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355 Cards in this Set
- Front
- Back
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***propranolol binds to:***
|
B1 and B2 adr's with equal affinity
- it's nonselective |
|
|
effects of propranolol on the CV system:
(3) |
1. dec. HR
2. dec. CO (with corresponding dec. in TPR initially) 3. dec. blood flow to most tissues |
|
|
**chronic effect of propranolol =**
|
dec. BP without postural hypotension
|
|
|
B-antagonists tend to be _______ - specific, b/c:
|
B1-specific,
b/c blocking B2 leads to lots of problems |
|
|
B2-antagonists are contraindicated in:
(3) |
1. asthma/bronchitis/emphysema (due to B2's relaxation of bronchioles)
2. insulin-dependent diabetes (due to B2-adr in liver increasing glycogenolysis) 3. serious allergies |
|
|
why is it bad to give EPI to someone on B2 blockers?
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b/c EPi will cause a serious increase in BP, due to no B2 relaxation but plenty of a1 constriction
|
|
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side-effects of blocking B1-adr's:
(3) |
1. potential inducement of CHF
2. potential life-threatening bradycardia 3. up-regulation of receptors |
|
|
B1-selective antagonists are NOT:
|
specific
- will invariably activate other kinds of B adr's, at least a little |
|
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there are different kinds of B-adr antagonists:
(3) |
1. B1-selective
2. B-antagonists with ISA 3. 3rd-gen Beta blockers |
|
|
examples of B1-selective antagonists:
(3) |
1. atenolol
2. metoprolol 3. esmolol |
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ISA =
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intrinsic sympathomimetic activity
|
|
|
prime example of Beta-adr antagonist with ISA -
|
pindolol
|
|
|
pindolol:
(2) |
1. nonselective
2. partial agonist |
|
|
partial agonist =
|
an antagonist that still causes some stimulation of the receptor
i.e. has a small amount of sympathomimetic effects |
|
|
administering pindolol =>
|
slightly elevated HR, despite blocking Iso, NOR, and EPI
|
|
|
sympathetic effects of partial agonist are less than:
|
that of sympathetic hormones/NT's, but greater than nothing
|
|
|
**3rd-gen Beat blockers like labet and carve block not only B1 but:**
|
1. other B-adr's
2. a1 adr's |
|
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what's the ultimate effect of 3rd-gen Beta-blockers?
|
**improve CHF**
|
|
|
therapeutic uses of Beta blockers:
(5) |
1. all heart problems
2. HTN 3. glaucoma (blocking B1 specifically) 4. stage fright 5. skel muscle tremors |
|
|
2 features of "classical" alpha blockers:
|
1. nonselective
2. dec BP |
|
|
side-effects of classic alpha blockers:
(2) |
1. postural hypotension
2. tachycardia |
|
|
why do nonselective alpha-blockers cause postural hypotension?
|
b/c of the decrease in BP that they cause - blood doesn't get to the head
|
|
|
why do nonselective alpha-blockers cause tachycardia?
(2) |
1. to make up for that postural hypotension
2. due to continuous release of NOR, because blocked a2 adr's can't participate in negative feedback |
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|
why are a1-selective blockers valuable?
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not blocking a2 => NO tachycardia
|
|
|
examples of a1-selective antagonists:
|
all the 'zosins
|
|
|
therapeutic uses of a-adr antagonists:
(3) |
1. HTN
2. CHF 3. urinary obstuction (BPH) |
|
|
BPH =
|
benign prostate hypertrophy
|
|
|
to treat BPH:
|
block a1 receptors
=> dec. SM contraction and cell proliferation of prostate and bladder neck |
|
|
what's the best drug for BPH, specifically?
|
tamsulosin
|
|
|
why is tamsulosin the best treatment for BPH?
|
because it targets the alpha1A-receptor subtype specifically
- allows you to treat BPH without messing other things up |
|
|
there are 3 types of alpha receptors:
|
a1A, a1B, a1D
|
|
|
to treat migraines, use:
|
sumatriptan, a 5HT1D-receptor agonist
|
|
|
the ANS is ALWAYS:
|
active
- continual, intrinsic tone |
|
|
the somatic NS is NOT always active - it's:
|
voluntary
|
|
|
rate-limiting factor of ACH synthesis =
|
**availability of choline**
|
|
|
choline is __________________
|
essential
- can only be obtained from the diet |
|
|
**the vast majority of choline from broken-dwon ACH is:**
|
reuptaken
|
|
|
what takes up choline after ACH breakdown?
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HAChTS
|
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HAChTS =
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high-affinity choline transport system
|
|
|
HAChTS:
(2) |
1. restricted to cholinergic nerve terminals
2. blocked by H3T |
|
|
all nerve terminals contain:
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alternate NT's and receptors
=> NT soup in the synapse |
|
|
ACHE:
(2) |
1. VERY fast - allows fine motor control
2. found presynaptically, postsynaptically, and at the NMJ |
|
|
pseudo/plasma/butyryl choine esterases are NOT:
|
found in the ANS
- but hydrolyze ACH in the blood |
|
|
what does botulinum toxin do?
|
blocks ACH release
|
|
|
what does nerve gas do?
|
irreversibly blocks ACHE's
|
|
|
muscarinic receptors:
(2) |
1. = GPCR's
2. really slow compared to ionotropic receptors |
|
|
what do muscarinic receptors cause, in general?
