Type I & II Alveolar Cells: Structure & Function

Type I and Type II Alveolar Cells

• Alveolar ducts are tiny tubes that bronchioles subdivide into
• Alveolar sacs are clusters of alveoli that alveolar ducts terminate
• Gas exchange occurs primarily in the alveoli, where oxygen enters the blood and carbon dioxide is removed
• Pores of Kohn are small channels that allow air to flow through the septa between alveoli
• Septa air movement from alveolus to alveolus improves collateral ventilation and even air distribution
• At birth, there are around 50 million alveoli
• Approximately 480 million alveoli are present in adulthood
• Alveolar septa lacks muscle layer
• Alveolar septa made of epithelial layer and thin, elastic basement membrane
• Type I alveolar cells provide structure
• Type II alveolar cells secrete surfactant (lipoprotein)
• Surfactant coats the inner alveolus surface and helps it expand when inhaled, lowering alveolar surface tension during exhalation to prevent lung collapse (atelectasis)
• Immune and inflammation-related cellular components (especially mononuclear phagocytes) are present in alveoli
• Alveolar macrophages are the most prevalent immune cells in the lung, providing innate immunity from bronchi to alveoli

Role of Surfactant

• Surfactant is a lipoprotein that coats the inner alveolus surface
• Surfactant lowers the alveolar surface tension during exhalation and facilitating alveolus exansion when inhaling
• Surfactant reduces lung collapse (atelectasis)
• Surfactant proteins help control lung inflammation by decreasing the release of proinflammatory mediators
• Surfactant proteins prevent oxidative damage and regulate fibroblast activity in airway remodeling
• Surfactant proteins are bacteriostatic and act as opsonins presenting pathogens to alveolar macrophages
• The normal pulmonary microbiota, surfactant, and alveolar macrophages work together to prevent lower lung infections

Mechanisms of Defense

• Upper respiratory tract mucosa maintains consistent temperature and humidity of air entering the lungs
• The Upper respiratory tract mucosa traps and eliminates foreign particles, bacteria, and noxious gases from inspired air
• Nasal hair and turbinates trap and eliminate foreign particles, bacteria, and noxious gases from inspired air
• Branching airways disrupt laminar flow and enhance particle and pathogen deposition on ciliated mucosa
• Mucous blankets protect the trachea and bronchi from injury, trap most foreign particles and bacteria that reach the lower airways
• Innate immune proteins include lysozyme, lactoferrin, defensins, collectins [surfactant protein A [SP-A] and surfactant protein D [SP-D]], and immunoglobulin A (IgA)
• Innate proteins recognize and promote killing of pathogens
• Cilia propel mucous blanket and entrapped particles toward the oropharynx, where they can be swallowed or expectorated
• Alveolar macrophages ingest and remove bacteria and other foreign material from alveoli by phagocytosis
• Surfactant enhances phagocytosis of pathogens and allergens in alveoli, down regulates inflammatory responses
• Irritant receptors in the nares Stimulation by chemical or mechanical irritants triggers sneeze reflex, which results in rapid removal of irritants from nasal passages
• Irritant receptors in trachea and large airways Stimulation by chemical or mechanical irritants triggers cough reflex, which results in removal of irritants from the trachea and large airways

Infant Surfactant

• Type II alveolar cells produce surfactant which is a lipid-protein mixture
• Surfactant is critical for maintaining alveolar expansion and allowing normal gas exchange
• Production begins around 20-24 weeks of pregnancy and is released into the fetal airways around 30 weeks
• Respiratory distress syndrome (RDS) is frequently caused by surfactant deficiency syndrome in premature newborns
• Hyaline membrane disease was the previous name
• RDS risk rises with increasing immaturity

