Acid-Base Disorders & Blood - PowerPoint Presentation

1. Acid-Base Disorders & Blood Gas Analysis(Part I)april 2018Clinical Pathology fellowship program

2. DefinitionsTermDefinitionAcid (HA)A substance that can yield a hydrogen\ hydronium ion when dissolved in water (gives off a H+).Base (A-)A substance that can yield hydroxyl ions (OH-).pHAn expression describing the [H+]. pH = - log [H+]Ionization constant (K)The relative strengths of acids and bases, their ability to dissociate in water, are described by their dissociation constant.pKaThe negative log of K, is also the pH in which protonated and unprotonated forms are present in equal conc.EquilibriumA state when there is no further change in conc. BufferThe combination of a weak acid or weak base and its salt, is a system that resists changes in pH. The effectiveness of a buffer depends on the pKa of the buffering system and the pH of the environment in which it is placed. e.g. proteins and plasma.

3. Conversion from pH to [H+ ]pH[H+ ] nM7.7207.65227.6257.55287.5317.45357.4407.35457.350Conversion between pH and [H+] for selected values within the limits compatible with lifeConversion from pH to [H+ ]pH[H+ ] nM7.25567.2637.15717.1797.058971006.951126.91256.851422 fold decrease in [H+] 0.3 increase in pH Log 2 = 0.3

4. Dissociation Constants (Ka)In any chemical reaction, there will ultimately occur an equilibrium. For acids, this refers to the [H+] at which the acid has half dissociated.The dissociation constant (Ka) describes the concentration of the acid and base generated when the acid dissociatespKa = - log KaIf we know the dissociation constant for an acid, we can use the concentrations of any 2 of the 3 compounds (hydrogen, acid, base) to solve for the unknown conc. of the third.HA H++ A-Weak acidprotonSalt or conjugate base

5. The Henderson-Hasselbalch EquationIt is an equilibrium equation. pH is used to express [H+]pHHA+ log=pKaA-pH HA- log=pKaA-H+ HAx=KaA-HA H++ A-(H+) HA=Ka(A-)Taking the log andX by (-1)Eliminating the minus sign

6. Carbonic Acid (C.A.)For carbonic acid:Ka = 8 x 10 -7 pKa = 6.1The source of carbonic acid in our body is dissolved CO2 (dCO2) gas, followed by hydration to form carbonic acid (H2CO3).The concentration of H2CO3 is proportional to the partial pressure excreted by dCO2. In plasma at 37°C, the value for the combination of the solubility constant for pCO2 and the factor to convert mm Hg to mmol/L is 0.0307 mmol/L/mm Hg.

7. CO2 + H2O H2CO3C.A.H2CO3 H+ + HCO3-C.A. = Carbonic Anhydrase

8. Example:H2CO3 H++ HCO3-Acid = HAProton = H+conjugate base = A-Ka = 8 x 10 -7 pKa = 6.1Solubility coefficient of CO2 = 0.0307 x pCO2H+ HAx=KaA-pHHA+ log=pKaA-

9. BuffersA buffer can be a mixture of a weak acid and its conjugate base.There must be about equal amounts of the weak acid and its conjugate base to allow the buffer to neutralize both acid and baseOptimum buffering capacity is reached when the ratio of acid to its conjugate base is ~ 1This will occur when the pH is near pKaThe buffering capacity is dependent on the:relative amount of buffer componentsabsolute amounts of buffer components

10. BuffersRelative amounts of buffer componentsA- Maximum buffering capacity:when the weak acid and its conjugate base are roughly equalB- Less, (but still working) buffering capacity:when the ratio of acid to base conc. ranged from 10:1 to 1:10 i.e. within  1 of the pKa of the weak acid.C- Ineffective buffering capacity:when the ratio of acid to base conc. is beyond 10:1 to 1:10 i.e. beyond  1 of the pKa of the weak acid.

