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Home , Chloride shift, Elastic recoil, Hemoglobin, Intrapleural pressure, Partial pressure, Perfusion

Chapter 22 The

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• Pulmonary ventilation (): movement of air into and out of the Respiratory system • External respiration: O2 and CO2 exchange between the lungs and the

• : O2 and CO2 in the blood • Internal respiration: O2 and CO2 exchange between systemic blood vessels and tissues

7/22/2015 MDufilho 2 Mechanics of Breathing

• Pulmonary ventilation consists of two phases 1. Inspiration: flow into the lungs 2. Expiration: gases exit the lungs

7/22/2015 MDufilho 3 Relationships in the

• (Patm) • Pressure exerted by air surrounding body • 760 mm Hg at sea level = 1 • Respiratory described relative to

Patm

• Negative respiratory pressure-less than Patm

• Positive respiratory pressure-greater than Patm

• Zero respiratory pressure = Patm

7/22/2015 MDufilho 4 Intrapulmonary Pressure

• Intrapulmonary (intra-alveolar) pressure (Ppul) • Pressure in the alveoli • Fluctuates with breathing

• Always eventually equalizes with Patm

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• Intrapleural pressure (Pip): • Pressure in the • Fluctuates with breathing

• Always a negative pressure (

7/22/2015 MDufilho 6 Intrapleural Pressure

• Negative Pip is caused by opposing • Two inward forces promote collapse • of lungs decreases lung size • of alveolar fluid reduces alveolar size • One outward tends to enlarge the lungs • Elasticity of the chest wall pulls the outward

7/22/2015 MDufilho 7 Figure 22.12 Intrapulmonary and intrapleural pressure relationships.

Atmospheric pressure (Patm) 0 mm Hg (760 mm Hg) Parietal pleura Visceral pleura Pleural cavity

Transpulmonary pressure 4 mm Hg (the difference between 0 mm Hg and −4 mm Hg)

– 4

0 Intrapleural pressure (Pip) −4 mm Hg (756 mm Hg) Lung Diaphragm Intrapulmonary pressure (Ppul) 0 mm Hg 7/22/2015 MDufilho (760 mm Hg) 8 Pulmonary Ventilation

• Inspiration and expiration • Mechanical processes that depend on changes in the thoracic cavity • Volume changes  pressure changes • Pressure changes  gases flow to equalize pressure

7/22/2015 MDufilho 9 Boyle’s Law

• The relationship between the pressure and volume of a • Pressure (P) varies inversely with volume (V):

P1V1 = P2V2 • P = pressure of a gas in mm Hg • V = volume of a gas in cubic millimeters • Subscripts 1 and 2 represent the initial and resulting conditions, respectively

7/22/2015 MDufilho 10 Figure 22.13 Changes in thoracic volume and sequence of events during inspiration and expiration. (1 of 2) Slide 1

Changes in anterior-posterior and Changes in lateral dimensions Sequence of events superior-inferior dimensions (superior view) 1 Inspiratory muscles contract (diaphragm descends; cage rises). are elevated and Thoracic cavity volume 2 increases. flares as

external intercostals 3 Lungs are stretched; contract. intrapulmonary volume increases. External intercostals

Inspiration 4 Intrapulmonary pressure contract. drops (to –1 mm Hg).

5 Air (gases) flows into lungs down its pressure Diaphragm gradient until intrapulmonary moves inferiorly pressure is 0 (equal to during atmospheric pressure). contraction.

7/22/2015 MDufilho 11 Factors That Diminish

• Scar or that reduces the natural resilience of the lungs • Blockage of the smaller respiratory passages with or fluid • Reduced production of • Decreased flexibility of the thoracic cage or its decreased ability to expand

7/22/2015 MDufilho 12 Figure 22.13 Changes in thoracic volume and sequence of events during inspiration and expiration. (2 of 2) Slide 1

Changes in lateral dimensions Sequence of events Changes in anterior-posterior and superior-inferior dimensions (superior view) 1 Inspiratory muscles relax (diaphragm rises; descends due to recoil of costal ). Ribs and sternum are Thoracic cavity volume 2 depressed decreases.

as external

intercostals 3 Elastic lungs recoil relax. passively; intrapulmonary Volume decreases. External intercostals

Expiration relax. 4 Intrapulmonary pressure rises (to +1 mm Hg).

