Lecture 11/12 Flashcards
The regulation of H+ is most important where? Why?
Intracellularly –> where most protein enzymes are located
The extracellular plasma H+ is mostly regulated by what two organs?
Kidneys & Lungs
What induces strong shifts in K+?
Weak shifts in K+?
- HCL/KCl –> mineral acids!
- Organic Acids
- lactic acidodis (metabolic acidosis)
- hypercarbia (respiratory acidosis)
- hypocarbia (respiratory alkalosis)
What are the three major systems responsible for maintaining Arterial Plasma [H+]?
- Chemical Buffering
- Renal System (slow responding)
- Respiratory System (rapidly responding)
Describe the 3 Chemical Buffering systems in the kidney. (3)
- Phosphate Buffer system
- Protein Buffers (hemoglobin, intracellular proteins)
- Bicarbonate Buffer
Describe how the Renal system is responsible for maintaining Arterial plasma H+.
- Kidney excretes 50 mol of H+ per day as H+, NH4+, and H2PO4 (urine is acidic)
- Kidney reabsorbs 5500 mol of HCO3- per day (bicarbonate is at renal plasma threshold)
Describe how the Respiratory system is responsible for maintaining Arterial plasma H+.
- Lung Ventilates off 12,000 mol of CO2 per day
2. Lung has 150 times the capacity of the kidney (13,000 - 5500)/50mmol
What is the bronzed lowry concept of acids and bases?
Acid (HA): is a proton donor
Base (A-) is a proton acceptor
If the Kd is small is this a weak or strong acid? If the Kd is large?
Kd is small = weak acid (dissociates poorly, therefor weak proton donor)
Kd = large –> strong acid & donates proton easily
pKd = -log (Kd)
What is more critical, the acid base ratio or the concentrations of acid or base?
Acid base ratio
What is the most important blood borne protein buffer?
Hemoglobin
- classified as extracellular despite the fact that it is intracellular and located within RBC’s
At a ph below the pKd, the acid is in its dissociated or undissociated state?
At pH ABOVE the pkd?
Undissociated –> still in acidic form
Dissociated –> in basic form
What is the equation for pH in the kidney/lung?
pH = 6.1 + log (kidney/lung)
CO2 in lung = acid
HCO3- = base –> kidney
pH = 6.1 + log (HCO3- / CO2)
What are the values of CO2 in the lung? Of HCO3- in the kidney?
CO2 in the lung = 0.3 mM * PaCO2
(PaCO2 in arterial blood = 40)
HCO3 - in the kidney = 24mM
Base/Acid = HCO3-/CO2 = 24mM/1.2mN = ratio of 20:1!!!
What is the importance of the bicarbonate buffer system?
3
- It is an open system
- CO2 is directly linked to the environment via the lungs (ventilation)
- H+ is directly linked to environment via the kidneys (excretion)
What does it mean that CO2 and H+ are in a steady state balance?
CO2 and H+ are continuously removed from the body at rates that match production
- they do not normally build up in body fluids
What is the isohydric principle?
Multiple acid/base pairs in solution will be in equilibrium with one another, tied together by their common reagent: H+ ion!
What will dictate the ratio of concentrations of a buffer’s base and weak acid forms at a given pH?
pKd for the buffer!
If a condition changes the balance of one buffer system, the other buffer systems are ALSO affected. True or False?
TRUE!
- the buffer systems actually buffer one another by shifting hydrogen ions back and forth from one to the other
Changing the H+ concentration can lead to changes in what? Specifically in regards to what aspects of this?
H+ are highly reactive cations that change the charge distribution on proteins
H+ + COO- ↔COOH and H+ + NH2 ↔NH3+
◆ altered charge distributions lead to protein conformational changes and
modified reaction rates
What are located intracellularly and function within very specific pH ranges?
protein enzymes
What compensates for the low pKd of the bicarbonate buffer system?
its OPEN nature!
- CO2 and H+ are continuously removed from the body at rates that exactly match production (“steady state” balance)
- normally, [CO2] and [H+] do not build up in body fluids
pathologically, [CO2] and [H+] can increase or decrease in body
fluids (respiratory and metabolic acidosis or alkalosis)
(constantly removed and reformed = steady state)
Answer the paradox as to why the quantitative assessment of a single buffer
system is adequate despite the presence of multiple buffer systems.
ISOHYDRIC PRINCIPLE
Any condition that changes the balance of one of the buffer systems, also changes
the balance of all the others because the buffer systems actually buffer one
another by shifting hydrogen ions back and forth from one to the other.
Because there are multiple buffer systems, which must be specifically examined to understand the H+ in plasma?
Which buffer system is MOST important?
only one buffer system needs to be closely examined to
understand the [H+] in the plasma space
This is possible because all buffer systems are linked
together through a common H+ (isohydric principle)
For biomedical purposes, the bicarbonate buffer system is
of primary importance: [H+] = 24 • (PaCO2)/[HCO3-]
Which buffering system is of secondary importance to the bicarbonate system?