11. BuffersAbsolute amounts of buffer componentswhen there is 1 mmol of the weak acid and 1 mmol of its conjugate base: the buffer is weaker (i.e. less resistant to the addition of acid or alkali) than would a solution containing 1 mol of the weak acid and 1 mol of its conjugate base .2 mixtures of buffer (acid and its conjugate base) will have the same pH when the ratio of acid to base is the same. However, their buffering capacity would be more in the mixture having higher molar conc. of the buffer components.

12. Physiological Buffers in our BodyBuffering agentpKa % of the blood buffering capacityCommentHemoglobin~ 6.8 80Although hemoglobin is the most abundant buffer; CA/Bicarb is the most important buffer system in vivo. WHY??The body can change the conc. of either CA (as pCO2) or bicarbonate relatively quickly, keeping CA:Bicarb relatively constant  minimizing pH changesSerum protein6-814Carbonic Acid /Bicarbonate system6.16

13. Health condition (physiological pH)In health, when the kidney and lungs are functioning properly, a 20:1 ratio of HCO3- will be maintained (resulting in a pH of 7.4) Adding the log of 20 (1.3) to the pKa (6.1)pHHA+ log=pKaA-pH=7.4(0.0307 mmol\L – mm Hg) x 40 mm Hg24 mmol\L=120

14. Acidosis vs. AcidemiaAcidosisA net increase in acid relative to baseAcidemiaAn increase in the blood [H+] and a decrease in pHAll individuals who are acidemic have an acidosis, but not all who are acidotic have acidemia

15. Changes in Simple Acid-Base Parameters in Various Acid-Base DisordersDisorderpHPrimary changeCompensation CommentsRespiratory Acidosis↓ ↑ pCO2↑ HCO3-Metabolic compensation works by changing HCO3- renal excretion (HCO3- retention by kidneys).It begins quickly.It does not reach maximum for 3-5 daysMetabolic Acidosis↓↓ HCO3-↓ pCO2Respiratory compensation works by changing pCO2 excretion (CO2 excretion by lungs).It begins quicklyIt does not reach max for 12 hr.Respiratory Alkalosis↑ ↓ pCO2↓ HCO3-Metabolic compensation (HCO3- excretion by kidneys).Metabolic Alkalosis↑↑ HCO3-↑ pCO2Respiratory compensation (CO2 retention by lungs).In simple Acid-base disorders, the change in HCO3- should be accompanied by an equal change in Cl- (equal in amount but in the opposite direction to maintain electronutrality)

16. Respiratory Compensation Mechanism(s)CO2 + H2O ⟷ H2CO3 ⟷ H+ + HCO3-CO2 + H2O ⟷ H2CO3 ⟷ H+ + HCO3-MetabolicacidosisalkalosisHyperventilationHypoventilation&/or&/or

17. Renal Compensation Mechanism(s)CO2 + H2O ⟷ H2CO3 ⟷ H+ + HCO3-CO2 + H2O ⟷ H2CO3 ⟷ H+ + HCO3-Respiratoryacidosisalkalosis

18. Changes in Mixed Acid-Base DisordersMixed Acid-base disorders are when patients have more than one disorder.They occur much more common than simple disorderUnlike in Simple Acid-Base disorders, in mixed Acid-Base disorders the change in pCO2 and HCO3- are in opposite directionsIt is important to be able to recognize what changes represents compensation and what changes indicate the presence of mixed acid-base disorders.

19. Lab Tests of Acid-Base Status:Serum electrolytesBicarbonate, Chloride, PotassiumBicarbonate: normal Bicarb, and Anion Gap (AG) rules out all acid-base disorders except for acute respiratory abnormalities.Most instruments currently measure bicarb directly by enzymatic methods or ion-selective electrodes.Some older method report total CO2 : this overestimates bicarb by ~ 1-2 mmol/L because it also measures any dCO2 gas or that bound to protein.

