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Arterial Blood Gas _ABG_ Analysis and Interpretation of Results

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Arterial Blood Gas _ABG_ Analysis and Interpretation of Results Powered By Docstoc
					                                            Undergraduate Medicine 2004/2005
                                            Phase 1, Year 1 MD
                                            217 PPSP students (28 repeat; 189 new)
                                            68 PPSG students
Renal Block                                 Total: 285 students



     Acid-Base Homeostasis: Renal Control of pH
                                Renal mechanism
      (Homeostasis Asid-Bes: Kawalan Renal ke atas pH;
                     Mekanisme renal)

              Assoc. Prof. Faridah Abdul Rashid
                             Dept. of Chemical Pathology
                             School of Medical Sciences
                              Universiti Sains Malaysia
                                faridah@kb.usm.my



              Lecture, Tuesday, 8 March 2005, 9.00 am – 10.00 am, DK4        1
                       Objectives
With regard to acid base balance

  A.       Describe/discuss regulation of acid base
           homeostasis
       •     Blood buffers (refer to Hemopoietic & Lymphoid Block)
       •     Respiratory mechanism (refer to Respiratory Block)
       •     Renal mechanism (Renal Block)



  B.       Describe/discuss acid-base disorders –
       •     Primary changes in acidosis and alkalosis
       •     Their compensatory mechanisms
               •    Respiratory
               •    Metabolic
                                                                     2
Mechanisms for Controlling pH
1. Blood buffers
2. Respiratory mechanism
3. Renal mechanism




                                3
                 1. Revision
1. Blood buffers
    •   Carbonic acid/bicarbonate buffer system
    •   Hemoglobin
    •   Chloride shift


2. Respiratory mechanism
    •   Hyperventilation
    •   Hypoventilation


                                                  4
Respiratory Centre




                     5
       Pulmonary Ventilation
• Normal, unassisted breathing:
  – An increase in arterial PCO2 acts through the
    respiratory centre to increase the rate of
    pulmonary ventilation
  – A decrease in arterial PCO2 reduces the rate
    of ventilation

• Assisted breathing:
  – A respirator is used to assist breathing by
    expelling CO2, thus reducing PCO2 in blood
                                                    6
                 SLU #1
• Huraikan peranan sistem darah dalam
  homeostasis asid-bes.
• Explain the role of blood in acid-base
  homeostasis. (15 minit)




                                           7
Panduan Jawapan SLU #1
                 Topik                         Masa
                                          (minit)=Markah
 Bentuk-bentuk CO2 dalam darah                  3

 Pembentukan asid karbonik dan t/b              1
 di tisu
 Peranan karbonik anhidrase di tisu             1

 Peranan hemoglobin di tisu                     1

 Pemindahan klorida (chloride shift) di         1
 tisu
 Pembebasan CO2 di paru-paru                    1

                                                           8
bersambung

Panduan Jawapan SLU #1
                  Topik                  Masa (minit) =
                                           Markah
   Peranan karbonik anhidrase di paru-         1
   paru
   Peranan hemoglobin di paru-paru             1

   Pemindahan klorida di paru-paru             1

   Kadar bertindak mekanisme                   1
   respiratori
   Nisbah bokarbonat/asid karbonik             1
   dalam darah
   Kepentingan pH darah dikekalkan             2
   dalam julat kecil
                                                          9
    Types of acid-base imbalance
•    Simple or primary acid-base imbalance:
      1.   Respiratory acidosis
      2.   Respiratory alkalosis
      3.   Metabolic acidosis
      4.   Metabolic alkalosis

•    Mixed acid-base imbalance
      pH remains normal
      (Reserve for Phase 2 MD)

                                              10
  Acid-base changes in acidosis and alkalosis


Acid-base Disturbance               pH     HCO3-   PCO2

Respiratory acidosis                             
Respiratory alkalosis                            
Metabolic acidosis                                

Metabolic alkalosis                               
Thicker arrows indicate primary disorder
                                                          11
Acid-base changes in acidosis and alkalosis

                                                             Memorise
Acid-base Disturbance               pH     HCO3-   PCO2

Respiratory acidosis                                   pH, PCO2 in
                                                          opposite
                                                          directions;
                                                          HCO3- will
Respiratory alkalosis                                  follow PCO2

                                                          pH, HCO3-
Metabolic acidosis                                     in same
                                                          direction;
                                                          PCO2
Metabolic alkalosis                                    will follow
                                                          HCO3-

Thicker arrows indicate primary disorder                         12
   Primary Conditions & Compensation

• Four primary conditions are possible:
  1. Respiratory acidosis
       + acute blood response     Rapid compensation (10 min)
       + chronic renal response   Slow compensation (4 days)
                                                                  Two-phase
  2. Respiratory alkalosis                                        process
       + acute blood response     Rapid compensation (10 min)
       + chronic renal response   Slow compensation (8 days)

  3. Metabolic acidosis
       + respiratory response     Fast compensation (24 h)
                                                                Single-phase
  4. Metabolic alkalosis                                        process
       + respiratory response     Fast compensation (24 h)
                                                                      13
                                            Gold trunk

             Compensation
• The purpose of the compensation is to return
  the blood pH to normal

• The change in the PCO2 in the metabolic
  disorders represents the lung‟s role in
  compensation

• The change in the bicarbonate level
  represents the kidney‟s attempt to
  compensate for the respiratory acidosis or
  alkalosis                                    14
Respiratory Compensation for Preventing
 Change in pH when lungs are normal

