Day 2: Acids/Bases and Acid/base Disorders Flashcards
Bronstead-Lowry definition of acid/base
Acid = proton donor
Base = Proton Acceptor
What are strong acids?
Essentially 100% dissociated (increase H+ significantly) HCl
What are strong bases
essentially 100% dissociated (increase in OH- significantly) NaOH
What are conjugate pairs?
Drugs have weak acids or bases and a drug that has both acidic and basic forms are the conjugate pairs
What is the pKa value?
The tendencu of the donor form of the pair to donate a proton.
is derived from the Ka and the Ka is the equilibrium constant that quantitates teh tendency of the donor form to donate its proton
What causes there to be a higher vs low Ka value?
If drug molecules are weak acids then they will have a low numerical value. (unlikely to donate a proton; base)
If a drug has a strong tendency to donate a protein the Ka will be higher and the log value will be lower. (donate a protein; acid)
What kind of molecules willl have a low pKa
Acids will have a lower pKa
Explain how the example of HQ has its conjugate base and how the pKa value determines the strength of its conjugate base
Q- (potential proton acceptor) is the conjugate base of HQ.
The strength of Q- as a proteon acceptor is inversely related to the strength of its conjugate acid.
EX: if the pKa is 4 it means its a stronger base (higher means higher base) than if the pKa was 2.
What is a major consideration for drug delivery ?
Whether or from where a drug will be absorbed from the digestive tract. This requires the ability of a molecule to pass thro lipophilic (hydrophobic) bio membranes
This is less likely to occur if the molecule is ionized. this makes it important to know the degree of ionization (charge) of the drug molecule within the body
Equation to find the pH
pH= -log[H+]
Equation for the pKa
pKa = -log_[H+][Q-]_/[HQ]
Equation to find pH using the pKa
pH= pKa+log[Q-]/[HQ]
How can you think about amines and carboxylic acids in terms if acids and bases
amines = bases
carboxylic acids = acids
What are the two forms of an amine and what are the charges of them
The acidic form (donor form, protonated form) is charged
the basic form (acceptor form, deprotonated form) is neutral
What is the forms of carboxylic acids and their charge?
Acidic form (donor form, protonayed form) is neutral
basic form (acceptor form, deprotonated form) is charged
Generally what are true for donors, or protonated forms?
- present at low pH
- on the left side of an equilibrium
- in the denominator of the Henderson-hasselbalch equation
What is the normal pH of arterial blood ?
7.40 with a reference range of 7.36-7.44)
What are the three major mechanisms that maintain pH?
- chemical buffering
- action of the lungs (respiratory regulation)
- action of the kidney (renal regulation)
What does the body do in order to prevent drastic changes in pH
It uses “buffering” by the action of weak acids and their conjugate bases that act to neutralize incoming H+ or incoming OH-
Explain how the body handles this in buffering its pH
If HA is a weak acid, it can donate a proton to water to yeild the conjugate acid and the weak base A-. If a strong acid is added to the system the rxn will move to the left (reducing the effect of excess H+)
If a base is added it will drive the rxn to the right
What is the bicarbonate buffer system?
Most important extracellular buffering system and the one generally considered cliniclally.
Carbonic acid (H2CO3) exists in very low concentrations in the body. For this reason CO2 is considered to be the weak acid in the system
What is the phosphate buffer system?
Plays an important role intracellularly as well as in the kidneys
What is the Ammonia buffer system?
Plays an important role in the kidneys. Ammonia is a by-product of amino acid metabolism and thus amino acids can serve as a source of buffers when metabolized in the kidney
How do proteins work as buffers?
Among the most plentiful buffers due to their high concentrations inside cells. The acidic side chains of amino acid residues on proteins are normally deprotonated at physiological pH. These side chains contribute to buffering by accepting or donating protons in reponse to changes in pH in the body
How does respiratory regulation of acid-base balance work?
The lungs act as a second line of defense againt changes in pH. They do so by regulating acid/base balance via removal of carbon dioxide in pulmonary expiration.
Since CO2 is effectively an acid, removal by the lungs serves to lower the concentration of H+ and raise the pH.
How do the lungs regulated CO2 in order to respond to acidic and alkaline conditions?
CO2 is continuously formed in the body (by product of carb metabolism) and it needs to be removed.
In acidic conditions, the lungs increase ventilation to hasten the removal of CO2
In alkaline conditions, ventilation of lungs can be dimisnished to enable retention of CO2, thus raising the pCO2 and lower the pH
How does the renal regulation of acid/bases effect pH in the body?
