Download Acid-Base 2013 - UMF IASI 2015

Acid-Base
Basic definitions
•An acid
–a substance that can donate hydrogen ions (H+)
•A base
–a substance that can accept H+ ions
H2 CO3 (acid)«H+ + HCO3 - (base)
•Strong acids
–completely ionized in body fluids
•Weak acids
–incompletely ionized in body fluids
Acid-Base
Basic definitions
•HCl«H+ + Cl–Hydrochloric acid (HCl)
–a strong acid - it is present only in a completely ionized form in the body
•H2 CO3 (acid)«H+ + HCO3 - (base)
–a weak acid - it is ionized incompletely
–at equilibrium, all 3 reactants are present in body fluids
Acid-Base
Basic definitions
H2 CO3 (acid) « H+ + HCO3 - (base)
•the law of mass action - the velocity of a reaction is proportional to the product of
the reactant concentrations  …………………………………………….
the addition of H+ or bicarbonate (HCO3 -) drives this reaction to the left
Acid-Base
Basic definitions
in body fluids
•the concentration of hydrogen ions - H+
–normal physiologic concentration = 40 nEq/L
–is maintained within very narrow limits
•the concentration of HCO3 - = (24 mEq/L)
–is 600,000 times that of [H+]
Acid-Base
Basic definitions
•
the tight regulation of [H+] at this low concentration is crucial for normal
cellular activities
•
H+ at higher concentrations can bind strongly to negatively charged proteins,
including enzymes, and impair their function (!!)
•
under normal conditions, acids and bases are being added constantly to the
extracellular fluid compartment
•
for the body to maintain a physiologic [H+] of 40 mEq/L, 3 processes must
take place:
1. Buffering by extracellular and intracellular buffers
2. Alveolar ventilation, which controls PaCO2
3. Renal H+ excretion, which controls plasma [HCO3 -]
Acid-Base
Acid-Base
Buffers
•weak acids or bases that are able to minimize changes in pH
–by taking up H+
–by releasing H+
Phosphate - effective buffer
HPO4 2- + (H+)«H2 PO4 •upon addition of an H+ to extracellular fluids, the monohydrogen phosphate binds
H+ to form dihydrogen phosphate, minimizing the change in pH
•when [H+] is decreased, the reaction is shifted to the left
Thus, buffers work as
–a first-line of defense (!!)
–to blunt the changes in pH that would result from the constant daily addition
of acids and bases to body fluids
Acid-Base
Buffers
HCO3 -/H2 CO3 buffering system
H2 O + CO2 «H2 CO3 «H+ + HCO3
•the major extracellular buffering system
•a very effective system
–has the ability to control PaCO2 by changes in ventilation
•increased carbon dioxide (CO2) concentration drives the reaction to the right, a decrease in
CO2 concentration drives it to the left
•H+ added to the body fluids  formation of carbonic acid = consumption of HCO3
•carbonic acid (H2 CO3 )  water + CO2  ventilation
•CO2 concentration is maintained within a narrow range via the respiratory drive,
which eliminates accumulating CO2
•the kidneys regenerate the HCO3 - consumed during this reaction
Acid-Base
Buffers
H2 O + CO2 «H2 CO3 «H+ + HCO3
•this reaction continues to move to the left
–as long as CO2 is constantly eliminated
–or until HCO3 - is significantly depleted, making less HCO3 - available to bind H+
•HCO3 - and PaCO2 can be managed independently
–HCO3 in the kidneys
–PaCO2 in the lungs
•that makes this a very effective buffering system
Acid-Base
Buffers
HCO3 -/H2 CO3 buffering system
H2 O + CO2 «H2 CO3 «H+ + HCO3
•Henderson-Hasselbalch equation
–pH = 6.10 + log ([HCO3 -]/0.03 X PaCO2)
–expresses the relationship between the 3 reactants in the reaction at equilibrium
–an alternative - [H+] = 24 X PaCO2/[HCO3 -]
•Henderson-Hasselbalch equation relates:
–dissolved CO2 (ie, H2 CO3)
–to the partial pressure of CO2 (0.03 X PaCO2)
Acid-Base
Buffers
pH = 6.10 + log ([HCO3 -]/0.03 X PaCO2)
•changes in pH or [H+] are a result of relative changes in the ratio of PaCO2 to
[HCO3 -] rather than to absolute change in either one
•if both PaCO2 and [HCO3 -] change in the same direction, the ratio stays the
same and the pH or [H+] remains relatively stable
•the alteration in pH occurs when either HCO3 - or PaCO2 changes the other
variable in the same direction
