miller - acid-base balance [2]

8/10/2019 Miller - Acid-Base Balance [2]

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ACID-BASE BALANCE

Dr Adrian G Miller PhD

Royal Liverpool Hospital


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Aims of the Lecture

Introduce you to some basic concepts ofacid- base physiology

Introduce you to important buffer systems

Discuss the role of the main organs involved inmaintaining acid-base homeostasis

Describe assessment and causes of acid-

base disorders

Apply knowledge to clinical scenarios (cases)


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Important Notice

Acid-base homeostasis is a large, complexsubject. Use the references cited to expand

your knowledge.

Dont be phased by some of the conceptsand terminologyitll all make sense (One day. Maybe.)

A good website to help you:

www.acid-base.com

Life is a struggle. Not against sin, not against the money power, not against

malicious animal magnetism, but against hydrogen ions! Mencken, 1919.


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The Basics In physiology, when we discuss acid-base, we are essentially

describing the activity of hydrogen ions (H+)

Acids are H+donors e.g. HCl (HCl H++ Cl-)

Bases are H+ acceptors e.g. OH-(OH-+ H+ H2O)

Strong acids readily give up H+, strong bases readily accept H+


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Hydrogen Ion Activity (pH) The pH of a solution is defined as the negative logarithm of the

hydrogen ion activity/concentration or :

pH = -log [H+]

The average pH of blood is 7.4, which = 0.00000004 mol/L (40 nmol/L)

The relationship between [H+] andpH is illustrated thus:

If [H+] > 45 nmol/L the person

is said to be acidaemic

If [H+] < 35 nmol/L the person

is said to be alkalaemic


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pKa

The pKa represents the negative logarithm of the ionisation constantof an acid (Ka).

In English, the pKa is the pH at which a buffer exists in equal

proportions with its acid and conjugate base e.g.

Acids have pKa values < 7.0

Bases have pKa values > 7.0

The LOWER the pKa, the stronger the acid (and vice versa for

conjugate base)


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Henderson-Hasselbalch Equation

Explains how acids and bases contribute to pH, ergo [H+]

In physiology, the [acid] is carbonic acid. We dont actually measure

carbonic acid but its concentration bears a linear relation to the amount

of dissolved carbon dioxide.

Well come back to this later but for now, remember this:

[dissolved carbon dioxide] is proportional to [H+]


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Acid-Base Physiology

Metabolic processes result in large amounts of carbonic, sulphuric,

phosphoric (et al.) acids. During a 24-hour period, a 70 kg individual:

Exhales ~20 mol of carbon dioxide (the volatile form of carbonic

acid) through the lungs

Excretes 70-100 mmol of non-volatile acids through the kidneys

These products of metabolism are transported to the excretory

organs via the ECF without producing an appreciable change in

pH

Arterial pH 7.367.44 Venous pH 7.327.38

This transport and excretion is achieved by a

combination of efficient buffer systems and

respiratory and renal mechanisms


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Physiological Buffering Systems

A buffer system consists of a weak (partly dissociated) acid

and its conjugate base (the anion that combines with a

hydrogen ion to form the acid).

Several buffer systems are used in physiology. These include:

Bicarbonate (HCO3-)

Phosphate (PO4-)

Haemoglobin (Hb-)

Proteins (anionic)

Ammonia (NH3)

All designed to ensure H+are transported and

excreted without causing damage to physiological

processes.


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Renal Processes

Yucha C. Renal regulation of Acid-Base Balance. Nephrology Nursing

Journal(2004) 31201-208


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Bicarbonate

If you remember nothing else from todays lecture, remember this:

This equation is CENTRALto acid-base balance. From it you can see:

When dissolved in blood, CO2becomes an acid

The more carbon dioxide added to blood, the more carbonic acid (H2CO3) is

produced, which readily dissociates to release H+

Blood pH depends, not on absolute amounts of CO2or HCO3-, but the RATIOof

the two.

Q. What will happen if the lungs cant expire sufficient CO2


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Renal H+Excretion and HCO3-Regeneration


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PhosphateMonohydrogen (H2PO4

2-) and Dihydrogen Phosphate (H2PO4-) form a buffer pair

with a pKa of 6.8

While this buffer system seems favourable, plasma concentrations of these

anions are too low. However, in the renal filtrate, they are present in higher

concentrations and are an important buffer in urine.

