Terminal respiratory unit

1. TERMINAL
RESPIRATORY UNIT
BY DR.SACHITHANANTHAM S
1ST YEAR PG RESIDENT
PILMONARY MEDICINE

2. INTRODUCTION TO RESPIRATORY SYSTEM
• Upper airway system
Nose, larynx, pharynx and its associated structure
• Lower airway system
Trachea, bronchi, lung

3. LOWER AIRWAY SYSTEM
• It consist of trachea , bronchi, lung

4. WEIBEL CLASSIFICATION AIRWAY GENERATION

5. AIRWAY GENERATION
AIRWAY
GENERATION
NUMBER OF
GENERATION
CHARACTER ROLE
Trachea 0 Cartilaginous Conducting
Bronchi 1-3 Cartilaginous Conducting
Bronchioles 4-13 Membranous Conducting
Terminal bronchioles 14 Membranous Conducting
Respiratory
bronchiole
16-18 Partially
membranous
Partially conducting
Alveolar duct 19-22 Gas exchange
Alveoli 23 Gas exchange

6. CHANGES IN RESPIRATORY EPITHELIUM

7. TERMINAL RESPIRATORY UNIT
• It consist of a respiratory bronchiole and all the alveolar ducts together with their
accompanying alveoli .
• In the human lung the unit contains approximately 100 alveolar ducts and 2000
alveoli
• At FRC , the unit approximately 5mm in diameter with a volume of 0.02ml, there
are1,50,000 such units in the lungs of normal adult humans

8. • The functional definition TRU is physiologic; gas phase diffusion is so rapid along
patent airways that the partial pressure of o2 and co2 are uniform throughout the
unit.
• Therefore physiologically o2 in the gas phase anywhere along the TRU will diffuse
along its concentration gradient across the extremely thin walls into RBC’S
following in the capillary where o2 combine with haemoglobin.

9. • Respiratory bronchiole is the connection between the alveoli and terminal bronchiole
• Respiratory bronchiole is similar to terminal bronchiole, except that the wall is
interrupted by numerous alveoli where gas exchange occurs
• Proceeding distally , the number of alveoli opening into the respiratory bronchioles is
greatly increased till we have only duct of alveoli
• The alveolar duct distally leads to distended spaces called alveolar sac , several alveoli
opens into the wall of these sacs.
• Alveoli are air spaces thus responsible for the spongy structure of the , lung gas
exchange occurs through the wall of the alveoli

10. ALVEOLAR DUCT
• Arises from the respiratory bronchiole which they differ from respiratory bronchiole by having no walls
other than the mouths of mural alveoli (approximately 20 in number).
• The alveolar septa comprise a series of rings forming the walls of the alveolar ducts and containing
smooth muscle.
• Approximately 35% of the alveolar gas resides in the alveolar ducts and the alveoli that arise directly
from them

11. • It is estimated that about 17 alveoli arise from each alveolar sac and account for about half of the total
number of alveoli which occurs in larger airways.
• Millions of alveolar ducts branch off the respiratory bronchioles.
• Alveolar ducts are tiny airways only 0.3 mm in diameter, and their walls are composed entirely of alveoli.
• Each alveolar duct ends in a cluster of alveoli, which is frequently referred to as an alveolar sac.
• Each alveolar sac opens into about 16 or 17 alveoli, and about one-half the total number of alveoli found in this
region

12. THE ALVEOLUS
• The major function of lung to facilitate the gas exchange process that takes place
in distal alveolar region the alveolar areas comprise of greater than 99.5% of the
large surface area of lung , estimated in adult human to be approximately 100 to
150 m2 .
• The adult human lung contains approximately 480 million alveoli each about
40×10 * 6 micrometer in size.
• The alveoli is , an intricate mixture of epithelial , mesenchymal and endothelial
lineages combine to form a thin air blood interface for efficient gas exchange.

13. TYPES ALVEOLAR CELL
• ALVEOLAR TYPE 1 CELL
• ALVEOLAR TYPE 2 CELL
• ALVEOLAR MACROPHAGES (ALVEOLAR DUST CELL)
• MESENCHYMAL CELL

14. ALVEOLAR TYPE 1 CELL (AT 1 CELL)
• AT 1 cell simple squamous cell which share a common fused basement
membrane with capillary endothelial cell to facilitate gas exchange
• It comprise of approximately 10% of the cells in the alveolar region but cover
approximately 95% of the internal surface area .
• Mean volume of the cell 2000 micrometer3.
• Increase in lung size with increase in body size thus result from increase of
alveolar cell number.

