Acid-base Balance And Imbalance - PowerPoint Presentation

Slide1

Acid-base Balance And Imbalance

Slide2

Learning Objectives

Describe

what is meant by acids, bases and

buffers. List

normal pH of the body fluids.

Describe

the processes involved in maintenance of normal blood pH

.

Describe

various types of acidosis and alkalosis

.

Describe

what is meant by anion

gap and its clinical significance.

Slide3

Normal

pH

Of The Body Fluids

The normal pH of arterial blood is

7.4

pH of venous blood and interstitial fluids is about

7.35

The pH of blood is maintained within a remarkable constant level of

7.35

to

7.45.

Slide4

Why maintenance

of a

pH

is

important

Slide5

The

activities of almost all

enzyme

systems in

the body

are influenced

by

hydrogen ion

concentration

.

C

hanges

in hydrogen

ion concentration alter:

all

cell and

body functions

the

conformation of

biological structural components

uptake

and release of oxygen

Slide6

Metabolic Sources Of Acids Which Alter

Blood

pH

Fixed acids or non-volatile acids:

Phosphoric

Sulphuric acids

Pyruvic acid,

Lactic acid

Keto acids

Volatile acids breathe out through the lungs :

Carbonic acid (H

2

CO

3

).

Slide7

Metabolic Sources Of Bases

Citrate salts of fruit juices may produce

bicarbonate salt

.

Deamination of amino acids produces

ammonia

Formation of

bis-phosphate

also contributes to

alkalinizing effect.

Slide8

Regulatory Mechanisms to maintain normal Blood pH

Buffer mechanism: First line of defense

The respiratory mechanism: Second line of defense

Renal mechanism: Third line of defense.

Slide9

What is Buffer

?

Buffer is a substance that can resist the change in pH even after addition of strong acid or base. It is a mixture

of a

weak acid

and a

salt of its conjugate

base

e.g. NaHCO

3

/

H

2

CO

3

If

one molecule differs from another by

only

a proton,

the two are

called as conjugate acid-base

pair.

Slide10

A buffer can

reversibly bind hydrogen

ions. The general form of the buffering reaction is:

Buffer systems

do not eliminate hydrogen ions

from the body or

add them to the body

but only

keep them tied up until balance can be re-established.

Slide11

Buffering capacity depends on

the:

Concentration

of the

buffer

.

Relationship

between the pKa of the buffer and the desired pH.

A

buffer has the maximum buffering capacity when its pKa equals the pH.

For

the maximum blood buffering, the pKa of the buffers should, therefore, be near

7.4

.

Slide12

Blood Buffer

Buffer System Extracellular buffer Intracellular buffer

Bicarbonate

NaHCO

3

/ H

2

CO

3

KHCO3

/H

2

CO

3

Phosphate

Na

2

HPO

4

/NaH

2

PO

4

K

2

HPO

4

/KH

2

PO

4

Protein

Na Protein/H. Protein KHb/

H.Hb

KHbO

2

/H.HbO

2

Slide13

The Bicarbonate Buffer System

(HCO

3

–

/

H

2

CO

3)The bicarbonate buffer system is the most important

extracellular buffer

.

It

plays an important role in maintaining blood pH, because of its high

concentration

.

Two

elements of the buffer system, HC

O

3

–

and H

2

CO

3

are regulated

by

the kidneys, and

by

the

lungs respectively.

Slide14

Mechanism of Action of Bicarbonate Buffer

When

a strong acid, such as

HCI

, is added to the bicarbonate

buffer

solution, the increased hydrogen ions are buffered

by

HCO

3

–

to form very weak acid H

2

CO3, which, in turn, forms CO2 and H2O.

Slide15

When

sodium hydroxide (NaOH)

, is added to bicarbonate buffer, hydroxyl ion (OH

–

) from NaOH combines with

H

2

CO

3 to form weak base HCO3

–

and

H

2

O

Slide16

Any nonvolatile acid stronger than carbonic acid can be buffered by bicarbonate (HCO

3

–

).

Plasma

bicarbonate is a measure of the base that remains after all acids, stronger than carbonic have been neutralized.

It

represents the reserve of alkali available for the neutralization of such strong acids and it has been termed as the

alkali reserve

.

Slide17

At pH 7.4

the

average normal ratio of the concentration of HCO

3

–

and H

2

CO

3

in plasma is 25 mmol/L to 1.25 mmol/L = 20:1. Subsequently any changes in the concentration of either bicarbonate (HCO

3

–

)

or carbonic acid (H

2CO3) and therefore in the ratio HCO3– :

H

2

CO

3

is accompanied

by a change in pH.

