Respiratory System

Path of air in respiratory system

1. air flows in through mouth and/or nose

2. Pharynx

   1. oropharynx

   2. nasopharynx

3. Larynx

4. Trachea

5. Bronchi

6. Bronchioles

7. Alveoli

Diaphragm

Muscle that controls breathing. Separates thoracic and abdominal cavity

Functions of respiratory system

• supply O2 to tissues

• get rid of waste like CO2

4 basic steps of respiration/ventilation

1. pulmonary ventilation (breathing)

2. external respiration (O2 moves into blood)

3. transport of gases through the blood

4. internal respiration (diffusion of gases in/out of tissues)

Respiratory zone

Where respiration actually occurs→alveolar sacs, ducts, and respiratory bronchioles

Conducting zone

“dead space”

• air moves in/out→bronchi, bronchioles, trachea

Trachea anatomy

• 3 layers

• goblet cells secrete mucus

• cilia beat to elevate trapped particles out of respiratory tract

Alveoli function

Where gas exchange directly occurs

Alveoli structure

• sacs

• air facing surface is lined with type I alveolar cells and is contiguous with respiratory tract

• type II alveolar cells scattered inside alveolus as well

• moist inside

Type II alveolar cells

produce surfactant

Surface area of alveoli

Huge surface area, which permits rapid gas exchange

Visceral pleura

Lines lungs

Parietal pleura

Lines chest wall

Intrapleural fluid

Fills the intrapleural space between the parietal and visceral pleura

Ventilation

exchange of air between atmosphere and alveoli

Flow of air equation

F=(Palv-Patm)/R

Pressure-volume relationship

P1V1=P2V2

• large volume=less molecules hitting vessel walls=lower pressure

4 lung pressures

intrapulmonary pressure (Palv)

intrapleural pressure (Pip)

transpulmonary pressure (Ptp)

chestwall pressure (Pcw)

Intrapulmonary pressure

• pressure inside alveoli

• rises and falls with breathing

• determines which way air flows

Palv<Patm

air flows in

Palv>Patm

air flows our

Intrapleural pressure

• pressure of intrapleural fluid in the intrapleural space

• also fluctuates with breathing

• always 4 mmHg less than Palv

Palv=Pip

lung collapse

transpulmonary pressure

Ptp=Palv-Pip

• pressure across lung wall

• governs properties of lungs→drive air in and out

• stops lung collapse and chest wall expansion

Chestwall pressure

Pcw=Pip-Patm

• pressure across chest wall

Steps of inspiration

1. Diaphragm and inspiratory intercostal muscles contract

   1. pulls ribcage out and up→thorax expands

2. Pip becomes more subatmospheric

3. Ptp increases

4. lungs expand

5. Palv becomes subatmospheric

6. air lows into alveoli

Steps of expiration

1. Diaphragm and inspiratory intercostal muscles stop contracting

2. Chest wall recoils inward

3. Pip moved back up towards preinspiration value

4. Ptp moved back down towards preinspiration value

5. lungs recoil back down

6. air in alveoli is compressured

7. Air flows out

Are expiration and inspiration passive or active processes?

Inspiration: active

Expiration: passive

What determines lung compliance?

• stretchability of lung tissue

• surface tension at air water interfaces within alveoli

Greater lung compliance means…

easier to expand lungs at any given Ptp

Lung compliance equation

C=deltaV/deltaPtp

Lung compliance curve

• decrease compliance means that less air feels lung even at higher Ptp

• both decreased and increased lung compliance are bad!

Effect of surfactant on lung compliance

surfactant reduces cohesive forces between water molecules on alveolar surface, which lowers surface tension and increases lung compliance

Pressure and surface tension relationship equation

P=2T/r

• T is surface tension

• r is airway radius

What would happens if no surfactant were present?

