生理學(xué)雙語泌尿

1、1,第八章 尿的生成和排出,2,3,4,腎的功能：機(jī)體重要的排泄器官1.排除機(jī)體的大部分代謝終產(chǎn)物及異物；2.調(diào)節(jié)水和電解質(zhì)的平衡:調(diào)整細(xì)胞外液量和滲透壓,電解質(zhì),5,3.維持酸堿平衡。4.腎具有內(nèi)分泌功能,分泌EPO,腎素.,6,尿的生成包括: 腎小球的濾過，腎小管和集合管的重吸收和腎小管和集合管的分泌三個(gè)基本過程。,7,8,,,,In the kidneys, a fluid that resembles plasm

2、a is filtered through the glomerular capillaries into the renal tubules (glomerular filtration).,9,10,As this glomerular filtrate濾出液passes down the tubules, its volume is reduced and its composition altered by the proces

3、ses 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 that enters the renal pelvis 腎盂.,11,A comparison of

4、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 metabolit

5、es are conserved.,12,Furthermore, 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 amo

6、unt of water and various specific solutes in the urine.,13,From the renal pelvis, the urine passes to the bladder and is expelled to the exterior by the process of urination, or micturition.,14,,,The kidneys are also end

7、ocrine organs, making kinins 激肽 and 1,25- dihydroxycholecalciferol二羥膽鈣化醇二羥維生素D3 and making and secreting renin.,15,第一節(jié) 腎的功能解剖和腎血流量一. 腎的功能解剖（一）腎單位和集合管,16,腎的功能：機(jī)體重要的排泄器官1.排除機(jī)體的大部分代謝終產(chǎn)物及異物；2.調(diào)節(jié)水和電解質(zhì)的平衡:調(diào)整細(xì)胞外液量和

8、滲透壓,電解質(zhì),17,腎單位是腎的基本功能單位，它與集合管共同完成泌尿功能 。人的兩側(cè)腎約有170-240萬個(gè)腎單位。,18,19,Each individual renal tubule and its glomerulus is a unit (nephron 腎單位). The size of the kidneys in various species is determined largely by the number of

9、 nephrons they contain. There are approximately 1.3million nephrons in each human kidney.,20,21,22,23,The glomerulus, which is about 200μm in diameter, is formed by the invagination 內(nèi)陷of a tuft of capillaries into the

10、dilated, blind end of the nephron (Bowman's capsule). The capillaries are supplied by an afferent arteriole and drained by a slightly smaller efferent arteriole.,24,The glomerulus is essentially a tuft of capillarie

11、s 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

12、 fluctuations in the systemic blood pressure.,25,26,27,There are two cellular layers separating the blood from the glomerular filtrate in Bowman‘s capsule: the capillary endothelium and the specialized epithelium of the

13、capsule that is made up of podocytes (足細(xì)胞：腎小球臟層的一種上皮細(xì)胞，有突起相互交錯(cuò)并包繞小球毛細(xì)血管的基底膜) overlying the glomerular capillaries (Figure 38-3).,28,,29,These layers are separated by a basal lamina. Stellate cells called mesangial cells〔

14、小球膜細(xì)胞 ）are located between the basal lamina and the endothelium. They are similar to cells called pericytes周細(xì)胞, which are found in the walls of capillaries elsewhere in the body.,30,Mesangial cells are especially common

15、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

16、filtration. They also secrete various 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 7

17、0-90 nm in diameter. The cells of the epithelium (podocytes) have numerous pseudopodia偽足that interdigitateto form filtration slits along the capillary wall. The slits are approximately 25 nm wide, and each is closed by

18、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 totally excludes those w

19、ith diameters greater than 8 nm. However, the charges on molecules as well as their diameters affect their pas­sage into Bowman's capsule . The total area of glomerular capillary endothelium across which filtrat

