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+ HCO3
CA
H+
CO2 + H2O
First half of proximal tubule
Tubular fluid 0rganics Na+ Cl-
blood
NaCl
H2O
org
Na+
anic Na+ Cl-
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
Objectiv
e
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
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.
