Alveolar ventilation equation
VA = (VCO2 x K)/PACO2
VA = alveolar ventilation (ml/min)
V¬CO2¬¬ = rate of CO2 production (mL/min)
PACO2 = alveolar PCO2 (mm Hg)
K = constant = 836 mm Hg @ BTPS (body temp {310 K}, ambient pressure {760 mm Hg}, and gas saturated with H2O vapor)
-equation describes the inverse relationship between ventilation and alveolar PCO2
alveolar ventilation can also be calculated using:
V¬A = f(VT – VPD)
f = frequency of breathing (/min)
VT = tidal volume (mL)
VPD = physiological deadspace (mL)
Alveolar gas equation
PAO2 = PIO2 – PACO2/R + F
PIO2 = PO2 of inspired air (mm Hg)
Ft = correction factor
R = respiratory exchange ratio = VCO2/VO2
-PIO2 = FIO2(PB – PH2O), where FIO2 = fraction of O2 in inspired gas, PB = barometric pressure, PH2O = water partial pressure in inspired gas due to humidification
-equation describes the inverse relationship of PA
-F is small and usually ignored
Normal #’s:
PAO2 = 100 mm Hg
PACO2 = 40 mm Hg
VT = 450-500 mL
f = 12/min
VCO2 = 200-250 mL/min
R = 0.8
Sources:
West Pulmonary Pathophysiology
Costanzo Physiology
Access Medicine
Tuesday, August 14, 2007
Respiratory Histology
I. Epithelial cells
a. All epithelia are supported by basement membranes of variable thickness, which separate epithelia from underlying supporting tissues and are never penetrated by blood vessels
i. Epithelia are thus dependent on the diffusion of oxygen and metabolites from adjacent supporting tissues
ii. Basement membrane composition
1. Heparin sulphate – glycosaminoglycan (acidic)
2. Collagen type IV
a. Mesh-like
b. Important constituent of basement membranes
3. Structural glycoproteins
a. Fibronectin
i. Produced by fibroblasts of supporting tissue
b. Laminin
c. Entactin
4. Consists of three layers
a. Lamina lucida
i. Against the basal membrane of the parenchyma
b. Lamina densa
c. Lamina fibroreticularis
i. Merges with the underlying supporting tissue
5. Glandular epithelia
a. Glands – epithelium which is primarily involved in secretion
i. Exocrine glands – glands which maintain their continuity with the epithelial surface discharging their secretions onto the free surface via a duct
ii. Endocrine/ductless glands – epithelial secretory tissue that lies deep within other tissues
1. Their secretion = hormones
6. Cytokeratin intermediate filaments are usually found within epithelial cells and can therefore be used as to recognize an epithelial phenotype
7. Simple epithelia
a. Found at interfaces involved in selective diffusion, absorption or secretion
b. Provide little protection against mechanical abrasion and are therefore not found on surfaces subject to such stresses
c. Flattened simple epithelia are conducive to diffusion and are therefore found in the lungs, mesothelium, endothelium (lining of blood vessels)
d. Tall columnar cells have a large volume and are therefore found in areas that require highly active epithelial cells, i.e. the small intestine
b. Epithelial are classified according to three morphological characteristics
i. Number of cell layers
1. Simple epithelium – single layer of epithelial cells
2. Stratified epithelium – several layers
ii. Shape of the component cells
1. Based on sections taken at right angles to the surface of the epithelium
2. In stratified epithelia, the shape of the outermost layer of cells determines the classification
3. Shape of the cell is usually reflected in the shape of the nuclei
iii. Presence of surface specializations
1. i.e. cilia or keratin
II. Upper respiratory tract
a. Structures
i. Nasal cavity
ii. Paranasal sinuses
1. Act as resonance chambers for speech; reduce the bony mass of the facial skeleton
iii. Nasopharynx
1. Connected via the Eustachian tubes to the middle ear cavities, permitting equilibration of air pressure in the middle ear with that of the external environment
b. Involved in filtering, humidifying and adjusting the temperature of inspired air
c. Lined by pseudostratified columnar epithelium with numerous goblet cells (modified columnar epithelial cells which synthesize and secrete mucous). The epithelium is supported by the lamina propria, a loose collagenous layer. Together, the epithelium and the lamina propria make up the respiratory mucous membrane/respiratory mucosa. This is supported by the submucosa, which separates the mucosa from underlying structures
III. Lower Respiratory tract
a. Structures
i. Begins at the larynx, continues into the thorax as the trachea
1. Vocal cords
a. Protect the lower respiratory tract against the entry of foreign bodies
b. Speech
c. Lined by stratified squamous (flattened) epithelium
i. Better adapted than respiratory epithelium to withstand frictional stress
2. Trachea – main bronchi – lobar bronchi – segmental bronchi – bronchioles – terminal bronchioles – respiratory bronchioles – alveolar ducts – alveolar sacs
a. Each type of airway has its own characteristic structural features, but there is a gradual transition from one type to the next
b. Trachea
i. Respiratory epithelium gradually transitions from tall, pseudostratified columnar ciliated cells in the larynx and trachea to simple, cuboidal, non-ciliated cells in the bronchioles.
