Myoglobin is an oxygen-carrying protein found in skeletal muscles.
The myoglobin dissociation curve is a rectangular hyperbola.
The venous P o2 is 5.3 kPa with a Hb saturation of 75%.
5.3 kPa
Due to perfusion failure.
Approximately 750 ml
The phenomenon where deoxyhemoglobin is better at combining with CO2 and H+ ions, aiding CO2 transport from tissues to lungs
PaO2 remains normal (>13.3 kPa).
15.2 ml of oxygen per dl
Stagnant hypoxia is characterized by normal PaO2 and oxygen-carrying capacity but reduced tissue and organ perfusion. An example cause is cardiogenic shock.
Arterial oxygen content = [Hb · 1.34 · SaO2] + [PaO2 · 0.0225].
CO2 + H2O ⇌ H2CO3 ⇌ H+ + HCO3-
5.3 kPa.
Fowler’s method.
3.5 kPa
PaO2 and PvO2 remain normal.
5% dissolved, 5% as carbamino compounds, 90% as bicarbonate
The haemoglobin molecule is a tetramer composed of four subunits, each consisting of a polypeptide chain (globin) in association with a haem group. A haem group consists of a central charged iron atom held in a ring structure called a porphyrin.
The subject must be breathing 100% oxygen.
Oxygen is carried mainly in combination with hemoglobin and also dissolved in plasma.
The difference between PAO2 and PaO2, which is influenced by V/Q imbalance and/or right-to-left shunting of blood past ventilating alveoli.
13.3 kPa
Increased oxygen extraction and venous desaturation.
Erythropoietin, a hormone produced in the kidneys, controls the production of RBCs.
Oxygen is carried in the blood in two main ways: combined with haemoglobin and dissolved in the plasma.
Hypoxic hypoxia is characterized by a PaO2 < 12 kPa. Causes include low FiO2 (e.g., inadvertent hypoxic gas delivery during anesthesia), hypoventilation (e.g., opiate-induced), diffusion impairment (e.g., pulmonary edema, pulmonary fibrosis), ventilation-perfusion mismatch (e.g., COPD, asthma, LRTI), and shunt (e.g., atelectasis causing intrapulmonary shunt).
Proerythroblast → Prorubricyte → Rubricyte → Normoblast → Reticulocyte → Erythrocyte.
The amount of shunt caused by the addition of venous blood to the arterial circulation.
RBCs survive for about 120 days.
In normal adults, 98% of all haemoglobin is in the form of HbA1 (2 α chains and 2 β chains), and the remaining 2% is in the form of HbA2 (2 α chains and 2 δ chains).
In the example, Hb is 15 g/dl, SaO2 is 100%, and PaO2 is 13.3 kPa.
The exchange of bicarbonate (HCO3-) and chloride (Cl-) ions across the red blood cell membrane.
The OHDC is a graph relating the percentage of haemoglobin saturated with oxygen to the partial pressure of oxygen (P o2).
In histotoxic hypoxia, PaO2 is normal, cells are unable to utilize oxygen resulting in high venous saturations, and cyanide poisoning will also be associated with a left shift of the oxyhaemoglobin dissociation curve.
Pico2: 0.03 kPa, Peco2: 4 kPa, Paco2 (arterial): 5.3 kPa, Paco2 (alveolar): 5.3 kPa, Pvco2: 6.1 kPa
The relationship between CO2 content in the blood and the partial pressure of CO2 (PCO2).
Anaemic hypoxia is characterized by normal PaO2 but inadequate oxygen-carrying capacity. Causes include low circulating hemoglobin levels (e.g., acute and chronic anemias) and normal circulating hemoglobin levels but reduced ability to carry oxygen (e.g., carbon monoxide poisoning).
Anatomical dead space and alveolar dead space.
Due to the presence of the enzyme carbonic anhydrase (CA) in RBCs
Because the shunted blood bypasses ventilated alveoli and is never exposed to the higher alveolar PO2.
PAO2 is a calculation based on known factors, while PaO2 is a measurement influenced by ventilation-perfusion imbalance, pulmonary diffusing capacity, and the oxygen content of blood entering the pulmonary artery.
Haemoglobin is split into haem and globin components; globin is broken down into amino acids, and haem is broken down into iron and biliverdin.
