Case 2 Sem 2 Flashcards
(104 cards)
1
Q
what is asthma?
A
Inflammation of air passages in lungs, sensitive nerve endings in airways become easily irritated. In an attack, lining of air passages swell causing them to narrow, reducing flow of air in and out of lungs
2
Q
Symptoms of asthma
A
Dysplasia, coughing, wheezing (varies over time), tightness of chest, feel worse at night (postural changes, triggers)
3
Q
Status asthmatics
A
A state of unremitting attacks
4
Q
Characteristics of asthma
A
Airflow limitation
Bronchial hyper responsiveness (easily triggered bronchospasm as a result of stimuli)
Inflammation of bronchi (T lymphocytes, mast cells, eosinophils (plasma exudation), oedema, smooth muscle hypertrophy, matrix disposition, mucus plugging and epithelial damage
5
Q
Chronic asthma
A
Inflammation accompanied by irreversible airflow limitation as a result of airway wall remodelling
6
Q
Atopic (extrinsic asthma)
A
Type 1 IgE mediated hypersensitivity reaction
Begins in childhood, triggered by environmental allergens
Family history of asthma
Family history of allergic rhinitis
7
Q
Non atopic (intrinsic)
A
No causative agent
No evidence of allergen sensitisation
Skin test results are negative
Family history of asthma less common
Respiratory infections due to viruses are common triggers, hyper irritability of bronchial tree
8
Q
Aspirin induced asthma
A
Aspirin sensitive asthma occurs with recurrent rhinitis and nasal polyps
Also experience urticaria
Aspirin inhibits cyclooxgenase pathway of arachidonic acid metabolism without affecting lipoxygenase route, thus tipping balance toward elaboration of the bronochonstrictor leukotrienes
9
Q
Propranolol induced asthma
A
Sympatholytic non selective beta blocker (antagonist)
Treats hypertension, anxiety and panic
10
Q
Sympatholytic (propranolol)
A
Inhibits post ganglionic functioning of sympathetic nervous system, achieved through blocking beta adrenergic receptors
11
Q
Occupational asthma
A
Minute quantities of chemicals induce attack, usually occurs after repeated exposure
Indulge type 1 hypersensitivity reactions, direct release of bronchocontrictor substances
12
Q
Clean hypothesis
A
Childhood exposure to germs and infections help the immune system to develop (immune system doesn’t overreact)
13
Q
Cold air and exercise
A
Cold air is less humid than warm air, cools and drys epithelial cells, immune cells etc, precipitating attack. Usually occurs after exercise
14
Q
Allergen induced asthma (atopic asthma)
A
1)Immediate asthma: airflow limitation starts within minutes of contact with allergen, max 15-20 minutes, subsides by 1 hour
2) dual and late phase reactions: follows immediate reaction, develop a prolonged and sustained airflow limitation which responds less well to inhalation of bronchodilators eg salbutamol
15
Q
Initial sensitisation to inhaled allergens stimulates
A
Th2 cells
16
Q
Th2 cells secrete
A
Cytokines that promote allergic inflammation and B cells to produce IgE and IL4, IL5, IL13
17
Q
IL4
A
Stimulates production of IgE by B cells
18
Q
IL5
A
Eosinophil chemotactic agent secreted by mast and epithelial cells, Th2
19
Q
IL13
A
Stimulates mucus secretion from bronchial submucosal glands and promotes IgE production by B cells
20
Q
Sensitisation
A
Fc part of IgE binds to FCER on mast cells/basophils, exposing its variable region (this IgE loading takes 10-15 days)
Mast cells are ready to work next time the allergen appears, causing an initial phase reaction and secondary reaction
21
Q
Initial phase reaction
A
Upon stimulation, mast cells undergo degranulation, secreting preformed primary mediators (histamine, proteases, neutrophil chemotactic factor and eosinophil chemotactic factor)
22
Q
Histamine effects
A
Vasodilation
Increase vascular permeability leading to partial edema
Spasmatogenic
Increase glandular secretions causing luminal obstruction (narrowing of lumen tract)
23
Q
Protease effect
A
Further tissue damage, causing release of more inflammation mediators. Convert C3 and C5 into C3a and C5a which bind to receptors on mast cells,stimulating mast cells further
