FISIOLOGI GINJAL

Shofa chasani

Bag. Fisiologi dan sub bag penyakit ginjal hipertensi Penyakit Dalam FK UNDIP/ RSUP DR Kariadi Semarang

Fisiologi Fisiologi GINJALGINJAL

1.1. Regulation of body fluid osmolality Regulation of body fluid osmolality and volumeand volume

2.2. Regulation of electrolyte balanceRegulation of electrolyte balance

3.3. Regulation of acid-base balanceRegulation of acid-base balance

4.4. Excretion of metabolic product and Excretion of metabolic product and foreign substanceforeign substance

5.5. Production and secretion of Production and secretion of hormoneshormones

PHYSIOLOGY OF PHYSIOLOGY OF BODY FLUIDBODY FLUID

1.PHYSICOCHEMICAL 1.PHYSICOCHEMICAL PROPERTIES OF ELECTROLYTE PROPERTIES OF ELECTROLYTE

SOLUTIONSOLUTION

2.VOLUME OF BODY FLUID 2.VOLUME OF BODY FLUID COMPARTMENTSCOMPARTMENTS

3.MESASUREMENT OF BODY 3.MESASUREMENT OF BODY FLUID VOLUMEFLUID VOLUME

4.COMPOSITION OF BODY 4.COMPOSITION OF BODY FLUID COMPARTMENTFLUID COMPARTMENT

5.FLUID EXCHANE5.FLUID EXCHANE

VOLUMES OF BODY FLUID VOLUMES OF BODY FLUID COMPARTMENTCOMPARTMENT

Total body water(TBW)=0,6BW=42 L

ECF=1/3 TBW=14L ICF=2/3 TBW=28L

Interstial fluid¾ ECF =10,5L

Plasma=1/4ecf3.5L

Cell mbr

Cap. endotel

FLUID EXCHANG BETWEEN BODY FLUID EXCHANG BETWEEN BODY FLUID COMPARTMENFLUID 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 Celluler fluid exchange :exchange :

osmotic pressure osmotic pressure difference between ECF difference between ECF and ICF are responsible and ICF are responsible

for fluid movement for fluid movement between these between these compartment compartment

ALTERATION IN STARLING ALTERATION IN STARLING FORCEFORCE

. Increasing in capillary hydrostatic . Increasing in capillary hydrostatic (Pc)(Pc)

Decrease in plasma oncotic Decrease in plasma oncotic pressure(Oc)pressure(Oc)

Lymphatic obstruction.Lymphatic obstruction. Increase in capillary permiabelity.Increase in capillary permiabelity.

THE ROLE OF THE KIDNEYTHE ROLE OF THE KIDNEY

VENOUS PRESSURE

CAPILLARY HYDROSPRESSURE

MOVE OF FLUID INTOINTERSTITIUM

PLASMA VOLUME

VOL RECEPTORSDETECT ECF

NaCl and H2OReabsorption by

The kidney

Restore plasmavolume

STRUCTURE AND FUNCTION OFTHE KIDNEYS AND THE LOWER URINARY TRACT

OBYECTIVES1.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 autoregulation11.Identify the major hormones that influence RBF.12.Explain how and why hormones influence RBF despite autoregulation.

RENAL CLEARENCE GLOMERULAR FILTRATION

REABSORBTION

SECRETION

C x= Ux X V Px

Cx=clearence xUx=conc. x in urineV= urine flow rate/minuteP= 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 GFR2. 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

Renin secretion

Plasma renin

Plasma angiotensinConstriction ofRenal arterioles

RBF and GFR

Activity of renalSymphatic nerves

Carotic sinus andAortic arch reflexs

RENAL TRANSPORT MECHANISMNaCL 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 URINESUBSTANCE 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

Paracellulerpathway

Transcellulerpathway

Tightjunction

Apical cellmembrane

Lateral intercellular space

blood

Na+

K+

Na+

Na+

Basolateralmembrane

CapillaryBasementmembrane

ATP

ATP

ATP

Tubular fluidblood

Na+

X

Na+H+

HCO3

K+

Na+ATP

X

CO2 + H2O

CA

First half of proximal tubule

Tubular fluid

blood

NaCl

H2O

Na+

Cl-

organics

H2O

0rganics Na+ Cl-

organic Na+ Cl-

organics Na+ Cl-

H2O

Tubular fluid

CL-Na+

Na+ Na+ Na+

H+HbaseBase

Cl-

Cl-Na+

Cl-

H base

K+ATP

K+Cl-

blood

Second half of proximal tubule

Some organic secreted by the proximal tubule

Endogenous anions Drug

cAMP acetazolamideBile salts chlorothiazideHippurate(PAH) furosemideOxalate penicillinProstaglandins probenecidUrate salicylate(aspirin) hidrochlorthiazide bumetanide

Some organic cations secreted by the proximal tubule

Endogenous cations Drugs

Creatinine atropineDopamine isoproterenolEpinephrine cimetidineNorepinephrine morphine quinine amiloride

Tubular fluid

A-

PAH(OA-)

Na+

K+

Na+

Di/tri carboxylaseDi/tri carboxylase

PAH(OA-)

ATP

BLOOD

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 inNaCl 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 systemHepatic

SIGNALS INVOLVED IN THECONTROL 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 THECONTROL 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. GFR2. Renin secretion.3. Aldosteron secretion4. 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

Angiotensin II

Lung Ang II

Adrenal

Aldosteron

Kidney

Na+ excretion H2O excretion

Angiotensin I

Angiotensinogen

Hepar

Renin

RAAS

RENINThree 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 RAAS1. Vasodelation of aff and eff ---GFR 2. Inhibition of renin secretion3. Inhibition of aldosteron secretion4. Inhibition of NaCl reabsorption5. 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-BASEBALANCE 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- -60Phosphate H3PO4 30TOTAL 70

Tubular fluid blood

Na

HCO3 + H+

H2CO3

CAH2O+CO2 CO2 + H2O

CA

H+

ATP

Na+

K+ATP

3Na+

HCO3

Cl-

PROXIMAL TUBULE85%

HCO3 + H+

H2CO3

CO2 + H2O

CO2 + H2O

CAH+ HCO3

Cl-

COLLECTING DUCT

5%

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 tubuleDecrease in ECF volume proximal tubuleDecrease in plasma HCO3 ( pH ) prox.,tub.collect.Increase in blood Pco2 idemAldosteron collecting duct.

Decreasing H+ secretionDecrease in filtered load of HCO3 proximal tubuleIncrease in ECF volume proximal tubuleIncraese 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, Pco2Metab.alkalosis plasma HCO3 idem. Pco2Respir. 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

Acidosis

HCO3 <24 mEq/L

Metabolic acidosis

Pco2>40 mmHg

Respiratory acidosis

pH> 7,40

Alkalosis

HCO3 > 24mEq/L Pco2 < 40 mmHg

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+ homeostasis2.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.