Midterm 3/Final Flashcards
what is the etiology of reperfusion injury?
- osmotic overload
- pH paradox
how does osmotic overload cause reperfusion injury?
- large increase in number of small molecules in the cytoplasm increases osmolarity from 300 mOsm/l to 400 mOsm/l
- causes water to enter the cell making them swell and rupture
- intracellular organelles also swell and rupture
how do the number of small molecules in the cytoplasm increase with reperfusion?
- breakdown to ATP -> ADP + Pi
- breakdown of phosphocreatine -> creatine + Pi
- breakdown of glycogen to lots of lactate molecules
what is the pH paradox?
rapid reperfusion causes further harm
- reperfusion washes away extracellular H+, creating a gradient for H+ to leave the cell (NHE1 - Na+/H+ exchanger)
- H+ in the cell inhibits Na/K-ATPase
- [Na+] in cell goes up, driving NCX to bring in Ca2+
- increased Ca2+ causes Ca2+ overload causing 1) activated proteases and 2) mitochondrial Ca2+ overload
- ultimately causes cell death
how does subendocardial ischemia present as a diastolic injury current?
- causes elevated (depolarized) RMP in injured subendocardium
- causes diastole to be more depolarized than systole (elevated T-Q segment)
- atrial depol. and ventricular repol. elevated (less potential difference between endo and epi)
how does subendocardial ischemia present as a systolic injury current?
occurs when ischemic injury prevents normal depolarization (Vepi > Vendo)
- net flow of positive charges is away from electrode during systole, displaying S-T depression
what is a transmural infarct? how does it show on ECG?
dead tissue from subendo to subepi
- some endocardial depol persists due to increased preconditioning in endocardium
- shows as S-T elevation (gradient towards electrode during systole)
what ECG changes are present with myocardial infarction?
- heightened T waves
- followed by T wave inversion (altered directionality of repolarization)
- ST segment elevation due to injury current
- deep Q waves
what serum changes occur during myocardial infarction?
- lactate dehydrogenase (LDH)
- creatine kinase (CK)
- Troponin I (TnI)
- cardiac myosin-binding protein C (CmyC)
how does TnI detect MI?
TnI:
- calpain degrades TnI
- blood TnI levels raise during infarct
what is preconditioning?
- repeated brief, mild ischemia
- multiple angina episodes may offer protection
- almost every insult (reduction in blood flow) in life offers protection
how does repeated brief, mild ischemia offer protection?
- increased Katp activity
- increased vasodilator metabolites (adenosine, CO2, hypoxia)
- release of NA, bradykin, opioids (activate G proteins, protein kinases (PKC, PI3-K))
what is postconditioning?
- restarting the flow in brief bursts rather than all at once
- short bursts of reperfusion produce the least damage
what consists of the upper and lower respiratory tracts?
upper:
- nasal cavity
- pharynx
- larynx
lower:
- trachea
- bronchi
what are the functions of the respiratory system?
1) gas exchange
2) conditioning inspired air
- warming and moisturizing
- filtering particles >10 um
3) secretion of mucus
- clear debris from airways
- host defense (immunoglobins, inflammatory mediators
4) filter small emboli from the blood (reduce blood clots)
5) secrete surfactant and ACE
6) acid-base balance of blood (CO2-HCO3- buffering)
7) vocalization at the larynx
8) olfaction (nerve endings in the roof of nose extend from olfactory epithelium to bulb)
9) heat loss
what makes up the physiological dead space?
- anatomical dead space: conducting airways
- alveolar dead space: alveoli that are ventilated but not perfused
what generations make up the conducting airways? have cartilage? have alveoli?
- conducting = 1-16
- cartilage = 1-10
- alveoli = 17-23
what makes up the respiratory epithelium in the conducting airways?
