midterm Flashcards
Function of the CV system
materials transported
- what area of the body especially needs o2
- hypoxia
a. Transport of material entering the body to sites for processing/use:
i. Nutrients – intestine all cells
ii. Oxygen – lungs all cells
1. Important to all cells – will otherwise become irreparably damaged & loss of consciousness without bloodflow to brain
2. Neurons – high o2 demand; can’t use anaerobic methods (low ATP yield)
a. Hypoxia – low oxygen
b. Body will deprive other cells of oxygen before the brain – must keep CFS levels high
iii. Water – intestine all cells
b. Transport of material between cells within the body:
i. Hormones – present when secreted by endocrine cells
ii. Antibodies – always present
iii. Platelets and Clotting proteins – always present
iv. Immune cells (leukocytes) – always present
v. Stored nutrients – glucose from liver and fatty acids from adipose tissue
c. Transport of material from cells to sites of elimination:
i. Wastes (urea, creatinine, bilirubin) – moved to kidneys for excretion
1. Some are transported to liver first – processing
ii. Carbon dioxide – moved to lungs
iii. Heat – moved to skin (sweat)
Heart and CV anatomy
- cyanosis
- resistance and pressure of pulm vs systemic
- positive pressure and valves
a. Heart
i. Hydraulic pump that creates a pressure gradient.
ii. Anatomy
1. Divided by septum – central wall; splits into right and left
2. Atrium – received blood returning to heart from blood vessels
3. Ventricles – pump blood out into blood vessels
a. Right – into pulmonary
b. Left – into systemic
iii. Cyanosis – low oxygen blood imparts blueish colour to areas of the skin (around mouth and under nails)
b. Vasculature – blood vessels
i. Closed (blood always carried in vessels)
1. Arteries – away from heart
a. To pulmonary – deoxygenated (doesn’t completely lack; just less); right ventricle
b. To systemic – oxygenated; left ventricle
2. Veins – towards the heart
a. From pulmonary – oxygenated; left atrium
b. From systemic – deoxygenated; right atrium
ii. Dual circuit that allows unidirectional blood flow
1. Pulmonary circulation – low pressure, low resistance vessels that carry blood to and from lungs
2. Systemic circulation – high pressure, high resistance vessels that carry blood to the remaining organs
c. Blood
i. Transport medium consisting of plasma and cells
d. Valves in heart and veins – unidirectional flow
i. Positive pressure behind – open
ii. Positive pressure ahead – closed
1. Usually facing you (right side is on left page)
paths of bloodflow
pulmonary vs systemic vs coronary
- hepatic & renal circulation
a. Pulmonary circulation: Right ventricle ➔ pulmonary arteries ➔ arterioles ➔ capillaries in lungs (where exchange takes place) ➔ venules ➔ pulmonary veins ➔ left atrium
b. Systemic circulation: Left ventricle ➔ aorta ➔ ascending arteries and abdominal aorta ➔ systemic arteries (e.g. carotid arteries, hepatic arteries, renal arteries, etc.) ➔ capillaries ➔ venules ➔ systemic veins (e.g. jugular vein, hepatic vein, renal vein, etc.) ➔ superior or inferior vena cava ➔ right atrium
i. Aorta
1. Ascending branches of aorta – arms, head, brain
2. Abdominal aorta – trunk, legs, internal organs (hepatic, digestive, renal)
ii. Hepatic circulation
1. Hepatic artery – directly from descending artery
2. Hepatic portal vein – from digestive trace liver
a. Liver – nutrient processing and detoxifying substances absorbed in intestines before releasing into general circulation
iii. Renal circulation – portal system between kidneys
iv. Venae cavae
1. Superior vena cava – upper body
2. Inferior vena cava – lower body
c. Coronary circulation: left ventricle –> aorta –> coronary arteries –> cardiac muscle capillaries –> coronary veins –> coronary sinus –> right atrium
i. Microcirculation – arterioles, capillary beds, venules
Rate of blood flow to tissues is determined by
- hydrostatic pressure
- where is pressure highest and lowest
- driving pressure
- what is direct, what is inversely
- equation for vascular resistance
Hydraulic pump
- when does it start beating
a. Pressure gradients (∆P) – differences in pressure between two locations in the cardiovascular system.
i. Pressure – force exerted on its container
1. Measured in CV in mmHg – 1 mm of mercury is equivalent in hydrostatic pressure exerted by a 1mm high column of mercury on an area of 1cm2
2. Hydrostatic pressure – exerted when fluid is not moving; equal in all directions
a. Still used in physio even through blood is flowing
3. Does not affect volume
4. P is not the same as absolute pressure – 2 tubes can have different absolute pressures but the same flow rate
ii. Pressure decreases with increasing volume blood flows passively into heart chambers between contractions
iii. Blood flows from areas of high pressure to areas of low pressure, (down the pressure gradient)
1. highest closest to the ventricles & aorta
2. driving pressure – created by the ventricles; drives blood through blood vessels
3. decreases as you move further away from this pump
4. lowest in vena cava & atria
iv. Blood flow –> directly proportional to change in P
1. greater the pressure difference - higher the flow.
2. smaller the pressure difference - lower the flow.
3. no pressure gradient (∆P = 0) - there is no flow.
b. Flow is inversely proportional to resistance (F proportional to P/R)
i. Vascular resistance – resistance to blood flow; caused by friction (of blood cells in contact with vessel walls and with each other).
ii. Increased surface area in contact with blood = increased resistance (L and r)
c. Vascular resistance - is determined by:
i. Vessel length (L) – smaller impacts
1. longer = increased resistance
ii. Internal vessel radius (r) – large impacts
1. Vasoconstriction – decreasing radius, increases resistance
2. Vasodilation – increasing radius, decreases resistance
iii. Blood viscosity (η) – friction between molecules in a flowing fluid; small impacts
1. proportional to hematocrit – the proportion of the blood volume that is red blood cells
a. Increasing hematocrit increases viscosity increases resistance
b. analogy: water (low viscosity) vs honey (high viscosity) moving through a tube
iv. The equation: R = 8Lη/ πr4
1. where 8 and π are constants.
2. L (vessel length) does not change in humans
a. exception – lengthening of blood vessels that occurs in obesity
3. η (viscosity) – relatively constant.
4. Radius (r) – main determinant in R (resistance)
a. Resistance is proportional to 1/r4
b. a small change in the radius, produces a large change in resistance – increasing the radius 2x decreases resistance by 16x
f. Hydraulic pump – required in order to sustain the pressure gradients needed to create the blood flow necessary to transport material (nutrients, gases, wastes, etc.) throughout the body
i. The heart is a fascinating organ in that begins beating after only 3-6 weeks after fertilization
ii. It will beat on average 3 billion times before we die, and even when removed from the body, it can continue to beat on its own, without any need for nervous stimulation.
- Poseuille’s law
2. Velocity of flow
d. Poseuille’s Law:
i. Equation that combines the effects that pressure gradients and the factors determining resistance have on blood flow:
1. IMPORTANT NOTE: Poseuille’s law as given in the text is not correct, as it only addresses resistance and does not incorporate pressure gradients.
