KINS 4500 chapter 9 respiration

you can hold your breath longer after hyperventilating. What makes you breathe again?

An increase in carbon dioxide (CO₂) levels in the blood—and the resulting drop in blood pH (acidification)—stimulates the medulla chemoreceptors in the brainstem to force you to breathe again

respiration is four processes, and only the first one is breathing

the four processes of respiration, each with the condition it falls in, and transport drawn as a step that is not one of the four. Acid base regulation is the fifth role and is the last slide of the second meeting

pulmonary ventilation

external respiration

internal respiration

cellular respiration

pulmonary ventilation

atmospheric air nose and mo9th

alveoli of lungs

falls in asthma

external respiration

alveoli of lungs

pulmonary capillary blood

falls in pulmonary edema

transport

not one of the four

falls in anaemia

internal respiration

systemic capillary blood

muscle cells

falls in carbon monoxide

cellular respiration

muscle cells

aerobic metabolism

yields ATP

falls in cyanide

one path from the nose to the alveolus and every branch is narrower

air travels a single branching path from the nose and mouth to the alveolar sacs, and the structures along that path are what the next slide divides into two functional zones

• Nose and mouth, then pharynx, larynx, and trachea

• The trachea divides into the left and primary bronchi

• Bronchi branch to secondary and tertiary bronchi, then to bronchioles

• Bronchioles at the terminal bronchioles

• past them: respiratory bronchioles, alveolar ducts, alveolar sacs

• each generation is narrower, and there are far more of them

• maximize surface area by branching

path of air

nose > mouth > pharynx > larynx > trachea > bronchi > bronchioles > alveolar ducts > alveolar sacs

conductive zone

nose and mouth to the terminal bronchioles

moves air, warms it, humidifies it, filters it

No gas exchange, anatomical dead space

trachea

respiratory zone

respiratory bronchioles

alveolar ducts and sacs

every gas exchange here

the conductive zone moves air and exchanges nothing

everything from nose to terminal bronchioles is plumbing, and the volume it holds is air you moved but could not use

• Conductive: nose and mouth to terminal bronchioles (brings air in)

• Transport air, warms it to 37 degrees C, humidifies it to 99.5% saturated, filters it

• No gas exchange, so it is also called anatomical dead space

• Respiratory zone: respiratory bronchioles, alveolar ducts, alveolar sacs

• Every gas exchange in the lungs happens here

Dead space is a fixed pipe, so it costs most when you breathe small

anatomical dead space scales with body size rather than with fat, and because the pipe does not change, the share of each breath it wastes falls as tidal volume rises

• About 1 mL per pound of LEAN body mass. A 150 lb adult: about 150 mL

• Fowler measured it by single-breath N₂ washout: 156 plus or minus 28 mL in 45 men That is 26% of their tidal volume, measured not assumed

• It is airway volume, so it scales with frame. That is why one rule fits a child and an adult

• At rest it wastes about a third of every breath In exercise it wastes about a fifth, because tidal volume rises and the airway does not

• Alveolar dead space: alveoli ventilated but not perfused. Minimal in healthy lungs

• Anatomical plus alveolar dead space is physiological dead space

• Physiological dead space needs an arterial sample: the Bohr equation

• Goes down with exercise

inspiration always costs muscle while

expiration is free until it is not

inspiration

• always needs muscle

• diaphragm contracts and flattens, ribs lift outward

• thoracic volume increases

• intrapulmonary pressure falls below atmospheric pressure air flows in

expiration

• passive at rest

• at rest: diaphragm relaxes, ribs fall, lungs recoils elastically. No muscle work

• thoracic volume decreases

• intrapulmonary pressure rises above atmospheric

• air flows out

• in exercise it turns ACTIVE: abdominals and internal intercostals drive it

airflow is a pressure gradient divided by a resistance

• V= delta P/ R

• V is airflow, in liters per second

• Delta P is the pressure gradient, P1-P2, in mmHg

• R is resistance, in mmHg per liter per second

• A bigger gradient gives more flow. More resistance gives less flow

• Resistance rises steeply as airway radius falls

• Breathing a little top of mouth, helps open nose open up and nose breathing

A 130 lb woman at her ideal weight gains 20 lb. What happens to her anatomical dead space?

