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What are the normal partial pressures of O2, H2O, and CO2 in the lung (no alveoli)? Recall that this is saturated air.
- O2: 150 mm Hg
- CO2: Essentially 0
- H2O: 47 mm Hg
What are the 2, 2, and 2 involved in the respiration pathway?
- 2 convective processes: breathing and circulation
- 2 respiratory media: air (external) and blood (internal)
- 2 diffusion barriers: alveolar walls and interstitial space between capillaries and cells
List and describe the 4 lung volumes and 4 capacitances
- Residual volume: amount of air left in the lung after forced expiration
- Inspiratory Reserve Volume: volume that can inspired from top of tidal curve to maximal inspiration
- Tidal Volume: the volume inhaled/exhaled during normal (quiet) breathing
- Expiratory Reserve Volume: volume that can be expired after the bottom of the tidal volume curve
- Functional Residual Capacity: equilibrium point, volume left in the lungs at end of quiet expiration
- Inspiratory capacity: volume that can be inhaled from quiet expiration to full inspiration
- Vital Capacity: volume from full inspiration to full expiration
- Total capacity: total volume of the lungs at full inspiration
What is the most commonly used method to measure FRC? Why is it better than the He dilution method?
plethysmography. Because He method doesnt measure the volume that is trapped by obstructed airways
What effects do fibrosis and emphysema have on lung compliance and FRC?
- Fibrosis (and Acute Respiratory Distress Syndrome): decreases compliance, decreases the FRC (TLC is low)
- Emphysema: lung becomes more compliant, increases the FRC (IRV is decreased)
- Breathing is difficult in both of these
What are the muscles involved in quiet breathing?
- Inhalation: Mostly diaphragm, external intercostals
- Exhalation: Mostly elastic recoil (almost no work done), internal intercostals
What nerve (coming from which spinal segments) innervates the diaphragm?
The L and R phrenic nerve (C3,4,5)
Explain the clinical significance of closing volume in lungs.
alveoli at the base of the lung inflate late in inspiration and close before full expiration. Small bronchioles collapse before alveoli, trapping a stagnant volume of air (the closing volume). Not good for gas exchange.
What forces need to be overcome when performing work to breathe
- airway flow resistance
- frictional forces
- elastic recoil of lungs
- inertia of air and lungs
What is surfactant made of?
- 90% phospholipids
- 10% proteins
What are 7 properties of surfactant?
- Production starts in third trimester
- Reduces mechanical work of breathing by reducing ST
- Stabalizes alveoli of different sizes
- Keep alveoli dry by reducing ST forces that would full fluid from capillaries
- Part of the mucociliary escalator
- Synthesized by type II alveolar cells
- Short halflife (about 2 hours)
describe the pressure, resistance, and flow in the pulmonary circulation
- Low pressure (14 mm Hg normally)
- Low Resistance: like pressure, an order of magnitude lower than seen in systemic circulation.
- High Flow
Why is pulmonary pressure and resistance so low compared to systemic?
- Pressure: Dont need to pump to head, high pressures would cause pulmonary edema
- Resistance: vessels are very compliant (not much smooth muscle)
Pressure wise, list the three functional zones of the lung
- Zone 1: PA>Pa>Pv (these blood vessels are compressed, no flow)
- Zone 2: Pa>PA>Pv (flow determined by Pa and PA gradient)
- Zone 3: Pa>Pv>PA (blood vessels are distended, flow is determined by Pa and Pv gradient)
How does the pulmonary circulation cope with the increased CO during exercise
- Initially, there is a recruitment of parallel vessels, lowering resistance
- Previously opened vessels also distend, reducing resistance
- This allows for increased flow without an increase in pressure, which would cause pulmonary edema
What is the purpose of hypoxic pulmonary vasoconstriction (HPV)?
To divert blood away from poorly ventilated parts of the lung (e.g. a consolidation). Why perfuse it if you can't have gas exchange, right?
What is the normal oxygen pressure gradient at the lung?
- 60mm Hg
- 100 in alveoli and 40 in arterial side blood
What is the normal CO2 pressure gradient at the lung?
- 5mm (but it is 20X more soluble than oxygen)
- 45 in arterial side, 40 in alveoli
What are N2O and CO good examples of?
