Respiratory System

Functions of the Respiratory System

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Primary function:

• Transport oxygen and Carbone dioxide between the environment and blood

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• Secondary functions:
• Phonation (Voice production)
• Results from vibration of vocal cords as air passes over them
• Nose, mouth, pharynx, and sinuses also contribute to sounds .

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• Body temperature regulation:
• Warming inhaled air through superficial blood vessels of the nasal passages
• evaporation of fluid from the respiratory passages and mouth by Panting

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• Acid-base balance:
• adjusting blood Co₂ through regulation of the respiratory rate

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• smell:
• contain the olfactory membrane which contain the receptors for the smell

Processes of respiration

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• Lung Ventilation

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• Distribution of gas within lung

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• Diffusion of gases between lung and pulmonary capillaries

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• Transport CO₂ and O₂ in the blood

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• Diffusion of gases between tissues and blood

Lung ventilation modified by the brain in response to O₂, CO₂ and H⁺ ion concentration

Function of nasal conchae

• Warm,
• Humidified
• filtrate the inhaled air

Organs of the respiratory system

• Air flow to the lung trough the conducting airways which is composed of nares, nasal cavity, pharynx, larynx, trachea, bronchi and bronchioles

No gas exchange occurs in the conducting pathways

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Gas exchange between the respiratory system and the blood occurs at the alveoli

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Ventilated areas of the respiratory system that does not contribute to gas exchange is called dead spaces

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• Anatomic dead spaces are the conducting pathways
• Alveolar dead spaces are the alveoli that are ventilated but not per fused.
• Physiologic dead spaces are the sum of anatomic and alveolar dead spaces.

Alveoli: are tiny thin-walled sacs that are surrounded by networks of capillaries.

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Their Walls is composed of three cell types

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• Type I Squamous Alveolar cells that form the structure of an alveolar wall

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• Type II Great Alveolar cells that secrete pulmonary surfactant to lower the surface tension

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• Macrophages that destroy foreign material, such as bacteria

Capillaries

Its function is to reduce the surface tension which tend to collapse the alveoli of the lung

Surfactant forms an overlying phospholipids film composed primarily of dipalmitoyl phosphatidylcholine

Surface tension is the tension of air-fluid interface.

Loss of surfactant results in large areas of collapsed alveoli (atelectasis)

Inflating the lung with normal saline required less pressure than inflating the lung with air because of the surface tension

Visceral layer

Parietal layer

• lung and chest wall are not physically attached to each others.

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• They are coupled by the negative plural pressure of the pleural space.

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• The pleural space is a potential space filled with a pleural fluid occurs between the visceral pleura of the lung and parietal pleura of the chest cavity.

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• The pressure of the pleural space is always negative (sub atmospheric) and this pressure keeps the lung inflated in the chest cavity.

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If the thorax is opened and pleural pressure become atmospheric the lung collapses to its minimal volume.

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The lung collapse because of the elastic properties of the lung which is generated by elastin and collagen tissue of the lung and the surface tension.

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The chest wall is also elastic but it is stiffer than that of the lung.

pleural space

Lung ventilation is the movement of air into and out of the lung

Inhalation is an active process required muscular energy

Inspiratory Muscle are

Diaphragm and External intercostal muscle

Exhalation is a passive process in most species, however, in other species such as horse expiratory muscles might be involve

Expiratory muscles

Abdominal muscle and Internal intercostal muscle

Lung volumes:

Tidal volume: the amount of air inspired or expired during normal breathing

Residual volume: the amount of air that is left in the lung after maximum expiration.

Expiratory reserve volume: the amount of air that is forcefully expired over the tidal volume

Inspiratory reserve volume: the amount of air that is inspired forcefully after normal inspiration.

Lung capacities:

Total lung capacity: the total amount of air the lung can hold from maximum inspiration

Functional residual capacity: the amount of air left in the lung after normal expiration.

Vital capacity: the total amount of air that can be expired from total lung capacity

Inspiratory capacity: the total amount of air that can be inspired from functional residual capacity

Mechanical interaction between lung and chest wall

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• At the total lung capacity both the lung and chest wall reached their elastic limits. Both chest wall and the lung pulling in

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• At functional residual capacity (FRC): the lung is stretched out and the rib cage is stretched in.

