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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
Fisiologi GINJAL
1.
1. Regulation of body fluid osmolality and volume
Regulation of body fluid osmolality and volume
2.
2. Regulation of electrolyte balance
Regulation of electrolyte balance
3.
3. Regulation of acid-base balance
Regulation of acid-base balance
4.
4. Excretion of metabolic product and foreign
Excretion of metabolic product and foreign
substance
substance
5.
5. Production and secretion of hormones
Production and secretion of hormones
PHYSIOLOGY OF
PHYSIOLOGY OF
BODY FLUID
BODY FLUID
1.PHYSICOCHEMICAL PROPERTIES
1.PHYSICOCHEMICAL PROPERTIES
OF ELECTROLYTE SOLUTION
OF ELECTROLYTE SOLUTION
2.VOLUME OF BODY FLUID
2.VOLUME OF BODY FLUID
COMPARTMENTS
COMPARTMENTS
3.MESASUREMENT OF BODY FLUID
3.MESASUREMENT OF BODY FLUID
VOLUME
VOLUME
4.COMPOSITION OF BODY FLUID
4.COMPOSITION OF BODY FLUID
COMPARTMENT
COMPARTMENT
5.FLUID EXCHANE
5.FLUID EXCHANE
VOLUMES OF BODY FLUID
VOLUMES OF BODY FLUID
COMPARTMENT
COMPARTMENT
Total body water(TBW)=0,6BW=42 L
ECF=1/3 TBW=14L
ICF=2/3 TBW=28L
Interstial fluid
¾ ECF =10,5L
Plasma=1/4ecf
3.5L
Cell mbr
Cap. endotel
FLUID EXCHANG BETWEEN BODY
FLUID EXCHANG BETWEEN BODY
FLUID COMPARTMEN
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 :
Celluler fluid exchange :
osmotic pressure difference
osmotic pressure difference
between ECF and ICF are
between ECF and ICF are
responsible for fluid movement
responsible for fluid movement
between these compartment
between these compartment
ALTERATION IN STARLING FORCE
ALTERATION IN STARLING FORCE
. Increasing in capillary hydrostatic (Pc)
. Increasing in capillary hydrostatic (Pc)
 Decrease in plasma oncotic pressure(Oc)
Decrease in plasma oncotic pressure(Oc)
 Lymphatic obstruction.
Lymphatic obstruction.
 Increase in capillary permiabelity.
Increase in capillary permiabelity.
THE ROLE OF THE KIDNEY
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 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
A
REABSORBTION
A
SECRETION
C x= Ux X V
Px
Cx=clearence x
Ux=conc. x in
urine
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.
3. The substance must not be reabsorbed or
secreted by the nephron .
5. 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 :
2. Determining the GFR
3. Modifying the rate of solute and water reabsorption by
the proximal tubule.
5. Participating in the concentration and dilution of urine.
6. 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 angiotensin
Constriction of
Renal arterioles
RBF and GFR
Activity of renal
Symphatic nerves
Carotic sinus and
Aortic arch reflexs
R E N A L T R A N S P O R T
M E C H A N IS M
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
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
Tubular fluid
blood
Na+
X
Na+
H+
HCO3
K+
Na+
ATP
X
CO2 + H2O
CA
First half of proximal tubule
Tubular fluid
blood
NaCl
H2O
Na+
Cl-
orga
nics
H2O
0rganics Na+ Cl-
org
anic Na+ Cl-
organics Na+ Cl-
H2O
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
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
A-
PAH
(OA-
)
Na+
K+
Na+
Di/tri carboxylase
Di/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.
4. Explain the concept of effective circulating volume
and its role in the regulation of renal Na+ excretion.
7. 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 )
4. Angiotensin II levels stimulate prox.
tubule NaCl reabsorption.
7. Aldosteron levels stimulate thick
ascend limb of Henle’s loop and
collect.Duct NaCl reabsorption.