15. • AT1 cell contains eccentric nuclei surrounded by perinuclear cytoplasm attenuated
cytoplasmic extensions that come in to close contact with the capillaries from to form
the epithelial component of air blood barrier
• The basal surface of the AT1 cell attached with the basement membrane, whereas the
apical surface come into contact with air, where epithelium lies directly over the
capillary endothelial cell, their basement membrane fuse
• AT1 cells are not only confined to alveolus their cytoplasmic extension penetrate
across several alveolar septa cross interalveolar pores to bridge two or three different
alveoli.

16. PHYSIOLOGY RELATED TO AT2 CELL

17. RESPIRATORY MEMBRANE (ALVEOLAR AIR BLOOD
BARRIER)
• Respiratory membrane is the surface where gaseous exchange between alveoli
and blood occurs in the lung
• It is a thin membrane composed alveolar and capillary wall

18. RESPIRATORY MEMBRANE
• Formed by the following structure
1)A layer of fluid lining the alveolus and containing surfactant
2)The alveolar epithelium composed of thin epithelial cell
3)AN epithelial basement membrane
4)A thin interstitial space between alveolar epithelium and capillary
membrane
5)Capillary endothelial membrane

19. FACTORS AFFECTING RATE OF GAS EXCHANGE
THROUGH RESPIRATORY MEMBRANE
• Thickness of membrane example in case of edema and fibrosis
• Surface area of membrane ex ; pneumonectomy, emphysema
• Solubility of gas
• Difference between the partial pressure gas in alveoli and in pulmonary capillary
bed

20. ALVEOLAR GAS EXCHANGE

21. ALVEOLAR GAS EXCHANGE
• Gas exchange to occur between the alveoli and pulmonary capillaries , a difference in
partial pressure p1-p2 must exist.
• In the normal lung , the alveolar po2 averages approximately 100 mmHg , alveolar Pco2 is
approximately 40mmHg
• The pressure gradient for o2 exchange approximately 60 mmHg
• The pressure gradient for co2 causes it to diffuse in the opposite direction , from blood
into the alveolus this diffusion continues until capillary pc02 equilibrates with the alveolar
level at approximately 40 mmHg
• Co2 diffuse approximately 20 times faster than o2 because its much higher solubility in the
plasma

22. • An erythrocyte spend an average of about 0.75 to 1.2 seconds inside the
pulmonary capillary at resting cardiac output this transit time depends on
pulmonary capillary blood volume and pulmonary blood flow
• Under resting conditions , the total transit time for blood to move through the
alveolar capillary system is about 0.75 second

23. PERFUSION LIMITED GAS FLOW
• When oxygen diffuse through the alveolar wall and in to the blood , it enter into
the blood , it enters the RBCs and combines with hemoglobin
• Hemoglobin quickly saturated with o2 and o2 molecules in the plasma stop
entering to RBC
• These causes partial pressure of oxygen in the plasma to increase .
• Po2 in the capillary blood equal the partial pressure of oxygen in the alveolar gas
when the blood is about one-third way through the capillary, beyond this point
oxygen is perfusion limited

24. DIFFUSION RELATED GAS FLOW
• Diffusion limited means that the movement gas of across the alveolar wall is a function of
the integrity of the alveolar capillary membrane itself.
• It is explained by when the CO moves across the alveolar wall and into the blood , it
rapidly enter in to the red blood cell to hemoglobin
• When a gas in chemical combination with hemoglobin it , it no longer exert a partial
pressure
• So no appreciable partial pressure of CARBON MONOXIDE at blood any time i,e ; stay
constant
• Carbon monoxide diffusion depends on only the diffusion characteristic of the alveolar
capillary membrane , not the amount blood flow through the alveolar capillary membrane

25. • In essence diffusion limited means that the structure of the alveolar capillary
membrane alone limits the rate of gas diffusion
• This property makes the carbon monoxide an excellent gas for evaluating the
lung’s ability of diffuse gases and is used in DLCO TEST
• Under normal circumstances the perfusion of oxygen is perfusion limited , but
under certain abnormal pulmonary conditions the transfer of oxygen is diffusion
limited

