泌尿系统教学课件：2泌尿系统2.ppt

单击此处编辑母版标题样式,*,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,Renal physiology,Major Functions of the Kidneys,produce urine?,Major Functions of the Kidneys,1.Regulation of:,(1)body fluid osmolarity and volume,Major Functions of the Kidneys,1.Regulation of:,(1)body fluid osmolarity and volume,(2),electrolyte balance,3),acid-base balance,(4),blood pressure,2.Excretion of,metabolic products,foreign substances(pesticides,chemicals etc.),excess substance(water,etc),3.Secretion of,erythropoitin,1,25-dihydroxy vitamin D,3,(vitamin D activation),renin,prostaglandin,Renal tubules and collecting duct,Functions of the Nephron,Filtration,Reabsorption,Secretion,Excretion,HUMAN RENAL PHYSIOLOGY,Functions of the Kidney:,Filtration:,First step in urine formation,Transport of fluid from blood to kidney tubule,Isosmotic filtrate,Blood cells and proteins don,t filter,GFR=180 L/day,HUMAN RENAL PHYSIOLOGY,Functions of the Kidney:,Reabsorption:,Process of returning filtered material to bloodstream,99%of what is filtered,involve transport protein(s),Normally glucose is totally reabsorbed,HUMAN RENAL PHYSIOLOGY,Functions of the Kidney:,Secretion:,Material added to lumen of kidney from blood,Active transport(usually)of toxins and foreign substances,-H+,K+,and NH4+,HUMAN RENAL PHYSIOLOGY,Functions of the Kidney:,Excretion:,Loss of fluid from body in form of urine,Amount =Amount +Amount -Amount,of Solute Filtered Secreted Reabsorbed,Excreted,Outline,1.Glomerular Filtration,2.,Sodium Reabsorption and Potassium Secretion,3.,Water reabsorption,4.,Hydrogen Secretion and Bicarbonate Reabsorption,SECTION 1,Glomerular Filtration,blood enters glomerular capillary,filters out of renal corpuscle,large proteins and cells stay behind,everything else is filtered into nephron,Glomerular filtration,Occurs as fluids move across the glomerular capillary in response to glomerular hydrostatic pressure,The Renal Corpuscle,Composed of Glomerulus and Bowmans capsule,Factors that determining the glumerular filterability,-Filtration Membrane,-Filtration Membrane,Factors that determining the glumerular filterability,Filtration Membrane,One layer of glomerular capillary cells,Filtration Membrane,One layer of glomerular capillary cells,-Basement membrane,-One layer of cells in Bowmans capsule:Podocytes,Factors that determining the glumerular filterability,1.Molecular weight,2.Charges of the molecule,Stanton BA&Koeppen BM:The Kidney in,Physiology,Ed.Berne&Levy,Mosby,1998,2934,Dextran filterability,Protein filtration,:,influence of negative charge on glomerular wall,Constituent,Mol.Wt.,Filteration ratio,Urea,60,1.00,Glucose,180,1.00,Inulin,5,500,1.00,Myoglobin,17,000,0.75,Hemoglobin,64,000,0.03,Serum albumin,69,000,0.01,Filterablility of plasma constituents vs.water,Factors that determining the glumerular filterability,-Filtration pressure,Glomerular filtration pressure,Types of pressure:,Favoring Force:Capillary Blood Pressure(BP),Opposing Force:Blood colloid osmotic pressure(COP),Capsule Pressure(CP),Amount of filtrate produced in the kidneys each minute.125mL/min=180L/day,Glomerular filtration rate(GFR),Measuring GFR,125ml of plasma is cleared/min in glomerulus(or 180L/day),If a substance is filtered but neither reabsorbed nor secreted,then the amount present in urine is its,plasma clearance,(amount in plasma cleared/min by glomerulus),If plasma conc.is 3mg/L then,3 180/day=540mg/day,(known)(unknown)(known),Renal handling of inulin,Amount filtered=Amount excreted,P,in,x GFRU,in,x V,Qualities of agents to measure GFR,Inulin:,(Polysaccharide from Dahalia plant),Freely filterable at glomerulus,Does not bind to plasma proteins,Biologically inert,Non-toxic,neither synthesized nor