Lung defence Flashcards
What is respiratory epithelium? 3 functions of this?
Ciliated pseudo stratified columnar epithelium?
1) Serves to moisten and protect the airways
2) Barrier to potential pathogens and foreign particles
3) Prevents infection and tissue injury by action of mucociliary escalator
Respiratory epithelia releases what substances? How does mucus provide protection? Various skin glands, salivary glands and lacrimal glands secrete what antimicrobial chemicals?
Mucus, anti-fungal peptides, anti-microbial peptides.
Contains antibodies and is sticky- particles adhere to it and swept by ciliary action into pharynx and swallowed or phagocytosed by macrophages
Antibodies, lysozyme, and lactoferrin- prevents bacteria obtaining iron
Where are receptors for the cough reflex? What neurons are stimulated? What things occur?
In the larynx, trachea and bronchi
The medullary inspiratory neurones– deep inspiration, epiglottis closes, vocal cords shut tightly, abdominal and internal intercostal muscles contract, pressure in lungs rises, trachea narrows.Vocal cords and epiglottis suddenly open widely– rapid flow rates and air is expelled.
What substance inhibits the cough reflex? Alcholics susceptible to what?
Alcohol– choking and pneumonia.
What does airway mucus contain? Transported from lower respiratory tract into pharynx by what? Consists of what 2 layers?
Viscoelastic gel containing water, carbohydrate, protein and lipids.
Mucociliary escalator
Superficial gel/ mucous layer and a liquid fluid layer bathing epithelial cilia (surfactant)
Following injury to the airway epithelium, how can it carry out a full repair? What happens if this process goes wrong?
Epithelium exhibits a level of functional plasticity
Results in pulmonary disease
Bronchoconstriction in asthma results in what? Can do what?
Excessive mucus production– mucus plugs (secretion of epithelia and submucosal glands)
Obstruct airways and are often fatal
Hypersensitivity is more prevalent in what immunity type?
Adaptive rather than innate (formation of immunological memory)
What things happen when bacteria are introduced to a wound? What is diapedesis? What then happens?
Chemical mediators cause vasodilation and capillary permeability and chemoattractants recruit neutrophils to the area
Leukocytes pass out of blood into surrounding tissue– neutrophils enter tissue where phagocytose bacteria
Capillaries return to normal as neutrophils continue to clear the infection
What is acute inflammation in lung initiated in and typically by what? They initiated what?
In tissues- by specialist tissue resident macrophages including:
Kupffer cells (liver)
Alveolar macrophages
Histiocytes (skin, bone)
Cascade of events that result in inflammation
Macrophages respond to pathogens/ tissue by recognising what?
PAMPs (pathogen-associated molecular patterns) and DAMPs (damage-associated molecular patterns)
Macrophages recognise new pathogens using what? What is one major receptor?
Pattern recognition receptors (PRRs)- part of innate immunity recognise common antigens on bacteria
Toll-like receptor (TLR)
What are TLRs expressed in? What do these recognised and bind to?
The plasma and endosomal membranes of macrophages and dendritic cells
PAMPs- e.g. viral and bacterial nucleic acids and protein found in flagellum of bacteria
When binding of TLR occurs on the plasma membrane of a macrophage, what are generated? This leads to the secretion of what? These stimulate what?
Second messengers within the immune cell
Inflammatory mediators e.g. IL-1, IL-12 and TNF-a
Immune cells involved in innate response e.g. neutrophils and some involved in adaptive immune response
Alveolar macrophages comprised what % of the pulmonary macrophages? What are they functionally similar to? Ari se from what and where?
93%
Macrophages
Monocytes- produced in the bone marrow
Monocytes have a high what capacity? They have susceptibility to what? What level of ATP generation?
Phagocytic
Apoptosis
Intermediate
Tissue macrophages have what level of phagocytic capacity? What level of ATP generation? What level of susceptibility to apoptosis?
High-intermediate
High
Low
Functions of alveolar macrophages? Meant to destroy bacteria how in what way? Can illicit huge response by calling in what? Leads to what condition?
