Chapter 4

Acid-base balance and

acid-base disorders

Department of Pathophysiology, the School of Medicine, Shandong University

薛冰

internal environment homeostasis

Water balance

homeostasis

acid-base balance electrolyte balance

1. Acid-Base BalanceAcid-base BiochemistryRegulation of pHLaboratory Tests

2. Simple Acid-base DisordersMetabolic AcidosisRespiratory AcidosisMetabolic Alkalosis Respiratory Alkalosis

3. Mixed Acid-base Disturbance

Contents

Part I:

Acid-base balance and its regulation

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

I 、 Concept of acid and baseacid ： An acid is a H+ donor, when it is dissolved in water. After the loss of H+, it becomes a base. HA (acid) → H+ + Aˉ(base) H2CO3 → H+ +HCO3ˉ H2SO4, H3PO4

base ： A base is a H+ acceptor, when it is dissolved in water. After the combining of H+, it becomes an acid Aˉ(base)+ H+ → HA (acid) HCO3ˉ +H+ → H2CO3 OH-, HCO3

-, SO42-, HPO4

2-, NH3

(I) Source of acid

volatile acid

fixed acid

II 、 Sources of acid and base

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

daily production ： 300-400L/d

Excretion:lung

1.volatile acid—— H2CO3

CO2CO2 ＋ H2OH2O H2CO3

CACA

metabolism of protein, carbohydrate and fat

H+ + HCO3-

Reabsorption in kidney

RBC 、 kidney tubulesepithelium 、 alveolar epithelial cell 、 gastric mucosa

2. unvolatile acid (fixed acid) ： (50-100mmol/d)

Uric acid, phosphoric acid (H3PO4) and sulfuric acid (H2SO4)

are the products in the metabolic process of proteins and nuclear

acids.

Lactic acid and ketonic bodies (β-hydroxybutyric acid and

acetoacetic acid) can be formed from the metabolic process of

carbohydrate and fat as intermediate products, when the oxygen

supply is not sufficiency.  

Exogenous acid(food and drug) ：

Excretion through kidney

(II) Sources of base

Origin of basesEndogenous ：

deamination―>NH3 Less than acid production

Exogenous input ： vegetables, and fruits

III 、 Regulation of acid-base balance

Henderson-Hasselbalch Equation Acid-base balance is mainly the balance between production and loss of acid and base.

pH=pKa+lgpH=pKa+lg[HCO[HCO33－－ ]]

[H[H22COCO33]]

=pKa+lg=pKa+lg2020

11

= 6.1 +1.3 = 7.4

[H+]↑

Buffer Respiratory Renal

ECF ICF & bone

(Immediately) ( 2~4h) (1~3min) (hs;1~3d)

Neutralize H+

paCO2 ↓

eH+ & iK+ exchange

Excrete H+

Keep NaHCO3

Acid-base balance ：pH∝ [HCO[HCO33

－－ ] / [H] / [H22COCO33]]oror pH∝ [HCO[HCO33

－－ ] / PaCO] / PaCO22

Source

Buffer system

RespiratoryRenal

Cellular

（ I ） blood buffer system

表 1 全血五种缓冲系统 表 2 全血中各缓冲体系的含量与分布缓冲酸 缓冲碱 缓冲体系 占全血缓冲体系 %

H2CO3 HCO3 ¯ + H+ 血浆 HCO3 ¯ 35

H2PO4- HPO4

2 ¯ + H+ 红细胞内 Hb 18

HPr Pr ¯ + H+ HbO2- 及 Hb- 35

HHb Hb¯ + H+ 磷酸盐 5

HHbO2 HbO2¯ + H+ 血浆蛋白 7

Buffer systems ： consists of a weak acid and its’ salt

※HCO3-/H2CO3 is the most important buffer pair.

Regulate CO2 or HCO3- through kidney and

lung ， the most important buffer pair (50%) 。fixed acid and base buffer system

HCO3-/H2CO3 buffer system

PH is dermatied by HCO3-/H2CO3 。

character: RBC specificity

volatile acid buffer

CO2

CA ： carbonic anhydrase

CO2+H2O

CA

H2CO3

CA

H+ HCO3-

Cl-

(RBC)

