Acid base balance and disorders [Recovered] final

8/7/2019 Acid base balance and disorders [Recovered] final

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Na+ K+

Ca++

Cl-PO4---

Cell

ECF


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Rate ofenzyme catalyzed reaction

Maintain stability & confirmation of

proteins

Interaction ofmacromolecules with

each other & with small ions

Analytical & purification techniques in

the laboratory

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HH++ ion -it must bemaintained in narrowrange in order to becompatible with livingsystems

Free HH++ ion 40nmol/L

Being small ion highlyreactive

Small fluctuation canaffect normal functions

Buffers regulate theHH++ ion concentration


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Creates a gradient acrossmembrane

Maintenance of PH of bodyfluids

Gradient is important

To stimulate oxidativephosphorylation

Ionisation of weak acids andbases and facilitates theirphysiological function

Affects surface charge of

Proteins11-Mar-11


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--- Ionic theory

1. Electrolyte splits into chargedparticles(ions) in solution .

2. Ions carry electric current

3. Positive charges = Negative charges.Solution is neutral.

4

. Degree of ionization increases with dilutionin weak electrolytes.

5. Chemical changes occur due to reactionbetween charges and not molecules.

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Acid is any substance whichdissociated in water to produce H+ ion

Base is any substance whichdissociated in water to produce OH-

ion

Holds good for aqueous solutions only

Cause for dissociation not explained

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Acid:Any Substance or particle or

Ion which donates Hydrogen ion. Eg: HCl, H2CO3.

Base: Any Substance or particle or Ionwhich accepts Hydrogen ion.

Eg: HCO3-, CH3COO-

Explains conjugate acid base pairs11-Mar-11


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Acids can be defined as a proton (HH++

) donor Hydrogen containing substances which

dissociate in solution to release HH++

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Click Here


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Acids can be defined as a proton (HH++

) donor Hydrogen containing substances which

dissociate in solution to release HH++

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ACIDS

Physiologically important acids include:Carbonic acid (HCarbonic acid (H

22COCO33))

Phosphoric acid (HPhosphoric acid (H33POPO44))

Pyruvic acid (CPyruvic acid (C33HH

44OO33)) Lactic acid (CLactic acid (C33HH66OO33))

These acids are dissolved in body fluids

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Bases can be defined as:A proton (HH++) acceptor

Molecules capable of accepting a hydrogenion (OHOH--)

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Click Here


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BASES

Physiologically important bases include:Bicarbonate (HCOBicarbonate (HCO33

-- ))

Biphosphate (HPOBiphosphate (HPO44--22))

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The acid and its corresponding base

or vice versa are called Conjugate

pair

Eg: HCl and Cl

-

, H2CO3 and HCO3-

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ACIDS

Gastric Juice-HCl

Cellular respiration- CO2

Metabolic end products -Organic acids

Blood- Carbonic acid

Amino acid/Protein

metabolism- Sulphuric,Phosphoric acid

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BASES

Protein metabolism

(deamination) -Ammonia

Blood, Pancreatic juice-

Bicarbonate

Dietary sources- Citrus

fruits - Bicarbonate,

Phosphates etc


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SOURCES OF ACIDS AND BASES IN BODYSOURCES OF ACIDS AND BASES IN BODY

Acids

Fixed acids

lactate, pyruvate,acetoacetate, uric acid

Volatile acids

carbon dioxide

Bases

Ammonia

Bicarbonate


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Definition: Negative logarithm of

hydrogen ion concentration

Expresses hydrogen ion concentration in solutions

Water ionizes to a limited extent to form equal amounts ofHH++

ions and OHOH-- ions.

It is Amphoteric

HH22OO HH++ + OH+ OH--

HH++ ion is an acid

Hydroxonium ion is an acidHydroxonium ion is an acid OHOH-- ion is a base

PH of 7 is said to be neutral PH (100nmol/L Hydrogen ion)

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Pure water is NeutralNeutral ( H+ = OH- )

pH = 7

AcidAcid ( H+ > OH- )

pH < 7

BaseBase ( H+ < OH- )

pH > 7

Normal blood pH is 7.357.35 -- 7.457.45

pH range compatible with life is6.86.8 -- 8.08.0

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OH-OH-

OH-

OH-

OH-

OH-

H+

H+

H+

H+

OH-OH-

OH-

OH-OH-

H+

H+

H+H

+

OH-

OH-

OH-H+

H+H+

H+H+

H+

H+

1

2

3


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pH = 4 is more acidic thanpH = 6

pH = 4 has 10 times morefree HH++concentration than

pH = 5 and 100

times morefree HH++ concentration thanpH = 6

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pH decrease (more acidic) depresses the

central nervous system

Can lead to loss of consciousness pH increase (more basic) can cause over-

excitability

Tingling sensations, nervousness,muscle twitches

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pH increase or decrease can alter the shape ofthe enzyme rendering it non-functional

Changes in enzyme structure can result in

accelerated or depressed metabolic actionswithin the cell

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Definition: It is a constant ratio between

dissociated and un dissociated particles

Ka= [H+] [A-] / [HA]

PH at which half ionization occurs is Pka

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Used for calculation of PH of solution

For an acid,

PH = Pka + Log [base]/[acid] or

PH = Pka + Log [Salt]/[acid]

PH =Pka when Concentration of acid =

concentration of base (half dissociated).