State the order of importance of the 3 buffering systems
Hemoglobin!
(phosphate is tertiary)
Bicarbonate>Hemoglobin> Phosphate
- The kidneys compensate for dysfunctional lungs (fast or slow?)
- The lungs compensate for dysfunctional kidneys (fast or slow?)
What compensates for extra-renal origin metabolic malfunction (excessive CO2 & H+ production)?
- Slow
- Fast (hypo/hyperventilate)
- Lungs and Kidneys both compensate for acid-base disturbances
How can acid base disturbances and presence of compensation be determined?
- Measurement of bicarbonate buffer system components & H+
2. Interpretation of plasma electrolyte concentrations
What allows us to measure blood electrolytes?
Anion Gap
A = Na - [HCO3-] - [Cl-]
- renal/Gi disorder = normal anion Gap
- metabolic disorder = HIGH ANION GAP
What is the equation to calculate pH, HCO3- and PaCO2?
pH = 6.1 + log ( HCO3-/ [0.03*PaCO2])
When does a normal Acid-Base Status Exist?
If bicarbonate system and anion gap variables are all within their normal limits
7.35 < pH< PaCO2 < 40mmHg
22mM< HCO3- < 28 mM
35mM < [H+] < 45 nM
10 med/l < [A-] < 15 meq/l
What is the pH in acidemia? Alkalemia?
- pH < 7.35 or H+ > 45nM
2. pH> 7.45 or H+ < 35 nM
Define the situations necessary for the following:
- Metabolic Acidosis
- Respiratory Acidosis
- Metabolic Alkalosis
- Respiratory Alkalosis
metabolic acidosis: [HCO3-]< 22 mM
respiratory acidosis: PaCO2 > 45 mmHg
metabolic alkalosis:[HCO3-] > 28 mM
respiratory alkalosis: PaCO2 < 35 mm Hg
Uncompensated acid base disturbance: primary cause can be determined from on bicarbonate system variable that is not normal
How can you evaluate respiratory malfunction?
◆ malfunctioning respiratory system
Insufficient CO2 removal (respiratory acidosis→acidemia)
Excessive CO2 removal (respiratory alkalosis →alkalemia)
What is a double disturbance? When does this exist?
a double acid-base disturbance exists if the plasma pH is abnormal and
both bicarbonate system variables are abnormal on the same side of pH
severe acidosis: [HCO3-] < 22 mM and PaCO2 > 45 mm Hg
severe alkalosis: [HCO3-] > 28 mM and PaCO2 < 35 mm Hg
What is a mixed acid-base disturbance?
◆ a mixed acid-base disturbance exists if the plasma pH is within its normal range (compensatory situation), but both bicarbonate system variables are not normal
[HCO3-] < 22 mM AND PaCO2 < 35 mm Hg
[HCO3-] > 28 mM AND PaCO2 > 45 mm Hg
large anion gaps are also classified as mixed disorders ([A-] > 15 meq/L)
When should a mixed acid-base disorder be suspected?
When the compensatory response is not appropriate
Describe the following in Primary Metabolic Acidosis
◆ initiating events:
◆ resultant effects: of [H+] and/or [HCO3-], pH
urine pH
◆ compensations:
- Primary Metabolic Alkalosis
◆ initiating events: renal and extra-renal-
a) chronic potassium ion depletion (aggressive diuretic therapy, hyperaldosteronism)
b) protracted vomiting and loss of gastric acids
(pyloric obstruction, gastric ulcers)
c)dehydration and depletion of extracellular fluid
volume (contraction alkalosis)
◆ resultant effects: ↓ [H+] and/or ↑[HCO3
-], ↑pH
urine pH will be paradoxically low (acidic) if there is chronic depletion of potassium ions
◆ compensations: 2̊ respiratory acidosis (with renal
participation if possible)
↑CO2 retention via ↓acid drive on ventilation
hypoventilation also ↓PaO2 which may limit compensation
(hypoxic drive on breathing)
Describe the diagnosis for the following case:
case C data pH = 7.55 units PaCO2 = 27 mm Hg [HCO3-] = 23 mmol/L PaO2 = 104 mm Hg SaO2 = 98%
diagnosis
1̊ respiratory alkalosis
no compensation whatsoever (“Get the bag out!”)
Describe the diagnosis for the following case:
pH = 7.30 units PaCO2 = 34 mmHg [HCO3-] = 24 mmol/L
diagnosis
data incompatibility
Describe the Diagnosis in the following case:
data:
pH = 7.35 units PaCO2 = 30 mmHg [HCO3-] = 16 mmol/L
diagnosis:
1̊ metabolic acidosis
2̊ respiratory alkalosis
full compensation!!
Describe the Diagnosis in the following case:
data
pH = 7.45 units
PaCO2 = 30 mmHg
[HCO3!] = 20 mmol/L
diagnosis
1̊ respiratory alkalosis
2̊ metabolic acidosis
full compensation
