Arterial Blood Gas

Interpretation

PRESENTER- Dr. Shankerdeep Sondhi

Resident IIInd Yr

Department of Medicine

OBJECTIVES

ABG Sampling

Interpretation of ABG

Case Scenarios

ABG – Procedure and Precautions

Site- (Ideally) Radial Artery

Brachial Artery

Femoral Artery

Ideally - Pre-heparinised ABG syringes

- Syringe should be FLUSHED with 0.5ml of 1:1000 Heparin solution and emptied.

DO NOT LEAVE EXCESSIVE HEPARIN IN THE SYRINGE

HEPARIN DILUTIONAL HCO3

EFFECT PCO2

Only small 0.5ml Heparin for flushing and discard it

Syringes must have > 50% blood.

Ensure No Air Bubbles. Syringe must be sealed immediately

after withdrawing sample.

◦ Contact with AIR BUBBLES

Air bubble = PO2 150 mm Hg , PCO2 0 mm Hg

Air Bubble + Blood = PO2 PCO2

ABG Syringe must be transported at the earliest to the

laboratory for EARLY analysis via COLD CHAIN

ABG ELECTRODES

A. pH (Sanz Electrode)

Measures H+ ion concentration of sample against a

known pH in a reference electrode, hence potential

difference. Calibration with solutions of known pH (6.384

to 7.384)

B. P CO2 (Severinghaus Electrode)

CO2 reacts with solution to produce H+

higher C02- more H+ higher P CO2 measured

C. P 02 (Clark Electrode)

02 diffuses across membrane producing an electrical

current measured as P 02.

Interpretation of ABG

Acid Base Homeostasis

1. Plasma Acid Homeomostasis: Chemical buffering

◦ H+ influenced by Rate of endogenous production

Rate of excretion

Buffering capacity of body

◦ Buffers effective at physiologic pH are Hemoglobin

Phosphate

Proteins

Bicarbonate

2. Alveolar Ventilation:pCO2 action is immediate. Stimulation of respiratory

center washes off the excess CO2 increasing pH, andvice versa

3. Excretion:Liver: uses HCO3

– to make urea which further prevents accumulation of ammonia and traps H+ in renal distal tubule

Kidney: regulate plasma [HCO3–] through three main

processes:

• reabsorption of filtered HCO3–

• formation of titratable acid

• excretion of NH4+ in the urine.

Proximal tubule reclaims 85% filtered HCO3–

Distal tubule reclaims 15%, and excretes H+

40–60 mmol/d of protons is excreted to maintain balance

Acid Base Balance H+ ion concentration in the body is

precisely regulated

The body understands the importance of H+

and hence devised DEFENCES against any

change in its concentration-

BICARBONATE

BUFFER

SYSTEM

Acts in few

seconds

RESPIRATORY

REGULATION

Acts in few

minutes

RENAL

REGULATION

Acts in hours to

days

BUFFER SYSTEM

1st line of defence in pH regulation.

Determine capacity of ECF to

transport acids from site of production

to site of excretion without undue

change in pH.

They resist change in pH on addition

of acid/alkali in media wherever they

are.

PLASMA

BUFFERSRBC BUFFERS

NaHCO3/H2CO

3

Na2HPO4/

NaH2PO4

Na-Pr/H-Pr

KHCO3/H2CO3

K2HPO4/KH2P4

KHb/HHb

BICARBONATE BUFFER

NAHCO3/H2CO3 = 20/1 = Alkali reserve.

conversion of strong & non volatile acid in ECF, in weak & volatile acid at the expense of NaHCO3 component of buffer.

H2CO3 thus formed is eliminated by lung as CO2.Directly linked with respiration & healthy lungs essential for its function.

High concentration in blood,so very good physiological buffer.

Weak chemical buffer.

Bicarbonate Buffer System

CO2 + H2O carbonic anhydrase H2CO3 H+ + HCO3-

In Acidosis - Acid = H+

H+ + HCO3 H2CO3 CO2 + H2O

In Alkalosis - Alkali + Weak Acid = H2CO3

CO2 + H20 H2CO3 HCO3- + H+

+

ALKALI

PHOSPHATE BUFFER

Na2HPO4/NaH2PO4 =

AlkPO4/AcidPO4 = 4/1.

NaH2PO4 excreted by kidneys.

Directly linked with kidneys & healthy

kidneys necessary for its functioning.

Concentration in blood is low so not

good physiological buffer.

Very good chemical buffer as pKa

aprroches pH.

PROTEIN BUFFER

Na+Pr- / H+Pr- = salt/acid.

Proteins can act as a base In acidic

medium nd as an acid in basic

medium..with COOH& NH2 group.

Buffering capacity of plasma proteins

is much less than Hb.

Respiratory Regulation of Acid Base

Balance-

H+ PaCO2

H+ PaCO2

ALVEOLAR

VENTILATION

ALVEOLAR

VENTILATION

Renal Regulation of Acid Base Balance

Kidneys control the acid-base balance by excreting

either an acidic or a basic urine,

This is achieved in the following ways-

Reabsorption Secretion of H+

of HCO3 ions in tubules

in blood and excretion

•Proximal Convulated

Tubules (85%)

•Thick Ascending Limb of

Loop of Henle (10%)

•Distal Convulated Tubule

•Collecting Tubules(5%)

ECF Volume

H+ ion

PCO2 in ECF

Angiotensin II

Aldosterone

K+

Definitions and Terminology

ACIDOSIS – presence of a process which tends to

pH by virtue of gain of H + or loss of HCO3-

ALKALOSIS – presence of a process which tends to pH by virtue of loss of H+ or gain of HCO3

-

If these changes, change pH, suffix ‘emia’ is added

ACIDEMIA – reduction in arterial pH (pH<7.35)

ALKALEMIA – increase in arterial pH (pH>7.45)

Simple Acid Base Disorder/ Primary Acid Base

disorder – a single primary process of acidosis or

alkalosis due to an initial change in PCO2 and HCO3.

Compensation - The normal response of

the respiratory system or kidneys to change in pH

induced by a primary acid-base disorder

The Compensatory responses to a primary Acid Base

disturbance are never enough to correct the change in

pH , they only act to reduce the severity.

Mixed Acid Base Disorder – Presence of more than

one acid base disorder simultaneously .

