ACID-BASE PHYSIOLOGY2

Dr. Ana-Maria Zagrean

Acid-base chemistry in the presence of both CO2/HCO3-and non-HCO3- buffers — THE DAVENPORT DIAGRAM

• Real biological systems are mixtures of CO2/HCO3− and many others non-HCO3− buffers

• The effects of respiratory and metabolic acid-base disturbances in a biological system depend on multiple competing equilibria - one for CO2 /HCO3− and one for each of the non-HCO3− buffers

• Final blood pH can be precisely determined using a computer or can be estimated intuitively using a graphical method - the Davenport diagram (the acid-base nomogram).

7.35-7.45 = normal extracellular (plasmatic) pH< 7.35= acidosis> 7.45= alkalosis

The Davenport diagram is a graphical tool for interpreting acid-base disturbances in blood

What is the pH of blood when PCO2 doubles ?

We consider the actions of all non-HCO3− buffers (B)H+ + B(n) ⇄ HB(n+1) represents the reactions of all non-HCO3− buffers.

When PCO2 raise, almost all of the newly formed H+ reacts with B(n) to formHB(n+1) so that the free [H+] rises only slightly.The final pH depends on two competing buffer reactions: one involving CO2 /HCO3− and the other involving HB(n+1)/B(n).

The CO2 /HCO3- Buffer

For a PCO2 = 40 mm Hg, the equation requires that [HCO3−] = 24 mM when pH = 7.40, as in normal arterial blood plasma.

If pH decreases by 0.3 at this same PCO2, [HCO3−] must fall by half to 12 mM.Conversely, if pH increases by 0.3, [HCO3−] must double to 48 mM.

Rearrangement of the Henderson-Hasselbalch equation

Davenport diagram: the three isopleths are CO2 titration curves.

CO2 isobar or isopleth is obtained by plotting [HCO3−] values against pH (blue curve labeled “PCO2 = 40 mmHg”); it represents all possible combinations of [HCO3−] and pH at a PCO2 of 40 mmHg.

At a PCO2=20 mmHg (orange column), representing respiratory alkalosis, [HCO3−] values are half those for a PCO2 of 40 mmHg at the same pH.

At a PCO2= 80 mmHg (green column), representing respiratory acidosis, [HCO3−] values are twice those at a PCO2 of 40 mmHg.

Buffer power βopen for CO2 /HCO3-

Non-HCO3- Buffers and their total buffering power

The titration curve of a single non-HCO3− buffer with a pK of 7 and total buffer concentration of 12.6 mM is given by the green curve (surrounded by black curves). At a pH of 10, [HB(n+1)] for this single buffer is extremely low because almost all of the “B” is in the form B(n).

The black curves are the titration curves for eight other buffers, each present at a [TB] of 12.6 mM, with pK values evenly spaced at intervals of 0.5 pH unit on either side of 7. The red curve is the sum of the titration curves for all nine buffers. Its slope—the negative of the of all nine buffers—is remarkably constant over a broad pH range.

A Davenport diagram combining three CO2 isopleths for pCO2 = 20, 40 and 80 mmHg, and the titration curve of non-HCO3- buffers.The red non-HCO3− titration line (representing non-HCO3− for whole blood, 25 mM/pH unit) intersects with the CO2 isopleth for a PCO2 = 40 mmHg at the point labeled “Start,” which represents the initial conditions for arterial blood. At this intersection, both CO2 /HCO3− and non-HCO3− buffers are simultaneously in equilibrium.

For a blood PCO2 increase from 40 to 80 mm Hg - respiratory acidosis, the final equilibrium conditions is described by a point that lies simultaneously on the red non-HCO3− titration line and the green CO2 isopleth for 80 mm Hg. Using the Davenport diagram requires:Step 1: to identify the point at the intersection of the initial PCO2 isopleth and the initial non-HCO3− titration line (“Start”). Step 2: to identify the isopleth describing the final PCO2 (80 mm Hg in this case).Step 3: follow the non-HCO3− titration line to its intersection with the final PCO2 isopleth; this intersection occurs at point A, which corresponds to a pH=7.19 and an [HCO3−]= 29.25 mM.

