FINAL Flashcards
contractile force vs resting length
↑ EDV due to ↑ venous return → ↑ developed force
- resting length = EDV
- mechanisms:
- maybe as we ↑ EDV we ↑ # of cross-bridges
- ↑ EDV (stretching walls of ventricle) ↑ geometric advantage: distance between thick & thin filaments decreases as the sarcomere is stretched ➔ as sarcomeres lengthen, they get smaller in diameter → develops force
- ↑ Ca affinity to troponin-C: stretch of muscle ↑ affinity of troponin-C to Ca → greater amount of time Tn-C is bound to Ca allows greater crossbridge cycling → greater force (depends on [Ca] & affinity)
frank-starling rule of the heart
as EDV ↑, ventricular force ↑
- ↑ venous return → ↑ EDV
- increased Ca sensitivity occurs at longer muscle fiber lengths
- more EDV = more preload = more SV = more forceful contractions
- preload: volume in ventricles (=EDV)
- afterload = back-pressure in the elastic arteries keeping semilunar valves closed (bad)
vessel layers
tunica adventitia/externa: outermost layer
- strong connective tissue, collagen, elastin, & fibroblasts to help create overall structure
- anchors vessels’s w/in tissue
tunica media: smooth muscle cells & connective tissue
- could be continuous in a distinct layer or discontinuous
- changes diameter of vessel
tunica intima/interna: endothelium
- sometimes can find elastin or connective tissue
elastic arteries
fill w/ blood, stretch (storing potential energy), & recoil ➔ squeezes blood ➔ ↑ pressure
- pressure reservoir allows us to drive bf during diastole
- has all 3 tissue layers
-
mean arterial pressure (MAP): driving force for bf from arteries ➞ capillaries
- homeostatically regulated but parameters can shift after years of consistency
- MAP = 1/3 SP + 2/3 DP or MAP = DP + 1/3 (SP−DP)
muscular arteries
distribution arteries: directs blood to certain regions
- changes proportion of bf allocated
- downstream of elastic arteries
- smaller than elastic arteries
arterioles
major resistance vessels
- vasoconstrict in response to ↑ SNS input
- vasodilate in response to ↓ SNS input & signal factors (local metabolites)
- varying number of tissue layers
- larger arterioles hav eall 3 layers w/ continuous SM
- smaller arterioles have discontinuous bands of SM
- avg diameter ~30 microns
vasoconstriction of arteriolar vsm:
- SNS-mediated vasoconstriction: ↑SNS activity to arterioles ➞ ↑ arteriolar R due to NE-binding to ⍺-adrenergic receptors
- vasopressin (AVP/ADH) from neurohypophysis
active hyperemia
↑bf to active tissue due to release of local metabolites causing vasodilation
- high blood flow to meet active muscles’ increased need for oxygen
reactive hyperemia
previously occluded tissue had ↓ in bf ∴ ECF has temporary ↑ in metabolites to vasodilate & bring blood back to occluded tissue
vasodilation mechanisms in arteriolar vsm:
-
SNS-mediated vasodilation: small portion of SNS neurons release ACh ➞ vasodilation
- ↑ SNS activity for same arterioles ➞ ↓ arteriolar R due to ACh binding β-adrenergic receptors on vsm in some skeletal muscle region
- only small subset of arterioles ∴ not mechanism of action
- EPI ➞ binds to β2-adrenergic receptors → vasodilation
-
local metabolites: anty chemical signal factors released in immediate vicinity by tissues that influence adjacent arterioles ➞ override SNS vasoconstriction ∴ induces vasodilation
- [adenosine]
- [K]
- PCO2
- PO2
- ↓ pH: active tissue undergoes glycolytic metabolism resulting in lactic acid build-up & CO2 production
- nitric oxide = gas released by tunica intima endothelium during sheer stress causes vasodilation to other vessels to redirect bf instead of forcing it through single stressed vessel to ↓ rubbing
stroke volume dependent on
- changes w/ activity/metabolic demand usually SNS-mediated: ↑ SNS activity ➞ ↑ SV
- venous return: blood flows passively from peripheral veins to central veins & ventricles down a pressure gradient → venous filling
- EDV determines SV (frank-starling rule): volume stretches ventricular wall
- ↑ optimal overlap btwn existing thick & thin filaments
- geometric advantage ↓ distance existing btwn myosin heads & thin filaments
- Ca interaction w/ troponin ➞ ↑ Ca affinity
- EDV in ventricles is dependent on passive filling & atrial contraction (pre-load = 135mL)