Normogram (for simple acid-base ds)

Characteristics of Primary ACID BASE

DisordersPRIMARY

DISORDER

PRIMARY RESPONSES COMPENSATORY

RESPONSESH+ ion pH Primary

Conc. Defect

Metabolic

Acidosis H+ pH HCO3

PCO2

Alveolar

Hyperventilation

Metabolic

Alkalosis H+ pH HCO3

PCO2

Alveolar

Hypoventilation

Respiratory

Acidosis H+ pH PCO2 HCO3

Respiratory

Alkalosis H+ pH PCO2 HCO3

Compensation

• For every 1mmol/l in HCO3 the PCO2 falls by 1.25 mm Hg

METABOLIC

ACIDOSIS

• For every 1mol/l in HCO3 the PCO2 by 0.75 mm Hg

METABOLIC ALKALOSIS

Metabolic Disorders – Compensation in these disorders leads to

a change in PCO2

In Respiratory Disorders

PCO2 Kidney HCO3 Reabsorption

Compensation begins to appear in 6 – 12 hrs and is fully

developed only after a few days.

1.ACUTE

Before the onset of compensation

Resp. acidosis – 1mmHg in PCO2 HCO3 by 0.1meq/l

Resp. alkalosis – 1mmHg in PCO2 HCO3 by 0.2 meq/l

2.CHRONIC (>24 hrs)

After compensation is fully developed

Resp. acidosis – 1mmHg in PCO2 HCO3 by 0.4meq/l

Resp. alkalosis – 1mmHg in PCO2 HCO3 by 0.4meq/l

Body’s physiologic response to Primary disorder

in order to bring pH towards NORMAL limit

Full compensation

Partial compensation

No compensation…. (uncompensated)

BUT never overshoots,

If a overshoot pH is there,

Take it granted it is a MIXED disorder

STEP WISE APPROACH

to

Interpretation Of

ABG reports

Normal Values

ANALYTE Normal Value Units

pH 7.35 - 7.45

PCO2 35 – 45 mm Hg

PO2 80 – 100 mm Hg`

[HCO3] 22 – 26 meq/L

SaO2 95-100 %

Anion Gap 10 + 2 meq/L

∆HCO3 +2 to -2 meq/L

STEP 0 • Is this ABG Authentic?

STEP 1 • ACIDEMIA or ALKALEMIA?

STEP 2• RESPIRATORY or METABOLIC?

STEP 3 • Is COMPENSATION adequate?

STEP 4 • If METABOLIC – ANION GAP?

STEP 5• If High gap Metabolic Acidosis–

GAP GAP?

Step 0 – Authentic or Not?

Verify that the ABG values are internally

accurate.

◦ The accuracy of the values can be established

by confirming that they satisfy a simplified form

of the Henderson-Hasselbalch equation:

[H+](nmol/L) = 24 × pCO2(mm Hg) ∕ [HCO3-]

(mEq/L)

◦ [H+] = 10 exp(-pH). Within the pH range of 7.26

to 7.45 [H+] in nmol/L = 80 − the decimal of the

pH

(e.g., for pH = 7.25, [H+] = 80 − 25 = 55

nmol/L).

Example: using Kassirer-

Bleich equation

ABG: pH = 7.25, pCO2 = 30, HCO3- = 22

55 = 24 x

55 ≠ 32

LAB ERROR

30

22

[H+](nmol/L) = 24 × pCO2(mm Hg) ∕ [HCO3-]

(mEq/L)

Look at pH

<7.35 - acidemia

>7.45 – alkalemia

RULE – An acid base abnormality is present even if

either the pH or PCO2 are Normal.

ACIDEMIA OR ALKALEMIA?STEP 1

IS PRIMARY DISTURBANCE RESPIRATORY OR

METABOLIC?

pH HCO3 or pH HCO3 METABOLIC

pH PCO2 or pH PCO2 RESPIRATORY

RULE- If either the pH or PCO2 is Normal, there is a

mixed metabolic and respiratory acid base disorder.

RESPIRATORY or METABOLIC?STEP 2

Step 3 Is Compensation

Adequate?

Disorder Prediction of Compensation pH HCO3– PaCO2

Metabolic

acidosis Low Low LowPaCO2 will 1.25 mmHg per mmol/L in

[HCO3-]

Metabolic

alkalosis

High High HighPaCO2 will 0.75 mmHg per mmol/L in

[HCO3-]

Disorder Prediction of Compensation pH HCO3– PaCO2

Respiratory

alkalosis

High Low Low

Acute [HCO3-] will 0.2 mmol/L per mmHg in

PaCO2

Chronic [HCO3-] will 0.4 mmol/L per mmHg in

PaCO2

Respiratory

acidosis

Low High High

Acute [HCO3-] will 0.1 mmol/L per mmHg in

PaCO2

Chronic [HCO3-] will 0.4 mmol/L per mmHg in

PaCO2

STEP 0 • Is this ABG Authentic?

STEP 1 • ACIDEMIA or ALKALEMIA?

STEP 2• RESPIRATORY or METABOLIC?

STEP 3 • If Respiratory – ACUTE or CHRONIC?

STEP 4 • Is COMPENSATION adequate?

STEP 4 • If METABOLIC – ANION GAP?

STEP 6• If High gap Metabolic Acidosis–

GAP GAP?

Electrochemical Balance in Blood

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

CATIONS ANIONS

Sulfate

Phosphate

Mg- OA

K - Proteins

Ca-HCO3

Na- Cl

UAUC

Na

Cl

HCO3

Anion Gap

AG based on principle of electroneutrality:

Total Serum Cations = Total Serum Anions

M cations + U cations = M anions + U anions

Na + (K + Ca + Mg) = HCO3 + Cl + (PO4 + SO4 + Protein + Organic Acids)

Na + UC = HCO3 + Cl + UA

But in Blood there is a relative abundance of Anions, hence

Anions > Cations

Na – (HCO3 + Cl) = UA – UC

Na – (HCO3 + Cl) = Anion Gap

METABOLIC ACIDOSIS-ANION GAP?

STEP 4

IN METABOLIC ACIDOSIS WHAT IS THE ANION GAP?

ANION GAP(AG) = Na – (HCO3 + Cl)

Normal Value = 10 + 2

Adjusted Anion Gap = Observed AG +2.5(4.5- S.Albumin)

50% in S. Albumin 75% in Anion Gap !!!

