Download (1) Metabolic acidosis

Section 2. Simple types of acid-base
disturbance
(1) Metabolic acidosis
(2) Respiratory acidosis
(3) Metabolic alkalosis
(4) Respiratory alkalosis
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(1) Metabolic acidosis
1) Concept
It is defined as a primary decrease in plasma
[HCO3¯], the pH tends to decrease.
[HCO3 ¯]
in serum pH = pKa + lg ---------------[H2CO3]
The meaning of “primary” indicates the
change happened firstly compared
with ”secondary” change of another parameter.
The metabolic acidosis is the most common
type of acid-base imbalance.
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In metabolic acidosis, the [HCO3¯] in plasma is
decreased firstly, the pH tends to decrease. The
[H2CO3] will decrease secondly.
The pH may be in normal arange
(compensatory acidosis).
The pH may be less than 7.35
(decompensatory acidosis)
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2) Classification
Metabolic acidosis is classified into two types:
(a)metabolic acidosis with normal AG ( with
increased Cl ¯ ) and
(b) metabolic acidosis with high AG (with normal
Cl ¯).
An increased AG means the accumulation
of nonvolatile acids in the body.
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3)Causes and Pathogenesis
(a) The decreased [HCO3¯ ]
(b) More acids buffered by [HCO3¯ ]
(c) Hyperkalemia
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(a) The decreased [HCO3¯ ]
The decreased [HCO3¯ ] is caused by
a) increased loss of HCO3¯ from kidneys,
b) increased loss of HCO3¯ from intestinal tract,
c) excessive production of Cl¯
d) dilution of HCO3¯ .
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a) Increased loss of HCO3¯ from
kidneys
In proximal renal tubular
acidosis (II type of tubular
acidosis), the activity of CA is
reduced.
H+ -Na+ exchange is
reduced.
The reabsorption of
HCO3¯ is reduced, which
leads to a massive
bicarbonate leak from kidney.
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In distal renal tubular acidosis (I type),
the capability of H+ excretion (H+-ATPase)
is decreased.
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b) Increased loss of HCO3¯
from intestinal tract
The main extrarenal loss of HCO3¯ is
from intestinal tract, like diarrhea and fistula
in intestinal tract, because there is more
HCO3 ¯ in intestinal juice than in serum.
(gastric juice has more H+)
(Effect of carbonic anhydrase in mucous
membrance of stomach)
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c) Excessive production of Cl¯
If excessive amount of substances
(ammonium chloride and lysine
hydrochloride ) have been administered,
those substances can yield hydrochloric acid .
For electrical neutrality, the [HCO3¯] is
reduced after the [Cl¯] increased.
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Replenish 0.9% NaCl to increase
the [Clˉ] in plasma.
[Na+]
[Cl-] ( mmol/L)
--------------------------------------------------------0.9%NaCl 154
154
Plasma
140
104
--------------------------------------------------------11
(b) More acids buffered by [HCO3¯ ]
The accumulation of organic acids
(nonvolatile acid) in blood due to more acids:
a) decreased excretion of organic acids
b) overproduction of organic acids.
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a) Decreased excretion of organic
acids
Nonvolatile acids are filtered off through
the glomerular membrane.
In acute (less renal flow) and chronic renal
failure (less permeability and area), the GFR
is reduced, which results in the retention of
nonvolatile acids in blood, so the AG is
increased.
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b) Incomplete catabolism of carbohydrates
and fatty acids.
Normally the complete catabolism of
carbohydrates and fatty acids produces CO2
and water.
The increased anaerobic glycolysis due to
hypoxia(shock, severe anemia, pulmonary
edema) results in lactic acidosis.
Can increased production of lactic acid
definitely cause metabolic acidosis?
14
In insulin lack, the catabolism of
carbohydrates is reduced, the lipolysis
( catabolism of fat) is increased, the
ketogenesis is accelerated.
If the production of keto-bodies is
more than the catabolism and excretion of
keto-bodies, accumulation of keto-bodies
will result in diabetic keto-acidosis.
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Alcoholic keto-acidosis occurs as the
result of accelerated lipolysis due to
reduced insulin secretion.
Starvation causes metabolic
acidosis due to the accelerated lipolysis,
which leads to the overproduction of
keto- bodies (accelerated ketogenesis).