HCO3-

Cl-HHO2 HbO2-

HHb Hb-←

hemoglobin buffer system (Hb-/HHb 、 HbO2-/HHbO2)

phosphate buffer system

HPO42-/H2PO4-

character: play a role in cell and kidney

protein buffer system

Pr － /HPr

Intracellular buffer

Mechanism of buffer

HCl+NaHCO3→NaCl+H2CO3→CO2+H2O

NaOH + H2CO3→NaHCO3 + H2O

Accept H+ or release H+ ，decrease the change of pH

Character of Buffer

Unvolatile acid ：HCO-

3/H2CO3 system:½ of the buffer capacityOpened regulation: respiratory and renal

Volatile acid ：Hb-/HHb 、 HbO2

-/HHbO2

（ II ） Mechanisms of respiratory control

change the depth or rate of respiration →change CO2

elimination→ [HCO3-]/ PaCO2 →Acid-base balance

1. central chemoreceptor

PaCO2 (N:40mmHg) ↑→ pH of CSF↓ →to stimulate central chemoreceptor → the respiratory ☆center→Pulmonary ventilation volume ↑

PaCO2 >60mmHg (8kPa) → Pulmonary ventilation

volume ↑10 times but, PaCO2 >80mmHg (10.7kPa) →inhibit

respiratory center ， named as carbon dioxide narcosis

The central chemoreceptor is sensitive to the change of CO2, which is easy to cross the blood-brain barrier. It takes time for the H+ to penetrate across the blood brain barrier into the interstitial fluid of the brain, the increase of [H+] in the brain is relatively slow, so the effect of H+ on the central chemoreceptor will be slow.

central chemoreceptor

2.peripheral chemoreceptor

PaO2 ↓ 、 pH ↓ 、 PaCO2↑ →to stimulate peripheral chemoreceptor → the respiratory cent☆er→ Pulmonary ventilation volume ↑

PaO2 ﹤60mmHg (8kPa) → the respiratory ☆center ； but PaO2 <30mmHg →inhibit respirator center 。Less sensitive than central chemoreceptor

3.Characteristic of respiratory compensation

(a) Timeliness.

The respiratory response begins within several minutes.

The respiratory response often takes 30 minutes for the respiratory compensation. 12~24 hours to get maximal compensation.

（ b) limited compensation

(III) Renal regulation of acid-base Balance

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.

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

Excrete the nonvolatile acid ， reabsorb the bicarbonate ，“排酸保碱”

→keep [HCO3-]→maintain acid-base balance 。

HCO3- filtrate through glomerulus freely （ 5000 mmol/

d ）， 85%~90% is reabsorbed by proximal

tubule ， others are reabsorbed by distal convoluted

tubule and collecting duct ， 0.1% is excreted→urine pH

6.0 。

urine pH vary from 4.4 to 8.0

1.in proximal tubule

(a) Na+-H+ exchange

2.in distal tubule & collecting duct

α-intercalated cell: secrete H+

upper membrane: (a) H+-ATPase; (b) H+-K+ ATPaseUrinary acidification （ H2PO4

-↑NH4+↑ ）

base membrane: Cl- /HCO3

- exchange

3. secretion of NH3/NH4+ in proximal tubule

4. competitive inhibition between K+-Na+ exchange and H+-Na+ in distal tubule

K+-Na+ exchange: secrete K+, reabsorb Na+ ，H+-Na+ exchange:secrete H+,reabsorb Na+acidosis ， H+-Na+ exchange↑→ K+-Na+ exchange↓→hyperkalemia 。

（ IV) Cellular regulation

(a) H+-K+ exchange

(b) Cl- - HCO3- exchange

(c) Utilizing of bone salt

(d) Synthesis of urea from NH3

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

2. Cl- - HCO3- exchange

When CO2 in ECF (serum) is increased, CO2 will move into the cells, CO2 combines H2O to form carbonic acid, then H2 CO3 dissociates to form H+ and HCO3¯ , the HCO3¯ moves out of the RBC, for neutrality, Cl ¯ moves into the cells.

3.Utilizing of bone salt

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).

  Ca3(PO4)2 + 4H+ ←→ 3 Ca2+ + 2 H2PO4 ¯

It is not a good way of regulating acid-base balance by utilization of bone salt.

4.Synthesis of urea from NH3 in liver cells

Source

Buffer system

RespiratoryRenal

Cellular

Part II laboratory tests of acid-base

disturbances

1. pH

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

The normal range in artery blood =7.35~7.45 (7.41)

The survival range of pH=6.8~7.8

According to the Henderson-Hasselbalch equation:

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

 

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).

24 [HCO3 ¯ ] metabolic factorpH =6.1+ log -------------------------------------------- 1.2 [H2CO3] respiratory factors

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

The purpose of secondary change is to restore the pH.

