Learning Objectives
By the end of the session should be able to comprehend:
•Defense mechanisms
•Buffer and its types
•Respiratory Control of acid base Imbalance
•Regulation of H ions
•Anion Gap
Buffer Power
•pH=pK
•Most effective when pKis near to pH in the central part of curve
•1.0 pH unit deviation —-reasonably effective
•Bicarbonate buffering power 6.1
•Can extend from 5.1 to 7.1
Phosphate Buffer System
•Not important in ECF buffers: H2PO4-/HPO4-2
•Strong acidsbind with HPO4-2(salt) to form salts
HCl+Na2HPO4→NaH2PO4+NaCl
•Strong bases bindwithH2PO4-(weak acid) to form weak acid and water
NaOH+NaH2PO4→Na2HPO4+H2O
•pK6.8
•About 8% in ECF
•Most efficient in renal tubules
Protein Buffer
•ICF buffer—60-70%
•Most powerful buffer in body
–Increased conc. of proteins in cells
•Slight diffusion of H+ between ECF & ICF
–Decreased pH in ECF also decreased pH in ICF
–Already less pH in ICF
•RBC –Hemoglobin: buffer action
–H+ + Hb—HHb
Respiratory control
•Second line of defense
•50% control of pH regulation -by lung
•50% -75% effective in reversing H+ conc. to normal (not 100%)
•Response in 3-12 minutes
•Role of lungs -alteration in breathing rate
–Minimum ventilation = pH drops to 6.95
–Maximum ventilation = pH rises to 7.63
•Continually formed during metabolic processes
•From cells reach lungs to be exhaled
•1.2mol/L of dissolved CO2impart PCO2of 40mmHg
•Metabolism increases CO2 formation increases
•If pulmonary ventilation decreases PCO2decreases
•CO2H2 CO3H+ionspH
Respiratory control
•Sensitivity –alveolar ventilation doubles with pH drop by 0.23
•As pH drops, sensitivity of respiratory center increase tremendously
The respiratory component responds less to alkalosis so at pH 7.4, the alveolar ventilation changes only 1 time
•Partial compensation in metabolic acidosis & alkalosis
•Respcompensation -More effective in acidosis than in alkalosis
•Not as effective as renal buffer system
•Mechanism
–< pH, more H2 CO3to CO2
–Central chemoreceptors stimulated, increased ventilation
Respiratory Regulation
•Hydrogen ions alveolar ventilation CO2
•Decreased CO2 will decrease H ions
•Returns pH back to normal
Regulation of H+ Ions
•More HCO3filtered more H+ ions secreted
•More loss of acid
•80mEq of non volatile acids are produced
•Elimination of non-volatile acids: (H2SO4H3PO4)
–Secretion of H +
•Kidney prevent loss of bicarbonate ions
•To preserve body buffer
•In alkalosis
–Less H+ ions are secreted
–Less HCO3 are filtered and reabsorbed
–Net loss of HCO3 ions and preservation of H+ ions
–Decreases ECF pH
•In acidosis
–More H+ ions are secreted
–More HCO3 are filtered and reabsorbed
–Netpreservation of HCO3 ions and loss of H+ ions
–Raises ECF pH
•Normally kidney regulates ECF pH
–Secretion of H+ ions
–Reabsorption/Filtration of HCO3 ions
–Production of new HCO3-ions
Renal buffer systems
Renal buffer systems:
1.Phosphate buffer system
2.Ammonia buffer system
3.Carbonic Acid buffer system
Less important are uratesand citrates
•Kidney’s acid-base regulatory potency is that it has ability to return the pH almost exactly to normal by:-
i. Active secretion of H+ions
ii. H+ ion buffering within tubular lumen:
a. Buffering with HCO-3;
Result in reabsorption of filtered HCO-3ions
b. Buffering with HPO–4 orNH3 ;
Result in H+ ion excretion & generation of new HCO-3ions
Outcome: by excreting acidic or basic urine
Phosphate buffers
•pH=6.8
•Renal tubular and intracellular buffer
•Only 8% in ECF
•Consists of
–HPO–4(salt)
–H2PO-4(acid)
(become concentrated in renal tubules by reabsorption of H2O).
