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Fluid & Electrolyte Balance Fluid Balance • • • • • • • • homeostatic value-must be maintained food & water are taken in what is not needed is excreted body is in constant flux must be a balance between amount of water gained & amount lost Ideally-should cancel each other out digestive system-major source of water gain urinary system-primary system for fluid removal The Body as an Open System “Open System”. The body exchanges material and energy with its surroundings. Electrolyte Balance • homeostatic value-must be maintained • electrolytes-Cl, Na, K, etc. are ingested everyday • water & sodium regulation are integrated defending body against disturbances in volume & osmolarity • K imbalance – trouble with cardiac & muscle functioning • Calcium imbalances – problems with exocytosis, muscle contraction, bone formation & clotting • H & HCO3- balance – determines pH or acid-base balance The Body as an Open System “Open System”. The body exchanges material and energy with its surroundings. Maintaining Fluid & Electrolyte Balance • homeostasis depends on integration of respiratory, cardiovascular, renal & behavioral systems • primary route for excretion of water & ions-kidneys – essential for regulating volume & composition of fluids • lungs remove H+ & HCO3by excreting CO2 • behavioral mechanisms – thirst & salt appetite aid in fluid & electrolyte balance Osmolarity • number of solute particles dissolved in 1liter of water • reflected in solution’s ability to produce osmosis & alter osmotic properties of a solvent • depends only on number of non penetrating solute particles in solution • 10 molecules of Na+ has same osmotic activity as 10 glucose or 10 amino acid molecules in same amount of fluid Osmolarity • • • • • • • important to maintain water balance since water can cross most membranes freely water balance determines osmolarity as osmolarity of ECF (extra cellular fluid) changeswater moves into or out of cells changing intracellular volumes & cell function excess water intakeosmolarity decreaseswater moves into cells swell Na intake (osmolarity increases) water moves out of cellsshrink changes in cell volume impairs cell function swelling – may cause ion channels to open – changing membrane permeability Water • major constituent of body • all operations need water as diffusion medium – to distribute gas, nutrients & wastes • distributed differently among various body compartments • 63-65%-intracellular fluid (ICF) • 35- 37%-extracellular fluid (ECF) • ECF-composed of three parts – interstitial or tissue fluid-25% – plasma-8% – transcellular fluid-2% • miscellaneous fluids such as CSF, synovial fluid, etc. Water Balance • obtained when daily gains & losses are equal • average intake and loss-2.5L each day • Gains – metabolism (200ml/day) – preformed water-food & drink • Losses – about 1.5L each day lost via urine – 200ml elmininated with feces – 300 ml is lost during breathing – 100 ml in sweat – 400ml in cutaneous transpiration • water that diffuses through epidermis & evaporates • output through breath & cutaneous transpiration is insensible water loss Regulation of Intake • Intake-governed mostly by thirst • Dehydration – reduces blood volume & blood pressure – raises blood osmolarity • Detected by thirst center – hypothalamus • salivate lessdry mouth sense of thirst • ingest water • cools & moistens mouth • rehydrates blood • distends stomachinhibits thirst Regulation of Output • only way to control water output significantly is through urine volume • kidneys cannot completely prevent water loss or replace lost water or electrolytes • changes in urine volume are usually linked to adjustments in sodium reabsorption – where sodium goes water follows • ADH is one way to control urine volume without sodium • ADHcollecting ducts synthesize aquaporins (water channels) water can diffuse out of ductwater reabsorbed Electrolytes • participate in metabolism • determine membrane potentials • affect osmolarity of body fluids • major cations – Na, K, Ca & H • major anions – Cl, HCO3 & P • intracellular fluid contains more K+ • extracellular fluid has more Na+ & Cl- Sodium • crucial role in water & electrolyte balance • involved in excitability of neurons & muscle cells (resting membrane potentials) • major solute in extracellular fluid • determines osmolarity of extracellular fluids Sodium Balance • • • • need about 0.5 grams of sodium each day typical American consumes 3-7 g/day kidneys regulate Na+ levels hormonal mechanisms control Na concentrations • Aldosterone – primary role • ADH • ANP ADH • NaCl added to body increased osmolarityADH (vaopressin) secretion & thirst increased • thirstdrink • osmolarity decreases • ADHkidneys • conserves water by concentrating urine • increased water reaborption increases BP • returned to normal with cardiovascular reflexes Aldosterone • Na regulation also mediated by aldosterone – steroid hormone produced by adrenal cortex • stimuli-more closely tied to blood volume & pressure & osmolarity than Na • Hyponatremia & hyperkalemiaadrenal cortexaldosterone • Hypotension reninaldosterone secretion Aldosterone • • • • • • • • tells kidneys to reabsorb Na in distal tubule & collecting ducts primary target-last 3rd of distal tubule increases activity of Na-K ATPase target cell-principal cell Apical membranes of P cells have Na & K leak channels Aldosterone enters by simple diffusion combines with membrane receptors Na channels increase time they remain open as intracellular Na increasesNa-K ATPase speeds up transport of Na into ECFnet result-rapid increase of Na reaborption that does not require synthesis of new channels or ATPase proteins slower phase of actionnewly made channels & pumps inserted into epithelial cell membranes Renin-Angiotensin-Aldosterone • primary signal for aldosterone releaseangiotensin II – component of reninangiotensin system • kidneys sense low blood pressure triggers specialized cells-juxtaglomerular cells (JG cells) in afferent arterioles to produce renin • angiotensinogen angiotensin I angiotensin II by ACE-angiotensin converting enzyme-found in lungs & on endothelium of blood vessels Renin-Angiotensin-Aldosterone Path • Angiotensin IIadrenal cortex aldosteronedistal tubule reabsorbs Na • ADH secretion is also stimulatedwater reabsorption increases • because aldosterone is also acting to increase Na reabsorption, net effect-retention of fluid that is roughly same osmolarity as body fluids • net effect on urine excretiondecrease in amount of urine excreted, with lower osmolarity • Aldosteronemore NaCl reabsorbed in DCT & collecting ductsreduces filtrate osmolarity Renin-Angiotensin-Aldosterone • stimuli that begin renin pathwayrelated directly or indirectly to blood pressure • JG cells are directly sensitive to pressure & respond to low pressure by releasing renin • sympathetic neurons are activated by cardiovascular control center when blood pressure dropsJG cellsrenin release • paracrine feedback from macula densa cells in distal tubule stimulate renin release • if fluid flow in distal tubule is highmacula densaNO-nitric oxideinhibits renin release • GFR or BP lowfluid flow low macula densa cellsNO loweredJG cellsrenin released Sodium & Blood Pressure • Na reaborption does not directly raise blood pressure • retention helps stimulate fluid intake & volume expansion which increases blood volume& blood pressure Angiotensin & Blood Pressure • • • • • • Angiotensin II has other effects on blood pressure increases it directly & indirectly through 4 pathways activates angiotensin II receptors in brainincreases vasopressin secretionfluid retained in kidneys constricts blood vessels Angiotensin II serves to stimulate thirstexpands blood volume & increases blood pressure Vasoconstriction-also stimulated by angiotensin II increases blood pressure without changing blood volume angiotensin II activates receptors in cardiovascular control centerincreases sympathetic output to heart & blood vesselsincreases cardio output & vasoconstriction increases blood pressure ANP • Na also regulated by ANP – atrial natriuretic peptide – peptide hormone made by heart atrial cells • released when walls of atria are stretched • ANP enhances Na excretion & urinary water loss • increases GFR by making more surface area available for filtration decreases Na & water reabsorption in collecting ducts • indirectly inhibits renin, aldosterone & vasopressin release • • • • • • • • K Balance most abundant cation of ICF – must be maintained within narrow range changes affect resting membrane potentials decreased Khypokalemiaresting membrane potential becomes more negative increased Khyperkalemiamore K inside celldepolarization Hypokalemiamuscle weakness – more difficult for hyperpolarized neurons & muscles to fire action potentials – very dangerous – respiratory & heart muscle might fail Hyperkalemia – more dangerous of two situations depolarization of excitable tissues make them more excited initiallycells unable to repolarize fully become less excitableaction potentials smaller than normal may lead to cardiac arrhythmias