Respiratory Lectures (8) Flashcards
4 primary functions of respiratory system?
L1
- Exchange of gases b/n atm and blood
- homeostatic regulation of body pH
- protection from inhaled pathogens and irritating substances
- vocalization
Air exchange occurs via ____.
L1
Bulk Flow
- blood flows from high to low pressures
- muscular pumps create pressure gradient (heart)
- resistance influenced most by diameter of tube that air is flowing through (length same, viscosity rarely changes in blood)
Why is it hard to breathe in a sauna?
L1
Air is more viscous (more water in it)
External Respiration
L1
movement of gases (mostly O2 and CO2) b/n enviro and cells
External Respiration steps
L1
- inhalation and exhalation -> exchange of air from atm to lungs & vice versa (ventilation)
- exchanging fresh O2 with CO2 into and out of body (lungs to blood) @ alveoli
- transport of gases in blood
- exchange of blood into the cells
Respiration requires coordination b/n ____.
L1
Respiratory and cardiovascular systems
:when you breathe slower your heart rate slows
Structures involved in ventilation and gas exchange
L1
→ conducting airways (upper and lower respiratory system)
→ alveoli
→ bones and muscles of thorax cavity (create force to move air)
Order the upper and lower respiratory system structures in order
L1
Nasal cavity pharynx larynx trachea (first of lower) L and R bronchi bronchioles alveoli
Where is the site of gas exchange in lungs?
L1
Alveoli
Bones and muscles in the thorax cavity
L1
Walls = spine, ribs, sternum, muscles Floor = diaphragm
What are the muscles of inspiration?
L1
Thorax cavity
-sternocleidomastoids, scalenes, external intercostals, diaphragm
What are the muscles of expiration?
L1
Thorax cavity
-internal intercostals, abdominals
Lungs composed of?
L1
light spongy tissue filled mostly by air-filled sacs (ALVEOLI)
- right lung slightly bigger than left (3 lobes)
- left has 2 lobes = cardiac notch
- each lung surrounded by pleural sac
Composition of pleural sac
L1
double-walled
- one layer connected to surface of LUNGS = visceral pleura, or wall of lungs (inside)
- other one connects to surface of thoracic CAVITY and DIAPHRAGM at bottom = parietal pleura (outside)
What’s the point of the pleural sac?
L1
- create moist slippery surface and prevent lungs from rubbing on walls during inhalation/exhalation (can move a bit)
- hold lungs to thoracic wall so they stay in an OPEN state since they are muscle tissue and naturally want to recoil (collapsed lungs)
How much fluid is inside the pleural sac?
L1
~10-20ml of fluid in entire lung since very small space b/n visceral and parietal layer
path air travels b/n coming into nasal cavity/mouth and ending in the alveoli
L1
nasal cavity → pharynx → larynx (vocal cords) → trachea (windpipe, semiflexible tube held open with ~20 cartilage rings) →L and R bronchi (going to L and R lungs) → smaller bronchi → bronchioles (no more cartilage on them, only smooth muscle, control amount of air coming to alveoli) → alveoli (air exchange)
Velocity of air ___ as it goes down the respiratory system.
L1
Decreases → important for alveoli to be able to properly do airflow exchange
- branching imc total cross sectional area
- velocity of air flow inversely proportional to total cross sectional area, V = Q/A
- only bronchioles and alveoli are exchange surfaces. All others are part of conducting system
Upper airways and bronchi play important role in _____.
i.e. Jobs?
L1
→ warm air to body (so body temp doesn’t fluctuate)
→ adding water vapor (alveoli need to be moist so gases can diffuse across → SALINE)
→ filter out foreign materials (traps them)
the 3 processes of upper airways and bronchi are more efficient with ___.
L1
Nose breathing:
→ nasal cavity has bigger SA, rich in blood supply and hair
→ shape of it allows air to come in fast so particles embed in mucus in back of pharynx and slide down to esophagus
Air is filtered in the ___.
Describe mucocillary escalator.
L1
Trachea and bronchi
→ saline produced by epithelial cells. Overtop saline is layer of mucus produced by goblet cells. Mucus contains immunoglobulins to neutralize pathogens
→ mucociliary escalator: cilia in epithelial cells beat, push saline up so it pushes mucus with pathogens into pharynx and down to stomach
What is necessary for the mucociliary escalator to function?