26. ALVEOLAR – ARTERIAL OXYGEN DIFFERENCE
• The arterial po2 is normally a few mmHg less then alveolar po2 . This normal
alveolar arterial oxygen difference , the (A-a)o2 caused by the normal anatomic
shunt , some degree of ventilation perfusion mismatch and diffusion limitation in
some part of the lung , of these v/q mismatch is very important
• The alveolar arterial po2 difference is normally about 5 to 15 mmHg in young
healthy person breathing at sea level , it increase with age because of the
progressive decrease in arterial po2 that occurs with aging

27. ALVEOLAR TYPE 2 CELL
• Second major epithelial cell lineage in the lung alveolus , it comprise of 3-5% of the
alveolar surface area , constitute 60% all alveolar epithelial cell 10 to 15% all lung cell
• It produce surfactant – is a vital substance to reduce the surface tension
• It express immunomodulatory substance that are necessary for host defense
• It facilitate transepithelial movement of water
• It has stem cell property and plays a important roll in regeneration of alveolar
epithelial cell after injury

28. • Primary role of AT 2 to produce the surfactant lipid and protein and transport it
into the alveolar space ,AT2 cell contains specialized cytoplasmic organelles
termed as lamellar bodies storage organelle for surfactant.
• AT2 cells are contains highly specialized transcriptome is highly enriched in genes
involved in lipid metabolism , and it contains a high density of mitochondria to
support lipid biosynthesis , processing of surfactant .

29. SURFACTANT
• Surfactant is a mixture of lipids and protein secreted into the alveolar space by
AT2 cell these lipid plays a important role in reducing surface tension of alveoli
prevent the collapse of alveoli
• Major phospholipids present in surfactant is dipalmitoyl phosphatidyl choline ,
other lipid are triglyceride, phosphatidyl glycerol
• Proteins part of the surfactant are called as specific surfactant protein( SP) , these
are four main protein called as SP-A, SP-B , SP-C,SP-D

30. • SP-A, SP-D hydrophilic , while SP-B SP-C are hydrophobic .
• SP-A , SP-D both are glycoprotein , involved in innate immunity in the alveoli
• SP-A large glycoprotein and has a collagen like domain with in its structure major
function SP-A to regulate the feedback uptake of surfactant into the type 2 alveolar
epithelial cell
• SP-B, SP-C smaller proteins which are the key protein of the monomolecular film of
the surfactant.
• Ions present in surfactant are mostly calcium and phosphate ions

31. FORMATION OF SURFACTANT
• Type 2 alveolar epithelial cell have special type of organelles called lamellar bodies they are the
intracellular source of surfactant.
• Lamellar bodies contains surfactant phospholipids and surfactant proteins these material are
synthesized from endoplasmic reticulum
• By means of exocytosis, lipids and proteins of lamellar bodies are released into surface of alveoli here
in the presence of calcium the phospholipid arranged in lattice meshwork called as tubular myelin
• Tubular myelin in turn converted into surfactant in the form of a molecular film that spreads that
spreads over the entire surface of alveoli
• Most of the surfactant is absorbed into the type 2 alveolar cell, catabolized and the products loaded in
to lamellar bodies for recycling

32. FUNCTIONS OF SURFACTANT
• Surfactant protein reduce the surface tension reduce the collapsing tendency
• It plays a important role in inflation of the lung after birth
• Hydrophobic protein like SPA , SPD destroy the microorganism by opsonization

33. SURFACTANT DEFICIENCY SYNDROME

34. PULMONARY ALVEOLAR PROTENOSIS

35. • It is a syndrome characterized by progressive accumulation of surfactant
phospholipids and proteins within alveoli and terminal airways
• The disease not associated with inflammation of airway, and architecture is
typically preserved

36. PATHOPHYSIOLOGY
• The alveoli is filled with proteinaceous material , that found to be normal surfactant
composed 90% lipids and 10% protein
• Defect in surfactant homeostatic mechanism result in increase production decreased
clearance of surfactant.
• It is due to defect in Gm-CSF that affect the maturation of alveolar macrophages,
render the surfactant catabolism and accumulation of surfactant
• Accumulation of surfactant fluid causing increase work of breathing, a diminished area
for gas diffusion and respiratory failure. Patient with pulmonary alveolar protenosis
commonly infected nocardia infection.