Slide18

The

two elements of the buffer system,

HCO

3

–

and

H

2

CO3

are

regulated by:

1. Increasing or decreasing the rate of reabsorption

of HCO3 by the

kidneys

2. By altering the rates of

removal

or

retention

of

H

2

CO

3

by the lungs

Slide19

The Phosphate Buffer System (HPO4

– –

/H2PO4

–

)

The

phosphate buffer system is not important as a

blood buffer

; it plays a major role in buffering

renal tubular fluid

and

intracellular fluids

.

Slide20

Mechanism of Action of Phosphate Buffer

(HPO4

– –

/H2PO4

–

)

When

a strong acid such as

HCI

is added to

phosphate buffer

the

H

+

is accepted by the base HPO4– – and converted to H

2

PO

4

–

and

strong acid

HCI is replaced by a weak acid NaH2PO4

Slide21

When strong

base, such as

NaOH

, is added to the

phosphate buffer the

OH

–

is buffered by the

H

2PO4– to form

HPO

4

– –

and water. Thus strong base NaOH is replaced by

weak base HPO4– –

At a plasma pH of 7.4 the ratio

HPO

4

– –

:

H2PO4–

is 4:1.

Slide22

Organic

phosphate in the form of

2,3

phosphoglycerate

(2, 3 BPG)

,

present in erythrocytes

accounts

for about 16% of the

non-carbonate buffer of erythrocyte fluid

Slide23

Protein Buffer

(Na

Protein/H Protein

)

In the blood, plasma proteins especially

albumin

acts as buffer

.

In

acid solution the basic amino group

(NH

2

)

takes up excess H

+ ions forming (NH3+

)

.

Whereas in basic solutions the acidic

COOH

groups

give up hydrogen ion forming

OH– of alkali to

water

.

Slide24

Other important buffer groups of proteins in the physiological pH range are the

imidazole

groups of

histidine

.

Each

albumin molecule contains 16 histidine residues.

Slide25

Hemoglobin Buffer

(

KHb/H Hb

and

KHbO

2

/HHbO

2)Haemoglobin

is the major

intracellular buffer

of

blood which is present in erythrocytes.Each Hb molecule contains 38 molecules of histidine

.

The imidazole group of histidine has a pKa of approximately 7.3, fairly close to 7.4

.

It

buffers

carbonic acid (H

2

CO3)

Slide26

Action

of hemoglobin

buffer

Hemoglobin works effectively in

co-operation

with the

bicarbonate system.

Slide27

Slide28

The transport of an appreciable quantity of the CO

2

released from the tissues without change in pH is called

isohydric transport of CO

2

.

Most

of the CO

2 is transported in the plasma as bicarbonate (HCO3

–  

).

Because

HCO

3 is much more soluble in blood plasma than is CO2, this indirect route increases the blood’s capacity to carry CO2 from the tissues to the lungs.

Slide29

Respiratory Mechanism

S

ec

ond

line of

defense

against acid-base

disturbances

It functions by

regulating the concentration of carbonic acid (H2

CO

3

) in

blood

and other body fluids by lungs. The respiratory center regulates the removal or retention of CO2 and thereby H2

CO

3

from the extracellular fluid by the lungs.

Slide30

Increase in (H

+

)

or

(H

2

CO

3

) stimulates the respiratory center to increase the rate of respiratory ventilation

and

excess acid (H

2

CO3) in the form of CO2 is quickly

removed

Increase in (OH

–

)

or

(HCO

3

–) depresses respiratory ventilation and release of CO

2

from the blood

The increased blood CO

2

will result in the formation of more H

2

CO

3

acid to neutralize excess alkali

(HCO

3

–

)

Slide31

Renal Mechanism In Acid-base Balance

Renal mechanism is the

third line of

defense

in

acid base

balance

.

Long term acid-base control is exerted by renal mechanisms.

Kidney

participates in the regulation of acid- base

balance by

conservation of HCO

3– (alkali reserve) and excretion of acid.

Slide32

The pH of the initial

glomerular filtrate

is

approximately

7.4

whereas the average

urinary pH

is approximately

6.0

due to excretion of non-volatile acids produced by metabolic processes.

The pH of the urine may vary from

4.5 to 8.0

corresponding to

the case of acidosis or alkalosis.

This ability

to excrete

variable

amounts of acid or

base makes

the kidney the

final defence mechanism against

change in body pH.