F = (change in P)(pi r ^4)/(8Ln)
e. Velocity of Flow – the distance a fixed volume of blood travels in a given period of time (how fast)
i. NOT the same as flow rate – the volume of blood that passes a given point in the system per unit time (how much)
1. Units: mL/min or L/min
ii. Formula: v = Q/A
1. Q = Flow rate – directly related
2. A = cross-sectional area of the tube – inversely related to velocity
a. Velocity increases when cross sectional area decreases (arteries)
b. Velocity decreases when cross sectional area increases (capillaries)
Heart structure
a. Center of the thoracic cavity – ventral side; between lungs
i. Apex – angles downward to the left; rests on the diaphragm
1. Must contract from apex up in order to push blood through aorta and trunk at the top of the ventricles
ii. Base – faces upward; major blood vessels emerge from
b. Four chambers
i. Left and right atria – much smaller walls than ventricles
1. Right atria – receives deoxygenated blood from systemic circuit via inferior and superior vena cava
2. Left atria – receives oxygenated blood from pulmonary circuit via 2 right and 2 left pulmonary veins
ii. Left and right ventricles – the majority of the heart
1. Right ventricles – sends deoxygenated blood into pulmonary circuit via pulmonary trunk 2 right and 2 left pulmonary arteries
2. Left ventricle – send oxygenated blood into systemic circuit via aorta
c. Walls of each chamber are composed of 3 layers:
i. Endocardium – inner epithelial lining of the heart (continuous with lining of blood vessels)
ii. Myocardium – cardiac muscle cells
1. joined together by intercalated disks that contain gap junctions – allow ions to flow directly between cells (electrical coupling)
iii. Epicardium (= visceral pericardium) – epithelial lining covering the outer surface of the heart
d. Pericardial sac – surrounds and protects the heart
i. 2 layers
1. Fibrous pericardium – thick layer of connective tissue; anchors the heart in place
2. Parietal pericardium – fused to fibrous pericardium; faces cavity
ii. Pericardial cavity – between pericardial sac and epicardium/visceral pericardium
1. Contains serous fluid – reduces friction during contraction
iii. Prevents overdistension of the heart and anchors it to surrounding structures.
iv. Pericarditis – inflammation of pericardium; friction rub against the heart
e. Heart Valves – passive unidirectional valves (open in response to changes in pressure); prevent the backflow of blood from the ventricles to the atria or from the large vessels to the ventricles.
i. Atrioventricular valves – between atria and ventricles
1. tricuspid valve – between right atrium and right ventricle.
2. Bicuspid valve (mitral) – between left atrium and left ventricle (bi people are left)
3. Respond to pressure gradients
a. High pressure in the ventricles due to ventricular contraction – closes them
b. Relaxation of ventricles causes ventricular pressure to fall below that of atria – opens them
4. Chordae tendineae – attach papillary muscles of the AV valves to the ventricular side; prevents opening into atrium from ventricular pressure
ii. Semilunar valves – between ventricles and larger arteries; each has 3 leaflets
1. aortic semilunar valve – between left ventricle and left
2. pulmonary semilunar valve – between right ventricle and pulmonary trunk
3. Respond to pressure gradients
a. High pressure in the ventricles due to ventricular contraction – opens them.
b. Relaxation of ventricles causes ventricular pressure to fall below that of the aorta – closes them
f. Fibrous skeleton – connective tissue rings that:
i. Prevent collapse of valve openings.
ii. Physically and electrically separate atria from the ventricles – allows independent contraction
1. allowing atria to contract as a unit to push blood down into ventricles
2. allow ventricles to contract as a unit to push blood upwards into the major blood vessels (aorta and pulmonary trunk/arteries)
Cardiac muscle
- characteristics
- conduction system
- types of cardiac cells
does not require a stimulus from the nervous system in order to contract. (unlike skeletal)
myogenic – originating within the heart itself
The conduction system – non contractile cells that are capable of spontaneously creating and conducting the action potentials & stimulate contractile cardiac cells
o Signal spreads through gap junctions (wavelike) – allows appropriate and simultaneous contraction of atria then ventricles to form heartbeat
Types of cardiac cells
o Normal – contractile cell; myocardium
99% of cells
Larger than noncontractile, smaller than skeletal
striated, mononucleated
o Modified/specialized – intrinsic conduction system; non contractile (not striated)
1% of cells
Auto-rhythmic cells – generate AP; pacemakers
Conducting cells
Non contractile cells
- how long is AV node delay
no sarcomeres/striation; generate and conduct action potentials.
- Autorhythmic pacemaker cells – AP of SA and AV are influenced by NS and endocrine (allows for regulation for sleep/exercise/etc)
a. Sinoatrial (SA) Node – In right atrium
i. generates action potentials (APs) at a rate of 100 APs/min - modified by PSNS – 75 APs/min at rest
ii. natural pacemaker – generates the fastest AP in the heart
iii. damage – atria may not contract - AP will be produced at the rate of the AV node (50 APs/min) – may not be high enough to sustain life functions.
- Artificial pacemaker with battery and electrode can be surgically implanted under the skin – artificially stimulate the AV node (not SA node) cells at a rate that is within normal range
b. Atrioventricular (AV) node – in right atrium
i. generates action potentials at a rate of 50 APs/min
ii. Small diameter cells with few gap junctions – slows down the conduction of AP; creates ~100 ms to ensures the atria contract and are fully empty before ventricular contraction begins
c. Purkinje fibres – in ventricles
i. Generates AP at 25-40 bpm - Conducting cells – large diameter conducting cells (can be autorhythmic)
a. Interatrial pathway
i. Carries signals from SA node (right atrium) left atrium
ii. Causes contraction of atrial myocardium
b. Internodal pathway
i. Carries signals from SA node to AV node
c. AV node – slowed conduction to allow atrial contraction
i. Signal must enter here – fibrous skeleton blocks elsewhere
d. Atrioventricular/AV bundle/Bundle of His
i. Pathway of AP from atria to ventricles.
ii. Carries quickly through ventricular septum – bundle splits into Bundle Branches that carry the signal to the apex
e. Purkinje Fibers (”subendocardial conducting network”)
i. Terminal branches – transmit impulses (AP) to contractile cells of ventricles & stimulates contraction upwards starting at apex
ii. Must start at apex in order to push blood upwards into blood vessels
Action potentials in
- Pacemaker cells
- Contractile cells
- Action Potentials In Pacemaker Cells (SA node and AV node)
a. Pacemaker potential – unstable membrane potentials that are capable of spontaneously producing AP
i. No RMP – cell is constantly depolarizing and hyperpolarizing
ii. Threshold is -40mv
iii. If (funny) channels open – Na+ enters the cell & depolarizes to threshold. - Funny – allows current to flow; unusual properties (allows both K+ and Na+ through but Na+ influx exceeds K+ outflux)
- Slow depolarization due to movement of K+ and Na+
b. Depolarization phase – at threshold
i. If (funny) channels close – Na+ influx stops
ii. Voltage gated Ca++ channels open – Ca2+ enters rapidly and depolarizes to peak
c. Repolarization phase
i. At peak (+20mv) – voltage gated Ca++ channels close & slow K+ channels open - K+ exits the cells – hyperpolarizes
ii. At -60mV voltage gated K+ channels close – If channels reopen & cycle begins again - Action Potentials In Myocardial Contractile Cells
Phases:
a. Phase 4: Resting Membrane Potential
i. Is -90mv in contractile cardiac cells
b. Phase 0: Depolarization phase
i. Depolarization of autorhythmic cells spreads through gap junctions to contractile cells.
ii. Voltage gated Na+ channels open – Na+ enters cell until membrane is depolarized to +20 mV.
c. Phase 1: Initial Repolarization Phase – slight drop
i. Na+ channels close, fast K+ channels open, K+ leaves cell causing repolarization.
d. Phase 2: Plateau
i. Voltage gated Ca2+ channels open, fast K+ channels close.
ii. Ca2+ entry & decreased permeability to K+ prolongs depolarization and slows hyperpolarization
e. Phase 3: Repolarization phase – large drop
i. Ca2+ close
ii. Voltage gated slow K+ channels open, K+ exits cell and membrane potential returns to resting levels.