9. ADH secretion
SIGNAL INVOLVED IN THE
CONTROL OF RENAL NaCl
AND WATER EXCRETION
cont
Atrial Natriuretic Peptide ( Secretion : NaCl
excretion)
2. GFR
3. Renin secretion.
4. Aldosteron secretion
5. NaCl reabsorption by the collecting duct.
6. 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
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
Tubular fluid
blood
Na
HCO3 + H+
H2CO3
CA
H2O+CO2 CO2 + H2O
CA
H+
ATP
Na+
K+
ATP
3Na+
HCO3
Cl-
PROXIMAL TUBULE
85%
HCO3 + H+
H2CO3
CO2 + H2O
CO2 + H2O
CA
H+ 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 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
3. VENTILATORY RATE OF THE LUNGS
5. 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
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+ 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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  • 1. FISIOLOGI GINJAL Shofa chasani Bag. Fisiologi dan sub bag penyakit ginjal hipertensi Penyakit Dalam FK UNDIP/ RSUP DR Kariadi Semarang
  • 2. Fisiologi GINJAL Fisiologi GINJAL 1. 1. Regulation of body fluid osmolality and volume Regulation of body fluid osmolality and volume 2. 2. Regulation of electrolyte balance Regulation of electrolyte balance 3. 3. Regulation of acid-base balance Regulation of acid-base balance 4. 4. Excretion of metabolic product and foreign Excretion of metabolic product and foreign substance substance 5. 5. Production and secretion of hormones Production and secretion of hormones
  • 3. PHYSIOLOGY OF PHYSIOLOGY OF BODY FLUID BODY FLUID 1.PHYSICOCHEMICAL PROPERTIES 1.PHYSICOCHEMICAL PROPERTIES OF ELECTROLYTE SOLUTION OF ELECTROLYTE SOLUTION 2.VOLUME OF BODY FLUID 2.VOLUME OF BODY FLUID COMPARTMENTS COMPARTMENTS 3.MESASUREMENT OF BODY FLUID 3.MESASUREMENT OF BODY FLUID VOLUME VOLUME 4.COMPOSITION OF BODY FLUID 4.COMPOSITION OF BODY FLUID COMPARTMENT COMPARTMENT 5.FLUID EXCHANE 5.FLUID EXCHANE
  • 4. VOLUMES OF BODY FLUID VOLUMES OF BODY FLUID COMPARTMENT COMPARTMENT Total body water(TBW)=0,6BW=42 L ECF=1/3 TBW=14L ICF=2/3 TBW=28L Interstial fluid ¾ ECF =10,5L Plasma=1/4ecf 3.5L Cell mbr Cap. endotel
  • 5. FLUID EXCHANG BETWEEN BODY FLUID EXCHANG BETWEEN BODY FLUID COMPARTMEN 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.
  • 6. Celluler fluid exchange : Celluler fluid exchange : osmotic pressure difference osmotic pressure difference between ECF and ICF are between ECF and ICF are responsible for fluid movement responsible for fluid movement between these compartment between these compartment
  • 7. ALTERATION IN STARLING FORCE ALTERATION IN STARLING FORCE . Increasing in capillary hydrostatic (Pc) . Increasing in capillary hydrostatic (Pc)  Decrease in plasma oncotic pressure(Oc) Decrease in plasma oncotic pressure(Oc)  Lymphatic obstruction. Lymphatic obstruction.  Increase in capillary permiabelity. Increase in capillary permiabelity.
  • 8. THE ROLE OF THE KIDNEY 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
  • 9. 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.
  • 10. 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.
  • 11. STRUCTURE OF THE KIDNEYS
  • 12.
  • 13.
  • 14.
  • 15. Yuxtaglom: is one component of an important feedback mechanism that is involved in the autoregulation of RBF and GFR
  • 16. 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.
  • 17. 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.
  • 18.
