By increasing the concentration of H^₊ (hydrogen ions).

When CO₂ is combined with H₂0, it then becomes H₂CO₃ (carbonic acid), which then spontaneously ionizes into

H⁺ and HCO₃^- (bicarbonate ions).

CO₂ + H₂0<---->  H₂CO₃<----> H⁺ + HCO₃^-

Respiration is the overall exchange of gases between the atmosphere, blood and body cells.

It includes:

1. Pulmonary ventilation (breathing)

2. Gas exchange at the lungs and cells

3. Transport of gases

1. Ventilation

2. Gas Conditioning

3. Produces sound

4. Provides olfactory sensations

5. Protects the body

Breathing:

Inhalation (inspiration) - draws gases into the lungs. Exhalation (expiration) - forces gases out of the lungs.

Gas conditioning

As gases pass through the nasal cavity and paranasal sinuses, inhaled air becomes turbulent. The gases in the air are:

1. warmed to body temperature

2. humidified

3. cleaned of particulate matter

This part of the respiratory system transports air. It is made up of passages that serve to warm, moisten, and filter the inhaled air:

nose, nasal cavity, pharynx, larynx, trachea, primary bronchi, secondary bronchi, tertiary bronchi, bronchioles, terminal bronchioles

The part of the respiratory system where gas exchange occurs.

It is made up of:

1. respiratory bronchioles

2. alveolar ducts

3. alveolar sacs

4. about 300 million alveoli

Nose > pharynx > larynx > trachea > primary bronchi > secondary bronchi > tertiary bronchi > terminal bronchioles > [respiratory bronchioles > alveolar ducts > alveolar sacs > alveoli (exchange) with pulmonary capillaries.

1. Transport gas to alveolar duct.

• Respiratory bronchioles are the first part of the respiratory zone. They have scattered alveoli in their walls, thus can exchange gases. 

1. Type I alveolar

2. Type II alveolar

3. Alveolar macrophages

• Simple squamous epithelial cells that form a nearly continuous lining of the alveolar wall.

• Predominant type of cells.

• Supported by a thin elastic basement membrane that they share with the basement membrane of the pulmonary capillaries (the main site of gas exchange)

Type II alveolar cells

• Few in number and are found between Type I alveolar cells. 
• Secrete alveolar fluid that keeps the surface between the cells and the air moist. 
• Part of the alveolar fluid is surfactant (a mixture of phospholipids and lipoproteins that lowers the surface tension of the alveolar fluid, which reduces the tendency of the alveoli to collapse.

A mixture of phospholipids and lipoproteins that lowers the surface tension of the alveolar fluid, which reduces the tendency of the alveoli to collapse

Dust cells; are wandering phagocytes that remove fine dust particles and other debris in the alveolar spaces that engulf foreign particles.

Physical movement of air into and out of the respiratory tract.

Expresses the inverse relationship between pressure and volume: As volume increases, pressure decreases As volume decreases, pressure increases

Pleural cavities

Each lungs sits in a pleural cavity. The surface of each lung sticks to the inner wall of the chest and the superior surface of the diaphragm; thus, any movement of the chest wall or diaphragm directly affects the volume of the lungs.

There is not much of a pressure gradient, but it is a little lower in the alveoli:

PCO₂ in alveoli = 40 mm Hg

PCO₂ in pulmonary capillaries = 46 mm Hg

Internal respiration involves oxygen diffusion from the blood into tissue cells, and CO₂ diffusing from tissue cells into the blood.

• The partial pressure of Oxygen (PO2) is higher in the blood than in the cells because cells use O₂ for cellular respiration, therefore, O₂ diffuses from blood into the body cells.

Internal respiration involves O₂ diffusion from the blood into tissue cells, and CO₂ diffusing from tissue cells into the blood.

• The partial pressure of carbon dioxide (PCO2) is higher in the body cells than in the blood because cells produce CO₂ as a waste product of cellular respiration. Therefore, CO₂ diffuses from body cells into the blood.

1. Partial Pressure Gradient

2. Gas Solubilities (CO2 is the most soluble, 20X moreso than O2, and nitrogen is practically insoluble in plasma)

3. Structure of the respiratory membrane

• Distance to diffuse - the basement membrane of the alveoli and pulmonary capillaries are fused; thus, the distance is short (0.5 - 1 micrometer)
• Large amount of surface area - In males: approx. 60 meters squared; about the size of a tennis court)

Ventilation and perfusion coupled together regulate for efficient gas exchange. Changes in PCO₂ in the alveoli cause changes in the diameters of the pulmonary arterioles: 

• Alveolar CO₂ is high/O₂ is low = vasoconstriction (decrease blood flow) -
• Alveolar CO₂ is low/O₂ is high = vasodilation (increase blood flow)

Protein made of 4 protein subunits (heme)

• Each heme has an FE atom, and each FE atom can carry an O₂ molecule. 
• Red blood cells care millions of Hb molecules.