20、ion occurs in humans is about 0.8 m2.,33,(二）皮質(zhì)腎單位和近髓腎單位腎單位按其所在部位不同，可分為質(zhì)腎單位和近髓腎單位兩類。,34,皮質(zhì)腎單位 主要分布于外皮質(zhì)層和中皮質(zhì)層。約占腎單位總數(shù)的85%-90%。入球小動(dòng)脈與出球小動(dòng)脈的口徑之比約為2：1,所以腎小球內(nèi)毛細(xì)血管血壓較高。,35,近髓腎單位 分布于靠近髓質(zhì)的內(nèi)皮質(zhì)層。其髓袢甚長(zhǎng)，可深入到內(nèi)髓質(zhì)層。出球小動(dòng)脈形成細(xì)而長(zhǎng)的U字形

21、直小血管。近髓腎單位在尿的濃縮與稀釋過程中起著重要作用。,36,37,The nephrons with glomeruli in the outer portions of the renal cortex have short loops of Henle (cortical nephrons), whereas those with glomeruli in the juxtamedullary region of the co

22、rtex (juxtamedullary nephrons) have long loops extending down into the medullary pyramids. In humans, only 15% of the nephrons have long loops.,38,（三）近球小體近球小體（juxtaglomerular apparatus）由顆粒細(xì)胞、系膜細(xì)胞和致密斑三者組成。,39,40,顆粒細(xì)胞位于入

23、球小動(dòng)脈的中膜內(nèi)，內(nèi)含分泌顆粒，顆粒內(nèi)含腎素。,41,致密斑位于遠(yuǎn)曲小管的起始部分，細(xì)胞為高柱狀。致密斑可感受小管液中NaCI含量的變化，并將信息傳遞至顆粒細(xì)胞，調(diào)節(jié)腎素的釋放。,42,近髓腎單位 分布于靠近髓質(zhì)的內(nèi)皮質(zhì)層。其髓袢甚長(zhǎng)，可深入到內(nèi)髓質(zhì)層。出球小動(dòng)脈形成細(xì)而長(zhǎng)的U字形直小血管。近髓腎單位在尿的濃縮與稀釋過程中起著重要作用。,43,The walls of the afferent arerioles conta

24、in the renin-secreting juxtaglomerular cells. At this point, the tubular epithelium is modified histologically to form the macula densa. The juxtaglomerular cells, the macula densa, and the lacis cells near them are know

25、n collectively as the juxtaglomerular apparatus .,44,（四）腎的神經(jīng)支配腎交感神經(jīng)主要從胸腰段脊髓發(fā)出，未發(fā)現(xiàn)腎有副交感神經(jīng)支配。,45,Functions of the Renal NervesStimulation of the renal nerves increases renin secretion by a direct action of released norep

26、inephrine on β-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 asc

27、ending limb of the loop of Henle are richly innervated.,46,When the renal nerves are stimulated at increasing strengths in experimental animals, the first response is an increase in the sensitivity of the juxtagloplerula

28、r cells , followed by increased renin secretion, then increased Na+ reabsorption, and finally, at the highest threshold, renal vasoconstriction with decreased glomerular filtration and renal blood flow.,47,It is still un

29、settled whether the effect on Na+ reabsorption is mediated via α- or β-adrenergic receptors, and it may be mediated by both. The physiologic role of the renal nerves in Na+ metabolism is also unsettled, in part because

30、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

31、 kidneys causes a marked decrease in renal blood flow. There is some tonic discharge in the renal nerves at rest in animals and humans.,49,When systemic blood pressure falls, the vasoconstrictor response produced by decr

32、eased discharge in the baroreceptor nerves includes renal vasoconstriction. Renal blood flow is decreased during exercise and, to a lesser extent, on rising from the supine position.,50,（五)腎的血流,51,腎小球毛細(xì)血管網(wǎng)介于入球小動(dòng)脈和出球小動(dòng)脈之間

33、，而且皮質(zhì)腎單位入球小動(dòng)脈的口徑粗。因此，腎小球毛細(xì)血管內(nèi)血壓較高，有利于腎小球的濾過作用。,,,52,腎血液循環(huán)的特征腎的血液供應(yīng)很豐富。其中約94%的血液分布在腎皮質(zhì)層，通常所說的腎血流量主要指腎皮質(zhì)血流量。,53,（一）腎血流量的自身調(diào)節(jié)不依賴神經(jīng)體液,當(dāng)動(dòng)脈血壓在一定范圍(80-180mmHg)內(nèi)變動(dòng)時(shí)，腎血流量仍然保持相對(duì)恒定。自身調(diào)節(jié)的機(jī)制，用肌源學(xué)說來解釋。,54,55,腎血流量和腎小球?yàn)V過率的自身調(diào)節(jié)RPF：腎血漿

