Fluid / / Acid-Base Balance Fluid, Electrolyte Body Fluids: & pH Balance function depends not only on continuous nutrient supply / waste removal, but also on the physical / chemical of surrounding fluids

1) Water: (universal solvent)

Body water varies based on of age, sex, mass, and body composition

H2O ~ 73% body weight Low body fat Low mass H2O (♂) ~ 60% body weight

H2O (♀) ~ 50% body weight ♀ =  body fat /  muscle mass H2O ~ 45% body weight

Fluid / Electrolyte / Acid-Base Balance Fluid / Electrolyte / Acid-Base Balance

Body Fluids: Clinical Application:

Cell function depends not only on continuous nutrient supply / waste removal, but also on the physical / chemical homeostasis of surrounding fluids The volumes of the compartments are measured by the dilution method 1) Water: (universal solvent)

Total Step 1: Step 2: Step 4: Volume = 40 L (60% body weight) Identify appropriate marker Inject known volume of Calculate volume of body substance marker into individual fluid compartment

Plasma Total Body Water: Amount Volume = A marker is placed in (L) Concentration the system that is distributed (mg)

Intracellular Fluid (ICF) Interstitial wherever water is found Volume3 = Volume = 25 L Fluid Amount: Marker: D2O (40% body weight) Volume = 12 L Step 3: Amount of marker injected (mg) – Amount excreted (mg)

L L Volume: Let marker equilibrate and

A marker is placed in measure marker Concentration: the system that can not cross • Plasma concentration Concentration in plasma (mg / L) cell membranes Extracellular Fluid (ECF) • concentration Volume = 15 L Marker: Mannitol Note: (20% body weight) ICF Volume = TBW – ECF Volume

Fluid / Electrolyte / Acid-Base Balance Fluid / Electrolyte / Acid-Base Balance have great osmotic power: Body Fluids: 2+ - - Fluid Movement Among Compartments: MgCl2  Mg + Cl + Cl Cell function depends not only on continuous nutrient supply / waste removal, The continuous exchange and mixing of body fluids are regulated but also on the physical / chemical homeostasis of surrounding fluids by osmotic and hydrostatic pressures 2) Solutes:

Plasma 300 mosm A) Non-electrolytes Hydrostatic Pressure (do not dissociate in solution – neutral) • Mostly organic molecules Interstitial 300 mosm (e.g., glucose, lipids, urea) Fluid Osmotic Pressure

B) Electrolytes Intracellular 300 mosm (dissociate into in solution – charged) Fluid Osmotic Osmotic • Inorganic salts Pressure Pressure • Inorganic / organic acids • Proteins

In a steady state, Although individual [solute] are different The volume of a particular The shift of fluids between intracellular osmolarity between compartments, the osmotic compartment depends on compartments depends on is equal to concentrations of the ICF and amount of solute present osmolarity of solute present ECF are usually identical… extracellular osmolarity

Marieb & Hoehn (Human Anatomy and Physiology, 8th ed.) – Figures 26.2

1 Fluid / Electrolyte / Acid-Base Balance Fluid / Electrolyte / Acid-Base Balance

Water Balance: Water Balance: ICF functions as a reservoir For proper hydration: Waterintake = Wateroutput Mechanism:  osmolarity /  volume Water Output (-) Water Intake of extra. fluid Feces (2%) < 0 Metabolism (10%) Sweat (8%) Osmolarity rises: Osmoreceptors stimulated • Thirst (Hypothalamus) Solid foods (30%) Skin / lungs (30%) • ADH release

 volume /  osmolarity of Sensation Drink > 0 extracellular fluid of thirst Osmolarity lowers: Ingested liquids (60%) Urine (60%) • Thirst • ADH release

Dry mouth 2500 ml/day 2500 ml/day = 0 (-)

Fluid / Electrolyte / Acid-Base Balance Fluid / Electrolyte / Acid-Base Balance

Pathophysiology: Pathophysiology:

Disturbances that alter solute or water balance in the body can Disturbances that alter solute or water balance in the body can cause a shift of water between cause a shift of water between fluid compartments Water intoxication : A decrease in ECF volume Volume Expansion: An increase in ECF volume

300 mOsm < 300 mOsm NaCl not reabsorbed Greater than normal from filtrate 300 mOsm NaCl water reabsorption IV bag Water Diarrhea deficiency insufficiency Osmotic IV Yang’s lunch SIADH

300 mOsm 300 mOsm > 300 mOsm < 300 mOsm 300 mOsm 300 mOsm > 300 mOsm < 300 mOsm

Extracellular Extracellular Extracellular Extracellular Extracellular Extracellular Extracellular Extracellular Fluid Fluid Fluid Fluid Fluid Fluid Fluid Fluid

300 mOsm 300 mOsm > 300 mOsm < 300 mOsm 300 mOsm 300 mOsm > 300 mOsm < 300 mOsm

Intracellular Intracellular Intracellular Intracellular Intracellular Intracellular Intracellular Intracellular Fluid Fluid Fluid Fluid Fluid Fluid Fluid Fluid

