Physiology: Respiratory System

Two Types of Respiration:

• External respiration
• Internal respiration

Anatomical order of air passage:
Nasal passages/mouth --> Pharynx --> Larynx --> Trachea --> Primary Bronchus --> Seocndary Bronchus --> Bronchiole --> Alveolus --> Alveolar Sac


Four steps to external respiration:

1. Ventilation - movement of air into and out of the lungs.
2. O2 and CO2 are exchanged between air in alveoli and blood within the pulmonary capillaries by means of diffusion.
3. Blood transports O2 and CO2 between lungs and tissues 
4. O2 and CO2 are exchanged between tissues and blood by process of diffusion across systemic (tissue) capillaries. 

Internal respiration:

Refers to metabolic processes that occurs in the mitochondria, which uses O2 to produce CO2.
Respiratory Quotient (RQ) = Ratio of CO2 produced to O2 consumed
---
Non-respiratory functions of the respiratory system:

• Enhances venous return
• Maintains pH balance
• Defends against foreign matter
• Nose serves as olfactory organ
• Route for water loss and heat elimination

Components: 

Upper Respiratory System = Above trachea

Lower Respiratory System = Below trachea until diaphragm.

Accessory muscles of inspiration: 

-Sternocleidomastoid

-Scalenus

Major muscles of inspiration: 

-Diaphragm (contract during inspiration) 

     -Innervated by phrenic nerve

-External intercostal muscles

     -Activated by intercostal nerves

Muscles of active expiration: only contract during active expiration (not passive)

-Internal intercostal muscles

-Abdominal muscles

___

Conducting Zone: The structures air passes through before reaching the respiratory zone. 

Functions:

1. Warms the air
2. Adds water vapor
3. Filters and cleans (via mucus to trap particles inside air, then moved by cilia to be removed)

Goblet cells secrete mucus. Located in the epithelium of the trachea. 

-Rings of cartilage prevent the collapse of the trachea & larger bronchi. 

-Although bronchi have discs, bronchioles have no discs and are contain smooth muscle innervated by the ANS. 

Blood supply to the Lungs: 

Bronchial arteries provide systemic blood to the lung tissue, which arises from the aorta and enters the lungs at the hilus (indentation of the surface of the lung). 

     -Supplies all lung tissue except the alveoli. 

Pulmonary veins  carry most venous blood back to the heart. 

---

Alveoli are lung air sacs made of simple squamous epithelial cells for diffusion of gases. 

-500 million air sacs (alveoli) in two adult lungs.

Alveolar walls contain:

• Type I alveolar cells (95%)
• Type II alveolar cells (5%) - Secrete pulmonary surfactant
• Alveolar Macrophages - Guard lumen 
• Alveolar dust cells - Wandering macrophages that remove debris
• Pores of Kohn - Permit airflow between adjacent alveoli (collateral ventilation)

Respiratory Mechanics: 

Inspiration lowers the intrapleural pressure, which causes expansion. The increase in volume lowers the intra-alveolar pressure to a level below atm pressure, by this difference, the air enters the lungs. 

When pressure increases to level above atm pressure, air is driven out - expiration occurs.

The 3 Pressures: 

• Atm pressure (aka barometric) - 760 mm Hg at sea level
• Intra-alveolar pressure (intrapulmonary pressure) 
• Intrapleural pressure (intrathoracic pressure) - normally less than atm

Law of LaPlace - If two alveoli of unequal size but the same surface tension are connected by the same terminal airway, the smaller alveoli will collapse into the lager one via air escaping the smaller one into the larger one. Pulmonary surfactant however, reduces the surface tension of the smaller one so that a collapse of the smaller alveoli does not happen. 

The equation also makes sense in the scope of the ideal gas law: PV = nRT

-Pneumothorax results in collapsed lung that cannot function normally. 

     -Air enters the intrapleural space, which is the only part of the lung that inherently has a subatmospheric pressure, which causes air to enter the intrapleural space, pushing against the lung.

Terms: 

• Compliance - Ability to stretch
• High compliance - Stretches easily
• Low compliance - Requires more force, or from restrictive lung diseases
• Diseases include fibrotic lung diseases, or inadequate surfactant production
• Elastance - Returning to its resting volume when stretching force is released
• Lungs have elastic recoil - rebound if stretched

Lung Compliance (CL) - Is a measure of the distensibility of the lung and is the inverse of the lung elastance. 