Gas Exchange

• The conducting airways terminate in the respiratory (terminal) bronchioles, alveolar ducts, and alveoli.
• The thin-walled structures participate in gas exchange.
• Acinus refers to the clusters of alveoli.
• Respiratory bronchioles are bronchioles from the 16th through 23rd division that have increasing numbers of alveoli
• Respiratory bronchioles have very thin walls, consisting of an epithelial layer with NO cilia and goblet cells
• Respiratory bronchioles have very little smooth muscle fiber, very thin, elastic connective tissue layer
• Respiratory bronchioles terminate in alveolar ducts, which lead to alveolar sacs (composed of numerous alveoli)
• Alveolar ducts are the lung's primary gas exchange units where 02 enters the blood, and carbon dioxide (C02) is removed
• Pores of Kohn: allows air to pass from alveolus to alveolus, promoting collateral ventilation and even distribution of air among alveoli
• Alveolar ducts contain cellular components of inflammation and immunity
• Alveolar ducts contain alveolar macrophages, and alveolar septa consist of an epithelial layer and thin, elastic basement membrane but no muscle layer

Circulation

• Pulmonary and bronchial circulation provides a large surface area for gas exchange
• Pulmonary and bronchial circulation delivers nutrients to lung tissues, is a blood reservoir for the left ventricle and serves as a filtering system that removes clots, air, and other debris
• Pulmonary vasculature is composed of three compartments connected in a series of arteries, capillaries, and veins
• Pulmonary artery branches with each main bronchus, and with the bronchi at every division, dividing at the terminal bronchiole to form a network of pulmonary capillaries
• Capillary walls in pulmonary capillaries consist of an endothelial layer and a thin basement membrane, which often fuses with the basement membrane of the alveolar septum
• The shared alveolar and capillary walls compose the alveolocapillary membrane, a very thin membrane made up of the alveolar epithelium, alveolar basement membrane, an interstitial space, capillary basement membrane, and capillary endothelium
• Gas exchange occurs across the alveolocapillary membrane
• Extremely thin alveolar walls are easily damaged and can leak plasma and blood into the alveolar space
• Any disorder that thickens the membrane impairs gas exchange (e.g., fibrotic lung disease)

Alveolar Ventilation

• The observation of ventilator rate, pattern, or effort does not accurately determine alveolar ventilation
• An arterial blood gas analysis must be performed to measure partial pressure of carbon dioxide (PaCO2)

Aging Effects

• Understanding the need to provide care and differentiate between normal and disease due to normal physiologic (developmental and degenerative) changes to occur from birth to old age
• Changes are commonly gradual and without consequences in healthy people
• Normal alterations in the pulmonary system include loss of elastic recoil and stiffening of the chest wall
• Normal alterations in the pulmonary system include changes in gas exchange and increases in flow resistance
• These changes are influenced by genetics, sociocultural factors, nutritional status, exercise, decreased immune function, respiratory disease, body size index, and race Environmental toxins (respiratory tract infections, tobacco smoke, air pollutions, and occupational dusts) contribute to reduced lung function with aging
• These changes affect increased lung disease morbidity and mortality in older adults (including chronic obstructive lung disease, lung cancer, pulmonary fibrosis, and infection)
• Advanced aging increased immune dysregulation, asymptomatic low-grade inflammation, and increased risk of infection

Advanced Age

• Mechanical and structural changes occur due to advanced aging alveolar walls and capillaries are lost, resulting in changes similar to emphysema and changes the elastic properties of the lungs
• Advanced age increases alveolar size and reduces alveolar surface area available for gas diffusion
• Advanced age decreases airway support provided by normal lung tissues
• Advanced age decreases chest wall compliance, ribs become ossified (less flexible), and joints become stiffer
• Advanced age decreases chest wall ability to expand, and respiratory muscle strength and endurance (up to 20% by age 70)
• Mechanical/structural alterations of alveoli can reduce ventilatory capacity
• Advanced age decreases vital capacity and increases residual volume; total lung capacity remains unchanged
• Decreased ventilatory reserves lead to decreased ventilation-perfusion ratios
• Alterations in gas exchange (pH and PaC02 levels) do not change much maximum PaCO2 at sea level is estimated by multiplying person's age by 0.3 and subtracting the product from 100].
• Structural and mechanical alterations (loss of alveolar surface area, thickening of plural septa, loss of lung elasticity, and increase in ventilation-perfusion mismatch) cause Pa02 to decline
• Advanced aging causes decreased compensatory response to hypercapnia and hypoxemia, and enhanced perception of dyspnea
• The decrease in PaO2 and diminished ventilatory reserve with age → decrease in exercise tolerance
• Advanced age decreases respiratory muscle strength and endurance which leads to a greater risk for respiratory depression due to medications
• A very active, physically fit person, will have fewer changes in function at any age than one who has been sedentary

