Control of Blood Flow

Hyperemia

increased blood flow to tissues

What is the relationship between mean arterial pressure and blood flow? Acute vs Long term? Explain control mechanism?

Acutely, Blood flow increases drastically with Increased arterial pressure. Long term, blood flow is controlled back to normal despite rising arterial pressure, because of the increase in the number and size of capillaries and arterioles as a mechanism of control.

Explain the changes in ECF, Blood Volume, Cardiac output, Total peripheral resistance, and arterial pressure during Volume Loading that leads to hypertension. Give the Acute and long term effects and why?

Acutely, ECF fluid volume increases Blood volume increases CO increases Total peripheral resistance decreases (due to baroreceptor mechanism) Arterial pressure increases Long term, (hypertension) ECF fluid volume goes back to normal Blood volume goes back to normal CO goes back to normal (long term blood flow auto regulation mechanism) Total peripheral resistance increases (baroreceptors no longer work after 2-4 days, new normal, caused by long term blood flow auto regulation mechanism ) Arterial pressure remains elevated

Explain how the renin-angiotensin system serves as a negative feedback system for decreased arterial pressure?

Angiotensin II results in renal retention of salt and water and vasoconstriction which functions to raise the arterial blood pressure back up to normal.

What is the relationship between arterial pressure, cardiac output, and total peripheral resistance?

Arterial pressure = CO x Total peripheral resistance

Explain the relationship between kidney output and arterial pressure and differentiate between pressure diuresis and pressure natriuresis?

As arterial pressure increases, kidney output increases Increase in arterial pressure leads to: Increase in urine output (pressure diuresis) AND Increase in sodium output (pressure natriuresis).

Describe the locations and characteristics of the baroreceptors involved in controlling arterial pressure?

Baroreceptors are located in almost every large artery of the thoracic and neck region, Mostly: Carotid Sinus - Signals via Glossopharyngeal nerves via small herring nerves. Simulated by Pressure > 60 mm Hg. Aortic Sinus - Aortic baroreceptor signals via vagus nerves. Stimulated by P>30 mm Hg

List humoral factors involved in vasodilation?

Bradykinins, histamine

Another name for Glossopharyngeal Nerve?

CN IX

Another name for Vagus nerve ?

CN X

Explain the effect of increasing blood volume (via infusion) on Kidney output and arterial pressure and cardiac output when nervous pressure control mechanisms have been blocked?

Cardiac output increases Kidney output increases Arterial pressure increases

Define chronic hypertension and give the arterial pressure ranges for normal, hypersensitive and severe hypersensitive conditions, including mean arterial pressures?

Chronic hypertension = mean arterial pressure is greater than the upper range of the accepted normal measure. Normal: 90 mm Hg (110/70) Hypertensive: 110 mm Hg (135/90) Severe hypertensive: 150 - 170 mm Hg (250/130)

List contributing factor causes of hypertension?

Contributing factor causes of hypertension: Genetic factors (essentially hypertension is a more complex multifactorial disease) Other single gene disorders that alter Na+ (sodium) reabsorption by the kidneys Genetic variants in the renin-angiotensin system Stress Obesity Smoking Physical inactivity Heavy salt consumption

What is the effect of endothelin on tissue blood flow?

Vasoconstriction

Oxygen (nutrient Lack) Theory

Decreased Oxygen leads to blood vessel relaxation, which leads to vasodilation

List lethal effects of chronic hypertension?

Early heart failure Coronary heart disease Heart attack Cerebral infarct (stroke) Destruction of areas of kidneys → kidney failure → uremia → death

List endocrine causes of hypertension?

Endocrine causes: Cushing syndrome (adrenocortical hyperfunction) Exogenous hormones (i.e., glucocorticoids, estrogen) Pheochromocytoma Acromegaly Hypothyroidism (myxedema) Hyperthyroidism (thyrotoxicosis) Pregnancy induced

List and describe steps in the pathogenesis of atheromas?

Endothelial injury or dysfunction of any kind: Results in intimal thickening (innermost layer vessel) May lead to formation of atheroma in presence of hyperlipidemia Factors related to endothelial dysfunction Hypertension, hyperlipidemia, smoking, homocysteine, infectious agents, hemodynamic disturbances, hypercholesterolemia Accumulation of lipoproteins: (esp LDL): Result of chronic hyperlipidemia (esp hypercholesterolemia) Lipoproteins accumulate in the intima and are oxidized by O2 free radicals made by macrophages or endothelial cells Oxidized LDL stimulates release of growth factors, cytokines and chemokines Oxidized LDL is toxic to endothelial cells and smooth muscle cells Monocyte adhesion to endothelium: Endothelial cells express VCAM-1 adhesion molecules that bind monocytes and T-cells to endothelium Monocytes transform into macrophages and engulf lipoproteins T-cells stimulate a chronic inflammatory response Activated leukocytes and endothelial cells release growth factors that promote smooth muscle cell proliferation Smooth muscle proliferation: Intimal smooth muscle cell proliferation and extracellular matrix deposition converted a fatty streak into a mature atheroma, causing thickening of intima

Explain how excess salt and water intake causes rise in arterial pressure?

