Respiratory Physiology

Dr Sherwan R Shal 2006-2007

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Respiration
Ventilation:
Action of breathing with muscles and lungs.

Gas exchange:
Between air and capillaries in the lungs. Between systemic capillaries and tissues of the body.

02 utilization:
Cellular respiration in mitochondria.

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Ventilation
Mechanical process that moves air in and out of the lungs. Diffusion of O2: air to blood. C02: blood to air. Rapid:
large surface area small diffusion distance.
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Respiratory structures

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Conducting Zone
Conducting zone: All the structures air passes through before reaching the respiratory zone. Mouth,nose, pharynx, trachea, glottis, larynx, bronchi.
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Conducting Zone
Conducting zone Warms and humidifies until inspired air becomes:
37 degrees Saturated with water vapor

Filters and cleans:
Mucus secreted to trap particles Mucus/particles moved by cilia to be expectorated.

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Respiratory Zone
Respiratory zone Region of gas exchange between air and blood.
-

bronchioles alveoli

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Respiratory Zone

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Respiratory Zone
Alveoli Air sacs Honeycomb-like clusters ~ 300 million. Large surface area (60 80 m2). Each alveolus: only 1 thin cell layer. Total air barrier is 2 cells across (2 Qm) (alveolar cell and capillary endothelial cell).

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Respiratory Zone
Alveolar cells: Alveolar type I: structural cells. Alveolar type II: secrete surfactant.

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Mechanics of breathing

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Thoracic Cavity
Diaphragm:
Sheets of striated muscle divides anterior body cavity into 2 parts.

Above diaphragm: thoracic cavity:
Contains heart, large blood vessels, trachea, esophagus, thymus, and lungs.

Below diaphragm: abdominopelvic cavity:
Contains liver, pancreas, GI tract, spleen, and genitourinary tract.
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Mechanics of breathing
Gas: the more volume, the less pressure (Boyle s law). Inspiration: lung volume increase -> decrease in intrapulmonary pressure, to just below atmospheric pressure -> air goes in! Expiration: viceversa

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Mechanics of breathing
Intrapleural space:
Space between visceral and parietal pleurae. Visceral and parietal pleurae (membranes) are flush against each other. Lungs normally remain in contact with the chest walls. Lungs expand and contract along with the thoracic cavity.

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Pleura

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Mechanics of breathing
Compliance: lungs can stretch when under tension. Elasticity: they recoil (to original shape). - elastin

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Inspiration
Inspiration Diaphragm contracts -> increased thoracic volume vertically. Intercostals contract, expanding rib cage -> increased thoracic volume laterally. Active More volume -> lowered pressure -> air in. Negative pressure breathing.
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Expiration
Expiration
Due to recoil of elastic lungs. Passive. Less volume -> pressure within alveoli is just above atmospheric pressure -> air leaves lungs. Note: Residual volume of air is always left behind, so alveoli do not collapse.
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Mechanics of breathing
Quiet breath: +/- 3 mmHg intrapulmonary pressure. Forced breath:
Extra muscles, including abs +/- 20-30 mm Hg intrapulmonary pressure

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Problems
Pneumothorax: a hole in chest can cause one lung to collapse.

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Surface tension

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Surface Tension
Very thin film of fluid in alveoli. Absorb: Na+ active transport. Secrete: Cl- active transport.

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Surface Tension
Surface tension: H20 molecules at the surface are attracted to other H20 molecules rather than to air.

Surface tension-> hard to expand the alveoli.
Small alveoli, more resistance to expansion.

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Surface tension
Surfactant produced by alveolar type II cells. Interspersed among water molecules. Lowers surface tension.
RDS, respiratory distress syndrome, in preemies. First breath: big effort to inflate lungs!

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Surface tension
Insert fig. 16.12

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Measuring pulmonary function

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Pulmonary Function
Spirometry: Breathe into a closed system, with air, water, moveable bell

Insert fig. 16.16

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Lung volumes
Tidal volume (TV): in/out with quiet breath (500 ml) Total minute volume: tidal x breaths/min
6 L/min Exercise: even 200 L/min!

Anatomical dead space:
Conducting zone Dilutes tidal volume, by a constant amount. Deeper breaths -> more fresh air to alveoli.
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Lung volumes
Inspiratory reserve volume (IRV): extra (beyond TV) in with forced inspiration. Expiratory reserve volume (ERV): extra (beyond TV) out with forced expiration. Residual volume: always left in lungs, even with forced expiration.
Not measured with spirometer

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Lung capacities

Vital capacity (VC): the most you can actually ever expire, with forced inspiration and expiration. VC= IRV + TV + ERV Total lung capacity: VC plus residual volume
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Pulmonary disorders

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Pulmonary disorders Stop
Restrictive disorder:
Vital capacity is reduced. Less air in lungs.

