Flashcards in Lecture 19 - Local Regulatory Mechanisms Deck (54):
What is the term for vessels that control blood FLOW? What are the 4 vessels?
3. Pre-Capillary Sphincters
4. Venous RESISTANCE
What structure in a vessel controls/determines the total peripheral resistance, arterial & venous tone, and blood FLOW throughout the body?
Vascular Smooth Muscle
Resistance and thus FLOW, is constant from organ to organ, the same mechanism is employed for every organ. True or False?
- resistance varies from organ to organ, and multiple mechanisms are responsible
1. Neural & Hromonal - GLOBAL
What is the term for the intrinsic property of an organ to maintain constant blood flow, regardless of changes to arterial or percussion pressure? Does this change with gravity?
- constant flow despite any changes in Gravity
What is the equation for flow?
Flow = change in Pressure / Resistance
Following an abrupt increase in arterial pressure, what happens to blood flow? Does this change stay constant? How is flow changed?
1. Initial INCREASE in flow followed by a gradual decline to baseline
- decrease in flow due to an INCREASE in resistance due to AUTOREGULATIOn
What happens to flow as arterial pressure increases and thus arterial RESISTANCE? Why does this occur?
FLOW STAYS CONSTANT!!
- due to AUTOREGULATION
When does auto regulation fail?
- very HIGH or very LOW pressures
What are the two primary mechanisms of auto regulation ?1
1. Myogenic Hypothesis
2. Metabolic Hypothesis
What is the Myogenic Hypothesis? What changes occur to resistance and flow upon an INCREASE or DECREASE in PRESSURE?
1. smooth muscle contracts in response to stretch (relaxes when stretch is reduced)
2. Increase in pressure = initial stretch of the vessel wall which causes smooth muscle to CONTRACT (vasoconstrictor)
= increase in resistance, reduction in flow
3. DECREASE in pressure = reduction in stretch
- smooth muscle RELAXES (vasodilation)
-decrease resistance, increase in FLOW
What is the metabolic hypothesis of Autoregulation? What occurs when pressure is increased and decreased?
1. Metabolic activity makes substances for VASODILATION ( adenosine, K+, H+)
2. When pressure increases: brief increase in FLOW so metabolites are removed and resistance vessels CONSTRICT
- increase in resistance, decrease in flow
3. Pressure DECREASES: less blood flow so metabolites ACCUMULATE and cause vasodilation!!
- dilation decreases resistance and INCREASES flow
What substances cause metabolic vasodilation? What determines their concentration in the body?
Adenosine, K+, H+
- BLOOD FLOW determines the concentration in the microvascular beds
Since auto regulation varies from organ to organ, which areas have:
1. Strong Autoregulation
1. Strong: heart, brain, kidney, skeletal muscle
2. Weak: Splanchnic
3. Little: skin, lungs
What happens to the diameter of an arteriole when transmural pressure INCREASES & flow is held constant?
What is this an example of? Is this endothelium dependent?
1. Diameter DECREASES (constricts)
2. example of AUTOREGULATION
3. NOT DEPENDENT ON ENDOTHELIUM!!!
When the pressure gradient (flow) through an arteriole is INCREASED (transmural pressure held constant), how does the diameter change? Is this Endothelium Dependent?
1. diameter is INCREASED (dilates)
2. YES dependent on endothelium; no dilation when the endothelium is removed
What is released in response to shear stress due to the increase in flow through a vessel? What changes occur to the FLOW? When does this occur, typically? (example)
EDRF (endothelium derived release factor) & NO
- increase in blood flow directly releases endothelial mediated vasodilators to increase flow EVEN MORE
- occurs during EXERCISE!
Are the following vasodilators or a vasoconstrictors?
Where is metabolic regulation most important? When is a SITUATION that metabolic activity is stimulated?
1. Skeletal muscle, Cardiac, Brain
2. Decrease in oxygen delivery to a tissue can stimulate the formation of METABOLITES that are vasodilators
What is ACTIVE hyperemia? What factors are responsible for this type of response? (3)
1. Increased blood flow caused by enhanced tissue activity
2. K+, inorganic Phosphate, and interstitial Osmolarity
What is Reactive/PASSIVE hyperemia? What kind of debt increases flow?