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• at FRC the lungs is pulling in and the rib cage is pulling out.

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• If the lung is removed from the rib cage the lung would collapse and the rib cage would expand.

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• At the residual volume the chest wall is compressed to the maximum and therefore, its elastic forces pulling out. lung did not reach its maximum collapse and therefore, it is pulling in

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Minute ventilation is Total amount of air breathed per minute

= The tidal volume (V_T ) X number of breathes per minute (frequency)

Part of the inspired air ventilate the dead spaces (V_D).

Alveolar Ventilation (V_A ) is the fraction of inspired air that ventilate the alveoli

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V_A = Frequency * (V_T – V_D)

Resistive properties of airways:

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• The upper airways (trachea and bronchi) behave as rigid tubes
• The lower airways (small bronchi and bronchioles) behave as flexible tubes

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• Resistance depends primarily on the radius of the air ways.

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• Resistance to Airflow is highest in the large airways and drop rabidly after the 5^th-8^th generation.

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• The drop in the resistance with airway generation is due to increasing total cross-sectional area.

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• High airflow velocity in the upper tracheobronchial tree (trachea and bronchi) produces turbulent flow which can be heard by the stethoscope.

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• Down the tracheobronchial tree velocity of air flow is low and laminar which cannot be heard by the stethoscope.

• Airways resistance is less during inspiration at increased lung volumes than expiration at low lung volumes.

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• Collapse of the respiratory passageway during expiration limits expiratory air flow rate

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• During inhalation: the pressure inside the airways is less than the atmospheric pressure which causes the passageways to collapse if they are not supported to keep them open.

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• The nares, pharynx, larynx are prevented from compression by the abductor muscles.

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• Roaring can happen when the abductor muscles of larynx fail to contract.

Effect of respiratory abnormalities on air flow

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• Constricted lungs (fibrosis):

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• Air expiratory flow cannot rise to equal that of the normal curve because the lung cannot expand to a normal volume

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• Both TLC and RV decrease

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• airway obstruction (asthma):

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• It is more difficult to expire than to inspire

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• Both TLC and RV increased

Regulation of airway smooth muscles

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• smooth muscles of the tracheobronchial tree regulate airways diameter and resistance.

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• Acetylcholine of parasympathetic vagus nerve causes bronchoconstriction.

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• Inhaled Dust stimulate irritant receptors which activated the parasympathetic and causes bronchoconstriction.

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• Allergic reaction (asthma and heaves) causes the mast cells to release inflammatory mediators such as histamine which directly affect the smooth muscles and causes bronchoconstriction.

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• Activation of β-adrenergic (β2) receptor by norepinephrine and epinephrine causes bronchodilation

Pulmonary Blood Flow:

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• Pulmonary Circulation: comes from the right ventricle, perfuse alveolar capillaries and participate in gas exchange.

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• Bronchial Circulation: a branch of systemic circulation provides nutrition to airways and other structures of the lung

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• Bronchial circulation from small airways can anastomose with pulmonary arteries and drain to the pulmonary vein, thus shunting blood from the lung

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• hypoxia causes local vasoconstriction of small pulmonary arteries and causes a decrease of blood flow to poorly ventilated portions of the lung

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Brisket disease

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• Caused by hypoxia which causes Vasoconstriction which have serious consequences on the cardiovascular system

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• when animals live at high altitude or have diffuse lung disease, the vasoconstriction causes an increase in pulmonary arterial pressure and increases right ventricle work load and causes right side heart failure and systemic edema

Gas Exchange

Inspired air contain different gases.

Each Gas exert a pressure proportional

to its concentration called partial pressure .

Partial pressure of O2 (PO₂) in dry air at sea level= P_B * FIO₂ =760 * 0.21 = 160 mmHg

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In the conducting pathways the air become Humidified and saturated with water vapor (PH₂O). PH₂O at body temperature is 47 mmHg

PO₂ after humidification = (P_B – PH₂O) FIO₂

Alveolar Partial Pressure

PAO₂ = (P_B – PH₂O) FIO₂ - PaCO₂/R

R is the respiratory exchange ratio

(760 – 47) * 0.21 = 149

149 – 45/R = 104

Air contain 21% O2 and therefore, fraction of O2 (FIO2) equals 0.21

Barometric pressure (P_B )at sea level is 760 mmHg

Exchange of O2 and CO2 between the alveolus and pulmonary capillaries

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• CO2 and O2 are lipid soluble and cross the Respiratory Membrane by simple diffusion. CO2 solubility is higher than O2 solubility.