In the absence of non-HCO3− buffers, this same doubling of PCO2 causes a larger pH decrease, from 7.4 to 7.1 !

Intersection of the red non-HCO3− titration line from “Start” to the orange CO2 isopleth for a PCO2 =20 mm Hg (point B), corresponds to a pH =7.60 and an [HCO3−]= 19 mM.

In a solution without non-HCO3− buffers, a PCO2 =20 mmHg would have caused a larger pH increase, from 7.4 to 7.7.

By following three similar steps, we can use the Davenport diagram to predict the final pH and [HCO3−] under conditions of a respiratory alkalosis, resulting from decreasing PCO2 by half, from 40 to 20 mmHg

The amount of HCO3- formed or consumed during “respiratory” acid-base

disturbances increases with non-HCO3- buffering power (ᵦnon-HCO3-)

29.25

The non-HCO3− buffers drive the conversion of CO2 to HCO3− and minimize the increase in free [H+] that a given flux of CO2 can produce.

βnon-HCO3− varies with the hemoglobin content of blood:-patients with anemia have a low βnon-HCO3

−

-patients with polycythemia have a high βnon-HCO3

−

Small change in HCO3- when doubling PCO2 from 40 to 80 (A); H+ is double and pH falls by 0.3

Major buffer systems and their importance in different fluid compartments

• Bicarbonate and Hemoglobin are the most efficient buffers (Hb in RBSs is most efficient and releases bicarbonate); anemia lowers buffering capacity

• Bicarbonate - most important extracellular

• Proteins and phosphates - most important intracellular, low concentration in plasma

Bicarbonate buffer

• The most important extracellular buffer (35% of total buffering capacity of total blood, 75% of plasmatic one)

• Sodium Bicarbonate (NaHCO3) and carbonic acid (H2CO3)

HCO3- : H2CO3 at a 20:1 ratio

HCl + NaHCO3 ↔ NaCl + H2CO3 H2O + CO2 (excess CO2 eliminated through respiration)

NaOH + H2CO3 ↔ H2O + NaHCO3 Na+ + HCO3- high HCO3- urine excreted

H2CO3 is consumed more CO2 is used to bring H2CO3back to normal low CO2 inhibits respiration

Protein buffer systems in the blood, intra- and extracellular

• Protein buffers in blood include hemoglobin (150g/l) and plasma proteins (70g/l). Buffering is by the imidazole group of the histidine residues which has a pKa of about 6.8 (effective buffering at physiological pH).

• Hemoglobin is quantitatively about 6 times more important then the plasma proteins• twice the concentration• contains about three times the number of histidine residues/molecule. • if blood pH changes from 7.5 to 6.5, hemoglobin buffers 27.5 mmol/l of

H+ and total plasma protein buffers only 4.2 mmol/l of H+.

Amino acids are amphoteric substances

• Proteins are highly concentrated inside the cells; intracellular- very imp Hbin RBCs !

• Plasmatic proteins – albumins (low concentration - 7% of buffering capacity of whole blood / 10% of plasmatic one; slow buffering process)

Protein buffer systems in the blood, intra- and extracellular

Hemoglobin buffer system

• Hemoglobin is the main non-bicarbonate buffer system in the blood

• In RBCs – equilibrium happens fast: H+ + Hb = HHb

35% of total blood buffering capacity

important role in extracellular acidity buffering (RBC membrane is highly permeable)

Hemoglobin affinity for O2 is influenced by CO2 and pH

• H+ in blood links to His residues and -NH2 terminal groups O2 release

• pCO2 in blood links to the 4 -NH2 globin groups carbaminoHb O2 release

Periphery Lungs

Interstitial buffer systems

• Bicarbonate- interstitial fluid volume = 3x plasma

- interstitial concentration = plasma one

• Phosphate- low importance (low concentration)