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

Clinical significance of PH

(anticoagulant artery blood, insulation of air)

A normal range of pH may represent three different situations:

① acid-base balance;

② compensatory acidosis or alkalosis;

③ a mixed decompensatory acidosis and decompensatory alkalosis.

Clinical significance

pH<7.35 decompensatory acidosis

( acidemia )

pH>7.45 decompensatory alkalosis

(alkalemia)

2.PaCO2 (partial pressure of carbon dioxide in arterial blood)

CO2 in blood: (a) 23% HbCO2 in RBC (b) 70% HCO3- in plasma (c) 7% CO2 molecule in plasma CO2 is determined by the rate of CO2 production and the rate of CO2 elimination. PaCO2 is the tension of CO2 caused by CO2 molecule movement. The normal range = 33~46(40) mmHg (4.39~6.25 kPa).

The capability of normal lung to eliminate CO2 is very good. CO2 retention will not occur with normal ventilation. Generally speaking, the PaCO2 is determined mainly by the respiration, so the PaCO2 is called the “respiratory factor”.

Higher PaCO2 is due to the inhibition of respiration. Lower PaCO2 is due to overventilation.

PaCO2

Significance PaCO2>46mmHg

Primary increase: respiratory acidosis

Secodary increase: metabolic alkalosis

(compensated by lung)

PaCO2<33mmHg

Primary decrease: respiratory alkalosis

Secodary decrease: metabolic acidosis

(compensated by lung)

3.[HCO3-]

Actual bicarbonate (AB) The normal [HCO3¯ ] is 22~27(24) mmol/L. AB is measured under “actual condition” in which both respiratory factor and metabolic factor affected the [HCO3¯ ].

CO2 +H2O=H2CO3=H++HCO3 ¯

Standard bicarbonate (SB)

SB is measured under “standard condition” (temperature 37~38 , full oxygenation of hemoglobin, ℃PaCO2 = 40 mmHg). Standard condition means that the respiratory factor is eliminated, then the [HCO3¯ ] is only affected by metabolic factor.Higher SB means metabolic alkalosis or respiratory

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

alkalosis compensated by kidneys.

Normally the AB=SB.

CO2 +H2O=H2CO3=H++HCO3-

If AB>SB (CO2 retention), the reason must be the effect of respiratory factor, which indicates respiratory acidosis or metabolic alkalosis compensated by lung.

If AB<SB (CO2 depletion), the reason must be the respiratory factor, which means respiratory alkalosis or the metabolic acidosis compensated by lung.

4.Buffer base (BB)

Sum of all buffer basees in bloodIn plasma: HCO3 ¯ =24 Protein¯ =17In RBC: Hb¯ HbO2¯ =6.3 HPO4 2¯ =1.0BB=45~55 mmol/LDetermined by metabolic factors

Significance

Normal BB:

acid-base balance

metabolic acidosis + metabolic alkalosis

Increased BB:

Primary increase: metabolic alkalosis

Secodary increase: respiratory acidosis

Decreased BB:

Primary decrease: metabolic acidosis

Secodary decrease: respiratory alkalosis

5. Base excess (BE)

Under “standard condition” (temperature 37~38 , ℃Under “standard condition” (temperature 37~38 , ℃full oxygenation of hemoglobin, PaCOfull oxygenation of hemoglobin, PaCO22 = 40 mmHg), = 40 mmHg),

titrate the whole blood to pH7.4 with how much acid titrate the whole blood to pH7.4 with how much acid or base (mmol/L).or base (mmol/L).

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

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

Significance

Normal BE= -3.0~+3.0 Normal BE= -3.0~+3.0

Only Only metabolic factormetabolic factor determines BE determines BE

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

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

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

UCUC

Na+ ClCl －－

HCOHCO33 －－AGAG

UAUA

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

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

=Na=Na++-(Cl-(Cl¯̄ + HCO3 + HCO3¯̄ ) )

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

    AG indicates those AG indicates those anions, other than HCO3anions, other than HCO3¯̄ and Cland Cl¯̄, which is required , which is required to counter-balance Nato counter-balance Na++..

