1、1,第八章 尿的生成和排出,2,3,4,肾的功能：机体重要的排泄器官1.排除机体的大部分代谢终产物及异物；2.调节水和电解质的平衡:调整细胞外液量和渗透压,电解质,5,3.维持酸碱平衡。4.肾具有内分泌功能,分泌EPO,肾素.,6,尿的生成包括: 肾小球的滤过，肾小管和集合管的重吸收和肾小管和集合管的分泌三个基本过程。,7,8,In the kidneys, a fluid that resembles plasma is filtered through the glomerular capillaries into the renal tubules (glomerular filtrat
2、ion).,9,10,As this glomerular filtrate滤出液passes down the tubules, its volume is reduced and its composition altered by the processes of tubular reabsorption (removal of water and solutes from the tubular fluid) and tubular secretion (secretion of solutes into the tubular fluid) to form the urine tha
3、t enters the renal pelvis 肾盂.,11,A comparison of the composition of the plasma and an average urine specimen illustrates the magnitude of some of these changes and emphasizes the manner in which wastes are eliminated while water and important electrolytes and metabolites are conserved.,12,Furthermor
4、e, the composition of the urine can be varied, and many homeostatic regulatory mechanisms minimize or prevent changes in the composition of the ECF （extracellular fluid ）by changing the amount of water and various specific solutes in the urine.,13,From the renal pelvis, the urine passes to the bladd
5、er and is expelled to the exterior by the process of urination, or micturition.,14,The kidneys are also endocrine organs, making kinins 激肽 and 1,25- dihydroxycholecalciferol二羟胆钙化醇二羟维生素D3 and making and secreting renin.,15,第一节 肾的功能解剖和肾血流量一. 肾的功能解剖（一）肾单位和集合管,16,肾的功能：机体重要的排泄器官1.排除机体的大部分代谢终产物及异物；2.调节水和电
6、解质的平衡:调整细胞外液量和渗透压,电解质,17,肾单位是肾的基本功能单位，它与集合管共同完成泌尿功能 。人的两侧肾约有170-240万个肾单位。,18,19,Each individual renal tubule and its glomerulus is a unit (nephron 肾单位). The size of the kidneys in various species is determined largely by the number of nephrons they contain. There are approximately 1.3million nephron
7、s in each human kidney.,20,21,22,23,The glomerulus, which is about 200m in diameter, is formed by the invagination 内陷of a tuft of capillaries into the dilated, blind end of the nephron (Bowmans capsule). The capillaries are supplied by an afferent arteriole and drained by a slightly smaller efferent
8、 arteriole.,24,The glomerulus is essentially a tuft of capillaries interposed插入between two resistance vessels, the afferent and efferent arterioles . This unique arrangement provides a mechanism to control the glomerular capillary hydraulic pressure within a narrow range, despite wide fluctuations i
9、n the systemic blood pressure.,25,26,27,There are two cellular layers separating the blood from the glomerular filtrate in Bowmans capsule: the capillary endothelium and the specialized epithelium of the capsule that is made up of podocytes (足细胞：肾小球脏层的一种上皮细胞，有突起相互交错并包绕小球毛细血管的基底膜) overlying the glome
10、rular capillaries (Figure 38-3).,28,29,These layers are separated by a basal lamina. Stellate cells called mesangial cells小球膜细胞 ）are located between the basal lamina and the endothelium. They are similar to cells called pericytes周细胞, which are found in the walls of capillaries elsewhere in the body.