L1
Saline
→ without saline layer, cilia become embedded in thick mucus and unable to move which can lead to infections, scarring of airways, inability to breath
Describe the CFTR channel
L1
Model of saline secretion by epithelial cells
→ A NKCC channel brings 2 Cl into epithelial cell from ECF
→ As 2 Cl- enter the epithelial cell, creates -ve charge
→ Na+ moves from ECF to cell paracellularly
→ this Na and Cl movement creates [ ] gradient for water to move from ECF to cell
→ anion channel on apical membrane allows Cl to enter lumen
*K that enters epithelial cell is removed by K channel
Cystic Fibrosis
L1
Autosomal recessive mutation in gene making CFTR (cystic fibrosis transmembrane conductance regulator)
→ less saline production: less Cl transport
→ mucus can’t be cleared properly, bacteria colonizes airways: recurrent lung infections
→ life expectancy ~40 yrs
→ affects pancreas (name: formation of cysts and fibrosis of pancreas)
Alveoli general facts (6)
L2
→ bulk of lung tissue
→ clustered at ends of bronchioles
→ heavy vascularized (covered in capillaries for gas exchange)
→ huge surface area
→ connective tissue tethers alveoli together
→ thin barrier where gases have to diffuse across: short distance = max diffusion
Types of alveoli
L2
Pneumocytes → bulk of wall of alveoli, for gas exchange. Make up 95% of SA
type 2 → 5% of epithelial cells. Make surfactant
resident alveolar macrophages → filter pathogens
Pulmonary Circulation
-why low pressure?
L2
High flow, low pressure
→ 0.5L (10%) of blood vol (75ml in capillaries)
→ rate of blood flow in lungs is high
→ low pressure circuit even w high flow: all blood goes through 10x/min i.e. 5L/min: bp of 25/8
→ low pressure bc of low resistance (short circuit, less gravity battle bc it mostly moves down, more distensible and more total CS area of arterioles (less smooth muscle)
Pulmonary Circulation: Low pressure means ___ out of capillaries but _____.
L2
minimal filtration of fluid out of capillaries but there’s lymphatic fluid to remove unfiltered fluid in lungs and keep min. diffusion distance
Both blood pressure and atm pressure are reported in ___.
What about respiratory pressure?
L2
→ mmHg
→ respiratory pressure: cmH2O
→ 1 mmHg = 1.36 cmH2O
→OR kPa: 760 mmHg = 101.325kPa
*normal sea level atm pressure is 760 mmHg but usually set to 0 cmH2O since we want to know pressure diff from enviro to inside body
Dalton’s Law
L2
total P exerted by gas mixture (atm air) is sum of P exerted by each gas (partial pressures)
→ depends on humidity of air
Partial pressure of gas =
Pgas in humid air =
L2
*partial P of gas = Patm x % of gas in atm
→ look at O2 and CO2 since their P drive diffusion
→ take account of water vapor P: in 100% humidity in 25 C, PH2O is 24 mmHg
*Pgas in humid air = (Patm - PH2O) x % of gas
Bulk flow described by:
P of inspiration and expiration?
L2
F = ΔP / P
→ ΔP: b/n alveoli and in atm (set to 0)
→if P in atm > alveoli = -F = inspiration
→ if P in alveoli > atm = +F = expiration
*control flow direction by changing lung size
Boyle’s Law
inc vol =
dec vol =
L2
P1V1 = P2V2 (inversely related)
→ helps to explain how change in lung vol creates change in lung P driving bulk flow
→ Alter P by changing V since gas exerts P on walls of alveoli/lungs
→ inc V = less bumping = dec P
→ dec V =more bumping = inc P
Inspiration and boyle’s law
L2
Lung V inc = alveoli V inc = P drop below atm = -F = P gradient = bulk flow of air into alveoli from atm
How is ventilation measured? What machine?
L2
1 respiratory cycle = inspiration and expiration
→ Spirometer measures lung V
→ inhale = bell sinks, water raises. Exhale = bell raises, water drops.
Spirometer tracing shows? (6)
L2
Tidal Volume Inspiratory reserve volume Expiratory reserve volume Total lung capacity Functional residual capacity Inspiratory capacity
Tidal Volume
L2
TV ~500ml
→ amount of air entering and exiting lungs during quiet respiration
→ total pulm ventilation = TV x freq of breaths
Inspiratory reserve volume
L2
IRV ~300ml
→ air that could be inspired beyond quiet inspiration
expiratory reserve volume
L2
ERV ~1100ml
→ air remaining within lungs that could be expired after quiet expiration
residual volume
L2
RV ~1200ml
→ can’t be measured with spirometer
→ amount of air left in lungs even with max expiratory (after you expire even your ERV)
→ prevents airway collapse since it takes LARGE P to re-inflate lungs → allows continuous gas exchange & prevents wasted energy of transporting useless blood
Total lung capacity
L2
sum of all 4 volumes
= TV + ERV + IRV + RV
= 3100 ml
functional residual capacity
L2
amount of air left in lungs after quiet expiration
→ ERV + RV (~2300ml)
inspiratory capacity & vital capacity
L2
max amount of air that can be inspired
→ IRV + TV (~800)
*vital capacity is max achievable (forced) tidal volume = IRV + TV + ERV (~1900ml)
Pulmonary function test
L2
someone’s forced vital capacity (FVC) compared to forced expired volume in 1 second (FEV1)
→ FEV1 is ~80% of VC (1520ml). Any lower: obstructive pulmonary disease (inc. resistance) **asthma
→ FVC ~3-4L. Any lower: restrictive pulmonary disease (dec lung compliance so harder to bring in/out enough air) ex, pulmonary fibrosis
*in these diseases, other one is a normal value
*inspiration occurs when alveolar pressure decreases so… how do we change alveolar pressure?