  • 19. RENAL CLEARENCE GLOMERULAR FILTRATION A REABSORBTION A SECRETION C x= Ux X V Px Cx=clearence x Ux=conc. x in urine V= urine flow rate/minute P= conc. x in plasma
  • 20. MEASUREMENT OF GFR — CLEARENCE OF INULIN Amount filtered = amount excreted GFR X Pin = Uin X V GFR = Uin X V Pin
  • 21. 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
  • 22. REQUIREMENTS FOR USE OF A SUBSTANCE TO MEASURE GFR 1. The substance must be freely filtered by the glomerulus. 3. The substance must not be reabsorbed or secreted by the nephron . 5. The substance must not be metabolized or produce by the kidney. 4. The substance must not alter GFR
  • 23.
  • 24. RENAL BLOOD FLOW RBF = 25% CARDIAC OUT PUT (1.25 L/min) THE IMPORTANT FUCTION OF RBF INCLUDING : 2. Determining the GFR 3. Modifying the rate of solute and water reabsorption by the proximal tubule. 5. Participating in the concentration and dilution of urine. 6. Delivering oxygen, nutrients and hormones to the nephron cell and returning CO2 and reabsorbed fluid and solute to general circulation.
  • 25. 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 and Aortic arch reflexs
  • 26. R E N A L T R A N S P O R T M E C H A N IS M 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.
  • 27. 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
  • 28. 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
  • 29. 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
  • 30. Tubular fluid blood Na+ X Na+ H+ HCO3 K+ Na+ ATP X CO2 + H2O CA First half of proximal tubule
  • 31. Tubular fluid blood NaCl H2O Na+ Cl- orga nics H2O 0rganics Na+ Cl- org anic Na+ Cl- organics Na+ Cl- H2O
  • 32. 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
  • 33. 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
  • 34. Some organic cations secreted by the proximal tubule Endogenous cations Drugs Creatinine atropine Dopamine isoproterenol Epinephrine cimetidine Norepinephrine morphine quinine amiloride
  • 36. REGULATION OF ECF OBJECTIVE 1. Recognize the vital role Na plays in determining the volume of the ECF compartment. 4. Explain the concept of effective circulating volume and its role in the regulation of renal Na+ excretion. 7. Describe the mechanisms by which the body monitors the effective circulating volume ( volume receptors)
  • 37. 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
  • 38. CONCEPT OF EFFECTIVE CIRCULATING VOLUME Effective circulating volume Volume sensors Kidney Alteration in NaCl excretion
  • 39. 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
  • 40. 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
  • 41. SIGNALS INVOLVED IN THE CONTROL OF RENAL NaCl AND WATER EXCRETION cont Renin –Angiotensin –aldosteron ( secretion : NaCl axcretion ) 4. Angiotensin II levels stimulate prox. tubule NaCl reabsorption. 7. Aldosteron levels stimulate thick ascend limb of Henle’s loop and collect.Duct NaCl reabsorption. 9. ADH secretion
  • 42. SIGNAL INVOLVED IN THE CONTROL OF RENAL NaCl AND WATER EXCRETION cont Atrial Natriuretic Peptide ( Secretion : NaCl excretion) 2. GFR 3. Renin secretion. 4. Aldosteron secretion 5. NaCl reabsorption by the collecting duct. 6. 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.
  • 43. Brain ADH Angiotensin II Lung Ang II Adrenal Aldosteron Kidney Na+ excretion H2O excretion Angiotensin I Angiotensinogen Hepar Renin RAAS
  • 44. 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
  • 45. 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.
  • 46. 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.
  • 47. 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.
  • 48. 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.
  • 49. 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.
  • 51. 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
  • 52. Tubular fluid blood Na HCO3 + H+ H2CO3 CA H2O+CO2 CO2 + H2O CA H+ ATP Na+ K+ ATP 3Na+ HCO3 Cl- PROXIMAL TUBULE 85%
  • 53. HCO3 + H+ H2CO3 CO2 + H2O CO2 + H2O CA H+ HCO3 Cl- COLLECTING DUCT 5% THICK ASC. LIMB 10%
  • 54. 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
  • 55. RESPONSE TO ACID-BASE DISORDERS 1. ECF AND ICF BUFFERING 3. VENTILATORY RATE OF THE LUNGS 5. RENAL ACID EXCRETION
  • 56. 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.
  • 57. 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
  • 58. 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.