Significance(i ）

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

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

Significance(ii)

For the classification of metabolic acidosis

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

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

Summary:pH ∝ [HCO[HCO33－－ ] / [H] / [H22COCO33]]

oror pH ∝ [HCO[HCO33－－ ] / PaCO] / PaCO22

1. pH 、 HCO3- 、 PaCO2 (H2CO3) 是决定体液酸碱平衡状

态的三个基本参数。

2. N [HCO[HCO33－－ ] / [H] / [H22COCO33] ] 比值为比值为 2020 ：： 11 ；其中一项变化，；其中一项变化，

则另一项通过机体的代偿活动按比例相应增减，比值维持则另一项通过机体的代偿活动按比例相应增减，比值维持 2020 ：：1 pH1 pH 正常；不能维持正常；不能维持 2020 ：： 1 pH1 pH 偏出正常范围。偏出正常范围。

酸碱平衡紊乱时，比值↑则碱中毒，比值↓则酸中毒。酸碱平衡紊乱时，比值↑则碱中毒，比值↓则酸中毒。

3. HCO3- 受肾的调节，即代谢因素的调节； PaCO2

(H2CO3) 受呼吸因素的调节。可见血液的 pH 值受呼吸因素和代谢因素 2 方面的影响。

Part III Acid–Base Disturbance

1. Simple Acid-base DisordersMetabolic AcidosisRespiratory AcidosisMetabolic Alkalosis Respiratory Alkalosis

2. Mixed Acid-base Disturbance

Contents

HH22COCO3 3 (1)(1)

HCOHCO3 3 (20)(20)－－

pH ∝pH ∝

metabolicmetabolic

respiratoryrespiratory

Metabolic acidosis

Respiratory alkalosis

Respiratory acidosis

Metabolic alkalosis

I 、 Metabolic acidosis

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.

1.Classification

Metabolic acidosis is classified into two types:

(1) metabolic acidosis with normal AG (with increased Cl-)

(2) metabolic acidosis with high AG (with normal Cl-).

  An increased AG means the accumulation of nonvolatile acids in the body.

2. Causes and Pathogenesis

(1) Metabolic acidosis characterized by normal anion gap (AG)

(2) Metabolic acidosis characterized by increased anion gap (AG)

(1)Metabolic acidosis characterized by normal AG

Normal AG means: a) the glomerular filtration rate

(GFR) is sufficient to excrete sulfate, phosphate and other nonvolatile acids,

b) normal production of organic acids

c) no accumulation of nonvolatile acids in the body.

d) Decreased HCO3- ： Cl- increase

Normal Acidosis

Metabolic acidosis characterized by normal AG

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-.

a) Increased loss of HCO3- from kidneys

proximal renal tubular acidosis (Renal tubular acidosis-II): the activity of CA is reduced; H+ -Na+ exchange reduced.

Causes that lead to Proximal RTA:

Congenital (Fanconi syndrome, cystinosis, Wilson’s disease);

Paraproteinaemia (myeloma);

Drugs (carbonic anhydrase inhibitor)

Distal renal tubular acidosis(Renal tubular acidosis-I)

Causes of distal RTA Classical type

Congential Hyperglobulinaemia Authoimmune connective tissue disease(e.g systemic lupus

erythematosus)Toxins and drugs(toluene,lithium,amphotericin)

Hyperkalemic type Hypoaldosteronism Obstructive nephropathy renal transplant rejection Drugs(amiloride,spironolactone)

Different between proximal RTA and distal RTA

Urine PH:Distal RTA: secretion of H+ in collecting duct dysfunction Urine PHProximal RTA: early of mild: [HCO3-]reabsorption Urine PHSerious acidosis: plasma [HCO3-] filtration of [HCO3-]

collecting duct secretion H+, Urine PH Effects on the other organ:

Proximal RTA: amino aciduria, glycosuria,phosphaturia. Distal RTA: nephrocalcinosis(calcium releasing to buffer

H+ in blood),stone, skeletal growth dysfunctionElectrolyte disturbance: hypovolaemia,hypokalemia

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.

c) Excessive production of Cl¯

Infusion /ingestion HCl,NH4Cl

2NH4Cl+CO2 (NH2)2CO+2HCl+H2O

For electrical neutrality, the [HCO3¯] is reduced after the [Cl¯] increased.

d) Dilution of [HCO3¯] e)hyperkalemia: paradoxical alkaline urine

(2)Metabolic acidosis characterized by increased AG

The reason of reduced [HCO3¯] is the accumulation of organic acids (nonvolatile acid) in blood due to more acids:

a) decreased excretion of organic acids

b) overproduction of organic acids.

(a) Causes :Endogenous acid load increasea) acute and chronic renal failure

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.

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 results in lactic acidosis.

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.

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).

The accelerated production of lactic acid and ketone acid must exceed the excretion capability in kidneys, then the lactic acidosis and keto-acidosis will occur.

(b)Cause :Administration of exogenous acid

Salicylate (for stop pain and anti-inflammation) can be converted to salicylic acid in the body.

