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Topics to Review. pH Buffers Diffusion Law of mass action (chemistry). Functions of the Respiratory System. Provides a way to exchange O 2 and CO 2 between the atmosphere and the blood oxygen is used by the cells of the body solely for the process of aerobic respiration

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topics to review
Topics to Review

pH

Buffers

Diffusion

Law of mass action (chemistry)

functions of the respiratory system
Functions of the Respiratory System

Provides a way to exchange O2 and CO2 between the atmosphere and the blood

oxygen is used by the cells of the body solely for the process of aerobic respiration

carbon dioxide is a waste product of aerobic respiration and must be removed from the body

Regulation of body pH

Protection from inhaled pathogens and irritating substances

Vocalization

the respiratory system
The Respiratory System

Together, the respiratory system and the circulatory system deliver O2 to cells and remove CO2 from the body through 3 processes

Pulmonary ventilation (breathing)

movement of air into and out of the lungs

Inspiration/inhalation and expiration/expiration

Gas Exchange

O2 and CO2 are exchanged between the air in the lungs and the blood

O2 and CO2 are exchanged between the blood and the cells

Transport

movement of O2 and CO2between the lungs and cells

organization of the respiratory system
Organization of the Respiratory System
  • Anatomically, the respiratory system includes the:
    • upper respiratory tract (mouth, nasal cavity, pharynx and larynx)
    • lower respiratory tract (the trachea, 2 primary bronchi, the branches of the primary bronchi and the lungs)
  • Functionally, the respiratory system includes the:
    • the conducting zone (semi-rigid airways) lead from the external environment of the body to the exchange surface of the lungs
    • the exchange surface (respiratory zone) consists of the alveoli which are a series of interconnected sacs (surrounded by pulmonary capillaries) which expand and collapse during ventilation and allows oxygen and carbon dioxide to be exchanged between the air in the lungs and the blood
the thorax and respiratory muscles
The Thorax and Respiratory Muscles

The bones of the spine and ribs and their associated skeletal muscles form the thoracic cage

Contraction and relaxation of these muscles alter the dimensions of the thoracic cage which promotes ventilation

2 sets of intercostal muscles connect the 12 pairs of ribs

additional muscles (sternocleidomastoid and scalenes) connect the head and neck to the sternum and the first 2 ribs

a dome-shaped sheet of skeletal muscle called the diaphragm forms the floor

the abdominal muscles also participate in ventilation

the pleural membranes and fluid
The Pleural Membranes and Fluid

Within the thorax are 2 double layered pleural sacs surrounding each of the 2 lungs

Parietal pleura

lines the interior of the thoracic wall and the superior face of the diaphragm

Visceral pleura

covers the external surface of the lungs (alveoli)

A narrow intrapleural space between the pleura is filled with 25 mL of pleural fluid which holds the 2 layers together by the cohesive property of water

serves to lubricate the area between the thorax and the outer lung surface

holds the lungs tight against the thoracic wall

prevents lungs from completely emptying even after a forceful expiration

proximal respiratory tract
Proximal Respiratory Tract

Air enters the upper respiratory tract through either the mouth or nose and passes through the pharynx

warms and humidifies (adds H2O) inspired air

hair in the nose filters inspired air of any dust

Air then passes through the larynx or“voice box”

contains the vocal cords (bands of connective tissue) which tighten and vibrate to produce sound

Air continues into the lower respiratory tract through the trachea which is a semi-flexible tube held open by C-shaped rings of cartilage

The distal end of the trachea splits into 2 primary bronchi which lead to the 2 lungs branch repeatedly into progressively smaller bronchi

the walls of the bronchi are supported by cartilage

slide14
The inner (mucosal) surface of the trachea and bronchi consists of epithelial tissue that functions as the mucocilliary escalator to trap and eliminate debris

