PULMONARY FUNCTION TEST

1. PULMONARY FUNCTIONTEST ARTERIAL BLOOD GASES AND ACID – BASE BALANCE

2. Evaluating acid-base disorders pH Total C02 PCO2 Measurement of Total CO2 PCO2 electrode to measure the rate of formation of released of CO2 specimen must be handled anaerobically to minimized atmosphere losses of CO2 and HCO3 ( converted to CO2 ) which would cause a falsely low total CO2 values

3. The body normally maintains the arterial bloodpH within a very strict range of 7 .35 to 7.45. This is accomplished through the buffering capacity of the interaction of the bicarbonate system, hemoglobin, phosphate, and proteins. Metabolic processes produce 15 to 20 mmol of hydrogen ions in the body each day. The body is capable of functioning with plasma levels between 36 and 44 mmol/L of hydrogen ions. Deviations from this hydrogen ion concentration cause changes in the rates of chemical reactions in cells and metabolic processes in the body. At concentrations greater than 44 nmol/L, consciousness is altered, leading to eventual coma and death.

4. At concentrations below 36 nmol/L, symptoms of neuromuscular irritability and tetany are evident, followed by loss of consciousness and eventual death.

5. ACID-BASE BALANCE a large quantity of acid is ingested in the normal diet and produced endogenously as a result of metabolism 13,000 to 20,000 mmol/L of CO2largely converted to H2CO3 is formed as a result of oxidation of carbohydrates, proteins and fats 40 to 60 mmol/L from ketoacids as a result of incomplete oxidation of lipids, and sulfuric and phosphoric acid from oxidation of sulfur- containing amino acids and phosphorous- containing compounds HCO3 is a volatile acid because It can be converted to CO2, which can be excreted by the LUNGS Other acids are nonvolatile or fixed acids which must be excreted in the URINE/KIDNEY

6. Mechanism that maintain the pH of both ECF and ICF within narrow limits usually 7.35 to 7.45 1. buffering the blood 2. respiration 3. renal Buffer is a weak acid in solution with its conjugate base which is in the form of a salt acid is added to a solution it combines with the conjugate base to form a weaker acid – result is a smaller decrease in pH ECF buffers 1. bicarbonate/carbonic acid equilibrium = H2O + CO2 H2CO3 H + HC03 2. hemoglobin/erythrocytes 3. plasma proteins 4. plasma phosphate

7. Henderson-Hasselbalch Equation Defined as the log expression of the ionization constant equation of a weak acid, is used to express mathematically the pH that is obtained as the components of the buffer system become altered: ( HCO3 ) pH = pKa + log --------------- ( H2CO3 ) The pKa of the bicarbonate system is 6.1 and the carbonic acid concentration may be expressed as the partial pressure of carbon dioxide (PCO2) multiplied by the solubility coeffcient or alpha factor (0.03). As a result, the pH is equal to the pKa added to the log of the ratio of bicarbonate to carbon dioxide.

8. In the normal pH range of 7.35 to 7.45, this ratio should be approximately 20:1. As the bicarbonate level rises or lowers, the pH will rise or lower in direct proportion. Conversely, as PCO2 rises or lowers, pH will be altered in inverse proportion. Hemoglobin is the second most important blood buffer owing to the fact that each Hb molecule contain 38 histidine residues that are able to bind with H and owing to its relatively high conc. (15g/dL) Plasma protein both their free carboxyl and amino grps are able to bind H Organic and Inorganic least important HPO4/H2PO4

9. The sum of all buffer in the blood is Buffer Base 46 to 52 mmol/L ave value = 49mmol/L Actual buffer base - Average value Base Excess = +/- 3mmol/L Base deficit negative base excess or decrease in blood buffering capacity

10. HC03¯ anionic fraction in serum dissociation of H2C03 produced from the formation of CO2 during metabolism C02 + H20 H2CO3 H + HC03 reconverted to H2C03 dissociate to H + C02 as the blood perfuse the lungs filtered freely by the kidney but little or no HC03 present in the urine when the diet is acidic reabsorption PCT = 85% DCT = 15% measured directly – titration with acid indirectly – using measured PC02 and H in an Henderson equation most commonly measured with other combined form of CO