1. K (Kulchitsky) cells are electron dense secretory granules that constitute part of the neuroendocrine system
a. Serotonin, bombesin, calcitonin
ii. Site of formation of polyps in the repiratory tract (http://www.ctsnet.org/doc/4481 )
iii. Polyps: found anywhere where there is a mucous membrane
iv. 
1. Baum’s textbook of pulmonary disease
v. Lamina propria consists of fibroelastic tissue which contains lymphoid aggregates
1. Produce IgA, secreted onto the mucosal surface as a defense against microorganisms
vi. Smooth muscle lies deep to the mucosa (except in the trachea) and becomes more prominent as airway diameter decreases
1. Modulated by the autonomic nervous system
2. Sympathetic activity causes relaxation and therefore dilation of the airways
3. Parasympathetic activity causes constriction – reducing dead space on expiration
vii. Submucosal layer under the smooth muscle contains serous and mucous glands; become less numerous in narrower airways and are not present beyond tertiary bronchi
viii. Cartilage supports the larynx, trachea, and bronchi; it lies outside the submucosa and diminishes as the airways decrease in size and is gone beyond the tertiary bronchi
ix. Adventitia surrounds the outermost layer, a fibroelastic tissue
IV. Specific breakdown of cells in lower respiratory tract
a. Trachea
i. 
(www.lab.anhb.uwa.edu.au/.../
1. Tall pseudo stratified columnar cells with cilia
2. Goblet cells
3. Serous cells
4. KCells
5. Stem/reserve cells which are able to divide and differentiate to replace other cell types
a. Perichondrium – a dense layer of dense connective tissue surrounding the cartilage of developing bone
b. Primary bronchus, secondary (lobar), tertiary (segmental)
i. Any airway greater than 1mm
ii. Characterized by presence of glands and supporting cartilage
iii. Epithelium corresponds to trachea and main bronchi
iv. Bronci are surrounded by a layer of smooth muscle b/t the cartilage and epithelium
c. Bronchiole, terminal b, respiratory b
i. Epithelium changes to a ciliated columnar epithelium, but still also maintains the same epithelial cells as the bronchi and trachea
ii. Glands are cartilage are absent
iii. In terminal and respiratory bronchioles, goblet cells are replaced by Clara cells, tall columnar non-ciliated cells which contain apical secretory granules. They secrete one of the components of surfactant and act as reserve cells
iv. The layer of smooth muscle is relatively thicker than in the bronchi
d. Alveoli (www.lab.anhb.uwa.edu.au/.../
i. Wall of alveoli is formed by a thin sheet of epithelial cells and loose collagenous/elastic fibers. B/t the fibers are a dense network of anastomosing pulmonary capillaries, the walls of which are in direct contact with the epithelium of the alveoli
ii. Epithelium is formed by two cell types
1. Alveolar type I cells (small alveolar cells or type I pneumocytes) – squamous (as thin as .05 µm) and make up 95% of the walls.
2. Alveolar type II cells (large alveolar cells or type II pneumocytes) – irregularly shaped or cuboidal, form small bulges on alveolar walls. Contain granules (cytosomes) which consist of precursors to pulmonary surfactant. There are an equal number of Type I and Type II cells, however, the Type II cells have a decreased surface area due to their shape and therefore make up only 5% of alveolar surface area.
a. 
