Respiratory System Dynamics

Respiratory System Functions

• Oxygen is delivered to the cardiovascular system for distribution to tissues
• Carbon dioxide is removed
• Gas exchange takes place in the alveoli
• The air-blood barrier is a thin, permeable membrane
• Serious effects occur if gas transfer is dysfunctional due to disease or compromised blood supply
• Plays a role in acid-base balance
• Acts as a blood reservoir
• Filters emboli (blood clot, air bubble, fat)
• Destroys emboli
• Metabolizes bioactive substances like serotonin
• Activates other substances

Oxygen Needs

• Metabolic Equivalent (MET): Amount of oxygen consumed at rest
• 1 MET equals 3.5 ml O2 per kg of body weight per minute.
• The average female in the United States weighs 77.5 kg
• The average female requires 271.25 ml of O2 per minute, 16,275 ml per hour, 390,600 ml per day, or 390 liters per day.

Upper Airway Anatomy

• Nasal Cavity (large surface area)
  • Lined with hair and mucus
    • Functions:
      • Air passage
      • Air filtration via hair and mucus secreted from Goblet cells
      • Air humidification and warming via mucosal secretions
• Pharynx (throat)
  • Interconnection between the nasal cavity and the larynx
  • Common pathway for both the respiratory and digestive systems

Goblet Cells

• Specialized epithelial cells form mucus barriers in the airways and intestines
• Secrete mucus and defensive peptides for infection protection
• Mucus composition: ~95% water, glycoproteins called mucins plus electrolytes, lipids, proteins, DNA, and cellular debris

Lower Respiratory Tract Anatomy

• Larynx (lined with cartilage)
  • Keeps airway open with ring structure
  • Epiglottis keeps food out
  • Produces sound via the glottis, which consists of the vocal cords and their opening, affecting voice modulation via expansion or contraction of cartilaginous fibers (vocal folds or cords)
• Trachea connects the the larynx to the bronchi
  • Has a U-shaped cartilaginous structure for support
  • The posterior is smooth muscle
  • Is lined with ciliated mucosal epithelial cells to move particulates to the larynx

Thorax

• Part of the body between the neck and the abdomen
• Includes the cavity enclosed by the ribs, sternum, and dorsal vertebrae
• Contains key organs for circulation and respiration
• Most people are born with 12 ribs on each side (24 total)

Lungs Anatomy

Major Structures:

• Larynx, Trachea, Carina, Primary Bronchus, Secondary Bronchus, Tertiary Bronchus, and Bronchiole
• Air passageways decrease in size but increase #
• The right lung has 3 lobes and is slightly larger than the left which has 2.

Pleural Space and Hilum

• Visceral pleura covers the outer lung surface and extends into interlobar fissures, continuous with parietal pleura at the hilum
• Parietal pleura attaches to the inner thoracic cavity surface
• Pleural space or cavity lies between the membranes, filled with fluid.
  • Pleural fluid decreases friction during breathing
  • Creates hydrostatic forces necessary for thoracic cavity expansion.
• Pleural effusion is excessive fluid in pleural space, causing dyspnea (difficult breathing), dry cough and chest pain.

Airway Branching and Club Cells

• There are 23 total divisions of the airways
• Conducting zone transmits air to the respiratory zone
  • Ciliated, secretory, and basal cells
  • Bronchioles and terminal bronchioles lack secretory cells and cartilage, having more smooth muscle and club cells
• Club cells (previously Clara cells) are in the ciliated simple epithelium and protect bronchiolar epithelium
• Pulmonary surfactant is a mixture of specific lipids, proteins, and carbohydrates
  • Produced in the lungs by type II alveolar epithelial cells
  • It reduces surface tension at the air-liquid interface of the alveoli
• Respiratory zone involved in:
  • Gas exchange
  • Adrenergic receptors
  • Contains 300 million alveoli and 70m^2 area
• Secondary pulmonary lobule: the smallest unit of lung structure, contains 30 acini, varying in size and shape.

