, Electrolyte & ph Balance / Electrolyte / AcidBase Balance Body s: Cell function depends not only on continuous nutrient supply / waste removal, but also on the physical / chemical homeostasis of surrounding fluids 1) Water: (universal solvent) Body water varies based on of age, sex, mass, and body composition H 2 O ~ 73% body weight Low body fat Low bone mass H 2 O ( ) ~ 60% body weight H 2 O ( ) ~ 50% body weight = body fat / muscle mass H 2 O ~ 45% body weight / Electrolyte / AcidBase Balance Body s: Cell function depends not only on continuous nutrient supply / waste removal, but also on the physical / chemical homeostasis of surrounding fluids 1) Water: (universal solvent) Total Body Water Volume = 40 L (60% body weight) (ICF) Volume = 25 L (40% body weight) Interstitial Volume = 12 L Plasma Volume = 3 L (ECF) Volume = 15 L (20% body weight) 1
/ Electrolyte / AcidBase Balance Clinical Application: The volumes of the body fluid compartments are measured by the dilution method Step 1: Identify appropriate marker substance Total Body Water: A marker is placed in the system that is distributed wherever water is found Marker: D 2O Volume: A marker is placed in the system that can not cross cell membranes Marker: Mannitol Step 2: Inject known volume of marker into individual (mg) Step 3: Let marker equilibrate and measure marker Plasma concentration Urine concentration Step 4: Calculate volume of body fluid compartment Amount Volume = (L) Concentration Amount: Amount of marker injected (mg) Amount excreted (mg) Concentration: Concentration in plasma (mg / L) Note: ICF Volume = TBW ECF Volume Body s: / Electrolyte / AcidBase Balance Cell function depends not only on continuous nutrient supply / waste removal, but also on the physical / chemical homeostasis of surrounding fluids 2) Solutes: Electrolytes have great osmotic power: MgCl 2 Mg 2+ + Cl + Cl A) Nonelectrolytes (do not dissociate in solution neutral) Mostly organic molecules (e.g., glucose, lipids, urea) B) Electrolytes (dissociate into ions in solution charged) Inorganic salts Inorganic / organic acids Proteins Although individual [solute] are different between compartments, the osmotic concentrations of the ICF and ECF are usually identical Marieb & Hoehn (Human Anatomy and Physiology, 8 th ed.) Figures 26.2 / Electrolyte / AcidBase Balance Movement Among Compartments: The continuous exchange and mixing of body fluids are regulated by osmotic and hydrostatic pressures Plasma Hydrostatic Pressure 300 mosm Interstitial Osmotic Pressure 300 mosm Osmotic Pressure Osmotic Pressure 300 mosm The volume of a particular compartment depends on amount of solute present In a steady state, intracellular osmolarity is equal to extracellular osmolarity The shift of fluids between compartments depends on osmolarity of solute present 2
/ Electrolyte / AcidBase Balance Water Balance: ICF functions as a reservoir For proper hydration: Water intake = Water output Water Intake Metabolism (10%) Solid foods (30%) Water Output Feces (2%) Sweat (8%) Skin / lungs (30%) < 0 Osmolarity rises: Thirst ADH release Ingested liquids (60%) Urine (60%) > 0 Osmolarity lowers: Thirst ADH release 2500 ml/day 2500 ml/day = 0 / Electrolyte / AcidBase Balance Water Balance: () Thirst Mechanism: osmolarity / volume of extra. fluid Osmoreceptors stimulated (Hypothalamus) volume / osmolarity of extracellular fluid Sensation of thirst Drink saliva secretion Dry mouth () / Electrolyte / AcidBase Balance Pathophysiology: Disturbances that alter solute or water balance in the body can cause a shift of water between fluid compartments Volume Contraction: A decrease in ECF volume < NaCl not reabsorbed from kidney filtrate Diarrhea Water deficiency Aldosterone insufficiency > < > < Isomotic Contraction Hyperosmotic Contraction Hyposmotic Contraction ECF volume = Decrease ECF volume = Decrease ECF volume = Decrease ECF osmolarity = No change ECF osmolarity = Increase ECF osmolarity = Decrease ICF volume = No change ICF volume = Decrease ICF volume = Increase ICF osmolarity = No change ICF osmolarity = Increase ICF osmolarity = Decrease 3
