Thursday, February 18, 2010


                                                            بسم الله الرحمن الرحيم 
Acid is a proton donor while base is proton acceptor: H2O  H+ + OH¯ From the equation, water can act both as an acid & as a base, for dissociation: ]O2H[]-][OH[H K It has been found that 1 mol of water contains 18 g, i.e. 1 L (1000 g) pure water is 55.56 molar. The probability that a H in pure water will exist as an H+ is 1.8 X 10-9, so the molar conc. of H+ or OH¯ in pure water = 55.56 X 1.8 X 10-9 = 1X10-7 mol/l mol/l 16-10 X 1.8 ]56.55[]-][OH[H K Kw = K [H2O] = [H+][OH¯] 1.8 X10-16 X 55.56 = 1 X 10-14 (mol/l)2 [H+] = [OH¯] = 1 X 10-7 (mol/l) PH = – log [H+]  PH = – log 10-7 = – (–7) = 7 PH + POH=14
Physiologic processes that generate H+
1- Complete metabolism
i- CHO, proteins & fats
ii- Conversion of amino nitrogen to urea
NH3 from NH4 & NH3 from asparate  urea + 2 H+
iii- Conversion of sulphur of SH containing AAs to sulphate
Cysteine metabolism, 2 H+ + SO4¯2
2- Incomplete catabolism
i) Incomplete metabolism of CHO to lactate
Glucose  2 pyruvate  2 lactate
ii) Incomplete metabolism of FAs & ketogenic AAs to ketoacids
In fasting & DM, acetyl CoA  > oxidative capacity of TCA  acetoacetate  β OH butyrate
Other metabolic processes release a net 50 – 100 mmol of H+ (nonvolatile acids: sulfuric & phosphoric acid) into ECF and normal [H+] is only 40 nmol/l so there must be an efficient 
ORGANS CONTROLLING H+ HOMEOSTASIS A 70 Kg man disposes 20 mol/day of CO2 through the lungs & 70 – 100 mmol/day of nonvolatile acids through the kidney. Lactate, acetoacetate & β OH butyrate are normally metabolized to CO2 & H2O before excretion. The lungs, controlled by the cerebral medullary respiratory center that adjusts EC [CO2] to 1.2 mmol/l. The kidneys, control the EC HCO3¯ through carbonic anhydrase system. These organs interact with each other mainly through CA system: HCO3- + H+  H2CO3  CO2 + H2O
— Water formed by buffering of H+ by HCO3-
— CO2 is constantly produced by aerobic metabolism.
— HCO3- are produced by CO2 + H2O
CO2 and O2 in blood
 CO2 is transported in the blood in the form of:
1. Bicarbonate (HCO3-) in plasma & RBCs.
2. Carbamino Hb (CO2Hb) in RBCs.
3. Dissolved CO2 (dCO2) in fluids of RBCs & plasma.
 O2 is transported to tissues in 2 forms:
1. Reversibly bound to Hb in RBCs (O2Hb).
2. Dissolved O2 (dO2) in fluids of RBCs & plasma.
 In plasma a small proportion of dCO2 reacts with plasma water to form H2CO3 & HCO3-
dCO2 + H2O  H2CO3  HCO3- + H+
 Another small amount reacts with amino groups of plasma proteins to form carbamino compounds.
Note: in RBCs the same reaction occurs in presence of intracellular water & amino groups of Hb & other proteins.