Slide33

Renal conservation of

HCO

3

and

excretion of

acid occur

through four key mechanisms

Exchange

of H

+ for Na+ of tubular fluid

.

Reabsorption of bicarbonate

from tubular

fluid.

Formation of ammonia and excretion of ammonium ion (NH4+) in the urine.

4. Excretion

of H

+

as H

2

PO

4– in urine

Slide34

Exchange of H+ for Na+ of tubular fluid and reabsorption

of bicarbonate from tubular fluid

.

Slide35

Excretion of H

+

as

H

2

PO

4

-

in urine.

Slide36

Formation of ammonia and excretion of ammonium

ions in the urine.

Slide37

Disorders

of Acid Base

Balance

Acidosis

Alkalosis

Slide38

Acidosis And Alkalosis

Acid-base balance depends on the

ratio

HCO

3

–

/

H

2

CO3

which

is constant at

20:1

at physiological pH.

Any alteration produced in the ratio between carbonic acid and bicarbonate results in an

acid-base imbalance

and leads

to

acidosis

or

alkalosis.

Slide39

Acidosis

may be defined as an abnormal condition caused by the accumulation of

excess acid

in

the body

or by the

loss of alkali

from the body. Alkalosis

is an abnormal condition caused by

the accumulation

of

excess alkali

in the body or by the loss of acid from the body.

Slide40

Acidosis and alkalosis are classified, in terms of their

cause :

1.

Metabolic acidosis

: Dec. in bicarbonate

(

HCO

3–) conc.

Respiratory acidosis

: Inc.

in

H

2CO3 concentration.

3

.

Metabolic alkalosis

: Inc.

in

bicarbonate

(

HCO3–) conc.

4. Respiratory alkalosis

: Dec. in

H

2

CO

3

concentration

.

Slide41

In

all these four conditions, if the ratio

HCO

3

–

/

H

2

CO

3 remains within normal limits, i.e. about

16:1

to

25:1

, corresponding to

pH 7.3 to 7.5, the condition results in compensated acidosis

and

alkalosis

.

When

the ratio actually changes and pH is outside of the normal range the term

uncompensated

is used.

Slide42

Metabolic Acidosis

A

fall in blood pH due to a

decrease in bicarbonate

levels of plasma

is called

metabolic acidosis

.

Decrease

in bicarbonate levels may be due to: – Increased production of

acids

e. g.,

i

n uncontrolled

diabetes mellitus and starvation – Excessive loss of bicarbonate e. g., in

renal

tubular

dysfunction

and

in severe diarrhoea.

Slide43

Compensatory

mechanisms for metabolic acidosis

Increasing

rate of respiration to wash out

CO

2

(hence

H

2

CO

3

) faster. Consequently, the ratio HCO3–

/

H

2

CO

3

is elevated. Increasing excretion of H+ ions as

NH

4+

ions

.

Increasing

elimination of

acid

H

2

PO

4

–

in the urine

.

All

these compensatory mechanisms tend to

reduce carbonic

acid

and a

compensated

acidosis

results.

Slide44

Respiratory

Acidosis

Acidosis results

from an

increase

in concentration of

H

2

CO3

An

increase in

concentration of

H

2CO3 is due to decrease

in alveolar

ventilation

,

which leads

to retention of

CO

2

Slide45

Decreased alveolar ventilation

may occur

in:

--

Obstruction

to respiration

:

in pneumonia, emphysema, asthma

, etc.

-- Depression

of respiration

:

administration of respiratory depressant toxic drugs like morphine which depresses the respiratory centre.

Slide46

Compensatory mechanisms

Increase

in renal reabsorption of

bicarbonate

.

Rise

in urinary acid

H

2

PO

4

–

and

ammonia.

Slide47

Metabolic

Alkalosis

A

rise

in blood

pH

due to

rise

in the

bicarbonate levels of plasma This

is seen

in the

following

conditions:

Loss of gastric juice along with H+ ions in prolonged and severe

vomiting.

Therapeutic

administration of

large dose of alkali

(in peptic ulcer) or

chronic intake of

excess antacids.

Slide48

Compensatory

mechanisms

Increased

excretion

of alkali

(

HCO

3

–

) by the kidney

.

Diminished formation of

ammonia

.

Respiration

is depressed to

conserve CO

2

.

Slide49

Respiratory Alkalosis

A

rise

in blood

pH

due to

lowered

concentration of

CO

2 or H2CO

3

,

due to hyperventilation.

This occurs in the following conditions: Anxiety or hysteria

Fever

Hot

baths

At

high altitude

Working

at high temperature, etc.