Salicylic acid is a kind of nonvolatile acid.

methanol poisoning

methanol formaldehyde formic acid

Early: formic acid deposition

Later: hypoxia, lactic acidosis

3.Compensation of metabolic acidosis

primary [HCO3-] ↓→secondary PaCO2↓ ， regulate

[HCO3-] / PaCO2 ， then pH

(1).Blood buffer ： H+↑+ HCO3-H2CO3

High PaCOHigh PaCO22 Low pHLow pH

via via chemoreceptorchemoreceptorss

stimulate the respiratory stimulate the respiratory centercenter

increase the rate and depth of increase the rate and depth of respirationrespiration

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

normal normal PaCOPaCO22

normal normal pHpH

Increased PaCOIncreased PaCO22 and and decreased pH will decreased pH will stimulate the stimulate the chemoreceptors located chemoreceptors located in respiratory center in respiratory center (central) and in carotic (central) and in carotic body (peripheral), and body (peripheral), and enhance the ventilation.enhance the ventilation.

(2) Respiratory (2) Respiratory compensationcompensation

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.

Deep,quick breathe is the main clinincal manifestation .

Rapid, powerful ： several minutes( respirator enhance),

30min(compensation), 12-24h (maximal compensation )

7.4 ,4L/min→7.0 , 30L/min.

Predicted compensatory formula

ΔPaCO2(mmHg) = 1.2 x ΔHCO3- ±2

Secondary compensation 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

Patient, diarrhoea,[HCO3-] 12 mmol/L, PaCO2 28 mmHg.

Type of acid-base disturbance ？ （ 18 ？， 38 ？）

ECF Renal tubule lumen

[H ＋ ] H ＋ +Pr-

→HPrserum[K ＋ ] K＋

H ＋ Na ＋

K ＋ Na ＋

(3).intracellular buffering

acidosis → hyperkalemia

Patient with serious diarrhoea ： pH7.2 ， serum[K ＋ ] 5.6 mmol/LCorrect acidosis ： pH7.4 ， serum[K ＋ ] 2.5 mmol/L

(4) 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.

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

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.

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.

4. Changes of laboratory parameters

pH PaCO2 SB ＞ AB BB -BE

[HCO3-] primary decrease

H2CO3 secondary decrease

Decrease

5 Effects on the body

The main manifestations are:

(A) effects on the cardiovascular system

(B) depression of mental activity

(C) hyperventilation

Impairment of myocardial contraction

Arrhthmias

The hemodynamic effect ： Bp↓

(1)cardiovascular system

(a) Impairment of myocardial contraction

Ca2+ combining with troponin 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.

② The protein expression of L-type of voltage-dependent calcium channel in myocardial cell membrane is reduced. Ca2+ in-flow is reduced.

③ The protein expression of calcium channel in sarcoplasmic reticulum(SR) membrane is reduced.

The release of Ca2+ from SR is reduced.

(b) Arrhythmia due to hyperkalemia

Causes of hyperkalemia:

H+-K+ exchange of cell

Decreased renal excretion of K+

Effect of hyperkalemia:

Ventricular ArrhythmiaVentricular Arrhythmia

(c) The hemodynamic effect: Low BP due to arteriole dilation

The reaction of arteriole to catecholamine (dopamine, adrenalin, noradrenalin) is decreased in acidosis, which leads to decrease of peripheral resistance and reduced venous return(precapillary sphincter dilate more obviously) .

(2) Depression of mental activity

(a) Manifestations: slowness,tired, confused,coma, paralysis of the

cardiovascular or respiratory centre (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 ATP production.

Glutamic acid

Glutamate decarboxylase

r-GABA, r- gamagama aminobutyric acid

γ-GABA transminase

Succinic acid

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

3. respiratory system

4. skeletal system

6. Principle of treatment for metabolic acidosisPrinciple of treatment for metabolic acidosis

treatment of primary disease

supplement of base: NaHCO3 , Sodium lactate

Prevent electrolytic disorder(hypokalemia, hypocaicemia )

Prevent the hypokalemia and hypocalcemia during treatment

After the correction of acidosis, the [K+] will fall down rapidly by moving into the cells. In acidosis, [Ca2+] increases, [Ca2+] reduces during the correcting of acidosis.

OH-

Ca2+ ------→combining calcium Ca2+ ←------combining calcium H+

II 、 Respiratory acidosis

Characterized by a primarily increase in the PaCO2 and a low pH.

1.concept

2. Causes and Pathogenesis

The basic reasons: (a) decreased ventilation, which leads to the

decreased elimination of CO2 from lung; (b) increased inhalation of CO2.

