Biology 2402  AP  II  Lecture Notes
Respiratory
Dr. Weis

Respiratory System ::  function --> provide O2, remove CO2

I. Anatomy  divided into upper respiratory and lower respiratory regions
Functionally divided into conducting and respiratory zones

Upper conducting respiratory :: conducting pathways to

Lower respiratory zones:: lung alveoli for gas exchange

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A. Nose :: functions

Divisions ::

  Areas of nasal cavity

The above two structures in creating air turbulence will trap nongaseous particles due to increased exposure to mucosal surface and thereby filter the air moving through.

Paranasal sinuses :: in the frontal, sphenoid, ethmoid, and maxillary bones.  Fxn: to lighten the skull, resonate speech, warm/moisten air which are lined with a mucus membrane

Problems :: sinusitis, nasal polyps, rhinitis

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1. Nasopharynx :: superior to the level of the soft  palate.

2. Oropharynx :: posterior to oral cavity and extends from the soft palate to the epiglottis. 

3. Laryngopharynx :: extends to larynx then is continuous with the esophagus.
Stratified squamous epithelium. Common passageway for food and air.

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C. Larynx ::

from C4 - C6 region, opens superiorly into the laryngopharynx and is continuous inferiorly with the trachea which will have respiratory epithelium

Fxn ::     

Structure ::

The vocal ligaments are intrinsic (between cartilages) and are elastic fibers that extend from the arytenoids to the thyroid cartilage.  Mucosal folds form the vocal  folds or true vocal cords and will vibrate with sound production.  Vestibular folds will form the false vocal cords and do not move to create sound production.

The glottis is the opening between the vocal cords and the air passageway that is closed off by the epiglottis as food enters the laryngopharynx.

Laryngeal muscles can be located intrinsically and will change the tension in the vocal ligaments as well as open and close the glottis.  Extrinsic muscles will move the larynx.

Problems in this area :: Laryngitis

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D. TRACHEA ::

from the larynx (cricoid cartilage) to the midthorax in the mediastinum.

            The first generation respiratory passageway.

     Wall is in layers ::

Last cartilage before the tracheal bifurcation is called the CARINA, which is a landmark area used in bronchoscopy and radiology.

Blood supply from the subclavian branches :: Thyrocervical to supply the larynx and trachea.

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E. Bronchi and branches ::

Division of trachea into Right/Left Primary Bronchi = (second generation conduction passageway) that enters the lung at the hilus at the level of the T7 vertebra. Also known as the extrapulmonary bronchi.

 Will divide into secondary bronchi (lobar bronchi) to enter each lung lobe.  The intrapulmonary bronchi will continue to divide into 3^rd, 4^th, 5^th, etc. segmental branches (generations) up to 20-25 branches to reach the level of the alveoli. Collectively called intrapulmonary bronchi.

Final branches of the bronchi are the respiratory bronchioles which are air passageways that a that are less than 1 mm diameter. Contain NO cartilage, or cilia.

The final bronchioles are the terminal bronchioles, that have cubiodal epithelium.

Composition of this region ::

Terminal bronchioles (respiratory bronchioles) will continue as alveolar ducts --> alveolar sacs --> alveoli

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Respiratory Zone:

Alveoli :: expansions along the wall of the alveolar sac.

The basement membrane of the alveoli and the pulmonary capillaries will fuse to form the RESPIRATORY MEMBRANE

Gas exchange will be by simple diffusion across the respiratory membrane based on the concentration gradient, lipid solubility, and distance.

Cuboidal cells called Type II alveolar cells will be scattered along the walls and are repsonsible for secreting a lipoprotein called SURFACTANT that is responsible for decreasing the surface tension.

Macrophages called alveolar macrophages or dust cells provide defense against bacteria/foreign particles.
Dead cells are eliminated by coughing and the mucociliary elevator mechanisms.

Alevolar capillary endothelial cells secrete ACE [angiotensin converting enzyme] to change Angiotensin I to Angiotensin II.

