FISIOLOGI GINJAL Shofa chasani Bag. Fisiologi dan sub bag penyakit ginjal hipertensi Penyakit Dalam FK UNDIP/ RSUP DR Kariadi Semarang Fisiologi GINJAL 1. Regulation of body fluid osmolality and volume 2. Regulation of electrolyte balance 3. Regulation of acid-base balance 4. Excretion of metabolic product and foreign substance 5. Production and secretion of hormones PHYSIOLOGY OF BODY FLUID 1.PHYSICOCHEMICAL PROPERTIES OF ELECTROLYTE SOLUTION 2.VOLUME OF BODY FLUID COMPARTMENTS 3.MESASUREMENT OF BODY FLUID VOLUME 4.COMPOSITION OF BODY FLUID COMPARTMENT 5.FLUID EXCHANE VOLUMES OF BODY FLUID COMPARTMENT Total body water(TBW)=0,6BW=42 L ECF=1/3 TBW=14L ICF=2/3 TBW=28L Cell mbr Interstial fluid Plasma=1/4ecf ¾ ECF =10,5L 3.5L Cap. endotel FLUID EXCHANG BETWEEN BODY FLUID COMPARTMEN Capillary fluid exchange : Fluid movement=Kf[(Pc +Oi)- (Pt=Oc)] Kf=filtration coeff of the cap. Wall Pc=hydrostatic pressure within the cap. Lumen. Oc= oncotic pressue of the plasma. Pt = hydrostatic pressure of the interstitium Oi = oncotic pressure of the interstitial fluid. Celluler fluid exchange : osmotic pressure difference between ECF and ICF are responsible for fluid movement between these compartment ALTERATION IN STARLING FORCE . Increasing in capillary hydrostatic (Pc) Decrease in plasma oncotic pressure(Oc) Lymphatic obstruction. Increase in capillary permiabelity. THE ROLE OF THE KIDNEY VENOUS PRESSURE CAPILLARY HYDROS PRESSURE MOVE OF FLUID INTO INTERSTITIUM Restore plasma volume PLASMA VOLUME VOL RECEPTORS DETECT ECF NaCl and H2O Reabsorption by The kidney STRUCTURE AND FUNCTION OF THE KIDNEYS AND THE LOWER URINARY TRACT OBYECTIVES 1.Describe the location of the kidneys and their gross anatomical feature. 2.Describe the defferent parts of the nephron and their location within the cortex and medulla. 3.Identify the components of the glomerulus and the cell types located in each component. 4.Describe the structur of glomerular capillaries and identify which structures are filtration barriers to plasma proteins. OBYECTIVE 5.Describe the components of the yuxtaglomerular apparatus and the cells located in each component 6.Describe the bood supply to the kidneys. 7.Describe the innervation of the kidneys. 8.Describe the anatomy and physiology of the lower urinary tract. STRUCTURE OF THE KIDNEYS Yuxtaglom: is one component of an important feedback mechanism that is involved in the autoregulation of RBF and GFR GLOMERULAR FILTRATION AND RENAL BLOOD FLOW OBJECTIVES 1. Describe the concepts of mass balance and clearence and explain how they are used to analyze renal trnsport 2. Define the three general process by which substances are handled by the kidneys:glom. Filtration, tub.reabsorb and tub. Secretion. 3. Explain the use of inulin and creatinine clearence to mea- sure the GFR. 4. Explain the use of p-aminohippuric acid (PAH) clearence to measure renal plasma flow(RPF) 5. Describe the composition of theglom.ultrafiltrate, and identify which molecule are not filtered by the glomerulus. OBJECTIVES (cont.) 6. Explain how the los of negative charges on the glom. capillaries results in proteinuri. 7.Describe starling forces involved in the formation of the glom. Ultrafiltrate , and explain how charges in each force affect the glom.filtration rate. 8.Explain how the starling force change along the length of the glom. Capillaries. 