Topics to Cover

• Oxygen Transport • Oxygen Dissociation Curve Module G: Oxygen Transport • Oxygen Transport Studies • Tissue • Cyanosis • Polycythemia

Oxygen Transport Dissolved Oxygen • As oxygen diffuses across the A-C membrane, it • Oxygen is carried from the lungs to the dissolves into the plasma and remains in that tissues in two different fashions: fashion until it reaches the tissue. • Oxygen Dissolved in the blood plasma (PO ) 2 • Expressed as a partial pressure - PO2

• Oxygen Combined with (SO2) • Normal arterial level = 80-100 mm hg • Normal venous level = 35 – 45 mm hg • The quantity of oxygen dissolves is a function of Henry’s law. •At 37 C 0.003 ml of oxygen will dissolve in 100 ml of blood. (Henry’s Law)

• At 100 mm hg PaO2, the amount of dissolved oxygen is 0.3 ml O2/100 ml blood (0.3 vol%).

Combined Oxygen

• Dissolved oxygen is inadequate for metabolic needs. • Need a substance which will bind to oxygen and carry it, BUT will release it when needed. • Voila! Hemoglobin! • Miracle #2…As we’ll see later, hemoglobin also carries carbon dioxide and is a key buffer of [H+].

1 Hemoglobin  chains • Each RBC contains approximately 280 million molecules of hemoglobin  chains • Adult Hemoglobin (Hb A) consists of • 4 Heme Groups – Primarily iron in the Fe+2 (ferrous) state. Heme • 4 Globulin – 4 amino acid chains (2  & 2 ) Units • One heme group binds with one of the amino acid chains and oxygen binds with the iron in the heme group in a reversible way. +2 O2 + Fe  FeO2 (Oxyhemoglobin) FERROUS

Hemoglobin & the RBC

• “Normal” hemoglobin level • 15 g/dl (men) & 13-14 g/dl (women) - Malley •15 +1.5 g/dl (men) & 13.5 + 1.5 g/dl (women) – Egan •15 +2 (men) & 14 + 2 (women) - Easy • Why do women have less? • The hemoglobin molecule resides in the erythrocyte and is responsible for giving the blood its red color. • The affinity of hemoglobin for oxygen • Hundreds of hemoglobin variants. increases with each oxygen molecule • Normal: A, A2, F • Abnormal: S, H attached • “All or Nothing”

Oxygen Saturation

• Saturation = Sites Filled Total Sites Available • Example: • 80 sites filled = 80% saturation 100 sites available

• Oxygen Saturation only talks about how much hemoglobin is saturated, NOT how much hemoglobin is present.

2 Quantity of Oxygen Bound to Combined Oxygen Hemoglobin • Each gram of Hemoglobin combines with • Not all hemoglobin molecules are bound with 1.34 mL of oxygen. oxygen. • Normal saturation •O2 bound to Hb = 1.34 mL O2 x 15 g Hb • Arterial (SaO ) – 97% = 20.1 vol% O 2 2 • Venous (SO2) – 75% • Some “desaturated” hemoglobin exists because of normal physiologic shunts: • Mixing of poorly saturated venous blood with arterial blood • Thebesian, bronchial, and pleural veins • Intrapulmonary shunts (perfused alveoli that are not ventilated)

• 20.1 vol% O2 x 0.97 = 19.5 vol% O2 • Hemoglobin not bound with oxygen is called reduced hemoglobin.

Oxygen Content Oxygen Dissociation Curve • The total amount of oxygen in 100 mL of blood is the sum of the dissolved oxygen & • The the oxygen bound to hemoglobin. relationship between the • Arterial Content partial •CaO = (Hb x 1.34 x SaO ) + (PaO x .003) 2 2 2 pressure of • Venous Content oxygen and •CO2 = (Hb x 1.34 x SO2) + (PO2 x .003) • Capillary Content the saturation of oxygen is •CćO2 = (Hb x 1.34 x SćO2) + (PćO2 x .003)

•SćO2 = Ideal Saturation = 100% not linear. •PćO = Ideal Partial Pressure = PAO 2 2 • 2 lines

Steep Portion of Curve Flat Portion of Curve

• “Dissociation Portion” of curve. • “Association Portion” of curve. • Between 10 and 60 mm Hg. • Greater than 60 mm Hg. • Large increases in PO2 yield small increases in • Small increases in PO yield large 2 SO2. increases in SO2. • At the pulmonary capillary, blood comes in contact with increased alveolar PO and oxygen • At the tissue capillary, blood comes in 2 diffuses from the alveolus to the capillary. As the contact with reduced tissue PO2 and PO2 rises, oxygen binds with the hemoglobin oxygen diffuses from the capillary to the (increasing SO2).

tissue. As the PO2 falls, oxygen bound to • Very little rise in oxygen saturation above 100 mm Hg of PaO . the hemoglobin (SO2) is released. 2

3 Key Points to Remember

• The amount of oxygen that is saturated on the

hemoglobin (SO2) is dependent on the amount

dissolved (PO2).

