cardiac work, metabolism and CV loads

Question 1

name the layers of blood vessels

Answer 1

tunica intima

tunica media

tunica adventitia

Question 2

how to calculate blood flow

Answer 2

blood flow (F) is directly proportional to pressure gradient between beginning / end of vessel (change in pressure = P1 - P2)

F is inversely proportional to resistance blood meets in vessel (R)

therefore F = change in pressure/R

R is directly proportional to viscosity of blood + length of vessel

R is inversely proportional to radius of vessel ^4

therefore R = (viscosity x length)/ r^4

Question 3

what affects blood viscosity

Answer 3

-hematocrit (% of blood by volume of RBC’s in blood)
5x viscosity of water
directly proportional
increased hematocrit, increases viscosity, increases R, decreases F

• conc. of plasma proteins
  1.5x viscosity of water

Question 4

what are the factors affecting blood flow

Answer 4

blood viscosity

diameter of vessel

Question 5

what are the effects of diameter of blood vessel on blood flow

Answer 5

directly proportional to F
indirectly proportional to R

changes in blood vessel diameter may be physiological (diverting blood to match metabolic needs) or pathological (atherosclerosis)

Question 6

what are the types of blood flow

Answer 6

streamline (laminar) flow - when all particles in fluid flow parallel to wall of vessel, don’t move at same velocity where particles at center flow fastest and further away from center move slower, helps eliminate energy loss

turbulent flow - any disruptions to laminar flow caused by changes in velocity

mean linear velocity = flow/ cross sectional area
velocity is indirectly proportional to cross sectional area
therefore velocity of blood flows is highest in arteries / lowest in capillaries

Question 7

what are the aims of changes in blood flow

Answer 7

increasing blood supply to active tissues

controlling heat loss

maintaining blood flow to vital organs

Question 8

how to achieve changes in blood flow

Answer 8

changing CO (directly proportional)

changing diameter of blood vessels (especially arterioles which control F to tissues locally)
VC = increased R / decreased F
VD = decreased R / increased F

Question 9

what is the molecular mechanism of vascular SM contraction/ vasoconstrictors

Answer 9

stretch caused by blood pressure opens ion channels which leads to a partial depolarization and partial contraction of SM

bayliss effect- vascular SM responds to stretch by contracting

physiological mediators can cause increased/decreased contraction as appropriate

Question 10

local regulation of blood flow can be achieved by

Answer 10

secretion of vasoactive agents by endothelial cells/platelets

metabolite control of local blood flow (pre capillary sphincter of arterioles, which are the main site of peripheral resistance, is regulated by local metabolite conc. which controls blood flow)/ auto regulation

local hormones / autocoids

Question 11

examples of endothelial/ platelet mediated vasodilators

Answer 11

NO / endothelium derived relaxing factor (EDRF)

endothelium derived hyperpolarizing factor (EDHF)

prostacyclin (PGI2)

Question 12

examples of endothelial/ platelet mediated vasoconstrictors

Answer 12

tromboxane A2 / TxA2

prostaglandin H2 / PGH2

endothelins (1/2/3)

Question 13

describe the effects of NO on blood vessels

Answer 13

short half life of a few seconds

must be generated continuously (triggered by increased stress on vessel wall by increased blood velocity)

causes short term changes in blood vessel diameter

main site of action is large diameter arterioles

Question 14

what are the effects of vasodilator drugs (nitrovasodilators) on the heart

Answer 14

on capacitance vessels, decrease VR therefore decreasing preload

on resistance vessels, decrease ABP therefore decreasing afterload

both these effects decrease cardiac metabolism + oxygen demand and may relief coronary spasm

Question 15

describe the effects endothelins and prostaglandins on blood vessels

Answer 15

ET-1 is the most potent and causes very strong vasoconstriction (mainly in veins)

platelets release tromboxane A2 causing vasoconstriction + increased platelet aggregation

endothelium releases prostacyclin (PGI2) causing vasodilation + decreased platelet aggregation

balance between thromboxane and prostacyclin maintains localized blood clots, preventing excessive extension which maintains blood flow

Question 16

define auto regulation of local blood flow

Answer 16

adjusting blood flow to tissues based on their metabolic activities so that blood flow remains constant in spite of any changes to ABP

Question 17

what are the mechanisms of autoregulation of blood flow

Answer 17

myogenic autoregulation - bayliss effect/intrinsic contractile response of vascular SM to stretch, increased ABP increases blood flow initially but also causes stretch of wall of arterioles which results in contraction of SM leading to VC + decreased blood flow back to normal

metabolic autoregulation - increased tissue metabolism results in relaxation of arterioles + precapillary sphincters leading to increased local blood flow + vice versa

Question 18

what is the mechanism of metabolic autoregulation

Answer 18

increased tissue metabolism leads to

• accumulation of vasodilator metabolites:
• CO2/ H+/ K+/ lactic acid in skeletal muscle/ adenosine in muscle/ histamine in injured tissue
• increased H+ conc. opens ATP-sensitive K+ channels on SM causing hyperpolarisation and relaxation/VD which increases blood flow
• decreased oxygen/ hypoxia + decrease in other nutrients needed to maintain vascular SM contraction
• hypoxia leads to opening of ATP sensitive K+ channels causing VD
• release of vasodilator PGs
• (except in pulmonary circulation where hypoxia causes constriction of pulmonary vessels

