Respiratory System Development Flashcards
What is needed to make a respiratory system?
- Conducting zone
- branches through which air flows from nose to terminal bronchioles
- Respiratory zone
- site of gas exchange
- From respiratory bronchioles → alveoli
- An effective vascular system feeding blood into gas exchange area
- Surfactant to facilitate/maintain inflation of alveoli and decrease work of breathing === serious consequence for premature babies
What is the conducting zone?
- ~14 rounds of branching, with each branch ending in a terminal bronchiole
- No gas exchange happens here
- Bronchioles have no cartilage
- Bronchi have cartilage in decreasing amounts as branches get smaller
The ______ are the functional units of the lung, and include _______, _______, and ________
The acini are the functional units of the lung, and include respiratory bronchioles, alveolar ducts and alveolar sacs
________ are organized packages for gas exchange => cluster of alveoli = _______
alveolar sacs are organized packages for gas exchange => cluster of alveoli = acinus
What is important about how the respiratory branches and pulmonary arteries/veins grow
- Blood supply (pulmonary artery/veins are very important)
- vessels grow alongside the branches (simultaneous development)
What are the five stages of lung development?
- Embryonic (3-6 weeks)
- Pseudoglandular (6-16 wks)
- Canalicular (16-26 wks)
- Saccular (26wks - term)
- Alveolar (postnatal)
These steps overlap → lung development begins in fourth week and is not complete until several years postnatally
What happens during the embryonic stage of lung development?
- Setting up the basic lung organization
- establish respiratory system as branch off ventral foregut
- two lungs
- lobes of lungs
- bronchopulmonary segments
What is the origin of the respiratory system?
Dorsal and ventral foregut originate from different regions of ____ in the ________
- Comes from primitive gut tube (tract)
- Dorsal and ventral foregut originate from different regions of endoderm in the trilaminar plate
What does the green and blue represent in the image?
- the image is the folding endoderm
- The green is posterior and becomes the esophagus
- The blue is anterior and becomes the respiratory tract
What factor controls what genes are expressed before body folding?
NKx2.1
What is Nkx2.1?
Nkx2.1 is a transcription factor specifically expressed in the ventral foregut tissue that will form the respiratory system (larynx and below)
Nkx2.1 is a ________ specifically expressed in the ______ tissue that will form the respiratory system (_____ and below)
Nkx2.1 is a transcription factor specifically expressed in the ventral foregut tissue that will form the respiratory system (larynx and below)
Label the image
Label the image
What is the respiratory bud and how does it form?
Respiratory bud (diverticulum) forms as an outpocketing of the ventral foregut
- outgrowth of specific region (caudal half) of ventral foregut
The cranial half of the ventral foregut will form the _______
The caudal half of the ventral foregut will make the ______ that forms the ______
The cranial half of the ventral foregut will form the laryngotracheal tube
The caudal half of the ventral foregut will make the respiratory bud that forms the bronchi and lungs
Label the image
The larynx and trachea precursor is the _______
The larynx and trachea precursor is the laryngotracheal tube (from tissue above respiratory bud (cranial half of ventral foregut))
What is the tracheoesophageal septum and how is it formed?
- septum between the larynx/trachea and the esophagus
- Walls of the foregut invaginate to form this septum separating the laryngotracheal tube (ventral) and the esophagus (dorsal)
If the tracheoesophageal septum grows in the wrong place (_____) can cut off the esophagus
If the tracheoesophageal septum grows in the wrong place (fistula) can cut off the esophagus
The epithelial linings of the airways are derived from ______
_______ surrounds the entire respiratory system → forms the connective tissue, muscle and vasculature of the respiratory system
The epithelial linings of the airways are derived from endoderm (inner lining)
Splanchnic mesoderm (outer coating) surrounds the entire respiratory system → forms the connective tissue, muscle, and vasculature of the respiratory system
The _______ of the airways are derived from endoderm (inner lining)
Splanchnic mesoderm (outer coating) surrounds the entire respiratory system → forms the __________
The epithelial linings of the airways are derived from endoderm (inner lining)
Splanchnic mesoderm (outer coating) surrounds the entire respiratory system → forms the connective tissue, muscle, and vasculature of the respiratory system
The respiratory bud branches into ________
The respiratory bud branches into two primary bronchial buds
The primary bronchial buds give rise to the right and left bronchi and lungs
The ________ branches into primary bronchial buds which give rise to the __________
The respiratory bud branches into primary bronchial buds which give rise to the right and left bronchi and lungs
The primary bronchial buds branch to form _______
How many on each side?
