Acid-Base Control - Sontag

8/3/2019 Acid-Base Control - Sontag

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Review ofReview ofAcid/Base ControlAcid/Base Control

Jean-Marie Sontag

COMMONWEALTH OF AUSTRALIA

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Medical Science Learning TargetsMedical Science Learning Targets

What is pH and how is it controlled?

What does the kidney do (in regards to pH control)?

pHpH

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)


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Blood pH=7.4Blood pH=7.4

The maintenance of blood pHThe maintenance of blood pH

Normal blood pH=7.4

Why is this important?

pHs 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


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Why does pH change?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 base-producing foods

Cell metabolism:

Anaerobic respiration of glucose produceslactic acid

Carbohydrate/fat/protein breakdown throughKrebs cycle leads to carbon dioxide

production. Transporting carbon dioxide as

bicarbonate releases hydrogen ions

Fat metabolism yields organic acids andketone bodies

Faeces production removes bicarbonate fromblood

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?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 bufferingII. CO2 transport by haemoglobin

3. Cellular exchange Acts within minutes

Intra/extracellular potassium-proton exchange

4. 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


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1.Chemical buffer systems1.Chemical buffer systems

Blood acids and basesBlood acids and bases

Acids and bases: overview

Strong acids: all their H+ isdissociated completely in water (HC)

Weak acids: dissociate partially inwater and are efficient at preventingpH changes (HA, HB, HD)

Strong bases: dissociate easily inwater and quickly tie up H+

Weak bases: accept H+ more slowly

and are efficient at preventing pHchanges (A, B, D)

Weak acids and their basecounterparts (HA and A, HB and B,

HD and D) act as chemical buffers

HA

A

+

HD D + H+ + B HB

+

C

HC

1.Chemical buffering systems1.Chemical buffering systems

Blood acids and basesBlood acids and bases

Definition: A buffer is a solutionthat resists a significant change inpH upon addition of an acid or abase.

A buffer is a mixture of a weakacid and its conjugate base

Biological systems use buffers tomaintain pH

There are three major chemicalbuffer 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: organicacids, sulphate, ammonia

Any drifts in pH are resisted by theentire chemical buffering system

Interaction between differentbuffer systems


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Distribution of Bicarbonate in the BodyDistribution of Bicarbonate in the Body

ECF: extracellular fluid

ICF: intracellular fluid

Bicarbonate distribution in the bodyBicarbonate distribution in the body


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Bicarbonate buffer systemBicarbonate buffer system

CO2 + H2O H2CO3 HCO3- + H+ CO3

2- + H+

NaHCO3 HCO3- + Na+

Respiratory component

Renal component

CA

CA: carbonic anhydraseControls reaction both waysRed blood cells, kidney, lungs, intestineInside/outside cells

Bicarbonate reserve in ECFStockpiles of HCO3

- as NaHCO3Or release of more HCO3

- when required

Buffer: H2CO3/ HCO3-

(volatile acid)(exhaled)

H2CO3

HCO3-

pKa= 6.4

Blood pH 7.4

Weak acid

Urine pH 6.0

Weak base


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

At urine pH 6.0 [H2CO3] [HCO3-]

This system is animportant ECFbuffer

CO2 + H2O H2CO3 HCO3- + H+ CO3

2- + H+

CA

pKa

Henderson-Hasselbalch:pH= pKa + log10 [A

-]/[HA]


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H2CO3 + OH- HCO3

- + H2O

NaHCO3 HCO3-

+ Na+

H2CO3 HCO3- + H+

NaHCO3 HCO3- + Na+

pH increase

pH decrease

CACO2 + H2O H2CO3 HCO3- + H+

OH-

H+

Summary

Combined responses/equilibriumpH maintained


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Distribution of Phosphate in the BodyDistribution of Phosphate in the Body

ECF: extracellular fluid

ICF: intracellular fluid

Phosphate distribution in the bodyPhosphate distribution in the body


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Phosphate buffer systemPhosphate buffer system

Phosphate reserve in ICF

Stockpiles of HPO42- as Na2HPO4

Or release of more HPO42- when required Buffer: H2PO4

-/ HPO42-

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

Na2HPO4 HPO42- + 2Na+


H3PO4 H2PO4- + H+ HPO4

2- + H+ PO43- + H+

Blood/Cell pH 7.4

This system is an effective buffer in urine andintracellular fluid

At blood pH 7.4 [HPO42-] [H2PO4]

At urine pH 6.0 [HPO42-]


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H2PO4- + OH- HPO4

2- + H2O

Na2HPO4 HPO42-

+ Na+

H2PO4- HPO4

2- + H+

Na2HPO4 HPO42- + 2Na+

pH increase

pH decrease

H2PO4- HPO42-+ H+

OH-

H+

Summary

Combined responses/equilibriumpH maintained


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Protein buffer systemProtein 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 OH-

depending on pH (mainly via COOH and NH2groups in amino acids/proteins)

Protein buffer systemProtein buffer systemExample: amino acidExample: amino acid

[H+][OH-]


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Protein buffer systemProtein 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 regulation2.Respiration regulation

COCO22 transport in the blood and heamoglobin bufferingtransport in the blood and heamoglobin buffering