L3
Use skeletal muscle pump to increase vol of lungs/alveoli creating P dec
→ ~70% of inspiratory volume change is DIAPHRAGM (main muscle of quiet ventilation)
→ ~30% of vol change is rib cage movement (external intercostals and scalenes)
Diaphragm positioning
L3
sheet of skel muscle at thoracic cavity base
resting position → curved up
contracting → flattens downwards and inc thoracic cavity volume by pulling lungs downward
External Intercostals and scalene movement
L3
external UPPER intercostals and scalenes contract in a “pump handle” motion, so they move out
→ scalenes move from neck to upper ribs and moves sternum outwards
external LOWER intercostals create “bucket handle” motion, so they move up
→ imagine each rib as handle of bucket: contraction causes them to lift upward and out so increases vol
Since expiration occurs when alveolar pressure increases… how do we do this?
L3
→ quiet expiration: passive relaxation of inspiratory muscles (external muscles and scalenes)
→ as everything relaxes: vol decreases in thoracic cavity = lung vol dec = alveoli pressure increases above atm = air flows out (follows pressure gradient)
Muscles involved in forced expiration?
L3
→ abs (contraction inc pressure in abdominal cavity, pushes diaphragm upward in its curved state, dec lung vol, inc pressure)
→ internal intercostals and triangularis sterni (depress sternum more, dec thoracic vol)
→ neck/back muscles (curl over, dec thoracic vol)
Muscles involved in forced inspiration?
L3
→ sternocleidomastoids (neck to front of sternum, lift sternum out, contribute to pump handle effect)
→ neck/back muscles (lift head, inc thoracic volume and extend back)
→ upper respiratory tract muscles (dec airway resistance; open larynx to let more air in)
Pleural sac helps to ___.
L3
hold thoracic cavity in inward position slightly
Intrapleural cavity fluid pressure?
L3
~-3mmHg
→ more positive at base of lung
→ more negative at apex of lung because of gravity pulling layers together more
Pleura during contraction (inspiration)
L3
Inspiratory muscles pull parietal layer away form visceral layer
→ inc vol of intrapleural cavity, dec pressure (more neg than normal)
→ neg pressure draws lungs outward to expanded state (VACUUM)
→ Palv dec, air flows in
Pleura during relaxation (expiration)
L3
As inspiratory muscles start to relax, chest wall recoils inward → intrapleural pressure goes normal -3mmHg as parietal layer moves towards visceral layer
→ neg pressure holding lungs open lessens so lungs recoil towards pre-inspiration site
→ Palv inc, air flows out
Pneumothorax (collapsed lung)
L3
If one of the pleura layers is ruptured, intrapleural pressure becomes atm as air rushes in to neg pressure
→ no negative pressure holding lungs open: recoil/collapses
→ traumatic pneumothorax: parietal layer ruptured by rib/stabbed….
→ spontaneous pneumothorax: diseases break down visceral layer, get bubbles and air leaks from lungs into cavity, pressure becomes atm.. (70% due to COPD)
Lung Compliance
L3
= change in lung vol / (Palv-P intrapleural)
i.e. ΔV / ΔP
→ basically how stretchy lungs are (how much can they expand in inspiration?)
→ inc compliance = small change in intrapleural pressure creates large change in lung vol (v stretchy). **Easy inspiration, hard expiration
Lung Elastance
L3
→ reciprocal of compliance
→ elastic recoil of lungs (how much can they resist being deformed?)
→ low elastance = can’t resist expansion
Pulmonary Fibrosis
L3
Decreased compliance due to formation of excess fibrous connective tissue in lungs (recoil tissue, lungs resist change in V/P
→ will only stretch with LARGE changes in intrapleural pressure (lots of effort to inspire since stiffer, easier to exhale tho since lots of connective recoil tissue)
→ increased elastance
→ some cases caused by pollutant inhalation/infections/spontaneous (idiopathic) causing fibroblasts form extra tissue in lungs
→ affects diffusion of gases since walls around alveoli become thicker and less gases go across
Increased compliance causes intrapleural pressure to ___.