Goblet cells

secrete mucus to trap debris in inspired air

Pseudostratified ciliated columnar epithelium

move debris trapped in mucus up towards the mouth for expectoration/swallowing

middle and distal respiratory tract
Middle and Distal Respiratory Tract

Bronchi send air into the bronchioles

these airways are supported by smooth muscle only

contraction causes bronchoconstriction which decreases the airway diameter and makes ventilation more difficult

increases airway resistance to decrease flow

relaxation causes bronchodilationincreases the airway diameter which makes ventilation easier

decreases airway resistance to increase flow

branch into respiratory bronchioles which begins the

Bronchioles move air into the blind sacs called alveoli where gas exchange occurs (respiratory zone)

approximately 150 – 300 million per lung

anatomy of alveoli
Anatomy of Alveoli

Composed of very thin(simple)epithelial tissue consisting of 2 predominant alveolar cell types

Type I (squamous)alveolar cells

allows for very rapid exchange of O2 and CO2

Type II or great (cuboidal) alveolar cells

secrete surfactant into the alveolar lumen

Exterior surface is surrounded by large numbers of blood capillaries for gas exchange and large numbers of elastic fibers to aid in lung recoil during exhalation

White blood cells (macrophages) within the lumen of the alveoli protect against inhaled pathogens

Alveoli represents an enormous surface area for gas exchange (2800 square feet or half of a football field)

properties of alveoli
Properties of Alveoli

Compliant

ability to be easily stretched or deformed

allows lungs to fill up with air during inspiration

attributed by the very thin Type I alveolar cells

Elastic

ability to resist being stretched or deformed

allows lungs recoil (deflate) during expiration

attributed by:

interior (luminal) surface covered with a thin film of water which creates surface tension at the air-fluid interface (surface) of the alveoli

the elastic fibers surrounding the alveoli

alveolar surface tension and elasticity
Alveolar Surface Tension and Elasticity

During inhalation the alveoli expand and adjacent water molecules on the luminal surface are pulled apart from one another causing the H-bonds between them to be stretched (like a spring) creating tension

During exhalation the tension within the H-bonds is released which returns the water molecules to their original spacing pulling the alveoli inward allowing them to recoil

surfactant
Surfactant

Type II alveolar cells secrete surfactant (“surface active agent”) which is a fluid consisting of amphiphilic molecules into the lumen of the alveoli

These molecules disrupt the cohesive forces between water molecules by inserting themselves between some of the water molecules preventing H-bonds from forming and thus decreases the surface tension of the water on the luminal surface

Reducing surface tension simultaneously increases compliance and reduces elasticity of the alveoli which greatly decreases the amount of effort needed to inflate the lungs while retaining the ability to deflate the lungs

Without surfactant, the muscles of respiration cannot contract with enough force to overcome the alveolar surface tension resulting in the inability to breathe

pulmonary ventilation
Pulmonary Ventilation

The movement of air into and out of the airways occurs as a result of increasing and decreasing the dimensions of the thoracic cavity through the contraction and relaxation of the skeletal muscles of respiration

Since the alveoli are “stuck” to the interior surface of the thorax via the pleura, dimensional changes in the thoracic cavity result in the same dimensional changes in the alveoli

Dimensional changes in the alveoli create air pressure changes in the alveoli as expressed by Boyle’s Law

boyle s law
Boyle’s Law

The mathematical inverse relationship that describes what happens to the pressure of a gas or fluid in a container following a change in the volume (dimensions) of the container

If the volume of a container increases, then pressurewithin the container mustdecrease

If volume of a container decreases, then pressure within the container mustincrease

V1xP1= V2xP2

V = volume of a container

P = pressure within the container

force of collisions between molecules within the container and the wall of the container

determined by the “concentration” of molecules within the container

pulmonary ventilation25
Pulmonary Ventilation

Changes in the pressure in alveolarair (alv) create air pressure gradients between the air in the alveoli and the atmospheric air that surrounds our bodies (atm) which drive air flow into and out of the lungs

