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Renal Physiology 肾动脉 肾静脉 肾盂 输尿管 最新WHO 泌尿系统疾病发病率(%) 发展中国家 泌尿系统疾病 发达国家 19.7 7.8 泌尿系感染 9.6 2.0 肾炎 8.6 2.9 结石 1.3 2.0 肿瘤 0.4 0.4 多囊肾 0.4 0.1 结核 0.3 < 0.1 糖尿病肾病 0.2 0.2 慢性肾功能不全 0.3 0.1 发 展 中 国 家 发 达 国 家 慢性肾功能不全 糖尿病肾病 结核 多囊肾 肿瘤 结石 肾炎 泌尿系感染 泌尿系统疾病 0.0% 5.0% 10.0 15.0 20.0 25.0 % % % % • 评价: 发展中国家泌尿系统疾病发病率高,主要是高发 的泌尿系感染、急性肾炎、间质性肾炎、结核等, 其主要原因包括: 1. 感染性疾病未得到足够控制,导致泌尿系感染、 急性肾炎、间质性肾炎和结核的发病率高 2. 严重的环境污染和生活毒素未得到控制,导 致肾小球和肾间质炎症的发病率高,也与高 发的肾肿瘤有关 3. 对遗传性疾病缺乏生育控制,与多囊肾 等先天性疾病的多发有关 4. 社会医疗服务经费的缺乏,使得较多患 者的疾病发展到慢性肾功能衰竭 5. 透析和移植治疗的缺乏,使得慢性肾功 能衰竭不能得到纠正,引起更多的感染 和肿瘤发生 Overview of kidney function • Excretion - the body substances of metabolic end products and do not need to or surplus material excreted process • The kidneys process the plasma portion of blood by removing waste materials that are either ingested or produced by metabolism. • In so doing, they perform a variety of functions. Overview of kidney function Urine: color: pallideflavens Specific gravity: 1.015~1.025 Osmotic pressure: higher than the plasma pH:5.0~7.0 urine volume :1000-2000ml/24h, Average :1500ml /24h Polyuria :>2500ml oliguresis :<100~500ml anuresis : < 100ml Major organ of the excretion oxygen intake food, water intake Respiratory System Digestive System nutrients, water, salts elimination of carbon dioxide oxygen carbon dioxide Urinary System Circulatory System water solutes elimination of food residues rapid transport to and from all living cells elimination of excess water salts, wastes Excretion Separating wastes & eliminating from body Organ systems – Respiratory – CO2, H2O Skin – H2O, inorganic salts, lactic acid, urea – sweat Digestive – H2O, CO2, salts, lipids, bile pigments, cholesterol, Urinary – metabolic wastes, toxins, drugs, hormones, salts, H+, H2O. Kidney Function Excretion of metabolic waste products and foreign chemicals Primary function Regulation of water and electrolyte balances Regulation of body fluid osmolality and electrolyte concentrations Regulation of acid-base balance Regulation of arterial pressure Secretion Kidney Function (continued) Secretion Renin prostaglandin 1,25-dihydroxy vitamin D3 (calcitriol) erythropoietin Urine formation • Three steps: 1. filtration of glomerulus ultrafiltrate formation ↓ 2.Selective reabsorption of renal tubule and collecting duct ↓ 3. Excretion of renal tubule and collecting duct Introduction to the Urinary System Structure of the Kidney Nephron Functional unit of the kidney. Consists of: Renal corpuscle Renal tubules: PCT. LH. DCT. CD. Descending limb Ascending limb Nephron glomerulus------------------------- nephron renal Bowman capsule-------------------corpuscle filtration proximal proximal convoluted limb tubule thick descending limb thin segment renal thin descending limb loop of tubule distal tubule thin ascending limb Renle reabsorption secretion excretion thick ascending limb distal convoluted tubule collecting duct -------------------------------- 肾小球 (毛细血管球) 肾 小 体 肾小囊 (脏层、囊腔、壁层) 近曲小管 近端小管 肾 单 位 髓袢降支粗段 髓袢降支细段 肾小管 髓袢细段 肾 髓袢升支细段 髓袢升支粗段 脏 远端小管 弓形集合管 集合管 直集合管 乳头管 远曲小管 髓 袢 Types of Nephron Cortical nephron: Originates in outer 2/3 of cortex. 85% of all nephrons Involved in solute reabsorption. Juxta medullary nephron: Originates in inner 1/3 cortex. Important in the ability to produce a concentrated urine. Has longer LH and vasa recta. Insert fig. 17.6 Cortical and Juxta medullary Nephron 皮质肾单位和近髓肾单位 项 目 皮质肾单位 近髓肾单位 肾单位数量 80-90% 10-15% 肾小球分布 皮质外1/3-2/3 皮质内1/3 肾小球体积 小 大 血管口径 入球〉出球小动脉2:1 入球〈出球小动脉 出球小动脉特点 为一支分布近、远段肾 小管周围 分两支分布近、远段肾 小管周围,另一支形成 U型直小血管 髓袢长度 短 长 近球小体 有 无 肾素颗粒 多 少 交感神经支配 分布入球小动脉 分布出球小动脉 血流量 多(〉90%) 少(〈10%) 功能特点 尿生成和肾素分泌 尿浓缩和稀释 Juxtaglomerular apparatus •Juxtaglomerular cells smooth muscle on afferent and efferent arterioles - dilate and constrict arterioles; renin secreted in response to < BP •Macula densa – patch of dense epithelial cells in DCT - monitor salinity of tubular fluids • Juxtaglomerular Apparatus • 主要分布在皮质肾单位,由近球细胞、系膜细胞和致密斑 组成 细 胞 位 置 功 能 接近肾小球的一段入球小动 脉中膜内 分泌肾素 致密斑细胞 远曲小管起始部(入、出球 小动脉) Na+感受器,能感受小管液中 Na+量的变化,调节近球细胞 释放肾素 间质细胞 入、出球小动脉和致密斑细 胞之间的细胞 可能与传递信息有关 近球细胞 肾脏的神经支配 •T12-L2发出 •经腹腔神经丛支配肾动脉、肾 小管和颗粒细胞。 •肾交感神经末梢释放去甲肾上 腺素,调节肾血流量、肾小球滤 过率、肾小管重吸收和肾素释放。 •肾的各种感受器可经肾神经传 入纤维进入脊髓,并从脊髓投射 到中枢的不同部位。 The Blood Supply to the Kidneys Blood flow to kidneys is normally about 22% of the cardiac output, or 1200 ml/min. Renal Blood Vessels (continued) Afferent arteriole: Delivers blood into the glomeruli. Glomerulus: Capillary network that produces filtrate that enters the urinary tubules. Efferent arteriole: Delivers blood from glomeruli to peritubular capillaries. Peritubular capillaries: Deliver blood to vasa recta. Two Capillary Beds Glomerular capillaries : High hydrostatic pressure --rapid fluid filtration Peritubular capillaries: Low hydrostatic pressure High plasma colloid osmotic pressure --rapid fluid reabsorption 肾血流量及其调节 (一)肾脏的血液供应特点 血液供应量大:1200ml/min,占心输出量的1/5 - 1/4 分布不均匀:皮质 94% 外髓质5 - 6% 内髓质<1% 毛细血管两次分布: 肾动脉分支入球小动脉肾小球毛细血管 出球小动脉肾小管旁毛细血管 肾小球毛细血管内压较高,利于滤过 肾小管旁毛细血管血压较低,有利于重吸收 直小血管有利于维持髓质的高渗梯度 肾血流量的调节 • 自身调节: 动脉血压变动于80~180mmHg范围内 时,肾血流量保持相对恒定,肌原学说 • 意义:使肾血流量相对稳定,保证泌尿正常进行 神经调节: a、交感神经在皮质肾单位的入球小动脉和近髓 肾单位的出球小动脉上分布密度大 b、兴奋时,肾血管收缩,血流量减少;冲动减 小时,肾血管舒张,肾血流量增加 体液调节: E、NE、ADH、血管紧张素能使肾血管收缩, 肾血流量减少 PGI2、PGE2、NO和缓激肽等血管舒张 Urine formation 1.Glomerular filtration 2.Tubular reabsorption 3.Tubular secretion Urine Formation by the Kidneys: Glomerular Filtration Urinary excretion = Filtration – Reabsorption+Secretion Renal handling of different substances (creatinine) (amino acids glucose ) (electrolytes) (Phenolphthalein, penicillin, ammonia ) Glomerular filtration -the first step in urine formation Mechanism of producing ultrafiltrate under hydrostatic pressure of the blood. Process similar to the formation of tissue fluid by other capillary beds. Glomerular Filtration Membrane Glomerular Filtration Membrane (continued) capillary endothelium: Endothelial capillary pores are large fenestrate. Negative charge. Pores are small enough to prevent RBCs, platelets, and WBCs from passing through the pores. Glomerular Filtration Membrane Filtrate must pass through the basement membrane: (continued) Thin glycoprotein layer. Strong negative charges. Can filter water and small solutes. Podocytes: Foot pedicels form small filtration slits. Passageway through which filtered molecules must pass. Except proteins and blood cells, other constituents, including most salts and organic molecules, can through the filtration membrane enter the glomerular capsule. So the filtered fluid is essentially protein-free and devoid of cellular elements, including red blood cells. The concentration of other constituents are similar to the concentrations in the plasma. Glomerular Filtration Glomerular Filtration Whether the substances can though glomerular filtration membrane: • size • type of electric charge Filterability of substances Substance Molecular Weight Filterability Water 18 1.0 Sodium 23 1.0 Glucose 180 1.0 5500 1.0 Myoglobin 17000 0.75 Albumin 69000 0.005 Inulin Glomerular Ultrafiltrate Fluid that enters glomerular capsule is called ultrafiltrate. Composition: Water & some solutes from blood electrolytes, glucose, amino acids, nitrogenous wastes, vitamins no protein(Plasma proteins are excluded by size and charge) no RBC’s Glomerular filtration rate(GFR) GFR: Volume of filtrate produced by both kidneys each minute. Averages 115 ml/min. in