12. TOTAL CO2 CO2, H2CO3, and Carbamino grp this value approximate the HCO3 very closely, bec. 89% to 90% of all the CO2 that can be liberated from serum is in the form of HCO3

13. The renal system controls the pH by altering the rates of reabsorption, secretion, and excretion. The kidney is able to increase either the excretion or reabsorptiom of hvdrogen ions in exchange for sodium and potassium ions to maintain electroneutralitv. The rate of bicarbonate reabsorption may also be altered in response to the pH as bicarbonate acts as a base in the carbonic acid system. Bicarbonate is exchanged for other anions such as chloride and phosphate to maintain electroneutrality. The kidney is also capable of increasing or decreasing the rate of ammonia (NH3) formation to either excrete excess hydrogen ions as ammonium ions (NH4+) in acidosis or conserve hydrogen ions in alkalosis.

14. Kidney regulate the hydrogen ion concentration principally by increasing or decreasing the bicarbonate ion concentration in the body fluid. 1. reaction for hydrogen ion secretions 2. sodium ion reabsorption 3. bicarbonate ion excretion in the urine 4. ammonia secretion in the tubule Tubular secretion of Hydrogen ion occurs in the luminal border of PCT, DCT, Thick Loop of Henle, and Collecting tubule - secrete hydrogen ions into the tubular fluid In collecting tubule secretions can continue until the concentration of hydrogen ions in the tubule becomes as much as 900 times that in the extracellular fluyid or, in other words, until the pH of the tubular fluids falls to about 4.5 – represent the limit to the ability of the tubular epithelium to secrete hydrogen ions

15. The greater the carbon dioxide conc. in the extracellular fluid, the greater the rateof hydrogen secretions 1. decrease respiration 2. increase metabolic rate At normal carbon dioxide conc. – rate of hydrogen ion secretion = 3.5mmol/minute About 84% of all the hydrogen ions secreted by the tubules are secreted in the PCT but the maximun conc. gradient that can be achieved here is only three-to four-fold instead of 900-fold that can be achieved in the collecting tubules. That is, the pH can be decreased only to about 6.9, 0.5 pH unit below the normal

17. Reabsorption of Sodium sodium ion are reabsorbed at the same time that hydrogen ions are secreted – one sodium for each hydrogen ion that is secreted occurs in the basal and lateral borders of the epithelial cells Reabsorption of Bicarbonate Ions bicarbonate conc. In the extracellular fluid plays an extremely important role in the acid-base buffer system – control the extracellular fluid hydrogen ion conc. therefore it is important that the tubules help to regulate the extracellular fluid bicarbonate ion conc. However the tubule is impermeable to bicarbonate normally cannot be reabsorbed

18. In order for it to be reabsorbed the filteredBicarbonate has to combined with secreted Hydrogen in the tubularfluid to form Carbonic Acid and then dissociate into H20 and CO2 in the tubular fluid and the CO2 diffuses into the epithelium (to combine with H20) or – to the extracellular fluid into the blood to combined with H20 to form Carbonic Acid and dissociate into Bicarbonate and Hydrogen ions became part of the buffering system – this is the contribution of the kidneys to control the extracellular hydrogen ion conc.

20. Renal sources of Bicarbonate 1. from the dissociation of carbonic acid inside the epithelial cells from the combination of C02 and H20 under the carbonic anhydrase the bicarbonate ions produce in this process diffuses into the peritubular fluid in combination with sodium ions that has been absorbed from the tubule 2. from the formation of carbonic acid in the lumen of the tubule as result of the combination of filtered bicarbonate and secreted hydrogen ions Hydrogen Ion secretion = 3.5mmol/minute Filtration rate of Bicarbonate = 3.49mmol/minute the difference is = 0.01mmol/minute - excess hydrogen ions that did not react with filtered Bicarbonate Excess Hydrogen – react with other subs. and excreted into the urine

