pulmonary physiology

Obstructive lung disease

Obstructive -

-something is obstructing the airflow,
- characterized by high airway resistance

• must be taught to breathe slowly and quietly (called pursed lip breathing

• asthma, emphsema

Restrictive lung disease

• something is restricting chest expansion,

• characterized by a low compliance

• small tidal volume with high RR

• stiff lungs

• fibrosis, tuberculosis, ARDs, intersitial lung disease

compliance

the change in pressure needed to inflate the lungs to a certain volume

lungs that are more compliant….

are stretchier — it takes a low pressure to inflate them

stiff lungs cause…

restrictive lung disease

emphysema

old stretched out sweater with holes

how does empysema increase compliance and airway resistance?

emphysema destroys the lung matrix, the
airways are very collapsable.
• Especially with forced expiration... the airways flatten out
such that air is hard to get through.

Vital capacity

-total amount of air that can be moved in and out of the lungs

~2.5-4.5 liters

-reduced with any kind of pulmonary disease

-size of vital capacity is indication of person’s pulmonary health

if ventialtion goes down…

↓ PO₂

Pulmonary vasoconstriction

If perfusion goes down///

↓ PCO₂

Bronchoconstriction

diffrence between hypoxic vasoconstriction and bronchoconstriction

Hypoxic vasoconstriction shunts blood away from poorly ventilated alveoli, while low CO₂ causes bronchoconstriction to shunt air away from poorly perfused regions—together preserving V/Q matching.

hypoxic vasoconstriction

low oxygen in the airways causes the blood vessels going to that part of the lung to constrict

commonalities between restricitve land obstructive lung disease

Both would have a reduced vital capacity
– R – difficulty expanding to get air in
– O – difficulty recoiling to get the air out
• Both would have a reduced flow rate
– See explanations above
• Both would have an increased work of breathing (WOB)

hypoxic vasoconstriction

Partial pressure (P) is:

• The pressure exerted by one specific gas in a mixture of gases

• determines direction of diffusion

Partial pressure values in pulmonary vs systemic circulation

Pulmonary circulation (lungs)

• Alveolar PO₂ (PAO₂) ≈ 100 mmHg

• Pulmonary venous PO₂ (PvO₂) ≈ 40 mmHg

➡ Large gradient (~60 mmHg) drives O₂ into blood

Systemic circulation (tissues)

• Arterial PO₂ (PaO₂) ≈ 100 mmHg

• Mitochondrial PO₂ ≈ 3 mmHg

➡ Huge gradient drives O₂ from blood → tissues

What are the gradients that permit O2 to diffuse into the blood from the alveoli?

• PAO2 = 100mmHg > PvO2=40 mmHg

What are the gradients that permit O2 to diffusion from the blood to the tissues?

• PaO2 = 100mmHg > Pmito 3mmHg

as blood flows past the alveoli….

O2 rapidly diffuses into blood

Where does blood become fully saturated?

• Blood becomes fully saturated within the first 1/3 of the capillary

• Remaining 2/3 = diffusion reserve

Oxygen is carried in blood in two forms:

1. Dissolved O₂ (very small amount)

2. Bound to hemoglobin (most important)

Why hemoglobin matters:

• One Hb molecule binds 4 O₂ molecules

• Binding removes dissolved O₂ → maintains diffusion gradient

• Allows massive increase in total O₂ carried

📌 Without hemoglobin:

• Blood could not carry enough oxygen to meet metabolic demands

Saturation

• Percentage of hemoglobin binding sites occupied

• Depends only on PO₂

• Independent of hemoglobin concentration

Oxygen content

• Amount of O₂ in blood (mL O₂ / 100 mL blood)

• Depends on:

  • PO₂

  • Hemoglobin concentration

• sum of bound oxygen and dissolved oxygen.

Mary has 12 gm% of hemoglobin and Frank has 13gm%

• At a pO2 of 100 mmHg of mercury – who is more saturated? - who has a higher content? Who has higher dissolved content? Bound content?

At a pO2 of 100 mmHg

Answer: Mary and Frank are equally saturated, Frank has a higher total content, they have equal dissolved content, and Frank has higher bound content. 

Bohr effect

describes how changes in the blood's environment affect hemoglobin's ability to bind and release oxygen. 

Right shift of Bohr effect

-promotes oxygen release (right-release)

-Occurs with high temperature,

CO2, and H+(low pH).

-This is beneficial in metabolizing tissues where these conditions are present, allowing oxygen to be released to the cells. 

-Result: Hemoglobin releases O₂ more easily to tissues

Left shift of Bohr effect

-promotes oxygen binding (left-bind)

-Occurs with low temperature,

CO2, and H+(high pH).