     -Measured as the change in lung volume resulting from a change in transpulmonary pressure, where transpulmonary pressure is the pressure across the lung, or the difference between alveolar and pleural pressure.

C=V(mL)/P(mmHg)

Fibrosis is a associated with a decrease in pulmonary compliance. Fibrosis is the thickening and scarring of connective tissue.

Emphysema/COPD may be associated with an increase in pulmonary compliance due to the loss of alveolar and elastic tissue.
     -Patients with emphysema have a high lung compliance due to poor elastic recoil. So there is extra work needed required to get air out of the lungs, where as in inhaling air is easily done.

Elastic lung recoil = alveolar pressure - pleural pressure
Elastic chest recoil = pleural pressure - atm pressure

Elastic recoil depends on elastic connective tissue in the lungs, and alveolar surface tension.
     -Surface tension reduces tendency of alveoli to recoil

Surfactant is a mixture containing proteins and phospholipids that reduce surface tension.
     -Premature babies have inadequate surfactant concentrations
          -Newborn respiratory distress syndrome
---

In any system, flow of air may be laminar or turbulent.

Laminar flow is seen with:

• Small peripheral airways where rate of airflow is low. Driving pressure is proportional to gas viscosity. 

Turbulent flow is seen with: 

• High flow rates
• Changes in diameter
• Angles
• Branching tubes
• Driving pressure is proportional to square of flow and is dependent on gas density.

Poiseuille's law - Resistance to laminar flow is inversely proportional to tube radius to the 4th power. It is also directly proportional to length of the tube. 

     -When radius is halved, resistance increases 16-fold. If driving pressure is constant, flow will fall to one 16th. 

     -Doubling length only doubles resistance. If driving pressure is constant, flow will fall to one half.

ANS controls contraction of smooth muscle in walls of bronchioles 

COPD abormally increasses airway resistance 

     -Expiration is more difficult than inspiration 

Chronic bronchitis, asthma and emphysema do the same. 

-Lungs normally operate at about "half full" 

Lung Volumes and Capacities:

Can be measured by a spirometer.

Spirogram is a graph that records inspiration and expiration. 

Total lung capacity at max inflation: 5700 mL
Normal breathing: 2200-2700 mL
Minimal lung volume (residual volume): 1200 mL
Tidal volume: 500 mL
Inspiratory reserve volume: 3000 mL
Inspiratory capacity: 3500 mL
Expiratory reserve volume: 1000 mL
Functional residual capacity: 2200 mL

Minute ventilation: Volume of air breathed in and out in one minute.
Total pulmonary ventilation (mL/min) = Tidal volume (mL/breath)  x Respiratory rate (breaths/min)
Normal ventilation rate = 12-20 breaths/min
Average tidal volume = 500 mL

At rest, a healthy adult requires about 250 mL/minute of oxygen to sustain life.
     -Respiration normally provides about 1000 mL/min at rest

Anatomic dead space = 150 mL

Alveolar ventilation less than pulmonary ventilation due to anatomic dead space.
     -Volume of air in conducting airways that is useless for exchange.

Alveolar Ventilation = Respiratory rate x (tidal volume-dead space volume)

Total pulmonary ventilation = 6 L/min
Total alveolar ventilation = 4.2 L/min
Maximum voluntary ventilation = 125-170 L/min
Respiration rate = 12-20 breaths/min

Obstructive lung diseases vs Restrictive lung diseases

Obstructive = asthma, bronchitis, COPD, emphysema
     -Total lung capacity increased because of increased RV and FRC. VC usually decreased but may be normal.

Restrictive = Loss of lung compliance and extra pulmonary lung diseases (including scoliosis)
     -TLC and VC decreased.

___________________________________________________________________________________

Respiratory Surface:

• Gas movement is by diffusion
• Gases are dissolved in water, so respiratory surfaces must be moist. 
• Respiratoary surfaces are usually thin and have large areas. 

