Acid-base

disorders
Derek Bunnachak, MD.
Renal division,
Department of Internal medicine,
Medicine, CMU.
lecture MED 401 (.. 401) ;2551
 Acid - base physiology

pH = -log[H+]
Buffers => substances that maintain a
constant hydrogen ion concentration in
solution despite addition of either acid
or base e.g.
HPO4= + H+ <--> H2PO4-
H+ + HCO3- <--> H2CO3
 Acid - base physiology

[H+] ECF~ 40 nanoEq./L : pH 7.40

ECF buffers; the most important is
HCO3-/H2CO3 buffer
H+ + HCO3- <--> H2CO3 <--> H2O + CO2
pH = pKa + log[base] / [acid]
pH = 6.1 + log [HCO3- ] / [H2CO3]
pH = 6.1 + log [HCO3- ] / 0.03 x pCO2
 pH = 6.1 + log ( [HCO3- ] / 0.03 x pCO2 )
pCO2 rate of alveolar
ventilation
[HCO3- ] rate of renal
tubular acid excretion
1 HCO3- reabsorption
(reclamation)
2 H+ secretion (new HCO3-
generation)
H+ + HPO4= <---> H2PO4-
H+ + NH3 <---> NH4+
. Net acid excretion (NAE)
= H2PO4- +NH4+ - HCO3-
 Arterial blood gases

pH 7.40 (7.35 - 7.45)

pCO2 40 mm Hg
[HCO3-] 24 mmol or mEq/L
systemic pH: => acidemia, acidotic
=> alkalemia,alkalotic
acidosis => pathologic process pH
alkalosis => pathologic process pH
 Acid loads
CO2 retention = respiratory acidosis
Nonvolatile acids = metabolic acidosis
exogenous acid loads (methanol, ethylene
glycol, salicylic acid)
excess endogenous acid production
(ketoacids, lactic acid)
decreased renal excretion of normal
endogenous acids produced ( renal failure,
distal renal tubular acidosis)
loss of alkali
GI losses (diarrhea)
urine losses ( proximal renal tubular acidosis)
 Alkali loads
Excess CO2 removal = Respiratory
alkalosis
Nonvolatile alkali = Metabolic
alkalosis
exogenous alkali (NaHCO3
administration)
loss of acid
GI losses (gastric fluid)
excess urine H+ losses
Disorders [H+] pH Primary Compensatory
response
Metabolic [HCO ]
3
-
PCO 2
acidosis
Metabolic [HCO ]
3
-
PCO 2
alkalosis
Respiratory PCO 2 [HCO ] 3
-

acidosis
Respiratory PCO 2 [HCO ] 3
-

alkalosis
 Logical approach to
management
Step1: suspect
Step2: identify major disorder
Step3: simple/mixed disorders
Step4: establish the cause
Step5: treatment
underlying
general state
 When to suspect
acid -base disorders
acid-base

Clinical manifestation
laboratory
serum total of CO2 content or
[HCO3-]
serum anion gap
AG = Na+ - (Cl- + HCO3-)
serum potassium concentration
How to identify the major
acid-base disorder
acid-base

Arterial blood gases analysis

pH
pCO2
[HCO3]
 How to judge
if it is simple or mixed
Check the directions of the
deviations of the buffer pair
check the magnitude of the
physiologic response of the buffer
pair
[HCO3-]
pCO2
Metabolic acidosis

[HCO3] 1.0 mEq/L

pCO2 1.2 mm Hg
Metabolic alkalosis

[HCO3] 1.0 mEq/L

pCO2 0.7 mm Hg
Acute respiratory acidosis

pCO2 10 mm Hg
[HCO3] 1.0 mEq/L
Chronic respiratory
acidosis

pCO2 10 mm Hg
[HCO3] 4.0 mEq/L
Acute respiratory alkalosis

pCO2 10 mm Hg
[HCO3] 2.0 mEq/L
Chronic respiratory
alkalosis

pCO2 10 mm Hg
[HCO3] 5.0 mEq/L
 METABOLIC ACIDOSIS

Derek Bunnachak, M.D.

Renal division, Internal
Medicine,
Chiang Mai University
Lecture Med401
 DEFINITION
[HCO3-]ecf pH pCO2

pathophysiology;

1. addition of H+ to ECF
2. loss of HCO3- from ECF
 Response to acid load
1. ECF buffering; HCO3- buffer
2. intracellular & bone buffering;
proteins, phosphate, bone carbonate
3. respiratory compensation;
[HCO3-] 1.0 mEq/L pCO2 ~ 1.2 mm Hg
4. renal excretion of the H+ load
 Acid load
Diet
Metabolism
GI base loss
Exogenous

Minutes Titrate intracellular

buffers

Titrate extracellular
buffers ( plasma HCO3-)

Hours Days

respiration Renal net acid excretion (NAE)

(pCO2)