it stays at about 130 mL, because airway volume has not changed

the whole breath happens between 758 and 762 mmHg

Boyle’s law > P x V= constant

chest height is volume from Boyle’s law, inverse in pressure, with the deviation from rest exaggerated 60 times. The real swing from full inspiration to full expiration is 0.53 percent of resting volume

lung pressure crosses atmospheric twice on every breath

the same breath as a pressure trace, so the size of the swing is visible. Four mmHg moves a half of liter of air

harder breathe more pressure gradient

the lung has two blood supplies and they do opposite jobs

pulmonary circulation and bronchial circulation

pulmonary circulation

• Right ventricle to pulmonary artery to alveolar capillaries

• Serves EXTERNAL respiration: takes up O2, unloads CO2

• Low pressure: about 25/10 mm Hg arterial, about 7 mmHg venous

• Carries deoxygenated blood in an artery

bronchial circulation

• Thoracic aorta to lung tissue, drains to the pulmonary veins

• Serves INTERNAL respiration of the lung tissue itself

• Part of the systemic circulation

• So not all pulmonary venous blood is fully oxygenated

ventilation and perfusion are matched, but not evenly

• V/Q is the ratio of ventilation to perfusion. Ideal is about 1.0

• Apex: relatively under perfused, so V/Q is above 1.0

• Base: relatively over perfused, so V/Q is below 1.0

• The best perfused region is also the best ventilated region

• Light exercise improves matching. Heavy exercise reintroduces inequality

• Lungs direct blood flow

apex

relatively under perfused, so V/Q is above 1.0

base

relatively over perfused, so V/Q is below 1.0

Example talked about he asked RPE during VO2 max and guy got distracted and flow ended

• During exercise > take more deeper breathes, because less dead space

• Want breaths to be matched, functional rate

• Deeper breaths more ventilation and surface area for gas exchange and blood exchange, there is a limit

there are only four volumes, and every capacity is a sum of them

inspiratory reserve volume IRV

the greatest amount of air that can be inspired at the end of a normal respiration

tidal volme

the amount of air that is inspired or expired in a normal breath

expiratory reserve volume ERV

the greatest amount of air that can be expired at the end of normal respiration

residual volume RV

the amount of air that is left in the lungs following a maximal exhalation

inspiratory capacity IC

the greatest amount of air that can be inspired from a resting expiratory level

IC= IRV + Vt

vital capacity VC

the greatest amount of air that can be exhaled following a maximal inhalation

VC= IRV + VT +ERV

functional residual capacity FRC

the amount of air left in the lungs at the end of a normal expiration

FRC= ERV + RV

total lung capacity TLC

the greatest amount of air that can be contained in the lungs

TLC= VC + RV

IC + FRC

IRV + VT + ERV + RV

a spirometer cannot see residual volume, and that matters twice

the shaded is the air in a spirometer never sees. Each capacity is drawn as the sum of the volumes beneath it

How much air you can movie one second predicts how long you live

FEV1 as a percentage of predicted is a long term predictor of all-cause mortality in the general population, not just a lung disease measure

• Buffalo Health Study, 29-year follow-up of a general population sample

• Low FEV1 percent-predicted predicted death from ALL causes, not only respiratory

• Aronson 2006 adds an inverse association between pulmonary function and CRP

• So lung function tracks something systemic, plausibly inflammation

• This is why a spirometry number is worth taking in an apparently healthy person

• All cause mortality > looking at causes of death, risks of dying

notation is a system, not a vocabulary list

• Capital letter is the variable: V volume, P pressure, S saturation, F fraction

• Capital subscript is the gas phase: A alveolar, I inspired, E expired, T tidal, D dead space

• Lowercase subscript is the blood phase: a arterial, v venous, c capillary

• A volume per unit time is a flow, so VO2max is a flow rate in mL . Min-1

• A bar means a mean, so bar v is MIXED venous, the average of all venous return

• A dot above means per unit time. A bar above means a mean value

• Lowercase f standing alone is frequency, breaths per minute, not the F above

• So PAO2 is alveolar and PaO2 is arterial. One letter apart

capital letter

variable

capital subscript

gas phase

lowercase subscript

blood phase

a volume per unit time is a

flow

so VO2max is a flow rate in mL . Min-1

bar

meanso bar v is MIXED venous, the average of all venous return

dot

above means per unit time. A bar above means a mean value

lowercase f

 standing alone is frequency, breaths per minute, not the F above

minute ventilation is what moved whereas

alveolar is what you used

minute ventilation

• VE= VT x f

• At rest: 12 breaths/min x 0.5 L- 6.0 L.min-1

• Counts every liter that moved, including the wasted ones

alveolar ventilation

• VA= (VT-VD) x f

• At rest: 12 (x 0.5-0.15)L- 4.2 L.min-1

• Counts only the liters that reached an alveolus

same 6 liters per minute. Short and Shallow, or slow and deep

Person 1 (Short and shallow)