The primary bronchial buds branch to form secondary bronchial buds
Three on right
Two on left
Become the lobes of the lungs
The _________ become the lobes of the lungs
The secondary bronchial buds become the lobes of the lungs
Initially, how are the lungs positioned in relation to the heart and the esophagus
Initially lungs are:
- Posterior to the heart
- Anterior to the esophagus
__________ give rise to the bronchopulmonary segments (8-10 per lung)
Tertiary bronchial buds give rise to the bronchopulmonary segments (8-10 per lung)
Tertiary bronchial buds give rise to the ______ (___ per lung)
Tertiary bronchial buds give rise to the bronchopulmonary segments (8-10 per lung)
Tertiary bronchial buds give rise to the ______ (___ per lung)
Tertiary bronchial buds give rise to the bronchopulmonary segments (8-10 per lung)
_________ are (mostly) self-contained units with bronchioles and arteries but have no visible boundary
BRONCHOPULMONARY SEGMENTS are (mostly) self-contained units with bronchioles and arteries but have no visible boundary
What are the morphological differences between the Right and Left main bronchi?
The Right Main Bronchus is larger, shorter and oriented more vertically; features that are conserved to adulthood
This is because the heart forces the Left main bronchus to move more to the left
An inhaled foreign body is more likely to enter the _______ main bronchus. Why?
An inhaled foreign body is more likely to enter the right main bronchus. Because the right main bronchus is larger, shorter and oriented more vertically
What happens in the pseudoglandular stage and when does this stage occur?
- 6-16 weeks
- Create all the conducting airway branches
- At this stage, lung tissue has many channels surrounded by lots of mesenchyme (connective tissue from splanchnic mesoderm)
- looks somewhat like a gland
Pseudoglandular stage
During weeks 6-16, bronchial buds undergo _____ more rounds of branching to produce the rest of the conducting airway tree, eventually giving rise to ________
During weeks 6-16, bronchial buds undergo ~12 more rounds of branching to produce the rest of the conducting airway tree, eventually giving rise to terminal bronchioles
What regulates the branching at the distal branch tips?
Signaling between mesoderm and endoderm → not fully understood
Does smooth muscle drive branching?
It was believed that it did, but in absence of smooth muscle branching still occurred, therefore debunked
Terminal bronchioles are ______, made of ______ epithelium and dense ______. Gas exchange?
Terminal bronchioles are thick-walled channels, made of columnar/cuboidal epithelium and dense mesenchyme. Gas exchange? No gas exchange
What major developments have happened by 16 weeks? (Pseudoglandular stage)
- all major elements of the lung have formed with exception of_______
- ______ will develop alongside the respiratory tree
- Breathing movements start at about _____ and are an important source of ________ for development
- all major elements of lung have formed with exception of those involved in gas exchange
- Vasculature will develop alongside the respiratory tree
- Breathing movements start at about 10 weeks and are an important source of mechanical stimulation for development
Pseudoglandular Stage:
- _______ are the end of the conducting airways; will branch into 2-11 ______ which are the start of the respiratory zone
- During pseudoglandular stage, all ______ are made, and maybe even some ________, but epithelium is still ________
Pseudoglandular Stage:
- Terminal bronchioles are the end of the conducting airways; will branch into 2-11 respiratory bronchioles which are the start of the respiratory zone
- During pseudoglandular stage, all terminal bronchioles are made, and maybe even some respiratory bronchioles, but epithelium is still columnar (thick walls)
What are 4 major events of the Canalicular Stage?
