REGULATION OF FLUIDS AND ELECTROLYTES

Fluid Compartments of the BodyIntracellular Fluid (ICF) 67%

Extracellular Fluid (ECF) 33%Plasma (6.6%)Interstitial fluid (26.4%)LymphCerebrospinal fluidSynovial fluidSerous fluidsAqueous humour

Plasma And Interstitial FluidSeparated by blood capillariesWater and solutes move by passive diffusionComponents similar except for plasma proteins and RBCs

ECF & ICFSeparated by cell membraneComponents differentCell proteins in ICF Unequal distribution of Na, K and their anions due to the Na/K pump (pumps Na out and K into cell)

Fluid BalanceMaintained by regulating the osmolarity of the ECF

Fluid Input and OutputInput (2500 ml)Eating 1000mlLiquids 1200mlMetabolic water 300mlOutput (2500ml)Urination 1200mlDefecation 150mlSensible perspiration 750mlInsensible perspiration 400ml

Regulation of WaterDehydration more water is lost than is gainedUnder conditions of excess water loss without comparable electrolyte loss the ECF becomes hypertonicWater moves from the ICF to the ECFBoth ECF and ICF are now more relatively concentrated and contain less water

Regulation of WaterDehydration (contd)Hypernatremia developsSevere thirst, dryness and wrinkling of the skinIf plasma volume decreases and bp decreases shock may developHypotension (90 mmHg and less)Confusion and disorientationHeart rate increases, rapid , weak pulseCessation of urinationA drop in pH of blood; due to lactic acid produced by O2 deprived cells

Regulation of WaterDehydration (contd)Homeostatic ResponsesADH and Renin SecretionIncreased fluid IntakeECF volume increases fluid shifts to ICF

Regulation of WaterExcess Water GainsWhen ECF volume increases due to increased water intake without corresponding increases in electrolytesECF becomes hypotonicWater shifts to ICFBoth ECF and ICF volumes larger than normal and lower osmotic concentrations

Regulation of WaterExcess Water gains (contd)Homeostatic ResponsesADH secretion decreases urine volume increases

Regulation of WaterExcess Water GainsIf not correctedOverhydrationCells become distortedSolute concentration around enzymes changeCell function is disrupted

Regulation of WaterOverhydration is caused byIngestion of large volumes of freshwaterInability to eliminate excess water due to chronic renal failure or heart failureEndocrine disorders excess ADH production

Signs of OverhydrationHyponatremiaDrunken behavior, confusion, hallucinations, convulsions, coma and then death

Regulation of WaterTreatment of OverhydrationAdministration of Diuretics Infusion of a concentrated salt solution causing a fluid shift from ICF to ECF

Electrolyte BalanceWhen the rates of gain and loss of each electrolyte are equal in the body

Electrolyte BalanceSodium (Na)Gain and lose 1.1 3.3g each dayWhen there is a change in the gain or loss of Na from the ECF there is no change in the concentration of Na because there is always a corresponding shift in water (ie osmosis occurs)

Electrolyte BalanceSodiumIf we eat a salty meal without adequate fluid intakeConcentration of Na in the plasma increasesFluid leaves the ICF and enters the ECF lowering Na concentrationsSecretion of ADH due to osmoreceptors in pharynx and hypothalamus

Electrolyte BalanceSodiumIn cases of dehydration where sodium is also lostRenin and Aldosterone are secretedOverhydrationPlasma volume increasesAtrial and ventricular walls stretchNatriuretic peptides secreted (ANP and BNP)Thirst is reduced; ADH and Aldosterone secretion blockedSalt and water losses increase at the kidneys

Electrolyte BalancePotassium (K)1.9 5.8g each dayHigher in the cellConcentration in the ECF is controlled by the rate of secretion along the DCT and collecting system

Electrolyte BalancePotassiumRate of secretion at the DCT depends on:Changes in K concentration in the ECFChanges in pH (if ECF pH decreases H is secreted in exchange for Na instead of K)Aldosterone levelsAldosterone acts on Na/K pumps causing reabsorption of Na in exchange for KWhen K is high in the ECF aldosterone is also secreted

Electrolyte BalanceCalcium (Ca)0.8 -1.2gMaintained by Parathyroid hormone, calcitriol (activated Vitamin D) and calcitoninPTH and Calcitriol increase calcium levels in the bloodCalcitonin decreases calcium levels

Electrolyte BalanceParathyroid Hormone and CalcitriolPTH is produced by the parathyroid glandCalcitriol is produced in the cells of the PCT in the presence of PTH

Enhance the release of calcium from bones (increase osteoclast activity)Enhance active reabsorption of calcium and magnesium at the distal tubulesEnhance the absorption of calcium in the intestine

