Fundamentals of Body Buffers and Gases (B2: W6)

Question 1

What systems are involved in homeostasis of the blood?

Answer 1

• Respiratory
• Renal
• Gastrointestinal
• Cardiovascular

Rate of acid production = rate of acid excretion

Rate of O₂ intake = rate of O₂ utilization

Question 2

How is pH of the blood determined?

Answer 2

• Intravascular pH is easily measured
  
  • ECF
  • Gives us a single view of the whole body pH status
  • Balance: ECF pH → balanced interstital pH → balanced ICF pH
• Intracellular pH is not easily measured
  
  • Responds to the change in pH of ECF
  • ∆pH of blood ⇔ interstitial ⇔ ICF pH
  • But: ∆pH blood ≠ interstitial pH ≠ ICF pH

Question 3

How is pH calculated?

Answer 3

pH = -log [H⁺]

Question 4

What is the healthy range for pH?

Answer 4

• Healthy
  
  • 7.35 to 7.45
  • Same as 45 nm and 35 nm
• Life between 6.8 and 7.8
• Patients within and outside healthy range can be sick

Question 5

Where does acid production originate?

Answer 5

Intracellularly

• Intracellular pH ~7.0
  
  • Proteins
  • Phosphates
  • Bicarbonate system

Question 6

Why is intracellular pH not equal to extracellular pH?

Answer 6

• Active exchange proteins maintain an imbalance on purpose
  
  • Na-H and K-H
  • Protons are charged and need exchangers to go across membranes
• Concentrations of buffers in the ICF are 3x higher than in the ECF

Question 7

How can H⁺ be so important when its concnetration is 40 nm at pH 7.4?

Answer 7

At pH 7.4, metabolic intermediates in the charged form are effectively trapped within the cell

• pK_a of most body acids << 7.4
• They are essentially fully ionized at pH 7.4

Question 8

How is K_a calculated?

Answer 8

K_a = [H⁺][A^-] / [HA]

If [H⁺] happens to equal the K_a, rearrange the equation to

Ka / [H⁺] = [A^-] / [HA]

Then A^- = HA and the ratio is 1/1, meaning that they are the same concentration

Question 9

Why does an alteration in pH affect relative concentrations of every conjugate acid and base of all the weak electrolytes?

Answer 9

Because they use the same pool of H⁺

• The common species to all is H⁺
• Isohydric principle

Question 10

What is the purpose of body buffer?

Answer 10

They maintain pH homeostasis

• Weak acid-base pair
• Lessen pH changes due to addition of strong acids or bases

Question 11

How are high capacity buffers different from low capacity buffers?

Answer 11

High capacity ones are higher in concentration

• pK_as are closer to the working pH of their environment

Question 12

What are the main buffers in the ECF?

Answer 12

• Non-bicarbonate buffers - non-volatile
  
  • Hemoglobin
  • Plasma proteins
  • Phosphates
• Bicarbonate buffer system - volatile
  
  • Volatile because CO₂ gas is involved

Question 13

Why is NH₄⁺ not a buffer?

Answer 13

It is toxic to the brain

Question 14

Which buffer has the highest buffer capacity of nonvolatile buffers?

Answer 14

Hemoglobin

• Abundant histidine side chains - pK_a ~6.5
  
  • HbH⁺ ⇔ Hb + H⁺
• Found inside RBC (intracellular)
  
  • RBC membranes are permeable to protons
  • Has an important and rapid impact on the ECF pH
  • Therefore considered an extracellular buffer

Question 15

Which is an important buffer in the renal tubular filtrate?

Answer 15

Phosphate

• Not an important blood buffer
  
  • 1 mM - a few % of Hb capacity
• ICF has high concentrations of others, ATP, ADP, phosphosugars, etc

Question 16

How good are plasma proteins as buffers?

Answer 16

• 20% of Hb buffering capacity
  
  • Also have histidine side chains
• Albumin is the most plentiful plasma protein

Question 17

What is the most important function of the non-volatile buffers?

Answer 17

Mitigate pH changes due to changes in volatile acid - CO₂

• Non-volatile buffers are the only ones that can do this
  
  • Bicarbonate system cannot!
• They also buffer endogenous acids

Question 18

Which is the _most powerful buffe_r of the ECF?

Answer 18

Bicarbonate buffer system

• High buffering capcity and an open system
• Does NOT buffer increases in CO₂!
• Unusual buffer
  
  • Involves a gas - CO₂ can go across membranes freely

Question 19

Define partial pressure

Answer 19

Partial pressure is the pressure that the gas would have if it alone occupied the volume

• In a gas, the relative concentration is simply the partial pressure
• Pressure of all gases in air add up to the barometric pressure = P_B
  
  • Depends on altitude

Question 20

What is the partial pressure of carbon dioxide?