High Anion Gap Metabolic Acidosis

Metabolic Acidosis

Normal Anion Gap Acidosis

CO EXISTANT METABOLIC DISORDER – “Gap Gap‖?

STEP 5

C/O HGAG METABOLIC ACIDOSIS,ANOTHER DISORDER?

∆ Anion Gap = Measured AG – Normal AG

Measured AG – 12

∆ HCO3 = Normal HCO3 – Measured HCO3

24 – Measured HCO3

Ideally, ∆Anion Gap = ∆HCO3

For each 1 meq/L increase in AG, HCO3 will fall by 1 meq/L

∆AG/ HCO3- = 1 Pure High AG Met Acidosis

AG/ HCO3- > 1 Assoc Metabolic Alkalosis

AG/ HCO3- < 1 Assoc N AG Met Acidosis

CLINICAL CASE

SCENARIO

Case Scenario

A patient with a severe postoperative

ileus requires the insertion of a

nasogastric (NG) tube for

decompression. After several days on

the floor, he develops a line infection and

is moved to the ICU once he becomes

pressor dependent. The patient's ABG

reveals a pH = 7.44, pCO2 = 12, and

[HCO3-] = 8. The [Na+] = 145 with [Cl-] =

102.

ABG: pH = 7.44, pCO2 = 12, [HCO3-] = 8,

[Na+] = 145 with [Cl-] = 102

◦ With knowledge of the common clinical scenarios leading to acid-base disturbances, this patient is at risk for developing a metabolic alkalosis from NG suction and a metabolic acidosis and respiratory alkalosis from sepsis.

◦ Step 1. [H+] = 80 − 44 = 36.

Does 36 = 24 × 12 / 8? It does.

◦ Step 2. The patient is mildly alkalemic, which can be explained by the low pCO2 but not by the low [HCO3

-], suggesting that a respiratory alkalosis may be the primary derangement.

ABG: pH = 7.44, pCO2 = 12, [HCO3-] = 8,

[Na+] = 145 with [Cl-] = 102

◦ Step 3

a. The drop in [HCO3-] might be an appropriate

compensation for a chronic respiratory alkalosis ([HCO3

-] is 0.4 mmol/L per mmHg in PaCO2) However, 24 − [(40 − 12) × 0.4] = 12.8, which is not close to the observed [HCO3

-] of 8. A mixed disorder is implied.

b. AG = 145 − 102 − 8 = 35. There is an elevated AG, suggests a concomitant metabolic acidosis.

c. Delta anion gap=35 − 10 = 25.

d. Delta bicarbonate= 24 − 8 =16.

Ratio of above two is more than 1 suggestive of associated metabolic alkalosis. This has proven to be a triple acid-base disorder with an elevated anion gap acidosis, a metabolic alkalosis, and a respiratory alkalosis, as was alluded to in Step 1

Metabolic Acidosis Metabolic acidosis can occur because of

◦ increase in endogenous acid production (lactate and ketoacids)

◦ loss of bicarbonate (as in diarrhea)

◦ accumulation of endogenous acids (as in renal failure).

Effects on the respiratory, cardiac, and nervous

systems.

◦ Kussmaul respiration

◦ Intrinsic cardiac contractility may be depressed, but inotropic

function can be normal because of catecholamine release.

◦ Both peripheral arterial vasodilation and central

venoconstriction can be present

◦ The decrease in central and pulmonary vascular compliance

predisposes to pulmonary edema with even minimal volume

overload.

◦ Central nervous system function is depressed, with

headache, lethargy, stupor, and, in some cases, even coma.

◦ Glucose intolerance may also occur.

Metabolic Acidosis: Essentials of

Diagnosis

Decreased HCO3– with acidemia.

Classified into high anion gap acidosis and normal anion gap (hyperchloremic) acidosis.

The high anion gap acidoses are seen in lactic acidosis, ketoacidosis, renal failure or toxins.

Normal anion gap acidosis is mainly caused by gastrointestinal HCO3

– loss or RTA.

Urinary anion gap may help distinguish between these causes.

Causes of High-Anion-Gap

Metabolic Acidosis1. Lactic acidosis Poor tissue perfusion (type A)

Aerobic disorders (type B)2. Ketoacidosis

Diabetic

Alcoholic

Starvation3. Toxins

Ethylene glycol

Methanol

Salicylates

Propylene glycol: as vehicle of medications

Pyroglutamic acid: acetaminophen toxicity

4. Renal failure (acute and chronic)

Ketacidosis –

Diabetic Ketoacidosis (DKA): DKA is caused by increased fatty acid

metabolism and the accumulation of ketoacids(acetoacetate and -hydroxybutyrate).

DKA usually occurs in insulin-dependent diabetes mellitus in association with

cessation of insulin or

an intercurrent illness, such as an infection, gastroenteritis, pancreatitis, or myocardial infarction, which increases insulin requirements temporarily and acutely.

The accumulation of ketoacids accounts for the increment in the Anion Gap and is accompanied most often by hyperglycemia [glucose > 17 mmol/L (300 mg/dL)].

Glucose,a mmol/L (mg/dL) 13.9–33.3 (250–600)

Sodium, meq/L 125–135

Potassiuma Normal to ↑

Magnesiuma Normal ( plasma levels may be normal or high at presentation, total-body stores are usually depleted)

Chloridea Normal

Phosphatea ↓

Creatinine Slightly ↑

Osmolality (mOsm/mL) 300–320

Plasma ketonesa ++++

Serum bicarbonate,a meq/L <15 meq/L

Arterial pH 6.8–7.3

Arterial PCO2,a mmHg 20–30

Anion gapa[Na - (Cl + HCO3)] ↑

Management

Confirm diagnosis (plasma glucose, positive serum ketones, metabolic acidosis).

Admit to hospital; intensive-care setting may be necessary for frequent monitoring or if pH < 7.00 or unconscious.

Assess:

Serum electrolytes (K+, Na+, Mg2+, Cl-, bicarbonate, phosphate)

Acid-base status—pH, HCO3-, PCO2, b-hydroxybutyrate

Renal function (creatinine, urine output)

Replace fluids:

2–3 L of 0.9% saline over first 1–3 h (10–15 mL/kg per hour);

subsequently, 0.45% saline at 150–300 mL/h;

change to 5% glucose and 0.45% saline at 100–200 mL/h when plasma glucose reaches 250 mg/dL (14 mmol/L).