20. Bicarbonate, Chloride, PotassiumChloride: normally changes in parallel with sodium.A change in Cl greater than any change in sodium: indicates the presence of an acid-base disorder.It changes in the opposite direction to bicarb, but by the same amount, in all acid-base disorder except increased anion gap metabolic acidosis.If chloride and bicarb change in the same direction, independent of a change in sodium, then more than one acid-base disorder is present.Potassium: Potassium (K+) is the major intracellular cation in the body, with a concentration 20 times greater inside the cells than outside. Only 2% of the body’s total K+ circulates in the plasma. K+ has several functions in the body including regulation of H+ concentration. Lab Tests of Acid-Base Status:Serum electrolytes

21. Anion GapIt is the difference between the major measured cations (Na+ and K+) and the major measured anions (Cl- and HCO3-). (Na+ + K+) - (Cl- + HCO3-)  normal state = 15Increased Anion gap: Occurs whenever there is production of a metabolic acid (e.g. lactate) that is buffered by HCO3- .What are the other major “unmeasured’ ions? Cations: Calcium, magnesium, and IgGAnions: albumin, phosphate, Amino Acids Low Anion gap is due to: increased IgG &/orDecreased albuminLow Anion gap is common in multiple myeloma, HIV*, and cirrhosis.*HIV patients may have lower serum albumin and higher serum globulin concentrations. 

22. Lab Tests of Acid-Base Status:Arterial Blood GasIt is the first line test for acid-base disorders, although it is done in far fewer individuals than electrolytes. Should be performed by a well trained personnel and following strict guidelines:Example of pre-analytical errors: The presence of excess liquid or gas in the syringe used to collect blood gas specimens  diffusion of CO2 out of the specimen (quick) and diffusion of O2 into the specimen (to a lesser extent). If Arterial pO2 is high, O2 will also diffuse out of the sample. Specimen is not adequately chilled  glucose metabolism will take place  acidic metabolites ↓ pHHow to verify the results of the Arterial Blood Gas? Check the bicarb calculated from the Arterial blood gasCompare it with the measured bicarb. from the electrolyte testsThe difference should not be > 2-3 mmol/L, with the calculated bicarb. always lower.

23. Lab Tests of Acid-Base Status:Second Line TestsKetone bodies, lactates, Osmotic gapKetone bodies: Acetoacetate, beta hydroxybutyrate are acids Acetoacetate and acetone are measured by the nitroprusside test.Lactate: the end product of anaerobic metabolism of Glucose.Blood should be collected without tourniquet (because lactate accumulates in tissues if venous drainage is impaired).

24. Osmotic gapOsmotic Gap: It is the difference in between the measured osmolality and the calculated osmolality (which is the molar conc. of the major plasma solutes (electrolytes, glucose, urea))The osmotic pressure is measured by: Decrease in freezing point (used to detect ingested toxins because they are usually volatile and will not affect the vapor pressure)Decrease in vapor pressureCalculated osmolality = 2 X (Na + Glc + BUN + Ethanol)The difference between them is the Osmotic gap.Normal osmotic gap is < 10Lab Tests of Acid-Base Status:Second Line Tests

25. Acidosis (due to increased acid production)Endogenous acids: increased generation of normal metabolic products (Ketone bodies, LA, congenital disorders of AA metabolism)Exogenous acids: addition of exogenous products that can be metabolized to acids (methanol, salicylates)Mechanisms of this type of acidosis:Metabolic acids have pKa 4-5 (& will be completely ionized at normal body pH)The released H+ will be buffered by HCO3-  increased Anion gap metabolic acidosisStart by measuring the KB (hydroxylbutyrate) and LA If the increase in the AG is not equal to the measured molar conc. of the endogenous acids  ingestion of exogenous products in suspected.