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StrongAcids andBases:Those which

dissociate completely.

Eg: HCl and NaOH

Weak acids andBases: Those which

dissociate incompletely < 50%.

Eg: H2CO3 and HCO3-

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A relative increase in

hydrogen ions results in

acidosisacidosis

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H+

OH-

A relative increase in

bicarbonate results in

alkalosisalkalosis

H

+

OH-


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H+

HCO3-


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Derangements ofhydrogen and

bicarbonate

concentrations in

body fluids are

common in disease

processes

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Definition : These are solutions

or substances which resist change

in PH which is expected on addition

of acid or base.

Weak acid and its salt with a strong base

Weak base and its salt with a strong Acid

Eg: carbonic acid and Sodium Bicarbonate buffer,

Acetic acid and Sodium acetate, Phosphate buffer.11-Mar-11


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1. Concentration of acid and salt

2. Value of PK

3. Most effective when pH = pKa

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Representation of Buffer on HH Equation,

Action of buffer will be maximum when

pH=pKa 1


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Acids are produced in body in excess of alkali

Neutralization requires more alkalicomponent of buffers .

Hence alkali is reserved in body more thanacids

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Intracellular

K+ Protein /

H+ Protein

K2HPO4 / KH2PO4

KHCO3 /

H2CO3

RBCs

KHbO2/

HHbO2

KH

CO3 /H2CO3

HbO2/

HHb

Extracellular

Na2HPO4 /NaH

2PO4

NaHCO3 /

H2CO3

Na+ Protein /

H

+

Protein

58% - tissues

6% RBCs

42% - -Bicarbonate,

Phosphate, Protein


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First line of defence against acid base

disturbance

Starts within seconds and brings the pH nearerto normal

Three buffers are most important

1. Bicarbonate buffer ( Most important)

2. Phosphate buffer ( Urinary buffer)

3. Protein buffer (Tissue, Hb, Plasma)

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Most important buffer

Main buffer in ECF (40%)65% in plasma, but also

ICF ( RBCs)

It converts strong non volatile to volatile acids

Works in association with renal and respiratory

system

Transporter of Carbon dioxide in plasma

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Predominates in extracellular fluid (ECFECF)

HCOHCO33-- + added H+ added H++ HH

22COCO33

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HCOHCO33--HH22COCO33


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This system is most important because the

concentration of both components can beregulated:

by the respiratory system

by the renal system

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Hydrogen ions generated by metabolism or by

ingestion react with bicarbonate base to form more

carbonic acid

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HCOHCO33--HH22COCO33

HH++ HCOHCO33--HH22COCO33HH22OOCOCO22 + ++


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PH= Pka+ log [ HCOHCO33--] / [HH22COCO33]

PH =7.4, [HCOHCO33--]= 24mEq/L,

[HH22COCO33]=1.2mEq/L

Hence on substituting ,

PKa= 6.1

PH>Pka Not an ideal buffer but

high concentration in plasma makes

it the best buffer

Replenished continuously

Base : Acid = 20:1 ( Alkali reserve)

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Regulates pHpH within the cells and the urine

Phosphate concentrations are higher

intracellularly and within the kidney tubules

Too low of a

concentration in

ECF to have muchimportance as an

ECFECF buffer system

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HPO4-2


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Behaves as a buffer in both plasma and cells

Hemoglobin is by far the most importantprotein buffer in RBCs

Plasma Proteins (Albumin) in ECF

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Most abun ant

in bo y( %)

Act instantly

itmillisec

Ionisable groups

-Acidic & Basic

Amphoteric nature

Na Pr/HPr

KPr/HPr

Carbamino compound

Carrier of CO2


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11-Mar-11Amino, Carboxyl, Guanidino & Imidazole groups

Pr - added H+ + Pr -


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11-Mar-11As hemoglobin releases OO22 it gains a great affinity for HH++

Hemoglobin is better buffer than plasma proteins

Histidine with

Imidazole ring

1gm Plasma protein binds 0.110meqH+

1gmHb binds --0.183meqH+

ISOHYDRIC TRANSPORT OF CARBON DIOXIDEISOHYDRIC TRANSPORT OF CARBON DIOXIDE


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Hemoglobin buffers HH++ from metabolically

produced COCO22 in the plasma only11-Mar-11



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HbHb

O2

O

O2

HH++ generated at the tissue level from the dissociation

of HH22COCO33 produced by theaddition of COCO22

Bound HH++ to HbHb (Hemoglobin) does not

contribute to the acidity of blood

As HH++HbHb picks up OO22

from the lungs the HbHb which

has a higher affinity for OO22

releases HH++ and picks

up OO22 Liberated HH++ from HH22OO combines with HCOHCO33--


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Venous blood is only slightly more acidic than

arterial blood because of the tremendous

buffering capacity ofHbHb

Even in spite of the large volume ofHH++

generating COCO22

carried in venous blood

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Cellular pH = 6.8-7.2 PH is important for optimum

functioning

Intracellular buffers areprotein,Phospahte andBicarbonate buffers

Ions like Na+,K+,Ca2+ plays an

important role trancellular shift is seen

Mainly in skeletal tissue & bone

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cell

HH++

KK++

HH++

KK++

cell


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When reabsorbing

NaNa++ from the filtrateof the renal tubules KK++

or HH++ is secreted(exchanged)