Answer 20

P_CO2 is so low that it is clinically considered zero

• Fraction = 0.03%
• 0.0003 • 760 mm Hg = 0.23 mm Hg = P_CO2 in air at sea level

Question 21

What is the partial pressure of oxygen?

Answer 21

• Fraction = 21%
• 0.21 • 760 mm Hg = 159 mm Hg = P_O2 at sea level
• 0.21 • 680 mm Hg = 143 mm Hg = P_O2 in Reno

Question 22

What is the partial pressure of a gas dissolved in a liquid?

Answer 22

• The partial pressure of a gas dissolved in a liquid is the partial pressure of that gas which would be generated in a gas phase in equilibrium with the liquid
  
  • P_gas = P_{dissolved gase}
• Dalton’s law: in a mixture of gases, the pressure exerted by any one gas is proportional to the fraction of the total number of molecules accounted for by that gas
  
  • “Partial pressure” - due to that one gas

Question 23

In an unopened bottle of soda water, the partial pressure of the gas above the liquid is…

Answer 23

The same as in the liquid

Question 24

Which way do gases travel in relation to the partial pressure and concentration gradients?

Answer 24

• Gases always travel down partial pressure gradients between biological compartments
• Gases may or may not travel down concentration gradients

Question 25

What does Henry's law say about how much gas dissolves in liquid?

Answer 25

* Henry's law: at equilibrium, the solubility of a gas in a liquid is _directly proportional_ to the partial pressure of the gas above the liquid P • K_H = C = Concentration K_H = Henry's constant is the proportionality factor, also called solubility coefficient * Different for every gas * Temperature dependent

Question 26

How much CO₂ dissolves in water in a beaker on the lab bench at 37˚C?

Answer 26

Use of Henry's law K_H for CO₂ in water at 37˚C = 0.03 mM/mmHg PCO₂ • K_H = C 0.23 • 0.03 = 6.9 µMolar * This is a *very* small number * Dissolved CO₂ is _not_ in the bubbles

Question 27

How much CO₂ dissolves in an artery?

Answer 27

Use Henry's law PaCO₂ = arterial partial pressure of CO₂ Normal PaCO₂ is 35-45 mmHg P • K_H = C 40 mmHg • 0.03 mmol/l/mmHg = 1.2 mM This value is \>\> 6.9 µM because humans are CO₂ making machines * Inhaled air is 0.03% CO₂ * Exhaled air is 4% CO2

Question 28

How does _alveolar_ partial pressure of CO2 (PACO₂) relate to _arterial_ partial pressure of CO2 (PaCO₂)?

Answer 28

* In normal lung function, PACO₂ = PaCO₂ = 40 mmHg * In veins, PvCO₂ = 45 mmHg * CO₂ goes into capillaries from tissues * Goes from capillareis to veins * From veins to alveoli

Question 29

What is the [HCO₃^-]/[CO₂] ratio in the blood?

Answer 29

[HCO₃^-]/[CO₂] ratio is **20** in normal human blood * Found by plugging in normal values for K_acid equation

Question 30

What is the Henderson equation?

Answer 30

* It is a clinician-friendly form of the K_acid equation * Magic value of 24!

Question 31

How is the Henderson equation used?

Answer 31

Solves for [H⁺] * [H⁺] is completely controlled by the PaCO₂/HCO₃^- ratio * This ratio dictates how acidic the blood will be * Can calculate [H⁺] when these values are known

Question 32

How much of a change in [H⁺] causes clinical deviation from normal pH?

Answer 32

Clinically significant deviations from normal pH correspond to ±2-fold changes in [H⁺]

Question 33

What is the clinical version of the Henderson Hasselbalch equation solving for pH?

Answer 33

pH = pKa + log )[HCO3-]/[CO2]) * Use PaCO2 * Use solubility coefficient of CO2 in water: 0.03 mM/mmHg * pKa = 6.1

Question 34

How is a buffer with a pKa of 6.1 physiologically important in the mainenance of the normal plasma pH of 7.4?

Answer 34

* The total concentration of the buffer system is high at 1.2 + 24 = 26 mM * The system is a cheater * It gets rid of the acid and adds base when you are not looking

Question 35

What is the significance of the bicarbonate system being open to the atmosphere?

