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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

Chapter 22.

Respiratory System

  • Respiratory anatomy
  • Respiration
  • Respiratory musculature
  • Ventilation, lung volumes and capacities
  • Gas exchange and transport
    • O2
    • CO2
  • Respiratory centers
  • Chemoreceptor reflexes
  • Respiratory Diseases
  • 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
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
organization 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
the respiratory tract
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
respiratory epithelia
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
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
respiratory defense system
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 tract13
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
the pharynx
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
Lower Respiratory Tract
  • Air flow from the pharynx enters the larynx, continues into trachea, bronchial tree, bronchioles, and alveoli
cartilages of the larynx
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
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
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
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
The Glottis

Figure 23–5

sound production
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
the trachea
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
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
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

Bronchial Tree

Figure 23–9

bronchial structure
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
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
The Bronchioles

Figure 23–10

conducting zones
Conducting Zones

Figure 22.7



Figure 23–7

the 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
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
respiratory zone
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
  • 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
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
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
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
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
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
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
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
  • 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
boyle s law
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
pulmonary ventilation
Pulmonary Ventilation

Respiration: Pressure Gradients

Figure 23–14

  • 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
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
gas pressure
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
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
the respiratory pump
The Respiratory Pump
  • Cyclical changes in intrapleural pressure operate the respiratory pump which aids in venous return to heart
lung collapse
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)
the respiratory muscles
The Respiratory Muscles

Figure 23–16a, b

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
muscles of active exhalation
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
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

modes of breathing
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 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
dead space
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
  • 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
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
lung volumes
Lung Volumes
  • Resting tidal volume
  • Expiratory reserve volume (ERV)
  • Residual volume
    • minimal volume (in a collapsed lung)
  • Inspiratory reserve volume (IRV)
calculated respiratory capacities
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
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
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
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
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
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
Henry’s Law

Figure 23–18

henry s law77
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
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

diffusion and the respiratory membrane
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
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

o 2 and co 2
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
gas pickup and delivery
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
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
Environmental Factors Affecting Hemoglobin
  • PO2 of blood
  • Blood pH
  • Temperature
  • Metabolic activity within RBCs

Respiration: Hemoglobin

Respiration: Percent O2 Saturation of Hemoglobin

hemoglobin saturation curve
Hemoglobin Saturation Curve

Figure 23–20 (Navigator)

oxyhemoglobin saturation curve
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)
oxygen reserves
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
carbon monoxide poisoning
Carbon Monoxide Poisoning
  • CO from burning fuels:
    • Binds irreversibly to hemoglobin and takes the place of O2
hemoglobin saturation curve91
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 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
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 hemoglobin95
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 PO2 decreases, hemoglobin releases oxygen
  • At a given PO2 hemoglobin will release additional oxygen if pH decreases or temperature increases

Carbon Dioxide Transport

Figure 23–23 (Navigator)

co 2 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
co 2 in the blood stream
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
co 2 inside rbcs
CO2 inside RBCs

CO2 + H2O H2CO3

(Enzyme = carbonic anhydrase)

H2CO3 H+ + HCO3-

co 2 in the blood stream101
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
influence of carbon dioxide on blood ph
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
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 o 2 transport
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)
ventilation perfusion coupling
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 coupling108
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

the respiratory rhythmicity centers
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
quiet 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
Forced Breathing
  • Increased activity in DRG:
    • stimulates VRG to become active
    • which activates accessory inspiratory muscles
  • After inhalation:
    • expiratory center neurons stimulate active exhalation
forced breathing112
Forced Breathing

Quiet Breathing

Figure 23–25b

centers of the pons
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
sensory modifiers of respiratory center activities
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
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)
chemoreceptors and oxygen
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)
effect of breathing on ventilation
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
Chemoreceptor Stimulation
  • Leads to increased depth and rate of respiration
  • Is subject to adaptation: decreased sensitivity due to chronic stimulation
changes in arterial p co 2
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
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
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
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
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
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
respiratory disorders
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
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
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
copd chronic bronchitis
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 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
Lung fluid
  • Pleural effusion – fluid buildup in pleural cavity/space (kind of like pericarditis)
  • Pulmonary edema – fills exchange surfaces
cystic fibrosis
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
  • 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
  • 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
  • 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
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