1 Section 2. Simple types of acid-base disturbance (1) Metabolic acidosis (1) Metabolic acidosis (2) Respiratory acidosis (2) Respiratory acidosis (3)

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Section 2. Simple types of acid-base Section 2. Simple types of acid-base disturbancedisturbance

(1) Metabolic acidosis(1) Metabolic acidosis

(2) Respiratory acidosis(2) Respiratory acidosis

(3) Metabolic alkalosis(3) Metabolic alkalosis

(4) Respiratory alkalosis(4) Respiratory alkalosis

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(1) (1) Metabolic acidosisMetabolic acidosis

  1) Concept 1) Concept It is defined as It is defined as a primary decreasea primary decrease in plasma in plasma

[HCO[HCO33¯̄], ], the pH tends to decrease. the pH tends to decrease.

[HCO[HCO3 3 ¯̄]]in serum pH = pKa + lg ----------------in serum pH = pKa + lg ---------------- [H[H22COCO33]]

The meaning of “primary” indicates the change The meaning of “primary” indicates the change happened firstly compared with happened firstly compared with ”secondary” ”secondary” changechange of another parameter. of another parameter.

The metabolic acidosis is the most common The metabolic acidosis is the most common type of acid-base imbalance.type of acid-base imbalance.

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In metabolic acidosis, the [HCOIn metabolic acidosis, the [HCO33¯̄] in plasma is ] in plasma is decreased firstly, the pH tends to decrease. The decreased firstly, the pH tends to decrease. The [H[H22COCO33] will decrease secondly. ] will decrease secondly.

The pH may be in normal arange The pH may be in normal arange (comp(compensatory acidosis).ensatory acidosis).

The pH may be less than 7.35 The pH may be less than 7.35 (decompensatory acidosis)(decompensatory acidosis)

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2) 2) ClassificationClassification Metabolic acidosis is classified into two types: Metabolic acidosis is classified into two types: (a)(a)metabolic acidosis with normal AGmetabolic acidosis with normal AG ( with ( with

increased Cl increased Cl ¯̄ ) and ) and (b) (b) metabolic acidosis with high AGmetabolic acidosis with high AG (with normal (with normal

Cl Cl ¯̄).). An increased AG means the accumulation of An increased AG means the accumulation of

nonvolatile acids in the body. nonvolatile acids in the body.

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3)Causes and Pathogenesis3)Causes and Pathogenesis

(a) The decreased [HCO(a) The decreased [HCO33¯̄ ] ]

(b) (b) More acids buffered by More acids buffered by [HCO[HCO33¯̄ ] ]

(c)(c) Hyperkalemia Hyperkalemia

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(a) The decreased [HCO(a) The decreased [HCO33¯̄ ] ]

The decreased [HCOThe decreased [HCO33¯̄ ] is caused by ] is caused by

a) increased loss of HCOa) increased loss of HCO33¯̄ from kidneys, from kidneys,

b) increased loss of HCOb) increased loss of HCO33¯̄ from from intestinalintestinal tracttract,,

c) excessive production of Clc) excessive production of Cl¯̄

d) dilution of d) dilution of HCOHCO33¯̄ ..

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a) Increased loss of HCO3a) Increased loss of HCO3¯̄ from from kidneyskidneys

In In proximal renal tubular proximal renal tubular acidosis (II type of tubular acidosis (II type of tubular acidosis)acidosis), the activity of CA is , the activity of CA is reduced.reduced.

HH++ -Na -Na++ exchange is exchange is reduced. reduced.

The reabsorption of The reabsorption of HCOHCO33¯̄ is reduced, which is reduced, which leads to a massive leads to a massive bicarbonate leak from kidney.bicarbonate leak from kidney.

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In In distal renal tubular acidosis (I distal renal tubular acidosis (I type)type), the capability of H, the capability of H++ excretion (H excretion (H++--ATPase) is decreased.ATPase) is decreased.

