Zhao Mingyao: Bmc.zzu

Acid-base disturbance Zhao Mingyao BMC.ZZU

Section 1

Acid-base biochemistry

What is acid? What is base? pH in arterial blood 7.35~7.45

1. Generation of Acid-Base (1) Sources of acid: 1 ） volatile acid H2CO3 → H2O + CO2↑

2 ） fixed acid (non-volatile acid)

(2) Sources of bases （ 1 ） products of metabolism （ small amounts ）。 Such as ammonia (NH 3) （ 2 ） dietary intake （ vegetables and fruits ） sodium citrate.

Normally,acids >bases

2. Henderson-Hasselbalch`s equation ?

(

)

2.Henderson-Hasselbalch Equation

pH=pKa+lg =pKa+lg

[HCO3 － ] [H2CO3] 20 1

= 6.1 +1.3 = 7.4 pH of A 7.35~7.45

pH

[HCO3 － ] [H2CO3]

Strong acid pulse

Strong base pulse

20 1 = 6.1 +1.3 = 7.4 pH of A 7.35~7.45

Mechanism of buffer HCl+NaHCO3→NaCl+H2CO3→CO2+H2O NaOH + H2CO3→NaHCO3 + H2O

Accept or release + H when face strong acid or strong base

What is compensatory acid-base imbalance? What is incompensatory acidbase imbalance?

Henderson-Hasselbalch Equation • Compensatory ~: pH normal, but ? change • Decompensatory ~: pH, HCO3 -,H2CO3 all change

Section 2 Regulation of acidbase in body fluid

Why does body keep acid-base balance of body fluid ?

[H+] → enzyme →ATP→ cell

ion distribution→ electrical action

body maintain humoral acidbase balance by 1. Blood buffer system 2. lung 3.kidney 4. cell

Blood buffer system

pH H

+

[HCO3 － ]

kidney

[H2CO3]

cell lung

20 1

1. Blood buffer system

[HCO3 － ] [H2CO3]

2. Pulmonary regulation

central control

PaCO2 + Peripheral chemoreceptor

PaO2 、 pH 、 PaCO2 peripheral regulation

CNS

3. Renal regulation

 excreting fixed acid  maintaining plasma [HCO3- ]

(1) bicarbonate reabsorption (NaHCO

3

~)

(2) phosphate acidification

(3) ammonia excretion

convert dibasic phosphate to the monobasic form.

• an oral phosphate load is as effective as a phosphate infusion in elevating the urinary PCO2 and, therefore, could have a wide application in the pathophysiologic evaluation of renal tubular acidosis. •

• 18 normal children, aged 3-13 years, were studied. Following the oral phosphate load, the urinary phosphate concentration increased to 44.8 +/- 4.7 mmol/l (mean +/SEM), and U-B PCO2 reached 68.8 +/- 7.0 mm Hg, with a urinary pH of 6.87 +/- 0.07. With a urinary phosphate concentration above 20 mmol/l, all children reached a U-B PCO2 above 40 mm Hg. 4 children with primary distal renal tubular acidosis were also studied. All exhibited a U-B PCO2 below 20 mm Hg despite values of urinary phosphate concentration at or above 20 mmol/l, indicating the presence of a true secretory defect in distal hydrogen ion secretion.

4. cellular buffer • H+-K+ exchange between intra- and extracell • Cl--HCO-3 exchange between intra- and extra - RBC

(1) phosphate buffer system Na2HPO4/NaH2PO4

In kidney and cell

(2) Pr

protein buffer system

－

/HPr In cell

(3) Hemoglobin buffer system Hb /HHb 、 HbO /HHbO -

2

2

specific in RBC ,

Section 3 Laboratory tests

the parameters of acid-base representing pH PaCO2 HCO3Annion gap(AG)

1.