Conductive Zone and Cilia

• Conductive zone lined with ciliated epithelium that heats/moistens air and removes foreign particles
• Cilia: tubulin forms a core structure to which other proteins contribute structures
• Mucociliary clearance (MCC) or escalator, describes the self-clearing airways mechanism
• Mucus layer moves at 4-20mm/min rate
• Single cigarette diminishes cilia action by 50%

Cellular Transitions

• Submucosal glands secrete mucus and antimicrobial proteins into the airway
• Surfactant reduces surface tension to function normally

Alveoli Structure

• The secondary pulmonary lobule a lung unit marginated by connective tissue, irregular/polyhedral shape, 1 to 2.5 cm in diameter, holds ~30 acini
• Is the site of gas exchange

Alveolar Cell Types

• Type I epithelial cells: squamous, thin and flat, involved in gas exchange.
• Type II pneumocytes: secrete lamellar bodies (LB), which convert to tubular myelin (TM)
  • The source of surfactant (SF)
• Macrophages: ingest particles, toxins, and pathogens with a 1-5 µm diameter, trapped in the mucus of bronchioles or liquid around alveoli

Cells Infected by SARS-CoV-2

• Virus attaches to angiotensin converting enzyme 2 (ACE2) protein, which is helped by transmembrane protease, serine 2 (TMPRSS2)
• The protein helps the virus enter host cells by cleaving & activating viral glycoproteins
• Viruses using this entry system: Influenza, human coronaviruses HCOV-229E, MERS-CoV, SARS-CoV, and SARS-CoV-2 (COVID-19)

Events During SARS-CoV-2 Infection

• As of January 2025, COVID-19 dominant variant is XEC (47% of cases)
• LP.8.1 makes up 15% of cases.
• Pyroptosis, a cell death form, is triggered by proinflammatory signals, associated with inflammation

Abnormal Mucus: Cystic Fibrosis

• Autosomal recessive disease in the CFTR gene
• The Chlorine channel on the apical membrane, which is used by a variety of secretive and absorptive epithelia, is mutated
• Results in suppressed chlorine secretion across the wall of the airways
  • Numerous mutations with varying severity
  • Reduced Chlorine secretion leads to increased Sodium reabsorption
  • Sticky mucus inhibits ciliated epithelium processes
  • Airways mucous plugging
  • Increases the chance of of repeated pulmonary infections (Pseudomonas aeruginosa)
  • Impacts surfactant dysfunction, as it is requires for alveolar integrity

Organs Affected by CF

• Lungs, sinuses, pancreas, liver, intestine, sweat gland, male reproductive organs
• https://www.cff.org/intro-cf/about-cystic-fibrosis
• Chronic Sinusitis: Long term inflammation
• Bronchiectasis: Abnormal widening of bronchi and branches
• Steatorrhea: Abnormal fat quantities in feces
• Pancreatic insufficiency is most common for cystic fibrosis patients (85%)
• Arthropathy is a disease of the joint

Mechanics of Breathing

Thorax volume is a major factor

• Inhalation (expanding volume):
  • Rib cage lifts
  • Diaphragm lowers
• Exhalation (decreasing volume):
  • Rib cage gets smaller
  • Diaphragm moves up

Muscles Used During Respiration

• Inspiration Muscles:
  • Sternocleidomastoid, Scalenes, External Intercostals, Interchondral part of Internal Intercostals, Diaphragm, Pectoralis Minor
• Expiration Muscles:
  • Internal Intercostals, Abdominals, Quadratus Lumborum (QL)
• Quiet Breathing: Results from the passive, elastic recoil of the lungs, rib cage, and diaphragm
• Active Breathing: Internal intercostals pull ribs down, abdominals depress, diaphragm elevates
• The Quadratus Lumborum stabilizes diaphragm at attachment points