    Cells/Tissue                Blood
     Acidosis
                                    Acidaemia
      CO2 
                                   pH , PCO2 
       H+

                                Lungs
                                   CO2 removal
                                   Via respiration
                                  Hyperventilate

                               Blood
                                    Normal pH

 Acidosis may be accompanied by acidaemia.
 The change in pH may be prevented by respiratory removal of CO2.
                                                                    15
Respiratory Compensation for Preventing
 Change in pH when lungs are normal

  Cells/Tissue                 Blood
    Alkalosis
                                     Alkalaemia
      CO2 
                                pH , PCO2 , HCO3-
     HCO3-
                               Lungs
                                    CO2 retention
                                   Via respiration
                                   Hypoventilate

                               Blood
                                       Normal pH


 Alkalosis will not be accompanied by alkalaemia
 if enough CO2 has been retained to prevent the change in pH.
                                                                16
                                                                    Gold trunk
Compensation in respiratory disorders
 • Compensation in respiratory disorders is a two-phase process:
    (i) Acute response: initial 10 minutes
         • Involves blood buffers
    (ii) Chronic (renal) adaptation: for up to 4-8 days
         • The change in the bicarbonate level represents the kidney‟s
           attempt to compensate for the respiratory acidosis or alkalosis
 • pH returns towards normal but not pH 7.4:
                                           10 min

pH 7.7                                       Acute response pH 7.77.6
pH 7.6                                          Chronic response pH 7.67.45
pH 7.5 10 min
pH 7.4
pH 7.3                        4 days                             8 days
pH 7.2      Chronic response pH 7.27.35   RESPIRATORY ALKALOSIS
pH 7.1   Acute response pH 7.17.2
                                                                          17
        RESPIRATORY ACIDOSIS
Changes in bicarbonate
                                                                       Gold trunk
 Compensation in respiratory disorders
    1. Compensation in respiratory disorders is a two-phase process:
        (i) Acute response occurs during initial 10 minutes
             •  This buffering by buffers in blood
             •  Changes in [HCO3-] occur within 10 minutes
        (ii) Chronic (renal) adaptation occurs for up to 4-8 days
             •  The change in the bicarbonate level represents the kidney‟s
                attempt to compensate for the respiratory acidosis or alkalosis
             •  Changes in [HCO3-] occur up to:
                    » 4 days in respiratory acidosis
                    » 8 days in respiratory alkalosis

    2. Changes in [HCO3-] and pH occur within 10 minutes, and up to:
               4 days in respiratory acidosis
               8 days in respiratory alkalosis                            18
1. Summary of changes in pH
                                                                     Gold trunk
Compensation in respiratory disorders
  1. Compensation in respiratory disorders is a two-phase process:
      (i) Acute response occurs during initial 10 minutes
           •  This buffering by buffers in blood
           •  Changes in pH occur within 10 minutes
      (ii) Chronic (renal) adaptation occurs for up to 4-8 days
           •  Changes in pH occur up to:
                  » 4 days in respiratory acidosis
                  » 8 days in respiratory alkalosis
  2. Changes in pH occur within 10 minutes, and up to:
             4 days in respiratory acidosis
             8 days in respiratory alkalosis

  3. pH returns towards normal but not pH 7.4:
              Final pH 7.35 in respiratory acidosis                     19
              Final pH 7.45 in respiratory alkalosis
2. Summary of changes in pH
                                                                  Gold trunk
Compensation in respiratory disorders
1. Compensation in respiratory disorders is a two-phase process

2. Changes in pH occur within 10 minutes, and up to:
    (i) 4 days in respiratory acidosis
    (ii) 8 days in respiratory alkalosis

3. When fully compensated, pH returns towards normal but not pH 7.4

4. pH Changes in RESPIRATORY ACIDOSIS are:
    (i) Acute response pH 7.17.2 (initial 10 minutes)
    (ii) Chronic response pH 7.27.35 (lower normal limit within 4 days)

5. pH Changes in RESPIRATORY ALKALOSIS are:
    (i) Acute response pH 7.77.6 (initial 10 minutes)
    (ii) Chronic response pH 7.67.45 (upper normal limit within 8 days)
                                                                      20
Respiratory acidosis   Gold trunk




                          21
Respiratory alkalosis   Gold trunk




                           22
 Respiratory Disturbance of pH
• The disturbances of pH caused by
  hypoventilation and by hyperventilation are
  known as „gaseous‟ or „respiratory‟
  acidosis and alkalosis

• They indicate that the disturbances arise
  from mishandling of the blood gases or
  from an inappropriate rate of pulmonary
  ventilation
                                              23
           Equivalences
Disorder    Cause        Mechanism

Respiratory Hypercapnia Alveolar
acidosis                hypoventilation

 pH         PCO2      CO2 retention

Respiratory Hypocapnia Alveolar
alkalosis              hyperventilation

 pH         PCO2      blow off CO2
                                          24
                                                                     Please read

Compensation in Respiratory Acidosis

• Assisted breathing:
  – A respirator is used to assist breathing by
    expelling CO2, thus reducing PCO2 in blood
• Bicarbonate is generated and reabsorbed
  by renal tubules
• Renal system excretes H+ in urine
• Renal bicarbonate is returned to blood to
  bring up pH to normal
 A respirator is a device (alat) to assist (help) a patient to breathe (bernafas).
                                                                                 25
http://www.immunize.org/images/ca.d/ipcd1861/img0008.htm


