Review of Acid/Base Control

Jean-Marie Sontag

COMMONWEALTH OF AUSTRALIA
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Medical Science Learning Targets

What is pH and how is it controlled? What does the kidney do (in regards to pH control)?

pH

pH is the measure of acidity or alkalinity of a solution pH in the body (ICF and ECF) is controlled by mechanisms involving acids and bases
Acids are proton (hydrogen ion H+) donors Bases are proton acceptors Weak acids and weak bases in body (except for HCl in stomach!)

In medicine, pH values refer to blood pH (arterial)

Blood pH=7.4

The maintenance of blood pH

Normal blood pH=7.4 Why is this important?
pHs <6.8 and >7.8 incompatible with life maintains protein shape (enzyme activity, binding proteins function etc.) maintains membrane gradients (neurons: action potential) hydrogen ions gradients generate ATP in mitochondria

Very dangerous pH levels

Why does pH change?

pH decreases=excess hydrogen ions in the blood
Most hydrogen ions originate from: Breakdown of food (e.g. proteins); body normally consumes more acid-producing foods than baseproducing foods Cell metabolism: Anaerobic respiration of glucose produces lactic acid Carbohydrate/fat/protein breakdown through Krebs cycle leads to carbon dioxide production. Transporting carbon dioxide as bicarbonate releases hydrogen ions Fat metabolism yields organic acids and ketone bodies Faeces production removes bicarbonate from blood

pH increases=decrease of hydrogen ions in the blood

Carbon dioxide expiration Kidney removal of H+

Hydrogen balance in the body

How is pH controlled?
The concentration of hydrogen ions is regulated by: 1. Chemical buffer systems:
First to respond Take less than one second Temporarily tie up excess acids and bases Control by blood acids and bases in body fluids (ECF, ICF)

2.

Respiratory regulation of acid/base balance:

Second to respond Acts within 1-3 minutes Respiratory centre is involved Regulating removal of CO2 (and therefore H2CO3): I. CO2 transport in the blood and heamoglobin buffering II. CO2 transport by haemoglobin

3. 4.

Cellular exchange
Acts within minutes Intra/extracellular potassium-proton exchange

Renal mechanisms :
Third to respond but most important Require hours to days to induce pH changes Kidneys excrete acid or alkaline urine

5.

Gastrointestinal tract :
Last to respond Requires days to induce pH changes Removing excess hydrogen ions or bicarbonate

Note: regulatory steps 2 and 3 act in concert

1.Chemical buffer systems Blood acids and bases

Acids and bases: overview Strong acids: all their H+ is dissociated completely in water (HC) Weak acids: dissociate partially in water and are efficient at preventing pH changes (HA, HB, HD) Strong bases: dissociate easily in water and quickly tie up H+ Weak bases: accept H+ more slowly and are efficient at preventing pH changes (A, B, D) Weak acids and their base counterparts (HA and A, HB and B, HD and D) act as chemical buffers

HA A + D + H+ + B + C HC

HD

HB

1.Chemical buffering systems Blood acids and bases

Definition: A buffer is a solution that resists a significant change in pH upon addition of an acid or a base. A buffer is a mixture of a weak acid and its conjugate base Biological systems use buffers to maintain pH There are three major chemical buffer systems in the body:
1. The bicarbonate buffer system 2. The phosphate buffer system 3. The protein (and amino acid) buffer system

Other buffer systems: organic acids, sulphate, ammonia Any drifts in pH are resisted by the entire chemical buffering system Interaction between different buffer systems

Distribution of Bicarbonate in the Body

ECF: extracellular fluid ICF: intracellular fluid

Bicarbonate distribution in the body

Bicarbonate buffer system

Renal component Respiratory component

(exhaled)

CO2 + H2O H2CO3 HCO3- + H+ CO32- + H+ CA (volatile acid) NaHCO3 HCO3- + Na+
CA: carbonic anhydrase Controls reaction both ways Red blood cells, kidney, lungs, intestine Inside/outside cells Bicarbonate reserve in ECF Stockpiles of HCO3- as NaHCO3 Or release of more HCO3- when required Buffer: H2CO3/ HCO3-

Bicarbonate buffer system

CO2 + H2O H2CO3 HCO3- + H+ CO32- + H+ CA
Weak base

pKa
This system is an important ECF buffer Blood pH 7.4 pKa= 6.4 Urine pH 6.0

HCO3-

Henderson-Hasselbalch: pH= pKa + log10 [A-]/[HA]