(3) |
1. dec. cAMP
2. inc. Ca2+ 3. inc. K+ efflux |
|
|
how many muscarinic receptor subtypes are there?
|
5
|
|
|
what do M1, 3, and 5 cause when bound?
|
increased PLC
=> increased Ca2+ => ***increased SM contractions, increased secretions*** |
|
|
secretions are caused by:
|
Ca2+
|
|
|
what do M2 and M4 cause?
(2) |
1. dec. adenylyl cyclase => dec. cAMP
2. inc. K+ efflux, via GIRK's => **decreased HR** |
|
|
2 types of nicotinic receptors:
|
N1 and N2
|
|
|
N1 =
|
skeletal nicotinic receptor
- N2 = neural |
|
|
both N1 and N2 are very, very:
|
fast
|
|
|
why are the nicotinic receptors very fast?
(2) |
1. high density of receptors
2. low affinity for receptors |
|
|
depolarization blockade =
|
inability to repolarize b/c agonist is continually binding
|
|
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how does depolarization blockade usually occur?
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via inhibition of ACHE's
|
|
|
cholinergic drugs should rarely be administered via:
|
IV or IM
|
|
|
how do direct-acting drugs act?
|
by binding to the receptor, activating it to cause ACH effects
|
|
|
how do indirect-acting drugs work?
|
they impair ACHE's, keeping ACH around longer
|
|
|
NO is an
|
NT
|
|
|
most common side effects of cholinomimetic drugs:
(2) |
1. SLUDS
2. vasodilation |
|
|
SLUDS =
|
salivation, lacrimation, urination, defecation, and sweating (via symp. NS)
|
|
|
**sweating is a:
|
sympathetic response**
|
|
|
most serious side effects of cholinomimetic drugs:
(3) |
1. hypotension
2. bradycardia 3. bronchial constriction |
|
|
methacholine:
(3) |
1. **direct-acting** cholinomimetic
2. long-lasting 3. diagnoses asthma |
|
|
how are some cholinomimetic drugs longer-lasting?
(2) |
1. impervious to plasma CHE's
2. resistant to ACHE's |
|
|
glaucoma ~~
|
increased ocular pressure
|
|
|
carbocal:
(3) |
1. long-lasting cholinomimetic
2. acts on muscarinic receptors 3. treats glaucoma |
|
|
pilocarpine treats:
|
glaucoma
[by increasing outflow] |
|
|
notable uses of direct-acting cholinomimetics:
(2) |
1. diagnose asthma
2. treat glaucoma |
|
|
sweating/flushing = sign of
|
ACH toxicity
|
|
|
contraindications for cholinomimetics:
(2) |
1. asthma
2. peptic ulcer |
|
|
total pressure of all gases =
|
760 mm HG
|
|
|
1 tor =
|
760 mmHg
|
|
|
big A =
|
Alveolar
|
|
|
small a =
|
arterial
|
|
|
**the body keeps PAO2 at _______ and PACO2 at ________
|
100;
40 |
|
|
conducting zone =
(4) |
trachea, bronchus, bronchioles, terminal bronchioles
|
|
|
conducting zone:
(2) |
1. NO O2 exchange - no caps nearby
2. = anatomic dead space |
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|
respiratory zone =
(3) |
respiratory bronchioles, alveolar ducts, and alveolar sacs
|
|
|
respiratory zone ~~
|
gas exchange
|
|
|
alveoli are HIGHLY ______________________
|
vascularized
- veins are red |
|
|
**csa ______________ as you move down the respiratory zone**
|
**increases**
- so air velocity slows down as a result |
|
|
expiration is ___________;
|
**passive**
- takes longer than inspiration |
|
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P x V = constant; significance?
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as one goes up, the other goes down
|
|
|
inhale => diaphragm contracts =>
|
increase in volume vertically => dec. Pressure => Patm greater than P Alveoli => air comes in
|
|
|
*Patm always =
|
zero, for reference**
|
|
|
the pleural space is filled with:
|
water, causing lungs to stick to chest wall
|
|
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what is intrapleural pressure during expiration?
|
-5 cmH2O
|
|
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what is intrapleural pressure during inspiration?