Cardiac contraction
- AP delay
- importance of refractory period - excitation contraction coupling
- graded contractions
- Cardiac contractile cell AP – are much longer (~250 ms) than in skeletal muscle cells (1-2 ms) due to the plateau phase.
a. Extends the Absolute refractory period
i. It is almost as long as the contractile response – contraction + relaxation
b. Long absolute refractory period has 2 important effects
i. Prevents tetanus – second AP/contraction can’t be initiated before first is complete; prohibits summation of contractions
ii. Allows for alternation of contraction and relaxation of the myocardium with enough time in between beats for the chambers to fill with blood (i.e. heartbeat). - Excitation Contraction Coupling in Myocardial Cells
a. AP arrives at the myocardial cell from contractile cell – travels across sarcolemma and infiltrates through t-tubules
b. Voltage gated L type Ca2+ channels of t-tubules open – Ca2+ enters cell
c. Ca++ binds to and opens ryanodine receptor (RyR) Ca++ release channel on the membrane of the sarcoplasmic reticulum (SR)
i. Provides 90% of Ca2+ needed – other 10% comes from ECF (t-tubules)
d. This process is Ca2+ induced Ca2+ release. – leads to a Ca2+ signal.
e. Ca2+ ions bind to troponin – initiates contraction cycle and crossbridge formation (myosin binds to actin, powerstroke, etc).
f. Relaxation of the cell
i. Ca++ ATPase pumping Ca++ into the SR
ii. Na+/ Ca++ Exchanger (NCX) – an antiport that moves Ca2+ into ECF in exchange for Na+. - Na+ that enters is removed by Na+ K+ ATPase
iii. As Ca++ levels in the cytosol decrease, Ca2+ unbinds from troponin, stopping the contraction cycle. - Cardiac muscle can execute graded contractions – fibre varies in the amount of force it generates
a. Skeletal muscle – all or nothing
b. Cardiac muscle – proportional to the amount of crossbridges that are active (determined by amount of Ca2+ is bound to troponin)
c. Also affected by length of sarcomere – a function of how much blood is present in the chambers of the heart (relationship between force and ventricular volume)
ECG
- how they work
- einthovens triangle
- shows what
waves vs segments vs intervals
- can you tell whether its de or repolarizing in waves
- Electrical activity in the heart can be measured using electrodes placed on the surface of the skin – salt solutions (NaCl) are good conductors
- Einthoven’s triangle – at least 3 electrodes are required, placed in a triangular formation on the arms and legs
o 6-12 electrodes are typically used in clinical practice - Shows the summed electrical activity generated by all of the cells in the heart during the cardiac cycle – net charge movements
o It is NOT the same as an action potential – it is summing multiple AP taking place
ECG tracing – waves and segments that correspond to electrical activity in the heart.
- Waves – parts that go above or below traceline
o You cannot tell if a wave if depolarizing or repolarizing by it’s shape relative to the baseline
- Segments – sections of baseline between 2 waves
- Intervals – combinations of waves and segments
Phases on ECG
- P wave – atrial depolarization quickly followed by atrial contraction
- PR Segment – spread of AP to AV node; AV node delay allows completion of atrial contraction
a. Atria pushes last 20% of blood into ventricles active filling of ventricles - QRS Wave (Complex) – Ventricular depolarization
a. atrial repolarization also occurring – masked by ventricular depolarization (large wave)
b. Spreads through AV bundles – ventricular contraction begins - ST segment – All fibers in the ventricles are contracted
a. Atria is relaxed - T wave – Ventricular repolarization
a. Ventricular contraction continues halfway through wave - TP segment – atria and ventricles relaxed and passively filling
- (80% of blood enters ventricles through passive filling)
Analysis of ECGs
- what info can be had
- what is normal, high, low
ECG abnormalities
What is the heart rate
o Normal range – 60-100 bpm
o Higher than 100 bpm – tachycardia
o Lower than 60 bpm – bradycardia
- Is the rhythm regular?
- Are all waves and segments present in a recognizable form?
ECG Abnormalities – result in arrythmias
- Heart Block – damaged AV node; conduction through AV node is delayed; longer PR segment
a. 1st Degree – all waves present; PR segment (AV node delay) longer than normal.
b. 3rd Degree - complete blockage of signal from atria to ventricles; ventricles contract at AV bundle action potential rate of 30 APs/min.
i. Results in asynchronous contraction and relaxation of atria and ventricles.
ii. Many P waves, fewer QRS waves. P waves not followed by QRS wave. - Ventricular fibrillation – heart muscle no longer depolarizing synchronously, making coordinated pumping action impossible.
Cardiac cycle
- lag
- 1 cycle
- 2 states
events of cycle
- Mechanical events (contraction and relaxation) lag slightly behind electrical signals (repolarization and depolarization)
1 cardiac cycle:
o systole + diastole of the atria
o systole + diastole of the ventricles
Two stages:
o Diastole – period of relaxation and filling.
o Systole – period of contraction and emptying.
Events (phases) of the cardiac cycle
- The heart is at rest and filling – period of both atrial and ventricular diastole
a. Pressure in ventricles is lower than in atria AV valves are open and passive ventricular filling occurs (80% of atrial blood)
b. Ventricular volume increases. - Atrial contraction – atrial systole, end of ventricular diastole
a. Last ~20% of atrial blood volume into the ventricles.
