(3) Metabolic alkalosis 1) Concept 2) Classification and Pathogenesis 3) Compensation 4) Effects on the body 5) Principle of treatment.

(3) Metabolic alkalosis

• 1) Concept

• 2) Classification and Pathogenesis

• 3) Compensation

• 4) Effects on the body

• 5) Principle of treatment

• 1)Concept• Metabolic alkalosis is defined as a primary

increase of [HCO3¯ ] in plasma, the pH has a tendency to increase. (means ?)

2) Classification and Pathogenesis

•  According to the therapeutic effect of 0.9% NaCl,

• (a) chloride-sensitive type

• (b) chloride-resistant type.

(a) Chloride-sensitive type Pathogenesis

a) Increased loss of H+ from stomach

• b) Increased loss of H+ from kidney

• c) H+ enters into cells

• d) Overload of HCO3¯

a) Increased loss of H+ from stomach

There is a lot of H+ in the gastric juice. Vomiting and gastric suction will lose gastric fluid .

HCO3- is absorbed into blood, then to

intestinal juice to neutralize H+.

b) Increased loss H+ from kidneys:

Some diuretics (e.g. furosemide速尿 ) can inhibit the reabsorption of Cl¯ and Na+ in loop, urine volume is increased (50~60L/24hs).

Increased loss H+ from kidneys

Concentrated [HCO3¯]

c) H+ enters into cells

• Hypokalemia

• Unusual aciduria

d) Overload of HCO3¯

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

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

Lactate and citrate can be catalyzed into HCO3¯ .

Transfusion of anticoagulant blood with sodium citrate.

(b) Chloride-resistant type

a) Primary hyperaldosteronism

Secondary hyperaldosteronism caused by hypovolemia

Effect:

Stimulate H+-ATPase.

b)Severe hypokalemia(??)

K+-Na+ exchange

H+ -Na+ exchange

c)Cushing Syndrome:

more glucocorticoids.

3) Compensation of metabolic alkalosis

The secondary change is the increased [H2CO3] in plasma.

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

(a) Buffering system in ECF (b) Pulmonary compensation (c) Cellular buffering (d) Renal compensation

(a) Buffering system in ECF

After the addition of alkali, the buffering system initiates immediately.

NaHCO3 Na2HPO4 Hb-

------------- -------------- ------- H2CO3 NaH2PO4 HHb H2CO3 combines the excessive OH¯ (strong)

to form HCO3¯ (weak alkaline).

increased pHincreased pH

Via central Via central chemoreceptorchemoreceptorss

inhibit the respiratory centerinhibit the respiratory center

slow shallow respirationslow shallow respiration

more carbon dioxide can be more carbon dioxide can be accumulated in bloodaccumulated in blood

decrease of pHdecrease of pH

(b) Respiratory (b) Respiratory compensationcompensation

Limitation:

High PaCO2 and low PaO2 stimulate the respiratory center.

(c) Cellular buffering

• The HThe H++ moves out of cells into ECF, at the moves out of cells into ECF, at the same time Ksame time K++ moves into the cells. moves into the cells.

(d) Renal compensation

The reabsorption of [HCO3¯ ] is decreased.

The acids excretion is decreased.

• In metabolic alkalosis, the activity of carbonic anhydrase (CA) decreases, the H+ production is decreased, the H+-Na+ exchange is decreased, the reabsorption of HCO3¯ is decreased.

• In metabolic alkalosis, the activity of glutaminase is decreased, less glutamine will be decomposed into HCO3¯ and NH3. Thus less HCO3¯ will be reabsorpted to the blood, more HCO3¯ will be eliminated.

Decreased net acid excretion with urine

• Less H2PO4 ¯ and NH4+ are in the end urine.

• The pH of urine will elevate due to the decreased net acid excretion with urine .

Changes of laboratory parameters

• Primary increase of [HCO3¯]:• AB,SB,BB ???• AB ?? SB• BE ?

• Secondary compensation:• PaCO2 ?• pH ?

Changes of laboratory parameters

• Primary increase of [HCO3¯]:

• AB,SB,BB increase

• AB > SB

• BE positive increase

• Secondary compensation:

• PaCO2 increase

• pH tends to increase.

Predicted compensatory formula

ΔPaCO2(mmHg) = 0.7 x ΔHCO3- ±5Secondary compensation primary change

Or: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

4) Effects on the body

 (a) The left-shift of oxygen-hemoglobin

dissociation curve

(b) Effects on the central nervous system.

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

plasma

(d) Hypokalemia

(a)The left-shift of oxygen-hemoglobin dissociation curve leads to 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)

(b) Effects on the central nervous system

• a) Manifestations:

• Excitability is increased.• dysphoria (agitation), • malaise (discomfort),• delirium ( mental disturbance with wild talk

and wild excitement),• confusion,

b)The reasons :

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

Glutamic acid

Glutamate decarboxylase

r-GABA, r-aminobutyric acid

r-GABA transaminase

Succinic acid

Kreb’s cycle

The production of GABA (gama The production of GABA (gama aminobutyric acid, a inhibitory transmitter) is aminobutyric acid, a inhibitory transmitter) is decreased due to the activity of enzyme for decreased due to the activity of enzyme for the production is reduced in alkalosis.the production is reduced in alkalosis.

(c) Decrease of Ca2+ in plasma

More calcium combines to the plasma proteins in alkalosis.

• OH-

• Ca2+ protein-bound calcium•  Ca2+ protein-bound calcium• H+

Manifestation:• The main character is the increased

neuromuscular excitability. • The symptoms include :• a) twitching 颤搐 (quick uncontrollable muscle

movement)• b) tetany手足搐搦• c) cramping (convulsions)

(d) 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) Less Hb) Less H++ -Na -Na++ exchange and more K exchange and more K++-Na-Na++ exchange leads more Kexchange leads more K++ excretion with urine. excretion with urine.

Manifestations: arrhythmiasManifestations: arrhythmias

(4) Principle of treatment.

• 1) For chloride-sensitive type • (A) Replenish 0.9% NaCl• [Na+] [Cl-]( mmol/L)

• ---------------------------------------------------------• 0.9%NaCl 154 154• Plasma 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 KCl for the patients with potassium deficiency.

2) For chloride-resistant type

Treating of underlying disorders

Antagonists of aldosterone

Replenish KCl

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

• A 25-year-old woman was brought to the emergency room by her husband. The patient had one-week history of weakness. She denied vomiting, diarrhea, or diuretic use (but a urine test for diuretics is positive). There was no history of fever or chills.

• Physical examination:• BP=110/80 mmHg,• Pulse=84/min, Temperature=37.C. • The neurological examination found weakness in

both lower extremities. • Laboratory results: • [Na+] = 138 mmol/L, [K+] = 2.1 mmol/L, • [Cl-] = 85 mmol/L, [HCO3-] = 41 mmol/L,• pH = 7.45, PaCO2=50 mmHg, • EKG: Sinus rhythm, flattened T-wave

• Hypokalemia,

• metabolic alkalosis.

ΔPaCO2(mmHg) = 0.7 x ΔHCO3- ±5

Secondary compensation primary change• (12) (41-24)

• 40+12=52 ±5