37. XRAY IN PAP
• A butterfly distribution typically bilateral symmetrical alveolar filling pattern seen .
close differential diagnosis are pulmonary edema, pneumocystis pneumonia.

38. CT SCAN
• Crazy paving that consist of
scattered or diffuse ground glass
attenuation superimposed
interlobular septal thickening and
intralobular lines

39. BAL FLUID
• Grossly milky and opaque, forming sediment when left to settle

40. HPE
• BAL sediment shows typically the gross appearance of the macrophages with
foamy vacuolated cytoplasm
• In HPE alveoli filled with eosinophilic material which is periodic acid shiff positive

41. RESPIRATORY DISTRESS SYNDROME
• It is a syndrome occurs in premature neonates due to deficiency of surfactant
production
• In fetus surfactant production starts at 24 weeks and peaks at 34 weeks.
• Risk factor for this syndrome includes prematurity, multiple birth ,maternal
diabetes, perinatal asphyxia
• Symptoms includes apnea, cyanosis, decreased urine output, grunting, nasal
flaring, rapid breathing respiratory rate more than 60/min

43. DIFFERENCE BETWEEN MATURE AND IMMATURE
LUNG
• MATURE LUNG
Thin blood gas barrier
Highly compliant
Mature epithelial cell
Adequate surfactant
Large area for gas exchange
Highly vascular
Low resistance to blood flow

44. IMMATURE LUNG
• Thick blood gas barrier
• Low compliance
• Immature epithelial cell
• Low surfactant level
• Small area for gas exchange
• Poorly vascularized
• High resistance to blood flow

45. XRAY IN RDS

46. MANAGEMENT
• It consist airway management and replacement of surfactant intratracheal route
and treatment of preceding complication like septicemia with iv antibiotics.
• Prevented by use of maternal corticosteroids.

47. EMPHYSEMA
• Abnormal permanent dilatation airspace distal to the terminal bronchiole,
accompanied by destruction of their walls and without obvious fibrosis
• It cause dilatation of air spaces by destruction of alveolar wall, leading to collapse
of alveoli during expiration

48. TYPES OF EMPHYSEMA

49. • Centrilobular emphysema ; dilatation of respiratory bronchiole , predominantly
involved in upper lobe , most commonly seen in smokers

50. PANACINAR EMPHYSEMA
• Whole of the acinus uniformly affected, lower lobe involved mostly associated
with alpha 1 antitrypsin deficiency , smoking.

51. PARASEPTAL EMPHYSEMA
• Localized along pleura –peripheral part of the acinus
• Predispose to the spontaneous pneumothorax

52. ALVEOLAR MACROPHAGES
• Alveolar macrophages otherwise known as dust cell
• There is no mucocilliary apparatus in a alveoli so alveolar macrophages plays a
important role in both immune and foreign body removal in lower airway.
• Macrophages engulf the dust particles and remove this through the lymphatics
• In case of heart failure, the lung become congested and the alveoli contain
erythrocytes where they are phagocytosed by alveolar macrophages which are
called as heart failure cell , otherwise known as hemosiderin laden macrophages

53. MESENCHYMAL CELLS OF ALVEOLI
• Fibroblast are mesenchymal cell located in the epithelial and endothelial layer of
alveolar walls .
• Fibroblast produce extracellular matrix components , direct cell growth and
differentiation of neighboring cells by cell-cell and cell-matrix interaction
• Lipofibroblasts are characterized by the presence of lipid droplets and located in
alveolar type2 cell provide source of lipid for surfactant production
• Lipofibroblasts reduced in individual with interstitial pulmonary fibrosis

54. ALVEOLAR SEPTA
• They are generally flat, making the alveoli polyhedral rather than spherical ,
• The septa are perforated by small fenestration known as the pores of kohn ,
which provide collateral ventilation between alveoli.
• It has two side
Active side
Service side

55. ALVEOLAR SEPTA
• Active side of alveolar septa the alveolar wall , the capillary endothelium and the
alveolar epithelium closely apposed , with almost no interstitial space, such that
the total thickness from gas to blood 0.3 micrometer
• Service side is more than 1 to 2 micrometer thick contains recognisable interstitial
space containing elastin and collagen fibres and nerve ending .

56. Thank you