- NO2 is a perfusion limited system (need new blood to come in to take more) (O2 is also usually perfusion limited)
- CO is a diffusion limited system (blood doesnt get saturated in the time it is in contact with the gas)
What can affect DLCO?
- change in membrane area
- change in membrane thickness
What are the three resistances for oxygen from alveoli to hemoglobin
- alveolar wall
- RBC membrane
- O2 hemoglobin reaction rate
What are the 4 (3 extrinsic and 1 intrinsic) factors that influence P50 at the tissues
- 1) temperature: increased temp, decreases affinity
- 2) CO2 concentration: increasing CO2, decreases affinity by increasing [H+] concentrations
- 3) [H+]: increasing [H+] (acidosis, decreasing pH), decreases affinity by strengthening salt bridge bonds
- 4) 2,3-DPG (intrinsic): increased synthesis in hypoxic conditions, strenghtens the DPG bond in hemoglobin and decreases oxygen affinity.
Describe what happens when CO2 is transported in the blood stream (usually)
- Most CO2 enters the RBC where it is combined with a water molecule to make carbonic acid (reaction facilitated by CARBONIC ANHYDRASE ENZYME)
- Almost all carbonic acid is converted to bicarbonate and a proton
- bicarbonate leaves the RBC
- acid strengthens the salt bonds in Hb, lowering its O2 affinity. Hb also acts as a buffer, mopping up the loose protons and allowing more CO2 to be converted to bicarbonate (Haldane effect)
What are the 4 causes of hypoxemia (low oxygen content of arterial blood)
- Alveolar capillary diffusion block
- Anatomical shunt
- Ventilation/Perfusion (V/Q) inequality (most common cause)
Explain how CO2 alone causes a response in the central receptors (which are on the ventral surface of medulla).
HCO3- and H+ are both not able to cross the BBB, but CO2 can. It directly stimulates chemoreceptors and also decreases the pH (increases H+) in the CSF (which has little or no protein to buffer), which also sets off some receptors
Besides peripheral and central receptors, list 5 sensors involved in respiration.
- 1) Pulmonary Stretch Receptors: mechano receptor in the lung, "inspiratory off switch"
- 2) Juxtapulmonary capillary receptors: found in alveolar walls, rapid shallow breathing, reduce heart rate, terminate exercise
- 3) Irritant receptors: airway epithelium, respond to irritants, causes aspiration, coughing, sighing depending on where they are located
- 4) Respiratory proprioceptors: in skeletal muscle, cause breathing response
- 5) Diaphragm muscle receptors
Describe the course of the trachea to its bifurcation
- Attaches to the cricoid cartilage at about C6
- Bifurcates at the sternal angle (T4/5), called carina to left and right bronchus
Why is the right bronchus more susceptible to aspiration than the left?
right brochus is wider, shorter, and more vertical than the left.
Describe the first three generations of bronchioles
- On right lung: right bronchus, the secondary bronchi, then segmental bronchi
- On left lung: same, but only two secondary (lobar) bronchi
What are the 4 surfaces on the lung? The fissures?
- Surfaces (Same on both):
- right: horizonal and oblique
- left: oblique only
Differentiate between R and L lung hilum
- Right brochus is to the Rear of the pulmonary artery
- Left bronchus is Lower than the pulmonary artery
- on both the pulmonary veins are lower than the bronchus
Describe the pulmonary innervation
- Sympathetic: from paravertebral ganglia
- brochodilation, vasoconstriction, less secretion
- Parasympathetic: vagus
- -motor (opposite of above)
- -sensory - various receptors
Describe the olfactory epithelium. How is it different from resp. epithelium?
