Respiration

Pulmonary structure and function

Functions of the respiratory system

1. Supply O2 required for metabolism

2. Eliminate CO2 produced in metabolism

3. Regulate H⁺ concentration to maintain acid-base balance

Anatomy of ventilation

• Nasal passage → trachea → lungs → 

Mechanics of breathing

Inspiration

• Pressure in the lungs is less than atmospheric pressure

Expiration

• Predominantly passive

• Recoil of stretched lung

Exercise

• More active, forceful

Lung Volumes & Capacities

Static Lung Volume = Dimensional Component for air movement, No time limit → VOLUME CANNOT CHANGE OVER TIME

Dynamic Lung Volume = Power component of pulmonary performance, Time limit → Incorporates muscle activation, measures how well we exhale 

We inhale more than we exhale, because you have more muscle that help inhale air then to exhale 

Dynamic Lung volumes

• Consider volume and speed of air movement

• Depends on resistance of pulmonary airways, chest wall and lung tissue

1. Forced expiratory volume: Forced vital capacity

• FEV_1.0 = % of FVC expelled in 1 second

• Reflects expiratory power and overall resistance to air movement in lungs

• Normal >85%

• COPD <40%

2. Maximum Voluntary Ventilation

• Healthy men: 140-180 L/min

• Healthy women: 80-120 L/min

• Cross country Skiing > 200 L/min

• COPD: ~ 40% of predicted normal

Cardiac output at rest = 5L

Cardiac output at moving = 20L

Minute ventilation (V_E)

• Breathing frequency x Tidal volume

• Increased rate or depth of breathing can increase minute ventilation 

Normal Values

• 6L/min = 12 x 0.5L/min (REST)

• 70L/min = 30 x 2.5L/min (Moderate exercise)

• 150L/min = 50 x 3.0L/min (Intense exercise) 

• 200L/min has been measured in elite

V_T rarely exceeds 55-65% of FVC

Alveolar Ventilation (V_A)

• The portion of V_E that mixes with the air in the alveolar chambers

DEAD SPACE

• Anatomical

  • Nose, mouth airways

  • 150-200mL (~30% resting V_T)

• Physiological

  • Alveoli under-perfused by blood 

  • Alveoli inadequately ventilated 

  • Negligible volume in healthy

  • Adequate gas exchange impossible if dead >60% of lung volume

MINUTE VENTILATION DOES NOT EQUAL ALVEOLAR VENTILATION

Gas exchange basics

• O2 supply depends on its:

  • Conteration

  • Pressure

• Ambient Air concentrations

  • O2: 20.93%

  • CO2: 0.03%

  • N2: 79.04%

• Sea level pressure = 760 mmHg

  • Changes slightly with weather

  • Decreased with altitude 

Concentrations and partial pressure

• Partial pressure = concentration % x Total pressure of gas mixture

Alveolar Air

• Differs considerably from ambient or tracheal air since CO2 constantly enters alveoli from the blood

• Partial pressure in alveolus = pressure O2 and CO2 exert on the alveolar side of respiratory membrane

• NOT constants, but continually vary slightly

Movement of Gases

Pressure differential: Net diffusion of gas occurs when a difference exists in partial pressure

Solubility: Reflects the quantity of gas dissolved in fluid at a given pressure

Solubility of CO2 in blood is 25x > than O2

Fick’s Law of Diffusion

Rate of gas diffusion = Tissue area X Gas diffusion coefficient X partial pressure difference between sites (P2-P1 Pressure differential)/ Tissue thickness

Alveoli: Very large surface area and very thin single cell membrane

Gas exchange in the body

Pressure gradients favour exchange by passive diffusion

Arterial blood has more O2 then CO2 until capillary

Partial pressure decreases more after skeletal muscle

DURING EXERCISE?

Arterial blood does not change during exercise, only under some sort of respiratory disease

VO2max at altitude

• Location impacts performance

• Lower the altitude, higher the VO2max

High Altitude Pulmonary Edema (HAPE)

At altitude: PO2 is low

• Hypoxia causes vasoconstriction of small arteries

• With the same cardiac output, this vasoconstrictions will increase pulmonary BP

• Force fluid into interstitial space or to alveoli causing pulmonary edema and decreased gas exchange

Hypercapnia → condition of high CO2

Hypocapnia → condition of low CO2

Hyperoxia → condition of high O2

Hypoxia → Condition of low O2

Hyperpnea → increased depth of breathing (with or without a increase in rate

O2 and CO2 transport in the blood

O2 and hemoglobin

O2 carrying capacity = Hb (g/100ml) x O2 capacity of Hb

Male = 15-16g Hb/100mL blood x 1g of Hb can combine with 1.34ml O2

Female 14g x 1g of Hb can combine with 1.34 O2

O2 carrying capacity = 15g Hb/100mL blood x 1.34 O2/g Hb = 20.1mL O2 / 100ml blood

%saturation = (total O2 combined with Hb / O2 carrying capacity of Hb) x 100

Oxyhemoglobin Dissociation Curve

• Partial pressure determines the oxygen binding to Hemoglobin

• 1 gram of oxygen bound to 3.41mL of oxygen

Bohr Effect

• Enhanced O2 offloading under metabolically active or acidic conditions

Tissue PO2

Transfer by diffusion

Exercise (tissue PO2)