pH in normal level

1. true normal 2. compensatory ~ 3. mixed ~ with opposite effect

Weak tolerance to alkalosis

pH

6.8

death 【 H+ 】 160

7.35

7.45

acidosis

alkalosis 40

7.8 death 16 nmol/L

2. partial pressure of carbon dioxide, PaCO2

definition: tension produced by CO2 dissolved physically in plasma normal: 40mmHg (35~45) [H2CO3]: 40 X 0.03=1.2mmol/L

primary↑—Res Acidosis primary↓—Res alkalosis

3. HCO

3

normal: 24 mmol/L(22~27) SB BB BE

and

AB

4. anion gap ， AG

AG = UA – UC UA:Undetermined anion UC:Undetermined cation

Na+

AG = UA - UC

Cl-

Na++ UC = Cl- + HCO3- + UA AG = Na - Cl - HCO = 140-104-24 = 12 (mmol/L) +

-

3

HCO3AG

UA

UC

normal 10 ～ 14 mmol/L

Significance: distinguish metabolic acidosis

Summary of indexes 1. pH 2. Metabolic factor HCO3-(SB, BB, BE), AG 3. Respiratory factor

PaCO2

Section 4 Simple acid-base disorders

• Concept • Compensation

Classification of ~ pH acidosis alkalosi s

causes metabolic(HCO3)

respiratory(H2C O )

Classification of ~ pH

acidosis

alkalosis

metabolic respiratory metabolic respiratory [HCO3-]↓

PaCO2↑

[HCO3-]↑

PaCO2↓

Part 1 Metabolic acidosis

concept [HCO3-]p ↓ primarily

Changes of laboratory test primary: pH ? HCO3- ↓ secondary: PaCO2 ↓ [K ＋ ]b↑

classification  Met acidosis with High

AG  Met acidosis with Normal AG

Na+

Na+

Cl-

Cl-

Cl-

HCO3-

HCO3AG

AG

UA

Na+

UC

normal

UA Met acidosis with High AG

UC

AG （）

HCO3-

UA

UC

Met acidosis with normal AG

Normal: 10~14

Comparison between Met acidosis with High AG and normal AG

1. Cause and mechanisms : fixed acid production↑ fixed acid removing↓ HCO3- loss↑ hyperkalemia hyperchloremia

causes 1.HCO3 － loss --- diarrhea , intestinal suction

2.Acid production↑or Acid intake ----lactic acidosis( 乳酸酸中毒 ) , ketoacidosis ( 酮 症酸中

, drugs RTA 急

毒 ) , excess acetylsalicylic acid

3.Excreting acid ↓---yielding hydrochloride acid

、慢性肾衰泌 H ＋ 减少

causes

4. HCO3-diluted 5.hyperkalemia * paradox alkaline urine

2. Compensation of body (1)plasma buffer H++ HCO3-→H2CO3 (2)respiratory regulation [H ＋ ]p↑→ventilation↑ → CO2 excretion↑

(3) renal compensation  excreting H ＋   excreting NH3↑  reabsorbing HCO3-↑  acidic urine

(4) Intracellular buffering Renal tubular lumen

ECF

[H ＋ ]↑ [K ＋ ]b↑

H ＋ +Pr→HPr K＋

H＋ Na ＋ exchange↑ ＋ K Na ＋ exchange ↓

acidosis→hyperkale mia

3.Effects on the body (1) cardiovascular system  inhibiting myocardial contraction  arrhythmia  responsibility↓of vessel to catecholamine

(2) central nervous system cerebral energy production↓  GABA ↑ ~ decarboxylae Glutamate (+)

GABA↑

4. Principle of prevention and treatment 1.treatment of primary disease 2.supplement of base NaHCO3 THAM(Tris) lactic sodium

3.correcting and preventing water, electrolytes disorders

Part 2 Respiratory acidosis concept

[H2CO3 ] p↑primarily

1. Causes and mechanisms  excreting CO2 ↓  inhaling excessive CO2

2. Compensation of

respiratory acidosis

(1) intracellular buffering  RBC

CO2 ↑

CO2+H2O→H2CO3

[HCO3- ] ↑

HCO3K

+

CO2+H2O→H2CO3

 plasma

H+

[K+]↑

H+ +HbHHb

Cl-

Cl-

(2) renal compensation Chronic Res acidosis: CO2 retention>24h

   

excreting H+↑ excreting NH3 ↑ reabsorbing HCO3- ↑ urinary pH↓

changes of laboratory test Acute : pH

PaCO2

HCO3-

PaCO2 10mmHg HCO3 － compensatary 1 mmol/L

Chronic : pH

PaCO2

HCO3-

PaCO2 10mmHg HCO3 － compensatary↑ 3.5 mmol/L

3. Effect of respiratory acidosis Similar to Met Acidosis, but obvious sign of CNS  CNS Acidosis  cerebral blood flow↑  with hypoxia in same