|
-8
|
|
|
the lung wants to:
|
collapse;
the chest wall wants to spring up |
|
|
**negetive Pressure =
|
suction**
|
|
|
***transpulmonary pressure = ***
|
difference between intrapleural pressure and alveolar pressure
|
|
|
***transpulmonary pressure equation: ***
|
P Alveoli - intrapleural pressure
|
|
|
***what does the transpulmonary pressure of +5 during expiration do?***
|
holds the lung open because it's pulling
|
|
|
***what does the transpulmonary pressure of +7 during inspiration do?***
|
**overcomes the elasticity of the lung, causing it to expand
- this is turn creates a sub-atm Pressure in the alveoli => air comes in |
|
|
lungs disorders are either:
(2) |
1. obstructive, like emphysema
2. restrictive |
|
|
minute ventilation =
|
Tidal Volume x RR
|
|
|
anatomic dead space =
|
portion of the minute ventilation that doesn't actually participate in gas exchange,
b/c it fills the conducting airways |
|
|
alveolar dead space =
|
alveoli NOT participating in gas exchange due to lack of blood flow past them
|
|
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physiological dead space =
|
anatomical + alveolar dead space
|
|
|
hysteresis =
|
lower volume at same pressure during inspiration, and greater volume during expiration
- remember chart - slope = compliance |
|
|
lung compliance is determined by:
(2) |
1. elastic recoil
2. ST |
|
|
elastic materials:
(2) |
1. resist stretching,
2. assist deflation |
|
|
water interacts better with:
|
itself than with air
=> will create tension on the water-air surface as it pulls in to itself |
|
|
direction of Tension vector of a bubble:
|
always IN
|
|
|
as Tension of a bubble pulls in,
|
internal Pressure pushes out
|
|
|
Pressure of a bubble =
|
2T/r
|
|
|
alveoli ~~
|
bubbles
|
|
|
without SFT, alveoli would be susceptible to **collapse** at:
|
end-expiration
|
|
|
why would alveoli without SFT be susceptible to collapse at end-expiration?
|
too great of a **ST**
|
|
|
alveolar collapse is prevented by:
(2) |
1. SFT
2. alveolar interdependence |
|
|
the majority component of SFT =
|
phosphatidylcholine (PC)
|
|
|
what are 2 critical proteins of SFT?
|
SPB, SPC
|
|
|
SPB and SPC:
(2) |
1. small, hydrophobic peptides
2. ***essential to formation of SFT layer*** |
|
|
what produces SFT?
|
Type II alveolar cells
|
|
|
SFT heads stick into:
|
H20,
and tails stick into air |
|
|
air is actually:
|
hydrophobic
|
|
|
***remember that air is on the:
|
INSIDE of the alveoli***
|
|
|
how does SFT decrease ST?
|
during expiration, alveoli deflate => dec. SA => inc. coverage of surface by SFT => dec. interface b/w air and water => dec ST
|
|
|
greater interface between air and water =
|
**greater total ST**
|
|
|
during inspiration, alveoli expand => inc. SA =>
|
dec. coverage by SFT => inc. interface between air and water => inc. ST
|
|
|
inc. SFT =>
|
***increased compliance***
|
|
|
what causes hysteresis between inspiration and expiration?
|
SFT
|
|
|
babies with RDS are born:
|
before Type II alveolar cells develop
|
|
|
result of not having developed Type II alveolar cells =
|
not enough SFT
=> dec. compliance, collapsed alveoli |
|
|
what's the big idea behind alveolar interdependence?
|
***when they are close enough,*** alveoli tug on each other to prevent collapse of any single alveolus
|
|
|
when is alveolar interdependence especially important?
|
during end-expiration,
when alveolar collapse is most probable |
|
|
alveolar interdependence explains why the compliance slope becomes more steep during inflation:
|
the more the alveoli inflate, the closer they are to each other, the more they tug on each other
|
|
|
in obstructive diseases, lung compliance:
|
increases
=> lungs inflate easily, like a condom - **but it's harder to expire** |
|
|
in restrictive disease, lung compliance:
|
decreases
=> **very hard to inflate, like a surgical hose** |
|
|
total compliance =
|
lung + chest wall compliance
|
|
|
chest wall compliance decreases with:
|
decreasing rib cage mobility, as in obesity
|
|
|
at FRC, chest wall Pressure and lung Pressure are:
|
equal
- tendency of the lung to collapse is opposed by tendency of chest wall to spring out |
|
|
what does pneumothorax do?
