The patient with acid-base

disorder
Students approach to the problem
 Introduction to acid-base disturbance
Acid-base balance is maintained by

Pulmonary excretion of CO2 (volatile)

Metabolic utilization of organic acids
Renal Excretion of Nonvolatile (fixed) acids

Acid-base status is usually assessed by

 CO2  +  H2O  ↔  H2CO3  ↔  HCO3-  +  H+

Henderson-Hasselbalch equation:
pH   =   6.10   +   log  ([HCO3-]  ÷  [0.03  x  PCO2])
Renal control of acid-base balance
How are kidneys regulating HCO3 balance?

1. Reabsorption of virtually all of the filtered

HCO3
2. Production of “NEW” HCO3 = increase of
amount of net acid excretion
Renal transport mechanisms of H and HCO3

Glomerulus filters an amount of HCO3

equivalent to the serum HCO3; not considered
in regulation of acid-base homeostasis

Under normal circumstances filtered load HCO3

4000mmol/day
Responsible for
basolateral NBCe1A
Proximal tubule
(SCL4A4)
80% of HCO3 reabsorbs in PT
Regulation of HCO3 reabsorption:
1.Intracellular and Extracellular pH
Mutation of NBCe1A sensors maintain balance
RTA proximal 2. Extracellular volume status
3. Hormones

HCO3− absorption from the tubular lumen

is mediated by H+ secretion across the
membrane

2/3 by NHE3
1/3 by H-ATPase

In the lumen H+
1. if combines with HCO3 = incorporates
into H2O
2. If combines with non-bicarbonate
(HPO42-) base = protonated H2PO4-
Mutation of CAII
RTA proximal and distal
During acid loading or acidosis,
NH41 excretion can increase
several fold
Ammonium transport along the tubule.

In the thick ascending limb,

NH4+ is reabsorbed by the Na2K22Cl transporter.
In the collecting duct, Rh proteins mediate ammonia
(NH3)/NH41 transport.
 Mutations in H+-ATPase
Type A (or a ICs), which secrete H+RTA distal
Into lumen by 2 pumps:
1. apical H+-ATPase (electrogenic)
2. apical H+/K+ ATPase Mutations in AE1 can also cause
RTA distal

HCO3 exit into blood by

Cl-/ HCO3- exchanger (AE1)

Regulated by:
1. pH changes
2. Potassium
3. Mineralocorticoids
4. Clorides

Type B (or 𝑏 ICs), which secrete HCO3

Into lumen by 2 pumps:
1. apical Cl-/ HCO32- exchanger
2. sodium–driven chloride/ HCO3- ex.

HCO3 exit into blood by

Cl2/ HCO3- exchanger (AE1)
Regulation of the renal handling of acids and
bases
Acid loads – increase in A ICs apical H-ATPase
and basolateral Cl-HCO3 antiporters (AE1)

Base loads – increase in B ICs apical pendrin and

basolateral H-ATPase

Appropriate shifts in Glutamin production and

ammonia transporters
 Approach to the patients with
acid-base disorder

Acid loads Alkali loads

CO2: Respiratory acidosis Excess CO2 exhalation: Respiratory
Nonvolatile acids: Metabolic acidosis alkalosis
Exogenous acids Nonvolatile alkali: Metabolic
(e.g., salicylate, methanol, and ethylene alkalosis
glycol) Exogenous alkali
Pathologic endogenous acids (e.g., NaHCO3 administration)
(e.g., ketoacids and lactic acid) Loss of acid, equivalent to alkali load
Decreased renal acid excretion Gastrointestinal losses (e.g., gastric fluid)
(e.g., renal failure and distal renal tubular Excess urine H+ losses and renal production of
acidosis) new HCO3- (most classic causes of metabolic
Loss of alkali, equivalent to acid load alkalosis, including chloride depletion
Gastrointestinal losses (e.g., diarrhea) metabolic alkalosis and mineralocorticoid
Urine losses (e.g., proximal renal tubular excess)
acidosis)
 Identification of a major acid-base
disorder
The basis of this approach
determine the direction in which the measured values
differ from arbitrary normal values:
pH 7,40 (7,36-7,44)
Pco
2 40mmHg (36-44mmHg)
HCO3‾ 24mmol/L
1. Acidemia or Alkalemia
2. Primary generating change
3. Compensating factor – changes in the same
direction
 Appropriate compensation in the
Acid-Base disorder
Change in Pco2 per Change in pH per change
change in HCO3‾ in HCO3‾
Matabolic acidosis 1.0-1.5 per 1 0.010 per 1
Metabolic alkalosis 0.25-1.00 per 1 0.015 per 1

