1 Chapter VII. Acid – Base Disturbance Section 1. Acid-Base Balance Section 1. Acid-Base Balance...

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Chapter VIIChapter VII..Acid –Base DisturbanceAcid –Base Disturbance

  Section Section 1. Acid-Base Balance1. Acid-Base Balance

SectionSection 2.  Simple types of acid-base 2.  Simple types of acid-base

disturbancedisturbance

SectionSection 3. Mixed Acid-base 3. Mixed Acid-base Disturbance Disturbance

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Section Section 1. Acid-Base 1. Acid-Base BalanceBalance

(1) Sources of acid and base(1) Sources of acid and base

(2) Regulation of acid-base balance(2) Regulation of acid-base balance

(3) Laboratory parameters of acid-base(3) Laboratory parameters of acid-base

balancebalance

   

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Homeostasis is very important Homeostasis is very important for life. Acid-base balance is one of for life. Acid-base balance is one of the major requirements ( volume, the major requirements ( volume, osmolarity of the body fluid, etc.). osmolarity of the body fluid, etc.).

The basic meaning of acid-base The basic meaning of acid-base balance is the stable [Hbalance is the stable [H++] in the body ] in the body fluid. fluid.

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(1) (1) Sources of acid and baseSources of acid and base

The main origin of acid and base The main origin of acid and base is the intracellular metabolism is the intracellular metabolism (catabolism of protein, carbohydrate (catabolism of protein, carbohydrate and fat). and fat).

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Two kinds of acids are formed Two kinds of acids are formed

from metabolism: from metabolism: 1) volatile acid,1) volatile acid,

2) nonvolatile acid.2) nonvolatile acid.

The volatile acid is the acid, The volatile acid is the acid,

which can be eliminated from lung which can be eliminated from lung

(respiration).(respiration).

The nonvolatile acid has to be The nonvolatile acid has to be

eliminated from kidneys within urine. eliminated from kidneys within urine.

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11) Volatile acid) Volatile acid

The COThe CO22 is the end-product of oxidative is the end-product of oxidative metabolism of protein, carbohydrate and fat. metabolism of protein, carbohydrate and fat. The daily production of HThe daily production of H++ (H (H22COCO33) is ) is 13~15(20) Mol. 13~15(20) Mol.

HH22COCO33 can be dissociated to form can be dissociated to form hydration (Hhydration (H22O) and COO) and CO22..

CA CA (carbonic anhydrase)(carbonic anhydrase) HH22COCO33 ←--→H ←--→H22O+ COO+ CO22 The COThe CO22 can be eliminated from pulmonary can be eliminated from pulmonary

expiration, so Hexpiration, so H22COCO33 is volatile acid. is volatile acid.

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2) unvolatile acid (fixed acid)2) unvolatile acid (fixed acid)

Uric acid, phosphoric acid (HUric acid, phosphoric acid (H33POPO44) and ) and

sulfuric acid (Hsulfuric acid (H22SOSO44) are the products in the ) are the products in the

metabolic process of proteins and nuclear acids.metabolic process of proteins and nuclear acids.

Lactic acid and ketonic bodies(Lactic acid and ketonic bodies(ββ--

hydroxybutyric acid hydroxybutyric acid ββ-- 羟 丁 酸羟 丁 酸 and acetoacetic and acetoacetic

acid acid 乙 酰 乙 酸乙 酰 乙 酸 ) can be formed from the ) can be formed from the

metabolic process of carbohydrate and fat as metabolic process of carbohydrate and fat as

intermediate products, when the oxygen supply intermediate products, when the oxygen supply

is not sufficiency.   is not sufficiency.  

([H([H+]=70~100 mmol/ per day) ]=70~100 mmol/ per day)

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3) 3) BaseBase

The production of acid (HThe production of acid (H22COCO33, organic , organic acids) is much more than the production acids) is much more than the production of base (deamination of AAof base (deamination of AA――>NH>NH33) from ) from the metabolism in normal diet.the metabolism in normal diet.

The vegetables, and fruits also The vegetables, and fruits also contains some base (such as citrate (contains some base (such as citrate ( 柠檬柠檬酸盐酸盐 ) ) oxalateis(oxalateis( 草酸盐草酸盐 ) ) the Hthe H+ + acceptor ).acceptor ).