L4
→ DECREASE; easy inhale, hard exhale
*decreased compliance causes intrapleural pressure to INCREASE; hard inhale, easy exhale
Emphysema
L4
proteolytic enzymes secreted by leukocytes attack alveolar tissue
→ causes loss of capillaries and reduction of SA as alveoli merge (# of individual alveoli dec) = less gas exchange
→ causes loss of lung recoil (inc compliance) leading to further dec gas exchange since stale air gets stuck in alveoli (can’t exhale)
→ weakens alveoli walls, airways eventually inc in resistance so inhalation gets harder too
→ CIGARETTES cause macrophages to release elastase which break down elastic layer
→ new treatment places coils in larger bronchi to return some elastic recoil in lungs
Main determinance of elastic recoil and compliance in healthy lungs is?
L4
Fluid lining inner walls of alveoli
→ surface tension of air-water interface of airways: H bonds b/n H2O molecules causes them to pull together when exposed to O2
Effect of surface tension of compliance?
L4
→ measure of force acting to pull a liquid’s molecules together at a water-air interface
→ if a lung was only filled with water, it is way more compliant so it takes LESS negative pressure in intrapleural cavity to cause inflation of lung
Laplace’s equation
L4
→ pressure needed to overcome the inward pressure
P = 2T/r
T = surface tension at pure air water interface, ~70dynes/cm
r = bubble radius
How does surface tension form?
L4
→ water forms H BONDS causing them to adhere to each other
→ DO NOT have pure water interface: if we had a pure water interface, smaller alveoli would not inflate since larger alveoli would have greater PRESSURE
Describe how an Alveoli is affected by surface tension?
L4
Inside the alveoli wall is a small liquid layer, then air taking up the entire inside area.
→ water H bonds try to pull alveoli inward since bonds getting tighter (smaller), increases pressure inside
→ have to overcome inward pressure caused by surface tension of water in walls of alveoli
Surfactant
L4
→ “detergent” secreted by type 2 alveoli
→ help to reduce surface tension (i.e. INC COMPLIANCE: easier to inflate, reduces “inward” pressure)
→ ENSURES ALVEOLI OF ALL SIZES FILL *more surfactant in smaller alveoli
→ breaks up surface tension by 25 dynes/cm
→ is amphipathic: wedges between water molecules and reduces H bonds
→ without surfactant, alveoli would collapse
→ ~90% phospholipids, 10% proteins
Surfactant with larger alveoli and smaller alveoli?
L4
→ the more an alveoli grows, the farther it’s surfactant moves apart, decreasing its effects and increasing surface tension, thus breaking expansion
→ this allows smaller and larger alveoli to grow at the same time, since larger alveoli will have more of this breaking occuring
Infant respiratory distress syndrome
L4
pree-mee’s born without surfactant development/immature lungs can’t breathe on their own or is hard to
→ surfactant begins forming ~25weeks. You have 50% prevalence by 26-28 weeks, 25% by 30-31 weeks
→ prevent it by injecting mom with glucocorticoid (if not enough surfactant in amniotic fluid)
→ treat baby with artificial surfactant, or intubate them, or give them continuous positive airway pressure (so tidal volume is higher up and airways remain open all time)
Based on poiseuille’s equation, F = ___
L4
F= ΔP x π (r^4) / 8nl
→ inverse of poiseuille’s x pressure gradient
→ in healthy person, ~90% of airway resistance occurs in trachea/bronchi & is constant since they have the smallest total cross-sectional area
→ more total cross sectional area going down to alveoli dec resistance
Factors that affect airway resistance?
L4
\ length of system → NOT a factor, constant
\ viscosity of air → humidity and altitude can alter it
\ diameter of upper airways → physical obstruction (mucus..)
\ diameter of bronchioles → bronchoconstriction (parasympathetic neurons, histamine, leukotrienes) or bronchodilation (CO2, epinephrine)
Bronchoconstriction and dilation factors
L4
→ commonly paracrine control (CO2 major one)
→ high levels of CO2 cause dilation to increase blood flow and get rid of as much CO2
→ histamine released from mast cells causes bronchoconstriction (allergy)
**parasympathetic nerves innervate bronchiole smooth muscle lining airways and, with irritants, activate PLC-IP3 pathway via M3 muscarinic receptors (release ACh, cause constriction so irritants don’t make it down)
**during activity, need more air in, so epinephrine binding B2 adrenergic receptors (activates adrenal cyclase pathway: reduces light chain activity, causes hyperpolarization) to cause dilation
Asthma
L4
bronchiole smooth muscle becomes hypersensitive to irritants causing spasms and constriction
→ infrequent attacks: can have a B-adrenergic agonist treatment to oppose constriction
→ frequent attacks: weekly inhaled corticosteroid to reduce inflammation
Efficiency of breathing (ventilation)?
L4
→ total pulmonary ventilation: volume of air moved into and out of lungs/minute
→ TPV = ventilation rate x tidal volume (Vt)
→ normal ventilation rate is 12-20 breaths/minute, Vt is 500ml
→ TPV ~ 6000ml/min
Is total pulmonary ventilation a good indicator of how much fresh air reaches the alveoli? What do we use to determine this?