Air always flows from an area of higher pressure to an area of lower pressure

When alv<atminspiration occurs

air flows into the lungs

When alv>atmexpiration occurs

air flows out of the lungs

When alv=atm no air flow occurs

at transition between inspiration and expiration

inspiration
Inspiration

Before inspiration (at end of previous expiration), the alv (0 mm Hg) = atm (0 mm Hg)(no air movement)

Expansion of the thoracic cavity (by the contraction of the diaphragm, the external intercostals, the scalenes and the sternocleidomastoid) pulls the alveoli open which increases their volume and decreases their pressure (-1 mm Hg)

the alveolar pressure decreasesbelowatmosphericpressure, creating a pressure gradient resulting in inspiration

As the alveoli fill with air (more molecules), the alv pressure increases until it equals atm pressure

Inspiration ends when alv (0 mm Hg) = atm (0 mm Hg)

expiration
Expiration

Expiration is a passive process that does not require muscle contraction to occur

Before expiration, (at end of previous inspiration), the alv (0 mm Hg) = atm (0 mm Hg)(no air movement)

Expiration begins as action potentials along the nerves that innervate the muscles of inspiration cease allowing these muscles to relax returning the diaphragm and ribcage to their relaxed positions

allows the alveoli to collapse which decreases their volume and increases their pressure (1 mm Hg)

the alveolar pressure increasesaboveatmospheric pressure, creating a pressure gradient resulting in quiet (passive) expiration

As the alveoli empty with air, the alv pressure decreases until it equals atm pressure

Expiration ends when alv (0 mm Hg) = atm (0 mm Hg)

control of ventilation
Control of Ventilation

Ventilation occurs automatically whereby the contraction of the skeletal muscles of respiration are controlled by a spontaneously firing network of neurons in the brainstem but can be controlled voluntarily up to an extent

respiratory centers of the medulla
Respiratory Centers of the Medulla

The dorsal respiratory group (DRG) is the pacesetter for ventilation where in a person at rest initiates bursts of action potentials every 5 seconds setting a quiet ventilation rate of 12 breaths/minute

action potentials travel down the phrenic nerve stimulating the diaphragm and the intercostal nerves stimulating the external intercostals

periods of time between these bursts action potentials allow for expiration as the muscles relax

receptors of respiration
Receptors of Respiration

Various chemoreceptors (monitoring changes in H+, CO2 or O2) initiate reflexes which alter the firing of action potentials by the DRG promoting different ventilation patterns

An increase in either CO2 (hypercapnia) or H+ will stimulate the DRG and result in an increase in respiration rateanddepth (hyperventilation)

A decrease in either CO2 or H+ will inhibit the DRG and result in a decrease in respirationrateanddepth (hypoventilation)

Only a substantialdecrease in systemic arterial O2(<60 mm Hg) will stimulate the DRG and result in hyperventilation

an increase in O2will inhibit the DRG and result in hypoventilation

respiratory centers of the medulla33
Respiratory Centers of the Medulla

The ventral respiratory group (VRG), or expiratory center is a group of neurons that fire action potentials only during forced expiration

forced expiration requires an additional decrease in thoracic and lung volume over what passive expiration can provide

stimulates the contraction of the internalintercostals (pull ribs inward) and the abdominals (decrease abdominal volume and displace the liver and intestines upward)

further decreases the thoracic cavity volume allowing the lungs to collapse to a greater extent increases the amount of air that exits the lungs

respiratory centers of the pons
Respiratory Centers of the Pons

Pneumotaxic center

sends action potentials every 5 seconds to the DRG which inhibits the DRG from firing action potentials to the diaphragm and external intercostals

ending inspiration

providing a smooth transition between inspiration and expiration

slide35

The amount (volume) of air that enters or exits the lungs during either quiet or forced breathing can be plotted on a graph called a spirogram

lung volumes
Lung Volumes

Tidal volume (TV)

volume of air that moves into and out of the lungs with each breath during quiet ventilation (500 ml)

Inspiratory reserve volume (IRV)

additional volume of air that can be inspired forcibly into the lungs after a tidal inspiration

Expiratory reserve volume (ERV)

additional volume of air that can be expired forcibly from the lungs after a tidal expiration

