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Water, Electrolyte, and Acid-Base Balance Function of Water: Most of cellular activities are performed in water solutions. 4% TBW 40% TBW Body Fluid - makes up ~60% of total body weight (TBW) - distributed in three fluid compartments. 16% TBW 4% TBW 40% TBW Fluid is continually exchanged between the three compartments. 16% TBW Exchange between Blood & Tissue Fluid 4% TBW 40% TBW - determined by four factors: capillary blood pressure plasma colloid osmotic pressure interstitium Hydrostatic Pressure Interstitium colloid osmotic pressure 16% TBW Exchange between Blood & Tissue Fluid 4% TBW 40% TBW - not affected by electrolyte concentrations - Edema = water accumulation in tissue fluid 16% TBW Exchange between Tissue Fluid & Intracellular Fluid 4% TBW 40% TBW - determined by two: 1) intracellular osmotic pressure electrolytes 2) interstitial osmotic pressure electrolytes 16% TBW Water Gain Water is gained from three sources. 1) food (~700 ml/day) 2) drink – voluntarily controlled 3) metabolic water (200 ml/day) --- produced as a byproduct of aerobic respiration Routes of water loss 1) Urine – obligatory (unavoidable) and physiologically regulated, minimum 400 ml/day 2) Feces -- obligatory water loss, ~200 ml/day 3) Breath – obligatory water loss, ~300 ml/day 4) Cutaneous evaporation -- obligatory water loss, ~400 ml/day 5) Sweat – for releasing heat, varies significantly Regulation of Water Intake - governed by thirst. blood volume and osmolarity peripheral volume sensors central osmoreceptors hypothalamus thirst felt Regulation of Water Output - The only physiological control is through variations in urine volume. - urine volume regulated by hormones 1) ADH dehydration blood volume and/or osmolarity hypothalamic receptors / peripheral volume sensors posterior pituitary to release ADH H2O reabsorption Water retention 2) Atrial Natriuretic Factor blood volume atrial volume sensors atria to release ANF inhibits Na+ and H2O reabsorption water output Dehydration - decrease in body fluid - Causes 1) the lack of drinking water 2) excessive loss of body fluid due to: overheat diabetes overuse of diuretics diarrhea Edema - the accumulation of fluid in the interstitial spaces caused by: 1) increased capillary filtration, or 2) reduced capillary reabsorption, or 3) obstructed lymphatic drainage ELECTROLYTE BALANCE Electrolytes = small ions that carry charges Major cations Na+ K+ Ca++ H+ Major anions ClHCO3PO4--- Distribution of Electrolytes Na+ Ca++ Cl- Extracellular space K+ Cell PO4--- Na+ Ca++ Sodium Na+ Cl- K+ Cell PO4--- Functions - involved in generating action membrane potential of cells - make a major contribution to extracellular osmolarity. Regulation of plasma Na+ 1) Aldosterone plasma Na+ aldosterone Na+ renal Na + excretion plasma Na + plasma 2) Renin-angiotensin-II renin angiotensin-II aldosterone renal Na+ excretion plasma Na+ Na+ plasma 3) ADH increases water reabsorption in kidneys water retention dilute plasma Na+ H2O Na+ plasma 4) Atrial Natriuretic Factor inhibits renal reabsorption of Na+ and H2O and the excretion of renin and ADH eliminate more sodium and water plasma Na + Na+ plasma Na+ Sodium imbalance hypernatremia plasma sodium > 145 mEq/L, hyponatremia plasma sodium < 130 mEq/L Potassium Functions K+ Na+ Ca++ Cl- K+ Cell PO4--- the greatest contributor to intracellular osmosis and cell volume - determines the resting membrane potentials - an essential cofactor for protein synthesis and some other metabolic processes. Regulation of Potassium - by aldosterone Aldosterone stimulates K+ secretion by the kidneys Plasma K+ K+ plasma K+ Potassium Imbalance hyperkalemia (> 5.5 mEq/L) hypokalemia (< 3.5 mEq/L) Na+ Ca++ Chloride Cl- K+ Cell PO4--- - makes a major contribution to extracellular osmolarity - required for the formation of stomach acid (HCl) Regulation of Cl– - No direct regulation - indirectly regulated as an effect of Na+ homeostasis. As sodium is retained or excreted, Cl– passively follows. Chloride Imbalance hyperchloremia (> 105 mEq/L) hypochloremia (< 95 mEq/L). Calcium Na+ Ca++ Cl- K+ Cell PO4--- Functions of Ca++ - lends strength to the skeleton Functions of Ca++ - lends strength to the skeleton - activates muscle contraction Excitation (Action Potentials) ++ [ Ca ]i Contraction (shortening) Functions of Ca++ - lends strength to the skeleton - activates muscle contraction - serves as a second messenger for some hormones and neurotransmitters Functions of Ca++ - lends strength to the skeleton - activates muscle contraction - serves as a second messenger for some hormones and neurotransmitters - activates exocytosis of neurotransmitters and other cellular secretions Functions of Ca++ - lends strength to the skeleton - activates muscle contraction - serves as a second messenger for some hormones and neurotransmitters - activates exocytosis