Acid base homeostasis according to course curriculum of medical biochemistry for MBBS

1. ACID BASE
HOMEOSTASIS
DR. FARHANA ATIA
Associate Professor
Department of Biochemistry
Nilphamari Medical College, Nilphamari

2. Acid-Base Balance
• Normal pH: 7.4 [ H⁺ : 40 nmol/L]
• Body fluids maintained pH between 7.35-7.45
• Clinically safe: 7.3-7.5
• Compatible to life: 6.8-7.8
• Recovery unusual: <6.8 & >7.8
• Low pH: Acidic
• High pH: Alkaline

3. Origin of acid
Volatile acid [H₂CO₃]
• Aerobic metabolism of carbohydrate & lipid
Non volatile acid [all except H₂CO₃]
• Anaerobic metabolism of carbohydrate: lactic acid
• Insulin lack: Ketoacids
• Diet (protein)
HCl
Phosphoric acid- arginine, histidine
Sulfuric acid- cystine, methionine

4. Origin of base
Base originates by metabolism of some food stuff
• Vegetables
• Fruits
• Vegetarian: ↑ base production
• Non-vegetarian: ↑ acid production

5. Our body is net acid producer
• Volatile acid
Basal CO₂ production 12000-15000
mmoles/day
Disposed by respiratory system
• Net production of non-volatile/ fixed production
70-100 mmoles of H⁺/day
Non volatile acids are disposed by kidney

6. 3 Systems that maintain pH
First line defense: Buffers
Moves or release hydrogen ions
Act within seconds
Second line defense: Respiratory system
Regulate volatile acid by eliminating or retaining CO2
Act within minutes
Third line defense: Renal system
Long term regulation of acid-base in body
Act within hours to days

7. Buffers
• Very rapid but temporary
• Can not remove H⁺ from body
• Act as shock absorbent to reduce free H⁺ ion
• Blood buffers are-
1. Bicarbonate buffer: Most predominant buffer
2. Phosphate buffer: Mainly intracellular
3. Protein buffer: Buffer capacity is only 2% of total

8. Bicarbonate Buffer System
• Serve an index to
understand acid base
disorder in body
• At blood pH 7.4, the ratio of
HCO₃⁻ to H₂CO₃ is 20:1
• According to Henderson
Hasselbalch Equation,
pH = pK + log
HCO₃⁻
H₂CO₃

9. Compensation & Correction of ABD
• How this ratio is maintained?
1.By increasing/decreasing
plasma [HCO₃⁻]
2.By reducing/increasing PCO₂
• Normal [HCO₃⁻]:[H₂CO₃] =
20:1
• Compensation:
Maintaining the ratio of
[HCO₃⁻]:[H₂CO₃] towards
normal, so pH become
normal
• Correction: Concentration
of [HCO₃⁻] & [H₂CO₃]
become normal.

10. Respiratory Mechanism for pH Regulation
• Rapid but short term regulation
• Regulate [H₂CO₃] concentration in blood
H₂CO₃ CO₂ + H₂O
• All CO₂ is eliminated via the lungs
Carbonic Anhydrase

11. Renal Mechanism for pH Regulation
• Permanent solution of ABD
• Kidney is the only route to eliminate H⁺
ions from the body
• By two mechanisms
1. HCO₃⁻ reabsorption mechanism -
PCT (90%)
2. HCO₃⁻ generation mechanism -
DCT (where there is no filtered
HCO₃⁻)

12. Lumen PCT cell Capillary
HCO₃⁻ reabsorption mechanism

13. HCO₃⁻ Generation Mechanism

14. Acid Base Disorders
Arterial blood pH is closely regulated to 7.4 ±0.05
Simple ABD: pH change occurs due to change of either PCO₂
or HCO₃⁻
• Respiratory acidosis: ↑ PCO₂
• Metabolic acidosis: ↓ HCO₃⁻
• Respiratory alkalosis: ↓ PCO₂
• Metabolic alkalosis: ↑ HCO₃⁻
Complex ABD
• Combination of 2-3 simple type
• Both HCO₃⁻ & CO₂ get abnormal value

