The document outlines the physiology and clinical management of acid-base disorders, focusing on the bicarbonate-carbonic acid buffer system as the primary mechanism of acid-base homeostasis. It details the roles of the kidneys in acid excretion and bicarbonate reabsorption, along with a clinical approach to diagnosing and treating various acid-base disorders. Additionally, it explores treatment strategies for both metabolic acidosis and alkalosis, highlighting the need to address underlying causes and adjusting electrolyte imbalances.

1. Yewondwossen Tadesse MD
August 2009

2. Acid Base Physiology
Acid – Proton donor
Base – Proton acceptor
Acid Base + H
↔ +
K = [H+
] x [base]
[acid]
[H+
] = K x [acid]
[base]

3. Acid Base Physiology
In Complex Solutions
[H+
] = K1 [acid1] = K2 [acid2] = K3
[base1] [base2]
PH = -log10[H+
]
K = [H+
] x [HCO3
-
]
[H2CO3]
[H+] = K x αPaCO2  Henderson Equation
[HCO3]
K= 24

4. Acid Base Physiology
PH = pK x log[HCO3
-
] Henderson
αPaCO2 Hasslebach equation
pK = 6.1
Normal pH = 7.35 to 7.45
Normal [H+
] = 40nEq/L
Volatility is the predominant feature of the
bicarb/carbonic acid system

5. Acid Base Physiology
Other buffers are
- Proteins (a.as as well as Hgb) more important in
the ICF
- Phosphate- Primarily intracellular & then CaPO4
in bone
- Bone-bicarbonate/carbonate & phosphate
- Buffering by ionic shifts

6. Acid Base Physiology
Buffering is the ability of solutions containing
acid/base pairs to resist changes in acidity & the
acid/base pairs themselves are termed buffers.
The isohydric principle – in any solution
containing various buffer pairs the buffers are
conjoined by the fact that all are in equilibrium
with the same proton concentration.

7. Acid Base Physiology
Therefore, pH of ECF determine ratio of all buffer pairs &
pH can be calculated from only one buffer ratio.
Carbonic acid – bicarbonate buffer system most
important because
i) it’s the most prevalent in the ECF
ii) the concentration of its components can be varied
independently by 2 independent physiologic
regulatory systems.
iii) HCO3 is the only base consumed that can be
generated de novo, thus it is the currency of the
system.

8. Acid Base Physiology
 In the kidneys, reabsorption & generation of HCO3
-
occur.
 Reabsorption of HCO3
-
primarily occurs in the proximal tubule
where 90% of filtered HCO3
-
is reabsorbed.
 The kidneys are responsible for excretion of fixed acids. Fixed
acid excretion is done through excretion of titratable acid and
through the excretion of urinary ammonium.
 Net urine acid excretion(NUAE)= (Urinary ammonium +
titratable acidity)- Urinary bicarbonate
 Rate of production of fixed acid is 1mEq/kg/day in adults
≈
and 2-3mEq/Kg/d in children.
 Normally NUAE is 70 mmoles of which 40 mmoles is urinary
≈
ammonium and 30mmoles titratable acid.
 In severe acidosis NUAE 600mmol in severe acidosis.

9. Mechanisms of HCO3
-
reabsorption

10. Titratable acid excretion

11. Ammonium Excretion

12. Bicarbonate secretion(Type B intercalated cells)

13. Acid Base Disorders
 The body responds to changes in pH in three
steps
1) Buffering
2) Compensation
3) Correction

14. Clinical Approach to Acid-Base
Disorders
1. Clinical suspicion from the history & physical
examination
2. Evaluation of acid-base variables to determine
type of disorder
- evaluate venous total CO2[Cl],[K] & AG
- obtain arterial pH, pCO2 and [HCO3]
3. Estimation of compensation/adaptation and
plotting of patient’s values on the acid-base
map

15. Clinical Approach to Acid-Base
Disorders
4. Determine all the acid-base disorders
present on the basis of 1,2 & 3
Single disorder vs two or three
5. List a differential diagnosis of the causes of
identified acid-base disorder/s
- Anion gap in Metabolic acidosis
- Urinary Cl-
in Metabolic alkalosis
6. Treatment of the cause of the acid base disorder
± treatment of acidosis or alkalosis.