• Proteins - low concentration

Cellular buffers - others than RBC

• Muscle and bone: 60-70% of the total chemical buffering of the body fluids

• Phosphate buffer system

• Protein buffer system

• Slight diffusion of elements of bicarbonate buffer through the cell membrane (except for RBCs where the diffusion is fast)

• Takes 2-4 hours to become maximally effective

Phosphate buffer system

• The phosphate buffer system operates in the urine and intracellular fluid similar to the bicarbonate buffer system (in the EC fluid, it’s concentration is 8% of the bicarbonate one)

• Sodium dihydrogen phosphate (NaH2PO4) is its weak acid, and monohydrogen phosphate (Na2HPO4) is its weak base.

HCl + Na2HPO4 NaH2PO4 + NaClNaOH + NaH2PO4 Na2HPO4 + H2O

• Low plasma concentration = 2mEq/l low importance in the plasma

• Its pK = 6,8 (intracellular pH)

• Basis/acid=4:1

Bone

• Bone represents an important site of buffering acid load.

• An acid load, is associated with the uptake of excess H+ ions by bone which occurs in exchange for Na+ and K+ and by the dissolution of bone mineral, resulting in the release of buffer compounds, such as carbonates (NaHCO3, CaHCO3), and CaHPO4.

• 40% of an acute acid load BONES

• Chronic metabolic acidosis bone demineralisation

Muscle

• Half the cellular mass

• Most intracellular buffering

• Low pH hyperventilation (ventilation increases 4-5 x when pH is 7)

• High pH hypoventilation

• CO2 formed by tissue metabolism is eliminated through respiration

• CO2 passes the blood-brain barrier, it hydrates (CA) and forms H2CO3H+ + HCO3- H+ influences central chemoreceptors CO2 regulates ventilation rate and depth indirectly by H+ increase

Acid-base balance and lungs

Acid-base balance and Kidneys

Kidneys excrete non-volatile acid load

H+ are buffered in the blood, they are not filtered, but secreted by the kidney

In the tubes:

1. H+ combines with filtered HCO3- HCO3- reabsorption

2. H+ combines with urinary buffers titrable acids (phosphates) and ammonium

3. Low H+ amount remains free in the urine

Acid-base balance and Kidneys

Urine formation

Bicarbonate reabsorption

• Bicarbonate freely filtrates

• But ... almost none excreted in urine:• Proximal tubule “reabsorption” 85%

- Na+/H+ exchanger

• Distal and collecting tubules - 15% -H+ pump (aldosterone)

Reabsorption of filtered HCO3- =new bicarbonate formation!

• HCO3- cannot pass the apical membrane of tubular cell

• They combine with H+ in the lumen H2CO3 H2O + CO2

• CO2 diffuses in the cell

• CO2+ H2O H+ + HCO3-

• HCO3- reabsorption in the blood

Secretion of H+ in proximal tubule

• For each H+ secreted, there is a HCO3- reabsorption

• Mostly in the proximal tube (85%)

• Secondary active secretion

• Na+ gradient established by Na+-K+ pump in basolateral membrane of tubular cells

Secretion of H+ in the late distal and collecting tubules

• In intercalated cells

• Primary active transport- H+ pump (aldosterone)

• For each H+ secreted, a HCO3- is reabsorbed by Cl-/ HCO3- antiporter

H+ secretion in the proximal tubule, the thick ascending segment of the loop of Henle, and the early distal tubule: (1) secondary active secretion of H+ into the renal tubule; (2) tubular reabsorption of HCO3- by combination with H+ to form carbonic acid, which dissociates to form CO2 and H2O; and (3) Na+ reabsorption in exchange for H+ secreted.

Primary active secretion of H+ through the luminal membrane of the intercalated epithelial cells of the late distal and collecting tubules. Note that one bicarbonate ion is absorbed for each H+ secreted, and a chloride ion is passively secreted along with the H+.