                                     Polio




                                                       Polio can cause severe
                                                       illness, long-term paralysis,
                                                       inability to breathe without
                                                       the help of a machine, and
                                                       even death.
     Hospital respiratory ward in Los Angeles,
     California in 1952. Thousands of people were
     dying of polio or were crippled by it. Patients
     are in “iron lungs” (breathing machines),
     unable to breathe on their own due to polio.                              26
                      Polio
• Infectious agent: Polio bacteria live in throat and
  intestines of an infected person
• Route of infection: Polio usually spreads to other
  people through contact with faeces (najis)
• Incubation: Once infected, it takes 6-20 days to
  get sick
• Symptoms: fever, severe muscle pain or spasm,
  paralysis, headache
• Carriers: Some people do not look or feel sick,
  but can still spread the disease to others
                                                    27
   2. Metabolic Control of pH
                 Please read…

3. Renal mechanism
    •   Bicarbonate regeneration
    •   H+ excretion:
           » Phosphate
           » Ammonia……glutamate….gluconeogenesis




                                                   28
Importance of Bicarbonate as Sole Buffer

 • Bicarbonate is the only important buffer base in ECF
 • Bicarbonate is practically the only buffer base in CSF
 • The pH of ECF can be regulated by mechanisms which
   control the concentration of bicarbonate and PCO2
 • Both bicarbonate and PCO2 are subjected to
   physiological control, each by a separate system




                                                       29
       Maintaining Bicarbonate
• The concentration of bicarbonate is
  regulated by the kidneys
• The tubular epithelium reabsorbs cations and anions
  from the glomerular filtrate in such a way that the sum of
  the concentrations of the cations in the plasma is
  normally kept greater than the sum of the concentrations
  of anions other than bicarbonate by about 24 to 27
  mmol/L
• The ready supply of CO2 from metabolic sources
  ensures that the balance of anions required for
  electroneutrality is made up by bicarbonate
                                                           30
Mechanisms Controlling [HCO3-]

• An acute increase in PCO2
  – sharply acidifies the CSF and greatly increases
    pulmonary ventilation
• A sustained increase in PCO2
  – leads to the secretion of a CSF which is richer in
    HCO3-, so that the initial stimulation of pulmonary
    ventilation is not maintained
  – Though PCO2 remains high, the pH of the CSF
    returns towards normal, and the respiratory
    stimulus fades - this fading takes some time
                                                          31
  Metabolic Disturbance of pH
• Metabolic disturbance of pH arise from the
  excessive production or absorption of
  acids or alkalis, or from disorders of the
  secretion of acid by the renal tubular
  epithelium

• A metabolic acidosis which occurs
  because the kidneys cannot excrete acids
  adequately may be called a „renal
  acidosis‟                               32
Patients with Metabolic Acidosis
• Excess acid in blood
   – removes HCO3- from the plasma, lowering pH and stimulating
     the peripheral chemoreceptors to increase breathing
   – lowers PCO2, making the CSF more alkaline, so that the central
     chemoreceptors act at first to oppose the respiratory stimulation
   – Consequently, the typical hyperventilation that accompanies a
     sustained acidosis takes 1 to 2 days to develop, while the
     [HCO3-] in the CSF is being reduced


• If the acidosis in the blood is suddenly relieved
   – the hyperventilation may still continue because the patient is
     like the acclimatised mountaineer who has come down quickly
   – the [HCO3-] in his CSF is low, and he must continue to
     hyperventilate until it rises to normal                        33
                 Metabolic Acidosis


 [HCO3-]
(mmol/L)




    Acid-base Disturbance                pH        HCO3-         PCO2
    Metabolic acidosis                                         
                                                                        34
   The primary lesion in metabolic acidosis is reduced [HCO3-]
               Metabolic Acidosis



PCO2                                                                 22.5
(mmHg)




    Compensation:
    In METABOLIC ACIDOSIS, PCO2  from 40  22.5 mmHg within 1 day   35
             Metabolic Acidosis


                                                                7.25
pH




     With compensation:
     pH returns towards normal (but is never normal)
     pH  in METABOLIC ACIDOSIS from pH 7.07.25 within 1 day    36
     Final pH is lower than in respiratory acidosis
Summary:

              Initial    1     Comp
Acid-base      pH       HCO3-   PCO2
Disturbance
Metabolic
                              
acidosis


•   The primary lesion in
    metabolic acidosis is
    reduced [HCO3-] from
    2510 mmol/L

•   The compensatory
    response to lowered
    plasma bicarbonate is
    decreased PCO2 from
    4022.5 mmHg

Observe pH  from 7.07.25

                                37
Metabolic acidosis   Gold trunk




                        38
                SLU #2
• Huraikan respons kompensatori
  (pampasan) dalam asidosis metabolik.
• Explain the compensatory response in
  metabolic acidosis. (15 minit)




                                         39
Panduan Jawapan SLU #2
      See next slide




                         40
                           START
Compensation in
Metabolic Acidosis
 • The primary lesion in
   metabolic acidosis is           BLOOD
   reduced [HCO3-] from
   2510 mmol/L

 • The compensatory
   response to lowered
   plasma bicarbonate is
   decreased PCO2 from
   4022.5 mmHg
 Observe pH  from
   7.07.25

                                           41
                 Metabolic Alkalosis


 [HCO3-]
(mmol/L)




