如大失血、缺氧、劇烈運動等)，全身血液將重新分配

1、Kidney Physiology II,YU Yanqin (虞燕琴), Zhejiang University, School of Medicine,Urinary concentration and dilution,Concentrative urine濃縮尿: Osmolality of urine > plasma osmolality (300mOsm/L H2O)Diluted urine稀釋尿: Os

2、molality of urine < plasma osmolality,Formation of Diluted Urine,Isosmotic reabsorption of water at proximal tubuleImpermeable of water at thick ascending limb?ADH? ?Reabsorption of water at distal tubule and coll

3、ecting duct ? Diluted urine,Formation of Concentrative Urine,?ADH? ? Reabsorption of water at distal tubule and collecting duct ? Concentrative UrineADH---key element of urinary concentration and dilution,What is the d

4、rive force of water reabsorption at distal tubule and collecting duct ?,The Osmotic Gradient of the Renal Medulla,Formation of Osmotic Gradient of the Renal Medulla,Permeability of the Tubular System,Permeability of the

5、Tubular System,,,The countercurrent theory 1. Countercurrent multiplication逆流倍增,A,C,B,Formation of Osmotic Gradient of the Renal Medulla,,,1.Countercurrent multiplication,Establishing of Osmotic Gradient of the Renal Me

6、dulla,? Outer medulla: reabsorption of NaCl at thick ascending limb ? hyperosmolality Inner medulla: 1) urea recycling2) reabsorption of NaCl at thin ascending limb? hyperosmolality,Urinary concentration and dilutio

7、n.swf,The Countercurrent Theory,2. Countercurrent exchange 逆流交換,2. Countercurrent exchange,Maintenance of the Osmotic Gradient in the Medulla,Vasa recta,Maintenance of the Osmotic Gradient in the Medulla,The vasa recta

8、: Countercurrent exchanger,Summary:Formation of Concentrated or Dilute Urine,In the presence of ADH Collecting duct permeable to water ? excretion of a concentrated urine In the absence of ADH Collecting d

9、uct impermeable to water ? excretion of a diluted urine,,Factors that affect the concentration and dilution of the urine,1) Damage of renal medulla Resulting in an impairment of the concentrating ability 2) Loop d

10、iuretics such as frusemide, inhibiting the Na+/ K+/ 2Cl- co-transport system in the thick ascending limb,Factors that affect the concentration and dilution of the urine,3) Lack of urea in the body such as malnu

11、trition, reducing the osmotic grat ent established in the renal medulla 4) Increased velocity of blood flow in the vasa recta carrying away amount of NaCl ? reducing the osmotic gradient in the medulla,Humoral Cont

12、rol of Renal Functions,Antidiuretic hormone (抗利尿激素，ADH) Synthesis in supraoptic and paraventricular nuclei（視上核與室旁核）Release from the posterior pituitary,Mechanism of ADH Antidiuresis,Increasing water permeability of col

13、lecting ductInsertion of aquaporins水通道 in apical membrane,Diabetes Insipidous尿崩癥,Regulation of ADH Release,Plasma osmolality Plasma osmolality ↑ →(+)hypothalamic osmoreceptors → production and release of ADH ↑ →u

14、rine ↓Blood volume Blood volume ↑ → (+)baroreceptor reflex & atrial stretch receptors → ADH release ↓ →urine ↑ → Blood volume ↓,,Water diuresis 水利尿,Physiologic water diuresis is a response to water load: Sli

15、ghtly decreased plasma osmolality (drinking bulk water)? ADH↓? Increased urine flow until plasma osmolality increases,Humoral Control of Renal Functions,Aldosterone 醛固酮Secreted by the glomerulosa 球狀帶 of the adrenal cort

16、ex To increase the reabsorption of Na+ in the distal tubule and early collecting duct, coupled to secretion of K+,Mechanism of Aldosterone Action,To increase number of Na+ channelsTo increase activity of Na+ pumps,Reg

17、ulation of Aldosterone Secretion,1. Renin-Angiotensin System （腎素-血管緊張素系統(tǒng)）,Regulation of Aldosterone Secretion,2. Plasma concentrations of sodium and potassium [K+] ? ? Aldosterone secretion ?? [Na+] ? ? Al

