1. Clinical Definitions and Diagnostic Aids
Respiratory acidosis = PaCO2 > 45 mmHg
Respiratory alkalosis = PaCO2 < 35 mmHg
Metabolic acidosis = HCO3- < 22 mmHg or Base Deficit of < -2
Metabolic alkalosis = HCO3- > 28 mmHg or Base Excess of > +2

2. Case #4 22 year old diabetic found unresponsive
P = 102, BP = 110/80, f = 20,
T = 36.2 C
ABG PaO2 = 90, PaCO2 = 36,
pH = 7.12, HCO3- = 8, BD = -20

3. Metabolic Acidosis Definition: low HCO3- <22 mEq/L or BD < -2
Cause: retained fixed acids (or HCO3- loss)
Treatment:
Correct cause!
Give NaHCO3 if necessary to correct pH to > 7.20

4. Anion Gap In Metabolic Acidosis
[Na+] - ([Cl-] + [HCO3-]) = 8-16 mmol/L
If > 18, there are unmeasured anions, such as:
lactate
ketones
salicylate
ethanol
ethylene glycol (anti-freeze)
Anion gap is another common diagnostic calculation. It is used to
help differentiate between causes of metabolic acidosis. It should be
emphasized that ECF is an electro-neutral solution in which
the total number of anions and cations must be equal, such that
there is no actual anion gap in plasma!
The calculation assesses the difference between unmeasured cations (other than
Na+) and unmeasured anions (other than Cl- and HCO3 -). In
most cases of metabolic acidosis, the addition of a fixed acid results in lowering of HCO3
through buffering and thus an increased anion gap, according to the calculation shown. In
effect the “anion gap” is occupied by the conjugate base anion of the fixed acid (e.g. lactate).
In most cases of metabolic acidosis anion gap is increased. If the cause of the metabolic
acidosis results in a rise in Cl- (for example diarrhea in which selective HCO3 loss occurs in
exchange for Cl), then metabolic acidosis results which is “hyperchloremic” and the anion
gap is found to be normal.

5. Compensation: Opposing Metabolic And Respiratory Effects Aimed At Returning pH Towards Its Normal Value
Primary Metabolic Acidosis
Acute or chronic
Decreased HCO3-
Response?
For every 1 mEq decrease in HCO3-
PaCO2 is expected to decrease mmHg
Secondary respiratory alkalosis

6. So what does this mean? Lactic Acid + HCO3 ↔ lactate- + H2O + CO2
So increasing Lactic acid leads to lactate replacing HCO3
If anion gap is unchanged in metabolic acidosis suggest other reason for acidosis (eg diarrhoea – loss of HCO3 but gain in Cl-

7. Diagram source unknown

8. Case #2
36 year old heroin addict found unresponsive with needle in arm
P = 102, BP = 110/80, f = 5, T = 35.2 C
ABG: PaO2 = 70, PaCO2 = 80,
pH = 7.00, HCO3- = 23

9. Ventilatory Acidosis Definition – PaCO2 > 45 mm Hg
Ventilatory insufficiency or failure
Cause:
Hypoventilation
Low VA (i.e., low VE and/or high VD)
Treatment:
Increase VE, lower VD/Vt
Eliminate CNS depression of ventilation

10. Compensation: Opposing Metabolic And Respiratory Effects Aimed At Returning pH Towards Its Normal Value
Primary Respiratory Acidosis
Increased PaCO2
Chronic (> 3-5 days)
Response?
For every 1 mm Hg increase in PaCO2
HCO3- is expected to increase 0.4 mEq
Secondary metabolic alkalosis

11. Case #5
6 week old infant is lethargic with history of vomiting increasing for 1 week
P = 122, BP = 85/60, f = 24,
T = 37.2 C
ABG PaO2 = 90, PaCO2 = 44,
pH = 7.62, HCO3- = 36, BE = +12

12. Metabolic Alkalosis Definition: high HCO3- >28 mEq/L or BE > +2
Cause: fixed acids loss
Treatment:
Correct cause!
Prevent HCO3- retention (correct pH to <7.50) (How?)
Give acetazolamide(CA inhibitor) or H+ in extremes

13. Compensation: Opposing Metabolic And Respiratory Effects Aimed At Returning pH Towards Its Normal Value
Primary Metabolic Alkalosis
Acute or chronic
Increased HCO3-
Response?
For every 1 mEq increase in HCO3-
PaCO2 is expected to increase mmHg
Secondary respiratory acidosis

15. Comments On Compensation…
Recall HH – compensation aims to normalize pH by restoring [HCO3]:PCO2 ratio towards normal.
The “Primary” disturbance is the one that is consistent with the pH

16. Case #3 16 year old with closed head injury after a fall from 15 feet
P = 132, BP = 115/90, f = 32,
T = 37.2 C
ABG: PaO2 = 110, PaCO2 = 26,
pH = 7.52, HCO3- = 22, BD = 1

