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Chapter 22. Respiratory System. Overview. Respiratory anatomy Respiration Respiratory musculature Ventilation, lung volumes and capacities Gas exchange and transport O 2 CO 2 Respiratory centers Chemoreceptor reflexes Respiratory Diseases. Oxygen.

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Chapter 22 l.jpg

Chapter 22.

Respiratory System

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  • Respiratory anatomy

  • Respiration

  • Respiratory musculature

  • Ventilation, lung volumes and capacities

  • Gas exchange and transport

    • O2

    • CO2

  • Respiratory centers

  • Chemoreceptor reflexes

  • Respiratory Diseases

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  • 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

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Functions of the Respiratory System

  • Supplies body with oxygen and get rid of carbon dioxide

  • 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

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Components of the Respiratory System

Figure 23–1

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Organization of the Respiratory System

  • Upper respiratory system

    • Nose, nasal cavity, sinuses, and pharynx

  • Lower respiratory system

    • Larynx, trachea, bronchi and lungs

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The Respiratory Tract

  • Conducting zone:

    • from nasal cavity to terminal bronchioles

    • conduits for air to reach the sites of gas exchange

  • Respiratory zone:

    • the respiratory bronchioles,alveolar ducts, and alveoli

    • sites of gas exchange

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Respiratory Epithelia

  • Changes along respiratory tract

  • Nose, nasal cavity, nasopharynx = pseudostratified ciliated columnar epithelium

  • Oropharynx, laryngopharynx = stratified squamous epitheium

  • Trachea, bronchi = pseudostratified ciliated columnar epithelium

  • Terminal bronchioles = cuboidal epithelium

  • Respiratory bronchioles, alveoli = simple squamous epithelium

  • Think about why each part has the lining that it does

    • For example, in alveoli

      • walls must be very thin (< 1 µm)

      • surface area must be very great (about 35 times the surface area of the body)

    • In lower pharynx

      • walls must be tough because food abrades them

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The RespiratoryMucosa

  • Consists of:

    • epithelial layer

    • areolar layer

  • Lines conducting portion of respiratory system

  • Lamina propria

    • Areolar tissue in the upper respiratory system, trachea, and bronchi (conducting zone)

    • Contains mucous glands that secrete onto epithelial surface

    • In the conducting portion of lower respiratory system, contains smooth muscle cells that encircle lumen of bronchioles

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Respiratory Defense System

  • Series of filtration mechanisms removes particles and pathogens

  • Hairs in the nasal cavity

  • Goblet cells and mucus glands: produce mucus that bathes exposed surfaces

  • Cilia: sweep debris trapped in mucus toward the pharynx (mucus escalator)

  • Filtration in nasal cavity removes large particles

  • Alveolar macrophages engulf small particles that reach lungs

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Upper Respiratory Tract

  • Nose :

    • Air enters through nostrils or external nares into nasal vestibule

    • Nasal hairs in vestibule are the first particle filtration system

  • Nasal Cavity :

    • Nasal septum divides nasal cavity into left and right

    • Mucous secretions from paranasal sinus and tears clean and moisten the nasal cavity

    • Meatuses Constricted passageways in between conchae that produce air turbulence:

      • Warm (how?) and humidify incoming air (bypassed by mouth breathing)

      • trap particles

  • Air flow: from external nares to vestibule to internalnares throughmeatuses, then to nasopharynx

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The Pharynx

  • A chamber shared by digestive and respiratory systems that extends from internal nares to the dual entrances to the larynx and esophagus at the C6 vertebrae

  • Nasopharynx

    • Superior portion of the pharynx (above the soft palate) contains pharyngeal tonsils; epithelium?

  • Oropharynx

    • Middle portion of the pharynx, from soft palate to epiglottis; contains palatine and lingual tonsils; communicates with oral cavity; epithelium?

  • Laryngopharynx

    • Inferior portion of the pharynx, extends from hyoid bone to entrance to larynx and esophagus

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Lower Respiratory Tract

  • Air flow from the pharynx enters the larynx, continues into trachea, bronchial tree, bronchioles, and alveoli

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Anatomy of the Larynx

Figure 23–4

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Cartilages of the Larynx

  • 3 large, unpaired cartilages form the body of the larynx (voice box)

    • thyroid cartilage (Adam’s apple)

      • hyaline cartilage

      • Forms anterior and lateral walls of larynx

      • Ligaments attach to hyoid bone, epiglottis, and other laryngeal cartilages

    • cricoid cartilage

      • hyaline cartilage

      • Form posterior portion of larynx

      • Ligaments attach to first tracheal cartilage

    • the epiglottis

      • elastic cartilage

      • Covers glottis during swallowing

      • Ligaments attach to thyroid cartilage and hyoid bone

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Small Cartilages of the Larynx

