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Fluid, & pH Balance

Fluid / Electrolyte / Acid-Base Balance

Body Fluids:

Cell function depends not only on continuous nutrient supply / waste removal, but also on the physical / chemical of surrounding fluids

1) : (universal solvent)

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

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

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

1 Fluid / Electrolyte / Acid-Base Balance

Body Fluids:

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 Volume = 40 L

(60% body weight) Plasma

Intracellular Fluid (ICF) Interstitial Volume =3 Volume = 25 L Fluid

(40% body weight) Volume = 12 L

L L

Extracellular Fluid (ECF) Volume = 15 L (20% body weight)

Fluid / Electrolyte / Acid-Base Balance

Clinical Application:

The volumes of the compartments are measured by the dilution method

Step 1: Step 2: Step 4: Identify appropriate marker Inject known volume of Calculate volume of body substance marker into individual fluid compartment

Total Body Water: Amount Volume = A marker is placed in (L) Concentration the system that is distributed (mg) wherever water is found Amount: Marker: D2O Step 3: Amount of marker injected (mg) – Amount excreted (mg) 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 • concentration Marker: Mannitol Note: ICF Volume = TBW – ECF Volume

2 Fluid / Electrolyte / Acid-Base Balance have great osmotic power: Body Fluids: 2+ - - MgCl2  Mg + Cl + Cl Cell function depends not only on continuous nutrient supply / waste removal, but also on the physical / chemical homeostasis of surrounding fluids

2) Solutes:

A) Non-electrolytes (do not dissociate in – neutral) • Mostly organic molecules (e.g., , lipids, urea)

B) Electrolytes (dissociate into ions in solution – charged) • Inorganic salts • Inorganic / organic acids •

Although individual [solute] are different between compartments, the osmotic concentrations of the ICF and ECF are usually identical…

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

Fluid / Electrolyte / Acid-Base Balance

Fluid Movement Among Compartments:

The continuous exchange and mixing of body fluids are regulated by osmotic and hydrostatic pressures

Plasma 300 mosm Hydrostatic Pressure

Interstitial 300 mosm Fluid Osmotic Pressure

Intracellular 300 mosm Fluid Osmotic Osmotic Pressure Pressure

In a steady state, The volume of a particular The shift of fluids between intracellular osmolarity compartment depends on compartments depends on is equal to amount of solute present osmolarity of solute present extracellular osmolarity

3 Fluid / Electrolyte / Acid-Base Balance

Water Balance: ICF functions as a reservoir For proper hydration: Waterintake = Wateroutput

Water Output Water Intake Feces (2%) < 0 Metabolism (10%) Sweat (8%) Osmolarity rises: • Solid foods (30%) Skin / lungs (30%) • ADH release

> 0 Osmolarity lowers: Ingested liquids (60%) Urine (60%) • Thirst • ADH release

2500 ml/day 2500 ml/day = 0

Fluid / Electrolyte / Acid-Base Balance

Water Balance:

Thirst Mechanism:  osmolarity /  volume (-) of extra. fluid

Osmoreceptors stimulated (Hypothalamus)

 volume /  osmolarity of Sensation Drink extracellular fluid of thirst

 saliva Dry mouth secretion (-)

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Pathophysiology:

Disturbances that alter solute or water balance in the body can cause a shift of water between

Volume Contraction: A decrease in ECF volume

300 mOsm < 300 mOsm NaCl not reabsorbed from kidney filtrate Water Diarrhea deficiency insufficiency

300 mOsm 300 mOsm > 300 mOsm < 300 mOsm

Extracellular Extracellular Extracellular Extracellular Fluid Fluid Fluid Fluid

300 mOsm 300 mOsm > 300 mOsm < 300300 mOsm

Intracellular Intracellular Intracellular Intracellular Fluid Fluid Fluid Fluid

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

Fluid / Electrolyte / Acid-Base Balance

Pathophysiology:

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

Greater than normal 300 mOsm NaCl water reabsorption IV bag Osmotic IV Yang’s lunch SIADH

300 mOsm 300 mOsm > 300 mOsm < 300 mOsm

Extracellular Extracellular Extracellular Extracellular Fluid Fluid Fluid Fluid

300 mOsm 300 mOsm > 300 mOsm < 300 mOsm

Intracellular Intracellular Intracellular Intracellular Fluid Fluid Fluid Fluid

Isomotic Expansion Hyperosmotic Expansion Hyposmotic Expansion IV bags of varying solutes ECF volume = Increase ECF volume = Increase ECF volume = Increase 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 osmolarity = No change ICF osmolarity = Increase ICF osmolarity = Decrease

5 Fluid / Electrolyte / Acid-Base Balance

Acid-Base Balance:

Acid-base balance is concerned with maintaining a normal hydrogen ion concentration in the body fluids

Compatible range for life + pH = -log10 [H ] -9 pH = -log10 [40 x 10 ] Normal [H+] pH = 7.4

Note: 1) [H+] and pH are inversely related 2) Relationship is logarithmic, not linear [H+] = 40 x 10-9 Eq / L Normal range of arterial pH = 7.37 – 7.42

Problems Encountered: 1) Disruption of stability 2) Alteration of structure 3) Enzymatic activity change