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c) Administration of excessive fixed acids
Salicylate水杨酸盐 (for stop pain and antiinflammation) can be converted to salicylic acid in the
body.
NH4Cl
urea+HCl
甲醇(假酒) 代谢成甲醛,再代谢成甲酸在体内的积
累，甲醇在体内可抑制某些氧化酶系统，使糖的需氧分解
及机体代谢发生障碍，导致乳酸及其他有机酸在体内积聚，
引起代谢性酸中毒
d)
喝醋？
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(c) Hyperkalemia
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4) Compensation of metabolic acidosis
(a) Compensation by buffering systems
(b) Respiratory compensation
(c) Renal compensation
(d) Compensation by cells and bone
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(a) Compensation by buffering
systems
Buffer pair (buffer system) consists of a weak acid
and its’ salt, such as
NaHCO3
------------H2CO3
Na2HPO4
-------------NaH2PO4
Hb--------HHb
H2SO4 + NaHCO3 = Na2SO4 + H2CO3
A strong acid becomes a weak acid after combining
to NaHCO3 -.
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The HCO3¯ will decrease and the
production of H2CO3 will increase, H2CO3
can be resolved into CO2 and H2O.
H2CO3 → CO2 +H2O
The CO2 will be eliminated by respiration.
[ H+]e will decrease, pH will increase.
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Na2HPO4
-------------NaH2PO4
Hb-------HHb
The other buffer alkaline (like HPO4
2¯/H2PO4 ¯) will be eliminated from kidneys.
The [H+]e will reduce, the pH will increase.
The HHb will keep H+ within RBC , the [H+]e
will reduce, the pH will increase.
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Low pH
central
chemoreceptors
(b) Respiratory
compensation
Via
stimulate the respiratory center
increase the depth of respiration
more carbon dioxide can be
eliminated from lung
normal pH
Decreased pH will
stimulate the
chemoreceptors
located in respiratory
center (central) and
in carotic body
(peripheral), and
enhance the
ventilation.
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Kussmaul respiration (deep sighing
respiration) is for increasing CO2 excretion.
More CO2 will be eliminated. The
[H2CO3] will decrease secondarily to the
decrease of [HCO3¯ ].
The ratio of [HCO3¯ ]/[H2CO3] will
tend to normal. The pH will tend to normal.
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Predicted compensatory formula
ΔPaCO2(mmHg)
Secondary compensation
= 1.2 x ΔHCO3- ±2
primary change
Or:
PaCO2=1.5xHCO3-+8 ±2
PaCO2 can decline maximal to 10 mmHg.
Value measured > value predicted: with respiratory
acidosis
Value measured < value predicted: with respiratory
alkalosis
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(c) Renal compensation
Renal compensation begins from several
hours after the addition of acid load, and it may
take 3~5 days to reach the maximum of this
compensatory capacity.
The reabsorption of HCO3¯ is increased.
Net acid excretion with urine is increased.
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a) In metabolic acidosis, the activity of
carbonic anhydrase (CA) increases, the H+
production is increased, the H+-Na+
exchange is increased, the reabsorption of
HCO3¯ is increased in proximal tubule,
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b) in distal tubule.
In metabolic acidosis, the activity of
carbonic anhydrase (CA) increases, the H+
excretion is increased, the reabsorption of
HCO3¯ is increased.
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c) In metabolic acidosis, the activity of
glutaminase is increased, more glutamine will be
decomposed into HCO3¯ and NH4+.
More NH4+ is excreted into tubular lumen.
Thus more HCO3¯ will be reabsorpted to the
blood.
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d) In metabolic acidosis, more H2PO4¯
is in the end urine, the end urine is more
acidic in metabolic acidosis.
Thus more HCO3¯ will be reabsorpted
to the blood.
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(d) Compensation by cells and bone
When [H+] in ECF (serum) is
increased in metabolic acidosis, the H+ will
move into the cells, as a exchange for
electrical neutrality, K+ will shift from ICF to
the ECF.
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In chronic metabolic acidosis, bone salt
[Ca3(PO4)2] is also utilized as a buffer base,
but the expense is decalcification of bone
and osteoporosis (loose and soft bone).
It is not a good way of regulating acidbase balance.
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Changes of laboratory parameters
Primary decrease of [HCO3 ]:
AB,SB,BB ???
