Acid Base Disorders for MBBS
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Transcript of Acid Base Disorders for MBBS
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Acid Base Disorders
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Acid Base Disorders
Hydrogen ion (H+) homeostasis
Essential for life:e.g. mitochondrial function
charge & shape of proteins
ionisation of Ca++, Mg++
The concentration H+ ion is 35-45
nmol/L
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Hydrogen ion units
H+ conc. as nanomoles per litre (nmol/L)
H+ as pH pH = 1/ log10H+ in mol/L
e.g. 100 nmol/L = 1/ log10100 x 10-9
pH = 1/log 10-7
pH = 7
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In vivo production of
protons
The human body is a net-producer of
protons (non-carbonic acids)
Intracellular and extracellular proton
concentration still needs to be kept withinnarrow limits
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Understanding Normal Acid-Base Handling
Metabolic processes in the body lead to the production of acid
The catabolism of glucose and fatty acids produces CO2and H2O,
effectively carbonic acid.
About 1 mmol/Kg body weight of H+is produced a day in the body.
Respiratory elimination of CO2and cellular buffers handle this acid load.
Renal excretion of acid must be maintained.
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Daily H+turnover (mmol/24hrs)
Source of acid Production Amount Disposal
CO2 tissue respiration 20,000 lungs
Lactate glycolysis 1300 gluconeogenesis
& oxidation
FF/acids lipolysis 600 re-esterification& oxidation
Ketoacids ketogenesis 400 oxidation
Urea synthesis ureagenesis 1140 oxidation ofamino
acids
H2SO4 S-containing 40 renal excretion &
amino acid buffered acids
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EXTERNAL
FLUID
BLOOD IN
CAPILLARIES
Sources of Daily acid load
CELL
METABOLISM
Volatile H+
CO2
Non-volatile H+
abnormal
metabolic acids
(lactic,
acetoacetic,
hydroxybutyric,
formic,glycolic)
DIET
Proteins,
acidic or alkali foods
Toxins
drugs
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Acid- tends to donate a proton
Definitions, buffers, equations, pH, pKa
Base- tends to accept a proton
HAH++ A-
pH -log[H+]
B + H+ BH+
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HAH++ A-
Taking minus logs:
Ka
[H+][A-]
[HA]
Rearrange: [H+]= Ka
[HA]
[A-]
-log [H+] = -log [Ka] - log[HA]
[A-
]pKa -log Ka
and pH = -log[H+]
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-log[H+
] = -log[Ka] - log
[HA]
[A-]
pH = pKa + log
[A-]
[HA]
This is the Henderson-Hasselbalch Equation
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Use of biological buffersNeeded for buffering of protons produced
by the production of CO2 from cells (15,000 mmol/24 h)
by catabolism of sulfuric amino acids (100 mmol/24 h)
by intermediary metabolism, e.g. lactic acid, acetoaceticacid, beta-hydroxybutyric acid
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plasma H++ HCO3- H2CO3 pKa ~ 6.1
Common buffer systems in the body
urine H++ NH3 NH4 + pKa = 9.0
urine H++ HPO4--H2PO4
- pKa = 6.8
cell H++ protein- proteinH pKa = 7.0
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Buffering
Buffering: Limitation of the change in H+in theface of a tendency to change
Base-
+ H+
Hbase
HBase + OH- H2O + Base-
HCO3-+ H
+ H2CO3
H2CO3 + OH- HCO-3 + H2O
Bicarbonate buf fer ing s ystem most important
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The CO2- HCO3-buffer system
is important in the plasma
The pKa = 6.1
pH = 6.1 + log
[HCO3-]
[H2CO3]
Since H2CO3= pCO2x (0.03)
H+
+ HCO3- H2CO3 CO2+ H2O
pH = 6.1 + log[HCO3
-]
[.03 x pCO2]
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Other buffers: haemoglobin
CO2
Cl- Cl-
CO2 + H2O H2CO3 H+ + HCO-3 HCO
-3
Hb-
HbH
CO2from tissue respiration
Carbonatedehydratase
erythrocyte
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Other buffers: haemoglobin
CO2
Cl- Cl-
CO2 + H2O H2CO3 H+ + HCO-3 HCO
-3
Hb-
HbH
CO2loss inalveoli
Carbonatedehydratase
erythrocyte
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Recovery of Filtered Bicarbonate in Kidneys
Recovery of Filtered Bicarbonate in Kidneys
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Generation of Additional Bicarbonate in Kidneys
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The Kidney
Reabsorbs 4500 mmol of HCO3 per day
Generates new HCO3 to replenish bufferstores
The Proximal tubule does most of the work
The Distal tubule eliminates H+ = to thenonvolatile acid production
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Hydrogen ion excretion
Lungs: rapid and sensitive compensation bycontrolling CO2 excretion
Kidneys: (only method for direct H+excretion)
H+ excretion directly and as H2PO42-
Ammonium excretion (oxoglutarate goes
to liver; H+used for gluconeogenesis)
Liver: Lactate used for gluconeogenesisOxoglutarate from kidney used for
gluconeogenesis
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Simple Acid-Base Disturbances
pH = pK + log10 [HCO3]
(0.030)(paCO2)
pH = 6. 1 + log ( metabolic component)
(respiratory component)
HCO3_ & CO2 = pH
CO2 & HCO3_
= pH
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DISORDERS OF ACID BASE
STATUS
RESPIRATORYACIDOSIS pCO2
ALKALOSIS pCO2
METABOLICACIDOSIS BICARB.ALKALOSIS BICARB.