O₂ bound to a hemoglobin

Males can carry about 200 mL 0₂/L blood

Females can carry about 175 mL 0₂/L blood

1. PCO₂ - If PCO₂ increases, the hemoglobin's affinity for O₂ decreases, thus, this will increase O₂ unloading from the blood.
2. pH - If there is an increase in hydrogen (H⁺) concentration, there will be a decrease in Hb affinity for O₂, thus, this will increase O₂ unloading from the blood. 
3. Temperature - If the temperature increases, hemoglobins affinity to O₂ decreases, thus, increasing the O₂ unloading from the blood. 
4. Concentration of 2, 3 DPG (an organic chemical produced by RBC metabolism when environmental O₂ levels is low):

• If the "2, 3 DPG" increases, hemoglobins affinity to O₂ decreases, thus, increasing the O₂ unloading from the blood. 

  5.  PO₂ - If PO₂ decreases, hemoglobins affinity to O₂ decreases, thus, increasing the O₂ unloading from the blood. 

1. About 10% is transported in the blood is dissolved in the plasma. 
2. About 20% is bound as carbaminohemoglobin (bound to Hb) 
3. The rest (70%) is transported as bicarbonate ion (HCO₃^-) in the plasma.

When CO₂ combines with H₂0 in the presence of carbonic anhydrase (enzyme), carbonic acid is formed; then the carbonic acid spontaneously dissociates into an hydrogen  ion and a bicarbonate ion.

CO₂ + H₂O <----> H₂CO₃<------->H⁺ + HCO₃^-

At the tissue/cell, to counterbalance the out-rush of negative bicarbonate ions (HCO₃^- ) from the RBCs, chloride ions (CI^-) move from the plasma into the RBCs. So, Cl^- ion are exchanged fro HCO₃^- ions released into the plasma.

HCO₃^- ions move into the RBCs and bind with H⁺ to form H₂CO₃ (carbonic acid); H₂CO₃ is then split by carbonic anhydrase --------> CO₂ + H₂O. CO₂ then diffuses from the blood into the alveoli.

HCO₃^- + H⁺<--------> H₂CO₃ <--------> CO₂ + H₂O

Dorsal Respiratory Group (DRG/Inspiratory Center)

• group of inspiratory neurons - excites the inspiratory muscles and sets eupnea (12-15 breaths/min) 
• these neurons cease firing during expiration 
• output goes via the phrenic nerve (stimulates diaphragm to contract) and the intercostal nerves (stimulates intercostals to contract) and cervical nerves (stimulates scalene to contract).

1. Dorsal Respiratory Group (DRG/Inspiratory Center
2. Ventral Respiratory Group (VRG)

• this is a group of inspiratory and expiratory neurons 
• involved in forced inspiration and expiration 
• they are inactive during quiet breathing

• This is a group of neurons in the pons that influence and modify activity of the DRG and VRG to smooth out inspiration and expiration transitions. 
• Dominates pneumotaxic centers and apneustic centers

PCO₂ levels are monitored by chemoreceptors in the brain stem.

1. Increased PCO₂ levels (hypercapnia) result in increased rate and depth of breathing (hyperventilation).
2. CO₂ in blood diffuses into CSF where it combines with H₂O to form H₂CO₃. H₂CO₃ dissociates to form HCO₃^- and H⁺.
3. At rest, it is H⁺ levels that controls breathing rate (even though CO₂ acts as original stimulus).
4. Hypoventilation is slow and shallow breathing due to abnormal low PCO₂ levels. Apnea (stop breathing) may occur until PCO₂ levels rise.
5. If CO₂ is not removed (as in emphysema and chronic bronchitis), chemoreceptors become unresponsive to PCO₂ stimulus and PO₂ levels become the main stimulus for ventilation (hypoxic drive).
6. Normally arterial O₂ levels are monitored by aortic and carotid bodies.
7. Substantial drops in arterial PO₂ (to 60 mm Hg or below) are needed before O₂ levels become a major stills for increased ventilation.