Excess salt causes person to be more

List factors resulting in increased cardiac output and increased peripheral resistance leading to increased blood pressure?

Factors resulting in increased cardiac output leading to increased blood pressure: Increased heart rate Increased contraction Increased blood volume Factors resulting in increased peripheral resistance leading to increased blood pressure: Increased angiotensin II Increased catecholamines (epinephrine, norepinephrine, dopamine) Increased thromboxane Increased neural factors (alpha-adrenergic)

Describe endothelial derived mechanisms for control of tissue blood flow, including the roles of NO, cGTP, and endothelin? Healthy endothelial cells vs damaged endothelial cells lining the blood vessels?

Healthy endothelial cells: Release NO, which acts on vascular smooth muscle cells by converting cGTP ----> cGMP. cGMP activates protein kinases, which cause vasodilation. Damaged endothelial cells (due to hypertension): Stop producing NO, and produce increased endothelin. Endothelin causes vasoconstriction.

Generally vasoconstriction effects heart rate and strength of contraction in what way?

Heart Rate increases and strength of contraction increase. Opposite true when vasoconstriction is inhibited.

Volume-loading Hypertension

Hypertension caused by excess accumulation of ECF in the body. (increase in salt and water; and/or reduction in kidney mass therefore reducing the kidney's ability to excrete salt and water)

List causes of secondary hypertension?

Hypertension secondary to some other cause: Tumor affecting renin-secreting juxtaglomerular cells Renal artery constriction Coarctation of the aorta Preeclampsia Neurogenic hypertension Genetic causes

Explain how atrial reflexes play an important role in minimizing arterial pressure changes in response to changes in blood volume; include the roles of ADH, GFR, and ANP?

Increase in atrial stretch results in: Reflex dilation of kidney afferent arterioles Increases kidney fluid loss and decreases Blood Volume Increase in heart rate (via CN X to medulla respiratory control center) Signals to hypothalamus → decreased [ADH] Atrial natriuretic peptide acts on Kidneys (ANP ---> Kidneys ----> increased GFR and decreased sodium resorption.) Therefore decreasing Arterial pressure back to normal.

Pressure natriuresis

Increase in sodium output

Pressure diuresis

Increase in urine output

What is active hyperemia?

When any tissue becomes active, rate of blood flow increases.

Give the mechanism by which increased ECF fluid volume may elevate arterial pressure if vascular capacity is not simultaneously increased? What happens if the kidney is functioning properly

Increased ECF volume --> increases the blood volume, which increases the Psf, which increases venous return of blood to the heart, which increases CO, which increases arterial pressure.. If Kidney is functioning properly then it will increase excretion of salt and water to return ECF fluid volume to normal.

List characteristics of primary hypertension?

Increased cardiac output Increased sympathetic nerve activity Increase in angiotensin II and aldosterone levels Impairment of renal-pressure natriuresis mechanism Inadequate secretion of salt and water

Vasodilatory Theory

Increased metabolism leads to decreased oxygen availability, which then triggers the formation of vasodilators (histamine, K+, H+, adenosine, adenosine phosphate, C02), and therefore vasodilation occurs.

Explain the role of the renin-angiotensin system in decreasing arterial pressure following increased salt intake?

Increased salt intake → increased arterial pressure → decreased renin and angiotensin → decreased renal retention of salt and water via excretion → return of extracellular volume to normal

What is reactive hyperemia?

When blood supply to a tissue is blocked for hrs and then unblocked: Blood flow increases 4-7x normal for some time.

Describe the vasodilator area?

Inhibits the vasoconstrictor area thus causing vasodilation.

Vasomotor tone

Is the partial state of contraction in the blood vessels due to impulses of the vasoconstrictor tone.

What is the big picture of blood flow auto regulation?

It brings blood flow back to normal.

Describe the location of chemoreceptors and compare their function with baroreceptors?

Located in 2 carotid bodies and usually one to 3 aortic bodies. Chemoreceptors excite the vasomotor center to elevate arterial pressure back to normal. At lower Pressure, this reflex becomes important <80 mm Hg. Important to respiratory control. Signals pass through Herrings nerves and vagus nerves just like baroreceptors. Baroreceptors have stretch receptors instead of chemoreceptors.

What happens to vasoconstrictor tone and vasomotor tone if you block sympathetic nerve signals? What happens to arterial pressure?

Loss of vasoconstrictor tone and therefore vasomotor tone. Arterial pressure drops.