Isomotic Contraction Hyperosmotic Contraction Hyposmotic Contraction Isomotic Expansion Hyperosmotic Expansion Hyposmotic Expansion ECF volume = Decrease ECF volume = Decrease ECF volume = Decrease IV bags of varying solutes ECF volume = Increase ECF volume = Increase ECF volume = Increase ECF osmolarity = No change ECF osmolarity = Increase ECF osmolarity = Decrease allow for manipulation of ECF osmolarity = No change ECF osmolarity = Increase ECF osmolarity = Decrease ECF / ICF levels… ICF volume = No change ICF volume = Decrease ICF volume = Increase ICF volume = No change ICF volume = Decrease ICF volume = Increase ICF osmolarity = No change ICF osmolarity = Increase ICF osmolarity = Decrease ICF osmolarity = No change ICF osmolarity = Increase ICF osmolarity = Decrease

Fluid / Electrolyte / Acid-Base Balance Fluid / Electrolyte / Acid-Base Balance

Acid-Base Balance: Acid-Base Balance:

Acid-base balance is concerned with maintaining a normal Acid production in the has two forms: hydrogen concentration in the body fluids volatile acids and fixed acids

Compatible range for life + 1) Volatile Acids: Acids that leave solution and enter the atmosphere pH = -log10 [H ] -9 pH = -log10 [40 x 10 ] Normal H CO HCO - + H+ [H+] pH = 7.4 CO2 + H2O 2 3 3 End product of carbonic Note: aerobic acid (13,000 – 20,000 mmol / day) Eliminated via the lungs 1) [H+] and pH are inversely related 2) Relationship is logarithmic, not linear [H+] = 40 x 10-9 Eq / L 2) Fixed Acids: Acids that do not leave solution (~ 50 mmol / day) Normal range of arterial pH = 7.37 – 7.42

Products of normal Products of extreme Ingested (harmful) Problems Encountered: catabolism: catabolism: products: 1) Disruption of stability Diabetes mellitus 2) Alteration of protein structure • Sulfuric acid (amino acids) • Acetoacetic acid • Salicylic acid (e.g., aspirin) (ketobodies) 3) Enzymatic activity change • Phosphoric acid (phospholipids) • B-hydroxybutyric acid • Formic acid (e.g., methanol) • (anaerobic ) • Oxalic acids (e.g., ethylene glycol) Eliminated via the kidneys Costanzo (Physiology, 4th ed.) – Figure 7.1

2 Fluid / Electrolyte / Acid-Base Balance Fluid / Electrolyte / Acid-Base Balance For the human body, the Acid-Base Balance: Acid-Base Balance: most effective physiologic buffers will have a pK at 7.4  1.0

H+ Gain: Distant from H+ Loss: one another The Henderson-Hasselbalch equation is used to calculate • Across digestive • Release at lungs the pH of a buffered solution • Cell metabolic activities • Secretion into urine

Chemical Buffer: A mixture of a weak acid and its conjugate base or a weak base and Henderson-Hasselbalch Equation: Most effective its conjugate acid that resist a change in pH -1 +1 [A-] buffering Robert Pitt: pH = pK + log [HA] + 150 mEq H 150 mEq H+ Brønsted-Lowry Nomenclature:

+ Weak acid: pH = -log10 [H ] Acid form = HA = H+ donor pK = -log10 K (equilibrium constant) [A-] = Concentration of base form of buffer (mEq / L) - + Base form = A = H acceptor [HA] = Concentration of acid form of buffer (mEq / L) 11.4 L Weak base: pK is a characteristic value for a buffer pair 11.4 L + + Acid form = BH = H donor (strong acid =  pK; weak acid =  pK) Base form = B = H+ acceptor

7.44  7.14 7.00  1.84 Costanzo (Physiology, 4th ed.) – Figure 7.2

Fluid / Electrolyte / Acid-Base Balance pK = 6.1 Fluid / Electrolyte / Acid-Base Balance - [HCO3 ] = 24 mmol / L Acid-Base Balance: Solubility = 0.03 mmol / L / mm Hg Acid-Base Balance: PCO2 = 40 mm Hg

The major buffers of the ECF are and The major buffers of the ECF are bicarbonate and phosphate

- - 1) HCO3 / CO2 Buffer: 1) HCO3 / CO2 Buffer:

- + CO2 + H2O H2CO3 HCO3 + H Acid-base map: (HA) (A-) Shows relationship between the acid and base forms of a buffer and the pH of the solution Utilized as first line of defense when H+ enters / lost from system: - (1) Concentration of HCO3 normally high at 24 mEq / L - Ellipse: (2) The pK of HCO3 / CO2 buffer is 6.1 (near pH of ECF) Normal values for (3) CO is volatile; it can be expired by the lungs 2 arterial

Note: The pH of arterial blood can - HCO3 24 Abnormal combinations of PCO2 be calculated with the pH = pK + log pH = 6.1 + log - Isohydric line and HCO3 concentration can Henderson-Hasselbalch equation 0.03 x PCO2 0.03 x 40 yield normal values of pH (‘same pH’) (compensatory mechanisms) pH = 7.4 Costanzo (Physiology, 4th ed.) – Figure 7.4

