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					 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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