A+P 2, Respiratory System

Respiratory system

Moves O2 and CO2. Closely tied to cardiovascular system, moves gasses and other things throughout the body

Oxygen (O2)

Used for aerobic cellular metabolism (occurs in cell mitochondria, how we are making ATP/energy)

Carbon dioxide (CO2)

Needs to be removed b/c it’s a byproduct of aerobic metabolism

Respiration

2 integrated processes.

1. External respiration

2. Internal respiration

Includes: exchange between blood and cells and cellular respiration (cellular metabolic use and production of gasses)

External respiration

Exchanging O2 and CO2 w/ the environment

Internal respiration

Involves uptake of O2 and production of CO2 by individual cells

Functions of the respiratory system

Main function: moves air to/from the lungs, where there is HUGE surface area for gas exchange between air and circulating blood

Other functions: Sense of smell, how we make noise/speak, protects respiratory surfaces from the outside environment (mucus and cilia), maintains blood pH

Major respiratory structures span the ______ to the ______

Nasal cavity, diaphragm

Respiratory tract

Made up of two zones:

1. Conducting zone

2. Respiratory zone

Also divided by location:

1. Upper respiratory tract

2. Lower respiratory tract

Conducting zone

From nasal cavity to terminal bronchioles

Respiratory zone

Respiratory bronchioles and alveoli (where gas exchange takes place)

Upper respiratory tract

Head and larynx

Lower respiratory tract

Neck and thorax

Cells in conducting zone

Contain cilia and produce mucus (pseudostratified ciliated columnar epithelium) (respiratory mucosa with mucous cells)

Filtering the air that comes through

Cells in respiratory zone

Thin, single layer of cells (simple squamous epithelium and simple cuboidal epithelium)

Easier for gasses to diffuse

Respiratory defense system

• Mucous cells produce mucous → bathes exposed surfaces and traps debris/pathogens

• Cilia sweep debris/pathogens trapped in mucus upward to be swallowed (mucus escalator)

• Hairs in nasal cavity traps large particles in air

• Alveolar macrophages - engulf small particles that reach lungs

Major functions of the conducting zone

• Conduct air into/out of respiratory zone

• Warm and humidify incoming air

  • Moist epithelium helps humidify air (mucus)

  • Superficial capillaries help warm air (easier for gas exchange than cold, dry air)

• Remove pathogens and debris from incoming air

Nose

External nose includes nasal bones and hyaline cartilages. Paired nostrils allow air to enter/exit nose. Internal nose includes a nasal septum that creates R & L nasal cavity. Septum is formed by hyaline cartilage (anteriorly) and perpendicular plate of the ethmoid (posteriorly)

Nose: Boundaries of the nasal cavity

Superior: Cranial base (where brain sits)

Inferior: Palate (roof of mouth)

Anterior: Vestibule (inside nostrils)

Posterior: Internal nares (where nasal cavity meets the pharynx)

Nasal cavity

Lateral wall of each nasal cavity has curled projections (turbinates) w/ spaces under them for air flow

• Olfactory mucosa - site of olfactory receptors (olfaction/smell)

Prevents stuff from going down

Turbinates

Create turbulent air flow that increases air contact w/ the warm, moist respiratory epithelium

• Helps warm and humidify the air

• Directs air/odorants to olfactory mucosa

• Also traps water during exhalation = keeps epithelium moist and reduce insensible (not easily measured) water loss from the respiratory system

Pharynx

A chamber shared by the digestive and respiratory systems. Extends from internal nares to entrances of the larynx (air) and the esophagus (food)

Divided into 3 regions:

1. Nasopharynx

2. Oropharynx

3. Laryngopharynx

Nasogastric tube

Enters through one nostril, ends in stomach

Larynx

Extends from the laryngopharynx to the trachea (suspended from hyoid bone).