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F. Lungs :: paired in the thoracic cavity within the right and left pleural cavities.

Connected to the mediastinum at the root formed by the entrance of the primary bronchi and blood vessels.

Anatomy -->

Left lung ::

Right lung ::

Each lobe is divdided into segments called the Bronchopulmonary segments that are served by their own arterial/venous branches and bronchus.  Divisions are created by connective tissue septae.

Stroma is elastic connective tissue which forms the basis for structure and anchoring the elastic CT.

Blood supply by

Lung Pleura :: serosal membrane called the PLEURA that is double layered to form the parietal pleura that is along the thoracic wall, diaphragm and heart visceral pleura that is lies external on the lung surface.

serous fluid --> plueral fluid is formed to decrease friction and will help create a negative intrapleural pressure.

Problems :: inflammation of the pleura called Pleurisy

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Respiratory Physiology involves 4 events ::

Mechanics of Pulmonary Ventilation (breathing) involves the physical movement of air in two phases :: inspiration & expiration.

Thoracic cavity pressure ::

The two pressures we deal with are :

Intrapulmonary or alveolar pressure are those pressures within the alveoli and will change with the breathing cycle between +1 and -1 mmHg and will equalize with atmospheric pressures (0 or 760 mmHg).

Intrapleural or pleural pressures are within the pleural cavity between the parietal and visceral pleura and will change with the breathing cycle to range from -4mmHg to -8mmHg.  These negative pressures are the result of interactions of forces.....those that pull the lungs to the thoracic wall and those that pull the lungs from the wall.

   Toward the wall factors ::

Away from the wall factors ::

NEGATIVE PRESSURE in the INTRAPLEURAL SPACE is IMPORTANT !!!

  If intrapleural = intrapulmonary (atmosphere) as in the case  of pneumothorax, the lung will collapse (atelectasis).

The pressure difference between alveoli and pleural pressures is called transpulmonary pressure or recoil pressure that is actually a measure of elastic forces in the lungs that tend to collapse the lung at each point of expansion.

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I. Pulmonary Ventilation or Breathing is a mechanical process that depends on the volume changes in the thoracic cavity.  The volume will lead to pressure changes that lead to flow of gases to equalize pressure.

            Pressure and Volume relationship given by Boyle's Law....at a constant temperature 

P1 x V1 = P2 x V2.  This is an inverse relationship....to have the equation equal on both sides, if the new volume (V2) is decreased, the new pressure (P2) will increase in order to maintain equilibrium (homeostasis).

Two phases of pulmonary ventilation :: inspiration & expiration

1. Inspiration :: the thoracic cavity changes--> enlarges by contraction of the diaphragm to flatten out and elevation of the rib cage by the scalenus muscle.

Therefore the lungs are stretched and Intrapulmonary volume is increased, so now the Intrapulmonary pressure will decrease (Boyle's law).  The decrease will be -1 mmHg.  Air will come in along its pressure gradient (atm = 0) until Intrapulmonary = atmospheric pressure. Meanwhile, intrapleural pressures will decline to -8 mmHg.

Additional changes in volume to enlarge the thorax are by accessory muscles such as the :: external intercostals, sternocleidomastoid, serratus anterior, spinal muscles, pectorals.

2. Expiration :: passive process due to lung elasticity.

 This will increase intra-abdominal pressure to force abdominal organs against the diaphragm, and also pull the rib cage downward (rectus abdominus m.) and depress the rib cage (internal intercostals).

Pulmonary Ventilation factors ::

1. Respiratory passageway resistance or friction of gas flow

Formula  F[gas] =  P1-P2 [gas]/ R[gas]  (same one for blood flow, now with the reference to gas).

Resistance is determined by diameter of the conducting tubes, but is usually not a problem due to the relatively large diameters and diffusion will occur at the smaller diameters to move the gases. However, if diameter changes can create problems.

