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Biochemistry > Fundamentals of Body Buffers and Gases (B2: W6) > Flashcards

Fundamentals of Body Buffers and Gases (B2: W6) Flashcards

1
Q

What systems are involved in homeostasis of the blood?

A
  • Respiratory
  • Renal
  • Gastrointestinal
  • Cardiovascular

Rate of acid production = rate of acid excretion

Rate of O2 intake = rate of O2 utilization

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2
Q

How is pH of the blood determined?

A
  • 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
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3
Q

How is pH calculated?

A

pH = -log [H+]

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4
Q

What is the healthy range for pH?

A
  • 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
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5
Q

Where does acid production originate?

A

Intracellularly

  • Intracellular pH ~7.0
    • Proteins
    • Phosphates
    • Bicarbonate system
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6
Q

Why is intracellular pH not equal to extracellular pH?

A
  • 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
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7
Q

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

A

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

  • pKa of most body acids << 7.4
  • They are essentially fully ionized at pH 7.4
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8
Q

How is Ka calculated?

A

Ka = [H+][A-] / [HA]

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

Ka / [H+] = [A-] / [HA]

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

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9
Q

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

A

Because they use the same pool of H+

  • The common species to all is H+
  • Isohydric principle
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10
Q

What is the purpose of body buffer?

A

They maintain pH homeostasis

  • Weak acid-base pair
  • Lessen pH changes due to addition of strong acids or bases
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11
Q

How are high capacity buffers different from low capacity buffers?

A

High capacity ones are higher in concentration

  • pKas are closer to the working pH of their environment
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12
Q

What are the main buffers in the ECF?

A
  • Non-bicarbonate buffers - non-volatile
    • Hemoglobin
    • Plasma proteins
    • Phosphates
  • Bicarbonate buffer system - volatile
    • Volatile because CO2 gas is involved
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13
Q

Why is NH4+ not a buffer?

A

It is toxic to the brain

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14
Q

Which buffer has the highest buffer capacity of nonvolatile buffers?

A

Hemoglobin

  • Abundant histidine side chains - pKa ~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
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15
Q

Which is an important buffer in the renal tubular filtrate?

A

Phosphate

  • Not an important blood buffer
    • 1 mM - a few % of Hb capacity
  • ICF has high concentrations of others, ATP, ADP, phosphosugars, etc
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16
Q

How good are plasma proteins as buffers?

A
  • 20% of Hb buffering capacity
    • Also have histidine side chains
  • Albumin is the most plentiful plasma protein
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17
Q

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

A

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
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18
Q

Which is the _most powerful buffe_r of the ECF?

A

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
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19
Q

Define partial pressure

A

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 = PB
    • Depends on altitude
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20
Q

What is the partial pressure of carbon dioxide?

A

PCO2 is so low that it is clinically considered zero

  • Fraction = 0.03%
  • 0.0003 • 760 mm Hg = 0.23 mm Hg = PCO2 in air at sea level
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21
Q

What is the partial pressure of oxygen?

A
  • Fraction = 21%
  • 0.21 • 760 mm Hg = 159 mm Hg = PO2 at sea level
  • 0.21 • 680 mm Hg = 143 mm Hg = PO2 in Reno
22
Q

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

A
  • 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
    • Pgas = Pdissolved 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
23
Q

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

A

The same as in the liquid

24
Q

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

A
  • Gases always travel down partial pressure gradients between biological compartments
  • Gases may or may not travel down concentration gradients
25
Q

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

A
  • 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 • KH = C = Concentration

KH = Henry’s constant is the proportionality factor, also called solubility coefficient

  • Different for every gas
  • Temperature dependent
26
Q

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

A

Use of Henry’s law

KH for CO2 in water at 37˚C = 0.03 mM/mmHg

PCO2 • KH = C

0.23 • 0.03 = 6.9 µMolar

  • This is a very small number
  • Dissolved CO2 is not in the bubbles
27
Q

How much CO2 dissolves in an artery?

A

Use Henry’s law

PaCO2 = arterial partial pressure of CO2

Normal PaCO2 is 35-45 mmHg

P • KH = 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
28
Q

How does alveolar partial pressure of CO2 (PACO2) relate to arterial partial pressure of CO2 (PaCO2)?

A
  • 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
29
Q

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

A

[HCO3-]/[CO2] ratio is 20 in normal human blood

  • Found by plugging in normal values for Kacid equation
30
Q

What is the Henderson equation?

A
  • It is a clinician-friendly form of the Kacid equation
  • Magic value of 24!
31
Q

How is the Henderson equation used?

A

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
32
Q

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

A

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

33
Q

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

A

pH = pKa + log )[HCO3-]/[CO2])

  • Use PaCO2
  • Use solubility coefficient of CO2 in water: 0.03 mM/mmHg
  • pKa = 6.1
34
Q

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

A
  • 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
35
Q

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

A
  • 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
36
Q

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

A

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-
37
Q

How does hemoglobin respond to changes in CO2?

A
  • 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
38
Q

What acids does the bicarbonate (volatile) system buffer?

A
  • Metabolic acid production (MAP)
  • Gastrointestinal acid production (GAP)
39
Q

What are the two main processes that acidify the body?

A
  • 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
40
Q

What are the waste products of metabolic acid production pathways?

A
  • 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
41
Q

What are the pKas like of organic acids?

A
  • 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
42
Q

What is the effect of the diet on metabolic acids?

A

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
43
Q

Which is produced more daily: CO2 or metabolic acid?

A

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

44
Q

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

A

Bicarbonate system serves as the buffer

  • Acid secreted by the gut into the blood
  • Consumes bicarbonate
45
Q

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

A
  • 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
46
Q

What portion of endogenous acid production is metabolic versus gastrointestinal?

A

EAP = MAP + GAP

  • MAP = metabolic acid production
    • 2/3 of EAP
  • GAP = acid secreted by the gut into the blood
    • 1/3 of EAP
47
Q

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

A

Normal lung and kidney function

  • Using the bicarbonate system and blowing of CO2
  • Adding bicarbonate back to the blood from the kidneys
48
Q

How does vomiting influence pH?

A
  • 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
49
Q

How does diarrhea influence pH?

A
  • Removes bicarbonate in intestine
  • Intestinal cells must replace bicarbonate to lumen
  • Process causes protons to enter blood
  • Prolonged diarrhea can lead to metabolic acidosis
50
Q

How do the kidneys handle bicarbonate?

A
  • 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

Biochemistry (3 decks)

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