The Respiratory System Part 2

Hemoglobin

• Most of the oxygen in arterial blood binds to hemoglobin
• Each hemoglobin molecule can carry 4 molecules of oxygen (O₂)
• Red blood cells each contain 280 million hemoglobin molecules
• Each red blood cell can carry over a billion O₂ molecules
• Hemoglobin increases the total blood oxygen carrying capacity seventy-fold
• Bound O₂ does not directly impact PaO₂
• Total O₂ content of blood is dependent on PaO₂ and hemoglobin concentration

Forms of Hemoglobin

• Hemoglobin comes in two forms: oxyhemoglobin and deoxyhemoglobin
• Oxyhemoglobin is bound to oxygen and gives blood a bright red color
• Deoxyhemoglobin has no or limited amounts of bound oxygen
• Deoxyhemoglobin blood has a dark red coloration and appears blue when viewed through the skin

Oxyhemoglobin Saturation

• Pulse oximeters read % of Hemoglobin saturation, or the ratio of oxyhemoglobin to total hemoglobin
• Oxyhemoglobin saturation is measured to assess how well the lungs have oxygenated the blood
• Normal oxyhemoglobin Saturation is 95-100%
• Pulse oximeters do not measure the O₂ content, concentration, or amount of O₂ in the blood

Hemoglobin Concentration

• The oxygen-carrying capacity of blood is assessed by hemoglobin concentration and red blood cell count
• Anemia is a condition of below-normal hemoglobin levels
• Normal hemoglobin level in females is 12-16 g/dl, anemia if Hb < 12 g/dl
• Normal hemoglobin level in males is 14-17.4 g/dl, anemia if Hb < 14 g/dl
• Polycythemia is a condition of above-normal hemoglobin levels and may occur due to high altitudes
• A Hemoglobin level >20 g/dl is considered polycythemia

Erythropoietin

• Erythropoietin is made in the kidneys
• Erythropoietin stimulates hemoglobin and red blood cell production in red bone marrow
• Decreased oxygen levels stimulate release of erythropoietin
• Erythropoietin is sometimes referred to as "EPO"
• Blood doping increases the amount of oxygen in the blood

Hemoglobin Loading and Unloading

• Loading is when hemoglobin binds to oxygen in the lungs
• Unloading is when oxyhemoglobin releases/drops off oxygen in the tissues
• The direction of reaction - either loading or unloading - depends on the PO₂ of the environment and the affinity for O₂
• High PO₂ favors hemoglobin loading
• Low PO₂ favors hemoglobin unloading

Oxyhemoglobin Dissociation Curve

• Systemic arteries have a PaO₂ of 100 mmHg
• 100 mmHg PaO₂ is a sufficient concentration of O₂ to oxygenate 97% of available hemoglobin to form oxyhemoglobin
• Blood also carries about 20 ml dissolved O₂/100 ml of blood
• Dissolved O₂ determines the PaO₂ pressure

Oxyhemoglobin Dissociation Curve- Loading

• Hemoglobin is loaded in the Lungs
• Hemoglobin loading requires a favorable pressure gradient and blood
• Alveoli have a pressure of 100 mmHg
• Blood has a pressure of 40-50 mmHg

Oxygen Dissociation Curve

• Shows how much oxygen is unloaded to tissues

Oxyhemoglobin Dissociation Curve- Unloading

• Unloading occurs In the tissue
• Hemoglobin unloading requires a favorable pressure gradient
• Arterial pressure is 100 mmHg
• Tissue pressure is 5-15 mmHg

Oxygen Dissociation Curve Shape

• The curve is sigmoidal (S-shaped)
• Small changes in PO₂ produce large changes in % saturation in the steep part of the curve
• In the steep part of the curve, patients "desaturate"
• At high PO₂, changes in PO₂ have little effect on loading
• Curve shape reflects progressive hemoglobin binding or unbinding of O₂

Oxygen Dissociation Curve -Unloading

• During exercise, oxygen unloading is even greater:
  • 22% of available O₂ is unloaded at rest
  • 39% of available O₂ is unloaded during light exercise
  • 80% of available O₂ is unloaded during heavy exercise