BALANCE ; daily NAE = daily Acid load

 Renal excretion of H+ load
1. filtered HCO3- must be reabsorbed
2. dietary acid load is excreted by H+
secretion H+ +
NH3 NH4+ ~ 30-60 mEq/D H+ +
HPO4= H2PO4- ~ 10-40 mEq/D
In metabolic acidosis
NH4+
 P
NH3
NH3

NH3
P
NH3

NH3
P
NH3
 Generation of metabolic
acidosis
1. Inability of the kidneys to excrete the
dietary acid load
2. Increase in generation of H+ due to either
the addition of H+
the loss of HCO3-
Causes of metabolic acidosis
Inability to excrete the dietary acid load
diminished NH4+ production
1. Renal failure (Uremic acidosis)
2. Hypoaldosteronism (type 4 RTA)
diminished H+ secretion
type 1 (distal) RTA (renal tubular acidosis)
Causes of metabolic acidosis
Increased H+ load or HCO3- loss
1. Lactic acidosis
2. Ketoacidosis
3. Ingestions;
salicylate sulfur
methanol formaldehyde
ethylene glycol paraldehyde
toluene hyperalimentation
ammonium chloride
Causes of metabolic acidosis
Massive rhabdomyolysis
Gastrointestinal HCO3- loss
diarrhea
pancreatic, biliary, intestinal fistulas
ureterosigmoidostomy
cholestyramine chloride (Questran)
Renal HCO3- loss
type 2 (proximal) RTA
Systemic effects of metabolic
acidosis
Cardiovascular
Heart: bradycardia, arrhythmias, reduced
contractility
Vascular; arteriolar dilatation, increased
venous tone
Pulmonary
Ventilation: Kussmual respiration
Oxygen delivery: increased in acute, normal
in chronic metabolic acidosis
Systemic effects of metabolic
acidosis
Gastrointestinal
Gastric distension
Renal
sodium, potassium wasting
Uric acid retention in organic acidosis
Hypercalciuria
Protein wasting
Catecholamines secretion ; increased
 Anion Gap (AG)
[Na+] + Unmeasured cation
= [Cl- + HCO3-] + Unmeasured anion
[Na+] [Cl- + HCO3-] = Anion Gap
= Unmeasured anion - Unmeasured cation
AG ~ [Proteins-]
1g/dL [albumin] 4 mEq/L AG
Normal anion gap ~ 8-16 (124) mEq/L
 High Anion Gap metabolic
acidosis (HAMA)
Accumulation of metabolizable acids
lactic acidosis
ketoacidosis
starvation
diabetic
alcoholic
betahydroxybutyric acidosis
alcoholic ketosis
ketosis with shock
 High Anion Gap metabolic
acidosis (HAMA)
Accumulation of nonmetabolizable acids
uremic acidosis in renal failure
poisons
salicylate; salicylic, lactic, ketoacids
methanol, formaldehyde; formic, lactic acids
ethylene glycol; glycolic, oxalic, lactic acids
toluene; hippuric acid
sulfur; sulfuric acid
paraldehyde; formic, lactic acids
Massive rhabdomyolysis
 Hyperchloremic metabolic
acidosis (HCMA)
Hypokalemic variants
gastrointestinal causes
diarrhea
pancreatic, biliary, intestinal fistulas
ureterosigmoidostomy
cholestyramine chloride ingestion
NH4Cl ingestion
renal causes
carbonic anhydrase inhibitor
posthypercapnic metabolic acidosis
RTA proximal, distal types
 Hyperchloremic metabolic
acidosis (HCMA)
Hyperkalemic variants
decreased mineralocorticoid secretion
Addisons disease
hypoaldosteronism
adrenogenital syndrome
hyporenin-hypoaldosteronism
decreased mineralocorticoid action
interstitial nephritis
hydronephrosis
early renal failure
hyperkalemia with ECF volume expansion
 AG / HCO3- = ( AG-12 )
(24-HCO3-)
<1 HAMA + HCMA
12 HAMA
>2 HAMA + metabolic
alkalosis
HAMA high anion gap metabolic acidosis
HCMA hyperchloremic metabolic acidosis
AG anion gap = [Na] [Cl] [HCO3]
 Urine anion gap (UAG)
helpful diagnostically in HCMA
UAG = Na + K Cl
UAG ~ U NH4+ (NH4Cl, NaCl, KCl)
metabolic acidosis U NH4+
most cases of MA negative value
renal failure, RTA type 1,4 U NH4+
UAG positive value
 Metabolic Alkalosis
Derek Bunnachak, M.D.
Renal division
Medicine, CMU.
For Med 401
 Definition
increased [HCO3-]ECF increased pHECF
increased pCO2
Caused by;
Net loss of H+ from ECF
e.g. gastric fluid loss
Net addition of HCO3 or its precursors to ECF
e.g. lactate, acetate, citrate
External loss of fluid containing chloride in
greater and HCO3- in lesser concentration than
in ECF
e.g. diuretic-induced and post-hypercapnic metabolic
alkalosis
 Pathophysiology
I. Generation of metabolic alkalosis
1. Loss of H+
GI loss
removal of gastric secretion (vomiting, NG-suction)
antacid therapy
chloride-losing diarrhea
Renal loss
Loop and thiazide diuretics
Mineralocorticoid excess
Post-chronic hypercapnia
high dose carbenicillin or other penicillin therapy
hypercalcemia, milk-alkali syndrome
H+ movement into cell
hypokalemia
refeeding
 I. Generation of metabolic alkalosis