Acid-Base
Buffers
intracellular buffers - hemoglobin, bone
•in chronic metabolic acidosis extracellular HCO3 level is low
•intracellular buffers are more important than HCO3
Acid-Base
Renal acid handling
Acids are added daily to the body fluids
•volatile acids - carbonic acid
–the metabolism of dietary carbohydrates and fat produces approximately 15,000
mmol of CO2 per day, which is excreted by the lungs
–failure to do so results in respiratory acidosis
•nonvolatile - eg, sulfuric, phosphoric acids
–the metabolism of proteins (ie, sulfur-containing amino acids) results in the formation
of H2 SO4
–dietary phosphate results in the formation of H3 PO4
Acid-Base
Renal acid handling
•these acids first are buffered by the HCO3 -/H2 CO3 system:
H2 SO4 + 2NaHCO3 «Na2 SO4 + 2H2 CO3 «2H2 O + CO2
•a strong acid (H2 SO4) is buffering by 2 molecules of HCO3 a weak acid (H2
CO3) is produced  this minimizes the change in pH
•the lungs excrete the CO2 produced
•the kidneys replace the consumed HCO3
–to prevent progressive HCO3 - loss and metabolic acidosis
–kidneys perform these principally by H+ secretion in the collecting duct
Acid-Base
Renal acid handling
prevention of metabolic acidosis  prevention of progressive HCO3 loss
–amino acids ( glutamate, aspartate)  formation of citrate and lactate  
 convertion to HCO3
–to maintain normal pH, the kidneys must
•“reabsorb” all the filtered HCO3 - (any loss of HCO3 - is equal to the
addition of an equimolar amount of H+) (in the proximal tubule)
•excrete the daily H+ load (loss of H+ is equal to addition of an equimolar
amount of HCO3 -) (in the collecting duct)
Acid-Base
Renal acid handling / HCO3 - reabsorption
•the daily glomerular ultrafiltrate in a healthy subject, contains 4300 mEq of
HCO3 – for
–a serum HCO3 - concentration of 24 mEq/L
–a daily glomerular ultrafiltrate of 180 L
•all of filtered HCO3 – has to be reabsorbed
–90% in the proximal tubule,
–the remainder in the thick ascending limb and the medullary collecting duct
•the energy for this process  the 3Na+ -2K+ «ATPase
–maintains a low intracellular Na+ concentration and a relative negative intracellular
potential  indirectly provides energy for the apical Na+/H+ exchanger - NHE3 (gene
symbol SLC9A3)  transports H+ into the tubular lumen  H+ in the tubular lumen
combines with filtered HCO3 –
HCO3 - + H+ «H2 CO3 «H2 O + CO2
Acid-Base
Renal acid handling / HCO3 - reabsorption
HCO3 - + H+ «H2 CO3 «H2 O + CO2
•the dissociation of H2 CO3 into H2 O + CO2 is accelerated by Carbonic anhydrase
(CA IV isoform)
–present in the brush border of the first 2 segments of the proximal tubule
–this shifts the reaction shown above to the right and keeps the luminal concentration
of H+ low
•CO2 diffuses into the proximal tubular cell, via the aquaporin-1 water channel
•carbonic anhydrase (CA II isoform) combines CO2 and water to form HCO3 and H+
•the HCO3 - formed intracellularly returns to the pericellular space and then to
the circulation via the basolateral Na+/3HCO3 - cotransporter, NBCe1-A (gene
symbol SLC4A4)
Acid-Base
Renal acid handling / HCO3 - reabsorption
In essence
•the filtered HCO3 - is converted to CO2 in the lumen
•CO2 diffuses into the proximal tubular cell
•in the tubular cell CO2 is converted back to HCO3 –
•HCO3 – is returned to the systemic circulation
•in this way the filtered HCO3 – is recuperated
Acid-Base
Renal acid handling
Acid excretion
•the daily acid load = 50-100 mEq of H+is excreted
–through H+ secretion
–by the apical H+ «ATPase
–in A-type intercalated cells of the collecting duct
Acid-Base
Renal acid handling / Acid excretion
•HCO3 - formed intracellularly is returned to the systemic circulation via the
basolateral Cl-/HCO3 - exchanger, AE1 (gene symbol SLC4A1)
•H+ enters the tubular lumen via 1 of 2 apical proton pumps, H+ «ATPase or H+ K+ «ATPase
•The secretion of H+ in these segments is influenced by Na+ reabsorption in the
adjacent principal cells of the collecting duct
–The reabsorbed Na+ creates a relative lumen negativity, which decreases the amount