  • 3 pairs of small hyaline cartilages:

    • arytenoid cartilages

    • corniculate cartilages

    • cuneiform cartilages

  • Corniculate and arytenoid cartilages function in opening and closing the glottis and the production of sound

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Larynx Functions

  • To provide a patent airway

  • To function in voice production

  • To act as a switching mechanism to route air and food into the proper channels

    • Thyroid and cricoid cartilages support and protect the glottis and the entrance to trachea

    • During swallowing the larynx is elevated and the epiglottis folds back over glottis prevents entry of food and liquids into respiratory tract

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Sphincter Functions of Larynx

  • The larynx is closed during coughing, sneezing, and Valsalva’s maneuver

  • Valsalva’s maneuver

    • Air is temporarily held in the lower respiratory tract by closing the glottis

    • Causes intra-abdominal pressure to rise when abdominal muscles contract

    • Helps to empty the rectum

    • Acts as a splint to stabilize the trunk when lifting heavy loads

  • Glottis also “closed” (covered) by epiglottis during swallowing

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The Glottis

Figure 23–5

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Sound Production

  • Air passing through glottis:

    • vibrates vocal folds and produces sound waves

  • Sound is varied by:

    • tension on vocal folds

    • voluntary muscles position cartilages

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Anatomy of the Trachea

Figure 23–6

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The Trachea

  • Extends from the cricoid cartilage into mediastinum where it branches into right and left bronchi

  • Has mucosa, submucosa which contains mucous glands, and adventitia

  • Adventita made up of 15–20 C-shaped tracheal cartilages (hyaline)strengthen and protect airway

    • Ends of each tracheal cartilage are connected by an elastic ligament and trachealis muscle where trachea contacts esophagus. Why?

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The Primary Bronchi

  • Right and left primary bronchi are separated by an internal ridge (the carina)

  • Right primary bronchus

    • larger in diameter than the left

    • descends at a steeper angle

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The Bronchial Tree

  • Formed by the primary bronchi and their branches

  • Each primary bronchus (R and L) branches into secondary bronchi, each supplying one lobe of the lungs (5 total)

  • Secondary Bronchi Branch to form tertiary bronchi

  • Each tertiary bronchus branches into multiple bronchioles

  • Bronchioles branch into terminalbronchioles:

  • 1 tertiary bronchus forms about 6500 terminal bronchioles

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Bronchial Tree

Figure 23–9

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Bronchial Structure

  • The walls of primary, secondary, and tertiary bronchi:

    • contain progressively less cartilage and more smooth muscle, increasing muscular effects on airway constriction and resistance

  • Bronchioles:

    • Consist of cuboidal epithelium

    • Lack cartilage support and mucus-producing cells and are dominated by a complete layer of circular smooth muscle

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Autonomic Control

  • Regulates smooth muscle:

    • controls diameter of bronchioles

    • controls airflow and resistance in lungs

  • Bronchodilation of bronchial airways

    • Caused by sympathetic ANS activation

    • Reduces resistance

  • Bronchoconstriction

    • Caused by parasympathetic ANS activation or

    • histamine release (allergic reactions)

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The Bronchioles

Figure 23–10

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Conducting Zones

Figure 22.7

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Figure 23–7

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The Lungs

  • Left and right lungs: in left and right pleural cavities

  • The base:

    • inferior portion of each lung rests on superior surface of diaphragm

  • Hilus

    • Where pulmonary nerves, blood vessels, and lymphatics enter lung

    • Anchored in meshwork of connective tissue

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Lung Anatomy

  • Lungs have lobes separated by deep fissures

  • Right lung is wider and is displaced upward by liver. Has 3 lobes:

    • superior, middle, and inferior

    • separated by horizontal and oblique fissures

  • Left lung is longer is displaced leftward by the heart forming the cardiac notch. Has2 lobes:

    • superior and inferior

    • separated by an oblique fissure

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Relationship between Lungs and Heart

Figure 23–8

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Respiratory Zone

  • Each terminal bronchiole branches to form several respiratory bronchioles, where gas exchange takes place (Exchange Surfaces)

  • Respiratory bronchioles lead to alveolar ducts, then to terminal clusters of alveolar sacs composed of alveoli

  • Approximately 300 million alveoli:

    • Account for most of the lungs’ volume

    • Provide tremendous surface area for gas exchange

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  • Alveoli Are air-filled pockets within the lungs where all gas exchange takes place

  • Alveolar epithelium is a very delicate, simple squamous epithelium

  • Contains scattered and specialized cells

  • Lines exchange surfaces of alveoli

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Alveolar Organization

Figure 23–11

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Alveolar Organization

  • Respiratory bronchioles are connected to alveoli along alveolar ducts

  • Alveolar ducts end at alveolar sacs: common chambers connected to many individual alveoli