• pressure would be determines by airway radius→air would flow from small to large airways

• small airways would collapse

Effect of surfactant on large vs small airways

• reduces surface tension in small airways specifically, which allows them to stay open

Premature babies and surfactant

Their type II alveolar cells are not yet mature so they cannot produce surfacant→alveoli collapse and inflate with every breath

Airway resistance

Usually very small, but radius does affect airway resistance

Things that alter airway radius

Physical, neural, chemical factors

Tidal volume

amount of air inhaled/exhaled in one normal breath

• 500 mL

Residual volume

amount of air remaining in lungs after maximum expiration, which keeps alveoli inflated between breaths

• 1200 mL

Inspiratory reserve volume

amount of air exhaled in excess when applying maximum effort

• 3000 mL

Expiratory reserve volume

amount of air exhaled in excess when applying maximum effort

• 1200 mL

Vital capacity

Amount of air that can be exhaled with maximum effort after maximum inspiration

• ERV+TV+IRV

• 4700 mL

Total lung capacity

Total amount of air that can fit in a lung

• RV+VC

• 5900 mL

Inspiratory capacity

Maximum amount of air that can be inhaled after a normal tidal expiration

• TV+IRV

• 3500 mL

Functional residual capacity

Amount of air remaining in the lungs after a normal expiration

• RV+ERV

• 2400 mL

Minute ventilation

amount of volume breathed in one minute

Minute ventilation equation

TV*RR

• 5-6 L/min

Alveolar ventilation

Air that enters alveoli for gas exchange

• 4.2 L/min

Alveolar ventilation equation

(TV-anatomical dead space)(RR)

What is more useful, minute ventilation or alveolar ventilation?

Alveolar ventilation because it does not take into account anatomical dead space where gas exchange does not occur

How much oxygen is introduced into the blood/dropped off at tissues per minute?

250 mL/min

How much CO2 is introduced into the blood/released into the lungs per minute?

200 mL/min

Partial pressures of O2 and CO2 in alveoli

PO2=105 mmHg

PCO2=40 mmHg

Partial pressures of O2 and CO2 in deoxygenated blood

PO2=40 mmHg

PCO2=46 mmHg

Partial pressures of O2 and CO2 in oxygenated blood

PO2=100 mmHg

PCO2=40 mmHg

Partial pressures of O2 and CO2 in the air

PO2=160 mmHg

PCO2=0.3 mmHg

Determinants of alveolar PO2

1. percent of oxygen in the air

2. ventilation rate

3. body’s rate of O2 consumption

Alveolar PO2 equation

(CO2 production)/alveolar ventilation=(O2 consumption)/alveolar ventilation

Hypoventilation

Decreased O2 concentration or decreased alveolar ventilation

• increase in the ratio

Hyperventilation

increased O2 or increased alveolar respiration

• decrease in the ratio

Gas exchange between alveoli and blood pressure curve

Healthy: oxygenation is super rapid

Diseased: oxygenation is slow and not efficient

What is the major reason for insufficiently oxygenated blood?

ventilation-perfusion mismatch

1. area of lung is receiving sufficient air flow but not blood flow

2. area of lung receiving sufficient blood flow but not air flow

How the body regulates ventilation-perfusion mismatch

Local controls decrease blood or air flow to the area

• if underperfused, body will decrease air saturation to that area

• if underventilated, body will decrease perfusion to the area

Transport of gases in hemoglobin-independent manner

CO2 and O2 can be directly dissolved in the plasm

What does solubility of a gas in a liquid depend on?

Directly proportional to its partial pressure (Henry’s law)

Percent of oxygen dissolved directly in plasma

1.5%

Percent of carbon dioxide dissolved directly

10%

Hemoglobin structure

• two alpha and two beta polypeptides joined together into a heterotetramer

• heme group made up of porphyrin ring and bivalent iron cation

What percent of oxygen is bound to hemoglobin?

95%

How many molecules of O2 can a hemoglobin bind?

