Respiratory System

1
Chapter 22.

• Respiratory System

2
Overview

• Respiratory anatomy
• Respiration
• Respiratory musculature
• Ventilation, lung volumes and capacities
• Gas exchange and transport
• O2
• CO2
• Respiratory centers
• Chemoreceptor reflexes
• Respiratory Diseases

3
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

4
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

5
Components of the Respiratory System
Figure 231
6
Organization of the Respiratory System

• Upper respiratory system
• Nose, nasal cavity, sinuses, and pharynx
• Lower respiratory system
• Larynx, trachea, bronchi and lungs

7
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

8
The Respiratory Epithelium
Figure 232
9
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 (lt 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

10
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

11
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

12
Upper Respiratory Tract
Figure 233
13
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

14
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

15
Lower Respiratory Tract

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

16
Anatomy of the Larynx
Figure 234
17
Cartilages of the Larynx

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

18
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

19
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

20
Sphincter Functions of Larynx

• The larynx is closed during coughing, sneezing,
  and Valsalvas maneuver
• Valsalvas 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

21
The Glottis
Figure 235
22
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

23
Anatomy of the Trachea
Figure 236
24
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 1520 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?

25
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

26
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

27
Bronchial Tree
Figure 239
28
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

29
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)

30
The Bronchioles
Figure 2310
31
Conducting Zones
Figure 22.7
32
Lungs
Figure 237
33
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

34
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

35
Relationship between Lungs and Heart
Figure 238
36
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

37
Respiratory Zone
38
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

39
Alveolar Organization
Figure 2311
40
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

41
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

42
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

43
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

44
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

45
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

46
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

47
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

48
Gas Pressure and Volume
Figure 2313
49
Boyles 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

50
Pulmonary Ventilation
Respiration Pressure Gradients
Figure 2314
51
Respiration

• Air flows from area of higher pressure to area of
  lower pressure (its 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)

52
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

53
Pressure Relationships
Figure 22.12
54
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)

55
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

56
P and V Changes with Inhalation and Exhalation
Figure 2315
57
The Respiratory Pump

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

58
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)

59
The Respiratory Muscles
Figure 2316a, b
60
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

61
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)

62
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
63
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

64
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

65
Dead Space

• Only a part of respiratory minute volume reaches
  alveolar exchange surfaces
• Volume of air remaining in conducting passages is
  anatomic dead space

66
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

67
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

68
Respiratory Volumes and Capacities
Figure 2317
69
Lung Volumes

• Resting tidal volume
• Expiratory reserve volume (ERV)
• Residual volume
• minimal volume (in a collapsed lung)
• Inspiratory reserve volume (IRV)

70
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

71
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

72
The Gas Laws

• Rate of diffusion depends on physical principles,
  or gas laws
• Boyles law P 1/V
• Daltons law each gas contributes to the total
  pressure in proportion to its number of molecules
• Henrys Law at a given temperature, the amount
  of a gas in solution is proportional to partial
  pressure of that gas

73
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
• Daltons Law says PO2 .209 x 760 160mmHg

74
Normal Partial Pressures

• In pulmonary vein plasma (after visiting lungs)
• PCO2 40 mm Hg
• PO2 100 mm Hg
• PN2 573 mm Hg

75
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)

76
Henrys Law
Figure 2318
77
Henrys 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

78
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

79
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)

80
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

81
Respiratory Processes and Partial Pressure
Figure 2319
82
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

83
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

84
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
85
Environmental Factors Affecting Hemoglobin

• PO2 of blood
• Blood pH
• Temperature
• Metabolic activity within RBCs

Respiration Hemoglobin
Respiration Percent O2 Saturation of Hemoglobin
86
Hemoglobin Saturation Curve
Figure 2320 (Navigator)
87
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)

88
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

89
Carbon Monoxide Poisoning

• CO from burning fuels
• Binds irreversibly to hemoglobin and takes the
  place of O2

90
pH, Temperature, and Hemoglobin Saturation
Figure 2321
91
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

92
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
93
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

94
Fetal and Adult Hemoglobin
Figure 2322
95
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

96
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

97
Carbon Dioxide Transport
Figure 2323 (Navigator)
98
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

99
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

100
CO2 inside RBCs

• CO2 H2O H2CO3
• (Enzyme carbonic anhydrase)
• H2CO3 H HCO3-

101
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

102
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

103
Summary Gas Transport
Figure 2324
104
Influence of Carbon Dioxide on Blood pH

• The carbonic acidbicarbonate 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

105
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

106
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)

107
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

108
Ventilation-Perfusion Coupling
PO2
PCO2
in alveoli
Reduced alveolar ventilation excessive perfusion
Reduced alveolar ventilation reduced perfusion
Pulmonary arterioles serving these
alveoli constrict
PO2
PCO2
in alveoli
Enhanced alveolar ventilation inadequate
perfusion
Enhanced alveolar ventilation enhanced perfusion
Pulmonary arterioles serving these alveoli dilate
Figure 22.19
109
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

110
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

111
Forced Breathing

• Increased activity in DRG
• stimulates VRG to become active
• which activates accessory inspiratory muscles
• After inhalation
• expiratory center neurons stimulate active
  exhalation

112
Forced Breathing
Quiet Breathing
Figure 2325b
113
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

114
Respiratory Centers and Reflex Controls
Figure 2326
115
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

116
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)

117
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)

118
Chemoreceptor Responses to PCO2
Figure 2327
119
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

120
Chemoreceptor Stimulation

• Leads to increased depth and rate of respiration
• Is subject to adaptation decreased sensitivity
  due to chronic stimulation

121
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

122
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?

123
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

124
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 cant deliver it to tissues
• Increase RR but not HR O2 is coming in more
  quickly but it cant get to the tissues
• Also, if BP falls, RR and HR rise and vice versa

125
The HeringBreuer 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

126
Changes in Respiratory System at Birth

• Before birth pulmonary vessels are collapsed and
  lungs contain no air
• During delivery blood PO2 falls, 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

127
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)

128
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

129
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

130
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.

131
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

132
Lung fluid

• Pleural effusion fluid buildup in pleural
  cavity/space (kind of like pericarditis)
• Pulmonary edema fills exchange surfaces

133
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 doesnt follow and neither does
  water.
• Sticky mucus builds up inside lungs and
  infections are common. Often fatal before age 30

134
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

135
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

136
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137
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

138
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