L4
NO
→ ~150ml of air brought in remains within conducting air space that doesn’t partake in gas exchange (ANATOMICAL DEAD SPACE, Vd)
→ use Alveolar ventilation (accounts for dead space)
→ AV = ventilation rate x (tidal volume - dead space)
→ AV = 12 breaths/min x (500 - 150 ml) = 4200 ml/min
*exhale 150ml of fresh air and ~350ml of stale air (what made it to alveoli), but 150ml of that stale air doesn’t leave
→ ALWAYS 150ml dead space
→ during inhalation, only ~350ml make it to alveoli
Gas composition in the alveoli? What do they determine?
L5
PO2 and PCO2 are relatively constant
→ fresh air (~350ml) is diluted upon entering lungs because there’s already air in there
→ determines rate of O2 and CO2 diffusion between alveoli and capillaries bc determines pressure gradient
Alterations in ventilation rates?
L5
→ independent of CV system
→ alters partial pressures of O2 and CO2, thus diffusion
HYPERVENTILATION → more O2 brought in (less CO2 too), so less diffused, pressure increases
HYPOVENTILATION → less O2 brought in (more CO2), so pressure drops. However, as keep going, more CO2 is in lungs not being breathed out so pressure will increase
Why are ventilation and alveolar blood flow (perfusion) matched? What controls them?
L5
→ blood flow must be high enough to pick up the O2 brought in. If diff, heart works harder than it has to: wasted ventilation/perfusion
Local regional control via GRAVITY
→ when you stand up, perfusion is highest at base of lung (Zone 3), lowest/absent at apex (zone 1) since less blood going up
→ low P circuit: bad at pushing blood up
→ upper regions (apex) capillaries ~closed since most negative IP pressure (bc of gravity) so they are filled even at rest & don’t take in much air in ventilation: creates more resistance/less flow
Other control of ventilation/perfusion (pulmonary bronchioles and arterioles)?
L5
→ gravity
→ little autonomic innervation
→ primarily influenced by dec O2 levels (causes constriction as cell depolarizes when K+ channels CLOSE)
→ inc CO2 levels causes dilation to let more O2 in
Ventilation-Perfusion Mismatch: what if bronchiole is blocked?
How does local control fix the problems?
L5
→ decreased ventilation causes alveolar CO2 to inc, but because same amount of blood pumping, O2 drops
→ If PCO2 increases, bronchioles dilate, and pulmonary arteries vaguely constrict
→ If PCO2 decreases, bronchioles constrict, pulmonary arteries dilate
→ if PO2 increases, bronchioles constrict, pulm arteries dilate
→ if PO2 decreases, bronchioles dilate, pulm arteries really constrict
Blood clot in the lungs preventing blood from going to alveoli causes?
L5
→ ventilation normal, perfusion decreases
alveolar/tissue’s around alveoli PO2 inc, PCO2 dec (because O2 still bring breathed in, but blood is not bringing back CO2 from tissues)
This affect surrounding bronchioles, and because of the drop in CO2 (most sensitive to CO2), they will CONSTRICT and redirect air/blood to different non affected alveoli
Bronchioles most sensitive to ___ levels, whereas arterioles most sensitive to ___.
L5
Bronchioles → CO2
arterioles → O2
Hypoxia and Hypercapnia?
L5
→ If diffusion from alveoli to blood (or blood transport) is impaired and THERE’S TOO LITTLE O2 = hypoxia
→ hypoxia often paired with hypercapnia = EXCESS CO2 which can cause pH to inc, and proteins unfold etc
Hypoxic hypoxia
L5
Low arterial PO2
→ high altitude, hypoventilation, decreased lung diffusion capacity
Anemic hypoxia
L5
decreased total O2 bound to hemoglobin
→ blood loss, anemia, carbon monoxide poisoning
Ischemic hypoxia
L5
reduced blood flow
→ heart failure (whole body hypoxia), shock, thrombosis
Histotoxic hypoxia
L5
failure of cells to use O2 bc they’re poisoned
→ cyanide, metabolic poisons
3 variables body responds to (to avoid hypoxia and hypercapnia)
L5
- amount of O2 in blood (for ATP production) → normal in arteries is 95mmHg +/- 7.5, in veins its 40mmHg
- amount of CO2 (CNS depressant/acid precursor) → arteries are 40mmHg +/- 5, veins is 46mmHg
- pH level → arteries 7.4 +/- 0.02, veins 7.37
How do O2 and PO2 levels fluctuate in body?
L5
→ O2 high in air, CO2 low
→ once in body, alveoli have 100mmHg PO2, PCO2 is 40mmHg
→ in arterial blood, O2 still 100mmHg, PCO2 still 40
→ once at the cells, PO2 ≤ 40, PCO2 ≥ 46
→ in venous blood, PO2 ≤ 40, PCO2 ≥ 46
Alveolar gas exchange influenced by?