Citrate + HCitrate + H+ + = citric acid= citric acid

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(2) (2) Regulation of acid-base balanceRegulation of acid-base balance

1) Chemical buffers1) Chemical buffers 2) Respiratory regulation2) Respiratory regulation 3) Renal regulation3) Renal regulation 4) Cellular regulation4) Cellular regulation

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1) 1) Chemical buffersChemical buffers

Buffer pair (buffer system) consists of a weak acid Buffer pair (buffer system) consists of a weak acid and its’ salt, such as and its’ salt, such as

NaHCONaHCO3 3 NaNa22HPOHPO4 4 HbHb- Pr- - Pr- HbOHbO--22

----------- ----------- ------------ ----- ----- ---------------------- ----- ----- ---------- HH22COCO3 3 NaHNaH22POPO4 4 HHb HPr HHbOHHb HPr HHbO22

HH22SOSO44 ( (sulfuric acid)sulfuric acid) + NaHCO + NaHCO33 = Na = Na22SOSO44 + H + H22COCO33

A strong acid (HA strong acid (H22SOSO4,4, HCl) become a weak acid after HCl) become a weak acid after

combining to NaHCOcombining to NaHCO3 3 --. A strong base becomes a weak base A strong base becomes a weak base

after combining to Hafter combining to H22COCO33.

Minimal changes of [Minimal changes of [HH+ ].+ ].

Immediately available (first defense line) Immediately available (first defense line)

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buffer systembuffer system the % account

----------------------------------------------------------------------------------- -----------------------------------------------------------------------------------

HCOHCO--33/H/H22COCO33 53%53%

HbHb--/HHb /HHb HbOHbO--

22/HHbO/HHbO2 2 35%35%PrPr--/HPr 7%/HPr 7%Phosphate 5% Phosphate 5% ----------------------------------------------------------------------------------------------------------------

NaHCONaHCO33 can be effectively eliminated by can be effectively eliminated by

kidneys and (Hkidneys and (H22COCO33 ←→ ←→HH22O + COO + CO22) CO) CO22 can can

be effectively eliminated by the lung.be effectively eliminated by the lung.

HCOHCO--33/H/H22COCO3 3 is the most important buffer pair.is the most important buffer pair.

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2) Respiratory regulation2) Respiratory regulation

Increased PaCOIncreased PaCO22 (>60mmHg, 8kPa) (>60mmHg, 8kPa) decreases pH of ESF, which can decreases pH of ESF, which can stimulate the respiratory center via stimulate the respiratory center via central chemoreceptors and increase central chemoreceptors and increase the depth of respiration the depth of respiration (hyperventilation, tidal volume increased)(hyperventilation, tidal volume increased). .

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High PaCOHigh PaCO22 Low pH Low pH of ESFof ESF

via central via central chemoreceptochemoreceptorsrs

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 PaCOPaCO22

normal normal pHpH

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Increased PaCOIncreased PaCO22 (>60mmHg, 8kPa) (>60mmHg, 8kPa) and decreased pH can both stimulate and decreased pH can both stimulate the respiratory center via peripheral the respiratory center via peripheral chemoreceptors and increase the depth of chemoreceptors and increase the depth of respiration respiration (hyperventilation, tidal volume (hyperventilation, tidal volume increased)increased). .

More COMore CO22 can be eliminated from can be eliminated from lung, so that the [Hlung, so that the [H22COCO33] in blood will fall ] in blood will fall to normal range, the pH will increase to to normal range, the pH will increase to normal by regulate the ratio of [HCOnormal by regulate the ratio of [HCO33--] and [H[H22COCO33] . ] .

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Higher pH and low PaCOHigher pH and low PaCO22 will will inhibit the respiratory center, the depth inhibit the respiratory center, the depth of respiration will decrease of respiration will decrease (hypoventilation), the CO(hypoventilation), the CO22 will increase will increase in the blood, then [Hin the blood, then [H22COCO33] in blood will ] in blood will increase to normal and pH will increase to normal and pH will decrease.decrease.

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Characteristic of respiratory Characteristic of respiratory compensationcompensation

(a) Timeliness. (a) Timeliness.

