Respiratory Physiology

Chapter 16

Respiratory Physiology

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Lecture mapPhysiology of respiration:

Definitions and structuresMechanics of breathingMeasurements of pulmonary functionPulmonary disordersBlood gassesNeural controlHemoglobin (and disorders)Transport of C02Acid/base balanceAdaptions


Why?!

Cellular respiration:uses 02

produces C02


Why?!

Cellular respiration:uses 02

produces C02


Why?!

Multicellular organism!

So…

02: air ---> lungs ---> blood ---> cells.

C02 : cells ---> blood ---> lungs --> air


Respiration is…


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.


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.

Insert 16.1


Respiratory structures


Conducting Zone

Conducting zone:All the structures air passes through before reaching the respiratory zone.

Mouth,nose, pharynx, trachea, glottis, larynx, bronchi.

Insert fig. 16.5


Conducting Zone

Conducting zone

Warms and humidifies until inspired air becomes:

37 degreesSaturated with water vapor

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


Respiratory Zone

Respiratory zone

Region of gas exchange between air and blood.

- bronchioles- alveoli


Respiratory Zone


Respiratory Zone


Respiratory ZoneAlveoliAir sacsHoneycomb-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 m)

(alveolar cell and capillary endothelial cell).


Respiratory Zone

Alveolar cells:

Alveolar type I: structural cells.

Alveolar type II: secrete surfactant.


Mechanics of breathing


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.



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



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.


Pleura



Compliance: lungs can stretch when under tension.

Elasticity: they recoil (to original shape).- elastin


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.


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.



Quiet breath: +/- 3 mmHg intrapulmonary pressure.

Forced breath:Extra muscles, including abs+/- 20-30 mm Hg intrapulmonary

pressure


Problems

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


Surface tension


Surface Tension

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

CF and CFTR


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.


Surface tension

Surfactantproduced 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!


Surface tension

Insert fig. 16.12


Measuring pulmonary function


Pulmonary Function

Spirometry:Breathe into a closed system, with

air, water, moveable bell

Insert fig. 16.16


Lung volumes

Tidal volume (TV): in/out with quiet breath (500 ml)

Total minute volume: tidal x breaths/min6 L/minExercise: even 200 L/min!

Anatomical dead space:Conducting zoneDilutes tidal volume, by a constant amount.Deeper breaths -> more fresh air to alveoli.


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


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


Pulmonary disorders


Pulmonary disorders

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

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


Disorders

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


Pulmonary Disorders

COPD (chronic obstructive pulmonary disease):AsthmaEmphysemaChronic bronchitis


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.

Insert fig. 16.17


Disorders

Asthma:Obstructive Inflammation, mucus secretion,

bronchial constriction.Provoked by: allergic,

exercise, cold and dry airAnti-inflammatories,

including inhaled epenephrine (specific for non-heart adrenergic receptors), anti-leukotrienes, anti-histamines.


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).


Blood gases


Blood gases

Barometers use mercury (Hg) as convenience to measure total atmospheric pressure.

Sea level: 760 mm Hg (torr)


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


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.


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:P02 = 105 mm Hg in alveoli.

In constrast, alveolar air is enriched in CO2, as compared to inspired air.

PCO2 = 40 mm Hg in alveoli.


Blood gases

Insert fig. 16.20


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…

P02 in alveolar air ~ = P02 in blood.


Blood gases

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

Good index of lung function.

Arterial P02 is only slightly below alveolar P02

Arterial P02 = 100 mm Hg Alveolar P02 = 105 mm Hg

P02 level in the systemic veins is about 40 mm Hg.


Blood gases


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


Problems

Decompression sickness:If diver ascends too rapidly, bubbles of

nitrogen gas can block small blood vessels producing the “bends.”

Can happen in accidentally depressurized airplane cabins,too!


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 bankslow pressure, low resistance.prevents pulmonary edema.pulmonary arteries dilate if P02 is low (opposite of

systemic)


Neural control


Neural control

Respiratory centers

In hindbrain

- medulla oblongata

- pons

automatic breathing

Insert fig. 16.25


Neural control

I neurons = inspiration E neurons = expiration

I neurons -> spinal motor neurons -> respiratory muscles.

