OS 213LEC 03: REVIEW OF NORMAL LUNG STRUCTURE AND FUNCTION: ALTERATIONS IN RESPIRATORY FUNCTION

OUTLINE:

I. Objectives

II. Important Physiologic Concepts to RecallIII. Important Things to Recall

A. Alveoli: The Egg

B. Airways: The Pipes

C. Mucociliary Elements: The Broom

D. Lymphatics: The Dust Pan

E. Lung Recoil: The Nylon Stockings

F. Surfactant: The Soap

G. Lung Mechanics: The Balloon

IV. Approach to Lung Disease

A. Problem-oriented approach

B. Normal breath sounds

C. Other Respiratory symptoms

Disclaimer: The focus of Dr. Balgos lecture are the topics under the second heading. There were some information omitted from the previous trans because they werent discussed. However, we retained some parts that were not discussed and just placed them in boxes.

OBJECTIVES

1. Review important concepts in pulmonary physiology and pathophysiology 2. Review chest/lung P.E. findings as they relate to natural history of pulmonary diseases3. Integrate knowledge of structure and function into physical diagnosis and history takingIMPORTANT PHYSIOLOGIC CONCEPTS TO RECALL

Mucociliary clearance, cough, and other defense mechanisms

Where is airway resistance highest?

Ventilation/perfusion matching and its effect on gas exchange

Equal pressure point (important for emphysematous patients) Effect of lung volume on ventilation and perfusion

IMPORTANT BASIC THINGS TO RECALL

The egg (Alveolus) The pipes (Airways)

The broom (Mucociliary Elements) The dust pan (Lymphatics) The nylon stockings (Lung Recoil) The soap (Surfactant) The balloon and syringe (Lung Mechanics)Alveoli: The Egg

Alveoli have a wider total surface than the skin (as wide as a tennis court: >120 m2)

Sunny side up arrangement of cells to increase surface area SHAPE \* MERGEFORMAT

Airways: The Pipes

1. Conducting Zone

No gas exchange

Consists of anatomic dead space (air that remains in the respiratory tract but is not involved in gas exchange);

~ 1st 16 generations of bronchioles

Trachea ( bronchi ( bronchioles ( terminal bronchioles

Trachea cartilaginous rings

Bronchi cartilaginous plates

Bronchioles no cartilaginous support

Also, at the terminal bronchiole:

No more goblet cells

No more cilia a.k.a. The Broom Clara cells: cuboidal, non-ciliated2. Transitional and Respiratory zone Gas exchange: no more muscularis layer, only simple epithelium adjacent to rich vascular bed Respiratory bronchioles ( Alveolar ducts ( Alveolar sacs

Generations from trachea to alveoli may vary from 10-27 SHAPE \* MERGEFORMAT

Figure 1. Transition from trachea to alveolar sac.Dr Balgos: 0 to 16th gen conducting zone. Try to remember the terminal bronchiole: beyond the terminal bronchiole gas exchange already happens. The epithelium also changes because lung has to promote gas exchange.

Figure 2. L-R Comparison of bronchus, bronchioles and alveolus3. Ventilation

Dynamics of Breathing (Airflow) Laminar - linear, found in small airways, relatively quiet airflow

Turbulent - characterized by eddy currents; found in large airways and at bifurcations; breath sounds are low-pitched and harsh

Figure 3. Laminar vs. Turbulent Flow

Airway Resistance Relationships: Diameter of the tube - INVERSE (increase in diameter, lower resistance) Length of the tube- DIRECT (increase in length, increase in resistance)

Flow- DIRECT (faster flow, more resistance) Theoretically, the smaller and longer the airway, the higher the resistance to airflow; however, the smaller airways ( 1 ventilation exceeds perfusion

V/Q < 1 perfusion exceeds ventilation

In individuals with cardiopulmonary disease, mismatching of pulmonary blood flow and alveolar ventilation is the most frequent cause of systemic arterial hypoxemia.

Because gravity evokes regional differences in ventilation and perfusion, even in the normal lung, V/Q ratio in different areas of the lung is greater than or less than the normal value of about 0.8.