- goblet cells (make mucus, secrete mucin - lubrication, chemical barrier, virus protection) - present as
~ every 5th cell in epithelial layer - submucosal glands (secrete water, ions, mucus, bactericidal compounds)
- sol layer (allows free movement of cilia)
- mucus layer (traps airborne particles)
how do goblets change in smokers?
increases with smoking (why you have more mucus)
when does respiratory epithelium lose submucosal glands and goblet cells? how does airway epithelium change with size of conducting airway?
- submucosal glands and goblet cells absent after gen 11-12 (at bronchioles)
- airway epithelium thins in small conducting airways
what is the function of cilia? of microvilli?
cilia:
- trap particles
- contain ATPase thought to mediate beating motion (active movement of wafting particles up mucus elevator)
- sweep mucus out of airways
microvilli:
- brush cells
- increase surface area for secretion
how does air move within airways?
- by convection (air moves from high to low pressure areas) in conducting airways
- by diffusion in alveolar airways
what are type I alveolar pneumocytes?
- flat, elongated, 95% of alveolus surface
- primary site for gas exchange
- fused to endothelium (to vasculature)
what are type II alveolar pneumocytes?
- small, cuboidal, 2% of alveolus
- synthesize surfactant
- can replicate if alveoli are damaged
what are type III alveolar pneumocytes?
- brush cells found throughout lung
- closely associated with nerves
what are Pores of Kohn?
inter-alveolar pores and canals (connect alveoli together)
- allow gas diffusion between alveoli and bronchioles (especially if an alveoli is congested)
- prevent alveolar collapse due to surface tension
where do the lungs receive their entire CO from? what are the 2 pulmonary blood supplies?
RV
1) pulmonary artery carrying deoxygenated blood supply
2) large airways receive dedicated bronchial artery supply (to keep tissues alive)
what are properties of the pulmonary artery blood supply?
- provide blood to pulmonary capillaries - enhanced gas exchange, single file RBC passage
- 750 ms transit time for each RBC
- very close to alveolus (short diffusion distance)
- like a sheet of blood surrounding alveoli
what are properties of the bronchial artery blood supply?
- oxygenated blood supply to bronchioles
- 1/3 drains to bronchial veins (RA)
- 2/3 drains to pulmonary veins (LA)
how is pulmonary vasculature different than systemic?
- pulmonary arteries and arterioles are thinner and larger in diameter than in the systemic circulation -> increases compliance of pulmonary circulation
1) can contain large volume of blood
2) reduces pulse pressure
3) distensibility protects against edema
how do pulmonary pressures differ from systemic pressures (mm Hg)?
- pulmonary a. vs aorta: 15 vs 95
- start of capillary: 12 vs 35
- end of capillary: 9 vs 15
- LA: 8 vs 2
- net driving P: 7 vs 93
pulmonary vasculature = low pressure system (highly compliant b/c receive blood from whole body at a lower P)
what is the pulmonary blood volume? how can it change?
~10% (500mL) of total blood volume
- can decrease by 50% or increase by 200% -> due to capillary recruitment
what is the driving force for convection?
difference between atmospheric (Pb) and alveoli pressure (PA)
what is Boyle’s Law? how is it relevant in breathing?
when temperature and mass are constant, P is inversely proportional to V
- changes in the volume of the lungs during inspiration and expiration generate the pressure changes required for ventilation
what muscles are recruited during quiet inspiration?
- diaphragm (increases thoracic volume)
- external intercostals (lift rib cage/lifts ribs up)
what muscles are recruited during forced inspiration?
- diaphragm
- external intercostals
- scalenes (lift first 2 ribs)
- sternocleidomastoids (lift sternum)
- neck and back muscles (trapezius)
- upper respiratory tract muscles (reduce airway resistance)
what muscles are recruited during quiet expiration?
none - passive process
what muscles are recruited during forced expiration?
- abdominal muscles (rectus abdominus, external obliques)
- internal intercostals (pulls ribs down)
- neck and back muscles
what nerves innervate the inspiratory muscles?