34、流量 GFR：腎小球?yàn)V過率。,56,（二）腎血流量的神經(jīng)和體液調(diào)節(jié)腎交感神經(jīng)活動(dòng)加強(qiáng)時(shí)，引起腎血管收縮，腎血流量減少。腎上腺素，去甲腎上腺素，血管升壓素和血管緊張素能使腎血管收縮，腎血流量減少。,57,Blood FlowIn a resting adult, the kidneys receive 1.2-1.3 L of blood per minute, or just under 25% of the cardi

35、ac output,58,Regulation of the Renal Blood FlowNorepinephrine constricts the renal vessels, with the greatest effect of injected norepinephrine being exerted on the interlobular arteries and the afferent arterioles. Dop

36、amine is made in the kidney and causes renal vasodilation and natriuresis 尿內(nèi)排鈉.,59,Angiotensin II exerts a greater constrictor effect on the efferent arterioles than on the afferent. Prostaglandins increase blood flow in

37、 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

38、the glomerular capillaries has been measured directly 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

39、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 further drop in the efferent arteriole so that the pressure in the peritubular capillaries is

40、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 arterial pressure.

41、,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

42、 in part by a direct contractile response of the smooth muscle of the afferent arteriole to stretch. NOnitric oxide may also be involved. At low perfusion pressures, angiotensin II also appears to play a role by constri

43、cting the efferent arterioles, thus maintaining the glomerular filtration rate.,64,第二節(jié) 腎小球的濾過功能,65,血液經(jīng)過腎小球毛細(xì)血管時(shí)，血漿中的水和小分子溶質(zhì)，濾入腎小囊的囊腔而形成濾過液，又稱原尿。,66,單位時(shí)間內(nèi)（每分鐘）兩腎生成的超濾液量稱為腎小球?yàn)V過率glomerular filtration rate, GFR。成人腎小球?yàn)V過率平均為12

44、5ml/min左右。,67,腎小球?yàn)V過率和腎血漿流量的比例稱為濾過分?jǐn)?shù)（filtration fraction）。濾過分?jǐn)?shù)為：125/660×100=19%。濾過分?jǐn)?shù)表明，流經(jīng)腎的血漿約有1/5濾入腎小囊囊腔中。,68,The first step in the process of urine formation is passage of a cell- and protein-free ultrafiltrate 超

45、濾液of plasma which contains 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 filtratio

46、n rateThe GFR in an average-sized normal man is approximately 125 ml/min. Its magnitude correlates fairly well with surface area, but values in women are 10% lower than those in men even after correction for surface are

47、a.,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/min, the kidneys filter in 1 day an amou

48、nt 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 gover

49、ning filtration across all other capillaries, 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、濾過膜及其通透性當(dāng)濾過面積減少，腎小

50、球?yàn)V過率降低，結(jié)果出現(xiàn)少尿（每晝夜尿量在100-500ml之間）以致無尿（每晝夜尿量不100ml）。,73,74,不同物質(zhì)通過腎小球?yàn)V過膜的能力決定于被濾過物質(zhì)的分子大小及其所帶的電荷。,75,PermeabilityThe permeability of the glomerular capillaries is about 50 times that of the capillaries in skeletal muscle. N

51、eutral 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, filtration i

52、s inversely proportionate to diameter.,77,The negative charges repel negatively charged substances in blood, with the result that filtration of anionic陰離子 的substances 4 nm in diameter is less than half that of neutral su

53、bstances of the same size.,78,This probably explains why albumin, with an effective molecular diameter of approximately 7 nm, normally has a glomerular concentration only 0.2% of its plasma concentration rather than the

54、higher concentration that would be expected on the basis of diameter alone; circulating albumin is negatively charged. Filtration of cationic substances is slightly greater than that of neutral substances.,79,The amount