++

H+H+

K+

RBC: red blood cellsCA: carbonic anhydraseHgb: haemoglobin

Lungs

H++

CO2CO2

- CO2 transport in the blood

- Haemoglobin buffering

H2O

H2O+


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2.Respiration regulation2.Respiration regulation

-- COCO22 transport by haemoglobintransport by haemoglobin

CA: carbonic anhydraseHb: heamoglobin

HCO3-

Lungs

CO2

1

2

Hb-

Hb .CO2

H+

H+

K+K+


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How acidHow acid--base balance affects oxygenationbase balance affects oxygenation

Effect of carbon dioxideEffect of hydrogen ions H+ (pH)

Oxygen-Haemoglobin binding curve

Respiratory regulation of acidRespiratory regulation of acid--base balancebase balance

Haemoglobin Buffer system

Only happening in RBC ICF

Helps prevent changes in pH when PCO2 CO2 + Hb HbCO2 O2 + HHb HbO2 + H

+

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)


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3.H/K Exchange3.H/K Exchange

K+ H+K+ 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 tobe moved extracellularly in exchange forhydrogen ions. Hyperkalemia may result.

The exchange of potassium and hydrogenions that can lead to hypokalemia in casesof alkalosis.


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4.Renal mechanisms of pH control4.Renal mechanisms of pH control

Chemical buffers can tie up excess acids or bases, butthey cannot eliminate them from the body

The lungs can eliminate carbonic acid (volatile acid) byeliminating carbon dioxide

Only the kidneys can rid the body of metabolic acids(phosphoric, uric, and lactic acids and ketones) andprevent metabolic acidosis

The ultimate acid-base regulatory organs are the kidneys

Renal mechanisms of pH controlRenal mechanisms of pH control

Location: proximal and distal tubulesLocation: proximal and distal tubules--collecting ductcollecting duct

illustration


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Secretion/AbsorptionSecretion/Absorption

Proximal and distal tubulesProximal and distal tubules--collecting ductcollecting duct

illustration

4.Renal Mechanisms of pH control4.Renal Mechanisms of pH control

The most important renal mechanisms forregulating 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


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Production/Reabsorption of BicarbonateProduction/Reabsorption of Bicarbonate

=> Renal regulation of H+ and HCO3-

General strategy

1. Balance the H+ intake and production with H+ excretion

2. Recover HCO3- to preserve buffering capability

Reabsorption/production of bicarbonateReabsorption/production of bicarbonate

Proximal Tubules


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HCOHCO33-- reabsorptionreabsorption

Basic Mechanism in theBasic Mechanism in the ProximalProximal TubuleTubule

1. CO2 and H2O form H2CO3, which splits into H+ and HCO3-

2. 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 bicarbonateReabsorption/production of bicarbonate

Collecting DuctCollecting Duct


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Phosphate buffering in the renal tubePhosphate buffering in the renal tubeBicarbonate production/ReabsorptionBicarbonate production/Reabsorption

H+H+

Phosphate buffering in the renal tubePhosphate buffering in the renal tube

Bicarbonate production/ReabsorptionBicarbonate production/Reabsorption


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Ammonium ion excretionAmmonium ion excretion

and buffering in the renal tubuleand buffering in the renal tubule

Bicarbonate production/ReabsorptionBicarbonate production/Reabsorption

Kidney Hydrogen Ion BalancingKidney 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 HCO3-

Type B intercalated cells absorb H+ and secrete HCO3-


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Renal SummaryRenal Summary

Bicarbonate buffers are important in the

blood and extracellular fluids

In the kidney: Bicarbonate allows for excretion of H+ aswater and preservation of HCO3

-

Phosphate and ammonia serve as tubule fluidspecific buffers and they allow for productionof new HCO3

-

Renal SummaryRenal Summary


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5.Gastrointestinal tract5.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 tractGastrointestinal 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 bloodalkalosis

Blood pH regulation is not a normal GIT task; usedby body as last resort when all other mechanismsare swamped or are failing


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Responses to acidResponses to acid--base imbalancebase imbalance

1. Fast - Fluid buffering systems as outlinedabove

2. Moderate Respiratory chemoreceptorssensitive to CO2 and [H

+] regulatebreathing and CO2 levels

3. Slow (days) Renal - adjust HCO3- and H+

handling and production of new HCO3-

ACIDOSIS AND ALKALOSISACIDOSIS AND ALKALOSIS

Respiratory Acidosis

Shallow breathing

CO2 exhaled or CO2 retained Lung diseases blocking gas diffusion e.g. pneumonia, emphysema

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


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illustration

Acid-Base

Disturbance PrimaryDisturbance CompensatoryResponse CompensatoryMechanismRespiratory

acidosis

Increased pCO2 Increase [HCO3-] Acidic urine

Respiratory

alkalosis

Decreased pCO2 Decreased [HCO3-] Alkaline urine

Metabolic

acidosis

Decreased [HCO3-] Decrease pCO2 Hyperventilation

Metabolicalkalosis

Increased [HCO3-] Increased pCO2 Hypoventilation

illustration


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ReferencesReferences

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

Acid-Base Control - Sontag

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