Oxygen and Carbon Dioxide Transport

• Approximately 1000mL (1L) of oxygen is transported to the cells of the body each minute
• Oxygen is carried in the blood by a small amount dissolves in plasma, and the remainder binds to hemoglobin molecules.
• Due to small amount dissolves in plasma. Without hemoglobin, oxygen would not reach the cells to properly maintain normal metabolic function
• The alveolocapillary membrane is the ideal medium for oxygen diffusion due to the large total surface area and thinness
• The partial pressure of oxygen molecules is much greater in alveolar gas than in capillary blood = rapid diffusion down the concentration gradient
• The amount of oxygen in the alveoli (𝑃𝑎𝑂2) depends on amount of oxygen in the inspired air and the amount that remains in the alveoli and tracheobronchial tree between breaths.
• The physiologic dead space, is the amount of oxygen that has not been consumed
• Blood remains in the pulmonary capillary for about 0.75 seconds; only 0.25 seconds is required for oxygen concentration to equalize across the alveolocapillary membrane
• Oxygen has ample time to diffuse into the blood even during increased cardiac output – which speeds blood flow and shortens the time the blood remains in the capillary
• As oxygen diffuses across the alveolocapillary membrane and dissolves in the plasma, it exerts pressure (the partial pressure of oxygen in arterial blood, or 𝑃𝑎𝑜2)
• As 𝑃𝑎𝑜2 increases, oxygen moves from the plasma into the red blood cells and binds with hemoglobin molecules, continuing until hemoglobin binding sites are filled or saturated
• The PO2 and PAO2 equilibrates to the point that it eliminates the pressure gradient across the alveolocapillary membrane and diffusion ceases, then oxygen continues to diffuse across the alveolocapillary membrane
• The majority (97%) of oxygen enters the blood is bound to hemoglobin with the remaining 3% still existing in the plasma.
• Doctors and clinicians can measure PO₂ by obtaining an ABG (Arterial Blood Gas)
• SaO2: percentage of the available hemoglobin that is bound to oxygen. It's measured by using an oximeter
• Doctors and clinicians can measure oxygen content (total amount of oxygen carried in the blood) using milliliters per deciliter.
• It's the combined value of the oxygen in oxygen-saturated hemoglobin and the oxygen dissolved in the blood
• Hemoglobin transports all but a small fraction of the oxygen carried in arterial blood
• Decreases in hemoglobin concentration (below the normal value of about 15 mL/dL of blood), reduce oxygen content
• Increases in hemoglobin concentration, may increase oxygen content, meaning it minimizes the effect of impaired gas exchange
• Increased hemoglobin concentration is a major compensatory mechanism in the setting of pulmonary diseases that impairs gas exchange

Hemoglobin Concentration

• body's initial response to low oxygen content is to accelerate cardiac output, especially for patients with no cardiovascular dysfunction. compensatory mechanism is ineffective for Cardiovascular disease, meaning elevated Hb improves because patient cannot accelerate its cardiac output, and elevated hemoglobin then matters more!

Carbon Dioxide

• byproduct of cellular metabolism elimination of C02 by the lungs plays an important role in the regulation of acid base balance
• Approximately 200 ml of C02 is produced by the tissue cells per minute at rest C02 is carried in the blood in three ways:

1. Dissolved in plasma
2. Transported as bicarbonate
3. Combined with blood proteins to form carbamino compounds

• C02 diffuses out of cells into blood and it dissolves in the plasma: → Approximately 10% of the total CO2 in venous blood and 5% of the CO2 in arterial blood are carried dissolved in the plasma → amount of dissolved CO2 is still able to exert pressure at normal amounts

• C02 moves into the blood and diffuses into red blood cells, CO2, with the help of enzyme carbonic anhydrase, combines with water to form carbonic acid- dissociates into H+ and HCO3- → As carbonic acid dissociates H+ binds to hemoglobin, where it's buffered, and then the HCO3 moves out of the red blood cell into the plasma.