- Establish separation between conducting and respiratory zone
- (ie start making distinct respiratory tissue)
- Beginning of cell differentiation in respiratory airways:
- Type I pneumocytes for gas exchange
- Type II pneumocytes make surfactant
- Increase in vascularization
- Decrease in mesenchyme (bring vessels closer to walls of resp tissue)
What are the two types of cells in the respiratory airways and what are their roles?
When do they start to differentiate?
-
Canalicular Stage: Beginning of cell differentiation in respiratory airways:
- Type I pneumocytes for gas exchange
- Type II pneumocytes make surfactant
What is the continued branching that occurs in the canalicular stage?
- Continued branching of respiratory airways to make respiratory bronchioles and alveolar ducts
What is the continued branching that occurs in the canalicular stage?
- Continued branching of respiratory airways to make respiratory bronchioles and alveolar ducts
What is the Bronchioalveolar duct junction (BADJ)? When is it established?
Transition from ciliated columnar epithelium of the conducting zone to squamous epithelium of the respiratory zone
- established at Canalicular stage
_______ cells are present at the BADJ
Stem cells are present at the BADJ (bronchioalveolar duct juntion)
- In case of tissue injury, they can divide and renew a variety of lung cells, including type 1 and type 2 pneumocytes
When is the Saccular stage and what primary developmental processes occur?
- when?
- An “______” phase
- ______ completes
- Basis is laid for _____ formation (_______)
- There are dif signalling pathways involved in ______ and _______ and this stage is the transition between the two processes (ie shift from ____ to _____)
- Respiratory airspaces expand into ____ lined by ________
- Between terminal sacs, creation of ______ containing a _______ of _______
- 26 weeks to term
- An “in-between” phase
- Branching completes
- Basis is laid for alveoli formation (terminal sacs)
- There are dif signalling pathways involved in airway branching and alveolar development and this stage is the transition between the two processes (shift from branching to maturing)
- Respiratory airspaces expand into sacs lined ty Type I pneumocytes
- Between terminal sacs, creation of Primary Septa containing a double layer of capillaries
What is the stage on the left?
Stage on the Right?
How can you tell?
- The Left is the Canalicular stage
- Made branches
- Right is Saccular
- Branching ceases
- Cell differentiation
- Walls thin (bring blood vessels closer)
Label the stages
Label the black line
What is the primary septum?
How is it formed?
- Region where mesenchyme becomes compressed because of growth of terminal sacs
- forms a double layer of capillary
- important because each capillary can only exchange gas with one sac
What is the difference between the way terminal sacs grow and the way alveoli grow?
When does alveoli grow?
Terminal sacs grow “like grapes”
Alveoli grow because of secondary septa separation
- Alveolar stage
What happens during the alveolar stage?
- Division of terminal sacs into alveoli by formation of secondary septa
- Subdivide into alveoli (NOT growth)
- Alveolar formation actively continues until 3 years of age but further formation/maturation may extend up to ~21 years of age
Division of terminal sacs occurs by ______ and forms ______
Division of terminal sacs occurs by formation of secondary septa and forms alveoli
Label the stages
Image labelled C shows:
D shows:
C = Primary septa
D = Secondary septa
What are the major differences between Primary and Secondary Septa?
- Primary Septa (between terminal sacs):
- Double layer of capillaries
- Blood exchanges gases with one alveolus/terminal sac at a time
- Formation is passive (from squishing of mesenchyme)
- Double layer of capillaries
- Secondary Septa:
- Single layer of capillaries
- blood can simultaneously exchange gases with two alveoli
- Formation is active (actively grow toward centre of terminal sac)
- Single layer of capillaries
Blue arrow=
Black arrow =
Blue arrow= Alveolar sac (mature terminal sac)
Black arrow = Alveolus
What are three epithelial progenitor cell markers that drive differentiation of alveolar epithelial cells?
- Id2
- Shh
- SOX9
What are six alveolar epithelium markers that promote development during the alveolar stage?