Resident phagocyte of the lungs, co-ordinates the inflammatory response and induction and clearance of apoptotic cells
With little help i.e. without inducing a massive immune response
Neutrophils
Pneumonia
Neutrophils contain which are released to help combat infection in what process? Primary granules contain what substances?
Degranulation
Myeloperoxidase- enzyme carries out anti-microbial activity, elastase- breaks down elastin in lungs and cathepsins+defensins- anti-bacterial proteins
Secondary granules contain what substances? Collagen particles from break down act as what mechanism type?
Receptors, lysozyme and collagenase (breaks down collagen)
Self-amplifying- causes more neutrophils to come to area
6 Functions of neutrophils?
Identify the threat- through receptors Activation Adhesion Migration/ chemotaxis Phagocytosis Bacterial killing
How do neutrophils identify a threat? Receptors detect what? Recognises what?
Via receptors- recognises bacterial structures
Host mediators- signal of attack; cytokines, lipids
Host opsonins- substance binding microbe to a phagocyte to promote phagocytosis e.g. FcR and CR3
How are neutrophils activated? Signal transduction pathways involves what?
Via stimulus response coupling
Calcium, protein kinases, phospholipase and G proteins
Neutrophils are loosely tethered to the endothelial cells of a blood vessel by what? Known as what? Exposes the neutrophil to what being released in the injured area? These induce the rapid appearance of what?
Selectins
Margination- as neutrophil rolls along the vessel surface
To chemoattractants
Integrins on plasma membrane- bind to matching molecules of endothelial cells so neutrophils collect along injury site rather than washed away with flowing blood
Once in interstitial fluid, neutrophils follow what gradient? Why is this?
A chemotactic gradient- migrate towards site of tissue damage= chemotaxis
Pathogen-stimulated innate immune cells release chemoattractants
What is one of the major triggers for phagocytosis? Why may engulfing not occur? Chemicals that bind phagocyte tightly to microbe known as what?
Interaction of phagocyte receptors with certain carbohydrates/ lipid in microbial cell wall
Bacteria surrounded with thick gelatinous capsule
Opsonin
What membrane complex generates hydrogen peroxide and nitric oxide in neutrophils? Hydrogen peroxide converted to what?
NADPH oxidase
Hydroxyl radical destroys the pathogen
What is necrosis? What substances released can damage surrounding tissue? Results in what?
What is apoptosis?
Cells swell, the lyse, reactive oxygen species and other enzymes
Results in inflammation and phagocytosis of necrosed cell
More controlled, cell turned off and packaged to then be phagocytosed by neutrophils with no surrounding tissue damage
Why can only macrophages, B cells and dendrite cells function as antigen presenting cells? After combing with antigen, do what? What 2 things induces B cell activation?
They express class II MHC proteins Undergo activation and migrate to site of B cell activation T helper cells making direct contact along with cytokine secretion
In cytotoxic T cell activation, T helper cell assists activation indirectly via what other cells?
Dendritic cells
Where are B cells stored? 5 types of antibody?
In secondary lymphoid organs
IgA, IgD, IgE( to things we’re allergic to,) IgG (most abundant) and IgM (made at beginning of infection)
Each antibody recognises a specific what?
Epitope- portion of antigen recognised by specific antibody
What is hypersensitivity?
The over-reaction by immune system to things you don’t need to react to. Responses to environmental antigens– inflammation and damaged to body itself.
Antibody involved in type 1 reactions? Also called what? Examples? What is atopy? Diagnosed via what?
IgE
IgE- mediated hypersensitivity/ acute anaphylaxis
Hayfever, asthma
Inherited tendency to exaggerated IgE response to antigen
Skin prick test
In type 1 reactions, initial exposure to antigen leads to production of what? Particular antigens in those with atopy stimulate production of what?
Some antibody synthesis and B memory cell production
Type IgE antibodies
Production of IgE requires participation of specific type of what? These cells trigger the mast cell to secrete what? Examples? If large amounts of mediators enter circulation, what can occur?
T helper cell that are activated by allergens presented by B cells
Inflammatory mediators
Histamine and chemokines
Systemic symptoms e.g. severe hypotension, vasodilation and bronchoconstriction– mucous hypersecretion= anaphylaxis.
