March 16Acid-base balance1 Kidneys and acid-base balance

March 16Acid-base balance2 ACID-BASE BALANCE

March 16Acid-base balance3 Terminologies  Acid  Molecules containing Hydrogen atom that can release H + in a solution. –e.g. HCl ⇌ H + +Cl -  Base  An ion or molecule that can accept H + –e.g HCO H + ⇌ H 2 CO 3

March 16Acid-base balance4 Terminologies  Strong acid  Rapidly dissociates and releases especially large amount of H + in a solution  Weak acid –Less tendency to dissociate their ions –releases H + with less vigor  Strong base –Reacts rapidly and strongly with H + –Quickly removes H + from solution.

March 16Acid-base balance5 Terminologies  Alkali –Alkaline metal + highly basic ion.  Weak base – binds with H + much more weakly.  Buffer –Substance that can reversibly bind H +

March 16Acid-base balance6  Activities of almost all enzyme systems – in the body are influenced by [H + ].  80mEq of H + is either ingested –or produced each day by metabolism  Normal [H + ] in ECF is mEq/L – (40nEq/L) – With normal variation of 3 – 5nEq/L

March 16Acid-base balance7  pH –-Log[H + ] – = log 1/[H + ] –Log[0.0004mEq/L] = -log 4 x Eq/L –= 7.4  pH is inversely related to [H + ]  Normal pH of arterial blood is 7.4 –Venous blood and ISF is  7.35.

March 16Acid-base balance8 Acid-base disorders  Acidosis  pH < 7.4  Alkalosis  pH > 7.4  Limits of pH at which a person can live –for > few hours 6.8 – 8.0  pH of urine can range from 4.5 –8.0

March 16Acid-base balance9 Regulators of [H + ] in the body fluids  Kidneys play a key role – in regulation of [H + ]  Excrete either acidic or alkaline urine  However precise control of ECF [H + ] – involve much more than simple elimination by kidneys  Also involve –Chemical acid-base buffer systems –Respiratory system

March 16Acid-base balance10 Regulators of [H + ] in the body fluids  Chemical acid-base buffer systems –Immediately combine with acid or base –to prevent excessive changes in [H + ]  Respiratory centers –regulate the removal of CO 2

3/9/2016Acid-base balance11 BUFFER SYSTEMS

3/9/2016Acid-base balance12 Buffer systems  Bicarbonate buffer system  Phosphate buffer system  Protein buffer system  Ammonium buffer system

3/9/2016Acid-base balance13 Buffer systems  Buffer + H + ⇌ H Buffer (Weak acid)  HBuffer can remain – as undissociate molecule – or dissociate back to Buffer + H +   [H + ] Shifts the reaction – to Rt as long as available buffer is present.   [H + ] Shifts the reaction to Lt.

3/9/2016Acid-base balance14 The bicarbonate buffer system  Consist of water solution with –Weak acid, H 2 CO 3 –Weak base, (HCO 3 - ) e,g NaHCO 3 -  CO 2 +H 2 O ⇌ H 2 CO 3 ⇋ H + + HCO 3 - CA CA

3/9/2016Acid-base balance15 The bicarbonate buffer system  Carbonic anhydrase –Abundant in lung alveoli –Epithelia cell of renal tubules  Because of weak ionization of H 2 CO 3, –[H + ] is extremely low  NaHCO 3 ionizes almost completely. –NaHCO 3 ⇌ Na + + HCO 3 -

3/9/2016Acid-base balance16 The bicarbonate buffer system  CO 2 + H 2 O ⇌ H 2 CO 3 ⇌ H + + HCO Na

3/9/2016Acid-base balance17 The bicarbonate buffer system   H+ from strong acid – are buffered by HCO 3 - –  H + + HCO 3 -  H 2 CO 3  H 2 O + CO 2  CO 2 stimulates respiration center

3/9/2016Acid-base balance18 The bicarbonate buffer system  Addition of strong base e.g.. NaOH –leads to formation of weak base. –NaOH + H 2 CO 3  NaHCO 3 + H 2 O  [H 2 CO 3 ] decreases – causing more –CO 2 + H 2 O  + H 2 CO 3   CO 2 inhibits respiration.   HCO 3 - are excreted by kidneys.

3/9/2016Acid-base balance19 Henderson Hasselbach equation  Defines the determinants of pH –regulation of acid-base balance in the ECF.  H + are from dissociation of acids.  H 2 CO 3 ⇌ H + + HCO 3 -  Dissociation constant,K  K=[H + ][HCO 3 - ] [H 2 CO 3 - ]  [H + ] = K x[ H 2 CO 3 [ HCO 3 - ]

3/9/2016Acid-base balance20 Henderson Hasselbach equation  BUT – H 2 CO 3 dissociates –to CO 2 + H 2 O or H + + HCO 3 - rapidly  [H + ] = K 1 x CO 2 = K 1 x (0.03 x Pco 2 ) [HCO 3 - ] [HCO 3 - ]

3/9/2016Acid-base balance21 Henderson Hasselbach equation  [H + ] = K 1 x CO 2 = K 1 x (0.03 x Pco 2 ) [HCO 3 - ] [HCO 3 - ]  pH = -Log[H + ]  -Log[H + ] = -Log ( K 1 x 0.03Pco 2 ) [HCO 3 -]

3/9/2016Acid-base balance22 Henderson Hasselbach equation  pH = - LogK 1 – Log( 0.03 Pco 2 ) [HCO 3 - ]  pH = pK 1 + Log [HCO 3 - ] ( 0.03PCO 2 )  pH = Log [HCO 3 - ] 0.03PCO 2

3/9/2016Acid-base balance23 Henderson Hasselbach equation  pH = pK – when [HCO3 - ] = [H 2 CO 3 ]or[CO 2 ]

3/9/2016Acid-base balance24 Henderson Hasselbach equation  [HCO 3 - ] is regulated –mainly by the kidneys.  PCO 2 in ECF is controlled – by the rate of respiration.