• Between a PaO2 of 60 and 100 mm Hg, the curve is flat.

• This means that small changes in PaO2 can occur without a big drop in saturation and oxygen content.

• At the tissues, where the PO2 is about 40 mm Hg, the curve is steep.

• This means that small changes in PO2 will result in a large amount of oxygen being unloaded.

Rules of Thumb of the P Oxyhemoglobin Curve 50 • The degree to which oxygen is attracted to hemoglobin can be assessed by

PO2 SO2 evaluating at what PO2 there is a 50% PO2 SO2 SO (P ). 27 50 2 50 •Normal P value is 27 mm Hg 40 70 50 40 75 •As P50 increases/decreases, we say the 50 80 “curve has shifted”. 60 90 •P less than 27: Shift to the left. 60 90 50 •P greater than 27: Shift to the right. 250 100 50

Leftward Shift of the OHDC Rightward Shift of the OHDC

• Left Shift. • Right Shift. • Increased oxygen affinity for hemoglobin. • Decreased oxygen affinity for hemoglobin. • This is the expected shift at the lungs (Left- • This is the expected shift at the tissues. Lungs). • For any given PO2, SO2 will be lower. • For any given PO , SO will be higher. 2 2 • Increasing P50. • Decreasing P50. • ELEVATED THINGS CAUSE A RIGHT SHIFT • LOW THINGS CAUSE A LEFT SHIFT (Up-Right) • H+ concentration (pH, alkalosis) • H+ concentration ( pH, acidosis) • Temperature (Hypothermia) • Temperature (Hyperthermia)

•  Carbon Dioxide (PCO2, Hypocarbia) •  Carbon Dioxide (PCO2, Hypercarbia) •  2,3 DPG •  2,3 DPG

4 2,3 DPG

• 2,3 DPG is an organic phosphate normally found in the RBC that has a tendency to bind with Hemoglobin and thereby decrease the affinity of Hemoglobin for oxygen.

• It promotes a rightward shift and enhances oxygen unloading at the tissues. This shift is + longer in duration than that due to [H ], PCO2 or temperature.

• A doubling of DPG will result in a 10 torr increase in P50.

2,3 DPG Bohr Effect • The levels increase with • The effect of CO on the OHDC is known • Cellular hypoxia. 2 • Anemia as the Bohr Effect. • Hypoxemia secondary to COPD • (OH – Bohr) • Congenital Heart Disease • High PCO2 levels and low pH decrease • Ascent to high altitudes affinity of hemoglobin for oxygen (a right- • The levels decrease with ward shift). • Septic Shock • Acidemia • This occurs at the tissues where a high • Stored blood level of PCO2 and acidemia contribute to • No DPG after 2 weeks of storage. the unloading of oxygen.

Arterial-Venous Oxygen Oxygen Transport Content Difference • The volume of oxygen leaving the left •C(a-)O2 •CaO–CO ventricle each minute. 2 2 • The venous blood is “mixed venous” blood •CaO2 x CO x 10 = 20 ml O2 x 5 L/min x 10 obtained from the pulmonary artery via a • Make sure to convert CO to L/min! pulmonary artery catheter. • Normal CaO : 20 vol% • Normal value is 1,000 mL O2 / min 2 • Normal CO : 15 vol% • Decreased oxygen delivery occurs when 2 • Normal CaO2 –CO2: 5 vol% there is: • Decreased with: • A decreased blood oxygenation • Increased CO • Decreased hemoglobin concentration • Certain Poisons •Hypothermia • Decreased cardiac output.

5 Oxygen Extraction Ratio Pulmonary Shunting • Def: The amount of oxygen extracted by the peripheral • PERFUSION WITHOUT VENTILATION. tissues divided by the amount of oxygen delivered to the • Pulmonary shunt is that portion of the cardiac peripheral cells. output that enters the left side of the heart • aka: Oxygen coefficient ratio & Oxygen utilization ratio without coming in contact with an alveolus. •O2ER = (CaO2-CO2)/CaO2 • “True” Shunt – No contact • Normal is 25% • Anatomic shunts (Thebesian, Pleural, Bronchial) •Increased with: •Decreased with: • Cardiac anomalies •Decreased .CO •Increased Cardiac Output • “Shunt-Like” (Relative) Shunt •Increased VO •Skeletal Muscle Relaxation 2 • Some ventilation, but not enough to allow for complete •Exercise •Peripheral Shunting equilibration between alveolar gas and perfusion. •Seizures •Certain Poisons • Shunts are refractory to oxygen therapy. •Shivering •Hypothermia •Hyperthermia •Increased Hemoglobin • Delivery of oxygen therapy will NOT help (at least to the expected degree). •Anemia •Increased PaO2

•Low PaO2

Venous Admixture Alveolar-arterial Gradient

• The mixing of oxygenated blood with •PAO2-PaO2 “contaminated” deoxygenated blood • More on this in today’s 1060 class. resulting in a reduction in:

