CV 3 Flashcards
Tissues control their own local blood flow in proportion to what?
Metabolic needs
Specific blood flow of Tissues: Liver
27% of CO
1350 mL/min
95 mL/100g of tissue
Specific blood flow of Tissues: Kidneys
22% of CO
1100 mL/min
360 mL/100g of tissue
What is the Vasodilation theory
The greater the rate of metabolism or the less availability of O2 or other nutrients, the greater the production of vasodilator substances
Examples of endogenous Vasodilator substances
Adenosine, CO2, Histamine, K+ions, H+ions
What is the Oxygen lack theory (Nutrient lack theory)
O2 is needed for contraction, so in the absence of O2 muscles will relax & naturally dilate
What other deficits can also potentially cause vasodilation?
~ Lack of glucose, AA, fatty acids
~ Lack of vitamins - vitamin B, (thiamine, niacin, riboflavin) = beriberi
~ Vitamins are needed for oxygen - induced phosphorylation = ATP
What happens when blockages are unblocked?
Reactive Hyperemia - rapid blood flow 4 - 7 x normal - this continues long after flow is restored to “repay” the O2 deficit
What is Active Hyperemia?
with an increase in activity - increase in local metabolism causes cells to devour tissue nutrients rapidly resulting in dilation and increased blood flow to sustain the new level of activity
Acute auto regulation: Metabolic theory
Arterial BP becomes too great, excess flow provides O2 and nutrients which “wash out” vasodilator substances causing constriction
Acute auto regulation: Myogenic theory
Sudden stretch causes smooth muscle to contract - vessel stretching causes reactive vasoconstriction decreasing blood flow to the tissues
What is tubuloglomerular feedback
Fluid composition detected by macula dense in distal tubule signals the juxtaglomerular apparatus when there is too much or too little blood flow causing dilation or constriction of the arterioles
What is one of the ways body temperature regulated
Hypothalamus regulates by controlling cutaneous and subcutaneous blood flow depending on core body temperature
How do endothelial cells help regulate BP
They synthesize substances that dilate & constrict the arterial wall
What is Nitric Oxide
Vasodilator, lipophilic gas
What is the half-life of Nitric Oxide
6 seconds
MOA of Nitric Oxide
NO activates guanylate cyclase in smooth muscle (vasculature) the activated guanylate cycles converts cGTP to its active form cGMP which activates cGMPdependent protein kinase (PKG) which moves calcium back into the SR and blocks phospholipase C activity reducing liberation of stored calcium, thus phosphorylated actin-myosin is dephosphorylated, resulting in relaxation
What is Shear stress?
Shear stress is the frictional force generated by blood flow. Shear stress acts at the apical cell surface to deform cells in the direction of blood flow
NO is released due to ______ _____ on endothelial cells from viscous blood flowing through vessels (mainly bigger arteries) this upstream dilation provides enough blood for downstream vasculature
Shear stress
What does cGMP dependent protein kinase (PKG) in smooth muscle (vasculature) do?
PKG promotes the opening of calcium-activated potassium channels, leading to cell hyperpolarization and relaxation, and blocks agonist activity of phospholipase C, reducing liberation of stored calcium
How is Nitric Oxide synthesized?
Nitric Oxide Synthase (NOS) in the presence of Nicotinamide Adenine Dinucleotide Phosphate (NADPH) (donates 2 electrons and a hydrogen to for NADP) and O2 converts Arginine into Citrulline producing Nicotinamide Adenine Dinucleotide Phosphate (NADP) and NO in the process
Nitric oxide production reduces with age
20s - 100%
30s - 80% - thickening arteries
40s - 50% - Inflammation plaque buildup
50s - 35% - Stiffening wall calcium buildup
60+ - 15% - rupture (possible heart attack)
~ As we age we loose 85% of our ability to make Nitric Oxide
What does Endothelin do?
Vasoconstricts
What causes a great increase in release of Endothelin?
