Respiratory Failure Flashcards
Respiratory failure
Failure of gas exchange - inability to maintain normal blood gases
Low PaO2 (with or without rise in PaCO2)
Respiratory failure blood gases: PaO2
<8 KPa
<60 mmHg
Respiratory failure blood gases: PaCO2
> 6.5 KPa
49 mmHg
Sea level PiO2
100 KPa x 0.21 = 21 KPa
Normal range PaO2
10.5-13.5
Normal range PaCO2
4.7-6.5
Acute respiratory acidosis secondary to opiate overdose treatment
IV fluids
Supportive care
Opiate antagonists
Possible need for non invasive or invasive ventilation
Type 1 respiratory failure: PaO2
Low (hypoxaemia)
Type 1 respiratory failure: PaCO2
Low/ normal (hypocapnia/normal)
Type 2 respiratory failure: PaO2
Low (hypoxaemia)
Type 2 respiratory failure: PaCO2
High (Hypercapnia)
Acute respiratory failure
Rapidly
Eg opiate overdose, trauma, pulmonary embolism
Chronic respiratory failure
Over a period of time
Eg COPD, fibrosing lung disease
Causes of type 1 respiratory failure
Most pulmonary and cardiac produce type 1 failure
Eg
infection = pneumonia, bronchiectasis
Congenital = cyanotic congenital heart disease
Neoplasm = lymphangitis carcinomatosis
Airway = COPD, asthma
Vasculature = pulmonary embolism, fat embolism
Parenchyma = pulmonary fibrosis, pulmonary oedema, pneumoconiosis, sarcoidosis
Causes of hypoxia
Mismatching of ventilation and perfusion
Shunting
Diffusion impairment
Alveolar hypoventilation
Similar effects on tissue as type 1 failure as seen with
Anaemia
Carbon monoxide poisoning
Methaemoglobinaemia
Hypoxia
A reduced level of tissue oxygenation
Hypoxaemia
A decrease in the partial pressure of oxygen in the blood
Hypopnoeic
Slow respiratory rate
Type 1 respiratory failure treatments
Airway patency
Oxygen delivery
Many differing systems
Increasing FiO2
Primary cause (eg antibiotics for pneumonia)
Type 2 respiratory failure mechanisms
Lack of respiratory drive
Excess workload
Bellows failure
Increased resistance
Type 2 respiratory failure types
Airway = COPD, asthma, laryngeal oedema, sleep apnoea syndrome
Drugs = suxamethonium (paralysis)
Metabolic - poisoning, overdose
Neurological = central, primary hypoventilation, head and cervical spine injury
Muscle = myasthenia
Polyneuropathy = poliomyelitis
Primary muscle disorders
Clinical features of hypoxia
Central cyanosis
- may not be obvious in anaemia patients
-Oral cavity
Irritability
Reduced intellectual function
Reduced consciousness
Convulsions
Coma
Death
What is the common cause of type 1 and 2 respiratory failure
COPD
Clinical features of Hypercapnia
Variable patient to patient
Irritability
Headache
Papilloedema
Warm skin
Bounding pulse
Confusion
Somnolence (tiredness/sleepy)
Coma
Treatments of type 2 respiratory failure
Airway patency
Oxygen delivery
Primary cause (eg antibiotics for pneumonia)
Treatment with O2 may be more difficult eg COPD rely on hypoxia to stimulate respiration
Assisted ventilation types
Invasive (facial mask) and non invasive (endotracheal tube)
Assisted ventilation type 2 respiratory failure
Inadequate PaO2 despite increasing FiO2
Increasing PaCO2
Patient tiring
Where to look for cyanosis
Under tongue
Oxygen treatments
5-10 litres/min face mask or 2-6 litres/min nasal cannulae
Aim for SpO2 of 94-98%
If saturation <85% and not at risk of hypercapnic respiratory failure
10-15 litres / minute reservoir mask
Patients with COPD and other risk factors for hypercapnia;
Aim for SpO2 of 88-92% pending blood gases
Adjust to SpO2 of 94-98% if CO2 normal unless previous history of high CO2 or ventilation
Common causes of acute type 1 respiratory failure
Pneumonia
Asthma
Common causes of acute type 2 respiratory failure
Overdose
Trauma
Common causes of chronic type 1 respiratory failure
Fibrosing lung disease
Common causes of chronic type 2 respiratory failure
COPD
neuromuscular
Why must you be cautious giving oxygen to type 2 respiratory failure
Patients have a new baseline due to habituation (normal level is hypoxaemia)
Giving oxygen will get rid of drive to breathe
Also, will change V/Q ratio due to reduced hypoxia related arterial vasoconstriction
Ageusia
Loss of taste
What range of values for SpO2 should aim for
94-98%
Rate of oxygen delivery for face mask