16. Pattern of Arterial Blood Changes and Adaptation
in Simple Acid Base Disorders
PrimaryDisor
der
pH
[H]
[ HCO
3] Adaptive pC O
Response
Limits of
adaptatiom
Metabolic
Acidosis
↓ ↑ ↓ ↓ pCO=1.5×[HCO]
+8±2
pCO not
<10mmHg
Metabolic
Alkalosis
↑ ↓ ↑ ↑ ↑pCO=0.5↑[HC
O]
pCO
not>55mmHg
Respiratory
acidosis-Acute
↓ ↑ ↑ ↑ ↑HCO=0.1↑pCO HCO not >
30mEq/L
Respiratory
acidosis-Chronic
↓ ↑ ↑↑ ↑ ↑HCO=0.4↑
pCO
HCO not
>45mEq/l
Respiratory
Alkalosis-Acute
↑ ↓ ↓ ↓ ↓HCO=0.2↓
pCO
HCO not < 17-
18 mEq/l
Respiratory ↑ ↓ ↓↓ ↓ ↓HCO=0.5↓pCO HCO not <12-

17. Metabolic Acidosis
Metabolic acidosis
- Primary in HCO
↓ 3
i) by addition of a readily dissociated acid
ii) by loss of HCO3 (GI, Kidneys)
iii) rapid dilution of ECF with non HCO3
-
solution
Responses
A.Buffering
B.Respiratory Compensation- never complete
C.Correction – by kidneys – by NAE
↑

18. Metabolic Acidosis
Clinical features
- Those of the primary disease
- Due to acidosis – RR(Kussmaul’s breathing)
↑
myocardial contractility, TPR
↓ ↓

19. Metabolic Acidosis
Major Adverse Consequences of Severe Acidemia
Cardiovascular
Impairment of cardiac contractility
Arteriolar dilation, venconstriction, and
centralization of blood volume
Increased pulmonary vascular resistance
Reductions in cardiac output, arterial blood
pressure, and hepatic and renal blood flow
Sensitization to reentrant arrhythmias and
Reduction in threshold of ventricular fibrillation
Attenuation of cardiovascular responsiveness to
catecholamines

20. Metabolic Acidosis
Major Adverse Consequences of Severe Acidemia
Respiratory
Hyperventilation
Decreased strength of respiratory muscles and promotion of muscle
fatigue
Dyspnea
Metabolic
Increased metabolic demands
Insulin resistance
Inhibition of anaerobic glycolysis
Reduction in ATP synthesis
Hyperkalemia
Increased protein degradation
Cerebral
Inhibition of metabolism and cell-volume regulation
Obtundation and coma

21. Metabolic Acidosis
Anion gap
Na+
+unmeasured=Cl-
+HCO3
-
+unmeasured
cations anions
Anion gap = [Na+
]-[Cl-
]+[HCO3
-
]
AG = 8-16mEq/L
- ↑Anion Gap metabolic acidosis - organic acidosis
or renal failure
- Normal Anion Gap(Hyperchloremic) metabolic
acidosis- excessive HCO3 losses.

22. Metabolic Acidosis
Normal AG met acidosis
i) GI losses- diarrhea, small bowel,
pancreatic/biliary drainage,
ureterosigmoidostomy
ii) Renal losses of HCO3-
- CA inhibtors, Renal tubular acidosis ,
hyperparathyroidism

23. Metabolic Acidosis
↑AG Metabolic Acidosis
- ↑acid production- Diabetic Ketoacidosis, Lactic
acidosis, starvation, alcoholic ketoacidosis
- Ingestion of toxins- Salicylates, Methanol,
ethylene glycol
- Failure of acid excretion – acute and chronic
renal failure.