intrinsic property of the heart
↑ pre-load/EDV = ↑ contractile strength
- built into heart ➞ happens automatically
- dose not require any hormones, drugs, neurotransmitters
- muscle is stretched ➔ automatic greater response
peripheral vein venous return mechanisms
- smooth muscle contraction in response to ↑ SNS allows us to ↑ peripheral venous P w/ no effect on radius: ↓ compliance (stiffer)
- skeletal muscle pump: muscle contracts ➞ squeezes peripheral veins ➞ ↑ venous P ➞ drives bf out to CVP
- venous valves: 1 way valves ensure 1-way flow
- cardiac suction & respiratory pump: ventricles relax ➞ V ↑ ➞ ventricle P↓ ➞ suction
- inspiration ➞ ↑ thoracic V ➞ ↓ intrapleural P ➞ SVC & IVC V↑ ➞ SVC & IVC P↓
contractility
Δ in contractile strength due to extrinsic forces
- act on muscle independently of intrinsic factors (can even act simulataneously e.g. exercise)
- SNS input to heart will ↑ contractile force
- in the atria: ↑ EDV
- in the ventricles: ↑ force of contraction ➞ ↑P ➞ ↑SV
- independent of EDV
- SNS neurons release NE ➞ binds to β-adrenergic receptors ➞ activates GPCR (Gs ⍺ subunit) ➞ PKA phosphorylates:
- L-type Ca channels ➞ ↑ Ca influx
- SERCa pumps ➞ ↑ rate of Ca removal ➞allows quick relaxation
- troponin ➞ ↑ off rate of tropomyosin ➞ allows thin filament to bind to myosin head
CO during exercise
CO ↑ due to ↑ HR & ↑ SV
- during exercise venoconstriction & skeletal muscle pump cause venous fx curve to shift ↑
- still work at CVP ≈ 1.8-2 mmHg
- ESV is smaller than normal ∴ ESP is smaller which facilitates ventricular filling
HR regulation of CO
- HR depends on:
- rate of depolarization in the SA node (during phase 4)
- duration of nodal delay in AV node
- conduction velocity in all conductive pathways
- an ↑ in HR is caused by ↑ SNS input + ↓ in PNS input
- myocytes only have sympathetic input but pacemaker & conduction pathways have both ANS & PNS
- SNS input from thoracic region
- SNS post-ganglionic neurons release NE
change of contractility & effect on PV loop
- ↑ SNS causes ↑ in contractile strength independent of EDV
- pressure at which semilunar valves open dependent on afterload
- point D determined by pressure in aorta (MAP) not contractile force
- force of contraction (∴ P developed) has ↑ at every point during contraction
- SV ↑
- ESV ↓ (∴ ↓ ESP) w/ ↑ contractility → start diastole w/ smaller pressure → advantageous for ventricular filling
- rate of pressure development ↑ ∴ faster contractions
- rate of relaxation ↑ due to SERCa pump activation
change in EDV & PV loop
- w/ an ↑ in EDV due to ↑ in venous return → larger SV
- change in SV due to change in EDV from vasoconstriction
exercise & PV loop
- during exercise we ↑ SNS output to heart
- contractility ↑
- ↑ SNS to veins → ↑ venous return → ↑ EDV
- contracting skeletal muscles ↑ venous return → ↑ EDV
- ↑ contractility + ↑ venoconstriction & venous return = ↑ EDV (venoconstriction = no change in contractility → making veins stiffer)
- ↑SV
combined cardiac & vascular fx curves
CO is matched by peripheral venous return at point A: @ 5 L/min CVP pressure = 2 mmHg
- CVP pressure must be higher than ESV in order for blood to flow
vascular (venous) fx curve
relates amount of blood coming out of peripheral veins & pressure in venous pool
- IVC, SVC, RA
- CVPP: central venous pool pressure
- CVP acts as back-pressure → prevents venous return
- CVP influences ventricular filling → P that pushes blood into ventricles
- ventricular filling dependent on CVP pressure & ESV
- CVP — ESP
- ESP acts as back-pressure stopping CVP pool from filling
vascular fx curve: blood volume
- ↑ volume = ↑ mean systemic filling pressure
- ↓ volume = ↓ mean systolic filling pressure
- sweat
- dehydration
- hemmorrhage
vascular fx curve: vasoconstriction/vasodilation
- mean systemic venous pressure stays constant: equal amount of blood flowing in/out
- vasoconstriction: less blood coming from cap ➔ veins = slower venous return
- vasodilation: more blood flows faster
vascular fx curve: venoconstriction
↑ SNS changes compliance ➞ stiffer walls ➞ ↑P in peripheral veins
TPR
total peripheral resistance
- affected by:
- Δ in SNS activity
- local metabolites
- local signal factors (i.e. histamines, N.O.)