L5
→ O2 reaching alveoli – depends on air composition,, alveolar ventilation: rate/depth of breathing, airway resistance, lung compliance)
→ gas diffusion b/n alveoli and blood – depends on concen’ gradient, partial pressures i.e. amnt of O2 coming in, SA, diffusion distance: barrier thickness, amnt of fluid
→ adequate perfusion of alveoli
Hypoxia causes (1)? L5
inadequate amounts of O2 reaching alveoli:
1 → inspired air having low O2 content (atm pressure, minimal until HUGE altitude diff)
2 → alveolar ventilation issue (hypoventilation, inc airway resistance, dec lung compliance, dec rate/depth of breathing *drugs, or CNS issue)
If hypoxia is not caused by inadequate amounts of O2 reaching alveoli, what else could it be?
L5
Problem with gas exchange b/n alveoli and blood
→ barrier thin b/n type 1 alveoli and endothelial cell, interstitial space in barrier where gases have to diffuse across can be expanded if inc fluid/connective tissue build up occurs, causing less gas exchange
Diffusion factors
L6
→ [ ] gradient (partial pressures, us. determinant of diffusion)
→ SA (inc SA = more chance gas hits and crosses/diffuses)
→ barrier permeability ( gas solubility)
→ diffusion distance (more distance dec diffusion rate)
*For maximum diffusion: want in SA, inc gradient, inc permeability and less distance
→ normally, SA, distance and permeability are constant
Diseases caused by diffusion issues: emphysema, fibrosis, edema, asthma
L6
Emphysema → dec SA as alveoli walls get destroyed
Fibrosis → barrier dec in permeability as it becomes more dense as fibrous connective tissue deposits
Edema → diffusion distance inc as pressure inc in pulmonary circuit causes more fluid into interstitial space
Asthma → pressure gradient dec as bronchioles restrict and let less O2 into alveoli
Gas solubility and diffusion?
3 factors affecting movement of gas from air to liquid?
L6
respiratory gases must be soluble in liquids as the interstitial space in the barrier is liquid and blood is liquid
1 → pressure gradient of gas
2 → solubility in liquid: CO2 is v soluble, so edema (inc fluid, inc distance) doesn’t affect PCO2
3 → temperature (rel constant)
*Concerning solubility, can have hypoxia but not hypercapnia because CO2 is soluble
O2 transport in the blood (FICKS EQUATION)
L6
→ depends on venous O2 transport, cellular O2 consumption (Qo2) and arterial O2 transport mL O2/min
→ Fick’s equation subs mass flow eq for O2 transport in mass balance eq:
→ Qo2 = CO x (Ao2 - Vo2)
*Ao2 usually 200ml O2/min
*Vo2 usually 150 ml O2/min
*CO usually 5L/min
so, Qo2 = 250 ml O2/min
How is O2 carried if its not soluble in liquid?
L6
Hemoglobin
→ tetramer that binds 4 O2 molecules
→ binds to heme group
→ ~250 Hb molecules in 1 RBC (98% of blood O2 bound to HB)
O2 binding to Hb creates?
What happens in the tissues?
L6
oxyhemoglobin – HbO2
→ as [free O2] inc, more taken up until plasma and Hb reach equilibrium for given O2 partial P: O2 diffuses into plasma, pressure gradient pulls O2 into RBC until Hb saturated
→ O2 transfer from alveolar air, to plasma, to RBC’s, onto Hb occurs FAST: saturated in 0.4sec
→ in tissues, process reverses: low PO2 in cell draws dissolved O2 out of plasma, disrupting equilibrium so HBO2 releases its O2 into plasma (then sent to mito for ATP creation)
→ at 100mmHg, Hb’s 98% saturated
Point of Hb?
L6
→ gases diffuse until equil reaches (all Hb binding sites taken up by O2)
→ O2 taken up until Hb saturated at given PO2
→ HB ensures enough O2 can be bound/transported before equil reached
→ Hb basically creates new pressure gradient: since O2 bound to Hb doesn’t count in gradient, more will continue to move until PO2 same on both sides & equilibrates between cells, plasma and RBC’s
Hemoglobin necessity
L6
→ at rest, consume ~250ml O2/min
→ plasma only carries ~3 ml O2/L blood i.e. 15 ml O2/min
→ Hb carries 197 ml O2/L blood i.e. 1000 ml O2/min (why we need it)
Amount of O2 binding to Hb depends on?