24
Q
Spasmatogenic
A
Histamine receptors found on smooth muscle lining of various tracts. Histamine causes them to contract
25
Secondary reaction
Inflammation with recruitment of leukocytes
Upon stimulation, nucleus of mast cell activated leading to protein synthesis of cytokines (small soluble proteins released by mast cell and epithelial cells, act as signalling molecules, secondary mediators)
Second wave of mediators stimulates late reaction (eotaxin, MBP - major basic protein)
Mast cells secrete leukotrienes, attract neutrophils
Eosinophils secrete granular contents (histamines and enzymes that destroy leukotrienes, reducing attraction of neutrophils)
26
IL3
Chemotactic agent for eosinophil, secreted by mast and epithelial cells, Th2
27
Eotaxin
Produced by airway epithelial cells, potent chemoattractant and activator of eosinophils
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MBP
Major basic protein of eosinophils causes epithelial damage and airway constriction
29
Mediators in asthmatic response
Leukotrienes C4, D4 and E4 (cause prolonged bronchoconstriction and increased vascular permeability, increased mucus secretion)
Acetylcholine (released from intrapulmonary motor nerves, cause airway smooth muscle constriction by directly stimulating muscarinic receptors)
30
Airway remodelling
1. Hypertrophy and hyperplasia of bronchial smooth muscle (hyperplasia of helical bands of airway smooth muscle, smooth muscle alters in function to contract more easily and stay contracted because of change in actin myosin cross link cycling) allowing the airways to contract too much/too easily
2. Epithelial injury in airways, loss of ciliated columnar cells into lumen. Metaplasia occurs with increase in number and activity of mucus secreting goblet cells
3. Increased airway vascularity
4. Increased subepithelial mucus gland hypertrophy/hyperplasia
5. Overall thickening of airway wall
6. Basement membrane thickened due to subepithelial fibrosis with deposition of types 3 and 5 collagen below true basement membrane
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Bronchospasm
Airways contract too easily
32
Mast cells are present in
Perivascular tissue (connective tissue around vessels ), under mucosal lining of skin, respiratory tract, GI tract, urogenital tract. Well distributed, increasing chance of free antigen binding to loaded mast cell
33
Mast cells can be stimulated by
Cross linking of loaded IgE by multivalent antigens
C3a, C4a, C5a (mast cells have receptors for these)
Drugs: codine and morphine
Venoms eg bee sting
34
status asthmaticus
Most severe form, severe acute paroxysm (sudden attack) persists for days/weeks
Lungs overdistended because of overinflation, with small areas of atelectasis
Airflow obstruction so extreme may cause severe cyanosis and even death
35
Atelectasis
Partial or complete collapse of lung
36
Curshmann spirals
Spiral shaped mucus plugs containing shed epithelium resulting from mucus plugging in subepithelial mucous gland ducts which later are forced out, plugs in bronchioles
37
Morphology of asthma
Occlusion of bronchi and bronchioles by thick mucus plugs, eosinophils and Charcot Leydin crystals
38
Acute asthma attack lasts
Up to several hours
39
Charcot Leyden crystals
In sputum (atopic asthma)
Collections of crystalloid made up of eosinophil lysophospholipase binding protein (galectin 10)
40
Diagnosis of asthma
Compatible clinical history
FEV1 15% or more (and 200ml) increase following administration of bronchodilator/trial of corticosteroids
20% diurnal variation on 3 or more days in a week for 2 weeks on PEF diary
FEV1 15% decrease or more after 6 mins of exercise
41
Treatment of asthma
Bronchodilators (reverse broncospasm of immediate phase)
Anti inflammatory agents (inhibit or prevent inflammatory components of both phases)
42
B2 adrenergic receptor agonists (bronchodilator)
Eg salbutamol, salmetrol
Dilate bronchi by direct action on B2 adrenergic receptors of smooth muscle
Inhibit mediator release from mast cells and TNF a release from monocytes
Increase mucus clearance by action on cilia