Four layers of membrane to cross (on the alveolar-capillary membrane: 

• Alveolar epithelial wall of type I cells
• Alveolar epithelial basement membrane
• Capillary basement membrane
• Endothelial cells of capillary 

The rate at which a substance can diffuse is given by Fick's Law 

Net diffusion rate of a gas across a fluid membrane is: 

• Proportional to the difference in partial pressure (steeper gradient)
• Proportional to the area of the membrane
• Inversely proportional to the thickness of the membrane. 

Gas percentages in air: 

Nitrogen (N2) = 78% 

Oxygen (O2) = 21%

Carbon Dioxide (CO2) = 0.033%

Water Vapor (very small, practically 0%)

Partial pressures of gases are different in different environments.

     -For example CO2 is higher in cells since they're creating the gas through their metabolism, while O2 is lower in cells. O2 is greater in systemic capillaries while CO2 is lower in systemic capillaries. 

     -Since gases go from higher to power (partial) pressure, O2 naturally goes from the systemic capillaries into the tissue cells. Similarly, CO2 goes from the cells into the systemic capillaries. This reverses the partial pressure of gases in the respective environments for some period of time. 

Henry's Law - Quantity of a gas that will dissolve in a liquid depends upon the amount of gas present and its solubility coefficient. Higher pressures will allow gases to be more soluble in liquids. 

O2 and CO2 are lipid soluble, but the diffusion capacity of CO2 is 20 times greater than O2. However, partial pressure for CO2 is less than that of O2. 

Diffusion capacity: 

O2 = 20 mL/min/mm Hg

CO2 = 400 mL/min/mm Hg

Blood Supply

Pulmonary artery - carries deoxygenated blood from the right ventricle to the lung.

Bronchial artery - Branches from aorta that supplies oxygenated blood to the bronachial tree.

Pulmonary Vein - Formed as the capillaries of the pulmonary artery and bronchial artery merge.

-

Ventilation-Perfusion ratio is the ratio between effective alveolar ventilation and pulmonary blood flow per minute. 

Since normal alveolar ventilation is 4L/min and total perfusion of lung is 5L/min, the ratio is 0.8

     -May differ

Increasing pulmonary blood flow allows more capillaries (that were previously closed) to open up. 

 Lower ventilation in alveoli causes the blood flowing through it to not get oxygenated, since CO2 goes up in alveoli and O2 goes down, essentially forming the environment where the alveoli have no O2 to give to the blood. This constricts the blood vessels to divert blood to better ventilated alveoli.

Hemoglobin + Oxygen = Oxyhemoglobin  (reversible, but favorable reaction)

     -Dissociation of oxyhemoglobin favorable only at the tissue level, for the tissues need oxygen.

Saturation of hemoglobin = 97.5% at 100 mm Hg  

Bohr effect - The shifting of the hemoglobin dissociation curve to the right. 

Caused by: 

• Increase in CO2
• Increase in acidity
• Increase in temperature
• Increase in 2,3, BPG (bisphosphoglycerate)

*Hemoglobin has more affinity for carbon monoxide (CO) than O2. 

     -This is why CO poisoning is dangerous. 

As '% hemoglobin saturation' raises in the graph, so does the 'volume % of O2 in the blood.'

Hemoglobin is expressed in grams per deciliter (g/dl)

     -Normal Hb is 15 g/dl

     -Partial pressure of oxygen is the MAIN factor determining the % of hemoglobin saturation.

Sickle Cell Disease - Sickle cell anemia is caused by an abnormal type of hemoglobin called hemoglobin S. 

Anemia - Hemoglobin below normal

Polycythemia - Hemoglobin above normal

Hemoglobin production controlled by erythropoietin

So, all in all, the Unloading/Loading depends on:

• Partial pressure of O2 of the environment
• Affinity between hemoglobin and O2

CO2 Transport

Bicarbonate ion (HCO3-) = 70%

Dissolved CO2 = 10%

Carbaminohemoglobin = 20%

Carbonic anhydrase facilitates the reaction in the erythrocyte

100 mL of blood carries 55 mL of CO2

Chloride shift - Plasma membrane of erythrocyte passively facilitates the diffusion of bicarbonate ions (out of the red cell) and chloride ions.

Haldane effect - Removal of oxygen from hemoglobin at the tissue cells increases the ability of hemoglobin to bind with CO2.  