baroreceptors
detect BP & innervate wall of vessels or chambers
- when blood fills the vessel/wall will stretch
- dendrites detect Δ in wall stretch (squeezes against dendrites)
- as vessel V↑ (P↑) → AP freq ↑
sensory processing of high-pressure baroreceptors
info processed by brain stem
- nucleus tractus solitarius (NTS) receives input from baroreceptors & sends output to the following:
- DMNX: dorsal motor nucleus of the 10th cranial nerve (vagus nerve): PSNS nuclei excited by NTS input
- nucleus ambiguous (NA): PSNS nuclei excited by NTS input
- rostral ventrolateral medulla (RVLM): SNS nuclei that receive inhibitory input from NTS ➞ regulates SNS output to arterioles & heart
- input from carotid receptors travels via glossopharyngeal crania nerve
- input from aortic arch travels via vagus cranial nerve
baroreceptor response to a rise in MAP
- high pressure baroreceptors ↑ firing rate from baseline activities
- input goes to NTS
- ↑ neuronal firing rate to the DMNX & NA ➞ ↑ PNS activity → slows heart
- ↑ activity to RVLM ➞ ↓ SNS → slows heart, ↓ contractility, ↓ venous return, causes arteriolar vasodilation
chemoreceptors influences on CO
peripheral chemoreceptors found in aortic arch & carotid bodies monitor blood pH, arterial PCO2, & arterial PO2
- exert a positive drive on vasomotor center causing vasoconstriction
CV response to hypoxia
- peripheral chemoreceptors ↑ firing rate → input to NTS
- activates SNS output → vasoconstriction (selective to drive bf to necessary areas)
- tachycardia (↑ HR = ↑ CO) can help to perfuse to important vessels (eg cerebral circulation, coronary circulation, kidneys)
baroreceptor response to sudden ↓ in MAP
- ↓ MAP detected by high pressure baroreceptors → ↓ rate of firing
- to the DMNX & NA of the PSNS: ↓ activation ➞ ↑ HR
- to the RVLM of the SNS: ↓ activation (of inactivation) ∴ allows activation of SNS ➞ ↑ HR, ↑ contractility, ↑ venous return, causes arteriolar vasoconstriction
- ↑ SNS & ↓ PSNS
↑ in SNS output effect on CO:
- ↑ contractility in ventricular muscle → ↑ SV
- venoconstriction of veins → ↑ venous return (lower compliance) → ↑ EDV
- stimulate pacemaker cells & conductive pathways → ↑ HR (chronotropy)
- arteriolar vasoconstriction → ↓ bf out of elastic arteries → ↓ blood V leaving elastic arteries → ↑ V in elastic arteries → ↑ MAP
↓ PSNS output effect on CO
- ↓ pacemaker cell activity (SA node) → ↑ HR (↑ chronotropy)
- conductive pathways → ↑ HR (↑ chronotropy)
CV response to exercise
↑ SNS output & ↓ PSNS output
- ↑ SNS:
- ↑ venous return → ↑ EDV → ↑ SV
- ↑ HR
- vasoconstriction of arterioles = ↑ TPR (↑ TPR would ↓ bf ➞ need local metabolites to vasodilate certain arterioles)
- active tissues release local metabolites into interstitium that vasodilate vessels supplying exercising muscles/organs
- H+ (↓ pH)
- ↓ PO2
- ↑ PCO2
- ↑ K+
- ↑ adenosine
- ↑ lacate
- overrides the SNS-induced ↑ in TPR in the local spot
- global ↑ in TPR except in the exercising muscle
- thermoregulation induduces ↑ bf to skin → sweat ➞ vasodilation to cutaneous tissue
regulation of microcirculation
- arterioles & capillaries
- ↑ SNS → precapillary sphincters contract
- ↓ SNS & local metabolites → pre-capillary sphincters vasodilate
- EDRF = endothelium-derived relaxation factor: causes arteriolar sm vasodilation & relaxes precapillary sphincters released in response to shear stress (e.g. NO)
- histamines can also cause vasodilation as inflammatory response
- ↑ bf into cap = Pcap↑
- bf in capillary is proportional to ΔP between arteriole & vein
autoregulation of cardiovascular system
yields constant bf in the face of changes in BP
- due to VSM cells of arterioles that supply those cap
- in order to maintain constant pressure to specific capillary beds
- if MAP ↑ → vsm cells automatically vasoconstrict
- if MAP ↓ → vsm cells automatically vasodilate
