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ACID BASE BALANCE

Lecture – 8

Dr. Zahoor

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ACID BASE BALANCE Acid Base Balance refers to regulation of free

(unbound) H+ concentration in the body fluids Acids liberate free H+ ion, whereas bases

accept them Strong acid gives greater percentage of free

H+ e.g. HCL is strong acid Weak acid give less H+ ion e.g. carbonic acid

H2CO3 is weak acid

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BASE Base is a substance that combines with free

H+ and removes it from the solution Strong base combines with H+ more readily

than weak base

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pH (Potential Hydrogen) pH is used to express H+ ion present H+ in ECF is normally 4×10-8 or 0.00000004

equivalent per liter (3 million times less than Na+ in ECF)

pH = log1/[H+] High H+ corresponds to low pH (acidity) Low H+ corresponds to high pH (towards

alkaline)

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pH Normal pH = 7.4 How it is calculated ? Normal H+ ion concentration is 40nEq/L and

can change normally 3-5nEq/L These small values are difficult to express,

therefore we express H+ concentration on logarithm scale using pH units

pH = log 1/[H+] OR pH= -log H+ Normal H+ is 40nEq/L (0.00000004Eq/L) Therefore Normal pH = - log [ 0.00000004] pH = 7.4

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Acid Base Balance pH 7 is neutral in CHEMISTRY H2O pH is 7 (equal number of H+ and OH- ions

are formed when H2O disassociates) Solution having pH less than 7.0 is acidic

(have more H+ ion) Solution having pH more than 7.0 is alkaline

(less H+ ion)

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pH consideration in chemistry and physiology

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ACIDOSIS & ALKALOSIS IN BODY Arterial blood pH is 7.45 Venous blood pH is 7.35 Average blood pH is 7.4 Acidosis when blood pH falls below 7.35 Alkalosis when blood pH is above 7.45

Remember – Reference point for body’s pH determination is 7.4. Why?

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ACIDOSIS & ALKALOSIS IN BODY Because body’s pH of 7.4 is taken neutral for

the body and is reference point for acidosis or alkalosis for the body.

PH compatible with life 6.8- 8

IMPORTANT – An arterial pH less than 6.8 or greater than 8.0 is not compatible with life

Death can occur in few seconds, therefore, pH of body fluids is carefully regulated

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ACIDOSIS & ALKALOSIS IN BODY pH regulation is important because changes in

H+, alter nerve, enzyme and K+ activity which will affect CVS, CNS and body metabolic processes

Acidosis causes depression of CNS, disorientation, coma and death

Alkalosis causes over excitability of CNS and peripheral nervous system (muscle twitches and muscle spasm)

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REGULATION OF H+ ION IN THE BODY There are 3 lines of defense against changes in

H+ ion to keep the pH of ECF 7.4 in the body 3 lines of defense are: 1. Chemical buffer system – respond in

seconds 2. Respiratory mechanism of pH control –

respond in minutes 3. Renal mechanism of pH control – respond in

hours to days

We will study each one, mainly renal mechanisms

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REGULATION OF H+ ION IN THE BODY1. Chemical Buffer System In Chemical Buffer System either an acid or

a base is added or removed from the solution

In body, 4 buffer systems are i). H2CO3 : HCO3 buffer system

ii). Protein buffer system iii). Hemoglobin buffer system iv). Phosphate buffer system

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2. Respiratory mechanism of pH control

Respiratory system regulates H+ by controlling the rate of CO2 removed

Respiration plays important role in acid base balance by pulmonary ventilation and excretion of H+ by generating CO2

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2. Respiratory mechanism of pH control

When there is metabolic acidosis, respiratory center in the brain stem is stimulated, therefore, increase ventilation occurs and CO2 is eliminated which helps to remove H+ ion

H + HCO3 H20 + CO2

CO2 is removed by ventilation, therefore, decreased H+ occurs in body fluid

Respiratory system is very important for every day removal of H+ ion

Respiratory system can bring pH back to normal only 50 to 75%

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3. Renal mechanism of pH control

Kidneys regulate acid base balance by 1. H+ secretion and excretion 2. HCO3 reabsorption

