What proportion of oxygen is dissolved in the plasma? What proportion is carried by Hb?
2% in plasma (PO2) 98% with Hb (SO2)
Define O2 content, O2 capacity and O2 saturation
O2 content: the total amount of O2 in the blood (dissolved and with Hb)
O2 capacity: the max amount of O2 that can be combined with Hb (20 mL/100mL blood)
02 saturation: is the % of Hb binding sites bound to O2 (oxyHb/O2 capacity)
What is the PO2 and SaO2 of arterial and venous blood?
- PaO2= 100
What is the oxy-Hb dissociation curve?
A curve representing the relationship of oxygen tension and hemoglobin saturation. Each hemoglobin can carry 4 molecules of oxygen that bind cooperatively.
Describe the portions of the Oxy-Hb curve that correspond to oxygen loading and unloading.
At the lungs, Hb becomes saturated. At the tissues, a small change in pO2 results in a loarge change in oxygen saturation.
What does a rightward shift of the oxyHb curve mean? A leftward shift?
Right: Hb has lower affinity for O2
Left: Hb has higher affinity for O2
What causes a rightward shift of the oxyHb curve?
decreased pH (Bohr Effect)
increased 2,3 BPG (from anaerobic metabolism)
**everything that happens with exercise!
What does the oxyHb curve look like in anemia (with O2 content, as opposed to Sa02 on the y-axis)?
What is the effect of CO on oxygen content and oxygen carrying capacity in the blood?
Oxygen content decreases (because it is outcompeted by CO) and O2 carrying capacity decreases (?)(because binding spots are taken up by CO)
What is the effect of erythropoeitin (EPO) on the oxygen capacity and content of the blood?
Increases both , because you have more RBCs
What color is oxy, deoxy and carboxyHb?
carboxyHb (COHb): cherry red (can be seen in deceased according to wikipedia)
What forms does Co2 in the blood exist in, and what is the percentage of each?
What is the role of carbonic anyhydrase in the transport of carbon dioxide?
Carbonic anhydrase lives in red blood cells. CO2 diffuses from tissues, into the plasma and into the RBCs. There. it can either combine with Hb (carbaminoHb) or be converted to carbonic acid via carbonic anhydrase. The proton from this reaction binds Hb and does not diffuse. The bicarbonate is transported out of RBCs and Cl- is transported into RBCs to counter the bicarbonate. This is called the chloride shift.
What is the Haldane effect? What produces it?
-Deoxygenation of the blood increases its ability to carry CO2
-This is good beacuse it permits high loading of CO2 at the tissues (low pO2), and unloading of CO2 at the lungs (high PO2)
-In high pO2, oxygen binding creates conformational changes that make CO2, H+ binding less favorable
-In low pO2 (at the tissues), H+ and 2,3 BPG bind to Hb and create conformational changes that make CO2 binding more favorable.
Define bronchiectasis and list possible etiologies
Irreversible dilatation of the bronchial tree (bronchi and bronchioles) (vs. the reversible that can accompany infectious pneumonia)
- cystic fibrosis
- primary ciliary dyskenesia
- kartagener syndromes
- necrotizing pneumonias (TB, HiB, S. aureus, viral, fungal (e.g. aspergillus)
- foreign body
- mucus impaction
- collagen vascular diseases (rheumatoid arthritis, lupus, scleraderma)
Pathophysiology of bronchiectasis
Infectious: inflammation, necrosis, fibrosis, dilatation
Obstructive: secretions build up below the obstruction and inflammation ensue
Define bronchiolitis obliterans
Irreversible narrowing/compression of small airways by fibrosis, with or without inflammation
Etiology of bronchiolitis obliterans
Envrionmental (fumes, dusts)
Other (post lung transplant, collagen vascular disease, drug-induced)
What is the common pathogenesis of all obstructive lung diseases?
What are common symptoms of chronic obstructive airway disease?
What are 2 sources of mucus in the lung?
1) goblet cells
2) mucous glands found in cartilagenous airways
What are mechanisms of increased lung resistance (x5)?
-increased wall thickness
- loss of elasticity
-smooth muscle contraction
-obliteration of airways
What are the the mechanisms of increased lung resistance in COPD, bronchiectasis, bronchiolitis obliterans and asthma?
COPD: loss of elasticity, obliteration
Bronchiectasis: wall thickening, lumenal occlusion, obliteration
Asthma: smooth muscle spasm, wall thickening
Bronchiolitis obliterans: wall thickening, obliteration
What is the natural progression of chronic obstructive airway diseases?
A long asymptomatic period because the changes occur primarily in the small airways, and the most physiological resistance is at gen. 4/5 ish, so it takes a long time for the pathophysiological resistance to show up.
exertional dyspnea usually comes first and progresses to dyspnea at rest.
What are the primary inflammatory triggers for COPD, bronchiectasis, asthma and bronchiolitis obliterans?