V. Blood supply
a. Pulmonary arterial vessels are relatively thin walled and large in diameter, with their diameter approximating that of the accompanying airway
b. P arteries have characteristics of elastic arteries rather than of muscular arteries, this maintains the pulmonary arterial pressure at a relatively constant level throughout the cardiac cycle
c. Bronchial vessels are similar to those found throughout the rest of the systemic circulatory system
Hi, I'm Jon. This is my first "blogging" experience so I'm kind of nervous. I'm really excited about "blogging" and can't wait to "blog" whenever the mood strikes... in the afternoon... in the evening... in the wee hours of the night before I cry myself to sleep. I hope everyone else on the internets want to "blog" with me. "Blogging" will be fun when lots of other curious internetters are "blogging" too. When I "blog", I hope the whole world "blogs" with me too!!!
Sunday, August 12, 2007
heart sounds
Heart Sounds
First sound (S1): described as a “low, slightly prolonged ‘lub’” (Ganong 569); vibrations caused by the closure of the mitral and tricuspid valves at the beginning of ventricular systole. It is soft when the heart rate is low. Normally, there is no splitting of this sound.
Normal duration: 0.15 s
Normal frequency: 25-45 Hz
Second sound (S2): a “shorter, high-pitched ‘dup’” (Ganong 569); caused by vibrations from the closure of the aortic and pulmonary valves, also known as the semilunar valves, just after the end of ventricular systole. The interval between the aortic and pulmonary valves shutting may split during inspiration (physiologic splitting) or in various diseases
Normal duration: 0.12 s
Normal frequency: 50 Hz
Clinical correlation—with increased respirations, S2 splits due to changes in intrathoracic pressure. The aortic valve closes before the pulmonary valve. (Michael Silverman, “Prehospital heart sounds”, EMSresponder.com)
Third sound (S3): a “soft, low-pitched sound” (Ganong 569); audible about one third of the way through diastole in many young adults. It is probably caused by an inrush of blood during rapid ventricular filling
Normal duration: 0.1 s
Fourth sound (S4): caused by ventricular filling and is usually association with a pathology. It is rarely heard in adults. It may be heard in cases of ventricular hypertrophy, where the ventricles are stiffer, or when atrial pressure is high.
First sound (S1): described as a “low, slightly prolonged ‘lub’” (Ganong 569); vibrations caused by the closure of the mitral and tricuspid valves at the beginning of ventricular systole. It is soft when the heart rate is low. Normally, there is no splitting of this sound.
Normal duration: 0.15 s
Normal frequency: 25-45 Hz
Second sound (S2): a “shorter, high-pitched ‘dup’” (Ganong 569); caused by vibrations from the closure of the aortic and pulmonary valves, also known as the semilunar valves, just after the end of ventricular systole. The interval between the aortic and pulmonary valves shutting may split during inspiration (physiologic splitting) or in various diseases
Normal duration: 0.12 s
Normal frequency: 50 Hz
Clinical correlation—with increased respirations, S2 splits due to changes in intrathoracic pressure. The aortic valve closes before the pulmonary valve. (Michael Silverman, “Prehospital heart sounds”, EMSresponder.com)
Third sound (S3): a “soft, low-pitched sound” (Ganong 569); audible about one third of the way through diastole in many young adults. It is probably caused by an inrush of blood during rapid ventricular filling
Normal duration: 0.1 s
Fourth sound (S4): caused by ventricular filling and is usually association with a pathology. It is rarely heard in adults. It may be heard in cases of ventricular hypertrophy, where the ventricles are stiffer, or when atrial pressure is high.
HYPERSENSITIVITY-Summary
Immediate Hypersensitivity: Mediated by IgE antibodies, mast cells, and eosinophils (type I)
Cytotoxic Hypersensitivity: Mediated by IgM or IgG antibodies (type II)
Immune-Complex Hypersensitivity: Mediated by antigen-antibody complexes deposited in tissue. (type III)
Delayed Hypersensitivity: Mediated by helper T cells and macrophages. Independent of antibodies. (type IV)
MECHANISMS
****Immediate Hypersensitivity (TYPE I) : Initial exposure leads to antibody synthesis and memory B-Cell production
Re-exposure: Antigen causes production of IgE antibodies.
HOW?? Allergens presented by B cells activate Helper T-cells. Helper T-cells
Release cytokines that cause B cells to turn into IgE-producing plasma cells.
