4 - HLTH3303_F2023 Lecture 4 - EMT and Respiratory Overview

The partial pressure gradient for CO2 is less steep, with venous blood P CO2 at 45 mm Hg and alveolar P CO2 at 40 mm Hg.

Cilia create a traveling wave through the coordinated activity of many cilia acting together.

EMT begins with the basement membrane.

9 months of smoke exposure destroys cilia and damages the epithelium.

Transitional EMT would show colocalization of stains.

The pleurae is a thin, double-layered serosal membrane that divides the thoracic cavity into two pleural compartments and the mediastinum.

0.75 seconds

O2 autoregulates arteriolar diameter, causing constriction when ventilation is less than perfusion and dilation when ventilation is greater than perfusion.

When V/Q is not matched, it can lead to inefficient gas exchange, even if total ventilation and blood flow volumes are normal. V and Q must match in all areas of the lung for optimal function.

Systemic arterioles dilate when oxygen is low and constrict when oxygen is high.

Type 1 EMT is associated with embryogenesis.

Mucus moves at approximately 0.5 - 1 mm/min.

1. Pulmonary ventilation (breathing): movement of air into and out of lungs. 2. External respiration: exchange of O2 and CO2 between lungs and blood. 3. Transport of O2 and CO2 in blood. 4. Internal respiration: exchange of O2 and CO2 between systemic blood vessels and tissues.

Green represents E. Cadherin, Red represents vimentin, and Blue represents DNA (nuclei).

Overactive myofibroblasts can prevent normal organ function.

Respiratory bronchioles lead into alveolar ducts.

A sheet of cells.

Usually one cell layer thick.

Type 1 EMT is related to embryogenesis, Type 2 EMT involves tissue regeneration and organ fibrosis, and Type 3 EMT is associated with cancer progression and metastasis.

104 mm Hg

Stomach and small intestine.

100 mm Hg

GGO indicates a loss of signal, characterized by increased attenuation.

Adherens, tight, desmosomes, and gap junctions.

Smoking inhibits ciliary action.

Cilia maintain airway homeostasis by facilitating the mucociliary escalator, which moves mucus and trapped particulates in the rostral direction.

ILK, GSK-3β, Rho.

About 2 - 3 minutes.

Normal pulmonary function is crucial for identifying and understanding respiratory pathologies, as deviations from normal function can indicate underlying issues such as obstructive or restrictive lung diseases.

The two zones are the respiratory zone and the conducting zone.

The respiratory zone is the site of gas exchange and consists of microscopic structures such as respiratory bronchioles, alveolar ducts, and alveoli.

The conducting zone serves as conduits that transport gas to and from gas exchange sites, cleansing, warming, and humidifying the air.

CO2 still diffuses in equal amounts with oxygen, even though the gradient is not as steep.

N-cadherin, vimentin, fibronectin, Snail-1, Snail-2, goosecoid, FOXC2, Sox10, MMP-2, MMP-3, MMP-9, Integrin αvβ6.

Pulmonary blood flow increases during exercise compared to rest, allowing for greater oxygen uptake.

During exercise, increased pulmonary blood flow enhances gas exchange, allowing for more oxygen to enter the bloodstream.

Alveolar sacs are clusters of alveoli, with about 300 million alveoli in most lungs, serving as sites of gas exchange.

The respiratory system is organized into upper and lower respiratory tracts, including structures such as the nasal cavity, pharynx, larynx, trachea, bronchi, and lungs.

The trachea divides into left and right main bronchi (primary bronchi).

E-cadherin, desmoplakin, cytokeratin, occludin.

β-catenin, Smad-2/3, NFκβ, Snail-1, Snail-2, Twist.

Normal pulmonary function includes adequate ventilation, gas exchange, and lung compliance, which are essential for maintaining oxygen levels and removing carbon dioxide.

Chest x-ray.

Cells lose their polarity and undergo changes in gene expression.

The key epithelium in the respiratory tract includes pseudostratified ciliated columnar epithelium, which helps in trapping and clearing particles from the airways.

It allows cells to adhere and interact with different environmental components.

Cartilage rings become irregular plates, and in bronchioles, elastic fibers replace cartilage altogether.

The important steps include the transition of epithelial cells to a mesenchymal phenotype, which is crucial for tissue development and organ formation.

The normal significance of EMT includes its role in tissue repair, organ development, and maintaining homeostasis.

Cilia and goblet cells become more sparse.

The amount of smooth muscle increases, allowing bronchioles to provide substantial resistance to air passage.

They must be matched for optimal, efficient gas exchange.

Trachea

The superior lobe of the left lung is associated with the lobar bronchus.

CO2 is 20 times more soluble in plasma and alveolar fluid than oxygen.

