1
Q
contractile force vs resting length
A
↑ 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)
2
Q
frank-starling rule of the heart
A
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)
3
Q
vessel layers
A
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
4
Q
elastic arteries
A
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)
5
Q
muscular arteries
A
distribution arteries: directs blood to certain regions
- changes proportion of bf allocated
- downstream of elastic arteries
- smaller than elastic arteries
6
Q
arterioles
A
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
7
Q
vasoconstriction of arteriolar vsm:
A
- SNS-mediated vasoconstriction: ↑SNS activity to arterioles ➞ ↑ arteriolar R due to NE-binding to ⍺-adrenergic receptors
- vasopressin (AVP/ADH) from neurohypophysis
8
Q
active hyperemia
A
↑bf to active tissue due to release of local metabolites causing vasodilation
- high blood flow to meet active muscles’ increased need for oxygen
9
Q
reactive hyperemia
A
previously occluded tissue had ↓ in bf ∴ ECF has temporary ↑ in metabolites to vasodilate & bring blood back to occluded tissue
10
Q
vasodilation mechanisms in arteriolar vsm:
A
- 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
11
Q
stroke volume dependent on
A
- 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)
12
Q
intrinsic property of the heart
A
↑ pre-load/EDV = ↑ contractile strength
- built into heart ➞ happens automatically
- dose not require any hormones, drugs, neurotransmitters
- muscle is stretched ➔ automatic greater response
13
Q
peripheral vein venous return mechanisms
A
- 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↓
14
Q
contractility
A
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
15
Q
CO during exercise
A
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
16
Q
HR regulation of CO
A
- 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
17
Q
change of contractility & effect on PV loop
A
- ↑ 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
18
Q
change in EDV & PV loop
A
- w/ an ↑ in EDV due to ↑ in venous return → larger SV
- change in SV due to change in EDV from vasoconstriction
19
Q
exercise & PV loop
A
- 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
20
Q
combined cardiac & vascular fx curves
A
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
21
Q
vascular (venous) fx curve
A
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
22
Q
vascular fx curve: blood volume
A
- ↑ volume = ↑ mean systemic filling pressure
- ↓ volume = ↓ mean systolic filling pressure
- sweat
- dehydration
- hemmorrhage
23
Q
vascular fx curve: vasoconstriction/vasodilation
A
- 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
24
Q
vascular fx curve: venoconstriction
A
↑ SNS changes compliance ➞ stiffer walls ➞ ↑P in peripheral veins
25
TPR
total peripheral resistance
- affected by:
1. Δ in SNS activity
2. local metabolites
3. local signal factors (i.e. histamines, N.O.)
26
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 ↑**
27
sensory processing of high-pressure baroreceptors
info processed by brain stem
1. **nucleus tractus solitarius (NTS)** receives input from baroreceptors & sends output to the following:
2. **DMNX: dorsal motor nucleus of the 10th cranial nerve (vagus nerve)**: PSNS nuclei excited by NTS input
3. **nucleus ambiguous (NA)**: PSNS nuclei excited by NTS input
4. **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**
28
baroreceptor response to a rise in MAP
1. high pressure baroreceptors ↑ firing rate from baseline activities
2. 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**
29
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
30
CV response to hypoxia
1. **peripheral chemoreceptors** ↑ firing rate → input to NTS
2. activates SNS output → **vasoconstriction** (selective to drive bf to necessary areas)
3. **tachycardia** (↑ HR = ↑ CO) can help to perfuse to important vessels (eg cerebral circulation, coronary circulation, kidneys)
31
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
32
↑ in SNS output effect on CO:
1. ↑ contractility in ventricular muscle → ↑ SV
2. venoconstriction of veins → ↑ venous return (lower compliance) → ↑ EDV
3. stimulate pacemaker cells & conductive pathways → ↑ HR (chronotropy)
4. arteriolar vasoconstriction → ↓ bf out of elastic arteries → ↓ blood V leaving elastic arteries → ↑ V in elastic arteries → ↑ MAP