Upright Subject

Ventilation and blood flow measured sequentially from the top to the bottom of the lung

Apex V/Q high

Base V/Q low

A normal V/Q ratio does not mean that ventilation and perfusion to that lung unit are normal; it simply means that the relationship between ventilation and perfusion is normal.

Lobar Pneumonia Ventilation to affected lobe is decreased

If perfusion remains unchanged, then it will exceed ventilation (V/Q < 1)

Decreased ventilation hypoxic vasoconstriction in pulmonary bed supplying the affected lobe

Decrease in perfusion normal V/Q Summary

Blood flow increased at base due to gravity Ventilation increased at base despite having larger alveoli at apex since as we could recall from the graph, alveoli in the base exhibit a greater change in diameter than those in the apex V/Q is increasing because blood flow > ventilation. In the equation, Q (perfusion) is in the denominator, thus plot is increasing

Figure 6. V/Q Ratio Dr B: Theres also an increase in ventilation, but blood flow increase is higher so V/Q decreases as you go from apex to the base. Lung compliance curve is sigmoidal. (compliance curve) alveoli in bases when you expand have a bigger increase in size, compare to alveoli in apex, where they are already maximally open. Ventilation is higher at the base bec of hydrostatic pressure and gravity.

SHAPE \* MERGEFORMAT

Ventilation-Perfusion Mismatch (not discussed) Most common cause of hypoxemia

V/Q < 1 decreased ventilation

V/Q > 1 increased ventilation Alveoli will have higher PO2 and lower PCO2

Arterial PO2 and PCO2 will vary depending on the relative contribution of the alveolar unit to the blood

Relative over-ventilation of one unit does not compensate for the under-ventilation of another

Increased ventilation raises only PO2 but adds little to the PO2 of the arterial blood Oxygen Transport Oxygen Carriage and Hemoglobin

A hemoglobin molecule is composed of four protein globin chains (2 alpha and 2 beta), each centered around a heme group

O2 combines loosely and reversibly with the heme portion of the hemoglobin. Hemoglobins affinity for O2 increases as successive molecules of O2 bind Oxygen-Hemoglobin Dissociation Curve (these factors were not discussed) The upper flat portion of the curve allows Hb saturation to remain relatively constant during considerable changes in PO2 At low PO2 levels, where the curve is steep, small changes in PO2 result in marked changes in saturation. Increased PCO2, lowered pH, and increased temperature shift the curve to the right and facilitate release of O2 to tissues Opposite changes in PCO2, pH, and temperature shift curve to the left Usually, the critical PO2 that needs to be maintained is at least 60 mmHg, because this is the pressure where the plateau begins. No significant increase in O2 saturation occurs even after increasing O2 concentration

Figure 7. Dissociation Curve SHAPE \* MERGEFORMAT

5. Control of Respiration (not discussed) Regulation of gas exchange is possible because the level of ventilation is so carefully controlled

3 basic elements of the control system

Sensors

Chemoreceptors, lung receptors, etc.

Gather information and feed it to the central controller

Central controller

In the brain (Pons, medulla, etc.) Coordinates the information and in turn, sends impulses to the effectors

Effectors

Respiratory muscles which cause ventilation

Figure 8. Regulation of Gas ExchangeMucociliary Elements: The Broom

1. Large Airways

Mucociliary escalation: has a mucociliary layer which functions as a secondary defense by bringing trapped particles in the airways up the trachea to be expectorated/swallowed Dr B : This is the most important defense mechanism. Next to this is cough. The mucous lining of the airways is composed of two physically and morphologically distinct layers:

GEL LAYER (mucoid) above - traps foreign particles (for movement up the trachea)

SOL LAYER (serous) below - allows cilia to move freely at the bottom

Cilia moves unidirectionally due to neurohumoral communication

Power stroke / upstroke: tip of cilium touches the gel layer

Relaxation stroke: cilium rotates downwards back to sol layer(recovery phase)

Dr. B: When you have a lot of mucoid secretion: the cilia will not be able to move well. The escalator system only happens because of the alternating system bet the two strokes. If at all parts, the gel layer is always touched, atras-abante ung movement.

