Asthma Flashcards
Definition (& citation)
“A Chronic INFLAMMATORY DISORDER of the airways…in susceptible individuals, inflammatory symptoms are usually associated with widespread but variable airflow obstruction and an increase in airway response to a variety of stimuli. Obstruction is often reversible, either spontaneously or with treatment”
(International consensus report 1992 in BTS guidelines for asthma 2007) - BUT - no internationally agreed definition
Symptoms of Asthma
What are they?
What qualities do these symptoms have? (& REF)
Wheeze
Shortness of breath
Chest tightness
Cough
Hallmark - these symptoms tend to be:
- variable
- intermittent
- worse at night
- Provoked by triggers
(BTS 2004)
Pathophysiology explaining symptoms (basic)
TH2 cell stimulation
IgE mechanism
Arachidonic acid metabolism
What are cytokines?
Play an important role in nearly all aspects of INFLAMMATION and IMMUNITY. They stimulate immune responses.
Interleukin’s (IL’s) are a group of naturally occurring proteins that mediate communication between cells.
Examples of cytokines?
IL-1,2,3,4,5,6,7,8,9,10,12
Tumour Necrosis Factor ‘TNF’
What do cytokines do, generally?
/ how do they do it?
Attract white cells to the area and an inflammatory response occurs
TH2 cells - what are they?
What do they secrete?
What are they implicated in?
Helper type 2 cells, distinct type of T cell that secretes:
Secrete:
IL-4,5,9,13,17,25 (inflammatory mediators)
Stimulate eosinophil activation and survival (IL-5) or promote mast cell activation (IL-9)
TH2 -type immune responses have been implicated in the development of chronic allergic inflammation and asthma.
THE INFLAMMATORY CASCADE
- TH2 stimulation
- Mediator/ cytokine / interleukin release
- Other white cell stimulation -?
- Mediator/ cytokine / interleukin release
- Emergence of symptoms of INFLAMMATION and asthma.
What effects do interleukins cause (in asthma)? (6)
- Obstruction of the smooth muscular walls of the bronchioles and terminal bronchioles.
- Oedema of airway mucosa
- Increased mucous secretion
- Cellular infiltration of the airway walls
- Injury to and shedding of the airway epithelium
- > this manifests as ASTHMA
Why is Asthma relevant?
Global
UK
Major non-communicable disease
WHO 2016; 383,000 deaths in 2015
80% asthma-related deaths occur in low and middle income countries
5.4 million people currently receiving treatment for asthma in the UK
Every 10 seconds someone is having a potentially life-threatening asthma attack - 3 people die of asthma attack every day in the UK
NHS spends £1 billion per year
Asthma relevance?
Mental health
Most common chronic disease
SU with MH issues and LD are at increased risk of developing respiratory conditions including asthma
Respiratory disease is the main cause of death in people with learning disabilities
What is the link between obesity and asthma?
Which sex is link strongest in?
Via the activity of pro-inflammatory cytokines
females - from epidemiological data
What are cytokines?
What other areas covered in module are cytokines important for?
Cytokines are white blood cells - pro-inflammatory mediators
Pneumonia & sepsis
Asthma - heritable?
chromosomes?
‘complex’ heritable disease
number of genes which contribute to persons susceptibility to disease - chromosomes 5,6,11,14
Chromome 5 one of most
Chromosome 5 codes for key molecules in the inflammatory response seen in asthma, including cytokines, growth factors and growth factor receptors
Risk factors for asthma?
- Genetic predisposition
- Environmental exposure to inhaled substances which provoke allergic reactions, e.g.
- indoor allergens e.g. house mites, pet dander
- outdoorallergens, e.g. moulds, pollens,
- tobacco smoke
also…
chemical irritants, air pollution, cold air, extreme emotional arousal - e.g. anger, fear , physical exercise, certain medications e.g. beta blockers, aspirin,anti-inflammatory
How can aspirin cause asthma attacks?
Aspirin acts as a de-regulator of leukotrines
Leukotrienes are substances in the body that cause inflammation and many of the symptoms of athma.
How can beta blockers trigger asthma?
beta 1 receptors in the heart and kidney
beta 2 receptors are found in the liver, lungs, skeletal muscles, uterus, gastrointestinal tract, vascular smooth muscle
beta 3 receptors found in the fat cells of the body
lower blood pressure but constriction in bronchial tree - can cause asthma
Functions of the respiratory system?
Adaptations?
(can then apply to symptoms)
Breathe in oxygen Breathe out carbon dioxide Breathe out water Heat regulation Influence pH balance, fluid balance Upper airways warm, moistens and filters Communication
Adaptions of Respiratory System?
- concentration gradient: high levels of Oxygen in alveoli, low levels in blood, oxygen diffuses across gradient
- Very large surface area (tennis court sized)
- Thin membrane ( encourages movement across)
- Very good blood supply
- Adaptable
Apply symptoms of asthma to functions of respiratory system?