15. Simple Method to Diagnose ABD
Look at the pH
• pH <7.35 (acidosis); pH >7.45 (alkalosis)
Is the CO₂ abnormal?
• CO₂ is an acidic gas; raised with acidosis, lowered with
alkalosis  Respiratory problem
• No change; or an opposite one ↑↑↓↓  compensatory change
Is the HCO₃⁻ abnormal? [Normal: 22-28mmol/L]
• Is the change in keeping with pH?
• HCO₃⁻ is alkaline; raised with alkalosis, lowered with
acidosis Metabolic problem

16. State of
ABD
Primary
defect
Consequ
ence
Compensation by Correction by
Metabolic
acidosis
↓ HCO₃⁻ ↓ pH Hyperventilation
(↓PCO₂)
Kidney
Treatment of cause
(↑ HCO₃)
Metabolic
alkalosis
↑ HCO₃⁻ ↑ pH Hypoventilation
(↑PCO₂)
Kidney
Treatment of cause
(↓ HCO₃)
Respiratory
acidosis
↑ PCO₂ ↓ pH Renal HCO₃⁻
retention (↑HCO₃⁻)
Hyperventilation
Treatment of cause
Respiratory
alkalosis
↓ PCO₂ ↑ pH Renal HCO₃⁻
excretion (↓ HCO₃⁻)
Hypoventilation
Treatment of cause

17. Causes of ABD
Metabolic acidosis
[↑ production /↓ removal of
fixed or organic acid]
Metabolic alkalosis
[Accumulation of base/ loss of
acid other than H₂CO₃]
• Diabetic ketoacidosis
• Acute MI
• Lactic acidosis
• CRF
• Renal tubular acidosis
• Watery diarrhea
• Intestinal fistula
• Vomiting
• K depletion (diuretics)
• Burns
• Ingestion of base
• Excessive infusion of NaHCO₃

18. Causes of ABD
Respiratory acidosis
[Impaired excretion of CO₂]
Respiratory alkalosis
[excessive ventilation]
• COPD
• Chronic bronchitis
• Pulmonary fibrosis
• Acute bronchial asthma
• Narcotic overdose
• Anesthesia
• Stroke
• SAH
• Meningitis
• High altitude
• Hysteria
• Fever
• Pulmonary emboli
• Salicylate poisoning
• Pregnancy

19. Acid base parameters
Blood gas analysis of
arterial blood
• pH: 7.35-7.45
• HCO₃⁻: 24-30 meq/L
• PCO₂ : 40 mm of Hg
Additional parameters
• Actual HCO₃⁻: HHE from pH &
PCO₂.
• Standard HCO₃⁻: 24 meq/L
Measured under standard
condition
T: 37-38⁰ c
Hb: full saturated
PCO₂: 40 mm of Hg
• Base excess: ±2
• Total CO₂: 24-30 mmol/L

20. • Buffer base: Anti acid component of buffer pair
HCO₃⁻, pr⁻, H₂PO₄⁻, Hb⁻, HbO₂⁻
• Base excess: Changes in the concentration of buffer
base from its normal value. It refers to the HCO₃⁻
BE = Measured HCO₃⁻- Standard HCO₃⁻
Metabolic acidosis <-2
Metabolic alkalosis >+2
• Alkali reserve: Sum of all buffer base present in blood
 48 mEq/L.

21. The anion gap
• Estimates unmeasured plasma anions (fixed or organic
acids such as phosphate, ketone and lactate- hard to
measure directly)
• Importance:
1. Determine the cause of metabolic acidosis
2. Reflect those anion actually present but routinely
unmeasured

22. The anion gap
• Difference between plasma anion
& cation. In Plasma,
Cation = Anion
Na⁺+ K ⁺ = HCO₃⁻+ Cl
Na⁺+K⁺ = HCO₃⁻+Cl⁻
136+4 = 100+25
• This difference is anion gap
• 12±4meq/L= 8-16meq/L

23. Causes of Metabolic Acidosis
 MA with high AG (HCO₃⁻ & unmeasured anions
associated with the acids accumulates)
• Urate (RF)
• Lactic acid (shock, infection, tissue ischemia)
• Ketone (DM, alcohol)
• Drugs, toxins (Salisylate poisoning)

24. Causes of Metabolic Acidosis
 MA with normal AG (loss of HCO₃⁻/ ingestion of H⁺)
• Diarrhea
• Pancreatic fistula
• Renal tubular acidosis
• Addison’s disease
• NH₄Cl ingestion