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b) Increased loss of HCO3b) Increased loss of HCO3¯̄ from intestinal tract from intestinal tract

The main extrarenal loss of The main extrarenal loss of HCO3HCO3¯̄ is is from intestinal tract, like diarrhea and fistula from intestinal tract, like diarrhea and fistula in intestinal tract, because there is more in intestinal tract, because there is more HCOHCO3 3 ¯̄ in intestinal juice than in serum. in intestinal juice than in serum. (gastric juice has more H(gastric juice has more H++))

(Effect of carbonic anhydrase in mucous (Effect of carbonic anhydrase in mucous membrance of stomach)membrance of stomach)

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    c) Excessive production of Clc) Excessive production of Cl¯̄ If excessive amount of substances If excessive amount of substances (ammonium chloride and lysine (ammonium chloride and lysine hydrochloride ) have been administered, hydrochloride ) have been administered, those substances can yield hydrochloric those substances can yield hydrochloric acid . acid .     For electrical neutrality, the [For electrical neutrality, the [HCO3HCO3¯̄] is ] is reduced after the [Clreduced after the [Cl¯̄] increased.] increased.

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Replenish 0.9% NaCl to increase Replenish 0.9% NaCl to increase the [Clthe [Clˉ̄] in plasma.] in plasma.

[Na+] [Cl-] ( mmol/L)[Na+] [Cl-] ( mmol/L)

------------------------------------------------------------------------------------------------------------------0.9%NaCl 154 1540.9%NaCl 154 154Plasma 140 104Plasma 140 104------------------------------------------------------------------------------------------------------------------

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(b) (b) More acids buffered by More acids buffered by [HCO[HCO33¯̄ ] ]

The accumulation of organic acids The accumulation of organic acids (nonvolatile acid) in blood due to more acids:(nonvolatile acid) in blood due to more acids: a) decreased excretion of organic acids a) decreased excretion of organic acids b) overproduction of organic acids.b) overproduction of organic acids.

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a) Decreased excretion of organic a) Decreased excretion of organic acidsacids

Nonvolatile acids are filtered off through Nonvolatile acids are filtered off through the glomerular membrane.the glomerular membrane.

In acute In acute (less renal flow)(less renal flow) and chronic renal and chronic renal failure (less permeability and area), the GFR failure (less permeability and area), the GFR is reduced, which results in the retention of is reduced, which results in the retention of nonvolatile acids in blood, so the AG is nonvolatile acids in blood, so the AG is increased.increased.

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b) Incomplete catabolism of carbohydrates b) Incomplete catabolism of carbohydrates and fatty acids.and fatty acids.

Normally the complete catabolism of Normally the complete catabolism of carbohydrates and fatty acids produces COcarbohydrates and fatty acids produces CO22 and water. and water.

The increased anaerobic glycolysis due to The increased anaerobic glycolysis due to hypoxia(shock, severe anemia, pulmonary hypoxia(shock, severe anemia, pulmonary edema) results in edema) results in lactic acidosis.lactic acidosis.

Can increased production of lactic acid Can increased production of lactic acid definitelydefinitely cause metabolic acidosis? cause metabolic acidosis?

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In insulin lack, the catabolism of In insulin lack, the catabolism of carbohydrates is reduced, the lipolysis carbohydrates is reduced, the lipolysis ( catabolism of fat) is increased, the ( catabolism of fat) is increased, the ketogenesis is accelerated.ketogenesis is accelerated.

If the production of keto-bodies is If the production of keto-bodies is more than the catabolism and excretion of more than the catabolism and excretion of keto-bodies, accumulation of keto-bodies keto-bodies, accumulation of keto-bodies will result in will result in diabetic keto-acidosisdiabetic keto-acidosis..

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Alcoholic keto-acidosis occurs as the Alcoholic keto-acidosis occurs as the result of accelerated lipolysis due to result of accelerated lipolysis due to reduced insulin secretion.reduced insulin secretion.