1. Transient increase of blood flow that follows a brief arterial occlusion
2. METABOLIC debt increases blood flow
What occurs to the blood flow following an occlusion? What type of hyperemia is this? If the occlusion is longer in duration, how does the response change?
1. Blood flow INCREASES following the period of occlusion
2. REACTIVE Hyperemia
3. Longer occlusion duration = GREATER RESPONSE (intuitive) - want to increase flow!
What can occur to small vessels & thus FLOW with an increase in tissue pressure?
Mechanical tissue pressure can COMPRESS small vessels and alter flow
What are 3 possible causes of Mechanical (Tissue) Pressure?
1. Muscle Contraction (heart, skeletal)
2. Alveolar Pressure (lungs)
3. Tumors (venous obstruction)
What are the 2 main factors affecting Total Peripheral Resistance?
1. Arteriolar Radius
2. Blood viscosity
What are the 3 types of extrinsic control of Arteriolar Radius? Intrinsic control?
1. baroreceptor Reflex
2. Hormonal effects (angiotensin, epinephrine)
3. Sympathetic Activity
1. Metabolic changes
(02, CO2, metabolites)
3. Myogenic response
Regulation of blood flow is primarily determined by what resistance vessel, specifically?
- these have little affect on capillary hydrostatic pressure because of the significant resistance they provide
Mechanical effects like compression via skeletal muscle has a larger affect on veins or arteries? Why?
1. larger affect on VEINS
2. Lower pressure than arteries/ AUTOREGULATION of arteries
What is the mechanism of E-C couple in vascular smooth muscle? (5 steps)
1. increased intracellular calcium binds calmodulin
2. activates myosin light chain kinase (MLCK).
3. MLCK phosphorylates the regulatory light chains of the myosin heads. (MLC)
4. Phosphorylated myosin heads are able to cross bridge-cycle
5. Myosin light chain phosphatase removes the phosphate groups from the myosin heads = relaxation
(and leaving the muscle in latch-state).
Auto regulation regulates pressure. True or False?
Regulates FLOW due to result in changes in pressure (standing up/gravity)
Auto regulation can only be applied to what type of conditions?
RESTING STATE CONDITIONS ONLY!
ex: during exercise, auto regulation is OVERCOME by local metabolic control
Flow increases when what is increased? How is it decreased after an abrupt change?
- increase in RESISTANCE causes flow to decrease
Why does arterial pressure not influence capillary hydrostatic pressure?
AUTO REGULATION of arteries
- instead venous system controls the capillary hydrostatic pressure
What occurs to auto regulation at high or low pressures? What is the flow at these pressures?
1. autoregulation no longer functions!
2. At high pressure = increased FLOW (resistance not increasing)
3. At low Pressure = decrease flow
(resistance not decreasing)
What are the 2 mechanisms involved in AUTOREGULATION?
The following muscles are under what type of auto regulatory control? (strong, weak, little)
- want to maintain constant flow to have constant urine output
2. STRONG - but overcome during exercise since no longer under resting conditions
3.Lungs = LITTLE AUTOREGULATION
-you do not want lungs to constrict when cardiac output is increasing
4. Splanchinc = WEAK
5. Skin = LITTLE
- it relies strictly on TEMP!
What is not involved in auto regulation?
When transmural pressure (static) is increased, does diameter increase or decrease? Is flow changing? What is this an example of?
1. DECREASE diameter = constrict
2. Flow is constant
With an increase in the pressure GRADIENT (thus increase in flow) what happens to a vessel? What is this called? This is due to the creation of what?
1. VASODILATION with increased flow
2. Endothelium-Mediated Regulation
- sensed by EDRF
3. SHEAR STRESS
- releases EDRF
During exercise, if you increase blood flow by vasodilation, what is the mediating factor? This is due to what on the endothelial wall?
2. SHEAR STRESS on endothelium causes release of EDRF & results in more dilation
When you increase oxygen consumption in the heart by increasing HR, Preload, and contractility, what happens to the coronaries? Is this an example of active or reactive hyperemia?
= ACTIVE HYPEREMIA
What is the area of the heart most prone to ischemia? Why? Under what conditions does this occur?
