Introduction to Human Physiology - 5 Respiratory System - Anatomy and Mechanics

Source: My personal notes from Introduction to Human Physiology | Coursera

How we get air in and out of our lungs

Respiratory System

Roles:

Provide O2 for metabolism
Regulate body pH
10,000 litres of air are coming into lungs, defence is required against pathogens

High level view of respiratory system

Air into body
Trachea (tube surrounded by rings of cartilage
Trachea branch in bronchi
Bronchi branch into bronchioles, lungs
Diaphragm sits below lungs and is skeletal muscle.

Lung Airways

Defense = cleaning of air via mucous. Mucous is moved up system while blocking debris
Bronchioles like arterioles have smooth muscle around them to change R (resistance).

Alveoli

Diagram shows 3 alveolar sacs. Sacs are made up of alveoli and inner part come into contact with air, outer parts are covered by capillaries
Type I cells come in contact with air and are thin and flat to make gas exchange easier
Type II stem cells

Ventilation and Lung Mechanics

Get air into lung through negative pressure breathing.
The diaphragm (a dome shaped muscle) contracts increasing chest that creates negative pressure in lungs.
During exercise, muscles in rib cage and chest wall can increase chest size. Ab and intercostal muscles in between ribs.
Exhalation - inspiration muscles relax and there is an elastic recoil where chest becomes smaller

In diagram - means negative pressure, + means positive pressure.

Ventilation Cycle

Tidal volume = amount breathed in

Minute ventilation = amount breathed in in a minute

Key Concepts

Respiratory System - Lung Volumes and Compliance

Lung Volumes and Capacity

Tidal volume = amount breathing in/out at resting state
Inspiratory Reserve Volume (IRV) = amount you’re able to breath in a deep breath (not normal).
Expiratory Reserve Volume (ERV) = like IRV except breathing out.
Residual volume (RV) = amount always left in lung; otherwise the lung would collapse though it is opposed by water surface tension. In obstructive disease, air can’t get it and RV increases.
Vital capacity = maximum amount you can take in, excluding the residual volume always there.
Total Lung capacity = amount of air the lung can hold in total. In restrictive disease, TLC decreases as lung cannot open up (VC and RV is lower).

Up and down lines show regular breathing (tidal volume only).

Lung Diseases

For COPD, if elastic tissue is destroyed, it will be ok to inhale; however, exhalation is difficult since elastic recoil (pressure increase in lung) does not happen easily.

Fibrosis = low elasticity connected tissue is attached to lung, reduces lung elasticity and capacity.

Compliance = Distensibility

Increased compliance (upper green line) means low resistance to lung have elastic recoil - there is nothing preventing the lung from opening up. Disadvantage is that recoil is low.

Think a brown paper bag. It has high compliance and is easy to fill, but deflates slowly

Decreased compliance (lower red line) means high recoil.

Think a balloon. Harder to fill and requires higher pressure, but deflates quickly.

Our lungs are somewhere in between a paper bag and a balloon.

Lung Compliance

Every time we breath, we have to overcome the surface tension of water.
Premature babies’ lungs may not be making surfactant yet and babies may die of exhaustion trying to open their lungs. Treatment is for babies to receive surfactant. Surfactant also contributes to lung defence.

Lung Surface Tension

Surfactant is able to equalize pressures in alveoli of different radii

Key Concepts

Pressure Changes and Resistance

Respiratory System - Anatomy Review

Pleural sacs = think two glass slides sitting on each other with water in between

Pressure and Lung Volumes

Assume Patm = 0 mm Hg for easier computations, but it is really 760 mm Hg

Pa is the pressure in alveoli

Pip is the pressure in the intrapleural fluid (fluid inside the pleural sac

For lung to stay open Pip < Pa so that Pip is negative compared to Pa and pulling the lung open

In pneumothorax, the chest is punctured and the Pip rises above Pa, causing the lung to collapse.

Pressure and Lung Volumes, Ventilation Cycle

End of expiration - Pip is negative
During inspiration - Pa becomes negative since lung is expanding and elastic recoil (negative pressure) is occurring. Air flow comes in since Pa < Patm
End of inspiration - recoil high, Pa = Patm for a small amount of time
During expiration - lung is getting smaller, but air volume remains the same to Pa goes up. Since Pa > Patm, air flows out.