5-10 L/min
Rate of oxygen delivery for nasal cannulae
2-6 L/min
Rate of oxygen delivery for reservoir mask
10-15 L/min
If saturation <85% and not at risk of hypercapnic respiratory failure
Aim for SpO2 for Patients with COPD and other risk factors for hypercapnia
88-92 % pending blood gases
94-98% if CO2 normal unless previous history of high CO2 or ventilation
Mask
Controlled oxygen therapy
Known FiO2
Nasal prongs
Uncontrolled oxygen delivery
More stable patients
Unknown FiO2- pockets of high FiO2 develop in nasopharynx
Respiratory alkalosis
During hyperventilation, large volume of CO2 lost—> as CO2 is acidic causes blood to become more alkaline (raising pH)
To compensate for loss of CO2, kidneys begin to secrete alkaline HCO3- into the urine in exchange for H+ ions
How does emphysema affect functional residual capacity
Increases due to reduced elastic recoil of lung tissue due to reduced elastic tissue
What are patients with chronic CO2 retention reliant on for control of ventilation
Hypoxic drive
Workplace causes of asthma- High molecular allergens:
Grain
Wood
Laboratory Animals
Fish
Latex
Enzymes
Workplace causes for asthma- low molecular allergens:
Glutaraldehyde
Isocyanates
Paints
metal working fluids
Metals
Chemicals
Sterilising agents
Asthma
common
chronic inflammatory disease of the airways characterized by
variable and recurring symptoms
reversible airflow obstruction and bronchospasm.
common symptoms include wheezing, coughing, chest tightness, and shortness of breath
Common symptoms of asthma
wheezing, coughing, chest tightness, and shortness of breath
Prevalence of asthma
5-16% of people worldwide have asthma
Wide variation between countries
Increase in prevalence second half of the 20th century
Now plateaued mostly
US study; Poorer individuals, African-Americans
Many studies identify a wide range of risk factors
Hygiene hypothesis, Berlin
Asthma pollens
Emergency attendances
Atlanta
Poaceace (grass) and Quercus (oak) species investigated
Levels associated with emergency room attendances
Oak pollens particularly important in children aged 5-17 years old
Australian thunderstorm data
Proportion of asthma caused by workplace environment
15-20%
Asthma infectious agents and microorganisms
Farm life protected the subsequent development of asthma
Early and in utero life seem to have an important role
Specific agents not identified, but likely to be a mix of bacterial and other agents, potentially altering gastrointestinal immune response
Airway bacteria may also play a role in causing asthma, role of rhinovirus
Asthma fungi
Important roles in the development of allergic illnesses
Birth cohort study
Development and severity of asthma @ 7 years
Children’s home sampling aged 8 months
24% had asthma aged 7
Associations with fungal exposure (aspergillus and penicillium) and subsequent asthma
Asthma pets
Cat ownership and exposure most implicated
Exposure at home is associated with sensitisation as judged by IgE, but;
Timing and intensity to pet exposures appear important
Asthma air pollution
Air pollution; aggravating lung diseases;
Responses to pollutants can be analogous to viral responses
Asthma hospitalisations relate to PM2.5 and PM10
Air pollution; inducing allergy less clear
Swedish birth cohort study
NO exposure in the first year of life related to pollen sensitisation at 4 years old
Increasing evidence
Asthma peak flow
Variable
Hypersensitivity pneumonitis
is an inflammation of the alveoli within the lung caused by hypersensitivity to inhaled agents
Acute, sub acute and chronic forms (fibrotic, non fibrotic)
Immune complex related disease
Antigen reacts with antibody
Normally IgG response
Very significant environmental influences; farmers lung, bird fanciers lung, metal working fluids
Hypersensitivity pneumonitis causes
Farmers lung (eg animals, mouldy straw and hay)
Bird fanciers lung
Metal working fluids
Musical instruments
Microbiological and chemical agents from the environment and work place
Hot tub lung
Hot tub use in general identified as a cause of EAA (hypersensitivity pneumonitis)
One of the first descriptions; 1997 (Kahana et al 1997)
Two recent cases of HP
