Lecture 5: Acid/Base Balance Flashcards
Acid produced from cellular metabolism is eliminated via the lungs in form of CO2, what is a product of the dissociation and what kind of acid is this?
- Carbonic acid
- Volatile acid
Acid produced from metabolism of protein and eliminated by the kidney is what kind of acid?
- Fixed acid
Calculation of pH
pH = log (1/H+)
What is the first line of defense against pH shift?
Chemical buffer system
1) HCO3- buffer
2) Phosphate buffer
3) Protein buffer
What is the second line of defense against pH shift?
Physiological buffers
1) Respiratory mechanism (CO2 excretion)
2) Renal mechanism (H+ secretion)
What is the biggest source of acid on a daily base?
Production of CO2 during aerobic respiration
CO2 from aerobic respiration combines with what molecules to form, and then dissociate into?
CO2 + H2O –>H2CO3 –> HCO3- + H+
What is the additional component of the bicarbonate buffer system, molecule involved, and where does it occur?
NaHCO3 in ECF
What does NaHCO3 ionize to?
Almost completely to HCO3- and NA+
What makes up the phosphate buffer system; when does each act?
- NaH2PO4 (acid) which donates H+ when the [H+] falls
- NaHPO4 (base) that can accept a free H+ when the [H+] rises
Where is phosphate significantly concentrated in the kidney?
The tubules, thereby increasing the buffering power of the phosphate system
What are the protein buffers in ICF and ECF?
ECF - albumin
ICF - hemoglobin
Which AA makes these proteins effective buffers, why?
Histidine - can bind or release H+
What is the role of hemoglobin as a buffer in the blood?
- Hb buffers the H+ generated from metabolically produced CO2 in transit between the tissues and the lungs.
- Venous blood is only slightly more acidic than arterial blood despite the large volumes of H+ generating CO2 carried in venous blood
What is the primary ECF buffer against noncarbonic acid charges?
H2CO3:HCO3- buffer system
What is the primary ICF buffer; that also buffers ECF?
Protein buffer system
We only measure the ECF pH clinically while managing patients, but is the ICF pH important; which is more efficient?
- Intracellular pH affects cell function
- Intracellular buffer system is more active and efficient in managing major pH changes
What is the most important buffer against carbonic acid changes and the most important urinary buffer?
Carbonic acid changes = Hemoglobin buffer
Urinary buffer = Phosphate buffer system
What is the calculation for pH when given HCO3- and PCO2?
pH = 6.1 + log ((HCO3-)/(0.03 x PCO2))
If asked to solved for [HCO3-], what is the rearranged equation?
[HCO3-] = 10^(pH-6.1) x 0.03 x PCO2
If asked to solve for PCO2, what is the rearranged equation?
PCO2 = ((HCO3-)/(10^(pH-6.1) x 0.03))
Why does faster, deeper breathing cause pH to rise?
More CO2 eliminated from lungs, which means less H2CO3 is formed, which means less H+ (higher pH)
Which physiologic buffer system responds quickest and which is needed for long term adjustments?
Respiratory = quickest (within minutes) by chemoreceptors sending pH
Renal system = long term adjustments (take 24 hour before kicking in)
How are the kidneys able to regulate pH?
Kindeys can produce HCO3- to replenish lost supplies
- When blood is acidic, kidneys reabsorb HCO3- and excrete H+
- When blood is alkaline, kidneys excrete HCO3- and retain H+
What is acidemia vs. alkalemia and what is the only value needed for measurement?
Acidemia indicated an acid pH (less than 7.35)
Alkalemia indicates an alkaline pH (greater than 7.45)
* Only refer to the pH of blood so this is the only value you need!
Respiratory acidosis; what values?
- Result of abnormal CO2 retention arising from hypoventilation
- pH <7.35 and a PaCO2 above 45 mmHg. HCO3- is normal
Respiratory alkalosis; what values?
- Lungs eliminating too much CO2
- pH > 7.45 and a PaCO2 below 35 mmHg. HCO3- is normal
Metabolic acidosis causes, values?
- Inability of the kidneys to excrete normal amounts of acid or a loss of base
- HCO3- <22 mEq/L and pH below 7.35, PCO2 is normal
Metabolic alkalosis causes, values?
- Loss of stomach acid, excess loss of Na+ or K+, renal loss of H+, or gain of base
- HCO3- >26 mEq/L and a pH >7.45, PaCO2 is normal
Normal range for pH, PaCO2, and HCO3- *KNOW THEM*
What is the mnemoic for determing the cause???
pH = 7.35 -7.45
PaCO2 = 35-45
HCO3- = 22-26
ROME = Respiratory Opposite Metabolic Equal
How to determine if complete or partial compensation?
Partial = pH not in normal range and opposite direction of HCO3- and PCO2
* If pH is acidotic and PCO2 is high you know its respiratory acidosis. If the HCO3- is not within the normal range you know you have respiratory acidosis w/ partial metabolic compensation
Complete = pH in normal range and opposite direction of HCO3- and PCO2
Label A-F in this diagram
A) Acute respiratory acidosis
B) Chronic respiratory acidosis
C) Metabolic alkalosis
D) Metabolic acidosis
E) Chronic respiratory alkalosis
F) Acute respiratory alkalosis
How would you interpret this?
Metabolic acidosis w/ partial respiratory compensation
Kidneys excreting acidic urine or basic urine reduces the amount in which compartment?
ECF
What occurs if more H+ is secreted in the tubular lumen than HCO3- that is filtered?