Asthma: allergen drive Th2 response
Bronchiolitis obliterans: various, including fumes and transplant rejection
What is the importance of the immune system in asthma?
An allergen causes a Th2 mediated response, mast cells unload IgE, everything together cause bronchoconstriction and inflammation.
What is the role of smoking in COPD development?
Cigarette smoke, along with genetic susceptibility and environmental exposure combines to cause:
- parenchyma inflammation---> emphysema
- airway inflammation--> remodelling and thickening-->small airway disease
Together these decrease expiratory flow, and cause hyperinflation of the lung with gas exchange abnormalities
centroacinar vs panacinar emphysema
centroacinar: starts in centre of lobule and works its way out
panacinar: occurs throughout the lobule
Chronic obstructive pulmonary disease (COPD), a common preventable and treatable disease, is characterized by airflow limitation that is usually progressive and associated with an enhanced chronic inflammatory response in the airways and the lung to noxious particles or gases.
a common chronic disorder of the airways that is complex and characterized by variable and recurring symptoms, airflow obstruction, bronchial hyperresponsiveness, and an underlying inflammation.
Classes of bronchodilators, and the indications for each
Beta agonists: asthma and COPD
anticholinergics: COPD (chronic and acute exacerbation) and acute asthma (but not commonly used)
methylxanthines: 2nd or 3rd line for asthma and COPD
What is the MOA of beta-agonists?
GPCReceptors on smooth muscle cells, cAMP 2nd messenger, bronchodilation
What are the different kinds of beta-agonists used for bronchodilation?
Short acting (SABA)
Long acting (LABA)
Ultra long acting
What is in a blue puffer, when is it used, and what are possible side-effects?
- Rescue puffer
SE: tremors, tachycardia. If these appear after the puffer has been used for some time it could be a sign that the asthma is getting worse because the patient is using the puffer more often.
What is an example of a LABA? What is it used for?
- long duration bronchodilator
- NOT a rescue puffer
- should be used in conjunction with corticosteroids
What is are 2 examples of anticholinergics used for asthma, COPD?
- It's a modified version of atropine designed to be more lipophobic so it doesn't cross membranes
- It's a selective M3 anticholinergic
What is the MOA of Ipratropium?
Acts on M2 (bronchial secretion) and M3 (bronchoconstriction) receptors in the lung
What are side effects of anticholinergics in their use in asthma/COPD?
Dry mouth: causes cavities, and is annoying
What is an example of a methylxanthine? What is the MOA? What are SE? When is it used?
Poorly define MOA, inhibits phosphodiesterase and supports bronchodilation
SE: nausea, vomiting, stimulation (insomnia, anxiety, tremor), arrhythmias
Used as a last line for asthma because the SE are so serious
How do corticosteroids work?
They act in the nucleus to inhibit the transcription of some genes and promote the transcription of other gene
- pro-inflammatory cytokines
They are immunosuppressants and metabolic modulators
What is an example of a systemic corticosteroid? What are side effects
- obesity, hyperglycemia, osteoporosis etc....
What are 2 examples of inhaled corticosteroids? What are side effects?
- oral thrush
- sore throat
What are broad categories of drugs that can be used to treat asthma/COPD?
Leuktriene receptor antagonists
What is the MOA of leukotriene receptor antagonists?
they block leukotriene receptors (LT2) and prevent bronchoconstriction and inflammation in the airways and mucus hypersecretion.
What is an example of a leukotriene receptor antagonist? Indication? What is the advantage? What is the disadvantage?
Montelukast - used for management of chronic asthma (not for acute)
Not as effective as other treatments
What is an example of a monoclonal antibody? When is it used? What is the route?
Omalizumab binds up IgE, used in asthma. Injected subcutaneously.
What is combination therapy and what is the rationale for it?
Usually a LABA and corticosteroid
long term beta-agonist use downregulates B2 receptors. Corticosteroids upregulate them
Advair (salmeterol + fluticasone)
Symbicort (formeterol + budesonide)
Zenhale (formoterol + mometasone)
Types of inhalation administration of drugs?
MDI (metered dose inhaler) (AKA puffer)
dry powder inhaler
When not to use beta-agonists?
In anyone who tachycardia could pose a problem (pre-existing arrhythmia, coronary artery disease, aortic stenosis)
When to not use anticholinergics?
In any patient who has a condition that would be exacerbated by cholinergic antagonism (e.g. glaucoma, urinary retention)
What is the mode of delivery for:
- corticosteroids (fluticasone, budesonide)
corticosteroids (fluticasone, budesonide)--> inhaled
What is the natural history of COPD in smokers and non-smokers, vs. a healthy age-matched subject (in terms of FEV1)?
Is inspiratory flow effort dependent? Is expiratory flow effort dependent?
Inspiratory flow is effort dependent, but expiratory flow is almost entirely effort independent.