Diz: Circulation And Bp Regulation

Front 1

SVR regulation

Back 1

Under normal physiologic conditions, SVR is regulated by changes in precapillary vessel (arterioles) diameter changes
Changes in vascular resistance are accomplished by either relaxing or further constricting these vessels
Vascular tone is regulated by both extrinsic (innervation and hormones) and intrinsic mechanisms (local factors) that may cause either vasoconstriction or vasodilation.

Front 2

Calculating SVR (TPR)

Back 2

SVR=(MAP-CVP)/CO

CVP=central venous pressure

Front 3

Resistance and flow

Back 3

Q=P/R

R=(viscosity*L)/r^4

Vessels in series (within an organ) increase resistance
-Resistance equal to sum of individual resistances

Vessels in parallel decrease vascular resistance
-Reciprocal of the sum of reciprocal of each segment (one over one over)

Front 4

Cross sectional area, flow, and volume

Back 4

Capillaries and venules have GREATEST CROSS SECTIONAL AREA, even though they contribute only a small amount to resistance and are associated with DECREASED VELOCITY of blood flow.

Majority of BLOOD VOLUME contained in the LOW PRESSURE systemic veins.

Arterial vessels are much stiffer than veins; veins are compliant and PROVIDE CAPACITANCE

Front 5

Neurohumoral reflexes

Back 5

Arterial: baroreflex
Cardiopulmonary: baroreflex
Chemoreceptor: reflex

These pathways play an important role in the rapid, short-term regulation of blood pressure and maintenance of volume homeostasis, integrating with emotional status

Front 6

Arterial baroreceptor

Back 6

Brainstem vasomotor center:
TPR
Cardiac performance
Sympathetic drive to kidney
Venous compliance

Front 7

Cardiopulmonary baroreceptor

Back 7

Brainstem vasomotor center:
-TPR
-Cardiac performance
-Sympathetic drive to kidney
-Venous compliance

Hypothalamus:
-ADH

Low pressure baroreceptors
Stretch receptors located in the heart and respond to atrial filling (stretch); increased volume leads to sympathetic activation
Increased blood volume and venous pressure activate other receptors that inhibit vasopressin release (causing diuresis)

Front 8

Intrarenal baroreceptors

Back 8

Renin-angiotensin system
GFR, salt and water reabsorption

Front 9

Reflex pathways in arterial baroreceptors

Back 9

Increase BP
Increase baroreceptor input
Decrease sympathetic nervous activation to heart and vessels
Increase parasympathetic nervous activation to heart

Decrease BP
Decrease baroreceptor firing
Medullary cardiovascular center
-Increase sympathetic
--Arteriolar tone
--Venous tone
--Cardiac contractility
--Heart rate
-Decrease parasympathetic
--HR

Front 10

Chemoreceptors

Back 10

Specialized cells that monitor oxygen, carbon dioxide and hydrogen ion; primary response is respiratory

Located both peripherally (arteries) and centrally (medulla)

Highest blood flow per gram tissue

Stimulated by CO2, pH, O2

Stimulated by blood flow through carotid and aortic bodies

Chemoreceptor afferents make first central synapse in NTS (solitary nucleus)

Stimulation of chemoreceptors in brain or periphery activates sympathetic nervous system

Front 11

Catecholamines

Back 11

Release by adrenal medulla in a ratio of 80% Epi and 20 % NE in response to stress

NE is also released by sympathetic nerve activation at the blood vessel

Stimulate renin release and subsequently Ang II and aldosterone

Front 12

Renin-Angiotensin-Aldosterone system

Back 12

Regulates:
-blood volume, SVR, blood pressure
-cardiac and vascular function
-neurohumoral effects modulates autonomic nervous system

Kidney is the most important site for the circulating RAS, but exists as an intrinsic system within most tissues and organs.