Renal Tubular Cell

http://www.nda.ox.ac.uk/wfsa/html/u13/u1312_02.htm


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Ammonia There are some myths surrounding the role of ammonia

in acid base balance. The pKa of ammonium (NH4+) is ~100 x lower than the

physiological [H+], so almost all of ammonia in the body is already

in the ammonium form.

Ammonia comes to the fore in a urinary context as it

provides a route for urea synthesis that does not result in

the generation of H+.


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Ammonia

Hye-Young Kim. Renal handling of ammonia and acid base regulation.Electrolytes and Blood Pressure(2009) 79-13


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Lung Processes


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HaemoglobinHb buffering of hydrogen ions is an important process in acid-base balance. In the

deoxy- state, Hb is reduced to HHb


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Oxygen Dissociation Curve


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The role of proteins

Proteins contain weakly acidic and basic groups due to

their amino acid composition.

Albumin is the predominant plasma protein and is the

main protein buffer in this compartment

Intra-cellularly, other proteins act as buffers

Bone proteins play a major role in acid-base

Protein buffering within bone matrix

Increased H+ stimulates bone resorption (alkaline

minerals act as buffers)

S. New. The role of the skeleton in acid-base homeostasis.

Proc. Nutr. Soc.(2002) 61 p 151-164


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Summary (I)

The key organs involved in acid-basehomeostasis are:

Lungs

Kidneys

In states of acid-base imbalance, other

systems contribute:

Liver Bones

Intracellular proteins


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Assessment of Acid-Base Status


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Assessment (Clinical)

Clinical features of acidosis and alkalosis are non-

specific and may only present when disturbances are

severe

Alterations of consciousness

Breathing irregularities

Nausea and vomiting

Clues should be derived from the organ(s) trying to

correct the abnormality


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Biochemical Investigations

These are vital to diagnose conditions, as well as

indicate their severity and management

The ABG may comprise:

Hydrogen ion concentration

Partial pressure of arterial carbon dioxide (PaCO2)

Partial pressure of oxygen (PaO2)

Standard bicarbonate

Anion gap

Electrolytes (optional) Co-oximetry (optional)


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What do the ABG machines measure?

Co-oximetry

Total Hb

sO2 O2Hb

CO Hb

Met Hb

H Hb

Reference ranges

11.8-16.7 g/dL

>97% 94.0-97.0%

0-2.0%

0-1.5%

0-5.0%

Your mission, should you choose to accept it, is to find out the difference

between sO2and O2Hb!!


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Hydrogen Ion Activity and PaCO2

Measured components (ion selective electrodes), usuallyon arterial blood (ABG)

The 2 most important values to determine the TYPE of

disturbance

Respiratory acidosis Respiratory alkalosis

Metabolic acidosis

Metabolic alkalosis

Mixed disorder


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Standard Bicarbonate

Derived from the Van Slyke equation

a- 24.4 = - (2.3 b+ 7.7) (c- 7.40) + d/(1 - 0.023 b)

a = bicarbonate concentration in plasma /(mmol/L)b = haemoglobin concentration in blood /(mmol/L)

c = pH of plasma at 37C

d = base excess concentration in blood /(mmol/L).

Must measure the pH, thepCO2, and the haemoglobinconcentration


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Base Excess

Amount of strong acid/alkali that would have to be added per unit

volume of whole blood to titrate it to pH 7.4

Blood with a pH of 7.40, pCO2=5.33 kPa and Hb=15.0 g/dL at 37oC has a

BE of zero.

Calculated as follows:

BE = (HCO3-- 24.4 + [2.3 Hb + 7.7] [pH - 7.4]) (1 - 0.023 Hb)

Hb: Assayed value from associated co-oximeter

Derived from a measured haematocrit Assumed value entered into the analyser set-up


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Anion Gap

In those analysers that measure electrolytes, the anion

gap represents the sum of the major cations in plasma

minus the major anions

Electroneutrality dictates that this should be equal andgaps show the presence of unmeasured species

(usually proteins) e.g. lactate, ketones etc.