H+ secretion and bicarbonate reabsorption

H+ free excretion is limited

Excretion of the daily production of 80 mEq non-volatile acids (resulted from metabolism) would require more than 2667 l of urine/day to be excreted if H+ would remain free in solution.

Minimum urinary pH in normal kidneys = 4.5 (0,03 mEq/l)

Any H+ that exceeds this limit (up to 500 mEq/day) is accomplished primarily by combining H+ with urinary buffers present in the tubular fluid - phosphate (titrable acidity) and NH4+, that DO NOT generate extra H+

When H+ is titrated in the tubular fluid with HCO3–, this results in CO2 production and the reabsorption of one HCO3– for each H+ secreted.

When there are excess H+ in the urine, they combine with buffers other than HCO3–, and this results in the generation of new HCO3– that can also enter the blood new HCO3– to replenish the one lost from the extracellular fluid in acidosis

Combination of excess H+ with phosphate (titrableacid) and ammonia buffers, present in the tubular fluid

• If high amounts of H+ are secreted (more then HCO3- is filtered), H+ is buffered by phosphate and ammonia systems in the tubular fluid

• H+ is eliminated by:• H+ + NaHPO4- NaH2PO4

• NH3 (ammonia) + H+ NH4+ (ammonium ion)

Formation and excretion of titrable acid - phosphate buffer (proximal and collecting tubules)

• pK HPO42- /H2PO4-= 6,8 and 90% of the buffering activity of HPO42- occurs above a pH of 6.8 - more efficient (more concentrated)

• Daily filtered dibasic phosphate accounts for the excretion of approx 50% of the daily fixed H+ excretion

• 30-40 mEq / day available to buffer H+

• Titrable acid because it is measured by back titration of the urine with NaOH to a pH of 7.4

• Limited by the quantity of dibasic phosphate filtered

Buffering of secreted H+ by filtered phosphate (NaHPO4–) in the tubular fluid. A new bicarbonate ion is returned to the blood for each NaHPO4– that reacts with a secreted hydrogen ion.

Ammonia buffer system: excretion of excess H+ & new HCO3- production

• Ammonium (NH4+) - synthesized in proximal tube by glutamine deamination

• Ammonia (NH3) diffuses into the collecting duct and is trapped in the increasingly acidic urine as NH4+, that cannot diffuses back (ammonium trapping)

• A HCO3- is released in the systemic circulation for each ammonium that is excreted in the urine

Production and secretion of ammonium ion (NH4+) by proximal tubular cells. Glutamine is metabolized in the cell, yielding NH4+ and bicarbonate. The NH4+ is secreted into the lumen by a Na+-NH4+ pump. For each glutamine molecule metabolized, two NH4+ are produced and secreted and two HCO3– are returned to the blood.

Buffering H+ secretion by ammonia (NH3) in the collecting tubules. Ammonia diffuses into the tubular lumen, where it reacts with secreted hydrogen ions to form NH4+, which is then excreted. For each NH4+ excreted, a new HCO3– is formed in the tubular cells and returned to the blood.

Chronic Acidosis Increases NH4+ Excretion

• One of the most important features of the renal ammonium-ammonia buffer system is that it is subject to physiologic control.

• An increase in extracellular fluid H+ concentration stimulates renal glutamine metabolism and, therefore, increases the formation of NH4+ and new HCO3–to be used in H+ buffering; A decrease in H+ concentration has the opposite effect.

• Under normal conditions, the amount of H+ eliminated by the ammonia buffer system accounts for about 50 % of the acid excreted and 50 % of the new HCO3– generated by the kidneys.

• With chronic acidosis, the rate of NH4+ excretion can increase to 500mEq/day. the dominant mechanism by which acid is eliminated is excretion of NH4+. This also provides the most important mechanism for generating new bicarbonate during chronic acidosis.

Isohydric Principle: All Buffers in a Common Solution Are in Equilibrium with the Same H+ Concentration

• whenever there is a change in H+ concentration in the extracellular fluid, the balance of all the buffer systems changes at the same time.