9.Describe how changes in the renal plasma flow rate influence the GFR. 10.Explain autoregulation pf renal blood flow and the GFR and identify the factors responsible for autoregulation 11.Identify the major hormones that influence RBF. 12.Explain how and why hormones influence RBF despite autoregulation. RENAL CLEARENCE GLOMERULAR FILTRATION REABSORBTION SECRETION Cx=clearence x Ux=conc. x in C x= Ux X V urine Px V= urine flow rate/minute P= conc. x in plasma MEASUREMENT OF GFR — CLEARENCE OF INULIN Amount filtered = amount excreted GFR X Pin = Uin X V GFR = Uin X V Pin MEASUREMENT OF RENAL PLASMA FLOW AND RENAL BLOOD FLOW. RPF= CLEARENCE OF PAH PAH LOW 0,12mg/ml RPF = Upah X V P pah RBF = RPF 1 - HCT REQUIREMENTS FOR USE OF A SUBSTANCE TO MEASURE GFR 1. The substance must be freely filtered by the glomerulus. 2. The substance must not be reabsorbed or secreted by the nephron . 3. The substance must not be metabolized or produce by the kidney. 4. The substance must not alter GFR RENAL BLOOD FLOW RBF = 25% CARDIAC OUT PUT (1.25 L/min) THE IMPORTANT FUCTION OF RBF INCLUDING : 1. Determining the GFR 2. Modifying the rate of solute and water reabsorption by the proximal tubule. 3. Participating in the concentration and dilution of urine. 4. Delivering oxygen, nutrients and hormones to the nephron cell and returning CO2 and reabsorbed fluid and solute to general circulation. REGULATION OF RENAL BLOOD FLOW hemorrhage Arterial blood pressure Intra renal receptors Carotic sinus and Aortic arch reflexs Renin secretion Activity of renal Symphatic nerves Plasma renin Plasma angiotensin Constriction of Renal arterioles RBF and GFR RENAL TRANSPORT MECHANISM NaCL AND WATER REABSORPTION ALONG THE NEPHRON OBJECTIVE 1.Explain the three processes involved in the production of urine a. filtration b. reabsorption c. secretion.. 2.Describe the magnitude of the processes of filtration and reab- sorption by the nephron. 3.Describe the composition of normal urine. 4.explain the basic transport mechanisms present in each nephron segment. 5.Describe how water reabsorption is “coupled” to Na+ reabsorp tion in the proximal tubule. 6.Explain how solutes, but not water , are reabsorbed by the thick ascending limb of Henle’s loop. OBJECTIVE - COUNT. 7. Describe how Starling forces regulate solute and water reabsorption across the proximal tubule. 8. Explain glomerulotubular balance and its phy- siological significance . 9. Identify the major hormones that regulate NaCl and water reabsorption by its nephron segment COMPOSITION OF URINE SUBSTANCE CONCENTRATION Na+ 50 - 150 meq/l K+ 20 - 70 meq/l NH4- 30 - 50 meq/l Ca++ 5 - 12 meq/l Mg++ 2 - 18 meq/l Cl - 50 - 130 meq/l PO4 20 - 40 meq/l Urea 200 – 400 mM Kreatinin 6 - 20 mM pH 5 - 7 Osmolality 500 - 800 mOsm/Kg H2O others 0 Tubuler fluid blood Paracelluler Lateral intercellular space pathway Transcelluler pathway Tight Na+ junction ATP Na+ K+ ATP ATP Capillary Na+ Basement Apical cell membrane Basolateral membrane membrane Tubular fluid blood Na+ Na+ ATP X K+ X Na+ CA HCO3 H+ CO2 + H2O First half of proximal tubule Tubular fluid 0rganics Na+ Cl- blood NaCl H2O org anic Na+ Cl- Na+ Cl- H2O orga nics organics Na+ Cl- H2O Tubular fluid Second half of proximal tubule blood CL- Na+ Na+ Na+ Na+ ATP K+ H+ Hbase H base Base K+ Cl- Cl- Cl- Cl- Na+ Some organic secreted by the proximal tubule Endogenous anions Drug cAMP acetazolamide Bile salts chlorothiazide Hippurate(PAH) furosemide Oxalate penicillin Prostaglandins probenecid Urate salicylate(aspirin) hidrochlorthiazide bumetanide Some organic cations secreted by the proximal tubule Endogenous cations Drugs Creatinine atropine Dopamine isoproterenol Epinephrine cimetidine Norepinephrine morphine quinine amiloride Tubular fluid BLOOD Na+ ATP A- K+ Na+ PAH (OA-) Di/tri carboxylase Di/tri carboxylase PAH(OA-) REGULATION OF ECF OBJECTIVE 1. Recognize the vital role Na plays in determining the volume of the ECF compartment. 2. Explain the concept of effective circulating volume and its role in the regulation of renal Na+ excretion. 