L6
→ Plasma O2, determined by composition of inspired air, alveolar ventilation rate, gas exchange efficiency (determines Hb % saturation)
→ PO2: can drop extremely low before it actually affects us: < 28 mmHg (v low), still delivers 500ml O2/min
→ amnt of Hb: which determines total # of binding sites since 4/Hb (calculated from Hb content/RBC x # of RBC’s). Relatively constant, unless lost a lot of blood or have disorder with reduced/abnormal Hb
Amount of O2 bound to hemoglobin at any given PO2 is expressed as ____.
O2/Hb binding curve?
L7
the % saturation of Hb
→ O2/Hb binding curve: Relatively flat so even if slight deviations in alveolar PO2, alveoli really good at picking up O2, and keep saturation: at 100mmHg its 98% saturation
→ really flattens out over PO2 of 100mmHg – nearly impossible to fully saturate Hb at physiological relevant values (saturation occurs at 650 mmHg)
→ steepens with PO2 lower than ~40 mmHg (40 mmHg is resting cell, % sat is 75%)
→ at low PO2 (like in an active cell), Hb has low affinity for O2 so it wants to drop its O2 off into tissue cells (Hb at 20 mmHg has 35% saturation so tissues take 65% of O2!
Physical factors altering Hb affinity for O2 (% saturation)? (4)
L7
pH → drop causes Hb dec affinity for O2 (shift right), 15% more O2 dropped off at tissues. Causes: anaerobic metabolism (lactic acid and inc H+ disrupts normal H bonding in Hb, can’t hold onto O2 as good)
PCO2 → inc CO2 dec Hb’s affinity for O2 as its converted to H+ (carbonic anhydrase) and binds to Hb which alters its conformation. Causes: inc aerobic metabolism causing inc CO2 production
Temp → inc temp dec Hb’s affinity for O2 as heat causes conformational change in Hb. Causes: active muscles produce more heat
2,3-bisphosphoglycerate → more 2,3-BPG dec Hb’s affinity for O2 as it means more ATP is being made (byproduct of glycolysis) which will inc blood flow, and O2 delivery
What is the Bohr Effect?
L7
A shift in Hb saturation as result of pH or CO2 levels
Maternal and Fetal hemoglobin curves?
L7
Different type of Hb in babies: higher affinity for O2 so they can pick up more O2 from their mother’s blood
→ mom’s blood feeds into placenta, baby has to be able to get enough O2 from this low PO2
→ babies have 2 gamma globin subunits, instead of 2 beta
Why does CO2 have to be removed from the body?
L7
→ inc CO2 causes low pH: acidosis (protein denature)
→ high CO2 causes CNS depression (confusion, coma, death – reduces neuronal activity)
How is CO2 transported in body?
L7
→ venous plasma carries 7%
→ RBC’s carry 93%
→ 23% binds to open sites on hemoglobin (HbCO2, carbaminohemoglobin)
→ 70% converted to HCO3-
Describe CO2 transportation process and how CO2 is dropped off in the lungs?
L7
→ blood arrives at systemic capillaries, PCO2 of RBC cytosol is 40 mmHg
→ PCO2 of cells is >46 mmHg (metabolism)
→ CO2 diffuses from cell to plasma, creates new gradient, 7% stays in plasma, 93% enters RBC cytosol - 23% of that binds open Hb sites
→cytosol: carbonic anhydrase turns the 70% into H+ & bicarbonate. Hb buffers H+ (HbH)
→ HCO3- enters plasma in exchange for Cl
→ transports to lungs
→lungs: pulm capillaries/alveoli - 40 mmHg
→ 7% CO2 in plasma diffuses into alveoli, creates new gradient, Hb unbinds the 23% CO2 (law of mass action): diffuses into alveoli
→ HCO3- renters RBC (Cl shift reversible) and CA converts it back to CO2 and H2O using the H+ from HbH, diffuses across
→ continues until PCO2 is equilibrated between cell, plasma and RBC ~46 mmHG
Purpose of CO2 to HCO3- conversion?
L7
→ inc CO2 transport from cells to lungs
→ HCO3- buffers metabolic acids, stabilizes pH (enters plasma, buffering any acid made e.g. lactic acid)
*depends on carbonic anhydrase and follows law of mass action
conversion of CO2 to HCO3- and H+ continues until ___.
L7
Equilibrium is reached @ 46 mmHg
→ as CO2 inc in RBC’s, rxn drives right
→ to keep driving rxn, Cl- shift remove HCO3- from RBC and Hb buffers (binds) excess H+ (makes hole)
→ prevents big pH change/respiratory acidosis
CO2 binding to Hb at tissues
L7
CO2 binds free Hb sites that O2 has just left, at exposed amino groups, forming HbCO2 (carbaminohemoglobin) *reversible
O2 pickup at lungs after CO2 is dropped off
L7
→ PCO2 drops in plasma, facilitates free O2 to diffuse into plasma & RBC
→ as Co2 levels in RBC dec, equilibrium lost and CA reverses rxn (shifts left) so HCO3- and H+ reform CO2 and H2O
What monitors ventilation?
