2019B10 Discuss the physiological responses to administration of 2 litres of Hartmann’s solution
intravenously over 1 hour to a conscious, healthy, euvolaemic 70kg adult.

 

List:

·         Summary

·         Composition

·         Ionic effects

·         Fluid effects

·         Metabolic effects

·         Cardiovascular effects

·         Neuroendocrine effects

·         Metabolic effects

 

Summary:

·         Significant initial plasma expansion, subsequent distribution to ISF > plasma > ICF

·         Distribution and excretion may depend upon hydration status

·         Multi-system response restores plasma volume to normal

·         Causes less electrolyte derangement than normal saline

 

Composition of CSL:

 

Concentration in Hartmann’s (mM)

Concentration in plasma (mM)

Na+

131

140

Cl-

111

100

HCO3-

29 (as lactate)

24

K+

5

4

Ca2+

2

2

Osmolality

278

290

Oncotic pressure

0

25

pH

5-7

7.4

 

Ionic effects:

 

Distribution

Effect

Cause

Na+

ECF

Mild ↓[Na+]

Active membrane transport (Na+K+ATPase)

Cl-

ECF

Mild ↑Cl-

Preservation of electrical neutrality

K+

ICF

Mild ↓

↑Distal nephron flow

-> ↑Activity ENaC and ROMK

-> ↑K+ excretion

Active membrane transport (Na+K+ATPase)

Ca2+

ECF

Active membrane transport (ATPases, exchangers)

HCO3-

ECF=ICF

-

 

Fluid effects:

Immediate distribution

·      Entire 2L into plasma (20% ↑blood volume)

·      Distribution half life ~5 minutes

Steady state distribution

·      479mL in plasma (10% ↑ volume)

·      1438mL in ISF (14% ↑ volume)

·      83mL in ICF (minimal %↑ volume)

Excretion

·      Glomerulotubular imbalance

o  ↓Oncotic pressure -> ↑GFR + ↓prox tubule reabsorption -> ↑urine flow rate

·      Pressure diuresis

o  ↑mAP -> ↑urine output (? mechanism)

·      Hormonal response

·      ↓ADH

·      ↓RAAS

·      ↑ANP

(Note excretion of both water and Na+ is faster than for normal saline)

 

Metabolic effects:

Acid-base

·      Metabolic alkalosis (wins)

o  58mmol lactate infused -> 58mM H+ consumed

o  Lactate + H+ -> CO2 + H2O

o  58mmol lactate infused -> 58mmol H+ consumed (≈ 58mmol HCO3- produced)

·      Metabolic acidosis (loses)

o  ↑[Cl-] -> ↓strong ion difference -> ↑dissociation of H2O -> ↑[H+]

Temperature

·      Effect: ↓core temp and skin temp (? >1°C)

·      Response: vasoconstriction, shivering, heat conservation behaviour

Osmolality

·      ↓2mM -> ↓<1% -> no response (ADH sensitivity ∆2%)

 

 

Cardiovascular effects:

Direct effects

·      ↑Blood volume -> distension of capacitance vessels -> ↑MSFP -> ↑venous return -> ↑preload -> ↑cardiac output -> ↑mAP

Response

·      High pressure baroreceptors

o  ↑mAP -> ↑stretch -> ↑afferents to NTS -> ↓SNS output, ↑PSNS output -> ↓HR, ↓contractility, vasodilatation

·      Low pressure baroreceptors

o  ↑CVP -> ↑stretch -> ↑afferents to NTS -> same

 

Neuroendocrine effects:

RAAS

·      ↑mAP -> ↑renal baroreceptor stretch -> ↓renin release -> ↓angiotensin 2

·      Vasodilatation

·      ↓Na+/H+/H2O reabsorption from proximal tubule

ADH

·      ↑Venoatrial stretch -> ↓ADH release (sensitivity ~∆10%)

·      Vasodilatation

·      AQP2 downregulation -> ↓H2O reabsorption from collecting ducts

·      Ureaporin downregulation -> ↓medullary interstitial osmolality -> ↓H2O reabsorption

ANP

·      ↑CVP -> ↑venoatrial stretch -> ↑ANP release

·      Dilatation of afferent arterioles -> ↑GFR, ↑vasa recta flow, washout of medullary interstitium

·      Inhibit NCC in distal tubule -> ↓Na+Cl- reabsorption

·      Inhibit ENaC in collecting ducts -> ↓Na+ reabsorption

 

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