3. Describe the mechanisms by which the body monitors the effective circulating volume ( volume receptors) OBJECTIVE cont. 4. Identify the major signals acting on the kidney to alter their excretion of Na+. 5. Describe the regulation of Na+ reabsorption in each of the various portion of the nephron and how changes in effective circulating volume affect these regulatory mechanisms. 6. Explain the pathophysiology of edema formation and the role of Na+ retention by the kidneys CONCEPT OF EFFECTIVE CIRCULATING VOLUME Effective circulating volume Volume sensors Kidney Alteration in NaCl excretion ECF VOLUME RECEPTORS Vasculer low pressure cardiac atria pulmonary vasculature high pressure carotid sinus aortic arch yuxtaglomeruler apparatus of the kidney (afferent arteriole) Central nervous system Hepatic SIGNALS INVOLVED IN THE CONTROL OF RENAL NaCl AND WATER EXCRETION Renal sympathetic nerves ( activity NaCl excretion ) 1. Glomerular filtration rate 2. Renin secretion 3. Prox, tubule and thick ascending limb of Henle’s loop NaCl reabsorption SIGNALS INVOLVED IN THE CONTROL OF RENAL NaCl AND WATER EXCRETION cont Renin –Angiotensin –aldosteron ( secretion : NaCl axcretion ) 1. Angiotensin II levels stimulate prox. tubule NaCl reabsorption. 2. Aldosteron levels stimulate thick ascend limb of Henle’s loop and collect.Duct NaCl reabsorption. 3. ADH secretion SIGNAL INVOLVED IN THE CONTROL OF RENAL NaCl AND WATER EXCRETION cont Atrial Natriuretic Peptide ( Secretion : NaCl excretion) 1. GFR 2. Renin secretion. 3. Aldosteron secretion 4. NaCl reabsorption by the collecting duct. 5. ADH scretion ADH ( secretion : H2O and NaCl excretion ) 1. H2O reabsorption by the collecting duct. 2. NaCl reabsorption by the thick asc,of Henle’s loop 3. NaCl reabsorption by the collecting duct. Brain ADH Renin Angiotensin II Kidney Lung Na+ excretion Ang II H2O excretion Angiotensin I Adrenal Angiotensinogen Aldosteron Hepar RAAS RENIN Three factors play an important role in stimulating renin secretion : 1. Perfussion presure 2. Sympathetic nerve activity 3. Delivery of NaCl to the macula densa ANP antagonize those of RAAS 1. Vasodelation of aff and eff ---GFR 2. Inhibition of renin secretion 3. Inhibition of aldosteron secretion 4. Inhibition of NaCl reabsorption 5. Inhibition of secretion and activity of ADH CONTROL OF Na+ EXCRETION WITH NORMAL ECF EUVOLEMIA: NaCl ingested and axcreted--- balance 1.Na+ reabsorption by the proximal tubule, Henle’s loop , and the distal tubule is regulate so that a re- latively constan portion of the filtered load of Na+ is diliveredto the collecting duct.. 2.Reabsorption of Na+ by the collecting duct is regu lated such that the amount of Na+ excreted in the urine matches the amount ingested in the diet. ------------ maintain the euvolemic state. CONTROL OF Na+ EXCRETION WITH INCREASE ECV The signal acting on the kidneys include: 1. Activity of the renal sympathetic 2. Release of ANP. 3. Inhibition of ADH secretion. 4. Renin secretion Three general responses to an increases in ECV : 1. GFR increases 2. Reabsorption of Na+ decreases in the prox. tubule. 3. Reabsorption of Na+ decreases in the collec. duct. CONTROL OF Na+ EXCRETION WITH DECREASES ECV The signal acting on kidneys include : 1. Increases renal sympathetic activity. 2. Increases secretion of renin. 3. Inhibition of ANP secretion. 4. Stimulation of ADH secretion. Three general respons to decreases ECV: 1. GFR decreases. 2. Increases of Na+ reabsorption in the prox. tubule. 