Plastic Lung Demonstration

When diaphragm becomes dome shaped and goes down, intrapleural pressure goes down and causes lung to expand.

When diaphragm dome goes up and decreases intrapleural space and raise Pip, lung gets smaller

If Pip equalizes with Patm due to a puncture, the lung will collapse. In this case the balloon in the canister collapses.

Resistance and air flow

Flow = (Pa - Patm) / R

Factors of resistance:

Airway diameter (smaller diameter/less tubes = more overall resistance)
Lung volume (greater lung volume = airways not compressed)
Muscle tone (parasympathetic vs. sympathetic)
Elastic recoil of airways
Forced exhalation can occur during exercise.
- Lung gets smaller due to contraction. Pressure remains high until later parts of respiratory system towards mouth.
- Need to ensure equal pressure point (where Pa = Pip) occurs in an airway with cartilage so that the greater Pip doesn’t cause collapse of the airway. In the diagram, it is indicated on the left side.
- Obstructive lung disease on right side shows Pa < Pip in area outside of cartilage, causing compression of the airway, making exhalation difficult due to resistance.

Key Concepts

Pulmonary function tests and alveolar ventilation

Look at volumes and composition of air in lung

Pulmonary Function Tests (FVC and FEV1)

Help diagnose patients with lung disease and disease progression.

Note FVC excludes residual volume.

Obstructive lung disease people have issues with exhalation.
Restrictive lung disease people have issues with lung capacity.

Pulmonary Function Test

Take normal breath, then fast exhalation
Measure FVC and FEV1

For X, note it takes multiple seconds for them to reach the 80% mark instead of 1 second

For Z, inhalation capacity is low, FEV1 is 80% but note FVC is low compared to normal.

Alveolar Ventilation

What is the composition of air in alveoli?

Normal tidal volume is 450ml, that volume is brought into the respiratory system during ventilation cycle.

Of the 450ml, only 300ml is reaching the respiratory portion where blood-air exchange can occur, the rest (150ml) is for conducting air. Only 10% of the capacity is used for exchange.

We should consider alveolar ventilation instead of overall tidal volume to check effective volume for exchange.
Assume dead space volume is same as conducting volume going through airways.
Note alveolar vent. Is higher during deep breathes (low resp. rate).

Gas Partial Pressures

Inspired air will have a PO2 of 150 mm Hg taking into account partial pressure and water vapour.

Alveolar Gas Pressure

PA O2 is less than P O2 because of oxygen gas exchange in lungs and reduced air due to anatomical dead space.
PA CO2 is more than P CO2 because of carbon dioxide gas exchange.
Arterial blood partial pressure in denoted by lower case “a”, Pa.
Alveoli partial pressure is close to arterial partial pressures.
Vein O2 partial pressure is lower than Pa and CO2 partial pressure is higher than Pa

Key Concepts

Physiologic dead space is where there is conducting volume AND parts of a (event normal) lung without ventilation and blood perfusion.

Oxygen transport

Alveolar gas equation

Alveolar partial pressure (PP) of O2 ~= arterial pp of O2

FiO2 = fraction of inspired air that is oxygen

Diet affects RQ = respiratory quotient. In a mixed diet, RQ = 0.8 . Mixed diet means fats, carbohydrates, etc.

Ventilation and Alveolar Gas Pressure

Partial pressures, normal conditions: O2 = 100 mm Hg, CO2 = 40 mm Hg

During hypo and hyperventilation oxygen consumption and CO2 production is the same, so volumes of each gas are affected by how much oxygen is taken in by the resp. system.

O2 Transport

Notice 1/3rd of the way through the capillary, the pulmonary capillary P02 is equalizing with the alveolus PO2 of 100 mm Hg. There is equilibrium for 2/3s of the capillary length.

Unfortunately there are disease states (shown in the graph) where PP02 is lower than PAO2. This limits the oxygen diffusion.

Hemoglobin (Hb)

Hemoglobin is a protein abundant in red blood cells. Each hemoglobin molecule can bind 4 oxygen molecules.