E neurons inhibit I neurons.


Neural control

Also: voluntary breathing controlled by

cerebral cortex.


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


Chemoreceptors

Oxygen: large “reservoir” attached to hemoglobin.

So chemoreceptors are more sensitive to changes in PC02

(as sensed through changes in

pH).

Ventilation is adjusted to maintain arterial PC02 of 40 mm Hg.

Chemoreceptors are located throughout the body (in brain and arteries).


chemoreceptors


Hemoglobin


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!


Hemoglobin


Hemoglobin

Oxyhemoglobin:Ferrous iron (Fe2+) plus 02.

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


Hemoglobin

Carboxyhemoglobin:carbon monoxide (CO) binds to heme

instead of 02

- smokers


Hemoglobin

Can tell % of types of hemoglobin by color!


Hemoglobin

Loading:Load 02 into the RBC.

Deoxyhemoglobin plus 02 -> Oxyhemoglobin.

Unloading:Unload 02 into the tissues.

Oxyhemoglobin -> deoxyhemoglobin plus 02.


Hemoglobin

Loading/unloading depends on:- P02

- Affinity between hemoglobin and 02

- pH- temperature


Hemoglobin

Dissociation curve: % oxyhemoglobin saturation at different values of P02.

Describes effect of P02 on loading/unloading.SigmoidalAt low P02 small changes produce large

differences in % saturation and unloading. Exercise: P02 drops, much more unloading

from veins.

At high P02 slow to change.


Oxyhemoglobin Dissociation Curve

Insert fig.16.34


Hemoglobin

Affinity between hemoglobin and 02:

- pH falls -> less affinity -> more unloading (and viceversa if pH increases)

- temp rises -> less affinity -> more unloadingexercise, fever


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 minexercise (can unload up to 80%!)


Hemoglobin

Fetal hemoglobin (F):- gamma chains (instead of beta)- more affinity than adult (A) hemoglobin


Anemias


Hemoglobin

Anemia:[Hemoglobin] below normal.

Polycythemia:[Hemoglobin] above normal.Altitude adjustment.


Disorders

Sickle-cell anemia:fragile, inflexible RBCinherited change: one base pair in DNA -> one

aa in beta chainshemoglobin Sprotects vs. malaria; african-americans

Thalassemia:defects in hemoglobin

type of anemia


Disorders


RBC


RBC

RBCno nucleusno mitochondria

Cannot use the 02 they carry!!!

Respire glucose, anaerobically.

(note: androgens stimulate erythropoiesis)


Transport of CO2


C02 Transport

H20 + C02

carbonic acid

bicarbonate

H2C03 H+ + HC03-


C02 transported in the blood:

- most as bicarbonate ion (HC03-)

- dissolved C02

- C02 attached to hemoglobin (Carbaminohemoglobin)

C02 Transport


C02 Transport

Carbonic anhydrase in RBC promotes useful changes in blood PC02

H20 + C02 -> H2C03 -> HC03-

high PC02

CA

H20 + C02 <- H2C03 <-

HC03- low PC02

CA


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


Acid-base balance


Acid-Base Balance

Normal blood pH: 7. 40 (7.35- 7.45, arterial)

Alkalosis: pH upAcidosis: pH down


Acid-Base Balance

H20 + C02

Hypoventilation: PC02 rises, pH falls (acidosis).

Hyperventilation: PC02 falls, pH rises (alkalosis).

H2C03 H+ + HC03-


Acid-Base Balance

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


Acid-Base Balance

Hyperventilation -> PC02 down -> pH of CSF up -> vasoconstriction -> dizziness.

If hyperventilating, should you breath into paper bag? Yes! It increases PC02!

Metabolic acidosis can trigger hyperventilation.

Diarrhea -> acidosis.Vomit -> alkalosis.


Adaptations


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?


Adaptations

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

Respiratory Physiology

Health & Medicine

residual volume of air

volume pressure

thoracic volume

fresh air

inspired air

total air barrier

structures air passes

surface tension surfactant