Pulmonary Capillaries

• Blood spends about ¾ of a second in the pulmonary capillaries
• Blood leaves the pulmonary capillaries completely oxygenated
• The anatomy of the alveoli/capillary interface is effecient
• Oxygen exchange is very quick

Lungs

• Lungs present the largest surface of the body to an environment that carries hostile molecules and particles
• Large particles are filtered out in the nose
• Smaller particles are trapped in mucus of the upper airways
• Macrophages are found in the endothelium of the alveoli

Ventilation-Perfusion Relationships

• Adequate blood flow and ventilation ensure maximal transfer of available oxygen and CO₂
• Blood flow pattern in the lungs helps to better match ventilation (air flow) to perfusion (blood flow)
• Areas of the lungs that are under-ventilated experience reduced perfusion
• Shunting is when the blood goes to parts of the lung that do not have oxygen

Ventilation

• Ventilation is controlled to maintain nearly constant levels of CO₂ in the blood
• Oxygen levels naturally cause changes in ventilation patterns
• PaCO₂ = 35 - 45 mmHg (40 mmHg)

PaCO2

• Tissue PCO₂ = 46 mmHg
• Venous PCO₂ = 45 mmHg
• Alveolar PCO₂ = 40 mmHg
• Small changes in CO₂ levels cause a much greater fractional change than a change in PaO₂ (100 mmHg)
• Changing the PaO2 and PaCO2 by 5 mmHg results in changes equal to 5% in oxygen content in the blood but 12.5% in CO₂ content

PaCO2 Index

• PaCO2 provides a sensitive index to ventilatory status
• PaCO2 can assess for control of ventilation
• PaCO2 provides info into negative feedback regulation

Stimulus for Defining CO₂ Levels

• The stimulus for defining CO₂ levels in the blood is primarily hydrogen ion concentration i.e. pH

Carbon Dioxide

• Freely reversible as driven by the relative concentrations of the components
• Loss of CO₂ shifts the reaction left ward resulting in in loss of CO2, HCO3-, H+, & CO32-
• Retention of CO₂ shifts the reaction right ward resulting in retention of H+
• Normal pH is 7.35-7.45
• Aortic and Carotid bodies can respond to changes in PaCO2 & H+ changes

Blood PH

• These chemoreceptors can respond quickly to changes in blood chemistry i.e. PaCO2 and H+
• Those responses are acute and lead to changes in respiratory rate and depth of inhalation
• Blood pH can quickly influence respiration

Peripheral Chemoreceptors

• Peripheral chemoreceptors located in the bifurcation of the carotid arteries and in the ascending aorta
• Located in the Carotid bodies and Aortic bodies
• The peripheral chemoreceptors respond to changes in:
  • Hydrogen ion concentrations [H+]
  • Significantly decreased PaO₂ (hypoxia)
• Peripheral chemoreceptors are stimulated by decreased blood pH independent of the effect of blood CO₂
• Peripheral chemoreceptors are not affected by changes in blood pH because H+ cannot cross the blood-brain barrier
  • Linear increase in ventilation as PaCO₂ increases and pH decreases i.e. acidosis
  • The response to decreasing PO₂ is nonlinear and slow

Chemoreceptors in the Medulla

• Located in the medulla and are very sensitive to changes in arterial PaCO₂
• Sensitive to H+ ions but these ions cannot cross the blood-brain barrier
• CO₂ can cross the blood-brain barrier
• Change in blood PaCO₂ changes the concentration of CO₂ in the spinal fluid which in turn changes the [H+] in the brain, which modifies respiration

Summary of Ventilation

• ↑ PaCO2
  • Medullary chemoreceptors are sensitive to change in CSF pH i.e. [H+] caused by change in ↑ PaCO2
• Carotid & aortic bodies
  • Directly sensitive to change in pH, fall in pH increases output from these sensors
• ↓ pH
  • Carotid & aortic bodies are stimulated by↓ blood pH i.e. independently of PaCO2 status
• ↓ Pa O₂
  • Carotid bodies: Low blood PO₂ adds to the input from PCO stimulate ventilation directly when the PO₂ falls below 70 mmHg