women; 125 ml/min. in men. 180 L/day 99% filtrate is reabsorbed – 1-2 L excreted /day Filtration fraction FF: filtration rate as percentage of the total renal plasma flow that pass through the both kidneys. Filtration fraction =GFR / Renal plasma flow =125 / (1200 x 55%) =0.2 Formation of Interstitial Fluid Net filtration pressure = Glomerular hydrostatic pressure _ Bowman’s capsule pressure _ Glomerular colloid osmotic pressure Filtration balance colloid osmotic pressure capillary pressure blood pressure(kPa) Filtration pressure capsule pressure afferent arteriole capillary length efferent arteriole Factors controlling the GFR Increased glomerular filtration membranous pores increases GFR Increased blood hydrostatic pressure increases GFR Increased Bowman’s capsule hydrostatic pressure decreases GFR Increased glomerular capillary colloid osmotic pressure decreases GFR Regulation of GFR Vasoconstriction or dilation of the afferent arterioles affects the rate of blood flow to the glomerulus. Affects GFR. Mechanisms to regulate GFR: Sympathetic nervous system. Autoregulation. Sympathetic activation Produces powerful vasoconstriction of afferent arterioles Decreases GFR and slows production of filtrate Changes the regional pattern of blood flow Alters GFR Stimulates release of renin by JGA Sympathetic Regulation of GFR Stimulates vasoconstriction of afferent arterioles. Preserves blood volume to muscles and heart. Cardiovascular shock: Decreases glomerular capillary hydrostatic pressure. Decreases urine output (UO). Renal Autoregulation of GFR Ability of kidney to maintain a constant GFR under systemic changes. Achieved through effects of locally produced chemicals on the afferent arterioles. When MAP drops, afferent arteriole dilates. When MAP increases, vasoconstrict afferent arterioles. Autoregulation of renal plasma flow and glomerular filtration rate Autoregulation of renal blood flow Ability of kidneys to maintain a stable GFR in spite of changes in BP Juxtaglomerular cells ––– renin secreted from cells in response to drop of BP Macula densa ––– monitor salinity of tubular fluids High GFR = high NaCl macula densa causes constriction of afferent arteriole GFR decrease Tubulo-glomerular feedback: Increased flow of filtrate sensed by macula densa cells in thick ascending LH. Signals afferent arterioles to constrict. The Response to a Reduction in the GFR Urine Formation by the Kidneys: Tubular Processing of the Glomerular Filtrate Functions of Tubule •Tubular reabsorption highly selective quantitatively large •Tubular secretion Tubular reabsorption Manner: •Active transport primary active transport: Na+, K+, Clsecondary active transport: glucose, amino acid •Passive transport: H2O, Cl-, HCO3- Filtrate side Tubular cells Capillary Tight junction Direction of reabsorption Apical membrane Active transport Proximal Tubular Reabsorption About 65% -70% of the filtered load of sodium and water and a slightly lower percentage of filtered chloride are reabsorbed. Passive water reabsorption by osmosis is coupled mainly to sodium reabsorption. Reabsorption of chloride, urea, and other solutes by passive diffusion Essentially all the filtered glucose and amino acids are reabsorbed. Isosmotic reabsorption Salt and Water Reabsorption in Proximal Tubule Reabsorption of Proximal Tubule Active Transport of Sodium Due to low permeability of plasma membrane to Na+. Active transport of Na+ out of the cell by Na+/K+ pumps -----Favors [Na+] gradient -----Na+ diffusion into cell. Ascending Limb LH NaCl is actively extruded from the ascending limb into surrounding interstitial fluid. Na+ diffuses into tubular cell with the secondary active transport of K+ and Cl-. Occurs