24. Metabolic Acidosis
Rx- Treat primary disease
- Treat acidosis only if it is causing serious
organ/system dysfunction
- NaHCO3= desired HCO3
-
-observed HCO3
-
dose x50% BW
Avoid over shoot alkalemia

25. Metabolic Acidosis
- Dialysis
Carbicarb- NaHCO3 + Na2CO3
NaHCO3 + H+
HCO
→ 3 + Na
CO3
2-
+ H2CO3 2HCO
→ 3
-
THAM- 0.3N tromethamine
THAM + H+
THAM
→ +
THAM + H2CO3 THAM + HCO
→ 3
-

26. Rx- Alkali 1-3 mmol/kg/day
- K+ supplement, mineralocorticoids or loop
diuretics as indicated
Proximal RTA:- defective proximal tubular
reclamation of HCO3
-Na+
& K+
lost with HCO3
-
-a.a, glucose, PO4
-
may be wasted
-Causes-
10
, amyloidosis, MM
Rx- Alkali 10-25 mmoles/kg/day

27. TABLE 1
Causes of Hyperchloremic (Normal AG)
Metabolic Acidosis
Administration of chloride-containing acid
NH4Cl, HCl
Hyperalimentation
Cholestyramine
Bicarbonate wastage
GI tract (diarrhea, ileus, fistula, villous adenoma)
Urinary tract diversions to intestine
(ureterosigmoidostomy, ilea conduit)

28. Impaired renal H+
secretion and reduced NH4
Excretion
Distal RTA (hypokalemic and some hyperkalemic
Types)
Posthypocapnia (transient)
Impaired NH3 formation and reduced NH4
Excretion
Advanced renal insufficiency (GFR<20mL/min)
Hyperkalemia
Aldosterone deficiency

29. Metabolic Alkalosis
- ↑pH due to primary increase in HCO3
-
Causes
- Net loss of H+
from ECF - GI, Kidneys
e.g. Loss of gastric acid, diuretic treatment
- Net addition of HCO3 or precursors to ECF
e.g. Administration of lactate, citrate
- External loss of fluid containing Cl-
in greater
conc. and HCO3
-
in lesser conc. than in ECF
e. g. Villous adenoma

30. Metabolic Alkalosis
Responses
 Buffering- H+
from ICF
 Resp. compensation- alveolar ventilation and
↓
retention of CO2. ( PCO
↑ 2= 0.25-1 x HCO
↑ 3
-
)
 Renal correction
Factors that maintain metabolic alkalosis
- Volume depletion & ↑Aldosterone
- Hypokalemia
- Anion availability for Na reabsorption & replacement of
HCO in ECF.

31. Metabolic Alkalosis
Major adverse consequences of Severe alkalemia
 Cardiovascular
Arteriolar constriction
Reductionin coronary blood flow
Reduction in anginal threshold
Predispostion to refractory supraventicular and
ventricular arrhythmias
 Respiratory
Hypoventilation with attendant hypercapnia and
hyposemia

32. Metabolic Alkalosis
Major adverse consequences of Severe alkalemia
 Metabolic
Stimulation of anearobic glycolysis and organic
acid production
Hypokalemia
Decreased plasma ionized calcium concentration
Hypomagnesemia and hypophosphatemia
 Cerebral
Reduction in cerebral blood flow
Tetany, seizures, lethargy, delirium and stupor

33. Metabolic Alkalosis
Treatment of Metabolic Alkalosis
 Treat the underlying disorder
Correct constraints on HCO excretion by
provision of volume and NaCl.
Correct potassium depletion with KCl.
Remove source of mineralocorticoid or block its
effects.
Acetazolamide
HCl if Acetazolamide is ineffective.