Neaam Al-Bahadili

Rana J. Rahhal

5

...

Mamoun Ahram

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In this sheet we will continue taking about Titration curve and Buffers in human body.

Let’s begin

Titration curve of phosphate buffer:

1. There are 3 buffering capacities (3 pKa values), where the buffer resists changes in

the pH in 3 regions, depending on the ability/easiness of the proton to be

dissociated from the acid.

2. First neutralization for acid/base is reached at 1 equivalent. (Specifically;

neutralization occurs between OH− and the proton of H3PO4).

3. In the first buffering capacity;

When pH < pKa H3PO4> H2P04- ( The group is Protonated)

When pH > pKa H2P04->H3PO4 ( The group is Deprotonated)

The titration curve of H2P04

-, showing the buffer region for the H2P04

-/ HP04

2- pair.

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Physiological Buffers in Human Body; pH inside our bodies (blood, cells, and

organelles) must be maintained by:

1. Carbonic acid-bicarbonate system in the blood.

2. Dihydrogen phosphate-monohydrogen phosphate system (intracellular), this is

where phosphate ion concentrations are high enough for the buffer to be

effective.

3. Proteins (haemoglobin in blood, and other proteins in blood and inside cells):

function as enzymes, binding proteins, cytoskeletal proteins. They can

maintain and regulate the pH inside our system because they are composed of

amino acids which have groups that accept and donate protons.

Bicarbonate Buffer

The buffering system in blood is based on the dissociation of carbonic acid into

CO2 and H2O enzymatically in the lungs (regulated by the respiratory system), or

into H+ and HCO-3 instantaneously in the blood (regulated by the kidneys).

Mainly in our bodies, the amount of Carbonic acid is minimal, it doesn’t even

exist, because it is rapidly dissociating.

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Notice pKa, even though the normal blood pH of 7.4 is outside the optimal buffering range of the bicarbonate buffer (5.1 – 7.1), this buffer pair is important because;

1. Bicarbonate is present in a relatively high concentration in the ECF (24mmol/L).

2. The components of the buffer system are under physiological control: the CO2 by the lungs, and the bicarbonate by the kidneys.

3. It is an open system that continuously interacts with its environment (influenced

by external factors).

Arterial Blood Gases (ABG):

It measures the amounts of certain gases (such as Oxygen and carbon dioxide) dissolved in arterial blood.

The ratio of bicarbonate to carbonic acid determines the pH of the blood; and it is normally about 20:1

And by applying the Henderson–Hasselbalch equation

Exercise:

Blood plasma contains a total carbonate (HCO3-and CO2) of 2.52 x 10-2M. What is the HCO3-/CO2 ratio and the concentration of each buffer component at pH 7.4?

We choose the acid to be CO2 instead of H2CO3 because H2CO3 is rapidly dissociated and not present in the

system. Note that CO2 is not represented by

concentration because it is a gas, so it must be converted by multiplying its

pressure by 0.03. H2CO3 = 0.03 x pCO2

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According to the equation, when we

add protons (0.01 M), the reaction will

shift to the right, resulting in the

decrease in the concentration of the

carbonate ion by 0.01, and increase in

the amount of CO2 by 0.01 because it is

a closed system

When adding a strong acid: What would the pH be if 0.01 M H+ is added and CO2 is NOT eliminated (closed system)?

What would the pH be if 0.01 M H+ is added under physiological conditions (open system)?

Acidosis and Alkalosis

Acidosis refers to an excess of acid in the blood that causes the pH to fall below 7.35

Alkalosis refers to an excess of base in the blood that causes the pH to rise above

7.45.

Both pathological conditions can be either metabolic or respiratory.

For example;

Acidosis:

1. Metabolic: production of ketone bodies (starvation)

2. Respiratory: pulmonary (asthma; emphysema)

Alkalosis:

1. Metabolic: administration of salts or acids

Because it is an open system, the

increase in the amount of CO2 will be

exhaled. So the concentration of CO2 will

be 0.0012 at the end.

The importance of the open system is to

make the effect on pH minimal.

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2. Respiratory: hyperventilation (anxiety/ panic attacks)

Remember; there are two organs that control the pH: the kidney (metabolic

conditions) and the Lungs (respiratory conditions).

Causes of Acidosis and Alkalosis

Respiratory conditions

(changes in the concentrartion of CO2)

Respiratory Acidosis

-increased concentrartion of CO2

-the reaction shifts to the left

-protons increase

-pH decreases

Respiratory Alkalosis

-decreased concentration of CO2

-the reaction shifts to the right

-protons decrease

-pH increases

Metabolic conditions

(changes in the concentrartion of H+)

Metabolic Acidosis

-increased conentartion of H+

-pH decreases

Metabolic Alkalosis

- decreased concentrartion of

H+

-pH increases

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Compensation

It is the change in HCO3

- or pCO2 that results from the primary event.

If underlying problem is metabolic, hyperventilation or hypoventilation occur: respiratory compensation.

If the problem is respiratory, renal mechanisms can bring about metabolic compensation.

May be complete: if pH is brought back to itsnormal limits.