4.Principle prevention and treatment

1.inproving alveolar ventilation 2.supplement of base

Part 3 Metabolic alkalosis 1. • • • •

Base intake H+ loss Hypokalemia hypochloremia

1.Causes and mechanisms Classification : saline-responsive alkalosis saline-resistant alkalosis

(1) H ＋ loss from the gastric lumen

(2) H ＋ Loss from the Kidney alkalosis induced by chloride depletion mineralocorticoid excess primary 、 secondary (ECBV decresased)

(3). alkalosis induced by potassium depletion

K

K

＋

＋

H+

Renal tubule

cell

[K ＋ ]b↓

H+

hypokalemia

K＋ H+

Na ＋ ↓ Na ＋ ↑

alkalosis

(4) hypochloremia Diuretic Cl- 、 Na ＋ 、 H2O reabsorbed in loop↓ urine flow velocity ↑in distal tubule K ＋ -Na ＋ exchange↑ Excreting H+↑, [HCO3-]reabsorbing↑, [K ＋ ]↓

(5) Excess bicarbonate intake

( 二 ) Compensation 1.plasma buffer HCO3-+HPr

H2CO3+Pr- limited

( 代偿有限 )

2.respiratory regulation [H ＋ ]↓ ventilation↓ exhaling CO2 ↓

3. intracellular buffering Renal tubular lumen

[H ＋ ]↓ in ECF

H＋ K＋ ＋

H ＋ +Pr←HPr K K＋ ↑

alkalosis

H＋ Na ＋ exchange↓ Na ＋ exchange

4. renal compensation  excreting H ＋ ↓  excreting NH3↓  reabsorbing HCO3- ↓  urinary pH ↑

( 三 ) Effects 1. central nervous system ？  GABA↓ ~ decarboxylae glutamate (-) γ –GABA

GABA↓

2. increase in neuromuscular excitability ( 神经肌肉应激性升高 ) mechanism: 1. pH↑ ， Free [Ca2+ ]b↓ 2.CNS + +

手足搐搦 (Carpopedal Spasm)

3. left-shift of oxygen dissociation curve ( 血红蛋白解离曲线左移 )

4. hypokalemia

5. changes of laboratory test 原发性 : pH SB AB BB BE正值 继发性 : PaCO2 ↑ 血 [K ＋ ]↓

( 四 ) Principle of prevention and treatment 1.treatment of primary disease

2.normal saline( 生理盐水 )

♣ saline-responsive alkalosis ( 盐 水反应性碱中毒 )

♣ saline-resistant alkalosis ( 盐水抵 抗性碱中毒 )

3. 含氯酸性药

Part 4 Rrespiratory alkalosis

( 一 ) Causes and mechanisms excreting excessive CO2 1. Hypotonic hypoxia 2. disease of CNS 3. psychological factors ( 精神因素 ) 4. hypermetabolism ( 高代谢 ) 5. drugs

( 二 ) Compensation of respiratory alkalosis

1. intracellular buffering [H2CO3]b↓

 RBC H2CO3 血 [K

HCO3- + H+ ＋

＋ K ]b↓ CO2

 plasma

H+

HHb

K＋ H2CO3 H++ HCO3ClCl-↑

HCO3-

2. renal compensation  excreting H ＋ ↓  excreting NH3↓  reabsorbing HCO3- ↓  urinary pH ↑

3. changes of laboratory test 急性 : pH

PaCO2

AB < SB

PaCO2 10 mmHg HCO3 － 代偿性 ↓ 2 慢性 : pH PaCO AB < SB 2 mmol/L PaCO2 10mmHg HCO3 － 代偿性 ↓ 4 mmol/L

( 三 ) Effect of respiratory alkalosis  similar to Met Alkalosis  PaCO2↓

cerebral blood flow ↓

Rapid and obvious

( 四 )Principle of prevention and treatment 1.treatment of primary disease 2. inhaling CO2 (Paper mask or 5% CO2 )

15.Why does the neuromuscular excitability increase during alkalosis?