5 Air (gases) flows out of Diaphragm lungs down its pressure moves gradient until intrapulmonary superiorly pressure is 0. as it relaxes.

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Figure 22.14 Changes in intrapulmonary and intrapleural pressures during inspiration and expiration.

Inspiration Expiration Intrapulmonary pressure. Intrapulmonary Pressure inside lung +2 pressure

decreases as lung volume

increases during 0 inspiration; pressure increases during expiration. Trans- –2 pulmonary Intrapleural pressure. pressure –4 Pleural cavity pressure becomes more negative as –6 chest wall expands during Intrapleural

inspiration. Returns to initial pressure atmospheric pressure Hg) (mm atmospheric

value as chest wall recoils. to Pressurerelative –8

Volume of breath. During Volume of breath each breath, the pressure 0.5 gradients move 0.5 liter of air into and out of the lungs.

0 Volume (L) Volume

5 seconds elapsed

7/22/2015 MDufilho 14 Clinical Applications

• – lung collapse – air entering plural cavity • • Tension pneumothorax • • IRDS – Idiopathic Respiratory Distress Syndrome

7/22/2015 MDufilho 15 Gas Exchanges Between Blood, Lungs, and Tissues • External respiration • Internal respiration • To understand the above processes, first consider • Physical properties of gases • Composition of alveolar gas

7/22/2015 MDufilho 16 Basic Properties of Gases: 's Law of Partial Pressures

• Total pressure exerted by of gases = sum of pressures exerted by each gas • • Pressure exerted by each gas in mixture • Directly proportional to its percentage in mixture

7/22/2015 MDufilho 17 7/22/2015 MDufilho 18 Table 22.4 Basic Properties of Gases: Henry's Law • Gas in contact with • Each gas dissolves in proportion to its partial pressure • At equilibrium, partial pressures in two phases will be equal • Amount of each gas that will dissolve depends on

• –CO2 20 times more soluble in water than O2; little N2 dissolves in water • –as temperature rises, solubility decreases

7/22/2015 MDufilho 19 External Respiration

• Exchange of O2 and CO2 across the respiratory membrane • Influenced by • Partial pressure gradients and gas • Ventilation- coupling • Structural characteristics of the respiratory membrane

7/22/2015 MDufilho 20 Figure 22.18 Oxygenation of blood in the pulmonary at rest.

150

100 P 104 mm Hg

O2

(mm Hg) (mm

2 50 O

P 40

0 0 0.25 0.50 0.75 Time in the pulmonary (s) Start of End of capillary capillary

7/22/2015 MDufilho 21 Ventilation-Perfusion Coupling

• Perfusion-blood flow reaching alveoli • Ventilation-amount of gas reaching alveoli • Ventilation and perfusion matched (coupled) for efficient • Never balanced for all alveoli due to • Regional variations due to effect of gravity on blood and air flow • Some alveolar ducts plugged with mucus

7/22/2015 MDufilho 22 Figure 22.19 Ventilation-perfusion coupling.

Ventilation less than perfusion Ventilation greater than perfusion

Mismatch of ventilation and perfusion Mismatch of ventilation and perfusion ventilation and/or perfusion of alveoli ventilation and/or perfusion of alveoli causes local P and P causes local P and P CO2 O2 CO2 O2

O2 autoregulates O2 autoregulates arteriolar diameter arteriolar diameter

Pulmonary Pulmonary arterioles serving these alveoli serving these alveoli constricts dilate

Match of ventilation Match of ventilation and perfusion and perfusion ventilation, perfusion ventilation, perfusion

7/22/2015 MDufilho 23 Internal Respiration

• Capillary gas exchange in body tissues • Partial pressures and gradients reversed compared to external respiration

• Tissue Po2 always lower than in systemic from blood to tissues

• CO2  from tissues to blood

• Venous blood Po2 40 mm Hg and Pco2 45 mm Hg

7/22/2015 MDufilho 24 Figure 22.17 Partial pressure gradients promoting gas movements in the body.