Change in HCO3‾ per Change in pH per change

change in Pco2 in Pco2
Respiratoy acidosis
Acute 1 per 10 0.08 per 10
Chronic 4 per 10 0.03 per 10
Respiratory alkalosis
Acute 1 per 10 0.08 per 10
Chronic 4 per 10 0.03 per 10
 Example of a simple acid-base
disorder
pH 7.55,Pco2 21 mmHg and HCO3‾ 20mmol/L
Step 1. pH is up = alkalemia
Step 2. HCO3‾ is low and cannot be responsible for
alkalemia
Step 3. Pco2 is low = respiratory alkalosis
Step 4. HCO3‾ change is consistent with compensation

Simple Respiratory alkalosis

 Example of a mixed acid-base
disorder
pH 7.55,Pco2 35mmHg and HCO3‾ 30mmol/L
Step 1. pH is up = alkalemia
Step 2. HCO3‾ ↑ and may be responsible for alkalemia
Step 3. Pco2 ↓ and may be responsible for alkalemia

?
 Example of a mixed acid-base disorder

pH 7.55,Pco2 35mmHg and HCO3‾ 30mmol/L

Step 1. pH is up = alkalemia
Step 2. HCO3‾ ↑ and may be responsible for alkalemia
Step 3. Pco2 ↓ and may be responsible for alkalemia

Mixed metabolic and respiratory alkalosis

Which is dominant?
 Example of a mixed acid-base disorder

pH 7.55,Pco2 35mmHg and HCO3‾ 30mmol/L

Step 1. pH is up = alkalemia
Step 2. HCO3‾ ↑ and may be responsible for alkalemia
Step 3. Pco2 ↓ and may be responsible for alkalemia
Step 4. HCO3‾ is 6/24 = 25% change
Pco 2 is 5/40

Metabolic alkalosis is dominant

Steps in judging whether a acid-base disorder
is simple
1. Check direction of changes from normal
HCO3‾ and Pco2
same direction = simple acid-base disorder
Opposite direction = mixed acid-base disorder
2. Compare the magnitude of the compensation
3. Check the AG for hidden metabolic disorder
AG = Na⁺ - (Cl‾ + HCO3‾ ) 9±3mEq/L
 Application of the rules
Primary event in metabolic acidosis
HCO3‾ falls to 14 mmol/L → Pco should be 25-30mmHg
2

24 – 14 = 10 (1.0-1.5) → 10 or 15 → 30 – 25

HCO3‾ falls to 14 mmol/L ; Pco 28mmHg

2

Primary metabolic acidosis with compensation

 Application of the rules
Primary event in metabolic alkalosis
HCO3‾ rises to 40 mmol/L → Pco should be 44-56mmHg
2

24 + 16= 40 (0.25-1.0)→ 4-16→44-56

HCO3‾ rises to 40 mmol/L ; Pco 50mmHg

2

Primary metabolic alkalosis with compensation

 Examples of mixed acid-base disorders
A patient with emphysema and carbon dioxide retention
(chronic respiratory acidosis)

Health Emphysema

pH 7.40 7.32
Pco2 40 80
Respiratory acidosis
HCO3‾ 24 40
 Examples of mixed acid-base
disorders
A patient with emphysema and carbon dioxide retention
(chronic respiratory acidosis) develops diarrhea (metabolic
acidosis).
Health Emphysema Emphysema and
diarrhea
pH 7.40 7.32 7.10
Pco2 40 80 80
HCO3‾ 24 acidosis + metabolic
Respiratory 40 acidosis24
Metabolic acidosis with increased AG