(1) Acute respiratory acidosis

a) depression of respiratory center by cerebral diseases (trauma, infections) and drugs (over-dosage of anesthetics, sedatives) b) neuromuscular disorders (acute hypokalemia, periodic paralysis , myasthenia gravis ,poliomyelitis, Guillain-Barre syndrome), c) cardiopulmonary arrest. d) obstruction of respiratory tract. e) mis-operating of respirator.

(2) Chronic respiratory acidosis

Chronic obstructive pulmonary diseases (emphysema, chronic bronchitis with hypoventilation) cause the chronic respiratory acidosis.

Chest wall diseases (fracture of rib)

Brain tumors (affecting the respiratory center in which the ventilation is decreased)

3. Compensation of respiratory acidosis

(1) Non-[HCO3¯ ]/[H2CO3] buffering systems(2) Cellular compensation H+ moves into the cell CO2 moves into the cell(3)The renal compensation

( How about buffer pair: [HCO3¯ ]/[H2CO3] and respiratory compensation? )

Intra-cellularIntra-cellular kidneykidney

S:H ＋

R:HCO3-

S:H ＋

R:HCO3-

10 ～ 30min10 ～ 30min 3 ～ 5d3 ～ 5d

Respiratory acidosis

Respiratory acidosis

H+-K+ exchangeH+-K+ exchange

(1)intracellular buffering:acute

RBCCO2+H2O→H2CO3

CO2+H2O→H2CO3

[HCO3- ] ↑

K+

[K+]↑

CO2 ↑

H+

HCO3- H+ +Hb-

HHbCl- Cl-

limited ，△ PaCO210mmHg/ △ [HCO3- ] 0.7-1mmol/L

CA

(2)renal compensation:chronic PaCO2↑, [H+] ↑→CA activity↑→ secrete H+ in kidney PaCO2↑, [H+] ↑→ GT activity↑→ secrete NH3 HCO3

- reabsorption urine pH↓

Powerful effect ，△ PaCO210mmHg/ △ [HCO3- ] 3.5-4.0mmol/L 。

Predicted compensatory formula of acute respiratory acidosis

ΔHCO3- = 0.1x ΔPaCO2 ± 1.5

HCO3- = 24+ 0.1x ΔPaCO2 ± 1.5

Secondary compensation primary change

The maximal increased value up to 30 mmol/L.

Decompensation

Predicted compensatory formula of chronic respiratory acidosis

ΔHCO3- = 0.4x ΔPaCO2 ± 3

HCO3- = 24+0.4x ΔPaCO2 ± 3

Secondary compensation primary change

Value measured > value predicted: with metabolic alkalosis

Value measured < value predicted: with metabolic acidosis.

Maximal compensatory value up to:45mmol/L

4. Changes of laboratory parameters(acute)

pH PaCO2 SB (±) ＜ AB BB (±) BE(±)

[HCO3-] secondary increase

H2CO3 primary increase

decrease

Changes of laboratory parameters(chronic)

pH PaCO2 SB ＜ AB BB +BE

[HCO3-] secondary increase

H2CO3 primary increase

decrease

5.Effect of respiratory acidosisSame as metabolic acidosis ， but CNS manefistation is more serious

cerebral blood flow increase （ CO2 dilate vessel ； contract vessel viaαreceptor ） :No αreceptor on cerebral vessels → CO2

dilate cerebral vessels→intracranial pressure ↑→headache

cardiovascular ： like metabolic acidosis

pulmonary encephalopathy ：carbon dioxide narcosis:PaCO2 > 80 mmHg

6. treatment priciples

(a) Treat the primary diseases which cause respiratory acidosis. (antibiotic, antispastic drugs) (b) Improve properly the ventilation.(c) Prevent from (respiratory alkalosis) over-ventilation during artificial respiration.（ d) Be careful to alkaline drug(NaHCO3) THAM

III 、 Metabolic alkalosis

Characterized by a primarily elevation in plasma HCO3

- concentration and

a high pH.

1.concept

2.Classification

 According to the therapeutic effect of 0.9% NaCl,

(A) saline-responsive alkalosis

(B) saline-resistant alkalosis

3. Pathogenesis

(1) saline-responsive alkalosis

(a) Increased loss of H+

(b) More administration of HCO3¯ or precursors of bicarbonate

(a) Increased loss of H+

a) from stomach There is a lot of H+ in the gastric juice. Vomiting and

gastric suction will lose H+ [HCO3- ] cl- is lost through gastric juice hypochloremic

alkalosis

HCO3- is absorbed into blood in stomach, then to

intestinal juice to neutralize H+.

