lecture 2

• all body fluids are aqueous :

  1. transport of nutrients and removal of waste
  2. chemical reactions of the body are conducted in water-based buffer
• total body water can be divided into

  1. intracellular compartment (2/3 of total body water)
  2. extracellular compartment (1/3 of total body water)
  3. Plasma 1/4 of ECF
  4. Interstitial 3/4 of ECF
• Sodium is the major extracellular cation, found in higher concentrations in the ECF
• Potassium is the major intracellular cation (found in higher concentrations in ICF)
• why do different compartments have different concentrations of ions?

  1.semi-permeable membranes separate various compartments

  2. water moves between the compartments

  3. small molecules (Na, K, Cl) move across membranes, but larger molecules (protein) cannot
• • Water is not actively transported in the body but moves between the ICF and ECF compartments
  • Typically, the osmotic concentrations (osmolalities) of ICF are equal (isotonic)
  • Water distribution in the ICF and ECF is determined by their osmotic contents
• Typically, most cell membranes tend to be impermeable to sodium,and gradient is maintained by the sodium-potassium pump
• Sodium input and output are normally balanced thanks to a greatturnover by the gut and kidneys
• Potassium is the predominant intracellular cation
• Potassium levels are important to consider because of its effect on membrane excitability

  • Potassium tends to diffuse from the ICF to the ECF but this action isopposed by the sodium-potassium-ATPase pump, which transports potassium into the cells
• Osmolality is primarily determined by sodium concentration
• ECF water volume is strictly dependent on total body sodium content
• • Changes in water intake/loss are regulated to maintain a constant osmolality and therefore also sodium concentration
  • Water volume and sodium concentration (osmolality) are the main controllers of electrolyte balance
• Sodium balance is mainly regulated in the kidneys
• 70% of filtered sodium is reabsorbed in the proximal tubules
• Less than 5% of sodium is reabsorbed in the distal tubes and collecting ducts→ fine tuning of sodium control (Controlled by RAAS)
• RAAS activated by a drop in renal perfusion/decrease in blood volume

  1. specialized cells in kidney produce prorenin
  2. cleaved to form renin, released in the blood and cleaves agiotensinogen in angiotensin 1
  3. converted to angiotensin 2 (which stimulates reabsorption in proximal tubules) And induces the release of aldosterone from adrenal cortex
  4. simulates water reabsorption in distal tubules
  5. stimulates thirst
  6. induces vasopressin (ADH) secretion + promotes water retention
• Aldosterone primarily controls sodium excretion• Secreted in response to a decrease in ECF volume• Causes sodium retention and loss of potassium
• Vasopressin (ADH) primarily controls water excretion• Secreted in response to an increase in the ECF osmolality and a decrease in ECF volume• Promotes water retention
• Natriuretic peptide hormones control sodium excretion
• Atrial natriuretic hormone→ secreted by cardiac atria in response to atrial stretch which can occur if the ECF volume is increased→ inhibits distal tubular sodium and water reabsorption; decreases renin and aldosterone secretion
• B-type natriuretic peptide → secreted by the ventricles in response to ventricular stretching, has similar action to the atrial natriuretic hormone
• Increase of osmolality→ loss of water from ECF (i.e. water deprivation) will:➢Determine movement of water from the ICF to the ECF➢Stimulate the hypothalamic thirst centre➢Stimulate the hypothalamic osmoreceptors causing the release of vasopressin(ADH) which induces water reabsorption in the kidney (concentrated urine)
• Decrease of osmolality→ increase of water in the ECF (i.e. drinking lots of water)➢Hypothalamic thirst centre is NOT stimulated → no thirst sensation➢Vasopressin (ADH) release is inhibited → diluted urine
• Sodium can be lost isotonically (i.e. in plasma) or hypotonically (i.e. sweat, diluted urine)

  • in all cases there will be a decrease in ECF volume
• which condition determines a greater loss of ECG volume

  1. difference between pure water loss and isotonic fluid loss
  2. determine how the body will compensate (loss of pure water increases osmolality, loss of isotonic saline, no change in osmolality)
• loss of pure water increases osmolality

  • Vasopressin (ADH) response to increase in osmolality

  • Aldosterone response to reduced renal blood flow
• loss of isotonic saline, no change in osmolality

  • When volume is depleted to a certain level – large vasopressin (ADH) response

  • Aldosterone response to reduced renal blood flow
• Indirect measure: measure of sodium concentration by diluting theplasma before the analysis (typical of laboratory analysis)
• Direct measure: measure of sodium concentration directly inundiluted plasma (typical of point-of-care testing instruments)
• All body fluids are aqueous

  * Transport of nutrients and removal of waste

  * Chemical reactions of the body are conducted in water-based buffer
• sodium is major extracellular cation
• potassium is the major intracellular cation
• typically the osmotic concentration (osmolality) of ICF and ECF are equal (isotonic)
• typically, most cell membranes are impermeable to sodium- gradient is maintained by sodium-potassium pump
• potassium tends to diffuse from ICF to ECF but opposed by Na-K ATP-ase pump, which transports potassium inside the cell
• osmolality is primarily determined by sodium
• sodium is low = hyponatremia
• alcohol intoxication = osmotic gap
• ECF water volume is depended on total body sodium content