Movement Of Air

• Inspiration muscles increase the thoracic cavity size (diaphragm, external intercostal muscles, pectoralis minor)
• Expiration is passive during quiet breathing, intercostal/abdominal muscle contraction increases it.
• The elastic recoil of the lungs is the major force for expiration
• Air moves from regions of high to low pressure
• Velocity of air movement measured as: ΔP/R
• Boyles Law: PV = PV

Pressures in the Lung

• Transpulmonary pressure holds the lungs open- transmural or transpulmonary: 760 mm Hg -756 mm Hg (4 mm Hg)
• Intrapleural pressure: 756 mm Hg (-4 mm Hg) or -5 mm Hg
• Intra-alveolar pressure: 760 mm Hg (0 mm Hg); aka intrapulmonary pressure

Pressure During Breathing

• Transmural pressure = pressure inside relative to outside of a compartment
• Static conditions, transmural pressure is equal to elastic recoil pressure _ Inspiration Events:
  • Diaphragm and IC muscles contract and pressure
  • Chest cavity volume
  • Intrapleural pressure
  • Alveolar pressure
  • Air flows in

Lung Pressure and Timeframe

• During Inspiration
  • Barometric air pressure is greater than alveolar pressure, and air moves into the lungs as thoracic volume increases and alveolar pressure decreases.
  • Normal Breaths for adults is 8-15 per minute
• During Expiration
  • Alveolar pressure is greater than barometric air pressure, air goes out as thoracic volume decreases/recoils releasing air

Collapsed Lung Information

• (pneumothorax): Air escapes from the lung and fills the pleural cavity, putting pressure on the lung which stops it from expanding
• Caused by injury, rib fractures, and medical procedures, or air blisters break open. Air pressure changes when scuba diving or going to high altitudes
• Risk factors: tall, thin, smokers, lung diseases (Asthma, COPD, cystic fibrosis, TB, Whooping Cough)
• Also can have no cause.
• Diagnosed by Chest radiography, ultrasonography, or CT

Resistance and Air Flow

• Airway resistance opposes airflow
• According to Poiseuille's Law: F = ΔP / R
• Flow rate Q can be defined by dividing the pressure difference by the resistance. Q = ΔP /R
• Resistance (R) dependent on tube length, η gas viscosity, r =radius of tube, defined with: R = 8ηl /πr4
• Thus, mild bronchial swelling causes emergency for infants

Homeostatic Mechanisms of Gas Exchange

Main pulmonary-cardiovascular goal is to efficiently oxygenate and remove CO2 by maintaining:

• Blood CO2 Levels, Blood 02 Levels, Blood pH levels (7.35-7.45) Accomplished by:
• Changes in blood flow and oxygen delivery, changes in respiration under brain control, blood pressure and cardiac output fluctuations

Local Regulatory Mechanisms

• At tissues, oxygen delivery and lung pickup is regulated at the local tissue level
• During cell activity: interstitial PO2 declines, PCO2 rises
• Arterioles/capillaries smooth muscles in the area relax
• At the lungs local factors: Lung Perfusion:
• Alveolar capillaries constrict with low local concentration, blood redirects to areas with high Alveolar Ventilation
• If PC02 goes up, bronchioles expand, PC02 declines, airways constrict directing air high 02

Regulation of Respiration

Chemical Control-chemoreceptors stimulate respiratory center

• CO2 sensed by:
  • Medulla from cerebrospinal fluid (central)
  • O2, CO2 & H+ carotid and aortic bodies (peripheral) Nonchemical control: Lungs, thalamus
• Vagal afferents from receptors in the airways and lungs
• Pons, hypothalamus, and limbic system. -Proprioceptors(Position), Baroreceptors (pressure) from sensors of arterial, atrial, ventricular, pulmonary

Regulation Of Respiration With Sensors

• Goal is to maintain normal O2 and CO2 levels, changes are sensed by chemoreceptors
• The ability to detect changes in H+ concentration, CO2, & O2
• Stretch receptors inhibit respiration along the Vagus nerve through the "respiratory center" in medulla/pons
• dominant PCO2 & pH control ventilation
• Effectors change rate/depth of breathing to bring O2/CO2 to normal