4

Hemoglobin saturation curve

• sigmoidal curve due to cooperative binding

• 4 sites are occupied in systemic arterioles

• 3 sites are occupied in venous arterioles

Steps of oxygen movement from lungs to tissues

1. O2 is inspired and makes its way to the alveolus

2. Pressure gradient causes oxygen to move into plasma as dissolved oxygen

3. As soon as O2 enters blood it binds to Hb due to yet another concentration gradient

4. RBCs move into systemic circulation

5. Metabolically active cells whos mitochondria are starved for oxygen receive O2

Reasons Hemoglobin offloads oxygen

• metabolically active cells are warm (since heat is generated as a byproduct of respiration), which induces a right shift of the curve

• Metabolically active cells are acidic (due to lactic acid and CO2 production), which induces a right shift of the curve

2,3-BPG effect on hemoglobin curve

Shift right

Things that shift Hb curve to the left

• cooler temperatures

• fetal Hb

Steps of loading CO2 into erythrocytes

1. metabolically active cells produce CO2

2. CO2 diffuses into plasma due to concentration gradient

3. 30% of CO2 binds to Hb, 10% stays in plasma, 60% is turned into carbonic acid via carbonic anhydrase

4. Carbonic acid dissociated into HCO3- and H+

5. HCO3 exits RBCs while Cl- enters via an antiporter

Steps of unloading CO2 in the lungs

1. Blood flows past alveolus

2. CO2 bound to hemoglobin is displaced by plentiful O2

3. Bicarbonate moves back into RBCs while Cl- moves out→chloride shift

4. Bicarbonate turned back into carbonic acid

5. Carbonic anhydrase turns carbonic acid back into CO2 and H2O

6. Dissolved CO2 and RBC bound CO2 can be moved out through alveolar exchange

Transport of hydrogen ions between tissues and lungs

Hemoglobin can bind free protons in tissues, acting as a buffer against pH changes

Neural regulation of respiration

dorsal and ventral respiratory groups in medulla

Function of dorsal respiratory group in medulla

Regulates contraction of intercostal muscles and diaphragm

Function of ventral respiratory group?

Control intercostals but mainly responsible for respiratory rythmicity/rate

Control of dorsal and ventral respiratory groups

Pneumotaxic and apneustic centres in pons can further fine tune medullary respiratory groups

What happens when one overdoses on a CNS depressant?

Respiratory function compromised

Peripheral chemoreceptors

Neurons located in the body’s periphery that sense O2 and H+ levels

Where are peripheral chemoreceptors located?

Largely in the same spot as arterial baroreceptors: carotid sinus and aortic arch

Graph of chemoreceptors that respond to O2 levels and conclusions

• as PO2 decreases, ventilation increases→but it takes quite a large drop in PO2 to trigger a response

• These chemoreceptors are not very sensitive

Graph of chemoreceptors that respond to CO2 levels and conclusions

• As PCO2 increases, ventilation increases

• much more sensitive

Cascade of chemoreceptor and body’s response based on O2 levels

1. inspired PO2 drops

2. Alveolar PO2 drops

3. Chemoreceptor firing increases

4. Medullary neuron firing increases

5. Respiratory muscle contraction increases

6. Ventilation increases

7. PO2 returns to normal

Cascade of chemoreceptor and body’s response based on acid levels

1. Increased production of CO2 and non-CO2 acid

2. increase arterial [H+}

3. increased firing of chemoreceptors

4. increased medullary neuron firing

5. increased respiratory muscle contractions

6. increased ventilation

7. decreased alveolar PCO2

8. decreased arterial PCO2

9. return of acid levels to normal

Is CO2 directly sensed?

No, H+ levels are sensed by chemoreceptors

Central chemoreceptors

A set of chemoreceptors in the brain that respond to H+ associated with CO2 levels

Central chemoreceptor pathway

1. increased arterial PCO2

2. increased brain extracellular fluid PCO2

3. increase brain extracellular fluid [H+]

4. same cascade as peripheral chemoreceptors leading to increase ventilation and decrease PCO2

Why does the brain sense H+ associated with CO2 specifically?

Because CO2 can cross the BBB while just protons or other acids cannot

What percentage of CO2-based response is mediated by central vs peripheral chemoreceptors?

70% mediated by central

Acclimatization

Adapting to lower oxygen environments

Hypoxia

inadequate oxygen delivery to tissues

Types of hypoxia

Anemic: not enough RBCs

Ischemic: impaired blood circulation

Histotoxic: impaired O2 metabolism

Hypoxemic: reduced overall oxygen tension in blood

Causes of hypoxemic hypoxia

lack of oxygenated air, lack of ventilation perfusion coupling, pulmonary problems