Respiratory Physiology

Bio 328, 2013

R. Clark, P.T., Ph.D.

I. Introduction: Function of the Respiratory System

A. Maintenance of normal arterial blood gases

1. PaO2 = 98-100 mmHg: Deliver oxygen to the body’s cells

2. Pa CO2 = 40 mmHg: Elimination of carbon dioxide

B. Major organ system for the removal of metabolic waste. Expiration of carbon dioxide from the

Lungs are the chief mechanism for removing volatile acids from the body. Decreased ability to

expire CO2 results in a clinical condition called respiratory acidosis.

C. Phonation: air flow causes vibration of the vocal cords

D. Nonrespiratory functions

1. Defense against inhaled microbes: macrophages, IgA

2. Removal of metabolic substances from the blood, e.g. converting enzyme, inactivation of

prostaglandin.

3. Addition of metabolic substances to the arterial blood, e.g. cytokines, histamine.

4. Traps and dissolves small blood clots.

II. Steps of Respiration: an overview

A. Ventilation: mechanical movement of air between the atmosphere and the lung alveoli.

Air moves by changes in Pressure represented by the equation:

Flow of Air = (Patm –Palv) / Resistance to air flow

B. Gas diffusion: exchange of oxygen and carbon dioxide between the alveolar air and the blood

perfusing the lung capillaries.

C. Transport of blood gases in the pulmonary and systemic circulations.

D. Diffusion of gases between the systemic capillaries and the respiring cells.

E. Cellular respiration: Utilization of oxygen as the final electron acceptor in the production of

ATP within the mitochondria.

III. Anatomy of the respiratory system

A. Conducting Zone: ~ 150 mL

Mouth/nose end of terminal bronchioles

Function includes: air flow, phonation, warms, saturation with water, traps foreign inhaled particles.

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B. Respiratory zone: respiratory bronchi alveolar ducts, and alveoli

Function is gas exchange by diffusion

C. Airway branching: airway generations

1. Smooth muscle: lines airways from trachea respiratory bronchi

Contraction or relaxation changes the radius of the airways therefore airway resistance

Airway constriction Airway Dilation

Parasympathetic-Ach (Muscarinic) Sympathetic-Epinephrine, Norepinephrine (β2)

Eicosanoids Eicosanoids

Histamine Transpulmonary pressure, lateral traction

2. Cartilage: Trachea and bronchi contain cartilage rings to help maintain cylindrical structure

3. Cilia: found on the epithelial surfaces of the airways down to the end of the respiratory bronchi

contains cilia that constantly beat directionally towards the trachea.

4. Glandular cells line the epithelium and secrete mucus

5. Epithelial cells secrete watery substance that that allows the mucus to freely float.

A genetic defect in the chloride channels that secrete the watery fluid causes Cystic Fibrosis.

6. Defense against inhaled foreign microbes is provided by the presence of macrophages and

IgA in the airways and the alveoli.

D. Pneumocytes (Alveolar Cells)

1. Type I cells: elongated, cover large surface area

2. Type II cells: round, most numerous, produce surfactant, regenerative capacity to become

Type 1 or Type 2 pneumocytes

Surfactant is a mixture of phospholipids and proteins that form a monolayer between the

interface of air and water in the alveoli. Surfactant functions to lower the surface tension at

the air water interface and therefore increases the compliance of the lung. When surfactant

is present the work of breathing is markedly reduced.

Surfactant is produced late in the third trimester of pregnancy. RDS (Respiratory distress

Syndrome) occurs in premature infants if they are born before the production of surfactant.

IV. Lung Pressures

A. Atmosphere Pressure = P atm

Pressure surrounding the body and in the nose and mouth

B. Alveolar Pressure = Palv Pressure of air in the alveolus

C. Intrapleural Pressure, also called intrathoracic pressure = Pip

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D. Transpulmonary Pressure: Palv - Pip

Transplumonary pressure is the pressure that acts to expand the lungs. The ability of transplumonary

Pressure to expand the lung depends upon the compliance of the lungs.

