03 acid base disturbance_pti

Dept. of PathologyMedical CollegeHunan Normal University()*Chapter 3Acid-Base Balance and Imbalance

*Disorders are big problems in clinic. http://v.qihuang99.com/player/1777.html?1777-0-2

*Acid-Base Balance and Imbalance Acid-base homeostasis Parameters of acid-base balance Simple acid-base disturbance Metabolic acidosis Respiratory acidosis Metabolic alkalosis Respiratory alkalosis

The process which is regulated automatically by the body to keep relatively stable between acidity and basicity.Q: Why balanced pH?Normal pH range: 7.35 ~ 7.45 Section 1 Acid-base Homeostasis

Outside the acceptable range of pH,proteinsare denatured and digested,enzymeslose their ability to function, anddeathmay occur.*

Concepts of Acid and Base 2. Base: an acceptor of H+. 1. Acid: a donor of hydrogen ions ( H+).

Normally, acid substances are much more than alkaline ones, when people take regular diet. *

Acids Volatile acid () Fixed acid ()

An acid excreted through the lungs as a gas.Volatile AcidSources of CO2: Metabolism of biomoleculesCO2H2O

H2CO3

(300-400 L/d)

H+

HCO3-

H2CO3 is the only volatile acid in our body (13-15 mol/d). *

Fixed (non-volatile) AcidAcid produced in the body from sources other than CO2.Excreted by the kidneys.Sources:From proteins:

sulfate, phosphate, urateFrom carbohydrates:

Lactate, pyruvate, glycerateFrom lipids:

Adenylate, pyrophosphate

All acids (except H2CO3) are fixed acids.*

Bases (Alkali)SourcesAmino acid metabolism (NH3) Fruits and vegetables Citric acid, maleic acid, oxalic acidWhy bases produced from acids?Fruits CO2, H2O and ions (e.g., Na+) Bases

2. Regulation of Acid-Base Balance Buffer SystemsBloodCellsBone Lungs Kidneys

Three Levels

Buffer systems in the bloodAbility53

5

7

35

All fixed acids can be buffered by these buffer systems. *

Bicarbonate/Carbonic Acid Buffer System HCO3-/H2CO3The ratio of HCO3- vs H2CO3 determines the blood pH.HCl + HCO3- Cl- + H2CO3 CO2 + H2O NaOH + H2CO3 NaHCO3 + H2O

H2CO3/HCO3- is an open buffer system, because CO2 can be eliminated from the lungs and HCO3- can be regulated by the kidneys.*

Phosphate Buffer SystemNa2HPO4/NaH2PO4Primarily functions in the kidneys and the cells.

Mainly functions in the cells Protein Buffer System Pr/HPr

Hb-/HHbHbO2-/HHbO2Hemoglobin Buffer SystemOnly in RBCRegulates volatile acid

Hb/HHb functions to regulate volatile (not fixed) acids. *

Mechanism of Buffering in the Plasma HCl + NaHCO3 NaCl + H2CO3 CO2 + H2O NaOH + H2CO3 NaHCO3 + H2O

Cl-Cl-HCO3-HCO3-Mechanism of Buffering in the Cells

Regulation of Acid-Base Balance by the LungsRegulation of Volatile Acid

Regulation Through Chemoreceptors

1) Regulation through central chemoreceptors. PaCO2 (main way) 2) Regulation through peripheral chemoreceptors in the carotid body and aortic body. PaO2*

3. Respiratory Regulation of Acid-Base Balance Pulmonary regulation Volatile acid

1) Regulation through central chemoreceptors. PaCO2 (main way) 2) Regulation through peripheral chemoreceptors in the carotid body and aortic body. PaO2

3) Other: nerve reflex regulation, central nervous regulation.

