Respiratory Physiology

General Functions of the Respiratory System:
- Ventilation - moving air into and out of the lungs
- Gaseous exchange - replacing O2 and removing CO2 from the blood.
- Regulation of acid-base balance
- Air conditioning
- Speech/smell
- (Temperature and Fluid Balance)

The structure of the respiratory system: 
- two lungs: covered by visceral pleural and connect to the inner thorax and diaphragm
- branching network of airways
- respiratory membrane
- supporting tissues
- ''separated'' into: conducting and respiratory exchange zones

Zones of the respiratory system:

Conducting zone:
- trachea
- segmental bronchi
- bronchioles
- terminal bronchioles

Humidify, warm and filter the air to PROTECT

Respiratory exchange zone:
- respiratory bronchioles
- alveolar ducts
- alveoli
Create large surface area and thin barrier to AID DIFFUSION

Know the functions of the lungs and respiratory system and the anatomical and functional zones of the respiratory system

NOW! Lets talk about the following
- The thorax and respiratory muscles
- Mechanics of breathing
- Pressure changes in ventilation

 

 Mechanics of Breathing video

What causes air to flow in bulk into and out of the lungs?
- Expiration: Diaphragm moves up
- Inspiration: Diaphragm moves down
Air Pressure Changes During Ventilation
Inspiration: P(atmosperic) > P(alveolar) = air moves into the lungs
Expiration: P(alveolar) > P(atmospheric) = air moves out of the lungs

Factors affecting lung mechanics
- Lung compliance - the distensibility of lung tissue
- Lung Elasticity - the ability to stretch and return to resting state
- Surfactant - produced by type II alveolar cells reduces surface tension in alveoli (caused by H2O) increases total lung compliance
- Airway resistance - air contact with walls of airways including narrowing of airways due to disease/infection etc like Asthma etc, This causes more energy to be required to deliver sufficient air

So to summarize the mechanics of breathing:
Inspiration: stimulus to diaphragm -> diaphragm contracts thorax expands -> pressure in lungs decreases Patm>Palv -> air flows in bulk from atmosphere to alveoli (from high pressure to low pres.)
Expiration: stimulus to diaphragm ends -> diaphragm relaxes and thorax mmoves inwards (passive) -> pressure in lungs increases Palv > Patm -> air flows in bulk from alveoli to atmosphere (from high to low pressure)


NOW! lets talk about:
- Lung volumes and ventilation rates
- Nervous control of ventilation
- Chemical control of ventilation
    - Carbon dioxide (PCO2)
    - Hydrogen Ions (H+)

Wet Spirometry

    - Oxygen (PO2)

 Ventilation rates:
At rest
- Pulmonary ventilation rate (minute volume) =
respiratory rate (RR) x tidal volume (Vt) = 12Br/min x 500ml = 6000ml/min
- Alveolar ventilation rate = (tidal volume - dead space vol.) x RR = (500-150) x 12 = 4200ml/min



Regulation of Ventilation: Neural generation of rhythmic ventilation
- Ventilation depends on rhythmic on-off stimmulation of respiratory muscles via nerves
- automatic stimulus comes from the respiratory control centre in Medulla of the brain stem.

at the end of expiration => resting muscle tone neurones rhythmically 'fire' => active inspiration and then 'cease fire' => passive expiration

 The neural pathways for ventilation
   DRG sends an excitatory stimulus to the phrenic and intercostal nerve and the Pons
 => Phrenic and intercostal nerve conduct the stimulus to diaphragm and intercostal muscles - Active inspiration
=> Pneumotaxic centre in Pons sends an inhibitory stimulus back to the DRG and inspiration stops - Passive expiration

 Control of ventilation by PCO2
- PCO2 of arterial blood is the main input regulating ventilation under normal conditions
- Increased PCO2 stimulates ventilation via central and peripheral chemo-receptors

Central chemoreceptors
- Ventral surface of Medulla is sensitive to CO2-generated [H+] in cerebro-spinal fluid (CSF) surrounding medulla.
     CO2 + H2O --> H2CO3 --> HCO3 + H+
- pH of CSF is more sensitive than blood as it contains fewer protein buffers
- Changes in PCO2 causes larger [H+] in CSF compared to blood.