21. Hydrogen ions and bicarbonate ions in the tubular fluid combined with each other to form CO2 and H20 - they titrate each other but titration ( 99% occurs in the PCT ) is not complete because there are always hydrogen excess ( 0.01mmol/minute ) over bicarbonate in the tubules This is the basic mechanism by which the kidney corrects either acidosis or alkalosis - by incomplete titration of hydrogen ions against bicarbonate ions, leaving one or the other of these to pass into the urine and therefore to be removed from the extracellular fluid

22. The ability of both the respiratory and renal systems to react to acid base disturbances by attempting to restore the pH to a normal level is termed compensation. The respiratory system is capable of immediate compensatory response The renal system may take several days to reach a detectable level of compensation. Compensation for ACIDOSIS and ALKALOSIS Blood buffers act instantaneously to minimize the change in pH, their capacity to do is limited Respiratory compensation is prompt Renal compensation is gradual and occurs over three to four day period after the acid-base imbalance occur ultimate regulation with regeneration of buffers

23. Renal correction of alkalosis decrease in HCO3 ions in the extracellular fluid Henderson-Hesselbalch equation ratio of HCO3 to dissolved CO2 increases when the pH rises into the alkalosis range above 7.4 the effect of this on titration process in the tubule is to increasethe ratio of HCO3 ions filtered into the tubules to hydrogen ions secreted – this increase occurs bec. the high extracellular HCO3 ion conc. also increases its conc. in the glomerular filtrate, and the low CO2 conc. decreases the secretion of Hydrogen

24. Since no bicarbonate ions can be reabsorbed without first reacting with hydrogen ions, all the excess HCO3 ions pass into the urine and carry with them sodium ions or other positive ions Thus, the effect, sodium bicarbonate is removed from the extracellular fluid - this shifts the pH of the body fluids back in the acid direction – alkalosis is corrected

25. Renal correction of acidosis Increase in bicarbonate ions in the extracellular fluid The ratio of the carbon dioxide to bicarbonate ions in the extracellular fluid increases the rate of hydrogen ion secretions rises to a level far greater than the rate of bicarbonate ion filtration into the tubules – excess hydrogen ions are secreted into the tubules and have no bicarbonate ions react with. Each time a hydrogen ions is secreted into the tubules two other effects occur simultaneously 1.HCO3 ions is formed in the tubular epithelial cell 2.Sodium is absorbed from the tubule into the epithelial cell Sodium and HCO3 then diffuse together from the epithelial cell into the peritubular fluid.

26. Thus the net effect of secreting excess hydrogen ions into the tubules is to increase the quantity of sodium bicarbonate in the extracellular fluid this increases the HCO3 salt portion of the Bicarbonate Buffering System - shifts all of buffering in the alkaline direction – increasing the pH – correcting the acidosis Tubular Buffers excess hydrogen ions are secreted into the tubules, only a small portion of these can be carried in the free form by the tubular fluid into the urine – because the maximum hydrogen ion conc that the tubular system can be achieve correspond to pH 4.5 At normal daily urine flow this hydrogen ion conc represents only 1% of the daily excretion of excess hydrogen ions.

27. To carry excess hydrogen ions into the urine it must combine with buffers in the tubular fluid to prevent itself from rising too high – otherwise, the high conc would limit further secretion by the tubules - bec of gradient limited Tubular buffer systems for transport of the excess hydrogen ions into the urine 1. phosphate buffer 2. ammonia buffer 3. weak buffer – citrate, urate, bicarbonate Phosphate Buffer System poorly reabsorbed, HPO4 (4x>)H2PO4 weak buffer in the blood more powerful buffer in the tubular fluid HPO4 + H = H2PO4 The net effect increase the NaHCO3 conc in the extracellular fluid

29. Ammonia Buffer System NH3 and NH4 - synthesize by the tubules except thin Loop of Henle deamination of glutamine and other amino acid by glutaminase, glutamate dehydrogenase or both Importance of ammonium ion transport mechanism in handling the excess hydrogen ions 1. More NH3 combined with hydrogen more NH3 are produced from the tubular cells and diffuse into the lumen 2. When hydrogen ions combine with NH3 and the resulting NH4 then combine with chloride NH3 ( ammonia ) + H = NH4 ( ammonium ion ) + Cl excreted into the urine The net effect is to increase the sodium bicarbonate conc in the extracellular fluid

