Fundamentals of Body Buffers and Gases (B2: W6) Flashcards
What systems are involved in homeostasis of the blood?
- Respiratory
- Renal
- Gastrointestinal
- Cardiovascular
Rate of acid production = rate of acid excretion
Rate of O2 intake = rate of O2 utilization
How is pH of the blood determined?
- 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
How is pH calculated?
pH = -log [H+]
What is the healthy range for pH?
- 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
Where does acid production originate?
Intracellularly
- Intracellular pH ~7.0
- Proteins
- Phosphates
- Bicarbonate system
Why is intracellular pH not equal to extracellular pH?
- 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
How can H+ be so important when its concnetration is 40 nm at pH 7.4?
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
How is Ka calculated?
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
Why does an alteration in pH affect relative concentrations of every conjugate acid and base of all the weak electrolytes?
Because they use the same pool of H+
- The common species to all is H+
- Isohydric principle
What is the purpose of body buffer?
They maintain pH homeostasis
- Weak acid-base pair
- Lessen pH changes due to addition of strong acids or bases
How are high capacity buffers different from low capacity buffers?
High capacity ones are higher in concentration
- pKas are closer to the working pH of their environment
What are the main buffers in the ECF?
- Non-bicarbonate buffers - non-volatile
- Hemoglobin
- Plasma proteins
- Phosphates
- Bicarbonate buffer system - volatile
- Volatile because CO2 gas is involved
Why is NH4+ not a buffer?
It is toxic to the brain
Which buffer has the highest buffer capacity of nonvolatile buffers?
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
Which is an important buffer in the renal tubular filtrate?
Phosphate
- Not an important blood buffer
- 1 mM - a few % of Hb capacity
- ICF has high concentrations of others, ATP, ADP, phosphosugars, etc
How good are plasma proteins as buffers?
- 20% of Hb buffering capacity
- Also have histidine side chains
- Albumin is the most plentiful plasma protein
What is the most important function of the non-volatile buffers?
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
Which is the _most powerful buffe_r of the ECF?
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
Define partial pressure
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
What is the partial pressure of carbon dioxide?
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
What is the partial pressure of oxygen?
- 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
What is the partial pressure of a gas dissolved in a liquid?
- 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
In an unopened bottle of soda water, the partial pressure of the gas above the liquid is…
The same as in the liquid
Which way do gases travel in relation to the partial pressure and concentration gradients?
- Gases always travel down partial pressure gradients between biological compartments
- Gases may or may not travel down concentration gradients
What does Henry’s law say about how much gas dissolves in liquid?
- 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
How much CO2 dissolves in water in a beaker on the lab bench at 37˚C?
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
How much CO2 dissolves in an artery?
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
How does alveolar partial pressure of CO2 (PACO2) relate to arterial partial pressure of CO2 (PaCO2)?
- 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
What is the [HCO3-]/[CO2] ratio in the blood?
[HCO3-]/[CO2] ratio is 20 in normal human blood
- Found by plugging in normal values for Kacid equation
What is the Henderson equation?
- It is a clinician-friendly form of the Kacid equation
- Magic value of 24!
How is the Henderson equation used?
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
How much of a change in [H+] causes clinical deviation from normal pH?
Clinically significant deviations from normal pH correspond to ±2-fold changes in [H+]
What is the clinical version of the Henderson Hasselbalch equation solving for pH?
pH = pKa + log )[HCO3-]/[CO2])
- Use PaCO2
- Use solubility coefficient of CO2 in water: 0.03 mM/mmHg
- pKa = 6.1
How is a buffer with a pKa of 6.1 physiologically important in the mainenance of the normal plasma pH of 7.4?
- 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
What is the significance of the bicarbonate system being open to the atmosphere?
- 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
Why can the bicarbonate system not act as a buffer in response to changes in CO2?
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-
How does hemoglobin respond to changes in CO2?
- 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
What acids does the bicarbonate (volatile) system buffer?
- Metabolic acid production (MAP)
- Gastrointestinal acid production (GAP)
What are the two main processes that acidify the body?
- 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
What are the waste products of metabolic acid production pathways?
- 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
What are the pKas like of organic acids?
- 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
What is the effect of the diet on metabolic acids?
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
Which is produced more daily: CO2 or metabolic acid?
Volatile acid production is ~ 100x more than non-volatile
What is the buffer used for gastrointestinal acid production (GAP)?
Bicarbonate system serves as the buffer
- Acid secreted by the gut into the blood
- Consumes bicarbonate
What is the role of the gut in acidifying the blood?
- 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
What portion of endogenous acid production is metabolic versus gastrointestinal?
EAP = MAP + GAP
- MAP = metabolic acid production
- 2/3 of EAP
- GAP = acid secreted by the gut into the blood
- 1/3 of EAP
How can the body maintain systemic pH even after consuming tons of meat?
Normal lung and kidney function
- Using the bicarbonate system and blowing of CO2
- Adding bicarbonate back to the blood from the kidneys
How does vomiting influence pH?
- 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
How does diarrhea influence pH?
- Removes bicarbonate in intestine
- Intestinal cells must replace bicarbonate to lumen
- Process causes protons to enter blood
- Prolonged diarrhea can lead to metabolic acidosis
How do the kidneys handle bicarbonate?
- 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
- New bicarbonate is made to replace that used to buffer endogenous acids