Problems -->

2. Lung Compliance...which is the destensibilty or ease of expansion of the lungs for each unit increase in transpulmonary pressure.  Depends on the elasticity of the lungs and the expansibility of the thoracic cavity.

Another way to put it -- the amount of transpulmonary pressure required to expand the lung volume.
Compliance curves can be plotted and will be determined by elastic forces such as the elastic/collagen fibers in the lungs and the surface tension.

It is deminished by blocked passageways, increases in alveolar surface tension, impared thoracic cage flexiblity.   {  (C  =  V/ P) FYI formula. }

3. Lung Elasticity ... lung distension and recoil due to fibroelastic tissue (collagen, elastin).

4. Alveolar Surface Tension

Surface tension is the elastic force at the gas-liquid boundary.  Liquid molecules are more strongly attracted to each other than gas and create tension at the liquid surface to resist forces to increase the area (spread out) and will cause collapse of the alveoli.  Water has a high surface tension and is the primary component of the liquid film on the alveolar walls, thereby acting to reduce alveoli to its smallest size.

Surfactant, a lipoprotein made of phospholipids, apoproteins and calcium, is secreted from Type II alveolar epithelial cells.  Since it does not dissolve in water, it interfers with H20 to decrease surface tension causing it to spread out and create a film over the surface.

 This prevents alveolar collapse and allows the lungs to expand by reducing the amount of transpulmonary pressure recquired to keep the lungs expanded. 
{ P = 2 x surface tension / radius of alveoli}

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IV. Lung Volumes and Function Tests ::

A. Respiratory Volumes and Capacities

  1. Volumes (#4)

  2. Capacities (#4)

B. Dead Space

If alveoli collapsed/obstructed will then create alveolar dead space...no gas exchange

The combined two for the total dead space is called the physiologic dead space.

C. Function Tests :: Instrument --> spirometer to measure the volumes.

Other tests ....

Gas Exchange ::

This is called Dalton's law and it deals with partial pressures.

The total pressure is directly proportional to the concentration of gas molecules.

Atmospheric air is our standard and its pressure is measured at 760 mm Hg and is composed of the following gases ::

Nitrogen   78.6 %         x  760 mm Hg  = 597 mm Hg  (PN2)

Oxygen     20.8 %        x  760 mm Hg  = 159 mm Hg  (PO2)

CO2          .04%          x  760 mm Hg  =  .3 mm Hg  (PCO2)

H2O          .5%            x  760 mm Hg    = 3.7 mm Hg  (PH20)             

         -------------------------                  ---------------------

            100%                                                   760 mm Hg

Therefore from Dalton's law, we have the sum of the partial pressures is equal to the total pressure, that is ::  PN2 + PO2 + PCO2 + PH2O  =  760 mmHg

Another gas law...Henry's Law deals with the solubility of gases in a liquid (water). 

Lets look at Alveolar Gas Composition vs Atomospheric air ::

PN2 = 573, PO2 = 100 , PCO2 = 40, PH2O = 47.

The net diffusion is determined by the partial pressure difference between the pulmonary blood and the alveoli.

To Summarize :: Alveolar air has a different concentration than atmospheric air

The slow replacement of alveolar air creates a more stable mechanism to help prevent excessive changes in levels of O2, CO2, and pH.

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EXTERNAL RESPIRATION ::

movement of O2/CO2 across the respiratory membrane depends on -->

  1. pressure gradient is created

  2. Respiratory membrane :: thin, will increase the surface area  so that gas is easily exchanged.

 In disease states -->

  3. Ventilation/Perfusion Ratio ::

Ventilation is the amount of gas reaching the capillaries and Perfusion refers to blood flow.

In the normal state, this is matched and synchronized and gives a normal ratio represented by Va / Q.
Whenever Va / Q is below normal (approaches 0), there is not enough ventilaton to provide O2 to oxygenate blood flowing through the alveolar capillaries, so some veinous blood does not become oxygenated and is called shunted blood.