43
Short action B2 adrenergic receptor agonist
Salbutamol
Given by inhalation
Max effect occurs within 30 minutes, duration of action (3-5 hours)
Used as needed to control symptoms
44
Longer acting B2 adrenergic receptor agonist
Salmetrol
Givin by inhalation
Duration of action (8-12 hours)
Not used as needed, given twice daily as adjunctive therapy in patients whose asthma is inadequately controlled by glucocorticoids
45
Side effects of B2 adrenergic receptor agonists
Tremor, tachycardia and cardiac dysrhythmia
46
Xanthine drugs (bronchodilator)
Theophylline
Inhibitor of phosphodiesterase, resultant increase in cAMP causing muscle relaxation
Bad risk:benefit ratio
47
Theophylline side effects
CNS: stimulant (tremor, sleep disturbance)
Cardiovascular (stimulates heart, vasodilation)
GI tract (anorexia, nausea, vomiting)
48
Muscarinic receptor antagonists (bronchodilator)
Ipratropium
Blocks actions of acetylcholine at receptor in parasympathetic nervous system
Low levels of acetylcholine released from cholinergic nerves in airways
Few muscarinic receptors activated
Inhibit elevated mucus secretion and cause bronchodilation
Well tolerated
49
Cysteinyl leukotriene receptor antagonists (bronchodilator)
Montelucast
Prevents exercise induced asthma, decreases early and late responses to inhaled allergen
Their action is additive with B2-Adrenoceptor agonists
Reduce sputum eosinophilia
Act as cysteinyl leukotriene receptors on bronchiole smooth muscle cells, blocking C4, D4
Prevent actions of bronchial spasmogens
Stimulate mucus secretion
50
Side effects of montelucast
Headache
GI disturbances
51
Anti inflammatory agents
Given by inhalation
Full effect usually takes a day or two
52
Glucocorticoid (asthma)
Beclometasome
Not bronchodilator
Prevent progression of chronic asthma (prophylactic)
Effective in acute severe asthma
Decrease formation of cytokines esp Th2 (recruit and activate eosinophils IL5)
Promote production of IgE and expression of IgE receptors
Inhibit generation of PGE2 and PGI2 vasodilators
53
Glucocorticoids reduce production of
Cytokines
Spasmogens (LTC4 and LTD4)
Leukocyte chemotaxins (LTB4, PAF)
54
Glucocorticoids reduce
Bronchospasm
Recruitment and activation of inflammatory cells
55
Mechanism of glucocorticoid action
Enter cells
Bind to Intracellular receptors in cytoplasm (GRa and GrB)
Receptor complex move to nucleus
Binds to DNA in nucleus
Alter gene transcription (eg induction of lipoprotein, repression of IL3)
56
Reduces synthesis of IL3 observations
Long term steroid treatment reduces the number of mast cells in respiratory mucosa, and suppresses early phase response to allergens and exercise
57
Side effects of glucocorticoids and asthma
Oral Candida
Sore throat
Croaky voice
58
Tidal volume
The volume of air displaced between normal inspiration and expiration (= 500ml)
59
Inspiratory reserve volume
Extra volume of air that can be inspired over and above the normal tidal volume when person inspires with full force (3000ml)
60
Expiratory reserve volume
The maximum extra volume of air that can be expired by forceful expiration after the end of a normal tidal expiration (=1100ml)
61
Residual volume
The volume of air remaining in the lungs after the most forceful expiration (=1200ml)
62
Maximum volume equation
Tidal volume + Inspiratory reserve volume + Exporatory reserve volume + residual volume
63
Pulmonary capacities
Considering two or more volumes together
64
Inspiratory capacity
Tidal volume + Inspiratory reserve volume (=3500ml)
The amount of air a person can breathe in, beginning at a normal expiratory level and distending the lungs to maximum amount
65
Functional residual capacity
Expiratory reserve volume + residual volume (=2300ml)
The amount of air that remains in the lungs at the end of normal expiration
66
Vital capacity
Inspiratory reserve volume + tidal volume + expiratory reserve volume (=4600ml)
Maximum amount of air a person can expel from lungs after first filling the lungs to their maximum extent and then expiring to the maximum extent
67
Total lung capacity