Starvation causes metabolic Starvation causes metabolic acidosis due to the accelerated lipolysis, acidosis due to the accelerated lipolysis, which leads to the overproduction of which leads to the overproduction of keto- bodies (accelerated ketogenesis).keto- bodies (accelerated ketogenesis).

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  c) Administration of excessive fixed acidsc) Administration of excessive fixed acids

SalicylateSalicylate 水杨酸盐 水杨酸盐 ((for stop pain and anti-for stop pain and anti-inflammation) can be converted to salicylic acid in the inflammation) can be converted to salicylic acid in the body.body.

NHNH44Cl urea+HClCl urea+HCl 甲醇甲醇 (( 假酒假酒 ) ) 代谢成甲醛代谢成甲醛 ,, 再代谢成甲酸在体内的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 聚，引起代谢性酸中毒

    d)d) 喝醋？喝醋？

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(c)(c) Hyperkalemia Hyperkalemia

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4) Compensation of metabolic acidosis4) Compensation of metabolic acidosis

(a) Compensation by buffering systems(a) Compensation by buffering systems

(b) Respiratory compensation(b) Respiratory compensation

(c) Renal compensation(c) Renal compensation

(d) Compensation by cells and bone(d) Compensation by cells and bone

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(a) Compensation by buffering (a) Compensation by buffering systemssystems

Buffer pair (buffer system) consists of a weak acid Buffer pair (buffer system) consists of a weak acid

and its’ salt, such asand its’ salt, such as

NaHCONaHCO3 3 NaNa22HPOHPO4 4 HbHb--

------------- ------------- -------------- ----------------------- --------- HH22COCO3 3 NaHNaH22POPO4 4 HHbHHb

HH22SOSO44 + NaHCO + NaHCO33 = Na = Na22SOSO44 + H + H22COCO33

A strong acid becomes a weak acid after combining to NaHCO NaHCO3 3 --.

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The HCOThe HCO33¯̄ will decrease and the will decrease and the production of Hproduction of H22COCO33 will increase, H will increase, H22COCO33 can be resolved into COcan be resolved into CO22 and H and H22O.O.

HH22COCO33 → CO → CO22 +H +H22OO

The COThe CO22 will be eliminated by respiration. will be eliminated by respiration.

  [ H[ H++]e will decrease, pH will increase.]e will decrease, pH will increase.

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NaNa22HPOHPO4 4 HbHb--

-------------- ---------------------- -------- NaHNaH22POPO4 4 HHbHHb

The other buffer alkaline (like HPOThe other buffer alkaline (like HPO44

22¯/H¯/H22POPO4 4 ¯) ¯) will be eliminated from kidneys. will be eliminated from kidneys. TThe [Hhe [H+]e will reduce, the pH will increase.]e will reduce, the pH will increase.

The HHb will keep HThe HHb will keep H++ within RBC , the [H within RBC , the [H+]e ]e will reduce, the pH will increase.will reduce, the pH will increase.

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Low pHLow pH

Via central Via central chemoreceptorchemoreceptorss

stimulate the respiratory stimulate the respiratory centercenter

increase the depth of increase the depth of respirationrespiration

more carbon dioxide can be more carbon dioxide can be eliminated from lungeliminated from lung

normal normal pHpH

Decreased pH will Decreased pH will stimulate the stimulate the chemoreceptors chemoreceptors located in respiratory located in respiratory center (central) and center (central) and in carotic body in carotic body (peripheral), and (peripheral), and enhance the enhance the ventilation.ventilation.

(b) Respiratory (b) Respiratory compensationcompensation

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Kussmaul respiration (deep sighing Kussmaul respiration (deep sighing respiration) is for increasing COrespiration) is for increasing CO22 excretion. excretion.

More COMore CO22 will be eliminated. The will be eliminated. The [H[H22COCO33] will decrease] will decrease secondarily secondarily to the to the decrease of [HCOdecrease of [HCO33¯̄ ]. ].