18、dosterone secretion ?3. Adrenocorticotrophin (促腎上腺皮質(zhì)激素，ACTH) Necessary for Aldosterone secretion, but little effect in controlling the secretion rate,Ingesting too muchpotassium stimulatesaldosterone secretion

19、from the adrenal cortex;aldosterone increases sodium reabsorption atthe “expense” of increased potassium secretion.Also shown here is anindication that morepotassium in the filtrateleads to greater potassium excr

20、etion in the urine.,Decreased blood volume and ingesting too muchpotassium both stimulatealdosterone secretion from the adrenal cortex;aldosterone increases sodium reabsorption atthe “expense” of increased potass

21、ium secretion.,Humoral Control of Renal Functions,Atrial natriuretic peptides (心房鈉尿肽，ANP) Synthesis in the cardiac atrial muscle cellLeading to increased excretion of salt & water Its mechanism:,Regulation of

22、 ANP Release,Stretch of the atriumExtracellular fluid volume and blood volume Plasma sodium concentration,Renal Clearance血漿清除率,Defined as the volume of plasma required to supply the amount of a substance X to be excret

23、ed in urine per unit time,,,Use of Clearance Methods to Quantify Kidney Function,UxV =GF – R + EG=GFRF=Filtration concentration,Use of Clearance Methods to Quantify Kidney Function,Inulin clearance as a measure of glom

24、erular filtration,Use of Clearance Methods to Quantify Kidney Function,Clearance of para-aminohippuric acid as a measure of renal plasma flow Para-aminohippuric acid (PAH) freely through the glomerulus Almost all the

25、 remaining PAH in the plasma is secreted into the tubule,Use of Clearance Methods to Quantify Kidney Function,Renal clearance as a calculation of tubular reabsorption or secretion By comparison of inulin clearance wi

26、th clearances of different solutes ? C125ml／min-----has secretion,Micturition 排尿,Innervation of the bladder and urethra,Micturition,Micturition,Innervation of the bladder and urethra 1) Parasympathetic pelvic nerve

27、s盆神經(jīng) To cause contraction of the detrusor muscle of the bladder and opening of the internal sphincter 2) Sympathetic hypogastric nerves腹下神經(jīng) To induce closure of the internal sphincter 3) Somatic puden

28、dal nerves陰部神經(jīng) To induce contraction of the external sphincter,Micturition Reflex,Micturition occurs when the intravesicular pressure reaches 70 cmH2O via a reflex action,,,500,Pdet, cm H2O,0 volum

29、e 300 ml,,,Higher Control of Micturition,Inhibitory and facilitatory centers in the cerebral cortex and pons,Pathways of Micturition Reflex,Micturition reflex,膀胱內(nèi)尿量達400~500ml→膀胱壁的牽張感受器(+)→盆神經(jīng)→骶髓的排尿反射初級中樞→腦干和大腦皮層

30、的排尿反射高級中樞→尿意→盆神經(jīng)→逼尿肌收縮，內(nèi)括約肌松弛→排尿入尿道→外括約肌松弛→排尿反射(正反饋)→尿液排完,Micturition reflex,,Enuresis遺尿,Summary,Terms:Water diuresisRenal clearanceList the factors that affect the concentration and dilution of the urine,General Ques

31、tion,What are the change of urine and its mechanism when one sweats a great deal and drinks little water?,Intensive Reading,Textbook of Medical Physiology (Guyton & Hall) Page 309 Page 313-324 Page

32、 366-368,Questions,１．血漿滲透壓的變化對腎臟泌尿的生理功能有何影響？２．大量出汗而飲水過少時，尿液有何變化？其機制如何？３．3Kg體重的家兔，耳緣靜脈注射20%葡萄糖溶液5ml，尿液有何變化？簡述其變化機制。４．通常情況和緊急情況下，腎血流量是如何調(diào)節(jié)的？各有何重要生理意義？５．試述腎臟的泌尿功能在維持機體內(nèi)環(huán)境穩(wěn)定中的作用。６．簡述直小血管的血流速度對尿液生成的影響。７．為什么說髓袢升支粗段主動吸收Na

