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
What inactivates bradykinin?
ACE
Remember this happens in the lungs!
The respiratory center (pons and medulla, bilateral has 3 collections of neurons. What are they and where are they located?
Dorsal group - dorsal portion of medulla
Ventral group - ventrolateral portion of medulla
Penumotaxic center- dorsal in superior portion of PONS
The dorsal group of neurons in the respiratory center has what function?
Causes inspiration
Most important role in control of respiration
Nucleus of the solitary tract is the sensory terminal of vagus and glossopharyngeal nerves which transmit signals from peripheral chemoreceptors, baroreceptors, and receptors in the lungs
The ventral group of neurons in the respiratory center has what function?
Causes expiration
The pneumotaxic center in the respiratory center has what function?
Controls rate and depth of respiration
Primary effect: control “switch off” point of the Inspiratory ramp (control duration of filling phase)
Secondary effect: increase rate of breathing
The central chemosensitive area is very responsive to changes in __ and __
CO2 and H+
The peripheral chemoreceptor system does what?
Transmits nervous signals to the respiratory center in the brain
Remember chemoreceptors are in the carotid body and aortic bodies
Type I receptors in carotid bodies respond to what?
Hypoxemia - type 1 receptors are glomus cells which respond to partial pressure of O2 and trigger action potentials in afferent nerves
What are mechanisms that lead to pleural effusion?
Lymphatic obstruction
Cardiac failure (modified trans update or chyle) - results from excessively high peripheral and pulmonary capillary pressures
Reduced plasma oncotic pressure (pure transudate)
Infection/inflammation - breaks down capillary membranes
Total protein and total NCC of pure transudate
TP: <2.5mg/dL
TNCC: <1500cells/uL
What causes pure transudate?
Hypoalbuminemia
Total protein and total NCC of modified transudate
TP: 2.5-3.5mg/dL
TNCC: 1000-7000cells/uL
What diseases can cause modified transudate
Heart disease
Neoplasia
Pericardial effusion
Diaphragmatic hernia
SIRS
Total protein and total NCC of exudate
TP: >3mg/dL
TNCC: >7000cells/uL
Two types of exudate and potential causes
Septic vs. non-septic
Non-septic: FIP, neoplasia
Septic: pyothorax
Hemorrhagic pleural effusion can result from
Traumatic/iatrogenic
Coagulopathy
Neoplasia
Lung lobe torsion
What tumor types are commonly associated with neoplastic pleural effusion
LSA
Mesothelioma
Carcinomas
Chylous effusion can be caused by
Idiopathic
Neoplasia
Heart disease - think CATS especially
Heart worm
Lung lobe torsion
Trauma
What is typically the main cellular component of chylous effusion?
Small lymphocytes
If chronic, may see neutrophils (especially in cats)
What are the most common causes of pleural effusion in cats? (4)
Pyothorax
Mediastinal lymphoma
Heart disease
FIP
What are the most common organisms isolated in feline pyothorax?
Anaerobic: Peptostreptococus, Bacteriodes, Fusobacterium, Prevatella
Aerobic: Pasteurella, Actinomyces
Diagnosis of FIP is supported when globulin concentration is __ of total protein in the effusion
> 32%
UNLIKELY if albumin component of effusion TP is >48% OR if the albumin:globulin ratio of the effusion is >0.81
Is unilateral or bilateral pleural effusion most common in cats?
Bilateral because their mediastinum is functionally incomplete
What are some non-septic causes of pleural effusion in dogs and cats?
Heart failure
Obstruction/thrombosis of cranial vena cava
Hypoproteinemia
FIP
Coagulopathy
Trauma
Lung lobe torsion
Diaphragmatic hernia
PTE
Neoplasia
What type of hypersensitivity reaction causes vasculitis and effusion in FIP?
Type 3 hypersensitivity - vasculitis is caused by immune complexes
Which of the following is the site of highest airway resistance?
Largest bronchi
Medium sized bronchi
Smallest bronchi
Alveoli
Medium sized bronchi
Which part of the airway is the site of lowest airway resistance?
Terminal bronchioles
What causes cyanosis?
Excessive amount of deoxygenated hemoglobin in the skin and blood vessels
Cyanosis is most likely associated with?
ANOXIA
NOT CO poisoning - the blood is hyperoxygenated in CO poisoning and can’t get delivered to the tissues/can’t unbind
Not anemia or hystiocytic hypoxia
What binds O2 in the red blood cell?