3. Increases of Na+ reabsorption in the collecting duct. REGULATION OF ACID-BASE BALANCE Objective 1. Explain the chemistry of the CO2/HCO3 buffer system and its role as the primary physiological buffer of ECF. 2. Describe the metabolic process that produce acid and al kali and their net effect on systemic acid-base balance. Distinguish between volatile and non volatile acids. 3. Explain the concept of net acid excretion by the kidneys and the importance of urinary buffers in this process. 4. Describe the mechanisms of H+ secretion in the various segment s of the nephron and how these mechanisms are regulated. 5. Distinguish between the reabsorption of filtered HCO3 and the formation of new HCO3. REGULATION OF ACID-BASE BALANCE objective cont 6. Describe the mechanisms of ammonia production and excretion by the kidneys, and explain their importance in renal acid exfretion and thus systemic A-B balance. 7. Describe the three general mechanisms used by the bo- dyto defend against acid-base disturbances: a. intra and extracelluler buffering. b. respiratory compensation c. renal compensation. 8. Distinguish between simple metabolic and respiratory acid-base disorders and the body’s response to them. 9. Analyze acid-base disorders and distinguis between simple and mixed disorders. HENDERSON-HASSELBALCH pH = 6,1 + log HCO3 pCO2 Metabolic production of non volatile Acid and alkali from the diet. Food source acid/alkali quantity produced (mEq/day) carbohydrates normally (none) 0 fats normally (none) 0 amino acids a.sulfur containing (cysteine,methionine) H2SO4 b.cationic (lysine, argi nine, histidine) HCL 100 c.anionic (aspartate, glutamate) HCO3- Organic anions HCO3- -60 Phosphate H3PO4 30 TOTAL 70 PROXIMAL TUBULE 85% Tubular fluid blood Na Na+ ATP HCO3 + H+ H+ K+ ATP 3Na+ H2CO3 CA HCO3 CA CO2 + H2O Cl- H2O+CO2 COLLECTING DUCT 5% HCO3 + H+ H+ HCO3 CA Cl- H2CO3 CO2 + H2O CO2 + H2O THICK ASC. LIMB 10% Factors regulating H+ secretion (HCO3 reabsorption) by the nephron Factors nephron site of action Increasing H+ secretion increase in filtered load of HCO3 proximal tubule Decrease in ECF volume proximal tubule Decrease in plasma HCO3 ( pH ) prox.,tub.collect. Increase in blood Pco2 idem Aldosteron collecting duct. Decreasing H+ secretion Decrease in filtered load of HCO3 proximal tubule Increase in ECF volume proximal tubule Incraese in plasma HCO3 ( pH ) prox, tub collect. Decrease in blood Pco2 idem RESPONSE TO ACID-BASE DISORDERS 1. ECF AND ICF BUFFERING 2. VENTILATORY RATE OF THE LUNGS 3. RENAL ACID EXCRETION SIMPLE ACID-BASE DISORDERS Characteristics of simple acid-base disorders. Diorders plasma pH primary defense alteration mechanism Metab.acidosis plasma HCO3 ICF and ECF buffer, Pco2 Metab.alkalosis plasma HCO3 idem. Pco2 Respir. Acidosis Pco2 ICF buffers, renal H excr. Respir. Alkalosis Pco2 ICF buffers , renal H excr. Approach for analysis of simple acid-base disorders Arterial blood sample pH <7,40 pH> 7,40 Acidosis Alkalosis HCO3 <24 mEq/L Pco2>40 mmHg HCO3 > 24mEq/L Pco2 < 40 mmHg Metabolic acidosis Respiratory acidosis Metabolic .alkalosis respiratory alkalosis Pco2 < 40 mmHg HCO3 > 24 mEq/L Pco2 > 40 mmHg HCO3 < 24 mEq/L Respiratory compensation renal compensation respiratory compensation renal compensation REGULATION OF POTASSIUM BALANCE OBJECTIVES 1.Explain how the body maintains K+ homeostasis 2.Describe the distribution of K+ within the body compart. 3.Identify the hormon and factors that regulate plaqsma K+ levels. 4.Describe the transport pattern of K+ along the nephron. 5.Describe the cellular mechanism of K+ secretion by distal tubule and collecting duct, and how secretion is regulated. 6.Explain how plasma K+ levels ,aldosteron, ADH, tubular fluid flow rate , acid-base balance , and Na+ concentra- tion in tubular fluid influence K+ secretion.
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