Electrolyte BalanceCalcitoninProduced by the thyroid glandInhibits calcium absorption at the intestinesInhibits osteoclast activity in bones (calcium conservation)Inhibits calcium and phosphorus reabsorption in the kidney tubules

Electrolyte BalanceCalciumHypercalcemia caused by:Hyperparathyroidism (high PTH in the blood)Cancers of the breast, lungs, kidneys and bone marrowExcessive calcium or vitamin D supplements

Electrolyte BalanceCalcium Hypocalcemia due toHypoparathyroidismVitamin D deficiencyChronic renal failure

Electrolyte BalanceMagnesium (Mg) BalanceMagnesium is higher in the ICF than the ECF0.3-0.4 g of Mg need to be consumed daily to maintain balanceMg is reabsorbed along the PCT

Electrolyte BalancePhosphate0.8 1.2 g needed each dayReabsorbed along the PCT stimulated by calcitriol

Electrolyte BalanceChlorideMost abundant anion in the ECF1.7 5.1 g needed each dayAbsorbed along the digestive tract with sodium and reabsorbed with sodium along the renal tubule

Acid-Base BalancepH of the ECF is 7.35 7.45We are unable to survive if the pH goes below 6.8 or above 7.7Acidosis the physiological state that results from plasma pH falling below 7.35Alkalosis the physiological state that results from plasma pH rising above 7.45

Acid-Base BalanceAcidosis and Alkalosis both affect most greatly the cardiovascular and nervous systemsHomeostatic control of pH is, therefore, of great importanceAcidosis is more prevalent as the body produces several acids through its cellular activities

Mechanisms of pH ControlAcid-base balance is achieved by balancing hydrogen ion gains and lossesi.e. that gained at the digestive tract and through metabolic activities must equal that produced in the urine and produced at the lungs

Mechanisms of pH ControlH+ are transported from their site of production to their site of elimination by a bufferThis prevents damage to tissues

Mechanisms of pH ControlThere are three types of acidsOrganic Acids participants in or by-products of aerobic metabolism eg lactic acidVolatile Acids can leave solution and enter the atmosphere eg. Carbonic acidFixed Acids do not leave solution; remain in body fluids until eliminated at the kidneys eg. Sulphuric and phosphoric acids (produced by catabolism of amino acids, phospholipids and nucleic acids

Buffer SystemsTypes of Buffer SystemsProteinCarbonic Acid BicarbonatePhosphate

Protein Buffer SystemsDepend on the ability of amino-acids to respond to pH changes by accepting or releasing H+

Contribute to regulating ECF and ICF pH

Protein Buffer SystemsIf pH increases the COOH (carboxyl) group on the amino acid loses its H+ to become a COO- (carboxylate ion) Some amino acids have an R group that can also donate an H+ if the pH increases above normalIf the pH decreases the COO- and NH2 can accept H+

Protein Buffer SystemsProteins that can act as buffers include:Plasma proteinsExtracellular protein fibres in interstitial fluidStructural proteins in the ICF

Protein Buffer SystemsIf pH of the ECF declines the H+ move into the ICF where they are bufferedIf pH increases in the ECF H+ move from the ICF to the ECF in exchange for potassium ionsThis system is slow and cannot make rapid and large-scale adjustments in the pH of the ECF

Protein Buffer SystemsHaemoglobin Buffer SystemThe only intracellular buffer system that has an immediate effect on the pH of the ECF and helps prevent drastic changes in the pH when the partial pressure of CO2 in the plasma increases or decreases

Carbonic Acid-Bicarbonate Buffer SystemCO2 + H2O H2CO3 H+ + HCO3

Prevents changes in pH caused by organic acids and fixed acids in the ECF

If pH decreases the H+ will be removed by HCO3- H2CO3 CO2 + H2OThe CO2 and H2O are released at the lungsThe reaction moves in the opposite direction if pH increases ie H+ is released

Phosphate Buffer SystemH2PO4- H+ + HPO42-i.e. Dihydrogen phosphate hydrogen + monohydrogen phosphateSupports the carbonic acid-bicarbonate buffer system in the ECF but is of utmost importance in the ICFAlso important in buffering urine

Respiratory CompensationA change in the respiratory rate that helps to stabilize the pH of the ECFWhen respiration rate increases or decreases the pH is altered by increasing or decreasing CO2 levelsRecall that when CO2 increases the pH decreases and visa versaRecall also that when CO2 increases the respiratory centre is stimulated and respiratory rate increases

Renal CompensationA change in the rates of H+ and HCO3- secretion and reabsorption by the kidneys in response to changes in plasma pH

