FISIOLOGI GINJAL

Fisiologi GINJAL
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Regulation of body fluid osmolality and volume Regulation of electrolyte balance Regulation of acid-base balance Excretion of metabolic product and foreign substance 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 ECF =10,5L Plasma=1/4ecf 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 PLASMA VOLUME VOL RECEPTORS DETECT ECF NaCl and H2O Reabsorption by The kidney

Restore plasma volume

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 measure 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 urine V= urine flow rate/minute P= conc. x in plasma

C x= Ux X V Px

MEASUREMENT OF GFR CLEARENCE OF INULIN

Amount filtered = amount excreted GFR X Pin GFR = Uin X V = 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 RPF 1 - HCT

RBF =

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 Activity of renal Symphatic nerves Renin secretion

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 reabsorption 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 Henles loop.

OBJECTIVE - COUNT.
7. Describe how Starling forces regulate solute and water reabsorption across the proximal tubule. 8. Explain glomerulotubular balance and its physiological significance . 9. Identify the major hormones that regulate NaCl and water reabsorption by its nephron segment

COMPOSITION OF URINE
SUBSTANCE CONCENTRATION

Na+ K+ NH4Ca++ Mg++ Cl PO4 Urea Kreatinin pH Osmolality others

50 - 150 meq/l 20 - 70 meq/l 30 - 50 meq/l 5 - 12 meq/l 2 - 18 meq/l 50 - 130 meq/l 20 - 40 meq/l 200 400 mM 6 - 20 mM 5 - 7 500 - 800 mOsm/Kg H2O 0

Tubuler fluid
Paracelluler pathway Lateral intercellular space

blood

Transcelluler pathway

Tight junction

Na+
ATP

Na+ K+
ATP Apical cell membrane ATP

Na+
Basolateral membrane

Capillary Basement membrane

Tubular fluid

blood

Na+ X Na+ H+
CA

ATP K+
X

Na+

HCO3

CO2 + H2O

First half of proximal tubule

Tubular fluid

0rganics

Na+ Clblood

NaCl H2O

Na+
Clorga nics

org anic

Na+ ClH2O

organics

H2O

Na+ Cl-

Tubular fluid

Second half of proximal tubule blood

CLNa+ Na+ Na+ H base ClK+ ClNa+ ATP

H+ Hbase Base
Cl-

K+

ClNa+

Some organic secreted by the proximal tubule

Endogenous anions cAMP Bile salts Hippurate(PAH) Oxalate Prostaglandins Urate Drug acetazolamide chlorothiazide furosemide penicillin probenecid salicylate(aspirin) hidrochlorthiazide bumetanide

Some organic cations secreted by the proximal tubule

Endogenous cations Creatinine Dopamine Epinephrine Norepinephrine

Drugs atropine isoproterenol cimetidine morphine quinine amiloride

Tubular fluid

BLOOD

Na+ APAH (OA-) K+

Na+ Di/tri carboxylase

ATP

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 Henles 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 Henles 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 Henles loop 3. NaCl reabsorption by the collecting duct.

Brain Renin Angiotensin II

ADH

Kidney Ang II Adrenal Aldosteron

Lung

Na+ excretion H2O excretion

Angiotensin I
Angiotensinogen 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. 2. 3. 4. 5. Vasodelation of aff and eff ---GFR Inhibition of renin secretion Inhibition of aldosteron secretion Inhibition of NaCl reabsorption 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, Henles loop , and the distal tubule is regulate so that a relatively 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 bodyto 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 bodys 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 produced quantity (mEq/day) 0 0

carbohydrates normally (none) fats normally (none) amino acids a.sulfur containing (cysteine,methionine) H2SO4 b.cationic (lysine, argi nine, histidine) HCL c.anionic (aspartate, glutamate) HCO3Organic anions HCO3Phosphate H3PO4 TOTAL

100

-60 30 70

PROXIMAL TUBULE 85%

Tubular fluid

blood

Na
HCO3 + H+
ATP H2CO3

H+

CA
H2O+CO2

CA
CO2 + H2O

K+ 3Na+ HCO3

ATP

Na+

Cl-

COLLECTING DUCT 5%

HCO3 + H+ H2CO3

H+

HCO3

CA
CO2 + H2O CO2 + H2O

Cl-

THICK ASC. LIMB 10%

Factors regulating H+ secretion (HCO3 reabsorption) by the nephron

Factors Increasing H+ secretion increase in filtered load of HCO3 Decrease in ECF volume Decrease in plasma HCO3 ( pH ) Increase in blood Pco2 Aldosteron
Decreasing H+ secretion Decrease in filtered load of HCO3 Increase in ECF volume Incraese in plasma HCO3 ( pH ) Decrease in blood Pco2

nephron site of action

proximal tubule proximal tubule prox.,tub.collect. idem collecting duct.

proximal tubule proximal tubule prox, tub collect. 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 alteration plasma HCO3 defense mechanism ICF and ECF buffer, Pco2 idem. Pco2 ICF buffers, renal H excr. ICF buffers , renal H excr.

Metab.acidosis

Metab.alkalosis Respir. Acidosis

Respir. Alkalosis

plasma HCO3 Pco2

Pco2

Approach for analysis of simple acid-base disorders

Arterial blood sample pH <7,40

pH> 7,40

Acidosis
HCO3 <24 mEq/L Pco2>40 mmHg Respiratory acidosis

Alkalosis
HCO3 > 24mEq/L Metabolic .alkalosis Pco2 < 40 mmHg respiratory alkalosis

Metabolic acidosis

Pco2 < 40 mmHg Respiratory compensation

HCO3 > 24 mEq/L renal compensation

Pco2 > 40 mmHg

HCO3 < 24 mEq/L

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+ concentration in tubular fluid influence K+ secretion.