metabolized in kidney,Neither absorbed nor secreted,Does not alter renal function,Can be accurately quantified,Low concentrations are enough(10-20 mg/100 ml plasma),Creatinine:,End product of muscle creatine metabolism,Used in clinical setting to measure GFR but less accurate than inulin method,Small amount secrete from the tubule,Qualities of agents to measure GFR,The factors that affecting GFR,1.Filtration Membrane,-Barrier,-Filtration membrane area,2.Filtration pressure,3.Renal blood flow,Regulation of renal blood,1.Renal Autoregulation,2.Neural regulation,3.Hormonal regulation,1.Renal autoregulation,Urine,(6 ml/min),ERPF:experimental renal plasma flow,GFR:glomerular filtration rate,Mechanism?,Blood Flow=Capillary Pressure/Flow resistance,1)Myogenic Mechanism of the autoregulation,2934,2)Tubuloglomerular feedback,2.Neural regulation of GFR,Sympathetic nerve fibers innervate afferent and efferent arteriole,Normally sympathetic stimulation is low but can increase during hemorrhage and exercise,Vasoconstriction occurs as a result which conserves blood volume(hemorrhage),and permits greater blood flow to other body parts(exercise),3.Hormonal regulation of GFR,Several hormones contribute to GFR regulation,(1)Angiotensin II.,Produced by Renin,released by JGA cells is a potent vasoconstrictor.Reduces GFR,(2)ANP,(released by atria when stretched)increases GFR by increasing capillary surface area available for filtration,(3)NO,Endothelin,Prostaglandin E2,SECTION 2,Sodium Reabsorption and Potassium Secretion,Two pathways of the absorption:,Lumen,Plasma,Cells,Transcellular,Pathway,Paracellular,transport,Mechanism of Transport,1,Primary Active Transport,2,Secondary Active Transport,3,Passive Transport,Primary Active Transport,Secondary active transport,Na,+,glucose,Na,+,H,+,out in,out in,co-transport counter-transport,(symport)(antiport),Co-transporters will move one moiety,e.g.glucose,in the same direction as the Na,+,.,Counter-transporters will move one moiety,e.g.H,+,in the opposite direction to the Na,+,.,Tubular,lumen,Tubular Cell,Interstitial,Fluid,Tubular,lumen,Tubular Cell,Interstitial,Fluid,Passive Transport,Diffusion,1.Transportation of Sodium,Sodium reabsorption in proximal tubule,Reabsorb about 65 percent of the filtered sodium,chloride,bicarbonate,and potassium and essentially al the filtered glucose and amino acids.,Secrete organic acids,bases,and hydrogen ions into the tubular lumen.,The first half of the proximal tubule,In the first half of the proximal tubule,sodium is reabsorbed by co-transport along with glucose,amino acids,and other solutes.,The sodium-potassium ATPase:major force for reabsorption of sodium,Sodium reabsorption in the first half of proximal tubule,HCO3-reabsorption in first half,Sodium reabsorption,in the second half of,proximal tubule,In the second half of the proximal tubule,sodium reabsorbed mainly with chloride ions.,the second half,HCO3-,-,Na+,Na+,The second half of the proximal tubule has a relatively high concentration of chloride(around 140mEq/L)compared with the early proximal tubule(about 105 mEq/L),In the second half of the proximal tubule,the higher chloride concentration favors the diffusion of this ion from the tubule lumen through the intercellular junctions into the renal interstitial fluid.,Sodium reabsorption in proximal tubule,(2)Sodium in the loop of Henle,The loop of Henle consists of three functionally distinct segments:,the thin descending segment,the thin ascending segment,and the thick ascending segment.,High permeable to water and moderately permeable to most solutes,but has few mitochondria and little or no active reabsorption.,Reabsorbs about 25%of the filtered loads of sodium,chloride,and potassium,as