Respiratory Flashcards
How much O2 is dissolved in plasma?
1-2% - this is PaO2
What percentage of O2 is bound to hemoglobin
98-99%
What is P50?
pO2 at which HgB is 50% saturated
A higher p50 = ___ affinity of hemoglobin for O2
A lower p50 = ___ affinity of hemoglobin for O2
Higher p50 = lower affinity
Lower p50 = greater affinity
Each increase in PaO2 of 100mmHg increases dissolved O2 ____ volumes of %
0.3% ** check this**
Which state of hemoglobin is the low oxygen affinity state?
T state (taut state)
Which state of hemoglobin has high oxygen binding affinity?
R state - relaxed state
What stabilizes hemoglobin in the taut state/T state?
Think things in the tissue where we want O2 to come off hemoglobin
Low pH/high H+ concentration
CO2
2,3-BPG/2,3-DPG (Same thing)
What stabilizes hemoglobin in the R state/relaxed form?
Oxygen - in areas of high oxygen concentration we want it to bind oxygen for transport - think the lungs
CO
What happens in carbon monoxide poisoning?
CO binds hemoglobin to make carboxyhemoglobin which is more stable in the relaxed state —> it will bind O2 but won’t be able to release it (b/c it can’t convert to the T state)
CO also binds to the oxygen site with higher affinity than O2 so you can’t load O2
What causes sickle cell anemia?
Mutation in Beta globulins of hemoglobin —> changes conformation of hemoglobin to an S form which makes RBCs more sickle shaped —> they get stuck in vasculature and have lower ability to bind O2
What causes a right shift in the O2-Hgb dissociation curve?
Right shift = decreased affinity for O2
1. Increased PCO2
2. Increased H+/decreased pH
3. Increased 2,3-DPG
4. Increased temp
What causes a left shift of the O2-Hgb Dissociation Curve?
Left shift = decreased affinity for O2
1. Decreased PCO2
2. Decreased H+
3. Decreased 2,3-DPG
4. Decreased temp
5. HbF
What is the Bohr effect?
Effect of CO2 and H+ (pH) on the affinity of hemoglobin for O2
Increasing CO2 and H+ decreases affinity promoting offloading (increased P50)
Decreasing CO2 and H+ increases affinity and enhances onloading of O2 (decreases P50)
In what three forms does CO2 exist in the bloodstream and in what percent?
Dissolved in plasma (pCO2) - 7%
Bicarb (HCO3-) - 70%
Hemoglobin - 23%
What catalyst accelerates rate of conversion of CO2 to carbonic acid?
Carbonic anhydrase
It is 5000x more concentrated in RBCs
Describe CO2 uptake/transformation in RBCs at the level of the tissues
CO2 taken into RBC and reacts with water —> forms H2CO3 catalyzed by carbonic anhydrase
H2CO3 dissociates to H+ and HCO3-
H+ binds hemoglobin to form carbamino compounds
HCO3- diffused out of the RBC and Cl- diffuses in - known as CHLORIDE SHIFT
CO2 that directly binds hemoglobin forms what?
Carbaminohemoglobin
Besides RBCs, carbonic anhydrase is also found where?
GI tract - parietal cells to cause acid secretion
Pancreatic cells - results in secretion of bicarb
Renal tubules - principle cells and intercalate cells of collecting ducts
What is the Haldane effect?
oxygenation of blood in the lungs displaces carbon dioxide from hemoglobin, increasing the removal of carbon dioxide.
O2 + hemoglobin results in a stronger acid
This leads to less tendency of hemoglobin to combine with CO2 to form carbaminohemoglobin, as well as release of excess H2 ions into blood (which form carbonic acid with bicarb, which then dissociates to water and CO2, which is exhaled)
What 4 things cause right shift of the O2-hemoglobin dissociation curve?
Remember Right = release of O2
Increased H+ (decreased pH drives the curve ~15% to the right)
Increased CO2 - Bohr effect promotes release of O2 from blood in peripheral tissues; as blood passes through peripheral tissues, CO2 diffuses into blood (increased PCO2) which raises carbonic acid and H+ concentrations; the curve will be forced to the right and O2 will come off hemoglobin into the peripheral tissues
Increased temperature (ie exercise)
Increased 2,3-biphosphoglycerate (2,3-BPG) - under hypoxic conditions, blood concentrations of BPG increase which promotes release of O2
What is tidal volume?
Volume of air inspired or expired with each breath
What is inspiration reserve volume (IRV)?
Extra volume of air that can be inspired beyond the tidal volume when the organism inspires with full force
What is expiratory reserve volume?
Maximum extra volume of air that can be expired by forceful expiration after normal tidal volume
What is residual volume?
Volume of air remaining in the lungs after forceful expiration
What is inspiration capacity?
Tidal Volume + Inspiratory Reserve Volume
The maximal amount of air you can breathe in
What is functional reserve capacity?
Expiratory Reserve Volume + Residual Volume
Amount of air that remains in the lungs at the end of normal respiration
What is vital capacity?