Object: Regulating CO2 eliminated content to keep HCO3- / H2CO3 = 20/1Method: CO2 can freely diffuse across the blood-brain barrier and result in H+ increased in CSF. The chemoreceptors in medullary respiratory center are very sensitive to the changes of H+ concentration. Increased H+ can excite respiratory center.Characteristics PaCO2 (+ breath) 80mmHg (- breath) CO2 anaesthesia (narcosis)Regulation through central chemoreceptors

Regulation by the Kidneys Excrete fixed acidsH+-Na+ (NH4+-Na+) exchange to excrete H+ (or NH4+)Retaining Na+ Maintain plasma [HCO3-]

Na+-HCO3- co-transported into capillaries

c. The effects of carbonic anhydrase CA on the apical side H+ + HCO3- H2CO3 CO2 + H2O*

Na+

Excretion of H+ and Reabsorption of HCO3- at the proximal tubule CapillaryEpithelial CellTubuleH2O + CO2H+

Na+H2CO3HCO3-H+CACA: Carbonic anhydrase

H2O + CO2H+

H2CO3HCO3-H+GlutamineNH3NH4++NH3NH3Na+NH4++Na+Excretion of NH4+CACapillaryEpithelial CellTubule

CellsLungsKidneysPlasmaProduction and Regulation of Acids and Bases

11.psd

12.bin

CO2 can also bind to HB in the plasma. *

Characteristics of Acid-Base RegulationsBuffer systems in the bloodFast;Buffer effect can not be sustained.Buffer in the cellsVery strong and fast (34 h);Electrolytes imbalance (hyperkalemia) may occur.Respiratory RegulationStrong and very fast (peak in 30 min);Eliminate volatile acid (CO2) [and fixed acids].Renal RegulationStrong in eliminating fixed acids and retaining HCO3-; Slow (3-5 days).

Section 2

Parameters of Acid-Base Balance(Blood Gas Analysis)1. pH2. PaCO23. SB 4. AB5. BB6. BE7. AG

1. pHpH < 7.35: AcidosispH > 7.45: Alkalosis 2. Normal value 7.35 7.45 (average7.40)

pH is the negative logarithm of H+ concentration. pH is measured in the artery blood. *

Henderson-Hasselbalch Equation= 6.1 + 1.3 = 7.4

2. PaCO2Partial pressure of carbon dioxide (CO2) in plasma (artery) Significance: respiratory parameterNormal Value: 33~46 mmHg (Average: 40PaCO2 : Respiratory Acidosis Metabolic Alkalosis after compensation

PaCO2 : Respiratory Alkalosis Metabolic Acidosis after compensation

PaCO2 is mainly regulated by respiration (elimination). PaCO2 is the best respiratory parameter. The respiratory control of CO2 is so efficient that CO2 retention does not develop even if CO2 production is largely increased (when respiratory function is normal). *

Normal Value: 2227 mmol/L (Average: 24)3. Standard Bicarbonate, SBSB : Metabolic Alkalosis SB : Metabolic AcidosisNot affected by respiration.Only reflecting metabolic factor.

Hb fully oxygenated meaning 100% oxygen saturation. SB increases also in respiratory acidosis after compensation of the kidneys.SB decreases also in respiratory alkalosis after compensation of the kidneys. *

Actual Bicarbonate, ABReflecting: Both metabolic and respiratory factorsNormal Value: the same as SB (24 mmol/L)

AB = [HCO3-]*

AB > SB, PaCO2 Respiratory acidosis (metabolic alkalosis after compensation)AB < SB, PaCO2 Respiratory alkalosis (metabolic acidosis after compensation)In physiological situation:AB = SBIn pathological situation: AB SBAB vs. SB

Not necessary to compare between AB and SB, since PaCO2 is the best respiratory parameter.ABSBABSB*

4. Buffer Base, BB Meaning: BB Metabolic alkalosisBB Metabolic acidosisNormal: 4552 mmol/L (Average: 48 )The sum of all alkaline buffer substances in plasma (HCO3-, HPO42-, Pr-, Hb-, HbO2-)

Reflects metabolic situation. *

5. Base Excess, BEThe amount of a fixed acid or base that must be added to a blood sample to achieve a pH of 7.4 under standard condition. Normal value: -3.0 - +3.0

For pH higher than 7.4, an acid must be added the BE value is positive. *

6. Anion GapAG The difference between undetermined anion (UA) and undetermined cation (UC) in the plasma (AG = UA - UC).AG (AG>16): Fixed acids(metabolic acidosis)AG: little clinic meaningAG = Na+ - (Cl- + HCO-3) = 140 - (104 + 24) = 12 mmol/L (10 ~ 14 mmol/L)

Na+, Cl-, HCO3- are determined ions. Undetermined anions include: negatively charged proteins, phosphate, sulfate, lactate, ketone bodies, etc. *

pHTypes of Acid-Base Disturbance

1) Concept 2) Causes* 3) Classification 4) Compensation* 5) Blood gas parameters 6) Effects on organism* 7) Principles of treatment1. Metabolic Acidosis (MAc) Metabolic acidosis

