Lecture Respiratory System Part II

Inspiration: gases flow into lungs

Expiration: gases flow out of lungs

P_atm is the pressure exerted by the air surrounding the body

P_atm=760 mm Hg at sea level or 1 P_atm

*respiratory pressures are described relative to P_atm

• Negative respiratory pressure is less than 1P_atm
• Positive respiratory pressure is more than 1P_atm
• Zero  respiratory pressure is 1 P_atm

Also called intra-alveolar pressure

• Pressure in the alveoli
• fluctuates with breathing

*P_pul always eventually equalizes with P_atm

• Pressure in the plural cavity
• fluctuates with breathing

• *always a negative pressure (< P_atm and < P_pul)
• ~4mm Hg below P_pul

• Two inward forces always promote lung collapse:
• 1. elastic recoil of lungs decrease its size
• 2. surface tension on the alveolar reduce its size

• One outward force tends to enlarge the lungs:
• 1. elasticity of the chest wall pulls the thorax outward

*the key is that the close proximity of the pleura holds it together and keeps it negative, like water holding 2 slides together

If P_ip=P_pul then the lungs collapse (Atelectasis)

• P_pul-P_ip= TRANSPULMONARY PRESSURE
• -keeps the airways open
• -the greater the P_trans, the larger the lungs
• 

Plugged bronciholes --> collapse of alveoli

wound that admits air into the pulmonary cavity (pneumothorax)

Inspiration and Expiration are mechanical processes that depend on the volume changes in the thoracic cavity

• Volume change leads to pressure change
• Pressure change leads to gas flow in order to equalize pressure

The relationship between the pressure and volume of gas at a constant temperature

An Active process

• 1. Inspiratory muscles contract (diaphram descends, rib cage rises)
• 2. Thoracic cavity volume increases
• 3. Lungs are stretched; intrapulmonary volume increases.
• 4. Intrapulmonary pressure drops to -1mm Hg
• 5. Air (gases) flow into lungs down its pressure gradient until intrapulmonary pressure is 0 (equal to atmospheric pressure)
• 

Quiet Expiration is normally a passive process

• 1. Inspiratory muscles relax (diaphram rises, rib cage descends due to recoil of costal cartilages)
• 2. Thoracic cavity volume decreases
• 3. Elastic recoil passively, intrapulmonary volume decreases.
• 4. Intrapulmonary pressure rises to +1 mm Hg
• 5. Air (gases) flow out of the lungs down the pressure gradient until the intrapulmonary pressure is at 0 (Atmospheric pressure)

• *forced expiration is an active process: it uses the abdominal and internal intercostal muscles
• 

• Inspiratory muscles consume energy to overcome 3 factors that hunder air passage
• 1. airway resistance
• 2. alveolar surface tension
• 3. lung compliance

Friction (drag) is the major nonelastic source of resistance to gas flow


-->the relationship between flow, pressure, and resistance

DeltaP is the pressure gradient between Ppul and Pip (2 mmHg or less during normal quiet breathing)

small changes to P lead to large changes in F

gas flows inversley with resistance

• 1. large airway diameters in the first part of the conducting zone
• 2. Progressive branching of airways as they get smaller, increasing the total cross-sectional area

The greatest resistance is at the medium sized bronci and resistance disappears at the terminal bronchioles when diffusion drives gas movement

Breathing movements become more strenuous

• Severely constricting or obstruction of bronchioles can:
• 1. prevent life sustaining ventilation
• 2. occur during acute asthma attacks and stop ventilation

Epinephrine dialates bronchioles and reduces R

TV (Tidal Volume): air in and out of lungs during normal quiet breathing-->500ml

IRV (Inspiratory Reserve Volume): amount of air that can be forced during inspiration -->2100-3200ml

ERV (Expiratory Reserve Volume): amount of air that can be forced during expiration --> 1000-1200ml

RV (Residual Volume): amount left in lungs after forced expiration (keeps alveoli open) --> 1200ml