well as large amounts of calcium,bicarbonate,and magnesium.,This segment also secretes hydrogen ions into the tubule,Mechanism of sodium,chloride,and potassium transport in,the thick ascending loop of Henle,(3)Mechanisms of sodium reabsorption by the principle cells of the late distal and collecting tubules.,Regulation of sodium transport,The sensing mechanisms,Volume receptors in the cardiac atria and intrathoracic veins,Pressure receptors in arterial basoreceptors and the afferent arterioles within the kidney,Tubular fluid NaCl concentration receptors within the macula densa,I Nervous Regulation,INNERVATION OF THE KIDNEY,Sympathetic nerve,innervate smooth muscle of afferent&efferent arteriolesregulates blood pressure&distribution throughout kidney,Effect:(1)Reduce the GFR through contracting the afferent and efferent artery(,receptor),(2)Increase the Na,+,reabsorption in the proximal tubules(,1,receptor),(3)Increase the release of renin(,1,receptor),Nerve reflex:,1.Cardiopulmonary reflex and Baroreceptor Reflex,2.Renorenal reflex,Sensory nerves located in the renal pelvic wall are activated by stretch of the renal pelvic wall,Activation of these nerves leads to an increase in afferent renal nerve activity,which causes a decrease in,ipsilateral and contralateral,efferent renal nerve activity,and an increase in urine flow rate and urinary sodium excretion.,This is called a renorenal reflex response.,II Humoral Regulation,1.Aldosterone,Sodium Balance Is Controlled By Aldosterone,Aldosterone:,Steroid hormone,Synthesized in Adrenal Cortex,Causes reabsorption of Na,+,in DCT&CDAlso,K+secretion,Effect of Aldeosterone:,The primary site of aldosterone action is on the principal cells of the cortical collecting duct.,The net effect of aldosterone is to make the kidneys retain Na,+,and water reabsorption and K,+,secretion.,The mechanism is by stimulating the Na,+,-K,+,ATPase pump on the basolateral side of the cortical collecting tubule membrane.,Aldosterone also increases the Na,+,permeability of the luminal side of the membrane.,Mechanisms of potassium secretion and sodium reabsorption by the principle cells of the late distal and collecting tubules.,2.Rennin-Angiotensin-Aldosterone System,Fall in NaCl,extracellular fluid volume,arterial blood pressure,Juxtaglomerular,Apparatus,Renin,Liver,Angiotensinogen,+,Angiotensin I,Angiotensin II,Aldosterone,Lungs,Converting,Enzyme,Adrenal,Cortex,Increased,Sodium,Reabsorption,Helps,Correct,Angiotensinase A,Angiotension IIIThe juxtaglomerular apparatus,Including macula densa,extraglomerular mesangial cells,and juxtaglomerular(granular cells)cells,Angiotension II,It directly acts to vasoconstrict small arterioles,It directly stimulates proximal tubular sodium,It causes the zona glomerulosa cells of the adrenal cortex to release the steriod hormore aldosterone,Regulation of the Renin Secretion:,Renal Mechanism:,Tension of the afferent artery(stretch receptor),Macula densa(content of the Na+ion in the distal convoluted tubuyle),Nervous Mechanism:,-Sympathetic nerve,Humoral Mechanism:,-E,NE,PGE,2,PGI,2,2934,Renal Response to Hemorrhage,3.Atrial natriuretic peptide(ANP),ANP is released by atrium in response to atrial stretching due to increased blood volume,ANP inhibits Na,+,and water reabsorption,also inhibits ADH secretion,Thus promotes increased sodium excretion(natriuresis)and water excretion(diuresis)in urine,Potassium reabsorption and secretion,Mechanisms of potassium secretion and sodium reabsorption by the principle cells of the late distal and collecting tubules.,H+,The factors regulating the extent of potassium secretion,Circulating factors,-high plasma aldosterone concentration,-high plasma potassium