Fluid / Electrolyte / Acid-Base Balance Fluid / Electrolyte / Acid-Base Balance H+ enters cells via a build up of

Acid-Base Balance: Acid-Base Balance: CO2 in ECF, which then enters cells, or to maintain electroneutrality

The major buffers of the ECF are bicarbonate and phosphate The major buffers of the ICF are organic and proteins

- 2- 2) H2PO4 / HPO4 Buffer: 1) Organic phosphates: • ATP / ADP / AMP - 2- + H2PO4 HPO4 + H • Glucose-1-phosphate pKs range from 6.0 to 7.5 (HA) (A-) • 2,3-diphosphoglycerate The most significant ICF protein buffer is 2) Proteins: R – COOH R – COO- + H+ If pH rises

Why isn’t inorganic phosphate the primary ECF buffer? + + If pH falls R – NH2 + H R – NH3 (1) Lower concentration than bicarbonate (~ 1.5 mmol / L) (2) Is not volatile; can not be cleared by lung Normal pH Acidemia Alkalemia Ca++ Ca++ Ca++ Ca++ + A relationship exists + Proteins also buffer H ++ H between Ca++, H+, H+ H+ Ca H+ Ca++ in the ECF and plasma proteins Ca++ A Ca++ H+ A Ca++ ++ Costanzo (Physiology, 4th ed.) – Figure 7.3 Normal circulating Ca Hypercalcemia

3 Fluid / Electrolyte / Acid-Base Balance Fluid / Electrolyte / Acid-Base Balance Kidneys are ultimate acid-base regulatory organs Doubling / halving of areolar ventilation - Maintenance of Acid-Base Balance: Maintenance of Acid-Base Balance: • Reabsorb HCO3 can raise / lower blood pH by 0.2 pH units • Secrete fixed H+ Buffers are a short-term fix to the problem; in the long term, Buffers are a short-term fix to the problem; in the long term, H+ must be removed from the system… H+ must be removed from the system…

- 1) Respiratory Regulation: 2) Renal Regulation: Process continues If HCO3 loads reach 40 mEq / L, until 99.9% of transport maximized and If H+ begins to rise in - - HCO - excreted. system, respiratory A) HCO3 reabsorption: HCO3 reabsorbed 3  CO2 leaves centers excited system - + CO2 + H2O H2CO3 HCO3 + H Net secretion of H+ does not occur carbonic ( H; homeostasis restored) acid THUS Net reabsorption of - pH of filtrate HCO3 does occurs If H+ begins to fall in does not significantly system, respiratory change  CO2 leaves centers depressed system (brush - + CO2 + H2O H2CO3 HCO3 + H border) carbonic ( H; homeostasis (intracellular) acid restored)

Costanzo (Physiology, 4th ed.) – Figure 7.5

Fluid / Electrolyte / Acid-Base Balance Kidneys are ultimate acid-base Fluid / Electrolyte / Acid-Base Balance Kidneys are ultimate acid-base regulatory organs regulatory organs - - Maintenance of Acid-Base Balance: • Reabsorb HCO3 Maintenance of Acid-Base Balance: • Reabsorb HCO3 • Secrete fixed H+ • Secrete fixed H+ Buffers are a short-term fix to the problem; in the long term, Buffers are a short-term fix to the problem; in the long term, H+ must be removed from the system… H+ must be removed from the system…

(Removes 40% of fixed acids – 20 mEq / day) (Removes 60% of fixed acids – 30 mEq / day) 2) Renal Regulation: 2) Renal Regulation: (1) Titratable Acid: (2) + B) Secretion of fixed H+: Excretion of H H+ excreted with buffer B) Secretion of fixed H+: Excretion of H+ + Diffusional trapping: as titratable acid as NH4 Lipid soluble NH3 is able to diffuse into tubule but once combined with + NH4 it is unable to leave Recall: Only 85% of phosphate reabsorbed from filtrate

Minimum urinary - pH is 4.4 New HCO3 replaces - (Maximum H+ gradient HCO3 that is lost when + H ATPase can CO2 exits blood

work against) CO2

Costanzo (Physiology, 4th ed.) – Figure 7.6 Costanzo (Physiology, 4th ed.) – Figure 7.8

Fluid / Electrolyte / Acid-Base Balance

Disturbances of Acid-Base Balance: In the short term, respiratory / urinary system will compensate for disorders… 1) Respiratory Acid / Base Disorders:

Cause: Cause: Hypoventilation (e.g., emphysema) (e.g., stress)

(Most common (Rarely persists long acid / base disorder) enough to cause clinical emergency)

Respiratory : B) Respiratory :

 CO2 retained in body  CO2 retained in body 2) Metabolic Acid / Base Disorders:

Causes: Starvation Causes: ( ketone bodies) Repeated vomiting (alkaline tide ‘amped’)  Alcohol consumption ( acetic acid) Antacid overdose

- Excessive HCO3 loss (Rare in body) (e.g., chronic diarrhea) A) : A) : -  fixed acids generated in body  HCO3 generated in body

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