  • Each individual alveolus has an extensive network of capillaries and is surrounded by elastic fibers

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Alveolar Epithelium

  • Consists of simple squamous epithelium (Type I cells)

  • Patrolled by alveolar macrophages, also called dust cells

  • Contains septal cells (Type II cells) that produce surfactant:

    • oily secretion containing phospholipids and proteins

    • coats alveolar surfaces and reduces surface tension

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Alevolar problems

  • Respiratory Distress: difficult respiration

    • Can occur when septal cells do not produce enough surfactant

    • leads to alveolar collapse

  • Pneumonia: inflammation of the lung tissue

    • causes fluid to leak into alveoli

    • compromises function of respiratory membrane

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Respiratory Membrane

  • The thin membrane of alveoli where gas exchange takes place. Consists of:

    • Squamous epithelial lining of alveolus

    • Endothelial cells lining an adjacent capillary

    • Fused basal laminae between alveolar and endothelial cells

  • Diffusion across respiratory membrane is very rapid because distance is small and gases (O2 and CO2) are lipid soluble

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Blood Supply to Respiratory Surfaces

  • Pulmonary arteries branch into arterioles supplying alveoli with deox. blood

  • a capillary network surrounds each alveolus as part of the respiratory membrane

  • blood from alveolar capillaries passes through pulmonary venules and veins, then returns to left atrium with ox. blood

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Blood Supply to the Lungs Proper

  • Bronchial arteries provide systemic circulation bringing oxygen and nutrients to tissues of conducting passageways of lung

    • Arise from aorta and enter the lungs at the hilus

    • Supply all lung tissue except the alveoli

  • Venous blood bypasses the systemic circuit and just flows into pulmonary veins

  • Blood Pressure in the pulmonary circuit is low (30 mm Hg)

  • Pulmonary vessels are easily blocked by blood clots, fat, or air bubbles, causing pulmonary embolism

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Pleural Cavities and Membranes

  • 2 pleural cavities are separated by the mediastinum

  • Each pleural cavity holds a lung and is lined with a serous membrane = the pleura:

    • Consists of 2 layers:

      • parietal pleura

      • visceral pleura

    • Pleural fluid: a serous transudate thatlubricates space between 2 layers

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  • Refers to 4 integrated processes:

    • Pulmonary ventilation – moving air into and out of the lungs (provides alveolar ventilation)

    • External respiration – gas exchange between the lungs and the blood

    • Transport – transport of oxygen and carbon dioxide between the lungs and tissues

    • Internal respiration – gas exchange between systemic blood vessels and tissues

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Gas Pressure and Volume

Figure 23–13

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Boyle’s Law

  • Defines the relationship between gas pressure and volume:

    P 1/V


    P1V1 = P2V2

  • In a contained gas:

    • external pressure forces molecules closer together

    • movement of gas molecules exerts pressure on container

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Pulmonary Ventilation

Respiration: Pressure Gradients

Figure 23–14

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  • Air flows from area of higher pressure to area of lower pressure (it’s the pressure difference, or gradient, that matters)

  • Volume of thoracic cavity changes (expansion or contraction of diaphragm or rib cage) creates changes in pressure

  • A Respiratory Cycle Consists of:

    • an inspiration (inhalation)

    • an expiration (exhalation)

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Lung Compliance

  • An indicator of expandability

  • Low compliance requires greater force to expand

  • High compliance requires less force

  • Kind of like capacitance

  • Affected by:

    • Connective-tissue structure of the lungs

    • Level of surfactant production

    • Mobility of the thoracic cage

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Gas Pressure

  • Normal atmospheric pressure(Patm)= 1 atm (or 760 mm Hg) at sea level

  • Intrapulmonary Pressure (intra-alveolar pressure) is measured relative to Patm

  • In relaxed breathing, the difference between Patm and intrapulmonary pressure is small: only -1 mm Hg on inhalation or +1 mm Hg on expiration

  • Max range: from -30 mm Hg to +100 mm Hg)

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Intrapleural Pressure

  • Pressure in space between parietal and visceral pleura

  • Actually a “potential space” because serous fluid welds the two layers together (like a wet glass on a coaster)

  • Remains below Patm throughout respiratory cycle due to:

    • Elasticity of lungs causes them to assume smallest possible size

    • Surface tension of alveolar fluid draws alveoli to their smallest possible size

  • These forces are resisted by the bond between the layers of pleura so there is always a negative pressure trying to pull the lungs into a smaller voluume

  • If lungs were allowed to collapse completely, based on their elastic content they would only be about 5% of their normal resting volume

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The Respiratory Pump

  • Cyclical changes in intrapleural pressure operate the respiratory pump which aids in venous return to heart

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Lung Collapse

  • Injury to the chest wallcan cause pneumothorax: when air is allowed to enter the pleural space.

