acid-base control - sontag
TRANSCRIPT
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Review ofReview ofAcid/Base ControlAcid/Base Control
Jean-Marie Sontag
COMMONWEALTH OF AUSTRALIA
Copyright Regulations 1969
WARNING
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The material in this communication may be subject to copyright under the Act. Anyfurther reproduction or communication of this material by you may be the subject of
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Do not remove this notice.
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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
Bicarbonate buffer systemBicarbonate buffer system
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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Bicarbonate buffer systemBicarbonate buffer system
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+
Phosphate buffer systemPhosphate buffer system
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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Phosphate buffer systemPhosphate buffer system
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