The respiratory response begins within The respiratory response begins within several minutes.several minutes.

The respiratory response often takes 30 The respiratory response often takes 30 minutesminutes for the respiratory compensation. for the respiratory compensation.

12~24 hours to get maximal 12~24 hours to get maximal compensation.compensation.

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(b) The degree of ventilatory response (b) The degree of ventilatory response (([H[H22COCO33]],PaCO,PaCO22) is proportional to the ) is proportional to the degree of metabolic acidosis or alkalosis degree of metabolic acidosis or alkalosis ([([HCOHCO33¯̄ ]). ]).

The degree of compensation The degree of compensation (decrease of [H(decrease of [H22COCO33]) may be ]) may be predicted by the decreased level of predicted by the decreased level of [HCO[HCO33¯̄ ]. Some equations have been ]. Some equations have been developed for the prediction.developed for the prediction.

There is s maximum of limitation of compensationThere is s maximum of limitation of compensation

Significance. Significance.

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(c) Normal PaCO(c) Normal PaCO22 = 40 mmHg = 40 mmHg

4040――>60mmHg: stimulates >60mmHg: stimulates respiratory respiratory

center.center.

80 mmHg80 mmHg――>: inhabits respiratory >: inhabits respiratory

center.center.

(CO(CO22 narcosis, CO narcosis, CO22 麻麻醉醉 ))

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3) Renal regulation3) Renal regulation

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

Kidneys play a major role in the Kidneys play a major role in the regulation of pH in the body.regulation of pH in the body.

The renal regulation consists of two The renal regulation consists of two processes.processes.

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(a) Excretion of acids(a) Excretion of acids

a)Secretion of Ha)Secretion of H+, NH4+

b)Excrete all the nonvolatile acid b)Excrete all the nonvolatile acid (70~100 mmol/ per day) produced from (70~100 mmol/ per day) produced from catabolism of food.catabolism of food.

(b) Reabsorb properly the bicarbonate(b) Reabsorb properly the bicarbonate filtered from glomerulus. filtered from glomerulus.

When the pH is decreased, more When the pH is decreased, more bicarbonate needs to be reabsorbed. bicarbonate needs to be reabsorbed.

If the pH is increased, more If the pH is increased, more bicarbonate will be eliminated.bicarbonate will be eliminated.

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Mechanisms of HMechanisms of H++excretion and excretion and HCO3HCO3–– reabsorption: reabsorption:① ① in proximal tubule:in proximal tubule:Via NaVia Na+ - H - H+ antiportor (NHE antiportor (NHE 反向转运体反向转运体 ))Via actively secretion of HVia actively secretion of H++

Via secretion of NHVia secretion of NH33/NH/NH44+

② ② in distal tubule+collecting ductin distal tubule+collecting ductHH+ --ATPaseATPaseHH+ -K -K+ATPaseATPaseClCl-- -HCO -HCO33- exchanger

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① ① in proximal tubule:in proximal tubule:(a)Na+-H+ 反向转运体 antiportor NHE

细胞内 CA 碳酸酐酶催化 H2O+CO2 形成 H2CO3, 再解离为 H+ 和 HCO3-

管腔膜有 Na+ -K+ ATP 酶保持低 [Na+]i( 浓度差 ), 促经 NHE, 细胞内 H+ 进小管液 ,

小管液 Na+ 进肾小管细胞 , 再结合 HCO3 -, 经基侧膜 Na+ -HCO3 - 载体同向重吸收 ,结果 : 小管上皮细胞向管腔液分泌 1mol H+, 同时血浆增 1mol HCO3- 肾小管细胞内 CO2 来自于肾小管

腔 . 管腔内 CO2 来自于上游 HCO3 -

实为血液中 HCO3-, 滤过后重吸收 .

由 NHE 排出的 H+, 和 HCO3 - 形成 H2CO3, 再形成 CO2, 也被重吸收入肾小管上皮细胞 . 最终只有 H2O 排出 .

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① ① in proximal tubule:in proximal tubule:

((b) Actively b) Actively secretion of Hsecretion of H++

通过管腔膜通过管腔膜 HH++--ATPATP 酶主动耗能将酶主动耗能将HH+ 分泌至肾小管腔内分泌至肾小管腔内 ..