1. Losses H+
2. Retention of bicarbonate
massive blood transfusion
administration of NaHCO3
milk-alkali syndrome
3. Contraction alkalosis
loop or thiazide diuretics
gastric losses in patient with
achlorhydria
sweat losses in patient with cystic
fibrosis
 II. Maintenance of metabolic alkalosis

1. Decreased of GFR
effective circulating volume depletion
Renal failure
2. Increased tubular reabsorption of
HCO3-
Effective circulating volume depletion
Chloride depletion
Hypokalemia
Hyperaldosteronism
 Effective circulating volume depletion

1. Increased proximal tubular HCO3-

reabsorption by;
increased angiotensin II
increased tubular fluid [HCO3-]
2. Increased distal tubular HCO3-
reabsorption by;
secondary hyperaldosteronism
chloride depletion
 Factors affecting bicarbonate
reabsorption by proximal tubule
Decreases reabsorption;
volume expansion
hyperkalemia
hypocapnia
hyperparathyroidism
phosphate depletion
hypocalcemia
 Factors affecting bicarbonate
reabsorption by proximal tubule
Increases reabsorption
hypercalcemia
volume contraction
hypercapnia
hypokalemia
glucose loading
 Chloride depletion
Effects on renal functions;
decreased GFR
stimulated RAAS increased renin,
AII, aldosterone
increased bicarbonate reabsorption in CD
decreased bicarbonate secretion in CD
increased potassium excretion
decreased urinary concentrating ability
 Chloride depletion
Mechanisms;
1. decreased chloride delivery to macula densa
increased renin release
secondary hyperaldosteronism
increased distal H+ secretion
increased HCO3- generation (reabsorption)
2. decreased tubular fluid [CL-]
increased chloride secretion
increased H+ secretion
increased HCO3- generation
3. decreased tubular fluid [CL-]
decreased CL- - HCO3- exchange
decreased HCO3- secretion
 Hypokalemia
increased HCO3- by;
1. intracellular acidosis
increased H+ secretion
2. increased K+-H+-ATPase
increased K+ reabsorption
increased H+ secretion
3. decreased CL- reabsorption in distal
nephron
increased lumen negativity
increased H+ secretion
 Hyperaldosteronism
Increased HCO3- reabsorption
by;
1. increased Na+ reabsorption in CCT
increased lumen negativity
increased H+ secretion
2. stimulate H+- ATPase pump
increased H+ secretion
Respiratory compensation
alkalemia inhibits respiratory
chemoreceptors
increased [HCO3-]
hypoventilation
increased pCO2
increase [HCO3-] 1 mEq/L
increase pCO2 ~ 0.7 mm Hg
 Symptoms
usually asymptomatic
related to volume depletion
weakness, muscle cramps, postural
dizziness
related to hypokalemia
polydipsia, polyuria, muscle weakness
related to decreased ionized calcium
paresthesia, carpopedal spasm or tetany
Adverse effects of metabolic alkalosis

Central nervous system

mental confusion, obtundation, delirium
decrease in seizure threshold
Neuromuscular
tetany, increased excitability
increased release of acetylcholine
Cardiovascular
decreased electrical stability, ventricular
fibrillation
increased sensitivity to cardiac glycosides
hypotension, decreased cardiac output
Adverse effects of metabolic alkalosis

Pulmonary
alveolar hypoventilation
Metabolic
hypokalemia
hypophosphatemia
decreased ionized calcium
increased glycolysis and lactate
production
shift of oxyhemoglobin curve to the left
 Diagnostic and therapeutic
classification of metabolic alkalosis
chloride-responsive: chloride-resistant:
urine [CL-] < 10 mEq/L urine [CL-] > 20 mEq/L

primaryaldosteronism
gastric fluid loss primary reninism
postdiuretic therapy hyperglucocorticoidism
DOC excess syndrome
posthypercapnia Liddles syndrome
congenital chloride licorice
diarrhea (cystic carbenoxolone
chloruretic (diuretic) agents
fibrosis) (early)
low chloride intake Bartters syndrome
Gitelmans syndrome
factitious diarrhea potassium depletion
(K < 2 mEq/L)
alkali load