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

· t_1/2_α ~5 minutes – i.e. immediate distribution

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:

Energy	· 58mmol lactate -> 29mmol glucose = 5g · i.e. minimal nutritive effect
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

· Minimal change in the healthy, euvolaemic subject when infused over 1h

Response

· Low pressure baroreceptors

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

· High pressure baroreceptors

o Minimal ↑mAP -> minimal effect

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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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.