Normally KK++ issecreted in muchgreater amounts

thanHH++

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KK++

KK++KK++KK++KK++KK++KK++ NaNa++NaNa++NaNa++NaNa++NaNa++NaNa++

HH++


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IfHH++ concentrations are high (acidosis) ,thenmore HH++ is secreted

This leaves less KK++ than usual excreted

The resultant KK++ retention can affect cardiacfunction and other systems

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KK++KK++KK++ NaNa++NaNa++NaNa++NaNa++NaNa++NaNa++

HH++HH++HH++HH++HH++HH++HH++

KK++KK++KK++KK++KK++


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1) Buffer Systems

2) Respiratory Responses3) Renal Responses

4) Intracellular Shifts of Ions

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Second line of defence Acts in minutes

Acts by,

1. Exchange of gases(regulates pCO2)

2. Regulates Carbonic acid levels (with

Bicarbonate buffer)

3. Chemo receptors are pH sensitiveregulating respiratory rate

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Respiratory centersMedulla oblongata

Pons

Stimulation and limitation of

respiratory rates are controlled by

the respiratory center

Neurons in the medulla

oblongata and pons

constitute the

Respiratory CenterRespiratory Center

Control is accomplished byControl is accomplished by

responding toresponding to COCO22

andand HH++

concentrations in the bloodconcentrations in the blood


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Chemo sensitive areas of the respiratory center

are able to detect blood concentration levels ofCO

2and H+

Increases in CO2

and H+ stimulate the respiratorycenter

The effect is to raiserespiration rates

But the effect

diminishes in1 - 2 minutes

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COCO22 COCO22

COCO22

COCO22

COCO22

COCO22

COCO22 COCO

COCO22

Click to increase CO2


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Chemo receptors are also present in the carotidcarotid

and aorticaortic arteries which respond to changes inpartial pressures ofO

2and CO

2or pH

Increased levels of

CO2 (low pHpH) ordecreased levels of

O2

stimulate

respiration rates

to increase

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Overall compensatory response is:

HyperventilationHyperventilation in response to increasedCO

2or H+ (low pHpH)

HypoventilationHypoventilation in response to decreased

CO2 or H+ (high pHpH)

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66pH ris s t r r l

r t pth f br thi g i cr s

CO2eli i ted i lu gs

H+ sti ul tes respir t ry center in edull bl ng t

H2CO3 H

+ + HCO3-

H+ cidosis; pHdrops

CO2

+ H2O H

2CO3

cell productionof CO2

increases


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1) Buffer Systems

2) Respiratory Responses

3) Renal Responses4) Intracellular Shifts of Ions

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The kidney compensates for AcidAcid -- BaseBase imbalancewithin 24 hours24 hours and is responsible for long term

control The kidney responds in 4 ways:

1. Excretion ofH+ Ion

2. Reabsorption ofHCO3

-

3. Excretion ofTitratable acid4. Excretion ofNH4

+ ions

InIn AcidosisAcidosis

Retains bicarbonate ions and eliminateshydrogen ions

InIn AlkalosisAlkalosis

Eliminates bicarbonate ions and retains hydrogen

ions 68


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H

CapillaryCapillary Distal Tubule CellsDistal Tubule Cells

TubularTubular

Na+ +HH22COCO33HCOHCO33-- ++

NaHCONaHCO33NaHCONaHCO

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HH++

Click Mouse to See

Animation Again

Notice the

H+ - Na+ exchange

maintain electricaneutrality

Dissociation ofDissociation of

carbonic acidcarbonic acid


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Tubular urine toTubular urine to

be excretedbe excreted

GlutamineGlutamine-- NHNH22

HH++

NH

NH

33

GlutamineGlutamine

HH++

NH

NH

33


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Tubular UrineTubular Urine

NHNH33

NaNa++ ClCl--+HH22COCO33

HCOHCO33--

++NaClNaCl

NaHCONaHCO33

Click Mouse to Start

Animation

NaHCONaHCO33 NHNH33ClCl--

HH++

NHNH44ClCl

Click Mouse to See

Animation A ain

Notice theNotice the

HH++ -- NaNa++

exchange toexchange tomaintainmaintain

electricalelectrical

neutralityneutralityDissociation ofDissociation of

carbonic acidcarbonic acid


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Documents

Acid base balance and disorders [Recovered] final