Ch 34: Control of Body Fluid Osmolality and VolumeCh 2 : Homeostasis of Body Fluids

Fluid and Electrolyte BalanceFluid and Electrolyte BalanceFluid and Electrolyte BalanceFluid and Electrolyte Balance

Myoung Kyu Park MD. PhD.Department of PhysiologySungkyunkwan University School of Medicine

Fluid and Electrolyte BalanceFluid and Electrolyte Balanceu d a d ect o yte a a ceu d a d ect o yte a a ce1. Distribution and measurement of body fluid compartmentsy p2. Compartmental fluid balance and compositions3. Systemic fluid balance : water intake & output4 Regulation mechanism of extracellular fluid volume4. Regulation mechanism of extracellular fluid volume5. Electrolytes balance

Body FluidBody FluidBody FluidBody FluidYoung men Young WomenYoung men Young Women

60% of body weight60% of body weight

50% of body weight50% of body weight

cf. water content ; fat tissue (10%), other tissues (70-75%)

Body Fluid CompartmentsBody Fluid Compartments70 kg man

Intracellular fluid (ICF) Extracellular Fluid (ECF)

40% 28L 15% 5%340%, 28L 10.5L 3.5L

interstitial Fluid Plasma 1-3%(ISF) Plasma

1/32/3 transcellularfluid

(ECF, 14L)

Total Body Water (42L)

60%

(ECF, 14L)CSFAquaous humorSynobial fluid

60%

Measurement of body fluid compartmentsMeasurement of body fluid compartments

Camount Substance Methods

TBW Tritiated water and D2O

V =amount

ECF sulfate, inulin, manitol

Plasma radioiodinated serum albumin, Evans blue

I t titi l ECF l l lV = concentration

Interstitial ECF vol – plasma vol

ICF TBW – ECF vol

Electrolyte Composition of the Body FluidsElectrolyte Composition of the Body FluidsElectrolyte Composition of the Body FluidsElectrolyte Composition of the Body Fluids

2 Osmolarity determines fluid volumes1. Key ions determine fluid volumes2.Osmolarity determines fluid volumes

Electrolyte composition between ICF and ECF is different but the osmolarity is the same

OsmECF = OsmICF

Electrolyte composition between ICF and ECF is different, but the osmolarity is the same

Osmotic Pressure determines Cell Volumes (ICF)( )

Hypertonic solution Isotonic solution Hypotonic solution

Solution glucose(g/dL) Na+ K+ Ca2+(mEq/L) Cl- lactate osmolarity(mOsm/L)

5% dextrose 5.0 Isotonic (278)10% dextrose 10.0 hypertonic (556)5% dextrose 5.0 154 hypertonic (586)in 0.9% saline

half strength 77 77 hypotonic (154)half strength 77 77 hypotonic (154)saline(0.45%)

normal saline 154 154 isotonic (308)(0.9%)

Lactated Ringer's 130 4 3 109 28 isotonic (274)solution

Importance ofImportance of ECFECF volumevolumeImportance of Importance of ECFECF volumevolume

ICF ISF Plasma

ISF is a diffusion medium between plasma and ICF.

Maintenance of ECF volumeis essential for the adequacy of the circulation.

[N +] ECF l

ECF volume is determined by mainly Na+ concentration

[Na+] ECF vol.

cf. cell memb. permeability

Evolutionary changes

j ll fi hsponges jellyfish

earthworm

Cariovascular system

separated from ECF

T bP

separated from ECF

TubesPump

HemoglobinRBC

concentratedand packed

Systemic circulation - High Pr, High Resis

RBCand packed

Pulmonary circulation - Low Pr, Low Resis

Two Important FactorsTwo Important FactorsTwo Important FactorsTwo Important Factors70 Kg man

Fl id V lFluid Volume Osmolarity

hyper-volemia hyper-osmolaritydemyelination

hypertensionedema

290 mOsm42 L

hypo-volemia hypo-osmolarity

swelling of brain cellsnausea, malaise, headache, confusion, lethargy, seizures, and coma

swelling of brain cellshypotensionshock

Shifts of water between compartmentsShifts of water between compartments

Add pure waterNormal300 mOsm

ysm

olal

ity

ECFICF

os

2/3 (28L) 1/3 (14L)

volume

2/3 (28L) 1/3 (14L)

Darrow-Yannet Diagram

Addition of Pure Water SIADH (ADH)Addition of Pure Water hyposmotic vol expansionProt conc.