About 3 days.

About 1 - 2 months.

The lower respiratory system consists of the larynx, trachea, bronchi, and lungs.

The parietal pleura attaches to the inner chest wall and covers the thoracic wall, the superior face of the diaphragm, around the heart, and between the lungs.

It indicates the RBC transit time in pulmonary capillaries.

Pulmonary arteries deliver systemic venous blood from the heart to the lungs for oxygenation, branching profusely to feed into pulmonary capillary networks.

Intrapleural pressure is subatmospheric as the chest wall tries to expand and the lungs try to recoil.

The costophrenic angles are the areas where the lowest margin of the diaphragm meets the chest wall.

The mucosa of the carina is highly sensitive.

The association is facilitated by cell adhesion molecules.

There are three lobar bronchi on the right and two on the left.

Perfusion is the blood flow reaching the alveoli.

All lung tissue except alveoli.

From the larynx into the mediastinum.

EMT is particularly prominent in women, especially in the mammary gland.

8 – 10 mm

The respiratory membrane is very thin, measuring 0.5 to 1 μm thick.

Increased migration, increased invasion, increased spreading, elongated shape, resistance to cell death (anoikis).

Elevated left hemidiaphragm due to diaphragmatic rupture.

EMT in adults is typically a pathological association related to wound healing, inflammation, fibrosis, and tumor progression.

The sequence is terminal bronchioles → respiratory bronchioles → alveolar ducts → alveolar sacs.

Consolidation describes opaqueness in lung scans.

Cuboidal epithelium replaces pseudostratified columnar epithelium.

They keep alveolar surfaces sterile by removing debris, with 2 million dead macrophages carried by cilia to the throat and swallowed each hour.

Smooth muscle and elastic fibers.

EMT is relevant in tissue fibrosis and scarring as it contributes to the excessive deposition of extracellular matrix components.

Bronchial veins anastomose with pulmonary veins.

Two main bronchi.

1. Mucosa, 2. Submucosa, 3. Adventitia.

Mesenchymal cells have more of a support role in tissue.

The total surface area of the alveoli is 40 times the surface area of the skin.

Nose, nasal cavity, paranasal sinuses, pharynx, and larynx.

Cilia trap and limit the spread of pathogens through the movement of mucus.

Myofibroblasts are activated fibroblasts that participate in wound healing.

The visceral pleura attaches to the lung's surface and is the membrane on the external lung surface.

Pulmonary veins carry oxygenated blood from respiratory zones back to the heart.

The respiratory membrane is very thin, approximately 0.5 μm, allowing gas exchange by simple diffusion.

The alveolar walls consist of a single layer of squamous epithelium (type I alveolar cells) and scattered cuboidal type II alveolar cells that secrete surfactant and antimicrobial proteins.

Type II alveolar cells secrete surfactant and antimicrobial proteins.

Capillaries surround the alveoli, facilitating gas exchange.

P O2 controls perfusion by changing arteriolar diameter.

Goblet cells are absent (0)

0

<0.5 mm

Trachea, bronchi and branches, lungs, and alveoli.

Fibroblasts accumulate at sites of tissue/organ injury, secrete ECM components, and are involved in chronic inflammation and progressive scarring.

The respiratory zone begins where terminal bronchioles feed into respiratory bronchioles.

Ground glass opacification (GGO) is evident in lung scans of COVID-19 patients.

The carina is the last tracheal cartilage that expands at the point where the trachea branches into the left and right bronchi.

The actin structure changes, allowing cells to become motile and invasive, forming lamellipodia and filopodia structures.

The ISB is the point at which air is 100% saturated and at 37 °C.

Pleural effusion is the presence of fluid in the pleural space.

~0.25 seconds

Thoracentesis is a surgical procedure for the removal of excess pleural fluid via tube insertion into the pleural cavity.

The steep partial pressure gradient for O2 between blood and lungs

The windpipe.

EMT is a normal process during tissue and organ development.

Mesenchymal cells move individually and create a trail as they travel.

Connective tissue with seromucous glands.

Changes in P O2 in alveoli cause changes in the diameters of arterioles. Where alveolar O2 is high, arterioles dilate; where alveolar O2 is low, arterioles constrict. This directs blood to alveoli with high oxygen for better oxygen uptake.

It causes a mismatch of ventilation and perfusion, leading to decreased P CO2 and P O2, resulting in pulmonary arterioles constricting.

The right bronchus deviates 20 to 30 degrees from midline, is smaller in diameter, and is twice as long compared to the left bronchus, which deviates 45 to 55 degrees from midline.

The right main bronchus is wider, shorter, and more vertical than the left.

Type 3 EMT focuses on cancer progression and metastasis.