Residual volume (RV)

volume of air left in the lungs after forced expiration

this air can NEVER be expired

lung capacities
Lung Capacities

The addition of 2 or more specific lung volumes is referred to as a capacity

Inspiratory capacity(IC)

total amount of air that can be inspired after a tidal expiration (IRV + TV)

Functional residual capacity(FRC)

amount of air remaining in the lungs after a tidal expiration (RV + ERV)

Vital capacity(VC)

the total amount air capable of entering/exiting the airways (TV + IRV + ERV) (4600 ml)

Total lung capacity(TLC)

sum of all lung volumes (5800 ml)

gas exchange and dalton s law
Gas Exchange and Dalton’s Law

The exchange of O2and CO2 between alveolar air and capillary blood and between capillary blood and body cells occur simultaneously by diffusion where each gas moves down its respective concentration gradient

The concentration of a gas can be expressed in terms of pressure (or as a partial pressure), typically in units of mmHg (millimeters of mercury)

Air found within the alveoli (at sea level) is a mixture of gasses and has a total pressure of 760 mmHg

13.2% of the molecules in alveolar air are O2, and therefore provides only 13.2% of 760 mmHg, or 100 mmHg, which is its partialpressure (PO2)

5.2% of the molecules in alveolar air are CO2, and therefore provides only 5.2% of 760 mmHg, or 40 mmHg, which is its partial pressure(PCO2)

simultaneous gas exchange
Simultaneous Gas Exchange

ALVEOLI of the lungs

Inhaled O2 diffuses out of the alveoli into the blood

the amount of O2 in the blood increases

the O2 is pumped by the heart to the cells of body

CO2 diffuses out the blood into the alveoli to be subsequently exhaled

the amount of CO2 in the blood decreases

CELLS of the body

O2 diffuses out of the blood and into the cells

the amount of O2 in the blood decreases

the O2 is used by the cells for aerobic cellular respiration

The CO2 produced as a product of aerobic cellular respiration diffuses out the cells and into the blood

the amount of CO2 in the blood increases

the CO2 is pumped by the heart to the lungs

alveolar gas exchange
Alveolar Gas Exchange

Blood that is flowing towards the lungs is:

low in O2 (PO2 = 40 mmHg)

high in CO2 (PCO2 = 46 mmHg)

O2 diffuses from the alveoli into the blood because:

the PO2 in the alveolus is greater (100 mmHg) than the PO2 in the blood (40mmHg)

CO2 diffuses from the blood into the alveoli because:

the PCO2 in the blood is greater (46 mmHg) than the PCO2 in the alveolus (40 mmHg)

Each gas diffuses until they reach equilibrium with the pressures in the alveoli which DO NOT CHANGE since ventilation continuously adds O2 and removes CO2

After gas exchange at the lungs has been completed, the blood leaving the lungs has a PO2 of 100 mm Hg and a PCO2 of 40 mm Hg

systemic gas exchange
Systemic Gas Exchange

Blood that is delivered to all the cells of the body is:

high in O2 (100 mmHg)

low in CO2 (40 mmHg)

O2 diffuses from the blood into the interstitial fluid

PO2 in the blood is greater (100 mmHg) than the PO2 in the interstitial fluid (40mmHg)

CO2 diffuses from the interstitial fluid to the blood

PCO2 in the interstitial fluid is greater (46 mmHg) than the PCO2 in the blood (40 mmHg)

Each gas diffuses until they reach equilibrium with the pressures in the cell which DO NOT CHANGEsincecell respiration continuously uses O2 and produces CO2

After gas exchange at the cells has been completed, the blood leaving the cells has a PO2 of 40 mm Hg and a PCO2 of 46 mm Hg

gas transport in blood
Gas Transport in Blood

The law of mass action plays an important role in how O2 and CO2 are transported

As O2 and CO2 are added to or removed from the blood their respective concentration changes in blood disturb the equilibrium of reactions, shifting the balance between reactants and products

oxygen transport in blood
Oxygen Transport in Blood

The vast majority of O2 (98%) in blood is found within erythrocytes (red blood cells (RBCs)) bound to the protein hemoglobin (Hb)

in pulmonary capillaries when plasma PO2 increases as O2 diffuses in from alveoli, O2 attaches to Hb