Hypercapnia - Having excess CO2 in arterial blood, caused by hypo ventilation. 

Hypocapnia - Having low arterial PCO2 levels, caused by hyperventilation 

     -Can be triggered by anxiety, fever and aspirin poisoning. 

Cystic Fibrosis is a heterogeneous recessive genetic disorder.

• Reflect mutationss in the CFTR (cystic fibrosis transmembrane conductance regulator) gene.
• Characterized by:
• Chronic bacterial infection of the airways/sinuses
• Lipids maldigestion due to pancreatic exocrine insufficiency 
• Infertility in males due to obstructive azoospermia
• Elevated concentrations of chloride in sweat
• Patients with nonclassic CF have partial functioning of the CFTR gene and do not experience maldigestion because some pancreatic exocrine function is preserved.  
• CFTR controls chloride ion movement in and out of the cell.
• Mutations in CFTR also disrupt sodium and water balance. This ion imbalance creates a thick sticky mucus layer that cannot be removed by cilia and traps bacteria, resulting in chronic infection. 

Alpha-1 antitrypsin (AAT) deficiency - is a condition in which the body does not make enough of a protein that protects the lungs and liver from damage. The condition can lead to emphysema and liver disease. AAT is protease inhibitor, and it is made in the liver.  

Causes/Symptoms:

• A genetic defect (cause)
• Shortness of breath
• Symptoms of COPD
• Symptoms of severe liver disease (cirrhosis) 
• Weight loss
• Wheezing 

___________________________________________________________________________________

Neural networks in the brain stem control ventilation

Medullary Respiratory Centers:

Inspiratory area - DRG - dorsal respiratory group neurons

Expiratory area - VRG - ventral respiratory group neurons 

Pontine Centers: 

Pneumotaxic Center - located in the upper pons ("switch off"). Dominates over apneustic center.

Apneustic Center - located in the lower pons (prevents "switch-off") 

Pulmonary Receptors:

Pulmonary stretch receptors (Hering-Breuer reflex) 

     -Triggered to prevent overinflation of the lungs.

DRG = Mostly inspiratory neurons

VRG = Both inspiratory and expiratory neurons 

     -Inspiratory and expiratory neurons inactive during a normal quiet breathing. 

Ventral medulla (Pre-Bötzinger Complex) probably generates respiratory rhythm.

Chemical factors that play a role in determining magnitude of ventilation: 

• Partial pressure of O2
• Partial pressure of CO2
• H+

***The motor neurons to the phrenic nerve (in C4 and C5), to the intercostal muscles, and the axiliary muscles of respiration are under the control of the expiratory and inspiratory center in the medulla oblongata, at the level of the inferior olive. These centers receive afferent fibers from the pneumotaxic center near the hypothalamus and from the solitary nucleus. The solitary nucleus is under the influence of messages sent be chemoreceptors of the carotid body over the glossopharyngeal (IX) and vagus (X) nerve, as well as by the stretch receptors in the lung sent over the vagus. 

Peripheral chemoreceptors:

Carotid bodies are located in the carotid sinus

Aortic bodies are located in the aortic arch

The peripheral chemoreceptors are located in carotid and aortic arteries, and senses changes in PO2, pH, and PCO2. Carotid body sensors more sensitive than aortic bodies. Central chemoreceptors sense changes in CO2 only. (In other words, all O2 sensing is in the peripheral!) 

Carotid body releases neurotransmitter when PO2 decreases. (Dopamine)

Since H+ passes poorly through the BBB, H+ is produced via accumulation of high PCO2. Stimulation of this system causes the urge to breath.

When arterial PCO2 > 70-80 mm Hg, negative feedback causes urge to breathe.

*Peripheral chemoreceptors are dominant for O2/H+, and central receptors are dominant for CO2.

All in all: Peripheral = Carotid and aortic chemoreceptors, and Central = Medullary chemoreceptors

-

The Respiratory System and Aging:

• Vital capacity in lungs decreases to 35% by age 70 
• Decreased macrophage activity
• Decreased ciliary action
• Decrease in O2 blood levels
• Higher susceptibility to pneumonia or bronchitis
• Chest wall becomes more rigid