When Va / Q is greater than normal (approaches infinity) ventilation is greater in some alveoli, but blood flow is low, so more oxygen is available that can be transported, so this oxygen is wasted and becomes part of the physiological dead space.

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INTERNAL RESPIRATION :: Gas exchange at the tissues.

PO2 in tissues is lower than blood

ICF --> 40 mm Hg   and     100 mm Hg  in blood

  therefore oxygen moves from blood into the tissues until  equilibrium (100 mm Hg).

PCO2 the same.  PCO2 blood is 40 mm Hg and tissue (ICF) is 45

  The exchanges take place by simple diffusion and are driven by partial pressure gradients that occur on either side of the membrane (move from high to low).

  Transportation of Respiratory Gases by Blood  (O2 and CO2)

Oxygen carried by blood 2 ways -->

In HgB the iron atoms in the heme are the Oxygen binding sites

Rate of hemoglobin binding and release is regulated by several factors ::

The affinity of Hemoglobin for oxygen will create a curve that is sloped because affinity increases the more oxygen that binds until fully saturated and will depend on the PO2.

The % of HgB bound to O2 will increase as PO2 increases.

The curve is called the Oxygen-Hemoglobin Dissociation Curve.

example points on the curve ::

The factors that affect the curve will cause a shift upward to the left or downward to the right. 
When the curve shifts to the right, there is a decreased affinity of HgB for oxygen and Oxygen is unloaded to the tissues.
Shifts of the curve upward/to the left will increase HgB affinity for oxygen so more oxygen is transported, but little is released to the tissues.

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A summary of factor influences ::

Shifting of the curve to the right caused by

Shifting of the curve to the left caused by

The shifting of the curve by changes in blood CO2, and hydrogen ion (H+) has a significant effect on the oxygenation of blood and the release of oxygen  from the blood to the tissues and is known as the Bohr effect.

DPG is 2,3 diphosphoglycerate and is formed from RBC glycolysis and keeps the curve slightly shifted to the right.
Increasing the metabolic rate of RBC, will increase DPG DPG binds to HgB and decreases the affinity for oxygen and causes oxygen release to the tissues.
Used to determine if stored blood is worthwhile for use in transfusions.

The RBC metabolic rate can be affected by hormones such as T3, T4, testosterone,

GH, and the catecholeamines (epinephrine, norepinephrine).

Fetal hemoglobin has a different structure and has a stronger affinity for oxygen, so curve is shifted to the left.

 
Problems with O2 transport ::

1. Hypoxia --> inadequate oxygenation to the tissues

2. Carbon Monoxide  (CO)

CO2 Transport ::

1. Dissolved in plasma...............7%

2. Bound to HgB.................... 23%  called carbaminohemoglobin, and will bind to the amino acid of the globin so it DOES NOT compete with oxyhemoglobin. This % amount is determined by the Haldane effect.        

3. Bicarbonate ion in plasma........70%

  Carbon dioxide binding is affected by PCO2 and degree of oxygenation of hemoglobin.

 Here's what happens ::

When CO2 diffuses into RBC's it reacts with water to form carbonic acid, then dissociates with the help of the enzyme carbonic anhydrase to form bicarbonate ion and hydrogen ion.  The formula below You MUST KNOW !!!

                            CO2 + H2O <========> H2CO3  <=======>  H+  +  HCO3-

  Then bicarbonate ion will diffuse into the plasma and chloride ion will diffuse into the RBC to cause the chloride shift.

  In the lungs the reverse takes place... HCO3- into RBC, Cl- out into the plasma.  HCO3- will recombine with H+ to form H2CO3 which is then split by carbonic anhydrase to form CO2 and H2O.

CO2 will diffuse along its partial pressure gradient into the alveoli (45 --> 40 mm Hg).

  The amount of CO2 transported is influenced by the degree of O2 saturation. 
The less PO2, the less O2 saturation of HgB, then the more CO2 can be carried by HgB in the blood. 