Anything that affects the ratio of the two layers (e.g., infection or asthma) would affect ciliary movement

Too much serous secretion (thick sol layer) prevents tip of cilium from reaching the gel layer, impairing mucociliary escalation

Treatment is geared toward equalizing the ratio between the two layers Dr. B: there is no mucociliary clearance once you reach terminal bronchioles One stick of cigarette paralyses the cilia for 24 hours Smokers cough is due to chronic paralysis of the cilia and overproduction of mucous (sol layer where cilia can move is overwhelmed by the thickening gel layer)

Figure 9. Cells of the large airways: brush, goblet, ciliated, undifferentiatedTable 1. Quick Reference to Differentiate Gel and Sol Layers

GelUpperMucousMucoidGoblet Cell

SolLowerSerousWaterySerous Cell

2. Smaller Airways

The interstitium between respiratory bronchioles and capillaries serves as blood-air barriers It also has membrane pump mechanism similar to that of the G.I. tract (Na-K-ATPase)

Supported by collagen and elastic fibers (to prevent collapse since there is no smooth muscle and cartilaginous support)

Lymphatics: The Dust Pan

Important in the balance of fluid and in the spread of cancer In general, the lymphatics on the R side re-enter the systemic circulation through the R subclavian vein Pulmonary lymphatics on the L side return to the systemic circulation through the thoracic duct or by directly emptying into the subclavian vein

However, recent findings claim that the R supracervical node/right scalene node (sentinel nodes Dr B:they are often the ones enlarged. thats why in pe, you have to palpate this ) also drains the L lobe and the R upper lobe and there is cross linking between the R and L lymphatic system, making it possible for cancer to spread from R to L lung and vice versa

Knowledge of this comes handy when dealing with patients having vena caval syndromes and tumor obstructions SHAPE \* MERGEFORMAT

Lung Recoil: The Nylon Stockings

1. Elasticity

Nylon is strong but not elastic. What do you do to make it elastic? You weave them together.

Recall the nylon stocking model. The lung fibers form a sort of syncytium. If you tug at one part of the lung, you also tug at the other parts.

Alveolar interdependence- implies that no single alveolus can change in dimension without affecting others

Destruction of the elastic fibers (e.g. in smoking, infection, emphysema) impairs the ability of the lungs to recoil. (analogy: a run in the stockings)

for the lung to preserve its elastic property: Elastic fibers are interspersed with the capillaries. When lungs are expanded, elastic fibers can impinge on these capillaries, resulting in increased alveolar size, increased alveolar volume, and increased pulmonary resistance.

2. Forces that Expand versus Forces that Collapse

The rib cage of the chest has both (+) and (-) effects on the lungs in terms of pressure. This is dependent on position.

The resting position of the lungs pertains to the functional residual capacity (FRC). It is at this point that the forces that expand and collapse the lungs are equal and balance each other out

Figure 10. Forces during Quiet Breathing

Surfactant: The Soap

Detergent that acts to decrease surface tension to prevent alveolar collapse

Mixture of phospholipids, neutral lipids, fatty acids, and proteins

Major phospholipid: phosphatidylcholine, 75% of which is present as dipalmitoylphosphatidylcholine (DPPC) Stored in lamellar bodies Greater amounts in smaller alveoli

In premature babies: Type II pneumocytes have not yet developed, leading to neonatal respiratory distress syndrome

Surfactant has both charged and uncharged ends (polar molecule) so it acts as a stabilizer on alveolar surface

Figure 11. Effect of surfactant in stabilizing lungs

Remember the Law of Laplace: P = 2T/r, wherein P is the pressure inside the alveoli, T is the surface tension and r is the radius of the alveoli. The pressure in an alveolus due to surface tension is inversely proportional to the radius. Therefore, the smaller the radius, the greater is the pressure inside the alveolus, hence the greater the need for surfactant.