i. Atrial contraction will play a larger role in ventricular filling when HR increases (ex. exercise)
ii. A small amount of blood will enter back into the veins because there is no valve – observed as a pulse
b. End diastolic volume (EDV) – the volume of blood at the end of ventricular diastole (~135mL)
i. Maximum ventricular volume - Isovolumetric contraction of ventricles – start of ventricular systole
a. Early ventricular contraction – occurs prior to a change in ventricular blood volume (isovolumetric)
b. Ventricular pressure increases – closes AV valves
i. Turbulent blood flow of AV valves closing causes first heart sound (“lub”)
ii. Pressure is not high enough to cause ejection
c. Atria are in diastole and filling - Ventricular ejection – ventricular systole, atrial diastole
a. Ventricular pressure increases further – opens semilunar valves
i. Pressure created is the driving force of movement of blood through CV system
b. Stroke volume – volume of blood ejected from each ventricle
i. SV = EDV – ESV
ii. ~ ½ of ventricular blood volume enters aorta & pulmonary arteries
c. End Systolic Volume (ESV) – volume of blood left in each ventricle at the end of ejection (~65mL)
i. Minimum ventricular volume - Isovolumetric relaxation of ventricles (start of ventricular diastole)
a. Aortic pressure increases above ventricular – semilunar valves close
i. Turbulent blood flow of semilunar valve closure causes second heart sound (“dup”)
b. ventricular tension decreases, and pressure falls – still too high for AV valves to open, so no blood enters ventricles (hence iso)
Cardiac output
- detemined by
- equation
- should be what
CO- volume of blood ejected by each ventricle over time (i.e. rate at which each ventricle pumps blood)
- Indicates how much blood is flowing through the body – doesn’t indicate how it’s being distributed to tissues (regulated at tissue level)
Determined by
a. Heart rate – the rate at which the ventricles contract (~72bpm)
b. Stroke volume – the volume of blood pumped per contraction (~70mL/beat)
i. SV = EDV (~135mL) – ESV (~65mL)
• Can also be expressed as ejection fraction (SV/EDV)
ii. ESV – safety reserve; more forceful contraction can decrease ESV
c. Values are variable and will depend on conditions – can be modified by nervous and endocrine system
Body can adjust CO to respond to body’s needs
HR (bpm) x SV (mL/beat) = CO (mL/min or L/min)
a. At rest: 72bpm x 70mL/beat = 5040mL/min = ~5.0L/min
b. Exercise: 200bpm x 125mL/beat = ~25000mL/min = ~25.0L/min
During exercise – cardiac output can increase up to 5X.
Cardiovascular athletic training/exercise – can further increase cardiac output up to 40 L/min by increasing difference between resting and exercise values for SV and HR
• Training increases heart muscle mass – increases SV
• Decreases resting heart rate – maximal HR remains the same
CO should be the same for each ventricle – can become imbalanced if one side of heart starts to fail; blood will accumulate on the weaker side
Factors that affect HR (4)
- where does neural control stem from
chronotropic agents
1. Chronotropic agents – will affect the autorhythmic cells
- Intrinsic control
a. SA node – ~100 AP/min
b. Modified by the ANS and endocrine - Neural Control – stem from medulla oblongata
a. Antagonistic tonic control – both SNS and PSNS are active at all times
i. Normally dominated by PSNS
ii. Increased SNS = decreased PSNS & vice versa
b. Parasympathetic (PSNS) – dominant at rest (~72bpm)
i. Mechanism: - Vagus nerve neurons (PSNS) – releases acetylcholine.
- ACh binds to mAChR of SA node cells – initiates signal transduction (muscarinic = GPCR); results in:
a. Increase in K+ permeability – hyperpolarizes the pacemaker potential and
b. Decrease in Na+ and Ca2+ permeability – slows the rate at which the pacemaker potential depolarizes. - Slows the time required to reach threshold – decreases the rate of AP and therefore the HR
- Slows the conduction through the AV node
c. Sympathetic (SNS) Control – required to increase HR above intrinsic rate (100bpm)
i. Mechanism: - Thoracic nerve neurons (SNS) – release norepinephrine (NE).
- NE binds to B1 NE receptors (GPCR) of SA node cells – increases cAMP second messenger system; results in:
a. Decrease in K+ permeability – depolarizes the pacemaker potential
b. Increase in Na+ and Ca2+ permeability – increases rate at which the pacemaker potential depolarizes. - Shortens the time required to reach threshold – increases the rate of AP and therefore the HR
- Also increases rate of conduction through the AV node
- Hormonal Control
a. Mechanism:
i. Epinephrine – secreted by the adrenal medulla as a result of increased SNS - reinforces the effects of the SNS action on the heart (increase HR)
- the effect of E is the same effect as NE released by neurons (binds to B1 receptors)
Factors that affect SV (6)
- Ionotropic agents – any factor that increases the force of ventricular contractility will increase SV or the length of the myocardium
a. Factors will affect the contractile cells of myocardium (not the autorhythmic) - Neural Control
a. Parasympathetic (PSNS) Control – none (little to no vagal innervation of contractile cells)
b. Sympathetic (SNS) Control
i. Mechanism: - SNS neurons release norepinephrine
- NE binds to B1 adrenergic receptors on contractile cells, stimulating the cAMP second messenger system. Effects:
a. Phosphorylation of L-type calcium channels – causes them to open wider; increases flow of Ca2+ into contractile cells from t-tubule after AP on sarcolemma
b. Increased release of Ca2+ from the sarcoplasmic reticulum (SR) (increased calcium induced calcium release).
c. More Ca2+ in the cytosol, increases the number of crossbridges between actin and myosin, and increases the speed of crossbridge cycling.
d. Phosphorylation of phospholamban – increases activity of Ca2+ ATPase in SR membrane, increasing the speed of relaxation (able to start filling again sooner) - i to iii increase ventricular contractility – at any given end diastolic volume (i.e. SNS stimulation operates independently of length tension relationships)
c. Significance: SNS stimulation:
i. Increases force of ventricular contraction – increases the ejection fraction which increases SV.
ii. Increases contraction/relaxation speed – shortens systole & increases duration of diastole. - SNS also increases heart rate (decreases the time for ventricular filling) – quicker relaxation compensates for shorter diastole; would otherwise not be able to maintain SV
a. Each cardiac cycle takes
i. ~0.8 sec at rest/72 bpm
ii. only 0.3 sec at 200 bpm.
iii. Increases the force of atrial contraction
iv. Increases vasoconstriction of peripheral veins – increases venous return to heart - blood enters the ventricles faster – ensuring sufficient filling and further compensation for increased HR
- overall effects – help to maintain/increase EDV, and help to maintain, if not increase SV
- Hormonal Control
a. Mechanism: The mechanism of action of hormonal epinephrine is the same as that for norepinephrine released by the SNS (cAMP second messenger is activated, etc). - Intrinsic Control (EDV affects ventricular preload. - the degree of myocardial stretch before contraction begins)
a. Length tension relationship – the force of ventricular contraction varies in response to how much the ventricular myocardium is stretched upon filling
i. At rest – cardiac fibers are at less than optimal length (which is 2.2 µm).
ii. Increasing EDV (ex. increasing venous return) – cause cardiac cells to stretch and approach optimal length; allows more crossbridges to form between actin and myosin & increases the force of contraction and SV
b. Frank Starling’s Law of the Heart – force of ejection (SV) is directly proportional to the EDV; determines the degree of stretch in the cardiac muscles.
i. i.e. the more blood in during diastole (increased EDV), the more blood comes out during systole (increased SV) and vice versa. - Venous Return – the amount of blood returning to the heart from veins; directly affects EDV and therefore SV and CO
a. Factors determining EDV:
i. Neural control: - Increases SNS activities blood vessels – NE binds to a1 receptors & causes vasoconstriction
- Vasoconstriction in response to decreased mean arterial pressure (or exercise) strongly increases venous pressure and therefore venous return.
