Topic 11: Cardiovascular Physiology Flashcards
Cardiac Physiology Parts
- Heart
- Conduction System
Heart
- dual pump with valves
- muscle cells connected by gap junctions
Conduction System
- non-contractile cardiac muscle cells – modified to initiate & distribute impulses throughout the heart
- produce APs spontaneously (no stimulus) BUT at different rates
Conduction System Parts
- Sinoatrial (SA) node – in right atrium
- Atrioventricular (AV) node – in right atrium
- Bundle of His (AV bundle)
- Purkinje fibers
Sinoatrial (SA) node
- rate = 100 APs/min (modified by PSNS to be 75 APs/min at rest)
- produces APs faster than other areas ∴ is the pacemaker
Atrioventricular (AV) node
-rate = 50 APs/min
Bundle of His (AV bundle)
- originates at AV node
- ONLY route for electrical activity to go from atria to ventricles + Bundle Branches (right and left)
- 30 APs/min
Purkinje fibers
- terminal fibers - stimulate contraction of the ventricular myocardium
- 30 APs/min
Pathway of APs in heart
- Interatrial
- Intermodal
- If conduction system damaged, next fastest part becomes pacemaker
i. e. if SA node damaged, AV node takes over (atria may not contract + ventricles contract at AV speed = 50 beats/min) - Artificial pacemakers – stim. if SA or AV nodes damaged
Interatrial
SA node through atrial contractile myocardium (rt and left) contract as a unit (gap junctions)
Intermodal
- SA node to AV node (delay of 0.1 sec to get through node due to small fibre size-allows vent. to fill with blood from atrial contraction)
- To bundle of his
- bundle branches
- purkinjie fibers
- Ventricular contractile myocardium (starts at apex, contracts as a unit-gap junctions)
APs of SA & AV nodes
- cells = non-contractile autorhythmic cardiac muscle cells (self-excitable)
- threshold = -40mV
Phases of Pacemaker Activity
- Pacemaker Potential
- AP Depolarization
- AP Repolarization
- Na+ channels open at -50 mV
Pacemaker Potential
- low K+ permeability (K+ voltage gates closed)
- slow inward leak of Na+ (Na+ voltage gates open)
- causes slow depolarization toward threshold (-40mV)
AP Depolarization
- at threshold ⇒ AP
- Ca2+ voltage gates open - Ca2+ moves in ⇒ depol. (Na+ voltage-gates close at threshold ∴ not involved in AP)
- Ca2+ voltage gates close at peak
AP Repolarization
- K+ voltage gates open at peak, K+ out ⇒ repol.
- K+ gates close below threshold
APs in Ventricular Myocardium
o cells = contractile
o Purkinje fiber AP ⇒ ventricular (contractile) myocardial AP (spread cell to cell by gap junctions)
o resting MP = -90mV
o Phases of Ventricular Myocardial APs
1) Depolarization
2) Plateau
3) Repolarization
1) Depolarization
Na+ voltage gates open (fast) = same gates as neuron, skel. muscle
MP to +30 mV
2) Plateau
Na+ channels close + inactivate (slight drop in MP)
Ca2+ slow voltage gates are open (Ca2+ influx maintains depolarization)
3) Repolarization
Ca2+ channels close
K+ voltage-gated channels open ⇒ ⇑ K+ outflux ⇒ ∴ MP ⇓ to resting
o Absolute Refractory Period
Long - Na+ channels inactivated until MP is close to - 70 mV
o Excitation-Contraction Coupling in Myocardial Cells
1) AP on sarcolemma of contractile cell triggers…
2) voltage-gated Ca2+ channels open (plateau of AP) = small ⇑ cytosolic Ca2+ (from ECF) ⇒ not enough to trigger contraction BUT…
3) opens chemically-gated Ca2+ channels on SR
4) ⇑⇑ cytosolic Ca2+
5) binds to troponin, etc, etc ⇒ leads to contraction
6) Contraction
6) Contraction
sliding filament mechanism
begins a few msec after AP begins
duration of AP = ~250 msec and duration of twitch = ~ 300 msec
∴ contraction almost over when AP ends
Result = NO summation ∴ NO tetanus - get alternation of contraction/relaxation
Cardiac Cycle
3 components
1) Electrical Activity (ECG)
2) Mechanical Activity
3) Blood flow through heart
1) Electrical Activity (ECG)
small currents due to depol/repol. of heart move through salty body fluids
potential difference measured on body surface using electrode pairs: one pair = a lead
recording seen as waves
o = sum of electrical activity of ALL myocardial cells (NOT an AP)
ECG Waves
a) P wave = atrial depol ⇒ followed by contraction
b) QRS wave = ventricular depolarization ⇒ contraction
also atrial repolarization (⇒ relaxation) - masked by larger vent. electrical event (larger muscle mass)