Smaller diameter, higher surface tension. Dr B: by age 10, you have 100-200 alveoli; by age 20, you have 300M alveoli. After this: downhill ( damage from smoking, pollution. Each of these have varying size. Smaller alveoli collapse first, and air will go to the larger alveoli.Surfactants have a greater effect in smaller alveoli because of bipolar molecules. If you increase the size of the alveoli, molecules become separated more and the repelling effect is less. What happens if you lose surfactants? (e.g. in ARDS.) Microatelectasis (collapse of airways) occurs and you have a big problem with gas exchange.

Dr. B: Surfactant is continuously produced by type 2 cells, stored in lamellar bodies, and released when needed. But if there is a pathology in type 2 cells, there is no immediate replenishment of surfactants. Tx: artificial surfactants.

Figure 12. Effect of surfactant on lung mechanics. Volume-pressure curves of lungs filed with saline and with air. Difference between inflation and deflation curve (hysteresis) is not present in the saline case because there is no surface tension. Inflection point: the point of sudden increase in volume per unit pressure which is important in monitoring patients in ventilators

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Lung Mechanics: The Balloon

1. Inspiration

an active process brought about by the contraction of the diaphragm, which adds to the (-) pressure in the lungs by increasing the volume of the thoracic cavity. (balloon-syringe plunger analogy) Muscles of Inspiration Diaphragm is the main muscle for inspiration. The external intercostals elevate the ribs thus increasing width of thoracic cavity

The interchondral part of internal intercostals also elevate the ribs

Accessory muscles: SCM elevates the sternum; scalenes elevate and fix upper ribs

Figure 13. Inspiration SHAPE \* MERGEFORMAT

Dr B: One of the key things you have to remember is that there must be an intact thorax.2. Expiration a passive process brought about by the relaxation of the inspiratory muscles and recoil of the elastic chest wall. These decrease the volume of the thoracic cavity, hence increasing the pressure. The positive pressure causes air to move out.

Muscles of Expiration

Internal Intercostals

Abdominals (rectus abdominis, external oblique, internal oblique, transversus abdominis) depress lower ribs and compress abdominal contents thus pushing up diaphragm

Figure 14. ExpirationDr B: Beyond terminal bronchiole, no cartilaginous support, airways can collapse during forced expiration.3. Equal Pressure Point

point where the pleural pressure is equal to the airway pressure no matter how hard one blows, there wont be any increase in pressure and flow

In the normal lung, this point occurs at the part where the airway still has cartilaginous support to prevent it from collapsing.

Important for patients with emphysema, where the EPP moves to the higher pressure areas (upstream or towards the alveoli) causing an increase in extra alveolar areas. Since airways upstream would no longer have cartilage to support them, they would collapse because pleural pressure is already higher than intra-airway pressure.

(not discussed) The location of EPP is dependent on Palv-Ppl difference, that is, on the lung recoil pressure. The lower the recoil, the more peripheral (upstream) is the EPP. Patients with emphysema have poor lung recoil. (not discussed) These patients experience no problems during inspiration but have difficulty in expiration. They compensate as thin-puffers by breathing out using the resistance of their pursed lips, creating an internal airway splint

Figure 15. Normal EPP

Figure 16. Abnormal EPPAPPROACH TO LUNG DISEASE

Problem-oriented Approach

Figure 17. Problem-oriented approach to evaluating lung diseases. Importance of Understanding Natural History of Disease

Symptoms often non-specific

Symptoms and times may vary over time

PE findings may also be non-specific

PE findings may also change as disease progresses

Sample Diseases and varied symptoms

1. Symptoms of Acute Hypoxia Neurologic: headache, mental confusion, anxiety, agitation, impaired judgment, emotional excitement, depression, drowsiness Cardiovascular: tachycardia, hypertension, arrhythmias

Respiratory: tachypnea, dyspnea2. Symptoms of Fibrosis

Dyspnea

Dry, Irritating, and Persistent Cough

Substernal Discomfort

Anorexia

Weight Loss

Arthralgia

And High index of Suspicion!!!3. Natural History of Pneumonia in Relation to History and PE Findings

Figure 18: Stages and corresponding symptoms of Pneumonia.