AB ?? SB
BE ?
Secondary compensation:
PaCO2 ?
pH ?
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Changes of laboratory parameters
Primary decrease of [HCO3-]:
AB,SB,BB all reduced
AB<SB
BE increased negative value
Secondary compensation:
PaCO2 reduced
pH decreased (tendency)
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5)Effects on the body
The main manifestations are:
(A) effects on the cardiovascular system.
(B) depression of mental activity
(C) hyperventilation
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(A) Effects on the cardiovascular system
(a) Impairment of myocardial contraction
(b) Arrhthmias
(c) The hemodynamic effect
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(a) Impairment of myocardial contraction
Ca2+ combining with troponin肌钙蛋白 will start the
myocardial contraction.
①H+ is a competitive inhibitor for Ca2+ combining
with troponin. After H+ moves into the myocardial cells,
the myocardial contraction is impaired.
Severe acidosis may cause myocardial failure
and low blood pressure because of the low cardiac
output.
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② The protein expression of L-type of
voltage-dependent calcium channel in
myocardial cell membrane is reduced. Ca2+ inflow is reduced.
③ The protein expression of calcium
channel in sarcoplasmic reticulum(SR) membrane is
reduced.The release of Ca2+ from SR is reduced.
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(b) Arrhthmias due to hyperkalemia
Causes of hyperkalemia:
H+-K+ exchange of cell
Increased renal excretion of H+
Effect of hyperkalemia:
Arrhthmias
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(c) The hemodynamic effect:
Low BP
Catecholamine (dopamine, adrenalin,
noradrenalin) can lead to the arteriole
contraction,and increase the BP.
The reaction of arteriole to catecholamine is
decreased in acidosis, which leads to the blood
dilatation ,decrease of peripheral resistance,
Reduced venous return,
Impairment of myocardial contraction
Hypotension.
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(B) Depression of mental activity
(a) Manifestations:
obtundation (thinking slowly), confused.
(b) Mechanisms
a) Increased [H+] causes cerebral
vasodilatation. More blood supply will increase the
CHP, then cause brain edema and high intracranial
pressure.
b) High [H+] increases the permeability of
cerebral blood vessels. Decreased plasma COP and
increased interstitial COP can lead to brain edema.
c) Reduced ATPl production.
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Glutamic acid
Glutamate decarboxylase
r-GABA, r- gama aminobutyric acid
r-GABA transaminase
Succinic acid琥珀酸
Kreb’s cycle
d) The production of GABA (gama aminobutyric
acid,γ-氨基丁酸, a inhibitory transmitter) is increased
due to the activity of enzyme for the production is
increased, and the activity of enzyme for the
decomposition is decreased in low pH (acidosis).
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(C) Hyperventilation for compensation.
Kussmaul respiration (deep sighing
respiration) is for increasing CO2 excretion.
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(6) Principle of treatment
For metabolic acidosis”
1) Treat the primary diseases which cause
metabolic acidosis.
2) Replenish alkaline (HCO3¯ ) to the
patients with normal respiratory function.
Sodium lactate 乳酸钠??
(liver function)
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3) Prevent the hypokalemia during
treatment. (reason?)
After the correction of acidosis, the [K+]
will fall down rapidly by moving into the
cells.
The hypokalemia can cause lifethreatening cardiac arrhthmias.
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4) In acidosis, [Ca2+] increases, [Ca2+]
reduces during the correcting of acidosis.
OHCa2+ ------→combining calcium
Ca2+ ←------combining calcium
H+
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Case Discussion
1. A 36-year-old man was hospitalized with a 3-day
history of fever and watery diarrhea. His blood pressure
was 90/60 mmHg, the pulse was 112/min, temperature is
38.0℃. The abdomen was distended and low skin
elasticity.
The laboratory results were:
pH=7.21,
PaCO2=28 mmHg,
PaO2= 108 mmHg.
[Na+]=135 mmol/L
[K+] =3.0 mmol/L
[HCO3-] = 16 mmol/L
ΔPaCO2(mmHg) = 1.2 x ΔHCO3- ±2
Secondary compensation
primary change
=1.2X8=8~12
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The patient’s problems were:
(1)isotonic dehydration
(2) decompensatory metabolic acidosis
(3)hypokalemia.
(after the correction of acidosis?)
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