尿液酸化尿液酸化 ..

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① ① in proximal tubule: in proximal tubule: (c)(c)Via secretion ofVia secretion of NH NH33/NH/NH44+

谷氨酰胺在谷氨酰胺酶 (GT) 作用下 , 形成谷氨酸 , 再形成 NH3 和 α-酮戊二酸, 后者再形成HCO3- 。

NH3+H+ 形成 NH4+ ,由 Na+-H+ 反向转运体( NHE )进入小管液。

HCO3- 经基侧膜Na+ - HCO3- 载体同向重吸收。

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非离子扩散形式泌 NHNH33 : 肾小管中的 NH4+ 在髓

袢升支粗段再分解为 H+

和 NH3 , H+ 通过NHE ( Na+-H+ 反向交换体)泌出,而 NH3 弥散到集合管,与集合管上皮泵出的 H+ 形成 NH4+ 排出。

使尿液进一步酸化 . NHNH44+ 是水溶性 .

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② ② in distal tubule+collecting ductin distal tubule+collecting duct αα 闰细胞(泌氢细胞)非闰细胞(泌氢细胞)非NaNa+ 依赖性向管腔泌依赖性向管腔泌 HH+

在管腔膜通过:在管腔膜通过: (a) H(a) H+-ATP-ATP 酶向管腔泌酶向管腔泌 HH+;; (b) H(b) H+-K-K+ ATP ATP 酶泌酶泌 HH+ 换换 KK+

使尿液酸化(使尿液酸化( HH22POPO44-- 和和NHNH44+ 增多增多)) 在基侧膜经交换在基侧膜经交换 ClCl--,, 回吸回吸收收 HCOHCO33-- 进血。进血。

β 闰细胞通过基侧膜闰细胞通过基侧膜HH+-ATP-ATP 酶向血液排酶向血液排 HH+ ;;通通过管腔膜向管腔排过管腔膜向管腔排 HCOHCO33-- 与与ClCl-- 交换,使尿液碱化。交换,使尿液碱化。

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PhosphatePhosphate

There are two kinds There are two kinds of phosphate in of phosphate in urine:urine: (1) dibasic form (1) dibasic form (Na(Na22HPOHPO44 ) and ) and (2) monobasic form (2) monobasic form (NaH(NaH22POPO44 ).).

NaNa22HPOHPO4 4 + H+ H++ ←→ NaH ←→ NaH22POPO44 + Na + Na++

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Most of the Most of the phosphate in the phosphate in the glomerular filtrate is glomerular filtrate is dibasic form (Nadibasic form (Na22HPOHPO44 ) ) with buffering function. with buffering function. There is more There is more NaHNaH22POPO44 in the final in the final urine as the result of urine as the result of combining Hcombining H++.. When the final When the final urine pH is 4.8, 99% of urine pH is 4.8, 99% of phosphate is NaHphosphate is NaH22POPO44 at the same time the at the same time the more NaHCOmore NaHCO33 is is reabsorpted. reabsorpted.

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4) Cellular regulation4) Cellular regulation

(a) H(a) H++-K-K++ exchange exchange

(b) Cl(b) Cl¯̄ - HCO - HCO33¯̄ exchange exchange

  (c) Utilizing of bone salt (c) Utilizing of bone salt ((d) Synthesis of urea from NHd) Synthesis of urea from NH33

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(a) H(a) H++-K-K++ exchange exchange

When [HWhen [H++] in ECF ] in ECF (serum) is increased, (serum) is increased, the Hthe H++ will move into will move into the cells, as a the cells, as a exchange for exchange for electrical neutrality, electrical neutrality, KK++ will shift from ICF will shift from ICF to the ECF. So the pH to the ECF. So the pH of ECF (serum) will of ECF (serum) will increase to normal, increase to normal, but hyperkalemia but hyperkalemia may occur.may occur.

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(b) Cl ¯ - HCO(b) Cl ¯ - HCO33¯ exchange¯ exchange

When COWhen CO2 2 in ECF(serum) is increased, in ECF(serum) is increased, COCO2 2 will move into the cells, COwill move into the cells, CO2 2 combines combines HH22O to form carbonic acid, then HO to form carbonic acid, then H2 2 COCO33 dissociates to form Hdissociates to form H++ and HCO and HCO33¯̄ , the , the HCOHCO33¯̄ moves out of the RBC,for neutrality, moves out of the RBC,for neutrality, Cl Cl ¯̄ moves into the cells. moves into the cells.

