Professional Documents
Culture Documents
Basic definitions
•An acid
–a substance that can donate hydrogen ions (H+)
•A base
–a substance that can accept H+ ions
•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
•the law of mass action - the velocity of a reaction is proportional to the product of
the reactant concentrations …………………………………………….
in body fluids
• the tight regulation of [H+] at this low concentration is crucial for normal
cellular activities
• under normal conditions, acids and bases are being added constantly to the
extracellular fluid compartment
•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
•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 -]
•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
•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
•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
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
•H+ enters the tubular lumen via 1 of 2 apical proton pumps, H+ «ATPase or H+ -
K+ «ATPase
•titratable acidity
–the amount of secreted H+ that is buffered by filtered weak acids is called titratable
acidity
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
•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
Transport activ
Na+ Na+ Na+ HCO3-
Na HCO3
HCO3- HCO3- + H+ contraschimb H+ + CO3-
H2CO3 H2 CO3
Anhidraza carbonică
Na2HPO4
NaHCO3- H2PO4-
- HCO3- H+ Na+
HCO3
eliminare
H2CO3
AC
NH3 NH4Cl
Na H CO3 glutamină
(acid slab)
HCO3- HCO3- H+ H+
H2CO3 eliminare
AC
CO2 CO2 + H2O
Echilibrul acidobazic – apărarea împotriva schimbării concetraţiei ionilor de H+
NH3 NH4Cl
Na H CO3 glutamină
(acid slab)
HCO3- HCO3- H+ H+
H2CO3 eliminare
AC
CO2 CO2 + H2O
Na+
CL- Cl-
Cl-
H+ HCO3- HCO3-
H2CO3 Na+
AC
CO2 CO2 + H2O NaHCO3
Alcaloză hipercloremică
Echilibrul acidobazic – apărarea împotriva schimbării concetraţiei ionilor de H+
Acid-Base
Metabolic acidosis / Pathophysiology
•the underlying disorders that lead to acidemia and alkalemia are acidosis and
alkalosis, respectively
•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
•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 increased unmeasured NH4 + increases the measured anion Cl- in the
urine, a negative AG == a normal response to systemic acidification
•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
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
•excessive NH3 then binds more H+ in the lumen of the distal nephron increased
urine pHsuggestion 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
•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
•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
Metabolic acidosis
–normal AG (ie, non-AG)
–high AG
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
7. diabetes
Acid-Base
Metabolic acidosis / Causes/ high-AG metabolic acidosis
•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
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
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
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
•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