- traps and SCM: C1-C2
- diaphragm: C3-C5
- scalenes: C4-C7
- external intercostals: T1-T12
what nerves innervate the expiratory muscles?
- internal intercostals: T1-T12
- abdominal muscles: T6-T12
how would different spinal cord injuries affect breathing (above T12, above C5, above C3)?
- above T12: will influence respiratory function (ex. during exercise - difficulty recruiting muscles)
- above C5: inspiration dependent on accessory muscles
- above C3: requires artificial ventilation
what makes up the intrapleural space? what is inside it?
space between parietal pleura (stuck to chest wall) and visceral pleura (stuck to lungs)
- filled with pleura fluid (allows lungs to slide over chest wall, sticks lungs to chest wall)
what kind of pressure is in the intrapleural space? why?
negative pressure
- counters elastic recoil of the alveoli + keeps the alveoli open
- becomes more negative towards end of inspiration, where recoil reaches maximum
- elastic recoil of lungs pulls visceral pleura inwards, chest wall expanding moves parietal pleura outwards -> countering forces make Pip negative
how does alveolar pressure change during the respiratory cycle?
when air is not moving, Palv=Pb (atmospheric)
- at the beginning/end of inspiration/expiration, Palv=0=Pb
- negative during inspiration
- positive during expiration
what is a pneumothorax?
puncture of pleural space; air enters the intrapleural space, making it no longer negative
- lung collapse, alveoli collapse = atelectasis
what is lung compliance (distensibility)? what is it determined by? what happens when compliance is decreased?
ease with which the lungs can expand under pressure
- compliance = change in V/change in P
- determined by elastin and collagen fibres in lung parenchyma -> lung inflation elongates these fibres, exerting more elastic force/recoil so lungs revert to initial size following distension
- decreased compliance = increased resistance to distension (inflation)
what is hysteresis?
more pressure is needed to open an airway than for it to collapse; lung inflation has to overcome:
- elastic recoil
- surface tension
- collapsed alveoli have high surface tension and less surfactant
inspiration is active, expiration is passive
what is emphysema? how does it affect compliance?
increased compliance (expiration difficult)
- easier to inspire but reduced stored elastic energy -> creates active expiration
- smoking: causes immune system to release elastase, breaking down elastin
what is fibrosis? how does it affect compliance?
decreased compliance (inspiration difficult)
- particulate matter (ex. from bad air quality) triggers immune response -> macrophages
- macrophages secrete growth factors causing proliferation of fibroblasts, which increase collagen deposition
what is LaPlace’s Law?
P=2T/r
- inward pressure trying to collapse a bubble
- it will take twice the inspiratory pressure to keep a small alveolus open compared to one twice as large
why don’t alveoli collapse?
- mechanical tethering: alveoli tend to open their neighbours during lung expansion
- alveoli contain surfactant: reduces surface tension
what is surface tension?
occurs at an air-fluid interface, fluid molecules create an inward directed pressure
what is the composition of surfactant? how does it work?
surface active agent
- 90% lipid (hydrophobic)
- 10% protein (hydrophilic)
- hydrophilic heads pull strongly upwards on h2o molecules, reducing the net force on h2o molecules to move into bulk water
- hydrophobic tails prevent surfactant from going deeper into water; exert counter-force that pull surfactant upward towards the air
why is it important that surfactant reduces surface tension?
- minimizes the tendency for small alveoli to collapse -> maximizes surface area for gas exchange
- increases compliance and decreases elastic recoil so the lungs are easier to inflate
- keeps the alveoli moist
- minimizes fluid accumulation in alveoli (prevents pulmonary edema)
- maintains alveolar size
how does alveolar surface tension affect compliance?
reduces compliance
- surface tension is responsible for most of the lung’s elastic recoil
how does surfactant equalize alveolar expansion?
prevents different alveoli from expanding at different rates
- in rapidly expanding alveoli, surfactant becomes more dispersed -> increases surface tension and slows down expansion
what is infant respiratory distress syndrome? what is its etiology? what are its symptoms? what are its treatments?
