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ACID BASE BALANCE (PH) ABG INTERPRETATION

IMAD AHMAD ALMASRI , MD .

GUIDELINES FOR STUDYING ACID-BASE BIOLOGYGuideline 1:Acids and Bases Obey the Balance Principle.

Guideline 2: Body Fluids Are Buffered.

Guideline 3: Input and Output of Acids Alter Bicarbonate But Not the Partial Pressure of CO2.

Guideline4:Excretion of CO2 and BicarbonateAre Independent of Each Other.

(the Henderson-Hasselbalch equation): Acid conjugate base + H+ [H] = K [acid]/[base] pH = pK + log [base/acid]

CO2 + H2O H2CO3 HCO3- + H+

CO2 +H2O HCO3- + H+ (carbonic anhydrase)

Sources of Acids and Bases:

metabolism oF dietary protein.metabolism oF dietary weak acids.GI Secretions.Anaerobic metabolism of Carbohydrate and Fat.

Buffer Systems of the Body:

Time-Frame of Compensatory Responses to Acute Acid Loading:

RENAL HANDLING OF ACIDS AND BASES: Normal contributions of tubular segments to renal hydrogen ion balance:

Proximal tubule

- Reabsorbs most filtered bicarbonate (normally about 80%)* -Produces and secretes ammonium

Thick ascending limb of Henles loop

- Reabsorbs second largest fraction of filtered bicarbonate (normally about 1015%)*Distal convoluted tubule and collecting-duct system

Reabsorbs virtually all remaining filtered bicarbonate as well as any secreted bicarbonate (Type A intercalated cells)* - Produces titratable acid (Type A intercalated cells)* - Secretes bicarbonate (Type B intercalated cells)

* Processes achieved by hydrogen ion secretion.

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Renal HCO3- Reabsorption Bicarbonate is freely fi ltered at the glomerulus and is reabsorbedalong the nephron through a process involving secretion of H+. Under normal conditions, 100% ofthe fi ltered bicarbonate is reabsorbed.

Predominant proximal tubule mechanism for reabsorption of bicarbonate.Hydrogen ions and bicarbonate are produced intracellularly. The hydrogen ions aresecreted via an Na-H antiporter (member of the NHE family), while the bicarbonate istransported into the interstitium via an Na-3HCO3 symporter (member of the NBC family).As more sodium enters via the Na-H antiporter than leaves via the Na-3HCO3 symporter,additional sodium is removed via the Na-K-ATPase.

Type A and Type B intercalated cells. A, Predominant collecting tubulemechanisms in Type A intercalated cells for the secretion of hydrogen ions that resultin the formation of titratable acidity. The apical membrane contains H-ATPases, whichtransport hydrogen ions alone or in exchange for potassium.B, The Type B intercalated cell secretes bicarbonate and simultaneously transports hydrogen ions into the interstitium.The difference between this cell type and the Type A cell and those in the proximaltubule is that the location of the transporters for hydrogen ions and bicarbonate areswitched between apical and basolateral membranes. ATP, adenosine triphosphate.

PHOSPHATE AND ORGANIC ACIDS AS BUFFERS:Excretion of hydrogen ions on filtered phosphate. Divalent phosphate (baseform) that has been filtered and not reabsorbed reaches the collecting tubule, where itcombines with secreted hydrogen ions to form monovalent phosphate (acid form) and isthen excreted in the urine. The bicarbonate entering the blood is new bicarbonate, not merely a replacement for filtered bicarbonate. ATP, adenosine triphosphate.

HYDROGEN ION EXCRETION ON AMMONIUM:Ammoniagenesis and excretion. A, Ammonium production from glutamine.Glutamine is originally synthesized in the liver from NH4+ and bicarbonate. Whenit reaches the proximal tubule cells, it is converted back to NH4+ and bicarbonate.There are more biochemical steps in the conversion of glutamine to ammonium and bicarbonatethan indicated here; only the end result is shown.

B, Ammonium reabsorption in the thick ascending limb. Ammoniumreaches the thick ascending limb from two sources. Most comes from secretion in the proximal tubule. Some also enters the thin limbs from the medullary interstitium in the form of neutral ammonia and is subsequently reprotonated in the lumen (ammonium recycling). Ammonium is reabsorbed in the thick ascending limb by several mechanisms,the predominant one being entrance via the NKCC multiporter (where ammonium substitutes for potassium).