- Increased tension in the vein wall decreases compliance (i.e. blood will not be able to pool in veins), which also increases venous return and therefore increase EDV, SV, and cardiac output.
ii. Skeletal muscle pump - Large muscle groups compress deep veins in the legs (and arms) when they contract.
- Compression & valves in large veins – prevent backflow of blood; ensures that when muscles are contracting (like during exercise) more blood is moved towards the heart.
- So exercise and contracting muscles – pushes blood back toward the heart, increasing venous return increases EDV, SV and CO
- At rest (sitting) – the skeletal muscle pump is usually not working (unless you are doing calf raises or other exercises while seated)
iii. Respiratory pump - Venous return depends on the pressure gradient (∆P) between peripheral veins and the right atrium.
- Right atrial & thoracic vena cava pressure – is affected by changes in thoracic cavity pressure.
a. During inspiration – contraction of the diaphragm decreases pressure in the thoracic cavity and increases pressure in the abdominal cavity; results in:
i. Compression of abdominal veins increasing their pressure
ii. Distension of thoracic cavity veins and the right atrium decreasing their pressure
b. Increased abdominal vein pressure and decreased pressure of thoracic veins/right atrium causes larger P and more blood to flow into thoracic veins and into the right atrium (i.e. increases venous return) - The larger the inhalation the greater the ∆P the greater the venous return.
- Afterload
a. SV depends on the arterial pressure against which it is pushing greater arterial pressure = smaller P
i. Semilunar valves only open once ventricular pressure becomes greater than aortic pressure.
ii. Increased MAP = increased aortic pressure = more force required to eject the same volume of blood from ventricles against the pressure in arteries
b. Increased afterload only becomes a problem in diseased states:
i. Chronic hypertension (>140/90 mmHg)
ii. Stenosis of the semilunar valves
iii. Coarctation of the aorta
Blood vessel structure
- what is constant and what can change
- structure
Blood flow to specific organs – can be modulated by changing the pressure gradients, radius, length, viscosity
o Length and viscosity – relatively constant
o Radius and P – able to modulate
Blood vessel structure – not all blood vessels have all components
- Tunica intima – innermost layer; single layer of endothelial cells.
a. Continuous with endothelial lining (endocardium) of heart.
b. Secrete paracrines – regulate blood flow, blood pressure, vessel growth, absorption of materials - Elastica interna – made of elastic protein fibers (elastin) that are capable of stretch and recoil.
- Tunica media – vascular smooth muscle; contraction and relaxation change radius; often partially contracted on most BV (muscle tone)
a. Contraction = vasoconstriction
i. Depends on entry of Ca2+ from ECF
b. Relaxation = vasodilation. - Elastica externa – layer of elastin
- Tunica externa – outer layer of connective tissue
Types of blood vessels
- what is in walls
- functions
- Arteries - thick walls with lots of elastic tissue.
a. Large elastic arteries (ex. aorta) - large diameters (radii) with little resistance to blood flow (F = ∆P/R)
b. Artery pressure reservoir helps to maintain:
i. maintain driving pressure of blood flow during ventricular relaxation (diastole) - stretch in order to accommodate blood during ventricular systole
- recoil during diastole maintains pressure
ii. constant flow of blood toward capillaries – maintains P
c. Elasticity – allows them to expand to accommodate ventricular ejection
d. Thickness – maintains pressure on blood that allows passive elastic recoil , pushing excess blood downstream.
e. Low compliance (low capacitance) vessels – low ability of the vessel to stretch and increase volume with increasing transmural pressure (∆ volume / ∆ transmural pressure = low)
i. Stiff fibrous tissue - Arterioles:
a. Thick walls – little elastic tissue & lots of smooth muscle
i. Innervated by sympathetic nerves (except penis and clitoris which have innervation from PSNS). - The amount of smooth muscle and innervation progressively decrease in the arterioles as they get closer to the capillaries.
- Arteries arterioles will have less elasticity and more muscle
ii. Metarterioles – do not have a continuous smooth muscle layer
b. Functions:
i. Determine the relative blood flow to individual organs/tissues through vasoconstriction and vasodilation.
ii. Help maintain mean arterial pressure (MAP).
iii. Eliminate the pulse pressure prior to it reaching the capillaries (eliminates pulsatile changes in flow/pressure in capillaries). - Capillaries:
a. Function in exchange between vessels and ISF – highly permeable to small lipid soluble substances (o2, co2, FA, steroids, anesthetics, etc)
i. Smallest, thinnest, most numerous blood vessels in body. - 5-10 µm in diameter – huge surface area (~6000 m2) for exchange
- Contain 5% of circulating blood at rest.
ii. A single layer of endothelial cells surrounded by thin glycoprotein/collagen matrix (basement membrane)
b. Two classes – allow differing levels of exchange
i. Continuous capillaries – cells connected by leaky junctions (small intercellular spaces)
ii. Fenestrated capillaries – large intercellular spaces (junctions) between cells and large channels (pores) passing through cells. - Found in kidney (glomerulus), intestines, liver, bone marrow (in liver and bone marrow = discontinuous capillaries).
c. Closely associated with pericytes – contractile cells that surround capillaries; determine “leakiness” by how many are present
i. Secrete factors – capillary growth, can differentiate to become new endothelium/smooth muscle cells - Veins
a. Venules converge & form – larger venules have some smooth muscle
i. Smaller – more similar to capillaries
b. Thin-walled, valved, high compliance vessels (expand easily with increasing pressure)
i. Contain less smooth muscle and elastin
ii. More collagen (connective tissue) than arteries
c. Enlarge as they travel towards heart – maintains P for blood flow
d. Functions:
i. Low resistance/high compliance vessels for blood flow - Mean driving pressure (P) for blood flow from veins to right atrium is only 10-15 mmHg.