P 50 is 3.5 kPa, which is the P o2 at which Hb is 50% saturated. It is the conventional point used to compare the oxygen affinity of Hb.
Myoglobin has a higher affinity for oxygen than hemoglobin.
PaO2 is reduced.
Myoglobin takes up oxygen from circulating hemoglobin and releases it into exercising muscle tissues at very low PO2, providing a source of oxygen when blood flow to muscles is constricted.
Huffner’s constant is 1.34, meaning each gram of haemoglobin combines with 1.34 ml of oxygen.
Approximately 40 ml/100ml blood.
The CO2 dissociation curve shifts depending on the oxygenation state of hemoglobin, with deoxyHb having a higher affinity for CO2.
Both PAO2 and PaO2 will decrease.
Shunt blood flow.
Due to reduced oxygen content.
The process of RBC production is called erythropoiesis.
Just over 1000 ml
Approximately 200 ml/min
Anatomical dead space constitutes the conducting airways (trachea, bronchi, bronchioles, and terminal bronchioles) and includes the mouth, nose, and pharynx.
Normal arterial oxygen content but circulatory dysfunction results in inadequate oxygen delivery and possibly increased venous saturations
The diffusion of Cl- ions into RBCs from plasma to maintain electrical neutrality as HCO3- diffuses out
Worn-out RBCs are removed and destroyed by fixed phagocytic macrophages in the spleen and liver.
2 mL/kg.
The CO2 dissociation curve is more linear, while the oxyhemoglobin dissociation curve is sigmoid in shape.
By the partial pressure of oxygen.
The arterial P o2 is 13.3 kPa with a Hb saturation of 97%.
Myoglobin can bind only one molecule of oxygen.
Due to venous admixture constituting a physiological shunt.
The myoglobin dissociation curve lies to the left of the oxyhemoglobin dissociation curve.
By multiplying oxygen content by cardiac output
Oxygen content is calculated by combining the proportion of oxygen bound to haemoglobin with that dissolved: Oxygen content = [Bound Oxygen] + [Dissolved Oxygen] = [Hb · 1.34 · SaO2] + [PaO2 · 0.0225].
Respiratory dead space is the volume of inspired gas that does not take part in gas exchange.
Reduced arterial oxygen content and increased oxygen extraction resulting in lower venous oxygen content
Hypoxia, such as from altitude or anemia, stimulates the kidney to release more erythropoietin.
Normal arterial oxygen content but cellular inability to utilize oxygen, resulting in high venous oxygen content
As CO2 enters RBCs, it causes more O2 to dissociate from hemoglobin, allowing more CO2 to combine with hemoglobin and more HCO3+ to be produced
When oxygen binds to hemoglobin, the R state is favored, increasing the affinity for oxygen and facilitating the uptake of additional oxygen. The affinity for the fourth oxygen molecule is much greater than for the first.
In methaemoglobinaemia, the ferrous iron (Fe2+) in haemoglobin is oxidised into the ferric (Fe3+) form.
The subject exhales maximally at a slow and constant rate to residual volume.
PvO2 is reduced with venous desaturation (<75%).
Hypoxia is defined as either an inadequate oxygen supply or the inability to utilize oxygen at a cellular level.
The four main types of hypoxia are hypoxic hypoxia, anaemic hypoxia, stagnant hypoxia, and histotoxic hypoxia.
RBCs start as immature cells in the red bone marrow and take about seven days to mature.
Significant reduction in arterial oxygen content and increased cardiac work to maintain oxygen delivery
Approximately 50 ml/100ml blood.
Histotoxic hypoxia is characterized by normal PaO2, oxygen-carrying capacity, and tissue perfusion but an inability of the tissues to utilize the oxygen at a cellular mitochondrial level. An example cause is cyanide poisoning.
Fetal haemoglobin (HbF) is composed of 2 α chains and 2 γ chains. HbF changes to HbA at around six months of life.
The calculated arterial oxygen content is 20.4 ml of oxygen per dl.
Sitting up, neck extension, jaw protrusion, increasing age, and increasing lung volume.
Total blood flow, measured via cardiac output monitors.
Alveolar dead space constitutes alveoli that are ventilated but not perfused, so no gas exchange occurs.
A nose clip is placed on the subject, and the subject breathes air in and out through their mouth via a mouthpiece.