Case of a 49 year old male, 2 months of fever, weight loss, shortness of breath and cough
Regular hot tub use
Sputum grew Mycobacterium fortuitum
The hot tub drain and shower drain swabs were smear positive, with cultures demonstrating M fortuitum
Re-presented with further problems 2 months later, and admitted a relapse of his ban on hot tubs
COPD
type of obstructive lung disease characterized by chronically poor airflow. It typically worsens over time, with the main symptoms include: shortness of breath, cough, and sputum production
COPD causes
Tobacco smoking main cause (contains cadmium)
Other causes include occupational exposures such as;
Silica, Coal, Grain, Cotton, Cadmium
PAH, Isocyanates, Iron/steel processing, Agricultural dust, biomass fuels, Wood dust
Infection
Lungs susceptible to infection from inhaled microbiological agents (i) bacteria [e.g. pseudomonas], viral [e.g. COVID-19]
Percentage of COPD caused by occupational exposures
10-15%
Which metal exposure is associated with emphysema development
Cadmium
What metal causes asthma
Chromium
Important COPD occupational exposures
Silica
Coal
Grain
cotton
Cadmium
Asbestos exposure associated conditions
Pleural plaques
Pleural thickening
Benign pleural effusions
Asbestosis
Lung cancer
Malignant mesothelioma
Effects of hypersensitivity pneumonitis
Regional variation in the lung
Inflammation of bronchioles
Silicosis
Turkish denim sandblasters
Low lung function growth trajectory due to
Genetics
Preterm birth
Early life environmental exposures
LRTI
Childhood persistent asthma
Asthma and genes
Asthma runs in families
Children of asthmatic parents are at increased risk of asthma
Asthma is not caused by a single mutation in one gene
Transmission of the disease through generations does not follow simple Mendelian inheritance typical of classic monogenic diseases
New genotyping technologies has made it possible to sequence the human genome for asthma-associated variants
Asthma personalised medicine
Individualise pharmacotherapy based on genetic polymorphisms
Certain drugs are administered only to those patients who are most likely to respond
Harmful effects are avoided in patients who are most likely to experience toxicity and adverse reactions
Candidate genes for such studies are those encoding receptor proteins and enzymes involved in drug transportation, processing, degradation and excretion.
Cystic fibrosis
Chronic genetic disease
Multi-organ involvement
In UK >10,000 people affected
Median age of death improving
Most common lethal autosomal recessive genetic disorder in Caucasians
Static incidence with an increasing prevalence
Cystic fibrosis genes
Defect in long arm of chromosome 7 coding for the cystic fibrosis transmembrane regulator (CFTR) protein (anion channel)
> 1600 mutations of CFTR gene identified
90% within a panel of 70 mutations
F508del most common mutation causing CF
Proportion of carriers of cystic fibrosis
1:25
CTFR protein
Transport protein on membrane of epithelial cells
Abnormal CFTR protein leads to dysregulated epithelial fluid transport
80% Lung and gastrointestinal involvement
15% Lung alone
Pathophysiology - cystic fibrosis
Bronchitis —> bronchiectasis —>fibrosis
Cystic fibrosis diagnosis
Genetic profile and neonatal screening (day 5 IRT)
Clinical symptoms – frequent infections, malabsorption, failure to thrive
Abnormal salt / chloride exchange – raised skin salt
Late diagnoses via infertility services – azoospermia or via gastroenterology team with recurrent pancreatitis / malabsorption
50% diagnosed @ 6 months
90% diagnosed @ 8 years of age
What percentage of patients with cystic fibrosis diagnosed at 6 months
50%
What percentage of patients with cystic fibrosis diagnosed at 8 years
90%
CF respiratory symptoms
Persistent cough with productive thick mucus
Wheezing and shortness of brewth]frequent chest infections
Sinusitis
Nasal polyps
CF digestive symptoms
Bowel disturbances
Weight loss
Obstructive
Constipation
CF MSK symptoms
Osteoporosis
Arthritis
Prevalence of CF
1 in 2500
CF reproductive symptoms
95% men and 20% women are infertile
Normal lung function growth trajectory
FEV1 increases to 100% as you age up until mid-20s as lungs are still growing
