Tissue oxygenation

TISSUE HYPOXIA

1. BY- DR. RAM GOPAL MAURYA TISSUE OXYGENATION

2. Antoine Lavoisier was an 18th-century French scientist who was the first to identify oxygen as the essential element for metabolism. The requirements of the oxygen transport system from the atmosphere to all organs, tissues, cells and mitochondria. This combined oxygen transport system is known as OXYGEN CASCADE. When the system fails to supply oxygen to meet the prevailing demand, a state of hypoxia is said to exist

3. OXYGEN CASCADE It describes the process of decreasing oxygen tension from atmosphere to mitochondria. Atmospheric air ↓ Alveoli ↓ Arterial blood ↓ Tissue capillaries ↓ Mitochondria

4. Atmospheric air Partial pressure of O2 in saturated moist air (PiO2) PiO2 = FIO2 (PB – PH2O) At sea level: Water vapour pressure at body temp = 47mmHg . Thus, Pressure exerted by gas in saturated moist air = 760-47 = 713mmHg. So the inspired oxygen partial pressure = [ 0.21 (760 – 47) ] = 149 mmHg This is the starting point of O2 cascade.

5. Alveoli Alveolar partial pressure Partial pressure of alveolar oxygen(PAO2 ) is calculated by alveolar gas equation PAO2= PiO2-PACO2/R PaCO ₂ = PACO₂ ( 40mmHg ) as CO₂ is freely diffusible. PAO2 =149-(40/0.8)~ 100mmHg.

6. ALVEOLI TO BLOOD Alveolar PAO2 is 100mmHg. Blood returning from tissues to heart has low PO2 (40mmHg). So oxygen diffuses from alveoli to pulmonary capillaries. After oxygenation,blood moves to pulm . veins→left side of heart→ arterial system → systemic tissues. In a perfect lung pO ₂ of pulm . Venous blood would be equal to pO ₂ in the alveolus

7. OXYGEN DELIVERY TO TISSUE ( DO2 ) DO2 = [(1.34 x HbxSaO2)+(0.003xPaO2)] x Q 10 O2 delivery to tissues depends on Hb concentration O2 binding capacity of Hb Saturation of Hb Amount of dissolved O2 cardiac output (Q).

8. UNLOADING OF O2 AT TISSUE LEVEL Initially the dissolved O2 is consumed. Then the sequential unloading of Hb bound O2 occurs. Transport of O2 from the capillaries to tissues is by simple diffusion. Pasteur point is the critical PO2 at which delivered O2 is utilised by the tissue & below which the O2 delivery is unable to meet the tissue demands.

9. Oxygen cascade refers to the progressive decrease in the partial pressure of oxygen from the ambient air to the cellular level. PO2 in inspired air 150-160 mm Hg PO2 in alveolar gas (PAO2) 100-110 mm Hg PO2 in arterial blood (PaO2) 90-100 mm Hg PO2 in Capillary blood 50-80 mm Hg PO2 in tissues 30-50 mm Hg PO2 in cell mitochondria 10-20 mm Hg

10. Factors affecting oxygenation at various levels in O2 cascade: PARTIAL PRESSURE AFFECTED BY: Inspired oxygen PiO2 Barometric pressure ( Pb ); FiO2 Alveolar gas PAO2 Oxygen consumption VO2 Alveolar ventilation VA Arterial blood PaO2 Dead space ventilation Shunt Decreased V/Q Cellular PO2 Cardiac output CO hemoglobin

11. Dead Space Ventilation Where ventilation is excessive relative to pulmonary capillary blood flow. In normal subjects, dead space ventilation (VD) accounts for 20% to 30% of the total ventilation (VT); i.e., VD/VT = 0.2 to 0.3 Dead space ventilation increases in the following situations: 1. When the alveolar–capillary interface is destroyed; e.g., emphysema 2. When blood flow is reduced; i.e., low cardiac output 3. When alveoli are overdistended ; e.g., during positive-pressure ventilation

12. Intrapulmonary Shunt The excess blood flow, known as intrapulmonary shunt, does not participate in pulmonary gas exchange. V/Q ratio below 1.0 The fraction of the cardiac output that represents intrapulmonary shunt is known as the shunt fraction . In normal subjects, intrapulmonary shunt flow (Qs) represents less than 10% of the total cardiac output (Qt), so the shunt fraction (Qs/Qt) is less than 10%.