of secreted H+ that back-diffuses from the lumen
Acid-Base
Renal acid handling / Acid excretion
Hydrogen ions secreted by the kidneys can be excreted
–as free ions
–> 99.9% of the H+ load - buffered by the weak bases NH3 or phosphate
•The reason for limited excretion of free H+ ions
– the lowest achievable urine pH = 5.0
– = 10 µEq/L H+
– would require excretion of 5,000-10,000 L of urine a day
–urine pH cannot be lowered much below 5.0
•because the gradient against which H+ «ATPase has to pump protons
(intracellular pH 7.5 to luminal pH 5) becomes too steep
Acid-Base
Renal acid handling / urine-buffering system
•titratable acidity
–the amount of secreted H+ that is buffered by filtered weak acids is called titratable
acidity
•buffers in this system
–phosphate as HPO4 2
–ammonia (NH3)
–uric acid
–creatinine
•H2 PO4 «H+ + HPO4 2–the amount of phosphate filtered is limited and relatively fixed only a fraction of
the secreted H+ can be buffered by HPO4 2-
Acid-Base
Renal acid handling / urine-buffering system / ammonia
Ammonia
NH3 + H+ «NH4 +
•ammonia is produced in the proximal tubule from the amino acid glutamine
•this reaction is enhanced by
–an acid load
–hypokalemia
Acid-Base
Renal acid handling / urine-buffering system / ammonia
•Intracellular - proximal tubules
–NH3 + H+ «NH4 +
–NH4 + is secreted into the proximal tubular lumen by the apical Na+/H+
(NH4 +) antiporter
•Intraluminal - thick ascending limb of the loop of Henle
–the apical Na+/K+ (NH4 +)/2Cl- cotransporter in the thick ascending limb of
the loop of Henle then transports NH4 + into the medullary interstitium
–it dissociates back into NH3 and H+
–NH3 diffuses into the lumen of the collecting duct - available to buffer H+
ions and becomes NH4 +.
–NH4 + is trapped in the lumen and excreted as the Cl salt
Acid-Base
Renal acid handling / urine-buffering system
NH3 + H+ «NH4 +
•the increased secretion of H+ in the collecting duct  shifts the equation to the
right  decreases the NH3 concentration  facilitates continued diffusion of NH3
from the interstitium down its concentration gradient  allows more H+ to be
buffered
•the kidneys and the liver can adjust the amount of NH3 synthesized to meet
demand, making this a powerful system to buffer secreted H+ in the urine
Acid-Base
•Renal acid handling / urine-buffering system
•every H+ ion buffered   an HCO3 - gained to the systemic circulation
Echilibrul acidobazic – apărarea împotriva schimbării concetraţiei ionilor de H+
Intervenţia rinichiului în condiţii de normalitate
Relaţia [H+] [NaHCO3-] la ph normal al mediului intern
Filtrare glomerulară
NaHCO3Lichid extracelular
Celulă tub proximal
Lumen tubular
Transport activ
Na+
Na+
HCO3-
HCO3- + H+
Na+
HCO3-
Na HCO3
H2CO3
contraschimb
H+ + CO3H2 CO3
Anhidraza carbonică
CO2
(rezultat din metabolism)
CO2 + H2O
CO2 + H2O
eliminată
Cantitate redusă, aciditatea urinii
Echilibrul acidobazic – apărarea împotriva schimbării concetraţiei ionilor de H+
Intervenţia rinichiului în acidoză
sistemul tampon fosfaţi
Lichid extracelular
Filtrare glomerulară
a Na2HPO4
Celulă tub proximal
Lumen tubular
Na2HPO4
Na+
Na+
HPO42-
NaHCO3-
H2PO4HCO3
-
HCO3-
H+
eliminare
H2CO3
AC
CO2
Na+
CO2 + H2O
Echilibrul acidobazic – apărarea împotriva schimbării concetraţiei ionilor de H+
Intervenţia rinichiului în acidoză
Formarea amoniacului din glutamină
Filtrare glomerulară
a NaCl
Lichid extracelular
Celulă tub proximal
Na+
Na+
Na+
Cl-
glutamină
NH3
NH4Cl
(acid slab)
Na H CO3
HCO3-
HCO3-
H+
H2CO3
CO2
AC
CO2 + H2O
Lumen tubular
H+
eliminare
Echilibrul acidobazic – apărarea împotriva schimbării concetraţiei ionilor de H+
•Din catobolismul normal
al proteinelor în ficat rezultă
•amoniac
•bicarbonat
•Din amoniac se formează uree
•Funcţie de necesităţi, o parte din amoniac
este transformată în glutamină
•acidoza stimulează
•alcaloza inhibă
•Glutamina trece în circulaţie
şi ajunge la nivelul celulei tubulare renale
•Dezaminarea glutaminei la nivelul celulei tubulare
determină refacerea de HCO3•acidoza stimulează
•alcaloza inhibă
•Acidoza favorizează eliminarea urinară
a NH4+ şi se evită transformarea lui în uree