HCt

300 mOsm

HCt

tysm

olal

it

ECFICF

os

volume0 28 42 L

Shifts of water between compartments(b) Add pure water(a) Normal hyposmotic vol expansion

Prot conc.

HCt

SIADH (ADH)

ECFICF ICF ECFos

mol

arity

HCt

(c) Add isotonic saline (0 9%NaCl) (d) Add pure NaClvolume

o

hyperosmotic vol expansion(c) Add isotonic saline (0.9%NaCl) (d) Add pure NaCl

isosmotic vol expansionProt conc.

0.9% saline IV

hyperosmotic vol expansionProt conc. HCtBP

ICFICF ECF ECFHCtBP

isosmotic vol contraction isosmotic vol contractionDiarrhea Hemorrage

hyperosmotic vol contractionSweating (hypotonic)

Prot conc. HCtBP

Prot conc. HCtBP

Prot conc.

HCt

ICF ISF Plasma

Fluid balance between ISF and Plasma : Starling's law

illcapillary

hydrostatic pressure osmotic pressure hydrostatic pressurey32 mmHg

p22 mmHg

y p12 mmHg

arterialend

venousend

Net Flow

(+10 mmHg) (-10 mmHg)

Oncotic proteins – albumin, globulin, fibrinogen

Disorders of Fluid BalanceDisorders of Fluid BalanceDisorders of Fluid BalanceDisorders of Fluid BalanceEtiology : liver, cardiovascular or renal disease, hormonal imbalance, or accidents

plasma-to-interstitial shift / plasma-to-transcellular space shift

Accumulation of fluid in interstices or connective tissues or transcellular spacesdue to increased hydrostatic pressure or decreased osmotic pressure (third space)

Edema, hydrothorax (pleural effusion), hydropericardium (pericardial effusion), hydroperitoneum (ascites)hydroperitoneum (ascites)

Edema: Increased hydrostatic pressureIncreased hydrostatic pressure

CHF, liver cirrhosis, constrictive pericarditis, venous obstruction, heat Reduced plasm osmotic pressure

nephrotic syndrome, Liver cirrhosis Lymphatic obstruction

inflamatory, neoplasmic, postsurgical Sodium Retention – pitting edema

Excessive salt intake Increased RAA systemExcessive salt intake, Increased RAA system Inflammation

Fluid and Electrolyte Balance

Maximum 4L/h

W t B lW t B lWater BalanceWater Balance

(at rest)habit

Water intake Water outputconstant

OsmICF effective circ. bl vol.

Thirst (emergency) KidneyCell vol. change

in ant HT osomoreceptor

baroreceptors in CV sys.

renin

hypothalamus

cortex ADHp

yp

cf. CHF – thirst feelingCirrhosis

Thirst : control mechanism for fluid intakeThirst

2

emergency mechanism controlled by hypothalamus i ti

PeripheralVolume

receptorsHigh threshold

conscious sensation

Osmoreceptorcells

Hypothalamus1

supraoptic nucleus

High threshold

ADH

paraventricular nucleusLow threshold

ADH

Posteriorpituitary

Release of ADHintocapillaries

Regulation of ECF VolumeRegulation of ECF Volumegg

OsmICFeffective circ. bl vol.5-10 % change

High pressure baroreceptors•carotid sinus & body

i h & b d

g

•organum vasculosum of the lamina terminalis

Circumventricular organs

•aortic arch & body•justaglomerular apparatus

(afferent arteriole)

of the lamina terminalis•subfornical organ

Low pressure baroreceptors Hypothalamus•supraoptic nucleus•atrial receptors – ANP

•artium, ventricle, pulmonary vein

•supraoptic nucleus•paraventricular nucleus

ADH(AVP)

FourFour Regulatory Pathways controlling Regulatory Pathways controlling g y y gg y y gECFECF volumevolume

1. Renin-Angiotensin-Aldosterone Axis2 Renal Sympathetic activation2. Renal Sympathetic activation3. Arginine Vasopressin (ADH)4 Arterial Natriuretic Peptide (ANP)4. Arterial Natriuretic Peptide (ANP)

1. Renin-Angiotensin-Aldosterone Axis

effective arterial blood volume

(Lung)

1. Renin-Angiotensin-Aldosterone Axis

AldosteroneAldosterone

principal cell

2. Renal Sympathetic activation

1 increases renal vascular resistance

Enhanced activity of the renal sympathetic nerves

1. increases renal vascular resistance2. enhances renin release from granule cells3. increases tubule reabsorption of Na+

