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Department of Physiology | School of 10/7/2020

Biomedical Sciences

Acid-Base
Physiology

Physiological Buffers

Yossi Rathner
Joseph.rathner@unimelb.edu.au

Department of Physiology
School of Biomedical Sciences

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Department of Physiology

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Department of Physiology | School of 10/7/2020
Biomedical Sciences

Major physiological buffers


• Bicarbonate • Bicarbonate
• HCO3-
• CO2 + H2O ⇌ H2CO3 ⇌ HCO3- + H+
• Phosphate
- Organic • Phosphate
▪ Nucleotides
• HPO4- + H+ ⇌ H2PO4-
- Inorganic
▪ HPO42-
▪ H2PO4-
• Ammonium/Ammonia
• Ammonium/Ammonia
• NH4+/NH3 • NH4+ ⇌ NH3 + H+
• Proteins
• Albumin • Hemoglobin
• intracellular
• Hemoglobin • Hb +H+ ⇌ H-Hb+

Department of Physiology

Location of Buffer Systems in the body

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Department of Physiology | School of 10/7/2020
Biomedical Sciences

Blood/plasma ECF Intracellular fluid

H+ +HPO42- ⇌H2PO4-
H+ 2-
+HPO4 ⇌H2PO4 -
Protein + H+ ⇌Protein-H

RBC
* H CO ⇌ H++HCO -
CO2 + H2O ⇌ 2 3 3

*
CO2 + H2O ⇌ H2CO3 ⇌ H++HCO3-

Albumin - H

Department of Physiology
* Regulated by the enzyme – carbonic anhydrase

H+ absorbed by the principal buffer


systems
Buffer Amount per litre of Mmol H+ absorbed
blood per litre
Bicarbonate 25 mmole 18 *
Phosphate 1.25 mmole 0.3
Plasma Protein 40 g 1.7
Haemoglobin 150 g 8
Total 28

• Note the relative importance of the bicarbonate buffer system:


• CO2 as a gas – open system, regulated by ventilation.

Department of Physiology

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Department of Physiology | School of 10/7/2020
Biomedical Sciences

Isohydric principle

All the buffer systems in the body are linked.


• Altering one = impact on all others.
• ∴ by knowing what happens in the bicarbonate
system in the body – we know what is happening
to all systems.
• ∴ we typically only assess the HCO3- system.

Department of Physiology

Acid-Base
Physiology

Physiological Acid Production

Yossi Rathner
Joseph.rathner@unimelb.edu.au

Department of Physiology
School of Biomedical Sciences

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Department of Physiology | School of 10/7/2020
Biomedical Sciences

Two basic forms of acids


1) Volatile acids
• Can be converted into a gas
• Eliminated via the lungs
• Most prominent = CO2/bicarbonate

2) Fixed acids
• “non-volatile” – cannot be made into a gas
• Eliminated via the kidneys
• Normal metabolism of proteins and phospholipids results in generation of sulfuric acid
• strenuous exercise can result in the generation of substantial lactic acid
• Ketoacidosis – large amounts of β-hydroxybutyric acid and acetoacetic acid
• Dietary and pharmacological acid
• E.g. asprin → salacyclic acid

Department of Physiology

Acid-Base
Physiology

Respiratory control of pH

Yossi Rathner
Joseph.rathner@unimelb.edu.au

Department of Physiology
School of Biomedical Sciences

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Department of Physiology | School of 10/7/2020
Biomedical Sciences

Alterations in PaCO2 alter pH CSF


• Respiration is involved in the short term control of pH
in the body.
• CO2 dissolved in water is an acid
• Central chemoreceptors are sensitive to changes in pH
• Increased ventilation, decreased PaCO2, increased pH

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Relationship between PaCO2 and CSF pH

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Department of Physiology | School of 10/7/2020
Biomedical Sciences

Central chemoreceptors are sensitive to


changes in pH

• Change in sensitivity
to PaCO2 in response
to change in CSF [H+]
- As ↓ pH,
respiratory rate ↑

Department of Physiology

Ventilation in the control of pH

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Department of Physiology | School of 10/7/2020
Biomedical Sciences

Acidosis

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Alkalosis

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Department of Physiology | School of 10/7/2020
Biomedical Sciences

Acid-Base
Physiology

Kidneys in long term regulation of pH

Yossi Rathner
Joseph.rathner@unimelb.edu.au

Department of Physiology
School of Biomedical Sciences

The kidneys are involved in long term


regulation of acid base balance
• Bicarbonate buffer system
• CO2 + H2O ↔ H2CO3 ↔ H+ + HCO3- (Carbonic anhydrase)
• CO2 is membrane permeable, HCO3- is not!
• Shifting this reaction to the right, recovers bicarbonate from the filtrate
→ lowers blood pH
• CO2 removed via lungs
• Phosphate buffer system
• H+ is actively pumped into filtrate
• H+ + HPO42- → H2PO4-
• Inside cell HCl →H+ + Cl-
• Cl- is exchanged for HCO3-
• Ammonium (NH4+)
• Not membrane permeable.

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Department of Physiology | School of 10/7/2020
Biomedical Sciences

Summary of secretion
and reabsorption in
kidneys

Proximal convoluted
tubules
NH4+ secretion

Distal collecting
ducts

Department of Physiology

Tubular regulation of Acid-Base balance

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Department of Physiology | School of 10/7/2020
Biomedical Sciences

Acid secretion coupled with phosphate


buffer

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Amino Acid metabolism – ammonia secretion


PCT

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Department of Physiology | School of 10/7/2020
Biomedical Sciences

Acid-base
physiology

Acidosis and alkalosis

Yossi Rathner
Joseph.rathner@unimelb.edu.au

Department of Physiology
School of Biomedical Sciences

Anion Gap

• Electroneutrality
• σ 𝑐𝑎𝑡𝑖𝑜𝑛𝑠 = σ 𝑎𝑛𝑖𝑜𝑛𝑠
• Measured ions
• HCO3-
• Na+
• (maybe – K+)
• Cl-
• Anion gap
• AG=[unmeasured anions]-[unmeasured cations]

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Department of Physiology | School of 10/7/2020
Biomedical Sciences

Acidosis and
Alkalosis

Acid-base nomogram

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Respiratory acidosis and alaklosis

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Department of Physiology | School of 10/7/2020
Biomedical Sciences

Metabolic Acidosis and alkalosis

Department of Physiology

Department of Physiology
School of Biomedical Sciences

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