⇒ IgE antibodies become attached to mast cells via binding sites on their Fc portions (cross over is important) -> Same antigen binds to IgE bound to mast cell and inflammatory mediators are activated (histamines, eicosanoids, chemokines) SEE DIAGRAM
Cytotoxic Hypersensitivity:
Immune-Complex Hypersensitivity:
-Many antibodies (IgG or IgM) combine with free antigens
-> antigen-antibody complexes precipitate out on the surface of endothelial cells or become trapped in capillary walls
-> complexes activate complement system (several proteins work together to kill target cells) and inflammatory response occurs
Delayed Hypersensitivity:
-Antigens in the area activate cytokines via helper T cells
-> cytokines act as inflammatory mediators and activate macrophages to secrete their potent mediators.
-> allergy develops in several days
Immediate Hypersensitivity: Mediated by IgE antibodies, mast cells, and eosinophils (type I)
Cytotoxic Hypersensitivity: Mediated by IgM or IgG antibodies (type II)
Immune-Complex Hypersensitivity: Mediated by antigen-antibody complexes deposited in tissue. (type III)
Delayed Hypersensitivity: Mediated by helper T cells and macrophages. Independent of antibodies. (type IV)
MECHANISMS
****Immediate Hypersensitivity (TYPE I) : Initial exposure leads to antibody synthesis and memory B-Cell production
Re-exposure: Antigen causes production of IgE antibodies.
HOW?? Allergens presented by B cells activate Helper T-cells. Helper T-cells
Release cytokines that cause B cells to turn into IgE-producing plasma cells.
⇒ IgE antibodies become attached to mast cells via binding sites on their Fc portions (cross over is important) -> Same antigen binds to IgE bound to mast cell and inflammatory mediators are activated (histamines, eicosanoids, chemokines) SEE DIAGRAM
Cytotoxic Hypersensitivity:
Immune-Complex Hypersensitivity:
-Many antibodies (IgG or IgM) combine with free antigens
-> antigen-antibody complexes precipitate out on the surface of endothelial cells or become trapped in capillary walls
-> complexes activate complement system (several proteins work together to kill target cells) and inflammatory response occurs
Delayed Hypersensitivity:
-Antigens in the area activate cytokines via helper T cells
-> cytokines act as inflammatory mediators and activate macrophages to secrete their potent mediators.
-> allergy develops in several days
Thursday, August 9, 2007
Learning Issues
6-6
o Respiratory center - Mike
o Medications – Jon
o Physical exams/family history – Dave
o Mechanism of shortness of breath/normal respiratory rate – Daria
o Blood flow to lung – Jon
o Gas exchange – Nik
o Flow rate, tidal volume, etc. – Nik
o Lung Anatomy – Matt
o Breathing mechanism – Daria
o Infection – Carolyn
o Coughing mechanism – Mike
o COPD – Carolyn
o Asthma – Dave
· 6-8
o Lymphatic system of the lung - Nik
o Hypoxia - Mike
o Hypercapnia - Matt
o High altitude breathing - Dave
o V/Q ratio - Jon
o Pulmonary drugs/mechanisms - Daria
o DPG - Carolyn
Nervous system – basic layout
o Cough reflex/chemoreceptors
DPG
2,3 Diphosphoglycerate (2,3 DPG, or 2,3 bisphosphoglycerate, or 2,3 BPG)
3 factors that affect oxygen binding:
• Hydrogen ions
• Covalent binding of CO2
• 2,3 DPG binding
Formation of 2,3 DPG
• formed in red blood cells from the glycolytic intermediate 1,3 bisphosphoglycerate through the Rapoport-Luberin shunt
• red blood cells contain 4-5 mM 2,3 DPG; trace amounts in other cells
• 2,3 DPG is a modulator of oxygen binding to hemoglobin that stabilizes the deoxy form of hemoglobin, facilitating oxygen release to tissues
General information about Hemoglobin (Hb)
• major transporter of oxygen from lungs to tissue
• there are a few different forms of Hb, w/ HbA being the major adult form
• Hb is tetrameric and has 2 alpha and 2 beta chains
• Hb operates as two αβ dimers. The α and β chains are bound tightly through electrostatic interactions***
• 1 Hb binds 4 molecules of oxygen, one/heme group
