Question 7

College Answer

Answering this question required the integration of information from areas of cardiovascular,  body fluid and renal physiology which proved difficult for most candidates. Both breadth and depth was expected so as to score well. This question is best answered using a time-based approach. For example, upon the rapid  infusion of a litre of normal saline there will be a brief period of hypervolemia, increase in arterial blood pressure and an associated physiological reflex response to these changes(e.g. baroreceptors, atrial stretch receptors, etc.). There will also be an associated increase in renal perfusion and stimulation of intrarenal receptors (e.g. juxtaglomerular apparatus).
Candidates were expected to outline these changes, their effector responses (e.g. autonomic nervous system reflexes and humoral changes) and their physiological consequences. A more prolonged redistribution phase of the administered saline then occurs. This saline redistributes throughout the extracellular fluid space. Candidates were expected to briefly describe this effect as well as the subsequent management of the sodium and water load by the kidney. Most candidates spoke about the pressure effects, and only some compared these with the volume effects. The effect of redistribution and other effects were not considered by the majority of the candidates.

Discussion

Immediate response

• Volume effect is greater during the infusion (prior to redistribution)
• During this time, the blood volume may be expanded by 50-70% of the infused volume
• This increases stroke volume by increasing preload, and therefore stimulates cardiovascular reflexes
• The reflex reaction is 
  • Initially, a short-lived increase in heart rate (Bainbridge reflex, atrial stretch)
  • Followed by a decrease in heart rate (baroreceptors)
  • Decrease in SVRI (baroreceptors)
  • Decreased secretion of renin by renal juxtaglomerualr cells, with subsequent decreases in angiotensin and aldosterone
  • Tubuloglomerular feedback activation: increased salt delivery to the nephron results in decreased glomerular blood flow, which decreases salt delivery (i.e. this is a negative feedback mechanism)
• Redistribution begins immediately, and is complete within 25-30 minutes

Distribution

• VOD=0.2L/kg, basically confined to the extracellular fluid
• (thus: 25% remains intravascular, 75% becomes interstitial)

Final volume expansion:

• By 25% of the infused volume, after 25-30 minutes (i.e. 250ml, or 5% of the total circulating volume)
• Thus, below the circulatory reflex activation threshold 
• Thus, following infusion, haemodynamic parameters return to normal

Change in osmolality:

• minimal (<1%) ; unnoticed by osmoreceptors (saline is isotonic)

Change in plasma oncotic pressure:

• Dilution of plasma proteins increases the fraction of filtered water at the glomerulus, increasing the urine output (i.e. excretion of both water and sodium)

Change in biochemistry:

• trivial sodium elevation (~0.5-.0 mmol/L)
• nontrivial chloride elevation (up to 3 mmol/L)
• decrease in bicarbonate and base excess (also up to 3 mmol/L)
• Metabolic acidosis (this fluid has SID = 0)

Hahn, Robert G., and David S. Warner. "Volume kinetics for infusion fluids." The Journal of the American Society of Anesthesiologists 113.2 (2010): 470-481.

Reddi, Benjamin AJ. "Why is saline so acidic (and does it really matter?)." International journal of medical sciences 10.6 (2013): 747.

Hahn, Robert G. "Clinical pharmacology of infusion fluids." Acta medica Lituanica 19.3 (2012): 210-212.

Griffel, Martin I., and Brian S. Kaufman. "Pharmacology of colloids and crystalloids." Critical care clinics 8.2 (1992): 235-253.