Administer short-acting insulin:

IV (0.1 units/kg) or IM (0.3 units/kg), then 0.1 units/kg per hour by continuous IV infusion;

increase 2- to 3-fold if no response by 2–4 h.

If initial serum potassium is < 3.3 mmol/L (3.3 meq/L), do not administer insulin until the potassium is corrected to > 3.3 mmol/L

Management Assess patient: What precipitated the episode

(noncompliance, infection, trauma, infarction, cocaine)? Initiate appropriate workup for precipitating event (cultures, CXR, ECG).

Measure capillary glucose every 1–2 h;

electrolytes (especially K+, bicarbonate, phosphate) and anion gap every 4 h for first 24 h.

Monitor blood pressure, pulse, respirations, mental status, fluid intake and output every 1–4 h.

Replace K+: 10 meq/h when plasma K+ < 5.5 meq/L, ECG normal, urine flow

and normal creatinine documented;

administer 40–80 meq/h when plasma K+ < 3.5 meq/L or if bicarbonate is given.

Continue above until patient is stable, glucose goal is 150–250 mg/dL, and acidosis is resolved. Insulin infusion may be decreased to 0.05–0.1 units/kg per hour.

Administer intermediate or long-acting insulin as soon as patient is eating. Allow for overlap in insulin infusion and subcutaneous insulin injection.

since insulin prevents production of ketones, bicarbonate therapy is rarely needed except with extreme acidemia (pH < 7.1), and then in only limited amounts.

Patients with DKA are typically volume depleted and require fluid resuscitation with isotonic saline.

Volume overexpansion is not uncommon after IV fluid administration, and contributes to the development of a hyperchloremicacidosis during treatment of DKA because volume expansion increases urinary ketoacid anion excretion (loss of potential bicarbonate).

The mainstay for treatment of this condition is IV regular insulin

Drug, Toxin-Induced Acidosis

Plasma osmolality is calculated according to the following

expression:

Posm = 2Na+ + Glu + BUN (all in mmol/L)

Posm = 2Na+ + Glu/18 + BUN/2.8 (milligrams per deciliter)

The calculated and determined osmolality should be within

10–15 mmol/kg H2O

When the measured osmolality exceeds the calculated

osmolality by >15–20 mmol/kg H2O, either prevails.

Either the serum sodium is spuriously low, as with

hyperlipidemia or hyperproteinemia

(pseudohyponatremia)

Osmolytes other than sodium salts, glucose, or urea

have accumulated in plasma. Examples include

mannitol, radiocontrast media, isopropyl

alcohol, ethylene glycol, propylene

glycol, ethanol, methanol, and acetone.

In this situation, the difference between the

calculated osmolality and the measured osmolality

(osmolar gap) is proportional to the concentration of

the unmeasured solute.

Alcohols: With an appropriate clinical history and index

of suspicion, identification of an osmolar gap is helpful

in identifying the presence of poison-associated AG

acidosis. Three alcohols may cause fatal intoxications:

ethylene glycol, methanol, and isopropyl alcohol

Salicylates: Salicylate intoxication in adults usually

causes respiratory alkalosis or a mixture of high-AG

metabolic acidosis and respiratory alkalosis. Only a

portion of the AG is due to salicylates. Lactic acid

production is also often increased

Renal failure Acidosis The hyperchloremic acidosis of moderate renal

insufficiency is eventually converted to the high-AG acidosis of advanced renal failure.

At GFRs below 20 mL/min, the inability to excrete H+ with retention of acid anions such as PO4

3– and SO42– results in an increased

anion gap acidosis

[HCO3–] rarely falls to <15 mmol/L, and the AG

is rarely >20 mmol/L, indicating that the acid retained in chronic renal disease is buffered by alkaline salts from bone.

Results in significant loss of bone mass due to reduction in bone calcium carbonate and increases urinary calcium excretion.

Treatment of high anion gap

acidosis Treatment is aimed at the underlying disorder, such as

insulin and fluid therapy for diabetes and appropriate

volume resuscitation to restore tissue perfusion. The

metabolism of lactate will produce HCO3– and increase

pH.

Controversy regarding administration of large

amounts of HCO3–

may have deleterious effects, including hypernatremia and

hyperosmolality.

Intracellular pH may decrease because administered HCO3–

is converted to CO2, which easily diffuses into cells, combines

with water to create additional hydrogen ions and worsening

of intracellular acidosis and this could impair cellular function

Alkali administration is known to stimulate

phosphofructokinase activity, thus exacerbating lactic acidosis

via enhanced lactate production. Ketogenesis is also

augmented by alkali therapy.

Treatment of high anion gap

acidosis…..◦ In salicylate intoxication, alkali therapy must be started unless blood

pH is already alkalinized by respiratory alkalosis, since the

increment in pH converts salicylate to more impermeable salicylic

acid and thus prevents central nervous system damage.

◦ In DKA, alkali must be administered in extreme alkalemia (pH<7.1)

◦ In alcoholic ketoacidosis, thiamine should be given together with

glucose to avoid the development of Wernicke's encephalopathy.

The amount of HCO3– deficit can be calculated as follows:

Amount of HCO3– deficit = 0.5 X body weight X (24 - HCO3

–)

◦ Half of the calculated deficit should be administered within the first

3–4 hours to avoid overcorrection and volume overload.

In methanol intoxication

◦ ethanol has been used as a competitive substrate for alcohol

dehydrogenase, which metabolizes methanol to formaldehyde

◦ or through direct inhibition of alcohol dehydrogenase by fomepizole

Hyperchloremic (Nongap)

Metabolic Acidoses: causesI. Gastrointestinal bicarbonate loss Diarrhea

External pancreatic or small-bowel drainage

Ureterosigmoidostomy, jejunal loop, ileal loop

Drugs - Calcium chloride , Magnesium sulfate (diarrhea), Cholestyramine (bile acid diarrhea)

II. Renal acidosis Hypokalemia

Proximal RTA (type 2)

Distal (classic) RTA (type 1)

Hyperkalemia

Generalized distal nephron dysfunction (type 4 RTA)

a. Mineralocorticoid deficiency

b. Mineralocorticoid resistance (autosomal dominant PHA I)

c. Voltage defect (autosomal dominant PHA I and PHA II)

d. Tubulointerstitial disease

III. Drug-induced hyperkalemia (with renal insufficiency)

◦ Potassium-sparing diuretics

(amiloride, triamterene, spironolactone)

◦ Trimethoprim

◦ Pentamidine

◦ ACE-Is and ARBs

◦ Nonsteroidal anti-inflammatory drugs

◦ Cyclosporine and tacrolimus

IV. Other

◦ Acid loads (ammonium chloride, hyperalimentation)

◦ Loss of potential bicarbonate: ketosis with ketone excretion

◦ Expansion /dilutional acidosis (rapid saline administration)

◦ Hippurate

◦ Cation exchange resins

Approach: Urinary Anion Gap Increased renal NH4

+Cl– excretion to enhance H+ removal is a normal

physiologic response to metabolic acidosis. NH3 reacts with H+ to

form NH4+, which is accompanied by the anion Cl– for excretion.