at a ratio of 1 Na+ and 1 K+ to 2 Cl-. Insert fig. 17.15 Reabsorption of Limb LH Reabsorption of Limb LH Early distal tubule Na+, Cl-, Ca2+, Mg2+ Reabsorption of distal tubule Late distal tubule H2O K+ Reabsorption of Collecting Duct H20 is drawn out of the CD by osmosis. Permeable to H20 depends upon the presence of ADH. Reabsorption of HCO3 Apical membranes of tubule cells are impermeable to HCO3-. Reabsorption is indirect. When urine is acidic, HCO3- combines with H+ to form H2C03-, which is catalyzed by CA located in the apical cell membrane of PCT. As [C02] increases in the filtrate, C02 diffuses into tubule cell and forms H2C03. - and H+. H2C03 dissociates to HCO3 HCO3- generated within tubule cell diffuses into peritubular capillary. Reabsorption of Bicarbonate Reabsorption of chloride and H2O Proximal Tubular Reabsorption Reabsorption of glucose and amino acids • secondary active transport • Co-transport with Na+ •Filtered glucose and amino acids are completely reabsorbed in the proximal convoluted tubule under normal conditions. Reabsorption of glucose Transport maximum is the maximum rate at which glucose can be reasorbed from the tubules, 320mg/min. Renal glucose threshold refers to the filtered load of glucose at which glucose first begins to be excreted in the urine, 220mg/min. Glycosuria •Glucose in urine •More glucose in filtrate than can be reabsorbed by tubule = glucose in urine = diabetes mellitus Significance of PCT Reabsorption 65% Na+, Cl-, and H20 reabsorbed across the PCT into the vascular system. 90% K+ reabsorbed. Essentially all the filtered glucose and amino acids are reabsorbed in the PCT. Reabsorption occurs constantly regardless of hydration state. Not subject to hormonal regulation. Energy expenditure is 6% of calories consumed at rest. Tubular Secretion Chemicals from capillaries secreted into tubular fluid. Mainly secret H+, K+, NH3(ammonia) Secretion of H+ Countertransport Secretion of H+ Regulation of extracellular pH through renal secretion of H+ and absorption of HCO3-. Tubular secretion of H+ leads to reabsorption of filtered HCO3-. Secretion of H+ Secreted H+ can protonate filtered phosphates. Secretion of H+ and NH3 Secreted H+ can protonate filtered ammonia. Reabsorption and Secretion of K+ Freely filtered; Reabsorbed in the proximal convoluted tubule; Secreted in the cortical portion of collecting duct. K+ Secretion Secretion of K+ occurs in CD. + secreted depends upon: Amount of K + delivered to the region. Amount of Na Amount of aldosterone secreted. + is reabsorbed, lumen of tubule becomes As Na charged. + into Potential difference drives secretion of K tubule. + Transport carriers for Na separate from transporters for K+. Functions of Secretion 1. Waste removal – urea, uric acid, bile salts, ammonia, catecholamines, creatinine, penicillin secreted 2. Acid-base balance – hydrogen ions & bicarbonate ions – regulate pH of body fluids Na+, K+, and H+ Relationship Na+ reabsorption in CD creates electrical gradient for K+ secretion. Plasma [K+] indirectly affects [H+]. When extracellular [H+] increases, H+ moves into the cell, causing K+ to diffuse into the ECF. In severe acidosis, H+ is secreted at the expense of K+. Insert fig. 17.27 Regulation of Tubular Reabsorption Glomerulotubular balance -the ability of the tubules to increase reabsorption rate in response to increased tubular load (increased tubular inflow). the percentage of GFR reabsorbed in the proximal tubular remains relatively constant at about 65 per cent. 