Obstructive disorder:
Rate of expiration is reduced. Lungs are fine, but bronchi are obstructed.

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Disorders
Restrictive disorder:
Black lung from coal mines. Pulmonary fibrosis: too much connective tissue.

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Pulmonary Disorders
COPD (chronic obstructive pulmonary disease):
Asthma Emphysema Chronic bronchitis

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Disorders
Obstructive disorder: FEV = forced expiratory volume. FEV1 = % of vital capacity expired in 1st second. Disorder if FEV1 is < 80% Note: same total amount expired.
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Disorders
Asthma:
Obstructive Inflammation, mucus secretion, bronchial constriction.
Provoked by: allergic, exercise, cold and dry air Anti-inflammatories, including inhaled epenephrine (specific for non-heart adrenergic receptors), anti-leukotrienes, anti-histamines.

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Disorders
Emphysema:
Alveolar tissue is destroyed. Chronic progressive condition
Cigarette smoking stimulates macrophages and WBC to secrete enzymes which digest proteins. Or: genetic inability to stop trypsin (which digests proteins).

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Blood gases

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Blood gases
Barometers use mercury (Hg) as convenience to measure total atmospheric pressure. Sea level: 760 mm Hg (torr)

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Blood gases
Total pressure of a gas mixture is = to the sum of the independent, partial pressures of each gas (Dalton s Law).

In sea level atmosphere:

PATM = 760 mm Hg = PN2 + P02 + PC02 + PH20

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Blood gases
Partial pressures: % of that gas x total pressure.
In atmosphere: 02 is 21%, so (.21 x 760) = 159 mm Hg = P02

Note: atmospheric P02 decreases on a mountain, increases as one dives into the ocean.

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Blood gases
But inside you, the air is saturated with water vapor.
PH20 = 47 mm Hg at 37 degrees

So, inside you, there is less P02:

P0 = 105 mm Hg in alveoli.
2

In constrast, alveolar air is enriched in CO2, as compared to inspired air. PCO = 40 mm Hg in alveoli.
2

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Blood gases
Insert fig. 16.20

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Blood gases
Gas and fluid in contact: [Gas] dissolved in a fluid depends directly on its partial pressure in the gas mixture. With a set solubility, non changing temp. (Henry s law) So

P0 in alveolar air ~ = P0 in blood.
2 2

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Blood gases
O2 electrodes can measure dissolved O2 in a fluid. (also CO2 electrodes.)

Good index of lung function. Arterial P0 is only slightly below alveolar P0
2 2

Arterial P0 = 100 mm Hg Alveolar P0 = 105 mm Hg
2 2

P0 level in the systemic veins is about 40 mm Hg.
2

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Blood gases

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Blood gases
Most O2 is in hemoglobin .3 ml dissolved in plasma + 19.7 ml in hemoglobin 20 ml O2 in 100 mls blood! But: O2 in hemoglobin-> dissolved -> tissues. Breathing pure O2 increases only the dissolved portion. - insignificant effect on total O2 - increased O2 delivery to tissues
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Pulmonary Circulation
L ventricle pumps to entire body, R ventricle only to lungs. Both ventricles pump 5.5 L/min! Pulmonary circulation: various adaptations.
as a mellow river, doesn t spill over the banks low pressure, low resistance. prevents pulmonary edema. pulmonary arteries dilate if P02 is low (opposite of systemic)
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Neural control

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Neural control
Respiratory centers In hindbrain - medulla oblongata - pons automatic breathing
Insert fig. 16.25

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Neural control
I neurons = inspiration E neurons = expiration I neurons -> spinal motor neurons -> respiratory muscles. E neurons inhibit I neurons.

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Neural control
Also: voluntary breathing controlled by cerebral cortex.

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Neural control
Ondine s curse: only voluntary breathing.
Ondine: water nymph, punished by gods, must stay awake in order to breath. Or: she so cursed her philandering husband, after she gave up immortality to join him, and he promised to love her with every waking breath http://www.silentpartners.org/sleep/sinfo/miscl/ondine.htm Gene mutation in fetus: http://news.bbc.co.uk/1/hi/health/2996791.stm Description: http://www.medterms.com/script/main/art.asp?articlekey=9634
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Chemoreceptors
Oxygen: large reservoir attached to hemoglobin. So chemoreceptors are more sensitive to changes in PC0 (as sensed through changes in pH).
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Ventilation is adjusted to maintain arterial PC02 of 40 mm Hg. Chemoreceptors are located throughout the body (in brain and arteries).
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chemoreceptors

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Hemoglobin

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Hemoglobin

Each hemoglobin has 4 polypeptide chains (2 alpha, 2 beta) and 4 hemes (colored pigments). In the center of each heme group is 1 atom of iron that can combine with 1 molecule 02. (so there are four 02 molecules per hemoglobin molecule.) 280 million hemoglobin molecules per RBC!
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Hemoglobin

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Hemoglobin
Oxyhemoglobin:
Ferrous iron (Fe2+) plus 02.