33
↓ PSNS output effect on CO
1. ↓ pacemaker cell activity (SA node) → ↑ HR (↑ chronotropy)
2. conductive pathways → ↑ HR (↑ chronotropy)
34
CV response to exercise
↑ SNS output & ↓ PSNS output
1. ↑ SNS:
- ↑ venous return → ↑ EDV → ↑ SV
- ↑ HR
- vasoconstriction of arterioles = ↑ TPR (↑ TPR would ↓ bf ➞ need local metabolites to vasodilate certain arterioles)
1. 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
1. thermoregulation induduces ↑ bf to skin → sweat ➞ **vasodilation to cutaneous tissue**
35
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
36
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
37
↑ capillary O2 extraction by:
1. ↑ tissue metabolism (cellular respiration)
2. ↓ bf rate
- **↓ in O2 extraction when bf rates ↑ (↑ MAP or exercise)**
- soln: **perfuse more capillaries w/in a given exercising tissue**
38
what determines gas extraction rate
bf rate & O2 utilization by tissues
- also depends on distance → shorter distances facilitate gas exchange
39
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
40
compensatory response to a drop in MAP
- ↑ SV
- ↑ HR
- ↑ venous return (venoconstriction)
41
cardiac drift
during exercise with constant effort: ↑ in HR to compensate for a ↓ in SV after loss of volume while maintaining a consistent CO
42
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
1. response to **↑ PSNS** input = bronchoconstriction → matching bf to lungs w/ air flow
2. response to **↑ SNS** input = bronchodilation & ventilate portions of lung not previously ventilated (**β-adrenergic response**)
3. ↑ **histamine release** from immune cells causes constriction of bronchioles & alveolar ducts (although alveolar ducts do not have SM)
43
airway resistances
1. static resistance from radius
2. dynamic resistance from airflow & the renold's number
3. autonomic input to bronchiolar sm
4. lung volume
5. luminar & interstitial gases
44
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
45
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
46
resistance to pulmonary bf factors
resistance is low
1. as perfusion ↑ (due to an ↑ CO) the resistance ↓ → **recruitment & distention of bv↓ resistance**
2. **lung volume** induces changes in resistance to blood vessels (effects on septum capillaries, extra-alveolar blood vessels, and zones of the lung)
3. lung interstitial/parenchyma **PCO2** content
47
resistance to pulmonary bf from recruitment & distention
↑ perfusion due to↑ CO:
1. **recruitment of blood vessels**: ↑ in bf to closed/unused blood vessels ➞ **↓R**
2. **distention** of pulmonary bv due to ↑ pulmonary arterial BP → **↓R**
48
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**
49
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**
50
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
51
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)
52
factors contributing to O2 unbinding
1. 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**)
2. in tissue: **↓pH** from CO2 → H2CO3 (**↑H+**) + **lactic acid** ➞ R shift in Hb-O2 saturation curve causes Hb-O2 to unbind O2 (**Bohr effect**)
3. **↑ temp** at active tissue ➞ heat causes R shift in Hb-O2 saturation curve which causes Hb-O2 unbinding of O2
4. tissue & interstitial **2-DPG** (diphosphoglycerate) produced during metabolic activity ➞ R shift in Hb-O2 saturation curve which causes Hb-O2 unbinding of O2
53
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
54
peripheral chemoreceptors
- in aortic bodies & carotid bodies
- stimulated by:
1. **↓ arterial PO2** → fall below 60 mmHg activates ventilation
2. arterial **acidity (↓pH/↑[H+])** usually due to ↑ activity/CO2 → ventilation ↑
- rapid response
- pH homeostasis response
- partial compensation of pH disturbance
3. **CO2 in arterial blood** → rise in arterial PCO2 due to ↑ metabolism &/or a ↓ in ventilation stimulates ventilation (**weak response**)
55
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
56
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
57
irritant receptors
- peripheral sensory afferents
- monitor noxious stimuli in lungs/airways
- itch, pain, temp
- induce sneeze, cough, or forced expiration
- induces bronchoconstriction → protective effect
58
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
59
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
NPB 113
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