    Acid-base Disturbance                pH        HCO3-           PCO2
    Metabolic alkalosis                                          
                                                                          42
   The primary lesion in metabolic acidosis is increased [HCO3-]
                 Metabolic Alkalosis


                                                                         50

PCO2
(mmHg)




         Compensation:                                              43
         In METABOLIC ALKALOSIS, PCO2  from 40  50 within 1 day
           Metabolic Alkalosis


pH




     With compensation:
     pH returns towards normal (but is never normal)
     pH  in METABOLIC ALKALOSIS from pH 7.67.5 within 1 day   44
     Final pH is higher than in respiratory alkalosis
Summary:
              Initial    1     Comp
Acid-base      pH       HCO3-   PCO2
Disturbance
Metabolic
                              
alkalosis

• The primary lesion in
  metabolic alkalosis is
  increased [HCO3-]
  from 2540 mmol/L
• The compensatory
  response to elevated
  plasma bicarbonate is
  increased PCO2 from
  4050 mmHg
• Observe pH  from
  7.67.5
                                 45
Metabolic alkalosis   Gold trunk




                         46
                SLU #3
• Huraikan respons kompensatori
  (pampasan) dalam alkalosis metabolik.
• Explain the compensatory response in
  metabolic alkalosis. (15 minit)




                                          47
Panduan Jawapan SLU #3
      See next slide




                         48
                            START
 Compensation in
Metabolic Alkalosis
 • The primary lesion in            BLOOD
   metabolic alkalosis is
   increased [HCO3-] from
   2540 mmol/L

 • The compensatory
   response to elevated
   plasma bicarbonate is
   increased PCO2 from
   4050 mmHg

 • Observe pH  from
   7.67.5
                                            49
Summary of changes in pH
                                                                      Gold trunk
 Compensation in Metabolic Disorders
   •      The change in the PCO2 in the metabolic disorders represents the
          lung‟s role in compensation
   •      Compensation may take up to 1 day (24 hours)
   •      pH returns towards normal (but is never normal) in metabolic disorders
   •      pH  in METABOLIC ACIDOSIS from pH 7.07.25 within 1 day.
          Final pH is lower than in respiratory acidosis
   •      pH  in METABOLIC ALKALOSIS from pH 7.67.5 within 1 day.
          Final pH is higher than in respiratory alkalosis
 pH 7.6
 pH 7.5
 pH 7.4
 pH 7.3                              24 hr                           24 hr
 pH 7.2
 pH 7.1
 pH 7.0
                     pH 7.07.25                  pH 7.67.5
                                                                          50
                  METABOLIC ACIDOSIS            METABOLIC ALKALOSIS
Summary of changes in PCO2
                                                              Gold trunk
      Compensation in Metabolic Disorders
  •    The change in the PCO2 in the metabolic disorders represents the
       lung‟s role in compensation
  •    Compensation may take up to 1 day (24 hours)
  •    pCO2 returns towards normal (but is never normal)?
  •    pCO2  in METABOLIC ACIDOSIS from 4022.5 mmHg within 1 day.
       Final pCO2 is lower than in respiratory acidosis
  •    pCO2  in METABOLIC ALKALOSIS from 4050 within 1 day.
       Final pCO2 is higher than in respiratory alkalosis




                                                                 51
           METABOLIC ACIDOSIS           METABOLIC ALKALOSIS
                                      Please read
         3. Renal Mechanisms
•   Consumption of bicarbonate
•   Formation of bicarbonate
•   Renal compartments
•   Glomerular filtrate
•   Reabsorption of bicarbonate*
    – Carbonic anhydrase inhibitors
    – Summary*
• Renal processes*
                                              52
                               Please read
Renal Mechanisms in Acid-Base Homeostasis

1. Penyerapan semula bikarbonat dari tubul
2. Penyerapan serta penjanaan bikarbonat
   dari tubul
3. Penjanaan serta penyingkiran ammonia
4. Peningkatan keasidan urin




                                         53
  Consumption of Bicarbonate
• For every hydrogen ion buffered by
  bicarbonate, a bicarbonate is consumed
• To maintain the capacity of the buffer
  system, the bicarbonate must be
  regenerated
• Yet, when bicarbonate is formed from
  carbonic acid (indirectly from carbon
  dioxide and water), equimolar amounts of
  hydrogen ions are formed simultaneously  54
     Formation of Bicarbonate
• Bicarbonate formation can only continue if
  these hydrogen ions are removed
             How are hydrogen ions removed?



• Bicarbonate formation occurs in the cells
  of the renal tubules
            Where/How is bicarbonate formed?



                                               55
Renal Compartments
      • Nephron structure:
         – Bowman‟s capsule
            • Glomerulus
         – Renal tubule
            • Proximal convoluted tubule (PCT)
            • Distal convoluted tubule (DCT)
            • Loop of Henle
         – Renal tubular lumen
         – Renal tubular cells

      • Interstitial fluid
                                          56
              Glomerular Filtrate
• The glomerular
  filtrate contains the
  same concentration
  of bicarbonate ions
  as the plasma


  Sodium and bicarbonate ions are
  filtered by the glomerulus. The
  glomerular filtrate contains both ions.