• Math: (30 times (0.20- 0.15)

• Result: = 1.5 L/min

Person 2 (Slow and deep))

• Math: 6 times (1.00 - 0.15)

• Math: (6 times 0.85)

• Result: = 5.1 L/min

Conclusion

Slow and deep breathing provides a much higher alveolar ventilation rate (5.1 L/min vs. 1.5 L/min), because short and shallow breathing wastes 75% of each breath just filling the dead space.

two people each move 6.0 L of air per minute with 0.15 L of dead space. One breathes 30 times at 0.20 L, the other 6 times at 1.00 L. Which one does more for their alveoli?

fast and shallower breather

RR >30 breaths/min

VT > 0.2 L

AV = 30 x (0.2-0.15) > 1.5 L/min

slow and deep breather

RR > 6 breaths/min

VT > 1.00 L

AV = 6 x (1.00-0.15) > 5.1 L/min

Person 2 delivers significantly more fresh air to their alveoli (5.1 L/min vs. 1.5 L/min). Because Person 1 has a very low tidal volume, a massive portion of each breath (75%) is wasted entirely on clearing the anatomical dead space.

one breath, three volumes, depending on where you measure it

three gas laws, three changes, every one of them staring from the same 5 liters on one shared axis

pressure falls > Boyle’s Law

temperature falls > Charles’ law

water vapor removed

pressure falls > Boyle’s Law

760 to 600 mmHg, held at 0 degrees Celsius and dry

temperature falls > Charles’ Law

 37 to 0 degrees Celsius, held at 760 mmHg and dry

water vapor removed

 saturated and dry, held at 37 degrees Celsius and 760 mmHg

breathing rhythm is generated in the medulla and smoothed by the pons

the control of breathing as a left to right flow. The limb from the medulla out to the muscles is added from the chapter text

Opigenetics > gene activation. Light activation

high brain centers (stimulate or inhibit)

cerebral cortex, voluntary control

hypothalamus strong emotion and pain

DRG

chemoreceptors (stimulate)

mental, in the medulla, rising PCD, falling pH

peripheral, carotid and aortic, also falling PO2, rising K+

DRG

lung and airway receptors (inhibit)

stretch, the Harling-Breur reflex, on overinflation

irritant, to fumes, mucus and particulates

DRG

muscle and joint receptors

proprioceptors, sensitive to movement

DRG

inspiratory muscles

diaphragm, external intercostals

VRG

expiratory muscles

internal intercostals, abdominals, only when breathing is forceful

ventilation is

12-15 breaths per minute

dorsal respiratory group integrates whereas

ventral respiratory group generates the rhythm

three classes of input reach the respiratory centers

higher brain centers, mechanical receptors and chemoreceptors all modulate breathing, and they do not matter equally

higher brain centers

• Hypothalamus: sympathetic drive, pain, strong emotion, cold water immersion

• Cerebral cortex: conscious control for speech, singing, lifting, swimming

mechanic receptors

• Lung stretch: the Hering- Breur reflex, which cuts off an over deep breath

• Irritant: cough and bronchoconstriction

• Muscle and joint: movement signals the centers

chemoreceptors

• Central, in the medulla: responds to CO2 by way of H+

• Peripheral, carotid, and aortic bodies: O2, CO2, H+ and K+

Arterial PO2 falls from 100 to 80 mmHg while arterial PCO2 rises from 40 to 45 mmHg. Which change drives ventilation harder?

The 5 mmHg rise in PCO2, which nearly doubles ventilation

The rise in PCO2 drives ventilation harder because central and peripheral chemoreceptors are acutely sensitive to even tiny increases in carbon dioxide and the resulting drop in pH, triggering an immediate surge in breathing to blow it off. Conversely, the drop in PO2 to 80 mmHg has almost no effect because oxygen levels must fall below a critical hypoxic threshold of roughly 60 mmHg before the hypoxic ventilatory drive is strongly activated.

over the same 35 mmHg, CO2 does everything and O2 does nothing

Both panels span 35 mmHg of their own gas. Carbon dioxide crosses that span from 4 to 39 liters a minute. Oxygen crosses it without responding at all

normal arterial PO2 is 95 mmHg and normal arterial PCO2 is

40 mmHg

makes cost you comfort, not performance, and UCONN ran one of the studies

three controlled trials found no performance, saturation or core-temperature cost to masked exercise; the real signals are retained CO2 under an N95 and breathing discomfort