Hb: Hemoglobin (g/dl), SaO2: Arterial oxygen saturation, PaO2: Partial pressure of arterial oxygen, 1.34: Huffner’s constant, 0.0225: ml of oxygen per dl per kPa of oxygen partial pressure.
Even though dissolved oxygen represents a small fraction of total oxygen-carrying capacity of the blood, it is important. For example, in severe anaemia, hyperbaric oxygen therapy can meet total body oxygen requirements. It also triggers the hypoxic respiratory drive, which is clinically significant in patients with COPD.
The shunted blood continues to depress the arterial oxygen content.
The OHDC has a characteristic sigmoid shape due to the binding characteristics of hemoglobin to oxygen, involving allosteric modulation and cooperative binding.
Iron combines with the plasma protein transferrin, which transports it in the bloodstream.
Oxyhemoglobin carries less CO2 than deoxyhemoglobin for the same partial pressure of CO2 (Pco2).
Biliverdin is converted into bilirubin, which is transported to the liver and secreted into the bile.
CO2 dissolves in plasma and then diffuses into red blood cells.
End-capillary oxygen content, estimated from the alveolar gas equation.
40% in the upper lung and 60% in the lower lung.
VD.PHYS / VT = (PaCO2 - PECO2) / PaCO2
70% in the upper lung and 30% in the lower lung.
The consequences are impairment of both O2 uptake and CO2 elimination.
Increase CaO2 by increasing hemoglobin concentration, maintaining high oxygen saturations, and increasing dissolved oxygen. Increase CO by optimizing heart rate and rhythm, stroke volume, and perfusion pressure.
By dividing Phase II so that areas A and B are equal and measuring from the start of exhalation.
Most lung diseases (especially pulmonary embolus), general anaesthesia, positive pressure ventilation, and positive end expiratory pressure.
Normally 35%.
It alters the orientation of the zones with respect to anatomic locations in the lung, but the relationship with respect to gravity and vascular pressure remains the same.
47 mmHg (6.3 kPa).
PiO2 becomes 0 because the barometric pressure equals the partial pressure of water vapor.
19.95 kPa.
Less than 2 kPa.
V/Q mismatch, shunt, and diffusion impairment.
In sickle cell anaemia, there is an abnormal β polypeptide chain due to a genetic mutation where valine is replaced by glutamic acid. This causes haemoglobin to form solid, non-pliable sickle-like structures when exposed to low PaO2, obstructing microcirculation and leading to painful crises and infarcts.
Each gram of hemoglobin combines with 1.34 ml of oxygen.
General anaesthesia, hypoventilation, intubation, and tracheostomy.
The two β chains move closer together, changing the position of the heme moieties to a 'relaxed' or R state.
Oxygen binds to the ferrous iron (Fe2+) in haemoglobin by forming a reversible bond. Each molecule of haemoglobin can bind four molecules of oxygen, one at each ferrous ion within each haem group.
Oxygen Content = [Bound Oxygen] + [Dissolved Oxygen] = [Hb × 1.34 × SaO2] + [PaO2 × 0.0225]
Up to about 10 kPa.
The overall V/Q ratio is 0.8.
The CO2 dissociation curve shifts depending on the oxygen saturation, with lower oxygen levels allowing more CO2 to be carried.
Ventilation of the lungs supplies oxygen to the alveolus, diffusion of oxygen across the alveolus to the pulmonary capillaries, oxygen carriage by blood (combined with hemoglobin and dissolved in plasma), and diffusion from capillary to mitochondria.
Alveolar plateau phase – exhalation of alveolar gas containing N2 from the alveoli.
Their volume reduces, resulting in increased compliance and improved ventilation.
At the apex, it is about -8 cm H2O, and at the base, it is about -1.5 cm H2O.
Alveolar partial pressure of oxygen.
Inspired pressure of oxygen.
It is the point where the PO2 is low enough that anaerobic metabolism begins to occur.
In Zone 2 (middle), pulmonary arterial pressure (Pa) exceeds alveolar pressure (PA), which in turn exceeds pulmonary venous pressure (Pv). Blood flow is determined by the difference between arterial and alveolar pressures.
21%
5.3 kPa.
13.3 kPa.
Single-breath nitrogen washout utilizing a rapid nitrogen gas analyser.