•PaO2

•SaO2

Shunt Equation Shunt Equation Example

• So just how much blood is shunted? You obtain the following data on you patient. • Q CcO CaO What is the percent shunt present? S  2 2 QT CcO2 CvO2 aCO aO aO • Where CćO2 = (Hb x 1.34) + (PAO2 * .003) pH: 7.25 P 2: 28 torr P 2: 68 torr S 2: 91% • You will need PB: 749 PO2: 38 torr SO2: 72 % Hb: 13 gm%

•PBARO – Barometric Pressure FIO2: .90

•PaO2 – Arterial Partial Pressure of Oxygen •Steps: • Calculate CaO •PaCO2 – Arterial Partial Pressure of Carbon Dioxide 2 • Calculate CO •PO2 – Venous Partial Pressure of Oxygen 2 •Calculate PAO • Hb – Hemoglobin concentration 2 • Calculate CćO •PAO – Alveolar Partial Pressure of Oxygen 2 2 • Plug in numbers & solve! •FIO2 – Fractional Concentration of Inspired Oxygen

6 Shunt – Clinical Significance Tissue Hypoxia

• Normal Shunt: 3 to 5% • Hypoxemia: Reduced oxygen in blood

• Shunts above 15% are associated with (PaO2). significant hypoxemia. • Hypoxia: Reduced oxygen at the tissue. • Four types: • Hypoxic (Hypoxemic) Hypoxia • Anemic Hypoxia • Circulatory Hypoxia • Histotoxic Hypoxia

Hypoxic Hypoxia Anemic Hypoxia

• Tissues have inadequate oxygen levels • Tissues have inadequate oxygen levels because there is inadequate levels in the secondary to reduced oxygen carrying O blood (reduced Pa 2). capacity. • Rule out causes of hypoxemia • No hypoxemia! • Low Alveolar Oxygen (reduced PAO ) 2 • Caused by • Altitude • Reduced Hemoglobin • Hypoventilation (increased PACO ) 2 • Defective Hemoglobin • Breathing of gas mixtures less than 21% • Carboxyhemoglobin • Diffusion Impairment • Methemoglobin • Intrapulmonary Shunt • Sulfahemoglobin • Ventilation/Perfusion Mismatch • Sickle Cell Anemia (HbS)

Carboxyhemoglobin • Carbon Monoxide has 245 times the affinity for hemoglobin as oxygen. • Causes a leftward shift (increased affinity of Oxygen) • Normal level is less than 3% • 10% is common with smokers. • Toxic at 20%; Lethal at 50%. • Suspect incomplete combustion if level is elevated. • Furnace, space heater • Treatment is 100% oxygen • Reduces half-life of HbCO from 5 hours to 20 minutes. • Hyperbaric treatment remains controversial.

7 Methemoglobin Sulfhemoglobin

• A normal variant of adult hemoglobin. • Sulfhemoglobin results from the union of • Ferrous to Ferric (loses an electron, Fe+3) hemoglobin with medications such as sulfonamides (antibiotics including Bactrim • Normal levels are less than 1%. & Septra). • Usually associated with excessive nitrate • The resultant form of hemoglobin is unable ingestion. to transport oxygen, and is untreatable. • Amyl Nitrate • The only treatment is to wait until the • Nitroglycerine affected red blood cells are destroyed as • Topical anesthetics part of their normal life cycle. • Treatment with methylene blue

Hemoglobin S Circulatory Hypoxia • Hemoglobin S is a abnormal variant of Hemoglobin A where • Tissues have inadequate oxygen levels one of the 146 amino acids in secondary to reduced oxygen delivery. the beta chain is altered. • Inherited disorder from both • Most significant cause is reduced cardiac parents. output or blood pressure abnormalities. • 1% of African Americans. • Recurrent painful episodes (Crisis) occur as sickled cells become obstructed. • Typical “anemic” symptoms. • Can lead to infections and .

Histotoxic Hypoxia Cyanosis • A clinical condition manifested by a bluish discoloration of the mucous membranes or nail beds. • Tissues have inadequate oxygen levels • Peripheral vs. Central secondary to inability of tissue to use • Present when 5 g/dl of hemoglobin is desaturated.

oxygen for metabolism. • This usually correlates with a SaO2 below 85%. • poisoning. • ANEMIC PATIENTS WILL NEVER BE CYANOTIC!

8 Polycythemia Fetal Hemoglobin (HbF) • Fetal hemoglobin (hemoglobin F) is the main • Response to chronic hypoxemia is the hemoglobin that transports oxygen around the release of erythropoietin and stimulation of body of the developing baby during the last 7 months of pregnancy. the bone marrow to produce more RBC • It has a greater affinity for oxygen than and hemoglobin. Hemoglobin A (P50 of 20 mm Hg). • At about 30 weeks gestation, the fetus begins to • Increased hemoglobin allows for greater make increasing amounts of hemoglobin A. carrying capacity BUT also results in • Hemoglobin F does not turn into hemoglobin A. increased viscosity of the blood. • As they grow babies automatically turn off the • Increased viscosity increases work of the production of hemoglobin F (usually complete by one year). Failure to stop Hemoglobin F heart. production is found in certain beta thalassemias. Possible link to SIDS.

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