Fluid Pharmacology

Master answer

Water

• Water is distributed across all body compartments
  • It is hypotonic compared to all body compartments
  • It theoretically gets distributed to ECF (Plasma and ISF) + ICF
• Absorption of ingested water occurs in proximal small intestine.
  • Absorption rate depends on rate of gastric emptying and creation of suitable osmotic gradient across the intestinal mucosa.
• 1L Oral ingestion of water is rapidly absorbed in the small intestine.

Mechanism of Absorption of water

• Sodium is absorbed from the intestinal lumen by several mechanisms, most prominently by cotransport with glucose and amino acids, and by Na+/H+ exchange, both of which move sodium from the lumen into the enterocyte.
• Absorbed sodium is rapidly exported from the cell via sodium pumps – when a lot of sodium is entering the cell, a lot of sodium is pumped out of the cell, which establishes a high osmolarity in the small intercellular spaces between adjacent enterocytes.
• Water diffuses in response to the osmotic gradient established by sodium – in this case into the intercellular space. It seems that the bulk of the water absorption is transcellular, but some also diffuses through the tight junctions.
• Water, as well as sodium, then diffuses into capillary blood within the villus.

Water compartments and Responses

• TBW is one-third ECF & two-thirds ICF
• ECF is one-quarter plasma & three-quarters ISF
• The threshold of the volume receptors is 7-10% change in blood volume
• The osmoreceptors are sensitive to a 1-2% change in osmolality.
• Plasma osmolality is normal prior to the transfusion (ie 287-290 mOsm/kg)

Effect of 1L oral intake

• Absorption of water causes a drop in plasma osmolarity without much effect on plasma volume.
• There is a brief period of hypervolemia, increase in arterial blood pressure and an associated physiological reflex response mainly by osmoreceptors
• There will also be an associated increase in renal perfusion and stimulation of intrarenal receptors (e.g. juxtaglomerular apparatus).

• Sensor: Osmoceptors in hypothalamus
• CPU: Hypothalamus
• Effector: ADH (and thirst, not significant in current scenario)

• Anti-diuretic hormone (ADH)
  • peptide hormone synthesised in the hypothalamus
  • released from the posterior pituitary
  • acts on the kidney via GPC V2 receptors
  • increases the synthesis of aquaporins
• ADH secretion is decreased,
  • ➔ water permeability in the nephrons is increased
  • ➔ leads to less water reabsorption
  • ➔ larger amount of dilute urine excretion
• Consequence is homeostasis by excretion of the 1L of water quite rapidly.

JC 2019

Answer by JC