care privează de regenerarea HCO3-
Echilibrul acidobazic – apărarea împotriva schimbării concetraţiei ionilor de H+
Intervenţia rinichiului în acidoză
Formarea amoniacului din glutamină
Filtrare glomerulară
a NaCl
Lichid extracelular
Celulă tub proximal
Na+
Na+
Na+
Cl-
glutamină
NH3
NH4Cl
(acid slab)
Na H CO3
HCO3-
CO2
HCO3H2CO3
AC
CO2 + H2O
H+
Lumen tubular
H+
eliminare
Eliminarea urinară de amoniu
•normal - 30 mmol/24 ore
•la nevoie - până la 300 mmol/zi
Echilibrul acidobazic – apărarea împotriva schimbării concetraţiei ionilor de H+
Intervenţia rinichiului / factori perturbatori, de reglare funcţie de necesităţi/ Ph-ul mediului
intern
Filtrare glomerulară
a NaCl
Lichid extracelular
Celulă tub distal
CL-
Cl-
H+
Na+
Cl-
HCO3H2CO3
CO2
Alcaloză hipercloremică
Lumen tubular
AC
CO2 + H2O
HCO3Na+
NaHCO3
Echilibrul acidobazic – apărarea împotriva schimbării concetraţiei ionilor de H+
Acid-Base
Metabolic acidosis / Pathophysiology
•In healthy people
blood pH is maintained at 7.39-7.41
•pH is the negative logarithm of [H+] (pH = - log10 [H+])
an increase in pH indicates a decrease in [H+] and vice versa
•an increase in [H+] and a fall in pH is termed acidemia
•a decrease in [H+] and an increase in pH is termed alkalemia
•the underlying disorders that lead to acidemia and alkalemia are acidosis and
alkalosis, respectively
•metabolic acidosis is a primary decrease in serum HCO3 - concentration and, in
its pure form, manifests as acidemia (pH <7.40)
Acid-Base
Metabolic acidosis / Pathophysiology
•rarely, metabolic acidosis can be part of a mixed or complex acid-base
disturbance
•2 or more separate metabolic or respiratory derangements occur together
pH may not be reduced
or the HCO3 - concentration may not be low
Acid-Base
Metabolic acidosis / Pathophysiology
•compensatory mechanism = alveolar hyperventilation  a fall in PaCO2
•normally, PaCO2 falls by 1-1.3 mm Hg for every 1-mEq/L fall in serum HCO3 compensatory response that can occur fairly quickly
•change in PaCO2 not within this range = a mixed acid-base disturbance
–ex, if the a less decrease in PaCO2 than the expected change = a primary respiratory
acidosis also present
Acid-Base
Metabolic acidosis / Pathophysiology
•often the first clue to metabolic acidosis is a decreased serum HCO3 concentration observed when serum electrolytes are measured
•remember, however, that a decreased serum [HCO3 -] level can be observed as a
compensatory response to respiratory alkalosis
•an [HCO3 -] level less than 15 mEq/L, however, almost always is due, at least in
part, to metabolic acidosis
Acid-Base
Metabolic acidosis / Anion gap
•plasma, like any other body fluid compartment, is neutral - total anions match
total cations
•the major plasma cation is Na+
•the major plasma anions are Cl- and HCO3 –
•in lower concentrations
–other cations: K+, Mg2+, and Ca2+
–other anions: phosphate, sulfate, and some organic anions
Acid-Base
Metabolic acidosis / Anion gap
•the anion gap (AG) = the difference between
–the concentration of the major measured cation Na+ (140 mEq/L) and the
major measured anions Cl- (108 mEq/L) and HCO3 –(24 mEq/L)
•the gap is usually between 6 and 12 mEq/L
Acid-Base
Metabolic acidosis / Anion gap
•the AG represents the difference between unmeasured anions and unmeasured
cations:
AG = [Na+]-([Cl-] + [HCO3 -]) = unmeasured anions - unmeasured cations
•an increase in the AG can result from:
–a decrease in unmeasured cations: hypokalemia, hypocalcemia, hypomagnesemia
–or an increase in unmeasured anions: hyperphosphatemia, high albumin levels
•in certain forms of metabolic acidosis, other anions accumulate
•by recognizing the increasing AG  a differential diagnosis for the cause of
acidosis
Horacio J. Andorgué & Nicolaos E. Midias
Acid-Base
Metabolic acidosis / Urinary AG
•helpful in evaluating some cases of non-AG metabolic acidosis
–the major measured urinary cations: Na+, K+
–the major measured urinary anion is Cl-
Urine AG = ([Na+] + [K+]) - [Cl-]
•the major unmeasured urinary anions HCO3 •the major unmeasured urinary cations NH4 +