Peripheral chemoreceptors
- carotid and aortic 'bodies'
- large blood supply
- both respond to PCO2 generated [H+] and blood pH
- Carotid also stimulated by decreased PO2
- PO2 only detected when it falls by ~40% (hypoxia/attitude)

 Other modulating factors include protective reflexes and higher brain centres

 Summary: lung volumes and ventilation rate, neural control of breathing and chemical control via central and peripheral chemoreceptors

Following topics about respiratory physiology to be discussed:
- partial pressure of gases
- O2 and CO2 transport in the blood
- ventilation and acid-base balance

Partial Pressure of gases
- Dalton's law: the total pressure of a gas mixture is equal to the sum of the pressures that each gas would exert independently when barometric pressure (Pb) is 760mmHg
    The composition of atmospheric air is:
  O2     20.93%    0.2093
  CO2  00.03%    0.0003
  N2     79.04%    0.7904

Calculation of partial pressures:
- the partial pressure of any gas can be calculated by multiplying Pb by the fraction of the gas
    Example:
                     PO2 = 760x0.2093= ...mmHg
                     PN2= 760x0.7904= ...mmHg

                    

O2 transport by the blood

 ...ml of O2 is carried by 100ml of blood. 0.3ml (...%) is dissolved in solution in plasma and the rest is combined with iron (Fe2+) on haem units of haemoglobin (Hb) molecules in red blood cells. Four O2 molecules combine with Hb forming oxy-haemoglobin in a reversible reaction.
........ arterial blood is fully saturated with O2.

Oxy-haemoglobin dissociation curve

Oxyhaemoglobin dissociation curve: This relates the percent % ........of Hb to the PO2 in blood. A high PO2 = loading (curve->right) whereas a low PO2 = reduced affinity = unloading (curve <- left)
This is described by the 'S' shaped.      O2-Hb ..............curve. Each O2 molecule binding to Hb increases the rate of binding of the next O2 molecule

Effects of pH, temperature, PCO2 on O2-Hb

 Effects of pH and temperature on O2-Hb:
- Active tissues = ..............= increased [H+]
- Increased [H+] weakens the bond between O2 and Hb. More is released for a given PO2 when pH .........  O2-Hb dissociation curve shifts to the right called the ........
A similar shift to the right occurs with increased blood temperature around exercising skeletal muscle.

 

 CO2 transport by the blood
- CO2 diffuses into blood in systemic tissue capillaries. .......% remains dissolved in blood plasma. The rest (93%) diffuses into red blood cell (rbc). In rbc - ......binds to Hb = carbamino-Hb -.........% converted into H2CO3
- H2CO3 dissociates into HCO3- and H+
- HCO3- diffuses into plasma in exchange with .......
- H+ binds to buffers (Hb)




Ventilation and acid-base balance
- An increase in blood PCO2 leads to increased [H+] and this increases blood acidity (lower pH)
- A decrease in blood PCO2 has the opposite effect and the blood becomes more alkaline.
- Excessive ventilation will exhale more CO2 and reduce blood PCO2. Insufficient ventilation will result in a build-up of CO2 and increased blood PCO2.

Factors affecting lung mechanics
- Trans-mural pressure gradient
- Compliance, elastance, airway resistance, ST

Lung Pressures

 Lung Pressures
- Intra-alveolar pressure (IAP) = Pb at rest -/+ ve 1mmHg midway through tidal breath
- Intra-pleural pressure (IPP) -4 to -8mHg <Pb (more -ve during inspiration)
- Transmural pressure gradient favours open airways (distending pressure)

Specific advantages of negative pump
Maintains:
- Alveoli patency
- Capillary patency
- Reservoir of air and blood
- Reduced fluid in alveoli
- Less energy needed to breathe

Pathophysiology

 Four Factors affecting lung mechanics:
- Lung compliance
- Lung elasticity
- Airway resistance
- Alveolar surface tension forces




The cost of breathing
- 'Quiet' breathing = ~3-5% of total energy
- Energy and disease places higher demands (~30%)
- Compliance and airway resistance main contributors

Lung Compliance (Cl)
- Cl defines distensibility of lung tissue
- Cl the change in lung volume (Vl change) with a unit change in IAP (P change)
- The more the lung expands for a given rise in pressure the greater the Cl