Ferrous iron
What is the treatment for tension pneumothorax?
Chest tube placement with intermittent or continuous suction
Thoracocentesis at 7-9th intercostal spaces
Chest tube placement: skin incision at 10th ICS, tunnel cranial 2 spaces and enter thorax at 8th ICS
Simonsiella is an __
Oral contaminant
What is the most common canine respiratory parasite?
Oslerus osleri
What is the infective stage of Oslerus osleri?
L1
Where in the trachea and bronchi are lesions seen with Oslerus osleri?
Nodules in tracheal bifurcation and primary bronchi
How is Oslerus osleri diagnosed
Fecal float (Zn sulfate) to see L1 and eggs
Bronchoscopy
How is Oslerus osleri treated
Fenbendazole or ivermectin
Eucoleus aerophilus is know by what other name
Capillaria aerophilia
Where does Eucoleus aerophilus cause lesions
Imbeds in the mucosa of the trachea, bronchi, and bronchioles to form white coiled masses and causes chronic inflammation
What respiratory parasite has zoonotic potential?
Eucoleus aerophilus
How is Eucoleus aerophilus diagnosed?
Airway/BAL: barrel shaped bipolar plugged yellow-brown eggs
PCR for fecal DNA detection - sensitive and specific
What are glomus cells
Antral chemoreceptors
They excite the respiratory center in response to decreased arterial PO2 and pH and increased arterial PCO2
Located in carotid > aortic bodies
Afferent nerve fibers from antral chemoreceptors travel via what nerve to what location?
Travel via the vagus nerve to the dorsal medullary respiratory area
The apneustic center is located where?
Lower pons
Has excitatory effect on the Inspiratory area of the medulla (dorsal respiratory group)
Excretion of CO2 is regulated by
Respiratory rate and minute ventilation
TV x RR
Chemoreceptors want to maintain PaCO2 at what level?
35-45mmHg
Hypercapnia results in
Respiratory acidosis
2/3 of chemical CO2 regulation is controlled by
Central chemoreceptors - this is slow
The other 1/3 is done by peripheral chemoreceptors which are faster
Describe what happens in glomus cells in response to decreased O2
Decreased O2 activates O2 sensitive K+ channels —> K+ efflux out of the cell, Ca2+ influx into cell —> depolarization —> dopamine release —> respiratory stimulation via cranial nerve IX (glossopharyngeal nerve)
CO2/O2 has a more potent effect on central chemoreceptors
CO2
O2 has more potent effect on peripheral chemoreceptors
Why does CO2 have a more potent effect in stimulating the central chemo sensitive neurons than hydrogen ions?
The blood brain barrier is not very permeable to hydrogen ions, but CO2 passes easily through the BBB
H+ ultimately is what stimulates the cells, but it can’t diffuse so the CO2 diffuses across, combines with H2O to form carbonic acid, which then dissociates to bicarb and H+ ions —> H+ acts on central chemoreceptors
What happens in the Hering-Breuer inflation reflex?
Sensory nerve signals from the lungs and stretch receptors located in muscular portion of the walls of the bronchi and bronchioles are stimulated and transmit signals to dorsal respiratory group when the lungs become overstretched.
This “switches off” the Inspiratory ramp
Conducting airways are important in thermoregulation in what species
Dogs
What functions does the lung have in coagulation?
Degradation of fibrin
Rich in thromboplastin —> thrombin generation
Rich in heparin
What component of surfactant is bactericidal?
Surfactant protein A
What disease is associated with dysfunctional cilia? What causes this condition?
Primary ciliary dyskinesia (PCD)
Mutation in microtubules (normally it’s a 9 + 2, 9 peripheral with 2 in the middle; altered in PCD)
What are the clinical signs of primary ciliary dyskinesia, what breeds are predisposed, and what does it cause?
Clinical signs: recurrent infections (pneumonia, URIs); nasal discharge; hydrocephalus (cilia line the ventricular system in the brain); male infertility; sinus inversus (organs on opposite side they should be on)
Old English Sheepdogs,= (also Alaskan Malamutes, English Pointers)
Parasympathetic ACh causes
Bronchoconstriction
Sympathetic epi/NE causes __ via what receptors
Bronchodilation
B2 adrenergic receptors
The nasal concha increase __ in the nose
Increase surface area of nose
Where does stertor originate?
