L9 Acid/Base Physiology Flashcards
Acid/base physiology describes the regulation of …
H+ concentrations in the ECF
The three main components of the homeostatic regulation of [H+] in the body
Buffered (fast): bicarbonate, proteins, phosphates, etc
Respiratory compensation: alters CO2 levels
Renal compensation (slow): alters HCO3- levels
____ is a short-hand method of expressing [H+]
pH
pH = -log[H+]
Plasma [H+] = 0.00000004 moles/L = 0.00004 mEq/L
So pH = -log[0.00000004] = 7.4
A 10-fold increase in [H+] = 1 unit change in pH
Normal blood pH = ?
7.4 (pH = -log[H+] = -log[0.00000004])
Normal range is 7.37-7.42 so [H+] can vary by +7 and -5 % around it’s mean of 40 nEq/L
pH and [H+] are related ________
Logarithmically
Increasing pH from 7.4 to 7.6 will decrease [H+] by 15 nEq/L
Decreasing pH from 7.4 to 7.2 will increase [H+] by 23 nEq/L
Normal [H+] ranges in different parts of the body
Gastric HCl [H+] = 0.15mol/L —> pH = 0.8
Max urine acidity [H+] = 3x10^-5 —> pH = 4.5
Normal plasma [H+] = 4x10^-8 —> pH = 7.4
Extreme acidosis pH = 7
Extreme alkalosis pH = 7.7
Pancreatic juice [H+] = 1 x 10^-8 —> pH = 8.0
13,000 to 20,000 mEq/day of H+ is produced from …
Respiratory CO2
Almost entirely handled by lungs
Known as volatile acid
Also, significant amounts of non-volatile, or fixed, acid arise from normal and abnormal processes:
• Degradation of certain amino acids
• Additional acid loads from exercise (lactate), diabetic kenos is (ß-hydroxy butyric & acetoacetic acides), and ingestion of acids
We produce ____ mEq/day of fixed (non-volatile) acid
50 mEq/day
From gluconeogenic utilization of AAs in the liver
Sulfuric acid from methionine and cysteine catabolism (75%); phosphoric acid from phospholipid degradation (25%)
Represent major acid load that kidney must eliminate
Acids are H+ ________ and bases are H+ ______
Acid = donor, base = acceptor
HA H+ + A- (A- = conjugate base)
The constant K can be defined as
The product of [H+] and [A-] divided by [HA]
K = [A-][H+]/[HA]
Rearranged:
[H+] = K[HA]/[A-]
What is the Henderson-Hasselbach equation?
Log[H+] = log K + log [HA]/[A-]
Since pH = -log[H+], we can rearrange:
pH = pK + log[A-]/[HA]
________ have lower affinities for hydrogen ions which dissociate easily from the conjugate base
Strong acids
They also have lower pK.
________ have higher affinities for hydrogen ions which do not dissociate as easily from the conjugate base
Weak acids
Have high pKs than strong acids
The first line of defense against pH changes?
Buffers
Located in the ECF, ICF, and bone
The effectiveness of a buffer is proportional to:
Its concentration and its pK
The most important buffer system in ECF?
Bicarbonate, due to its high concentration (22-26 mEq/L).
Both CO2 and HCO3- are tightly regulated by the following equation:
CO2 +H2O H2CO3 H+ + HCO3-
________ consist of acid and conjugate base pairs (ie HA/A-)
Buffers
At low pH’s, [HA] > [A-]; at high pH’s, [A-] > [HA]
Under base load, HA can contribute H+; under acid load, A- can absorb H+. pH changes little
Because titration curves for acids are not linear, most effective buffering is …
+/- one pH unit from pK
What are the acid/conjugate base pairs for the bicarbonate and phosphate buffers systems?
HCO3-/H2CO3 (CO2)
HPO4^2-/H2PO4-
Since the pH of blood is 7.4, which would you THINK would be the better buffer, phosphate (pK = 6.8) or bicarb (pK = 6.1)?
You would think phosphate because its pK (6.8) is within 1 pH unit of the homeostatic pH.
Bicarb is still more important in the blood though…
Well then what ARE the important buffers of the blood?
1) Bicarbonate (53% of total buffering capacity) - pK is low (6.1) but it’s effective due to its concentration and because both the acid (H2CO3) and base (HCO3-) are regulated
2) Hemoglobin (35%): Hb- + H+ HHb
Imidazole groups on histidine and alpha amino groups are the primary buffer sites on all proteins
3) Proteins (7%): Prot- + H+ HProt
Have good pKs (6.4-7.9) but concentrations are too low
4) Phosphate (5%)
Unimportant in blood due to low concentration
VERY important in urine where concentrations are higher
The primary INTRACELLULAR buffers are …
Proteins: high [IC], pK’s close to 7.4
Phosphate has the same advantages as proteins
Bicarb is a secondary intracellular buffer because concentration is low
Why are bones a special case in the world of buffering?
They take up [H+] in exchange for Na+ and K+
Bone minerals may account for a significant amount of body buffering capacity during acute acid loads.
The __________ buffer system is the most important blood buffer for pH regulation
Bicarbonate
The pH of blood, as determined by the Henderson-Hasselbach equation
pH = pK + log [HCO3-]/(0.03 x Pco2)
pK of bicarb = 6.1
HCO3- = 24 mEq/L
Pco2 = 40 mmHg
pH = 6.1 + log(24/(0.03x40)) = 7.4
Decreasing bicarbonate concentration OR increasing Pco2 is called…
Acidosis
Increasing bicarbonate concentration OR decreased Pco2 is called…
Alkalosis
Regulation of pH is called …
Compensation
Buffers respond quickly to acid/base disturbances, but they can’t return pH to normal (only minimize pH change)
Compensation occurs as lungs and kidneys regulate CO2 and HCO3- respectively, such that the ration of [HCO2-] to dissolved CO2 remains near 20
Changes in [HCO3-] are termed ________ disturbances
Metabolic disturbances
Loss or gain of HCO3- is compensated for by both the kidneys and the lungs
After initial buffering, changes take minutes to days
In metabolic disturbances, the _________ is quick to respond and the ________ are slow.
Respiratory system is quick, kidneys are slow
Kidneys sometimes CAUSE the metabolic defect, in which case, the __________ can compensate
Respiratory system
Changes in CO2 levels are termed ___________ disturbances and must be compensated for by __________.
Respiratory disturbances, compensated for by the kidneys
After initial buffering, compensation takes days
Examples of metabolic acidosis
Plasma HCO3- decreases, caused by ingestion of acid, formation of metabolic acids (ie lactic acid) etc
How does the body respond in cases of metabolic acidosis?
Respiratory system: By increasing ventilation to expel CO2
Kidneys: Synthesize new HCO3-
Examples of metabolic alkalosis
Plasma HCO3- increases, due to ingestion of excessive antacids or vomiting (loss of gastric acid)
How does the body respond to metabolic alkalosis?
Respiratory system: Reduces ventilation to retain CO2
Kidneys: excrete excess HCO3-
Examples of Respiratory Acidosis
Plasma Pco2 increases, due to decreased ventilation (drug overdose, airway obstruction etc)
How does the body respond to respiratory acidosis?
If condition persists, the kidneys will synthesize new HCO3- and excrete H+ in the urine to raise blood pH
Examples of respiratory alkalosis
Plasma Pco2 decreases due to hyperventilation (stress, high altitude, etc)
How does the body respond to respiratory alkalosis?
Kidneys will excrete HCO3-, causing the urine to become alkaline; blood HCO3- and pH will decrease
