2. Pathology of the Respiratory System

Joiner- Pulmonary cell types, secretions & other components

what cell type lines the entire respiratory tract

epithelium

what are the specialized types of epithelia found in the respiratory tract?

1. olfactory neuroepithelium (smell receptors)

2. stratified squamous epithelium

3. ciliated (pseudostratified) respiratory epithelium

where is olfactory neuroepithelium found?

present in portions of the nasal cavity near the ethmoturbinates

t/f: olfactory neuroepithelial cells have limited regeneration capacity

true

what do olfactory neuroepithelial cells contain that metabolizes inhalants

cytochrome P450 mixed function oxidases

what are the consequences of olfactory neuroepithelium containing cytochrome P450 mixed function oxidases?

metabolites may have enhanced toxicity & cause tissue damage

what type of epithelial cells covers the nares & larynx

stratified squamous epithelium (resistant to injury)

what type of epithelial cells covers ~95% of the conductive system

ciliated epithelial cells

where are non-ciliated (Club or Clara) cells found?

small bronchioles

what cell is considered to be the stem cell of the upper and lower respiratory tract

Non-Ciliated (Club) cells

what do non-ciliated (club) cells secrete?

tin, proteinaceous fluid (sol layer)

t/f: Non-ciliated (club) cells are metabolically active

true, they contain mixed function oxidases that detoxify compounds

cell types in the gas exchange system

Alveolar epithelium (Type 1 pneumocytes, Type 2 pneumocytes), Macrophages, Endothelium, Fibroblasts

very thin cells that line the alveolar spaces

Type 1 pneumocytes

Type ___ pneumocytes are metabolically inactive

1

Type 1 pneumocytes over ___% of the alveolar surface

1

what is the function of Type 1 pneumocytes

gas exchange & prevent leakage of fluid / protein from alveolar intersititium into airspace

t/f: Type 1 pneumocytes are very susceptible to hypoxic damage

true

Type ___ pneumocytes are metabolically active cells

2

Type ___ pneumocytes produce surfactant to prevent alveolar collapse & atelectasis

2

Type __ pneumocytes replace themselves and the other type of pneumocytes

2

how does surfactant work?

reduces the surface tension of the alveolus

what are the distinct types of macrophages in the gas exchange system (3)

Pulmonary alveolar macrophages, Interstitial macrophages, Pulmonary intravascular macrophages

Pulmonary alveolar macrophages are derived from

blood monocytes

Function of pulmonary alveolar macrophages

phagocytosis of infectious agents and particulates; migrate to the intersititium or lymph nodes

pulmonary interstitial macrophages are derived from

bone marrow

_______ _______ macrophages express MHC1 & MHC2 antigens

Pulmonary intersitial

______ ______ macrophages are a vital component of antigen capture, processing, and presentation for adaptive immune responses

Pulmonary intersitial

Pulmonary intravascular macrophages have been identified in what spp?

cattle, sheep, goats, pigs, cats, & horses

_______ _____ macrophages adhere to the pulmonary alveolar capillary endothelium

Pulmonary intravascular

______ ______ macrophages function in clearance of circulating bacteria and particulates

Pulmonary intravascular

t/f: pulmonary intravascular macrophages respond to endotoxin

true

what are the classes of surfactant?

Hydrophilic: SP-A & SP-D (the “collectants”)

Hydrophobic: SP-B & SP-C

What is surfactant comprised of?

phospholipids, proteins, peptides

(lecithin & phosphatidyl glycol)

what is necessary for the production of surfactant

oxygen

which classes of surfactant lowers the surface tension in the alveolus, allowing the alveolar space to remain patent

SP-B & SP-C

what upregulates SP production?

B catecholamines

Loss of surfactant results in

pooling of fluid in the alveolar space w/ decreased function in gas exchange

which classes of surfactant are involved in innate immunity?

SP-A & SP-D (Collectins that help phagocytes attach to and ingest bacteria)

t/f: surfactant decreases immune mediated pulmonary injury

true

a1-anti-trypsin is a glycoprotein produced by the

liver & lung

what does a1-anti-trypsin do?

inhibits the proteolytic enzymes (elastase, collagenase, trypsin & chymotrypsin)

Definciency in a1-anti-trypsin results in

balance in favor of the proteolytic enzymes with increased tissue destruction which is associated with emphysema

t/f: lower respiratory tract is essentially sterile

true

Portals of entry into the lung; How do pathogens make their way into the lungs? (3)

Aerogenous: inspired air

Hematogenous: septicemia, protozoal infections, viruses that target endothelial cells; carried in circulating leukocytes

Direct extension: penetrating injuries, ruptured esophagus, perforated diaphragm

mechanisms of particle deposition

impaction, sedimentation, deposition (there is a balance between deposition of particles onto the surfaces in the respiratory tract and the clearance of the particles)

_____ _____ determines the fate of inhaled particles

particle size

particles >10 um are

filtered (impaction) in nasal cavity

particles 2-10 um; what happens?

impaction at bifuraction of tracheobronchial tree

when you inhale particles 0.3-2 um in size; what happens?

sedimentation at bronchiolar alveolar junction

particles <0.3 um in size; what happens?

diffusion, most remain suspended and are exhaled

Function of mucociliary escalator

removed particles by flow of mucus toward the mouth and nose; ciliated cells propel the mucus upward toward nasopharynx

Anatomy of mucociliary escalator

double layer of mucus:

surface layer of thick mucus (gel)

underlying layer of thin serous fluid (sol)

_____ _____ macrophages phagocytize particulates & bacteria in alveoli

pulmonary alveolar macrophages

_____ ____ macrophages produce inflammatory mediators, especially in response to endotoxin

pulmonary intravascular

the rate of phagocytosis depends on the

bacterial spp.

what factors decrease the rate of phagocytosis?

hypoxia, acidosis, high levels of cortisol

immunity in the upper and lower airways is typically

humoral

sensitized plasma cells secrete ___ into the mucus of BALT for antigen specific (adaptive) immunity

sIgA

Immunity in the alveolar space is

humoral or cell mediated

Humoral alveolar immunity is a ______ response

systemic

what systemic antibody is found in alveolus

IgG

cell mediated immune responses in the alveoli are often dependent on

pathogens

t/f: alveolar immune responses can damage the lung

true (due to the delicate nature of the alveoli)

Benefits of IgA (mucosal immunity)

1. sIgA binds to antigens without activating complement

2. prevents adhesion of bacteria, viruses, and allergens

3. pathogen is cleared by the mucociliary escalatory without inflammation

Benefits of IgG (alveolar immunity)

1. systemic long-lived immunity w/ memory

Bronchial immunity is typically associated with Ig__

IgA

______ infections are often a leading cause of impaired pulmonary immunity

viral

How do viruses impair pulmonary immunity

1. depress macrophage & immune functions

2. reduce mucociliary clearance

3. predispose to secondary bacterial infections (viral-bacterial synergism)