Endothelial cell injury
What is a function thought to be related to Endothelin
Vasoconstriction prevents excessive bleeding (released with endothelial cell injury
Endothelin ETa-receptor signaling has been demonstrated to play a role in:
chronic disease due to its growth promoting and pro inflammatory properties
With acute change in BP (e.g. BP increases 100-150 mmHg), what percentage increase will you likely see in blood flow
100% increase (this will decrease to 10-15% above normal shortly after initial change)
With increases in tissue demand what will occur?
Angiogenesis
Angiogenesis definition
Formation of new blood vessels. This process involves the migration, growth, & differentiation of endothelial cells, which line the inside wall of blood vessels. The process of angiogenesis is controlled by chemical signals in the body.
What effects Angiogenesis
~ Age - occurs more quickly in younger individuals
~ Tissue growth - Occurs with weight gain, tumors, scar tissue, muscle, etc.
How will excess oxygen effect Angiogenesis?
Excess oxygen will stop angiogenesis almost immediately and may even cause degeneration of vessels that have just been formed
Effect of excess oxygen in premature babies
Once excess O2 is taken from baby rapid regrowth of vessels occurs to the point where vessels grow from the retina into the vitreous humor causing blindness (retrolental fibroplasia - also called retinopathy of prematurity)
What does Angiotensin II do
increases total peripheral resistance - increases arterial BP
What is vasopressin?
Antidiuretic Hormone (ADH)
What is more powerful, Vasopressin or Angiotensin II?
Vasopressin
Where is Vasopressin formed and released from?
Formed in the hypothalamus and released from the posterior pituitary
What receptors does Vasopressin act on and what does each do?
V1 - Vasoconstriction of vascular smooth muscle (associated with Gq pathway and increased Ca++)
V2 - Uses the Gs pathway to Induce Aquaporin-2–mediated water reabsorption in the kidney (renal tubules)
V3 - receptors in the anterior pituitary gland are associated with corticotropin (adrenocorticotropic hormone [ACTH]) release
What is Bradykinin’s role in circulatory control?
Arteriolar dilation and increased capillary permeability
What is Histamine’s role in circulatory control?
~ Arteriolar dilation and increased capillary permeability
~ Released during tissue damage or inflammation (allergic reactions)
~ Derived from mast cells from damaged tissue & basophils in the blood
Ions and chemicals associated with Vasodilation:
K+, Mg+, H+, Acetate, Citrate, CO2 (marked in brain)
Ions and chemicals associated with Vasoconstriction:
Ca++, pH, Angiotensin II, Vasopressin
Explain the vertebral relationship and control by the SNS
T1 - L2 - leaves through ventral horn, to sympathetic chain entering through the white ramous - can go up down or out but eventually leaves through the gray ramous - to organ. Sympathetic preganglionic neurons are short, postganglionic neurons are long (mostly)
The SNS innervates what vessels?
~ All blood vessels except for capillaries
~ Not found as extensively in small arteries, arterioles, and veins due to auto regulation (local tissue factors regulate more at this level)
PNS originates from
Cranial Nerves 3, 7, 9 and 10 and S1 - S4 ( sacral nerves )
What is the Parasympathetic Nervous System’s most important role in circulation?
Heart rate control via vagus innervation
Where is the Vasomotor center located?
Bilateral Reticular Area of the Medulla & lower 1/3rd of the Pons
How does the Vasomotor center receive its input?
Receives Transmission of Parasympathetic impulses via the Vagus nerve
How does the Vasomotor center send signals
Transmission of sympathetic impulses are via spinal cord & peripheral sympathetic nerves
Vasoconstrictor Area is also know as:
Rostral Ventrolateral Medulla (RVM)
Vasodilator Area is also know as:
Caudal Ventrolateral Medulla (CVM)
Cardioinhibitory center is also known as:
Nucleus Tractus Solitarius (NTS)
Where does the NTS receive signals from?