The process of elimination of H+ is dependent on the availability of buffers in the renal tubulei.e. the secretion of H+ cannot continue if the tubular fluid declines to 4.0-4.5. At this point the H+ will leak out of the tubular fluid (back into the blood) as fast as it is secreted

Renal CompensationThe buffers involved in renal compensation are:Carbonic acid-bicarbonate placed in the Phosphatetubule by filtrationAmmonia produced by tubular cells

Renal CompensationRenal Responses to Acidosis

Secretion of H+Buffer activity in tubulesRemoval of CO2Reabsorption of NaHCO3

Renal CompensationRenal Responses to Alkalosis

H+ secretion decreasesTubular cells do not reclaim the bicarbonates in the tubular fluidHCO3- secreted and a strong acid such as HCl is reabsorbed along the collecting duct

Disturbances of Acid-Base BalanceCan occur under the following circumstances:Cardiovascular Conditions eg heart failure and hypotensionAffect pH of internal fluids by causing fluid shifts and by changing glomerular filtration rates and respiratory efficiencyDisorders that affect circulating buffers, respiratory performance or renal function eg emphysema or renal failureConditions affecting the CNSWill affect respiratory and cardiovascular reflexes

Respiratory AcidosisDevelops when the respiratory system cannot eliminate all the CO2 generated by tissuesPrimary sign is low plasma pH due to hypercapnia (elevated plasma CO2) BUT the usual cause is HYPOVENTILATION (abnormally low respiratory rate) CO2 increases and pH declines

Respiratory AcidosisThe body normally responds by increasing respiratory rateIf respiratory rate does not increase because the chemoreceptors fail to respond to the decline in pH, breathing rate does not increase or circulatory supply to the lungs is inadequate pH will continue to decline causing Acute Respiratory Acidosis

Respiratory AcidosisChronic Respiratory AcidosisDevelops when normal respiratory function is compromised but the compensatory mechanisms have not failed completely Eg. Persons who have CNS injury and persons whose respiratory centres have become desensitized by alcohol or barbiturates

Respiratory AlkalosisOccurs when respiratory activity lowers plasma CO2 to below normal levels (Hypocapnia)

Hypocapnia is caused by Hyperventilation

Respiratory AlkalosisWhen pH increases (low CO2) due to hyperventilation the condition corrects itself by the chemoreceptors not being stimulated so we do not get the urge to breathe

Respiratory Alkalosis rarely persists to cause a clinical emergency

Respiratory AlkalosisCommon causes of HyperventilationPhysical stresses eg painPsychological stresses eg extreme anxiety

Respiratory AlkalosisInitial Symptoms:Tingling of hands, lips and feetLight-headedness

If pH continues to increase one may become unconscious which removes any psychological stimuli, therefore, breathing rate decreases

Breathing into a paper bag is a simple treatment for respiratory alkalosis

Metabolic AcidosisCAUSESProduction of a large number of fixed or organic acids eg. Lactic Acidosis and KetoacidosisImpaired ability to excrete H+ at the kidneys due to glomerulonephritis or diuretics which inhibit the Na/H transport systemSevere bicarbonate loss due to diarrhea

Metabolic AcidosisCompensatory Mechanisms:Respiratory Mechanism H+ interacting with HCO3- CO2 and H2ORenal Mechanism H+ secreted and HCO3- reabsorbed

Combined Respiratory & Metabolic AcidosisDue to drowningLactic acid produced due to struggling musclesCO2 increases if breathing stops

Treatment Artificial and Mechanical Respiratory Assistance along with intravenous infusion of isotonic solutions such as sodium lactate, sodium gluconate or sodium bicarbonate (release anions that can bind with the H+)

Metabolic AlkalosisResults when HCO3- increases HCO3- binds with H+ H2CO3The resulting decline in H+ produces symptoms of alkalosis

Metabolic AlkalosisCan develop when HCl is secreted by the stomach causing HCO3- to increase in the ECF (Alkaline Tide)

Metabolic AlkalosisThe temporary increase in pH due to the release of HCO3- is not seriousBUT serious metabolic alkalosis can occur due to bouts of repeated vomitingVomiting removes stomach acids, therefore, the parietal cells are stimulated to produce more HCl and therefore more HCO3-

Metabolic AlkalosisCompensation Mechanisms and TreatmentsBreathing rate declines CO2 increases pH declinesIncreased loss of HCO3- from urineTreatment of vomiting by using sodium chloride or potassium chloride solutionsAcute cases treated with Ammonium ChlorideMetabolism of ammonium chloride releases HCl H+ lowers pH