c) T wave = ventricular repolarization ⇒ followed by relaxation
ECG Intervals
a) P-Q = atria contracted, signals passing through AV node
b) S-T = ventricles contracted, atria relaxed
c) T-P = heart at rest
Abnormalities of Heart Beat
a) Tachycardia = resting HR more than 100 bpm
b) Bradycardia = resting HR less than 60 bpm
c) Heart block = when conduction through the AV node slowed, get an increased P⇒Q interval ⇒ ventricles may not contract after each atrial contraction
e.g. 3rd degree heart block - no conduction through AV node - atria fire at SA node rate (∼ 75 APs/min), ventricles at Bundle/Purkinje rate (∼ 30 APs/min)
2) Mechanical Activity
2 main events:
a) Systole = contraction, emptying
b) Diastole = relaxation, filling
both events initiated by electrical activity
1 complete heartbeat = diastole + systole of atria AND diastole + systole of ventricles
Timing of mechanical events
o average resting Heart Rate (HR) = 75 beats/min
o ∴ 0.8 sec/beat = 1 cardiac cycle (60 sec/min÷75 beats/min)
o In 0.8 sec (start with atrial contraction at time 0):
atria in systole for 0.1 sec, then diastole for 0.7 sec
ventricles enter systole after atria (0.1 sec delay at AV node) ∴ ventricles begin systole as atria begin diastole ⇒ in systole for 0.3 sec, then diastole for 0.5 sec
3) Blood flow through heart
Due to:
a) emptying pressure changes (high P ⇒ low P)
b) valves
c) myocardial contraction (raises P)
Path of Blood Flow
- large veins (venous return)
- atria relaxed (80% of blood into centrical passively)-diastole
- ventricles relaxed-diastole
- atria contract (increase in atrial pressure, remaining 20% of blood delivered to ventricle)-systole
- ventricles contract-systole-and atria relax-diastole
- ventricles relas
During Ventricular Systole
a) higher P in ventricles than atria forces AV valves shut ⇒ turbulence of blood gives first heart sound (= LUB) - shortly after QRS wave starts
b) P rises - higher P in ventricle than aorta/pulm trunk pushes semilunar valves open ⇒ blood enters vessels
During Ventricular Diastole
a) P drops - higher P in aorta/pulmonary trunk than ventricles forces semilunar valves to shut ⇒ turbulence ⇒ 2nd heart sound (= DUB) – mid-T wave
b) AV valves open when P in ventricles drops below P in atria
Heart Sounds
o Turbulent flow – noisy due to blood turbulence when valves shut
o Laminar flow - no sound
Korotkoff Sounds
o turbulence heard in brachial artery during blood pressure measurements:
begin = systolic pressure
stop = diastolic pressure
due to cardiac cycle events
Cardiac Output (CO):
volume of blood ejected by each ventricle in 1 min (ml/min)
-heart rate multiplied by stroke volume
Stroke Volume (SV)
-volume ejected by each ventricle per beat
o is equal to the difference between EDV and ESV (i.e. EDV – ESV)
End Diastolic Volume (EDV) = volume of blood in each ventricle at end of ventricular diastole (= preload)
o i.e. max ventricular volume ~ 120 ml
End Systolic Volume (ESV) = volume of blood in each ventricle at the end of ventricular systole (i.e. what’s left after ejection) ~ 50 ml
o therefore SV = 120ml – 50ml = 70ml
Control of CO
1) Control of Heart Rate
2) Stroke Volume
1) Control of Heart Rate
basic rate set by SA node = intrinsic control (built in)
modifiers of HR = extrinsic control
o change pacemaker potential (AP does not change)
types of extrinsic control
a) Neural
b) Hormonal
c) Other Factors
a) Neural
i. SNS (thoracic nerves)
ii. PSNS (Vagus nerve)
i. SNS (thoracic nerves)
Na+ channels open wider ∴ ⇑ Na+ permeability at SA node ∴ ⇑ slope of pacemaker potential ∴ reach threshold faster ∴ ⇑ HR
ii. PSNS (Vagus nerve)
keeps resting HR lower than pace set by SA node alone (sends continuous impulses)
⇑ K+ permeability at SA node ∴ more –ve on repol. ∴ further to go to get to threshold ∴ takes longer ∴ ⇓ HR
b) Hormonal
epinephrine, NE - ⇑ HR - same mechanism as SNS
thyroid hormone - directly ⇑ HR (but slow, so takes days)
o also ⇑ # of epi receptors ∴ more sensitive to epi
c) Other Factors
i. ions
ii. fever
⇑ temp - ⇑ HR
iii. age
newborn = high
iv. fitness
⇑ fitness = ⇓ HR
i. ions
e.g.1: High K+ in ISF
o MP more +ve than normal ⇒ pacemaker Na+ channels may not open
o also slows repol.