Approximately → 60% of C02 in venous blood and 90% of C02 in arterial blood are carried in the form of bicarbonate→ the remainder combines with blood proteins, hemoglobin

Solubility and diffusion: → **C02 is 20 times more soluble than O2 and diffuses quickly from the tissue cells into the blood.

amount of C02 able to enter into the blood: Amount of C02 able to enter the blood is ENHANCED by diffusion O2 out of the blood and into the cells

Solubility of hemoglobin: → Reduced hemoglobin is able to CARRY MORE CO2 than hemoglobin that is saturated with O2 THE DROP IN and SaO2 (at the tissue level) INCREASES THE ABILITY OF HEMOGLOBIN ΤΟ CARRY C02 BACK INTO THE LUNG EFFECT OF OXYGEN ON CO2 TRANSPORT = HALDANE EFFECT

Pulmonary Compliance

• (ADULTS) compliance measure lung and chest wall distensibility Represents relative ease which these structures can be stretched which is the reciprocal of elasticity Determined by alveolar surface tension and elastic recoil of lung and chest wall
• Compliance formula

where C = compliance in liters per centimeter of water,Δ𝑉 = volume change (usually tidal volume), and Δ𝑃 = pressure change (airway or pleural pressure) in centimeters of water.

• Increased compliance (HIGH) Lungs/chest wall have lost some elastic recoil which is abnormally easy to inflate

• Increases with normal aging and disorders like emphysema Decreased compliance (LOW) Lungs or chest wall is abnormally stiff or difficult to inflate

• Decreases with acute respiratory distress syndrome, pneumonia, pulmonary edema, fibrosis chest wall compliance will decrease

• More muscular effort is required(pulmonary edema) and decreased chest wall compliance (spinal deformity or obesity) increase in 02 consumption and metabolic demand

• Compliance (CHILDREN / INFANTS) Chest wall compliance is HIGH in infants, especially premature infants Cartilaginous structures of the thoracic cage aren't well ossified + chest wall is easily collapsible

Brain Controls

• Respiratory center : brainstem, controls respiration by transmitting impulses to respiratory muscles causing cause contractions/relaxing Composed of several groups of neurons located bilaterally in the brainstem: Dorsal respiratory group (DRG) → cluster of inspiratory nerve cells on medulla → carries efferent impulses to diaphragm → controls automatic rhythm of respiration (peripheral chemo detection Pao2)

Ventral respiratory group (VRG) → receptors in lungs stimulates the VRG through the afferent nerves → contain insparatory and expiratory nerves → almost inactive during normal quiet respiration and becomes active when increased ventilatory effor is needed (Pneumotaxic and Apneustic are both situtated in pons)

• -> don't generate the primary breath of rhythm
• -- Act as modifiers pattern of breathing: influenced by emotion and diseases

Lung Innvervation

Three types of lung receptors send impulses from lungs to dorsal respiratory groups: (Irritant- rapidly adapting/Stretch -slowly adapting/J-receptors(juxta-pulmonary respiratory) Irritant receptors:(Mostly Proximal Larger Airways/Absent from distal) sensitive to noxious aerosols - particulates dust and gas initiate the cough reflex

Stretch: located in smooth muscle decrease ventilatory rate and volume once stimulated newborns with the reflex active but adults generally have it only working at high tidal

J : located near alveolar septum increase stimulus leads to shallow breathing-laryngeal constriction-mucus secretion- hypotension -bradycardia

Two branches of innveration into the longs -- Autonomic System Controls the diameter of air lumen and bronchical tone to create equilibrium

Parasympathetic: Fibers travel the Vagus. causes smooth muscle to contract. main controller of airway (epithelium stimulation)

Sympathetic: the upper portion branches causes those muscle to relax

Chemicals

Chemoreceptors respond to pH levels, and PaCO chemical monitors arterial blood and PH → Located near respiratory center→ increased h+ will stimulate depth of respiration (returns ph to normal)

Sensitive to arterial oxygen level in blood and all the increase at ventilation in response to arterial hypoxemia

• PaCO2 levels will cause peripheral chemorecptors and stimulate centres to increase the O2

Childrens breathing

for three weeks newborns will have a stunted hypoxia compared to that of adults

• This will result that that center for oxygen will be blocked as well.