Hypokalemia alkalosis

Effective blood volumedecrease

secondary aldosterone increase

Some diuretics (e.g. furosemide) can inhibit the reabsorption of Cl¯ and Na+ in loop, more Na+ is reabsorpted with HCO3¯ (without Cl ¯) in distal tubules; renal fluid folw rate increase

b) Increased loss H+ from kidneys

(b) More administration of HCO3¯ or precursors of bicarbonate

a) Patients with gastric ulcer may be orally given excessive NaHCO3 to neutralize gastric juice .

b)Sharp correction of acidosis by excessive alkali administration can lead to metabolic alkalosis.

c) Transfusion of anticoagulant blood with sodium citrate citrate.

.

(2) Chloride-resistant type

Primary hyperaldosteronism

Secondary hyperaldosteronism caused by: hypovolemia

Cushing’s syndrome

severe hypokalemia:Paradoxical acid urine

4.Compensation of metabolic alkalosis

The compensation of metabolic alkalosis is the opposite direction of the compensation in metabolic acidosis.

(1) Respiratory compensationRespiratory compensation ： [H ＋ ] →pulmonary ventilation volume → CO2 elimination → PaCO2↑ →HCO3

-/H2CO3(quickly,limted)

But 46<PaCO2<60 mmHg, respiratory center is excited ，PaCO2 seldom higher than 55 mmHg

△ PaCO2=0.7× [ HCO△ 3－

]±5

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

[H ＋ ] in ECF

Renal tubule lumen

H ＋

H ＋ +Pr-HPr

K ＋ Na ＋

alkalosis → hypokalemia

(2) intracellular buffering

血 K ＋ K ＋H ＋ Na ＋

(3) ． renal compensation

secrte H+ ↓ secrete NH3↓ reabsorb HCO3

-↓ urine pH

But hypokalemia-alkalosis excrete aciduria

cell

paradoxical aciduria

Serum [K ＋ ]↓

H+H+K＋

K＋

Renal tubule lumen

H+ Na ＋↑

K ＋ Na ＋↓

Hypokalemia alka

Urine [H+ ] ↑

5.Effects on the body

a) Effects on the central nervous system.

b) The left-shift of oxygen-hemoglobin dissociation curve

c) Decrease of ionized calcium (Ca2+) in plasma

d) Hypokalemia

(1) Effects on the central nervous system

Manifestations: Excitability is increased.dysphoria (agitation), fatigue (very tired), malaise (discomfort),delirium ( mental disturbance with wild talk and wild excitement),confusion, stupor coma.

The production of GABA (gama aminobutyric acid, a inhibitory transmitter), The production of GABA (gama aminobutyric acid, a inhibitory transmitter),

is decreased due to the activity of enzyme for the production is reduced in alkalosis.is decreased due to the activity of enzyme for the production is reduced in alkalosis.

HypoxiaHypoxia

(2). increase in neuromuscular excitability

pH ，

[Ca2+]↓ 手足搐搦(Carpopedal Spasm)

The left-shift of oxygen-hemoglobin dissociation curve leads to brain hypoxia.

This “left –shift” means the Hb combines more oxygen under the same PaO2 and the O2 is more difficult to dissociate from Hb. (hypoxia)

(3)The left-shift of oxygen-hemoglobin dissociation curve

(4)Hypokalemia

Causes:

(a)H+ shifts out of the cells as the compensation of alkalosis. Therefore the K+ moves into the cells as an exchange for electro-equilibrium.

(b) More K(b) More K++ is in the cells including in the renal is in the cells including in the renal tubular cells, so the excretion of Ktubular cells, so the excretion of K++ from kidneys is from kidneys is increased.increased.

Manifestations: arrhythmiasManifestations: arrhythmias

Predicted compensatory formula

ΔPaCO2(mmHg) = 0.7 x ΔHCO3- ±5Secondary compensation primary changeOr:PaCO2=40+0.7xHCO3-±5PaCO2 can increase maximal to 55 mmHg.Value measured > value predicted: with respiratory acidosis Value measured < value predicted: with respiratory alkalosis

pH PaCO2 SB ＜ AB BB BE

[HCO3-] primary increase

H2CO3 secondary increase

6. Changes of laboratory parameters

increase

7. Principle of treatment.For chloride-sensitive type

(A) Replenish 0.9% NaCl [Na+] [Cl-]( mmol/L)---------------------------------------------------------0.9%NaCl 154 154Plasma 140 104---------------------------------------------------------

a) Dilute the [HCO3-]b) Increase the blood volume, reduce the reabsorption of HCO3-.c) increased Cl- in distal tubule leads to increased excretion of HCO3- in collecting duct.