o ∴ ⇓ HR ⇒ may lead to cardiac arrest
e.g.2: Low K+ in ISF
o evidence that K+ channels in some cells change specificity: allow Na+ through instead of K+ ∴ depolarizes membrane ⇒ ⇑ HR - feeble beat, abnormal rhythms
Control of Stroke Volume
a) Intrinsic Control: (heart’s built-in ability to vary SV - adjust to demands)
b) Extrinsic Controls:
a) Intrinsic Control: (heart’s built-in ability to vary SV - adjust to demands)
⇑ venous return ⇒ ⇑ EDV ⇒ ⇑ heart muscle stretch ⇒ ⇑ force of contraction (at rest, cardiac fibers are at less than optimal length ∴ stretch ⇒ approach optimal length = more cross bridges attach = more force) ⇒ ⇑ SV (within physiological limits)
o i.e. more blood in ⇒ more blood out
relationship between EDV and SV
o Frank-Starling’s Law of the Heart: ⇒ force of ejection is directly proportional to length of ventricular contractile fibers (within physiological limits).
Get ⇑ venous return due to:
o exercise – venous return speeded up
o lower HR - has longer to fill ⇒ less of an effect than exercise
b) Extrinsic Controls:
i. ANS – SNS
ii. Hormones
iii. Other Factors
i. ANS – SNS
⇑ force of contraction (for a given EDV) ∴ ⇑ SV (SNS stimulation ⇑ opening of Ca++ channels ⇒ ⇑ Ca++ into cytosol ∴ more cross bridges ∴ ⇑ force)
BUT SNS also ⇑ HR = less time to fill ∴ have ⇓ EDV at higher HR. However, ⇑ force ⇒ ⇓ ESV - compensates for ⇓ in EDV
By ⇑ both force + HR, allows at least maintenance of SV even at high HR (usually an increase)
PSNS – no significant effect
Overall: SNS ⇑ CO; PSNS ⇓ CO
ii. Hormones
Epi, NE - same mechanism as SNS - ⇑ force
thyroid hormone - ⇑ force (+ ⇑ epi receptor #)
iii. Other Factors:
force ⇑ by:
o ⇑ external Ca++ (more Ca++ moves in on AP)
o digitalis (drug) - ⇑ Ca++ inside
force ⇓ by:
o acidosis
o ⇑ external K+
o Ca++ channel blockers (drugs) e.g. verapamil
Blood Circulation
Blood flow = volume of blood flowing through any tissue/min (i.e. ml/min)
Blood flow in a vessel is determined by pressure and resistance
Blood flow calculated as
f=change in P/R
o Where:
1) F = Flow
2) ΔP = blood pressure gradient (difference) between 2 points
⇓ blood pressure from: aorta ⇒ arterioles (resistance vessels) ⇒ large veins (capacitance vessels).