                                            57
                       Glomerular
Plasma       Plasma
                         filtrate                 Urine [HCO3-]                 Urine pH
  pH         [HCO3-]
                        [HCO3-]
Acidosis:                           H+ excretion stops; urine pH is limiting;
<6.8                                At pH 4.6, the amount of hydrogen ions      <4.6
              20          20        excreted in urine = 30-40 mmol/1.5L/24
6.8                                  h, mostly as H2PO4- (monobasic form)
                                                                                 4.6
Normal:
7.35          24          24                                                     5.0
7.38          25          25               All [HCO3-] reabsorbed;               6.0
                                       [HCO3-] regenerated; acidic urine
7.40          26          26                                                     6.4
7.42          28          28                                                     6.8
                                       Some [HCO3-] excreted in urine;
7.45          32          32                   neutral urine                     7.0
Alkalosis:
 7.6          36          36                                                     7.4
                                           [HCO3-] excreted in urine;
 7.8                                            alkaline urine                   8.0
              40          40                                                     58
> 7.8                                                                           > 8.0
        Reabsorption of Bicarbonate
                 ACIDOSIS
                             • If the filtered bicarbonate were
                               not reabsorbed, copious
                               amounts would be excreted in
                               the urine, depleting the body‟s
                               buffering capacity and causing
                               an acidosis:
                                       – If filtered [HCO3-] reabsorption = 0%
                  X                    – Excreted [HCO3-] = 
                   Urine HCO3-
                                       – Urine [HCO3-] = 
 BUT THIS DOES NOT HAPPEN! – Plasma [HCO -] = 
                                                        3
                                       – Plasma [HCO3-] = < 24 mmol/L
What is normal urine bicarbonate levels?                                  59
                                       – Acidosis will prevail
What is urine bicarbonate levels in acidosis?
       Reabsorption of Bicarbonate
       Blood [HCO3-] = 24 mmol/L
                              • In health, at normal plasma
                                bicarbonate concentration,
                                virtually all the filtered
                                bicarbonate is reabsorbed:
                                   – Plasma [HCO3-] = 24 mmol/L
100%                               – Bicarbonate reabsorption =
                                     100%
                      X
                      Bicarbonate is not excreted
   5    1     2 3,4


  HOW IS BICARBONATE REABSORBED?
  WHAT HAPPENS AT EACH STAGE (1-5)?
                                                                  60
  Reabsorption of Bicarbonate
                               • The luminal surface of
                                 renal tubular cells is
                                 impermeable to
                                 bicarbonate and
                                 therefore direct
                                 reabsorption cannot
            X                    occur
Bicarbonate cannot enter
renal tubular cells directly



                                                          61
     Reabsorption of Bicarbonate
                                  • Within the renal tubular
                        Na+
                                    cells, carbonic acid is
                                    formed from carbon dioxide
                                    and water
                                  • This reaction is catalysed
 5              2
                                    in the kidney by the
                                    enzyme carbonic
                              3
                                    anhydrase
           CA
                                  • Carbonic anhydrase is also
                    4
                                    called carbonate
          1
                                    dehydratase
                                  • The carbonic acid formed
WHAT HAPPENS AT STAGE 1?            dissociates into hydrogen
CA = Carbonic anhydrase                                      62
                                    and bicarbonate ions
     Reabsorption of Bicarbonate
                      Na+
                                • The hydrogen ions are
                                  secreted across the
                                  luminal membrane in
 5            2                   exchange for sodium
                                  ions
                            3


                  4
          1



WHAT HAPPENS AT STAGE 2?
                                                     63
     Reabsorption of Bicarbonate
                      Na+
                                • In the tubular fluid, the
                                  hydrogen ions which
                                  are secreted across
 5            2                   the luminal membrane
                                  combine with filtered
                            3     bicarbonate to form
                                  carbonic acid
                  4
                                • Most of the carbonic
          1
                                  acid formed
                                  dissociates into carbon
WHAT HAPPENS AT STAGE 3?          dioxide and water 64
     Reabsorption of Bicarbonate
                      Na+
                                • Some of the carbon
                                  dioxide diffuses back
                                  into the renal tubular
 5            2                   cells
                                • The remainder of
                            3     carbon dioxide is
                                  excreted in urine
                  4
          1                     • Water is excreted in
                                  urine
WHAT HAPPENS AT STAGE 4?
                                                           65
     Reabsorption of Bicarbonate
                      Na+
                                • The sodium ions
                                  accompany
                                  bicarbonate ions into
 5            2                   the interstitial fluid
                                • These bicarbonate ions
                            3     then diffuse into the
                                  plasma
                  4
          1



WHAT HAPPENS AT STAGE 5?
                                                     66
MEQ: Describe the reabsorption of filtered bicarbonate by renal tubular cells (10 min)


       Reabsorption of Bicarbonate
                                       Answer:
                                       • Bicarbonate cannot be reabsorbed directly
                                       • Hydrogen and bicarbonate ions are
                                         generated in renal tubular cells
                                       • The hydrogen ions are secreted in
                                         exchange for sodium into the tubular lumen
                                       • In the tubular lumen, the hydrogen ions
 5                  2                    combine with filtered bicarbonate to form
                                         carbon dioxide and water
                                       • Carbon dioxide is partially absorbed by
                                         renal tubular cells
                              3
                                       • Bicarbonate ions are secreted with sodium
               CA                        from the tubular cells into the interstitial fluid
                        4              • These bicarbonate ions then diffuse into the
                                         plasma
              1                        • This whole process effectively results in the
                                         reabsorption of filtered bicarbonate
Diagram of reabsorption of filtered    • The formation of bicarbonate and hydrogen
bicarbonate by renal tubular cells.      ions is promoted by their continuous
                                         removal and by the presence of carbonic
CA = carbonic anhydrase or               anhydrase                                  67
carbonate dehydratase
 Carbonic Anhydrase Inhibitors
• Carbonic anhydrase is located in the proximal
  renal tubule:
  – on the brush border membrane
  – inside renal tubule cells
• „Reclamation‟ or regeneration of bicarbonate
  that is filtered at the glomerulus, takes place
  here
• This reaction is the most important contribution
  to bicarbonate homeostasis
• Acetazolamides inhibit carbonic anhydrase
  activity                                           68
                   Summary
• Hydrogen and bicarbonate ions are generated in
  equimolar amounts in renal tubular cells
• This is essential for the reabsorption of filtered of
  filtered bicarbonate but also means that when a
  hydrogen ion is excreted in the urine, a
  bicarbonate ion is produced and retained
• This process effectively regenerates the
  bicarbonate ions consumed when hydrogen ions
  are buffered