- myogenic response: muscle cells contract in response to stretch
↑ capillary O2 extraction by:
- ↑ tissue metabolism (cellular respiration)
- ↓ bf rate
- ↓ in O2 extraction when bf rates ↑ (↑ MAP or exercise)
- soln: perfuse more capillaries w/in a given exercising tissue
what determines gas extraction rate
bf rate & O2 utilization by tissues
- also depends on distance → shorter distances facilitate gas exchange
starling law of fluid transfer:
- J = flux of water occurring across the vasculature
- Jv = water flux across a cap
- SA = surface area
- Lp = hydraulic conductivity: a measure of how easily water can pass through a membrane
- more pores or AQP = ↑ Lp
- Pcap = BP in cap → pushes water out of vessel
- PIF = P in interstitium/interstitial fluid: pushes water into vessel
- σ = reflection coefficient: varies from 0 → 1
- when σ = 1: wall of cap does not allow proteins to move across capillary → maintains capacity for filtration
- when σ = 0: capillary wall is permeable to proteins → dangerous (e.g. burns having edema)
- 𝜋cap = oncotic pressure in blood due to proteins: attracts water into cap → opposes hydrostatic pressure
- 𝜋IF = oncotic pressure in interstitium that pulls water out of capillary
- hydrostatic pressure difference: net force of water moving out of blood because of BP → hydrostatic force pushing water out
- oncotic/osmotic pressure difference: net force of water moving out of blood because of blood proteins
compensatory response to a drop in MAP
- ↑ SV
- ↑ HR
- ↑ venous return (venoconstriction)
cardiac drift
during exercise with constant effort: ↑ in HR to compensate for a ↓ in SV after loss of volume while maintaining a consistent CO
autonomic input to bronchiolar SM
- autonomic input changes radius & primarily affects static resistance
- SMC contract → makes bronchioles smaller in diameter (bronchoconstriction) → ↑ R
- SMC relax = bronchodilation → ↓ R
- bronchioles = primary resistance sites
- response to ↑ PSNS input = bronchoconstriction → matching bf to lungs w/ air flow
- response to ↑ SNS input = bronchodilation & ventilate portions of lung not previously ventilated (β-adrenergic response)
- ↑ histamine release from immune cells causes constriction of bronchioles & alveolar ducts (although alveolar ducts do not have SM)
airway resistances
- static resistance from radius
- dynamic resistance from airflow & the renold’s number
- autonomic input to bronchiolar sm
- lung volume
- luminar & interstitial gases
lung volume effect on resistance
as lung V↑ → R in bronchioles ↓
- alveoli ↑ in size & are mechanically tethered to the bronchioles
- enlarged alveoli pull on the wall of the bronchiole → ↑ radius
- maybe allows bronchioles to overcome collapsing transmural forces
luminar & interstitial gases effect on resistance
- as interstitial PCO2 ↑ → causes causes SMC to relax ∴ bronchodilation ➞ R↓ → ↑ airflow
- more predominant effect than PO2
- as interstitial PO2 falls → bronchodilation (SMC relax) ➞ R↓ → ↑ airflow
- matching ventilation to perfusion
resistance to pulmonary bf factors
resistance is low
- as perfusion ↑ (due to an ↑ CO) the resistance ↓ → recruitment & distention of bv↓ resistance
- lung volume induces changes in resistance to blood vessels (effects on septum capillaries, extra-alveolar blood vessels, and zones of the lung)
- lung interstitial/parenchyma PCO2 content
resistance to pulmonary bf from recruitment & distention
↑ perfusion due to↑ CO:
- recruitment of blood vessels: ↑ in bf to closed/unused blood vessels ➞ ↓R
- distention of pulmonary bv due to ↑ pulmonary arterial BP → ↓R
resistance to pulmonary bf from lung volume
- bv sitting in between alveoli/in septum get squished during inspiration → ↑ R
- extra-alveolar blood vessels are not in septum ∴ do not get squished during inspiration, but actually expand due to transmural force ➞ ↓R