Lung elasticity
- Provided by fibro-elastic network
- Allows passive expiration
- Helps keep alveoli patent
- Losses with age/disease

Alveolar surface tension forces
- At air-liquid interface
- Surface tension (ST)
     a. draws liquids closer together
     b. resists increase in surface area

Law of Laplace

Law of Laplace
- ST directs force/pressure to centre of bubble
- Consequences: small alveoli may have greater P, may create pressure gradients between opposing alveoli causing 'lung instability'


Surfactant
- Phospholipid produced by type II cuboidal alveolar cells
- More concentrated in smallest alveoli
- Sighing replenish levels
- Prevents small alveoli emptying into larger ones
- Prevents collapse of alveoli
- Keeps lungs dryish (osmotic>hydrostatic pressure)
- Reduces surface tension and increases total lung compliance
- Increases lung 'stability'
- Reduces work of breathing

Surfactant: Pathophysiology
-  Adequate levels 6weeks before birth
- NRDS - requires +ve pressure breathing and synthetic surfactant
- Levels reduced by alveolar damage and increased macrophage activity
- Energy is needed to overcome 'elastic resistance' of lungs and thorax.
- Posture: lying=decrease in compliance
- Disease: if FRC is increased, Cl is increased and vice versa

So lung compliance is affected by?
- Fibrosis - decrease
- Oedema - decrease
- Age - decrease
- Airway blockage - decrease
- Emphysema - increase

Airway Resistance
- Gas flow proportional to pressure gradient and inversely proportional to resistance
- Poiseuilles Law
Resistance proportional to length (L) and viscocity (η) and inversely proportional to Radius (R)

     R proportional to Lxη/r^4
     If radius = 1:1/1^4 => R=1
     If radius = 2: 1/2^4 => R=
   Therefore double the radious = 1/16th the resistance and vice versa
- Radius is primary source
- Trachea and bronchi (rigid and small XS area) = 90%
- Bronchioles=10% (large XS area)
- Narrowing of smaller airways
problems depends on number affected and collapse

Brionchioles
- Reflex control by PSNS and hormones
- Local control by paracrines

Topics to be discussed now in greater detail:
- Gas pressures and gas exchange (recap - above)
- Types of ventilation
- Ventilation and perfusion
- Factors affecting gas exchange

Remember composition of atmospheric air 

O2  20.90%, 0.2090 (fraction), 159mmHg (partial pressure)
CO2 0.04%, 0.0004,    0.3mmHg
N2   78.60%, 0.7860,  597mmHg
H20  0.46%,  0.0046,  3.7mmHg
total  100%,    1.0,        760mmHg
 in reality there are some other components in the air as well but in very low concentrations that we can actually neglect

Partial Pressure: the partial pressure of any gas can be calculated by multiplying Pb by the fraction of the gas
      Example:                
                               PO2=760x0.2090=159mmHg
                               PN2= 760x0.7860=597mmHg

(missing 5th slide of pulm3 BS2049 module)

Composition of alveolar gas
- Affected by:
Ambient air composition and flow, gas exchange, mixing of gases, humidity

 

 Types ventilation
- Upnea
- Hypernea
- Hyperventilation
- Hypoventilation
- Tachypnea
- Dyspnea
- Apnea

10, 12 slide not included - put it in...

V/Q matching
- Local mechanisms adjust for poor air flow and/or poor blood flow
- Capillaries collapsible
- Regulation of arterioles and bronchioles

Va/Qa ratio
- Alveolar blood flow decreases from base to the apex
- Ratio = 3.0 in apex and 0.5 in base
- Average = 0.8
- (Va=5L  Qa=6L)
- Perfusion > Ventilation at rest
 

Above we discuss: partial pressures, effects of breathing pattern, defining types of ventilation, effects of hyper/hypoventilation on PAO2/PACO2, V:Q matching, local control of air and blood flow

Topics
- Fick's law of diffusion
- Oxygenation of blood in pulmonary capillaries
- Gas exchange: problems

Types of Hypoxia:
- Hypoxic: low arterial O2
- Anaemic: low HbO2
- Ischemic: low PO2 delivery
- Histotoxic: low O2 use