Lung compliance is defined by the equation:

Compliance lung = Change in Volume / change in Transpulmonary Pressure

Lung compliance is determined by:

Elastic connective tissue properties of the lung

Surface tension at the air-water interface

Deep breaths stimulate the secretion of surfactant

E. P atm - Palv is the pressure that determines the movement of air in and out of the lungs

F. Boyle’s Law

Pressure of a fixed amount of gas is inversely related to the volume of the container

V. Ventilation: The Movement of Air in and out of the lung

A. Diaphragm is innervated by alpha motor neurons arising from Cervical Spinal Cord segments

The major contribution of innervation comes from C4

Contraction of the diaphragm causes a change in the volume of the thorax.

Accessory muscles of inspiration:

External Intercostal muscles

Anterior neck muscles

Accessory muscle of expiration (relaxed expiration is a passive phenomenon)

Internal Intercostal muscles

Abdominal muscles, primarily the oblique abdominal muscles

B. Sequence of events in the process of one respiratory cycle: Inspiration / Expiration

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VI. Lung Volumes and Capacities: spirometer measurements, see figure

Additional Definitions:

Forced Vital Capacity

Minute Ventilation

Alveloar Ventilation

Maximum Voluntary Ventilation

VII. Pulmonary Function Tests

A. Forced Expiratory Volume FEV1 : volume of vital capacity that can be exhaled in 1 sec.

B. Ratio of FEV1 / FVC expressed as a %

1. Obstructive Lung Diseases (COPD)

Examples include emphysema, asthma

See decreased VC, decreased FEV1 and

decreased FEV1 / FVC %

2. Restrictive Lung Diseases

Examples: kyphosis, scoliosis, fibrotic diseases

See decreased VC, decreased FEV1

however a normal or better FEV1 / FVC %

C. Maximum Expiratory Effort: point of maximum airflow where an increase in effort cannot cause

a greater flow rate. Observe closing tendency of the small airways.

1. Obstructive Lung Disease

Advanced disease states see Increased Total Lung Capacity, increased residual volume,

decreased vital capacity, and decreased maximum expiratory flow rate

2. Restrictive Lung Diseases

Observe reduced total lung capacity and residual volume, also see decreased vital capacity

Maximum expiratory flow rate is decreased because lungs cannot fully expand

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VIII. Exchange of Gases in Alveoli and Tissues

A. Determinants of Gas Diffusion

1. pressure differences

2. area available for diffusion

3. diffusion coefficient

4. thickness of the membrane for diffusion

B. Anatomy of the Membrane for Diffusion: approximately 0.2 - 0.6 microns

Oxygen must diffuse from the alveolus alveolar cells meager interstitium

Capillary endothelium RBC membrane

C. Composition of Alveolar Air

Alveolar Air is not = Atmospheric Air because:

Alveolar air is partially replaced with each breath

Oxygen and carbon dioxide are constantly diffusing

Alveolar air is saturated with water

1. Composition of alveolar oxygen is determined by

Rate of absorption of oxygen into the blood

Rate of alveolar ventilation

2. Composition of alveolar carbon dioxide is determined by

Rate of excretion of carbon dioxide

Rate of alveolar ventilation

3. Alveolar Gas Equation: calculation to approximate PAO2

4. Difference between PAO2 - PaO2 should be less than 10-15 mmHg pressure, if pressure

difference is greater than 15 mmHg there is a diffusion problem

D. Respiratory Quotient R.Q. = ratio of CO2 produced to O2 consumed

On a mixed diet R.Q. is about 0.8

On a pure CHO diet R.Q. is 1.0

E. Summary of Partial Pressures of gases in the atmosphere, alveoli, circulation and cells

F. Definitions

1. Hyperventilation

increased ventilation not matched with an increase in metabolic need for O2

see elevated PAO2 and decreased PACO2

2. Hypoventilation

Decreased ventilation not matched with a decrease in metabolic need for O2

see decreased PAO2 and increased PACO2

3. Hyperpnea

Increased Ventilation matches increased O2 consumption

Normal PaO2 and PaCO2

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G. V/Q ratios: Goal of the lung is to match ventilation to perfusion.