-This is beneficial in the lungs where these conditions help hemoglobin bind oxygen more readily

CO₂ is transported in three forms:

• Dissolved in plasma (small amount)

• Bound to hemoglobin (carbaminohemoglobin)

• Converted to bicarbonate (MOST IMPORTANT)

• Increased CO₂ → increased H⁺ → ↓ pH

location of chemoreceptors

Central chemoreceptors Location:

• Medulla

• In contact with cerebrospinal fluid (CSF)

Peripheral chemoreceptors Location:

• Carotid bodies (at carotid bifurcation)

• Aortic bodies (aortic arch)

function of central chemoreceptors

-sense: H⁺ in CSF, Indirectly sense arterial PCO₂

-Function: Major driver of ventilation at rest, Very sensitive to small changes in CO₂

—> Chemoreceptors regulate breathing by sensing chemical changes in blood and CSF.

function of peripheral chemoreceptors

What they sense:

• ↓ PO₂

• ↑ PCO₂

• ↑ H⁺ (metabolic acidosis)

Function:

• Rapid response to blood chemistry

• Essential during:

  • Hypoxemia

  • Metabolic acidosis

  • Exercise

all chemoreceptors regulate arterial blood gases, not alveolar gas

true

why CO2 is the most important regulator for ventilation:

Why CO₂ matters most:

• Small increases in arterial PCO₂ → large increases in ventilation

• Acts on both central and peripheral chemoreceptors

A competitive bicyclist takes erythropoietin and experiences an increase in red blood cell count.  As a result, this bicyclist would experience which of the following changes?

B. is correct because more hemoglobin means that there will be more bound content.

how does CO2 control ventilation?

Mechanism:

1. ↑ Arterial PCO₂

2. CO₂ diffuses into:

   • Blood → ↑ H⁺

   • CSF → ↑ H⁺

3. H⁺ stimulates chemoreceptors

4. Ventilation increases

5. CO₂ is blown off

📌 PCO₂ is the primary stimulus for breathing at rest
📌 Major contributor to dyspnea (shortness of breath)

O₂ — only important at LOW levels for controlling ventilation

Above 60 mmHg:

• Changes in PO₂ have little effect on ventilation

Below 60 mmHg:

• Peripheral chemoreceptors strongly stimulate ventilation

how does H⁺ act as metabolic control?

Effect:

• Acidosis → ↑ ventilation

• Purpose: remove CO₂ to help buffer pH

Detected by:

• Peripheral chemoreceptors ONLY

Source of H⁺:

• Metabolic acids (lactic acid, ketoacids)

• Independent of CO₂

lung tissue matrix

a weave of collagen and elastic fibers

stiff lungs

less stretchy, slow to inflate, small wheezing strengths

-cause restrictive lung disease

empysema

-destroys the lung tissue matrix

-lungs are very compliant

-makes lungs easy to stretch but difficult to recoil

Transpulmonary pressure

alveolar pressure minus the intrapleural pressure

how does alveolar pressure usually relate to intrapleural pressure ?

In physiology, intrapleural pressure (Pip) is always more negative (lower) than alveolar pressure (Palv), creating a pressure gradient (transpulmonary pressure) that keeps the lungs inflated and prevents collapse, even though both pressures change during breathing

what happens to intrapleural pressure during inspiration

During inspiration, Pip becomes even more negative as lungs stretch, causing Palv to drop below atmospheric pressure to draw air in

what happens to intrapleural pressure during expiration

during expiration, Pip becomes less negative (more positive), and Palv rises above atmospheric pressure to push air out, always maintaining Palv > Pip

when is the lowest transpulonary pressure measured

The lowest transpulmonary pressure (PL) is typically measured at the end of expiration (E-E PL), representing the pressure keeping the lungs open (avoiding collapse, or atelectasis), while the highest is at end-inspiration (E-I PL) to prevent overdistension

surface tension

-allows particles to stick together

-high surface tension in lungs makes alveoli more likely to collapse

how does CO2 affect central chemoreceptors

-cross blood brain barrier and reacts with water

-form carbonic acid

-disassociate into H+ and bicarbonate

-increased H+ in CSF stimulates brains respoiratory center

-inc ventilation

build up of CO2 causes…

build up of acid (low pH)

why mgiht a person hypoventilate

-head injury, drug overdose

-a person can stimulate this by holding their breath

why is it important for the membrane to be thing?

