capillaries.Sx = Ex − FLxRenal handling of key substances will be discussed inChapter 17.RENAL CLEARANCEBecause GFR is a primary measure of the health of kidneyfunction, GFR is routinely analyzed.
This can be done inseveral ways. The physical factors and pressures can all bemeasured experimentally, but this is not practical in humans.Instead, the principle of renal clearance is utilized. Renalclearance is the volume of plasma cleared of a substance per unittime. The clearance equation incorporates the urine andplasma concentrations of the substance, and the urine flowrate and is usually reported in mL/min or L/day:If the clearance of inulin (Cin) is 100 mL/min, it meansthat 100 mL of plasma is completely cleared of inulineach minute.
Contrast that to the clearance of glucose, which is0 mL/min in a normal person, indicating that no plasma iscleared of glucose (and therefore there is no glucose in theurine). The renal clearance of any filtered substance can be calculated, and when the clearance is compared with the GFR, itgives a general idea of whether there was net reabsorption ornet secretion of the substance—this is because the GFR is thetotal rate of filtration that is occurring at any given time.■■If the clearance of X is less than the GFR, there is netreabsorption.If the clearance of X is greater than the GFR, there is netsecretion, because more was cleared from the plasma thancan be accounted for by GFR alone.206Renal PhysiologyXX XX X XX X X X X X X X X XX X X X X X X X XX X X X X X X X X XXX X X X XX X X X XX X X XX X X XX X X XX X X XX X X XX X X XX X X XX X X XX X X XX X X XX X X XX X X XX X X XX X X XX X X XX X X XX X X X X X X X X X X XX X X X X X X X X X X XX X X X X X X X X X X XX X X X X X X X X X X XX X X X X X X X X XX X X X X X X X X XXXXXXXXXXXXConcentrationUX of substance (X)in urinePXXⴛX X X XX X X XXXXXXXXVolume ofV urine perunit timeConcentration ofsubstance (X) in plasmaSubstance (X) filteredthrough glomeruli andnot reabsorbed orsecreted by tubules(inulin)⫽ CXXXSubstance (X) filteredthrough glomeruli andsecreted by tubulesClearance of X equalsglomerular filtrationrate plus tubularsecretion rateCX ⴝ GFR ⴙ TXCX ⬎ CINULINSubstance (X) filteredthrough glomeruli andreabsorbed by tubulesClearance of X equalsglomerular filtration rateminus tubular reabsorptionrateCX ⴝ GFR – TXCX ⬍ CINULINClearance of X equalsglomerular filtration rateCX ⴝ GFRXVolume ofplasma clearedof substance (X)per unit time(clearance of X)XXSubstance (X) filteredthrough glomeruli,reabsorbed by tubules, andalso secreted by tubulesClearance of X equalsglomerular filtration rateminus net reabsorption rateor plus net secretion rateCX ⴝ GFR ⴞ TXCx ⬍ or ⬎ CINULINFigure 16.6 Renal Clearance Principle “Clearance” describes the volume of plasma that is clearedof a substance per unit time.
The renal clearance of a substance provides information on how the kidneyhandles that substance. Since inulin is freely filtered, and not reabsorbed or secreted, all of the filtered inulinis excreted in the urine. Thus, Cin is equated with the glomerular filtration rate (GFR), and the net handlingof other substances can be determined, depending on whether their clearance is greater than (net secretion),less than (net reabsorption), or equal to Cin.Plasma creatinine is used clinically to estimate GFR.
Inmost cases, the body produces creatinine at a constantrate, so the excretion rate is also constant. Since .GFR is equatedwith the clearance of creatinine[GFR = (UCr × V) ÷ PCr], if cre.atinine excretion (UCr × V) is constant, the GFR is proportionalto 1/PCr. So, when the GFR decreases, less creatinine is filteredand excreted, and plasma creatinine builds up.
As a clinicalapplication, this allows a rapid approximation of the GFR bysimply analyzing the PCr. PCr is normally ∼1 mg%, so GFR isproportional to 1/1, or 100%. If PCr rises to 2, GFR is ½, or 50%,and so on.collections are made. The calculated clearance of inulin canbe equated to the GFR (see Fig.