Inspiratory Reserve Volume + Tidal Volume
Max amount of air expelled from the lungs after filling to maximum extent and expiring to maximum extent
What is total lung capacity?
Vital Capacity + Residual Volume
Maximum volume to which the lungs can be expanded with the maximum effort
What is the limiting factor in terms of how much air can be expelled during maximal expiration?
Intrathoracic pressure/thoracic compression of airways
What are 5 causes of hypoxia?
Decreased FiO2
Pulmonary disease/diffusion impairment (think interstitial fibrosis, interstitial pneumonia, granulomatosis, neoplasia)
VQ Mismatch (areas of the lung are perfused but not ventilated, or vice versa; this is the most common cause of hypoxemia)
Hypoventilation (drugs, chest wall damage, high resistance to breathing)
Shunts (anatomical = AV fistula, ASD, VSD, reverse PDA; physiologic = diffuse pleural effusion, ARDS)
Does hypoxia from shunts improve with O2 supplementation?
No!!
Every other type of hypoxia does
What is the most common clinical sign of bronchiectasis?
Cough
What breeds are overrepresented in bronchiectasis?
American cockers
Westies
What is bronchiectasis?
Chronic, irreversible dilation of diseased bronchi
What is the pathophysiology of bronchiectasis?
Destruction of elastic and muscle layers of bronchial walls causes dilation of the bronchi which will lead to bronchial wall thickening (mucosal hypertrophy and hyperplasia)
Dilation occurs in proximal subdivisions of bronchi containing cartilaginous walls.
What can cause bronchiectasis?
Impaired pulmonary clearance mechanisms lead to stagnant mucosal secretions —> endoluminal pressure rise —> creates ideal environment for infection
Additionally bacteria/pathogens remain in the punching for long periods which predisposes to bronchial wall inflammation
Bronchiectasis is a manifestation of bronchial obstruction, untreated or chronic infection, diffuse pulmonary pathology, or a systemic disorder
Pre-existing abnormalities in immune and inflammatory host response or pulmonary clearance mechanism may play a role in development of bronchiectasis
What are the two morphological forms of bronchiectasis and which is more common?
Cylindrical - more common
Saccular
What is cylindrical bronchiectasis?
Uniform tubular dilation of PROXIMAL bronchial tree segments
What is saccular bronchiectasis?
Balloon-like dilation of DISTAL/terminal branch bronchi
What are the spatial classifications for bronchiectasis?
Focal - think infection or obstruction
Multifocal
Diffuse - can indicate congenital or acquired deficiencies in host defense mechanisms
What organisms can cause primary canine tracheobronchitis?
Bordetella bronchiseptica - most common
Streptococcus zooepidemicus
Mycoplasma spp.
What organisms can cause secondary/opportunistic tracheobronchitis?
E. Coli
Pasturella multocida
Pseudomonas spp.
Klebsiella pneuomoniae
Which immunoglobulin is most present on respiratory epithelium?
IgA
Which cells produce surfactant?
Type II pneumocytes (alveolar epithelial cells)
What is surfactant composed of?
Phospholipids
Proteins
Ions
Most important components: dipalmitoylphosphatidylcholine, apoproteins, Ca2+
What does dipalmitoylphosphatidylcholine do?
Reduces surface tension of water - creates a surface with 1/12 to 1/2 the surface tension of pure water
This prevents the lungs from collapsing at the end of expiration
How does surfactant effect respiratory effort?
Reduced pressure in the alveoli from surfactant substantially reduces the amount of effort needed to expand the lungs
What is activated in lung tissue?
Angiotensin I - converted to angiotensin II via ACE in capillary endothelial cells
What substances are inactivated in the lungs?
Bradykinin (up to 80%)
Prostaglandins E2 and F2alpha - almost completely inactivated via enzymes
What substances are cleared by the lungs?
Serotonin - almost completely removed via update and storage
Norepinephrine - removed up to 30%
Leukotrienes - almost completely removed
What substances are unaffected as they pass through the lungs?
Angiotensin II
Vasopressin/ADH
Histamine
Dopamine
PGA2
PGI2/prostacyclin
The lungs metabolize arachadonic acid metabolites through what two major pathways?
Lipoxygenase - produces leukotrienes (inflammatory responses, airway constriction, asthma)
Cyclooxygenase - produces prostaglandins (vasoconstriction or vasodilation, affect platelet aggregation) and thromboxane A2
What hormone is inactivated in the lungs?
Bradykinin (inactivated by ACE)
Describe how bradykinin is produced
Formed kallikrein (in blood and tissues) becomes activated due to inflammation and cats on alpha2-globulin to cause release of kallidin
Kallidin is converted to bradykinin via tissue enzymes
In addition to production from kallikrein activation, what cells can release bradykinin?
Mast cells
What effects does bradykinin have in the body?
Causes profound vasodilation
Increases capillary permeability
Contraction of non-vascular smooth muscle in bronchi