  • Caused by equalization of the intrapleural pressure with the intrapulmonary pressure (the bond between lung and pleura breaks)

  • Causes atelectasis (a collapsed lung)

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The Respiratory Muscles

Figure 23–16a, b

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Respiratory Muscles

  • Inhalation: always active

    • Diaphragm: contraction flattens it, expanding the thorax and drawing air into lungs, accounts for 75% of normal air movement

    • External intercostal muscles: assist inhalation by elevating ribs, accounts for 25% of normal air movement

  • Exhalation: normally passive

    • Relaxation of diaphragm decreases thoracic volume

    • Gravity causes rib cage to descend

    • Elastic fibers in lungs and muscles cause elastic rebound

    • All serve to raise intrapulmonary pressure to +1atm

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Muscles of Active Exhalation

  • Internal intercostals actively depress the ribs

  • Abdominal muscles compress the abdomen, forcing diaphragm upward

    Both serve to greatly decrease the thoracic volume, thus increasing the pressure  more air leaves (and does so faster)

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Resistance in Respiratory Passageways

  • As airway resistance rises, breathing movements become more strenuous

  • Severely constricted or obstructed bronchioles:

    • Can prevent life-sustaining ventilation

    • Can occur during acute asthma attacks which stops ventilation

  • Epinephrine release via the sympathetic nervous system dilates bronchioles and reduces air resistance

Figure 22.15

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Modes of Breathing

  • Quiet Breathing (Eupnea) involves active inhalation and passive exhalation

    • Diaphragmatic breathing or deep breathing:

      • is dominated by diaphragm

    • Costal breathing or shallow breathing:

      • is dominated by ribcage movements

      • usually occurs due to conscious effort or abdominal/thoracic obstructions (e.g. pregnancy)

  • Forced Breathing(hyperpnea) involves active inhalation and exhalation

  • Both assisted by accessory muscles

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Respiratory Rates and Volumes

  • Respiratory system adapts to changing oxygen demands by varying:

    • the number of breaths per minute (respiratory rate)

    • the volume of air moved per breath (tidalvolume)

      Both can be modulated

  • Minute Volume (measures pulmonary ventilation)=respiratory ratetidal volume

    • kind of like CO = HR x SV)

  • Both RR and TV can be modulated

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Dead Space

  • Only a part of respiratory minute volume reaches alveolar exchange surfaces

  • Volume of air remaining in conducting passages is anatomic dead space

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Alveolar Ventilation

  • Alveolar ventilation is the amount of air reaching alveoli each minute = respiratory rate  (Tidal Volume - anatomic dead space)

    • for a given respiratory rate:

      • increasing tidal volume increases alveolar ventilation rate

    • for a given tidal volume:

      • increasing respiratory rate increases alveolar ventilation

  • Alveoli contain less O2, more CO2 than atmospheric air because inhaled air mixes with exhaled air

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Mammalian Respiratory System – poor design?

  • Inhaled air mixes with exhaled air

  • Lots of dead space in the system

  • These are the results of a bi-directional, blind ended ventilation system – what if water entered and left your sink through the same spout?

  • Birds, fish have unidirectional circuits so fresh and stale air never mix

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Respiratory Volumes and Capacities

Figure 23–17

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Lung Volumes

  • Resting tidal volume

  • Expiratory reserve volume (ERV)

  • Residual volume

    • minimal volume (in a collapsed lung)

  • Inspiratory reserve volume (IRV)

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Calculated Respiratory Capacities

  • Inspiratory capacity

    • tidal volume + IRV

  • Functional residual capacity (FRC):

    • ERV + residual volume

  • Vital capacity:

    • ERV + tidal volume + IRV

  • Total lung capacity:

    • vital capacity + residual volume

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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 in response to concentration or pressure gradients

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The Gas Laws

  • Rate of diffusion depends on physical principles, or gas laws

    • Boyle’s law:P 1/V

    • Dalton’s law: each gas contributes to the total pressure in proportion to its number of molecules

    • Henry’s Law: at a given temperature, the amount of a gas in solution is proportional to partial pressure of that gas

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Composition of Air

  • Nitrogen (N2) = 78.6%

  • Oxygen (O2) = 20.9%

  • Water vapor (H2O) = 0.5%

  • Carbon dioxide (CO2) = 0.04%

  • Atmospheric pressure produced by air molecules bumping into each other = 760 mmHg

  • Partial Pressure = the pressure contributed by each gas in the atmosphere

  • Dalton’s Law says PO2 = .209 x 760 = 160mmHg

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Normal Partial Pressures

  • In pulmonary vein plasma (after visiting lungs):

    • PCO2 = 40 mm Hg

    • PO2 = 100 mm Hg

    • PN2 = 573 mm Hg

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Mixing in Pulmonary Veins

  • Oxygenated blood mixes with deoxygenated blood from conducting passageways that bypasses systemic circuit

  • Remember the bronchial arteries? There are no bronchial veins – these venules join the pulmonary veins that otherwise have oxygenated blood.