16.5):Cinulin = GFRInfusing inulin to determine clearance is not routinely usedbecause of the invasive nature of the procedure. Instead, therenal clearance of the endogenous substance creatinine is usedto approximate GFR. Creatinine is a by-product of musclemetabolism and is freely filtered by the kidneys. It is not reabsorbed, but there is ∼10% secretion into the renal tubules fromthe peritubular capillaries, and thus, creatinine clearance overestimates GFR by ∼10% (Fig. 16.6).Overview, Glomerular Filtration, and Renal ClearanceREGULATION OF RENAL HEMODYNAMICSRegulation of the GFR occurs by changes in blood flow to theglomeruli via intrinsic feedback systems, hormones, vasoactive substances, and renal sympathetic nerves.Intrinsic systems include the myogenic mechanism and tubuloglomerular feedback (TGF).
Utilizing the myogenic mechanism, the renal arteries and arterioles respond directly toincreases in systemic blood pressure by constricting, therebymaintaining constant filtration pressure in the glomerularcapillaries. Tubuloglomerular feedback (TGF) is a regulatorymechanism that involves the macula densa of the juxtaglomerular apparatus. The kidney is unique in that the glomerular capillaries have arterioles (resistance vessels) on eitherend of the capillary network.
Constriction of the afferentor efferent arterioles can elicit immediate effects on the HPGC,controlling GFR. Because the juxtaglomerular apparatusfunctionally associates the distal tubule to the afferent arteriole, the tubular flow past the macula densa can control afferent arteriolar resistance (see Fig. 16.3). Decreases in flow andtubular fluid sodium concentration in the distal tubule willdecrease afferent arteriolar resistance and increase GFR in thatnephron; conversely, if distal tubular flow or osmolarity ishigh, TGF will increase afferent arteriolar resistance, decreasing GFR. These systems allow minute-to-minute regulation ofGFR over a wide range of systemic blood pressures (MAP 80to 180 mm Hg).Many substances (including nitric oxide and endothelin)regulate renal hemodynamics, but this section will focus onthe renin-angiotensin-aldosterone system (RAAS), atrial natriuretic peptide (ANP), sympathetic nerves/catecholamines,and intrarenal prostaglandins.
Although angiotensin II andthe sympathetic nervous system are activated to preserve systemic blood pressure, the kidneys will respond to excessiveconstriction by intrarenal autoregulation, preserving bloodflow to the glomeruli. This balance between extrarenal andintrarenal control is necessary to maintain proper GFR.Control of renal hemodynamics occurs through the followingneurohumoral and paracrine mechanisms:■The renin-angiotensin-aldosterone system (RAAS) isactivated in response to low renal vascular flow. Renalvascular baroreceptors stimulate renin secretion by thejuxtaglomerular cells at the ends of the afferent arterioles. This, in addition to the modulation of renin secre-■■■■207tion by the macula densa, will activate the RAAS (seedetailed description in Chapter 19).
The renin will actlocally and through the systemic circulation to produceangiotensin II, and thus control GFR.Angiotensin II exerts both direct and indirect effects onthe GFR. It is a vasoconstrictor, and in the kidneys, itacts directly on the renal arteries, and to a greater extentat the afferent and efferent arterioles, increasing resistance, reducing HPGC, and decreasing GFR; angiotensinII actually has greater effect on the efferent arteriole thanafferent arteriole.
At the same time, it can constrict glomerular mesangial cells, reducing Kf, and thus, GFR.Atrial natriuretic peptide (ANP) is released from theright cardiac atrial myocytes in response to stretch (athigh blood volume). To regulate GFR, ANP dilates theafferent arteriole, and constricts the efferent arteriole,increasing HPgc, and thus, GFR. The enhanced flowincreases sodium and water excretion, reducing bloodvolume.Sympathetic nerves and catecholamine secretion (NEand Epi) are stimulated in response to reductions insystemic blood pressure and cause vasoconstriction ofthe renal arteries and arterioles.
![](https://s.studizba.com/z.php?f=/templates/si/i/noavatar.png&w=100&h=100&t=1"){kind=avatar}