• any condition that changes the balance of one of the buffer systems also changes the balance of all the others because the buffer systems actually buffer one another by shifting H+ back and forth between them.

The net acid excretion by the kidneys:-To maintain acid-base balance, the net acid excretion must equal the nonvolatile acid production in the body. -The net acid excretion also equals the rate of net HCO3– addition to the blood.

Net acid excretion =

NH4+ excretion + Urinary titratable acid – Bicarbonate excretion

In acidosis:-the net acid excretion increases markedly, especially because of increased NH4+ excretion, thereby removing acid from the blood. -there is a net addition of HCO3– back to the blood as more NH4+ and urinary titratable acid are excreted.

In alkalosis:-titratable acid and NH4+ excretion drop to 0, whereas HCO3– excretion increases. -there is a negative net acid secretion there is a net loss of HCO3– from the blood (which is the same as adding H+ to the blood) and that no new HCO3– is generated by the kidneys.

pH regulation of intracellular fluid

• The most important biological fluid for pH regulation is the cytosol, as the number of biochemical reactions and other processes that occur inside a cell surpass the ones outside the cell.

• Acid loader: Cl-HCO3 or anion exchanger (tends to lower pHi, is a chronic acid load when active)

• Acid extruders: electroneutral Na/HCO3 cotransporter (NBCn1), Na-H exchanger (NHE1) (tends to increase pHi)

• The chronic acid extrusion via NBCn1 and NHE1 balances the chronic acid loading via AE2, producing a steady state.

• Several other acid extruders and acid loaders may contribute to pHiregulation, and each cell type has a characteristic complement of such transporters.

Recovery of a cell from intracellular acid and alkali loads

CA II, carbonic anhydrase II

Acid-extrusion rates tend to be greatest at low pHi values and fall off as pHi rises. Low pHi also inhibits anion exchangers (AE2) and thus acid loading. The response to low pHitherefore involves two feedback loops operating in push-pull fashion, stimulating acid extrusion and inhibiting acid loading.

In addition to pHi, hormones, growth factors, oncogenes, cell volume, and extracellular pH (pHo) all can modulate these transporters. The pHo effect is especially important: a low pHoslows the rate of pHi recovery from acute acid loads and reduces the final steady-state pHi.

AB balance parameters to detect AB balance/imbalance in extracellular fluid

• Bicarbonate excretion = urine flow rate x urinary bicarbonate concentration

• Sampling of arterial blood: PO2, PCO2

• CO2 elimination through respiration

• Oxygenation of blood level through gas exchange in the lungs (SaO2, pO2)• 100 mmHg when breathing room air; increases x10 - x20 in fitness - athletes

• falls with age: pO2= 104 - (age x 0,27)

• Hypoxia pO2< 90 mmHg; SaO2 < 95%

• Hyperoxia pO2>100 mmHg

• Oxidative metabolism of carbohydrates/fats CO2 (15000-20000 mEq/day)

• When hypoxia lactic acid

• Check if patient is breathing room air (21% O2) or not

AB balance parameters

• pO2 = 100 mmHg when breathing room air

• pCO2= 38- 42 mmHg= mean pressure of carbon dioxide in arterial blood

• Blood H+ conc = 0.00004 mEq/l (40 nM)

• Alkaline reserve= actual HCO3- = 21- 24 mEq/l = content of HCO3- in patients’ blood at actual pCO2; it represents the metabolic component of the buffer system, and it is usually modified by kidneys.

Standard bicarbonate

• [HCO3-] in standard conditions: standard pCO2 and complete Hb oxygenation (thus eliminating the influence of the lungs on blood base concentration); normal values= 21-27 mEq/l;

• What bicarbonate concentration would have been after pCO2 is corrected to 40 mmHg

• It is derived from actual bicarbonate value after changes associated with respiratory disturbances have been eliminated; reflects pure metabolic changes

• high [HCO3-] means metabolic alkalosis and low [HCO3-] means metabolic acidosis.

