kuliah blok 5 ginjal

7/30/2019 KULIAH Blok 5 Ginjal

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FISIOLOGI GINJAL


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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 foreignsubstance

5. Production and secretion of hormones


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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


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VOLUMES OF BODY FLUID

COMPARTMENT

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

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

Interstial fluid

ECF =10,5L

Plasma=1/4ecf

3.5L

Cell mbr

Cap. endotel


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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.


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Celluler fluid exchange :

osmotic pressure differencebetween ECF and ICF are

responsible for fluid movement

between these compartment


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ALTERATION IN STARLING FORCE

. Increasing in capillary hydrostatic (Pc) Decrease in plasma oncotic pressure(Oc)

Lymphatic obstruction.

Increase in capillary permiabelity.


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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


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STRUCTURE AND FUNCTION OF

THE KIDNEYS AND THE LOWER

URINARY TRACT

OBYECTIVES

1.Describe the location of the kidneys and their gross anatomicalfeature.

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.


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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 thelower urinary tract.


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STRUCTURE OF THE KIDNEYS


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Yuxtaglom: is one component of an important feedback mechanism

that is involved in the autoregulation of RBF and GFR


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GLOMERULAR FILTRATION

AND RENAL BLOOD FLOW

OBJECTIVES1. 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 arehandled 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.


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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.


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RENAL CLEARENCE

GLOMERULAR FILTRATION

REABSORBTION

SECRETION

C x= Ux X V

Px

Cx=clearence x

Ux=conc. x in

urine

V= urine flowrate/minute

P= conc. x in

plasma


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MEASUREMENT OF GFR

CLEARENCE OF INULIN

Amount filtered = amount excreted

GFR X Pin = Uin X V

GFR = Uin X V

Pin


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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


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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


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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 nephroncell and returning CO2 and reabsorbed fluid and solute to

general circulation.


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REGULATION OF RENAL BLOOD FLOW

hemorrhage

Arterial blood pressure

Intra renal receptors

Renin secretion

Plasma renin

Plasma angiotensin

Constriction of

Renal arterioles

RBF and GFR

Activity of renal

Symphatic nerves

Carotic sinus andAortic arch reflexs


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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 Henles loop.


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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


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COMPOSITION OF URINE

SUBSTANCE CONCENTRATION

Na+ 50 - 150 meq/l

K+ 20 - 70 meq/l

NH4- 30 - 50 meq/l

Ca++ 5 - 12 meq/lMg++ 2 - 18 meq/l

Cl - 50 - 130 meq/l

PO4 20 - 40 meq/l

Urea 200400 mM

Kreatinin 6 - 20 mM

pH 5 - 7

Osmolality 500 - 800 mOsm/Kg H2O

others 0


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Tubuler fluid

Paracelluler

pathway

Transcelluler

pathway

Tight

junction

Apical cell

membrane

Lateral intercellular space

blood

Na+

K+

Na+

Na+

Basolateral

membrane

Capillary

Basement

membrane

ATP

ATP

ATP


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Tubular fluidblood

Na+

X

Na+H+

HCO3

K+

Na+ATP

X

CO2 + H2O

CA

First half of proximal tubule


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Tubular fluid

blood

NaCl

H2O

Na+

Cl-

orga

nics

H2O

0rganics Na+ Cl-

org

anic Na+ Cl-

organics Na+ Cl-

H2O


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Tubular fluid

CL-

Na+

Na+ Na+ Na+

H+

Hbase

Base

Cl-

Cl-

Na+

Cl-

H base

K+ATP

K+

Cl-

blood

Second half of proximal tubule


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Some organic secreted by the proximal tubule

Endogenous anions Drug

cAMP acetazolamideBile salts chlorothiazide

Hippurate(PAH) furosemide

Oxalate penicillin

Prostaglandins probenecid

Urate salicylate(aspirin)

hidrochlorthiazide

bumetanide


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Some organic cations secreted by the

proximal tubule

Endogenous cations Drugs

Creatinine atropineDopamine isoproterenol

Epinephrine cimetidine

Norepinephrine morphine

quinineamiloride


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Tubular

fluid

A-

PAH

(OA-)

Na+

K+

Na+

Di/tri carboxylaseDi/tri carboxylase

PAH(OA-)

ATP

BLOOD


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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)


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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


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CONCEPT OF EFFECTIVE CIRCULATING VOLUME

Effective circulating

volume

Volume sensors

Kidney

Alteration in

NaCl excretion


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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


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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


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SIGNALS INVOLVED IN THE

CONTROL OF RENAL NaCl AND

WATER EXCRETION cont

ReninAngiotensinaldosteron

( secretion : NaCl axcretion )

1. Angiotensin II levels stimulate prox.

tubule NaCl reabsorption.

2. Aldosteron levels stimulate thick

ascend limb of Henles loop andcollect.Duct NaCl reabsorption.

3. ADH secretion


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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.


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Brain ADH

Angiotensin II

Lung Ang II

Adrenal

Aldosteron

Kidney

Na+ excretion

H2O excretion

Angiotensin I

Angiotensinogen

Hepar

Renin

RAAS


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RENIN

Three factors play an important role in stimulatingrenin 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 secretion3. Inhibition of aldosteron secretion

4. Inhibition of NaCl reabsorption

5. Inhibition of secretion and activity of ADH


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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 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 theurine matches the amount ingested in the diet.

------------ maintain the euvolemic state.


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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.


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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.


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REGULATION OF ACID-BASE

BALANCE

Objective1. 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.


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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 respiratoryacid-base disorders and the bodys response to them.

9. Analyze acid-base disorders and distinguis between

simple and mixed disorders.


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HENDERSON-HASSELBALCH

pH = 6,1 + log HCO3

pCO2


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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 acidsa.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


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Tubular fluidblood

Na

HCO3 + H+

H2CO3

CA

H2O+CO2 CO2 + H2O

CA

H+

ATP

Na+

K+ ATP

3Na+

HCO3

Cl-

PROXIMAL TUBULE85%

COLLECTING DUCT


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HCO3 + H+

H2CO3

CO2 + H2O

CO2 + H2O

CAH+ HCO3

Cl-

COLLECTING DUCT

5%

THICK ASC. LIMB 10%

F t l ti H+ ti


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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+ secretionDecrease 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


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RESPONSE TO ACID-BASE DISORDERS

1. ECF AND ICF BUFFERING

2. VENTILATORY RATE OF THE LUNGS

3. RENAL ACID EXCRETION


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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


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Approach for analysis of simple acid-base disorders

Arterial blood sample

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


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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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