Urinary anion gap from a random urine sample ([Na++ K+]– Cl–)

reflects the ability of the kidney to excrete NH4Cl as in the following

equation:

Na+ + K+ + NH4+ = Cl– + 80

urinary anion gap is equal to (80 – NH4+)

Gastrointestinal HCO3– loss (diarrhea), the renal acidification ability

remains normal and NH4Cl excretion increases in response to the

acidosis. urinary anion gap is negative (eg, –30 mEq/L).

Distal RTA, the urinary anion gap is positive (eg, +25 mEq/L), since

the basic lesion in the disorder is the inability of the kidney to excrete

H+ and thus the inability to increase NH4Cl excretion.

Proximal (type II) RTA, the kidney has defective HCO3–

reabsorption, leading to increased HCO3– excretion rather than

decreased NH4Cl excretion. Thus, the urinary anion gap is negative

in proximal (type II) RTA.

Urinary pH may not as readily differentiate between the two causes because volume depletion or potassium depletion, which can accompany diarrhea (and surreptitious laxative abuse) may impair renal acidification.

Thus, when volume depletion is present, the urinary anion gap is a better measurement of ability to acidify the urine than urinary pH.

When large amounts of other anions are present in the urine, the urinary anion gap may not be reliable. In such a situation, NH4

+ excretion can be estimated using the urinary osmolar gap.

NH4+ excretion (mmol/L) = 0.5 x Urinary osmolar

gap = 0.5 [U osm – 2(U Na++U K+) + U urea + U glucose]

where urinary (U) concentrations and osmolalityare in millimoles per liter.

Renal Defect

Serum

[K+]Urinary NH4

+ Plus Minimal Urine pH

Titratable Acid

Urinary Anion Gap

Treatment

Gastrointestinal HCO3

– lossNone ↓ < 5.5 ↑↑ Negative Na+, K+, and

HCO3– as

required

Renal tubular acidosis

I. Classic distal Distal H+

secretion↓ > 5.5 ↓ Positive NaHCO3 (1–3

mEq/kg/d)

II. Proximal secretion

Proximal HCO3

–

abspn

↓ < 5.5 Normal Negative NaHCO3 or KHCO3 (10–15 mEq/kg/d), thiazide

IV. Hyporeninemic hypoaldosteronism

Distal Na+

reabsorption K+ secretion, and H+

secretion

↑ < 5.5 ↓ Positive Fludrocortisone(0.1–0.5 mg/d), dietary K+ rstrn, furosemide (40–160 mg/d), NaHCO3 (1–3 mEq/kg/d)

Treatment of normal Anion gap

Acidosis Gastrointestinal: Correction of the contracted ECFV with NaCl

and repair of K+ deficits corrects the acid-base disorder, and chloride deficiency.

RTA : administration of alkali (either as bicarbonate or citrate) to correct metabolic abnormalities and prevent nephrocalcinosis and renal failure.

◦ Proximal RTA : Large amounts of alkali (10–15 mEq/kg/d) may be required to treat proximal RTA because most of the alkali is excreted into the urine, which exacerbates hypokalemia. Thus, a mixture of sodium and potassium salts, such as K-Shohlsolution, is preferred. The addition of thiazides may reduce the amount of alkali required, but hypokalemia may develop.

◦ Distal RTA : Correction of type 1 distal RTA requires a smaller amount of alkali (1–3 mEq/kg/d) and potassium supplementation as needed.

◦ Type IV RTA: dietary potassium restriction may be needed and potassium-retaining drugs should be withdrawn. Fludrocortisonemay be effective in cases with hypoaldosteronism, but should be used with care, preferably in combination with loop diuretics. alkali supplementation (1–3 mEq/kg/d) may be required.

Metabolic Alkalosis

Essentials of Diagnosis

◦ High HCO3– with alkalemia.

◦ Evaluate effective circulating volume by

physical examination and check urinary

chloride concentration. This will help

differentiate saline-responsive metabolic

alkalosis from saline-unresponsive

alkalosis

Metabolic Alkalosis Occurs as a result of net gain of [HCO3

–] or loss of nonvolatile acid (usually HCl by vomiting) from the extracellular fluid.

The disorder involves

a generative stage, in which the loss of acid usually causes alkalosis

maintenance stage, in which the kidneys fail to compensate by excreting HCO3

–.

Classified based on "saline responsiveness" or urinary Cl–, which are markers for volume status

Saline-responsive metabolic alkalosis is a sign of extracellular volume contraction

Saline-unresponsive alkalosis implies a volume-expanded state

Symptoms With metabolic alkalosis, changes in central and

peripheral nervous system function are similar to those of hypocalcemia : symptoms include Mental confusion

Obtundation

Predisposition to seizures

Paresthesia

Muscular cramping

Tetany

Aggravation of arrhythmias

Hypoxemia in chronic obstructive pulmonary disease.

Related electrolyte abnormalities include Hypokalemia- Weakness and hyporeflexia

hypophosphatemia.