Answer 35

* What if we added 5 mmol Hcl to 1 L blood? * Closed system (hold breath): pH = 6.6 * Open system (breathing): pH = 7.3 * The open system allows for removal of CO2 * Gives effective buffering even though the pKa = 6.1 is far from pH 7.4

Question 36

Why can the bicarbonate system not act as a buffer in response to changes in CO₂?

Answer 36

A buffering system cannot act as its own buffer * If the PaCO₂ increases - hypoventilation * If the system was acting as a buffer, it would require the reversal of the reaction (back to the lef), which would simply reverse the hypoventilation * CO₂ + H₂O → H⁺ + HCO₃^-

Question 37

How does hemoglobin respond to changes in CO₂?

Answer 37

* PaCO₂ increases from hypoventilation * System is driven to the right * There is a shift in equilibrium * Hb absorbes some of the protons produced by the equilibration of the bicarbonate system * This mitigates the increase in H⁺ caused by the added CO₂ * Hb is acting as a buffer

Question 38

What acids does the bicarbonate (volatile) system buffer?

Answer 38

* Metabolic acid production (MAP) * Gastrointestinal acid production (GAP)

Question 39

What are the two main processes that acidify the body?

Answer 39

* Metabolism produces CO₂, a weak acid * C₆H₁₂O₆ + 6 O₂ → 6 CO₂ + 6 H₂O + heat * CO₂ is exhaled * Does not consume bicarbonate, it generates it * Endogenous acid production (EAP) * All other acidifying processes, aside from CO2 * Strong acids (from body's perspective) * Metabolic * Gastrointestinal * All EAP _consumes_ bicarbonate

Question 40

What are the waste products of metabolic acid production pathways?

Answer 40

* **Carbs and lipids** - net acidifying effect * **Proteins** - _the major source_ of metabolic acid production * Higher % on average of cationic and sulfur containing amino acids * Amino acid backbone - no effect * **Organic anions** found in fruits and vegetables * E.g. potassium salts of acids (the A^- part) * Net _alkanizing_ effect

Question 41

What are the pKas like of organic acids?

Answer 41

* All of the pKa values are well below 7.4 * Lower than the normal pH * The HA will be very small and the A^- will be high * Essentially completely dissociated * Anion and proton

Question 42

What is the effect of the diet on metabolic acids?

Answer 42

Different diets produce different amounds of metabolic acids * Non-industrialized * More fruits and veggies * Lower rates of metabolic acid production * Industrialized * Higher in meats and eggs * Lower in fruits and veggies * Higher rates of metabolic acid production * Hospitalized patients * If not eating, high metabolic acid production * Eating their own protein - producing metabolic acid

Question 43

Which is produced more daily: CO₂ or metabolic acid?

Answer 43

Volatile acid production is ~ 100x more than non-volatile

Question 44

What is the buffer used for gastrointestinal acid production (GAP)?

Answer 44

Bicarbonate system serves as the buffer * Acid secreted by the gut into the blood * Consumes bicarbonate

Question 45

What is the role of the gut in acidifying the blood?

Answer 45

* Upper gut: gut cells can selectively dump protons into the gut lumen * Bicarbonate goes into the blood * As you eat, blood gets a little bit basic * Lower gut: bicarbonate goes in * Protons goe into the blood * Net result: more acid than base gets dumped into the blood stream

Question 46

What portion of endogenous acid production is metabolic versus gastrointestinal?

Answer 46

EAP = MAP + GAP * MAP = metabolic acid production * 2/3 of EAP * GAP = acid secreted by the gut into the blood * 1/3 of EAP

Question 47

How can the body maintain systemic pH even after consuming tons of meat?

Answer 47

Normal lung and kidney function * Using the bicarbonate system and blowing of CO₂ * Adding bicarbonate back to the blood from the kidneys

Question 48

How does vomiting influence pH?

Answer 48

* Reduces acid from the stomach lumen * Gut cells must make more acid for stomach lumen * Proces causes bicarbonate to enter blood * Prolonged vomiting can lead to **metabolic alkalosis**

Question 49

How does diarrhea influence pH?

Answer 49

* Removes bicarbonate in intestine * Intestinal cells must replace bicarbonate to lumen * Process causes protons to enter blood * Prolonged diarrhea can lead to **metabolic acidosis**

Question 50

How do the kidneys handle bicarbonate?

Answer 50

* Bicarbonate filtration * Bicarbonate passes through the glomeruli into the tubular fluid of the nephron * Bicarbonate reabsorption * Filtered bicarbonate is actively returned to the blood to make sure that plasma HCO₃^- does not fall * Bicarbonate regeneration (acid excretion) * New bicarbonate is made to replace that used to buffer endogenous acids * Ammonium excretion * Titratable acid excretion