• PO2 of tissue drops as O2 is used i.e., greater pressure gradient

• Increased capillary flow/capillary recruitment = smaller diffusion distance

Myoglobin 

• The hemoglobin of the MUSCLE

  • Only contains 1 iron group as opposed to 4 in blood hemoglobin

• Dashed yellow line in a dissociation curve

• Considered to acts as as O2 reserve,  immediate source of O2 at exercise onset, facilitates O2 at exercise onset, facilitates O2 diffusion by altering PO2 gradient

Rhabdomyolysis

• Damaged muscle cells release myoglobin which can be toxic to the renal tubular epithelium

• Can be caused by excessive exercise

CO2 transport in the blood

• Metabolic production of CO2, in the cells; must be transported in the blood to the lungs and disposed of through exhalation

Travels in 3 ways:

1. In physical solution in plasma (10%)

2. In loose combination with hB (20%)

3. Combined with H2O as bicarbonate (70%)

CO2 in solution

• Small quantity (7-10%)

• Important role

  • Establish PCO2 of the blood

  • 30-50ml CO2/L

Carbamino Compounds

CO2 + Hb → HbCO2

• 20% of produced CO2 reacts with Hb to form carbamino compounds

• Reaction reverses in lungs as PCO2

• Concurrently O2 is loaded on to HB

• Haldane effect

CO2 as bicarbonate (HCO3^-)

70% of CO2 combines with water to form carbonic acid (H2CO3^-)

• Catalyzed by carbonic anhydrase

TISSUES:

CO2 + H20 → H2CO3 → H⁺ + HCO3^-

LUNGS (Opposite):

H⁺ HCO3^- → H2CO3^- → CO2 + H20

Control of ventilation

Neural control of breathing

Afferent inputs

• Pulmonary stretch

• Irritant receptors

• Bronchial receptors

• Joint and muscle receptors

• Baroreceptors

• Pain and temperature

• Central command

Brainstem

• Medullary respiratory centre

• Inspiratory and expiratory areas

• Normal, automatic breathing patterns

Cortex

• Can override medulla

• Voluntary control

• Hyper,hypoventilate

Regulation of pulmonary ventilation

Stimulus → receptor through Afferent pathway → integrating center through efferent pathway → effector → response → feedback → stimulus

Central chemoreceptors

• Most important for min-by-min steady state control

• Ventral surface of medulla

• Sensitive to PCO2, not PO2

• Response to change in pH of CSf

Peripheral chemoreceptors

• Carotid & aortic bodies; important for rapid responses

• Respond to both decrease PaO2 and increase in PaCO2 and hydrogen

• Only receptors to sense change in O2

• Can also sense CO2 (like central, but only about 20% of response

• Can also sense CO2 (like central, but only about 20% of response

• Can also respond to K+, adenosines, ANG ll and many more

CO2 and O2 as ventilator stimuli

• An increase in PCO2 is much greater stimulus to ventilate than a decrease in PO2

Hyperventilation

• Record how long you can hold your breath for

• Hyperventilate (rapid shallow breaths with a focus on full exhalation) for 30-60 seconds and immediately try to hold your breath again

CHEAT SHEET

Pulmonary ventilation during exercise

O2 cost of ventilation during exercise

• Respiratory muscles also require O2 during exercise and can become fatigued

• High respiratory oxygen cost can steal blood from skeletal muscle 

What happens to arterial PO2 during exercise

• It stays the same, PO2 does not change

Mechanisms controlling ventilation during exercise

1. Skeletal muscle afferent feedback → passive movement of limbs stimulates ventilation

2. Central command → cortical influence, anticipation

3. Reset chemoreflex – increase chemosensitivity or activity → Ve response to hypoxia > during exercise than rest

4. Oscillations in arterial CO2/H+ → the average might be the same but increased variability around the mean

5. Cardiac afferent feedback → Stretch of the heart by returning blood sends afferent signals to alter ventilation

6. Arterial potassium and/or catecholamines → humoural factor affecting chemoreceptors

7. Learned response → our brain must be trained

8. Temperature → increased body temp excites neurons of respiratory centre (but temp changes are slow)

Steady state exercise

• Ve (minute ventilation) increase with VO2 during mild to moderate workloads

  • Mainly due to increase tidal volume early on, Fb later

Non-steady state exercise

• Disproportionate increase in Ve for the increase in VO2

Onset of blood lactate accumulation (OBLA)

• Point where blood lactate begins to accumulate; usually around 4mM/L

• Identifies an imbalance between production and removal

• 55-65% VO2 max in healthy untrained; 80% VO2 max in highly trained endurance

  • Increase endurance performance without VO2 max

IMPORTANT: at steady state, lactate production is matched by removal so no accumulation

Volume < Demand in healthy young trained adults

• Inability to increase ventilation any further constrains hyperventilation

• 15-20% of oxygen and blood flow sent to respiratory muscles

• Increased expiratory pressure = decreased diastolic ventricular filling and thus stroke volume

Intense exercise induced laryngeal narrowing

• Dynamic airway collapse

• Hypoventilation, hypoxemia, dyspnea, performance limitation

• High prevalence in athletes

• Often misdiagnosed as asthma