3) R = Resistance
3) R = Resistance
opposes flow - friction of blood rubbing against vessel walls
depends on:
a) vessel length
b) blood viscosity
c) radius of arterioles (major resistance vessels) controlled by smooth muscle innervated by SNS
vasodilation = ⇑ radius ∴ ⇓ R, ⇑ F
vasoconstriction = ⇓ radius ∴ ⇑ R, ⇓ F
Blood Flow to Organs Controlled by
1) Vasoconstriction
2) Vasodilation
a) = opposite of constriction
1) Vasoconstriction
a) ⇓ radius ∴ ⇑ R, ⇓ F
b) P in artery ⇑ (backs up)
c) P in organ ⇓ (less blood flows into organ capillaries)
Blood Flow to Organs
o If vasoconstriction/dilation is local (i.e. to 1 organ) - no observable change in systemic (arterial) BP
o If vasoconstriction/dilation is systemic, then systemic BP will change
Control of vasoconstriction/dilation (arteriolar radius)
1) Intrinsic Regulation-allows organ to control its own blood flow
a) myogenic regulation
b) metabolic regulation
both a) and b) - maintain blood gases + pH levels - very important in heart, skeletal muscle, brain
2) Extrinsic Regulation-external control by Nervous System and Endocrine System
a) neural regulation (SNS)
b) hormonal regulation
a) myogenic regulation
when smooth muscle is stretched, it contracts ∴ if ⇑ systemic bp ⇒ arterioles constrict
e.g. on standing ⇒ high arterial bp in feet (gravity) ∴ arterioles constrict ⇒ ⇓ flow into capillaries
e.g. on standing ⇒ low arterial bp in brain (gravity) ∴ arterioles dilate ⇒ ⇑ flow into capillaries
b) metabolic regulation
blood levels of ⇓ O2, ⇑ CO2, ⇓ pH (⇑ metabolism in organ) - endothelial cells + hemoglobin release nitric oxide ⇒ vasodilation ⇒ ⇑ blood flow to organ
if ⇑ O2, pH ⇑, CO2 ⇓ (= low metabolism) - endothelial cells release endothelins ⇒ vasoconstriction ⇒ ⇓ blood flow to organ
a) neural regulation (SNS)
arteriolar vasocon. (except in brain - intrinsic regulation only)
vasodilation due to ⇓ SNS signals (only important PSNS effect = dilation of arterioles of penis/clitoris)
also venoconstriction (vein constriction)
b) hormonal regulation
i. epinephrine
vasoconstriction - skin, viscera - reinforces SNS
vasodilation - heart, skeletal muscle, liver - opposes SNS
ii. other hormones
angiotensin II, ADH – vasoconstriction
histamine – vasodilation
Blood Pressure
= hydrostatic P exerted by blood on wall of vessel (clinically on the walls of the arteries) – results when F is opposed by R
What we measure in an artery: 120/80 = syst./diast.
Systolic pressure
produced by ventricular contraction against vascular resistance
Diastolic pressure
produced by elastic arteries against vascular resistance (when ventricles are relaxed)
Pulse Pressure
systolic - diastolic
Mean Arterial Pressure (MAP)
=regulated by the body i.e. what the body measures
o = average blood P through cardiac cycle BUT diastole is longer than systole, so:
o MAP = diast P + 1/3 pulse P
MAP Regulation
MAP= Cardiac Output multiplied by Total Peripheral Resistance
o MAP is regulated by controlling:
1) Cardiac Output
2) TPR (arteriolar radius)
3) Blood Volume (affects venous return ∴ SV; also MAP directly)
o Extrinsic Regulation of MAP
1) Neural Control
2) Hormonal Control
1) Neural Control
a) Baroreceptor Reflexes - short term changes e.g. standing
b) Chemoreceptor Reflexes
a) Baroreceptor Reflexes - short term changes e.g. standing
stretch receptors - monitor MAP in:
i. carotid sinus (brain bp)
ii. aortic arch (systemic bp)
-increase in MAP, increase baroreceptor impulses, medulla, increases PSNS (decreases CO), decreases SNS impluses (decrease epidemic secretion, vasoconstriction, venoconstriction-blood pools in veins decreasing venous return and CO), decreases MAP
b) Chemoreceptor Reflexes