                                                     69
            Renal Processes
• Two important renal processes are:
  – Hydrogen ions are secreted into the urine
  – Bicarbonate is generated and retained in the
    body
           What is normal pH of urine?

           What is normal plasma bicarbonate levels?




• Please learn more about:
                                             HOW DO THESE RENAL
  – Bicarbonate Reabsorption                 PROCESSES OCCUR?
  – Hydrogen Ion Excretion
                                                             70
            4. Urinary System
•   Hydrogen ion secretion vs. excretion*
•   Urinary pH
•   Urinary hydrogen ion excretion
•   Urinary buffers*
    – Urinary phosphate (HPO42-); (H2PO4- is excreted)




                                                  71
Hydrogen Ion Secretion vs. Excretion
• Although hydrogen ions are secreted into the
  tubular fluid during bicarbonate reabsorption,
  there is no net acid excretion

• The formation of these hydrogen ions merely
  provides the means for the reabsorption of
  bicarbonate

• Net acid excretion depends upon the same
  reactions occurring in the renal tubular cells but,
  in addition, requires the presence of a suitable
  buffer system in the urine                        72
               Urinary pH
• The minimum urinary pH that can be
  generated, 4.6, is equivalent to a hydrogen
  ion concentration of approximately 25
  mmol/L

• Minimum urine pH = pH 4.6
• Minimum urine [H+] = 25 mmol/L
• Normal urine pH = pH 5 - 7
                                           73
Urinary Hydrogen Ion Excretion
• Given a normal urine volume of 1.5 L/24 h,
  free hydrogen ion excretion can account
  for less than a thousandth of the total
  amount that has to be excreted

• Normal urine volume = 1.5 L/24 h
• How much hydrogen ion is excreted per
  day?
                                           74
Urinary Hydrogen Ion Excretion
              Renal hydrogen ion excretion:

              • Hydrogen and bicarbonate
                ions are generated in renal
                tubular cells from carbon
                dioxide and water by the
                reversal of the buffering
                reaction

              • The hydrogen ions are
                excreted in the urine buffered
                by phosphate and ammonia
                while the bicarbonate enters
                the ECF, replacing that
                which was consumed in
                buffering                  75
            Urinary Buffers
• What are the urinary buffers?
     Phosphate, ammonia, creatinine
• Which urinary buffers are involved in the
  regeneration of bicarbonate?
     Phosphate, ammonia
• Write the reactions of two (2) urinary
  buffers


                                              76
              Urinary Phosphate
• The principal urinary buffer is phosphate
• This is present in the glomerular filtrate,
  approximately 80% being in the form of
  the divalent anion, HPO42-
• This combines with hydrogen ions and is
  converted to the monovalent anion,
  H2PO4- Reaction of urinary phosphate in glomerular filtrate:
     HPO42- +           H+                   H2PO4- (3.3)
         (80%)         Hydrogen ions
                                          Monovalent anion
     Divalent anion      secreted by
                                           Monobasic ion
      Dibasic ion       renal tubular                        77
                                            is excreted
    combines with H+   cells into lumen
             Urinary Phosphate
• At the minimum urinary pH, virtually all the phosphate is
  in the H2PO4- form
• About 30-40 mmol of hydrogen ions are normally
  excreted in this way every 24 h

•   Minimum urine pH = pH 4.6
•   Minimum urine [H+] = 25 mmol/L
•   Normal urine pH = pH 5 - 6
•   Normal urine volume = 1.5 L/24 h
•   Hydrogen ions excreted in urine = 30-40 mmol/24 h

• At pH 4.6, the amount of hydrogen ions excreted in urine
  = 30-40 mmol/1.5L/24 h, mostly as H2PO4- form, i.e.,
  monovalent anion
• Hydrogen ions are excreted as monovalent anion,        78
  H2PO4 -
             5. Ammonia
1. Ammonia
    • Ammonia (NH3) is a urinary buffer
    • Ammonium (NH4+) is excreted

2. Gluconeogenesis
    • Process related to ammonia formation


                                          79
               Ammonia
• Ammonia (NH3) is an important urinary
  buffer
• Ammonia is produced by the deamination
  of glutamine in renal tubular cells
• The enzyme which catalyses this reaction,
  glutaminase, is induced in states of
  chronic acidosis, allowing increased
  ammonia production and hence increased
  hydrogen ion excretion via ammonium
  (NH4+) ions                             80
               Ammonia
• Ammonia (NH3) can readily diffuse across
  cell membranes
• Ammonium ion releases H+ to form
  ammonia
• Ammonium ions (NH4+) cannot diffuse
  across cell membranes
• Passive reabsorption of ammonium ions is
  therefore prevented
      NH3 + H+  NH4+              (3.4)
   Ammonia         Ammonium              81
                                Ammonia
At normal intracellular [H+]:



                         At normal intracellular [H+],
                          most ammonia is present
                             as ammonium ions


       NH3               +        H+                    NH4+
     Ammonia                                             Ammonium
                                 H+ is present mostly
                                as ammonium in cells




                                                                    82
                               Ammonia
If ammonia diffuses out of cells:
                                    Will [H+] rise in cells? No

                                                       Ammonium
                                                       releases H+

             NH3                      +         H+                     NH4+
              Ammonia                                                   Ammonium
                                    Diffusion of ammonia out of
                                         the cell disturbs the         (NH4+ cannot
 NH3 can readily                     equilibrium, causing more        diffuse across
diffuse across cell                                                  cell membranes)
                                       ammonia to be formed
    membranes
                      Diffusion of
                      ammonia out
                      of cells


            H+ excretion                                                          83
           via NH4+ ions
In chronic acidosis:
                                Ammonia
                Glutamine
      Ammonia is       Glutaminase is
  produced by the      induced in states of     Glutamate         GLUCONEOGENESIS
   deamination of      chronic acidosis
glutamine in renal                                 H+ combines with glutamate
   tubular cells by
      glutaminase                             [H+] rises in cells? No
                       Increased
                       ammonia
                       production                       Ammonium
                                                        releases H+

             NH3
             Ammonia
                                      +         H+                      NH4+
                                                                          Ammonium
Diffusion of                        Diffusion of ammonia out of           (NH4+ cannot
ammonia out of                           the cell disturbs the           diffuse across
cells                                equilibrium, causing more          cell membranes)
                                       ammonia to be formed
           H+ excretion                                                            84
          via NH4+ ions
         Gluconeogenesis
• The simultaneous production of hydrogen
  ions would seem to negate the process

• However, these H+ ions can be used up in
  gluconeogenesis when they combine with
  glutamate formed by the deamination of
  glutamine


                                            85
         6. Titratable Acidity
• Titratable acidity of urine
• Determination of titratable acidity of urine
• Urinary acidification tests




                                                 86
     Titratable Acidity of Urine
• Every H+ that reacts with urinary buffers
  contributes to titratable acidity of urine
• Titratable acidity only measures one
  fraction of acid that is excreted, as it
  cannot determine the amount of H2CO3
  that has been converted to H2O and CO2
• pK‟ for ammonia system = 9.0
• But titratable acidity only titrates urine to
  pH 7.4, so ammonia system contributes
  very little to titratable acidity
                                                  87
           Determination of
      Titratable Acidity of Urine
• Titratable acidity of urine is determined by
  measuring the amount of alkali which
  needs to be added to urine to return the
  pH of urine to 7.4, i.e., the pH of
  glomerular filtration




                                             88
     Urinary Acidification Tests
Urine pH:
• Urine is normally acidic (as compared with
  plasma) in healthy subjects on a meat-
  containing diet
• An alkaline urine may be found in:
  – vegans
  – patients ingesting alkali
  – patients with urinary tract infections
• Urine pH is determined using a urine dipstick on
  freshly voided urine specimens
                                                 89
      Urinary Acidification Tests
• Urine acidification is a function of the distal nephron
  which can secrete H+ until the limiting intraluminal pH of
  ≤ 5.0 is reached
• Acidification occurs as a result of the kidney:
   – reabsorbing large amounts of the HCO3- that has been filtered at
     the glomerulus, and
   – excreting H+ produced as non-volatile acids during tissue
     metabolism
• The amount of H+ which can be secreted into the tubules
  before the limiting intraluminal pH of ≤ 5.0 is reached
  depends upon the presence of urine buffers
• The H+ in urine is only partly eliminated as free H+
• The H+ in urine is mostly excreted as NH4+ or H+
  combined with buffer ions, principally inorganic        90
  phosphate (Pi)
     Urinary Acidification Tests
• It is possible to assess the capacity of the kidney
  to produce an acid urine after a metabolic
  acidosis has been induced by administering
  ammonium chloride (NH4Cl)
• In response to the NH4Cl load, urine pH normally
  falls to below 5.3 in at least one specimen
• It is essential to check that a satisfactory
  acidosis was induced and this is assumed to
  have occurred if plasma [total CO2] falls by
  about 4 mmol/L after NH4Cl ingestion

                                                   91
    Urinary Acidification Tests
• More elaborate tests of urinary
  acidification are needed to differentiate
  between proximal and distal renal tubular
  acidosis
  – E.g., determining the renal threshold for
    HCO3-




                                                92
7. Blood Gas Analysis
   Please read re ABG




                        93
Normal values for arterial blood gases
     Blood Gas Parameter              Abbreviation        Normal Value*

                                                     35 – 45 mm Hg
Carbon dioxide tension                  PCO2         (average, 40)

Oxygen tension                            PO2        80 – 100 mm Hg

Oxygen percent
saturation                                SO2        97

Hydrogen ion
                                              pH     7.35 – 7.45
concentration

Bicarbonate                             HCO3-        22 – 26 mmol/L
*Values given in exams may differ slightly.                               94
Table 2: Arterial blood parameters used
  for the analysis of acid-base status

