pulmonary defense

1. Pulmonary Defense
Dr. Manu Mohan K

2. Introduction
•Lungs are daily exposed to 10,000
liters of air which contain noxious
particles, infectious agents, etc
•Respiratory system must recognise
and eliminate unwanted elements in
inspired air to keep pulmonary
structures free of infection.

3. •The fact that the normal
respiratory tract is free of
infection is a testimony to the
efficiency of a defense system
•Elements of defense system
spread through out the
respiratory tract

4. Nose and oropharynx
•Formidable barrier
•Nasal hair exclude large particles
•Sneezing and blowing
•Rhinorrhoea
•Mucociliary clearance
•Air conditioning

5. Nose and oropharynx
(contd.)
•Nasal secretion
•Oral cavity – tongue movements
•Secretory IgA in saliva

6. Cough
•Most important protective reflex as
well as most common symptom of
respiratory diseases.
•Provoked by number of stimuli
•Afferent – myelinated irritant nerve
endings, intravascular nonmyelinated
J receptors, via C fibers and
myelinated fibers

7. Cough (contd.)
•Center - medulla 5 HT receptors
•Efferent – nerve supply to larynx,
ribcage and diaphragm

8. Cough (contd.)
•Phases
•Inspiration
•Compression of intrathoracic gas
against closed glottis
•Explosive expulsion as glottis opens
•Relaxation of airways

9. Cough (contd)
•Result
•Expectoration of foreign debris and
mucus from the larger airways due to
extremely high local turbulence by the
reflex
•Chronic bronchitis – 50% clearance is
contributed by cough

10. Cough (contd)
Cough reflex is inhibited by
•physiological – swallowing
•central action – codeine
•blocking the afferent signal – local
anesthetics

11. Mucociliary clearance
• In healthy subjects cough ineffective
in removing inhaled small particles
• Mucociliary clearance almost entirely
responsible for tracheobronchial
cleanliness
• Complex interaction between cilia
and mucus

12. Mucociliary clearance
• 200 cilia per one bronchial epithelial cell.
• Cilia composed of contractile protein tubulin
arranged as nine outer and one central micro
tubular pairs
• Outer microtubule has a pair of dyneine arms
• Mucus forms a raft on top of cilia which
sweeps in the cephalad direction.
• Cilia carry about 10 grams with out slowing
• Cilia beats @ 12-14 times per second

13. Ultra structure of cilia

14. Mucociliary clearance
Test for ciliary motility
•Saccharin test
•Cine bronchography
•Imaging technique

15. Mucociliary clearance
• Mucus secreted by goblet cells and
submucosal glands of the first
several bronchial generations
• Secretions controlled by
neuropeptides like substance P,
Vasoactive intestinal peptide,
bombesin, vagal stimulation -
acetylcholine.

16. Mucus
Physical function
•To trap and clear particles
•Dilute noxious influences
•Lubricate airway
•Humidify inspired air

17. Mucociliary clearance
• The viscoelastic or rheological properties of
mucus determined probably by
concentration of different type of mucins
• External factors influencing mucociliary
clearance
– direct ciliary damage
• cigarette smoke, pollutants, local and
general anaesthetics, bacterial and viral
products, eosinophil products in
asthma, etc

18. Primary Ciliary
Dyskinesia
• Autosomal recessive
• Ciliary dynein may be defective
• Male infertility
• Situs inversus
• Result in repeated sinusitis and
respiratory infection and severe
bronchiectasis

19. Surfactants
•Complex surface active material lining
the alveolar surface
•Reduces surface tension and prevent
lungs from collapsing
•Simple and elegant way of alveolar
clearance
•At end expiration surface tension
decrease and the surface film moves
from the alveoli towards bronchioles

20. Surfactants
•4 types – sp-A, sp-B, sp-C, sp-D
•Functions
•On alveolar macrophages
–Chemotaxis, enhancement of
phagocytosis and killing of
microorganisms

21. Surfactant proteins
•SP- A most abundant
•Closely resemble complement c1q
•Enhances alveolar macrophage
phagocytosis of microorganisms
like staph aureus, pneumocystis
carinii
•SP- D share same effect
•Inhibit endotoxin stimulated
release of interleukin-1, IL-6, TNF

22. Surfactant
•Can be damaged by noxious stimuli
•Alteration of surfactant quantitatively
and qualitatively in ARDS
•Loss of lung function and gas
exchange
•Susceptibility of injured lung to
bacterial colonization and infection
•Surfactant replacement therapy

23. Protective Proteins of
Lung
Antibacterial
surfactant proteins ( A & D),
immunoglobulin ( IgA), defensin,
lactoferrin, lysozyme, complement
Antiproteinases
alpha 1 proteinase inhibitor, alpha 1
antichymotrypsin, alpha 2
macroglobulin

24. Immunoglobulins
•IgA abundant
•IgG and IgM in small quantities
•Produced by B lymphocytes and
plasma cells often associated with
bronchial epithelial cells
•IgA deficiency associated with
local defects in immunity to
bacterial infections