1. Alveolar blood gas exchange in the pulmonary capillaries

2. Mechanisms to correct V/Q imbalances

a. decreased alveolar oxygen see hypoxic vasoconstriction

b. decreased alveolar carbon dioxide see airway constriction

c. increased alveolar carbon dioxide see airway dilation

3. Physiologic Dead Space: ventilated alveoli with no perfusion

V/Q ratios approach infinity

4. shunt: perfusion to areas with no ventilation

V/Q ratios approach 0

IX. Transport of Gases in the Blood

A. Transport of Oxygen

1. 98% is carried reversibly bound to hemoglobin

2. 2% is carried physically dissolved

3. Oxygen-hemoglobin dissociation curve depicts the relationship of PaO2 to the %saturation

of hemoglobin with oxygen

4. Factors that shift the oxygen-hemoglobin curve to the right result in greater unloading of

oxygen to the tissues

increased temperature

increased H

increased 2,3-diphosphoglycerate (DPG)

B. Transport of Carbon Dioxide

1. ~10% is physically dissolved

2. ~30% is carried as a carbamino compound

3. ~60% is carried as plasma bicarbonate

C. Transport of Hydrogen

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X. Control of Respiration

A. Medullary neurons comprise the Respiratory Rhythm Generator for Breathing

1. Dorsal Respiratory group: cells that are active during inspiration

2. Ventral Respiratory group: cells that are active during inspiration and expiration

B. Peripheral feedback to Medullary Respiratory neurons

1. Chemoreceptors

a. peripheral chemoreceptors: aortic and carotid bodies

stimulated primarily by a decrease in PaO2 or an increase in H+

b. central chemoreceptors: located in the medulla, these cells are bathed by the

interstitial fluid of the medulla and respond to changes in H+ concentration

2. Stretch receptors: Hering-Breuer reflex, prevents overinflation of the lungs

3. Irritant receptors

4. Summary of arterial blood gas concentration on ventilation rate

a. effects of PaO2

b. effects of PaCo2

c. effects of H+

XI. Hypoxia: a Deficiency of Oxygen at the tissue/cell level

A. Hypoxemia

B. Anemic Hypoxia

C. Ischemic Hypoxia

D. Histotoxic Hypoxia

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XII. Ventilation During Exercise

A. Ventilation increases in proportion to Exercise Intensity (e.g. oxygen consumption)

B. Blood Lactate Levels: see increased rate of ventilation as blood lactate levels increase

XIII. Acclimatization to Altitude: decreased PO2

A. A progressive decline in VO2max occurs at a rate of 10% per 1000 meters

B. Immediate response is to increase ventilation.

C. Increase Erythropoietin secretion increase in RBC number and hematocrit

D. Cardiovascular Responses: at submaximum exercise intensity see increased heart rate and

cardiac output compared to sea level.

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Dissolved Oxygen in Blood Henry’s Law: the concentration of a dissolved gas in a liquid is directly proportional to the partial pressure of the gas in the atmosphere to which the liquid is exposed. Solubility of oxygen at body temperature:

0.003 mL of oxygen/mm Hg PO2 in 100 mL of blood.

At a PaO2 in a normal healthy person with a PaO2=100 mm Hg the amount of dissolved oxygen

in the arterial blood is 0.3 mL O2/100 mL blood.

Oxygen Binding Capacity O2 binding capacity = (1.34 mL O2/g Hgb) X (g Hgb/100 mL Blood Assuming a normal Hgb concentration of 15 g/100 mL blood the oxygen binding capacity becomes: (1.34 mL O2/g Hgb) X (15 g Hgb/100 mL blood) = 20.1 mL O2/100 mL blood Total Oxygen Content = (% saturation X oxygen binding capacity) + dissolved oxygen

To calculate normal healthy values assume: o normal Hgb of 15 g/100 mL blood o 100 % saturation o PaO2 of 100 mm Hg

100% x (1.34 mL O2/g Hgb) X (15 g Hgb/100 mL blood) + (0.003 mL O2/100 mL blood/mm Hg) X 100 mm Hg = 20.4 mL O2/100 mL blood Sample problem: Calculate the total oxygen content in an individual with a hemoglobin content of 10 g/ 100 mL blood. Assume arterial partial pressure of PaO2 of 100 mm Hg, saturation = 98%. Answer: 13.4 mL O2/100 mL blood How would the hemoglobin dissociation curve look?