(2) |
1. uncouples chest wall from lung
2. increases work of breathing |
|
|
tension pneumothorax ~~
|
collapsed lung
|
|
|
the lung:chest energy transfer system:
(4) |
1. as lungs deflate, they give energy to ribs to spring out
2. as chest expands, it inflates the lungs 3. think potential and kinetic energy - always equal a constant 4. decreases work of breathing |
|
|
the work of breathing is increased in:
(4) |
1. obesity
2. RDS 3. obstructive diseases 4. restrictive diseases |
|
|
flow of air Q =
|
P/R
|
|
|
Resistance of the lungs is HIGHLY dependent on:
|
radius,
as well as on flow |
|
|
trachea, mainstem bronchi flow =
|
turbulent flow
|
|
|
most of bronchial tree flow =
|
transitional flow
|
|
|
small airways' flow =
|
laminar flow
|
|
|
***total airway Resistance ___________ as you go down the lungs***
|
**decreases**
|
|
|
relative csa's:
|
respiratory bronchioles >>> terminal bronchioles >>> trachea/bronchi
|
|
|
increased csa in respiratory bronchioles =>
|
decreased velocity => O2 moves faster by diffusion than by flow
=> gas exchange |
|
|
small airways contribute only slightly to overall lung resistance in healthy lungs; significance:
(2) |
1. called the silent zone b/c changes in R here are hard to notice
2. disease must become well-advance before it can be detected |
|
|
**as Volume of airways increases (with inspiration), radius ____________ and Resistance _______________**
|
increases;
decreases - vice versa for expiration |
|
|
at a certain point of forced expiration, the amount expired will NOT:
|
increase,
**even though effort might** |
|
|
effort-independent expiration is a result of:
|
transmural pressure
(the pressure between any 2 compartments) |
|
|
with every forced expiration, P of Alveoli is dissipated/decreases along the length of the airway =>
|
P.Alveoli reaches the point where it's equal to pleural Pressure == point of max expiratory flow, independent of effort
|
|
|
if the point of equal pressure between the pleural and Alveolar pressure occurs in non-cartilagenous airway, the airway will:
|
collapse
(not fully though, due to alveolar interdependence |
|
|
why does outflow of air continue despite collapsed airway during forced expiration?
|
b/c of elastic recoil of the lungs
|
|
|
emphysema ~~
|
**premature** small airway collapse,
due to higher R along length of the airway |
|
|
coping strategies of people with obstructive pulm diseases:
(3) |
1. exhale slowly
2. breathe off the top of the lungs 3. purse lips for back pressure |
|
|
what does exhaling slowly do?
|
results in a lower intrapleural Pressure
|
|
|
what does breathing off the top of the lungs do?
|
increase diameter, decrease R
|
|
|
all 3 coping strategies force the equal pressure point closer to:
|
the cartilagenous airways, preventing airway collapse
|
|
|
both obstructive and restrictive pulm diseases have a lower:
|
peak flow rate than normal
|
|
|
large airways:
(2) |
1. lowest individual R due to large diameters
2. but largest fraction of total lung R due to smallest aggregate csa |
|
|
small airways:
(2) |
1. high R per individual segment
2. but smallest fraction of total lung R due to huge aggregate csa |
|
|
in the small airways, Resistance is **dynamic**;
|
decreases during inspiration, increases during expiration
|
|
|
FEV1 =
|
volume of air expired in the first second of max expiration
|
|
|
FEV1 is expressed as:
|
a % of FVC
|
|
|
FVC =
|
forced vital capacity
|
|
|
healthy YA's have a FEV1 of:
|
>80%
|
|
|
FEF 25-75% reflects:
|
Resistance of small airways
|
|
|
FEV1 and FVC are decreased in:
|
both obstructive diseases AND restrictive diseases
(but less so in restrictive diseases, and their FEV1/FVC *ratio* is greater than normal) |
|
|
a1 adr's activate Gq => inc. Ca2+ =>
|
**constriction of blood vessels**
|
|
|
what's the most important function of a2 adr's?
|
to regulate NOR release from sympathetic nerves (via negative feedback)
|
|
|
B1 adr's cause:
(3) |
1. inc. HR at SA node
2. inc. contractility at atria and ventricles 3. inc. aqueous humor released from ciliary body |
|
|
B2 adr's cause:
(3) |
1. **relaxation of blood vessels**
2. **bronchodilation** 3. outflow of aq. humor |
|
|
main muscarinic receptor of the heart =
|
M2
|
|
|
SLUDGE =
|
salivation,
lacrimation, urination, defication, GI motility, emesis |
|
|
Atropine:
(3) |
1. classic muscarinic antagonist
2. nonselective 3. opposes nerve gas |
|
|
what do *indirect-acting* cholinergic blockers do?