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Disorders of Hydrogen Ion

Homeostasis


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Reminder The types of disturbance are:

Respiratory acidosis

Respiratory alkalosis

Metabolic acidosis

Metabolic alkalosis

Mixed disorder

The processes involved are

Generation of the disorder Buffering

Physiological compensation

Correction (hopefully)


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Respiratory Acidosis

A consequence of carbon dioxide retention (lungs)

Buffering by haemoglobin limits the process

Compensation is achieved by Hyperventilation

Increased renal H+excretion

Increased bicarbonate regeneration (renal)

pH [H+] PaCO2 HCO3-

N /


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Causes of a Respiratory Acidosis

CNS disorders

Depression of respiratory centre(e.g. opiates, sedatives,anaesthetics)

CNS trauma, infarct, haemorrhageor tumour

High central neural blockade

Poliomyelitis

Tetanus

Cardiac arrest with cerebral hypoxia

Nerve or Musc le Disor ders

Guillain-Barre syndrome

Myasthenia gravis

Muscle relaxant drugs Toxins e.g. organophosphates,

snake venom

Lung o r Chest Wall Defects

COPD

Chest traumahaemothorax,pneumothorax

Diaphragmatic paralysis

Pulmonary oedema

ARDS

Restrictive lung disease

Airway Disorders

Upper Airway obstruction

Laryngospasm

Bronchospasm/Asthma

External Factors

Inadequate mechanical ventilation


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Respiratory Alkalosis

A consequence of increased carbon dioxide excretion through

the lungs

Compensation is achieved by increased renal bicarbonate

excretion

pH [H+] PaCO2 HCO3-

N /


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Causes of a Respiratory Alkalosis

Central Causes (direct

action via respiratory centre) Head Injury

Stroke

Anxiety-hyperventilationsyndrome (psychogenic)

Supra-tentorial' causes (e.g.

pain, fear) Drugs (e.g. analeptics,

salicylateintoxication)

Endogenous compounds (e.g.progesterone duringpregnancy, cytokines duringsepsis, toxins in patients with

chronic liver disease)

Pulmonary Causes (act viaintrapulmonary receptors)

Pulmonary Embolism

Pneumonia

Asthma

Pulmonary oedema (all types)

Iatrogenic (act directly on

ventilation)

Excessive controlled ventilation


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Metabolic Acidosis

Can develop as a consequence of:

Increased acid formation

Decreased acid excretion

Decrease in buffering capacity

Increased acid ingestion

pH [H+] PaCO2 HCO3-

N /

Compensation is achieved by increasing carbon dioxide

excretion (lungs)


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Causes of a Metabolic Acidosis

Raised Anion-Gap

Ketoacidosis

Diabetic, alcoholic, starvation

Lactic Acidosis

Impaired perfusion

Impaired carbohydrate metabolism

Renal Failure

Uraemic acidosis

Acidosis with acute renal failure

Toxins

Ethylene glycol

Methanol/ethanol

Salicylates

Normal Anion-Gap

Renal Causes Renal tubular acidosis

Carbonic anhydrase inhibitors

GI Causes Severe diarrhoea

Drainage of pancreatic or biliarysecretions

Small bowel fistula

Other Causes Recovery from ketoacidosis

Addition of HCl, NH4Cl

MUDPILES


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Metabolic Alkalosis

Can develop due to:

Loss of hydrogen ions

Decreased generation of hydrogen ions

Exogenous administration of alkali

Potassium losses

pH [H+] PaCO2 HCO3-

N /

Compensation is achieved by retaining carbon dioxide


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Causes of a Metabolic Alkalosis

Addition of Base to ECF

Milk-alkali syndrome

Excessive NaHCO3intake

Recovery phase from organicacidosis (excess regenerationof HCO3)

Chloride Depletion

Loss of acidic gastric juice

Diuretics

Excess faecal loss (e.g. villousadenoma)

Potassium Depletion

Primary hyperaldosteronism

Cushings syndrome

Some drugs (e.g.Carbenoxolone)

Kaliuretic diuretics

Excessive liquorice intake(glycyrrhizic acid)

Bartter's syndrome

Severe potassium depletion

Other Disorders Laxative abuse


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Summary (II)

Respiratory disorders are compensated by

metabolic processes

Metabolic disorders are compensated by

respiratory processes

Over-compensation does not occur.


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Clinical Cases

pCO2 B I t t tipH


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pCO2 Base excess Interpretation

Acidaemia

Low pH(6kPa)

Normal (4.5-6kPa)

Low (2.5)

Normal

(-2.5 to +2.5)

Negative

(


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pCO2 Base excess Interpretation

Alkalaemia

High pH

(>7.45)

Low (6kPa)

Positive

(>2.5)

Normal

(-2.5 to +2.5)

Negative

(2.5)

Positive

(>2.5)

Mixed respiratory

and metabolic

alkalosis

Primary respiratory

alkalosis

Primary respiratory

alkalosis with renal

compensation

Primary metabolic

alkalosis with

respiratory

compensation

Primary metabolic

alkalosis

pH


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Case 1A 34 year old female, presents to her GP complaining of breathlessness

On metforminBMI of 49

Parameter Result Range

H+ 45 3545 nmol/L

pH 7.35 7.357.45

PaCO2 7.3 4.76.0 kPa

PaO2 9.6 >10.6 kPa

Bicarbonate 29 2228 mmol/L

Base Excess -3.8 -2 to +2

O2Sat 96% >98%

Lactate 1 0.41.5 mmol/L

Hb 13 1318 g/dL

Glucose 9 3.56 mmol/L


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Case 1

Is it a respiratory acidosis with metabolic compensation?