- Combined with the large cross-sectional area – low velocity of flow & pooling of blood in veins forming volume reservoir
ii. Volume reservoir – hold a much greater volume of blood than arteries, even though pressure is much lower - Reservoir can rapidly be drawn on when required
a. Constriction of veins prevents pooling of blood & increases venous return
b. Dilation of veins allows blood to pool inside of them and decreases return
Distribution of blood throughout the body
main site of resistance
- modulating resistance
- vascular tone modulation
• Different organs require different amounts of blood flow both at rest and as activity changes – body needs a way to allow for changes in blood flow to different organs
• CO from the left ventricle is ~5.0 L/min (based on average HR and SV)
o Most blood from the left ventricle at rest goes to the liver flow rate to the liver is 27% x 5.0L/min = 1.35L/min
o The least amount goes to the heart (4%) and skin (5%) at rest – these increase with increased activity
o 20% goes to skeletal muscle at rest – can increase to as much as 85% during exercise
o Total blood flow through all the arterioles of the body always equals the cardiac output
• Pulmonary circuit – blood flow to the lungs occurs at 5.0L/min coming from the right ventricle the entire volume of the body’s blood passes through the lungs each minute
- F = P/R
- Arterioles – main site of variable resistance (>60% of total resistance); due to smooth muscle in walls
- Controlled by
a. Changing arteriolar resistance (not “regulation”) – blood will be diverted to arterioles with less resistance
i. Arteriole radius can be adjusted independently of one another – allows for specific changes in different organs - Smooth muscle can contract (vasoconstriction) or relax (vasodilation) to produce changes in R and F
ii. Rate of blood flow to each organ – depends on the degree of contraction and relaxation in the arterioles that supply blood
b. Contraction/relaxation of precapillary sphincters – bands of smooth muscle at junction between arterioles and capillaries
i. Open – blood flows into capillary bed
ii. Closed – blood flows directly from arteriole to venule through metarterioles (connecting vessels); does not enter capillaries - Vascular tone – state of partial contraction independent of neural signaling and chemical effects (hormones, vasoactive mediators)
a. Baseline constriction of arterioles – can be modified by external signals to increase or decrease concentration of cytosolic Ca2+ in smooth muscle
i. Increasing Ca2+ increases tension
ii. Decreasing Ca2+ decreases tension
Regulation of blood flow (not pressure)
- Intrinsic mechanisms
- extrinsic mechanisms
local is dominant
- Intrinsic (local) autoregulation mechanisms:
a. Heart & brain – tissue metabolism is the primary factor that determines arteriolar resistance
i. Brain tissue – high sensitivity to oxygen and glucose levels; relatively constant under normal circumstances
1. Increases in systemic BP – may trigger myogenic responses; causes vasoconstriction to regulate
2. Metabolism is the primary factor
a. Buildup of co2 – vasodilation (can be observed at PET and fMRI scans)
ii. Coronary blood flow – myocardium takes up 75% of oxygen
1. Whereas only 25% of o2 sent to systemic tissues is taken up – 75% is still present
2. Lack of oxygen (myocardial hypoxia) causes the release of adenosine – causes vasodilation and increased blood flow
b. Myogenic control – ability of vascular smooth muscle within vital organs to regulate its tone in response to changes in blood pressure
i. Increasing blood pressure stretches the smooth muscle in the arteriole
1. Stretching causes opening of mechanically gated Ca2+ in smooth muscle membrane – allows Ca2+ to enter & form crossbridges to increase tension
ii. Example 1: when you stand, the arterial pressure and flow in the feet increase increase in pressure in the feet causes the arterioles to stretch & allows more Ca2+ into the cells the smooth muscle contracts, resulting in vasoconstriction (increased tone) reduces flow in the feet.
iii. Example 2: When you stand up (from a supine position), the cerebral arterial pressure decreases reduces the amount of stretch in the arterioles smooth muscle relaxes (less stretch, less Ca2+) vasodilation (decreased tone) increases blood flow to the brain
c. Local Metabolic Control – many tissues can control blood supply be releasing paracrine molecules in response to changes in metabolic activity
i. Paracrine release into ECF endothelium of the arterioles release vasoactive mediators – directly effects arteriole smooth muscle and causes either contraction or relaxation (e.g. nitric oxide, (NO))
ii. Active hyperemia – increase in blood flow in tissue in response to increase in tissue activity (metabolism)
1. O2 decrease and co2 increases with increasing metabolism – causes relaxation of smooth muscle and increased blood flow to organ/tissue
iii. Reactive hyperemia – increase in tissue blood flow following a period of low perfusion (waste removal is not occurring at optimal level)
1. Vasodilation – caused by autoregulatory myogenic and metabolic factors
a. Myogenic – reduced flow/pressure decreases stretch and causes relaxation (vasodilation)
b. Metabolic – local hypoxia (lack of o2) and accumulation of metabolic byproducts causes vasodilation through synthesis of NO
2. Triggering of myogenic and metabolic – causes rapid restoration of local cellular conditions
iv. Exercise
1. Rapid contraction in skeletal (and cardiac) muscle leads to:
a. Local reductions in O2 levels (hypoxia)
b. Local increases in CO2, H+, K+, and adenosine levels (metabolic waste products)
2. Causes vascular endothelial cells to secrete nitric oxide at these sites – reduces Ca2+ entry into adjacent smooth muscle cells causing local vasodilation of
a. Arterioles – increases blood flow to active tissues
b. Precapillary sphincters – increases number of open capillaries in active tissues
3. Result in increased O2 delivery and increased waste removal by blood.
d. Non-metabolic chemical mediators
i. Endothelin-1 – released from arteriolar cells in response to an increase in pressure.
1. Causes vasoconstriction – opening non-stretch sensitive Ca2+ channels and enhancing Ca2+ release by the sarcoplasmic reticulum in smooth muscle cells.
ii. Histamine – released by mast cells of the immune system.
1. Causes vasodilation and plays a role in inflammation – localized release occurs during allergic reactions (quick onset) or in response to injury/infection (2-8hr onset); causes swelling and redness
iii. Serotonin – In the blood, serotonin is released from platelets in response to a wound.
1. Causes vasoconstriction – vascular spasm is part of hemostasis; acts to reduce blood flow to the site of the wound (prevents blood loss)
- Systemic (extrinsic) mechanisms – signaling from NS or endocrine
a. Can create body wide changes in blood flow and blood pressure (systemic).
i. Extrinsic control of arteriolar radius across multiple organ systems alters Total Peripheral Resistance (TPR) – an important regulator of Mean Arterial Pressure (MAP). - F = P/R P = F x R
a. Sub: CO for F, MAP for P, TPR for R
b. MAP = CO × TPR
ii. Increasing or decreasing TPR by systemic vasoconstriction or vasodilation will change: - The blood flow in those systems
- Will also have a measurable effect on blood pressure – unlike myogenic/metabolic (local)
b. Neural Control – SNS only (except for penis and clitoris)
i. Sympathetic neurons mainly release NE – binds to arteriolar smooth muscle a1 adrenergic receptors vasoconstriction
1. brain arterioles lack a1 adrenergic receptors (as do terminal arterioles) – their radius/diameter is entirely controlled by local mechanisms (i.e myogenic/metabolic control).
ii. Sympathetic nerves constantly discharge at an intermediate rate (in addition to basal tone) – firing rate is controlled by the cardiovascular center in the medulla oblongata of the brain.