11、,30,Mesangial cells are especially common between two neighboring capillaries, and in these locations the basal membrane forms a sheath shared by both capillaries (Figure 38-3). The mesangial cells are contractile and play a role in the regulation of glomerular filtration. They also secrete various
12、substances, take up immune complexes, and are involved in the production of glomerular disease.,31,The endothelium of the glomerular capillaries is fenestrated, with pores that are 70-90 nm in diameter. The cells of the epithelium (podocytes) have numerous pseudopodia伪足that interdigitateto form filt
13、ration slits along the capillary wall. The slits are approximately 25 nm wide, and each is closed by a thin membrane. The basal lamina does not contain visible gaps or pores.,32,Functionally, the glomerular membrane permits the free passage of neutral substances up to 4 nm in diameter and almost tot
14、ally excludes those with diameters greater than 8 nm. However, the charges on molecules as well as their diameters affect their passage into Bowmans capsule . The total area of glomerular capillary endothelium across which filtration occurs in humans is about 0.8 m2.,33,(二）皮质肾单位和近髓肾单位肾单位按其所在部位不同，可分为
15、质肾单位和近髓肾单位两类。,34,皮质肾单位 主要分布于外皮质层和中皮质层。约占肾单位总数的85%-90%。入球小动脉与出球小动脉的口径之比约为2：1,所以肾小球内毛细血管血压较高。,35,近髓肾单位 分布于靠近髓质的内皮质层。其髓袢甚长，可深入到内髓质层。出球小动脉形成细而长的U字形直小血管。近髓肾单位在尿的浓缩与稀释过程中起着重要作用。,36,37,The nephrons with glomeruli in the outer portions of the renal cortex have short loops of Henle (cortical nephrons), where
16、as those with glomeruli in the juxtamedullary region of the cortex (juxtamedullary nephrons) have long loops extending down into the medullary pyramids. In humans, only 15% of the nephrons have long loops.,38,（三）近球小体近球小体（juxtaglomerular apparatus）由颗粒细胞、系膜细胞和致密斑三者组成。,39,40,颗粒细胞位于入球小动脉的中膜内，内含分泌颗粒，颗粒内含
17、肾素。,41,致密斑位于远曲小管的起始部分，细胞为高柱状。致密斑可感受小管液中NaCI含量的变化，并将信息传递至颗粒细胞，调节肾素的释放。,42,近髓肾单位 分布于靠近髓质的内皮质层。其髓袢甚长，可深入到内髓质层。出球小动脉形成细而长的U字形直小血管。近髓肾单位在尿的浓缩与稀释过程中起着重要作用。,43,The walls of the afferent arerioles contain the renin-secreting juxtaglomerular cells. At this point, the tubular epithelium is modified histologic
18、ally to form the macula densa. The juxtaglomerular cells, the macula densa, and the lacis cells near them are known collectively as the juxtaglomerular apparatus .,44,（四）肾的神经支配肾交感神经主要从胸腰段脊髓发出，未发现肾有副交感神经支配。,45,Functions of the Renal NervesStimulation of the renal nerves increases renin secretion by a
19、 direct action of released norepinephrine on -adrenergic receptors on the juxtaglomerular cells and it increases Na+ reabsorption, probably by a direct action of norepinephrine on renal tubular cells. The proximal and distal tubules and the thick ascending limb of the loop of Henle are richly innerv
20、ated.,46,When the renal nerves are stimulated at increasing strengths in experimental animals, the first response is an increase in the sensitivity of the juxtagloplerular cells , followed by increased renin secretion, then increased Na+ reabsorption, and finally, at the highest threshold, renal vas
21、oconstriction with decreased glomerular filtration and renal blood flow.,47,It is still unsettled whether the effect on Na+ reabsorption is mediated via - or -adrenergic receptors, and it may be mediated by both. The physiologic role of the renal nerves in Na+ metabolism is also unsettled, in part b
22、ecause most renal functions appear to be normal in patients with transplanted kidneys, and it takes some time for transplanted kidneys to acquire a functional innervation.,48,Strong stimulation of the sympathetic nerves to the kidneys causes a marked decrease in renal blood flow. There is some tonic
23、 discharge in the renal nerves at rest in animals and humans.,49,When systemic blood pressure falls, the vasoconstrictor response produced by decreased discharge in the baroreceptor nerves includes renal vasoconstriction. Renal blood flow is decreased during exercise and, to a lesser extent, on risi