peripheral chemoreceptors – respond to pH, CO2 (and O2)
found in aortic arch and carotid sinus (called “bodies”)
involved in regulation of respiration, but affect bp
-increase CO2 and decrease pH or O2, increase chemoreceptor impulses, medullary cardiovascular centre, increase SNS and epinephrine, increase vasoconstriction and heart rate and force of contraction, increase MAP
2) Hormonal Control
a) Epinephrine
⇑ HR, force of contraction ∴ ⇑ CO ⇒ ⇑ MAP
b) Renin-Angiotensin System
c) Atrial Natriuretic Peptide (ANP) causes
b) Renin-Angiotensin System
-plasma angiotensinogen (renin), angiotensin I (angiotensin-converting-enzyme (ACE)), angiotensin II
Angiotensin II causes:
o ⇑ vasocon, ⇑ venocon ∴ ⇑ MAP
o ⇑ aldosterone, ADH ∴ ⇑ renal Na+, H2O abs; ⇑ thirst ∴ ⇑ blood vol ⇒ ⇑ MAP
c) Atrial Natriuretic Peptide (ANP) causes
o ⇓ renin (∴ ⇓ angio II) ⇓ aldosterone, ⇓ ADH = ⇑ urine production ∴ ⇓ blood vol
o ⇓ vasoconstriction
o so overall = ⇓ MAP
Capillary Exchange
between blood and ISF
solutes enter and leave capillaries by
1) Diffusion = major route (except brain)
CO2, O2, ions, aa, glucose, hormones etc
usually between endothelial cells
2) Vesicular transport – large proteins (e.g. antibodies)
occurs via transcytosis
o = endocytosis from blood into endothelial cell, then exocytosis from endothelial cell into ISF
3) Mediated Transport – requires a membrane carrier protein
Important mainly in the brain
Fluid (H2O) enters (absorption) or leaves (filtration) capillaries by
1) Osmosis
2) Bulk Flow – due to pressure differences
4 pressures involved
a) blood hydrostatic P (BHP) = blood pressure
b) blood osmotic P (BOP) – mainly due to plasma proteins
c) ISF hydrostatic pressure (IFHP) = 0 mmHg
d) ISF osmotic pressure (IFOP) – mainly due to ISF proteins
Net Filtration Pressure (NFP)
o sum of hydrostatic and osmotic pressures acting on the capillary
NFP=(BHP+IFOP)-(BOP+IFHP)
o In the body:
90% of filtered fluid reabsorbed to blood
10% enters lymph
∴ ISF vol remains relatively constant
o Clinical Application: Edema
= accumulation of fluid in the tissue (ISF) causing swelling
due to:
1) High blood pressure (⇑ BHP)
2) leakage of plasma proteins into ISF ⇒ inflammation (⇑ IFOP)
3) ⇓ plasma proteins (malnutrition, burns) (⇓ BOP)
4) obstruction of lymph vessels - elephantiasis, surgery
Circulatory Shock
= inadequate blood flow (⇓ O2, nutrients to cells)
1) Hypovolemic Shock
⇓ blood volume
due to: blood loss, severe burns, diarrhea, vomiting
2) Vascular Shock
blood volume normal, but vessels expanded
due to: systemic vasodilation of blood vessels ⇒ ⇓ bp
examples:
a) anaphylactic shock - allergic reactions
due to: = lots of histamine released from mast cells
b) septic shock
due to: bacterial toxins
c) cardiogenic shock
pump failure ⇒ ⇓ CO
heart cannot sustain blood flow
stages of shock
1) Compensatory
2) Progressive
3) Irreversible
1) Compensatory
mechanisms can restore homeostasis by themselves involves: a) baroreceptors b) chemoreceptors c) ischemia (lack of O2) of medulla all trigger SNS
all trigger SNS:
o ⇑ HR, generalized vasoconstriction (except to heart, brain) = ⇑ bp
o ⇓ blood flow to kidneys triggers renin release - get angio II, aldosterone, ADH release ∴ vasocon, ⇑ Na+, H2O retention (maintain blood volume), ⇑ thirst
2) Progressive
mechanisms inadequate to restore homeostasis - requires intervention
⇓ CO ∴ ⇓ bp in cardiac circulation ∴ ⇓ cardiac activity
⇓ blood to brain ⇒ ⇓ cardiovascular control
damage to viscera due to ⇓ blood flow, especially kidneys (can lead to renal failure)
3) Irreversible
⇓ CO ⇒ too little blood to heart ⇒ ⇓ CO
self-perpetuating cycle - leads to death
Blood contains:
1) Plasma
2) Formed Elements
1) Plasma