• Epiglottis - folds down during swallowing to block respiratory tract from 3 large, unpaired cartilages form most of the larynx (plus ligaments, muscles, and smaller cartilages)

• 1. Thyroid cartilage (front of larynx)

• 2. Cricoid cartilage (below thyroid cartilage)

• 3. Epiglottis (top, blocks respiratory tract)

Vocal folds

Vibrate to produce sounds (folds consist of ligaments, muscles, and mucus membranes). Muscles are used to open/close vocal folds and change tension on the folds = alters sound

True vocal folds - mucus membrane removed

• Larynx only first step of sound production - throat, tongue, and mouth shape sound into words, etc.

• Forcing air over the true vocal folds makes them vibrate - produces sound

*Fun fact: Males typically have lower pitched voices b/c longer and thicker vocal folds vibrate slower

Trachea

Descends inferiorly from larynx, connecting the upper respiratory structures to those in the thorax. First in a series of progressively branching tubes that conduct air to areas where gas exchange takes place (gas exchange takes place in alveoli)

• Structure: 16-20 c-shaped pieces of hyaline cartilage provide structural support. Trachealis muscle (posterior aspect) allows for slight expansion/contraction

• Anterior to the esophagus (part of the digestive tract)

• Bronchi - in the thorax, trachea splits into R and L primary bronchi. Each primary bronchi travels to an opening (hilum) on the medial surface of the R and L lung, respectively

*Note: R primary bronchus has larger diameter and descends at a steeper angle

• Carina - ridge at the bifurcation point. Contains specialized nervous tissue that induces coughing if something is aspirated

Carina

Ridge at the bifurcation (split) point. Contains specialized nervous tissue that induces coughing if something is aspirated

Hilum

Medial aspect of the left or right lung. Anything that enters the lungs enters at the hilum

Lungs

• Location: each lung is in a pleural cavity. Base of each lung (inferior portion) rests on the superior surface of the diaphragm

• 2 pleural cavities - separated by mediastinum. Each one:

  • Holds a lung

  • Is lined w/ a serous membrane (pleura) (reduce friction, allows better movement)

  • Consists of 2 layers (parietal and visceral pleura) w/ fluid between lubrication

  • Protective layer

• Divided into lobes via deep fissures (deep indents that separate lobes)

  • Left lung = 2 lobes (superior and inferior) (heart is on left side, less space)

  • Right lung = 3 lobes (superior, middle, inferior)

• Bronchi - each primary bronchi further subdivides, creating secondary and tertiary bronchi, and further branches. Contain cartilaginous rings or pieces (depending on their size)

Bronchopulmonary segments

Each lobe of the lung can be further divided = discrete regions supplied by a specific tertiary bronchi and branch of the pulmonary artery (tertiary bronchi are also called segmental bronchi)

Bronchioles

What tertiary bronchi branch into. Lack cartilage and are dominated by smooth muscle. Continue to branch (about 20+ times). Terminal bronchioles are the last structure of the conducting zone. Branch into respiratory bronchioles (start of respiratory zone)

Has mucus membrane to trap particulates

Asthma

Chronic condition typified by inflammation of the airways and muscle spasms of the bronchiole smooth muscle

• Attacks: can have many possible triggers, such as foreign debris, temp change, exercise, etc.

• Treatment: drugs that stimulate epinephrine receptors (dilates the bronchi) in the lungs → Beta-2 adrenergic receptor agonist or corticosteroids (reduces inflammatory response)

  • Potential side effect: tachycardia (elevated heart rate)

Alveoli (singular = alveolus)

Where gas exchange takes place

• Respiratory bronchioles end in alveolar ducts

• Alveolar ducts lead to a collection of alveoli (called an alveolar sac)

• Highly elastic structures that are externally covered by dense capillary beds (about 300 million alveoli per lung)

• Alveolar walls are a single cell layer thick (easy gas exchange)

  • Type 1 alveolar cells - mostly thin, delicate cells. Squamous epithelial cells; 95% of total surface area (white, delicate cells in between alveoli and capillaries)