|
**tie up or inhibit ACHE**
|
|
|
**3 kinds of indirect-acting ChE inhibitors:**
|
1. quaternary alcohols
2. carbamate esters 3. organophosphates |
|
|
quaternary alcohols:
(2) |
1. only form ionic bonds
2. => very short-acting |
|
|
best example of a quaternary alcohol =
|
Edrophonium
|
|
|
Edrophonium:
(2) |
1. quaternary alcohol (short-lasting indirect-acting cholinergic blocker)
2. diagnoses MG if patient gets stronger after dose |
|
|
MG:
(2) |
1. autoimmune disease
2. destroys nicotinic receptors |
|
|
carbamate esters bind as:
|
substrates
=> **long-lasting** ChE inhibitors |
|
|
best example of a carbamate ester =
|
Neostigmine
|
|
|
Neostigmine:
(5) |
1. long-lasting
2. improves transmission at NMJ 3. stimulates GI and urinary contraction/secretion 4. also treats MG 5. problem: nonselective |
|
|
**problem with Neostigmine:**
|
it's NONSELECTIVE
|
|
|
problem with Neostigmine being a nonselective ChE inhibitors:
|
ACH/ACHE is used **everywhere**
=> inhibited ACHE everywhere => unintended ACH-less consequences everywhere (however, desensitization occurs over time) |
|
|
***normal ACH effects:***
(4) |
1. SLUDGE
2. bradycardia 3. bronchial constriction 4. constriction of pupil |
|
|
ChE inhibitors treat:
(3) |
1. MG (also diagnose)
2. glaucoma 3. overdoses of muscarinic blockers |
|
|
side-effects of ChE inhibitors =
|
excessive ACH/parasympathetic effects, b/c ACH is sticking around longer
|
|
|
organophosphates:
(2) |
1. **irreversibly** inhibit AChE's
2. **nonselective** => taken up e/w |
|
|
***what does irreversibly inhibiting AChE's lead to?***
|
***respiratory paralysis***
|
|
|
2 best examples of irreversible ChE inhibitors:
|
1. DFP
2. Sarin (nerve gas) |
|
|
DFP treats ______________, but only as ________________________________________________________________
|
glaucoma;
last resort, because it causes cataracts |
|
|
***treatments of organophosphates:***
(3) |
1. ventilator, immediately
2. atropine 3. pralidoxine |
|
|
pralidoxine =
|
fast-acting ACHE regenerator;
must be administered soon after poisoning |
|
|
cholinergic blockers are used for:
|
anything that requires a dec. in ACH/parasymp. activity, like mydriasis or excessive secretions
|
|
|
mydriasis =
|
chronic dilation of the pupil
|
|
|
cycloplegia =
|
paralysis of the ciliary muscles
=> loss of accomodation |
|
|
***3 types of cholinergic blockers:***
|
1. muscarinic receptor blockers
2. nicotinic ganglionic receptor blockers 3. nicotinic neuromuscular blockers |
|
|
most important feature of ***muscarinic blockers:***
|
they are **competitive**
|
|
|
best example of a muscarinic blocker =
|
atropine
|
|
|
atropine:
(3) |
1. antimuscarinic
2. enters CNS 3. results in atropine flush, mild tachy |
|
|
atropine flush =
|
dilation of facial blood vessels
|
|
|
toxicity of muscarinic blockers is NOT:
|
lethal
|
|
|
all nicotinic ganglionic receptor blockers are:
|
nonselective
- and b/c ganglia are everywhere, they block everywhere |
|
|
side effects of nicotinic ganglionic blockers:
(7) |
1. vasodilation
2. dec. venous return 3. tachy 4. dec. tone/motility of GI 5. urinary retention 6. dry mouth 7. mydriasis |
|
|
there are 2 types of nicotinic ganglionic receptor blockers:
|
1. competitive/nondepolarizing
2. noncomp/depolarizing |
|
|
best example of a competitive nicotinic ganglionic blocker =
|
trimethaphan
|
|
|
**trimethaphan:**
(3) |
1. competitive nicotinic ganglionic blocker
2. **very short-lasting** 3. used ONLY during hypertensive crises |
|
|
best example of a noncomp/depol nicotinic ganglionic blocker =
|
nicotine
|
|
|
nicotine:
(3) |
1. noncomp nicotinic blocker
2. highly toxic 3. NO therapeutic uses |
|
|
effects of nicotine:
(4) |
1. n/v
2. headache 3. dizziness 4. weakness |
|
|
there are 2 types of nicotinic neuromuscular receptor blockers:
|
1. competitive
2. depolarizing |
|
|
***which ACH receptor is used at the NMJ?***
|
**nicotinic**
|
|
|
best example of a competitive nicotinic NM blocker =
|
curare
(D-Tubo) |
|
|
curare (D-Tubo):
(2) |
1. competitive nicotinic NM recept. blocker
2. paralyzes skeletal muscle |
|
|
**how is curare overcome?**
|
by AChE *inhibitors*
|
|
|
best example of noncomp. nicotinic NM receptor blocker =
|
succinylcholine
|
|
|
succinylcholine:
(2) |
1. **very** rapid and brief
2. => rapid paralysis but rapidly broken down by plasma AChE |
|
|
what is the advantage of using succinylcholine over curare?
