RESPIRATORY - Acid Base Balance
what two bodily systems regulate blood pH?
Respiratory and renal
What is the pK of the carbon dioxide/bicarbonate
The pK of carbon dioxide/bicarbonate buffer is 6.1 The pK of the phosphate buffer is 6.8
Differentiate between respiratory acidosis, respiratory alkalosis, metabolic acidosis, and metabolic alkalosis and identify the simple pathologies that would cause/drive each. (this is one of the lecture objectives)
-Respiratory acidosis: increase in PaCO2 driven by lungs -Respiratory alkalosis: decrease in PaCO2 driven by lungs -Metabolic acidosis: decrease in blood pH via a metabolic, drug, or toxin disturbance Typically driven by muscles, liver, or GI -Metabolic alkalosis: increase in blood pH via metabolic, drug, or toxin disturbance Typically driven by GI
Explain the chemical basis of a generalized buffer, the primary buffering systems of the blood, and why buffers are essential to life.
Body is very sensitive to changes in pH/H+ concentration. Consequently, in an ever changing environment buffers are necessary. Buffers "soak up" extra H+ or OH- Buffers in the human body: H+ + HCO3- H2CO3 (most important; extracellular) H+ + Protein H-Protein (intracellular in plasma) H+ + HPO4- H2PO4(intracellular and extracellular)
Explain what happens during metabolic alkalosis and describe how this would be demonstrated on a davenport diagram.
Both HCO3- and pH have increased Move along PaCO2 isopleth (40 mm Hg) to higher blood pH To new buffer line, which is parallel to the old buffer line
Explain what happens during metabolic acidosis and describe how this would be demonstrated on a davenport diagram.
Both blood pH and HCO3- have decreased Move along PaCO2 isopleth (40 mm Hg) to lower blood pH New buffer line, which is parallel to the old buffer line
What is the significance of a buffers pK
Buffers work best at a pH that is close to the buffer's pK. This is because when the pH of a solution is equal to the pK of the buffer, there are equal quantities of acid and its conjugate base.
Describe the CO2/carbonic acid/bicarbonate relationship and predict how a change in one of the substances in this biochemical reaction will affect the relative concentration of the other substances and, ultimately, pH.
CO2 + H2O <--> H2CO3 <--> H+ + HCO3- Le Chatliers priciple
What are common causes for respiratory alkalosis?
Causes: Hyperventilation due to anxiety Hyperventilation due to high altitude
What are common causes of metabolic acidosis?
Causes: Ketone bodies (weak acids) produced in diabetes Lactate produced by hypoxic tissues during surgery or tissue stress Kidney failure (inability to excrete fixed acid)
What are common causes of metabolic alkalosis?
Causes: Loss of gastric acid (hyperemesis), such in pregnancy, cholera Overuse of antacids due to heart burn/ulcers/other
What are common causes of respiratory acidosis?
Causes: Respiratory depression due to sedative overdose (opioid, benzodiazepines, or others) Mismatch of ventilation and perfusion Severe emphysema or pneumonia
Use Davenport diagrams to understand the relationship between PCO2, pH, and HCO3-, including the meaning of a PCO2 isopleth and a buffer line. (this is one of the lecture objectives)
Changes in PaCO2 (usually due to respiratory changes) will move values along the Buffer Line Addition of acid or base to the blood (not associated with the respiratory system) will move values along a PaCO2 isopleth
What is a davenport diagram
Davenport Diagram is a plot between pH and HCO3- at various PaCO2 (plot of three variables) Blood is typically at "A" pH of 7.4 HCO3- of 24 mM (mEq/l)
Under what conditions will the pH = the pK? Under what conditions will the pH be greater than the pK? Under what conditions will the pH be less than the pK?
If the [A-] = [HA], then pH = pK If HA > A-, then pH < pK If HA < A-, then pH > pK
Explain what happens during metabolic acidosis with respiratory compensation and describe how this would be demonstrated on a davenport diagram.