When do type 2 reactions occur? Leads to what 2 things? Example of the hypersensitivity?
When antibodies IgM/ IgG bind to cell-surface-associated antigens
Tissue injury/ altered receptor function
Haemolytic disease of the newborn
Antibody involved in type 3 reactions? Binds to what to form what? Deposited where? Activates what 2 things?
IgG
Soluble antigen forming a circulatory immune complex.
In skin, lung, kidneys etc.
Immune response and local inflammation– tissue damage
Examples of type 3 reactions?
Farmers lung- inhale mouldy hay resulting in flu-like illness
Malt-workers lung
Mushroom workers lung
Pigeon fanciers lung
What are type 4 reactions mediated by? due to secretion of what by helper T cells?
Helper T cells and macrophages.
Cytokines- act as inflammatory mediators and activate macrophages to secrete their potent mediators
Type 4 reactions known as what? Reactions to what disease? Seen in granulomatous diseases such as what? What from poison ivy?
Delayed hypersensitivity
TB
Sarcoidosis
Contact dermatitis
Some changes to lungs with ageing?
Delayed response to hypercapnia and hypoxia
FEV and FVC decreases, so FEV1/ FVC decreases- spirometry may indicate obstructive
Why is gas exchange impaired as you get older?
Costal cartilage becomes stiffer, respiratory muscle decreases in mass, reduction in type IIA muscle fibres, denervation of muscle fibres, loss of elastic recoil, elastin fibres in alveoli and bronchioles degenerate
Other changes to lungs as you get older?
Ventilation- perfusion (V/Q( mismatch increases, alveolar SA decreases, lung capillary and blood flow reduced, oxygen saturation of haemoglobin declines
Why does immune system function decreases in lungs as get older?
Glandular epithelia cells decrease thus less protective mucus, decrease sputum clearance, less effective mucociliary system
How is Pi(pressure of inspired gas) calculated? PiO2 at sea level? How many feet is extremely high altitude?
Patm x FiGas(fraction of inspired gas)
100kPa x 0.21= 21KPa
18,000 feet
How is PaO2 calculated? What is A-aD? Tends to be what value?
PaO2= PAO2- A-aDO2
Arterial-alveolar difference
1kPa-gravity increases filling of blood in vessels in bottom of lung– ventilation-perfusion inequalities
Normal blood gases at sea level?
PaO2= 10.5-13.5kPa PaCO2= 4.5-6.0 kPa pH= 7.36- 7.44
As altitude increases, what happens to pressure? FiO2 remains at what value? What happens to PiO2?
It decreases, but is not a linear relationship
0.21
It falls with altitude
Normal response to high altitude? How is alkalosis compensated for?
Hypoxia– hyperventilation (normally at 10,000 feet), results in; increased minute ventilation, lowers PaCO2, alkalosis initially and tachycardia
Renal bicarbonate excretion
Acute mountain sickness above what height? Lake Louise score greater than what? Must have what symptoms? Only treated how? Who at risk?
Above 2500m Score of 3 Headache and one other e.g. lethargy, shortness of breath With descent Younger people at risk
High altitude pulmonary oedema affects who? What 3 things? Caused by what? Risk is less if you do what? Treat with what?
Unacclimatised individuals Acute mountain sickness, cough and shortness of breath Rapid ascent above 8000ft If you sleep below 6000ft Oxygen and descent
Atmospheric cabin pressure in a plane? Cabin atmosphere?
21kPa
8000ft,breathing 15.1% O2 at sea level(fraction still 21%, pressure lower so equilibrates to 15.1%)
Every 10m of water is how many atm? What is Boyle’s law?
10m= 1atm
At constant temperature, absolute pressure of a fixed mass of gas is inversely proportional to its volume
P1V1= P2V2
What is Henry’s law? How much gas dissolves in tissues at depth? What if divers ascend too quickly?
The amount of a gas dissolved in a liquid at a given temperature is directly proportional to the partial pressure of the gas.
More gas dissolves at depth, so if ascend at rate that exceeds body’s capacity to clear excess gas- inert bubbles may form in tissues– decompression illness
What is the diving reflex with free diving?
Aponea (stop breathing,) bradycardia and peripheral vasoconstriction