13. Intrapulmonary shunt fraction is increased in the following situations: 1. When the small airways are occluded; e.g., asthma 2. When the alveoli are filled with fluid; e.g., pulmonary edema, pneumonia 3. When the alveoli collapse; e.g., atelectasis 4. When capillary flow is excessive; e.g., in nonembolized regions of the lung in pulmonary embolism.

14. Assessment of Tissue Oxygenation Symptoms of hypoxemia Eg : tachycardia, tachypnoea , hypertension, cyanosis, dyspnoea , disorientation. AVAILABLE CLINICAL TOOLS OXYGEN DERIVED VARIABLES 1. PaO2, SaO2, SpO2 monitoring 2 . Oxygen delivery (DO2) 3. Oxygen uptake (VO2) 4. Oxygen extraction ratio (O2ER) 

15. 5. The A-a PO2 Gradient 6.PaO2/FIO2 Ratio 7. Mixed venous saturation of oxygen & central venous oxygen saturation METABOLIC PRODUCT 8. Lactate 9. Arterial Base Deficit GASTRIC TONOMETRY NEAR INFRARED SPECTROSCOPY (NIRS)

16. Oxygen Delivery (DO2) The rate of O2 transport from the heart to the systemic capillaries is called the oxygen delivery (DO2) DO2 = CO × CaO2 × 10 ( mL /min) (The multiplier of 10 is used to convert the CaO2 from mL / dL to mL /L.) The DO2 in healthy adults at rest is 900–1100 mL /min, or 500–600 mL /min/m2 when adjusted for body size.

17. Oxygen uptake (VO2). The rate of O2 transport from the systemic capillaries into the tissues is called the oxygen uptake (VO2). The VO2 can be described as the product of the cardiac output (CO) and the difference between arterial and venous O2 content (CaO2 – CvO2). VO2 = CO × (CaO2 – CvO2) × 10 ( mL /min) This equation is a modified version of the Fick equation for cardiac output (CO = VO2/CaO2 – CvO2). The CaO2 and CvO2 in equation share a common term (1.34× [ Hb ]), so the equation can be restated as: VO2 = CO × 1.34 × [ Hb ] × (SaO2 – SvO2) × 10 The VO2 in healthy adults at rest is 200–300 mL /min, or 110–160 mL /min/m2 when adjusted for body size

18. The two conditions associated with a low VO2 are a decreased metabolic rate ( hypometabolism ) and inadequate tissue oxygenation. Hypometabolism is uncommon in ICU patients, an abnormally low VO2 (<200 mL /min or <110 mL /min/m2) can be used as evidence of inadequate tissue oxygenation. VO2 may be a more sensitive marker of inadequate tissue oxygenation than the serum lactate level.

19. Oxygen Extraction The fractional uptake of O2 into tissues It is the ratio of O2 uptake (VO2) to O2 delivery (DO2 ). O2ER = VO2/DO2 O2ER = (SaO2 – SvO2)/ SaO2 . The VO2 is normally about 25% of the DO2, so the normal O2ER is 0.25 (range = 0.2–0.3 ) . Thus, only 25% of the O2 delivered to the capillaries is taken up into the tissues when conditions are normal. T he point where O2 extraction is maximal is the anaerobic threshold.

20. RELATIONSHIP BETWEEN DO2 & VO2

21. 1. The normal (SaO2 – SvO2) is 20% to 30 %. 2. An increase in (SaO2 – SvO2) above 30% indicates a decrease in O2 delivery (i.e., usually anemia or a low cardiac output ). 3. An increase in (SaO2 – SvO2) that approaches 50% indicates either threatened or inadequate tissue oxygenation 4. A decrease in (SaO2 – SvO2) below 20% indicates a defect in O2 utilization in tissues, which is usually the result of inflammatory cell injury in severe sepsis or septic shock.