Renal Renin release stimulated by:
-Sympathetic stimulation
-Hypotension
-Decrease sodium delivery to distal tubule

Front 13

Angiotensin variables

Back 13

Ang II
Pro-hypertensive, vasoconstrictor,
Pro-growth and fibrosis, pro-inflammation
Attenuates Baroreceptor reflex

Ang (1-7)
Anti-hypertensive, vasodilator,
Anti-growth, reduces fibrosis, anti-inflammatory
Enhances baroreceptor reflex
Neprilysin converts Ang 1 to Ang (1-7) and converts Ang II to Ang (1-4)

Front 14

Vasopressin

Back 14

Released by the posterior pituitary
-Angiotensin II stimulation, hyperosmolarity, decreased atrial receptor firing, sympathetic stimulation
Stimulates thirst
Acts at kidneys to increase blood volume and constricts blood vessels
Important for long term blood pressure control

Front 15

Atrial natriuretic peptide

Back 15

Responsible for long-term sodium and water balance, blood volume and arterial pressure
Counter-balances the RAAS

Front 16

Local control of vascular tone

Back 16

Vessels under tonic partial constriction: "vascular tone"
-myogenic tone: generated by vascular smooth muscle that resists stretch

Calcium:
-important agent for constriction
-most vasoconstrictors work to increase Ca
--depolarization and contraction
--PLC to IP3 which causes sarcoplasmic reticulum to release Ca
-most vasodilators work to block calcium into cell or from intracellular stores
--hyperpolarization

Front 17

Tissue factors

Back 17

Originate in tissue around vessel, often as metabolic products
Can act as either constrictors or relaxants; may differ in different vascular beds (eg. Low oxygen is generally a vasodilator except in the pulmonary vasculature)
Examples: Carbon dioxide, H+, K+, lactate, adenosine
Paracrine factors: histamine, bradykinin, prostacyclin, leukotrienes

Front 18

Endothelial factors

Back 18

Can be endocrine, paracrine or autocrine
Physical factors (shear stress – releases NO)
May act via endothelial receptors or directly on smooth muscle
Examples: Nitric oxide, prostacyclin (dilators); endothelin, leukotrienes, thromboxanes (constrictors)

Front 19

Receptor dependent and independent vasodilators

Back 19

Cause release of NO

Sodium nitroprusside is NO donor (doesn't need NO synthase)
-direct cGMP effects

Front 20

Vasodilators, source, effectors

Back 20

Prostaglandins, PGI2
-Endothelial cells source
-VSM effector

Adenosine
-Parenchymal cells source
-VSM effectors

Epinephrine
-Adrenal medulla source
-Beta2R: VSM effectors

H,CO2, K
-Skeletal muscle source
-VSM effector

Decreased pO2
-Blood source
-unknown effector

EDHF
-EC source
-VSM, K channels effectors

Angiotensin (1-7), bradykinin, substance P
-Blood, local tissue source
-NO or PGs:VSM effectors

Front 21

Vasoconstrictors, source, effectors

Back 21

Angiotensin II
-Kidney, blood, local tissue source
-AT1R:VSM effector

Arginine vasopressin
-Posterior pituitary source
-V1R:VSM effector

NE, Epi
-Adrenal medulla source
-a1R: VSM

Endothelin
-EC source
-ET1R: VSM effector

Increased pO2
-Blood/tissue source
-unknown effector

Front 22

Vasodilator reserve

Back 22

the difference between basal and maximum flow
-kidney has low vasodilator reserve

Front 23

Autoregulation of blood flow

Back 23

The ability of an organ to maintain a constant blood flow despite changes in perfusion pressure. This occurs in the absence of neural and hormonal influences and is, therefore, intrinsic to the organ.
-Changes in resistance can autoregulate flow for a given pressure

Occurs over a wide range of perfusion pressures (60-70 mm Hg for maximal dilation and ~170 mmHg for maximal constriction)

Why?
If blood loss leads to generalized vasoconstriction, the brain, kidney and heart continue to require adequate blood delivery

Front 24

Active and reactive hyperemia

Back 24

Transient increase in local blood flow in response to metabolic need mediated by local metabolites