2. coronaries get smaller as they reach endocardium so during SYSTOLE there is a large mechanical force that squeezes vessels
3. bad under TREMENDOUS AFTERLOAD
- increased end-systolic pressure = blood flow to endocardial surface CUT OFF because these small arteries are squeezed shut
What does expanding the lungs do to the blood flow? What is this called? What are the first vessels to be compressed with an obstruction (tumor)?
1. DECREASES blood flow due to increased alveolar pressure
2. MECHANICAL (tissue) Pressure
3. VEINS - have low pressure
- thus venous return is LOW when they are compressed due to a tumor
What is SHOCK? What is a common point that results from shock?
- when cardiovascular system is unable to supply enough blood flow to the body = inadequate tissue perfusion
- LOW BLOOD VOLUME/PRESSURE
Describe the following:
1. Cardiogenic Shock
2. Causes of this (2)
heart muscle damaged (severe MI) and not able to pump blood to meet needs of body
1. Ventricular Tachycardia or Bradycardia caused by complete heart block
2. Cardiac temponade (pericardium filled with blood/fluid and ventricles cannot fully expand & fill with blood)
Describe the following:
1. Hypovolemic Shock
2. Causes of this (4)
1. blood loss/inadequate blood volume so heart cannot supply enough blood to body
- 10-20% loss results in clinical symptoms
3. burns - increase capillary permeability = cannot maintain BP
Describe the following:
1. Anaphylactic Shock
2. Causes of this (4)
Severe allergic reaction
- death results from obstruction to breathing or extremely low blood pressure
(vasodilates al vessels so diastolic pressure DROPS OUT)
3. Insect stings
Describe septic shock
Inflammatory (immune response) that results from a severe infection & sepsis
- causes MASSIVE VASODILATION
- increased capillary permeability
- decreased systemic vascular resistance
Extreme vasodilation causes what to drop out?
What is neurogenic shock? What is this usually caused by?
1. Disruption of signals that maintain autonomic nervous system control over vasoconstriciton
- result = HYPOTENSION
2. Acute spinal cord injury that blocks sympathetic activity
What are the 7 ways to cause VASOCONSTRICTION? What is the common mechanism among all of these?
1. Voltage Gated Ca channels open
2. Voltage gated Na channels open
3. Stretch-Activated (SA) non-selevtice cation channels open
4. Receptor-operated Calcium Channels (ROCS) (agonist = adenosine)
5. Adrenergic Receptors
- NE opens ROC (via ALPHA receptor)
6. Endothelic Receptor
(Gq-- IP3 = increased calcium)
7. Na-Ca exchanged slowed
- via depolarization and entry of Na into cell, which slows Na/Ca and leaves more Ca in cell
- increased Calcium influx!
What are 10 Vasodilating mechanisms?
1. Voltage gated K channels open (hyperpol = Ca channels close)
2. Ca-dependent K channels (close voltage gated Ca channels upon hyper polarization)
3. ATP sensistive K channels
- decrease ATP K atop opens = hyperpolarization
4. NO receptor
- phosporylation of MLCK results in decreased phosphorylation of MLC and activation of CA-ATPase pump
5. Adrenergic Receptor
(B2 on smooth)
- decreases phosphorylation of MLC
6. Prostacyclin (PGI2)
- decreases phosphorylation of MLC
7. Histaming receptor H2
- decrease MLC phosphorylation
8. Purigenic Receptor/Adenosine
- decrease Calcium
- increases NOS NO release
9. SERCA pump
- decreases Na in = activates the Na/Ca exchange which decrease Calcium
Which adrenergic receptor(s) cause vasoconstriction? Vasodilation?
1. ALPHA 1 receptor
2. BETA 2 on smooth muscle= vasodilation
(beta 1 & 2 on CARDIAC muscle both increase HR and contractility)
What are the two ways Purigenic Receptors (ADENOSINE) cause vasodilation?
How does Na/K cause vasodilation?
1. hyperpolarization via KATP channels closes voltage-gated Ca channels
2. ATP - activates Gq --> increase PLC --> increase Ca in = NOS NO release
3. Na/K causes less Na in which activates the Na/Ca exchanger and causes an efflux of CA