Clinical biochemistry P1

• Homeostasis


  Term used by physiologists to mean maintenance of nearly constant conditions in the internal environment
• Composition and volume of extracellular fluids

  • Regulated by complex hormonal and nervous mechanisms that interact to control osmolality, volume, and pH
• The average water content of the human body varies from 40% to 75% of total body weight, with values declining with age and especially with obesity
• Women have lower average water content than men due to higher fat content
• Free exchange of water between compartments

  Ongoing, as water easily and rapidly crosses selectively permeable cell membranes
• Fluid compartments


  • Intracellular fluid (ICF) accounts for 2⁄3 of total body water (TBW)
  • Extracellular fluid (ECF) accounts for 1⁄3 of TBW
• Subdivisions of Extracellular fluid (ECF)

  • Interstitial (≈75% of ECF)
  • Intravascular (≈25% of ECF)
• Fluid compartments are separated by

  The capillary endothelium
• Extracellular compartments

  • Plasma
  • Interstitial fluid
• Plasma constitutes approximately 5% of the body volume
• Plasma has a higher content of proteins compared with interstitial fluid
• Interstitial fluid is essentially an ultrafiltrate of blood plasma
• In some pathologic conditions causing "shock"

  The permeability of the vascular endothelium increases dramatically, resulting in leakage of albumin, a reduction in the effective circulating volume, and hypotension
• If not aggressively treated with intravenous fluids and/or vasopressors, shock can result in death due to decreased cerebral perfusion
• Dehydration is the loss of fluid from all fluid compartments of the body
• Overhydration is the accumulation of fluids in all fluid compartments
• Main signs of disturbance of hydration are related to osmosis
• Electrolytes


  Substances that dissociate into ions in solution and acquire the ability to conduct electricity
• Extracellular Electrolytes


  • Na+, Cl-, HCO3-
• Intracellular Electrolytes


  • K+, HPO42-, proteins
• Osmotic pressure


  Governs the movement of solvent across membranes that separate two solutions
• Osmolality


  A physical property of a solution based on the concentration of solutes per kilogram of solvent (1 Osmol/kg H2O)
• The reference interval for plasma osmolality is 275 – 300 mOsmol/kg
• Comparison of measured osmolality versus calculated osmolality can reveal the presence of an osmolal gap, which can be important in determining the presence of exogenous osmotic substances
• Expected plasma osmolality can be calculated using the empirical equation: mOsmol/kg = 1.86·[Na+] + [glucose] + [urea] + 9 ≈ 2·[Na+]
• Typical daily intakes and outputs of water depend on various factors including water drunk, water in food, water from metabolism of food, urine volume controlled by vasopressin (ADH), water content of feces, and losses in expired air and insensible perspiration
• Sodium (Na+) is the most abundant cation in the ECF, with total body sodium of the average 70 kg man approximately 3700 mmol, of which approximately 75% is exchangeable (ECF)
• Regulation of sodium intake

  1. Variable intake ranging from less than 100 mmol/day to more than 300 mmol/day

  2. Total body sodium remains constant even with intake as low as 5 mmol/day or exceeding 750 mmol/day
• Sodium losses


  • Urinary sodium excretion matches sodium intake
  • Most sodium excretion is via the kidneys
  • Approximately 5 mmol/day lost in sweat
  • Approximately 5 mmol/day lost in feces
• In disease


  Gastrointestinal track is often the major route of sodium loss
• Regulation of urinary sodium excretion

  1. Controlled by the renin-angiotensin-aldosterone system

  2. Controlled by atrial natriuretic peptide (ANP)

  3. Controlled by the glomerular filtration rate (GFR)
• Renin-angiotensin-aldosterone system


  1. Aldosterone decreases urinary sodium excretion by increasing sodium reabsorption in the renal tubules at the expense of potassium and hydrogen ions

  2. Aldosterone stimulates sodium conservation by the sweat glands and the mucosal cells of the colon

  3. Aldosterone secretion is stimulated by the volume of the extracellular fluid (ECF)
• Atrial natriuretic peptide (ANP)


  1. Secreted by the cardiocytes of the right atrium of the heart

  2. Promotes Na+ excretion by the kidney

  3. Increases urinary sodium excretion
• Regulation of volume


  1. Water remains in the extracellular compartment if held there by the osmotic effect of ions

  2. Sodium in the ECF determines the volume of the compartment

  3. Aldosterone and ADH interact to maintain normal volume and concentration of the ECF
• Hypernatremia
• Cause of hypernatremia


  • Water depletion due to decreased intake or excessive loss
  • Water and sodium depletion
  • Excessive sodium intake or retention in the ECF
• Other osmolality disorders


  • Increased urea in renal disease
  • Hyperglycemia in diabetes mellitus
  • Presence of ethanol or some other ingested substance
• Excessive aldosterone secretion leads to sodium retention by the renal tubules
• Other osmolality disorders


  • Increased urea in renal disease
  • Hyperglycemia in diabetes mellitus
  • The presence of ethanol or some other ingested substance
• A large discrepancy between measured osmolality and calculated osmolality is called the osmolar gap