Weak acid

H2CO3

At blood pH 7.4 [HCO3-] >> [H2CO3] At urine pH 6.0 [H2CO3] [HCO3-]

Bicarbonate buffer system

H2CO3 + OH- HCO3- + H2O NaHCO3 HCO3- + Na+

pH increase

H2CO3 HCO3- + H+ NaHCO3 HCO3 +

-

pH decrease

Na+

OHSummary

CO2 + H2O H2CO3 HCO3- + H+

CA
Combined responses/equilibrium pH maintained

H+

Distribution of Phosphate in the Body

ECF: extracellular fluid ICF: intracellular fluid

Phosphate distribution in the body

Phosphate buffer system

H3PO4 H2PO4- + H+ HPO42- + H+ PO43- + H+ Na2HPO4 HPO42- + 2Na+

Phosphate reserve in ICF
Stockpiles of HPO42- as Na2HPO4 Or release of more HPO42- when required Buffer: H2PO4-/ HPO42-

Phosphate buffer system

H3PO4 H2PO4- + H+ HPO42- + H+ PO43- + H+

pKa

Blood/Cell pH 7.4

Urine pH 6.0 This system is an effective buffer in urine and intracellular fluid

At blood pH 7.4 [HPO42-] [H2PO4] At urine pH 6.0 [HPO42-] << [H2PO4]

Phosphate buffer system

H2PO4- + OH- HPO42- + H2O Na2HPO4 HPO42- + Na+

pH increase

H2PO4- HPO42- + H+ Na2HPO4 HPO4 +

2-

pH decrease

2Na+

Summary
Combined responses/equilibrium pH maintained

OH-

H2PO4- HPO42-+ H+
H+

Protein buffer system

Amino Acid Buffers Plasma Protein Buffers (all proteins including haemoglobin in red blood cells) Slower than other chemical buffers Remove either excess H+ or excess OHdepending on pH (mainly via COOH and NH2 groups in amino acids/proteins)

Protein buffer system

Example: amino acid

[H+]

[OH-]

Protein buffer system

Plasma and intracellular proteins are the bodys most plentiful and powerful buffers

Proteins use COO- and NH2 groups at each end and side chains for buffering

2.Respiration regulation CO2 transport in the blood and heamoglobin buffering - CO transport in the blood - Haemoglobin buffering
2

K+

Lungs

H+

H+ +

+
H2O

CO2

CO2
H2O

+ H+

RBC: red blood cells CA: carbonic anhydrase Hgb: haemoglobin

2.Respiration regulation - CO2 transport by haemoglobin

CA: carbonic anhydrase Hb: heamoglobin HCO31 H+ K+ K+ HbHb .CO2 Lungs H+

CO2

How acid-base balance affects oxygenation

Effect of carbon dioxide

Effect of hydrogen ions H+ (pH)

Oxygen-Haemoglobin binding curve

Respiratory regulation of acid-base balance

Haemoglobin Buffer system
Only happening in RBC ICF Helps prevent changes in pH when P
CO2 + O2 + Hb HHb HbCO2 HbO2 + H+
CO2

There is a reversible equilibrium between dissolved carbon dioxide and water, carbonic acid and the hydrogen and bicarbonate ions CO2 + H2O H2CO3 H+ + HCO3 During carbon dioxide unloading, hydrogen ions are incorporated into water When hypercapnia or rising plasma H+ occurs:
Deeper and more rapid breathing expels more carbon dioxide Hydrogen ion concentration is reduced

Alkalosis causes slower, more shallow breathing, causing H+ to increase Respiratory system impairment causes acid-base imbalance (respiratory acidosis or respiratory alkalosis)

3.H/K Exchange

K+

K+

H+

H+

Acid-base disturbances cause disturbances in K+ balance (hyper and hypokaelemia) Disturbances in K+ homeostasis affect intracellular pH

Acidosis will cause more potassium ions to be moved extracellularly in exchange for hydrogen ions. Hyperkalemia may result.

The exchange of potassium and hydrogen ions that can lead to hypokalemia in cases of alkalosis.

