Bioc L09 Lungs

Question 1

What enables sufficient gas exchange between blood and air space?

Answer 1

large alveolar surface and thin epithelium

Question 2

What are three of the lung epithelium’s strategies for dealing with airborne material?

Answer 2

1. secretion of mucous substance
2. mechanical (ciliary) movement
3. antibacterial products (proteins, enzymes, macrophages)

Question 3

What does the conducting portion of the lung do?

Answer 3

bronchi and bronchioles support the lung as well as filter, moisten and warm inspired air

Question 4

What does the respiratory portion of the lung do?

Answer 4

includes respiratory bronchioles and alveoli

alveoli are where actual exchange of oxygen for carbon dioxid occurs.

Lung is 90% alveolar tissue

Question 5

What does respiratory epithelium secrete in the large airways?

Answer 5

mucus

Question 6

What does respiratory epithelium secrete in the small airways?

Answer 6

pulmonary surfactant–type II pneumocytes

Question 7

Where is mucus made, and what is it made from?

Answer 7

mucus is made in goblet cells and the submucosal glands

consists of two layers:

1. gel=sticky and binds to bacteris
2. sol=more watery

Question 8

What is the main component of mucus?

Answer 8

Mucin, a large glycoprotein

Mucin goes through rapid hydration after release into airways and expands mucus 500-1000 fold

Mucin also prevents the binding of enteric pathogens to the cell surface receptor via steric hindrance (creates a sticky and narrow space)

Question 9

What is mucociliary clearance?

Answer 9

the coordinated beating of the cilia that moves the mucis and particulate matter out of the lungs

Question 10

What does the sol layer of mucus do?

Answer 10

low viscosity and allows free movement of the cilia

Question 11

What does the gel layer of mucus do?

Answer 11

floating on the sol, it traps particulate matter like bacteria and virusus

Question 12

What is one disease that causes impaired mucociliary clearance that predisposes to tracheobronchial infection?

Answer 12

Cystic Fibrosis

autosomal recessive, defective CFTR gene

most common death in CF patients is respiratory infection caused by impaired mucociliary clearance and the inhibition of beta-defensin

Question 13

How does impaired mucociliary clearance cause frequent respiratory infections in patients with CF?

Answer 13

the quality and composition of the mucus are influenced by electrolyte transport across airway epithelial cells

chloride transport is defective in cystic fibrosis, which is caused by mutations on the CFTR gene.

this chloride channel defect leads to thick mucus secretions, which impaire mucociliary action and predisposes to infection

Question 14

How does the inhibition of beta-defensin cause frequent infections in patients with CF?

Answer 14

beta-defensin is an antimicrobial human pulmonary protein

in CF lungs, high salt in the extracellular environment inhibits beta-defensin

Question 15

What is primary ciliary dyskinesia?

How is it inherited?

Answer 15

autosomal recessive, multiple genes that are involved in axonemal dynein structure

PCD is caused by dysfunction of the axonemal dynein arm of microtubules in the cilia/flagella

compromises pulmonary mucociliary clearance, which predisposes to infection

Question 16

What is Kartagener syndrome?

How is it related to PCD?

Answer 16

50% of the patients with PCD also exhibit situs inversus, when the major visceral organs are reversed or mirrored

cilia in the heart are crucial for transporting signaling molecules that facilitate and regulate so that the heart loops left

in the absence of cilia, the heart randomly loops in either direction

Pathology: recurrent pulmonary infections and male infertility

Question 17

Describe type I and II alveolar cells.

Answer 17

Type I take up 95% of alveolar surface, where Type II take up only 5%.

However, type I is only 40% of the cells, highly attenuated and thin, where as type II accounts for 60% are are granular and roughly cuboidal

Type I has few mitochondria and rER, whereas type II has numerous mitochondria and rER

Type I functions mainly for gas exchange, where type II functions for pulmonary surfactant synthesis and structural support

Question 18

What is the purpose of the thin side of alveolar walls?

Answer 18

Basal lamina of type I alveolar cells and endothelial cells are thin and fused to minimize diffusion path for oxygen and carbon dioxide

In other words, the BM between type I cells and endothelial cells is small to allow for gas exchange

Question 19

What is the purpose of the thick sides of the alveolar walls?

Answer 19

The CT is rich in elastic fibers (elastin) and reticular fibers (type III collagen) that are secreted by type II alveolar cells.

Elastic fibers are important in compliance of lung movement (inspiration and expiration)

Reticular fibers aid in maintaining the structure of the alveoli

Question 20

What cell secretes pulmonary surfactant, and when does this production start?

Answer 20

type II pneumocytes

production begins at 24 weeks in utero

Question 21

How is surfactant synthesized?

Answer 21

surfactant lipids and proteins are synthesized on the SER and rER of type II cells, modified in the golgi apparatus, exocytosed from trans-golgi network into secretoy vesicles leading to formation of lamellar bodies

the lamellar bodies are then secreted with components of surfactant (by both constitutive and regulatory exocytosis) in response to mechanial stimuli such as labor/delivery and hyperventilation

Question 22

What happens to the lamellar bodies in the watery hypophase layer of the type II pneumocyte?

Answer 22

they are transformed into a broad lattice like network known as tubular myelin, where lipid portions and protein portions are separated

tubular myelin acts as a reservoir that provides surfactant lipid to the monolayer

in adult lung, 50% of surfactant is present as a monoloayer and 50% in the form of inactive small vesicles

Question 23

What is the composition of pulmonary surfactant?

Answer 23

90% phospholipids, 5-10% of surfactant proteins A, B, C, D that assemble the monolayer, and 1% carbs

80% of the lipids are phosphatidylcholines, 60-70% are dipalmitoyl phosphatidylcholine (DPPC)

DPPC is a sold at 37 degrees C because of high melting point of palmitate moiety

Question 24

What are two physiological functions of pulmonary surfactant?