Sodium & Water Balance • Na & water reabsorption are separately regulated in distal nephron • water does not automatically follow Na reabsorption here • vasopressin (ADH) must be present • proximal tubule – water reabsorption automatically follows Na reaborption Acid-Base Balance • water must be strictly monitored to keep it at a certain pH – not too acidic or too alkaline • metabolism depends on functioning enzymes – very sensitive to changes in pH • pH changes also disrupt stability of cell membranes – alter protein structure • normal pH range 7.35 7.45 • neutral side • pH measurement of hydrogen ion concentration – lower pH indicates higher hydrogen concentration-higher acidity – higher pH indicates lower hydrogen concentration-higher alkalinity • • • • • HNO2 H+ + NO2 pH-below 7.35-acidosis pH-above 7.45-alkalosis Strong acids dissociate readily in water giving up H which lowers pH Weak acids ionized slightly – keep most of hydrogen bound • bases accept hydrogen ions – strong base has strong tendency to bind hydrogen ions – raises pH • weak base binds less hydrogen ions – less effect on pH HNO2 H+ + NO2 Disruptions of Acid-Base Balance • pH imbalances produce problems that can be life threatening • intracellular proteins comprising enzymes, membrane channels, etc • very sensitive to pH • functions of proteins depend on 3-d shape can become altered by pH changes • must balance gain & loss of H ions • Compensations for Acid-Base Imbalances Buffers – first line of defense – always present – attempt to suppress changes in H+ • Kidneys – change in rate of hydrogen ion secretion by renal tubules – greatest effect – requires days to take effect • Lungs – can have rapid effect – cannot change pH as much as urinary system – change pulmonary ventilationexpel or retaining carbon dioxide Chemical Buffers • any substance that can bind or release H ions such that they dampen swings in pH • three major chemical buffer systems of body • Bicarbonate System • Phosphate System • Protein System Carbonic Acid-Bicarbonate Buffer System • most important extracellular buffer system • CO2 + H2OH2CO3 H+ + HCO3-__ • add H equation shifts to leftmore HCO3 made increases CO2 & H2O Phosphate Buffer System • important in buffering ICF & urine • H2PO4H + HPO4 • H + HPO4 H2PO4 Protein Buffer System • involves amino acids accepting or releasing H+ • pH: COOH COO- + H+ • • pH: NH2 + H+ NH3 + amino group accepts H Respiratory Compensation • change in respiratory rate directly affects carbonic acidHCO3 buffer system • any change in PCO2 affects H ion & HCO3 concentrations • increasing or decreasing rate of respiration alters pH by lowering or raising PCO2 • PCO2 increasespH decreases • PCO2 decreasespH increases • excess CO2 ventilation increases to expel more • low CO2 ventilation is reduced Renal Compensation • slower than buffers or lung compensation • changes rate of H & HCO3 secretion or reabsorption in response to changes in pH • directly-excretes or reabsorbs H ions • indirectly-changes reabsorption or excretion of HCO3 • during times of acidosis renal tubule secretes H+ into filtrate • HCO3- & K+ blood pH increases • pH levels-secretion of H ions decreased & bicarbonates not reclaimed Disorders of Acid-Base Balance • Acidosis – low pHneurons less excitableCNS depressionconfusion & disorientation comadeath • Alkalosis – high pHneurons hyperexcitable numbness & tinglingmuscle twitches tetanus • Acid-base imbalances fall into two categories • Respiratory • Metabolic Respiratory Acidosis • respiratory system cannot eliminate all CO2 made by peripheral tissues • accumulates in ECF lowers its pH • primary symptom of hypercapnia-respiratory acidosis • typical cause • Hypoventilation-low respiratory rate Respiratory Alkalosis • uncommon • usually due to hyperventilation (plasma PCO2 decreases) • can be modulated by breathing into paper bag & rebreathing exhaled CO2 Metabolic Acidosis • due to drop in blood bicarbonate levels drop – lost due to renal dysfunction – lost through severe diarrhea • due to accumulation of nonvolatile acids-organic acid • Lactic acidosis • Ketoacidosis – generation of large amount of ketone bodies • occurs during starvation & diabetes • may also be caused by impaired ability to excrete H ions at kidneys or by severe HCO3 loss as occurs during diarrhea or overuse of Metabolic Alkalosis • HCO3 ions become elevated • Rare • can be due to non respiratory loss of acid • excessive intake of alkaline drugs • excessive vomiting causes a loss of HCl. Compensations for Decreased pH Compensations for Increased pH
