Acid base balance and disorders [Recovered] final
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Transcript of 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
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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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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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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
ISOHYDRIC TRANSPORT OF CARBON DIOXIDEISOHYDRIC TRANSPORT OF CARBON DIOXIDE
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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++
575757
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
5858
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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ISOHYDRIC TRANSPORT OF CARBON DIOXIDEISOHYDRIC TRANSPORT OF CARBON DIOXIDE
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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
33
HH++
Click Mouse to See
Animation Again
Notice the
H+ - Na+ exchange
maintain electricaneutrality
Dissociation ofDissociation of
carbonic acidcarbonic acid
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CapillaryCapillary Distal Tubule CellsDistal Tubule Cells
Tubular urine toTubular urine to
be excretedbe excreted
GlutamineGlutamine-- NHNH22
HH++
NH
NH
33
GlutamineGlutamine
HH++
NH
NH
33
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CapillaryCapillary Distal Tubule CellsDistal Tubule Cells
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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