Inspired air: Alveoli of lungs: P 160 mm Hg P O2 O2 104 mm Hg P 0.3 mm Hg P CO2 CO2 40 mm Hg

External respiration

Alveoli Pulmonary Pulmonary (P O2 100 mm Hg)

Blood leaving Blood leaving tissues and lungs and entering lungs: entering tissue P 40 mm Hg capillaries: O2 P 45 mm Hg PO 100 mm Hg CO2 2 P 40 mm Hg CO2

Heart

Systemic Systemic veins arteries

Internal respiration

Tissues: P less than 40 mm Hg O2 P greater than 45 mm Hg CO2

7/22/2015 MDufilho 25 O2 Transport

• Molecular O2 is carried in the blood • 1.5% dissolved in plasma • 98.5% loosely bound to each Fe of (Hb) in RBCs

• 4 O2 per Hb

7/22/2015 MDufilho 26 O2 and Hemoglobin

• Oxyhemoglobin (HbO2): hemoglobin-O2 combination • Reduced hemoglobin (HHb): hemoglobin that

has released O2

7/22/2015 MDufilho 27 O2 and Hemoglobin

• Loading and unloading of O2 is facilitated by change in shape of Hb

• As O2 binds, Hb affinity for O2 increases

• As O2 is released, Hb affinity for O2 decreases • Fully (100%) saturated if all four groups

carry O2 • Partially saturated when one to three

carry O2

7/22/2015 MDufilho 28 Poisoning

• CO competes with O2 • Hemoglobin has higher affinity for CO • Treatment – 100% O2 • has bluish color due to increased of deoxyhemoglobin (HHb)

7/22/2015 29 MDufilho CO2 Transport

• CO2 is transported in the blood in three forms • 7 to 10% dissolved in plasma • 20% bound to of hemoglobin ()

– • 70% transported as (HCO3 ) in plasma

7/22/2015 MDufilho 30 Transport and Exchange of CO2

• CO2 combines with water to form carbonic (H2CO3), which quickly dissociates

• Occurs primarily in RBCs, where reversibly and rapidly catalyzes

7/22/2015reaction MDufilho 31 Transport and Exchange of CO2

• In systemic capillaries

– • HCO3 quickly diffuses from RBCs into the plasma

– • The occurs: outrush of HCO3 from the RBCs is balanced as Cl– moves in from the plasma

7/22/2015 MDufilho 32 Figure 22.22a Transport and exchange of CO2 and O2.

Tissue Interstitial fluid (dissolved in plasma) Binds to Slow plasma

Chloride shift Fast (in) via transport Carbonic anhydrase

(Carbamino- hemoglobin)

(dissolved in plasma)

Oxygen release and pickup at the tissues

7/22/2015 MDufilho 33 Transport and Exchange of CO2

• In pulmonary capillaries

– + • HCO3 moves into the RBCs and binds with H to form H2CO3

• H2CO3 is split by carbonic anhydrase into CO2 and water

• CO2 diffuses into the alveoli

7/22/2015 MDufilho 34 Figure 22.22b Transport and exchange of CO2 and O2.

Alveolus Fused basement membranes (dissolved in plasma)

Slow

Chloride shift Fast (out) via transport Carbonic protein anhydrase

(Carbamino- hemoglobin)

(dissolved in plasma) Blood plasma

Oxygen pickup and carbon dioxide release in the lungs

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• The lower the Po2 and hemoglobin saturation with O2, the more CO2 can be carried in the blood • At the tissues, as more carbon dioxide enters the blood • More oxygen dissociates from hemoglobin ()

• As HbO2 releases O2, it more readily forms bonds with CO2 to form carbaminohemoglobin

7/22/2015 MDufilho 36 Influence of CO2 on Blood pH

– • HCO3 in plasma is the alkaline reserve of the –bicarbonate buffer system • If H+ concentration in blood rises, excess H+ is – removed by combining with HCO3 + • If H concentration begins to drop, H2CO3 dissociates, releasing H+