33、Cl是形成髓質(zhì)高滲的動力？８．體循環(huán)血壓明顯降低時對尿液生成有何影響？９．影響腎小球濾過作用的因素有哪些？,血漿滲透壓的變化對腎臟泌尿的生理功能有何影響？,1．血漿膠體滲透和晶體滲透壓變化時均可影響腎臟的尿生成，但各自的機理不同。⑴血漿膠體滲透壓一般維持穩(wěn)定，如因某種原因使之降低，腎小球有效濾過壓將升高，原尿生成增多，尿排出量增加；血漿膠體滲透壓升高時，與上述作用相反，可使尿量減少。⑵血漿晶體滲透升高時，可刺激位于下丘腦前部室周

34、器的滲透壓感受器，引起ADH的合成和釋放增加，遠曲小管和集合管對水的通透性增加，水重吸增加，排出尿量減少；而晶體滲透壓降低時，作用相反，使排出的尿量增加，如水利尿產(chǎn)生的原理即為血漿晶體滲透壓降低所致。,大量出汗而飲水過少時，尿液有何變化？其機制如何？,2．汗為低滲溶液，大量出汗而飲水過少時，尿液排出量減少，其滲透壓升高。大量出汗：（1）組織液晶體滲透壓升高，水的滲透作用使血漿晶體滲透壓也升高，下丘腦滲透壓感受器興奮。（2）血容量減少，

35、心房及胸內(nèi)大靜脈血管的容積感受器對視上核和旁室核的抑制作用減弱。上述兩種途徑均使視上核和旁室核合成和分泌ADH增加，血液中ADH濃度升高，使遠曲小管和集合管對水的通透性增加，水重吸收增加，尿量減少，尿滲透壓升高。此外，大量出汗，還可能使血漿膠體滲透壓升高，腎小球有效濾過壓降低，原尿生成減少，尿量減少。,3Kg體重的家兔，耳緣靜脈注射20%葡萄糖溶液5ml，尿液有何變化？簡述其變化機制。,3．尿量增加，尿液滲透壓變化不明顯。3Kg家兔，

36、血液量約240ml，注入血中的葡萄糖為5ml×20%=1（克），將使血糖升至約500mg/100ml，明顯超過腎糖閾，導致遠曲小管和集合管小管液內(nèi)含大量的葡萄糖，阻礙水的重吸收，產(chǎn)生滲透性利尿，尿量增加，出現(xiàn)糖尿，但尿液滲透壓變化不明顯。,通常情況和緊急情況下，腎血流量是如何調(diào)節(jié)的？各有何重要生理意義？,4．安靜情況下，血壓基本穩(wěn)定，腎動脈壓波動在80-180mmHg(10.7-24Kpa)范圍內(nèi)，通過腎臟的自身調(diào)節(jié)，維持腎血

37、流量穩(wěn)定，從而保證了腎臟的泌尿功能。當機體受到強烈刺激時，如大出血，將使交感－腎上腺髓質(zhì)系統(tǒng)強烈興奮，產(chǎn)生應急反應，使腎血管特別是入球動脈收縮，腎血流量減少，有效濾過壓也降低，濾過減少而重吸收增加，尿量減少，既能維持一定的血容量，又能使血液重新分配，對于緊急情況下保證心腦重要器官的血液供應具有重要意義。,試述腎臟的泌尿功能在維持機體內(nèi)環(huán)境穩(wěn)定中的作用。,5．腎臟的泌尿功能表現(xiàn)在對代謝終產(chǎn)物及其他無用物質(zhì)的排泄，而吸收和保留機體需要的物質(zhì)

38、，參與機體水鹽平衡，酸堿平衡的調(diào)節(jié)，有效地維持機體內(nèi)環(huán)境的穩(wěn)定。⑴在中樞神經(jīng)的參與下，根據(jù)機體對水的需求，通過ADH，調(diào)節(jié)遠曲小管和集合管對水的通透性，維持水代謝的平衡和血容量的穩(wěn)定。⑵體內(nèi)許多電解質(zhì)濃度的維持，受腎臟的調(diào)節(jié)，如Na+、K+、Ca2+等，當Na+/ K+降低時，醛固醇分泌增加，腎臟保Na+排K+作用增強，使Na+/ K+恢復正常；當Na+/ K+升高時，情況相反，從而使Na+、K+維持在較恒定的水平。此外對Ca2+也