•75% of filtered HPO–4is reabsorbed
•Remaining 25% is available for buffering, concentrated in tubules
•Under normal conditions 30-40 mEq/day filtered phosphate is available for buffering H+.
•Operates when secreted [H+]is in excess than filtered [HCO-3]
•Renal tubules has relatively less pH than ECF
Ammonia buffer
•2ndSpecial Buffer System
•Consists of NH3 & NH+4
•More important ‘quantitatively’than phosphate buffer system
•50 % of H+ secreted in kidneys –handled by NH3 buffer
•NH4 ions are synthesized from glutamine in PCT, LOH & DT
•Secreted into tubular fluid by Na+-H+exchange (counter transport)mechanism i.e. NH+4 is secreted in place of H+.
•Main buffer system in renal tubules in chronic acidosis
•Production of NH3+ from glutamine in liver mainly
•From 01 glutamine molecule, 02 NH4 & 02 ‘NEW’ HCO3 molecules generated in renal tubules
•PCT, LOH, DCT -permeable to NH4 –Na+-NH4+ counter-transport secreted as NH4Cl
•CD -impermeable to NH4 –NH3 secreted & combine with H+
•For each NH4 secreted one ‘NEW’ HCO3 generated
When there is excess H+ions in ECF:
•Kidneys tackle it by;
1.Reabsorption of all filtered HCO-3
2.Generation of new HCO-3(to replenish decreased level of HCO-3in ECF)
Regulation of H+ Ions
•Maximum H+ conc. –900 folds in DCT & CD
•Reabsorption of all filtered HCO3
•Production of new HCO3 (In PCT, DCT & CD)
–PO4 buffer (one new HCO3 for each H+ secreted)
–Ammonia buffer (two new HCO3 for each H+ secreted)
•In chronic acid-base disorder –NH3 buffer most effective
•Partial compensation in respiratory and non-renal metabolic acid base disorders
Renal buffer systems
•H+ ion secretion in excess of HCO3 ions
•Urine minimal pH 4.5
•H+ ion concentration 0.03mEq/L
•80mEq/L non-volatile acid require 2667L of urine to be excreted
•Large amount of H+ ions excreted with buffers
Renal Acid Base Excretion
•Bicarbonate excretion is calculated as urine flow rate multiplied by urinary bicarbonate concentration
•Bicarbonate reabsorption= H+ ion secretion or NH4+ ions
•Titrableacids —non bicarbonate buffers excreted in urine
Net acid excretion=NH4+ excretion+ urinary titratableacids –bicarbonate excretion
Anion gap
•Anion gap derives from the principle of ‘electroneutrality’.
•Routinely some cations& anions are measured and others are not (Na+,HCO-3, Cl-)
•When conc. of Na+ is compared to sum of HCO-3 & Cl-, there is an anion gap i.e. conc. of Na+ is greater than sum of HCO-3 & Cl-.
•To keep electroneutrality, plasma must contain unmeasured anions to make up difference.
•Plasma anion gap = 8-16 mEq/L.
=[Na+] -([HCO-3] + [Cl-])
= 144 –24 –108
= 12 mEq/L (Normal)
Anion gap
•Plasma anion gap is primarily useful in differential diagnosis of metabolic acidosis.
•Increased anion gap: e.g. metabolic acidosis, starvation, CRF
•An accumulation of an organic anion; e.g. ketoacid, lactate, formate, salicylate.
•[Unmeasured cations include; Ca++, Mg++ & K+]
Anion gap
•No accumulation of an organic anion, but decrease in HCO-3 conc. is offset by an increase in conc. of Cl-
•‘Hyperchloremicmetabolic acidosis’ with normal anion gap (e.g. diarrhea, renal tubular acidosis)—-‘non anion gap’.