3. Renal buffers i). Phosphate buffers ii). Ammonia mechanism

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3. Renal mechanism of pH control1. H+ ion secretion The proximal, distal and collecting tubule all

secrete H+ ion Normally urine pH is 6 as H+ is excreted Mechanism of H+ ion secretion H+ secretary process begins in the

tubular cells with CO2 diffused into tubular cells from plasma, tubular fluid or CO2 metabolically produced in tubular cell

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Active Secretion of H+ ion in to tubular cell and reabsorption of HCO3 ion

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1. H+ ion secretion H+ ion is secreted in PCT by both primary H+

ATP pump and secondary active transport via Na+ - H+ anti-porters (anti-porters transport Na+ and H+ in opposite directions where Na+ is reabsorbed and H+ is secreted)

H+ secretion in distal and collecting tubule occurs in intercalated cells type A

Intercalated cells type A secrete H+ ion and reabsorb HCO3

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Primary Active Secretion of H+ ion in the intercalated epithelial Type A cell in DCT and CT

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2. HCO3 Reabsorption

As we have seen in previous diagram ( slide 18 )

Filtered HCO3 disappears, but is coupled with appearance of another HCO3 from the cell into the plasma

Two HCO3 are different, but HCO3 going to the plasma is considered to have been reabsorbed

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3. Renal buffersi) Filtered Phosphate bufferii) Secreted ammonia

Filtered Phosphate buffer Secreted H+ ion is buffered by phosphate

buffer system H+ secreted in the tubule combines with

phosphate

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Buffering of Secreted H+ by Filtered phosphate (NaHPO4

-) and Generation of “New” HCO3

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Secreted ammonia as Urinary Buffer When acidosis exist, the tubular cells secrete

NH3 in the tubular fluid, once normal urinary phosphate buffers are saturated

NH3 is synthesized from amino acid glutamine within the tubular cell

NH3 combines with H+ in the tubular fluid to form ammonium (NH4)

NH4 is excreted from tubular fluid

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Production and Secretion of NH4+ and HCO3

- by Proximal Tubular Cell

“New” HCO3-

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Buffering of Hydrogen Ion Secretion by Ammonia (NH3) in the Collecting Tubules

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pH Regulation Kidneys are powerful third line of defense

against changes in H+ ion Kidneys requires hours to days to compensate

for changes in body fluid pH H+ is secreted by energy depending H+

carrier until tubular fluid (urine) becomes 800 times more acidic than plasma

At this point, kidney can not acidify urine any more and pH of urine is 4.5

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pH Regulation In Alkalosis, H+ ion is secreted less in PCT and

type A intercalated cells There is decreased HCO3 reabsorption

Secretion of HCO3 occurs by intercalated type B-cells in DCT and CT. HCO3 is excreted in urine.

In Alkalosis, kidney makes urine alkaline

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ACID BASE DISORDERS Acid Base imbalance can occur from

respiratory dysfunction or metabolic disturbances

Acid Base disorders - Respiratory acidosis – increased CO2

- Respiratory alkalosis – decreased CO2

- Metabolic acidosis – decreased HCO3

- Metabolic alkalosis – increased HCO3

There can be combined disorders

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ACID BASE DISORDERSRespiratory Acidosis Occurs due to CO2 retention, therefore, there

is increased CO2 due to hypoventilation

Increased CO2 generates more H+ ion Causes - Depression of respiratory center e.g. drugs - Nerve and muscle disorders

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ACID BASE DISORDERSRespiratory Alkalosis Occurs due to decreased CO2

e.g. hyperventilation, therefore, decreased H+ is formed

Causes of Respiratory Alkalosis - Fever - Anxiety - Aspirin poisoning - High altitude

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ACID BASE DISORDERSMetabolic Acidosis It is characterized by decreased HCO3

CO2 remains normal Causes of Metabolic Acidosis - Severe Diarrhea – HCO3 is lost from GIT

- Diabetes mellitus – there is keto acidosis due to abnormal fat metabolism

- Renal failure – kidney can not excrete H+ ion, therefore, there is increase H+ ion

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ACID BASE DISORDERSMetabolic Alkalosis In Metabolic Alkalosis, there is increased HCO3

and decreased H+ ion Causes - Vomiting – Loss of H ion due to loss of

gastric juice - Ingestion of alkaline drugs e.g. NaHCO3 for

acidity

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pH in Uncompensated Acid-Base Abnormalities

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Analysis of Simple Acid-BaseDisorders

Figure 30-10; Guyton and Hall

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