  • Type 2 alveolar cells - interspersed, cuboidal epithelial cells: 5% of total surface area (yellow blobs)

• Alveolar macrophages (dust cells) - immune system cells that patrol the alveoli

Type 1 alveolar cells

Gas exchange. Thin, elongated cells (squamous epithelial cells) that are the site of gas exchange from the air into the blood capillaries (95% of total surface area)

Type 2 alveolar cells

Secrete surfactant, which coats the inner surface of the alveoli. Reduces surfaces tension (disrupts bonds between water molecules), making it easier to expand the alveoli (5% of total surface area)

Respiratory membrane

Gas exchange between the alveoli and capillaries occurs across the respiratory membrane (which is very thin). Made of 3 layers:

1. Type 1 alveolar cells (squamous epithelium)

2. Endothelial cells of an adjacent capillary wall (squamous epithelium)

3. Basement membrane between alveolar and endothelial cells

Ventilation

Act of bringing air in and out of the lungs. Air flows from higher pressure towards lower pressure. Just like with blood, air flows from higher pressure towards lower pressure areas. Air is highly compressible

Boyle’s law

Describes relationship between volume and pressure of a gas (at a constant temp). Pressure and volume changes are inversely related (P1V1=P2V2)

• As volume increases, pressure decreases

• As volume decreases, pressure increases

Pulmonary ventilation

Dependent on 3 types of pressure:

1. Atmospheric

2. Intra-alveolar

3. Intrapleural

Atmospheric pressure

Force exerted by gasses in the air, Depends on altitude. Low altitude = higher pressure b/c the weight of the overlying molecules compresses the lower gas regions

Sea level atmospheric pressure: about 760 mmHg

Intra-alveolar pressure

Pressure of the air in alveoli. When the lungs are not contracting/expanding, intra-alveolar pressure = atmospheric pressure

*Note the 0 mmHg - typically ventilation pressure values are discussed in relation to atmospheric pressure (negative value would imply less pressure than atmospheric, and vice versa)

Ex: If alveolar volume increases, how would that affect intra-alveolar pressure? Pressure would decrease

Ex: If pressure decreases, in which direction will air flow? Into the lungs (flows from high conc to low conc)

Intra-pleural pressure

Pressure between pleural membranes. Negative intra-pleural pressure means the pleural layers are “pulled” toward one another (‘stuck together’)

*Note the -4mmHg means intra-pleural pressure is 4mmHg less than intra-alveolar pressures

If we use muscles to change thoracic volume = alveoli volume will also change

Pneumothorax

Collapsed lung. Results when intrapleural pressure is disrupted. If the thorax is punctured from the outside, intrapleural pressure equals atmospheric pressure. Puncture of intra-pleural space. Allows alveoli to completely collapse (due to natural elastic recoil of the alveoli - no longer being held open)

Treatment: Many different treatments depending on size and type of pneumathorax. All involve regeneration of the negative intrapleural pressure. Ex: this chest tube allows air to leave the intrapleural space (but not re-enter)

Inspiration

Bringing air into the alveoli. At rest (quiet breathing). Diaphragm contracts, moving downward. Ribcage expands (aided by intercostal muscles). These actions increase thorax volume, which increases alveoli volume = air is pulled into lungs

Muscles involved: core (external intercostals, diaphragm) and accessory (sternocleidomastoid, pectoralis minor)

Forced inspiration

When more air needs to be brought into the lungs, such as during exercise or singing…accessory muscles are used to further expand the thorax

Compliance

Elasticity of the thoracic cavity. Effort needed to expand the lungs is dependent on this. Flatter curve = more force needed to expand lung volume (less compliance)

Depends on: 1. connective tissue structure of the lungs, 2. mobility of the thoracic cage, 3. level of surfactant production (more compliant with more surfactant, reduces surface tension)