肾小管 Regulation of Tubular Reabsorption Glomerulotubular balance (reabsorbed 65%). GFR proximal tubular loading of distal tubule(change) reabsorption 100 65 35 (- 8.75) 125 81.25 43.75 (0) 150 97.5 52.5 (+8.75) Prevent overloading of distal tubule when GFR increases. Regulation of Tubular Reabsorption Tubular solute concentration increase, tubular reasorption decrease. Glycosuria Blood sugar exceed renal glucose threshold---more glucose in filtrate than can be reabsorbed by tubule ---- glucose in urine --- tubular solute concentration increase ---inhibit H2O reasorption ---- urine increase ---diuresis(osmotic diuresis) Regulation of Tubular Reabsorption Peritubular capillary hydrostatic pressure increase, tubular reabsorption decrease; Peritubular capillary colloid osmotic pressure increase, tubular reabsorption increase. Renal Clearance Renal Clearance The volume of plasma which would be completely cleared must be the volume o plasma containing the relevant amount of solute. Renal Clearance Determine the clearance for substance X(C): Collect urine over a known period of time; Measure urinary volume(V); Measure the urinary concentration of the relevant solute(U) The plasma concentration of the solute(P) The total amount of solute in the urine = U•V ∴ C=Plasma volume containing(U•V) of solute ∴ C= Volume=Amount/Concentration U•V (ml/min) P Renal Clearance V • U P V = urine volume per min. U = concentration of substance in urine P = concentration of substance in plasma Compare renal “handling” of various substances in terms of reabsorption or secretion. Renal clearance(C) = Renal Clearance Substance is filtered, but not reabsorbed: All filtered will be excreted. Substance filtered, but also secreted and excreted will be: > GFR (GFR = 125 ml/ min.). Measurement of GFR A substance obeys the required criteria for renal handing: It must be freely filtered in the glomerulus; It must not be reabsorbed from the nephron; It must not be secreted into the nephron; It must not be metabolized in the nephron. Excretion(U•V)=Filtration – Reabsorption + Secretion =Filtration – 0 + 0 = GFR • P ∴GFR = U•V = C P (Inulin, Creatinine) Measurement of GFR • Ability of the kidneys to remove molecules from plasma and excrete those molecules in the urine. If a substance is not reabsorbed or secreted, then the amount excreted = amount filtered. Quantity excreted = V x U Quantity excreted = mg/min. V = rate of urine formation. U = inulin concentration in urine. If a substance is neither reabsorbed nor secreted by tubule: The amount excreted in urine/min. will be equal to the amount filtered out of the glomeruli/min. Rate at which a substance is filtered by the glomeruli can be calculated: Quantity filtered = GFR x P P = inulin concentration in plasma. Amount filtered = amount excreted GFR = V x U P The polysaccharide inulin is one such material which may be injected into the subject, allowing plasma concentration and urinary excretion to be measured. In clinical practice, however, creatinine clearance is usually measured. Creatinine is a metabolic of muscle creatine and, as a naturally occurring substance, does not have to introduced into the circulation artificially. Urine is collected over 24 hours and a plasma sample taken during this period is used to determine the circulating creatinine concentration. This represent total filtration in both kidneys. Renal Clearance of Inulin Insert fig. 17.22 Measurement of Renal Blood Flow Be completely removed from the plasma in a single circuit through the kidneys, i.e. its concentration reduced to zero (filtration, secretion, no reabsorption) before the plasma reaches the renal venous system. (para-aminohippuric acid, PAH) Measurement of Renal Blood Flow (continued) Delivery in the arterial blood = Urinary excretion Delivery = Renal plasma flow • Plasma concentration(P) Excretion = Urine concentration(U) • volume(V) ∴ Renal plasma flow • P = U • V Renal plasma flow = U•V P = C PAH clearance actually measures renal plasma flow. Averages 625 ml/min. Measurement of Renal Blood Flow Total Renal Blood Flow 45% blood is RBCs 55% plasma Total renal blood flow = PAH clearance 0.55 Insert fig. 17.23 Regulation of Extracellular Fluid Osmolarity and Sodium Concentration Formation of Hyperosmotic Renal Medullary Interstitium Osmolality of Different Regions of the Kidney Insert fig. 17.19 Countercurrent Multiplier System Outer medulla Different parts of the loop are permeable to different molecules. Multiplies the [interstitial fluid] and [descending limb fluid]. Flow in opposite directions in the ascending and descending limbs. Inner medulla Ascending limb LH and terminal CD are permeable to urea; Urea diffuses out CD and into ascending limb LH. NaCl Recycle urea. Thin ascending limb LH passively reabsorption NaCl. Urea Countercurrent Multiplier Function of juxta-medullary nephron loops Descending limb – permeable to water , not salt; water leaves, salt stays; concentration 1200 mOsm/L Ascending limb – impermeable to water; Na, K, CL out of tubule; tubular fluid more dilute = 100 mOsm/L at top of loop The loop acts to continually recapture salt & return it to deep medulla; multiplies salinity in deep medulla Countercurrent exchange system Vasa recta. Recycles NaCl in medulla. Transports H20 from interstitial fluid. Descending limb: Urea transporters. Aquaporin proteins (H20 channels). Ascending limb: Fenestrated capillaries. Insert fig. 17.17 Countercurrent exchange Vasa recta – blood supply Blood exchanges water for salt when surrounding descending limb Exchanges salt for water when surrounding the ascending limb of the loop This maintains the osmolarity of the medulla Removes solutes and water Balances solute reabsorption and osmosis in the medulla Mechanism of Concentrated Urine Concentrated urine (hypertonic) Urinary osmolality > Plasma osmolality Isosmotic urine Urinary osmolality = Plasma osmolality Dilute urine (hypotonic) Urinary osmolality < Plasma osmolality Mechanism of Concentrated Urine • Countercurrent multiplier of Henle’s loop produces a hyperosmotic renal medullary interstitium; • Countercurrent exchange of vasa recta maintains the osmolarity of the medulla. Mechanism of Concentrated Urine Medullary area impermeable to high [NaCl] that surrounds it. The walls of the collecting duct (CD) are permeable to H20. H20 is drawn out of the CD by osmosis. Permeable to H20 depends upon the presence of ADH. Regulation of Extracellular Fluid Volume and Osmolality Regulation of Renal Na+ and Water Reabsorption Nervous regulation Renal sympathetic nerve Strong activation constrict the renal arterioles and decrease renal blood flow and GFR; Moderate or mild activation has little influence on renal blood flow and GFR. Humoral regulation Antidiuretic hormone (ADH) Aldosterone Atrial natriuretic hormone Antidiuretic Hormone (ADH) Is manufactured by cells in the supraoptic nucleus of the hypothalamus; Is stored and released from the posterior pituitary. ADH secretion is stimulated by: Increased osmolality in the extracellular fluid, which is detected by osmoreceptors within the hypothalamus; these also stimulate drinking. Decreased circulating blood volume, as detected by cardiovascular volume receptors. Decreased arterial pressure as detected by cardiovascular baroreceptors. Function of ADH Increase the water permeability in the distal convoluted tubule and collecting duct. • This promotes reabsorption of water under the influence of the high medullary osmolality and so helps expand the extracellular fluid volume while reducing its osmolality. ADH can help