•HCO3 - excretion in healthy subjects - usually negligible
•NH4 + daily average excretion - approximately 40 mEq/L
–results in a positive or near-zero gap
Acid-Base
Metabolic acidosis / Urinary AG
Urine AG = ([Na+] + [K+]) - [Cl-]
•in metabolic acidosis
–the kidneys increase the amount of NH3 synthesized to buffer the excess H+
 NH4 Cl excretion increases
•the increased unmeasured NH4 +  increases the measured anion Cl- in the
urine,  a negative AG == a normal response to systemic acidification
•the finding of a positive urine AG in a non-AG metabolic acidosis == a renal
acidification defect: renal tubular acidosis [RTA]
Acid-Base
Metabolic acidosis / Urinary AG
Caveats
•the presence of ketonuria makes this test unreliable
•the negatively charged ketones are unmeasured  urine AG will be positive or
zero despite the fact that renal acidification and NH4 + levels are increased
•severe volume depletion from extrarenal NaHCO3 loss  avid proximal Na+
reabsorption little Na+ reaching the lumen of the collecting duct is reabsorbed
in exchange for H+
•limited H+ excretion  reduced NH4 + excretion  positive urinary AG
Acid-Base
Metabolic acidosis / Effect of potassium balance on acid-base status
•transcellular shift of K+
–intracellular K+ is exchanged for extracellular H+ or vice versa influence on renal
acid secretion
in hypokalemia  intracellular acidosis
in hyperkalemia  intracellular alkalosis
Acid-Base
Metabolic acidosis / Effect of potassium balance on acid-base status
Hypokalemia
–increased renal production of NH3  increase in renal acid excretion _____ __
–relative intracellular acidosis  increased HCO3 - reabsorption
–relative intracellular acidosis  high activity of the apical Na+/H+ exchanger
The increase in NH3 production by the kidneys may be significant enough to
precipitate hepatic encephalopathy in patients who have advanced liver disease.
Correcting the hypokalemia can reverse this process.
Acid-Base
Metabolic acidosis / Effect of potassium balance on acid-base status
•increased renal ammoniagenesis  relatively alkaline urine
•excessive NH3 then binds more H+ in the lumen of the distal nephron  increased
urine pHsuggestion of RTA as an etiology for non-AG acidosis
–differential diagnoses  urine AG
•negative in patients with normal NH4 + excretion
•positive in patients with RTA
Acid-Base
Metabolic acidosis / Effect of potassium balance on acid-base status
•causes for hypokalemia + metabolic acidosis
–most common - GI loss: diarrhea, laxative use
–less common - renal loss of potassium secondary to RTA or salt-wasting
nephropathy
•differential diagnoses
–the urine pH
–the urine AG
–the urinary K+ concentration
Acid-Base
Metabolic acidosis / Effect of potassium balance on acid-base status
•Hyperkalemia
–opposite effect to hypokalemia
–reduction of NH3 synthesis in the proximal tubule  reduction of NH4 +
reabsorption in the thick ascending limb  reduced medullary interstitial NH3
concentration  decrease in net renal acid secretion
•causes for hyperkalemia + metabolic acidosis
–primary or secondary hypoaldosteronism
•treatment for hyperkalemia + metabolic acidosis
–hyperkalemia has the central role in the generation of the acidosis  lowering
serum the K+ concentration  correction of the associated metabolic acidosis
Acid-Base
Metabolic acidosis / History
•symptoms - not specific
–patients may report varying degrees of dyspnea
•hyperventilation
•respiratory center stimulation in an effort to compensate for the acidosis
–nausea, vomiting, and decreased appetite
•clinical history
–helpful in establishing the etiology (related to the underlying disorder )
–the age of onset and a family history – to point to inherited disorders
Acid-Base
Metabolic acidosis / History
•important points in the history:
–diarrhea - GI losses of HCO3 –history of diabetes mellitus, alcoholism, or prolonged starvation accumulation of ketoacids
–polyuria, increased thirst, epigastric pain, vomiting - diabetic ketoacidosis
(DKA)
–nocturia, polyuria, pruritus, and anorexia - Renal failure4