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© Utilizing of bone salt© Utilizing of bone salt

In chronic metabolic acidosis, In chronic metabolic acidosis, bone bone salt, Casalt, Ca33(PO(PO44),), 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).

    CaCa33(PO(PO44))22 + 4H + 4H+ + ←→←→ 3 Ca 3 Ca2+2+ + 2 H + 2 H22POPO4 4 ¯̄ Is it a good way of regulating acid-base Is it a good way of regulating acid-base

balance ?balance ?

((d) Synthesis of urea from NHd) Synthesis of urea from NH3 3 in liver cells.in liver cells.

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(4) (4) Laboratory parameters of acid-Laboratory parameters of acid-base balancebase balance

1) pH1) pH 2) PaCO2) PaCO22 (partial pressure of carbon (partial pressure of carbon

dioxide indioxide in arterial blood)arterial blood) 3) Standard bicarbonate (SB)3) Standard bicarbonate (SB) Actual bicarbonate (AB)Actual bicarbonate (AB) 4) Buffer base (BB)4) Buffer base (BB) 5) Base excess (BE)5) Base excess (BE) 6) Anion gap (AG)6) Anion gap (AG)

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1) 1) pHpH

pH is the negative logarithm (-log) of pH is the negative logarithm (-log) of [H[H++] in a solution. [H] in a solution. [H+]=40nmol/L ]=40nmol/L (pH=7.4)(pH=7.4)

The normal range in artery blood =7.35~7.45 (7.41)The normal range in artery blood =7.35~7.45 (7.41) The survival range of pH=6.8~7.8The survival range of pH=6.8~7.8

According to the Henderson-According to the Henderson-Hasselbalch equation:Hasselbalch equation:

The pKa is the dissociation constant of carbonic acid The pKa is the dissociation constant of carbonic acid (=6.1)(=6.1)

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24 [HCO24 [HCO33 ¯ ] metabolic factor ¯ ] metabolic factorpH =6.1+ log --------------------------------------- pH =6.1+ log --------------------------------------- 1.2 [H1.2 [H22COCO33] respiratory factors] respiratory factors 20 20 = 6.1+ log---------- =6.1+1.3=7.4= 6.1+ log---------- =6.1+1.3=7.4 11

The pH is determined by the ratio ofThe pH is determined by the ratio of

[HCO[HCO33¯ ] 20¯ ] 20 --------------=-----------------------=--------- [H[H22COCO33] 1] 1 No matter how the absolute amounts of HCONo matter how the absolute amounts of HCO33¯ ¯ and Hand H22COCO33 change, once the ratio remains 20/1, the change, once the ratio remains 20/1, the pH would be 7.4 (normal). pH would be 7.4 (normal).

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24 [HCO3 ¯ ] metabolic factor24 [HCO3 ¯ ] metabolic factorpH =6.1+ log --------------------------------------- pH =6.1+ log ---------------------------------------

1.2 [H2CO3] respiratory 1.2 [H2CO3] respiratory factorsfactors

The primary changes determines The primary changes determines the nature of the acid-base imbalance.the nature of the acid-base imbalance.

The purpose of secondary change is The purpose of secondary change is to restore the pH. to restore the pH.

According to the pH:According to the pH: compensatory acid-base disturbancescompensatory acid-base disturbances decompensatory acid-base decompensatory acid-base

disturbancesdisturbances

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Clinical significanceClinical significance

(anticoagulant artery blood, insulation of (anticoagulant artery blood, insulation of air)air)

A normal range of pH may represent A normal range of pH may represent three different situations:three different situations:

① ① acid-base balance;acid-base balance;

② ② compensatory acidosis or alkalosis; compensatory acidosis or alkalosis; (causes??)(causes??)

③ ③ a mixed decompensatory acidosis and a mixed decompensatory acidosis and decompensatory alkalosis. decompensatory alkalosis.