Dr. B: fremitus solidification of lobe transmission of sound increased; hepatization maraming plema, maraming crackles4. Natural History of Lung Malignancy in Relation to History and PE Findings

Figure 19. Symptoms and corresponding symptoms of Lung Malignancy.Dr. B: Wala masyadong pain receptor sa lung. Unless naginvade na sa mediastina, pleura, chest wall, walang symptoms. Depending on stage, you have to make use of all info from hx pe to come up with good dx5. Natural History of COPD

Figure 20. The COPD Escalator.Normal Breath Sounds

Figure 21. Normal Breath Sounds (not discussed)Figure 22. Classification of Adventitious Breath Sounds. Dr. B: Ronchi: low pitched( obstruction involves larger airway;Wheeze: very severe obstructionOther Respiratory Symptoms

1. Sputum Production2. Hemoptysis: Dr B - Black or red sputum3. Chest Pain: Dr. B - Pain receptors are only found in pleura, chest wall and mediastinal structures. Even if you prick the lung itself, there is no pain. You will feel pain when you STRETCH it. The moment there is pain, you should think pleural, thoracic wall or mediastinal involvement. 4. Wheezing 5. Hoarseness and Snoring

6. Non-specific Symptoms: anorexia, weight loss, bone painDr B: increase in volume and viscosity of mucus: major manifestation of lung diseaseEND OF TRANSCRIPTION

Type 1 for gas exchange (recall: sunny side up analogy)

Type 2 for surfactant production

Type 3 absorb excess fluid (similar to Clara cells)

Question: At which boundary do many changes occur?

Terminal bronchioles: from pseudostratified columnar ciliated epithelium, it gradually turns to cuboidal then to squamous. It also loses its linings and submucosal serous glands. At this level, gas change may occur due to the thinner epithelium.

Question:

What causes turbulence?

Very fast flow and bifurcation; related to increasing resistance

In Large Airways: Turbulent flow

In Smaller Airways: Laminar Flow

Therefore, resistance is higher in larger airways.

Small airways have greater total surface area than large airways thus, airways resistance is smaller.

In summary, resistance is higher in larger airways due to TURBULENT FLOW and LESSER SURFACE AREA

Questions:

Alveoli are largest at what level of the lungs at resting?

At apex; due to hydrostatic pressure

What causes the kind of blood flow distribution in the lungs (greater blood flow at base, less at apex)?

Because of gravity and because we walk upright.The hydrostatic pressure of the lung base is higher (except in space)

Questions:

Why is the dissociation curve sigmoidal?

Because when one O2 atom is attached, the other subunits uncoil, making it easier to bind to the next O2 atom (steep part). Once all molecules of Hb are occupied, the curve plateaus.

What factors change affinity of O2 to Hemoglobin?

pH, PCO2, temperature

Lymphatics

Used in determining malignancy (i.e. grading)

Sentinel Node: usually the right supraclavicular node (for both lungs)

Human gas exchange is not the most efficient. (Birds have the most efficient gas exchange.)

Role of surfactants

Principle of water tension (Imagine a RAINDROP)

When water forms a surface with air, the water molecules on the surface of water have an extra strong attraction for one another. As a result, the water surface is always attempting to contract ( this is what holds raindrops together

Alveolar surface tension

The water surface on the inner surface of the alveoli also attempts to contract

This attempts to force the air out of the alveoli through the bronchi, and in doing so, it causes the alveoli (and other air spaces in the lungs) to collapse

Surfactant and its effect on surface tension

Surfactant is a surface active agent, which means that when it spreads over the surface of a fluid, it greatly reduces the surface tension

They do not dissolve in the fluid, instead they spread over its surface because one portion of each phospholipid molecule is hydrophilic and it is attracted to the water lining the alveoli, whereas the lipid portion of the molecule is hydrophobic and oriented toward the air, forming a lipid hydrophobic surface exposed to the air

Recall: Boyles Law

When the temperature of a gas is held constant, the pressure it exerts is inversely proportional to its volume.

The intra-thoracic volume increases with movement of the inspiratory muscles. Following Boyles Law, with chest expansion, a negative pleural (suction) pressure is consequently generated pulling the lungs outwards to effect expansion

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