The Respiratory System

The Respiratory System Cells produce energy: for maintenance, growth, defense, and division through mechanisms that use oxygen and produce carbon dioxide

Oxygen Is obtained from the air by diffusion across delicate exchange surfaces of lungs Is carried to cells by the cardiovascular system which also returns carbon dioxide to the lungs

5 Functions of the Respiratory System Provides extensive gas exchange surface area between air and circulating blood Moves air to and from exchange surfaces of lungs Protects respiratory surfaces from outside environment Produces sounds Participates in olfactory sense

External & Internal Respiration External Respiration Mechanics of breathing The movement of gases into & out of body Gas transfer from lungs to tissues of body Maintain body & cellular homeostasis Internal Respiration Intracellular oxygen metabolism Cellular transformation Krebs cycle – aerobic ATP generation Mitochondria & O2 utilization

Organization of Respiratory System Nose Nasal cavities Paranasal sinuses Pharynx Larynx Trachea Bronchi and lungs Bronchioles Alveoli

Airway Branching Trachea Main Bronchi 1 Lobar Bronchus 2 Main Bronchi 1 Lobar Bronchus 2 Segmental Bronchus 3-4 Bronchioles 5-15 Terminal Bronchioles 16 Resp. Bronchioles 17-19 Alveolar Ducts 20-22 Alveolas Sacs 23 Source: SEER Training Website (training.seer.cancer.gov)

Alveoli ~ 300 million air sacs (alveoli). 2 types of cells: Large surface area (60–80 m2). Each alveolus is 1 cell layer thick. 2 types of cells: Alveolar type I: Structural cells. Alveolar type II: Secrete surfactant.

Alveolar Organization Respiratory bronchioles are connected to alveoli along alveolar ducts Alveolar ducts end at alveolar sacs: common chambers connected to many individual alveoli

Respiratory Mechanics Multiple factors required to alter lung volumes Respiratory muscles generate force to inflate & deflate the lungs Tissue elastance & resistance impedes ventilation Distribution of air movement within the lung, resistance within the airway Overcoming surface tension within alveoli

The Breathing Cycle Airflow requires a pressure gradient Air flow from higher to lower pressures During inspiration alveolar pressure is sub-atmospheric allowing airflow into lungs Higher pressure in alveoli during expiration than atmosphere allows airflow out of lung Changes in alveolar pressure are generated by changes in pleural pressure

diaphragm-most important External intercostals Accessory muscles : Muscles of inpiration Muscles of expiration diaphragm-most important External intercostals Accessory muscles : Sternocleidomastoid Serratus anterior scaleni Abdominal recti Internal intercostal muscles

The Respiratory Muscles Most important are: the diaphragm external intracostal muscles of the ribs accessory respiratory muscles: activated when respiration increases significantly

The Respiratory Muscles Figure 23–16c, d

The Mechanics of Breathing Inspiration: always active Expiration: active or passive

3 Muscle Groups of Inspiration Diaphragm: contraction draws air into lungs 75% of normal air movement External intracostal muscles: assist inhalation 25% of normal air movement Accessory muscles assist in elevating ribs: sternocleidomastoid serratus anterior pectoralis minor scalene muscles

Muscles of Active Expiration Internal intercostal and transversus thoracis muscles: depress the ribs Abdominal muscles: compress the abdomen force diaphragm upward

Movement of Thorax During Breathing Cycle

Movement of Diaphragm

Pleura and Pleural Cavities The outer surface of each lung and the adjacent internal thoracic wall are lined by a serous membrane called pleura. The outer surface of each lung is tightly covered by the visceral pleura. while the internal thoracic walls, the lateral surfaces of the mediastinum, and the superior surface of the diaphragm are lined by the parietal pleura. The parietal and visceral pleural layers are continuous at the hilus of each lung.

Pleural Cavities The potential space between the serous membrane layers is a pleural cavity. The pleural membranes produce a thin, serous pleural fluid that circulates in the pleural cavity and acts as a lubricant, ensuring minimal friction during breathing. Pleural effusion – pleuritis with too much fluid

Intrapleural Pressure Pressure in space between parietal and visceral pleura Averages —4 mm Hg Maximum of —18 mm Hg Remains below Patm throughout respiratory cycle

Intrapulmonary Pressure Also called intra-alveolar pressure Is relative to Patm In relaxed breathing, the difference between Patm and intrapulmonary pressure is small: about —1 mm Hg on inspiration or +1 mm Hg on expiration

Transpulmonary Pressure The pressure difference between the alveolar pressure & pleural pressure on outside of lungs The alveoli tend to collapse together while the pleural pressure attempts to pull outward The elastic forces which tend to collapse the lung during respiration is Recoil Pressure

Physical Properties of the Lungs Ventilation occurs as a result of changes in lung volume of given pressure difference Physical properties that affect lung function: Compliance. Elasticity. Surface tension.