When hemoglobin binds O2 molecules, the partial pressure of O2 is reduced in the bind since O2 is now bound to hemoglobin and there are less “free” oxygen molecules in the blood. In the second rectangle, PO2 in the blood will become less than the PAO2, diffusion will occur and move oxygen into the blood.

98-99% of oxygen in blood is bound to Hb. Only 1-2% of oxygen in blood is free.

Relative partial pressures of O2 in lung, blood, and tissues

Differences in partial pressures accounts for diffusion. It causes oxygen to be exchanges on Hb.

Note there is still some oxygen on Hb even at 40 mm Hg. Hb always has some level of saturation at the lowest oxygen levels.

O2 - Hb Dissociation Curve

Graph shows Hb saturation relative to PO2

Notice the curve is steep at lower partial pressures. Hb releases lots of oxygen at low O2 partial pressures.

Left shift occurs with babies (fetal Hb), they have a higher affinity to O2. This allows baby to take O2 off of maternal Hb which may already have a higher O2 partial pressure. Favours loading of Hb
Right shift occurs as an example in exercising. Favours unloading of Hb. More oxygen is dumped and high partial pressures of O2 are required for Hb saturation.

Key Concepts

CO2 transport and V/Q mismatch

CO2 Transport in Blood

PCO2 in blood is low since it is bound to Hb like oxygen and much of it is carried as a bicarbonate ion (HCO3-)

H2O + CO2 = H2CO3 ———————————————————————-> HCO3- and H+

Water and carbon dioxide goes into carbonic acid …. Which disassociates in to bicarbonate and a H proton

So there is an increase in bicarbonate and protons which affects pH levels.

CO2 Transport in Blood and CO2 Partial Pressures

Partial pressures (written in diagram) cause diffusion in respiratory and circulatory systems.

V/Q Mismatch - Ventilation/Perfusion Mismatch

Perfusion is not perfect in a lung, mostly due to gravity. So top of the lung has lower V and Q.

Top of the lung is actually more stretched than the bottom since the rest of the lung is hanging from the top. So the top of the lung has lower compliance (can’t stretch as much due to gravity’s stretch), the bottom has higher compliance. Ventilation is highest at bottom of lung.
- V > Q
Bottom of the lung is below the heart, so blood flow is better at bottom. Lung tissue from the bottom to the top is different in that the top of the lung capillaries are more compressed (due to stretching). The compression at the top reduces blood flow.
- Q > V
In both cases, V and Q are lower at top of lung than bottom of lung. Overall V:Q is 0.8

Diseases processes affecting V/Q

Decreased blood flow - e.g. blood clot, obstructive blood flow - bronchoconstriction cuts/reduces supply of blood to the part of the lung where there is decreased blood flow and diverts it to areas that have better flow.

Decreased air flow - e.g. inhalation of debris into bronchiole - similarly to decreased blood flow, vasoconstriction occurs so that blood is diverted to areas with healthier lung tissue and better O2 flow (ventilation) to capillaries.

High altitude means lower oxygen flow - decreased air flow, true of whole lung. This situation can cause universal vasoconstriction as body is sensing lowered oxygen and constricting surrounding blood vessels.
(V) Ventilation mismatch with (Q) Perfusion is greater for entire lung, so the body compensates to lower blood flow to try to equalize V and Q.
Vasoconstriction can cause a leak leading to pulmonary edema. The edema makes the situation worse as diffusion barrier is greater, make oxygen diffusion more difficult.

The body senses a large V/Q mismatch and tries to narrow the mismatch.

Key Concepts

Exercise and Hypoxia

Consider disturbances in air and proton balances and hypoxia when blood oxygen levels are lowered

Ventilation during Exercise

Rest -> vigorous exercise means rising pH (H+ protons), increasing ventilation (hyperventilation), reduced arterial PCO2.

For trained individuals, people who exercise frequently, they have a feed forward which jump starts ventilation in a non-linear increase.

Exercise reduces energy stores such as myoglobin in muscle.

After exercise, myoglobin and creatine phosphates needs to be replaced and pH levels balanced

Types of Hypoxia (deficiency of O2 in tissues)

Hypoxic hypoxia - low O2 in blood
Anemic hypoxia - low red blood cells, so low amount of Hb oxygen carriers
Ischemic hypoxia - low O2 delivery due to low blood flow (e.g. some kind of constriction)
Histotoxic hypoxia - decrease O2 metabolism, O2 cannot be used. Like cyanide poisoning.

