1. Dr Alan Richardson26 April 2013

2. Learning Objectives Logically investigate the causes of high and low levelsof electrolytes through case study review Compare and contrast the principles of vapourpressure and freezing point osmometry Evaluate the use of the water deprivation test in theinvestigation of diabetes insipidus 3. Total Body Water 50-70% of body weight is water (lower in females,higher in males) about 42L 2/3rds is intracellular (about 28L) Remaining 14L is spread between interstitialcompartments (3/4), plasma compartments andtranscellular compartments 4. Vanders Renal Physiology. Eaton andPooler 6th Ed 2004* 5. Body Fluid Compartments How do we work out total body water and itsdistribution? TBW deuterated or tritiated water ECF sucrose, mannitol, inulin Plasma 131I-albumin, 31Cr-erythrocytes Interstitial ECW plasma Intracellular TBW - ECW* 6. Changes to ECF volume Decreased Acute blood loss Vomiting and diarrhoea Diuretics Salt wasting diseases of renal or adrenal origin Increased Congestive heart failure Hepatic cirrhosis Nephrotic syndrome Iatrogenic 7. Third Space Losses Loss of volume to compartments of the body at theexpense of intravascular volume This can include interstitial and transcellularcompartments Bowel obstruction Peritonitis Pancreatitis Burns Sepsis Multitrauma* 8. Vanders Renal Physiology. Eaton andPooler 6th Ed 2004 9. Osmolality What is osmolality? Osmolality is a measure of the number of dissolvedparticles per kg of water Essentially a measure of the osmotic pressure exertedby a solution How do we measure it?* 10. Freezing Point Depression Solution supercooledbelow its freezing pointwith gentle stirring Rapid stirring or vibrationinitiated to start freezingprocess Heat of fusion warms thesolution Freezing completes*http://www.iupui.edu/~cletcrse/380/ch3suppos.htm 11. Loser Messtechnik Osmometersproduct application website.Accessed 12/04/13 12. Vapour Pressure Depression Change in vapour pressure measured indirectlythrough a decrease in dew point Sample placed in a vaporisation/condensationchamber Temperature is then manipulated to establish thermaland vapour equilibrium Cooling of the sample then occurs to below the dewpoint of the sample causing condensation to occur This increases the temperature of the sample until thedew point is achieved* 13. Wescor Biomedical Systems. Accessedfromhttp://panza.uchicago.edu/Phys.261/materials/Osmometer/ on the 12/04/13 14. Vapour Pressure Depression Relies on the vapour released by a liquid condensingagain as the temperature is manipulated within anarrow range Thus volatiles within a sample will easily becomegaseous but will not condense again at thetemperatures we are using Volatiles include ethanol, methanol, ethylene glycoland even dissolved CO2 15. Calculated osmolalityOsm(calc) = 1.86 (Na+) + Glu + Urea + 9 Osmolal gap (measured calculated) Alcohols methanol, ethanol, ethylene glycol Sugars mannitol, sorbitol Ketoacidosis, lactic acidosis Lipids hypertriglyceridaemia Proteins multiple myeloma, WaldentromsmacroglobulinaemiaDorwart and Chalmers Clin Chem 1975 21:190-194* 16. Sodium and Water Water balance in adults Intake Oral fluid 1200ml Dietary 1000ml Metabolism 300ml 2500ml Output Insensible 700ml Sweat 100ml Faeces 200ml Urine 1500ml 2500ml 17. Sodium and Water Total body sodium 70kg human contains about 4200 mmol of sodium 50% in ECF 40% in bones 10% in ICF Abnormal plasma sodium concentrations are mostusually related to an abnormality in water balance,rather than a primary abnormality in sodium balance 18. Sodium and Water Water balance is maintained primarily by sensation ofthirst (intake) and production of anti-diuretichormone (output) Control of ADH (vasopressin) is through two primarytriggers Osmolality Blood pressure Other less important factors include