Base excess

• Base excess (BE)- the amount of base that needs to be removed to bring pH level back to normal when pCO2 is corrected to 40 mmHg

• Negative (base deficit) in metabolic acidosis and positive in metabolic alkalosis.

• Normal value= +2.5 -2.5 mmol/l.

Anionic gap

• Anionic gap- the difference between cations and anions which are normally determined in the plasma.

AG = (Na+ + K+) – [(Cl-) + (HCO3-)]; normal value = 16 ± 2 mmol/l.

AG = (Na+) – [(Cl-) + (HCO3-)]; normal value= 12 ± 4 mmol/l.

• Corrected AG in case of low albumin level:

AG corrected = AG + 0,25×(Albumin normal – Albumin measured)

Kassirer-Bleich equation

• [H+] = 24 × PCO2/ [HCO3-]

• predicts that the ratio of dissolved CO2 to HCO3- , rather than their actual concentrations, determines [H+] and pH.

• A drop or rise in PCO2 will result in a drop or rise in [H+] respectively.

• [HCO3-] on the other hand is inversely related to H+ concentration whereby a drop in HCO3- levels result in an increase in H+ concentration while a rise in HCO3- levels result in a reduction in H+ concentration

• This buffer system is of physiologic importance because both the pulmonary and renal mechanisms for regulating pH work by adjusting this ratio.

• The PCO2 can be modified by changes in alveolar ventilation, while plasma [HCO3-] can be altered by regulating its generation and excretion by the kidneys.

AB balance disorders

• An acid base disorder is a change in the normal value of extracellular pH that may result when renal or respiratory function is abnormal or when an acid or base load exceeds the excretory capacity.

• pH PCO2 HCO3-Range: 7.35- 7.45 36-44 22-26Optimal value 7.40 40 24

• Acid-base status is defined in terms of the plasma pH.

• Acidemia - decrease in the blood pH below normal range of 7.35 -7.45Alkalemia - Elevation in blood pH above the normal range of 7.35 - 7.45

• Clinical disturbances of acid base metabolism classically are defined in terms of the HCO3- /CO2 buffer system.

• Acidosis – process that increases [H+] by increasing PCO2 or by reducing [HCO3-]Alkalosis – process that reduces [H+] by reducing PCO2 or by increasing [HCO3-]

• It is important to note that though acidosis and alkalosis usually leads to acidemia and alkalemia respectively, the exception occurs when there is a mixed acid-base disorder. In that situation, multiple acid-base processes coexisting may lead to a normal pH or a mixed picture

AB balance disorders

Respiratory versus metabolic

• Since PCO2 is regulated by respiration, abnormalities that primarily alter the PCO2 are referred to as respiratory acidosis (high PCO2) and respiratory alkalosis (low PCO2).

• In contrast, [HCO3-] is regulated primarily by renal processes. Abnormalities that primarily alter the [HCO3-] are referred to as metabolic acidosis (low [HCO3-]) and metabolic alkalosis (high [HCO3-]).

Simple vs mixed

• Simple acid-base disorders : Disorders that are either metabolic or respiratory.

• Mixed acid-base disorders: More than one acid-base disturbance present. pH may be normal or abnormal

Compensation

• Acid Base disoders are associated with defense mechanisms referred to as compensatory responses that function to reduce the effects of the particular disorder on the pH.

• They do not restore the pH back to a normal value. This can only be done with correction of the underlying cause. In each of these disorders, compensatory renal or respiratory responses act to minimize the change in H+ concentration by minimizing the alteration in the PCO2 /[HCO3-] ratio.

Compensatory resposes

1. Compensatory responses never return the pH to normal.

2. The basis of compensatory responses is to maintain the PCO2/[HCO3-] ratio.

3. Therefore, the direction of the compensatory response is always the same as that of the initial change.

4. Compensatory response to respiratory disorders is two-fold; a fast response due to cell buffering and a significantly slower response due to renal adaptation.

5. Compensatory response to metabolic disorders involves mainly an alteration in alveolar ventilation.

6. Metabolic responses cannot be defined as acute or chronic in terms of respiratory compensation because the extent of compensation is the same in each case.