Causes of Decreased PaO2 (Hypoxic Hypoxia)

Low arterial pressure of oxygen

Hypoventilation (low oxygen intake)
Diffusion impairment (decrease blood uptake of oxygen, like pulmonary edema)
V-Q mismatch (high altitude)

Sleep Apnea

What wakes us up during sleep apnea? The medulla which detects PaCO2

Treatment is surgery or mask that generated air pressure.

Key Concepts

Regulation of Breathing

Reflex Loop Regulates Breathing

Medulla in the brain detects partial pressures and pH

Chemoreceptors

About pH

Decrease in pH means increase in the activity of H+ protons due to breathing out CO2.

A lower pH means a higher acidity, and thus a higher concentration of positive hydrogen ions in the solution. Chemicals or substances having the property of an acid are said to be acidic.

From <https://en.wikipedia.org/wiki/Acid>

pH is not a direct measure of concentration of H ions, though the measurement works outs to be close.

High pH above 7 = 7 base (or alkali), low pH below 7 = 7 acid, water pH = 7

The pH of pure water decreases with increasing temperatures. For example, the pH of pure water at 50 °C is 6.55. Note, however, that water that has been exposed to air is mildly acidic. This is because water absorbs carbon dioxide from the air, which is then slowly converted into bicarbonate and hydrogen ions (essentially creating carbonic acid).

From <https://en.wikipedia.org/wiki/PH>

CO2 crosses the blood-brain barrier so PCO2 can be detected by the central system. The PCO2 reflects H+ concentrations.

Inspiratory Receptors of the Lung

Pulmonary stretch receptors fire when lung is stretched a lot.
J receptors fire when pathological situations occurs. They help alert person of pathological issues through abnormal breathing.
Pulmonary irritant receptors fire when there are pathogens - cause cough and bronchoconstriction to reduce pathogen inhalation.

Transport of H+ and pH

CO2, O2, and protons affect breathing

In tissues, O2 will be released by Hb —> deoxy-Hb. The O2 binds newly generated H+ (from venous blood) to buffer the blood. Hb buffers blood otherwise pH in venous blood would have a lower pH (more acidic due to higher H ion activity due to carbon anhydrase). In venous blood, the Hb binds H as shown in #1 below.
1. So pH of venous blood slightly less than arterial blood.
pH in alveoli is balanced
Problems in resp. system can cause pH balance problems as PaCO2 affects pH levels and acid-base balance.
Respiratory acidosis - Ventilation fall = hypoventilation. PaCO2 increase, H+ increase, pH decreases (more acidic).
Respiratory alkalosis - hyperventilation. PaCO2 decrease, H+ decrease, pH increase (more alkaline/base).

H+ binding to Hemoglobin

In Tissues where O2 concentration is low

O2 goes into tissues, CO2 goes into blood.

Effects of PaO2 and PaCO2 On minute ventilation

Normal Pa02 = 100 mmHg
Notice around 100, ventilation doesn’t change much. Only at low PaO2 does the body increase ventilation. This slope is explained by Hb saturation at different PaO2
Normal PaCO2 = 40 mmHg
Since PaCO2 is related to [H] (hydrogen ion concentration), minute ventilation vs. PaCO2 slope is steep. The body is trying to balance pH through ventilation.

Effects of plasma [H+] - hydrogen ion concentration

Higher ventilation (hyperventilation) reduces PaCO2 and decreases H+ due to set of chemical reactions involving CO2, increasing pH.
Metabolic acidosis - could be caused by exercise with increased lactic acid, reducing pH. Body compensates by hyperventilating to increase pH.
Metabolic alkalosis - could be caused by stomach bug and vomiting. In vomiting, lots of protons are lost, decreasing overall [H+], increasing pH (more alkaline/base). Ventilation is slowed to compensate to increase PaCO2.
Note the chart entries shows different combinations of plasma [H+] and PaCO2. During patient care, knowing [H+] and PaCO2 will help you determine what is the cause of the pH level differences.
These concepts will be applied when talking about the renal system.