• it will take less time for O2 to diffuse in and Co2 to diffuse out

dissolved oxygen

-only depends on PO2

-small amount

-responsible for: partial pressure (PaO2) and diffusion gradients

hemoglobin bound oxygen

-depends on hemoglobin concentration and hemoglobin saturation

-makes up 98% of total oxygen concentation

-total oxygen concentration = dissolved O2 and hemoglobin bound O2

total oxygen concentration =

dissolved O2 and hemoglobin bound O2

lowering PCO2 leads to

• makes the blood more alkaline (increases pH)

• Respiratory alkalosis

• increased oxygen-hemoglobin binding

*a lowered partial pressure of carbon dioxide (PCO2) in the blood causes breathing to slow down (hypoventilation) and become shallower

relationship between hemoglobin and oxygen content

increasing hemoglobin directly increases the blood's oxygen carrying capability —> more oxygen can be transported from lungs to tissues

role of hemoglobin

preimary protein responsible for binding and delivering oxygen

-more hemoglobin =means more binding sites for oxygen —> boosting total oxygen content

• important in high altitudes or smoking when the body needs more oxygen

increasing PCO2 :

-makes blood more acidic

-triggers brain to increase breathing

-causes blood vessels to dilate

Chemoreceptors detect high PCO2….

…. and go to signal the brainstem to increase ventilation (breathing faster and deeper) to blow off excess CO2.

Respiratory Acidosis:

too much CO2 in the blood leads to the CO2 combines with water to form carbonic acid, increasing hydrogen ions (𝐻+) and lowering pH (making blood acidic).

what does arterial PCO2 tell us?

arterial partial pressure of Carbon dioxide reflects ventilation and how well you brathe out CO2 and its impact on blood pH

*PCO2 is a primary driver of respiratory control, influencing acid-base balance by forming carbonic acid

what does arterial PO2 tell us?

partial pressure of oxygen reflects oxygenation (how well oxygen gets into the blood)

*PO2 indicates lung efficiency in oxygen transfer, with both critical for assessing overall respiratory and metabolic health

Tidal volume (TV) ~500mL

TV: air moves in or out during normal, quiet breathing

• TV + IRV = IC

Total Lung capacity (TLC) ~6000 mL

TLC= entire volume of air lungs can hold

*IRV + ERV+ TV+ RV

Inspiratory capacity (IC) ~3500 mL

IC= max amount you can inhale after a normal exhale

• TV + IRV = IC

4 lung volumes

Tidal volume, inspiratory reserve volume, expiratory reserve volume, residual volume

Inspiratory Reserve Volume (IRV) ~3000mL

IRV = extra air you can inhale after a normal inhalation

*IRV + TV = IRC

Expiratory Reserve volume (ERV) ~1200mL

ERV = extra air you can exhale after a normal exhalation

*ERV + RV = Functional Residual capacity

Residual volume (RV) ~1200mL

RV= air remaining in your lungs after maximal exhalation

!CANNOT be exhaled!

Which values can a spirometer not measure?

residual volume (RV), and therefore FRC + TLC becasue they contain RV

Vital Capacity (VC) ~4700mL

VC= total amount of air you can move in and out - max inhale and max exhale

*IRV + TV + ERV

!vital capacity: you would use all of the air possible if it was vital!

Functional Residual Capacity (FRC) ~ 2400ml

FRC= air left after normal exhalation (lung’s resting volume

*FRC= ERV + RV

4 lung capacities and equations

• Inspiratory capacity(IC) = TV

• = IRV

• Vital Capacity (VC) = IRV + TV + ERV

• Functional Residual Capacity(FRC) = ERV + RV

• Total Lung Capacity(TLC) = TV + IRV + ERV + RV

MINUTE VENTILATION

respiratory rate(RR) x tidal volume (TV)

asthma

bronchoconstriction —> airway narrowing —> increased resistance

fibrosis

stiff lungs —> hard to expand —> low compliance

what does alveolar ventilation measure?

measures the fresh air reaching the gas exchange areas (alveoli) per minute

alveolar ventilation equation

𝑉𝐴=(𝑇𝑖𝑑𝑎𝑙𝑉𝑜𝑙𝑢𝑚𝑒(𝑉𝑇)−𝐷𝑒𝑎𝑑𝑆𝑝𝑎𝑐𝑒(𝑉𝐷))

×𝑅𝑒𝑠𝑝𝑖𝑟𝑎𝑡𝑜𝑟𝑦𝑅𝑎𝑡𝑒(𝑓)

NORMAL PARTIAL PRESSURES:

Arterial : PaO2 =~ 100mmHg, PaCO2 = ~40mmHg

Venous: PvO2= ~40 mmHg, PvCO2 = ~46mmHg