Respiratory acidosis

• Increase of pCO2 in respiratory diseases

• Elevation in the PCO2/[HCO3-] ratio which subsequently increases the hydrogen ion concentration according to the following equation: [H+] = 24 × PCO2 / [HCO3-]

• Compensation - increase of HCO3- by

a) rapid cell buffering of H+ (Hb and proteins) ACUTE

H2CO3 + Hb- → HHb + HCO3-

b) an increase in net acid excretion (plus bicarbonate reabsorption) CHRONICAL

ACUTE vs CHRONIC Respiratory Acidosis

ACUTE - buffers

• As shown above, each buffering reaction produces HCO3-, which leads to an increase in plasma [HCO3-].

• Due to this process, acutely, there is an increase in the plasma [HCO3], averaging 1 mEq/L for every 10 mmHg rise in the PCO2.

CHRONIC- kidneys

• A 3.5 mEq/L increase in the plasma HCO3- concentration for every 10 mmHg increase in the PCO2; metabolic compenation is not obvious for a few hours and takes 4 days to complete

• Renal compensation offers more significant pH protection in the setting of chronic respiratory acidosis in contrast to intracellular buffering in the acute situation.

• Chronic respiratory acidosis is commonly caused by COPD. These patients can tolerate a PCO2 of up to 90-110 mmHg and not have a severe reduction in pH due to renal compensation.

ACUTE vs CHRONIC Respiratory Acidosis

Respiratory acidosis

Causes:

• Alveolar hypoventilation• CNS depression (meds, trauma)• Myopathic diseases• Restrictive pulmonary disease• Obstructive pulmonary disease

• High CO2 production- hyperthyroidism, malignant hyperthermia, seizure VERY RARE

• Decrease of pCO2 due to hyperventilation is followed by increased pH.

• Net reduction in PCO2 and subsequently a reduction in the PCO2 / [HCO3-] ratio which reduces the hydrogen ion concentration (and increases the pH) according to the following equation:[H+] = 24 × PCO2 / [HCO3-]

Respiratory alkalosis

Compensation

• Rapid cell buffering - ACUTE

• Kidneys decrease H+ secretion and increased HCO3- excretion -CHRONICAL

Causes:

• Peripheric stimulation (hypoxemia, anemia, altitude)

• Central stimulation (pain, anxiety, meds)

• Metabolic encephalopathy (hepatic cirrhosis)

ACUTE Respiratory alkalosis

• About 10 minutes after the onset of respiratory alkalosis, H+ move from the cells into the extracellular fluid, where they combine with HCO3-

• The H+ are primarily derived from intracellular buffers such as hemoglobin, protein and phosphates. The reaction with bicarbonate ions in this reaction leads to a mild reduction in plasma [HCO3-].

• In acute respiratory alkalosis, as a result of cell buffering, for every 10 mmHg decrease in the PCO2, there is a 2mEq/L decrease in the plasma HCO3- concentration.

CHRONIC Respiratory alkalosis

• If respiratory alkalosis persist for longer than 2- 6 hours, the kidney will respond by lowering H+ secretion, excretion of titrable acids, ammonium production and ammonium excretion. There will also be an increase in the amount of HCO3 in the urine- excreted due to decreased reabsorption of filtered HCO3- .

• Completion of this process occurs after 2-3 days after which a new steady state is achieved.

• Renal compensation result in a 4 mEq/L reduction in plasma [HCO3-] for every 10 mmHg reduction in PCO2.

Metabolic acidosis

• Decrease in [HCO3-] followed by plasma pH decrease.

• Elevation in the PCO2/HCO3- ratio and thus an elevation in hydrogen ion concentration according to the following equation: [H+] = 24 ×(PCO2 / [HCO3-])

•Compensation• Respiratory - LOW CO2 through hyperventilation

• Renal - if the cause is not kidney disfunction- H+ excretionenhanced high ammonia (NH4+)

• The reduction in PCO2 is accomplished by increasing alveolar ventilation- quick response

• The drop in arterial pH stimulates central and peripheral chemoreceptors controlling respiration, resulting in an increase in alveolar ventilation.