Ketoacidosis
Lactic acidosis
Intoxications
Renal failure
 Metabolic acidosis with increased AG
Ketoacidosis in diabetes
Lack of insulin → excess of glucagon generates acetoacetic and β-hydroxibutiric
acids↑ → H⁺↑ → HCO3‾ ↓

Ketoacidosis in alcoholics (usually in malnourished patients)

Ethanol ingestion ceased → Increased levels of catecholamins (norepinephrine)
→ α-adrenergic suppression of insulin release → marked increase in lypolysis

Ketoacidosis in starvation
Use of fatty acids for energy maintenance

β-hydroxibutirate/ acetoacetate
In diabetic ketoacidosis – 5:2
In alcoholic may reach 20:1
 Metabolic acidosis with increased AG
organic metabolic acidosis
Lactic acidosis
Type A – primary inadequate delivery of oxygen to tissues
(shock)

Type B – tissue oxygenation N, but tissue cannot use the

oxygen – deranged oxidative metabolism (hepatic failure,
malignancy, drug, seizures)

D-lactic acidosis – colon bacteria metabolize malabsorbed

sugers into both L-and D-lactate (metabolic encephalopathy in
jejunoileal bypass, short bowel syndrome, intestinal
obstruction)
 Metabolic acidosis with increased AG
Intoxication
Salicylates (at the extremes of age)
Pyroglutamic acidosis from acetaminophen
(malnourished individuals, many with renal failure)
Alcohols (ethylen glycole, methanol and isopropyl)

A clue to the presence of early stages alcohol

intoxication is an increased
OSMOLAL GAP
 OSMOLAL GAP
Difference between measured and calculated
osmolality
P = 2Na⁺ + Gluc + BUN ( all in mmol/L)
osm

If OG > 25mOsm/ kg of H₂O:

1. Na⁺ ↓ - hyperlipidemia, hyperproteinemia
2. Accumulation other osmolytes than Na⁺ , Gluc or BUN
(mannitol, radiocontrast agent, ethano, isopropyl (AG is
normal), ethylene glycol, propylene glycol, methanol)
OG is proportional to unmeasured solute!
Metabolic acidosis with normal AG
HCO3‾ loss GI
HCO3‾ loss Renal
Acid retention/Inorganic acid intake
Metabolic acidosis with normal AG
HCO3‾ loss GI
Distal to stomach has the capacity to absorb Cl‾ and
secrete HCO3‾
1. Diarrhea
2. External pancreatic or small-bowel drainage
3. Ureterosigmoidostomy, jejunal loop
4. Drugs (calcium chloride, magnesium sulfate,
cholestyramin)
Cause external losses of bicarbonate-rich fluid!!
Metabolic acidosis with normal AG
HCO3‾ loss Renal
Proximal renal tubular acidosis ( old type IIRTA)
Distal RTA (old type I) – collecting duct defect:
1. Hypokalemic –unable to acidify urine in
response to an acid challenge (Genetic or
secondary: autoimmune disease, drugs,
nephrocalcinosis, tubulointerstitial diseases)
2. Hyperkalemic – hypoaldosteronism (old type IV;
diabetes mellitus, mild CKD, old age)
Metabolic acidosis with normal AG
Diagnosis of Distal RTA – urinary ammonium excretion ↓ in
hyperchloremic metabolic acidosis (normal AG)

Urinary anion gap (UAG)

UAG = (Na⁺ + K⁺) - Cl‾

UAG negative value (-20mEq/L) = urine ammonium NH4 high - in

HCO3‾ loss by GI (diarrhea)

