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Chapter 22.

Respiratory System

Overview• Respiratory anatomy• Respiration• Respiratory musculature• Ventilation, lung volumes and capacities• Gas exchange and transport

– O2– CO2

• Respiratory centers • Chemoreceptor reflexes• Respiratory Diseases

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

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

Figure 23–1

Components of the

Respiratory System

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

The Respiratory Epithelium

Figure 23–2

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

The Respiratory Mucosa• 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

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

Upper Respiratory Tract

Figure 23–3

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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 internal naresthrough meatuses, then to nasopharynx

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

Lower Respiratory Tract

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

Anatomy of the Larynx

Figure 23–4

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

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

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

The Glottis

Figure 23–5

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

Anatomy of the Trachea

Figure 23–6

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

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 terminal bronchioles:• 1 tertiary bronchus forms about 6500 terminal

bronchioles

Figure 23–9

Bronchial Tree 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

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)

Figure 23–10

The Bronchioles

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Conducting Zones

Figure 22.7 Figure 23–7

Lungs

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

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. Has 2 lobes: – superior and inferior– separated by an oblique fissure

Relationship between Lungs and Heart

Figure 23–8

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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Respiratory Zone Alveoli

• 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

Figure 23–11

Alveolar Organization 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

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

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

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

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

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

Respiration

• 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

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

OrP1V1 = P2V2

• In a contained gas:– external pressure forces molecules closer together– movement of gas molecules exerts pressure on

container

Respiration: Pressure Gradients

Figure 23–14

Pulmonary Ventilation

Respiration

• 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)

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

Pressure Relationships

Figure 22.12

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

P and V Changes with Inhalation and Exhalation

Figure 23–15

The Respiratory Pump

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

Lung Collapse

• Injury to the chest wall can causepneumothorax: when air is allowed to enter the pleural space.

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

• Causes atelectasis (a collapsed lung)

Figure 23–16a, b

The Respiratory Muscles 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)

Resistance in Respiratory Passageways

Figure 22.15

• 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

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

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 (tidal volume)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

Dead Space

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

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

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

Respiratory Volumes and Capacities

Figure 23–17

Lung Volumes

• Resting tidal volume• Expiratory reserve volume (ERV)• Residual volume

– minimal volume (in a collapsed lung)• Inspiratory reserve volume (IRV)

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

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

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

Normal Partial Pressures

• In pulmonary vein plasma (after visiting lungs):– PCO2

= 40 mm Hg– PO2

= 100 mm Hg– PN2

= 573 mm Hg

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)

Henry’s Law

Figure 23–18

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

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)

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

Figure 23–19

Respiratory Processes and Partial Pressure

O2 and CO2

• Blood arriving in pulmonary arteries has low PO2and

high PCO2• The concentration gradient causes: O2 to enter blood and CO2 to leave blood

• Blood leaving heart has high PO2and lowPCO2• Interstitial Fluid has low PO2

= 40 mm Hg and high PCO245 = 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

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

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

• PO2of blood

• Blood pH• Temperature• Metabolic activity within RBCs

Respiration: Hemoglobin

Respiration: Percent O2 Saturation of Hemoglobin

Hemoglobin Saturation Curve

Figure 23–20 (Navigator)

Oxyhemoglobin Saturation Curve

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

• Higher PO2results 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)

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 PO2

drops to 15 mm Hg

Carbon Monoxide Poisoning

• CO from burning fuels:– Binds irreversibly to hemoglobin and takes the

place of O2

Figure 23–21

pH, Temperature, and Hemoglobin Saturation

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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

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 pHHemoglobin and pH

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

Fetal and Adult Hemoglobin

Figure 23–22

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

KEY CONCEPTS• 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 PO2decreases, hemoglobin releases

oxygen • At a given PO2

hemoglobin will release additional oxygen if pH decreases or temperature increases

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Figure 23–23 (Navigator)

Carbon Dioxide

Transport

CO2 Transport

• 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

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

CO2 inside RBCs

CO2 + H2O H2CO3

(Enzyme = carbonic anhydrase)

H2CO3 H+ + HCO3-

Bicarbonate ion

HCO3–

Hydrogen ion

H+↔+ H2O

Water

↔Carbonic

acidCarbon dioxide

+H2CO3CO2

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

KEY CONCEPT

• 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 Hband even fewer molecules are dissolved in plasma

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Summary: Gas Transport

Figure 23–24

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

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

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 PO2and low PCO2

(opposite of tissue)– PCO2

levels control bronchoconstriction and bronchodilation: high PCO2

causes bronchodilation(just like with blood in the tissues)

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

Ventilation-Perfusion Coupling

Figure 22.19

Reduced alveolar ventilation;excessive perfusion

Reduced alveolar ventilation;reduced perfusion

Pulmonary arteriolesserving these alveoliconstrict

Enhanced alveolar ventilation;inadequate perfusion

Enhanced alveolar ventilation;enhanced perfusion

Pulmonary arteriolesserving these alveolidilate

PO2

PCO2

in alveoli

PO2

PCO2

in alveoli

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The Respiratory RhythmicityCenters

• Respiratory rhythmicity centers 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

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

Forced Breathing

• Increased activity in DRG:– stimulates VRG to become active– which activates accessory inspiratory muscles

• After inhalation:– expiratory center neurons stimulate active

exhalation

Figure 23–25b

Forced BreathingQuiet Breathing

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 medullarycenters

– Smooth out inspiration and expiration transitions and vice versa

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

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

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 O2levels, 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)

• 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 PCO2chemical stimuli

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

Chemoreceptors and oxygen Chemoreceptor Responses to PCO2

Figure 23–27

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

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

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?

Baroreceptor Reflexes

• Carotid and aortic baroreceptorstimulation: affects both blood pressure and respiratory centers

• When blood pressure falls:– respiration increases

• When blood pressure increases:– respiration decreases

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

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

Changes in Respiratory System at Birth

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

2. During delivery blood PO2falls, PCO2

rises3. At birth newborn overcomes force of surface

tension to inflate bronchial tree and alveoli and take first breath

4. Large drop in pressure at first breath pulls blood into pulmonary circulation, closing foramen ovale and ductus arteriosusredirecting fetal blood circulation patterns

5. 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)

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

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 neutrophilelastase; without it, elastase eats away the elastic fibers

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.

Altitude• 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

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

Others

• 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

Pneumothorax• 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 intrapleuralpressure and collapsing the lung

SIDS

• Sudden infant death syndrome• Disrupts normal respiratory reflex pattern• May result from connection problems

between pacemaker complex and respiratory centers

• See extra credit options

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