 The amount of O2 that the blood can carry is determined by:
1. Amount of functional Hb.
2. PO2 that determines how much O2 will dissolve in the blood.
3. Affinity of the available Hb for O2.
Hb – O2 dissociation The degree of association or dissociation of O2 with Hb is determined by PO2 and Hb affinity for O2 which in turn dependent on:
1. Temperature
2. PH
3. PCO2
4. 2,3 DPG
BUFFERS A buffer pair is made up of a weak acid (little dissociated) and its conjugate base. If either acid or base is added to a solution of such pair it's neutralized, e.g. H+B¯ weak acid. H+ + B¯  HB OH¯ + HB  H2O + B¯ If [H+] > [B¯]  ineffective buffer [B¯]   HB increases rate of reverse reaction [B¯] = [HB]  more effective buffer Thus, [B¯] > [HB]  more effective buffer to H+ than to OH- So the buffering capacity partly depends on the concentration of buffers and also depends on the PKa of the buffer, At equilibrium: ]B[[HB] Ka ][H [HB] Ka ]-][B[H ]HB[]-][B[H Ka In effective buffer [B¯] = [HB]  ]B[[HB]  = 1  [H+] = Ka Using Henderson – Hasslbalch equation, PH = PKa + log]HB[]B[  Anti log 1 = 0 so PH = PKa PH of blood is 7.4 & PKa range for buffers to be effective 7.4 ± 1.5. Buffers outside this range in PKa (5.9 – 8.9) will have little useful effect. Metabolic reactions or processes generate H+ rather than OH- & PKa nearer the lower end of the range, i.e. [B¯] > [HB], is less physiologically disadvantageous than one at the upper limit. Types of buffers
2- It's enclosed by CA system, allowing it to interact with HCO3¯
Deoxy form is better than oxy form (free site for binding of H+) and H+ deceases the affinity of Hb for O2. Other proteins; The total blood molar concentration of plasma protein is lower than that of Hb and their concentration in interstitial fluid are very low  buffering capacity/mole is less and they don’t work with CA system  they are unimportant as EC buffers. Their increased IC concentration allow them to play a relatively important part in buffering H+ before its release from the cells.
3. H2PO4¯/HPO4¯2
Mono & dihydrogen phosphate form a buffer pair with PKa ~ 6.8. PH = PKa' + log]4PO2H[]24HPO[ ; ]4PO2H[]24HPO[  = 4/1 Plasma concentration is ~ 2 mmol/l and glomerular filtrate concentration is identical to that of plasma but during selective water reabsorbtion from the tubular lumen the concentration  to become 20 mmol/l in urine and this explains why EC phosphate contributes little to buffer despite the favorable PKa.
Isohydric shift A shift in concentrations of components such that the concentration of H+ remains essentially unchanged. CO2 entering the plasma
o A small portion stays as dCO2.
o The majority reacts with water to form carbonic acid, which dissociates into H+ and HCO¯ H+ production is buffered by the plasma buffers, including the proteins.
o Another small portion combines with the amino groups of proteins and forms carbamino compounds (PrCO2).
CO2 entering RBCs
o Most of the CO2 reacts with water to form carbonic acid.
o Some remains as dCO2, and combines with (HHb) to form carbamino hemoglobin (HHbCO2).
Chloride shift
o The remainder of the H+ is buffered by the nonbicarbonate buffers of the RBC fluid, whereas [HCO3]  to the same extent that the concentration of Hb anions falls.
o The [HCO3]  relatively more in RBCs than in the plasma, the pH of plasma  relatively more than the pH of RBCs, and the  in protonation of proteins and hemoglobin  [protein anion] in the RBCs .
o The RBCs membrane potential becomes less negative HCO3 moves out and Cl- moves into RBCs (to provide electrochemical balance)  small amount of H2O will pass from the plasma into RBCs.
In the alveoli chloride shift is reversed
o The venous blood is transported to the pulmonary capillaries, where PO2 & PCO2  shift of CO2 from & shift of O2 into the plasma and RBCs.
o The removal of CO2 from the blood and the oxygenation of the blood are the major reactions that convert venous blood into arterial blood.
Respiratory response The respiratory mechanism contributes to the maintenance or restoration of normal body pH through retention of CO2 in metabolic alkalosis and increased elimination of CO2 in metabolic acidosis. The respiratory system responds immediately to a change in acid-base status, but about 3 to 6 hours are required for the central and peripheral chemoreceptors to be fully stimulated.

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