Deoxyhemoglobin:
Still ferrous iron (reduced). No 02.

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Hemoglobin

Carboxyhemoglobin:
carbon monoxide (CO) binds to heme instead of 02 - smokers

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Hemoglobin
Can tell % of types of hemoglobin by color!

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Hemoglobin
Loading: Load 02 into the RBC. Deoxyhemoglobin plus 02 -> Oxyhemoglobin. Unloading: Unload 02 into the tissues. Oxyhemoglobin -> deoxyhemoglobin plus 02.

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Hemoglobin
Loading/unloading depends on: - P0
2

- Affinity between hemoglobin and 02
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pH temperature

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Hemoglobin
Dissociation curve: % oxyhemoglobin saturation at different values of P0 .
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Describes effect of P0 on loading/unloading.
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Sigmoidal At low P0 small changes produce large differences in % saturation and unloading.
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Exercise: P0 drops, much more unloading from veins.
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At high P0 slow to change.
2

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Oxyhemoglobin Dissociation Curve

Insert fig.16.34

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Hemoglobin
Affinity between hemoglobin and 02: - pH falls -> less affinity -> more unloading (and viceversa if pH increases) - temp rises -> less affinity -> more unloading
exercise, fever

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Hemoglobin
Arteries: 97% saturated (i.e. oxyhemoglobin) Veins: 75% saturated. Arteries: 20 ml 02 /100 ml blood. Veins: ~ 5 ml less Only 22% was unloaded! Reservoir of oxygen in case: - don t breathe for ~5 min - exercise (can unload up to 80%!)
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Hemoglobin
Fetal hemoglobin (F): - gamma chains (instead of beta) - more affinity than adult (A) hemoglobin

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Anemias

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Hemoglobin
Anemia:
[Hemoglobin] below normal.

Polycythemia:
[Hemoglobin] above normal. Altitude adjustment.

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Disorders
Sickle-cell anemia:
fragile, inflexible RBC inherited change: one base pair in DNA -> one aa in beta chains hemoglobin S protects vs. malaria; african-americans

Thalassemia: defects in hemoglobin type of anemia
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Disorders

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RBC

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RBC
RBC no nucleus no mitochondria Cannot use the 02 they carry!!! Respire glucose, anaerobically. (note: androgens stimulate erythropoiesis)
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Transport of CO2

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C02 Transport
H20 + C02

H2C03
carbonic acid

H+ + HC03bicarbonate

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C02 Transport C02 transported in the blood:
- most as bicarbonate ion (HC03-) - dissolved C02 - C02 attached to hemoglobin (Carbaminohemoglobin)

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C02 Transport
Carbonic anhydrase in RBC promotes useful changes in blood PC02 CA

H20 + C02 -> H2C03 -> HC03high PC0
2

CA

H20 + C02 <- H2C03 <HC03low PC0
2

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C02 Transport
Chloride shift: Chloride ions help maintain electroneutrality. HC03- from RBC diffuses out into plasma. RBC becomes more +.
Cl- attracted in (Cl- shift).

H+ released buffered by combining with deoxyhemoglobin.

Reverse in pulmonary capillaries
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Acid-base balance

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Acid-Base Balance
Ventilation is normally adjusted to keep pace with metabolic rate, so homeostasis of blood pH is maintained.

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Acid-Base Balance
Hyperventilation -> PC0 down -> pH of CSF up -> vasoconstriction -> dizziness.
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If hyperventilating, should you breath into paper bag? Yes! It increases PC0 !
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Metabolic acidosis can trigger hyperventilation.
Diarrhea -> acidosis. Vomit -> alkalosis.
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Adaptations

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Exercise
During exercise, breathing becomes deeper and more rapid. Yet blood gas levels instantly stay about the same. Huh?! Neurogenic: sensory response from muscles? Humoral: homones? Local differences we can t sense in a lab?

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Adaptations
Frequent exercise, or high altitudes -> series of changes in oxygen consumption, or [hemoglobin], etc.

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