Lung function then plateaus and begins to decrease
CF pathophysiology : in the pancreas
blockage of exocrine ducts, early activation of pancreatic enzymes, and eventual auto-destruction of the exocrine pancreas
Most patients require supplemental pancreatic enzymes
Asthma inheritance
Does NOT follow Mendelian inheritance
But runs in families
CF pathophysiology : in the intestine
Bulky stools can lead to intestinal blockage
CF pathophysiology : in the respiratory system
mucus retention, chronic infection, and inflammation that eventually destroy lung tissue
There are multiple hypotheses regarding the pathogenesis of lung disease, each of which is supported by data in vitro and in vivo
Lung disease is the most common cause of morbidity and mortality
Which chromosome codes for CFTR protein
Long arm of chromosome 7
7q
Most common mutation causing CF
F508del
2 abnormal genes
Number of CFTR gene mutations identified
> 1600
Mutant CFTR channels
Does not move Cl-, causing sticky mucus to build up on the outside of the cell
Leads to dysregulated epithelial fluid transport
The vicious cycle
Respiratory tract infection (microbial insults OR defect in host defence) —> bronchial inflammation—> respiratory tract damage —> more liable onto infection…
Progressive lung disease
Clinical symptoms cystic fibrosis diagnosis
Frequent infections
Malabsorption
Failure to thrive
Abnormal salt/chloride exchange
A mild electrical current pushes medicine into skin to cause sweating
Sweat is collected and salt content measured
CF general treatment strategy
Maintenance and prevention management
Rescue
Personalised approaches
CF prevention management
Segregation
Surveillance- frequent reviews minimum every 3 months
Airway clearance- physio and exercise
Nutrition- pancreatic enzymes, diet high calorie and fat, supplements including vitamins, percutaneous feeding
Psychosocial support
CF geneotype classification
Class I: no functional CFTR protein is made (e.g. G542X)
Class II: CFTR protein is made but it is mis-folded (e.g. F508del)
Class III: CFTR protein is formed into a channel but it does not open properly (e.g. G551D)
Class IV: CFTR protein is formed into a channel but chloride ions do not cross the channel properly (e.g. R347P)
Class V: CFTR protein is not made in sufficient quantities (e.g. A455E)
Class VI: CFTR protein with decreased cell surface stability (e.g. 120del123)
More than 2000 CF - causing CFTR mutations have been found
Most common of which is F508del [a class II mutation found in up to 80% to 90% of patients]
Classes of CF
Different classes of genotype abnormality for development of CTFR protein
Class I- Class VI
CF medications
Suppression of chronic infections – antibiotic nebulisation
Bronchodilation – salbutamol nebulisation
Anti inflammatory – azithromycin, corticosteroids
Diabetes – insulin treatment
Vaccinations – influenza, pneumococcal, SARS CoV 2
CF rescue antibiotics
2 week course IV antibiotics
Home vs hospital
Issues with frequent antibiotics
Allergies
Renal impairment
Resistance
Access problems
Issues with frequent antibiotics
Allergies
Renal impairment
Resistance
Access problems
CF personalised approaches
Individual tailored or targeted medicine
Move away from a ‘one size fits all’ approach
Stratified based on predicted response or risk of disease
Genetic information major factor
Monogenic disorder (i.e. is the result of mutation(s) in a specific gene)
Well-characterised pathophysiology with clear therapeutic targets
Genotype directed therapies
Targeted treatments based on infectious organisms and resistance patterns
Ivacaftor (kalydeco)
CFTR potentiator- potentiates chloride secretion via increased CFTR channels opening time
Class III mutations
Lumacaftor (orkambi)
CFTR corrector - corrects cellular misprocessing of CFTR (e.g. folding) to facilitate transport from the endoplasmic reticulum
Class II mutation - F508del/F508del
CF phage therapies
Bacteriophage therapy is the use of lytic phases to kill infectious diseases
Challenges treating CF
adherence to treatment
High treatment burden
High cost of certain treatments
Allergies/intolerances to treatment
Different infectious organisms and resistance to drugs