25. Complement proteins
•Alveolar macrophage secrete c3a,
c3b and c5a
•C3 deficiency – recurrent
infections
•Enhances removal of bacteria by
macrophages and other
phagocytes

26. Antiproteinases
•High molecular ( alpha 1
antiproteinase, alpha 2
macroglobulin)
•Low molecular (secretory
leukoproteinase inhibitor and elafin)
•Protect local tissue against
damage that would occur due to
release of proteinases by
inflammatory cells

27. Alveolar macrophages
•Derived from blood borne
monocytes
•Patrol the alveolar lining
•Live for several weeks

28. Functions
• Primary host defense - phagocytosis
• Inflammatory response:
– Initiation
• Generation of neutrophil chemokines ( IL-8)
• Generation of monocyte chemokines (MIP-12)
• Generation of agents that activate endothelial
cells (IL-1, TNF alpha)
– Amplification
• stimulate bone marrow generation of
leucocytes ( IL-1, TNF alpha, IL-3)
– Resolution
• scavenging of necrotic and apoptotic cell
debris

29. Functions
• Repair and fibrosis
• Remodeling: elastase, collagenase
• Scar formation: IL-1, PDGF, FGF
• Immune response
• Antigen presentation
• Anti tumour effect
– Lysis of tumor cells by TNF alpha and nitric oxide
dependent mechanisms

30. Pulmonary marginated
pool of neutrophils
• Circulating pool
• Marginated pool
• Dynamic equilibrium
• Exercise and epinephrine
• Vascular bed of the lung and spleen
• Neutrophils loitering in pulmonary
microvasculature- local immunity

31. Defense mechanism in the alveolar
spaces

32. Effects of Smoking

33. `

34. Pulmonary function test

35. PFT
•Objectively measure the ability of
lungs to ventilate and carry out gas
exchange

36. Components
• Tests of airway function
• Tests of pulmonary volume
• Tests of gas exchange
• Tests of respiratory muscle function
• Tests of ventilatory control
mechanism
• Tests of exercise performance

37. Indications
• Establishing or excluding a respiratory
cause of dyspnea
• Diagnosis of obstructive airway disease
• Localize site of obstruction
• Prognostic purpose
• Evaluation of pulmonary involvement in
systemic diseases or side effect of drugs
like amiodarone
• Preoperative evaluation
• Epidemiological observations
• Evaluation of exercise performance

38. Principle
•Measure either displaced
volume or air velocity
•All volumes are expressed at
BTPS (body temperature ambient
barometric pressure and
saturation)

39. Tests of Airway Function
• Peak expiratory flow
• Most widely used
• Measure maximum expiratory
flow rate over the first 10
milliseconds of an expiration
• Effort dependent
• Reduced in airway obstruction
and expiratory muscle weakness

40. Forced expiratory
volume
• Integrated flow over first second of expiration
• Normal 70 – 80%
• Airway obstruction
• FeV1 reduced more than forced vital capacity
so that FeV1/FVC is reduced below 70%
• Restrictive
• Both FeV1 and FVC are reduced
proportionately, so that the FeV1/FVC is
normal.

41. Normal flow volume loop

42. Flow volume loop in severe
airway obstruction

43. Flow loop in restrictive
lung disease

44. Maximum midexpiratory
flow rate (MMEFR)
•FeF(25-75%) is the average expiratory
flow during middle half of the forced
vital capacity
•More variable than FeV1
•Sensitive index of small airway
function

45. Flow volume loop
•Is also useful for localizing the site
of obstruction
•Whether intrathoracic or
extrathoracic
•Whether fixed or variable

46. Flow volume loop in
extrathoracic obstruction

47. Flow volume loop in
variable intrathoracic
obstruction

48. Flow volume loop in fixed
airway obstruction

50. Test of Lung Volume
• Measurement of lung volumes
provides valuable and functional
information.
• Total lung capacity and residual
volume measurement require
indirect methods such as gas
dilution technique or
plethysmography

52. • Airway disease increase residual
volume, the RV/TLC % is
increased.
• Parenchymal diseases produce a
restrictive ventilatory defect
reducing total lung capacity and
vital capacity with RV unaffected.

53. Respiratory muscle
function
•Peak inspiratory and Peak
expiratory maximal mouth pressure
by sucking at and breathing out
respectively against the shutter of
pressure transducer device

54. Diffusing capacity
•Carbon monoxide gas transfer
•Mixture of helium and carbon
monoxide 0.03%
•The change in the concentration of
gases are measured by automated
equipment.
• DLCo reduced in ILD,Pneumonia

55. Exercise test
• Measure integrated
cardiorespiratory functions
• 6 or 12 minute walk test
• Plotting heart rate and minute
ventilation against o2 uptake with
estimation of respiratory quotient–
cycle ergometer or tread mill.

56. •Arterial blood gas measurement
•Noninvasive oxymetry