alveolar ventilation/gas equations

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

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/.../respir.htm)

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/.../respir.htm)

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

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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.

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

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