C, Ammonium secretion in the inner medulla. Several mechanisms are involved. A prominent one involves uptake and secretion of neutral ammonia via specific transporters in parallel with hydrogen ion secretion, resulting in reformation of ammonium in the lumen. In the innermost medulla, the high interstitial ammonium concentration allows ammonium to substitute for potassium on the Na-K-ATPase.

Summary of renal ammonia metabolism. The proximal tubule produces ammonia, as NH 4 + , from glutamine.NH 4 + is then secreted preferentially into the luminalfluid, primarily by NHE-3. It is then reabsorbed by theTAL, primarily by NKCC2. This results in ammonia deliveryto the distal nephron accounting for ~20% of final urinary ammonia; the remaining ~80% is secreted in the collecting duct through parallel NH 3 and H + transport.Numbers in red indicate proportion of total urinary ammonia present at the indicated sites under baseline conditions

CONTROL OF RENAL GLUTAMINE METABOLISM AND NH4+EXCRETION:Glutamine metabolism and NH4 excretion are increased during acidosis and decreased during alkalosis. The signal is unknown.Tubular hydrogen ion secretion is -Increased by the increased blood Pco2 of respiratory acidosis and decreased by the decreased Pco2 of respiratory alkalosis. -Increased, independently of changes in Pco2, by the local effects of decreased extracellular pH on the tubules; the opposite is true for increased extracellular pH

QUANTIFICATION OF RENAL ACID-BASE EXCRETION: How much bicarbonate is excreted in the urine?

How much new bicarbonate is contributed to the plasma by secretion of hydrogen ions that combine in the tubular lumen with non-bicarbonate urinary buffers?

How much new bicarbonate is returned to the plasma by secretion of hydrogen ions that are excreted as ammonium?

Summary of processes that acidify or alkalinize the bloodNonrenal mechanisms of acidifying the blood -Consumption and metabolism of protein (meat) containing acidic or sulfur-containing amino acids -Consumption of acidic drugs- Metabolism of substrate without complete oxidation (fat to ketones and carbohydrate to lactic acid)-GI tract secretion of bicarbonate (puts acid in blood)Nonrenal mechanisms of alkalinizing the blood -Consumption and metabolism of fruit and vegetables containing basic amino acids or the salts of weak acids- Consumption of antacids- Infusion of lactated Ringers solution -GI tract secretion of acid (puts bicarbonate in the blood)Renal mechanisms of acidifying the blood

-Allow some filtered bicarbonate to pass into the urine- Secrete bicarbonate (Type B intercalated cells)

Renal means of alkalinizing the blood

- Secrete protons that form urine titratable acidity (Type A intercalated cells) -Excrete NH4-synthesized from glutamine

Causes of Metabolic Acidosis:High anion gap typeKetoacidosisDiabeticAlcoholicStarvationLactic acidosisType AType BD-Lactic acidosisIntoxicationsEthylene glycolM ethanolSalicylatePyroglutamic acidosis from acetaminophenAdvanced renal failure

Normal anion gap typeI. Gastrointestinal bicarbonate lossA. DiarrheaB. External pancreatic or small-bowel drainageC. Ureterosigmoidostomy, jejunal loop, ileal loopD. Drugs 1. Calcium chloride (acidifying agent) 2. Magnesium sulfate (diarrhea) 3. Cholestyramine (bile acid diarrhea)III. Drug-induced hyperkalemia (with renal insufficiency) A. Potassium-sparing diuretics (amiloride, triamterene, spironolactone) B. Trimethoprim C. Pentamidine D. ACE-Is and ARBs E. Nonsteroidal anti-inflammatory drugs F. Cyclosporine and tacrolimus

Renal acidosisA. Hypokalemia 1. Proximal RTA (type 2) Drug induced: acetazolamide, topiramate 2. Distal (classic) RTA (type 1) Drug induced: amphotericin B, ifosfamideB. Hyperkalemia 1. Generalized distal nephron dysfunction (typ4 RTA) a. Mineralocorticoid deficiency b. Mineralocorticoid resistance (autosomal dominant PHA c. Voltage defect (autosomal dominant PHA I and PHA II) d. Tubulointerstitial diseaseIV. OtherA. Acid loads (ammonium chloride, hyperalimentation)B. Loss of potential bicarbonate: ketosis with ketone excretionC. Expansion acidosis (rapid saline administration)D. HippurateE. Cation exchange resins

Causes of Metabolic Alkalosis:Volume-depleted typeGastric acid lossVomitingGastric suctionRenal chloride lossDiureticsPosthypercapniaCystic fibrosisVolume-replete typeMineralocorticoid excessHyperaldosteronismGitelman's syndromeBartter's syndromeCushing's syndromeLicorice excessProfound potassium depletion