In response to a drop in blood pH, peripheral chemoreceptors will stimulate respiratory drive, increasing both tidal volume exchanges and respiratory rate The increase in respiratory drive, PaCO2 will decrease, moving along the new buffer line Blowing off CO2 Compensation will almost always be incomplete
Explain what happens in respiratory acidosis with metablolic compensation. How is this shown on a Davenport Diagram?
In response to a drop in blood pH, the kidneys excrete acid. The kidneys are unable to affect the PaCO2, which stays constant (80 mm Hg here) Move along 80 mm Hg PCO2 isopleth to a new pH Compensation will almost always be incomplete
Explain what happens in respiratory alkalosis with metablolic compensation. How is this shown on a Davenport Diagram?
In response to a rise in blood pH, the kidneys excrete HCO3- The kidneys are unable to affect the PaCO2, which stays constant (20 mm Hg here) Move along 20 mm Hg PCO2 isopleth to a new pH Compensation will almost always be incomplete
Explain what happens during metabolic alkalosis with respiratory compensation and describe how this would be demonstrated on a Davenport Diagram.
In response to an increase in blood pH, peripheral chemoreceptors may reduce respiratory drive, but this usually doesn't occur The decrease in respiratory drive, will cause PaCO2 to increase, moving along the new buffer line to a lower pH Retaining CO2
Reaching the same point on Davenport Diagram in different ways. How to know what is happening? ...
Presents with blood pH of 7.39 and bicarb of 10 mM What is happening? Respiratory alkalosis with metabolic compensation? Metabolic acidosis with respiratory compensation? How would we know? ABG values Other: Hyperventilation Ketoacidosis (see slide #19)
If normal pH in the blood is 7.4, at what pH values does the body start experiencing problems? What pH values would cause death?
Problems occur when pH is below 7.2 (6.3 x 10-8 M) or above 7.55 (2.8 x 10-8 M). Death occurs outside of 6.9 and 7.8
Differentiate between volatile acid and fixed acid in the human body.
Respiratory system excretes about 10,000 mmol of carbonic acid per day in the form of CO2 (volatile acid) Kidneys excrete about 100 millimoles of acid per day (fixed acid) Therefore, the respiratory system potentially has a much larger impact on blood pH than does the kidneys
What is the typical concentration of hydrogen ions in the blood? How about sodium ion concentration?
Typical blood [H+] is 4 x 10-8 M (40 nEq/L) Typical blood [Na+] of 0.14 M (140 mEq/L) Blood [Na+] is 3.5 million times higher than is blood [H+]!
What is the normal pH in the blood? What is the equation used to determine pH?
Under normal conditions, blood pH is: pH = -log[H+] = -log[4 x 10-8] = 7.4
In respiratory acidosis, what are the [H+], pH, and plasma [HCO3-] values relative to normal physiological values? How would this be demonstrated on a Davenport Diagram?
[H+] = elevated pH = decreased plasma [HCO3-] = increased Thus on a davenport diagram -> Move up the buffer line to a new PaCO2 (80 mm Hg in this case)
In respiratory alkalosis, what are the [H+], pH, and plasma [HCO3-] values relative to normal physiological values? How would this be demonstrated on a Davenport Diagram?
[H+] has decreased Blood pH has increased Plasma HCO3- has decreased Move down the buffer line to a new PaCO2 (20 mm Hg in this case)
Understand and appreciate how the Henderson-Hasselbalch equation permits us to calculate the pH of a buffered solution.
𝑝𝐻=𝑝𝐾+log((𝐶𝑜𝑛𝑗𝑢𝑔𝑎𝑡𝑒 𝐵𝑎𝑠𝑒)/𝐴𝑐𝑖𝑑) pH = pK + log [A-]/[HA]
How would we use the Henderson Hasselbach equation to figure out the pH of blood?
𝑝𝐻=𝑝𝐾+log((𝐻𝐶𝑂_3^−)/(0.03×𝑃𝑎CO_2 )) Under normal conditions: HCO3- = 24 mM PCO2 = 40 mm Hg So: pH=6.1+log(24/(0.03×40)) pH=6.1+log(20) pH = 7.4