–ingestion of drugs or toxins - Salicylates, acetazolamide, cyclosporine,
ethylene glycol, methanol
–visual symptoms - methanol ingestion
–renal stones - RTA or chronic diarrhea
–tinnitus - salicylate overdose
Acid-Base
Metabolic acidosis / Physical
•Kussmaul respirations = the best recognized sign
–a form of hyperventilation  increase minute ventilatory volume
–slow, deep breathing  an increase in tidal volume rather than respiratory rate
•stunted growth and rickets  chronic metabolic acidosis in children
•coma and hypotension  acute severe metabolic acidosis
•other physical signs  the underlying cause
–xerosis, scratch marks on skin, pallor, drowsiness, fetor, asterixis, pericardial
rub  renal failure
–reduced skin turgor, dry mucous membranes, fruity smell  DKA
Acid-Base
Metabolic acidosis / Causes
Metabolic acidosis
–normal AG (ie, non-AG)
–high AG
Non-AG metabolic acidosis
•also characterized by hyperchloremia (hyperchloremic acidosis)
•causes of non-AG metabolic acidosis (mnemonic ACCRUED )
–acid load
–chronic renal failure
–carbonic anhydrase inhibitors
–renal tubular acidosis
–ureteroenterostomy
–expansion/extra-alimentation
–diarrhea
Acid-Base
Metabolic acidosis / Causes
The conditions that may cause a non-AG metabolic acidosis
1.
GI loss of HCO3 - - Diarrhea, enterocutaneous fistula (eg, pancreatic), enteric
diversion of urine (eg, ileal loop bladder), pancreas transplantation with
bladder drainage
2.
Renal loss of HCO3 - - Proximal RTA (type 2), carbonic anhydrase inhibitor
3.
Failure of renal H+ secretion - Distal RTA (type 1), type 4 RTA, renal failure
4.
Acid infusion - Ammonium chloride, hyperalimentation
5.
Other - Rapid volume expansion with normal saline, urinary diverting
surgical procedures (eg, ureteroenterostomy)
Acid-Base
Metabolic acidosis / Causes
RTA
metabolic acidosis occurs from decreased net renal acid secretion
Acid-Base
Metabolic acidosis / Causes / RTA
Characteristics
Proximal (Type 2)
Distal (Type 1)
Type 4
Primary defect
Proximal HCO3 reabsorption
Diminished distal
H+ secretion
Diminished
ammoniagenesis
Urine pH
<5.5 when serum
HCO3 - is low
>5.5
<5.5
Serum HCO3 -
>15 mEq/L
Can be <10 mEq/L
>15 mEq/L
Fractional excretion
of HCO3 (FEHCO3)
>15-20% during
HCO3 - load
<5% (can be as high
as 10% in children)
<5%
Serum K+
Normal or mild
decrease
Mild-to-severe
decrease*
High
Associated features
Fanconi syndrome
Alkali therapy
High doses
Low doses
Complications
Osteomalacia or
rickets
Nephrocalcinosis,
nephrolithiasis
Diabetes mellitus,
renal insufficiency
Low doses
Acid-Base
Metabolic acidosis / Causes
The conditions that may cause a high-AG metabolic acidosis
1.
Azotemia
2.
Ketoacidosis
3.
Lactic acidosis
4.
Salicylate overdose
5.
Ethylene glycol poisoning
6.
Methanol poisoning
7.
Paraldehyde poisoning
Acid-Base
Metabolic acidosis / Causes / high-AG metabolic acidosis
mnemonic = SLUMPED
1.
salicylate
2.
lactate
3.
uremia
4.
methanol
5.
paraldehyde
6.
ethylene glycol
7.
diabetes
Acid-Base
Metabolic acidosis / Causes/ high-AG metabolic acidosis
to narrow the differential diagnosis of high-AG acidosis - osmolar gap
•plasma osmolality
–can be calculated using the following equation:
Posm = [2 X Na+]+[glucose in mg/dL]/18+[BUN in mg/dL]/2.8
–can also be measured in the laboratory
•other solutes normally contribute minimally to serum osmolality  the difference
between the measured and the calculated value (osmolar gap) is no more than 1015 mOsm/kg
•some osmotically active toxins = methanol, ethylene glycol, acetone
–cause a high-AG acidosis
–increase the osmolar gap
•measuring the osmolar gap  narrowing the differential diagnosis of high-AG
acidosis
Acid-Base
Metabolic acidosis / Causes / non-AG metabolic acidosis
AG = [Na+] - ([Cl-] + [HCO3 -])
•for a patient with metabolic acidosis (with a decrease in HCO3 -) to maintain a
normal AG, an equal increase in [Cl-] must occur hyperchloremic metabolic
acidosis
•hyperchloremic metabolic acidosis
–HCO3 - lost
•GI tract
•the kidneys
–renal acidification defect
Acid-Base
Metabolic acidosis / Causes / non-AG metabolic acidosis
non-AG metabolic acidosis mechanisms
1.