• The increase in ventilation is characterized more by an increase in tidal volume than by an increase in respiratory rate, and, if the acidemia is severe, may reach a maximum of 30L/min (normal = 5-6 L/min).

Metabolic acidosis

Kussmaul breathing

• Kussmaul breathing is respiratory compensation for a metabolic acidosis, most commonly occurring in diabetics in diabetic ketoacidosis.

• https://www.youtube.com/watch?v=TG0vpKae3Js

Metabolic acidosis causes

1. most frequent:

Increased extracellular buffering of an increased acid load

2. less frequent:

Loss of bicarbonate ions in the urine

Evaluation of metabolic acidosis

• Anionic gap= Na+ - [Cl- - HCO3-]= 12 +/- 4

• High AG= H+ excess• AG↑ = (Na+) – [(Cl-) + (HCO3-↓)]

• Exogenous intoxication (ethylene glycol, salicylates, methanol)

• Endogenous ketoacidosis, lactic acidosis, renal failure

• Normal AG (hyperchloremic acidosis)= HCO3- loss• AG normala = (Na+) – [(Cl-↑) + (HCO3-↓)]

• Organism retains one Cl- for each lost HCO3-• Digestive (intestinal fluid)

• Renal (renal tubular acidosis)

UAG - Urinary Anionic Gap

• Index of NH4+ excretion in the urine

• If digestive loss of bases (extrarenal) normal renal functionurinary ammonia excretion UAG <0

• If renal loss of bases- kidneys cannot eliminate the excess H+ through ammonia low ammonia excretion UAG >0

Metabolic alkalosis

• Increased [HCO3-], followed by increased arterial blood pH.

[H+] = 24 ×(PCO2 / [HCO3-]) organism tries to increase pCO2 low alveolar ventilation

• Compensation:

• Respiratory - hypoventilation

• On average the pCO2 rises 0.7 mmHg for every 1.0 mEq/L increase in the plasma [HCO3-].

Metabolic alkalosis

Causes:

• Digestive loss (gastric acid)

• Renal loss (diuretics)

• Primary hyperaldosteronism

Cause evaluation in metabolic alkalosis

• Cl responsive-urinary Cl < 20 mEq/l

• Digestive- vomiting- gastric acid loss:

loss of fluid and NaCl higher HCO3- reabsoption to compensate Cl- loss

• Renal- diuretics:

Cl- loss in the urine- furosemide, thiazide

• Cl unresponsive- urinary Cl > 20 mEq/l

• Endocrine- primary hyperadosteronism

When to suspect a mixed acid-base disorder:

• Mixed acid base disorders occur when there is more than one primary acid-base disturbance present simultaneously. They are frequently seen in hospitalized patients, particularly in the critically ill.

• The expected compensatory response does not occur, or

• Compensatory response occurs, but level of compensation is inadequate or too extreme

• Whenever the PCO2 and [HCO3-] becomes abnormal in the opposite direction. (i.e. one is elevated while the other is reduced).

! In simple acid-base disorders, the direction of the compensatory response is always the same as the direction of the initial abnormal change.

• pH is normal but PCO2 or HCO3- is abnormal

• In simple acid-base disorders, the compensatory response should never return the pH to normal. If that happens, suspect a mixed disorder.

Algorithm for diagnosing acid-base disturbance from pH, pCO2(a) and bicarbonate

Steps to follow in diagnosis of AB disorders

1. pH evaluation- acidosis or alkalosis

2. establish cause- metabolic/respiratory in simple ones

3. compensation degree present/absent

4. AG calculus If metabolic acidosis

If AG is high delta ratio

If AG is normal- Urinary AG- renal or digestive?

5. Urinary ClIf metabolic alkalosis

6. think of possible diagnosis and order further tests