Classification and etiologyI. Saline-Responsive (UCl < 10 mEq/d)

Excessive body bicarbonate content Renal alkalosis Diuretic therapy Poorly reabsorbable anion therapy:

carbenicillin, penicillin, sulfate, phosphate Posthypercapnia

Gastrointestinal alkalosis Loss of HCl from vomiting or nasogastric suction Intestinal alkalosis: chloride diarrhea

Exogenous alkali NaHCO3 (baking soda) Sodium citrate, lactate, gluconate, acetate Transfusions Antacids

Normal body bicarbonate content

"Contraction alkalosis"

II. Saline-Unresponsive (UCl > 10 mEq/d)

Excessive body bicarbonate content

Renal alkalosis Normotensive

Bartter's syndrome (renal salt wasting and secondary hyperaldosteronism)

Severe potassium depletion

Refeeding alkalosis

Hypercalcemia and hypoparathyroidism Hypertensive

Endogenous mineralocorticoids

Primary aldosteronism

Hyperreninism

Adrenal enzyme deficiency: 11- and 17-hydroxylase

Liddle's syndrome

Exogenous mineralocorticoids

Licorice

Treatment Mild alkalosis is generally well tolerated. Severe or

symptomatic alkalosis (pH > 7.60) requires urgent treatment.

Saline-Responsive Metabolic Alkalosis◦ Aimed at correction of extracellular volume

deficit. ◦ Depending on the degree of

hypovolemia, adequate amounts of 0.9% NaCl and KCl should be administered.

◦ Discontinuation of diuretics and administration of H2-blockers in patients whose alkalosis is due to nasogastric suction can be useful.

◦ If impaired pulmonary or cardiovascular status prohibits adequate volume repletion, acetazolamide, 250–500 mg intravenously every 4–6 hours, can be used.

Treatment….. One must be alert to the possible development of

hypokalemia, since potassium depletion can be induced by forced kaliuresis via bicarbonaturia.

Administration of acid can be used as emergency therapy. HCl, 0.1 mol/L, is infused via a central vein (the solution is sclerosing). Dosage is calculated to decrease the HCO3

– level by 50% over 2–4 hours, assuming an HCO3

– volume of distribution (L) of 0.5% body weight (kg).

Patients with marked renal failure may require dialysis.

Saline-Unresponsive Metabolic Alkalosis

surgical removal of a mineralocorticoid-producing tumor

blockage of aldosterone effect with an ACE inhibitor or with spironolactone.

primary aldosteronism can be treated only with potassium repletion.

Respiratory Acidosis

Central

◦ Drugs (anesthetics, morphine, sedatives)

◦ Stroke

◦ Infection

Airway

◦ Obstruction

◦ Asthma

Parenchyma

◦ Emphysema

◦ Pneumoconiosis

◦ Bronchitis

◦ Adult respiratory distress syndrome

◦ Barotrauma

Neuromuscular

◦ Poliomyelitis

◦ Kyphoscoliosis

◦ Myasthenia

◦ Muscular dystrophies

Miscellaneous

◦ Obesity

◦ Hypoventilation

◦ Permissive hypercapnia

Results from decreased alveolar ventilation and hypercapnia both due to pulmonary and non pulmonary disorders

Respiratory Acidosis Acute respiratory failure associated with severe acidosis and only a small increase

in the plasma bicarbonate.

After 6–12 hours, the primary increase in PCO2 evokes a renal compensatory response to generate more HCO3

–

, which tends to ameliorate the respiratory acidosis. This takes several days to complete.

Chronic respiratory acidosis seen in patients with underlying lung disease, such as

chronic obstructive pulmonary disease.

Urinary excretion of acid in the form of NH4+ and Cl– ions

results in the characteristic hypochloremia of chronic respiratory acidosis.

When chronic respiratory acidosis is corrected suddenly, especially in patients who receive mechanical ventilation, there is a 2- to 3-day lag in renal bicarbonate excretion, resulting in posthypercapnic metabolic alkalosis.

Symptoms and Signs◦ With acute onset, there is somnolence and confusion, and

myoclonus with asterixis

◦ Coma from CO2 narcosis may ensue

◦ Severe hypercapnia increases cerebral blood flow and cerebrospinal fluid pressure. Signs of increased intracranial pressure (papilledema, pseudotumor cerebri) may be seen.

Laboratory Findings◦ Arterial pH is low

◦ PCO2 is increased

◦ Serum HCO3– is elevated, but not enough to completely

compensate for the hypercapnia.

◦ If the disorder is chronic, hypochloremia is seen.

Treatment◦ In all forms of respiratory acidosis, treatment is directed at the

underlying disorder to improve ventilation.

◦ Because opioid drug overdose is an important reversible cause of acute respiratory acidosis, naloxone, 0.04–2 mg intravenously is administered to all such patients if no obvious cause for respiratory depression is present.

◦ Mechanical ventilation for oxygenation till it restores back to normal maybe needed

Respiratory Alkalosis(Hypocapnia)

Respiratory alkalosis, or hypocapnia, occurs when hyperventilation reduces the PCO2, which increases the pH

Symptoms and Signs In acute cases (hyperventilation), there is light-headedness,

anxiety, paresthesias, numbness about the mouth, and a tingling sensation in the hands and feet. Tetany occurs in more severe alkalosis from a fall in ionized calcium.

In chronic cases, findings are those of the responsible condition.

Laboratory Findings Arterial blood pH is elevated, and PCO2 is low. Serum

bicarbonate is decreased in chronic respiratory alkalosis.

Determination of appropriate compensatory changes in the HCO3

– is useful to sort out the presence of an associated metabolic disorder

the changes in HCO3– values are greater if the respiratory

alkalosis is chronic

Although serum HCO3– is frequently below 15 mEq/L in

metabolic acidosis, it is unusual to see such a low level in respiratory alkalosis, and its presence would imply a superimposed (noncompensatory) metabolic acidosis.

Causes of respiratory alkalosis.

Hypoxia : Decreased inspired oxygen tension

High altitude

Ventilation/perfusion inequality

Hypotension

Severe anemia

CNS-mediated disorders Voluntary hyperventilation

Anxiety-hyperventilation syndrome

Neurologic disease:

Cerebrovascular accident (infarction, hemorrhage)

Infection

Trauma

Tumor

Causes… Pharmacologic and hormonal stimulation :

Salicylates, Nicotine, Xanthines ,Pregnancy (progesterone)

Hepatic failure

Gram-negative septicemia

Recovery from metabolic acidosis

Heat exposure

Pulmonary disease Interstitial lung disease

Pneumonia

Pulmonary embolism

Pulmonary edema

Mechanical overventilation

Treatment

Treatment is directed toward the underlying cause.

In acute hyperventilation syndrome from anxiety, reassurance , attention to underlying psychological stress and rebreathing into a paper bag will increase the PCO2.