Granular cells

RenalnervesAfferent

arteriole

H2O and Na+ retension

P i l

Bowman’s capsule

Urinary space

Thickascendinglimb

Proximaltubule

Maculedensa

Glomerularcapillaries

Efferentarteriole

Extraglomerularmesangial cells

3. Arginine Vasopressin (ADH)

Antidiuretic Hormone (ADH)

hi h th h ld thirst Factors to release ADH1. stretch receptors in heart LA

and Pul Vein

2 Pr in carotid sinus and

low threshold

high thresholdOsmoreceptors

thirst 1

2. Pr. in carotid sinus and aortic arch

3. kidney-granular cells – renin- angiotensin II

2

Raise plasma

Vasopressin – high conc of ADH by more than 10% loss of blood volume

Raise plasma osmolality shrink hypothal. osmoreceptors ADH cells

ADH release

Control of Secretion of Antidiuretic Hormone (ADH)

Osmolality Volume

set pointset point

• Continuous control of ADH level over the set point (278mOsm) and under the 10%• Continuous control of ADH level over the set point (278mOsm) and under the -10% change in circulating blood volume

• Osmolarity and effective circulating blood volume work together and reinforce each other

Cellular mechanisms of ADH action

1. Insertion2. Expression

AQP2AQP2

Water AbsorptionWater AbsorptionADH

Diabetes insipidus – ADH deficiency (nephrogenic or neurogenic)20 L/day urine

Systemic responses to changes in blood osmolarity and volume

4. Atrial Natriuretic Peptide (ANP)

ANP t i•ANP - atrium•BNP - ventricle•Urodilantin - kidney

BNP / urodilantin

vasodilation

Feedback Control of Effective Circulating Volume

Na+ ion

• determines ECF volume

• generates electrical activities

• supplies energy for cellular transport

Na+

Na+ Transport GFR = 180 L/day, PNa+ = 142 mM Filtered Load = 25,500 mmole/day (1.5kg) Diet 120 mmole/day

ADH

Paracellular pathway

Transcellular pathway

Regulation of Na+ Transport

100

33

8

3

0.4

cortex

medulla

67%

25%

5 %

3 %

Na/K/2Cl transporter

Na cotransporter

Na/H exchanger

Solvent drag

Na channels

Na-Cl transporter

Na channels

1. Glomerulotubular balance

2. Aldosterone

3. Sympathetic nerves

1. Decrease RBF & GFR

2. Release renin

3. Stimulate tubular Na+ reabsorption (activates NHE3 & Na pump)

4. Arginine vasopression –ADH

5. Atrial Natriuertic Hormone

1. increase RBF & GFR

2. inhibit Na reabsorption in

the medulla

6. PG, bradykinin, & dopamine

inhibit Na+ reabsorption

1

2 3

4

5

5

4

inhibition

stimulation

H2O channels

Sodium Balancemajor factor determining ECF Vol.

Sodium in diet100 - 300 mEq/dayINPUT

Extracellular fluid

95%small

Gastrointestinallosses (diarrheavomiting)

Skin (sweat,burns,hemorrhage)

KidneysOUTPUT

vomiting)hemorrhage)

positive Na+ balance ECF vol. generalized edema

High intake hypertension

Renal Responses to Na+ intakewater intake ECF Wt gain

( 198 )

Higher Na+ intake pos. sodium balance increase excretion restore equal balance

(Walser, 1985, Kidney Int)

• hypernatremia > 148 mEq/Lhyperaldosteronism sweatinghyperaldosteronism, sweatingburns, diabetes indipidus, diarrhea

• hyponatremia < 135 mEq/Ldiuretics, hypoaldosteronismSIADH, CHF, RF

Kidney FailureUremia (urine in blood)

Lack of erythropoietin anemia

Plasma urea creatinine and uric acid azotemia

( )

Lack of vitamin D activation bone disease

Increased ECF hypertension yp

Decreased H+ secretion metabolic acidosis

decreased GFR hyperkalemia decreased GFR hyperkalemia

ERDS: End State Renal Disease, GFR <10% of Normal

From dialyzerT di l

Superficialvein Hemodialysis: pump y

To dialyzer blood through dialyzer; more efficient than peritoneal dialysis

ArteriovenousfistulaRadial

artery

p y

Bubble trap

F h di l i

Dialyzer membrane

Fresh dialyzingsolution

Used dialyzingsol tion

Constanttemperat re bath

(c) 2003 Brooks/Cole - Thomson Learningsolutiontemperature bath