Renal Response to Hypovolaemia

Distribution of Body Water

• Total body water in an adult male is 42 litres in a 70kg man, or 60% of total body weight (55% in females)

• 55% ICF
• 45% ECF, made up of:

• 20% interstitial fluid
• 7.5% intravascular fluid
• 2.5% transcellular fluid - this is in contact with intracellular water across the epithelial cell membrane, rather than ISF

(fluid formed from transport activities of cells, found in epithelial lined spaces, including CSF, joint fluid, aqueous humour, bile, bowel fluid, urine)

(the above 3 make up the functional ECF)

• 7.5% water in dense CT
• 7.5% water in bone

• The ratio of ICF to functional ECF is almost 2:1
• The distribution of water between intracellular and extracellular compartments is determined by the amount of solutes present in each
• Water can cross nearly all cell membranes easily, but most solutes cannot
• Sodium is the major cation in ECF, and must be associated with anions of equal total charge for electrical neutrality - making up 86% of ECF osmolality and 92% of ECF tonicity
• Cells also have the ability to regulate intracellular solute content which allows adjustment of cell volume against extracellular tonicity

• This is especially important in the brain which is constrained to a fixed volume by the boney skull
• Neurones can produce "idiogenic osmoles" when their cell volumes decrease due to extracellular hypertonicity, drawing water back into the cell

Water Losses

• 900mls insensible from respiratory tract
• 50mls from sweat
• 100msl from faeces
• 430mls minimum urinary losses → to excrete daily solute load (1400mosmol)

• Control of body water is a negative feedback loop:

• Sensors: Osmoreceptors, volume receptors, high pressure baroreceptors
• Central controller: Hypothalamus
• Effectors: Thirst and ADH

• Excessive water losses cause increased osmolality (normally 280-295mosmol/L)
• Changes to ECF osmolality is detected by osmoreceptors in hypothalamus - this is very sensitive, detecting changes of 1-2%.
• This stimulates ADH production in hypothalamus which is released from posterior pituitary, which causes:

• V2 receptors activation in renal collecting ducts → Increased aquaporin expression → increased H2O reabsorption → Concentrated urine
• Increased urea reabsorption in collecting ducts → Increase renal loop of henle urinary concentrating ability
• V1 activity → ↑cAMP → ↑Ca → vasoconstriction
• Activation of thirst response.

• This response has a short half life ~15mins
• Negative feedback → correction of osmolality → ↓ADH secretion

• Large water deficits cause volume loss, sensed by:
• Low pressure baroceptors (Volume receptors) → less sensitive require 10-15% change.

• Atrium and Vena Cava.

• Increase ADH production → more potent
• Decreased stretch → ↓ANP production

• Increased Na / H2O reabsorption
• Increased Na channels expression

• High pressure baroreceptors - more sensitive ↓MAP 10-15% (Carotid sinus/aortic arch)

• Increased Renin production, stimulated by 3 mechanisms:

• β1 stimulation
• Infra-renal stretch receptors
• ↓Na past macula densa

• ↑Angiotensin II

• Peripheral vasoconstriction
• Efferent arteriole constriction > afferent arteriole
• ↑Aldosterone release

• Aldosterone

• ↑Na and H2O reabsorption in principle cells of collecting ducts.
• No aldosterone releases inhibition.