The ratio of [HCOThe ratio of [HCO33¯̄ ]/[H ]/[H22COCO33] will ] will tend to normal. The pH will tend to normal.tend to normal. The pH will tend to normal.

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Predicted compensatory formulaPredicted compensatory formula

ΔPaCOΔPaCO22(mmHg) = 1.2 x ΔHCO(mmHg) = 1.2 x ΔHCO33- ±2±2

Secondary compensation primary changeSecondary compensation primary change

Or:Or:

PaCOPaCO22=1.5xHCO=1.5xHCO33-+8 ±2+8 ±2

PaCOPaCO22 can decline maximal to 10 mmHg. can decline maximal to 10 mmHg.

Value measured > value predicted: with respiratory Value measured > value predicted: with respiratory acidosis acidosis

Value measured < value predicted: with respiratory Value measured < value predicted: with respiratory alkalosis alkalosis

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(c) Renal compensation(c) Renal compensation

Renal compensation begins from several Renal compensation begins from several hours after the addition of acid load, and it may hours after the addition of acid load, and it may take 3~5 days to reach the maximum of this take 3~5 days to reach the maximum of this compensatory capacity.compensatory capacity.

The reabsorption of HCOThe reabsorption of HCO33¯̄ is increased. is increased.

Net acid excretion with urine is increased.Net acid excretion with urine is increased.

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a) a) In metabolic acidosis, the activity of In metabolic acidosis, the activity of carbonic anhydrase (CA) increases,carbonic anhydrase (CA) increases, the H the H++ production is increased, the Hproduction is increased, the H++-Na-Na++ exchange is increased, exchange is increased, the reabsorption of the reabsorption of HCOHCO33¯̄ is increased in proximal tubule, is increased in proximal tubule,

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b) in distal tubuleb) in distal tubule..

In metabolic acidosis, the activity of In metabolic acidosis, the activity of carbonic anhydrase (CA) increases,carbonic anhydrase (CA) increases, the H the H++ excretion is increased, excretion is increased, the reabsorption of the reabsorption of HCOHCO33¯̄ is increased. is increased.

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c) c) In metabolic acidosis, the activity of In metabolic acidosis, the activity of glutaminase is increased,glutaminase is increased, more glutamine will be more glutamine will be decomposed into HCOdecomposed into HCO33¯̄ and NH and NH44++. .

More NHMore NH44+ + is excreted into tubular lumen.is excreted into tubular lumen.

Thus more HCOThus more HCO33¯̄ will be reabsorpted to the will be reabsorpted to the blood.blood.

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d) In metabolic acidosis, more Hd) In metabolic acidosis, more H22POPO44¯̄ is in the end urine, the end urine is more is in the end urine, the end urine is more acidic in metabolic acidosis. acidic in metabolic acidosis.

Thus more HCOThus more HCO33¯̄ will be reabsorpted will be reabsorpted to the blood.to the blood.

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(d) Compensation by cells and bone(d) Compensation by cells and bone

When [HWhen [H++] in ECF (serum) is ] in ECF (serum) is increased in metabolic acidosis, the Hincreased in metabolic acidosis, the H++ will will move into the cells, as a exchange for move into the cells, as a exchange for electrical neutrality, Kelectrical neutrality, K++ will shift from ICF to will shift from ICF to the ECF. the ECF.

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In chronic metabolic acidosis, bone salt In chronic metabolic acidosis, bone salt [Ca[Ca33(PO(PO44))22] is also utilized as a buffer ] is also utilized as a buffer base, but the expense is decalcification of base, but the expense is decalcification of bone and osteoporosis (loose and soft bone and osteoporosis (loose and soft bone).bone).

It is not a good way of regulating acid-It is not a good way of regulating acid-base balance.base balance.

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Changes of laboratory parametersChanges of laboratory parameters

Primary decrease of [HCOPrimary decrease of [HCO33-]:]:

AB,SB,BB ???AB,SB,BB ???