nausea, atrialnatriuretic peptide and angiotensin II Drugs including nicotine (stimulates) and ethanol(inhibits) also affect its release 19. Sodium and Water Osmotic control of ADH secretion Changes in plasma osmolality are sensed byosmoreceptor cells in the hypothalamus which respondby either swelling or shrinking Osmoreceptor cells do not respond to all moleculesequally (respond well to changes in sodium, do notrespond at all to changes in urea) ADH has a half-life of 15-20 minutes so is rapidly brokendown when secreted* 20. *Physiology. Berne et al.5th Ed 2004 21. Sodium and Water Haemodynamic control of ADH secretion Baroreceptors located both in the high pressurecirculation (aortic arch and carotid sinus) and the lowpressure circulation (left atrium and large pulmonaryvessels) Signals sent by Vagus and Glossopharyngeal nerves tothe brain stem which then relays the signal to thehypothalamic neuroendocrine cells Signals from these baroreceptors change both the setpoint and the sensitivity of the neuroendocrine cells toosmoreceptors* 22. Physiology. Berne et al.5th Ed 2004* 23. Principles of Anatomy and Physiology.Tortora and Grabowski. 9th Ed 2000* 24. Sodium and Water Actions of ADH Primary action is to increase the permeability of therenal collecting ducts to water (and the medullaryportion of the collecting duct to urea) Acts via a G-protein coupled receptor to causeintracellular vesicles containing specific water channels(aquaporin type 2) to fuse with the apical cell membrane(basolateral membranes are freely permeable to water) Also has the long term effect of altering the expressionof the aquaporin 2 gene 25. http://www.studyblue.com/#flashcard/view/1161375 accessed 12/04/13 26. Sodium and Water Thirst Perception of thirst initiated by changes in plasma osmolality,blood volume and arterial pressure Hyperosmolality is more potent (2-3% increase in osmolality)than a decrease in blood volume (10-15% decrease) Thirst centre is located in the hypothalamus Angiotensin II also acts on the hypothalamus to evoke asensation of thirst Sensors in the oropharynx and upper GIT detect the ingestionof liquid and temporarily decrease the thirst impulse* 27. Syndrome of Inappropriate ADH Continued ADH secretion in the presence of decreased plasmaosmolality causing the body to retain water inappropriately Causes a euvolaemic hyponatraemia and an inappropriatelyconcentrated urine Aetiology CNS pathology infections, stroke, tumours, trauma, Guillain-Barre Syndrome Lung disease infections, cystic fibrosis, tuberculosis Malignancy SCLC, oropharynx, GI tumours Drugs antiepileptics, anticonvulsants, antipsychotics, MDMA Transient nausea, pain, stress (HOSPITAL PATIENTS!) Hereditary 4 different types of ADH problems - A (high ADH),B (high basal ADH), C (low setpoint) and D (active receptor)* 28. Diabetes Insipidus Inadequate effect of ADH results in the excretion oflarge volumes of dilute urine (polyuria) which causesthe individual to consume large quantities of fluid(polydipsia) Several forms Neurogenic decreased ADH production Causes - hypothalamic or pituitary stalk lesion, idiopathic andinherited forms Nephrogenic defect in the renal receptor causingdecreased response to ADH Causes genetic defects, metabolic abnormalities, drugs,heavy metals, chronic kidney disease* 29. Water Deprivation Test Used to investigate a patient with polyuria and polydipsiato determine if the cause is psychogenic (primary)polydipsia, neurogenic DI or nephrogenic DI Check thyroid, adrenal function and ensure K+ and Ca2+ arenormal Patient deprived of fluid for up to 8 hours and thefollowing parameters are measured Body weight Urine output Serum and Urine osmolality 30. Water Deprivation TestDiagnosis Fluid deprivation DesmopressinPrimary polydipsia >600 >600Neurogenic DI 50% increaseNephrogenic DI