- SPC
- AEC2
- HOPX
- Pdpn
- Ager
- AEC1
What are the three layers gas exchange occurs across in the mature lung? From Airspace to blood:
- Thin processes of type i pneumocytes (2 membranes)
- Fused basal lamina (2 membranes)
- Capillary endothelium (1 membrane)
3 layers, 5 membranes
What process brings vasculature closer to respiratory airways (resp bronchioles & alveolar ducts)?
Decrease in mesenchyme
Why are elastin fibres in the ECM important for alveolar formation and support?
→ Recoil during exhalation
emphysema = loss of elastic tissue
Label the image of the mature respiratory system
Fully mature alveoli are not present until ______
Fully mature alveoli are not present until 5 weeks postnatally
How do the lungs change at birth?
What 2 shunts close?
- Prenatally, blood is shunted away from the lungs
- At birth the two shunts close
-
foramen ovale, which moves blood from the right atrium of the heart to the left atrium, and the ductus arteriosus, which moves blood from the pulmonary artery to the aorta.
- Increased O2 in lungs decreases resistance to blood flow
-
foramen ovale, which moves blood from the right atrium of the heart to the left atrium, and the ductus arteriosus, which moves blood from the pulmonary artery to the aorta.
- Fluid filling the alveoli in utero is removed through absorption into blood and lymph
A preterm baby born in the pseudoglandular phase: survive?
No chance of survival because there are no airspaces = no possibility for gas exchange
Preterm baby born in canalicular stage: survive?
- In canalicular stage, have started making airspaces and reducing the barrier between air and blood (thinning walls)
- Survival becomes possible in later half (with assistance)
- Surfactant
What is surfactant?
- Surfactant is a complex mixture of proteins and phospholipids
- Hydrophilic/Hydrophobic = breakdown surface tension from water
- Allows lungs to inflate
When does surfactant production start?
22-24 weeks in small amounts
Increases at ~ 30 weeks
Pre-term baby and surfactant: treatment?
- Preterm infants need to be given artificial surfactant (from cows or pigs)
- Or, if preterm birth is anticipated, mother is given steroids to stimulate surfactant production
Surfactant isn’t produced until 22-24 weeks (canalicular stage)
Increases production at ~30 weeks (Saccular stage)
The intraembryonic coelom becomes divided into 4 separate spaces:
- Pericardial cavity (heart)
- Two Pleural cavities (lungs)
- Peritoneal cavity (abdomen/pelvis)
What separates the peritoneal cavity from the pericardial and pleural cavities?
The diaphragm
Where does the diaphragm originate?
Pleuroperitoneal Folds (Splanchnic mesoderm → CT)
- folds of mesoderm from posterior body wall that grows over the septum transversum → part of ventral mesentery right overtop the liver
How does the diaphragm develop?
- Folds of (mesoderm) tissue (pleuroperitoneal folds PPF) emerge from the posterolateral wall of the intraembryonic coelom (between presumptive pleural and peritoneal cavities) and grow over septum transversum and liver to form the diaphragm
Diaphragm
- ________ forms connective tissue of diaphragm
- _______ form skeletal muscle
- Nerves from _____ follow _____
Diaphragm
- Pleuroperitoneal folds (PPFs; splanchnic mesoderm gives rise to CT_)_ forms connective tissue of diaphragm
- Myoblasts from adjacent somites form skeletal muscle
- Nerves from adjacent cervical levels follow _myoblasts (_to innervate the muscle cells)
Pleuroperitoneal folds (PPFs) form ____ around muscle and the ________
Pleuroperitoneal folds (PPFs (spl. mesoderm)) form fascia around muscle and the central tendon
________ grow from the neck, through thorax, to innervate the diaphragm
Phrenic nerves grow from the neck, through thorax, to innervate the diaphragm
______ nerve fibres come together to make phrenic nerves which innervate the ______. Relevance to spinal cord injury?
C3-C5 nerve fibres come together to make phrenic nerves (innervate the diaphragm). Relevance to spinal cord injury?
- Sp cord injury below C3-C5 = preserve diaphragm function