Ventricular for hypercabia is normal in full term infants but reduced in premature.

Lesions of the Central Nervous System may cause and apnea Maternal smoking causes abnormalities and can lead to disorder

Pulmonary Function

Aspiration; passage of fluids and Solid Particles into Lungs

• Aspiration in individuals who swallow Mechanism w cough with depressed LOC or CNS abnormality

right lung particularly the right lower lobe" branches and is straighter to be more likely for aspertation Foreign Objects body- cough and refractary of something

Hyporemia

• Reduce Oxgen of Blood
• Caused to respiratory for others
• Lead to tissue of another common chemical causes and mechanism
• Decrase insprired oxygen, and other mechansims

Chronic bronchitis

hyperscrection of mucus and productive cough for 3 months and two Consecutive yesrs

• Chronic exposure to recuitis tobacco smoke (injures the lining cells)

Asymptic Asthma

(childhood and adult)- inflamaory disorder of Bronchial Mucosa that is REVERSIBLE

• Increase number of genes role is in Susptability- pathogenesis
• IgE ,esinophils with transmembrane proteins in endoplasmin Recul

Causes increased bronchial spasms and permeability

Mediatioas of Adulthood

IL-4 -Activate B - Eisinaphil - 5-Activate to tissue 8- activiate neutril- exaggerate Inflammation-

13 -Impairment is in mucosillary, enhanced secretation contributes to air remodeling increases Neu.

• Increase Inflammation 25- Bronchial constrictors

Adulthood

acute phase reaches max in 30 min

• broncial muscose exp to agent triggers th2 cells- inflammatory cytokins and all others

Clinal MANIFEST ADULTHOOD

• Asypmatic with function between attacks 1- Constriction .ex wheezing , and dyspnea Status asthma-Not reversed by use of measures low O2 level increase co2 symptoms 1-Wheezing heard insp+ exp. 2-pulse paradox - lower syst BP during inspiration.

Eval

spitiro - document and decres increase rapid assessment- and evaluate peak flow etc- Early in it is good to test

Rx for ad

Steadline Education, in step by step manner

(mild with sort term)

• im admin of O2
• monitor gas + airflow

Treatment for Asthma + long acting (better) + Immuno Therapy+

• Educate with peak + flow

Chidhood

more prevelent more in African American + pureto

• From the interactions of genes and environmental
• increase all of those Early Exposure to allergins increases risk in young blood

Pathysio - 1-Chronic disorder with causes Episodic attacks and inflamations

Initiated by - type 1 and all cells teach + prep and avoidance. - is the most important thing there after

Symptoms

80% is - upper respriratory inf and the sinus

Know Pulmonary Compliance

• ADULT complies measures wall distance ease in which can be stored/Reciporical
• determined by tension elastically

increased when - lost elastic or ab Easy to inflate decreased- abnormal stiff can increase in spinal issue

kids- wall very high cartilideous isn't we ossified

• Respiratory rate is in stem and causes contract

• -> Dorsal group inspir cells in Medulla Efferent,

• Ventral stimulation and Efferent. during normal quiet pneuo ( in pons ) =modifies input from cortex and hyo JReceptors stimulated

Treatment

• Airways interior diameter stimulate contractions 1--Branch fro spine smooth muscle in cord + causes relaxations

Parasym : Travels through Vagus+ causes muscle contractions the.

Chemicals reponds

Arterial , and sensitivty in oxygen responsible for all that occurs in arterial hypoxemia !