AB ?? SBAB ?? SB

BE ?BE ?

Secondary compensationSecondary compensation::

PaCOPaCO2 2 ? ?

pH ?pH ?

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Changes of laboratory parametersChanges of laboratory parameters

Primary decrease of [HCOPrimary decrease of [HCO33-]:]: AB,SB,BB all reducedAB,SB,BB all reduced AB<SBAB<SB BE increased negative valueBE increased negative value Secondary compensationSecondary compensation:: PaCOPaCO2 2 reduced reduced pH decreased (tendency)pH decreased (tendency)

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5)Effects on the body5)Effects on the body

    The main manifestations are:The main manifestations are:

(A) effects on the cardiovascular system.(A) effects on the cardiovascular system.

(B) depression of mental activity(B) depression of mental activity

((C) hyperventilationC) hyperventilation

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(A) (A) Effects on the cardiovascular systemEffects on the cardiovascular system

(a) Impairment of myocardial contraction(a) Impairment of myocardial contraction

(b)(b) ArrhthmiasArrhthmias

(c) The hemodynamic effect(c) The hemodynamic effect

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(a) Impairment of myocardial contraction(a) Impairment of myocardial contraction

CaCa2+2+ combining with troponin combining with troponin 肌钙蛋白 肌钙蛋白 will start will start the myocardial contraction.the myocardial contraction. ①①HH++ is a competitive inhibitor for Ca is a competitive inhibitor for Ca2+2+ combining combining with troponin. After Hwith troponin. After H++ moves into the myocardial cells, moves into the myocardial cells, the myocardial contraction is impaired. the myocardial contraction is impaired. Severe acidosis may cause myocardial failure Severe acidosis may cause myocardial failure and low blood pressure because of the low cardiac and low blood pressure because of the low cardiac output.output.

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② ② The protein expression of L-type of The protein expression of L-type of voltage-dependent calcium channel in voltage-dependent calcium channel in myocardial cell membrane is reduced.myocardial cell membrane is reduced. CaCa22+ in- in-flow is reduced.flow is reduced.

③ ③ The protein expression of cThe protein expression of calcium alcium channel in channel in sarcoplasmic reticulum(SR) sarcoplasmic reticulum(SR) membrane is membrane is reduced.The release of Careduced.The release of Ca22+ from SR is reduced. from SR is reduced.

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(b)(b) Arrhthmias due to hyperkalemia Arrhthmias due to hyperkalemia

Causes of hyperkalemia:

H+-K+ exchange of cell

Increased renal excretion of H+

Effect of hyperkalemia:

ArrhthmiasArrhthmias

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(c) (c) The hemodynamic effect:The hemodynamic effect: Low BPLow BP

Catecholamine (dopamine, adrenalin, Catecholamine (dopamine, adrenalin, noradrenalin) can lead to the arteriole noradrenalin) can lead to the arteriole contraction,and increase the BP.contraction,and increase the BP. The reaction of arteriole to catecholamine is The reaction of arteriole to catecholamine is decreased in acidosis, which leads to the blood decreased in acidosis, which leads to the blood dilatation ,decrease of peripheral resistance, dilatation ,decrease of peripheral resistance, Reduced venous return,Reduced venous return, Impairment of myocardial contractionImpairment of myocardial contraction Hypotension. Hypotension.