The kidneys regulate acid-base balce by excreting acidic or basic urine depending on what conditions require.
Under acidic conditions: excess H+ is removed in the urine thereby raising the pH in the blood
Under basic conditions: HCO3 _ is removed via urine in oder to lower pH
Kidneys are the most effective but slowest line of defense against disturbances in acid base balance.
How does filtering and reabsorption of bicarbonate work?
As bicarb enters inot the tuble lumen (inside part of the kidney), if its not reabsorbed (back into bloodstream) it will be excreted.
What is the process of bicarbonate being reabsorbed?
Bicarb by itself is not well reabsorbed
It can combine with a proton to form CO2 and water and then enter the renal tubule cell.
Once in the renal tuble cell the CO2 and water forms carbonic acid which quickly dissociayes to a proton and bicarb.
This newly formed bicarb can pass back into the capillary and back into the bloodstream.
Around 90% of bicarb is reabsorbed this way.
How does the kindey use bicarb reabsorption to control acid/base balance.
When the plasma has excess acid, the kidney can reabsorb ALL the bicarb and raise the pH level.
In the cass of alkalosis, less bicarb is reabsorbed (more is excreted) this will lower the pH in order to restore it to normal.
What are the two major categories for acid/base disorders?
Acidosis = blood pH is below normal (pH<7.36)
Alkalosis = blood pH is above normal (pH>7.44)
What are the 4 possible disorders for classification of acid/base balance?
Respiratory acidosis
Metabolic acidosis
Respiratory alkalosis
Metabolic alkalosis
What is Respiratory acidosis?
Cause: Failure of the lungs to adequately remove CO2
EX: Advanced pulmonary disease
Measures: low pH, increased pCO2 normal bicarb
What is mebabolic acidosis?
Cause: addition of acid to the body
EX: excess aspirin ingestion, DKA, diarrhea
Measures: low pH, normal pCO2 and low bicarb
what is Respiratory Alkalosis?
Cause: excessive expulsion of CO2 by the lungs
EX: hyperventilation
Measures: high pH, normal bicarb, low pCO2
What is metabolic alkalosis?
Cause: addition of base or loss of acid by the body
EX: excessive ingestion of bicarb, protracted vomiting
Measures: high pH, high bicarb, normal pCO2
What do the kindeys do when it comes to compensation?
They will respond by modulating bicarb concentrations.
EX: in the case of respiratory acidosis, the kindeys will reabsorb more bicarb in order to restore normal pH
What will the lungs do in order to compensate in cases of primary metabolic disorders?
By appropriately increasing or decreasing the expiration of CO2
EX: in metabolic alkalosis, repiration will slow which will result in an increase in the pCO2 and lower pH
What is an Arterial Blood Gas (ABG, “blood gas”)
Test to evaluate respiratory diseases and conditions that affect the lungs
It determines the body’s acid/base balance (which, in turn, is regulated by the kidneys and lungs)
Normal Value for Partial pressure of oxygen (PaO2)
75-100 mmHg
Normal values of Partial pressure of carbon dioxide (PaCO2 or PCO2)
36-44 mmHg
normal values for arterial blood pH
7.36-7.44
Normal values for oxygen saturation (SaO2)
94-100%
Normal level for bicarbonate (HCO3)
22-28 mEq/L
Respiratory Acidosis in terms of pH, HCO3 and pCO2
pH = decreased
HCO3 = normal
pCO2 = increased
respiratory acidosis (compensated) in terms of pH, HCO3 and pCO2
pH = decreased
HCO3 = increased
pCO2 = increased
Metabolic acidosis in terms of pH, HCO3 and pCO2
pH = decreased
HCO3 = decreased
pCO2 = normal
Metabolic acidosis (compensated) in terms of pH, HCO3 and pCO2
pH = decreased
HCO3 = decreased
pCO2 = decreased
Respiratory alkalosis in terms of pH, HCO3 and pCO2
pH = increased
HCO3 = normal
pCO2 = decreased
Respiratory alkalosis (compensated) in terms of pH, HCO3 and pCO2
pH = increased
HCO3 = decreased
pCO2 = decreased
Metabolic alkalosis in terms of pH, HCO3 and pCO2
pH = increased
HCO3 = increased
pCO2 = normal
Metabolic alkalosis (compensated) in terms of pH, HCO3 and pCO2
pH = increased
HCO3 = increased
pCO2 = increased
What is the anion gap?
Parameter to help distinguish between types of acidosis.
Anion gap = [Na+] - [Cl- + HCO3 _]
Reference range = 6-16 mEq/L