The Respiratory Centers of the Brain

• In medulla oblongata set pace via dorsal respiratory group (DRG), and ventral respiratory group (VRG), whether breathing is quiet or and VRG helps during forced breathing
• Apneustic and pneumotaxic centers of the pons regulate depth and rate in response to sensory Stimuli

Neural Control of Breathing

• Voluntary cortex impulses to respiratory neurons, driven by pace making cells in medulla
• Pre-Botzinger complex generates spontaneous rhythmic impulses and increases with hypoxia
• Opioids inhibit discharge slowing Activate Motor neuron
• Phrenic nerves to diagram and external coastal muscles Reciprocal Innervation: Expiratory, inspiration muscles inhibited
• Brainstem nuclei modulate breathing
• Hypoxia is when oxygen is insufficient to adequate homeostasis because of low blood supply or content

Opioid Induced Respiratory Depression (OIRD)

• Opioid deaths 112,000 in 2023
• Opioids lead to shallow breath as μ receptors activate in key areas
• Narcan reverses this by impacting opioid receptors and blocking acting as an antagonist

Regulation of Respiration Summary

• Respiratory cycle in response to:
  • Plasma and chemical changes. PO2, arterial level
• Sensory input from spinal cords- and receptors
• Respiratory response will stimulate or contract respiratory muscles

Peripheral/Central Chemoreceptors

Central:

• chemosensitive medulla detects PH changes, impulses set to respiratory center only respond tp PCO2 Peripheral:
• senses arterial blood only primarily focus on PO2 second on high concentrations on PCO2 and PH
• Carotid stimulate through 9, Aortic arch 10 cranial Nerves

Gas Transport

• Chemoreceptors detect pH, O2 and CO2 levels: Sends spinal cord signals to change breathing ↓ pH and ↑ CO2 → ↑ Heart Rate and Stroke Volume ↑ pH and ↓ CO2 →↓Heart Rate and Stroke Volume
• infant death due to medullar respiratory center abnormality

Chemoreceptors: Structure and Function

• Carotid and Aortic Bodies have two cell types type 1 and 2,
• have fine capillaries
• Type 1 has chemoreceptors stimulated by dopamine.
• Nerve stimulates
• O2 is sensed through anemia, which will signal with nicotine/cyanide exposure
• Type 2 cell will support structure and function of type 1

Respiratory Centers and Reflex Controls

• Reg resp under cerebral and sensory control to respond to change, ⬆️ ventilation
• Behavior, and emotion impacts breathing
• Hormones that impact are, adrenaline, vessels, hormones
• O2/CO2, are regulated

Receptor Effects of Respiration

• Breathing driven by other parts of brain, peripheral and central lungs with mechanical and irritative influences from joint

Ventilation During Exercise

• Breathing caused by afferent drive and voluntary motor commands
• pulmonary blood increases, blood levels drop
• Exercise, increases stimulation causes discomfort
• Over time lactate builds up as tolerance is built.

Relation Of Blood in Lactic Acid

• Lactic acid increase and can push oxygen up to certain point

pH

• =-log H, and is important b pH regulates cellar function, enzymes/
• electrolyte distribution
• nerve and muscle cell activity, effects mediction
• Acid disorders cause growth to be altered, cause arrhythmias fatigue and bone weakening.

Blood pH Is Important

• Acid base impacts H concentration as level is important - PCO 7.4 changes causes acid, H units
• Body will use fluid buffer and chemorec for PCO2 to regulated

Fluid Buffers

• Convert acids and bases to dampen change
• Bicarbonate
• Phosphate
• Protein

Henderson-hasselbach Equation

• pH = pKa+log[Conjugate base]/[Acid]

Explore scenarios affecting respiration rate and the roles of brainstem regions like the pons and medulla oblongata. Understand the impact of the ventral respiratory group during exercise and the body's response to changes in blood oxygen levels.