• Shaw 2020: randomized crossover, n=14, cloth vs surgical vs none, maximal cycling

• No difference in time to exhaustion, peak power, SaO₂, tissue oxygenation, RPE or HR

• Epstein 2020: ramp protocol, n=16, none vs surgical vs N95

• No difference in HR, respiratory rate, BP, saturation or time to exhaustion

• BUT significantly higher end-tidal CO₂ with the N95, rising with intensity

• Yoshihara 2021, OUR DEPARTMENT: n=12, 60 min in 32 °C heat, 4 masks vs none

• No difference in rectal temperature or heart rate. Breathing discomfort DID rise

• All three studied healthy young adults only

only some of those inputs actually drive exercise hypernea

the inputs that dominate at rest are not the ones that drive exercise hyperpneas and the mechanism is still not fully explained

what drives exercise hypernea

• pH, by way of CO2 and of lactate

• Potassium, released from working muscle

• Muscle and joint mechanoreceptors

• Central command, feeding forward

what does not drive exercise hypernea

• PaO2, flat as a stimulus above 60 mmHg

• PaCO2, tightly regulated, barely rises

• Hering-Breuer reflex, minimal even in exercise

what is not explained about exercise hypernea

• Nothing explains how closely VE tracks metabolic rate

• No single stimulus accounts for the match, after seventy years

shallow water blackout: it kills in guarded pools, and that is the point

hyperventilation extends breath hold time by lowering Co2, not by adding oxygen, so it removes the warning without adding the reverse

• The name for it is shallow-water blackout, or hypoxic blackout

• The urge to breathe comes from rising CO₂, not from falling O₂

• Hyperventilation blows off CO₂, so the urge arrives late or not at all

• Oxygen keeps falling on the same schedule. Nothing has been added

• Craig 1976: 58 cases of loss of consciousness in underwater swimming and diving

• 23 of the 58, 40%, were fatal. Most occurred in GUARDED pools

• Swimming continues for a short time after blackout, so it is hard to spot

• Recommendation: limit underwater swimming to one length of a 25 yd or 25 m pool

Fick’s Law of diffusion (this chapter)

• Vgas= (A x D X delta P) divided by T

• A area, D diffusion coefficient, which rises with solubility

• Delta P the pressure gradient, T the thickness of the barrier

• Governs how fast a gas crosses the alveolar membrane

• Answers: why does oxygen get into the blood at all

Fick equation chapter 11

• VO2= Q x a-vO2 diff

• Relates oxygen uptake to cardiac output and extraction

• Introduced in session 7 as equations 11.3 and 11.13

Why does hyperventilating before an underwater swim make blackout more likely?

hyperventilating lowers CO2, delaying the urge to breathe past safe oxygen

four things that se how fast a gas crosses the membrane

diffusion rate rises with the pressure gradient, the surface area and the gas’ solubility and falls as the barrier thickens

1. The pressure gradient across the barrier, in ,mmHg

2. The surface area available for diffusion

3. The thickness of the barrier between two locations

4. The solubility of the gas in the barrier liquid

altitude does not change the percentage of oxygen, only the pressure

percent times barometric pressure equals partial pressure, there times over. the oxygen percentage is identical at sea level and at altitude, only the pressure it multiples has changed

partial pressure changes

oxygen crosses downhill at both ends of the circuit

arrow size is the LOCAL gradient, so it falls nothing as the blood equilibrates

both panels share one 0 to 110 mmHg axis

deep breaths better

carbon dioxide crosses downhill at both end of the circuit

Arrow size the LOCAL gradient, so it falls to nothing as the blood equilibrates. Both panels share 0 to 110 mmHg axis

working muscle holds a gradient 1.7 times the resting one, and never lets the blood catch up

exercising muscle PO2 of 3.8 mmHg is MEASURED, by myoglobin desaturation and is invariant beyond 60 percent of maximal work rate

without hemoglobin, blood would

carry 1/70th of the oxygen

dissolved in plasma, 1.5 to 3% blood

• Solubility constant 0.00304 mL.dL-1 mmHg-1 at 37 degrees C

• At PaO2, 95 mmHg: 95 x 0.00304=0.29 mL.dL-1

• Tiny, and it is what SETS the partial pressure of oxygen

• Only dissolved gas exerts pressure, so only is drives diffusion

bound to hemoglobin, 97 to 98.5% blood

four heme groups per hemoglobin, one O2 each

binding capacity is constant 1.34 mL O2 per g Hb

fully saturated means all four hemes occupied

SbO2% is how much of that capacity is in use

it multiples the blood’s oxygen capacity about seventyfold

hemoglobin is four subunits, and its shape is the point

binding one oxygen makes the next easier to bind, which gives the dissociation curve its S shape