24、ng from the supine position.,50,（五)肾的血流,51,肾小球毛细血管网介于入球小动脉和出球小动脉之间，而且皮质肾单位入球小动脉的口径粗。因此，肾小球毛细血管内血压较高，有利于肾小球的滤过作用。,52,肾血液循环的特征肾的血液供应很丰富。其中约94%的血液分布在肾皮质层，通常所说的肾血流量主要指肾皮质血流量。,53,（一）肾血流量的自身调节不依赖神经体液,当动脉血压在一定范围(80-180mmHg)内变动时，肾血流量仍然保持相对恒定。自身调节的机制，用肌源学说来解释。,54,55,肾血流量和肾小球滤过率的自身调节RPF：肾血浆流量 GFR：肾小球滤过率。,56,（
25、二）肾血流量的神经和体液调节肾交感神经活动加强时，引起肾血管收缩，肾血流量减少。肾上腺素，去甲肾上腺素，血管升压素和血管紧张素能使肾血管收缩，肾血流量减少。,57,Blood FlowIn a resting adult, the kidneys receive 1.2-1.3 L of blood per minute, or just under 25% of the cardiac output,58,Regulation of the Renal Blood FlowNorepinephrine constricts the renal vessels, with the greate
26、st effect of injected norepinephrine being exerted on the interlobular arteries and the afferent arterioles. Dopamine is made in the kidney and causes renal vasodilation and natriuresis 尿内排钠.,59,Angiotensin II exerts a greater constrictor effect on the efferent arterioles than on the afferent. Prost
27、aglandins increase blood flow in the renal cortex and decrease blood flow in the renal medulla. Acetylcholine also produces renal vasodilation. A high-protein diet raises glomerular capillary pressure and increases renal blood flow.,60,The pressure in the glomerular capillaries has been measured dir
28、ectly in rats and has been found to be considerably lower than predicted on the basis of indirect measurements. When the mean systemic arterial pressure is 100 mm Hg, the glomerular capillary pressure is about 45 mm Hg.,61,The pressure drop across the glomerulus is only 1-3 mm Hg, but there is a fur
29、ther drop in the efferent arteriole so that the pressure in the peritubular capillaries is about 8 mm Hg. The pressure in the renal vein is about 4 mm Hg. Pressure gradients are similar in the monkey and presumably in humans, with a glomerular capillary pressure that is about 40% of systemic arteria
30、l pressure.,62,Autoregulation of Renal Blood FlowWhen the kidney is perfused at moderate pressures the renal vascular resistance varies with the pressure so that renal blood flow is relatively constant。,63,It is probably produced in part by a direct contractile response of the smooth muscle of the a
31、fferent arteriole to stretch. NOnitric oxide may also be involved. At low perfusion pressures, angiotensin II also appears to play a role by constricting the efferent arterioles, thus maintaining the glomerular filtration rate.,64,第二节 肾小球的滤过功能,65,血液经过肾小球毛细血管时，血浆中的水和小分子溶质，滤入肾小囊的囊腔而形成滤过液，又称原尿。,66,单位时间
32、内（每分钟）两肾生成的超滤液量称为肾小球滤过率glomerular filtration rate, GFR。成人肾小球滤过率平均为125ml/min左右。,67,肾小球滤过率和肾血浆流量的比例称为滤过分数（filtration fraction）。滤过分数为：125/660100=19%。滤过分数表明，流经肾的血浆约有1/5滤入肾小囊囊腔中。,68,The first step in the process of urine formation is passage of a cell- and protein-free ultrafiltrate 超滤液of plasma which co
33、ntains small solutes (such as urea尿素creatinine肌酐, sodium,potassium, and uric acid) and water, albumin (MW 69,000) and globulins球蛋白are filtered in very small amounts.,69,Normal GFR glomerular filtration rateThe GFR in an average-sized normal man is approximately 125 ml/min. Its magnitude correlates f
34、airly well with surface area, but values in women are 10% lower than those in men even after correction for surface area.,70,A rate of 125 ml/min is 7.5 L/h, or 180 L/d, whereas the normal urine volume is about 1 L/d. Thus, 99% or more of the filtrate is normally reabsorbed. At the rate of 125 ml/mi
35、n, the kidneys filter in 1 day an amount of fluid equal to 4 times the total body water, 15 times the ECF volume, and 60 times the plasma volume.,71,Control of GFRThe factors governing filtration across the glomerular capillaries are the same as those governing filtration across all other capillarie
36、s, ie, the size of the capillary bed, the permeability of the capillaries, and the hydrostatic and osmotic pressure gradients across the capillary wall.,72,一、滤过膜及其通透性当滤过面积减少，肾小球滤过率降低，结果出现少尿（每昼夜尿量在100-500ml之间）以致无尿（每昼夜尿量不100ml）。,73,74,不同物质通过肾小球滤过膜的能力决定于被滤过物质的分子大小及其所带的电荷。,75,PermeabilityThe permeabilit
37、y of the glomerular capillaries is about 50 times that of the capillaries in skeletal muscle. Neutral substances with effective molecular diameters of less than 4 nm are freely filtered,76,and the filtration of neutral substances with diameters of more than 8 nm approaches zero. Between these values