17. Ventilatory Alkalosis
Definition – PaCO2 < 35 mm Hg
Hyperventilation
Cause:
High VA (i.e., high VE = f x Vt)
Treatment: (usually none!)
Decrease VA
Sedation

18. Compensation: Opposing Metabolic And Respiratory Effects Aimed At Returning pH Towards Its Normal Value
Primary Ventilatory Alkalosis
Decreased PaCO2
Chronic (> 3-5 days)
Response?
For every 1 mm Hg decrease in PaCO2
HCO3- is expected to decrease 2-5 mEq
Secondary metabolic acidosis

20. Normally blood has a PCO2 of 40 mm Hg which gives us a blood pH of 7
Normally blood has a PCO2 of 40 mm Hg which gives us a blood pH of 7.4, and a HCO3
- concentration of
24 mM. So PCO2, H+ and HCO3
are all dependent variables – i.e. changing 1 changes the others.
The Davenport diagram can be used to quickly ascertain if alkalosis is respiratory or metabolic in origin –
and is a graphical representation of the above chemical equilibrium.
The x-axis represents the pH, the y-axis the HCO3
- concentration, and the back vertical lines are PCO2
isopleths (20, 40 and 60 mm Hg PCO2). A PCO2 of 40 mm Hg with a pH of 7.4 gives a HCO3 -
concentration of 24 mM – this is normal for blood values. The red diagonal arrow is called the buffer line
and represents what happens to HCO3
- and pH if the PCO2 is changed, e.g. if PCO2 rises to 60 mm Hg, then
moving the black dot up the buffer line (to the left) until we reach PCO2 of 60 mm Hg, would give us a pH
of 7.25 and a HCO3
of just below 30 mM. This would represent the effects of hypoventilation; as PCO2
increases the reaction (H2O + CO2 reaction) is driven to the right to form more H+ (a drop in pH) and more
HCO3
-. On the other hand if the PCO2 falls to 20 mm Hg, then following the buffer line to the right, we see
that pH increases and the HCO3
- falls (pH now 7.55 and HCO3
- ~ 20 mM). Remember that the Davenport
diagram is just a graphical representation of the CO2 + H2O ↔ H+ + HCO3
equilibrium reaction.
On the other hand if a patient has the following parameters pH 7.2, HCO3
- 15 mM and PCO2 40 mm Hg,
we can immediately see that the patient has acidosis (pH 7.2!), but with a PCO2 of 40 mm Hg (normal) this
is not primarily caused by a respiratory process. Therefore this patient would have metabolic acidosis. You
can see that with metabolic acidosis HCO3
- concentrations fall as pH becomes more acidic, whereas with
respiratory acidosis HCO3
- levels rise with increasing acidity.
Davenport diagram showing the relationships among HCO3-, pH, and PCO2. A shows the normal buffer line BAC

21. pH 7.2, HCO3- 15 mM and PCO2 40 mm Hg ?
metabolic acidosis

22. Davenport diagram showing the relationships among HCO
3, pH, and PCO2. . B shows the changes/compensation occurring in respiratory and metabolic acidosis and alkalosis

23. Overview of Potassium Homeostasis
1) Internal potassium homeostasis.
Cells exist in a steady state where potassium uptake via the Na/K-ATPase is balanced by
potassium leak through ion channels. Regulation of exchange between intra- and extracellular
fluid is known as internal potassium homeostasis.
Factors which affect internal potassium balance
are important in the regulation of plasma [potassium]. Skeletal muscle cells are the major single pool of potassium in the body and are the most important cells in relation to internal potassium homeostasis.
2)External potassium homeostasis.
The typical Western diet contains around 80mEq of potassium per day. Maintenance of
potassium homeostasis requires that the rate of potassium excretion matches daily intake. This is known as external potassium homeostasis.
Fine regulation of renal potassium output is the major control mechanism ensuring external balance.
Losses from the GI tract in feces are generally about 10% of dietary intake, though this can become a large source of potassium loss in diarrhea.