Reduced HgB can form carbaminohemoglobin and buffer H+ by binding.  As more CO2 enters the systemic blood, the more O2 dissociates from HgB which allow more CO2 to combine with HgB and more HCO3- to be formed.

In the pulmonary system, the reverse occurs... increased O2 causes release of H+ from HgB.  H+ will combine with HCO3- to form CO2 and water, so CO2 is released.

  pH and CO2 ::

If increase in H+, then combines with HCO3 to form H2CO3

If decrease in H+, then H2CO3 dissociates releasing H+ and lowering the pH

pH = negative logrithm of H+ concentration

Respiratory rate / depth can modify the amount of H2CO3 -->

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1. Medullary Respiration Centers

a. Inspiratory Centers....nuclei in the dorsal respiratory group (DRG)

 Spontaneously fire creating action potentials increasing in strength to cause a wave and initiating inspiration. 
Gives the rate and rhythm to breathing.  Normal rate/rhythm is called EUPNEA.  (12 - 18 breaths / min)

b. Expiratory center...nuclei in the ventral respiratory group (VRG).

2. Pons Respiratory Centers

two centers that affect the DRG (changes in inspiration)

inhibitory to medullary inspiratory center to end inspiration and permit expiration fine tunes and prevents overinflation of the lungs.

Affects the rate and pattern of breathing.

stimulates medullary center to prolong inspiration and control the depth.

Factors that affect rate and depth ::

* irritants......causing sneezing, coughing, bronchiole constriction

* stretch receptors... in the lungs/bronchi/bronchioles as a protective mechanism to prevent overinflation by causing negative feedback to the medullary inspiratory center.

* higher brain....

* chemical.....chemoreceptors in the central medulla and in the carotid bodies and aortic arch

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Central controls for respiration

1. PCO2

Peripheral control for respiration  

2. PO2 will affect peripheral receptors (those in the large vessels) and  will be stimulated when the pressure is between 30-60 mm Hg.

3. Arterial pH affects peripheral chemoreptors in the great vessels

A decrease in pH (acidosis) can have many causes.

 To compensate, the respiratory rate & depth is increased to remove CO2 and increase pH.

4. Factors that influence respiratory rate and depth

In Summary::

The stimulus for breathing  --> Removal of CO2

a. CO2 accum in CSF --> central chemoreceptors to be stimulated to increase the rate and depth to decrease CO2

b. PO2  if arterial PO2 drops below 60 mm Hg will stimulate peripheral chemoreceptors to stimulate the respiratory centers to create 50% increase in respiration.

c. pH .... arterial changes stimulate peripheral chemoreceptors

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Problems ::   Constrictive and Obstructive Lung Diseases

1. Constrictive...lungs cannot expand to normal volume.

2. Obstructive :: difficult to expire, air in lungs gets trapped.

   Diseases :: asthma, emphysema @ some stages

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Summary of other diseases -->

*Emphysema.....loss of lung parenchyma, Va/Q mismatch

*Pneumonia.....any inflammatory condition, alveoli filled with fluid/cells, large areas consolidated

*Atelectasis... collapse of alveoli due to obstruction from mucus or cancer ; decreased surfactant

*Asthma....spastic contraction of the bronchiolar smooth muscle to change the diameter

*TB...bacilli walled off to form tubercle, if not walled off,  then creates large abscess cavities and fibrosis

*Hypoxia :: different causes --> extrinsic (outside air change) pulmonary, cardiac, circulatory

*Hypercapnia.........increased PCO2

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Fetal Circulation ::

            lungs are filled with fluid

            and blood is diverted from the pulmonary circuit by way of the --> ductus arteriousus  between the pulmonary trunk and the aortaforamen ovale  between right and left atria in the atrial septal wall

 These vascular shunts will close at birth as increased PCO2 will stimulate breathing. 

Lungs will completely inflate within two weeks.

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Aging Changes ::