|
**it's rapid and brief**
|
|
|
***what is a disadvantage of using succinylcholine?***
|
it's got **no antagonists**
- cannot be overcome - must be broken down by plasma AChE's |
|
|
phase II block =
|
desensitization to succinylcholine after repeated administration
|
|
|
minute ventilation = MV =
|
TV x RR
|
|
|
**alveolar ventilation** =
(how much ventilation actually occurs at the alveoli) |
MV - dead space ventilation
|
|
|
**at constant CO2 production, doubling alveolar ventilation => **
|
halving PACO2
|
|
|
**at constant CO2 prouction, halving alveolar ventilation => **
|
doubling PACO2
|
|
|
b/c COs2 is so soluble, PACO2 =
|
PaCO2
|
|
|
***regulation of ventilaiton is driven primarily by:***
|
PaCO2
|
|
|
hyperpnea =
|
the normal increase in ventilaiton due to increase in metabolism
- e.g. exercise => inc. CO2, so ventilation increases to maintain normal PCO2 |
|
|
hyperventilation =
|
disproportionate increase in ventilation relative to metabolism, causing a dec. in PCO2
|
|
|
hypoventilation =
|
disproportionate decrease in ventilation relative to metabolism
=> *increase in PCO2* |
|
|
if the lung is functioning properly, the pressures of O2 and CO2 at the end of the cap will be:
|
the same as those in the alveoli
|
|
|
***normal A-a difference = ***
|
age/4 +4
|
|
|
ventilation is NOT uniformly distributed throughout the lung; apical alveoli:
|
remain open during expiration => more distended
|
|
|
alveoli at the base of the lung are more:
|
compliant
=> more ventilation to the bottom |
|
|
features of the pulmonary circulation:
(2) |
1. low Pressure
2. high volume |
|
|
low pressure of pulmonary circulation prevents:
|
fluid extravasation/edema
|
|
|
arterioles of the pulmonary circulation are:
|
numerous, short, thin, and have *little*SM
(unlike systemic arterioles) |
|
|
airway caliber =
|
diameter
|
|
|
pulmonary caps are highly:
|
compliant
|
|
|
2 classes of pulmonary vessels:
|
1. extra-alveolar
2. alveolar |
|
|
extra-alveolar vessels:
(2) |
1. *not adjacent* to alveoli
2. increase caliber/decrease R when inflating |
|
|
alveolar vessels:
(2) |
1. adjacent to alveoli
2. when alveoli are inflating, they get squished (=> dec. caliber, increased R) |
|
|
blood flow to the lung is different depending on:
|
which region of the lung you're looking at
|
|
|
zone 1 of the lungs:
(3) |
1. top
2. ~ pinched off/collapsed caps due to PA > Pa > Pv 3. => **least perfusion** |
|
|
zone 2 of the lungs:
(2) |
1. Pa > PA > Pv
2. collapse/pinch occurs near venules on the right, due to pressure dissipating until it falls below PA |
|
|
zone 3 of the lungs:
(4) |
1. bottom
2. Pa > Pv > PA 3. airway at the alveoli is wide open 4. ~ greatest perfusion (draw it out) |
|
|
ventilation and perfusion at the apex of the lungs:
(5) |
1. stretched out due to higher intrapleural P
2. low compliance 3. low ventilation, even lower Q 4. ***=> high V/Q*** 5. higher PaO2 |
|
|
***V/Q is directly proportional to:***
|
PAO2
|
|
|
ventilation/perfusion at the bases of the lungs:
(5) |
1. not stretched
2. high compliance 3. high V, higher Q 4. ***=> low V/Q*** 5. lower PAO2 |
|
|
hypoxic pulmonary vasoconstriction =
|
how pulmonary arteries *constrict* if PO2 is low in certain alveoli, thereby shunting blood to perfuse well-ventilated ones
- preserves V/Q ratio of 1:1 |
|
|
hypoxia =
|
inadequate oxygenation of blood
|
|
|
widespread alveolar hypoxia (via hypoxic pulm. vasoconstriction, due to late-stage disease) =>
|
increase in pulmonary artery pressure
=> pulmonary HTN |
|
|
long-standing pulmonary HTN =
|
cor pulmonale
|
|
|
O2/CO2 exchange occurs via
|
passive diffusion
|
|
|
CO2 is much more __________ than O2
|
permeable
|
|
|
increased SA of diffusion barrier =>
|
increased diffusion
|
|
|
SA of the blood-gas barrier is very:
|
large
|
|
|
thickness of the blood-gas diffusion barrier is:
|
miniscule;
allows for tons of gas exchange despite many layers of tissue in the diffusion pathway |
|
|
lung = sheet of blood b/w:
|
2 thing papers of exchange membranes
|
|
|
***PO2 and PCO2 equilibrate in about the same amount of time, ***
|
0.25 sec
|
|
|
time it takes for RBC to flow past alveoli =
|
0.75 sec
|
|
|
since it takes an RBC 0.75 sec to pass through the cap, and, and only 0.25 secs for the gases to equilibrate, there is:
|
reserve time for additional gas exchange,
as during exercise, when blood flow rate is increased, or for altitude, when O2 gradient (drive) decreases |
|
|
O2 takes _____ secs to bind to Hb
|
0.20
|
|
|
**O2 bound to Hb does NOT factor into:**
|
the partial pressure of O2 at the caps
|
|
|
N2O:
(4) |
1. perfusion-limited
2. highly permeable gas 3. equilibrates so fast that blood will *always* leave with full N2O, no matter the transit time 4. => greater perfusion just means more N2O is taken up |
|
|
CO (gas):
(4) |
1. diffusion-limited
2. very low permeability 3. binds nearly irreversibly to Hb => enters Hb sink 4. blood will *never* be full equilibrated with CO, even if flow rate slows down significantly |
|
|
pathologies that increase the diffusion barrier can turn O2 from ___________________ to _________________
|
perfusion-limited;
diffusion-limited |
|
|
turning O2 into a diffusion-limited gas ~~
|
blood leaves alveoli before O2 is fully equilibrated
=> PAO2 > PaO2 |
|
|
some pathologies may allow O2 equilibration at rest, but not:
|
during exertion
|
|
|
DL-CO =
|
reflection of all diffusion parameters:
SA, permeability, thickness, Hb sink, etc. |
|
|
2/3 of O2 consumed goes to:
|
skeletal muscle, brain, and liver,
in equal parts |
|
|
1/3 of O2 consumed goes to;
|
the rest of the body
|
|
|
O2 is carried through blood in 2 forms:
|
1. bound to Hb - 98%
2. dissolved in blood - 2% |
|
|
dissolved O2 is insufficient for:
|
metabolic needs
|
|
|
P50 of the O2 dissociation curve is the point at which:
|
Hb is 50% saturated
|
|
|
significant decline in O2 sat. occurs rapidly after:
|
60 mmHg of PO2
|
|
|
placing patients on supplemental O2 has little affect until around:
|
70 mmHg of PO2
|
|
|
low O2 ~~ systemic cap's ~~
|
**lower part of the curve**
- Hb is unloading O2 for the tissues to use |
|
|
venous blood curve is shifted ____________ relative to the O2 dissociation curve (arterial)
|
rightward;
~~ decreased affinity of Hb for O2 |
|
|
***Bohr Effect*** =
|
righward shift of the O2 curve
|
|
|
the Bohr effect is the result of:
(3) |
1. low pH
2. high CO2 3. high Temp |
|
|
the Bohr effect indicates:
|
**increased release of O2 due to decreased affinity of Hb for O2**
|
|
|
the Bohr effect occurs at:
|
**metaboli/systemic tissues**
|
|
|
CO2 is carried in the blood in 3 forms:
|
1. dissolved (10%)
2. carbamino cmpnds (30%) 3. as HCO3 (60%) |
|
|
"carbamino cmpd" ~~
|
bound to protein, usually Hb
|
|
|
in the tissues, O2 is converted into:
|
CO2
|
|
|
pathway of CO2 from systemic tissue:
(7) |
1. pumped out to blood
2. 10% of it dissolves 3. rest enters RBC's 4. 60% converted to HCO3 via CA 5. HCO3 is pumped out of RBC and into blood, in exchange for Cl- 6. H+ binds HbO2, kicks off O2 => O2 to tissues 7. 30% of CO2 binds to proteins like Hb, forming carbamino cmpds |
|
|
CO2 pathway is _____________ in the lungs
|
reversed
=> CO2 taken up from blood and into alveoli |
|
|
what is the Halldane Effect?
|
oxygenation of hemoglobin (Hb) decreases the affinity of Hb for CO2;
- most important for the liberation of CO2 into the alveoli |
|
|
CO2 dissociation curves are nearly:
|
linear
|
|
|
CO2 curve: ***lower PCO2 = ***
|
***lower blood/tissue content of CO2***
|
|
|
PCO2 is directly proportional to:
|
CO2 content of the tissue
|
|
|
physiological pH =
|
7.4
|
|
|
primary buffer system of the body =
|
HCO3 and CO2
- they regulate phys pH |
|
|
***kidneys control the concentration of:
|
HCO3
- lungs control PCO2 |
|
|
buffering =
|
keeping pH steady despite changes to acid/base concentrations
|
|
|
when CO2 production = elimination, pH is:
|
constant
|
|
|
2 kinds of acid in the body:
|
1. volatile/respiratory
2. nonvolatile/fixed acids |
|
|
2 examples of volatile / respiratory acids:
|
HCO3 and CO2
|
|
|
HCO3 is considered a volatile acid b/c:
|
it drives production of CO2
|
|
|
volatile acids are eliminated by:
|
the lungs
|
|
|
nonvolatile/fixed acids are:
|
end products of metabolism
(lactic acid, HCL, etc.) |
|
|
nonvolatile acids are eliminated by:
|
the kidneys
|
|
|
good buffers are effective within:
|
1 pH unit in both directions of their pKa
|
|
|
pKa of HCO3 =
|
6.1
|
|
|
why is HCO3 an excellent buffer?