Fick's law of diffusion:
 Diffusion is proportional to:
- partial pressure difference (gradient)
- surface area
Diffusion is inversely proportional to:
- membrane thickness
- diffusion distance





Gas exchange: Problems
 Cause hypoxia and hypercapnia:
Inadequate:
- O2 in alveoli
- Transfer of O2 from alveoli to blood
- Transport ....
Gas exchange: Inadequate O2
- abnormal air
- inadequate alveolar Ve

 Gas exchanges: inadequacies in tranfer
- decrease in SA for exchange
- increase in thickness of membrane
- increase in diffusion distance

Some essay-question that are seen in exams:

- The impact of emphysema on respiratory function

- Gas exchange: loss of alveolar tissue; decreased SA for gas exchange, loss of traction>obstruction of airways, gas trapping>diffusion gradient affected 

- Local regulation of ventilation and perfusion (V/Q) in the lungs

- Mechanics that regulate ventilation and perfusion (V/Q) in the lung

- Factors that affect the efficiency of gas exchange in the lungs

- Factors that affect lung mechanics and gas exchange in health and disease

- Factors that affect the efficiency of gas exchange between the lungs and blood

Respiratory control

now we have done this above but we will extend abit further on some things particularly on exercise (just abit)
Neural and chemical control of ventilation
- the main areas of the brain responsible for normal control of normal ventilation
- chemoreception and other influences
- responses during exercise

CONTROL CENTRES

 Respiratory control during exercise:
- The Oxygen uptake response
- Ventilatory control:
      - mechanisms
      - relationships with energy demand

The oxygen uptake response for a constant workload

 On the curve on the left, at 50sec there is oxygen deficit;   at 150sec  VO2 at steady state

Aerobic metabolism
- Supplies 100% of energy requirements to match low to moderate demands
- Processes are rate limited
- Relatively slow to adapt
- Supported by anaerobic processes to meet demand at the start
- Supported by anaerobic processes to meet demand for moderate to heavy demand.

Ventribular control during exercise
- Associated with combination and/or simultaneous effect of:
      a. chemical factors
      b. neurological factors

The Ve response for a constant workload

We can see three different states at right curve for a constant workload

Non-Chemical control
- Ve rises instantly when exercise starts followed by a short (<20s) plateau
- Ve rises then rises slowly until 'steady state' is reached
- When exercise stops Ve falls abruptly to ~40% of end-exercise value; therefore other control mechanisms are involved

Neurogenic Factors
- Cortical and peripheral
- Neural flow from motor cortex and centres involved in anticipation stimulate respiratory centre
- Sensory input from joints, tendons and muscles adjust Ve during exercise (mechano-reflex)
- Temperature has slow effect

Chemical Control
- Cannot fully explain total rise in Ve
- PaO2 in exercise does not stimulate Ve
- During light-moderate exercise (<2L/min) PaO2 and PaCO2 maintained at normal levels
- In hard exercise CO2/H+ provide stimulus to increase Ve via chemo-R. But PaO2 and PaCO2 maintained at approximately normal levels by ventilation and chemoR on arterial side?
- Ventilatory response slightly lags behind rise in CO2 and H+
- And/or other sensory info exists (from muscle)?

Therefore the Current model of response:
 Phase I
Neurogenic stimuli from cerebral cortex and limbs cause abrupt rise/fall in Ve
Phase II
After a short plateau Ve rises to a steady level that meets demand of metabolism intrinsic medullary control and peripheral stimuli modify rate
Phase III
'Fine-tuning' of Ve via peripheral sensory feedback (temperature CO2/H+,K+)

The Ventilatory Threshold (Tvent)

Ventilation and energy demand
- Light - moderate exercise:
Ve increases linearly with VO2. Mainly by increases in tidal volume Ve/VO2 ratio indicates breathing economy (ventilation for a given volume of oxygen utilized VO2)
    Healthy = 25 (25L air/L VO2)
- Moderate - severe exercise
Ve increases nonlinearly with VO2. Mainly by increases in tidal volume and RR. Ve/VO2 ratio=~35 in severe exercise. 'Ventilatory threshold' (Tvent) also called the 'anaerobic threshold' relates to 'additional' CO2 and H+ from lactate production stimulating chemo-R