Nasopharyngeal meatus
What is the most common fungal cause of rhinitis in dogs?
Aspergillus
Rhinosporidium can also occur, usually causes granulomatous mass in rostrum nasal cavity
Cryptococcus can be seen in cats, not aspergillus
Where does stridor originate?
Larynx - sign of laryngeal disease
What is GOLPP ?
Geriatric onset laryngeal paralysis polyneuropathy
Unilateral lar par is most commonly what side?
Left
What cells produce surfactant?
Type II pneumocytes
Type I pneumocytes are involved in what?
Gas exchange
Type __ pneumocytes are sensitive to oxygen toxicity and type __ are resistant
Type I are sensitive to oxygen toxicity
Type II are resistant
Lung compliance is determined by what?
- Elastic forces of lung tissue (1/3) = elastin and collagen fibers
- Elastic forces caused by surface tension of the fluid that lines the inside of the alveoli (2/3) - surfactant
What decreases lung compliance?
High lung volume
Surfactant deficiency
Pulmonary edema
Atelectasis or alveolar collapse
Pulmonary fibrosis
Smooth muscle constriction in the small airways (asthma)
What increases lung compliance?
Age (changing geometry of elastin/collagen)
Emphysema
Body size (lung volume increase)
What conditions can cause an obstructive pattern of flow volume loop?
Think things that hinder expiration
Asthma
Bronchiectasis
COPD
Emphysema
What conditions can cause a restrictive pattern of flow volume loop?
Think things that hinder inspiration (expansion of the lung)
Pulmonary fibrosis
What breed gets idiopathic pulmonary fibrosis?
Westies
MEMORIZE THESE Lung volumes
Tidal volume: 10-15mL/kg - volume of air inspired or expired with each normal breath
Inspiratory reserve volume: The extra volume of air that can be inspired OVER the normal tidal volume when the individual inspires with a full force
Inspiratory capacity: Tidal volume + Inspiratory reserve volume - this is total amount of air an individual can breathe in distending the lungs to the maximum amount
Expiratory reserve volume: extra volume of air that can be expelled by an active expiratory effort after passive expiration
Residula volume: volume of air remain in in the lungs after the most forceful expiration
Functional residual capacity: Expiratory reserve volume + Residual volume - amount of air that remains in the lungs at the end of normal expiration
Vital capacity: Tidal volume + Inspiratory reserve volume _ Expiratory reserve volume - this is the maximum amount of air an individual can expel from the lungs after filling their lungs to the maximum extent and then expiring to the maximum extent
Total lung capacity: Vital capacity + Residual volume - this is maximum amount of air the lungs can be expanded with the greatest amount of effort
What factors affect diffusion across the respiratory membrane?
Thickness of membranes - altered by edema and fibrosis
Surface area - lung lobectomy, emphysema (alveoli coalesce)
Diffusion coefficient of gas
Partial pressure difference - difference between pressures of gas across the membrane; O2 is higher in alveoli than blood leading to net diffusion from the alveoli to blood; CO2 is high in the blood than in alveoli leading to net diffusion into alveoli
What is the pressure of the right ventricle during systole and diastole?
Systole 25mmHg
Diastole 0-1mmHg
What is the pressure of the pulmonary artery during systole and diastole?
Systole 25mmHg
Diastole 8mmHg
What happens when O2 in alveoli decrease?
Adjacent blood vessels constrict which increases vascular resistance. This distributes blood flow to where the lungs are better aerated.
PO2 and PCO2 in the alveoli are determined by what?
Rate of alveolar ventilation
Rate of transfer of O2 and CO2 through the respiratory membrane
What happens to V/Q without ventilation?
V/Q approaches/equals 0
What happens to V/Q without perfusion?
Approaches infinity
What things cause a low V/Q?
This is poor ventilation and decrease in PaO2, so think things that affect ventilation = AIRWAY PROBLEM
Chronic bronchitis
Asthma
Pulmonary edema
Ventral lungs have slightly lower V/Q
What things cause high V/Q?
Think things that cause poor perfusion which will increase PaCO2 = VESSEL PROBLEM
Pulmonary thromboembolism
Dorsal lungs have high V/Q
80% of feline URIs are caused by what two agents?
FHV-1 or feline calico virus
What ocular finding is pathognomonic for FHV-1?
Dendritic ulcers