Alpha-1 antitrypsin deficiency (AATD)
Autosomal recessive genetic disorder
80 different mutations of SERPINEA1 gene on chromosome 14
Serum antiprotease
M phenotype normal and healthy
S and Z phenotypes major disease associations
Which gene is mutated AATD
SERPINEA1 gene on chromosome 14
AATD M phenotype
Normal and healthy
PiMM
AATD S and Z phenotypes
Major disease associations
Consequences of AATD
Early onset emphysema (proteases in lung breakdown lung proteins) and bronchiectasis
Liver cirrhosis
Unopposed action of neutrophil elastase in the lung
Flat diaphragm
Sign of emphysema
Dyspnoea
Sense of awareness of increased respiratory effort
Inappropriate
Orthopnoea
Breathless on lying down
Tachypnoea
Increased respiratory rate
Bradypnoea
Reduced respiratory rate
Hyperventilation
Inappropriate over breathing
Paroxysmal nocturnal dyspnoe
Episodes of shortness of breath
Genetic inheritance of asthma
Is not caused by a single mutation (at least chromosome 2,6,9,15,17 and 22 are involved)
Type I respiratory failure
• involves low oxygen, and normal or low carbon dioxide levels. (hypoxaemia (PaO2 <8 kPa / 60mmHg) with normocapnia (PaCO2 <6.0 kPa / 45mmHg))
• It usually occurs due to ventilation/perfusion (V/Q) mismatch –the volume of air flowing in and out of the lungs is not matched with the flow of blood to the lung tissue
• As a result of the ventilation/perfusion mismatch, PaO2 falls, and PaCO2 rises. The rise in PaCO2 rapidly triggers an increase in a patient’s overall alveolar ventilation, which corrects the PaCO2 but not the PaO2 due to the different shapes of the CO2 and O2 dissociation curves.
Entire lung failure…
Type II respiratory failure
COPD and type II respiratory failure
COPD causes habituation of high PaCO2
Begin to rely on low PaO2 for drive to breathe
What causes the drive to breathe
PaCO2
Small changes causes difference as very sensitive
Type II respiratory failure flow diagram
Hypoventilation —> increase PCO2 (acidic) —> increase H2CO3 —> decrease pH
Respiratory acidosis
Acute phase of type II respiratory failure
CO2 moving into RBCs combines with H2O- carbonic anhydride converts to H2CO3 which dissociates into HCO3 -
Chronic phase of type II respiratory failure
Renal:
Increased HCO3 - reabsorption
Increased H+ excretion in ammonia (NH3+ -> NH4)
Causes of decreased pH (metabolic acidosis)
Renal failure
GI HCO3 - loss eg cholera
Diabetic ketoacidosis
Dilution of blood with H2O
Failed H+ excretion (hypoalosteronism)
Metabolic acidosis pathway
Decreased pH—> chemoreceptors increase respiratory rate —> decreases PCO2 —> decreases H2CO3
Causes of increased pH (metabolic alkalosis)
Vomiting (HCL loss)
Alkali ingestion
Renal acid loss: hyperaldosteronism, hyperkalaemia
Metabolic alkalosis pathway
Increased pH —> chemoreceptor inhibition —> decrease’s respiratory rate- hypoventilation—> increases PCO2 —> decreases pH
Type I respiratory failure flow diagram
Hyperventilation—> decreases PCO2 (acidic) —> decreases H2CO3 —> increases pH
Respiratory alkalosis
Chronic type I respiratory failure
Renal:
Decreased HCO3 - reabsorption
Decreased H+ excretion
Gaseous diffusion impairment
Pulmonary oedema
Blood diffusion impairment
Anaemia
Membrane diffusion impairment
Interstitial fibrosis
Complete airway blockage
Shunt
V/Q= 0
Partial airway blockage
Decreased V/Q
Local hypoxia
Complete blood blockage
V/Q = infinty
Partial blood blockage
Increased V/Q
What is V/Q mismatch counteracted by
Local Bronchoconstriction
Hypoxic pulmonary vasoconstriction (weak-little muscle) diverts blood to better-oxygenated lung segments
FeNO (fractional expired nitric oxide)
Marker of eosinophilic airway inflammation
>50 ppb
Chronic bronchitis
Inflammation
Increased mucus
Emphysema
Decreased lung surface area
Destruction of alveoli and capillaries
Decreased elastic recoil
Distended thorax (barrel chest)
Class 2 CF
Misfolded CFTR
Eg F508del (most common)
Class 3 CF
CFTR channel doesn’t open properly
Treatment of AATD
Antiproteases inhibit neutrophil elastase from damaging elastin
which is the most clinical significant form of alpha 1 anti trypsin deficiency
PiZZ
A 67 year old patient is being investigated for shortness of breath.
