Lecture 15: CV Control through Regulation of Systemic Vascular Resistance and Flow Distribution

Question 1

What is the regulation of the circulation like?

Answer 1

It’s like the federal government
Individual organ vascular beds are each looking out for their own local requirements
(like senators look out for their constituents)

Question 2

What is the difference between ischemia and hyperemia?

Answer 2

Ischemia = too little blood
Hyperemia = excessive blood flow

Question 3

What are the Wood units?

Answer 3

Wood unit = mmHgmin/L = dyness*cm^-5

Question 4

What is the role of vascular resistance?

Answer 4

Regulation of vascular resistance controls circulation (as it relates CO)
Macro vs. micro regulation (interlinked with one another)

Question 5

What are the characteristics of the macro regulation of vascular resistance?

Answer 5

Global regulation of entire circulation

Ex: Systemic arterial pressure, Cardiac output

Question 6

What is considered microregulation of vascular resistance?

Answer 6

Regulation at individual organ and tissue perfusion

Won’t work properly at micro level if macro is not working

Question 7

Where is vascular resistance controlled?

Answer 7

At the level of the systemic arteriole

Specifically the diameter of the arteriole

Question 8

What is a kind of healthy hyperemia?

Answer 8

Vasodilation when you are running during a hot day

Question 9

What is the significance of Poiseuille’s law?

Answer 9

Pressure is inversely related to radius^4

Reducing the radius by just a little bit increases P by a lot

Question 10

What are metarterioles?

Answer 10

Connections directly from arterioles to venules
This can be pathologic (if blood is going through here
Instead of the capillaries)

Question 11

What are the effectors in the arterioles?

Answer 11

Vascular smooth muscle cells

Question 12

What are the characteristics of the vascular smooth muscle cells?

Answer 12

Spindle-shaped
Arranged in circular or helical bundles
Tone regulates arteriolar diameter
Can maintain tone chronically with minimal energy expenditure
In direct contact with endothelium (no elastic lumina)
Gap junctions connect adjacent cells
Are in DIRECT contact with endothelium (unlike in larger arteries in veins)

Question 13

How does vascular smooth muscle maintain their tone?

Answer 13

They do not regularly cycle between systole and diastole (like striated muscle)
Controlled by cytosolic Ca concentration
Calcium concentration is affected by rate of entry of calcium ions into cell through receptor operated and voltage operated channels
Majority of calcium influx is through receptor operated channels

Question 14

What are the two types of control vascular SMC are under?

Answer 14

1. intrinsic control (control by tissue’s local requirements)
2. extrinsic control (control by neural and circulating mediator influences governed by circulations overall requirements)

Question 15

What is the significance of having a higher actin:myosin ratio in smooth muscles?

Answer 15

Allows myosin thick filaments to change the actin filaments with which they form cross bridges at different degrees of distension for the SMC
Allows for greater degrees of contraction
Allows for maintenance of maximal contractile force at varying cell lengths (plasticity of the force/length relationship)

Question 16

What are variables that can increase SMC cytosolic Ca?

Answer 16

1. angiotensin II
2. serotonin
3. endothelin
4. CO2, K+, H+
5. bradykinin, NO, etc.

Question 17

How do receptors change among SMC location?

Answer 17

SMCs in different vascular beds have different surface receptors that may evoke different responses to the same agonists

Question 18

What are the types of intrinsic vascular SMC control?

Answer 18

1. Myogenic autoregulation
2. endothelium mediated autoregulation
3. metabolic mediated autoregulation

Question 19

What are the characteristics of myogenic autoregulation?

Answer 19

Increased arterial inflow pressure = increased SMC tone
Mechanism = stretched activated Ca channels
Major player in renal vascular bed regulation

Question 20

What are the characteristics of endothelium mediated autoregulation?

Answer 20

Increeased endothelial shear stress = NO release = DECREASE SMC tone
Mechanism = endothelial cell surface receptors
Operates primarily in distributing arteries rather than in the resistance vessels

Question 21

What are the characteristics of the metabolic mediated autoregulation?

Answer 21

Increased tissue metabolic activity = decreased SMC tone
Mediator = adenosine
Example: reactive hyperemia

Question 22

What controls the extrinsic VSMC control?

Answer 22

Mediated predominately by the adrenergic nervous system and by the RAAS system
Orchestrated by medulla
Regulates arterial pressure and orchestrates stress response
Effectors:
i. systemic arterioles
ii. systemic veins

Question 23

What are the types of extrinsic VSMC control?

Answer 23

1. coronary and cerebral = little responsiveness (mostly under autoregulatory control)
2. renal, mesenteric, cutaneous = vasoconstriction (abundant extrinsic activity)
3. Skeletal muscle = vasodilation (abundant extrinsic activity)
4. Skin = vasodilation under withdrawal of adrenergic tone and addition of bradykinin

Question 24

Are the different points of resistance in the CV system

In series or in parallel? Significance?

Answer 24

In parallel
Increasing resistance of any individual vascular bed
Increases the total resistance and shunts blood flow away from that bed, preferentially distributing it to the vascular beds whose resistance did not increase

Question 25

What are the two purposes that extrinsic manipulation of local vascular resistance can achieve?

Answer 25

1. alteration of total systemic vascular resistance
   
   • used to regulate systemic arterial pressure to the desired value
2. Repartitioning of CO among vascular beds
   
   • used to preferentially increase blood flow to a vascular bed that requires increased flow (mesenteric or skeletal) or to divert flow from a bed that can get along without it for a period (renal, cutaneous) to somewhere it is needed (skeletal muscle)

Question 26

What happens when the regulation of vascular resistance goes awry?

Answer 26

1. Hypertension
2. Congestive Heart failure
3. Sepsis

Question 27

How is regulation of vascular resistance pathologic in HTN?

Answer 27

Disease process perturbs regulation of SVR, causing it to be set at abnormally highlevel
Leads to pathologically sustained elevation of systemic arterial pressure

Question 28

How is regulation of vascular resistance pathologic in CHF?

Answer 28

Increased afterload to an already poorly functioning heart

Further impairs ejection and CO

Question 29

How is regulation of vascular resistance pathologic in sepsis?

Answer 29

Loss of normal vascular resistance regulation mediated by circulating cytokines
Inappropriate opening of metarterioles allowing blood to bypass capillaries (from arterioles to venules)
Leads to low systemic arterial pressure in setting of increased CO
Causes tissue ischemia in setting of increased blood flow

Question 30

What happens in CO shock?

Answer 30

Decrease CO, decrease systemic arterial pressure
Need to increase systemic vascular resitance to restore systemic arterial pressure
-done through vasoconstriction of renal, cutaneous and GI
Thus renal dysfunction is the first thing you see (low urine output)
Restoration of pressure at price of renal and hepatic dysfunction

Question 31

When you are managing a patient in shock, after restoring systemic arterial pressure, what is the next question you ask?

Answer 31

How much urine is the patient making?
Renal dysfunction would be the first to show
Increasing urine output = shock patient doing better
Urine = great window of how the CV system is doing