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• Respiratory membrane consists of surfactant, type I epithelial cells, interstitial fluid, endothelial cells, blood plasma, and erythrocyte membrane.

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• gases diffuse across the blood-gas barrier down their partial pressure gradients.

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• Thickness and the surface area of the respiratory membrane affect the rate of gas diffusion.

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• Edema increase the thickness of the membrane and causes a decrease of gas diffusion

Factors affect Alveolar PO2

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• Rate of Alveolar Ventilation: increasing alveolar ventilation causes an increase in alveolar PO2

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• Rate of Oxygen Transfer:

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• increasing the rate of O2 transfer from alveoli to the blood causes a decrease in alveolar partial pressure.

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• ventilation rate must be increased to maintain alveolar PO2 at normal level

Ventilation/Perfusion Ratio determine adequacy of pulmonary gas exchange

Shunt

Dead-Space

PO2 = 40

PCO2 = 45

PO2 = 149

PCO2 = 0

PO2 = 104

PCO2 = 40

VA/Q is ideal when lung alveoli receives adequate blood flow. This rarely occurs.

• Dead space: V/Q ratio is high. The alveoli are ventilated but not perfused. This occur when blood flow to the lung is reduced by vascular obstruction or by pulmonary hypotension.

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• Pulmonary shunt: V/Q ratio is low. The alveoli are perfused but hypo-ventilated. This occurs in the cases of airway obstruction.

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• Right to left shunt occurs when blood leaves the lung with the same composition of O2 and CO2 as venous blood. Bronchial circulation which drain into the pulmonary circulation is an example of blood shunt

Hemoglobin is composed of 4 polypeptide chain, two α- and two β-chains (α2β2).

Each chain has 1 heme group; hemoglobin can bind up to 4 molecules of O₂

Blood transport of oxygen

Most of O2 is transported in blood in combination with hemoglobin

Small amount of oxygen is transported dissolved in the plasma and depends on the arterial partial pressure of O2

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Dissolved O2 = PO2 X Soulability

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If PAO2 is 100 mmHg

100 X 0.003 = 0.3Vol% dissolved

If Hb concentration is 15 gm/dl

15X1.34 = 20 ml O2/dl or Vol%

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In the case of anemia where the Hb is low the carrying capacity is decreased

Each gram of Hb carry 1.34 ml of O2

• Oxyhemoglobin curve

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• Binding of O2 to hemoglobin is reversible and depends primarily on PO2

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• In the pulmonary capillaries where the PO2 is above 70 mmHg the O2-Hb dissociation curve is flat and the hemoglobin is about 100% saturated.

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• When PO2 reach about 40 mmHg which is the range of tissue PO2, the hemoglobin is still about 75% saturated.

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• The 75% saturation reflects the ability of hemoglobin to act as reservoir to deliver more O2 to the tissue when needed if PO2 decreases to less than 40 mmHg

• The shift in Oxyhemoglobin curve resulting from a change in PCO₂ and H⁺ ion concentration called Bohr effect.

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• In the lung: PCO2 is low and the curve is shifted to left which facilitate O2 loading
• In tissue: PCO2 is high the curve is shifted to the right and facilitate O2 unloading.

Affinity of Hb to O2 is influenced by

Temperature, pH, PCO2, and Diphosphoglycerate (DPG)

• Hb affinity to O2 is determined by the P50 which is the partial pressure at which Hb is 50% saturated with O2.

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• Increased temperature, CO₂, H⁺ ion and DPG shifts the curve to the right.

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• Shift to the right means an increases of the P50 and a decrease of the affinity between O2 and Hb (facilitate the dissociation of O2 from Hb).