(B) Replenish NH4Cl to increase the [Clˉ] and blood volume.

(C) Replenish KCl for the patients with potassium deficiency.

(D) secerious metabolic alkalosis:

For chloride-resistant type

Treating of underlying disorders

Antagonists of aldosterone

Replenish KCl

Acetazolamide (inhabit the CA activity) for the patients with edema with alkalosis.

IV Respiratory alkalosis

Characterized by a primarily reduction in the PaCO2 and a high pH.

1.concept

2.Causes and Pathogenesis

The only pathogenesis is the increased alveolar ventilation (hyperventilation). The basic reason of hyperventilation is the stimulation of respiratory center.

Anxiety Hysteria

Central nervous diseases Gram-negative septicemia

Fever Salicylate intoxication

Hypoxia due to high altitude,pulmonary disease

Mis-operation of mechanical ventilator

[H2CO3]↓

HCO3- + H+H2CO3

K ＋ K ＋[K ＋ ]↓

HCO3-

HCO3-H++H2CO3CO2

Cl-

Cl-

(1)intracellular buffering ： acute alkalosis

H+ HHb

RBC

plasma

3.Compensation of respiratory alkalosis

Predicted compensatory formula for acute respiratory alkalosis

ΔHCO3- = 0.2x ΔPaCO2 ± 2.5

HCO3- = 24+0.2x (PaCO2 -40)± 2.5

Secondary compensation primary change

Value measured > value predicted: with metabolic alkalosis

Value measured < value predicted: with metabolic acidosis.

Maximal compensatory value up to:18 mmol/L

(2)renal compensation:chronic alaklosis

Secrete H+ ↓ Secrete NH3↓ HCO3

- reabsorption↓ Urine pH

Compensation [ HCO△ 3－

] =0.5 × PaCO△ 2 ±2.5

Predicted compensatory formula for chronic respiratory alkalosis

ΔHCO3- = 0.5x ΔPaCO2 ± 2.5

HCO3- = 24+0.5x (PaCO2 -40)±2.5

Secondary compensation primary change

Value measured > value predicted: with metabolic alkalosis

Value measured < value predicted: with metabolic acidosis.

Maximal compensatory value up to:12 mmol/L

4.Changes of laboratory parameters(acute)

pH PaCO2 SB(±) ＞ AB BB (±) BE (±)

[HCO3-] secondary decrease

H2CO3 primary decrease

increase

Changes of laboratory parameters(chronic)

pH PaCO2 SB ＞ AB BB -BE

[HCO3-] secondary decrease

H2CO3 primary decrease

increase

5.Effect of respiratory alkalosis

1. CNS dysfunction ： GABA↓ ， cerebral blood flow ↓2. increased neuromuscular excitability(hypocalcemia ) tingling,twitching

3. hypokalemia

4. hypophosphatemia

6. treatment priciples

Primary disease

Prevent mis-operation of mechanical ventilator

5 ％ CO2 mixtrue gas inhalation or mask

V. Mixed Acid-base Disturbances

Concept Metabolic acidosis, metabolic alkalosis, respiratory acidosis and respiratory alkalosis are four types of simple acid-base disturbance when these disturbances occur separately. A mixed acid-base disturbance is defined as the simultaneous co-existence of two or more simple disorders in the same patient. Double acid-base disorders Triple acid-base disorders

Any two or three simple acid-base disturbances can occur simultaneously in a patient except the respiratory acidosis and respiratory alkalosis, because one can never have hypoventilation and hyperventilation at the same time.

Mixed acid-base disturbances occur frequently as a part of severe underlying illness with a high mortality.

Mixed Acid-base Disturbances

Case discussion

A 45-year-old man had chronic cough for 20 years. He had a shortness of breath, orthopnea with edematous ankles for 1 month. The laboratory findings were:

pH = 7.26 PaO2=55 mmHg

PaCO2=60 mmHg AB = 22 mmol/L

Predicted: ΔHCO3- = 0.4x ΔPaCO2 ± 3

HCO3- = 24+0.4x 20 ± 3=29~35

Measured: 22

pH reduced severely.

No respiratory compensation for M. acidosis

No renal compensation for R. acidosis

Respiratory acidosis + metabolic acidosisRespiratory acidosis + metabolic acidosis