Is it a metabolic alkalosis with respiratory compensation?

Remember, over-compensation does not occur.

Obesity hypoventilation syndrome (OHS)is a well-known cause of

hypoventilation. Abnormal central ventilatory drive and obesity contribute to

the development of OHS. OHS is defined as a combination of obesity,

body mass index greater than or equal to 30 kg/m2with awake chronichypercapnia (PaCO2>6 kPa) and sleep-disordered breathing.

DxCompensated respiratory acidosis


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Case 2

A 35 year old male is brought to A&E after being found unconscious at home by

his wife. She tells the Clinician her husband has:

PMH of Type 1 Diabetes Mellitus

Has not been eating well for the past 2 days due to vomiting bug

Has missed taking some insulin due to not eating

Patient was administered 10 L of O2by mask in ambulance

O/E

Pulse 130 bpm

BP 100/60

Respiratory rate 22 breaths per minute


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H+ 90 3545 nmol/LpH 7.05 7.357.45

PaCO2 1.5 4.76.0 kPa

PaO2 28.5 >10.6 kPa

Bicarbonate 6 2228 mmol/LBase Excess -25.2 -2 to +2

O2Sat 99.8% >98%


Hb 12 1318 g/dLGlucose 35 3.56 mmol/L

Ketones Positive

Case 2


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Case 2

Parameter Result RangeSodium 141 135145 mmol/L

Potassium 4.6 3.55.5 mmol/L

Chloride 96 95105 mmolL

Ionised calcium 1.25 11.25 mmol/LGlucose 35 3.56 mmol/L


What is the anion gap?

AG = (141 + 4.6)(96 + 6)

AG = 43.6(normal 1018)


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Case 2

Uncompensated metabolic acidosisthe lungs are trying to blow off

as much CO2as possible but the degree of acidosis is such that thepatient is dangerously acidotic

Dx of Diabetic Ketoacidosis (DKA)


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Charfen & Fernandez-Freckleton. Diabetic ketoacidosis. Emerg Med Clin N Am

(2005) 23609-628

DKA

Lack of insulin stimulates

lipolysis

Results in generation ofketones (weak acids but

accumulate in DKA)

Buffering system is

overwhelmed

Metabolic acidosis ensues

Management revolves

around fluid resuscitation

and insulin administration

Beware The Refeeding

Syndrome!!


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Case 3

A 79 year old female presents to the General Surgery ward to have a

large bowel tumour removed

The tumour was found after the patient complained of 6/12 rectal

bleeding

Presented to the ward feeling tired and short of breath (SOB)

O/E

Pulse 100 bpm (tachycardic)

BP 100/80 (hypotensive)

Respiratory rate 26 breaths/min


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Case 3


H+ 32.3 3545 nmol/L

pH 7.49 7.357.45

PaCO2 3.31 4.76.0 kPa

PaO2

11.9 >10.6 kPa


Base Excess +2 -2 to +2

O2Sat 99.8% >98%


Hb 6.8 1318 g/dL

Glucose 3.9 3.56 mmol/L


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Case 3

What is the acid base disorder?

Uncompensated respiratory alkalosiscaused by anaemia (probably

due to chronic blood loss)

In this patient, there is no impairment of oxygen transfer or

ventilation so the PaO2

and O2

Sat are normal. However, because of

the low Hb, her blood O2content is low (hypoxaemic)

Hyperventilation is a normal response and will cause her to blow off

CO2, causing a respiratory alkalosis

Condition is treated with a blood transfusion

Why do we not give her more oxygen?


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Summary

Acid-base can be difficult to master, use the many resources

available to help you.

Learning basic concepts will help (HH equation, acid-base disorders

and compensatory mechanisms etc.)

Practising ABG interpretation is an excellent way to improve your

understanding of the physiological mechanisms of acid-base

balance

Dont panic! People spend whole careers hating acid-base because

they dont get it make a friend of it and talk to those in your

department who do! (if they exist)

miller - acid-base balance [2]

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