Compliance Compliance describes the dispensability of the system Ease with which the lungs can expand Thus the lung compliance describes how volume changes for the given change in pressure Change in lung volume per change in transpulmonary pressure. DV/DP

Compliance of the lungs Measurement of lung compliance requires simultaneous measurement of lung pressure & volume .

Compliance of the lungs(continued) The characteristics of the compliance diagram are determined by the elastic forces of the lungs .these can be divided into two parts Elastic forces of lung tissue itself Elastic forces caused by surface tension .

Surface Tension Force exerted by fluid in alveoli to resist distension. Lungs secrete and absorb fluid, leaving a very thin film of fluid. This film of fluid causes surface tension. The attractive forces between adjacent molecules of liquid are stronger than forces between molecule of liquid and a molecule of gas in the alveoli H20 molecules at the surface are attracted to other H20 molecules by attractive forces. Force is directed inward, that tends to collapse the alveoli

Surface Tension (continued) Law of Laplace: Pressure in alveoli is directly proportional to surface tension; and inversely proportional to radius of alveoli. Pressure in smaller alveolus would be greater than in larger alveolus, if surface tension were the same in both. Insert fig. 16.11

Surfactant Surfactant is surface active agent in water that greatly reduces the surface tension . Secreted by type II alveolar epithelial cells , it lines the alveoli & reduces their surface tension. Complex mixture of phospholipids, dipalmotylphophotidylcholine & surfactant apoprotien

Role of surfactant

Role of surfactant Surfactant provides two functions Reduces the surface tension thereby reducing the collapsing forces in alveoli It increases the lung compliance . In neonatal distress syndrome, surfactant is lacking Surfactant not begin to secret normally before gestational ages of 24 to 28 week

Dead Space The volume of the airways that does not participate in gas exchange Anatomical dead space – volume of the conducting respiratory passages (150 ml) Functional dead space – alveoli that cease to act in gas exchange due to collapse or obstruction Physiological dead space – sum of alveolar and anatomical dead spaces

tidal volume — anatomic dead space  respiratory rate Alveolar Ventilation Amount of air reaching alveoli each minute Calculated as: tidal volume — anatomic dead space  respiratory rate Alveoli contain less O2, more CO2 than atmospheric air: because air mixes with expiration air

Alveolar Ventilation Rate Determined by respiratory rate and tidal volume: for a given respiratory rate: increasing tidal volume increases alveolar ventilation rate for a given tidal volume: increasing respiratory rate increases alveolar ventilation

4 Calculated Respiratory Capacities Inspiratory capacity: tidal volume + inspiratory reserve volume Functional residual capacity (FRC): expiratory reserve volume + residual volume Vital capacity: expiratory reserve volume + tidal volume + inspiratory reserve volume Total lung capacity: vital capacity + residual volume

Diffusion of Gases

Gas Movement due to Diffusion Diffusion - movement of gas due to molecular motion, rather than flow. Akin to the spread of a scent in a room, rather than wind. Random motion leads to distribution of gas molecules in alveolus.

Gas Movement due to Diffusion Source: Jkrieger (wikimedia.org)

Diffusion Driven by concentration gradients: differences in partial pressure of the individual gases. Movement of O2 and CO2 between the level of the respiratory bronchiole and that of the alveolar space depends only on diffusion. The distances are small, so diffusion here is fast.