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(( 教材教材 106106 页表下一段有错)页表下一段有错)

pH<7.35 decompensatory acidosis pH<7.35 decompensatory acidosis

acidemia (causes??)acidemia (causes??)

pH>7.45 decompensatory alkalosis pH>7.45 decompensatory alkalosis

alkalemia (causes??)alkalemia (causes??)

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2) 2) PPaaCOCO22

COCO2 2 in blood:in blood: (a) 23% HbCO(a) 23% HbCO22 in RBC in RBC (b) 70% HCO(b) 70% HCO33- in plasma- in plasma (c) 7% CO(c) 7% CO22 molecule in plasma molecule in plasma PaCOPaCO22 is the tension of CO is the tension of CO22 caused by caused by COCO22 molecule movement. molecule movement. The normal range = 33~46(40) mmHg The normal range = 33~46(40) mmHg (4.39~6.25 kPa).(4.39~6.25 kPa). PaCOPaCO22 is almost equal to P is almost equal to PAACOCO22. .

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The capability of normal lung to The capability of normal lung to eliminate COeliminate CO22 is very good. CO is very good. CO22 retention retention will not occur with normal ventilation. will not occur with normal ventilation. Generally speaking, the PaCOGenerally speaking, the PaCO22 is is determined mainly by the respiration, so determined mainly by the respiration, so the PaCOthe PaCO2 2 is called the “respiratory is called the “respiratory factor”. factor”.

Higher PaCOHigher PaCO22 is due to the inhibition of is due to the inhibition of respiration. respiration.

Lower PaCOLower PaCO22 is due to overventilation. is due to overventilation.

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Significance Significance

PaCOPaCO22>46mmHg>46mmHg

Primary increase: respiratory acidosisPrimary increase: respiratory acidosis

Secodary increase: metabolic alkalosisSecodary increase: metabolic alkalosis

(compensated by lung)(compensated by lung)

PaCOPaCO22<33mmHg<33mmHg

Primary decrease: respiratory alkalosisPrimary decrease: respiratory alkalosis

Secodary decrease: metabolic acidosisSecodary decrease: metabolic acidosis

(compensated by lung)(compensated by lung)

Normal PaCONormal PaCO22 means ??? means ???

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3) 3) Actual bicarbonate (AB)Actual bicarbonate (AB) Standard bicarbonate (SB), Standard bicarbonate (SB),

The normal [HCOThe normal [HCO33¯̄ ] is 22~27(24) ] is 22~27(24) mmol/L.mmol/L.

AB is measured under “actual AB is measured under “actual condition”condition” in which both respiratory in which both respiratory factor and metabolic factor affected factor and metabolic factor affected the [HCOthe [HCO33¯̄ ]. ].

COCO22 +H +H22O=HO=H22COCO33=H=H+++HCO+HCO3 3 ¯̄

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SB is measured under “standard SB is measured under “standard condition”condition” (temperature 37~38℃, full (temperature 37~38℃, full oxygenation of hemoglobin, PaCOoxygenation of hemoglobin, PaCO2 2 = 40 = 40 mmHg). Standard condition means that mmHg). Standard condition means that the respiratory factor is eliminated, then the respiratory factor is eliminated, then the [HCOthe [HCO33¯̄ ] is only affected by ] is only affected by metabolic factor. metabolic factor.

Higher SB means metabolic alkalosis or Higher SB means metabolic alkalosis or respiratory acidosis compensated by kidneys. respiratory acidosis compensated by kidneys.

Low SB means metabolic acidosis or Low SB means metabolic acidosis or respiratory alkalosis compensated by kidneys.respiratory alkalosis compensated by kidneys.

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Normally the AB=SB.Normally the AB=SB.

If AB>SB (COIf AB>SB (CO22 retention), the retention), the reason must be the effect of reason must be the effect of respiratory factor, which indicates respiratory factor, which indicates respiratory acidosis or metabolic respiratory acidosis or metabolic alkalosis compensated by lung. alkalosis compensated by lung.

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If AB<SB (COIf AB<SB (CO22 depletion), the depletion), the reason must be the respiratory reason must be the respiratory factor, which means respiratory factor, which means respiratory alkalosis or the metabolic acidosis alkalosis or the metabolic acidosis compensated by lung.compensated by lung.