1. increased firing – generalized* vasoconstriction (↑ TPR) & venoconstriction (constriction of veins)
2. decreased firing – generalized vasodilation (↓ TPR)
c. Hormonal Control
i. Epinephrine – released from adrenal medulla in response to SNS stimulation
1. In skin and most abdominal viscera – binds to smooth muscle a1 receptors; reinforces SNS vasoconstriction (promiscuous receptors)
2. In heart, liver and skeletal muscle – binds with greater affinity to non-innervated B2 receptors that bind epinephrine with higher affinity
a. Vasodilation in these tissues – increased local metabolic control mechanisms (ex. during exercise)
3. Think about which ones need to be active during exercise (fight or flight) – will require vasodilation via B2 receptors (as well as local control mechanisms)
a. If the organs mainly function for resting and digesting – the generalized response of vasoconstriction will apply
ii. Other hormones – closely linked to control of blood volume via affects on kidney arterioles
1. Angiotensin II – activated due to decreased renal perfusion pressure (ex. decreased MAP) causes renin secretion by kidneys activates angiotensin II system increase in blood volume
a. Causes arteriolar vasoconstriction (increases TPR)
2. Vasopressin (ADH) – released from posterior pituitary in response to signaling from atrial receptors stimulated by decrease in blood volume & MAP
a. Causes vasoconstriction (increases TPR)
3. Atrial Natriuretic Peptide (ANP) – synthesized and released by specialized atrial cells in response to excess stretch in the heart (ex. increased venous return due to increased blood volume/pressure)
a. Causes relaxation of vascular smooth muscle and vasodilation (decreases TPR)
Blood reg during exercise
blood reg during hemorrhage
Ex. blood regulation during exercise – combination of metabolic (local), neural, and hormonal
1. Local metabolic factors
a. Inactive muscles – dominated by local factors
- High local o2, low co2 & H+ vasoconstriction
b. Active muscles
- High co2 and H+, low o2 vasodilation
2. Increased SNS
o Cause increased HR, SV, CO
o NE – bind alpha receptors in non essential organs constriction
o E – bind beta receptors in heart, liver skeletal muscle vasodilation
Ex. blood flow during severe hemorrhage – causes MAP to decrease
1. Local Effect (e.g. at brain, or heart)
a. Decreased arteriolar stretch – myogenic
b. Decreased [oxygen] and increased [metabolic waste] at tissues – metabolic paracrines
- Result – dilation of these arterioles; increased blood flow to brain/heart
• This causes MAP to decrease further – must combine with SNS response
2. Sympathetic response
a. Increased sympathetic stimulation
- NE – vasoconstriction of smooth in non-essential organs
- E – vasodilation of skeletal muscle arterioles; this is opposed by (dominant) local metabolic effects
b. Increased plasma [vasopressin] and [angiotensin II] – prevents water loss at kidneys (affects volume)
- Result – attempt to increase MAP towards pre-hemorrhage values
• increased smooth muscle tone of most arterioles (except brain, heart) – attempt to preserve if not increase blood volume
Blood pressure
- types of pressure
- 4 important pressures
• Hydrostatic pressure – a result of blood pushing against walls of blood vessels; pressure falls over distance as blood moves through CV system
o Highest pressure in arteries closest to pump (ventricles)
o Lowest pressure in veins (in the circulatory route these are furthest from ventricular pump)
o Results when flow (F) is opposed by resistance (R).
• All body pressure are given relative to atmospheric pressure and are measured in mmHg (millimeters of mercury).
o Ex. 100 mmHg = 100 mmHg above atmospheric pressure (at sea level = 760 mmHg)
• Ventricular pressure – difficult to measure; assume arterial BP is indicative of ventricular
- Systolic Pressure (SP) – max pressure in aorta (~120mmHg)
a. Reached ~ half way through ventricular ejection (i.e. during ventricular systole/contraction). - Diastolic Pressure (DP) – min pressure in aorta (~80mmHg)
a. Reached at end of isovolumetric contraction of ventricles
i. technically during ventricular systole – just after diastole ends and before ejection begins
b. high diastolic pressure represents ability of aorta to capture and store energy during diastole - Pulse Pressure (PP) – strength of pressure wave produced by ventricular contraction
a. PP = SP - DP = ~40mmHg
b. Decreases over distance due to friction
c. Pressure wave travels 10x faster than blood itself – pulse in arm is occurring slightly after ventricular contraction
i. Pulse is not felt in veins – pressure wave no longer exists; blood moves continuously - Mean Arterial Pressure (MAP) – average aortic pressure over entire cardiac cycle (~93mmHg); instead of pulsating pressure
a. Driving force pushing blood through the systemic circuit
b. Homeostatically regulated by body to ensure adequate perfusion of organs.
c. Calculated clinically as: MAP = DP + 1/3(SP – DP)
i. Heart spends more time in diastole, so diastolic pressure has a larger contribution to MAP
Sphygmomanoetry
- Method of measuring systolic and diastolic pressure clinically – uses a blood pressure cuff attached a pressure gauge (sphygmomanometer) and a stethoscope.
- Inflate cuff to occlude brachial artery (~140mmHg on the gauge) – make pressure higher than systolic pressure driving arterial blood; causes blood flow to stop; blood flow will return when pressure no longer exceeds SP
- Slowly release the pressure and listen for Korotkoff sounds – soft tapping sounds heard in the in vessel as blood begins to spurt through in turbulent blood flow
a. Pressure when you hear the first sound is the systolic pressure – highest pressure in the artery
b. Pressure when you hear the last sound is the diastolic pressure – lowest pressure in the artery after flow has returned to normal laminar flow
c. Sounds will stop when cuff no longer compresses artery – flow will become smooth (not turbulent) - Average should be 120/80 mmHg – there is a high degree of variability.
a. Hypertension – systolic over 140 at rest and diastolic over 90
Regulation of blood pressure (not flow)
- brain centers
- controlling MAP
• The body homeostatically regulates blood pressure by regulating mean arterial pressure (MAP)
• Blood pressure is regulated by higher brain centers as well
o Hypothalamus – mediates vascular responses for body and fight or flight responses
o Cerebral cortex – learned and emotional responses (ex. blushing, fainting in response to blood or needles)
• Respiratory and CV system work in tandem – increased CV activity usually results in increased respiration
MAP = CO x TPR (where CO = HR x SV).
MAP can be regulated by controlling (all will affect accumulation of blood in blood vessels):
1. Cardiac output
a. By increasing or decreasing heart rate
b. By increasing or decreasing the force of contraction – alter stroke volume.
c. By increasing or decreasing venous return.
2. TPR (Total Peripheral Resistance)
a. By increasing or decreasing vasoconstriction/vasodilation (arteriolar radius) – this is what is believed to cause hypertension most of the time
3. Blood Volume
a. Can influence MAP indirectly – Increasing/decreasing blood volume increases/decreases venous return increases/decreases stroke volume.