7/22/2015 MDufilho 37 Influence of CO2 on Blood pH

• Changes in can also alter blood pH • For example, slow allows

CO2 to accumulate in the blood, causing pH to drop • Changes in ventilation can be used to adjust pH when it is disturbed by metabolic factors

7/22/2015 MDufilho 38 Control of Respiration - Medullary Respiratory Centers 1. Dorsal respiratory group (DRG) • Integrates input from peripheral stretch and 2. Ventral respiratory group (VRG) • Rhythm-generating and integrative center • Sets (12–15 breaths/minute) • Inspiratory neurons excite the inspiratory muscles via the phrenic and intercostal • Expiratory neurons inhibit the inspiratory neurons

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Figure 22.23 Locations of respiratory centers and their postulated connections.

Pons Medulla Pontine respiratory centers interact with medullary respiratory centers to smooth the respiratory pattern. Ventral respiratory group (VRG) contains rhythm generators whose output drives respiration. Medulla Dorsal respiratory group (DRG) integrates peripheral sensory input and modifies the rhythms generated by the VRG. To inspiratory muscles

External

7/22/2015 MDufilho Diaphragm 40 Depth and Rate of Breathing

• Depth is determined by how actively the stimulates the respiratory muscles • Rate is determined by how long the inspiratory center is active • Both are modified in response to changing body demands

7/22/2015 MDufilho 41 - Compensatory • Hyperventilation – increased depth and rate of breathing that: • Quickly flushes carbon dioxide from the blood

• Occurs in response to (high CO2 )

• Though a rise CO2 acts as the original stimulus, control of breathing at rest is regulated by the concentration in the brain • • Drugs affecting CNS

7/22/2015 42 MDufilho Hyperventilation – Non-compensatory

• Rapid or extra deep breathing leads to

-(low CO2) • Can lead to alkalosis with and spasms • Causes – acute or emotional tension

• CO2 is vasodilator – low PCO2 results in LOCAL vasoconstrictions = /

• How do you fix it?

7/22/2015 43 MDufilho – Non-compensatory

• Hypoventilation – slow and shallow breathing

due to abnormally low PCO2 levels (initially)

• (breathing cessation) may occur until PCO2 levels rise

• Leads to too much CO2which leads to drop in pH =

7/22/2015 44 MDufilho Summary of Chemical Factors

• Rising CO2 levels are the most powerful respiratory stimulant

• Normally blood Po2 affects breathing only indirectly by influencing peripheral sensitivity to

changes in Pco2

• When arterial Po2 falls below 60 mm Hg, it becomes the major stimulus for respiration (via the peripheral chemoreceptors)

• Changes in arterial pH resulting from CO2 retention or metabolic factors act indirectly through the peripheral chemoreceptors

7/22/2015 MDufilho 45 Influence of Higher Brain Centers

• Hypothalamic controls act through the limbic system to modify rate and depth of respiration • Example: breath holding that occurs in anger or gasping with • A rise in body temperature acts to increase respiratory rate • Cortical controls are direct signals from the cerebral motor cortex that bypass medullary controls • Example: voluntary breath holding

7/22/2015 MDufilho 46 Figure 22.24 Neural and chemical influences on brain stem respiratory centers.

Higher brain centers (—voluntary control over breathing)

Other receptors (e.g., pain) +– and emotional stimuli acting through the hypothalamus

+ – Respiratory centers (medulla and pons)

Peripheral chemoreceptors +

– Stretch receptors + in lungs – Irritant + receptors Receptors in muscles and

7/22/2015 MDufilho 47 Respiratory Diseases

OYO • • • Effects of Cigarette Smoke on Cilia • COPD •

7/22/2015 48 MDufilho What if ????

• Alveolar PO2 is 100, alveolar Pco2 is 38 and alveolar PCO is 1 • A child eats 20 asprin tablets (aspirin is acetylsalicylic acid…. How will respiratory rate be affected? • A few hours after surgery I am experiencing lots of pain, so I take a dose of my narcotic pain killer… 5 minutes later it still hurts so I

take another ….How will RR be affected?

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