Describe and compare the metabolic and myogenic theories of blood flow auto regulation?

Metabolic theory: Increase blood flow due to increate arterial pressure -> too much Oxygen or nutrients --> "washes out" vasodilator ---> then vessels constrict and return flow to normal despite increased arterial pressure. Myogenic theory: Increased arterial pressure stretches vessel walls which causes vasculature constriction that reduces flow nearly back to normal.

Define the near infinite feedback gain principle and describe the primary determinants of the long-term arterial pressure level?

Near infinite feedback gain principle = return of the arterial pressure always goes back to equilibrium point Primary determinants long-term arterial pressure level: Degree of pressure shift of the renal output curve for water/salt Level of water/salt intake

Describe and compare non-modifiable and modifiable risk factors for atherosclerosis?

Non-modifiable risk factors: Age: Risk increases between ages of 40 and 60 Increases risk of ischemic heart disease (IHD) with each decade Gender: Risk increases after menopause and eventually exceeds risk in men Genetics Some Mendelian disorders associated with atherosclerosis but most mostly multifactorial Modifiable risk factors: Hyperlipidemia (esp hypercholesterolemia): Major risk factor Correlated with high levels of LDL (carries cholesterol to peripheral tissues) as opposed to HDL (carries cholesterol to liver) Hypertension: Increases risk of IHD by 60% Most important cause of left ventricular hypertrophy Cigarette smoking Diabetes

List non-modifiable and modifiable risk factors for atherosclerosis.

Non-modifiable risk factors: Age, Gender, Genetics Modifiable risk factors: Hyperlipidemia (esp hypercholesterolemia), hypertension, cigarette smoking, diabetes.

Vasoconstrictor tone

Normal continuous sympathetic signals from the vasoconstrictor area result in slow continual firing of fibers in blood vessels.

Describe the Sensory area?

Receives signals via the Vagus nerve and the Glossopharyngeal nerves. Has a reflex control which controls the vasoconstrictor and vasodilator areas.

List renal causes of hypertension?

Renal Causes: Chronic renal disease Renal artery Stenosis Renin-producing tumors Acute glomerulonephritis Polycystic disease Renal vasculitis

Be familiar with the components of the renin-angiotensin system, including organs of secretion and roles of renin, angiotensinogen, angiotensin and II, aldosterone, ACE, and ANP?

Renin-angiotensin system responds to decreased arterial pressure and results in vasoconstriction Renin secreted by juxtaglomerular cells in kidney Renin catalyzes formation of Angiotensin I from Angiotensinogen Angiotensin I converted to Angiotensin II by ACE (lungs) Angiotensin II results in renal retention of salt and water by activation of aldosterone and vasoconstriction, which Increases arterial pressure, which causes volume overload and then ANP causes vasodilation.

Baroreceptors

Respond to changes in arterial pressure to return pressure to normal (feedback mechanism). So if arterial pressure increases baroreceptors inhibit the vasoconstrictor center/stimulates the vasodilator center to cause vasodilation.

Which higher nervous centers control the vasomotor center?

Reticular substance (RAS), Hypothalmus, Cerebral cortex

Describe the function of norepinephrine?

SYMPATHETIC VASOCONSTRICTION Neurotransmitter secret at ends of vasoconstrictor (sympathetic) nerves. Acts directly on alpha adrenergic receptors of vascular smooth muscle to cause vast constriction.

Define vasomotion?

The cyclical opening and closing of pre capillary sphincters. Duration of the open phases are promotional to the metabolic needs of the tissues for Oxygen.

Describe the role of the sympathetic system in regulating blood pressure?

The sympathetic system innervates all vessels except capillaries. Stimulation results in vasoconstriction, which means increased resistance and decreased blood flow.

Describe the vasoconstrictor area?

Transmits continuous signals to blood vessels to constrict

Uremia

Urea in the blood

List and describe Humoral factors involved in vasoconstriction and in vasodilation?

Vasoconstriction: Norepinephrine, epinephrine = think sympathetic nerve stimulation Angiotensin II = normally acts to increase total peripheral resistance Vasopressin (ADH) = major function to control body fluid, specifically to increase water reabsorption. Vasodilation: Bradykinins = causes both vasodilation and increased capillary permeability Histamine = derived from mast cells and basophils.

List the components of the vasomotor center in the brain?

Vasoconstrictor area, vasodilator area, sensory area.

What is the effect of NO on tissue blood flow?

Vasodilation

Theories of Acute Control

Vasodilatory Theory and Oxygen (nutrient Lack) Theory

List humoral factors involved in vasoconstriction?

norepinephrine, epinephrine, angiotensin II, vasopressin (ADH).

Chemoreceptors

sensitive to low Oxygen, CO2 excess, and H+ ion excess.