Fluid settles into the costophrenic angles, blunting their outline on a chest x-ray.

~0.75 seconds

Resident fibroblasts become activated and transform into myofibroblasts.

Mesenchymal cells have stem cell properties and can give rise to other cell types.

Mesenchyme is mostly found in the embryo and is not prominent in adults.

The left main (primary) bronchus leads to the lobar (secondary) bronchus.

C-shaped cartilage rings.

Epithelial cell-cell contacts disassemble, losing tight junctions, adherens junctions, desmosomes, and gap junctions.

This mismatch causes local decreases in P CO2 and increases in P O2, leading to dilation of pulmonary arterioles serving those alveoli.

Pleural fluid fills the pleural cavity, providing lubrication and surface tension that assists in the expansion and recoil of the lungs, lubricates membranes during breathing, and provides molecular cohesive forces that keep membranes from separating.

The vulnerable cellular anatomy includes ciliated epithelial cells, goblet cells, and basal cells, which can be affected by various respiratory diseases.

The respiratory membrane is a blood-air barrier that consists of alveolar and capillary walls along with their fused basement membranes.

The traditional view was that all cells in the body are derived from a single cell zygote.

Oxygenated blood.

They arise from the aorta.

Mesenchyme has embryonic origins.

Mesenchyme consists of loosely organized stellate-shaped cells that form with proteins and fluid to create the extracellular matrix (ECM).

Terminal bronchioles are the smallest branches, measuring less than 0.5 mm in diameter.

12 – 16 mm

The trachea serves as the main airway leading to the bronchi.

The basement membrane is composed of proteins that make an extracellular matrix.

Each main bronchus enters the hilum of one lung.

Each main bronchus branches into lobar bronchi (secondary bronchi).

Ventilation refers to the amount of gas reaching the alveoli.

High pressure, low volume.

There is degradation of the basement membrane and loss of polarity.

Mesenchymal cells have weak connective tissue, weak adhesions, and are less rigid and regimented in structure.

The exception is mesenchymal stem cells, which are present in adults.

Epithelial cells are more plastic than others and can convert between epithelial and mesenchymal cell types.

Cells express matrix metalloproteinases (MMPs) that degrade the ECM.

Fine elastic fibers and pulmonary capillaries.

104 mm Hg

Cells are specified and further specialized during development and the transition to postnatal life.

The dogma was that terminally differentiated cells no longer transform or undergo phenotypic changes.

It was discovered that some cells were more plastic in nature, challenging the idea that terminally differentiated cells do not change.

20 – 25 mm

P CO2 controls ventilation by changing bronchiolar diameter.

About 4 inches long and ¾ inch in diameter.

Cartilage is present in plates (++)

40 mm Hg

It is a low-pressure, high-volume system.

Lung capillary endothelium contains many enzymes that act on different substances in blood, such as angiotensin-converting enzyme which activates blood pressure hormone.

Fibrosis in these organs often gives rise to Epithelial-Mesenchymal Transition (EMT).

Co-expression of FSP1, α SMA, and other epithelial specific markers are identified.

The structures involved in gas exchange include the alveoli and capillaries.

Bronchioles are less than 1 mm in diameter.

Most venous blood.

Cell division generates more cells and expands tissues.

Epithelial cells have a tissue-specific function.

Type 2 EMT involves tissue regeneration and organ fibrosis.

The basement membrane attaches to epithelial cells at the basal side.

They are closely coupled to accomplish the exchange of oxygen and carbon dioxide.

It also functions in olfaction (sense of smell) and speech.

Each lobar bronchus supplies one lobe of the lung.

Mesenchyme forms undifferentiated cells during embryogenesis.

Mesenchyme produces connective tissues such as bones, cartilage, and lymphatics.

Both are controlled by local autoregulatory mechanisms.

The right lung has the superior lobe, middle lobe, and inferior lobe.

Larynx (35 – 45 mm)

To supply the body with oxygen for cellular respiration and dispose of carbon dioxide, a waste product of cellular respiration.

They connect adjacent alveoli to equalize air pressure throughout the lung and provide alternate routes in case of blockages.

The pathological significance of EMT includes its involvement in cancer metastasis, fibrosis, and other diseases.

Important factors include growth factors, cytokines, and transcription factors that regulate the transition process.

Segmental bronchi branch into smaller bronchioles.

Cells either undergo apoptosis or Epithelial-Mesenchymal Transition (EMT).

Mesenchymal cells have a nonuniform appearance and no topical specialization (without apical/basal polarity).

Developing cells specialize and differentiate into specific cell types.

Adventitia.

Ciliated pseudostratified epithelium with goblet cells.

Smooth muscle is present (++)