39、有調(diào)節(jié)作用。⑶酸中毒時，體內(nèi)H+增加：①腎內(nèi)碳酸酐酶活性增強，腎HCO3-重吸收增加。②H+- Na+交換增強，腎排H+增加。③NH3分泌增加，NH4Cl排出增加。使體內(nèi)[H+]降低，恢復酸堿平衡。堿中毒時情況相反，從而使體內(nèi)pH維持在相對穩(wěn)定的水平。,６．簡述直小血管的血流速度對尿液生成的影響。,6．腎遠曲小管和集合管不斷重吸收水和其它物質(zhì)，將破壞腎髓質(zhì)高滲狀態(tài)，影響泌尿功能。腎髓質(zhì)直小血管的血供特點，能及時將重吸收的物質(zhì)和水分帶回

40、血液，維持腎髓質(zhì)的高滲狀態(tài)。如果直小血管血流減慢，重吸收的水分不能及時運至血液循環(huán)，使髓質(zhì)滲透壓下降。而當其中的血流增快時，將過多地帶走髓質(zhì)內(nèi)的NaCl和尿素，也會使髓質(zhì)滲透壓降低。故直小血管中血流過慢和過快，都將影響尿液的生成。所以，穩(wěn)定的直小血管血流，是維持腎髓質(zhì)高滲的必要條件和影響尿液生成的重要因素。,為什么說髓袢升支粗段主動吸收NaCl是形成髓質(zhì)高滲的動力？,7．引起腎髓質(zhì)高滲的NaCl和尿素來自小管液。腎小管和集合管各段對H2

41、O、NaCl和尿素的通透性和轉(zhuǎn)運方式不同。降支細段對H2O通透，對NaCl和尿素不通透；升支細段對NaCl和尿素通透，對水不通透，升支粗段主動吸收NaCl而對水和尿素不通透；內(nèi)髓集合管允許尿素通透。小管液流經(jīng)升支粗段，主動吸收NaCl，產(chǎn)生外髓高滲，濃縮管內(nèi)尿素；內(nèi)髓集合管中高濃度的尿素向管外擴散，形成內(nèi)髓高滲；降支細段H2O進入髓質(zhì)，NaCl被濃縮；升支細段NaCl向外擴散，內(nèi)髓滲透壓進一步升高，形成髓質(zhì)高滲。若抑制升支粗段主動吸收N

42、aCl，外髓高滲不能形成，尿素和NaCl不被濃縮，內(nèi)髓滲透壓也不能升高。故升支粗段主動重吸收NaCl是形成髓質(zhì)高滲的動力。,體循環(huán)血壓明顯降低時對尿液生成有何影響？,8．體循環(huán)血壓因某種原因明顯降低，使腎動脈血壓低于80mmHg(10.7Kpa)時，尿排出量將減少。（1）體循環(huán)血壓下降，減壓反射減弱，交感神經(jīng)興奮，引起應急反應，入球動脈收縮，濾過減少。（2）血壓下降，血容量相對不足，視上核和室旁核合成和釋放ADH增加，腎遠曲小管和集

43、合管對水的重吸收增多，（3）血壓下降，腎素-血管緊張素-醛固酮系統(tǒng)活動增強，醛固酮分泌增加，促進腎保Na+排K+和對水的重吸收。以上三方面的共同作用，使尿量減少。,影響腎小球濾過作用的因素有哪些？,9．腎小球濾過作用主要受下列因素的影響：（1）濾過膜的通透性。即膜孔的大小和濾過膜上負電荷的多少。（2）濾過面積的大小。在其它因素不變的情況下，面積越小，單位時間濾過量也越少。（3）腎小球有效濾過壓。包括腎小球毛細血管內(nèi)壓的高低，血