Normal compliance - most people

Some have genetic or trained caused high compliance

Premature birth

Respiratory distress syndrome. Premature infants = less alveoli and surfactant (starts being produced at about 20-24 weeks). Low surfactant = increased muscular effort to ventilate lungs → possible exhaustion and death

• Synthetic surfactant and assistive ventilation methods - have saved the lives of many pre-term infants

Expiration

Pushing air out of the alveoli. Primarily a passive process. Diaphragm and inspiratory muscles relax, and stretched elastic tissues (e.g., alveoli and muscle fibers) recoil. These actions decreases thorax volume = air is pushed out of the lungs

Muscles involved: core (internal intercostals, diaphragm) and accessory (abdominals, quadratus lumborum)

Forced expiration

When more air needs to be brought into the lungs, such as during exercise or singing…accessory muscles are used to further contract the thorax (so more fresh air can be brought in during the next breath). Active process driven by muscular actions

Respiratory system responds to changing oxygen demands by varying:

1. The # of breaths per minute (respiratory rate)

2. Volume of air moved per breath (tidal volume)

*Lung health can be evaluated by measuring respiratory volumes (e.g., tidal, residual, inspiratory reserve, respiratory reserve, etc.)

How to measure lung volumes and capacities?

Person breathes through mouthpiece (spirometer) and the computer (flow meter) plots changes in lung volume. Resulting hills/valleys represent the volume of air moved into and out of lungs. Can also use mechanical spirometers to get the same volume data

Tidal volume

Volume of air inhaled/exhaled in a breath when resting

Vital capacity

Max volume that can be inhaled/exhaled

Residual volume

Amount of air that cannot be exhaled from the alveoli

Dead space

Does not participate in gas exchange

• Anatomical dead space

• Alveolar dead space

Makes up total dead space (physiological dead space)

Anatomical dead space

Air in the conducting zone that doesn’t reach alveoli

Alveolar dead space

Air in alveoli that doesn’t exchange w/ blood (e.g., because of disease or abnormal blood supply)

Emphysema

Type of chronic obstructive pulmonary disease (COPD). COPDs - group of chronic, inflammatory, conditions that affect airflow/respiration. Inflammatory response, typically caused by smoking, degrades alveolar walls and capillaries

Alveolar dead space will be increased. Lose a lot of gas exchange capability and reduces surface area

Neural control of ventilation

Respiratory groups (in medulla oblongata and pons) control respiratory rate/depth based on input from sensors in the body… but other brain areas can influence the respiratory groups ((because of emotional state, temperature, voluntary control (desire to take a deeper breath), etc.))

Respiratory groups

• Dorsal respiratory group (DRG) - medulla

• Ventral respiratory group (VRG) - medulla

• Pontine respiratory group (PRG) - pons

Dorsal respiratory group (DRG)

Medulla oblongata. Maintains constant breathing rhythm; pulses of stimulation go to the diaphragm and intercostals (causes them to contract)

Ventral respiratory group (VRG)

Medulla oblongata. During active (forced) breathing, stimulates contraction of accessory muscles

Pontine respiratory group (PRG)

Pons. Modifies medulla oblongata DRG to fine-tune breathing depth and rate

Factors that stimulate ventilation

CO2 (and H+) is one of the main determinates of ventilation (increased CO2 = increased ventilation)

• Monitored by: Sense changes in chemical output

  • Central chemoreceptors (brain)

  • Peripheral chemoreceptors (aorta/carotid bodies)

• O2 level in plasma is also monitored

  • Most blood O2 is stored in hemoglobin, however, so plasma O2 levels are more stable over time

• Other info, such as actions in muscles/joints, and stretch and irritant receptors in lungs also impact respiratory system

Sleep apnea

Cessation of breathing during sleep

• Obstructive: caused by blockage of the airway

• Central: Respiratory centers don’t properly respond to rising CO2 levels

Treatment: often consists of a machine that applies continuous positive airway pressure (CPAP machine) to help keep airways open and increase ventilation