concentration,-high plasma pH,Luminal factors,-High sodium delivery rate,-High luminal flow rate,-Negative lumen potential difference,-bicarbonate accompanying sodium through the kidneys,(bicarbonate increases the excretion of potassium),Why a diuretic drug acting to inhibit loop of Henle sodium reabsorption would lead to potassium depletion?,The potassium nornally reabsorbted across the thick ascending limb is lost into the urine,Mechanism of sodium,chloride,and potassium transport in,the thick ascending loop of Henle,The sodium not reabsorbed in the loop passes through to the distal tubule and cortical collecting duct where it is available for increased exchange for potassium through the principal cell mechanisms,Mechanisms of potassium secretion and sodium reabsorption by the principle cells of the late distal and collecting tubules.,The increased flow of fluid accompanying sodium,dilutes the luminal fliud and provides an increased gradient for potassium,The volume depletion-aldosterone,Causes of hypokalaemia,Redistribution into cells,e.g.Alkalosis,Inadequate K intake,Starvation,Increased external K losses,-Gastrointestinal trace,-Kidney(hyperaldosteroneonism,diuretics),SECTION 3 Water reabsorption,Obligatory water reabsorption,:,Using sodium and other solutes.,Water follows solute to the interstitial fluid(transcellular and paracellular pathway).,Largely influenced by sodium reabsorption,Obligatory water reabsorption,Facultative(selective)water reabsorption:,Occurs mostly in collecting ducts,Through the water poles(channel),Regulated by the ADH,Water reabsorption-,2,Facultative water reabsorption,Formation of Water Pores:Mechanism of Vasopressin Action,SECTION 4 Hydrogen Secretion and Bicarbonate Reabsorption.,Hydrogen secretion through secondary Active Transport.,Mainly at the proximal tubules,loop of Henle,and early distal tubule;,More than 90 percent of the bicarbonate is reabsorbed(passively)in this manner.,Secondary Active Transport,(2)Primary Active Transport,Beginning in the late distal tubules and continuing,It occurs at the luminal membrane of the tubular cell,Hydrogen ions are transported directly by a specific protein,a hydrogen-transporting ATPase(proton pump).,Primary Active Transport,ATP,H,+,K,+,Hydrogen Secretionthrough proton pump:,accounts for only about 5 percent of the total hydrogen ion secreted,Important in forming a maximally acidic urine.,Hydrogen ion concentration can be increased as much as 900-fold in the collecting tubules.,Decreases the pH of the tubular fluid to about 4.5,which is the lower limit of pH that can be achieved in normal kidneys.,Excretion of Excess Hydrogen Ions and Generation of New Bicarbonate by the,Ammonia Buffer System,Production and secretion of ammonium ion(NH,4,+,)by proximal tubular cells.,Production and secretion of ammonium ion(NH,4,+,)by proximal tubular cells.,For each molecule of glutamine metabolized in the proximal tubules,two NH,4,+,ions are secreted into the urine and two HCO3,-,ions are reabsorbed into the blood.,The HCO,3,-,generated by this process constitutes,new bicarbonate.,Buffering of hydrogen ion secretion by ammonia(NH,3,)in the collecting tubule.,NH,4,+,NH,3,.H,+,Renal ammonium-ammonia buffer system is subject to physiological control.,An increase in extracellular fluid hydrogen ion concentration stimulates renal glutamine metabolism and,therefore,increase the formation of NH,4,+,and new bicarbonate to be used in hydrogen ion buffering;,a decrease in hydrogen ion concentration has the opposite effect.,with chronic acidosis,the dominant mechanism by which acid is eliminated of NH,4,+,.,This also provides the most important mechanism for generating new bicarbonate during chronic acidosis.,