Hb + O2 HbO2

at cells where O2 is being used and plasma PO2 decreases, O2 detaches from Hb and enters the cell

HbO2 → Hb + O2

Overall the binding of oxygen to hemoglobin is reversible and is expressed as Hb + O2 ↔ HbO2

if O2 increases, then reaction shifts to the right

if O2 decreases, then reaction shifts to the left

Plasma (fluid portion of blood) cannot hold much O2 (2%) since it is only slightly soluble in water

hemoglobin hb
Hemoglobin (Hb)

Protein made of 4 polypeptide chains (subunits) each containing a heme group

each heme group contains one atom of iron (Fe) (makes RBCs/blood red) in the center which is capable of binding to one molecule of O2

A single molecule of hemoglobin can load, carry and drop off up to 4 O2 between the alveoli of the lungs and respiring tissues of the body

Each RBC is filled with 280 million molecules of Hb

can carry 1.12 billion molecules of O2

Since there are 25 trillion RBCs in circulation

the blood can theoretically transport up to 28,000,000,000,000,000,000,000 molecules of O2

oxygen transport vs oxygen consumption
Oxygen Transport vs. Oxygen Consumption

In a person at rest, 1000 mL of O2 per minute is delivered to respiring tissues

plasma can carry 15 mL of O2 per minute

RBCs can carry 985 mL of O2 per minute

In a person at rest, respiring tissues use only 250 mL of O2 per minute and accordingly the blood drops off only what the cells need, or 25% of its “payload”

the remaining oxygen circulates back to the lungs

The remaining 75% of the oxygen that remains in blood is regarded as a reservoir which is available to respiring cells when their use of oxygen increases such as during exercise

factors that influence o 2 and hb binding
Factors that Influence O2 and Hb Binding

5 parameters influence both the loading of O2 onto and unloading of O2 off from Hb which determines the the number of O2 molecules that are bound to a single Hb either at the lungs or at respiring tissues

the PO2of the blood

100 mmHg at the lungs

40 mmHg at the respiring tissues

the PCO2of the blood

46 mmHg at the respiring tissues

40 mmHg at the lungs

the temperature of the blood

the [H+] (pH) of the blood

the[2,3-DPG] in red blood cells

carbohydrate intermediate of glycolysis

changes as metabolic rate changes

influence of p o2 on hemoglobin saturation
Influence of PO2 on Hemoglobin Saturation

An oxygen-hemoglobin association (or dissociation) curve relates the amount of oxygen that is bound to hemoglobin (expressed as % hemoglobin saturation with O2)at a particular PO2 in the blood

the greater the PO2 in the blood, the more O2 is bound to Hb

The Hb at the lungs (PO2 = 100) is 100% saturated (bound to 4 O2)

In a person who is at rest the Hb at the cells (PO2 = 40) is 75% saturated (bound to 3 O2)

one molecule of O2 moves off of Hb and enters the cells of the respiring tissues

If the cells of the respiring tissues use more O2, the blood PO2 at the cells will decrease below 40 mmHg promoting more O2 to be unloaded off of Hb

other factors influencing hemoglobin saturation
Other Factors Influencing Hemoglobin Saturation

Blood temperature, blood [H+], blood PCO2 and concentrations of 2,3-DPG in RBCs each influence the binding (affinity/attractiveness) of O2 to Hb

An increase in any of these factors in the blood at respiring cells willdecrease the affinity of Hb for O2at respiring tissues

increase O2 unloading at respiring tissues

“right shift” of the O2 -Hb dissociation curve

Adecrease in any of these factors in the blood at respiring cells will increase the affinity of Hb for O2at respiring tissues

decrease O2 unloading at respiring tissues

“left shift” of the O2 -Hb dissociation curve

carbon dioxide transport
Carbon Dioxide Transport

CO2 that diffuses out of a respiring cell is transported in the blood in 3 forms:

as bicarbonate ion (HCO3–) in plasma (70%)