Costanzo (Physiology, 4th ed.) – Figure 7.1

Fluid / Electrolyte / Acid-Base Balance

Acid-Base Balance:

Acid production in the has two forms: volatile acids and fixed acids

1) Volatile Acids: Acids that leave solution and enter the atmosphere

- + CO2 + H2O H2CO3 HCO3 + H End product of carbonic aerobic metabolism acid (13,000 – 20,000 mmol / day) Eliminated via the lungs

2) Fixed Acids: Acids that do not leave solution (~ 50 mmol / day)

Products of normal Products of extreme Ingested (harmful) catabolism: catabolism: products: Diabetes • Sulfuric acid (amino acids) • Acetoacetic acid mellitus • Salicylic acid (e.g., aspirin) (ketobodies) • Phosphoric acid (phospholipids) • B-hydroxybutyric acid • Formic acid (e.g., methanol)

• Lactic acid (anaerobic respiration) • Oxalic acids (e.g., ethylene glycol) Eliminated via the kidneys

6 Fluid / Electrolyte / Acid-Base Balance

Acid-Base Balance:

H+ Gain: Distant from H+ Loss: one another • Across digestive epithelium • Release at lungs • Cell metabolic activities • Secretion into urine

Chemical Buffer: A 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 150 mEq H+ Brønsted-Lowry Nomenclature: Weak acid: Acid form = HA = H+ donor Base form = A- = H+ acceptor 11.4 L Weak base: 11.4 L Acid form = BH+ = H+ donor Base form = B = H+ acceptor

7.44  7.14 7.00  1.84

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

The Henderson-Hasselbalch equation is used to calculate the pH of a buffered solution

Henderson-Hasselbalch Equation: Most effective -1 +1 [A-] buffering pH = pK + log [HA]

+ pH = -log10 [H ]

pK = -log10 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, 4th ed.) – Figure 7.2

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

PCO2 = 40 mm Hg The major buffers of the ECF are bicarbonate and phosphate

- 1) HCO3 / CO2 Buffer:

- + CO2 + H2O H2CO3 HCO3 + H (HA) (A-)

Utilized as first line of defense when H+ enters / lost from system: - (1) Concentration of HCO3 normally high at 24 mEq / L - (2) The pK of HCO3 / CO2 buffer is 6.1 (near pH of ECF)

(3) CO2 is volatile; it can be expired by the lungs

The pH of arterial can - HCO3 24 be calculated with the pH = pK + log pH = 6.1 + log Henderson-Hasselbalch equation 0.03 x PCO2 0.03 x 40 pH = 7.4

Fluid / Electrolyte / Acid-Base Balance

Acid-Base Balance:

The major buffers of the ECF are bicarbonate and phosphate

- 1) HCO3 / CO2 Buffer:

Acid-base 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 PCO2 - Isohydric line and HCO3 concentration can yield normal values of pH (‘same pH’) (compensatory mechanisms)

Costanzo (Physiology, 4th ed.) – Figure 7.4

8 Fluid / Electrolyte / Acid-Base Balance

Acid-Base Balance:

The major buffers of the ECF are bicarbonate and phosphate

- 2- 2) H2PO4 / HPO4 Buffer:

- 2- + H2PO4 HPO4 + 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, 4th ed.) – Figure 7.3

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

Acid-Base Balance: CO2 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 • Glucose-1-phosphate pKs range from 6.0 to 7.5 • 2,3-diphosphoglycerate The most significant ICF protein buffer is hemoglobin 2) Proteins: R – COOH R – COO- + H+ If pH rises

+ + If pH falls R – NH2 + H R – NH3

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++ Normal circulating Ca++ Hypercalcemia Hypocalcemia

9 Fluid / Electrolyte / Acid-Base Balance

Maintenance of Acid-Base Balance: Doubling / halving of areolar ventilation can raise / lower blood pH by 0.2 pH units

Buffers are a short-term fix to the problem; in the long term, H+ must be removed from the system…

1) Respiratory Regulation: If H+ begins to rise in system, respiratory  CO2 leaves centers excited system - + CO2 + H2O H2CO3 HCO3 + H carbonic ( H; homeostasis restored) acid

If H+ begins to fall in system, respiratory  CO2 leaves centers depressed system - + CO2 + H2O H2CO3 HCO3 + H carbonic ( H; homeostasis acid restored)

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

- 2) Renal Regulation: Process continues If HCO3 loads reach 40 mEq / L, until 99.9% of transport maximized and - - HCO - excreted. A) HCO3 reabsorption: HCO3 reabsorbed 3

Net secretion of H+ does not occur

THUS Net reabsorption of - pH of filtrate HCO3 does occurs does not significantly change

(brush border)

(intracellular)

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

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

(Removes 40% of fixed acids – 20 mEq / day) 2) Renal Regulation: (1) Titratable Acid: + B) Secretion of fixed H+: of H H+ excreted with buffer as titratable acid

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

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

(Removes 60% of fixed acids – 30 mEq / day) 2) Renal Regulation: (2) B) Secretion of fixed H+: Excretion of H+ + Diffusional trapping: as NH4 Lipid soluble NH3 is able to diffuse into tubule but once combined with + NH4 it is unable to leave

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

11 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 Hyperventilation (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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