4.Renal mechanisms of pH control

Chemical buffers can tie up excess acids or bases, but they cannot eliminate them from the body The lungs can eliminate carbonic acid (volatile acid) by eliminating carbon dioxide Only the kidneys can rid the body of metabolic acids (phosphoric, uric, and lactic acids and ketones) and prevent metabolic acidosis The ultimate acid-base regulatory organs are the kidneys

Renal mechanisms of pH control Location: proximal and distal tubules-collecting duct

illustration

Secretion/Absorption Proximal and distal tubules-collecting duct

illustration

4.Renal Mechanisms of pH control The most important renal mechanisms for regulating acid base balance are:
Production/reabsorption of new bicarbonate ions Kidney tubules secretion into urine of: 1. Hydrogen ions 2. Phosphate ions 3. Ammonium 4. Bicarbonate

Production/Reabsorption of Bicarbonate
=> Renal regulation of H+ and HCO3General strategy 1. Balance the H+ intake and production with H+ excretion 2. Recover HCO3- to preserve buffering capability

Reabsorption/production of bicarbonate

Proximal Tubules

HCO3- reabsorption Basic Mechanism in the Proximal Tubule

1. CO2 and H2O form H2CO3, which splits into H+ and HCO32. HCO3- moves to the interstitial fluid and blood 3. H+ is secreted into tubule, where it reacts with filtered HCO3- to regenerate CO2 and H2O 4. For every HCO3- filtered, an HCO3- is formed within the tubular cell & transported to the interstitial fluid and blood

Reabsorption/production of bicarbonate
Collecting Duct

Phosphate buffering in the renal tube

Bicarbonate production/Reabsorption

H+

H+

Phosphate buffering in the renal tube Bicarbonate production/Reabsorption

Ammonium ion excretion and buffering in the renal tubule Bicarbonate production/Reabsorption

Kidney Hydrogen Ion Balancing

Proximal Tubule
H+ , NH3 and HPO42- are secreted into lumen and excreted H+ ions are secreted as CO2, NH4+ and H2PO4- molecules HCO3- is reabsorbed

Collecting Duct
Type A Intercalated cells excrete H+ and absorb HCO3Type B intercalated cells absorb H+ and secrete HCO3-

Renal Summary
Bicarbonate buffers are important in the blood and extracellular fluids In the kidney: Bicarbonate allows for excretion of H+ as water and preservation of HCO3 Phosphate and ammonia serve as tubule fluid specific buffers and they allow for production of new HCO3-

Renal Summary

5.Gastrointestinal tract
Healthy individual
H+ ion secretion into stomach HCO3- ion secretion in pancreas and liver H+/K+ exchange in colon Cl-/HCO3- exchange in colon

Gastrointestinal tract
Individual with blood acidosis
H+ ion secretion into stomach HCO3- ion secretion in pancreas and liver Cl-/HCO3- exchange in colon H+/K+ exchange in colon: more H+ in cells, more K+ outside

Opposite situation with individual having blood alkalosis Blood pH regulation is not a normal GIT task; used by body as last resort when all other mechanisms are swamped or are failing

Responses to acid-base imbalance

1. Fast - Fluid buffering systems as outlined above 2. Moderate Respiratory chemoreceptors sensitive to CO2 and [H+] regulate breathing and CO2 levels 3. Slow (days) Renal - adjust HCO3- and H+ handling and production of new HCO3-

ACIDOSIS AND ALKALOSIS

Respiratory Acidosis
Shallow breathing CO2 exhaled or CO2 retained Lung diseases blocking gas diffusion e.g. pneumonia, emphysema CO2 H+ pH <7.35

Respiratory Alkalosis
CO2 exhaled Hyperventilation, e.g. anxiety, hysteria CO2 H+ pH > 7.45

Metabolic Acidosis
Renal disease Diarrhoea Starvation H+ pH < 7.35

Metabolic Alkalosis
Vomiting Ingestion of Bicarb of Soda (NaHCO3) o H+ pH > 7.45

illustration

illustration

Acid-Base Disturbance Respiratory acidosis Respiratory alkalosis Metabolic acidosis Metabolic alkalosis

Primary Disturbance Increased pCO2 Decreased pCO2 Decreased [HCO3-] Increased [HCO3-]

Compensatory Response Increase [HCO3-] Decreased [HCO3-] Decrease pCO2 Increased pCO2

Compensatory Mechanism Acidic urine Alkaline urine Hyperventilation Hypoventilation

illustration

References

Clinical Chemistry in diagnosis and treatment Philip D Mayne Arnold London Clinical Biochemistry Gaw et al., Churchill Livingston Edinburgh Other clinical Biochemistry texts Harrisons Textbook of Medicine