Increased metabolic activity
-active hyperemia

Brief period of hypoxia or ischemia
-reactive hyperemia

Front 25

Coronary circulation: reserve and perfusion

Back 25

Little oxygen extraction reserve; changes in oxygen demand must be met with changes in oxygen delivery
Large vasodilator reserve (80 ml/min/100g vs >400 ml/min/100g)
Highly regulated by tissue metabolism (esp ADO)
Innervated by both sympathetic and parasympathetic nerves; local metabolites can override nervous input
Pulsatile perfusion: diastolic flow in left ventricle

Front 26

Coronary circulation: extravascular compression

Back 26

Pressure generated by the myocardium effects coronary blood flow

Left ventricle (LCA)
-Flow is increased to Left Ventricle during Diastole

Right Ventricle (RCA)
Phasic changes not as prominent
-Flow follows Aortic pressure during systole; increased blood flow to RV during Systolic phase

Front 27

Cerebral circulation: overview

Back 27

Blood flow is tightly coupled to oxygen demand (metabolism or oxygen consumption)
This occurs regionally within the brain as well
Predominant control of cerebral circulation is determined by local factors (esp. carbon dioxide); heavily relies on autoregulation
However, adequate cerebral perfusion is also importantly determined by systemic arterial pressure, and hence regulation of blood flow to other organs

Front 28

Cerebral circulation: local control

Back 28

Cerebral blood flow is linearly related to arterial CO2 tension (PaCO2) over normal PaCO2 (40 mm Hg) ± 20 mm Hg.

Increased K+, increased H+ and increased adenosine promote cerebral vasodilation

Cerebral blood flow (CBF) is tightly linked to changes in neural activity.

Sites of epileptic seizures have exceedingly high CBF

Front 29

Skeletal muscle circulation

Back 29

Satisfy nutritional needs and remove waste

Because exercise substantially changes the metabolic demands of muscle, skeletal muscle exhibits the greatest range of blood flow of any regional circulation

Vascular anatomy is highly organized
-Capillaries run parallel to muscle fibers (3-4/fiber)
-During rest (low metabolic demand), only ~25% of capillaries are open
-Capillary recruitment helps satisfy metabolic demand

Physical factors impact flow – phasic or sustained contraction

Local myogenic tone and metabolites (ADO and K+) as well as hypoxia greatly influence blood flow (20-30 fold - vasodilator reserve)

Also influenced by innervation, but local factors may compete with this regulation

Front 30

Cutaneous circulation: overview

Back 30

Maintenance of a constant body temperature

Blood flow exceeds nutritive needs of this tissue

Regulation occurs predominantly through neural (hypothalamic) and physical factors.
Capacious venous plexes near the skin surface

Resistance vessels: arterioles and A-V anastomoses

Front 31

Cutaneous circulation: neural control

Back 31

Tonic sympathetic nerve vasoconstrictor outflow
-Low to no tone in thermo-neutral environment
-High vasoconstrictor tone in cold environment
-Raynaud’s Syndrome: Excessive sympathetic vasoconstriction to cold; may even lead to ischemia

Reflex effect of core temp on skin vascular resistance (CutVR)
-decrease Tcore: Increase vasoconstriction via SNA to cutaneous arterioles, increase CutVR
-Increase Tcore: decrease vasoconstriction via SNA to cutaneous arterioles, decrease CutVR
-Increase Tcore: increase SNA to sweat glands, increase vasodilation (Ach), decrease CutVR

Front 32

Splanchnic circulation: overview

Back 32

Absorption of water, electrolytes and nutrition

Receives ~20% of the CO and contains ~15% of the circulating blood volume.

Redistribution of blood flow and volume from splanchnic circulation is important to preserve flow to vital organs (heart and brain).

Venous outflow from GI tract collects in portal vein that supplies ~70% of BF to liver; hepatic artery provides remaining inflow (~30%); outflow by hepatic vein.