                                Definition and
 Parameter  Normal Value
                                 Implications
                          Partial pressure of
                          oxygen, O2, in the
   PO2     80 – 100 mm Hg arterial blood
                          (it  with age)
                          Partial pressure of
  PCO2     40(±5.0) mm Hg carbon dioxide, CO2,
                          in the arterial blood
                                              95
Table 2: Arterial blood parameters used
  for the analysis of acid-base status
 Parameter       Normal Value      Definition and Implications

   pH        7.40(±0.05 [2SD]) Identifies whether there
             7.40(±0.02 [1SD]) is acidemia or alkalemia;
                               the value using 2SD
                               from the mean is the
                               common clinical value
  [H+]       40(±2) nmol/L     The hydrogen ion
                               concentration may be
                               used instead of the pH
                                                                 96
Table 2: Arterial blood parameters used
  for the analysis of acid-base status
  Parameter   Normal Value           Definition and Implications

   CO2   25.5(±4.5)          Classic method of estimating
                             [HCO3-]; measures HCO3- +
 content mmol/L              dissolved CO2 (latter is generally
                             quite small except in respiratory
                             acidosis)
Standard 24(±2)              Estimated HCO3- concentration
                             after fully oxygenated arterial blood
 HCO3- mmol/L                has been equilibrated with CO2 at a
                             PCO2 of 40 mm Hg at 38 C;
                             eliminates the influence of
                             respiration on the plasma HCO3-
                             concentration                      97
Table 2: Arterial blood parameters used
  for the analysis of acid-base status
  Parameter   Normal Value           Definition and Implications

  Base 0(±2)                 Reflects pure metabolic component
 excess mmol/L               Base excess = 1.2 x deviation from 0
                             Negative in metabolic acidosis
                             Positive in metabolic alkalosis
                             Misleading in respiratory and mixed
                             acid-base disturbances
                             Not essential for interpretation of
                             acid-base disturbances

                                                                   98
Collection of blood for blood gas analysis

• Obtaining the blood sample is usually
  performed by the intensive care nurse

• Usually a sample of arterial blood is used
  for the blood gas analysis

• Heparinised syringe is used for blood gas
  analysis
          Heparin is an anticoagulant. Check type, quality and
          quantity of heparin to use. How much heparin is needed?   99
Technique for drawing a blood sample
 • The radial (or brachial) artery is often chosen
   because of its accessibility

 • The wrist is extended by positioning it over a
   rolled towel

 • After the skin has been sterilised, the artery is
   stabilised with 2 fingers of one hand while the
   arterial puncture is made with the other hand
   using a heparinised syringe
    Identify the artery to be used for drawing arterial blood sample.   100
    Which other arteries can be used?
Technique for drawing a blood sample
 • After 5 ml of blood has been drawn into the
   syringe, air is removed and the syringe is
   capped

 • The syringe is placed inside an air tight plastic
   bag

 • The plastic bag containing the syringe is placed
   in an ice-water slurry and taken immediately to
   the Chemical Pathology Routine Lab for blood
   gas analysis

                                                       101
Dept. of Chemical Pathology, Routine Lab.

 Radiometer ABL5 Blood Gas Analyser




                                            Arterial blood gas sample   102
 Receiving Blood Gas Sample




How are ABG samples despatched to Chem Path Routine Lab?                 103
Which form is used? What do you need to check for upon sample arrival?
         Arterial Blood Gas Sample




Check sample status. How will you ensure that sample is suitable for ABG analysis?

                                                                             104
  Blood Gas Analyser
     Radiometer ABL5 Blood Gas Analyser




Know how to calibrate, maintain and operate ABL5   105
               The ABG Workbench
              Radiometer ABL5 Blood Gas Analyser. Check ABL5 status




                                                                   Waste
                                                                   container.
ABG record                                                         Need to
book. Check                                                        check?
calibration
status




                                Arterial blood gas sample inside       106
                                Check sample status
     ABG Measured Parameters
•    These parameters are measured by ion
     selective electrodes (ISE):
      1. [H+]
      2. PCO2
      3. PO2

Homework:
What are ISEs? They are sensors which can measure pH and blood gases
Briefly describe the principle of measurement for each parameter listed above
Find the formulae for converting [H+]  pH and pH  [H+]
                                                                           107
Reference and pH electrodes




                              108
PCO2 and PO2 electrodes




                          109
Human Errors in Blood Gas Analysis
• There are many variables which can adversely affect
  blood gas analysis:
   – Pre-analytical
       •   Sample source (child, anaemia, fever, etc)
       •   Sample collection*
       •   Sample composition (high Hb F, high reticulocytes, low iron, drugs)
       •   Sample transportation* (delayed dispatch, improperly transported)
   – Analytical
       •   Programmed parameters (assumed values)
       •   Did not rub syringe to mix tube contents
       •   Used ice-cold samples
       •   Switched samples
       •   Delayed analysis
   – Post-analytical
       • Transcription errors

                                                                            110
Factors affecting arterial blood gas analysis

Collection stage:
• Venous blood sample
• Wrong syringe (non-heparinised)
• Wrong artery is chosen
• The wrist is not extended and positioned
  properly
• Non-stabilised artery while the arterial
  puncture is made
                                             111
Factors affecting arterial blood gas analysis

Transportation stage:
• Air is not removed from the syringe
• The syringe is not capped
• The syringe is not placed inside an air tight
  plastic bag
• The plastic bag containing the syringe is
  placed on ice but not in an ice slurry

                                             112

				
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