The processes are usually self-limited since muscle weakness caused by hyperventilation-induced alkalemia will suppress ventilation.

Sedation may be necessary if the process persists however Antidepressants and sedatives should be avoided

Adrenergic blockers may ameliorate peripheral manifestations of the hyperadrenergic state.

Rapid correction of chronic respiratory alkalosis may result in metabolic acidosis as PCO2 is increased in the setting of previous compensatory decrease in HCO3

–.

If respiratory alkalosis complicates ventilator management, changes in dead space, tidal volume, and frequency can minimize the hypocapnia

Conclusion

Clinical suspicion according to scenario

Primary disorder from pH and bicarbonate or CO2

values

Degree of compensation…? Inappropriate? mixed

disorder

Anion gap (corrected for serum albumin

change)…? Primary metabolic acidosis

Corrected bicarbonate levels…?

More than normal- associated metabolic alkalosis

Less - associated metabolic non-anion gap acidosis

Review compensation for metabolic ds…confirm if

initially suspected respiratory disorder exists

Metabolic acidosis: ..see AG High AG: …plasma osmolal gap

more.. Toxins

Less.. KA, RF, LA,

Normal AG acidosis:

urine AG….negative..GI

urinary pH ….high..RTA 1

serum potassium….high..RTA4

Metabolic alkalosis:

◦ Urinary Chloride…

Less..saline responsive…ECF contraction

more ..saline non responsive

Plasma Potassium…low..K depletion

High…Blood pressure

Plasma renin

1.PaCO2 equation:

VCO2 x 0.863 VCO2 = CO2 production

PaCO2 = ----------------- VA = VE – VD

VA VE = minute (total) ventilation

VD = dead space ventilation0.863 converts units to mm Hg

Condition State ofPaCO2 in blood alveolar ventilation

>45 mm Hg Hypercapnia Hypoventilation

35 - 45 mm Hg Eucapnia Normal ventilation

<35 mm Hg Hypocapnia Hyperventilation

PaCO2 reflects ratio of metabolic CO2 production to alveolar ventilation

Hypercapnia

VCO2 x 0.863

PaCO2 = ------------------

VA

The only physiologic reason for elevated PaCO2 is inadequate alveolar ventilation (VA) for the amount of the body‘s CO2 production (VCO2). Since alveolar ventilation (VA) equals minute ventilation (VE) minus dead space ventilation (VD), hypercapnia can arise from insufficient

VE, increased VD, or a combination.

Hypercapnia

VCO2 x 0.863

PaCO2 = ------------------

VA VA = VE – VD

Examples of inadequate VE leading to decreased VA and increased PaCO2: sedative drug overdose; respiratory muscle paralysis; central hypoventilation

Examples of increased VD leading to decreased VA and increased PaCO2: chronic obstructive pulmonary disease; severe pulmonary embolism, pulmonary edema.

Physiologic effects of

hypercapnia

◦ 1) An elevated PaCO2 will lower the PAO2 (see Alveolar gas

equation), and as a result lower the PaO2.

◦ 2) An elevated PaCO2 will lower the pH (see Henderson-

Hasselbalch equation).

◦ 3) The higher the baseline PaCO2, the greater it will rise for a

given fall in alveolar ventilation, e.g., a 1 L/min decrease in

VA will raise PaCO2 a greater amount when baseline PaCO2

is 50 mm Hg than when it is 40 mm Hg.

Assessment of Oxygenation

Status

2.Alveolar gas equation Oxygenation(alv)

3.Oxygen content equation Oxygenation(tissue)

Oxygenation

Parameters: /limitations

O2 Content of blood:(Hb x1.34x O2 Sat + 0.003x Dissolved O2 )Remember Hemoglobin

Oxygen Saturation:( remember this is calculated …error prone)

Alveolar / arterial gradient:( classify respiratory failure)

Arterial / alveolar ratio:Proposed to be less variableSame limitations as A-a gradient

-----XXXX Diagnostics-----

Blood Gas Report328 03:44 Feb 5 2006Pt ID 3245 / 00

Measured 37.0 0CpH 7.452 pCO2 45.1 mm HgpO2 112.3 mm Hg

Corrected 38.6 0CpH 7.436pCO2 47.6 mm HgpO2 122.4 mm Hg

Calculated Data

HCO3 act 31.2 mmol / LHCO3 std 30.5 mmol / LB E 6.6 mmol / LO2 ct 15.8 mL / dlO2 Sat 98.4 %ct CO2 32.5 mmol / LpO2 (A -a) 30.2 mm Hg pO2 (a/A) 0.78

Entered DataTemp 38.6 0CFiO2 30.0 %ct Hb 10.5 gm/dl

Alveolar Gas Equation

PAO2 = PIO2 - 1.2 (PaCO2)where PAO2 is the average alveolar PO2, and PIO2 is the partial pressure

of inspired oxygen in the trachea

PIO2 = FIO2 (PB – 47 mm Hg)FIO2 is fraction of inspired oxygen and PB is the barometric pressure. 47

mm Hg is the water vapor pressure at normal body temperature.

Alveolar Gas Equation

If FIO2 and PB are constant, then as PaCO2 increases both PAO2 and PaO2 will decrease (hypercapnia causes hypoxemia).

If FIO2 decreases and PB and PaCO2 are constant, both PAO2 and PaO2 will decrease.

If PB decreases (e.g., with altitude), and PaCO2 and FIO2

are constant, both PAO2 and PaO2 will decrease (mountain climbing causes hypoxemia).

P(A-a)O2

P(A-a)O2 is the alveolar-arterial difference in partial pressure of

oxygen. It is commonly called the ―A-a gradient‖. It results from

gravity-related blood flow changes within the lungs (normal

ventilation-perfusion imbalance).

Normal P(A-a)O2 ranges from 5 to 25 mm Hg breathing room air

(it increases with age). A higher than normal P(A-a)O2 means the

lungs are not transferring oxygen properly from alveoli into the

pulmonary capillaries. Except for right to left cardiac shunts, an

elevated P(A-a)O2 signifies some sort of problem within the lungs.

Physiologic causes of low PaO2

NON-RESPIRATORY P(A-a)O2

Cardiac right to left shunt Increased

Decreased PIO2 Normal

RESPIRATORYPulmonary right to left shunt IncreasedVentilation-perfusion imbalance IncreasedDiffusion barrier IncreasedHypoventilation (increased PaCO2) Normal

Ventilation-Perfusion imbalance

A normal amount of ventilation-perfusion (V-Q) imbalance accounts for the normal P(A-a)O2.