38、, filtration is inversely proportionate to diameter.,77,The negative charges repel negatively charged substances in blood, with the result that filtration of anionic阴离子 的substances 4 nm in diameter is less than half that of neutral substances of the same size.,78,This probably explains why albumin,
39、with an effective molecular diameter of approximately 7 nm, normally has a glomerular concentration only 0.2% of its plasma concentration rather than the higher concentration that would be expected on the basis of diameter alone; circulating albumin is negatively charged. Filtration of cationic subs
40、tances is slightly greater than that of neutral substances.,79,The amount of protein in the urine is normally less than 100 mg/d, and most of this is not filtered but comes from shed脱落tubular cells. The presence of significant amounts of albumin in the urine is called albuminuria. In nephritis, the
41、negative charges in the glomerular wall are dissipated消散, and albuminuria can occur for this reason without an increase in the size of the pores in the membrane.,80,Filtration FractionThe ratio of the GFR to the renal plasma flow (RPF), the filtration fraction, is normally 0.16-0.20. The GFR varies
42、less than the RPF. When there is a fall in systemic blood pressure, the GFR falls less than the RPF because of efferent arteriolar constriction, and consequently the filtration fraction rises.,81,肾小球滤过作用的动力是有效滤过压。肾小球有效滤过压=（肾小球毛细血管压+囊内液胶体渗透压）-（血浆胶体渗透压+肾小囊内压）。,82,由于肾小囊内胶体渗透压很小忽略不计。因此有效滤过压= 肾小球毛细血管压 -（
43、血浆胶体渗透压+肾小囊内压）。,83,For each nephron:GFR = Kf (P GC - PT) - (GC T)Kf ,the glomerular ultrafiltration coefficient, is the product of the glomerular capillary wall hydraulic conductivity (ie, its permeability) and the effective filtration surface area.,84,PGC is the mean hydrostatic pressure in the glo
44、merular capillaries, PT the mean hydrostatic pressure in the tubule, GC the osmotic pressure of the plasma in the glomerular capillaries, and T the osmotic pressure of the filtrate in the tubule.,85,The pressure in the glomerular capillaries is higher than that in other capillary beds because the af
45、ferent arterioles are short, straight branches of the interlobular arteries. Furthermore, the vessels downstream from the glomeruli, the efferent arterioles, have a relatively high resistance.,86,The capillary hydrostatic pressure is opposed by the hydrostatic pressure in Bowmans capsule. It is also
46、 opposed by the osmotic pressure gradient across the glomerular capillaries (GC T). T is normally negligible, and the gradient is equal to the oncotic胶体渗透压pressure of the plasma proteins.,87,在血液流经肾小球毛细血管时，不断生成滤过液，血浆蛋白浓度就会逐渐增加，血浆胶体渗透压也随之升高。因此，有效滤过压也逐渐下降。当有效滤过压下降到零时，就达到滤过平衡（filtration equilibrium），滤过便
47、停止了。,88,只有从入球小动脉端到滤过平衡这一段才有滤过作用。滤过平衡越靠近入球小动脉端，有效滤过面积就越小，肾小球滤过率就低。,89,三、影响肾小球滤过的因素（一）肾小球毛细血管血压当动脉血压降到80mmHg以下时，肾小球毛细血管血压可明显降低，有效滤过压降低，肾小球滤过率也减少。入球小动脉由于硬化而缩小，肾小球毛细血管血压可明显降低，导致少尿。,90,（二）囊内压 输尿管阻塞，使囊内压升高，使有效滤过压降低，肾小球滤过率减少。病理因素堵塞肾小管，也会导致囊内压升高而影响肾小球滤过。,91,（三）血浆胶体渗透压由静脉快速注入生理盐水时，血浆胶体渗透压降低，滤过增加。,92,（四）肾血浆流量
48、肾血浆流量加大，肾小球毛细血管内血浆胶体渗透压的上升速度减慢，滤过平衡就靠近出球小动脉端，肾小球滤过率将随之增加。,93,Table 38-4. Factors affecting the GFR.Changes in renal blood flowChanges in glomerular capillary hydrostatic pressureChanges in systemic blood pressureAfferent or efferent arteriolar constrictionChanges in hydrostatic pressure in Bowmans c
49、apsuleUreteral obstructionEdema of kidney inside tight renal capsule,94,Changes in concentration of plasma proteins:dehydration, hypoproteinemia, etc (minor factors)Changes in Kf .Changes in glomerular capillary permeabilityChanges in effective filtration surface area,95,Changes in GFRVariations in the factors listed in Table 38-4 have predictable effects on the GFR. Changes in renal vascular resistance as a result of autoregulation tend to stabilize filtration pressure, but when the mean systemic arterial pressure drops below 90 mm Hg, there is a sharp drop in GFR.,