2. Causes Acids too much

Bases too little Metabolic acidosis is defined as a decrease of pH induced by primary decrease in plasma HCO3- concentration. 1. Concept Metabolic acidosis

Production of fixed acids Lactic acidosis ( glycolysis)Ketoacidosis ( lipolysis) Excessive intake of acids Aspirin (acetylsalicylic acid) poisoning Excessive intake of NH4Cl, etc. 1) Acids too much (consuming HCO3-) Elimination of acidsRenal failure (GFR)Renal Tubule Acidosis (RTA): excretion of H+ in the collecting tubule. Hyperkalemia H+-K+ exchange Metabolic acidosis

RTA type IHypoxia (shock) and some drugs like metformin can cause lactic acidosis. (by increasing intracellular glycolysis)NH4Cl is used as the acid to correct metabolic acidosis. NH4Cl is used as a (expectorant eliminating sputum)*

HCO3- loss Loss from intestinal juice(diarrhea) HCO3- dilutionmassive infusion of glucose or NS in a short time. HCO3- reabsorption 2) Bases too littleRenal Tubular Acidosis (RTA) Metabolic acidosis

RTA type II (Inhibition of Carbonic Anhydrase HCO3- reabsorption)*

3. Classification 2) High AG metabolic acidosis primary HCO3- AG due to any kind of fixed acids except Cl- (Normochloremic MAc)e.g., shock, renal failureNormal AG metabolic acidosis

primary HCO3- compensatory of Cl- (Hyperchloremic MAc)HCO3- losing : diarrhea, intestinal fistulas;HCO3- reabsorption : RTA Normal Normal AG MAc High AG MAc Metabolic acidosis

*

4. Compensation

Pulmonary regulation is a main way in metabolic acidosis. Metabolic acidosis

Compensation limit by the lungs: PaCO2 = 10 mmHg*

Example 1. 1 diabetes patient pH 7.32, HCO3- 15 mmol/L, PaCO2 30 mmHg predict PaCO2 = 1.515 + 82 = 30.52 = 28.532.5 measured PaCO2 = 30, within 28.532.5; Therefore, simple MAcEquationpredict PaCO2 = 1.5[HCO3- ] 82 JudgementIf measured PaCO2 within predicted PaCO2 , simple MAcIf measured > predicted maximum, CO2 retention, MAc + RAcIf measured < predicted minimum, CO2 too less, MAc + RAl Metabolic acidosis

1.2 shock patient with pneumonia: pH 7.26HCO3- 16 mmol/LPaCO2 37 mmHg predicted PaCO2 = 1.516 + 82 = 322 = 3034 measured PaCO2 =37, exceed predict maximum 34; Therefore, MAc + RAc Metabolic acidosis

*

pH PaCO2

HCO3-

AB

SB BB

BE (negative value increased)(in the case of simple MAc) 5. Changes of blood gas parameters : Metabolic acidosis

AB < SBTo distinguish the type of acid-base disturbance, examine pH, PaCO2, HCO3- and AG. *

6. Effects on organism1) Cardiovascular system Cardiac arrhythmias in connection with hyperkalemia Metabolic acidosis

Causes?*

Negative inotropic (contractive) action

inhibit the binding of Ca2+ with troponin inhibit the influx of Ca2+ from extracellular space

inhibit the release of Ca2+ into cytoplasm from endoplasmic reticulum.H+ directly impairs myocardial contraction

Response of vascular smooth muscle to catecholamine (CA). Metabolic acidosis

Endoplasmic reticulum in myocardial cells is called sarcoplasmic reticulum.*

2) Central nervous system The main manifestations are inhibitory: lethargy, disorientation, unconsciousness, or coma.Mechanism: 4) Respiratory system:deep and rapid respiration ( Kussmauls breathing).3) Osseous system: calcium phosphate in bone buffers chronic metabolic acidosis rickets and osteodystrophy (in chronic renal failure).GABA (Gamma-aminobutyric Acid) (inhibitory neurotransmitter) Glutamate decarboxylasepHGluGABA Metabolic acidosis

Effect on the nervous system: GABA (=Gamma-aminobutyric Acid) (inhibitory neurotransmitter).Effect on respiration: H+ excites respiratory center through peripheral chemoreceptors.*