of neurotransmitters and other cellular secretions - essential factor in blood clotting. Functions of Ca++ - lends strength to the skeleton - activates muscle contraction - serves as a second messenger for some hormones and neurotransmitters - activates exocytosis of neurotransmitters and other cellular secretions - essential factor in blood clotting. - activates many cellular enzymes Dynamics of Calcium Ca++ Ca++ Ca++ plasma Ca++ Regulation of calcium 1) parathyroid hormone (PTH): Regulation of calcium 1) parathyroid hormone (PTH): - dissolving Ca++ in bones - reducing renal excretion of Ca++ Ca++ Ca++ plasma 2) calcitonin (secreted by C cells in thyroid gland): 2) calcitonin (secreted by C cells in thyroid gland): depositing Ca++ in bones Ca++ Ca++ plasma 3) calcitrol (derivative of vitamin D): - enhancing intestinal absorption of Ca++ from food Ca++ Ca++ plasma Ca++ Calcium imbalances hypocalcemia (< 4.5 mEq/L) hypercalcemia (> 5.8 mEq/L). Phosphates - needed for the synthesis of: ATP, GTP DNA, RNA phospholipids Regulation of Phosphate - by parathyroid hormone PTH increases renal excretion of phosphate decrease plasma phosphate - no real phosphate imbalances PO4--- plasma PO4--- ACID-BASE BALANCE Acid An acid is any chemical that releases H+ in solution. Base A base is any chemical that accepts H+. pH is the negative logarithm of H+ concentration, and an indicator of acidity. pH = - log [H+ ] Example: [H+ ] = 0.1 M = 10 –7 M pH is the negative logarithm of H+ concentration, and an indicator of acidity. pH = - log [10 –7 ] = 7 log 10 = 7 Example: [H+ ] = 0.1 M = 10 –7 M pH is the negative logarithm of H+ concentration, and an indicator of acidity. pH = - log [10 –8 ] = 8 log 10 = 8 [H+ ] = 0.01 M = 10 –8 M Example: 0.01 M [ H+ ] 0.1 M [ H+ ] = pH 8 = pH 7 [ H+ ] = pH [ H+ ] = pH Normal functions of proteins (especially enzymes) heavily depend on an optimal pH. pH7.35-pH7.45 Regulation of acid-base balance 1) Chemical Buffers 2) Respiratory Control of pH 3) Renal Control of pH Buffer is any mechanism that resists changes in pH. acid acid H2O pH 7.0 Buffer pH 7.0 pH 3.0 pH 6.8 base base H2O pH 7.0 Buffer pH 7.0 pH 11.0 pH 7.2 Chemical Buffers There are three major buffers in body fluid. 1) The Bicarbonate (HCO3-) Buffer 2) The Phosphate Buffer 3) The Protein Buffer 1) The Bicarbonate (HCO3-) Buffer System H + HCO3- H2CO3 H2O + CO2 - reversible depending on the equilibrium between the substrates and products. - The lungs constantly remove CO2. 2) The Phosphate Buffer System H + HPO42– H2PO4– + H H3PO4 3) The Protein Buffer System - more concentrated phosphate buffers than either bicarbonate or - accounts for about three-quarters of all chemical buffering ability of the body fluids. - The carboxyl groups release H+ when pH rises and amino groups bind H+ when pH falls. H+ H+ NH2-CH2-CH2 CH2-CH2-COOH Properties of Chemical Buffers - respond to pH changes within a fraction of a second. - Bind to H but can not remove H out of the body - Limited ability to correct pH changes 1) H + HCO3- 10 2) 10 H + HCO3- 20 10 3) H + HCO310 0 H2CO3 H2O 10 10 H2CO3 H2O 10 10 H2CO3 H2O 20 10 H2CO3 H2O 10 20 + CO2 10 + CO2 10 + CO2 10 + CO2 20 Respiratory Control of pH H + HCO- H + HCO- H2CO3 CO2 + H2O H2CO3 CO2 + H2O pH stimulate peripheral/central chemoreceptors pulmonary ventilation removal of CO2 and pH H + HCO3- H2CO3 H2O + CO2 Limit to respiratory control of pH The respiratory regulatory mechanism cannot remove H+ out of the body. Its efficiency depends on the availability of HCO3- . H + HCO3- H2CO3 H2O + CO2 Renal Control of pH 1. The kidneys can neutralize more acid or base than both the respiratory system and chemical buffers. a. Renal tubules secrete hydrogen ions into the tubular fluid, where most of it combines with bicarbonate, ammonia, and phosphate buffers. b. Bound and free H+ are then excreted in urine. 2. The kidneys are the only organs that actually expel H+ from the body. Other buffering systems only reduce its concentration by binding it to another chemical. 3. Tubular secretion of H+ continues as long as a sufficient concentration gradient exists between the tubule cells and the tubular fluid. Disorders of Acid-Base Balance Acidosis: < pH 7.35 , Alkalosis: > pH 7.45 - Mild acidosis depresses CNS, causing confusion, disorientation, and coma. - Mild alkalosis CNS becomes hyperexcitable. Nerves fire spontaneously and overstimulate skeletal muscles. - Severe acidosis or alkalosis is lethal. Respiratory vs Metabolic Cause Respiratory acidosis / alkalosis - caused by hypoventilation or hyperventilation Initial change H + HCO- H2CO3 H2O + CO2 Emphysema Respiratory acidosis / alkalosis - caused by hypoventilation or hyperventilation Metabolic acidosis or alkalosis - result from any causes but respiratory problems Diabetes production of organic acids metabolic acidosis Chronic vomiting loss of stomach acid metabolic alkalosis