Answer 24

1. surfactant reduces surface tension and prevents alveolar deflation at low lung volumes
2. surfactant forms a hydrophobic barrier between air space and alveolar cells

Question 25

How does the reduction of surface tension by surfactant work?

Answer 25

When alveolar surface area is reduced at low lung volumes, DPPC forms a monolayer, with hydrophilic polar head group aligned along the air-liquid interface and the hydrophobic fatty acid tail extending into the air space Because the tail is fully saturated, it is arranged in a straight line, which allows close packing of DPPC With close packing, there is mutual repulsion of DPPC at their hydrophilic portion, which lowers surface tension and prevents alveolar collapse

Question 26

The presence of surfactant decreases the pressure needed for expansion of alveoli and is...

Answer 26

important is maintaining the patency of the alveoli

Question 27

How does surfactant form a hydrophobic barrier between air space and alveolar cells?

Answer 27

prevents transudation of interstitial fluid into air space (ie. keeps the lungs dry) prevents penetration of intruders from air space into tissue 

Question 28

What is Neonatal Respiratory Distress Syndrome?

Answer 28

it is caused by a deficiency in surfactant secondary to prematurity, elective C-section, and multiple births more of an issue in preterm infants where the lungs have not yet produced surfactant or not adequate amounts the infant is often normal at birth, but within a few hours develops incrasing respiratory effort, tachypnea, use of accessory muscle of respiration, an expiratory grunt cyanosis

Question 29

What is the treatment for NRDS?

Answer 29

a combination of synthetic surfactant and replacement and oxygen

Question 30

What are some complications of oxygen treatment in newborns?

Answer 30

Bronchopulmonary dysplasia and retinopathy of prematurity The myelin sheaths of nerves in infants is very sensitive to free radicals, so you can get damage to retinal cells and alveoli due to oxygen therapy

Question 31

How can you prevent NRDS?

Answer 31

Glucocorticoid therapy can be administered to mothers with threatened premature delivery at 24-34 weeks this glucocorticoid stimulates type II cells to produce surfactant by increasing the surfactant protein synthesis it is common practice to delay premature delivery so glucocorticoids can be administered to the mother to increase surfactant protein gene expression (SP-B) in the fetus

Question 32

What lab tests can you do to test for fetal lung maturity?

Answer 32

you can use amniotic fluid to test the lecithin/spingomeylin (L/S) ratio \< 2 suggests increased risk of RDS an immunoassay for surfactant protein A can also be used to estimate fetal lung maturity

Question 33

What causes adult respiratory distress syndrome (ARDS)?

Answer 33

ARDS is caused by damage of alveolar epithelium and capillaries, resulting in progressive respiratory failure that is unresponsive to oxygen aspiration some causes include emphysema, sepis, trauma, gastric aspiration, radiation, oxygen toxicity, and pulmonary infections loss of type I pneumocytes and proliferation of type II pneumocytes are typically observed

Question 34

How do alveolar macrophages maintain lung sterility?

Answer 34

sterility is due to mucociliary clearance and the production of reactive oxygen species by alveolar macrophages alveolar macrophages (dust or sentinel cells) are derived from blood monocytes. they migrate betweent type I cells and enter the lumen of the alveolus pulmonary injury or irritants in the inhaled air trigger this migratino and increase the phagocytic activity of the alveolar macrophages which phagocytose particulate matter and maintain a sterile lung environment

Question 35

How do alveolar macrophages kill what they phagocytose?

Answer 35

macrophages produce superoxide anion via a plasma membrane NADPH-oxidase complex during phagocytosis, the exterior plasma membrane surface becomes the interior surface of a phagosome and is thus posed for microbicidal activity

Question 36

What are the 3 main functions that the alveolar macrophage plays in the distal airways?

Answer 36

1. provides microbicidal activity by releasing oxygen radicals as well as proteases to degrade bacteria. Thus, it is termed a sentinel cell. Proteases are used to damage and increase the permeability of the bacterial cell wall 2. involved in acute inflammatory response by having antigenic activity 3. involved in tissue repair process by releasing signaling factors such as cytokines which trigger collage synthesis and fibrosis

Question 37

How do lung tissues protect themselves from being damaged by the action of the macrophages?

Answer 37

even though these proteases and oxygen free radicals can kill bacteria, they can also injure surrounding tissue alveoli, the gas exchange unit of lungs, are protected from attack by neutrophil elastase using alpha1-antitrypsin, a serine protease inhibitor

Question 38

What is alpha1-antitrypsin?

Answer 38

it is made by the liver and is a serum glycoprotein that is secreted constitutively into the blood. It is sufficiently small to diffuse from the plasma into the tissue spaces via clefts between endothelial cells it binds to any active serine protease (particurally neutrophil elastase) in an irreversible and non covalent manner this alpha1-antitrypsin-elastase complex is then removed and degraded in this way, it provides more than 90% of the neutrophil elastase protection in the respiratory tract. since lung tissue cannot be regenerated, proctection of alveoli is very important. alpha1-antitrypsin safeguards the lungs against the destructino of elastic fibers by elastase secreted by neutrophils

Question 39

How can emphysema be caused by alpha1-antitrypsin deficiency?

Answer 39

alpha1-antitrypsin is a polymorphic protein and has more than 70 variants in humans, some of which exhibit low alpha1-antitrypsin activity the protein deficiency typically manifests itself as emphysema before 50 years of age oxidation of a critical methionyl reside by superoxide can lead to inactivation of alpha1-antitrypsin smoking increases superoxide several fold, so people with reduced alpha1-antitrypsin should avoid smoking in order to avoid early onset of emphysema