Net loss of acid from the ECF
What happens if more HCO3- is filtered than H+ is secreted?
There will be a net loss of base
Large numbers of HCO3- and H+ enter the tubular lumen how?
- Large amounts of HCO3- are filtered continuously
- Large numbers of H+ are secreted into the tubular lumen by tubular epithelial cells
What is the major mechanisms by which the kidneys maintain pH; what 2 steps are involved?
Regulation of serum bicarbonate concentration by promoting bicarbonate reabsorption and H+ excretion in the urine.
1) Proximal tubule reabsorb majority of HCO3- filtered from the blood, then…
2) Distal tubular secretion of H+ ions occurs
If the PCT reabsorbs all of the bicarbonate what occurs to H+; what cells involved in what part of nephron?
The late DCT intercalated cells will secrete more H+, and the HCO3- will be left behind in the body
If you are in alkalosis what will the PCT do and the late DCT?
PCT will not reabsorb all the HCO3-, and late DCT has nothing to do with alkalosis, just acidosis
Why is there a net gain of HCO3- in the kidney?
Since H+ has a new buffer (NH3 or phosphate), and the H+ is secreted, leaving behind the HCO3-
Intercalated cells are inolved in?
FIne regulation of acid-base balance
2 types of intercalated cells; which is most abundant?
Type A (most abundant): H+-secreting, HCO3-reabsorbing, K+-reabsorbing cells
Type B: HCO3-secreting, H+-reabsorbing, K+ secreting cells, oppostie actions of type A
How do Type A intercalated cells function; what 2 pumps?
They actively secrete H+ into tubilar lumen via 2 types of primary active transport mechanisms: H+ ATPase pumps and H+-K+ ATPase pumps
*Important for helping us when we are acidotic
In contrast to Type A cells, where are the pumps for Type B cells and what are they?
Active H+-ATPase pumps and H+-K+-ATPase pumps are located at the basolateral membrane and the Cl2-HCO3 antiporters are located at the luminal membrane
In the intercalated cells of the dital tubule, a H/CL co-transport is involved with secretion of?
H+
What does the formationof the H+ inside the cell provide?
A gradient for the secretion of more H+ into the lumen to complex with and reabsorb more HCO3-
Why is the distal pathway a major site for creating an acidic urine pH 4.5
Accounts for only 5% of secreted H+, but the H+ gradient it can form is 900x!
What are the 2 main urinary buffers; which is the major?
- Phosphate buffer (major buffer)
- Ammonia buffer
The concentration of phosphate in the urine depends on (aka what is the rate limiting step)?
Amount of dietary intake and the amount filtered and later reabsorbed in the proximal tubules
What is the phosphate buffer rxn?
H+ + HPO4 —> H2PO4-
The phosphate that is filtered is in what forms; what happens to the phosphate as it moves through the PCT?
20% H2PO4
80% HPO4
As H+ secretion decreases the pH in the PCT, up to 50% of the phosphate in the lumen goes to the H2PO4 form.
Luminal Na+ is reabsorbed in exchange for, and what does the Na+ leave with?
Na+ is reabsorbed in exchange for H+ and the Na+ exits together with the HCO3- formed in the cell, across the basolateral membrane
What is the amount of HCO3 generated for each H+ secreted due to what?
One HCO3- is generated for each H+ secreted due to titration of the phosphate from the mono- to the di-protonated form. Diprotonated phsophates (H2PO4 is excreted)
What is the most abundandnt naturally occuring AA that provides an unending substrate for renal ammoniagenesis?
Glutamine
Where is glutamine absorbed from and what is it converted to; what else is produced by this rxn?
Proximal tubule cells absorb glutamine from peritubular capillaries and convert glutamine into ammonium (NH4) and alpha-ketoglutarate; this rxn also generates 2 HCO3- ions, which are returned to systemic circulation
What happens to the NH4 produced from glutamine?
Transported across the apical membrane via NHE, and is eventually eliminated in the urine
What is the sum of the NH4+ excretion and the titratable acids excreted (in mEq/L) minus the HCO3- (mEq) that might escape in urine called?
NET ACID EXCRETION
How does RAAS play a role in acid-base of the kidneys?
- Primary role is the aldosterone on the distal tubule and collecting duct to stimulate Na+ reabsorption by principal cells
- Stimulates intercalated cells in these segments to secrete H+, this effect is both direct and indirect.
Explain the direct and indirect effect of aldosterone on acid-base maintenacne?
- Stimulating Na+ reabsorption by principal cells hyperpolarizes the transepithelial voltage
- Change in transepithelial voltage facilitates the secretion of H+ by the intercalated cells (type A) = indirect effect
- Aldosterone (and angiotensin II) acts directly on intercalated cells to stimulate H+ secretion via the H+ ATPase
Calculation for Anion Gap
AG = [Na+] - ([Cl-] + [HCO3])
What constitutes a high anion gap metabolic acidosis; what does this mean?
Range of 30 mEq/L or more = high anion gap acidosis is virtually always present regardless of what the pH and the [HCO3-] are
What is a increases anion gap called; and what causes it?
Normochloremia
- Diabetes mellitus (ketoacidosis)
- Lactic acidosis
- Chronic renal failure
- Aspirin poisoning
- Methanol poisoning
- Ethylene glycol poisoning
- Starvation
What is normal anion gap called metabolic acidosis called; what causes it?
Hyperchloremic
- Diarrhea
- Renal tubular acidosis
- Carbonic ahydrase inhibitors
- Addison’s disease