(3) |
1. it's abundant
2. it's part of an open system 3. PCO2 and HCO3 can be regulated independently (by kidney and lung, respectively) |
|
|
"open system" refers to how the body is:
|
connected to the air via the lungs
|
|
|
other buffers apart from HCO3 exist, like:
|
Hb
- rich in Histidine = good buffer |
|
|
buffering occurs both intra- and extracellularly; volatile acids are buffered ______________________, and fixed acids are buffered _____________________________
|
intracellularly;
both intra- and extracellularly |
|
|
acid-base disturbance =
|
departure from normal values of pH, PaCO2, and HCO3
|
|
|
acidosis =
|
pH below 7
|
|
|
***hypoventilation => HIGH:***
|
PCO2
|
|
|
changes in ventilation can eiterh disrupt pH or:
|
compensate for a disruption in pH
|
|
|
HCO3 is a:
|
base
|
|
|
hyperventilation => LOW
|
PCO2
|
|
|
time difference between renal and respiratory compensation:
|
renal compensation takes hours to days;
respiratory compensation is immediate |
|
|
renal compensation:
(2) |
1. eliminate acids
2. reclaim HCO3 |
|
|
**PCO2 is proportional to:
|
[ HCO3 ]
|
|
|
HCO3 is proportional to:
|
pH
- as HCO3 increases, pH increases (less H+) |
|
|
conditions that cause respiratory acidosis:
(2) |
1. HYPOventilation
2. obstructive lung disease (fibrosis, asthma, emphysema) |
|
|
conditions that cause resp. alkalosis:
(2) |
1. hyperventilation
2. asthma |
|
|
compensation for resp. acidosis:
(2) |
1. kidneys eliminate nonvolatile/fixed acids
2. kidneys retain more HCO3 net effect = increase plasma HCO3, inc. pH |
|
|
compensation for resp. alkalosis =
|
less excretion of acid by kidneys
|
|
|
***metabolic acidosis and alkalosis occur WITHOUT:***
|
changes in PCO2
|
|
|
metabolic acidosis occurs b/c of:
|
overproduction of metabolic products (lactic acid, keto acids)
|
|
|
compensation for metabolic acidosis =
|
**hyperventilation**
to decrease CO2 and increase HH equation's PCO2 ratio to HCO3=> increase in pH |
|
|
causes of metabolic alkalosis:
(2) |
1. vomiting
2. diuretics |
|
|
compensation for metabolic alkalosis =
|
HYPOventilation
|
|
|
5 causes of hypoxemia:
|
1. reduced PIO2
2. hypoventilation 3. diffusion impairment 4. anatomic shunt 5. V/Q mismatch |
|
|
reduced PIO2 ~~
|
higher elevation,
=> lower PO2 from the start => lower driving force all the way down in alveoli |
|
|
hypoventilation is improved with:
|
supplemental O2
- O2 problem is easy to fix; it's the increased CO2 and dec. pH that are the real problems |
|
|
diffusion impairment =
|
increased diffusion barrier
=> lung becomes diffusion-limited |
|
|
diffusion impairment is HIGHLY:
|
treatable with O2
=> supplemental O2 increases the driving force => increased diffusion |
|
|
anatomic shunt (bean in bronchus):
(3) |
1. usually an extra-pulmonary cause, like airway block
2. **supplemental O2 will NOT help** 3. PCO2 can be normal, due to elevated ventilation |
|
|
**why doesn't an anatomic (airway) shunt respond to supp. O2?**
|
b/c alveoli are not being ventilated;
perfusion can be high, but it doesn't matter |
|
|
anatomic shunts are different from anatomic dead space, which refers to:
|
alveoli not being **perfused**
|
|
|
if a patient doesn't respond to O2, they probably have:
|
anatomic shunt
|
|
|
detailed - why anatomic shunts can't be helped with O2:
(3) |
1. Hb from well-ventilated alveoli is already saturated with O2
2. extra O2 from well-ventilated areas is dissolved O2 3. dissolved O2 is not enough to saturate Hb from poorly-ventilated areas |
|
|
pulmonary venous admixture has low:
|
O2 content
|
|
|
best V/Q ratio =
|
1
|
|
|
even a normal lung has some:
|
V/Q mismatch
|
|
|
what is the single biggest cause of hypoxemia?
|
V/Q mismatch
|
|
|
different regions of the lung have different:
|
V/Q ratios
|
|
|
V = zero corresponds to:
|
anatomic shunt, i.e. no ventilation
|
|
|
emphysema V/Q ratio is:
|
high, due to poor perfusion
|
|
|
bronchitis V/Q ratio is:
|
low, due to blocked ventilation
|
|
|
during exercise, BOTH:
|
V and Q increase, in proportion
=> maximum drive, without hypoxemia |
|
|
in diseases, only one or the other:
|
changes
(referring to V and Q) |
|
|
what is the rate-limiting factor of exercise?
|
CO,
not ventilation |
|
|
V/Q mismatch responds to:
|
supplemental O2
|
|
|
which of the 5 causes of hypoxemia respond to supplemental O2?
(4) |
1. hypoventilation
2. diffusion impairment 3. V/Q mismatch 4. altitude |
|
|
which conditions cause an increase in the A-a difference?
(4) |
1. V/Q mismatch
2. physiological shunt 3. diffusion impairment 4. intracardiac right-to-left shunt |
|
|
which conditions do NOT change the A-a difference?
(3) |
1. hypoventilation
2. reduced arterial O2 content due to dec. carrying capacity 3. low barometric pressure |