16.Why are some metabolic alkalosis sensitive to NS(NaCl), but some not?

Proton-secreting cells in the wall of the vas deferens glow brightly when stained with an antibody against H+ ATPase

Section 5 Mixed acid-base disorders

一、 A mixed respiratory acidosismetabolic acidosis 1. causes

( 呼酸合并代酸 )

呼吸心跳骤 停

2. characteristics

 pH↓↓  PaCO2↑  [HCO3-]↓

二、 A mixed respiratory alkalosismetabolic alkalosis

1. causes

( 呼碱合并代碱 )

高热合并呕吐 肝硬化应用利尿 剂

2. characteristics

 pH ↑↑  PaCO2 ↓  [HCO3-] ↑

三、 A mixed respiratory acidosismetabolic alkalosis

1. causes

( 呼酸合并代碱 )

慢性肺疾患应用利 尿剂或合并呕吐

2. characteristics  pH (-) 、 ↑、 ↓  PaCO2↑  [HCO3-] ↑

四、 A mixed respiratory alkalosis-metabolic acidosis 1. causes

水杨酸中毒 肾衰合并通气过 度

2. characteristics  pH (-) 、 ↑、 ↓  PaCO2 ↓  [HCO3-] ↓

五、 A mixed metabolic acidosis- metabolic alkalosis( 代酸合 并代碱 )

1. causes

呕吐伴有腹 泻 肾衰伴呕吐

2. characteristics  pH 、 PaCO2 、 [HCO3-] 不 定

Triple( 三重性 ) Acid-base disturbances



呼酸 + 代酸

+ 代碱

 呼碱 + 代酸 + 代碱

End

05-09-10

9.Why does acidosis inhibit CNS , but alkalosis exciting CNS?

10.What are affects of acidosis to circulatory system?

11.What are affects of acidosis to bone?

12.How do we treat acidosis? cause ventilation drug NaHCO3 lactate Tris(THAM)

Birds have one-way airflow through their lungs. This has two advantages in extracting oxygen from the air: Birds have one-way airflow through their lungs. This has two advantages in extracting oxygen from the air:

•

1. No dead space. Your lungs can't completely collapse (well, if they do, you're in trouble) and thus some old air is always left in the lung to mix with air from each new breath; in humans this is about 30%. In birds, every breath completely replaced the air in the lungs.

•

2. Countercurrent exchange. Your lungs can only extract about half of the oxygen in the air (which is already depleted by #1), because oxygen can only diffuse into blood until air and blood have an equal oxygen concentration. Countercurrent exchange means that blood and air flow in opposite directions, so the most oxygenated blood is in contact with the most oxygenated air, and vice versa. This means that oxygen can always diffuse into blood with a lower oxygen concentration, and birds are able to extract nearly all the oxygen from the air.

The sample of human lung tissue illustrated in the digital image above was labeled with wheat germ agglutinin (WGA) conjugated to Texas Red-X. WGA, which selectively binds to N-acetylglucosamine and N-acetylneuraminic (sialic acid) residues, is well suited for staining the Golgi complex in mammalian cells. The tissue sample was also labeled with Alexa Fluor 488 conjugated to phalloidin (targeting F-actin) and DAPI (targeting DNA in cell nuclei). Images were recorded in grayscale with a 12-bit digital camera coupled to either a Nikon E-600 or Eclipse 80i microscope equipped with bandpass emission fluorescence filter optical blocks. During the processing stage, individual image channels were pseudocolored with RGB values corresponding to each of the fluorophore emission spectral profiles.

Lung cell