The V/Q ratio is calculated by dividing alveolar ventilation by cardiac output.
The Bohr equation.
Nitrogen concentration against volume using a rapid nitrogen analyser.
Ventilation-perfusion mismatching, diffusion impairment, and anatomical shunt.
Nitrogen concentration increases as alveolar gas begins to mix with anatomical dead space gas.
Alveolar pressure (PA), pulmonary arterial pressure (Pa), and pulmonary venous pressure (Pv).
The V/Q ratio is highest (about 3.0), resulting in the highest PaO2 and lowest PaCO2.
The V/Q ratio is lowest (about 0.6), resulting in the lowest PaO2 and highest PaCO2.
1 atmosphere (or 101 kPa).
Ventilation/perfusion mismatch, shunt, and diffusion impairment.
LRTI or atelectasis.
Thalassaemia is an inherited autosomal recessive blood disorder where the genetic defect results in a reduced rate of synthesis of one of the globin chains that make up haemoglobin, causing anaemia. It can be α or β depending on which globin chain is underproduced.
The V/Q ratio is the ratio between the amount of air getting to the alveoli (alveolar ventilation, Va, in l/min) and the amount of blood entering the lungs (cardiac output, Q, in l/min).
Haemoglobin increases the oxygen-carrying capacity of blood approximately 70-fold, as oxygen is relatively insoluble in water.
A defect in gas transfer within the lungs, usually due to V/Q imbalance.
Arterial oxygen content = [15 × 1.34 × 1.0] + [13.3 × 0.0225] = 20.4 ml of oxygen per dl.
60% in the upper lung and 40% in the lower lung.
The V/Q ratio in areas of shunt is zero.
Just under 5 ml of oxygen per dl.
Tidal volume, measured with a spirometer.
Arterial partial pressure of CO2, measured from an arterial blood gas.
Their volume reduces, leaving them less compliant and reducing ventilation.
A shunt is an extreme form of V/Q mismatch where blood enters the arterial system without passing through ventilated areas of the lung.
Pulmonary blood flow is preferentially directed to the base of the lungs.
It may approach 70%, which has obvious implications for CO2 removal.
Because the V/Q ratio is highest at the apex, resulting in the highest PaO2.
It gets humidified by water vapor.
Severe hypotension, COPD, LRTI, or asthma.
Approximately 1.3 kPa (10 mmHg).
Carbaminohemoglobin.
The Bohr effect describes the right shift in the OHDC associated with increased PaCO2 and hydrogen ion concentration.
As minute ventilation increases, PaCO2 and PACO2 decrease, resulting in a reciprocal increase in PAO2.
DO2 = CO × CaO2, where CO is cardiac output (heart rate × stroke volume).
21 kPa (101.3 kPa x 0.21).
The alveoli at the base are more compliant and fill to a greater extent for a given change in intrapleural pressure during inspiration compared to the alveoli at the apex.
Ventilation is preferentially distributed to the basal alveoli.
1-2 kPa.
Respiratory Quotient (CO2 production / O2 consumption).
Barometric pressure falls with increasing altitude, halving every 18,000 ft.
By multiplying atmospheric pressure by the percentage of oxygen in the air, resulting in 21 kPa.
13.3 kPa.
Pulmonary edema and pulmonary fibrosis.
It catalyzes the conversion of CO2 and H2O to carbonic acid (H2CO3).
Mixed venous oxygen content, calculated from a mixed venous blood sample.
Initial expired gas from the conducting airways containing 100% O2 and no N2.
The relationship between the pressure in the alveoli, arteries, and veins.
Closing capacity, where airways at the lung bases close as the lung approaches residual volume.
It reduces the PO2 to approximately 19.7 kPa ((101.3 - 6.3) x 0.21).
Hemoglobin combines with oxygen to carry it in the blood.
Exercise increases pulmonary artery pressure, eliminating Zone I and moving the boundary between Zone III and Zone II upward.
In Zone 1 (apex), alveolar pressure (PA) exceeds both pulmonary arterial pressure (Pa) and pulmonary venous pressure (Pv), resulting in capillary collapse and no blood flow.
In Zone 3 (base), both pulmonary arterial pressure (Pa) and pulmonary venous pressure (Pv) exceed alveolar pressure (PA), and blood flow is driven by the difference between arterial and venous pressures.