3/9/2016Acid-base balance25 Henderson Hasselbach equation  Acid-base disorder occur – when one or both of these –control mechanisms are impaired.  Acid-base disorder –resulting from a primary change – in ECF [HCO 3 - ] is referred as metabolic.  Resulting from changes in Pco 2 –is referred as respiratory

3/9/2016Acid-base balance26 TITRATION CURVE FOR BICARBONATE BUFFER SYSTEM pK Acid added % of buffer in form of H2CO3 and CO2 Base added % of buffer in form of HCO 3 -

3/9/2016Acid-base balance27 Henderson Hasselbach equation  Buffer system is most effective –in the central part of the curve – when pH is near the pK of the system.  When pH is near the pK – the change in pH is least –following addition of a base or an acid  The bicarbonate buffer system –is the most powerful ECF buffer in the body. –Mainly because HCO 3 - and CO 2 – are regulated by kidneys & lungs respectively.

3/9/2016Acid-base balance28 The phosphate buffer system  Main elements are –H 2 PO 4 - and HPO 4 2-  It plays major role –in buffering renal tubular fluid and ICF’s  HPO 4 2- accepts H + –from strong acids –to form weak acid H 2 PO 4 - –and  in pH is minimized  e.g. HCl + NaHPO 4  NaCl + NAH 2 PO 4.

3/9/2016Acid-base balance29 The phosphate buffer system  Strong bases –are converted to weak based – by H 2 PO 4 - –causing only a slight increase in pH.  e.g NaOH + NaH 2 PO 4  Na 2 HPO 4 + H 2 O.

3/9/2016Acid-base balance30 The phosphate buffer system  Has pK of 6.8 –near normal pH of body fluids. –Allows the system to operate –near its maximum buffering power.  Its total buffering power in ECF – is much less than that of Bicarbonate buffer system – because its concentration in ECF –is low, about 2mOsm/L  (  8% of HCO 3 - buffer)

3/9/2016Acid-base balance31 The phosphate buffer system  Important in buffering ICF’s because –[phosphate] in ICF’s is many times – that in ECF,11mOsm/L –pH of ICF’s is closer to pK of phosphate buffer.(pH = )

3/9/2016Acid-base balance32 The phosphate buffer system  The phosphate buffer system –is especially important in the renal tubular fluids because.  Phosphate usually becomes – greatly concentrated in these tubules. –Tubular fluid usually has lower pH  than ECF(thus pH closure to pK of the phosphate buffer)

3/9/2016Acid-base balance33 Proteins  Important ICF buffer because –of their high concentration within the cells.  Proteins can accept or release H + –e.g hemoglobin in RBC, H + Hb ⇌ HHb  pKs of many protein buffer systems – are fairly close to 7.4   60 –70% total chemical buffering –of the body fluids is inside the cells – and most of this results from intracellular proteins.

3/9/2016Acid-base balance34 Proteins  pH changes in ICF’s – is approximately in proportion to ECF pH changes. –Slight amount of Diffusion of H + and HCO 3 -  through the cell membranes  However CO 2 diffuses rapidly – through all cell membranes, –this causes pH change in ICF –when there are changes in ECF pH.  For this reason, ICF buffer systems –help to prevent pH changes of ECF, – but may take several hours to become maximally effective.

3/9/2016Acid-base balance35 Ammonia buffer system  Composed of –NH 3 and NH 4 +  2 nd buffer system in the tubular fluids  More important quantitatively  than the phosphate buffer system.

3/9/2016Acid-base balance36 Buffer systems  All buffers in a common solution –are in Equilibrium with the same [H+] –HA ⇌ H + + A - –K = [H + ] [A - ] [HA]  H + = K x [HA] = K,[HA] = K 2 [HA 2 ] =K 3 x [HA 3 ] [A - ] [A1 - ] [A 2 - ] [A 3 - ]

3/9/2016Acid-base balance37 Respiratory control of acid-base balance  2 nd line defense against – acid-base disturbances –is regulation of CO 2 removal by lungs  CO 2 is continuously formed –in the body by intracellular metabolic processes   1.2 mol/L of dissolved CO 2 is in ECF

3/9/2016Acid-base balance38 Respiratory control of acid-base balance  If the rate of metabolic formation – of CO 2 ↑ –↑Pco 2 in ECF, –And the vice versa  ↑pulmonary ventilation →↓ Pco 2 in ECF –And vice versa.

3/9/2016Acid-base balance39 Respiratory control of acid-base balance  Changes in either – pulmonary ventilation –or rate of CO 2 formation – can change ECF P CO 2  Rate of alveolar ventilation – is the only factor that affect P CO 2 in ECF –provided metabolic formation of CO2 is constant.

3/9/2016Acid-base balance40 Respiratory control of acid-base balance  ↑alveolar ventilation –↓PCO 2, ↓H 2 CO 3, ↓[H + ], ↑pH,of ECF. –And vice versa.  Increased alveolar ventilation –to about twice the normal – raises the ECF pH by about 0.23

3/9/2016Acid-base balance41 Respiratory control of acid-base balance  ↑[H + ] stimulates alveolar ventilation.  ↓[H + ] causes a decrease –in ventilation rate.  The respiratory system acts as typical –negative feedback controller of [H + ]  Efficiency of respiratory control of [H + ] – is 50-75%.

3/9/2016Acid-base balance42 Respiratory control of acid-base balance  when cause of acid-base disturbance – is outside the respiratory system. –Response occurs within 3-12 minutes.  The overall buffering power –of respiratory system –is 1-2 times that of total chemical buffers in the ECF.