Question 19

what are the mechanisms of systemic regulation of blood flow

Answer 19

occurs mainly in arterioles

hormonal/ humoral regulation
nervous control

Question 20

what hormones are involved in the hormonal control of regulation of blood flow

Answer 20

local hormones/autocoids (mainly part of pathological events)
- histamine (VD)
- bradykinin (indirect VD)
- serotonin/ 5-HT (VC)
- endothelium derived mediators (NO/ PGI2 - prostacyclin/ endothelins)

systemic hormones
- renin angiotensin system
- ADH (vasopressor)
- adrenal medulla catecholamines
- ANP

Question 21

what are the effects of the local hormone histamine

Answer 21

synthesized and stored in mast cells/ basophils/ skin/ lung/ gut

action is mediated via receptors H-1/2/3

H1 - mediates vascular actions, inflammatory response to trauma/ allergy
- increases capillary permeability in edema
- in severe conditions, leads to arterioles/ capillary dilation which reduces circulating volume (hypovolemia), causes hypotension and anaphylactic shock

H2 - controls gastric acid secretion

H3 - acts as a neurotransmitter in nervous system

Question 22

what are the effects of the local hormone bradykinin

Answer 22

generated during inflammatory response

binds to endothelial cell receptors, increases production of NO (VD) therefore lowering BP

increases capillary permeability + attracts leukocytes

dilation of arterioles

increase in venule permeability

increases blood flow to actively secreting glands (sweat/ salivary/ exocrine pancreas)

most potential autocoid/ local hormone in pain responses

*inactivated by angiotensin converting enzyme (ACE)

Question 23

what are the effects of the local hormone serotonin

Answer 23

contributes to inflammatory response

VC of large arteries/ veins

increased permeability of venules

platelet released 5-HT causes local VC, limits blood loss at site of injury

5-HT released from argentaffin cells in intestine contribute to (local) regulation of blood flow

5-HT in cerebral circulation, induces arterial vasospasm (vessel narrows, blocking blood flow), associated with onset of migraines + response to subarachnoid hemorrhage

Question 24

what are the effects of the systemic renin-angiotensin system

Answer 24

renin hormone is secreted by the kidney if
- ABP falls/ hypotension
- ECF volume is decreased/ hypovolemia

renin splits plasma angiotensinogen releasing AgI (inert) + AgII, catalyzed by angiotensin-converting enzyme/ ACE

ACE is bound to endothelial cells

angiotensinases rapidly inactivates AgII in blood

AgII, potent VC, released when ABP falls very low, acts on AT1 receptor

actions of AT1 receptor include:
- direct pressor/ VC via receptors on vascular SM
- indirect pressor/ VC effect by promoting formation of endothelial VC’s (ET-1 / TxA2)
- potential ion of sympathetic NS activity
- stimulates aldosterone synthesis in adrenal cortex (increases Na + water reabsorption from kidney which increases blood volume)
- increases ADH secretion from posterior pituitary gland, inducing thirst response/ dispogenic action (drink more, increase blood volume)

Question 25

what are the effects of the systemic hormone ADH

Answer 25

potent VC, on systemic + peripheral arteries

reduces urine formation by kidney (more water is reabsorbed therefore decreasing volume of urine)

formed in hypothalamus, stored in posterior pituitary gland

released into circulation when:
- osmotic pressure of blood is increased (dehydration/ high salt intake)
- reduced stimulation of atrial B receptors (discharge during atrial diastole) (hypovolemia)

Question 26

what are the effects of the systemic adrenal medullary hormones

Answer 26

noradrenaline has more significant effect on circulatory function than adrenaline (VC)

stimulation of B1 receptors in heart = +inotropic (force of contraction) / +chronotropic effect (rate of contraction)

stimulation of a1 receptors in blood vessels = VC

stimulation of a2 receptors in peripheral circulation = VC

stimulation of B1/B2 receptors in blood vessels = VD

Question 27

what are the effects of the systemic hormone ANP

Answer 27

when ECF volume increases, VR increases causing stretch of atrial stretch receptors, ANP gets released

ANP regulates blood volume/ pressure

potent diuretic (increased water in urine) + natriuretic (increased Na in urine) effect on kidney = decreased circulatory volume

dilates resistance (decreases ABP) + capacitance (decreases VR) blood vessels

Question 28

how does the ANS control peripheral circulation

Answer 28

SNS
- VC mediated by a1 receptors (found mainly in peripheral blood vessels)
- skeletal muscle/ coronary blood vessels have some B1/B2 receptors that can cause VD when stimulated

PNS
- no parasympathetic nerve supply to most of peripheral circulation
- PNS activation = VD + erection in genitalia
- VD in pancreas/ salivary glands, increases secretions (rest and digest)

Question 29

what are the secondary causes of HT

Answer 29

renal disease (increased activity of RAAS)

pheochromocytoma (increase catecholamines secretion)

conn’s syndrome (increases adrenal cortex aldosterone secretion)

Question 30

what are the 2 types of atherosclerosis and the differences between them

Answer 30

hyaline atherosclerosis - associated with benign HT, lesion is caused by leakage of plasma components into vessel wall
appearance = homogenous pink material + increased ECM production by SM

hyperplasticity atherosclerosis - associated w/ malignant atherosclerosis, fibrinoid deposits, necrotising arteriolitis
appearance = concentric laminations of SM + reduplicated basement membrane

Question 31

what are the other vascular disorders associated with HT

Answer 31

aortic dissection
subarachnoid hemorrhage
intracerebral hemorrhage