Which of the following conditions would normally lead to Type 2 Respiratory Failure?
Increased airways resistance - chronic obstructive pulmonary disease
Reduced breathing effort (drug effects, brain stem lesion, extreme obesity)
A decrease in the area of the lung available for gas exchange (such as in chronic bronchitis)
Neuromuscular problems
70 year old has an X-ray to investigate their shortness of breath. It reveals a suspicious lesion associated with the pleura.
What is the term used to describe a malignant tumour of the pleural membranes?
Mesothelioma
An 83 year old patient is admitted with shortness of breath and is diagnosed with Type 1 respiratory failure.
Which of the following arterial blood gas results characterizes Type 1 Respiratory Failure?
low pO2, normal/low pCO2
A 67 year old patient is being investigated for shortness of breath.
Which of the following arterial blood gas results is typical of chronic Type 2 Respiratory Failure?
low pO2, high pCO2, normal-high HCO3-
type 1 respiratory failure is caused by conditions that affect oxygenation such as:
Low ambient oxygen (e.g. at high altitude)
Ventilation-perfusion mismatch (parts of the lung receive oxygen but not enough blood to absorb it, e.g. pulmonary embolism)
Alveolar hypoventilation due to reduced respiratory muscle activity, e.g. in acute neuromuscular disease (this form can also cause type 2 respiratory failure if severe)
Diffusion problem (oxygen cannot enter the capillaries due to parenchymal disease, e.g. in pneumonia)
Shunt (oxygenated blood mixes with non-oxygenated blood from the venous system, e.g. right to left shunt)
A 5 year old is scheduled for theatre to remove an inhaled peanut.
Where is the inhaled peanut most likely to become lodged in their airway?
Right main bronchus
In chronic hypercapnia, which pathway controls respiratory drive
Chemoreceptors in the carotid bodies detect low blood oxygen and send signals via cranial nerves to the dorsal respiratory group.
Motor output is sent via the phrenic nerve to stimulate contraction of the diaphragm and increase respiratory rate
Chronic hypercapnia and respiratory drive
Central chemoreceptors in dorsal medulla less able to respond to carbon dioxide levels
Body becomes reliant on peripheral chemoreceptors and hypoxic drive
Respiratory acidosis blood gases
PaO2 <8 KPa
PaCO2 > 6KPa
What is the effect of a marked increase in pulmonary capillary pressure in lung compliance
Decrease in compliance as pulmonary oedema occurs
How does emphysema affect lung compliance
Increases due to loss of elastic tissue
How does pulmonary fibrosis affect lung compliance
Decrease
Flapping tremor/ asterixis
Sign of CO2 retention - type 2 respiratory failure
Shallow breathing leads to
Respiratory acidosis
Hyperventilating leads to
Respiratory alkalosis
Joe is a 50 year old man who has just returned to Blackburn after living in Thailand for a year. Over the next few days he notices that he’s finding it more difficult to breathe, and that when he does he feels a sharp pain. He goes to his GP who diagnoses him with a pulmonary embolism. What is the main kind of hypoxia that a pulmonary embolism would cause
V/Q mismatch