i. Kidney – can decrease or conserve water volume; cannot increase
ii. Drinking or IV – required to increase volume
iii. CV compensation – constriction/dilation through SNS; has limitations
b. Also increases MAP directly – increases the hydrostatic pressure of the blood (pressing harder against the walls of the vessels)
4. MAP will also depend on distribution of blood in arteries and veins
a. Arteries – low volume; only contain ~11%
b. Veins – high volume; contain ~60%; can act as a reservoir where venous constriction causes increase in venous return & redistribution of blood to the arterial side (SNS can cause)
Regulating MAP
- baroreceptor reflex
- blood volume control
- Baroreceptor reflex control – autonomic reflex; single most important mechanism for short term regulation of MAP (causes changes in TPR and CO); extremely fast response; always functioning
a. Process
i. Stimulus: changes in blood pressure (MAP) and pulse pressure
ii. Receptors: Mechanical stretch receptors (baroreceptors) in aortic arch (monitors BP flowing to body) and carotid sinuses (measures BP flowing to brain) - Tonically active – frequency of firing AP in baroreceptor cells is directly proportional MAP within physiological limits
- Exhibit adaptation – firing will initially increase/decrease; prolonged exposure to higher/lower MAP causes them to adapt firing to normal levels (hence short term)
iii. Sensory nerves (input signal) project from the baroreceptors to the cardiovascular control center in the medulla (CVCC, integration center). - Medullary CVCC – controls output by sending signals through vagus nerve (PSNS) and sympathetic nerves (SNS) to heart and blood vessels (effectors); antagonistic control
- Effector response that is opposite to initial stimulus – neg feedback
b. At any given MAP, if pulse pressure increases, firing rate also increases
c. Decreased MAP
i. Ex. hemorrhage – causes a decrease in MAP and blood volume
ii. Baroreceptor – only works to bring back towards normal MAP - Decreased MAP decreased arterial wall stretch decreased baroreceptor firing CV control increases SNS (NE, E) and decreases PSNS
a. SNS (NE, E) – increases vascular tone, increases ventricular contraction, increases SA node firing
b. PSNS (Ach) – decreases effect on SA node - Results in – increased vascular constriction & increased TPR, increased EDV, increased SV, increased HR increased MAP
iii. to restore MAP – lost fluid must be replaced by shift in fluid balance or blood transfusion - decreased capillary hydrostatic pressure decreased capillary filtration
- increased AVP and angiotensin II increased blood volume
d. Increased MAP
i. increased MAP increased firing of baroreceptors in carotid artery and aorta activation of sensory neurons CV control
1. increased PSNS (Ach) – slowing of SA node
2. decreased SNS (NE, E) – arteriolar smooth muscle, ventricular myocardium, SA node
ii. result in – decreased heart rate, decreased force of contraction, vasodilation & decreased TPR decreased MAP
e. Changes in BP can change – CO, TPR, or both (only one may be effective at a specific time)
i. Can be activated as a result of local regulation
ii. ex. increased BP causes vasoconstriction (local regulation) – constriction causes increase in MAP – activates baroreceptor
1. vasoconstriction has already been activated – CV center will likely decrease CO in order to decrease MAP
f. Orthostatic hypotension triggers baroreceptor reflex – standing causes pooling of blood at feed & decreases venous return
i. Venous return falls from 5L/min to 3L/min – causes decrease in MAP
ii. Baroreceptor response – causes increased CO and TPR & increase MAP
iii. Skeletal muscle pump – increased venous return when abdominals and leg muscles contract to maintain upright position
- Blood volume control – long term regulation of MAP
a. Indirect effect of blood volume on MAP
i. Changes in blood volume increase/decrease MAP influences venous pressure, venous return, EDV and SV all affect cardiac output
ii. MAP = CO x TPR change in CO due to a change in volume will change MAP
b. Direct effect of blood volume on MAP
i. Increased blood volume increases the hydrostatic pressure on the walls of the arteries.
c. Blood volume is regulated by hormones secreted by the brain, kidneys and heart – hormones influence fluid intake and urine output.
i. Vasopressin (ADH) – from posterior pituitary; increases blood volume - Increases H2O reabsorption by the kidneys (diuretics increase the volume of urine produced and decrease blood volume; ADH does the opposite)
- Also causes vasoconstriction
ii. Renin – from kidney; increases blood volume - Triggers the conversion of plasma angiotensinogen into angiotensin II
- Stimulates ADH release – increases H2O reabsorption by the kidneys
iii. Atrial Natriuretic Peptide (ANP) – from heart; decreases blood volume - Increases Na+ and H2O excretion by the kidneys
- Inhibits vasopressin secretion
- Inhibits renin secretion (and production of angiotensin II).
- Result: all together these responses increase urine output and reduce thirst
Hypo vs hypertension
- primary & secondary
- Failures of pressure homeostasis – slow changes in MAP result in “resetting” of baroreceptors (adaptation) and CV responses
a. Opposes minute to minute changes but are only activated at the adjusted higher or lower pressure level – response to deviations from new set point - Hypotension – low MAP; flow out exceeds flow in & volume decreases
a. Perfusion is not fast enough to clear wastes and bring in nutrients and oxygen
b. May not be able to overcome gravity and o2 supply to brain is impaired (causes dizziness) - Hypertension – high MAP; typically due to chronic increase in TPR
a. Flow in exceeds flow out & blood volume increases
i. Perfusion is too fast to allow for adequate exchange between the blood and tissues
ii. Walls of BV may cause weakened areas to rupture and bleed into tissues - cerebral hemorrhage – rupture occurs in brain; can cause stroke
- can be fatal if it occurs in a major artery
b. Primary hypertension
i. Causes – obesity, stress, cholesterol, smoking, genetics, Na+ retention, and immune system responses - Initially – leads to ventricular hypertrophy (increase in cell size)
- Eventually – myocardial contractile function diminishes over time & leads to congestive heart failure and edema
- Increases risk of atherosclerosis, heart attack, kidney damage, and stroke
ii. Treatments - Exercise, ↓ Na+ intake, and weight loss – lower resting MAP
- Ca2+ channel blockers – promote vasodilation of vascular smooth muscle; decreases heart contractility and the rate of SA node depolarization
- Diuretics (opposite function of ADH) – increase urinary excretion of Na+ and H2O; decreases CO with little effect on TPR
- b-adrenergic receptor blockers – target b1 receptors; decreases NE and E stimulation of CO
- Angiotensin-converting enzyme (ACE) inhibitors – blocks production of angiotensin II; decreases TPR
c. Secondary Hypertension
i. increase in MAP arising from other conditions (e.g. pregnancy)
Capillary movement
- 2 modes of transport
- capillary density
- structure
- 2 functions
- 2 modes of transport – depends on lipid solubility
a. Protein channels (intracellular channels) in endothelial cell membranes – transcellular
b. Intercellular pores between adjacent cells – paracellular - Capillary density is directly proportional to metabolic activity of tissue’s cells
a. Subcutaneous and cartilage – lowest concentration of capillaries
b. Muscles and glands – highest - Structure – thinnest walls; only simple squamous endothelial layer & basal lamina
a. Diameter is barely size of RBC; RBC must go singe file – allows maximum transfer of o2 - 2 functions
a. Rapid movement between capillaries and tissues – down partial pressure, electrochemical, concentration gradients
i. Allows exchange sites for H2O, Na+, K+, glucose, amino acids, gases - Diffusion rate – determined by concentration between plasma and ISF
- CO2 and O2 diffuse freely – will establish equilibrium by venous end
ii. Mostly impermeable to macromolecules - Plasma proteins (e.g. albumin) are too large – they remain in capillary
- Certain proteins can use transcytosis – selective; endocytosis into endothelial cell from plasma/ISF, exocytosis from cell on the other side
iii. Velocity of flow through capillaries is very slow – due to total cross sectional & summed diameters (usually smaller = faster); there are a lot of them - Allows for max exchange of gases between tissues & RBC
b. Maintain fluid balance between plasma and interstitial fluid.
i. Distribution of ECF between plasma (25%) and ISF (75%) – state of dynamic equilibrium due to filtration and absorption of protein free fluid by capillaries
ii. Due to bulk flow – driven through channels & fenestrations by hydrostatic and colloid osmotic pressure gradients (Starling forces) that augment diffusion process - Absorption – into capillary
a. ISF hydrostatic pressure
b. Plasma colloid osmotic pressure - Secretion – out of capillary
a. Capillary hydrostatic pressure
b. Colloid osmotic pressure