Glossopharyngeal (CN IX), Vagus (CN X), and sensory area
What does the Rostral Ventrolateral Medulla (RVM) do?
Direct acting: impulse triggers NT release, acts on nerves, acts on vessels
What does the Caudal Ventrolateral Medulla (CVM) do?
Fibers project upward to vasoconstrictor area (RVM) - inhibit vasoconstrictor activity causing vasodilation indirectly (modulator)
Where is the Nucleus Tractus Solitarius (NTS) located?
In the posterolateral area of medulla and lower pons
Blood vessel tone caused by sympathetic vascular tone is caused by how many impulses per second?
0.5 - 2 impulses / second
What areas of the brain also send signals to the Vasomotor Center?
Reticular activating system and the anterior and posterior portions of the Hypothalamus
What does the Lateral portion of the Vasomotor Center do?
Controls excitatory impulse transmission to the heart when in-trophy & chronotropy are needed
What does the Medial portion of the Vasomotor Center do?
Sends signals to dorsal motor nuclei of vagus nerve, transmitting parasympathetic impulses via vagus nerves to the heart when a decrease in heart rate and contractility is needed
What effect does epinephrine have?
On some tissues Epi causes vasodilation by stimulation of Beta receptors. Vascular effects of epilepsy depend on dosage and location as vasoconstriction (mediated by Alpha1 receptors) and vasodilation (mediated by Beta2 receptors) are both possible. Vasoconstriction predominates in the skin and kidneys whereas vasodilation predominates in the liver and skeletal muscle
What are the big 3 involved in rapid control of BP?
~ Arterioles constrict
~ Veins constrict
~ Direct stimulation of heart by SNS (cardiac pumping enhanced)
What is the “Baroreceptor reflex”?
Rise in BP causes stretch of baroreceptor which sends signals to vasomotor center, ANS feedback to reduce arterial BP to normal
Where are the baroreceptors primarily located?
In almost every larger artery in the neck and thorax (extremely abundant) but the extremely important ones are located at the bifurcation of the Carotids (AKA carotid sinus) and in the wall of the aortic arch
Physical characteristics of Baroreceptors:
~ Spray-like nerve ending
~ Mechanoreceptors, myelinated
Chemoreceptors located near the baroreceptors at the carotids are called the:
Carotid Bodies (baroreceptors here are called carotid sinus)
Carotid sinus (baroreceptors) send signals through what nerve pathway?
Hering’s nerves to Glossopharyngeal nerve to Nucleus Tractus Solitarius (NTS)
Aortic arch baroreceptor send signals through what nerve pathway?
Vagus nerves to Nucleus Tractus Solitarius (NTS)
Carotid sinus Baroreceptors are stimulated only if pressures rise above:
50-60 mmHg. As pressures rise, the more rapid the response to a max of 180-200 mmHg
Aortic Baroreceptors are stimulated only if pressures rise:
30 mmHg above carotid barroreceptors
Long term blood pressure control is generally more controlled by what?
The kidneys
What does Angiotensin II do?
1: Increases sympathetic activity
2: Increases tubular NA+ and Cl- reabsorption K+ excretion and H2O retention
3: Stimulates secretion of ADH form the posterior pituitary
4: Direct Arteriolar vasoconstriction
5: Stimulates the adrenal cortex to secrete Aldosterone
What do ACE Inhibitors do?
Prevent conversion of Angiotensin I to Angiotensin II by blocking Angiotensin converting enzyme
What 3 major “legs” of BP maintenance control blood pressure?
~ SNS input
~ RAS
~ Vasopressin system
What are Chemoreceptors sensitive to?
Lack of O2, CO2 excess, and H+ excess
Chemoreceptor location and physical characteristics
~ 2mm in size
~ 2 carotid bodies (1 in each bifurcation of the carotid arteries)
~ 1 - 3 aortic bodies (adjacent to the aorta)
Chemoreceptor pathway
Excite nerve fibers that pass through Hering’s nerve & the vagus nerves into the VMC (like the baroreceptors)
Why are chemoreceptors supplied by a nutrient artery?