Diffusion of Gas Through the Alveolar Wall Alveolar airspace Pathway of diffusion Source: Undetermined

Diffusion of Oxygen Across the Alveolar Wall Pulmonary Surfactant Diffuses/Dissolves Alveolar Epithelium Diffuses/Dissolves Alveolar Interstitium Diffuses/Dissolves Capillary Endothelium Diffuses/Dissolves Plasma Diffuses/Dissolves Red Blood Cell Binds Hemoglobin

Fick’s Law for Diffusion Vgas = A x D x (P1 – P2) T Vgas = volume of gas diffusing through the tissue barrier per time, in ml/min A = surface area available for diffusion D = diffusion coefficient of the gas (diffusivity) T = thickness of the barrier P1 – P2 = partial pressure difference of the gas

Gas Exchange Occurs between blood and alveolar air Across the respiratory membrane Depends on: partial pressures of the gases diffusion of molecules between gas and liquid

Oxygen Transport Due to low solubility, only 1.5 % of oxygen is dissolved in plasma 98.5 % of oxygen combines with hemoglobin

Each Hb consists of a globin portion composed of 4 polypeptide chains Each Hb also contains 4 iron containing pigments called heme groups Up to 4 molecules of O2 can bind one Hb molecule because each iron atom can bind one oxygen molecule There are about 250 million Hb hemoglobin molecules in one Red Blood Cell When 4 oxygen molecules are bound to Hb, it is 100% saturated, with fewer, it is partially saturated Oxygen binding occurs in response to high partial pressure of Oxygen in the lungs

Oxygen + Hb  Oxyhemoglobin (Reversible) Cooperative binding  Hb’s affinity for O2 increases as its saturation increases (similarly its affinity decreases when saturation decreases) In the lungs where the partial pressure of oxygen is high, the rxn proceeds to the right forming Oxyhemoglobin In the tissues where the partial pressure of oxygen is low, the rxn reverses. OxyHb will release oxygen, forming again Hb (or properly said deoxyhemoglobin)

Hemoglobin Saturation Curve

BOHR EFFECT

Bohr Effect Bohr Effect refers to the changes in the affinity of Hemoglobin for oxygen It is represented by shifts in the Hb-O2 dissociation curve Three curves are shown with progressively decreasing oxygen affinity indicated by increasing P(50)

SHIFT to the RIGHT Decreased affinity of Hb for Oxygen Increased delivery of Oxygen to tissues It is brought about by Increased partial pressure of Carbon Dioxide Lower pH (high [H+]) Increased temperature Increased levels of 2,3 DPGA Ex: increased physical activity, high body temperature (hot weather as well), tissue hypoxia (lack of O2 in tissues)

SHIFT to the LEFT Increased affinity of Hb for Oxygen Decreased delivery of Oxygen to tissues It is brought about by Decreased partial pressure of Carbon Dioxide Higher pH (low [H+]) Decreased temperature Decreased levels of 2,3 DPGA Ex: decreased physical activity, low body temperature (cold weather as well), satisfactory tissue oxygenation

The Effect of pH and Temperature on Hemoglobin Saturation

A Functional Comparison of Fetal and Adult Hemoglobin

Carbon Dioxide Transport Produced by cells thru-out the body CO2 diffuses from tissue cells and into the capillaries 7% dissolves in plasma 93% diffuses into the Red Blood Cells Within the RBC ~23% combines with Hb (to form carbamino hemoglobin) and ~ 70% is converted to Bicarbonate Ions which are then transported in the plasma

In the lungs, which have low Carbon Dioxide partial pressure, CO2 dissociates from CarbaminoHemoglobin, diffuses back into lungs and is exhaled Within the RBC, CO2 combines with water and in the presence of carbonic anhydrase it transforms into Carbonic acid Carbonic acid then dissociate into H+ and HCO3- In the lungs CO2 diffuses out into the alveoli. This lowers the partial press. Of Co2 in blood, causing the chemical reactions to reverse

Summary: Gas Transport Figure 23–24

Control of Respiration

Respiratory centers of the brain Medullary centers Respiratory rhythmicity centers set pace Dorsal respiratory group (DRG)– inspiration Ventral respiratory group (VRG)– forced breathing

Respiratory centers of the brain Pons Apneustic and pneumotaxic centers: ● regulate the respiratory rate and the depth of respiration in response to sensory stimuli or input from other centers in the brain

Respiratory Centers and Reflex Controls

Mechanism of rhythmic breathing

Respiratory reflexes Hering-breuer reflexes Hering-breuer inflation reflex Hering-breuer deflation reflex Reflex from lung irritant receptors Reflex from J receptors

Chemical regulation of respiration Chemoreceptors Chemoreceptors are located throughout the body (in brain and arteries). chemoreceptors are more sensitive to changes in PCO2 (as sensed through changes in pH). Ventilation is adjusted to maintain arterial PC02 of 40 mm Hg.

Central chempreceptors Peripheral chemoreceptors Presence of hypoxia together with rise in pCO2 Hypoxia

Medullary Respiratory Centers