- Concentration gradient - less oxygen in alveoli, could be full of fluid
- Very large surface area (tennis court sized)
- Thin membrane - thicker in asthma
- Very good blood supply
- Adaptable
Similar to pneumonia
Oxygen, carbon dioxide, nitrogen
IN (conc. in atmosphere)
OUT
Oxygen IN = 21%
Oxygen OUT = 16.5% (use a quarter)
Carbon dioxide IN - 0.04%
Carbon dioxide OUT - 4%
Nitrogen IN 76%
Oxygen Journey in the body…?
Mouth -> Respiratory system -> Cardiovascular system -> where does it end up?
Enters nose / mouth,
Nasopharynx, oropharynx, laryngopharynx, larynx, down trachea, trachea splits at carina to right and left bronchus, through bronchial tree, through bronchus, through bronchioles, terminal bronchioles, down into alveoli
In alveoli it diffuses across alveoli capillary membrane, into red cell erythrocytes, binds to haemoglobin (forming oxyhaemoglobin)
oxyhaemoglobin is pumped into tissues
Out of red cell, through interstitial space, through cell membrane, through cytoplasm, ends up in mitochondria
How is oxygen used by mitochondria?
AKA Aerobic Respiration
Glucose + oxygen -> mitochondria-> Adenosine Triphosphate (ATP) , CO2 and H2O, and heat)
ATP is the energy source for muscles to work
More ATP required? more heat, water and carbon dioxide generated
Normal vital signs:
Respiratory rate, depth, pattern
Blood pressure - systolic and diastolic
Heart rate, rhythm and amplitude
Temperature
Blood
RCUK
12-20 resp rate, normal depth and regular
60-100 BPM
110-140 / 60-90
36.0-37.5 centigrade
Blood glucose 4-8mmol)
Normal arteriole blood gas values?
pH - 7.35 - 7.45
PaO2 - 11-14 Kpa (kilapascals - British) -OR- 80-100 mmHg (mercury based scale)
PaCO2 - 4.7-6.0 Kpa -OR- 25-45mmHg
Lactate (0.5-1.00mmol/l)
Respiratory (organ) Failure Type 1:
Type 1 - Characterised by:
Arteriole oxygen level less than 8Kpa, CO2 level is normal (less than 6Kpa)
Respiratory (organ) Failure Type 2:
Type 2 - Characterised by:
Arteriole oxygen level is less than 8Kpa, CO2 level is higher than 6Kpa
(tends to be COPD, emphysema)
Raised CO2 - AKA Hypercapnia - occurs as a result of decreased alveolar ventilation
Aerobic Respiration - Process?
Glucose -> glycolysis in cytoplasm -> pyruvate -> Kreb’s cycle -> electron transport phosphorylation
= 36 ATP (38 including ATP used in process)
Relationship Between pH and Respiratory Rate
MEGA PRINCIPLE
What happens to resp rate with asthma attack? chest infection? low BP? stop excreting urine?
Respiratory rate will increase
Whenever acidotic, pH calls.
Chemo-receptors
Carbon dioxide - how is it carried in blood stream?
- 7% dissolved in plasma
- 23% is combined with globin to form carbinohaemoglobin
- 70% COMBINED WITH WATER AS CARBONIC ACID
How does Carbonic Acid break down?
In the presence of the enzyme carbonic anhydrase, carbonic acid breaks down into HYDROGEN and BICARBONATE ions
(water) + (carbon dioxide)
(2 x hydrogen + 1 x oxygen) + (1 carbon + 2 x oxygens)
H2O + CO2 = H2CO3 (carbonic acid)
Splits (dissociates) in bloodsteam to H(hydrogen) and HCO3 (bicarbonate)
travel to alveoli, reform to H2CO3, this dissociates into water and carbon dioxide - we breathe these out
pH - what is the H?
pH of stomach
P = power
H =hydrogen
More hydrogen in body, more acid (pH goes down) Stomach =1-3
Less hydrogen in body, less acid
Really strong acid? Loads of hydrogen…
Carbon dioxide essentially functions as an acid, as CO2 goes up, acid goes up
pH
Normal pH? Compatible with life?
- 35-7.45
- 8 - Non-compatible with life (cell death)
Nucleus won’t work, mitochondria, golgi apparatus, Endoplasmic reticulum
Excessive acidosis? Heart, brain won’t work,
Humans are acid producers - how?
making acids all the time
Breakdown of proteins, fats, carbohydrates,
Factors Affecting pH
- Carbon dioxide - more CO2 = more hydrogen
- Renal System - urine is acidic, if not excreting= retaining
- The Buffer system - Chemicals like haemoglobin, fibrinogen, co2 to a degree, ‘cancel out’ acids with alkalines
- Cell Activity - lactic acids if starved of oxygen, basicallly
Falling pH?
Process
Detected by chemo-receptors
Medulla Oblongata (brainstem)->
Phrenic and respiratory nerves (neck)->
Stimulate lungs - Increased respiratory rate (to breathe out CO2)
Acidosis - generally bad for you, sub-optimal organ function, 6.8 = cell death