UAG positive value (+23mEq/L) = urine ammonium low - in Distal RTA

Metabolic acidosis with normal AG
Inorganic acid intake
1. Ingestion of ammonium chloride (reduce
appetite)
2. Toluene inhalation (from paint or glue
sniffing)
3. Cation exchange resins
4. Rapid saline administration
 Metabolic alkalosis
• Loss of volume
• Gain of volume due to mineralocorticoids
• Miscellaneous
 Metabolic alkalosis of the volume-depleted variety
chloride-responsive metabolic alkalosis

External loss of fluids rich in H⁺ and Cl‾

The stomach, kidney or skin may be the culprit:
Gastric acid loss
Vomiting
Gastric suction
Renal chloride loss
Diuretics
Posthypercapnia
Cystic fibrosis
Metabolic alkalosis of the volume-repleted
variety
chloride-resistant metabolic alkalosis
Enhanced renal H⁺ secretion stimulated by
aldosterone ( or relative) or major cellular potassium
depletion
Mineralocorticoid excess
Hyperaldosteronism
Gitelman’s syndrome
Bartter’s syndrome
Cushing’s syndrome
Licorice excess
 Respiratory acidosis
Two ventilatory abnormalities ↑ Pco2
1. Alveolar hypoventilation
2. Severe ventilation-perfusion mismatch

A. Central (drugs, stroke, infection)

B. Airway (obstruction, asthma)
C. Parenchyma (emphysema, pneumoconiosis, bronchitis,
ARDS, barotrauma)
D. Neuromuscular (poliomyelitis, kyphoscoliosis, myasthenia,
muscular dystrophies)
E. Miscellaneous ( obesity, hypoventilation)
 Respiratory alkalosis
Disorders that drive ventilation independent of Pco2 can cause
hyperventilation and hypocapnia:
A. CNS stimulation (pain, anxiety, psychosis, meningitis, tumor,
trauma)
B. Hypoxemia or tissue hypoxia (high altitude, pneumonia,
pulmonary edema, aspiration, severe anemia)
C. Drugs or hormones ( pregnancy, progesterone, salycilates,
cardiac failure)
D. Stimulation of chest receptors (hemothorax, PE, flail chest)
E. Miscellaneous (mechanical hyperventilation, heat exposure,
recovery from metabolic acidosis)
 Case report 1.
A woman, who was vomiting for 3 days was
taken to the ED, where the following blood
levels were measured:
pH 7.50, Pco 48mmHg, HCO3‾ 37mmol/L
2

Does she have simple or mixed acid-base disorder?

 Case report 2.
A 56-year-old woman has a 15-year history of DM type
I, which has been controlled by dietary monitoring and
with sc injections of insulin. A recent viral illness results
in loss of appetite, fever and vomiting. She becomes
short of breath and is admitted to ICU.
Lab test on her blood yield the following:
pH 7.07, Pco2 18mmHg, HCO3‾ 5mmol/L;
Na⁺132mmol/L, Cl‾ 94mmol/L, K⁺5,9mmol/L, Glucose
650mg/dl.
Interpret acid-base disorder and treatment option
 Case report 3.
A 35-year-old man is admitted to the hospital for evaluation of
severe epigastric pain. For several days prior to admission he has
had persistent nausea and vomiting. On physical examination he
had midepigastric tenderness. His BP 120/80mmHg when supine
and 100/60mmHg when standing. Upper GI endoscopy reveals
pyloric ulcer with partial gastric outlet obstruction. Lab tests:
pH 7.53, Pco2 45mmHg, HCO3‾ 38mmol/L, Na⁺137mmol/L, Cl‾
82mmol/L, K⁺ 2,8mmol/L

Does he have simple or mixed acid-base disorder?

 Case report 4.
A 68-year-old man has smoked 3 packs of cigarettes per
day for 40 years. He has a history of producing morning
sputum, cough and dyspnea. He has had frequent
episodes of asthmatic bronchitis. He is admitted to the
hospital with a low grade fever, dyspnea and wheezing.
The following lab tests were obtained:
pH 7.29, Pco2 70mmHg, HCO3‾ 30mmol/L,
Na⁺139mmol/L, Cl‾ 90mmol/L

Does he have simple or mixed acid-base disorder?