What parts in the brain are involved in ventilation, and regulating it?
L8
→ central and peripheral chemoreceptors monitor blood gases and pH
→mechanoreceptor reflexes monitor irritants
→ “pacemaker” in brainstem creates positive feedback loop which initiates inspiration, when it stops: passive expiration
→ pons integrates sensory info/info from upper areas and interacts with medulla to influence ventilation: PRG
→ medulla is main respiratory control center: DRG, VRG, NTS
Neuron groups in Medulla/pons that control breathing (4)
L8
→ dorsal respiratory group (DRG)
→ (ventral) VRG
→ (pontine) PRG
→ nucleus tractus solitarius (NTS)
DRG
L8
controls quiet inspiration
→ sends outputs to inner intercostal muscles and diaphragm and gets sensory input from lung walls and airways to alter breathing rate
→ recruit somatic motor nerves for active inspiration
VRG & Pre-botzinger complex
L8
→ controls muscles of active inspiration and expiration (not the ones DRG controls)
→ always active to some degree (keep upper airways open, but can slow down too much while sleeping - snoring, sleep apnea)
→ Within the VRG is the pre-botzinger complex: has pacemaker neurons that may initiate respiration, continuously sends input to DRG about diaphragm/intercostal muscles for inspiration
PRG
L8
→ takes in sensory info to create/maintain SMOOTH respiratory rhythm
→ provides tonic input to DRG to help coordinate smoothness
→ gets continuous sensory info from DRG (doesn’t create rhythm, could live without it)
NTS
L8
→ has DRG of neurons that control inspiratory muscles via phrenic nerve and intercostal nerve
→ input via peripheral mechan/chemoreceptors
CO2, O2, and pH sensed by?
L8
Peripheral chemoreceptors: aortic/carotid bodies
→ sense changes in artial’s, send input to RCC (medulla) to adjust ventilation
→ swollen region of aortic arch/carotid sinus
→ Type 1 glomus cells (carotid bodies) sense changes and synapse on a sensory neuron going back to RCC for adjustment
Glomus Cells
L8
→ sense changes in CO2, O2, pH
→ send info back to RCC
→ function via K+ channel inhibition since they’re O2 sensitive
→ large drop in O2 = K+ closes = depolarized cell = Ca+2 channels open = neurotransmitter release to send back to RCC
→ takes large drop (under 60 mmHg) in arterial PO2 to trigger
→ only respond to PO2 in plasma, not blood
→ can respond to inc in H+ and CO2 (still K+ channels)
Central Chemoreceptors
L8
→ in medulla
→ give continuous input to RCC (tonic)
→ maily respond to PCO2 changes by: pH changes in the cerebrospinal fluid caused by CO2 (HCO3- since CA converts it in the fluid). *Not plasma pH changes
→ neurons here have H+ sensitive channels (ASIC) that open with inc H+ and transmit AP’s to RCC
Effect of decreased arterial O2
L8
→ as PO2 drops under 60mmHg, ventilation drastically inc since Hb loses its saturation
→ If arterial PO2 drops under 60, peripheral chemoreceptors (carotid bodies!!) start inc their firing to inc respiratory muscle contraction (inc rate/depth of breathing)
Effect of increased arterial H+
L8
→ production of non-CO2 acid inc = arterial H+ inc → sensed by peripheral chemoreceptors, they inc firing, which inc respiratory muscles contraction and ventilation = reduce CO2 → shifts CA equation left, reducing H+ concentration
Effect of increased arterial CO2
L8
→ mediated by both central (70%, most sensitive to CO2) and peripheral chemoreceptors (30%)
→ *PCO2 >70 mmHg depresses ventilation bc of inc electrical activity in RCC
→ causes inc respiratory muscle contraction, as central and peripheral chemoreceptors inc firing, so faster breathing gets rid of excess CO2 quickly
Reflexes protecting lungs from pathogens
L8
*irritant receptors in lungs send input to CNS which sends parasympathetic output as:
→ bronchoconstriction
→ rapid shallow breathing leads to turbulent airflow (to deposit irritant in mucosa)
→ coughing/sneezing
*Stretch receptors prevent over inflation of lungs
→ Hering-Breuer inflation reflex
We can actively hold our breath until ____.
What else can inc breathing?
L8
Chemoreceptor take over → pain: medulla → excitement/nervousness: limbic system → emotions: hypothalamus → conscious control: cerebral cortex
Exercise and ventilation
L8
→ some of motor cortex output goes to RCC: since activating lots of muscles, good to increase breathing rate at same time
→ ventilation doesn’t inc bc of the gases
→ feed forward loop: sensory input comes into RCC, ventilation jumps 20 fold as soon as exercise starts, even though neither arterial PO2 or PCO2 has changed