a) H2O (90.5%) transport medium and carries heat b) Proteins (7%) c) Electrolytes (ions) functions: i. membrane excitability ii. buffers (HCO3-) d) Other solutes nutrients, wastes, gases, hormones
b) Proteins (7%)
albumins (58% of proteins)
globulins (38%)
fibrinogen (4%)
functions:
i. produce osmotic pressure (especially albumins)
ii. buffer pH (7.35-7.45) - keep it from changing
iii. α, β globulins - transport lipids, metal ions, hormones
iv. γ (gamma) globulins = antibodies
v. clot formation
2) Formed Elements
a) Red Blood Cells (RBCs)
b) White Blood Cells (WBCs)
c) Platelets
a) Red Blood Cells (RBCs) functions
i. transport – O2 on iron (Fe) of heme; CO2 on globin
ii. buffer – globin binds to H+ reversibly
iii. carbonic anhydrase (CA) – important for CO2 transport in blood
Hemoglobin
o Hb = 4 hemes + 4 globins (protein) o 1 iron (Fe)/heme ∴ 4 Fe/Hb o broken down by macrophages into i. heme ii. globin converted to amino acids – recycled
i. heme
Fe removed and stored (liver, muscle, spleen)
from stores (or diet) ⇒ bone marrow cells make heme ⇒ RBCs
non-iron portion ⇒ bilirubin ⇒ excreted in bile from liver
jaundice = excess bilirubin in blood because:
o excess RBC breakdown; or
o liver dysfunction (neonates ⇒ liver immature); or
o blockage of bile excretion
b) White Blood Cells (WBCs)
i. Granulocytes
ii. Agranulocytes
i. Granulocytes
Neutrophils
phagocytic
1st to enter infected area
Eosinophils
attack parasites
break down chemicals released in allergic reactions
Basophils
secrete histamine (increases inflammation)
secrete heparin (inhibits local clotting)
ii. Agranulocytes
Monocytes
enter tissues, enlarge to become phagocytic macrophages
Lymphocytes
Lymphocytes
T lymphocytes - Helper T (TH) + cytotoxic T (CTLs) lymphocytes
B lymphocytes - when activated, give rise to plasma cells - secrete antibodies
Natural Killer Cells - attack foreign cells, abnormal cells (non-specific)
c) Platelets
cell fragments from megakaryocytes
functions:
o form platelet plug – prevents excess blood loss
o contain granules = coagulation factors (proteins/chemicals involved in clotting)
Hemostasis
= process of stopping bleeding involves: 1) Vascular Spasm 2) Platelet plug formation 3) Clot Formation 4) Clot Retraction + Repair 5) Fibrinolysis thrombus = a stationary clot in an undamaged vessel embolus = free floating clot Hemophilia – clotting abnormal/absent o about 83% = type A - lack clotting factor VIII
1) Vascular Spasm
= vasoconstriction of damaged arteries, arterioles - ⇓ blood flow (minutes to hours)
2) Platelet plug formation
platelets stick to damaged blood vessel, release chemicals (factors) which:
a) cause more platelets to stick (+ve feedback)
b) promote clotting
c) begin healing
neighbouring healthy endothelial cells release a chemical preventing spread of plug
plug formation requires a prostaglandin - inhibited by aspirin
3) Clot Formation
3 stages:
a) production of prothrombin activator
b) Prothrombin converted to thrombin
c) Fibrinogen converted to fibrin
Thrombin - +ve feedback to ⇑ its own formation
NOTE: ~ 2 doz. factors involved
o from diet, liver (plasma proteins), damaged tissue, platelets
o e.g. vitamin K required for synthesis of 4 factors
a) production of prothrombin activator
i. extrinsic pathway – uses factors released by damaged tissues
ii. intrinsic pathway - uses factors contained in blood
usually both occur together - require Ca2+, tissue, platelet and/or plasma factors
4) Clot Retraction + Repair
retraction – blood vessel edges pulled together
repair - fibroblasts form new CT, new endothelial cells repair lining
5) Fibrinolysis
clot dissolution
fibrin digesting enzyme = plasmin
phagocytes then remove clot in clumps