/ Electrolyte / AcidBase Balance Pathophysiology: Disturbances that alter solute or water balance in the body can cause a shift of water between fluid compartments Volume Expansion: An increase in ECF volume Water intoxication IV bag Osmotic IV NaCl Yang s lunch Greater than normal water reabsorption SIADH > < > < Isomotic Expansion Hyperosmotic Expansion Hyposmotic Expansion IV bags of varying solutes allow for manipulation of ECF / ICF levels ECF volume = Increase ECF osmolarity = No change ICF volume = No change ICF osmolarity = No change ECF volume = Increase ECF osmolarity = Increase ICF volume = Decrease ICF osmolarity = Increase ECF volume = Increase ECF osmolarity = Decrease ICF volume = Increase ICF osmolarity = Decrease / Electrolyte / AcidBase Balance Acidbase balance is concerned with maintaining a normal hydrogen ion concentration in the body fluids Compatible range for life Normal [H + ] [H + ] = 40 x 10 9 Eq / L ph = log 10 [H + ] ph = log 10 [40 x 10 9 ] ph = 7.4 Note: 1) [H + ] and ph are inversely related 2) Relationship is logarithmic, not linear Normal range of arterial ph = 7.37 7.42 Problems Encountered: 1) Disruption of cell membrane stability 2) Alteration of protein structure 3) Enzymatic activity change Costanzo (Physiology, 4 th ed.) Figure 7.1 / Electrolyte / AcidBase Balance Acid production in the human body has two forms: volatile acids and fixed acids 1) Volatile Acids: Acids that leave solution and enter the atmosphere CO 2 + H 2 O H 2 CO 3 HCO 3 + H + End product of aerobic metabolism (13,000 20,000 mmol / day) carbonic acid Eliminated via the lungs 2) Fixed Acids: Acids that do not leave solution (~ 50 mmol / day) Products of normal catabolism: Sulfuric acid (amino acids) Phosphoric acid (phospholipids) Eliminated via the kidneys Products of extreme catabolism: Diabetes Acetoacetic acid mellitus (ketobodies) Bhydroxybutyric acid Lactic acid (anaerobic respiration) Ingested (harmful) products: Salicylic acid (e.g., aspirin) Formic acid (e.g., methanol) Oxalic acids (e.g., ethylene glycol) 4
/ Electrolyte / AcidBase Balance H + Gain: Across digestive epithelium Cell metabolic activities Distant from one another H + Loss: Release at lungs Secretion into urine Chemical Buffer: A mixture of a weak acid and its conjugate base or a weak base and its conjugate acid that resist a change in ph Robert Pitt: 150 meq H+ 11.4 L 11.4 L 150 meq H + BrønstedLowry Nomenclature: Weak acid: Acid form = HA = H + donor Base form = A = H + acceptor Weak base: Acid form = BH + = H + donor Base form = B = H + acceptor 7.44 7.14 7.00 1.84 / Electrolyte / AcidBase Balance For the human body, the most effective physiologic buffers will have a pk at 7.4 1.0 The HendersonHasselbalch equation is used to calculate the ph of a buffered solution HendersonHasselbalch Equation: [A ] ph = pk + log [HA] 1 +1 Most effective buffering ph = log 10 [H + ] pk = log 10 K (equilibrium constant) [A ] = Concentration of base form of buffer (meq / L) [HA] = Concentration of acid form of buffer (meq / L) pk is a characteristic value for a buffer pair (strong acid = pk; weak acid = pk) Costanzo (Physiology, 4 th ed.) Figure 7.2 / Electrolyte / AcidBase Balance pk = 6.1 [HCO 3 ] = 24 mmol / L Solubility = 0.03 mmol / L / mm Hg P CO2 = 40 mm Hg The major buffers of the ECF are bicarbonate and phosphate 1) HCO 3 / CO 2 Buffer: CO 2 + H 2 O H 2 CO 3 HCO 3 + H + (HA) (A ) Utilized as first line of defense when H + enters / lost from system: (1) Concentration of HCO 3 normally high at 24 meq / L (2) The pk of HCO 3 / CO 2 buffer is 6.1 (near ph of ECF) (3) CO 2 is volatile; it can be expired by the lungs The ph of arterial blood can be calculated with the HendersonHasselbalch equation ph = pk + log HCO 3 24 ph = 6.1 + log 0.03 x P CO2 0.03 x 40 ph = 7.4 5