  • Lowers the PO2 of blood entering systemic circuit (about 95 mm Hg)

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Henry’s Law

Figure 23–18

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Henry’s Law

  • When gas under pressure comes in contact with liquid, gas dissolves in liquid until equilibrium is reached

  • At a given temperature, the amount of a gas in solution is proportional to partial pressure of that gas

  • The amount of a gas that dissolves in solution (at given partial pressure and temperature) also depends on the solubility of that gas in that particular liquid : CO2 is very soluble, O2 is less soluble, N2 has very low solubility

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Overview of Pressures in the Body

PO2 (atmosphere) = 160 mm Hg

PO2 (lungs) = 100 mm Hg [104]

PO2 (left atrium) = 95 mm Hg

PO2 (resting tissue) = 40 mm Hg

PO2 (active tissue) = 15 mm Hg

PCO2 (lungs) = 40 mm Hg

PCO2 (tissue) = 45 mm Hg

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Diffusion and the Respiratory Membrane

  • Direction and rate of diffusion of gases across the respiratory membrane are determined by:

    • partial pressures and solubilities

    • matching of alveolar ventilation and pulmonary blood perfusion (gotta have enough busses)

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Efficiency of Gas Exchange

  • Due to:

    – substantial differences in partial pressure across the respiratory membrane

    – distances involved in gas exchange are small

    • O2 and CO2 are lipid soluble

      – total surface area is large

      – blood flow and air flow are coordinated

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Respiratory Processes and Partial Pressure

Figure 23–19

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O2 and CO2

  • Blood arriving in pulmonary arteries has low PO2 and high PCO2

  • The concentration gradient causes: O2 to enter blood and CO2 to leave blood

  • Blood leaving heart has high PO2 and lowPCO2

  • Interstitial Fluid has low PO2 = 40 mm Hg and high PCO2 45 = mm Hg

  • Concentration gradient in peripheral capillaries is opposite of lungs so CO2 diffuses into blood and O2 to enter tissue

  • Although carbon dioxide has a lower partial pressure gradient (only 5mmHg)

    • It is 20 times more soluble in plasma than oxygen

    • It diffuses in equal amounts with oxygen

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Gas Pickup and Delivery

  • Red Blood Cells (RBCs): transport O2 to, and CO2 from, peripheral tissues

  • Remove O2 and CO2 from plasma, allowing gases to diffuse into blood

  • Hb carries almost all O2, while only a little CO2 is carried by Hb

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Oxygen Transport

  • O2 binds to iron ions in hemoglobin (Hb) molecules in a reversible reaction

  • Each RBC can bind a billion molecules of O2

  • Hemoglobin Saturation: the percentage of heme units in a hemoglobin molecule that contain bound oxygen

Respiration: Oxygen and Carbon Dioxide Transport

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Environmental Factors Affecting Hemoglobin

  • PO2 of blood

  • Blood pH

  • Temperature

  • Metabolic activity within RBCs

Respiration: Hemoglobin

Respiration: Percent O2 Saturation of Hemoglobin

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Hemoglobin Saturation Curve

Figure 23–20 (Navigator)

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Oxyhemoglobin Saturation Curve

  • Graph relates the saturation of hemoglobin to partial pressure of oxygen

  • Higher PO2 results in greater Hb saturation

  • Is a curve rather than a straight line because Hb changes shape each time a molecule of O2 is bound. Each O2 bound makes next O2 binding easier (cooperativity)

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Oxygen Reserves

  • Notice that even at PO2 = 40 mm Hg, Oxygen saturation is at 75%. Thus, each Hb molecule still has 3 oxygens bound to it. This reserve is needed when tissue becomes active and PO2drops to 15 mm Hg

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Carbon Monoxide Poisoning

  • CO from burning fuels:

    • Binds irreversibly to hemoglobin and takes the place of O2

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Hemoglobin Saturation Curve

  • When pH drops or temperature rises:

    • more oxygen is released

    • curve shift to right

  • When pH rises or temperature drops:

    • less oxygen is released

    • curve shifts to left

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The Bohr Effect

  • The effect of decreased pH on hemoglobin saturation curve

  • Caused by CO2:

    • CO2 diffuses into RBC

    • an enzyme, called carbonic anhydrase, catalyzes reaction with H2O

    • produces carbonic acid (H2CO3)

  • Carbonic acid (H2CO3):

    • dissociates into hydrogen ion (H+) and bicarbonate ion (HCO3—)

  • Hydrogen ions diffuse out of RBC, lowering pH

Hemoglobin and pH

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2,3-biphosphoglycerate (BPG)

  • RBCs generate ATP by glycolysis, forming lactic acid and BPG

  • BPG directly affects O2 binding and release: more BPG, more oxygen released

  • There is always some BPG around to lower the affinity of Hb for O2 (without it, hemoglobin will not release oxygen)

  • BPG levels rise:

    • when pH increases

    • when stimulated by certain hormones

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Fetal and Adult Hemoglobin

  • At the same PO2:

    • fetal Hb binds more O2 than adult Hb, which allows fetus to take O2 from maternal blood

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  • Hemoglobin in RBCs:

    • carries most blood oxygen

    • releases it in response to low O2 partial pressure in surrounding plasma

  • If PO2 increases, hemoglobin binds oxygen

  • If PO2 decreases, hemoglobin releases oxygen

  • At a given PO2 hemoglobin will release additional oxygen if pH decreases or temperature increases

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Carbon Dioxide Transport

Figure 23–23 (Navigator)

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  • CO2 is generated as a byproduct of aerobic metabolism (cellular respiration)

  • Takes three routes in blood:

    • converted to carbonic acid

    • bound to protein portion of hemoglobin

    • dissolved in plasma

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CO2 in the Blood Stream

  • 70% is transported as carbonic acid (H2CO3) which dissociates into H+ and bicarbonate (HCO3-)

  • Bicarbonate ions move into plasma by a countertransport exchange mechanism that takes in Cl- ions without using ATP (the chloride shift)

  • At the lungs, these processes are reversed

    • Bicarbonate ions move into the RBCs and bind with hydrogen ions to form carbonic acid

    • Carbonic acid is then split by carbonic anhydrase to release carbon dioxide and water

    • Carbon dioxide then diffuses from the blood into the alveoli, then is breathed out

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CO2 inside RBCs

CO2 + H2O H2CO3

(Enzyme = carbonic anhydrase)

H2CO3 H+ + HCO3-

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CO2 in the Blood Stream

  • 20 - 23% is bound to amino groups of globular proteins in Hb molecule forming carbaminohemoglobin

  • 7 - 10% is transported as CO2 dissolved in plasma

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  • CO2 travels in the bloodstream primarily as bicarbonate ions, which form through dissociation of carbonic acid produced by carbonic anhydrase in RBCs

  • Lesser amounts of CO2 are bound to Hb and even fewer molecules are dissolved in plasma

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Summary: Gas Transport

Figure 23–24

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Influence of Carbon Dioxide on Blood pH

  • The carbonic acid–bicarbonate buffer system resists blood pH changes

  • If hydrogen ion concentrations in blood begin to rise, excess H+ is removed by combining with HCO3–

  • If hydrogen ion concentrations begin to drop, carbonic acid dissociates, releasing H+

  • Changes in respiratory rate can also:

    • Alter blood pH

    • Provide a fast-acting system to adjust pH when it is disturbed by metabolic factors

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Control of Respiration

  • Ventilation – the amount of gas reaching the alveoli

  • Perfusion – the blood flow reaching the alveoli

  • Ventilation and perfusion must be tightly regulated for efficient gas exchange

  • Gas diffusion at both peripheral and alveolar capillaries maintain balance by:

    • changes in blood flow and oxygen delivery

    • changes in depth and rate of respiration

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Regulation of O2 Transport

  • Rising PCO2 levels in tissues relaxes smooth muscle in arterioles and capillaries, increasing blood flow there (autoregulation)

  • Coordination of lung perfusion (blood) and alveolar ventilation (air):

    • blood flow is shifted to the capillaries serving alveoli with high PO2 and low PCO2 (opposite of tissue)

    • PCO2 levels control bronchoconstriction and bronchodilation: high PCO2 causes bronchodilation (just like with blood in the tissues)

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Ventilation-Perfusion Coupling

  • In tissue high CO2 causes vasodilation, in lungs, high CO2 causes vasoconstiction (Why?)