31. Anion Gap mathematical approximation of the difference between the anion and cation routinely measured in serum Na, K, Cl and HCO3(as total CO2) unmeasured cations – Ca, Mg = ave 7 mmol/L unmeasured anions – PO4, SO4, protein and anion of organic acids = ave 24 mmol/L Na – (Cl + total CO2) = less than 17mmol/L if the anion gap exceed 17mmol/L usually indicate significantly increased conc. of unmeasured anions Causes fro this condition are 1. uremia with retentions of fixed acids anions such as PO4 and SO4 2. ketotic states – DM, alcoholism or starvation 3. lactic acidosis - shock

32. Chloride Hypochloridemia 1.GIT losses 2.diabetic ketoacidosis 3.mineralocorticoid excess 4.salt-losing renal dis 5.high serum HCO3 This is a result of intracellular shift and increased renal excretion of Cl in these conditions 6. low serum Na in chronic diseases Hyperchloridemia GIT losses – diarrhea Renal tubular acidosis Mineralocorticoid difficiency

33. 4. Ingestions of toxin – methanol, salicylate, ethylene glycol, and paraldehyde 5. increased plasma proteins - dehydration 6. metabolic alkalosis due to the titration of plasma proteins resulting in loss of H and the consequent increase in the net negatively charge proteins Decreased anion gap ( < 10 mmol/L) can result in either an increase in unmeasured cations or a decrease in unmeasured anions increased in unmeasured cations 1. Li intoxication 2. hypermagnesemia 3. multiple myeloma 4. polyclonal gammopathy gamma globulin +charge at physiologic pH 5. polymyxin ( polycationic)B therapy

34. Decreased unmeasured anions 1. hypoalbuminemia 2. hyponatremia with normal or increased ECF(SIADH) due to selective renal excretion of unmeasured anions in this condition. Some form of acidosis fall in HCO3 is balanced by an elevation of Cl owing to loss of HCO3 rich and Cl poor fluid and retention of dietary Cl – anion gap remains within normal limits hyperchloridemic acidosis are associated with loss of HCO3 through GIT or kidney Increased anion gap develops in Lactic, Diabetic, or Uremic or secondary to ingestion of foreign acids minimal or slight depression of Cl Chronic Renal failure increased anion gap due to retention of PO4 and SO4 and organic anions

35. The presence or absence of an increase anion gap is characteristic of certain disorders and is helpful in diagnosing the underlying etiology of metabolic acidosis Increased anion gap in metabolic alkalosis may be moderately increased owing to hemoconcentration, increased blood lactate or increased negative charges on circulating proteins serum Cl is usually decreased Modest increased in aniop gap is not diagnostic When the anion gap exceeds 30mmol/L, the presence of anorganic acidosis is highly likely In organic acidosis increase in the blood acid anion conc. parallel the increase in the anion gap

36. and both values closely approximate the decrement in plasma HCO3 AG/HCO3 ratio = > 1 suggest a superimposed metabolic alkalosis AG/HCO3 ratio = < 0.8 is consistent with hyperchloridemic component of acidosis AG is useful also for quality of laboratory results for Na, K, and Cl and total CO2

37. Laboratory Measurement of Acid-Base Parameters it can evaluate the acid-base status it can identify the cause Determine the following 1.pH 2.one or both total CO2(really the HCO3) PCO2 3. in addition AG determination if metabolic acidosis is present Renal function studies that measure the ability of the kidneys either to excrete an acid load or to reabsorb an alkali load are useful for confirming renal tubular diseases resulting in hypochloridemic acidosis