- Olfactory (receptor) cells (bipolar neurons)
- Supporting Cells
- Basal cells
- Brush Cells
- Parts of Bowman's glands (secrete odorant binding protein, short lifespan)
- No goblet cell or mucous glands in olfactory
- many nerve fibres in olfactory
- respiratory is thinner
Cells of the respiratory epithelium
- Ciliated columnar
- Goblet Cells
- Basal Cells
- Brush Cells
- Neuroendocrine cells
- Clara Cells
- Lymphyocytes and Mast cells
Describe the progression of the following throughout the bronchial tree:
- Cartilage: Trachea to bronchi (segmental)
- SM: Trachea to alveolar ducts
- CT glands: Trachea to larger bronchioles
- Goblet Cells: Trachea to bronchioles (large ones only)
- Clara Cells: Only in bronchioles (mostly terminal and respiratory)
- Elastic Tissue: Trachea to alveoli
- Ciliated Cells: Trachea to bronchioles
Describe the layers in a mature trachea
- respiratory epithelium
- lamina propria
- sub mucosa
- fibroelastic tissue
Differences between trachea, bronchi, and bronchioles
- Trachea: rings of cartilage, smooth muscle in non cartilage regions
- Bronchi: plates of cartilage, helical rings of SM
- Bronchioles: no cartilage,
Describe structure, function, and location of Clara cells
- Structure: tall and domed
- function: secrete surfactant and anti-inflammatory
- location: mostly found in terminal and resp. bronchioles
Describe the roles of the following during ventilation.
- Conducting Portion: warms, moistens and filters air. mucociliary escalator
- Epithelium: MC escalator, source of mucus, facilitate gas exchange, secrete surfactant
- Hyaline Cartilage: Strength without hindering changes in length and diameter
- Smooth Muscle: spiral arrangement provide changes in length and diameter in response to neural input
- Elastic Tissue: permits expansion and recoil
What effect does asthma have on lungs?
Allergen causes mast cell to release interleukin 13 which causes edema, excessive mucus production, attracts eosinophils, contracts SM. All of these cause bronchoconstriction
What effect does systic fibrosis have on the lungs
There is a defective Cl- channel, which causes the mucus to become dehydrated (viscous), which interferes with the MC escalator and causes build up of mucus on the walls of passageways.
What effect does emphysema have on the alveolar walls?
destruction of alveolar walls causing larger and larger air spaces. Usually caused by smoking.
What effect does pneumonia have on lungs?
air spaces fill with exudate and neutrophils and other leucocytes. Capillaries become large and congested too.
What are the differences between O2 saturation and partial pressure between fetus and adult. Why is smoking bad for baby?
- PO2 is much lower in fetus than adult
- This is because fetal Hb has a much higher O2 affinity than adult Hb
- The dissociation curve is steeper, therefore there is a narrower window where the oxygen disassociates, cannot handle stress as well (smoking lowers PO2 in mom's blood)
What are the 5 stages of lung development?
- 1) limb bud pinches off and divides 3 times (4-5 weeks)
- 2) Pseudoglandular period (5-16 weeks): formation of bronchioles (to terminal), no gas exchange possible
- 3) Canalicular period (16-26 weeks): development of resp. bronchioles, not much gas exchange, small chance of survival
- 4) Terminal sac period (26-36 weeks): primitive alveoli (terminal sacs) formed, some gas exchange, chances of survival increase with time
- 5) 36 weeks to 8 years: most (5/6) of the alveoli developed during this time
What is the purpose of fetal breathing movements?
- stimulates lung development
- conditions/strengthens respiratory muscles
Describe the resporption of fluid during vaginal birth.
- labour causes the fluid in the lungs to be resorbed into the pulmonary circulatory and lymphatic systems
- some fluid squeezed out of the lungs during passage through the vaginal canal
What is a tracheoesophageal fistula? How would you diagnose?
abnormal connection between the esophagus and the trachea. Acid reflux into trachea. commonly associated with blind ending esophagus.
What is Esophageal Atresia? How would you diagnose?
A blind-ending esophagus. Usually associated with tracheoesophageal fistula. immediate regurgitation
What is a diaphragmatic hernia? What can it cause?
It is a failed closure of the diaphragm, most commonly on the left side. This can lead to pulmonary hypoplasia (small lungs), because abdominal organs invade the thorax and push everything over. Can also be caused by excessive uterine pressure and a weak diaphragm.
What are some of the common causes of respiratory distress syndrome? How can you treat?
- 1) Immaturity of lung tissue and alveoli: lower surfactant production can lead to alveoli collapsing
- 2) Poor diffusing capacity: thick walls, inadequate surface area because of inadequate alveoli development.
- Treatment: glucocorticoid injection increases alveolar development, ventilatory support, artificial surfactant