Transcript Chapter 23.

Chapter 22.
Respiratory System
Overview
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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
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
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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
Components
of the
Respiratory
System
Figure 23–1
Organization of the
Respiratory System
• Upper respiratory system
– Nose, nasal cavity, sinuses, and pharynx
• Lower respiratory system
– Larynx, trachea, bronchi and lungs
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
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 nares
through 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
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?
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
Bronchial
Tree
Figure 23–9
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)
The Bronchioles
Figure 23–10
Conducting Zones
Figure 22.7
Lungs
Figure 23–7
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
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
Alveolar
Organization
Figure 23–11
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
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 that
lubricates 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
Boyle’s Law
• Defines the relationship between gas pressure
and volume:
P
1/V
Or
P1V1 = P2V2
• In a contained gas:
– external pressure forces molecules closer together
– movement of gas molecules exerts pressure on
container
Pulmonary
Ventilation
Respiration:
Pressure Gradients
Figure 23–14
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)
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 pressure
operate the respiratory pump which aids in
venous return to heart
Lung Collapse
• Injury to the chest wall can 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)
The Respiratory Muscles
Figure 23–16a, b
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
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
• As airway resistance
rises, breathing
movements become
more strenuous
• Severely constricted or
obstructed bronchioles:
– Can prevent lifesustaining 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
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
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
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):
– PCO = 40 mm Hg
2
– PO = 100 mm Hg
2
– PN = 573 mm Hg
2
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
PO (atmosphere) = 160 mm Hg
2
PO (lungs) = 100 mm Hg [104]
2
PO (left atrium) = 95 mm Hg
2
PO (resting tissue) = 40 mm Hg
2
PO (active tissue) = 15 mm Hg
2
PCO (lungs) = 40 mm Hg
2
PCO (tissue) = 45 mm Hg
2
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
Respiratory
Processes
and Partial
Pressure
Figure 23–19
O2 and CO2
• Blood arriving in pulmonary arteries has low PO and
2
high PCO
2
• The concentration gradient causes: O2 to enter blood
and CO2 to leave blood
• Blood leaving heart has high PO and lowPCO
2
2
• Interstitial Fluid has low PO = 40 mm Hg and high PCO
2
2
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
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
Environmental Factors
Affecting Hemoglobin
•
•
•
•
PO of blood
2
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 PO results in greater Hb saturation
2
• 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 PO = 40 mm Hg,
2
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 PO drops to 15 mm
2
Hg
Carbon Monoxide Poisoning
• CO from burning fuels:
– Binds irreversibly to hemoglobin and takes the
place of O2
pH, Temperature, and
Hemoglobin Saturation
Figure 23–21
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 pH
Hemoglobin 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 PO :
2
– 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 PO increases, hemoglobin binds
2
oxygen
• If PO decreases, hemoglobin releases
2
oxygen
• At a given PO hemoglobin will release
2
additional oxygen
if pH decreases or
temperature increases
Carbon
Dioxide
Transport
Figure 23–23 (Navigator)
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)
H+ + HCO3-
H2CO3
CO2
Carbon
dioxide
+
H2O
Water

H2CO3
Carbonic
acid

H+
Hydrogen
ion
+
HCO3–
Bicarbonat
e ion
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 Hb
and even fewer molecules are dissolved in
plasma
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 PCO levels in tissues relaxes smooth
2
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 PO and low PCO (opposite of tissue)
2
2
– PCO levels control bronchoconstriction and
2
bronchodilation: high PCO causes bronchodilation
2
(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
PO2
PCO2
in alveoli
Reduced alveolar ventilation;
excessive perfusion
Pulmonary arterioles Reduced alveolar ventilation;
serving these alveoli reduced perfusion
constrict
PO2
PCO2
in alveoli
Enhanced alveolar ventilation;
inadequate perfusion
Pulmonary arterioles Enhanced alveolar ventilation;
serving these alveoli enhanced perfusion
dilate
Figure 22.19
The Respiratory Rhythmicity
Centers
• 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
Quiet Breathing
Forced
Breathing
Figure 23–25b
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
Respiratory
Centers
and Reflex
Controls
Figure 23–26
Sensory Modifiers of
Respiratory Center Activities
• Chemoreceptors are sensitive to:
– PCO , PO , or pH of blood or cerebrospinal fluid
2
2
• 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
PCO , to a lesser extent to changes in PO
2
2
• 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)
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)
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
Changes in Arterial PCO
2
• Hypercapnia: an increase in arterial PCO
– Stimulates chemoreceptors in the medulla
oblongata to restore homeostasis by
increasing breathing rate
• Hypocapnia: a decrease in arterial PCO
– Inhibits chemoreceptors, breathing rate
decreases
2
2
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 PCO (hypocapnia)
2
– Stimulates chemoreceptors to decrease respiratory
rate
– Treatment? Why?
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
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 PO falls, PCO rises
2
2
3. 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 arteriosus
redirecting fetal blood circulation patterns
5. Subsequent breaths fully inflate alveoli
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 antitrypsin 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
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
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 intrapleural
pressure 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