IC (inspiratory capacity): TV+IRV = IC

FRC (functional residual capacity): RV+ERV=FRC

VC (Vital Capacity): TV+IRV+ERV=VC

• TLC (Total lung capacity): RV+VC=TLC
• 

Some inspired air never contributes to gas exchange

Anatomical dead space: volume of the conducting zone (~150ml)

Alveolar dead space: alveoli that cease to act in gas exchange due to collapse or obstruction

Total dead space: sum of both anatomical and alveolar dead space volumes

intrument used to measure respiratory volumes and capacities

• Spirometry can distinguish between:
• 1. obstructive pulmonary disease--> increased airway resistance like bronchitis (increases in TLC, FRC, RV)
• 2. restrictive disorders-->reduction in the TLC, VC, FRC, and RV  due to structural or function lung changes such as fibrosis or TB

these are pulmonary function tests

Minute ventilation: total amount of gas flow into or ou fo the respiratory tract in one minute (normal is about 12 breaths a minute)

FVC (forced vital capacity): gas forcibly expelled after taking a deep breath

FEV (forced expiratory volume): the amount of gas expelled during specific time intervels of FVC

FEV₁: what is expelled in the 1st second, normally about 80% of lungs volume

flow of gases in or out of alveoli in a certain amount of time

AVR= minute ventilation x (TV-dead space)

dead space is constant. rapid, shallow breathing decreases the AVR

AVR is normally 4200ml/min

most are a result of a reflex action

cough, sneeze, crying, laughing, hiccups, and yawns

Total pressure exerted by a mixture of gases is the sum of the pressured exerted by each gas

• the partial pressure of each gas is directly proportional to its percentage in the mixure
• 

When a mixture of gases is in contact with a liquid, each gas will dissolve in the liquis in proprtion to its partial pressure

At equilibrium, the partial pressure in both phases with be equal

• The amount of gas that will dissove in a liquid also depends upon soluability
• -CO₂ is 20x more soluble in water than O₂
• -Very litte N₂ dissolves in water

• It contains more CO2 and water vapor than atmospheric are
• -gas exchange in lungs
• -humidification of air
• -mixing of alveolar gases that occur with each breath

The exchange of O₂ and CO₂ across the respiratory membrane (lung to blood)

• Influenced by:
• 1. partial pressure gradients and gas solubilities
• 2. ventilation-perfusion coupling
• 3. structural characteristics of the respiratory system

• partial pressure gradient for O₂ in the lungs is steep
• -venous blood= 40mm Hg
• -alveolar P_O2 = 104 mm Hg
• *reaches equilibrium of 104 mm Hg in about .25 seconds, abouit 1/3 the time a red blood cell is in the pulmonary capillary

• partial pressure gradient for CO2 is less steep than O2 in the lungs
• -venous blood Pco₂ = 45 mm Hg
• -Alveolar Pco₂ = 40 mm Hg

• **BUT CO₂ is 20x more soluable in plasma than O₂, therefore it diffuses in equal amount with oxygen
• 

• ventilation: amount of gas reaching the alveoli
• perfusion: blood flow reaching the alveoli
• *ventilation and perfusion must be matched (coupled) for efficient gas exchange

• Changes in Po₂ in the alveoli cause changes in the diameters of the arterioles
• -where alveolar O₂ is high, arterioles dialate
• -where alveolar O₂ is low, arterioles constrict

• Changes in Pco₂ in the alveoli cause changes in the diameters of the bronchioles
• -where alveolar CO₂ is high, bronchioles dialate
• -where alveolar CO₂ is low, bronchioles constrict
• 

internal respiration is the capillary exchange of gases in the body tissue though blood

• Partial pressure and diffusion gradiient are reversed compared to external respiration
• -Po₂ in tissue is alweays lower than systemic arterial blood
• -Po₂ of venous blood is 40mm Hg and Co₂ is 45 mm Hg

• 3 ways:
• -1.5% dissolved in plasma
• -98.5% loosely bound to each Fe of Hb in RBCs
• (4 O₂ per Hb)