resistance to pulmonary bf from lung volume based on zones
- in an upright indiv: blood perfuses zone 3 > zone 2 > zone 1
- selectively perfusing bottom 1/2 - 2/3
-
at apex: ↓ in bf due to gravity + bv are squished down by larger alveoli
- transmural force expanding bv is weaker than squishing force of lung tissue ∴ bv at top get squished - at base: blood selectively perfuses lower bv + lung tissue is not as expanded so not much squishing force on bv ∴ more overall blood flow into the lower vessels
resistance to pulmonary bf from lung interstitial/parenchyma PO2/PCO2 content
- local effect
- low O2 content w/in parenchyma causes local vasoconstriction of the pulmonary arterioles → shunts blood away from region that is poorly ventilated
- high PO2 content → vasodilation of pulmonary arterioles → ↑ bf to that ventilated region
- allows us to match blood flow to ventilation
- PCO2 effects are not as influential as PO2
- high CO2 causes local vasoconstriction
- low CO2 causes vasodilation
ventilation-perfusion ratios
- ideal lung VA (alveolar ventilation) should match bf to that alveolus
- VA/QC should be 1 → ratio is actually ≈ 0.8 (in middle)
- apex is over-ventilated compared to blood flow (1.2)
- base is under-ventilated compared to blood flow (0.6)
factors contributing to O2 unbinding
- tissue is producing CO2 → ↑ PCO2 causes ↓ in affinity of Hb to O2 which causes causes Hb-O2 to unbind O2 (R shift of dissociation curve = ↓ affinity ➞ Bohr effect)
- in tissue: ↓pH from CO2 → H2CO3 (↑H+) + lactic acid ➞ R shift in Hb-O2 saturation curve causes Hb-O2 to unbind O2 (Bohr effect)
- ↑ temp at active tissue ➞ heat causes R shift in Hb-O2 saturation curve which causes Hb-O2 unbinding of O2
- tissue & interstitial 2-DPG (diphosphoglycerate) produced during metabolic activity ➞ R shift in Hb-O2 saturation curve which causes Hb-O2 unbinding of O2
Hb binding in the lungs
↑ affinity of Hb to O2 (lower saturation at lungs) → left shift of curve
- interstitial CO2 is low
- pH is more neutral (7.4)
- temp is cooler
peripheral chemoreceptors
- in aortic bodies & carotid bodies
- stimulated by:
- ↓ arterial PO2 → fall below 60 mmHg activates ventilation
- arterial acidity (↓pH/↑[H+]) usually due to ↑ activity/CO2 → ventilation ↑
- rapid response
- pH homeostasis response
- partial compensation of pH disturbance
- CO2 in arterial blood → rise in arterial PCO2 due to ↑ metabolism &/or a ↓ in ventilation stimulates ventilation (weak response)
central chemoreceptors
- found in the brain stem in the medulla
- primary sensor, strong response
- detects [H+] which is proportional to blood PCO2
- ↑ brain ECF [H+] stimulates ventilation
pulmonary stretch receptors
- peripheral sensory afferents
- in lung parenchyma
- monitor volume of lungs
- inspire: lung volume ↑ → AP freq ↑ → brainstem NTS → inhibits ventilation
- expire: ↓ lung volume ➞ AP freq ↓ → brainstem NTS → activates ventilation
- can influence respiration independently of gas content
irritant receptors
- peripheral sensory afferents
- monitor noxious stimuli in lungs/airways
- itch, pain, temp
- induce sneeze, cough, or forced expiration
- induces bronchoconstriction → protective effect
metaboreceptors
- peripheral sensory afferents
- chemoreceptors found in tissues
- monitor ECF chemicals (CO2, pH)
- ↑ tissue metabolism releases CO2 that metaboreceptors detect → activates ventilation
- contributes to fine-tuning respiration
BP during exercise
- SP: initial ↑ until plateau
- DP: very slight change, slight drop ➞ local metabolites cause vasodilation in skeletal muscle vessels
- MAP: slight ↑ at very beginning
with heavy sweating:
- sweating = losing blood V
- ↓ venous return ➞ ↓ EDV ➞ ↓ SV ➞ ↓CO ➞ SP↓
- SP starts to fall
- DP: slight decrease (mainly constant)
- MAP: fairly constant