38. ACID-BASE IMBALANCES Acidemia blood pH of less than 7.35 / H>45nmol/L result from accumulation of CO2 in the body Respiratory acidosis result of hypoventilation or ventilation/perfusion inequalities Renal compensation – reabsorption of HCO3 reflected by an increase in total CO2 and in HCO3 also occur from an accumulation of fixed acids or loss of HCO3 result in a primary decrease in total CO2 – Metabolic acidosis two types acidemia with an increased AG (>17) acidemia with normal AG (<17) hyperchloridemic metabolic acidosis Respiratory compensation – increase rate and depth of respiration

39. Alkalemia blood pH greater than 7.45 / H less than 35nmol/L decreased PCO2 conc. in the blood Respiratory alkalosis bec. it secondary to hyperventilation Renal compensation – decreasing the reabsorption of HCO3 Total circulating HCO3 is decreased also occur when there is loss of fixed acids or an increase in blood alkali such as HCO3 Primary increase in HCO3 – Metabolic alkalosis loss of fixed acids due to prolonged vomiting or to nasogastric suctioning alkali excess in excessive ingestion of basic subs., such as antacids

40. also occur in disease state in which there is excessive intracellular movement of H from the extracellular space ( often induced by hypokalemia) or excess excretion of H into the urine or both excess excretion of H mineralocorticoids – hyperaldosteronism, Cushing syndrome, or Prolonged administration of corticosteroids Respiratory compensation – decrease rate of respiration

41. Mixed Acid-Base Disturbances respiratory disturbances are frequently associated with simultaneous metabolic pertubations these can be detected if the compensatory response falls short or exceeds that expected AG or the ratio change in anion gap to that of HCO3 (AG/HCO3) is abnormal Common combinations making H pertubation worse Respiratory acidosis ad Metabolic acidosis acute pulmonary edema and cardiorespiratory arrest – poor tissue perfusion(lactic acidosis) and pulmonary edema(poor alveolar ventilation) Respiratory alkalosis and metabolic alkalosis vomiting and hyperventilating secondary to such disturbance as pain or psychogenic stress

42. Common combination lessening H pertubations Respiratory acidosis and Metabolic alkalosis COPD receiving diuretics Metabolic acidosis and Respiratory alkalosis CRF and hyperventilation Metabolic acidosis and Metabolic alkalosis CRF complicated by severe vomiting or nasogastric suction

43. Blood Gases The process of respiration supplies oxygen to tissues and removes the carbon dioxide produced by cellular metabolic activity. External respiration takes place at the alveolar surface in the lung where oxygen in the air is exchanged with carbon dioxide in the blood. Internal respiration takes place at the body tissues where oxygen in the blood is delivered to the cells and carbon dioxide is transferred from the cells to the blood for disposal.

44. Regulation of respiration is carried out through neurochemical mediation. The medullary respiratory center of the brain stem is capable of altering the rate and depth of respiration. Central chemoreceptors at the medulla oblongata respond only to an increased carbon dioxide level. Peripheral chemoreceptors in the carotid bodies and aortic bodies regulate the medullary respiratory center. are stimulated by either a decreased oxygen or an increased carbon dioxide level

46. The exchange of gases is dependent on the partial pressure gradients at the surfaces of the cells involved in the exchange. For example, at the alveolar surface, the partial pressure of oxygen in the air is greater than that in the blood; therefore, oxygen moves into the blood. Hemoglobin in the red blood cell is responsible for transportation of oxygen and carbon dioxide through the circulatory system. Theoxygen saturation refers to the amount of hemoglobin that is saturated with oxygen at the time of sampling.

50. The respiratory system controls the body pH through removal of the waste product of carbon dioxide, a component of the bicarbonate system. The chemical reactions of' the bicarbonate system are as follows: H20 + CO2 H2CO3 H + HC03 In the tissues, Hemoglobin picks up a portion of the cellular carbon dioxide forming carbaminohemoglobin. The remainder of the carbon dioxide combines with water to form carbonic acid, which dissociates to form hydrogen ions and bicarbonate ions. The hydrogen ions will bind to deoxygenated hemoglobin and the bicarbonate will move out of the cell in exchange for chloride moving into the cell, referred to as the chloride shift.