• Oxyhemoglobin (HbO₂): Hb-O₂ combo
• Reduced Hemoglobin (deoxyhemoglobin)(HHb): hemoglobin that has released it O₂

• Loading and unloading is faciliated by change in shape of Hb
• -As O₂ binds, Hb affnity for O₂ increases
• -As O₂ is released, Hb affinity for O₂ decreses
• (like a following the leader style thing)

*Hb is fully saturated with 4 O₂ or partially saturated with 1-3 O₂

• Po₂
• Temperature
• Blood pH
• Pco₂
• Concentration of BPG

• The oxygen-hemoglobin dissociation curve
• Hb saturation plotted against Po₂ is not linear, but S-shaped
• shows how binding and release of O₂ is influence by the Po₂
• 

• In arterial blood (away from heart):
• -Po₂ = 100 mm Hg
• -Contains 20 ml O₂ per 100 ml blood (20% vol)
• -Hb is 98% saturated
• *any further increases in Po₂ (ex. breathing deeply) produce minimal increases in O₂ binding

• In venous blood (towards heart):
• -Po2 = 40 mm Hg
• -contains 15% vol O₂
• -Hb is 75% saturdated

• *Hb is almost completely saturated at Po₂ of 70 mm Hg
• *further increases in Po₂ produce minimal increase in O₂ binding
• *O₂ loading and delivery to tissues adequate when Po₂ is below normal levels
• *only 20-25% of O₂ is unloaded during on systemic circulation (Rest in venous blood called venous reserve)

• If O₂ levels in tissues drop:
• -more O₂ dissociated from Hb and is used in cells
• -respiratory rate or cardiac output need not increase

Modify structure of Hb and decrease its affinity for O₂

Occur in systemic capillaries

enhance O₂ unloading

• shift the O₂ Hb dissociation curve to the right (decreases shift to the left)
• 

• As cells metabolize glucose...
• -Pco₂ and H+ increase in concentration in capillary blood
• -this declining pH weakens (acidosis) the Hb-O₂ bond (BOHR EFFECT) as the O₂ is unloaded where it is most needed.
• -Heat production then increases which directly and indirectly decreases Hb affinity for O₂

The inadequate delivery of O₂ to tissues

caused by: too few RBCs

• -Anemichypoxia: abnormal or too little Hb
• -Ischemic/Stagnant hypoxia: blocked circulation
• -Histoxic hypoxia: metabolic poisons
• -Hypoxemic hypoxia: pulmonary diseases
• -Carbon monoxide which displaces O₂ from Hb

• 3 Ways:
• - 7-10% dissolved in plasma
• -20% chemically bound to globin of Hb (Carbinohemoglobin)
• -70% as bicarbonate ions (HCO₃^-) in plasma

CO₂ combines with water to form carbonic acid (H₂CO₃) which quickly dissociated into hydrogen and bicarbonate ions


Most of this occurs in RBCs where carbonic anhydrase reversibly and rapidly catalyzes the reaction

• In pulmonary capillaries:
• -HCO₃^- quickly moces into the RBCs and binds with H⁺ to form H₂CO₃
• -H₂CO³ is split by carbonic anhydrase into CO₂ and water
• -CO₂ diffuses into teh alveoli
• 

• In systemic Capillaries:
• -HCO₃^- quickly diffuses from RBCs to plasma
• -the chloride shift occurs: outruse of HCO₃^- from the RBCs is balance as Cl^- moves in from the plasma
• 

The amount of CO₂ transported if affected by the Po₂

The lower the Po₂ and Hb satururation with O₂ the more Co₂ can be carried in the blood

• As more CO₂ enters the blood at the tissues...
• -more O₂ dissociated from Hb (bohr effect)
• -as HbO₂ releases O₂, it more readily forms bonds with Co₂ to form carbinohemoglobin

HCO3^- in plsma is the alkaline reserve of the carbonic acid-bicarbonate buffer system

If H⁺ concentration in the blood rises, excess H⁺ is removed by combining with HCO₃^-