to elevate arterial blood pressure by direct vasoconstriction, leading to its alternative name of vasopressin. COLLECTING DUCTS – begin in cortex, enter medulla; reabsorb water , concentrate urine Produce concentrated urine because osmolarity of medulla is 4X greater than that of cortex CD is permeable to water not salt As urine passes down CD water leaves tubule by osmosis and becomes more concentrated Control by state of hydration & ADH ADH released - dehydration – more water reabsorbed, urine output < Collecting duct can adjust water reabsorption to produce urine – hypotonic = 50 mOsm/L Or Hypertonic = 1200mOsm/L Depending on the water needs of the body ADH – makes the CD permeable to water and reabsorbed water = concentrated urine The Effects of ADH on the DCT and Collecting Ducts ADH Secretion regulated by negative feedback Hypothalamic osmoreceptors regulate secretion of ADH in response to changes in blood osmolarity ADH regulates facultative water reabsorption in last part of DCT and collecting ducts Stimulates insertion of water channel into apical membranes of principal cells Sweat vomiting diarrhea Extracellular volume and osmolarity comeback What effects would drinking 500 ml of water have on fluid handling in the kidney? What difference would there be if you drank 500 ml of an isotonic sports drink instead? Aldosterone Release from the adrenal cortex Stimulated as Na+ levels decrease and K+ levels increase Reabsorb more Na+ and water; secrete more K+ from DCT and Collecting duct Salt and water help maintain blood volume and pressure, control of electrolyte and acid-base balance The Renin-angiotensin-aldosterone system E Blood Na+↓, K+ ↑ Na+ Reabsorption 90% filtered Na+ reabsorbed in PCT. In the absence of aldosterone, 80% of the remaining Na+ is reabsorbed in DCT. Final [Na+] controlled in CD by aldosterone. When aldosterone is secreted in maximal amounts, all Na+ in DCT is reabsorbed. Insert fig. 17.26 K+ Secretion Final [K+] controlled in CD by aldosterone. When aldosterone is absent, no K+ is excreted in the urine. High [K+] or low [Na+] stimulates the secretion of aldosterone. Only means by which K+ is secreted. Insert fig. 17.24 Atrial natriuretic hormone Produced by atria due to stretching of walls. Antagonist to aldosterone. Increases Na+ and H20 excretion. Acts as an endogenous diuretic. Urine production Homeostasis of body fluid volume depends in large part on the ability of the kidneys to regulate the rate of water loss in urine ADH controls whether dilute or concentrated urine is formed Micturition Reflex Actions of the internal urethral sphincter and the external urethral sphincter are regulated by reflex control center located in the spinal cord. Filling of the urinary bladder activates the stretch receptors, that send impulses to the micturition center. Activates parasympathetic neurons, causing rhythmic contraction of the detrusor muscle and relaxation of the internal urethral sphincter. Voluntary control over the external urethral sphincter. When urination occurs, descending motor tracts to the micturition center inhibit somatic motor fibers of the external urethral sphincter. Clinical note – Edema In some kidney diseases glomerular capillaries are damaged Plasma proteins enter glomerular filtrate Reduces blood colloid osmotic pressure More fluid moves into tissues Causes edema Clinical note - diuretics Diuretics slow renal reabsorption of water + transporters Most act by blocking Na + reabsorbed Less Na Less water reabsorbed by obligatory reabsorption Cause diuresis (increased urine production) Reduces plasma volume Reduces edema A Representative Nephron An Overview of Urine Formation A Summary of Renal Function