Mechanism of Production of -GABA Metabolic acidosis

5) Urinary system Urine is usually acidic in MAc. But: paradoxical alkaline urine (hyperkalemia) Metabolic acidosis

7. Principles of prevention and treatment ) Correction of underlying disorders. ) Administration of NaHCO3 1.5% NaHCO3 or 1/6 M sodium lactate After the correction of acidosis, attention should be paid to prevent hypokalemia and convulsion () (induced by decreased free Ca2+ (hypocalcemia)). 3) Correction of water-electrolyte disturbances : Metabolic acidosis

Aconvulsionis a medical condition where body muscles contract and relax rapidly and repeatedly, resulting in an uncontrolled shaking of the body.*

Hypocalcemia convulsion Metabolic acidosis

This happens in metabolic acidosis or alkalosis?*

H+: hydrogen ion H+: hydrogen ionsK+: potassium ionsNa+: sodium ionsCl-: chloride ionsCa2+:Calcium ionsNH4+: ammonium ionsHCO3-:bicarbonate ionsHPO2- :phosphatic ionsCO2: carbon dioxideH2CO3:carbonic acidNH3: ammonia

mmol: millimolnmol: nanomolmmHg: millimetre of mercury column

*Disorders are big problems in clinic. http://v.qihuang99.com/player/1777.html?1777-0-2Outside the acceptable range of pH,proteinsare denatured and digested,enzymeslose their ability to function, anddeathmay occur.*Normally, acid substances are much more than alkaline ones, when people take regular diet. *H2CO3 is the only volatile acid in our body (13-15 mol/d). *All acids (except H2CO3) are fixed acids.*Fruits (even tasted acid) can be metabolized to CO2, H2O and inorganic ions (such as Na). The latter becomes base when dissolved in water. *All fixed acids can be buffered by these buffer systems. *H2CO3/HCO3- is an open buffer system, because CO2 can be eliminated from the lungs and HCO3- can be regulated by the kidneys.*Hb/HHb functions to regulate volatile (not fixed) acids. * 1) Regulation through central chemoreceptors. PaCO2 (main way) 2) Regulation through peripheral chemoreceptors in the carotid body and aortic body. PaO2* c. The effects of carbonic anhydrase CA on the apical side H+ + HCO3- H2CO3 CO2 + H2O*CO2 can also bind to HB in the plasma. *pH is the negative logarithm of H+ concentration. pH is measured in the artery blood. *PaCO2 is mainly regulated by respiration (elimination). PaCO2 is the best respiratory parameter. The respiratory control of CO2 is so efficient that CO2 retention does not develop even if CO2 production is largely increased (when respiratory function is normal). *Hb fully oxygenated meaning 100% oxygen saturation. SB increases also in respiratory acidosis after compensation of the kidneys.SB decreases also in respiratory alkalosis after compensation of the kidneys. *AB = [HCO3-]*Not necessary to compare between AB and SB, since PaCO2 is the best respiratory parameter.ABSBABSB*Reflects metabolic situation. *For pH higher than 7.4, an acid must be added the BE value is positive. *Na+, Cl-, HCO3- are determined ions. Undetermined anions include: negatively charged proteins, phosphate, sulfate, lactate, ketone bodies, etc. *RTA type IHypoxia (shock) and some drugs like metformin can cause lactic acidosis. (by increasing intracellular glycolysis)NH4Cl is used as the acid to correct metabolic acidosis. NH4Cl is used as a (expectorant eliminating sputum)*RTA type II (Inhibition of Carbonic Anhydrase HCO3- reabsorption)*

*Compensation limit by the lungs: PaCO2 = 10 mmHg*

* AB < SBTo distinguish the type of acid-base disturbance, examine pH, PaCO2, HCO3- and AG. *Causes?*Endoplasmic reticulum in myocardial cells is called sarcoplasmic reticulum.*Effect on the nervous system: GABA (=Gamma-aminobutyric Acid) (inhibitory neurotransmitter).Effect on respiration: H+ excites respiratory center through peripheral chemoreceptors.*Aconvulsionis a medical condition where body muscles contract and relax rapidly and repeatedly, resulting in an uncontrolled shaking of the body.*This happens in metabolic acidosis or alkalosis?*

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03 acid base disturbance_pti