If H⁺ concentration in the blood drops, H₂C0₃ dissociated releasing H+

• Changes in the respiratory rate can also alter the blood pH
• -example: slow shallow breathing allows CO₂ to accumulate in the lungs causing pH to drop
• -As a result, changing ventilation can be used to adjust pH when it is disturbed by metabolic factors (deep breathing with flush out CO₂)

• 1. Dorsal Respiratory group (DRG)
• -near the root CN IX
• -integrates input from peripheal stretch and chemoceptors
• (relays the messages to the VRG)

• 2. Ventral Respiratory group (VRG)
• -rhythm generating and integrative center
• -sets eupnea (12-15 breaths/minute)

Inspiratory neurons excite inspiratory muscles via the phrenic and intercostal nerves

• Expiratory neurons simply inhibit the inspiratory neurons
• 

They influence and modify the activity of the VRG

Smooth out transition between inspiration and expiration

Reciprocal inhibition of two cets of interconnected neuronal netowkds in the medulla sets the rhythm

Depth: how activily the respiratory center stimulates the respiratory muscles

Rate: how long the respiratory center is active

• Influence of CO₂:
• -If Pco₂ levels rise (hypercapnia), CO₂ accumulates in the brain
• -H+ stimulates the central chemoceptors of the brain stem
• -Chemoceptors synapse with the respiratory regulatory centers, increasing the depth and rate of breathing
• *Rising CO2 levels are the most powerful respiratory stimulant
• 

• Hyperventilation: increased depth and rate of breathing that exceeds the body's need to remove CO2
• -causes hypocapnia
• -may cause cerebral vasocronstriction that occurs when Pco2 is abnormally low

Apnea: period of breathing ceccation tha toccurs when Pco2 is abnormally low

• Influence of Po2
• -peripheal chemoceptors in the aortic and carotid bodies are O2 sensors
• -when excited, they cause the respiratory centers to increase ventilation
• -substantial drops in Po2 (to 60 mm Hg) must occur in order to stimulate increased ventilation

• Influence of the arterial pH
• -decreased pH may reflect CO2 retention, accumulation of lactid acid, excess keton bodies in those with diabetes
• -respiratory sustem contraols will attempt to raise the pH by increasing the respiratory rate and depth

• Hypothalamic controls act through the limbic system to modify the rate and depth of respiration for emotion of pain
• ex: breath holding that occurs during anger or gasping with pain

a rise in body temp acts to increase respiratory rate

cortical controls are direct signals from the cerebral motor cortex that bypass medullary cords-->voluntary control like breath holding

Receptors in the bronchioles respond to irritants

promote reflexive constriction of air passages

receptors in te larger airways mediate the cough and sneeze reflexes

• stretch receptors in the plurae and airways are stimulated by lung inflation
• -inhibitory signals to the medullary respiratory centers end inhalation and allow expiration to occur
• -acts more as a protective response to stop over stretching of lungs

Adjustments are geared to both the intestity and the duration of the work out

Hyperpnea: increase in ventilation (10-20 fold) in response to metabolic needs

Pco₂, Po₂, and pH remain suprisingly constant during respiration

• 3 neural factors cause increase in ventilation at start
• 1. Psychological stimuli-anticipation of work out
• 2. Simultaneous cortical motor activiation of skeletal muscles and respiratory centers
• 3. exictatory impulses reaching respiratory center from propricenters in moving muscles, tendons, and joints

• When exercise ends:
• -ventilation declines suddenly as the three neural factors shut off

• Quick travel to altitudes above 8000ft may produce symptoms of Acute Mountain Sickness (AMS)
• -heaches, shortness of breath, nausea, and dizziness
• -in severe cases, lethal cerebral and pulmonary edema

• Acclimization: respiratoy and hematopoietic adjustments to altitude
• -chemoreceptors become more responsive to Pco₂, Po₂ declines
• -substantial deline in Po₂ directly stimulates peripheal chemoreceptors
• -result: minute ventilation increases and stabilizes in a few days to 2-3L/min higher than at sea level

decline in blood O₂ stimulates the kidneys to accelerate production of EPO, RBC numbers increase slowly to provide long term compensation