26. Acidosis (due to decreased acid excretion)Renal FailureDisorders interfering with the ability of the lungs or kidney to excrete acids.Renal failure acidosis (because organic acids (LA, AA) & inorganic acids (phosphoric, sulfuric) cannot be cleared at a normal rateWith acute RF, glomerular filtration is rapidly impaired quick development of this acidosisWith chronic RF, excretion of the anions is preserved till glomerular filtration is severely impaired (occurs when the S creatinine is 10-12 mg/dL i.e. 880-1000 µmol/L)  acidosis in the very late stages of chronic RF

27. Respiratory acidosis differs from other forms of acidosis in that the serum HCO3- and pCO2 are increased rather than decreased.Causes of Respiratory acidosis:Severe pneumonia Adult and neonatal respiratory distress syndromesDecrease gas expiration with acute or chronic airway obstructionChest wall injuriesSevere muscle weaknessAcidosis (due to decreased acid excretion)Respiratory Failure

28. Case 1A 75-year-old widow, a known heavy smoker and chronic bronchitic, and a patient in a long-stay hospital, became very breathless and wheezy. The senior nurse called the doctor who was on duty, but he was unable to come at once because he was treating another emergency. He asked the nurse to start the patient on 24% oxygen. One hour later, when the doctor arrived, he examined the patient and took an arterial specimen to determine her blood gases. The results were as shown below. (Lecture Notes, 9th ed, p 34, case 3.1)How would you describe the patient's acid-base status? Do you think that she was breathing 24% O2?Blood gas analysisResultsRef rangeH+ (nM)9737-45pCO2 (kPa)21.84.5-6HCO3- (mM)4221-29pO222.512-15

29. Case answer:Blood gas analysisResultsRef. rangeCommentH+ (nM)9737-45acidosis (high [H+] and low pH). pCO2 (kPa)21.84.5-6Respiratory acidosis (the only acidosis where both the pCO2 and HCO3- are high)HCO3- (mM)4221-29Because the renal compensation by retention of HCO3- requires few days to be maximum, this cannot be the reason for her high HCO3-, since her recent illness is short in time despite her long history of chest complaints.pO222.512-15Alveolar PO2 must be greater than arterial PO2, so it was possible to conclude that the patient must have been breathing O2 at a concentration of at least 40%. On checking, it was found that the wrong mask had been fitted, and that O2 was being delivered at 60%.

30. A young man sustained injury to the chest in a road traffic accident. Effective ventilation was compromised by a large flail segment. Investigations: What is your comment?Arterial blood parametervalueReference rangepO2 (kPa)812-15pCO2 (kPa)84.5-6[H+] nM5837-45HCO3- mM2521-29Case 2

31. There is severe acidosis, and the raised pCO2 indicates that it is respiratory. The magnitude of the increase in [H+] suggests that no renal compensation has occurred. Such compensation can take several days to become fully effective, in contrast to the rapid respiratory compensation in non-respiratory disorders. Arterial blood parametervalueReference rangeCommentpO2 (kPa)812-15hypoxemiapCO2 (kPa)84.5-6respiratory[H+] nM5837-45acidosisHCO3- mM2521-29No renal compensationCase answer:

32. An elderly man was brought into the A&E department after collapsing in the street. He was deeply comatose and cyanosed, with unrecordable blood pressure. The results of acid–base analysis were as shown below. (Lecture Notes, 9th ed, p 39, case 3.4)What is you comment?Arterial blood parametervalueReference rangeCommentpO2 (kPa)4.812-15pCO2 (kPa)10.44.5-6[H+] nM12437-45HCO3- mM15.421-29Case 3

33. He has combined metabolic and respiratory acidosis. Such results are seen in patients with markedly impaired circulatory and respiratory function, such as that which occurs after a cardiac arrest. The man was found to have a large abdominal aortic aneurism that had ruptured. Arterial blood parametervalueReference rangeCommentpO2 (kPa)4.812-15Hypoxemia pCO2 (kPa)10.44.5-6Respiratory[H+] nM12437-45AcidosisHCO3- mM15.421-29MetabolicCase answer:

34. Acidosis (due to increased base excretion)Characterized by decreased blood level of HCO3- and increased Cl- WHY?Because the kidneys are forced to reabsorb increased amounts of Cl- along with sodium to maintain electroneutrality (since this acidosis is due to increased net excretion of HCO3-)

35. Followed in Part II of The Lecture