Diffusion

Gases move into/out of and through the body via passive diffusion: movement from HIGH to LOW concentration. No energy expended. Can be very slow

Passive diffusion

Gases are exchanged between surrounding air and internal body fluids by passive diffusion. Governs the movement of gases within the body (e.g., between body fluids/extracellular matrices and cellular cytoplasm)

Partial pressure

B/C gasses are highly compressible, concentration is dependent on pressure

• Instead of “concentrations,” we use partial pressures

• Contribution of each gas in a mixture to the total pressure of the gases

• To find partial pressure of a gas, multiply total pressure of the mixture by the molar fraction of that gas

Ex: dry air is 20.9% O2, what is partial pressure O2 at sea level (760mmHg)

PO2 = 760 mmHg x 0.209 = 159mmHg

As altitude increases, atmospheric pressure decreases and PO2 is reduced = less O2 per volume of air (why it’s harder to breath at high altitudes!)

Atmospheric pressure (sea level): Nitrogen + O2 + CO2 + other = 760 mmHg

What happens to partial pressure of a gas as atmospheric decreases? Decrease

Diffusion rate (Fick’s law of diffusion)

For gas exchange across cell membranes can be described by Fick’s law of diffusion:

Diffusion rate = DA P1-P2/L

D = Diffusion coefficient (molecule, medium, and temp specific)

A = area over which diffusion occurs: greater area = quicker diffusion

P1 - P2 = partial pressure gradient: greater difference on either side of the membrane = quicker diffusion rate

L = diffusion distance (length): smaller diffusion distance = quicker diffusion rate

Which variable is effected?

Emphysema: walls of the alveoli break down, and small alveoli merge to become a large alveolus = A (surface area)

Pneumonia: Fluid/mucus builds up in the alveoli = L (diffusion distance/length)

Diffusion rate (diffusion coefficient)

Humans maximize D by using air as a respiratory medium instead of water. Air holds more O2 (amount of O2 in air and water differ substantially b/c O2 is not very soluble in water)

Our lungs are designed to ensure a fast rate of gas diffusion (between air and blood)

Diffusion rate (partial pressure gradient)

Lungs increase gas exchange rates by: Ventilation and perfusion.

For optimal diffusion, ventilation and perfusion volumes should be balanced

*certain conditions can cause imbalances, e.g., when perfusion in an area of the lungs is inadequate such as w/ emphysema

Ventilation

Maximizes P1-P2. Fresh air is brough into the alveoli

Perfusion

Maximizes P1-P2. Fresh blood is brought into the alveoli

How is homeostasis maintained

• Unique to lungs, arteries constrict when local O2 levels are low (shunts blood to better ventilated areas of the lung)

• Bronchioles are sensitive to CO2. When CO2 increases, they dilate to better ventilate those areas of the lung w/ good perfusion (blood flow)

Lungs also increase gas exchange rates by:

• Decreasing diffusion distance - gases only need to pass through 2 cell layers to enter the blood stream

• Increasing surface area - numerous alveoli (around 300 million per side) w/ large surface areas

Problems with tidal ventilation

Limits effectiveness of gas exchange. Not all features of the lung improve diffusion rate

Tidal ventilation

Air is brought into the lungs and then out. no continuous, unidirectional flow of ‘new,’ highly oxygenated air throughout the breathing cycle.

*Fish don’t have tidal ventilation; there is unidirectional flow of water over their gas exchange organ (gills)

Results in a lower partial pressure of O2 in the lungs compared to outside air

Residual volume

O2 depleted air (‘stale air’) mixes with fresh inspired air

• PO2 of air in alveoli = about 104 mmHg

• PO2 of atmospheric air = 159 mmHg

Hemoglobin

Acts as an O2 carrier protein in our RBCs that enables our blood to contain much more more O2 than would be possible otherwise. Also a reserve of oxygen (only 25% of O2 in arterial blood is released to tissues during “rest” conditions: blood leaving lungs is 100% oxygenated, blood returning to the heart from systemic circulation is 75% oxygenated, so 75% of oxygen is held in reserve by hemoglobin - to be used when metabolic activity increases in tissues, e.g., muscles in legs during running, etc.)