• Oxygen binding is cooperative in that once one oxygen unit binds, it facilitates binding to other subunits—why the oxygen dissociation curve is sigmoidal
• Two forms of Hb, relaxed, “R”, or taut, “T”. The relaxed form is the oxygenated state, and the taut form is the deoxygenated state
Binding
• 2,3 DPG binds to the beta-chain of Hb in the central cavity formed by the 4 subunits, which increases the energy required for conformational changes that normally facilitate binding of oxygen
• when Hb contains 2,3 DPG, there is less affinity for oxygen binding
• less oxygen is bound and therefore is more available to tissues
• has the Bohr effect, shifts the oxygen dissociation curve to the right
• oxygen does not bind as easily to Hb and is released more easily from Hb
Conditions that increase levels of 2,3 DPG (and better delivery of O2 to tissues)
• emphysema
• high altitudes (decreased partial pressure of O2)
• chronic anemia
Resources:
Mark’s Medical Biochemistry A Clinical Approach by Smith, Marks, and Lieberman p808-815
Harper's Illustrated Biochemistry 27th Edition by Murray, Granner, Rodwell (online book) Chapter 6
Carolyn
3 factors that affect oxygen binding:
• Hydrogen ions
• Covalent binding of CO2
• 2,3 DPG binding
Formation of 2,3 DPG
• formed in red blood cells from the glycolytic intermediate 1,3 bisphosphoglycerate through the Rapoport-Luberin shunt
• red blood cells contain 4-5 mM 2,3 DPG; trace amounts in other cells
• 2,3 DPG is a modulator of oxygen binding to hemoglobin that stabilizes the deoxy form of hemoglobin, facilitating oxygen release to tissues
General information about Hemoglobin (Hb)
• major transporter of oxygen from lungs to tissue
• there are a few different forms of Hb, w/ HbA being the major adult form
• Hb is tetrameric and has 2 alpha and 2 beta chains
• Hb operates as two αβ dimers. The α and β chains are bound tightly through electrostatic interactions***
• 1 Hb binds 4 molecules of oxygen, one/heme group
• Oxygen binding is cooperative in that once one oxygen unit binds, it facilitates binding to other subunits—why the oxygen dissociation curve is sigmoidal
• Two forms of Hb, relaxed, “R”, or taut, “T”. The relaxed form is the oxygenated state, and the taut form is the deoxygenated state
Binding
• 2,3 DPG binds to the beta-chain of Hb in the central cavity formed by the 4 subunits, which increases the energy required for conformational changes that normally facilitate binding of oxygen
• when Hb contains 2,3 DPG, there is less affinity for oxygen binding
• less oxygen is bound and therefore is more available to tissues
• has the Bohr effect, shifts the oxygen dissociation curve to the right
• oxygen does not bind as easily to Hb and is released more easily from Hb
Conditions that increase levels of 2,3 DPG (and better delivery of O2 to tissues)
• emphysema
• high altitudes (decreased partial pressure of O2)
• chronic anemia
Resources:
Mark’s Medical Biochemistry A Clinical Approach by Smith, Marks, and Lieberman p808-815
Harper's Illustrated Biochemistry 27th Edition by Murray, Granner, Rodwell (online book) Chapter 6
Carolyn
PULMONARY PHARMACOLOGY
Bronchodilators: relax constricted bronchiolar smooth muscle and open blocked airways. B-adrenergic receptor agonists are used to treat bronchospasm. drugs relax bronchial smooth muscle. B-adrenergic receptor agonists mimick a normal B-receptor response (which is usually stimulated by mostly epinephrine and at times norepinephrine). ALBUTEROL See diagram
(http://cvm.msu.edu/RESEARCH/PULMON/site/respiratory_diseases/diseases/Heaves/MOA_of_BDD.html)
Methylxanthines: Only salts of theophylline are used as bronchodilators (including aminophylline). http://ajrccm.atsjournals.org/cgi/content/full/167/6/813
Mechanism of theophylline.
Some bronchodilator effects: inhibits phosphodiesterases which normally hydrolyze cAMP. cAMP increases and causes smooth muscle relaxation. Also, theophylline is believed to inc. diaphragm contractions and decrease diaphragm fatigue but this has not been proven.