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(B) (B) Depression of mental activityDepression of mental activity

(a) Manifestations:(a) Manifestations: obtundation (thinking slowly), confused.obtundation (thinking slowly), confused.(b) Mechanisms(b) Mechanisms a) Increased [Ha) Increased [H++] causes cerebral ] causes cerebral vasodilatation. More blood supply will increase the vasodilatation. More blood supply will increase the CHP, then cause brain edema and high intracranial CHP, then cause brain edema and high intracranial pressure. pressure. b) High [Hb) High [H++] increases the permeability of ] increases the permeability of cerebral blood vessels. Decreased plasma COP and cerebral blood vessels. Decreased plasma COP and increased interstitial COP can lead to brain edema.increased interstitial COP can lead to brain edema. c) Reduced ATP production.c) Reduced ATP production.l

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Glutamic acidGlutamic acid

Glutamate decarboxylase

r-GABA, r- gamagama aminobutyric acid

r-GABA transaminase

Succinic acid 琥珀酸

Kreb’s cycle

d) The production of GABA (gama aminobutyric d) The production of GABA (gama aminobutyric acid,acid,γ-γ- 氨基丁酸氨基丁酸 , , a inhibitory transmitter) is increased a inhibitory transmitter) is increased due to the activity of enzyme for the production is due to the activity of enzyme for the production is increased, and the activity of enzyme for the increased, and the activity of enzyme for the decomposition is decreased in low pH (acidosis).decomposition is decreased in low pH (acidosis).

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((C) Hyperventilation for compensation.C) Hyperventilation for compensation.

Kussmaul respiration (deep sighing Kussmaul respiration (deep sighing respiration) is for increasing COrespiration) is for increasing CO2 2 excretion. excretion.

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(6) Principle of treatment(6) Principle of treatment

For metabolic acidosis”For metabolic acidosis”

1) Treat the primary diseases which cause 1) Treat the primary diseases which cause metabolic acidosis.metabolic acidosis.

2) Replenish alkaline (HCO2) Replenish alkaline (HCO33¯̄ ) to the ) to the patients with normal respiratory function.patients with normal respiratory function.

Sodium lactate Sodium lactate 乳酸钠乳酸钠 ????

((liver function) liver function)

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3) Prevent the hypokalemia during 3) Prevent the hypokalemia during treatment. (reason?) treatment. (reason?) After the correction of acidosis, the [KAfter the correction of acidosis, the [K++] ] will fall down rapidly by moving into the will fall down rapidly by moving into the cells. cells. The hypokalemia can cause life-The hypokalemia can cause life-threatening cardiac arrhthmias.threatening cardiac arrhthmias.

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4) In acidosis, 4) In acidosis, [[CaCa2+]] increases, increases, [[CaCa2+] ] reduces during the correcting of acidosis.reduces during the correcting of acidosis.

OHOH-

CaCa2+ ------ ------→combining calcium→combining calcium

CaCa2+ ←------combining calcium ←------combining calcium

HH+

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Case DiscussionCase Discussion

1. A 36-year-old man was hospitalized with a 3-day 1. A 36-year-old man was hospitalized with a 3-day history of fever and watery diarrhea. His blood pressure history of fever and watery diarrhea. His blood pressure was 90/60 mmHg, the pulse was 112/min, temperature is was 90/60 mmHg, the pulse was 112/min, temperature is 38.0 . The abdomen was distended and low skin ℃38.0 . The abdomen was distended and low skin ℃elasticity. The laboratory results were:elasticity. The laboratory results were:

pH=7.21, PaCOpH=7.21, PaCO22=28 mmHg,=28 mmHg, PaOPaO22= 108 mmHg. [Na= 108 mmHg. [Na++]=135 mmol/L]=135 mmol/L [K[K++] =3.0 mmol/L [HCO] =3.0 mmol/L [HCO33--] = 16 mmol/L] = 16 mmol/L

ΔPaCOΔPaCO22(mmHg) = 1.2 x ΔHCO(mmHg) = 1.2 x ΔHCO33- ±2±2Secondary compensation primary changeSecondary compensation primary change =1.2X8=8~12 =1.2X8=8~12

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The patient’s problems were:The patient’s problems were:

(1)isotonic dehydration(1)isotonic dehydration

(2) decompensatory metabolic acidosis(2) decompensatory metabolic acidosis

(3)hypokalemia.(3)hypokalemia.

(after the correction of acidosis?)(after the correction of acidosis?)