*O2 has low solubility in water → very little O2 can be delivered to tissues by simply being dissolved in blood plasma

*About 98% of the O2 in our blood is reversibly bound to hemoglobin, about 2% is dissolved in the plasma

• Binds O2 when plasma PO2 is HIGH: Hb + O2 → HbO2

• Releases O2 when plasma PO2 is low: HbO2 → Hb + O2

*Dissolved O2 in the plasma is what contributes to partial pressure gradients and what is sensed by chemoreceptors, etc.

Hemoglobin structure

• Contains 4 heme groups (subunits), each of which, can bind a single O2 molecule (each one can bind up to 4 O2 molecules)

• Around 250-300 million hemoglobin molecules in each red blood cell

• Allosteric protein: binding of an O2 molecule results in protein confirmation changes that increases subsequent bind affinity for O2

  • Sigmoidal relationship between hemoglobin saturation and partial pressure of oxygen

Sigmoidal relationship is caused by:

1. Positive cooperativity

2. Probability phenomenon

Positive cooperativity

Binding affinity of O2 increases as more subunits are occupied

Probability phenomenon

As more subunits are occupied, it becomes less likely that O2 will find an empty binding site

• At low PO2, only one O2 is bound to Hb

• When one O2 is bound to Hb, its affinity for O2 is greater

• when 3 O2 are bound, it takes a greater increase in PO2 to reach 100% binding

A right shift of hemoglobin’s O2 affinity

Results in MORE unloading of oxygen to tissues (doesn’t want to stick as well anymore)

Send more oxygen to the tissues

Causes:

• Bohr effect

• Increased 2,3-Bisphosphoglycerate (BPG) production in RBCs

• Higher temp

Bohr effect

Decreased pH (e.g., active tissues produce acidic metabolic byproducts)

Increased 2,3-Bisphosphoglycerate (BPG) production in RBCs

Occurs when tissues need more oxygen delivery (e.g., when starting an exercise regiment, pregnancy, breathing at higher altitudes, anemia, etc.)

Higher temp (in relation to a right hemoglobin shift)

Active tissues produce more heat than usual resulting in higher metabolic rates

Myoglobin

In muscles, higher affinity for O2 than hemoglobin

• Single polypeptide molecule that can bind one molecule of O2

• This O2 is used when contracting muscles squeeze and blood flow is interrupted

• Myoglobin contains O2 reserve for metabolic demands

Fetal hemoglobin

Exhibits a left shift compared to adult hemoglobin

When CO2 is produced by tissues:

• 10% of blood CO2 is dissolved in the plasma

• Other CO2 diffuses into RBCs and is either:

  • Reversibly bound to a protein in hemoglobin (about 20% of blood CO2)

  • Converted to a bicarbonate that diffuses back into the plasma (about 70% of blood CO2)

CO2 + H2O ←→ H2CO3 ←→ H+ + HCO3-

*Conversion to bicarbonate keeps PCO2 in the blood plasma low, facilitating diffusion away from the tissues

How CO2 in blood is related to acidity (H+)

• Less CO2: drives reaction toward production of CO2 and water

• More CO2: Drives reaction toward production of H+ and bicarbonate

CO2 at the tissues

PCO2 is high and diffusion of CO2 into the blood favors the formation of HCO3-

• Reaction can occur without this enzyme, but proceeds more slowly

CO2 at the lungs

PCO2 is low in the alveoli and diffusion of CO2 out of the blood reverses everything (CO2 movement in the image is driven by partial pressure gradients → movement toward lower PCO2 area)