Respiratory Acid-Base Disorders:I. AlkalosisA. Central nervous system stimulationD-Stimulation of chest receptors

1. Pain2. Anxiety, psychosis3. Fever4. Cerebrovascular accident5. Meningitis, encephalitis6. Tumor7. Trauma1. Hemothorax2. Flail chest3. Cardiac failure4. Pulmonary embolism

B. Hypoxemia or tissue hypoxiaE. Miscellaneous

1. High altitude2. Pneumonia, pulmonary edema3. Aspiration4. Severe anemia1. Septicemia2. Hepatic failure3. Mechanical hyperventilation4. Heat exposure5. Recovery from metabolic acidosis

C. Drugs or hormones1. Pregnancy, progesterone2. Salicylates3. Cardiac failure

Causes of Respiratory Acidosis:Acute :Airway obstruciontaspiration of foreign body or vomitus , laryngospasm , generalized bronchospasm , obstructive sleep apnea.

Respiratory center depressiongeneral anesthesia , sedative overdosage , cerebral trauma or infarction,central sleep apnea

Circulatory catastrophes cardiac arrest , severe pulmonary edema.

Neuromuscular defects high cervical cordotomy , botulism , tetanus , Guillain-Barr syndrome , crisis in myasthenia gravis , familial hypokalemic periodic paralysis , hypokalemic myopathy , toxic drug agents(eg , curare , succinylcholine , aminoglycosides , organophosphates ).

Restrictive defects pneumothorax , hemothorax , fl ail chest , severe pneumonitis , hyaline membraneDisease , adult respiratory distress syndrome.

Pulmonary disorders pneumonia , massive pulmonary embolism , pulmonary edema , mechanicalUnderventilation.

Chronic: Airway obstruction: chronic obstructive lung disease (bronchitis , emphysema) .

Respiratory center depression: chronic sedative depression , primary alveolar hypoventilation , obesity hypoventilation syndrome , brain tumor , bulbar poliomyelitis .

Neuromuscular defects: poliomyelitis , multiple sclerosis , muscular dystrophy , amyotrophic lateral sclerosis , diaphragmatic paralysis , myxedema, myopathic disease (eg , polymyositis , acid maltase deficiency ) .

Restrictive defects: kyphoscoliosis , spinal arthritis , fi brothorax , hydrothorax , interstitial fi brosis , decreased diaphragmatic movement (eg, ascites) , prolonged pneumonitis , obesity .

II. AcidosisA. CentralDrugs (anesthetics, morphine, sedatives)2. Stroke3. InfectioB. AirwayObstruction2. AsthmaParenchyma1. Emphysema2. Pneumoconiosis3. Bronchitis4. Adult respiratory distress syndrome5. BarotraumaD. NeuromuscularPoliomyelitis2. Kyphoscoliosis3. Myasthenia4. Muscular dystrophiesE. Miscellaneous1. Obesity2. Hypoventilation3. Permissive hypercapnia

Stepwise approach:Step 1: assess oxygenation status .

Step 2: Measure pH. This identifies acidemia or alkalemia.Step 3: Determine partial pressure of CO2 .Step 4: Determine The change in bicarbonate . simple or mixed. Calculate the serum anion gap (AG)

Step 5: Determine the cause of the acidbase disorder from the clinical setting and laboratory tests.Treat the underlying disorder .

pHPaCO2HCO3-normal7.35 7.45(3545 mmHg)22 26 mmol l-1 acidotic457,4526

Expected PaO2FiO2 * 5

*Metabolic acidosis with compensation respiratory *Respiratory acidosis with compensation kidneyNMetabolic alkalosisNRespiratory alkalosis pHNPaCO2Metabolic acidosis Respiratory acidosis

NHCO3-

Metabolic and respiratory alkalosis

Metabolic and respiratory acidosis * *pHPaCO2metabolic alkalosis with compensation respirtoryRespiratory alkalosis with compenasation kidneyHCO3-

CASE 156 F with vomiting and diarrhea 3 days ago her last urine output was 12 hours ago .

BP 80/60 HR 110 RR 28 Poor skin turgor

NA130PH7,30K2,5P co230CL105Hco315BUN42Po290CREA2

Pre-renal azotemia.

Metabolic acidosis.

Simple.

NAG.

Hydrate + Correct hypokalemia.

QUESTIONS?

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