By far the most common cause of low PaO2 is an abnormal degree of ventilation-perfusion imbalancewithin the hundreds of millions of alveolar-capillary units. Virtually all lung disease lowers PaO2 via V-Q imbalance, e.g., asthma, pneumonia, atelectasis, pulmonary edema, COPD.

Diffusion barrier is seldom a major cause of low PaO2

(it can lead to a low PaO2 during exercise).

SaO2 and oxygen content

How much oxygen is in the blood? Oxygen content = CaO2 (mlO2/dl).

CaO2 = quantity O2 bound + quantity O2 dissolvedto hemoglobin in plasma

CaO2 = (Hb x 1.34 x SaO2) + (.003 x PaO2)

Hb = hemoglobin in gm%; 1.34 = ml O2 that can be bound to each gm of Hb; SaO2 is percent saturation of hemoglobin with oxygen; .003 is solubility coefficient of oxygen in plasma: .003 ml dissolved O2/mm Hg PO2.

Given arterial oxygen saturation (SpO2) = 100%, Hb = 15 g/100 ml and arterial partial pressure of oxygen (PaO2) = 13.3 kPa, then the oxygen content of arterial blood (CaO2) is:

CaO2 = 20.1 +0.3 = 20.4 ml/100 ml

Similarly the oxygen content of mixed venous blood can be calculated. Given normal values of mixed venous oxygen saturation (SvO2) = 75% and venous partial pressure of oxygen (PvO2) = 6 kPa, so:

CvO2 = 15.2 + 0.1 = 15.2 ml/100 ml

Oxygen dissociation curve: SaO2 vs. PaO2Also shown are CaO2 vs. PaO2 for two different hemoglobin contents: 15 gm%

and 10 gm%. CaO2 units are ml O2/dl. P50 is the PaO2 at which SaO2 is 50%.

SaO2 – is it calculated or measured?

SaO2 is measured in a ‗co-oximeter‘. The traditional ‗blood gas machine‘ measures only pH, PaCO2 and PaO2,, whereas the co-oximeter measures SaO2, carboxyhemoglobin, methemoglobin and hemoglobin content. Newer ‗blood gas‘ consoles incorporate a co-oximeter, and so offer the latter group of measurements as well as pH, PaCO2 and PaO2.

Always make sure the SaO2 is measured, not calculated. If it is calculated from the PaO2 and the O2-dissociation curve, it provides no new information, and could be inaccurate --especially in states of CO intoxication or excess methemoglobin. CO and metHb do not affect PaO2, but do lower the SaO2.

Carbon monoxide – an important cause

of hypoxemia

Normal %COHb in the blood is 1-2%, from metabolism and small amount of ambient CO (higher in traffic-congested areas)

All smokers have excess CO in their blood.

CO binds @ 200x more avidly to hemoglobin than O2, displacing O2

from the heme binding sites.

CO : 1) decreases SaO2 by the amount of %COHb present, and 2) shifts the O2-dissociation curve to the left, retarding unloading of oxygen to the tissues.

CO does not affect PaO2, only SaO2. To detect CO poisoning, SaO2 and/or COHb must be measured (requires co-oximeter). In the presence of excess CO, SaO2 (when measured) will be lower than expected from the PaO2.

CO does not affect PaO2!

A patient presented to the ER with headache and dyspnea.

His first blood gases showed PaO2 80 mm Hg, PaCO2 38 mm Hg, pH 7.43. SaO2 on this first set was calculated from the O2-dissociation curve at 97%, and oxygenation was judged normal.

He was sent out from the ER and returned a few hours later with mental confusion; this time both SaO2 and COHb were measured (SaO2 shown by ‗X‘): PaO2 79 mm Hg, PaCO2 31 mm Hg, pH 7.36, SaO2

53%, carboxyhemoglobin 46%.

CO poisoning was missed on the first set of blood gases because SaO2 was not measured!

Causes of Hypoxia

1. Hypoxemia (=low PaO2 and/or low CaO2)

◦ a. reduced PaO2 – usually from lung disease (most common physiologic mechanism: V-Q imbalance)

◦ b. reduced SaO2 -- most commonly from reduced PaO2; other causes include carbon monoxide poisoning, methemoglobinemia, or rightward shift of the O2-dissociation curve

◦ c. reduced hemoglobin content -- anemia

2. Reduced oxygen delivery to the tissues

◦ a. reduced cardiac output -- shock, congestive heart failure

◦ b. left to right systemic shunt (as may be seen in septic shock)

3. Decreased tissue oxygen uptake

◦ a. mitochondrial poisoning (e.g., cyanide poisoning)

◦ b. left-shifted hemoglobin dissociation curve (e.g., from acute alkalosis, excess CO, or abnormal hemoglobin structure)

Arterial Oxygen Tension (PaO2)

Normal value in healthy adult breathing room air at sea level 97 mm Hg.

progressively with age

Dependant upon 1. FiO2

2. Patm

Hypoxemia is PaO2 < 80 mm Hg at RA

Most pts who need ABG usually req O2 therapy

O2 therapy should not be withheld/interrupted ‗to determine PaO2 on RA‘

Acceptable PaO2 Values on Room

Air

Age Group Accepable PaO2

(mm Hg)

Adults upto 60 yrs

& Children

> 80

Newborn 40-70

70 yrs > 70

80 yrs > 60

90 yrs > 50

60 yrs 80 mm Hg 1mm Hg/yr

Inspired O2 – PaO2 Relationship

FIO2 (%) Predicted Min

PaO2 (mm Hg)

30 150

40 200

50 250

80 400

100 500

If PaO2 < FIO2 x 5, pt probably hypoxemic at RA

Hypoxemia on O2 therapy

Uncorrected: PaO2 < 80 mm Hg

(< expected on RA & FIO2)

Corrected: PaO2 = 80-100 mm Hg

(= expected on RA but < expected for FIO2)

Excessively Corrected: PaO2 > 100 mm Hg

(> expected on RA but < expected for FIO2)

PaO2 > expected for FIO2:

1. Error in sample/analyzer

2. Pt‘s O2 consumption reduced

3. Pt does not req O2 therapy (if 1 & 2 NA)

Thanks