Front 33

Splanchnic circulation: neural control and excercise adjustments

Back 33

Sympathetic innervation of arterioles and veins

Neurally released NE acts at alpha1 adrenergic receptors on vascular smooth muscle.

High resting sympathetic vasocontrictor tone; denervation or alpha1 adrenergic blockade increases splanchnic blood flow by ~1.5 times.

Exercise decreases splanchnic blood flow:
-Redistribution of CO to exercising muscle; redistribution of blood flow to skin – dissipation of heat
-Increased sympathetic activity results in constriction of both arterial and venous resistance vessels leading to increased venous return

Front 34

Renal circulation: overview

Back 34

Excrete waste products and maintenance of salt and water balance

Kidneys receive ~20% of CO; very high blood flow per gram tissue (400 ml/min/100 gm)

Renal plasma flow ~1000 L/day; 170 L/day filtered into renal tubules; only 1.5 L/day excreted as urine

Kidney exhibits strong autoregulation: Blood flow and filtration are tightly coupled so that filtration occurs over a range of pressures
-Afferent arteriole is primary location of resistance regulation.
-Tubuloglomerular feedback: mechanism by which the macula densa senses osmolarity of fluid in distal collecting ducts and regulates filtration.

Front 35

Renal circulation: anatomy

Back 35

Two capillary segments arranged in series

Glomerular capillaries high pressure (~50 mm Hg) to drive filtration.
Peritubular capillaries (vasa recta) low pressure to facilitate reabsorption.

Renal artery branching:
-interlobular arteries,
-afferent arteriole
-glomerular capillaries
-efferent arteriole
-peritubular capillaries
-veins

Changes in afferent and efferent arteriole resistances regulate blood flow as well as hydrostatic pressure in glomerular and peritubular capillaries.

Front 36

Renal circulation: control of BP

Back 36

Renal circulation responds strongly to sympathetic stimulation
-Little resting sympathetic tone
-Under strenuous exercise or hemorrhage, sympathetic outflow can almost completely stop renal blood flow; increased resistance
-Because of the large % of CO the kidney receives, this is an important mechanism for maintaining blood pressure
-Downside: can lead to compromised kidney function

Kidney is source of vasodilators (kinins, prostaglandins) and vasoconstrictors (angiotensin II) released into the systemic circulation.

Kidney control of fluid balance impacts blood volume and CO.

Front 37

Pulmonary circulation: pulmonary and bronchial

Back 37

Pulmonary: supplies blood to alveoli for gas exchange
-Derived from right ventricle
-Low resistance, low pressure, high compliance
-Hypoxia causes vasoconstriction (different than other organs!) as a means to maintain proper ventilation-perfusion ratios
-Sympathetic activation increases pulmonary vascular resistance and PA pressures; this mobilizes blood to the systemic circulation

Bronchial: nutritive flow to trachea and bronchial structures
-Derived from aorta (left side)

Front 38

Hemorrhage

Back 38

Multi-system compensation:
Short-term (sec to min): baroreflex, chemoreflex, ischemic response

Intermediate (min to hrs): renin angiotensin system, fluid shifts

Long term (hrs to days): salt and water conservation, new red cells, thirst, fluid replacement


Decompensation:
Shock = inadequate tissue perfusion and progressive deterioration of blood pressure

In contrast to the negative feedback control systems that provide beneficial compensation, shock is associated with positive feedback mechanisms. In part this results from actions of the competing mechanisms for local and systemic regulation.

The response to the initial insult leads to an error signal that perpetuates the error, making it larger.

Concept of a “vicious cycle”

Front 39

Hemorrhagic shock: positive feedback mechanisms

Back 39

Cardiac failure (cardiogenic shock)
-Decreased MAP leads to reduced coronary BF and cardiac function, resulting in lower CO and lower MAP
-Lower MAP decreases perfusion to other beds (kidney, brain, gut) leading to ischemia

Acidosis
-Stagnant BF leads to increased acid metabolites
-Impairs renal function
-Causes vasodilation
-Reduces cardiac function

CNS depression

Clotting abnormalities