55、of protein in the urine is normally less than 100 mg/d, and most of this is not filtered but comes from shed脫落tubular cells. The presence of significant amounts of albumin in the urine is called albuminuria. In nephritis

56、, the 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

57、GFR to the renal plasma flow (RPF), the filtration fraction, is normally 0.16-0.20. The GFR varies less than the RPF. When there is a fall in systemic blood pressure, the GFR falls less than the RPF because of efferent a

58、rteriolar constriction, and consequently the filtration fraction rises.,81,腎小球?yàn)V過作用的動(dòng)力是有效濾過壓。腎小球有效濾過壓=（腎小球毛細(xì)血管壓+囊內(nèi)液膠體滲透壓）-（血漿膠體滲透壓+腎小囊內(nèi)壓）。,82,由于腎小囊內(nèi)膠體滲透壓很小忽略不計(jì)。因此有效濾過壓= 腎小球毛細(xì)血管壓 -（血漿膠體滲透壓+腎小囊內(nèi)壓）。,83,For each nephron:&

59、#160;GFR = Kf [(P GC - PT) - (πGC –πT)] Kf ,the glomerular ultrafiltration coefficient, is the product of the glomerular capillary wall hydraulic conductivity (ie, its permeability) and the effective filtration s

60、urface area.,84,PGC is the mean hydrostatic pressure in the glomerular capillaries, PT the mean hydrostatic pressure in the tubule, πGC the osmotic pressure of the plasma in the glomerular capillaries, and πT the osmotic

61、 pressure of the filtrate in the tubule.,85,The pressure in the glomerular capillaries is higher than that in other capillary beds because the afferent arterioles are short, straight branches of the interlobular arteries

62、. 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 Bowman'

63、;s capsule. It is also opposed by the osmotic pressure gradient across the glomerular capillaries (πGC –πT). πT is normally negligible, and the gradient is equal to the oncotic膠體滲透壓pressure of the plasma proteins.,87,在血

64、液流經(jīng)腎小球毛細(xì)血管時(shí)，不斷生成濾過液，血漿蛋白濃度就會(huì)逐漸增加，血漿膠體滲透壓也隨之升高。因此，有效濾過壓也逐漸下降。當(dāng)有效濾過壓下降到零時(shí)，就達(dá)到濾過平衡（filtration equilibrium），濾過便停止了。,88,只有從入球小動(dòng)脈端到濾過平衡這一段才有濾過作用。濾過平衡越靠近入球小動(dòng)脈端，有效濾過面積就越小，腎小球?yàn)V過率就低。,89,三、影響腎小球?yàn)V過的因素（一）腎小球毛細(xì)血管血壓當(dāng)動(dòng)脈血壓降到80mmHg以下時(shí)，腎

65、小球毛細(xì)血管血壓可明顯降低，有效濾過壓降低，腎小球?yàn)V過率也減少。入球小動(dòng)脈由于硬化而縮小，腎小球毛細(xì)血管血壓可明顯降低，導(dǎo)致少尿。,90,（二）囊內(nèi)壓 輸尿管阻塞，使囊內(nèi)壓升高，使有效濾過壓降低，腎小球?yàn)V過率減少。病理因素堵塞腎小管，也會(huì)導(dǎo)致囊內(nèi)壓升高而影響腎小球?yàn)V過。,91,（三）血漿膠體滲透壓由靜脈快速注入生理鹽水時(shí)，血漿膠體滲透壓降低，濾過增加。,92,（四）腎血漿流量腎血漿流量加大，腎小球毛細(xì)血管內(nèi)血漿膠體滲透壓的上升速

66、度減慢，濾過平衡就靠近出球小動(dòng)脈端，腎小球?yàn)V過率將隨之增加。,93,Table 38-4. Factors affecting the GFR. Changes in renal blood flowChanges in glomerular capillary hydrostatic pressureChanges in systemic blood pressureAfferent or efferent art

67、eriolar constrictionChanges in hydrostatic pressure in Bowman's capsuleUreteral obstructionEdema of kidney inside tight renal capsule,94,Changes in concentration of plasma proteins:dehydration, hypoproteinemia

68、, 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