So they always know what is going on with the blood composition / BP
What do chemoreceptors detect?
Reduction in O2 and buildup of CO2 & H+ (metabolic waste)
What happens to BP with chemoreceptor stimulation and what is the threshold for stimulation?
Not a powerful regulator of BP, pressures need to fall below 80mmHg but when they do they stimulate the vasomotor center (VMC)
What happens when Atrial Stretch receptors are stretched?
~ Stretch in Atria = Reflex dilation of afferent arterioles - glomerular capillary pressure rises (more fluid through kidneys)
~ Release of ANP
~ Decreases blood volume
~ Increases HR
~ Decrease ADH
What does the Bainbridge Reflex do?
~ Stretch in Atria = Increase in HR (sometimes as much as 75%)
What is the % increase in HR from SA node stretch and % from Bainbridge reflex?
~ SA node stretch alone increases HR 15%
~ in conjunction with Bainbridge reflex (40-60%)
(total increase up to 75%)
What is the Bainbridge Reflex?
A nervous reflex initiated by RA stretch
Baroreceptor reflex triggers _____ in HR while the Bainbridge reflex triggers a _____ in HR
Barorectptor = decrease
Bainbridge = increase
Cushing Reflex:
A stimulus causes increased ICP which causes CSF pressure to rise (brain in a box) once BP > CSF pressure - blood supply returns to the brain
What is the Valsalva Maneuver?
Forced pressure agains a closed glottis slows HR and drops SVR
What is the Oculocardiac Reflex?
Traction on eye muscles leads to increased PNS tone and subsequent bradycardia (think pediatrics)
What is the Bezold-Jarish Reflex?
Ventricular stimuli sensed by chemoreceptors and mechanoreceptors within LV wall induce the triad of hypotension, bradycardia, and vasodilation (think Pregnant women, spinal anesthesia, dehydration)
Respiratory waves in Arterial BP rise and fall
4 - 6 mmHg
During what portion of the respiratory cycle do Arterial BP rise and fall?
~ Early part of expiration - increase in Arterial BP
~ During the rest of the respiratory cycle - decrees in Arterial BP
What 4 factors directly affect CO
1: Body metabolism
2: Rest vs. exercise
3: Age (increasing age likely means a reduction in muscle has & body activity)
4: Body size
CO increases in proportion to:
Surface area
Cardiac Index =
CO per square meter of BSA
Increasing XI is likely due to:
declining mass and/or activity level provided CO stays the same
Venous return is the primary controller of CO, why?
Frank Starling’s - heart automatically pumps whatever amount of blood flows to the RA
CO =
The sum of peripheral blood flow
Decreased CO caused by what cardiac factors:
~ CA blockage
~ Valvular disease
~ Myocarditis
~ Cardiac Tamponade
Decreased CO caused by what non cardiac peripheral factors?
~ Decreased BV
~ Acute venous dilation
~ Venous obstruction
~ Nutrient or O2 demands of tissue decrease (ie. bedrest) reduced metabolic rate = reduced tissue blood flow and CO
Decreased CO = Shock. If this is directly related to cardiac causes it is called:
Cariogenic Shock (MI, Severe valve dysfunction, Arrhythmias)
Decreased CO = Shock. If this is related to decreased venous return what can be the cause?
~ Diminished blood volume
~ Obstruction to blood flow
~ Decreased vascular tone (pooling)
What happens when CVP falls to -1 mmHg?
Veins entering thorax collapse. Negative pressure in RA suck walls of veins together preventing blood flow from periphery to the heart (venous return stops)
Coronary venous blood flow from LV muscle to RA equates for what percentage of total coronary blood flow?
75%
What are Thebesian veins?
Coronary venous blood flows back from the heart into all chambers
What is resting Coronary blood flow?
70mL / min / 100g
225mL / min
4 - 5% of CO