6.3 kPa.
Right to left cardiac shunt.
Physiological and pathological processes.
Factors that shift the OHDC to the right include ↓ pH, ↑ temperature, ↑ 2,3-diphosphoglycerate, ↑ PaCO2, HbS, anemia, pregnancy, and post-acclimatization to altitude.
Arterial oxygen content, calculated from arterial blood gas (ABG) measurements.
55% in the upper lung and 45% in the lower lung.
The V/Q ratio in areas of dead space is infinity.
Venous oxygen content = [15 × 1.34 × 0.75] + [5.3 × 0.0225] = 15.2 ml of oxygen per dl.
Anaesthesia affects lung volume and changes the compliance of different areas of the lung, moving alveoli in the upper lung to a steeper portion of the compliance curve and those in the lower lung to a flatter, less compliant part.
The alveolar partial pressure of oxygen for a given inspired pressure of oxygen and a given alveolar pressure of carbon dioxide.
Physiological and pathophysiological changes.
Mixed expired partial pressure of CO2, measured from end-tidal CO2.
In cases of severe hypotension or with a pulmonary embolus.
Alveolar partial pressure of carbon dioxide.
PiO2 = FiO2 · (Patm − PH2O), where FiO2 is the fractional inspired oxygen, Patm is the barometric pressure, and PH2O is the partial pressure of water vapor.
The increase in blood flow is due to the recruitment and distention of pulmonary vessels with increasing intravascular pressures down the lung.
About 15 kPa.
1-5 kPa.
Low inspired oxygen, hypoventilation, anaemic hypoxia, stagnant hypoxia, histotoxic hypoxia, V/Q mismatch, diffusion impairment, and shunt.
Physiological dead space represents the combination of anatomical and alveolar dead space.
Factors that shift the OHDC to the left include ↑ pH, ↓ temperature, ↓ 2,3-diphosphoglycerate, ↓ PaCO2, HbF, methemoglobin, carboxyhemoglobin, and stored blood.
The guidelines recommend that oxygen be administered to patients whose oxygen saturations fall below the target range (94–98% for most acutely ill patients and 88–92% for those at risk of type 2 respiratory failure with raised CO2 levels in the blood).
The double Bohr effect refers to the situation in the placenta where the Bohr effect operates in both maternal and fetal circulations, facilitating the reciprocal exchange of oxygen for carbon dioxide.
The Haldane effect describes the increased ability of deoxygenated hemoglobin to carry carbon dioxide, while oxygenated blood has a reduced capacity to carry carbon dioxide.
Intrapleural pressure increases by about 0.2 cm H2O for every centimeter of vertical displacement from the apex to the base of the lung.
PAO2 = PiO2 - (PACO2 / R)
Because arterial pressures are just sufficient to raise blood to the top of the lung and exceed alveolar pressure.
Cyanotic congenital heart disease, such as right-to-left intracardiac shunting (e.g., Tetralogy of Fallot).
Zone 1 may be present in cases of severe hypotension or if alveolar pressure is raised, such as during positive pressure ventilation.
No, it does not vary with altitude.
From the high pressure in the alveoli (15 kPa) to the lower pressure in the blood (5.3 kPa).
Anatomical dead space and alveolar dead space.
The arterial oxygen tension based on a given inspired oxygen fraction in the presence of various degrees of shunt.
Physiological dead space.
The oxygen cascade describes the sequential reduction in PO2 from the atmosphere to cellular mitochondria.
Because the apical alveoli are on a flatter part of their pressure–volume (compliance) curve compared to the basal alveoli, which are on the steep portion of the compliance curve.
Because the intrapleural pressure is more negative at the apex than at the base.
Physiological causes include bronchial arterial blood passing into the pulmonary veins and coronary venous blood draining into the left ventricle. Pathological causes include lung collapse or consolidation with loss of ventilation.
It increases alveolar pressures, which can result in substantial areas of the lung falling into Zone I.
The metabolic substrates used: Carbohydrate (RQ 1.0), Protein (RQ 0.8–0.9), Fat (RQ 0.7).
The removal of oxygen by the pulmonary capillaries and its continual supply by alveolar ventilation.
6-7 kPa.
Hypoxia at the mitochondrial level.