/ Electrolyte / AcidBase Balance The major buffers of the ECF are bicarbonate and phosphate 1) HCO 3 / CO 2 Buffer: Acidbase map: Shows relationship between the acid and base forms of a buffer and the ph of the solution Ellipse: Normal values for arterial blood Note: Abnormal combinations of P CO2 and HCO 3 concentration can yield normal values of ph (compensatory mechanisms) Isohydric line ( same ph ) Costanzo (Physiology, 4 th ed.) Figure 7.4 / Electrolyte / AcidBase Balance The major buffers of the ECF are bicarbonate and phosphate 2) H 2 PO 4 / HPO 4 2 Buffer: H 2 PO 4 HPO 4 2 + H + (HA) (A ) Why isn t inorganic phosphate the primary ECF buffer? (1) Lower concentration than bicarbonate (~ 1.5 mmol / L) (2) Is not volatile; can not be cleared by lung Costanzo (Physiology, 4 th ed.) Figure 7.3 / Electrolyte / AcidBase Balance H + enters cells via a build up of CO 2 in ECF, which then enters cells, or to maintain electroneutrality The major buffers of the ICF are organic phosphates and proteins 1) Organic phosphates: ATP / ADP / AMP Glucose1phosphate 2,3diphosphoglycerate 2) Proteins: pks range from 6.0 to 7.5 The most significant ICF protein buffer is hemoglobin R COOH R COO + H + If ph rises R NH 2 + H + R NH 3 + If ph falls Proteins also buffer H + in the ECF A relationship exists between Ca ++, H +, and plasma proteins A Ca ++ Ca ++ H + H + Ca++ Normal ph Ca ++ Normal circulating Ca ++ Acidemia Alkalemia Ca ++ Ca A ++ Ca ++ H H + Ca ++ + H + Ca ++ Hypercalcemia Hypocalcemia 6
/ Electrolyte / AcidBase Balance Maintenance of Doubling / halving of areolar ventilation can raise / lower blood ph by 0.2 ph units Buffers are a shortterm fix to the problem; in the long term, H + must be removed from the system 1) Respiratory Regulation: CO 2 leaves system If H + begins to rise in system, respiratory centers excited CO 2 + H 2 O H 2 CO 3 HCO 3 + H + carbonic acid ( H; homeostasis restored) CO 2 leaves system If H + begins to fall in system, respiratory centers depressed CO 2 + H 2 O H 2 CO 3 HCO 3 + H + carbonic acid ( H; homeostasis restored) Maintenance of / Electrolyte / AcidBase Balance Kidneys are ultimate acidbase regulatory organs Reabsorb HCO 3 Secrete fixed H + Buffers are a shortterm fix to the problem; in the long term, H + must be removed from the system 2) Renal Regulation: A) HCO 3 reabsorption: Process continues until 99.9% of HCO 3 reabsorbed If HCO 3 loads reach 40 meq / L, transport maximized and HCO 3 excreted. Net secretion of H + does not occur THUS ph of filtrate does not significantly change Net reabsorption of HCO 3 does occurs (brush border) (intracellular) Costanzo (Physiology, 4 th ed.) Figure 7.5 Maintenance of / Electrolyte / AcidBase Balance Kidneys are ultimate acidbase regulatory organs Reabsorb HCO 3 Secrete fixed H + 2) Renal Regulation: B) Secretion of fixed H + : Buffers are a shortterm fix to the problem; in the long term, H + must be removed from the system (Removes 40% of fixed acids 20 meq / day) (1) Excretion of H + as titratable acid Titratable Acid: H + excreted with buffer Recall: Only 85% of phosphate reabsorbed from filtrate Minimum urinary ph is 4.4 (Maximum H + gradient H + ATPase can work against) CO 2 New HCO 3 replaces HCO 3 that is lost when CO 2 exits blood Costanzo (Physiology, 4 th ed.) Figure 7.6 7
Maintenance of 2) Renal Regulation: B) Secretion of fixed H + : / Electrolyte / AcidBase Balance Buffers are a shortterm fix to the problem; in the long term, H + must be removed from the system (Removes 60% of fixed acids 30 meq / day) (2) Excretion of H + as NH 4 + Kidneys are ultimate acidbase regulatory organs Reabsorb HCO 3 Secrete fixed H + Diffusional trapping: Lipid soluble NH 3 is able to diffuse into tubule but once combined with NH 4 + it is unable to leave Costanzo (Physiology, 4 th ed.) Figure 7.8 / Electrolyte / AcidBase Balance Disturbances of 1) Respiratory Acid / Base Disorders: In the short term, respiratory / urinary system will compensate for disorders Respiratory Acidosis: CO 2 retained in body Cause: Hypoventilation (e.g., emphysema) (Most common acid / base disorder) 2) Metabolic Acid / Base Disorders: A) Metabolic Acidosis: fixed acids generated in body Causes: Starvation ( ketone bodies) Alcohol consumption ( acetic acid) Excessive HCO 3 loss (e.g., chronic diarrhea) B) Respiratory Alkalosis: CO 2 retained in body A) Metabolic alkalosis: HCO 3 generated in body Cause: Hyperventilation (e.g., stress) (Rarely persists long enough to cause clinical emergency) Causes: Repeated vomiting (alkaline tide amped ) Antacid overdose (Rare in body) 8