  • In lungs high CO2 causes bronchodilation (Why?) while low CO2 causes constriction

     Blood goes to alveoli with low CO2 , air goes to alveoli with high CO2

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Ventilation-Perfusion Coupling



in alveoli

Reduced alveolar ventilation;

excessive perfusion

Pulmonary arterioles

serving these alveoli


Reduced alveolar ventilation;

reduced perfusion



in alveoli

Enhanced alveolar ventilation;

inadequate perfusion

Pulmonary arterioles

serving these alveoli


Enhanced alveolar ventilation;

enhanced perfusion

Figure 22.19

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The Respiratory RhythmicityCenters

  • Respiratoryrhythmicitycenters in medulla set the pace of respiration

  • Can be divided into 2 groups:

    • dorsal respiratory group (DRG)

      • Inspiratory center

      • Functions in quiet breathing (sets the pace) and forced breathing

      • Dormant during expiration

    • ventral respiratory group (VRG)

      • Inspiratory and expiratory center

      • Functions only in forced breathing

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Quiet Breathing

  • Brief activity in the DRG stimulates inspiratory muscles

  • After ~2 seconds, DRG neurons become inactive, allowing passive exhalation

  • Note that VRG is not involved

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Forced Breathing

  • Increased activity in DRG:

    • stimulates VRG to become active

    • which activates accessory inspiratory muscles

  • After inhalation:

    • expiratory center neurons stimulate active exhalation

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Forced Breathing

Quiet Breathing

Figure 23–25b

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Centers of the Pons

  • Paired nuclei that adjust output of respiratory rhythmicity centers:

    • regulating respiratory rate and depth of respiration

  • Pons centers:

    • Influence and modify activity of the medullary centers

    • Smooth out inspiration and expiration transitions and vice versa

  • The pontine respiratory group (PRG) – continuously inhibits the inspiration center

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Respiratory Centers and Reflex Controls

Figure 23–26

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Sensory Modifiers of Respiratory Center Activities

  • Chemoreceptors are sensitive to:

    • PCO2, PO2, or pH of blood or cerebrospinal fluid

  • Baroreceptors in aortic or carotid sinuses:

    • sensitive to changes in blood pressure

  • Stretch receptors respond to changes in lung volume

  • Irritating physical or chemical stimuli in nasal cavity, larynx, or bronchial tree promote airway constriction

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Chemoreceptor Reflexes

  • Respiratory centers are strongly influenced by chemoreceptor input from:

    • carotid bodies (cranial nerve IX)

    • aortic bodies (cranial nerve X)

    • receptors in medulla that monitor cerebrospinal fluid

  • All react more strongly to changes in pH and PCO2, to a lesser extent to changes in PO2

  • So in general, CO2 levels, rather than O2 levels, are primary drivers of respiratory activity

  • At rest, it is the H+ ion concentration in brain CSF (which is a proxy measure of CO2 levels)

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Chemoreceptors and oxygen

  • Arterial oxygen levels are monitored by the aortic and carotid bodies

  • Substantial drops in arterial PO2 (to 60 mm Hg) are needed before oxygen levels become a major stimulus for increased ventilation

  • If carbon dioxide is not removed (e.g., as in emphysema and chronic bronchitis), chemoreceptors become unresponsive to PCO2 chemical stimuli

  • In such cases, PO2 levels become the principal respiratory stimulus (hypoxic drive)

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Chemoreceptor Responses to PCO2

Figure 23–27

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Effect of Breathing on Ventilation

  • Breathing faster and deeper gets rid of more CO2 , takes in more O2

  • Breathing more slowly and shallowly allows CO2 to build up, less O2 comes in

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Chemoreceptor Stimulation

  • Leads to increased depth and rate of respiration

  • Is subject to adaptation: decreased sensitivity due to chronic stimulation

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Changes in Arterial PCO2

  • Hypercapnia: an increase in arterial PCO2

    • Stimulates chemoreceptors in the medulla oblongata to restore homeostasis by increasing breathing rate

  • Hypocapnia: a decrease in arterial PCO2

    • Inhibits chemoreceptors, breathing rate decreases

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Ventilation Issues

  • Hypoventilation

    • A common cause of hypercapnia

    • Abnormally low respiration rate allows CO2 build-up in blood, should result in increased RR

  • Hyperventilation

    • Excessive ventilation

    • Results in abnormally low PCO2 (hypocapnia)

    • Stimulates chemoreceptors to decrease respiratory rate

    • Treatment? Why?

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Baroreceptor Reflexes

  • Carotid and aortic baroreceptor stimulation: affects both blood pressure and respiratory centers

  • When blood pressure falls:

    • respiration increases

  • When blood pressure increases:

    • respiration decreases

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Breathing and Heart Rate

  • Your ventilation and perfusion must be coordinated, otherwise the circulatory and respiratory systems not efficient.