Partial compensation: if pH range is still outside norms.

The basis of compensatory responses is to maintain the PCO2/[HCO3

-] ratio

The direction of the compensatory response is always the same as that of the initial change.

Acid-Base Disorder Primary Change Compensatory

Respiratory Acidosis pCO2 up HCO3- up Respiratory Alkalosis pCO2 down HCO3- down Metabolic Acidosis HCO3- down pCO2 down Metabolic Alkalosis HCO3- up pCO2 up

Full Compensation:

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Partial Compensation:

Examples:

1. Mrs. X is admitted with severe attack of asthma. Her arterial blood gas result is as follows:

pH: 7.22

pCO2: 55

HCO3

-: 25

Answer: Respiratory Acidosis pH is below normal range – acidosis

pCO2 is high – in the opposite direction of the pH – respiratory

HCO3

- is normal

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2. Mr. D is admitted with recurring bowel obstruction has been experiencing intractable vomiting for the last several hours. His ABG is:

pH: 7.5

pCO2: 42

HCO3

- : 33

Answer: Metabolic alkalosis pH is high – alkalosis pCO2 is normal

HCO3

-is high – metabolic

-------------------------------------------------------------------------------------------------- 3. Mrs. H is kidney dialysis patient who has missed his last 2 appointments at the

dialysis centre. His ABG results: pH: 7.32

pCO2: 32

HCO3

-: 18

Answer: Partially compensated metabolic Acidosis pH is low – acidosis pCO2 is low

HCO3

- is low

- How can I decide if it is metabolic or respiratory? Taking example 3 into consideration; pH is below normal range – acidosis

Both concentrations (pCO2/ HCO3

-) are abnormal; the first probability is that pCO2 is

the primary change (decrease), then the reaction will be shifted to the right, HCO3

-

will also decrease, and H+ will decrease, causing increased pH, however the question gave us decreased pH so the primary change is NOTpCO2, therefore it is not respiratory. It is metabolic.

- How do I know if compensation started or not? And how can I decide if it is full or

partial compensation? If one of the concentrations is changed and the other is normal, then the

compensation has not started yet.

If both the CO2 and HCO3

- concentrations are abnormal > there is compensation

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If the pH reaches normal range, then it is full compensation, but if the pH doesn’t reach normal range, then it is partial compensation

4. Mr. K with Chronic obstructive pulmonary disease (COPD). His ABG is: pH: 7.35

pCO2: 48

HCO3

-:30

Answer: Fully compensated Respiratory Acidosis ---------------------------------------------------------------------------------------------------------

5. Mr. S is a 53-year-old man presented to ED with the following ABG. pH: 7.51

pCO2: 50

HCO3- : 40 Answer: Metabolic alkalosis with partial compensation

Practice examples

Answers:

Sorry for any mistake.

1. Respiratory alkalosis 6.Compensated Respiratory acidosis

2.Respiratory acidosis 7.Compensated Metabolic alkalosis

3.Metabolic acidosis 8.Metabolic acidosis

4.Compensated Respiratory acidosis 9.Respiratory acidosis

5.Metabolic alkalosis 10.Metabolic alkalosis

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If you find any,please contact our correction team …. GOOD LUCK:D

Past papers

Q1/a person had a surgery to remove his upper gastrointestinal tract. After the surgery,

his blood pH was 7.55 and HCO3=40 mM and PCO2= 52…. His condition is

a-metabolic acidosis

b-respiratory acidosis

c-metabolic alkalosis

d-respiratory alkalosis

e-none of the above

Q2/100 mmol of a triprotic acid were titrated with KOH. PKa values = 3, 6, 9.

How many mmoles of KOH must be added to have pH=6?

a- 100

b- 150

c- 200

d- 250

e- 300

Q3\The two most important buffer systems in blood are:

A. Phosphorylated organic metabolites and hemoglobin

B. Inorganic phosphate and hemoglobin

C. phosphorylated organic metabolites and pyruvate

D. hemoglobin and albumin

E. hemoglobin and bicarbonate

Q4- In protein buffers, which factor has the highest buffering contribution?

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Answer: Histidine content of the protein (from dr.diala don’t care if you cant solve it )

Q5/- One of the following statements is not true about Carbonic acid/Bicarbonate buffer:

a- The most common extracellular buffer.

b- Under physiological conditions the ratio of [HCO3-]/ [H2CO3] = 20.

c- Its buffering range is less than the desirable pH and that's compensated by CO2

mobility.

d- When adding a strong acid, it will react with HCO3-

e- When adding a strong base, it will react with CO3-2

Q6/- All of the following will cause mild or severe acidosis except:

a- the presence of ketone bodies in untreated diabetic patient

b- The production of acids like lactic acid during metabolism

c- Excessive breathing d- Repeated vomiting from the stomach containing HCL.

Q7/- Buffers work the best at all these conditions except :

a- when the pH to be maintained using the buffer has a value close to the pKa of its acid

component.

b- When the concentration of the acid component is equal to that of the base component.

c- When the acid component is completely dissociated

Answers:

1: C 2: B 3: E 5:e 6:d 7: c