COCO22 +H +H22O=HO=H22COCO33=H=H+++HCO+HCO33--

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4) Buffer base (BB)4) Buffer base (BB)

Sum of all buffer basees in bloodSum of all buffer basees in blood In plasma: HCOIn plasma: HCO3 3 ¯̄ =24 =24 ProteinProtein¯̄ =17 =17 In RBC: HbIn RBC: Hb¯̄ HbOHbO22¯̄ =6.3 =6.3 HPOHPO44 22¯̄ =1.0 =1.0 BB=45~55 mmol/LBB=45~55 mmol/L Determined by metabolic factorsDetermined by metabolic factors

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SignificanceSignificance

Normal BB: Normal BB:

acid-base balanceacid-base balance

metabolic acidosis + metabolic alkalosismetabolic acidosis + metabolic alkalosis

Increased BB: Increased BB: metabolic alkalosismetabolic alkalosis

Decreased BB:Decreased BB:metabolic acidosismetabolic acidosis

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5) Base excess (BE)5) Base excess (BE)

Under “standard condition” (temperature Under “standard condition” (temperature 37~38℃, full oxygenation of hemoglobin, PaCO37~38℃, full oxygenation of hemoglobin, PaCO22 = = 40 mmHg), titrate the whole blood to pH7.4 with how 40 mmHg), titrate the whole blood to pH7.4 with how much acid or base (mmol/L).much acid or base (mmol/L).

If with acid, there is must more base (excess) in If with acid, there is must more base (excess) in the blood, BE is expressed with positive valuethe blood, BE is expressed with positive value

If with base, there is must more acid (deficit) in If with base, there is must more acid (deficit) in the blood, BE is expressed with negative valuethe blood, BE is expressed with negative value

Normal BE= -3.0~+3.0 Only metabolis factor Normal BE= -3.0~+3.0 Only metabolis factor determines the BE.determines the BE.

In metabolic alkalosis the positive BE increases.In metabolic alkalosis the positive BE increases.

In metabolic acidosis the negative BE increases.In metabolic acidosis the negative BE increases.

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6) Anion gap (AG) 6) Anion gap (AG) AG=UA-UCAG=UA-UC

UCUCUAUA

Na+

ClCl -

HCOHCO33 --

Determined Determined cationcation

Determined Determined anionanion

undetermined anions

undetermined cations

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UCUC

Na+ ClCl --

HCOHCO33 --AGAG

UAUA

The AG can be The AG can be calculated by: calculated by:

UA+ HCO3¯ + Cl¯ UA+ HCO3¯ + Cl¯ =UC+Na=UC+Na++

UA-UC=NaUA-UC=Na++-(Cl-(Cl¯̄ + + HCOHCO33¯̄ ) )

The normal The normal range is 10~14 range is 10~14 mmol/L.mmol/L.

    AG indicates AG indicates those anions, other those anions, other than HCOthan HCO33¯̄ and and ClCl¯̄, which is , which is required to required to counter-balance counter-balance NaNa++..

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Actually the AG represents the Actually the AG represents the proteins with negative charge, proteins with negative charge, phosphate, sulfate and organic phosphate, sulfate and organic anions (lactic acid, keto-acid, etc.). anions (lactic acid, keto-acid, etc.).

An increased AG is the same An increased AG is the same meaning as the accumulation of meaning as the accumulation of nonvolatile acids in the body and nonvolatile acids in the body and must be the metabolic acidosis.must be the metabolic acidosis.

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SignificanceSignificance

(a) For the classification of metabolic acidosis(a) For the classification of metabolic acidosis

a)metabolic acidosis with normal AG a)metabolic acidosis with normal AG ( with increased Cl ( with increased Cl ¯̄ ) and ) and

b) metabolic acidosis with high AG (with b) metabolic acidosis with high AG (with normal Cl normal Cl ¯̄).).

(b) Diagnosis of mixed acid-base imbalances(b) Diagnosis of mixed acid-base imbalances

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Reported by special instrument Reported by special instrument with expensive reagents.with expensive reagents.

COCO22CP indicates the [HCOCP indicates the [HCO33¯̄ ] in ] in venous blood sample under “actual venous blood sample under “actual condition”, that can be measured condition”, that can be measured easily without expensive instrument.easily without expensive instrument.