Mucolytic agents: alter the characteristics of respiratory tract fluids
They help reduce the viscosity of sputum (expectorated mucus mixed with serum proteins, lipids, electrolytes, calcium, and DNA from white blood cells) by depolymerizing mucopolysaccarides into smaller, more soluble molecules. Acetylcysteine (mucomyst, mocosol) is used in asthma. The free sulfhydryl group reacts with disulfide bonds in mucoproteins and breaks them up. Acetylcysteine is also a free radical scavenger that protects the airways against oxidant damage.
HSCH2CHCOOH
|
NHCOCH3 Acetylcysteine May be given orally or by nebulization
Antibiotics: Combat infections
Glucocorticoids: reduce inflammation within the respiratory tract and cause other bronchoreactivity. Two possible mechanisms: 1) enhance the action of adrenergic agonists on B2 receptors. 2) modulate eicosanoid production and reduce the synthesis of prostaglandins and leukotrienes. Prostaglandins and leukotrienes are bronchoconstrictors
PREDNISONE
Nasal decongestants: constrict dilated vessels in the nasal mucosa
What happens in the nose?
Resistance to airflow in the upper airways is regulated by autonomic control of smooth muscle within mucosal blood vessels. Allergies, viruses, and inflammatory conditions can cause these vessels to dilate which causes congestion. All act by the same mechanism but vary in duration of action. Direct application: constricts the mucosal vessels through alpha-adrenergic mechanisms. Common drugs: phenylehrine, oxymetazoline, ephedrine, xylometazoline (Goth’s medical pharmacology).
Antitussives: reduce coughing.
Norma Jean’s Drugs:
Aminophylline
Ventolin (albuterol)
Prednisone
Daria
Bronchodilators: relax constricted bronchiolar smooth muscle and open blocked airways. B-adrenergic receptor agonists are used to treat bronchospasm. drugs relax bronchial smooth muscle. B-adrenergic receptor agonists mimick a normal B-receptor response (which is usually stimulated by mostly epinephrine and at times norepinephrine). ALBUTEROL See diagram
(http://cvm.msu.edu/RESEARCH/PULMON/site/respiratory_diseases/diseases/Heaves/MOA_of_BDD.html)Methylxanthines: Only salts of theophylline are used as bronchodilators (including aminophylline). http://ajrccm.atsjournals.org/cgi/content/full/167/6/813
Mechanism of theophylline.
Some bronchodilator effects: inhibits phosphodiesterases which normally hydrolyze cAMP. cAMP increases and causes smooth muscle relaxation. Also, theophylline is believed to inc. diaphragm contractions and decrease diaphragm fatigue but this has not been proven.
Mucolytic agents: alter the characteristics of respiratory tract fluids
They help reduce the viscosity of sputum (expectorated mucus mixed with serum proteins, lipids, electrolytes, calcium, and DNA from white blood cells) by depolymerizing mucopolysaccarides into smaller, more soluble molecules. Acetylcysteine (mucomyst, mocosol) is used in asthma. The free sulfhydryl group reacts with disulfide bonds in mucoproteins and breaks them up. Acetylcysteine is also a free radical scavenger that protects the airways against oxidant damage.
HSCH2CHCOOH
|
NHCOCH3 Acetylcysteine May be given orally or by nebulization
Antibiotics: Combat infections
Glucocorticoids: reduce inflammation within the respiratory tract and cause other bronchoreactivity. Two possible mechanisms: 1) enhance the action of adrenergic agonists on B2 receptors. 2) modulate eicosanoid production and reduce the synthesis of prostaglandins and leukotrienes. Prostaglandins and leukotrienes are bronchoconstrictors
PREDNISONE
Nasal decongestants: constrict dilated vessels in the nasal mucosa
What happens in the nose?
Resistance to airflow in the upper airways is regulated by autonomic control of smooth muscle within mucosal blood vessels. Allergies, viruses, and inflammatory conditions can cause these vessels to dilate which causes congestion. All act by the same mechanism but vary in duration of action. Direct application: constricts the mucosal vessels through alpha-adrenergic mechanisms. Common drugs: phenylehrine, oxymetazoline, ephedrine, xylometazoline (Goth’s medical pharmacology).
Antitussives: reduce coughing.
Norma Jean’s Drugs:
Aminophylline
Ventolin (albuterol)
Prednisone
Daria
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