addition of HCl to body fluids: H+ buffers HCO3 - and the added Cl- results
in a normal AG
2.
loss of HCO3 - from the kidneys or the GI tract: the kidneys reabsorb
sodium chloride to maintain volume
3.
rapid volume expansion with normal saline: this results in an increase in the
chloride load that exceeds the renal capacity to generate equal amounts of
HCO3 -
Acid-Base
Metabolic acidosis / Causes / non-AG metabolic acidosis
Specific causes of hyperchloremic metabolic acidosis
•Loss of HCO3 - via the GI tract
–the secretions of the GI tract, with the exception of the stomach, are relatively
alkaline -high concentrations of base (50-70 mEq/L)
–significant loss of lower GI secretions  metabolic acidosis, especially when
the kidneys are unable to adapt to the loss by increasing net renal acid excretion
–such losses - diarrheal states, fistula with drainage from the pancreas or the
lower GI tract, vomiting if it occurs as a result of intestinal obstruction, laxatives
abuse
–treatment - replacing the lost HCO3 –
–urine
•pH < 5.3
•a negative urine AG (normal urine acidification)
•increased NH4 + excretion
•if distal Na+ delivery is limited because of volume depletion, the urine pH
cannot be lowered maximally
Acid-Base
Metabolic acidosis / Causes / non-AG metabolic acidosis
Specific causes of hyperchloremic metabolic acidosis
1.Distal RTA (type 1)
•a decrease in net H+ secreted by the A-type intercalated cells of the collecting
duct
•H+ is secreted by the apical
–H+ –ATPase and
–K+/H+ –ATPase(more important in K+ regulation than in H+ secretion)
•the secreted H+ is excreted
–as free ions (urine pH value)
–titrated by urinary buffers, phosphate, and NH3
• decreased secreted H+ amount
– reduction in its urinary concentration (ie, increase in urine pH)
– reduction in total H+ buffered by urinary phosphate, NH3
Acid-Base
Metabolic acidosis / Causes / non-AG metabolic acidosis
Specific causes of hyperchloremic metabolic acidosis
Type 1 RTA
•should be suspected in any patient with non-AG metabolic acidosis and a urine
pH greater than 5.0
•patients have a reduction in serum HCO3 - to various degrees, in some cases to
less than 10 mEq/L
•mechanisms implicated in the development of distal RTA
–a defect in 1 of the 2 proton pumps, H+ –ATPase or K+ -H+ –ATPase
•acquired or congenital
–a defect in the basolateral Cl-/HCO3 - exchanger, AE1, or the intracellular
carbonic anhydrase that can be
•acquired or congenital
–back-diffusion of the H+ from the lumen via the paracellular or transcellular
space (lost integrity of the tight junctions)
Acid-Base
Metabolic acidosis / Causes / non-AG metabolic acidosis
Specific causes of hyperchloremic metabolic acidosis
Early renal failure
•metabolic acidosis is usual in patients with renal failure
•in early to moderate stages of chronic kidney disease (glomerular filtration rate of
20-50 mL/min), it is associated with a normal AG (hyperchloremic)
•in more advanced renal failure, the acidosis is associated with a high AG
•in hyperchloremic acidosis, reduced ammoniagenesis (secondary to loss of
functioning renal mass) is the primary defect, leading to an inability of the kidneys to
excrete the normal daily acid load
•NH3 reabsorption and recycling may be impaired, leading to reduced medullary
interstitial NH3 concentration
•In general, patients tend to have a serum HCO3 - level greater than 12 mEq/L, and
buffering by the skeleton prevents further decline in serum HCO3 •!!! patients with hypobicarbonatemia from renal failure cannot compensate for
additional HCO3 - loss from an extrarenal source (eg, diarrhea) and severe metabolic
acidosis can develop rapidly
Acid-Base
Metabolic acidosis / Causes / high-AG metabolic acidosis
Specific causes of metabolic acidosis
Lactic acidosis
–L-lactate = a product of pyruvic acid metabolism in a reaction catalyzed by
lactate dehydrogenase that also involves the conversion of nicotinamide
adenine dinucleotide (NADH) to the oxidized form of nicotinamide adenine
dinucleotide (NAD+). This is an equilibrium reaction that is bidirectional, and the
amount of lactate produced is related to the reactant concentration in the
cytosol (pyruvate, NADH/NAD+)