Shift to the right

Fetal hemoglobin (HbF):

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• HbF is composed two α- and two γ-chains whereas HbA is composed two α- and two β-chains

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• Fetal dissociation curve is shifted to the left relative to normal adult

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• HbF has higher affinity to bind oxygen at lower levels of partial pressure in the fetus to allow diffusion of oxygen across the placenta.

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• 2,3-BPG binds more strongly to adult hemoglobin, causing HbA to release more oxygen for uptake by the fetus, whose HbF is unaffected by the 2,3-BPG

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• Myoglobin has no affinity for 2,3-BPG and therefore, has higher affinity for O₂

O₂ Saturation

Mechanisms of CO2 transport

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• Dissolved from: only 7% of CO2 is transported

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• Bicarbonate form: CO₂ diffuses into the RBCs and binds to H₂O and form H₂CO₃, which is then dissociate into HCO^-₃ and H⁺.

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• Carbonic anhydrase of the erythrocyte accelerate this reaction

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• The reaction is kept moving to the right because H is buffered by Hb.

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• Coupled to the amino group of hemoglobin to from Carbaminohemoglobin

Binding of CO2 to hemoglobin is influenced by O2 partial pressure.

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binding of O2 to hemoglobin decreases the affinity of hemoglobin binding to CO2 which is called Haldane effect

Deoxygenated blood

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• has grater capacity to carry CO2 than does oxygenated blood Oxyhemoglobin is a strong acid

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• Decreased CO₂ binding affinity

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• Release Hydrogen Ion

Control of respiration

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• breathing regulated by the respiratory center in the brain stem and modified by input of systemic receptors.

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• Components of the respiratory center

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• Pneumotaxic center: Located in the Pons and receive vagal input related to lung volume and modulate respiratory frequency

• Dorsal respiratory group:
• located in the medulla and regulate inspiratory muscles (primarily the diaphragm).
• When the activity of those neurons is inhibited by Pneumotaxic neurons or by pulmonary stretch receptors, inhalation is terminated and exhalation starts passively because of the elastic recoil of the lung or by activation or expiratory muscles.

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• Ventral respiratory group: Located in the medulla and is involved in the regulation of inspiratory and expiratory muscles.

Control of Ventilation

• Mechanical feedback from the lung and airway receptors

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• Slow adapting stretch receptors: Lie within airway smooth muscles and stimulated by stretch of the airway during increasing lung volume.

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• Stimulated as the lung volume increased and causes inhibition of inspiration.

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• The response from those stretch receptors called Hering-Breuer reflex

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• Termination of input from these receptors by vagotomy leads to slow respiration and increase tidal volume

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• Irritant receptors or rapidly adapting receptors: Lie in the large airways such as larynx, trachea, large bronchi
• Stimulated by irritant such as dust histamine
• Responses to these stimuli cause
• Cough
• Bronchoconstriction
• Mucus secretion
• Pulmonary C fibers: Distribute throughout the airways and close to the pulmonary capillaries (juxtacapillary receptors). They respond to lung injury and inflammation and causes rapid and shallow breathing (tachypnea)

Chemical regulation of breathing

• Chemoreceptor monitor the concentration of O₂, CO₂ and H⁺ ions

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• located in the ventral medulla and separated from the blood by the blood-brain barrier which is permeable for CO2 but less permeable to H ions and HCO3.

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• Although the primary stimulus of those receptors is the H ion, blood H ions can not stimulate these receptors because they can not cross the blood brain barrier.

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• H ions that stimulate those receptors comes from the Blood CO2 which cross the blood brain-barrier easily and form H2CO3 and then dissociate into H and HCO3.

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• Respiratory acidosis (due to increased PaCO₂) has greater effect on ventilation than does metabolic acidosis ( due to metabolic accumulation of H) because of poor diffusability of H across the blood-brain barrier.

Peripheral receptor:

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Carotid and Aortic bodies are located close to the bifurcation of carotid artery and around the aortic arch respectively.

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Vagus nerve carry response from aortic body to the brainstem

Glossophayngial nerve carry action potential from the carotid body

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Those receptors respond primarily to hypoxemia which is a decrease of PO2.

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A decrease of PO2 to less than 60 mmHg causes an increase in firing rate of those receptors and lead to an increase in the ventilation rate.