24. Factors Affecting Internal K+ Exchanges
K+ ingestion
insulin liver, skeletal muscle
Exercise
epinephrine skeletal muscle (beta2 receptors) K+
cell
aldosterone (skeletal muscle)
High plasma [K+]
Insulin/glucose infusions are used clinically to
control hyperkalemia.
The final common pathway for increased cellular potassium uptake with insulin,
aldosterone and epinephrine is increased Na/K-ATPase activity.
Hormonal regulation of internal potassium exchange is an important aspect of potassium
balance. Insulin, even at basal levels, affects potassium uptake by liver and skeletal muscle cells.
At high concentrations, following a meal, insulin accelerates potassium uptake. Considering that
we may eat our entire extracellular potassium content in a single meal, it is vital that ingested
potassium be quickly sequestered intracellularly to prevent hyperkalemia. Insulin is very
important to physiological potassium balance. Insulin/glucose infusions are used clinically to
control hyperkalemia.
Aldosterone is secreted in direct response
to a rise in plasma potassium. Aldosterone
produces a modest increase in uptake of
potassium by skeletal muscle. Its more
important action is increased renal
potassium excretion.
Epinephrine and other beta receptor
agonists stimulate potassium uptake in
skeletal muscle. Its effects are additive
with those of aldosterone and insulin.
There is increased epinephrine secretion
after a potassium rich meal. Epinephrine is
also important during exercise. Dynamic
exercise is associated with release of potassium from working muscle cells, which is an important
aspect of the locally controlled increase in blood flow to working muscle. During intense work,
enough potassium may be released to produce potentially dangerous levels of plasma potassium.
Trained altheletes have adaptive changes that increase the rate of potassium re-uptake. The high
levels of epinephrine associated with exercise are important for stimulating potassium re-uptake.
The final common pathway for increased cellular potassium uptake with insulin,
aldosterone and epinephrine is increased Na/K-ATPase activity.

25. Alkalosis: Acidosis: Acid/Base Balance (hyperkalemia) (hypokalemia)
• As hydrogen ions move into and out of the cells in the body, there is a corresponding movement of potassium in the opposite direction by ion transport proteins that link hydrogen ion movement to potassium ion movement. This movement helps maintain electrical balance inside the cells.
Alkalosis:
Acidosis: H+
K+o 
(hypokalemia) K+ H+
K+o  H+
(hyperkalemia)

26. A K+ Load Must Be Quickly Removed To Protect Plasma [K+]
100
K+ moved into cells
% response 50
Renal K+ excretion
potassium normally enters the ECF via the
GI tract, but may also be released from the
ICF for example during exercise, acidemia,
tissue damage and treatment with betaadrenergic
receptor antagonists. The renal
response to hyperkalemia is slow, taking
minutes to hours to produce. Maintenance
of optimal serum potassium therefore
requires a control system to temporarily
sequester potassium inside cells. These
hormonal responses, described above, occur
in a few minutes. Time courses for the renal
and extrarenal control systems are shown in
the slide. 6 12
Hours
K+ load

27. Renal K+ Handling Involves Filtration, Reabsorption And Secretion
PCT (FE=30%), TALH (FE=10%)
Secretion:
DCT & CCD
(FE = 10 to 150%)
 In states of low dietary potassium intake
The rate of renal potassium excretion varies over a wide range according to changes in dietary
intake.
The rate of renal potassium excretion varies over a wide range according to changes in dietary
intake. In states of low dietary potassium intake, renal tubular reabsorption is stimulated and
almost all filtered potassium is reabsorbed. More commonly the kidney must deal with the
problem of dietary potassium excess. The renal system has a large capacity to increase potassium
excretion, with fractional excretion reaching maximally %, compared to a typical value of
10-20% of the filtered load.
At all rates of excretion the majority of filtered potassium is first reabsorbed. About 70% of the
filtered potassium load is reabsorbed in the
proximal tubule and a further 20% is
usually reabsorbed in the thick ascending
limb of Henle’s loop.
In contrast to sodium, potassium is able to
enter the urine via secretion. This occurs in
the late distal tubule and cortical collecting
duct. When potassium excretion is
increased, it is potassium secretion that
increases. When potassium excretion is
reduced, secretion is inhibited and net
potassium reabsorption occurs in the
collecting duct.
 dietary potassium excess
FE K+ =
10 – 150+%

28. K+ Excretion Is Determined By K+ Secretion In The Collecting Duct
aldosterone +
3Na+
Lumen
Blood K+
Principal cell

29. Case #6 63 year old with history of COPD due to tobacco abuse
P = 92, BP = 135/90, f = 26,
T = 37.0 C
ABG PaO2 = 65, PaCO2 = 55,
pH = 7.34, HCO3- = 31, BE = +9
Acid-base status?
Primary disorder?
Secondary disorder?
Compensation?

30. Case #7
39 year old with history of chronic renal insufficiency due to hypertension
P = 82, BP = 148/95, f = 20, T = 36.1 C
ABG PaO2 = 88, PaCO2 = 30, pH = 7.33, HCO3- = 14, BD = -11
Acid-base status?
Primary disorder?
Secondary disorder?
Compensation?

31. Mixed Acid-Base Disorders
Most common acid-base disorders
Multiple disorders
Usually one acidosis and one alkalosis
pH usually partially or completely corrected

32. Case #1 Review 26 YO male involve in MVC
Hypotensive and tachycardia at crash scene
Altered mental status and multiple severe injuries
pH = 7.38; PaCO2 = 30 mm Hg;
HCO3- = 18 mEq/L, BD = -8 mEq/L
Acid-base status?
Primary disorder?
Secondary disorder?
Compensation?

33. Key Points
Acid-base disorders are common and important clinical concerns
Accurate diagnosis is essential to proper treatment
Primary disorders are complicated by secondary disorders occurring at a different time course