–daily lactate production in a healthy person is substantial (approximately 20
mEq/kg/d), and this is usually metabolized to pyruvate in the liver, the
kidneys, and, to a lesser degree, in the heart. Thus, production and use of
lactate (ie, Cori cycle) is constant, keeping plasma lactate low
–the major metabolic pathway for pyruvate is to acetyl coenzyme A, which
then enters the citric acid cycle
–in the presence of mitochondrial dysfunction, pyruvate accumulates in the
cytosol and more lactate is produced
Acid-Base
Metabolic acidosis / Causes / high-AG metabolic acidosis
Specific causes of metabolic acidosis
Lactic acidosis
•lactic acid accumulates in blood whenever production is increased or use is
decreased
•a value greater than 4-5 mEq/L is considered diagnostic of lactic acidosis
–type A lactic acidosis occurs in hypoxic states
–type B occurs without associated tissue hypoxia
–D-lactic acidosis is a form of lactic acidosis that occurs from overproduction of Dlactate by intestinal bacteria- it is observed in association with intestinal bacterial
overgrowth syndromes
Echilibrul acidobazic
Acid-Base
Metabolic acidosis / Causes / high-AG metabolic acidosis
Specific causes of metabolic acidosis
Ketoacidosis
–free fatty acids released from adipose tissue have 2 principal fates. In the
major pathway, triglycerides are synthesized in the cytosol of the liver
–in the less common pathway, fatty acids enter mitochondria and are
metabolized to ketoacids (acetoacetic acid and beta-hydroxybutyric acid) by the
beta-oxidation pathway
–ketoacidosis occurs when delivery of free fatty acids to the liver or preferential
conversion of fatty acids to ketoacids is increased
–this pathway is favored when insulin is absent (as in the fasting state), in
certain forms of diabetes, and when glucagon action is enhanced
Acid-Base
Metabolic acidosis / Causes / high-AG metabolic acidosis
Specific causes of metabolic acidosis
•Ketoacidosis
–alcoholic ketoacidosis occurs when excess alcohol intake is accompanied by poor
nutrition
–alcohol inhibits gluconeogenesis, and the fasting state leads to low insulin and high
glucagon levels
–these patients tend to have a mild degree of lactic acidosis
–this diagnosis should be suspected in alcoholic patients who have an unexplained AG
acidosis, and detection of beta-hydroxybutyric acid in the serum in the absence of
hyperglycemia is highly suggestive
–patients may have more than one metabolic disturbance (eg, mild lactic acidosis,
metabolic alkalosis secondary to vomiting)
Acid-Base
Metabolic acidosis / Causes / high-AG metabolic acidosis
Specific causes of metabolic acidosis
•Ketoacidosis
–starvation ketoacidosis can occur after prolonged fasting and may be
exacerbated by exercise
–type 1 diabetes by stressful conditions (eg, infection, surgery, emotional
trauma), but it can also occur in patients with type 2 diabetes.
•hyperglycemia, metabolic acidosis, and elevated beta-hydroxybutyrate
confirm the diagnosis.
•the metabolic acidosis in DKA is commonly a high-AG acidosis secondary to
the presence of ketones in the blood
•after initiation of treatment with insulin, ketone production ceases, the
liver uses ketones, and the acidosis becomes a non-AG type that resolves in
a few days (ie, time necessary for kidneys to regenerate HCO3 -, which was
consumed during the acidosis
Horacio J. Andorgué & Nicolaos E. Midias
Echilibrul acidobazic
Acid-Base
Metabolic acidosis / Causes / high-AG metabolic acidosis
Specific causes of metabolic acidosis
Advanced renal failure
–patients with advanced chronic kidney disease (glomerular filtration rate of
less than 20 mL/min)
–present with a high-AG acidosis
–the acidosis occurs from reduced ammoniagenesis leading to a decrease in the
amount of H+ buffered in the urine
–the increase in AG is thought to occur because of the accumulation of sulfates,
urates and phosphates from a reduction in glomerular filtration and from
diminished tubular function
–in persons with chronic uremic acidosis, bone salts contribute to buffering, and
the serum HCO3 - level usually remains greater than 12 mEq/L
–this bone buffering can lead to significant loss of bone calcium with resulting
osteopenia and osteomalacia