Hypoventilation

• Ventilation is inadequate to perform needed gas exchange
• Hypoventilation Results in CO₂ retention, (↑ PaCO2 or hypercapnia), a fall in pH, and an increase in [H+] (respiratory acidosis)

Hyperventilation

• Alveolar ventilation of CO₂ exceeds production of carbon dioxide
• Hyperventilation is blowing off CO
• Can be voluntary or involuntary

Carbon Dioxide Transport

• Carbon dioxide is carried in the blood in three forms:
• Dissolved in plasma and is more soluble than O₂
• As carbaminohemoglobin, CO₂ is attached to hemoglobin
• As bicarbonate ions accounts for the majority of transport

Carbon Dioxide Transport

• CO₂ produced in the cells diffuses into the blood plasma and then into the red blood cells
• Carbon dioxide in the red blood cells is transported as:
  • Dissolved CO₂
  • Combined with hemoglobin
  • Bicarbonate ion which is the largest fraction and is freely reversible
• Carbon dioxide readily reacts with water in the red blood cell of the systemic capillaries and plasma
• Carbonic anhydrase is the enzyme that catalyzes the reaction to form carbonic acid

Acid-Base Balance

• Blood plasma pH is maintained within a constant range by the actions of the lungs and kidneys in a freely reversible process.
• pH ranges from 7.35 to 7.45
• Kidneys help maintain pH by secreting H+ into the urine and by generating more bicarbonate
• Carbonic acid is converted into a gas, CO₂, it can be regulated by breathing and exhaling
• The amount of CO2 exhaled regulates the pH
• Normal blood pH : 7.35 – 7.45

PH Balance

• Regulate blood pH by the active transport of H+ ions into the filtrate
• Buffer system: -CO2 actively transported out of peritubular capillaries -CO₂ combines with water to form HCO3 or H+ -Secretion of H+ ions either slows or increases until the pH returns to normal -Excess H+ buffered by bicarbonate ions
• Urine pH is between 4.5 and 8.0

Blood PH

• Acidosis is when blood pH falls below 7.35
  • Respiratory acidosis- caused by hypoventilation where there is (CO₂ retention which increases H+ (lowers pH)
  • Metabolic acidosis- caused by excessive production of acids (uncontrolled diabetes) or loss of bicarbonate (diarrhea)
• Alkalosis is when blood pH rises above 7.45
  • Respiratory alkalosis- caused by hyperventilation where (blow off” CO₂, [H+] decreases and pH increases to cause death.
  • Metabolic alkalosis- caused by inadequate production of acids or overproduction of bicarbonates and loss of digestive acids from vomiting
• The body compensates for the metabolic component of through ventilation where defects in respiration can be compensated through metabolism.

Blood Acid-Base Blanace

• Ventilation can compensate for the metabolic component through compensating a defective respiratory condition:
  • A person with metabolic acidosis will hyperventilate and blow off CO₂ as [H+] decreases and pH rises
  • A person with metabolic alkalosis will hypoventilate where slow respiration will retain CO2 and [H+]increases as pH lowers
• Terms used to describe an adequate Acid-Base Balance are Alkalosis, Acidosis where high CO2 retention due to hypoventilation can be an accumulation of the carbonic acid to fall below the normal blood pH.
• Acids are produced in their “nonvolatile” forms such as lactic acids, or ketone bodies (diarrhea) where bicarbonates contribute to a fall in to normal below the normal blood pH. Conversely , in both of theses instances and when the blood acidity changes from metabolism can be offset for an increase or decrease with normal breathing conditions.
• An effective ventilation results with blood PH can happen due to a loss of CO2 and can also happen from excessive amounts of vomitting or non volatile carbonic acids that accumulate at an accelerated pace.
• Any person experiencing issues of the two listed defects can have respiratory defects compensated through urine retention, or be properly ventilated , and in turn the bodies chemistry would balance.
• The body and lungs operate in blood regulation chemistry for balance by being responsive to acidity and ventilation from acidosis, and blood alkalinity and lung function through compensation and maintenance to assist any compensation .