Inspiratory reserve volume + tidal volume + expiratory reserve volume + residual volume (=5800ml)
The maximum volume to which the lungs can be expanded with the greatest possible effort
68
Gender and athleticism (pulmonary volumes and capacities)
Pulmonary volumes and capacities are 20-25% less in women than men, greater in large and athletic people
69
Arterial blood gases
Blood test that measures:
Arterial oxygen tension (arterial partial pressure of O2 = PaO2)
Arterial carbon dioxide tension (arterial partial pressure of CO2 = PaCO2)
Acidity of arterial blood (pH)
70
Normal range of arterial oxygen tension
12.0-13.3kPa (80-100mmHg)
71
Hypoxaemia
PaO2 below normal range
72
Hypoxia
Failure of oxygenation at tissue level
73
Normal range of arterial carbon dioxide tension
4.8-6.1kPa (35-45mmHg)
74
Hypercapnia
Increased PaCO2, results in decreased pH (more acidic) of blood due to its conversion into carbonic acid which then dissociates into H+ ions and bicarbonate ions (HCO3-), causes increased respiratory rate to get more blood to the lungs for gas exchange (of CO2 out of the body)
75
Normal range of acidity of arterial blood
7.35-7.45
76
Pulse oximetry
Pulse oximeters with finger/ear probes, non invasive continuous assessment of oxygen saturation in patients, assesses hypoxaemia and its response to therapy. Measures the difference in absorbence of light by oxygenated and deoxygenated blood to calculate its oxygen saturation (SaO2)
77
Peak Expiratory Flow Rate (PEFR)
Maximum rate at which a person can forcibly expel air from their lungs at any time
Expressed in litres per minute (L/min)
Values dependent on height (1.8m = 500L/min)
Low value can diagnose asthma
Subjects asked to take full inspiration to total lung capacity and blow out forcibly into peak flow meter
78
Spirometry
Person inspires maximally to the total lung capacity and exhales into the spirometer with the maximum expiratory effect as rapidly and as completely as possible
Measures forced expiratory vital capacity (FVC) and the forced expiratory volume at the end of the first second (FEV1)
FEV1 expressed as percentage of FVC (ie how much of the FVC is exhaled by the end of the first second)
Image compares FVC of a normal person to a person with airway obstruction
Healthy person: larger lung volume, larger FEV1 (80%)
Airway obstruction: lower lung volume, lower FEV1 (47%)
In serious acute asthma, FEV1 can decrease to less than 20%
79
Type 1 respiratory failure
Hypoxia without hypercapnia
80
Type 2 respiratory failure
Hypoxia with hypercapnia
81
Source of energy for diffusion
Kinetic motion of gas molecules. Free molecules have linear movement at high velocity until they strike other molecules, then they are deflected in a new direction and collisions occur (rapid and random movement of gas molecules)
82
Direction of net gas diffusion
Diffuse from area of high conc to area of low conc along the conc gradient
The rate of diffusion from a high to low conc is faster than from low to high conc
83
Pressure caused by
Multiple impacts of moving molecules against a surface
84
Pressure is directly proportional to
The concentration of the gas molecules
85
Partial pressure
The rate of diffusion of a gas is directly proportional to the pressure caused by that gas alone
86
The partial pressure of a gas in solution is determined by
It’s concentration
The solubility coefficient of the gas
87
Solubility coefficient
Attracted to water = soluble (more dissolved gas molecules without a change in partial pressure within solution)
Repel water = less soluble (high partial pressure with fewer dissolved gas molecules)
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Higher the solubility coefficient, the lower the
Partial pressure
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Henry’s law
Partial pressure = conc of dissolved gas/solubility coefficient
90
Partial pressure of carbon dioxide and oxygen
At atmospheric pressure (760mmHg), CO2 is 20x more soluble than oxygen (solubility coefficient which is 20 times greater than oxygen), therefore the partial pressure of CO2 is 1/20 that exerted by oxygen.