22. Venous Oxygen Saturation Mixed venous oxygen saturation ( SvO2) The SvO2 is ideally measured in mixed venous blood in the pulmonary arteries, which requires a pulmonary artery catheter. The normal range for SvO2 in pulmonary artery blood is 65% to 75 %. Continuous SvO2 monitoring is associated with spontaneous fluctuations that average 5%. A change in SvO2 must exceed 5% and persist for longer than 10 minutes to be considered a significant change.

23. Central Venous O2 Saturation (ScvO2) The O2 saturation in the superior vena cava, known as the “central venous ”. An alternative to the mixed venous O2 saturation (SvO2) because it eliminates the need for a PA catheter . Scvo2 is usually 2-3% lower than Svo2 . This is because the lower half of the body extracts less oxygen and the brain extracts more oxygen than other  organs  of the body . Normal oxygen extraction is 25–30% corresponding to a ScvO2 >65%

24. situations where ScvO2 > SvO2 : -> anaesthesia – because of increase in CBF and depression of metabolism -> TBI where cerebral metabolism depressed -> shock – because of diversion of blood from splanchnic circulation + increased oxygen extraction and therefore IVC saturation decreases.

25. The A-a PO2 Gradient A n indirect measure of ventilation–perfusion abnormalities. The normal A-a PO2 gradient rises steadily with advancing age. It ranges from 5 to 25 mmHg breathing room air. T he normal A-a PO2 gradient increases 5 to 7 mm Hg for every 10% increase in FIO2.

26. The PaO2/FIO2 Ratio The PaO2/FIO2 ratio is used as an indirect estimate of shunt fraction. The following correlations have been reported PaO2/FIO2 Qs/Qt <200 > 20% > 200 < 20%

27. Lactate P roduct of anaerobic glycolysis . LEVELS normal range: 0.6-1.8mmol/L hyperlactaemia : a level from 2 to 5 mmol /L severe lactic acidosis: > 5 mmol /L high mortality with lactate > 8mmol/L PHYSIOLOGY 1. Daily production: ~ 1500 mmol of lactate each day ( mmol of lactate each day ( 15 to 30 mmol /kg per day) . all tissues can produce lactate under anaerobic conditions Metabolized mainly by the liver ( Cori cycle )

28. Lactate producing and consuming tissue under resting condition... PRODUCER skin erythrocytes brain intestinal mucosa leucocytes platelets skeletal muscles Renal medulla tissue of eyes CONSUMER liver renal cortex heart

29. Lactic acidosis occurs whenever there is an imbalance between the production and use of lactic acid. Causes of Lactic acidosis •Type A •Type B

30. Arterial Base Deficit “base deficit” is considered a more specific marker of metabolic acidosis than the serum bicarbonate. The normal arterial base deficit is ≤2 mmol /L; increases above 2 mmol /L are classified as mild (2 to 5 mmol /L), moderate (6 to 14 mmol /L), and severe (≥15 mmol /L ). Arterial base deficit has been a popular marker of impaired tissue oxygenation in acute surgical emergencies, especially trauma

31. GASTRIC TONOMETRY Technique used to assess regional perfusion.  Assesses splanchnic perfusion based on stomach’s mucosal pH by measuring gastric luminal PCO2 using a fluid filled balloon permeable to gases. Luminal CO2 reflects intramucosal CO2 . Several limitations to using gastric tonometry routinely: – takes about 90 minutes for CO2 to equilibrate between the balloon and the lumen – Luminal CO2 may be affected by acid secretion and feeding – No convincing evidence to support its routine use in the intensive care as several trials have failed to show benefit in using this form of monitoring

32. NEAR INFRARED SPECTROSCOPY (NIRS) A noninvasive method of measuring the venous O2 saturation in tissues using the optical properties of hemoglobin in the oxygenated (HbO2) and dexoxygenated ( Hb ) state. The most exciting feature of NIRS is the potential to monitor mitochondrial O2 consumption.