CO2 can be converted into bicarbonate ions and bicarbonate ions can be converted into CO2 through the reversible chemical reaction

CO2 + H2O ↔ H2CO3 ↔ H+ + HCO3-

which obeys the laws of mass action

as carbaminohemoglobin

bound to amino acids (not heme) of Hb (23%)

as dissolved gas in plasma (7%)

CO2 is 20 times more soluble in plasma than O2 therefore more can be carried by plasma

conversion of co 2 to hco 3
Conversion of CO2 to HCO3–

CO2 + H2O → H2CO3 → H+ + HCO3-

CO2 diffuses out of a respiring systemic tissue cell and enters a RBC, which increases the amount of CO2 in the RBC

inside the RBC,carbonic anhydrase combines CO2 and H2O forming carbonic acid (H2CO3)

H2CO3 quickly dissociates into hydrogen ions (H+) and bicarbonate ions (HCO3-) in the RBC

creates a high [HCO3-] in the RBC

creates a high [H+] in the RBC

Hb (which just dropped off some of its O2) acts as a buffer by binding to the H+ produced in order to prevent a decrease in the pH of the RBC

respiratory acidosis
Respiratory Acidosis

CO2+ H2O↔H2CO3 ↔H+ + HCO3–

  • An increase in the PCO2 of the body will drive the above reaction to the right resulting in the synthesis of excessive amounts of H+ causing the body pH to decrease (acidic)
    • respiratory acidosis (pH < 7.4) can denature proteins and depress the CNS
  • Chemoreceptors will stimulate the DRG to increase the ventilation rate and depth (hyperventilation)
    • removes CO2 from the body faster resulting in a decrease in CO2 levels
    • causes the above reaction to proceed to the left decreasing the amount of H+
      • increasing the pH of the body back to 7.4
respiratory alkalosis
Respiratory Alkalosis

CO2+ H2O↔H2CO3 ↔H+ + HCO3–

  • A decrease in the PCO2 of the body will drive the above reaction to the left resulting in a decrease in the amount of H+ causing the body pH to increase basic (alkaline)
    • respiratory alkalosis (pH > 7.4) can denature proteins and depress the CNS
  • Chemoreceptors will inhibit the DRG to decrease the ventilation rate and depth (hypoventilation)
    • removes CO2 from the body more slowly resulting in an increase in CO2 levels
    • causes the reaction to proceed to the right increasing the amount of H+
      • decreasing the pH of the body back to 7.4
transport of co 2 as hco 3
Transport of CO2 as HCO3–

Thehigh [HCO3-] in the RBC promotes the diffusion of HCO3-outof the RBC into blood plasma

HCO3- is more soluble than CO2 therefore more can be carried

the volume of plasma is greater than the collective volume of the cytosol of the RBCs and thus has a greater capacity to carry HCO3- (CO2)

Cl- diffuses from the plasma into the RBC to electrically counterbalance the diffusion of HCO3-out of the RBC (chloride shift)

HCO3- circulates back to the lungs in the plasma

conversion of hco 3 to co 2
Conversion of HCO3– to CO2

H+ + HCO3-→ H2CO3 → CO2 + H2O

  • As the blood flows through the pulmonary capillaries, CO2 diffuses out of the plasma and RBCs and enters the alveoli, which decreases the amount of CO2 in the RBC
  • HCO3- diffuses from the plasma into the RBCs which increases the amount of HCO3- in the RBC
    • Cl- diffuses out of the RBC (reverse chloride shift)
  • In the RBC, H+ and HCO3- combines to form H2CO3
    • H2CO3 is then converted by carbonic anhydrase to CO2and H2O
      • CO2 diffuses out of the RBC and into the alveoli and removed from the body on the next expiration