91
Diffusion of gases between the gas phase in the alveoli and the dissolved phase in the pulmonary blood
The partial pressure of each gas in the alveolar respiratory gas mixture forces molecules of that gas into solution in the blood of alveolar capillaries. Molecules of the same gas already dissolved in blood bounce randomly, some bounding back into alveoli
The rate of escape is directly proportional to their partial pressure in the blood
92
If the partial pressure is greater in the gas phase in the alveoli (oxygen)
More molecules diffuse into the blood
93
Partial pressure of gas greater in the dissolved state in the blood (CO2)
Diffusion occurs toward the gas phase in the alveoli
94
Vapour pressure of water
Partial pressure that water molecules exert to escape through the surface
If non humidified air is inspired into respiratory passages, water evaporates from the passage surfaces and humidifies.
At normal body temp, vapour pressure is 47mmHg
Once the gas mixture has fully humidified (once at equilibrium with water) the partial pressure of the water vapour (PH2O) in the gas mixture is 47mmHg
95
Vapour pressure of water is dependent entirely on
Temperature of water
The greater the temp, greater kinetic energy of molecules, greater the vapour pressure, greater likelihood that water molecules will escape from the surface of the water into the gas phase
96
Factors that affect rate of gas diffusion in a fluid
1. Pressure difference
2. Solubility of gas in fluid (greater the solubility of gas, the greater the number of molecules available to diffuse for any given partial pressure difference)
3. Cross sectional area of the fluid (greater the cross sectional area of diffusion pathway, the greater the total number of molecules that diffuse)
4. The distance through which the gas must diffuse (the shorter the distance the molecules must diffuse, the less time it will take)
5. The molecular weight of the gas (less molecular weight = greater molecular velocity)
6. Temperature of fluid (greater kinetic activity)
97
Composition of alveolar air
Alveolar air doesn’t have the same conc of gases as atmospheric air because
1. Alveolar air is only partially replaced by atmospheric air with each breath
2. Oxygen is constantly absorbed into pulmonary blood from alveolar air
3. Carbon dioxide is constantly diffusing from pulmonary blood into alveoli
4. Dry atmospheric air that enters respiratory passages is humidified before it reaches the alveoli (as soon as atmospheric air enters respiratory passages it is exposed to fluids that cover respiratory surfaces)
Alveolar air has more CO2 and less O2 than inhaled air
98
Exhaled air
During exhalation, alveolar air mixes with air in dead space of the lungs producing exhaled air
99
Partial pressure of water vapour in alveolar air
The partial pressure of water vapour at normal body temp is 47mmHg,(therefore, 47mmHg)
100
Total pressure in alveoli cannot rise to
More than the atmospheric pressure (760mmHg at sea level), therefore water vapour dilutes all the other gases in the inspired air
101
Rate at which alveolar air is renewed by atmospheric air
Average male functional residual capacity of lungs is 2300ml. Only 350ml of new air is brought into the alveoli with each inspiration, 350ml alveolar air expired. Therefore, multiple breaths required to exchange most of the alveolar air.
102
Why is slow replacement of alveolar air important?
Prevents sudden changes in gas concentrations in the blood, making the respiratory control mechanism more stable. Prevents excessive increases and decreases in tissue oxygenation, tissue carbon dioxide concentration, tissue pH (when respiration is temporarily interrupted)
103
Oxygen concentration in alveoli and its partial pressure controlled by
The rate of absorption of oxygen into the blood (decreases alveoli oxygen concentration)
The rate of entry of new oxygen into the lungs by ventilation (increases alveoli oxygen concentration)
(Oxygen is continually being absorbed from alveoli into pulmonary blood, new oxygen continually inspired into alveoli from atmosphere)
104
Carbon dioxide concentration and partial pressure in alveoli
C02 continually formed in body and carried to blood to alveoli, continually removed from alveoli by ventilation
1. Alveolar PCO2 increases directly in proportion to rate of CO2 excretion
2. Alveolar PCO2 decreases in inverse proportion to alveolar ventilation