  • Examples:

    • Increase HR but not RR – no more O2 coming in than before so blood can’t deliver it to tissues

    • Increase RR but not HR – O2 is coming in more quickly but it can’t get to the tissues

  • Also, if BP falls, RR and HR rise and vice versa

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The Hering–Breuer Reflexes

  • 2 baroreceptor reflexes involved in forced breathing:

    • inflation reflex:

      • Caused by stretch receptor in lungs

      • prevents lung overexpansion

    • deflation reflex:

      • inhibits expiratory centers and stimulates inspiratory centers during lung deflation so inspiration can start again

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Changes in Respiratory System at Birth

  • Before birth: pulmonary vessels are collapsed and lungs contain no air

  • During delivery blood PO2falls, PCO2 rises

  • At birth newborn overcomes force of surface tension to inflate bronchial tree and alveoli and take first breath

  • Large drop in pressure at first breath pulls blood into pulmonary circulation, closing foramen ovale and ductus arteriosus redirecting fetal blood circulation patterns

  • Subsequent breaths fully inflate alveoli

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Respiratory Disorders

  • Restrictive disorders: lung cancer, fibrosis, pleurisy

    • Fibrosis: decreases compliance

    • harder to inhale

  • Obstructive disorders: emphysema, asthma, bronchitis (COPD)

    • Loss of elasticity: increases compliance

    • Harder to exhale (FRC increased)

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COPD – Chronic Obstructive Pulmonary Disease

  • Includes: emphysema, chronic bronchitis, asthma. Often, both emphysema and bronchitis are present but in differing proportions

  • Symptoms

    • difficult to exhale

    • May have barrel chests due to trapped air in lungs

    • dyspnea (shortness of breath) accompanied by wheezing, and a persistent cough with sputum

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COPD - Emphysema

  • Loss of elastic tissue in the lung alveoli lead to their enlargement and degeneration of the respiratory membrane leaving large holes behind

  • Suffers are called “pink puffers” because they are thin, usually maintain good oxygen saturation, and breathe through pursed lips (Why?)

  • Caused by smoking or (rarely) by alpha1 anti-trypsin deficiency – this is a congenital lack of the gene for alpha1 antitrypsin which normally protects alveoli from enzyme neutrophil elastase; without it, elastase eats away the elastic fibers

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COPD - Chronic Bronchitis

  • Inflammation of airways causes narrowing of bronchioles and a buildup of mucus, both of which restrict air flow

  • During exhalation, airways collapse (why not during inhalation?)

  • These patients are often called “blue bloaters” because they have low oxygen saturation (cyanosis), and often have systemic edema secondary to vasoconstriction and right-sided heart failure

  • Adaptation of the chemoreceptors occurs especially in the ones sensitive to CO2

  • Thus, their only drive to breathe is provided by low O2 levels! This is why they are always blue. DO NOT GIVE THESE PATIENTS O2 ! They will stop breathing totally.

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  • Altitude sickness: low pressure leads to hypoxia, can cause cerebral and pulmonary edema

  • Normal response to acute high altitude exposure include:

    • Increased ventilation – 2-3 L/min higher than at sea level due to Increased RR and tidal volume

    • Increased HR

    • Substantial decline in PO2 stimulates peripheral chemoreceptors:

    • Chemoreceptors become more responsive to PCO2

  • Over time

    • Increased hematocrit

    • Increased BPG causes a right shift in Hb making it easier to offload oxygen at the tissues

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Lung fluid

  • Pleural effusion – fluid buildup in pleural cavity/space (kind of like pericarditis)

  • Pulmonary edema – fills exchange surfaces

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Cystic Fibrosis

  • Recessive genetic disease caused by simple mutation in both copies of the gene for a chloride transporter.

  • Without it, Cl- cannot be pumped onto the lung surface, Na+ doesn’t follow and neither does water.

  • Sticky mucus builds up inside lungs and infections are common. Often fatal before age 30

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  • Decompression sickness –the bends, nitrogen bubbles exit the blood, enter the tissues: painful and dangerous

  • Shallow water blackout: hyperventilation leads to artificially reduced CO2, allows you to hold your breath to the point of passing out

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  • Hole in pleural membrane causes lung collapse (atelectasis)

  • Non-tension pneumothorax – a hole through both lung and pleural membrane breaks tension between the pleura, lung elasticity causes it to pull away from the chest wall

  • Tension pneumothorax – a hole in the lung allows air to escape into the pleural space with each breath, further raising in the intrapleural pressure and collapsing the lung

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  • Sudden infant death syndrome

  • Disrupts normal respiratory reflex pattern

  • May result from connection problems between pacemaker complex and respiratory centers

  • See extra credit options

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Lung cancer

  • 50% die within one year of diagnosis

  • Only 20% or so survive 5 years

  • Around 90% of cases are due exclusively to smoking