• Four globin chains, each wrapped around one iron containing heme

• One O2 binds per heme, so four per hemoglobin

• The four do not bind at the same time

• Binding the first changes the shape, making the second easier

• This cooperativity is why the curve is sigmoid, not straight

• RBC count: 4.3 to 5.2 million per cubic female, 5.1 to 5.8 male

arterial blood carries 19.79 mL of oxygen per deciliter

oxygen content is hemoglobin times its binding constant times saturation, plus dissolved fraction and the dissolved fraction is not optimal in the arithmetic

Take Hb = 15 g·dL−1, SaO₂ = 97%, PaO₂ = 95 mmHg

1.34 is hemoglobin's oxygen-binding capacity, in mL O₂ per g Hb

Bound: 15 × 1.34 × 0.97 = 19.50 mL·dL−1

Dissolved: 95 × 0.00304 = 0.29 mL·dL−1

Total: 19.50 + 0.29 = 19.79 mL·dL−1

Venous, at 75% and PvJO₂ 40 mmHg: 15.08 + 0.12 = 15.20 mL·dL−1

• Looking at stuff as a whole

• Hydrogen drives change

the a-vO2 difference is what the tissues actually took

arterial content minus venous content is the oxygen extracted in one pass, and at rest that is only about a quarter of what was carried

• A-vO2 diff= arterial O2 content- venous O2 content

• At rest: 19.79-15.20=4.59 mL.dL-1

• Only about 25% of the oxygen carried, extracted in one pass

• The other 75% returns to the lungs unused

• It is the shaded band at the top of the figure

exercise double extraction without changing the arterial side

• At rest

• Arterial O2 content: 19.79 mL.dL-1

• Venous O2 content 15.20 mL.dL-1

• A-vO2diff= 19.79-15.20=4.59

• 4.59 mL.dL-1, about 25% extracted

• During heavy exercise

• Arterial O2 content: 19.79 mL.dL-1, essentially unchanged

• Venous O2 content: about 10.00 mL.dL-1

• A-vO2diff=19.79-10.00=

• 9.79 mL.d-1. more than double

the S shape is a safety margin on top, a delivery zone below

the curve is flat above about 60 mmHg and steep below it, so loading is protected and unloading is sensitive

• Flat above about 60 mmHg: big falls in PO2 cost little saturation

• That is the loading safety margin, at altitude and in lung disease

• Steep below about 40 mmHg: small falls in PO2 release a lot of oxygen

• That is the unloading zone, at the working tissue

• Arterial sits at about 97%, on the flat part

• Venous sits at about 75%, on the shoulder

• Loading easy, unloading hard

three things shift the curve right and they live in chapter 10

decreased pH

increased temperature

increased 2, 3 DPG

decreased pH

• Lowers Hb-O2 affinity, shifts the curve right

• Favours offloading O2 to the tissues

• This the bohr effect

increased temperatures

• Lowers Hb-O2 affinity, shifts the curve right

• A working muscle is warm, so it unloads more

increased 2,3 DPG

• A byproduct of glycolysis in the red cell

• May shift the curve right

• Rises at ALTITUDE. Not a major cause during exercise

• Inflamed good > muscle will get remodeled

inside the muscle cells the carrier is myoglobin

myoglobin has a higher affinity for oxygen than hemoglobin, so it accepts oxygen at low PO2 inside the cell and shuttles it to the mitochondria

Myoglobin, Mb, sits inside the muscle fibre

Shuttles O₂ from the cell membrane to the mitochondria

Higher O₂ affinity than hemoglobin, so O₂ moves Hb to Mb, not the reverse

Also a small O₂ store for the onset of exercise

One heme per molecule, not four: no cooperativity, no S curve

carbon dioxide travels three ways, mostly as bicarbonate

about 70% of Co2 moves as bicarbonate which is why CO2 transport and acid base balance are the same mechanism

can also be dissolved or carbamino

dissolved

5-10% of CO2

• Dissolved in plasma

• Set the partial pressure of CO2

• So it is what the chemoreceptors read