Slide50

Compensatory mechanisms

Increased

excretion of

bicarbonate

.

Reduction

of urinary

ammonia

formation

Slide51

Causes of acidosis and alkalosis.

Slide52

Slide53

Slide54

Arterial Blood Gas Analysis In Acid-base Imbalance

Slide55

Arterial blood gas (ABG) analysis is a common investigation in emergency departments and intensive care units for monitoring patients with acute respiratory failure.

An

arterial blood gas result can help in the assessment of

a patient’s

gas exchange, ventilatory

control, and

acid base balance

.

Slide56

Slide57

The ABG analysis becomes necessary in view of the

following advantages:

––

Aids

in establishing diagnosis.

––

Guides

treatment plan.

––

Aids in ventilator management.–– Improvement

in acid/base management.

––

Acid/base

status may alter electrolyte levels

critical to a patient’s status.

Slide58

Slide59

Anion Gap

Slide60

The

concentration of

anions

and

cations

in plasma must be

equal

to maintain electrical neutrality. Therefore, there is no real anion gap in the

plasma. Anion

gap is not a physiological reality.

Slide61

The

concept of anion gap originally

was developed when

it was found that if

the sum

of the

Cl

–

and

HCO3_ values

was

subtracted from

the

Na

+ and K+ values the difference or ‘gap’ averaged 16 mmol/L in healthy individuals.

Slide62

Anion

gap =

([Na

+

] + [K

+

]) – ([Cl

–

] + [HC

O3– ]) = (142 + 4) – (103 + 27) = 146 – 130 = 16 mEq/L

Slide63

The most important unmeasured cations

include

Ca, Mg

,

and the major

unmeasured anions

are

albumin

, phosphate, sulphate and other

organic

anions

.

The anion

gap ranges between 8 –16 mEq/L.

Slide64

Slide65

Acid base disorders are often associated

with alterations

in the anion gap

.

In

metabolic acidosis

the anion gap can

increase

or remain normal depending on the cause of acidosis

.

Slide66

Metabolic

Acidosis Associated with Increased Anion

Gap

In metabolic acidosis, the plasma HCO

3

–

is reduced. To keep electroneutrality, the concentration of anions (either Cl

–

or an unmeasured anion) must increase.

If the decrease in plasma HCO

3

–

is not accompanied by increased Cl

–

, the anion gap value will increase and referred to as increased anion gap acidosis or normochloremic acidosis.

Slide67

Metabolic Acidosis Associated with Normal Anion Gap

If the decrease in plasma HCO

3

–

is accompanied by increased Cl

–

,

the

anion gap is remained normal, this referred to as

Hyperchloremic metabolic acidosis or normal anion gap acidosis

.

Slide68

Slide69

Clinical Significance of Anion

Gap

The anion gap is a biochemical tool which

sometimes helps

in assessing acid-base problems. It is used for

the diagnosis

of different causes of metabolic acidosis.

Slide70

A 38-year-old man reported in the emergency ward of a hospital emergency with complaints of persistent vomiting for one week. He had generalized muscular cramps. On examination, he appeared dehydrated and had shallow respiration. Blood sample was analyzed with the following results:

Slide71

pH = 7.8 (normal 7.35- 7.45)

Bicarbonates = 35 m

e

q/L (normal 22- 30 m

e

q/L)

pCO2 = 50 mm Hg (normal 30- 45 mm Hg)

Na+= 145 m

e

q/L (normal 136- 145 me

q/L)

K+ = 2.9 m

e

q/L. (normal 3.5 -5 m

eq/L)Questions1. Identify the nature of acid-base disorder.

2. What could be the cause of this acid-base disorder?

3. What is the cause of shallow respiration?

4. Give reason for development of muscle cramps.

Slide72

A 50-year-old male was admitted with a history of chronic obstructive airways disease for many years. On examination, he was found cyanosed, and breathless. Blood sample was analyzed with the following results:

Blood pH = below normal

pCO2 = markedly elevated

(HCO3–) = markedly elevated.

Slide73

Questions

1. Identify the nature of acid-base disorder.

2. What could be the cause of elevated pCO2?

3. What could be the cause of elevated (HCO3–)?

Slide74

A person presents himself with untreated diabetes mellitus. He is treated for acidosis

.

1

. What is the type of acidosis?

2. What is the normal bicarbonate/carbonic acid ratio? What will happen to the ratio in this patient?

3. How will compensation occur?

4. What is the role of kidney in correcting acidosis?

Slide75

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