- most common for births <28 weeks; reduced/absent surfactant (high surface tension)
- shortness of breath (high breathing rate), lungs are stiff and hard to inflate (alveoli collapse in exhalation)
- treated with high O2 + humidity, artificial ventilation, artificial surfactant
what are the pressures of the respiratory cycle?
- Pip (intrapleural pressure): always negative, driven by thoracic volume (how much the chest wall moves)
- Ptp (transpulmonary pressure): reflects elastic recoil of the lungs, determined by VL (more VL = more recoil)
- PA (alveolar pressure): equal to atmospheric pressure (Pb) when flow stops
what equation connects all the relevant pressures?
what is the flow of air equal to?
PA = PIP + PTP
- PTP = PA - PIP = 0 - (-4) = 4 mmHg
V (flow) = change in P (PA)/Raw (airway resistance)
what to the segments on the pressure-volume loop represent?
- 0AECD: total mechanical work of inspiration (PxV)
- 0ABCD: inspiratory work to overcome elastic resistance (to stretch the lungs) = potential energy available for passive expiration
- AECB: inspiratory work to overcome non-elastic resistance (airway resistance)
- ABCF: energy required to overcome resistance to airflow during expiration
if ABCF is less than 0ABCD, expiration can be passive (stored energy is enough to expire)
how does restrictive lung disease affect the P-V loop?
ex) pulmonary fibrosis (tissue stiffens)
- decreased compliance
- increased work of breathing
- shallow and faster breathing
how does obstructive lung disease affect the P-V loop?
ex) asthma or bronchitis (inflammed tissue)
- increased resistance
- increased inspiratory work
- increased expiratory work
- deeper and slower breathing
what is Poiseuille’s Law?
airway resistance (Raw) is proportional to viscosity of gas and length of tube, and inversely proportional to the fourth power of radius
Raw = 8nL/pir^4
- for laminar flow
what is the primary site of airway resistance?
large bronchi
- bronchi are in series -> resistance sums
what is Reynold’s number? what is turbulent flow? what is transitional flow?
Re (turbulence) = 2rvd/n
- 2000 < Re < 3000 = transitional flow (generations 1-6)
- Re > 3000 = turbulent flow -> trachea during cough (gen 0, high velocity, large air flow)
what factors influence airway resistance?
- lung volume: decreased volume = increased resistance
- mucus: decreases airway calibre
- edema: decreases airway calibre
- density of the air: increases when diving -> increases turbulence
- smooth muscle contraction/relaxation
- local effects of CO2
- cold/hypoxia
calibre = distensibility
what is the mechanism of bronchodilation?
sympathetic nerves release NA/A onto bronchial membrane
- NA/A bind to B2-adrenergic receptors, activates Gs pathway (increased AC, increased ATP -> cAMP -> activates PKA -> phosphorylates PLB -> disinhibits SERCA -> faster Ca2+ re-uptake -> faster relaxation)
- faster relaxation = bronchodilation
what are the mechanisms of bronchoconstriction?
- histamine is released and binds H1 receptors on bronchial membrane -> activates Gq -> activates PLC -> increases IP3 -> SR Ca2+ release -> bronchoconstriction
- vagus nerve releases ACh on M2-muscarinic receptors on bronchial membrane -> activates Gi -> inhibits AC pathway -> bronchoconstriction
how does CO2 have local effects in the upper airways?
upper airways may have CO2 chemoreceptors
increased upper airway CO2 (hypercapnia):
- increased ventilation
- decreased airway resistance (dilates airways)
decreased upper airway CO2 (hypocapnia):
- increased airway resistance
- particular in asthmatics
how does cold air and hypoxia affect airway resistance?
- increased secretion
- decreased mucociliary clearance
- pulmonary vasoconstriction
- decreased chemosensitivity
- decreased ventilation
- bronchoconstriction
- airway congestion -> increased resistance