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Metabolic acidosis
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Anion GapA mathematical concept
(Na+ + K+ ) - ( Cl- + HCO3-) < 7-17 mmol/L
The gap consists of other ions, mainly Ca2+, Mg+, PO42-,
sulfate-, organic anions (e.g. lactate, acetoacetate)
The sum of anion and cation in plasma must be the same
(electroneutrality)
Overproduction of e.g. lactate will increase the anion gap,
indicating that the concomitant acidosis is of the metabolic type
as will decreased excretion of acid anions as in renal failure.
Therefore an increased anion gap is a useful marker of
metabolic acidosis
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Evaluating a low serum
HCO3-
A low serum HCO3- can be due to:
Metabolic acidosis
High anion gap acidosis Hyperchloremic acidosis
Respiratory alkalosis
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High anion gap: MUDPILES
Methanol
Uremia
Diabetic ketoacidosis
Paraldehyde
Isopropyl alcohol
Lactic acidosis
Ethylene glycol
Salicylates
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Classification of Metabolic Acidosis
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Compensatory Response
In simple metabolic acidosis the high [H+] stimulates
respiration resulting in a compensatory fall in the
PCO2 (secondary respiratory alkalosis) which
brings the [H+] back towards, but never to,
normal.
(1) Maximum compensation occurs in 12-24 hours
(2) For a given [HCO3] the final PCO2 level can be
calculated from:PCO2 = 1.5 x [HCO3] + 8 (+/- 2)
(3) The limit of compensation is a PCO2 of about 10
mmHg
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Metabolic alkalosis
Loss of Hydrogen IonsVomiting
Ingestion of Alkali
Potassium Deficiency
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Metabolic alkalosis
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MetabolicAlkalosisSaline Responsive (ECV contraction, Urine [Cl] 20
mmol/L)
Mineralocorticoid excess
Primary hyperaldosteronism,
Cortisol & Mineralocorticoid excess
Cushing's syndrome
Metabolic Alkalosis: pathophysiology
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Metabolic Alkalosis: pathophysiology
Pathophysiology:The development of a metabolic alkalosis
requires two simultaneous processes: bicarbonate generation, &plasma bicarbonate maintenance
(1) Generation of bicarbonate:
Loss of H+:Gut, Renal, Exogenous HCO3
The normal kidney responds to a high plasma [HCO3] by
increasing urinary excretion of the ion. This is a very efficient
process and for the development of a metabolic alkalosis a
second mechanism to maintain the high plasma [HCO3] is
required: the maintenance mechanism.
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Metabolic Alkalosis:
pathophysiology (Cont'd)
Maintenance of high plasma bicarbonate:
This is carried out by the kidney (renal bicarbonate retention)
and occurs in the following situations:
Volume depletion
Potassium depletion
Hypercapnia
Thus when evaluating the subject with metabolic alkalosis
attention should be given to the possible causes of generation
and of maintenance.
From a management point of view metabolic alkalosis can be
classified as either saline responsive or saline unresponsive
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Metabolic Alkalosis: pathophysiology(Cont d)Response to IV saline therapy
The response of the subject with metabolic alkalosis to a saline
(NaCl) infusion provides a further classification of the disorder.
Saline responsive metabolic alkalosis
If the patient is hypovolaemia (dehydrated) a saline infusion willresolve the disorder, ie remove the maintenance process and
allow bicarbonate to be excreted by the kidney; hence "saline
responsive"
Saline unresponsive metabolic alkalosisIf the patient is euvolaemic, eg the metabolic alkalosis of
mineralocorticvoid excess, a saline infusion will not alleviate the
condition: hence "saline unresponsive".
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Compensation
The compensatory process is decreased respiratory
exchange and high pCO2
Response reaches its maximum in 12-24 hpCO2~ 60 mmHg.
For each 1mmol/L rise of HCO3-, pCO2should increase
by 0.7 mmHg
Expected pCO2mm Hg: 0.9 X (HCO3-) + 9
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Respiratory disorders
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Compensation by increase
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Compensation by increase
in HCO3
In the acute phase there is a rise of 2-4 mmol/L of HCO3Will result in plasma level 28-30mmol/L
In the chronic phase there is a slow, consistent increase
in the HCO3 due to renal generation
reaches maximum in 2-4 days
The maximum level is 45 mmol/L(HCO3) mmol/L = 0.44 X pCO2+7.6
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Compensatory response
Secondary metabolic acidosis
HCO3level will decrease
Acute: HCO3will decrease upto 18mmol/L
Chronic:HCO3 will decrease upto 12 mmol/L
Resp.alkalosis; Can be completely compensated.
pH will be normal