Lecture 12: Control Of Blood Flow Flashcards Preview

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Flashcards in Lecture 12: Control Of Blood Flow Deck (53):

What are the two phases and characteristics of each for local blood flow control?

* Acute control:
- Rapid changes in local vasodilation/vasoconstriction
- Occurs in seconds to minutes
- Basic theories:
-- Vasodilator theory
-- Oxygen (nutrient) lack theory
* Long-term control:
- Increase in sizes/numbers of vessels
- Occurs over a period of days, weeks, or months


Describe the vasodilator theory

- As metabolism increases, oxygen levels decrease.
- This initiates the formation of Vasodilators
- Examples: Adenosine Carbon dioxide Adenosine phosphate compounds Histamine Potassium ions Hydrogen ions


Describe the oxygen (nutrient) Lack Theory:

As Oxygen levels go down, the blood vessels must relax through Vasodilation


Define Vasomotion

Def: Cyclical opening and closing of precapillary sphincters.

- Number of precapillary sphincters open at any given time is roughly proportional to nutritional requirements of tissues. The assumption is that smooth muscles require oxygen to remain contracted.


Describe Hyperemia

Can be either reactive or active.
- Reactive:
-- Tissue blood flow is blocked; can be for seconds, hours, or more.
-- When unblocked, blood flow increases up to 4-7x normal. This is Reactive Hyperemia
- Active:
-- When any tissue becomes active, rate of blood flow 8 Active: increases.
- See Slides 9-11


Describe autoregulation.

What are two views that potentially explain autoregulation

In any tissue:
- Rapid increase in arterial pressure leads to increased blood flow.
- Within minutes, blood flow returns to normal even with elevated pressure.

Views to explain autoregulation:
- Metabolic theory
- Myogenic theory


What are the basic differences between metabolic and myogenic theory?

Increase in Blood Flow -> Too Many Nutrients or Too Much Oxygen -> Washes out Vasodilators, allowing reconstriction

Stretching of Vessels -> Reactive Vasoconstriction

We aren't sure which theory is true.
- See Slide 14


Describe Blood Flow control Measures in the kidneys, brain, and skin

* Kidneys:
- Tubuloglomerular feedback:
-- Involves the macula densa/juxtaglomerular apparatus

* Brain
- Hydrogen and/or CO2 goes up -> Verebral Vessel Dilation -> Washing out of excess CO2/H+

* Skin
Blood flow linked to body temperature
- Sympathetic nerves via CNS
- 3 ml/min/100 g tissue →7-8 L/min for entire body


Describe Endothelial-Derived Mechanisms (For Control of Tissue Blood Flow)

- Healthy Endothelial Cells -> Nitric Oxide Release
- Nitric Oxide allows cGTP to be converted to cGMP in vascular smooth muscle cells...
- ...which activates protein kinases that lead to Vasodilation

Hypertension occurs when:
- Damaged Cells, such as those that prevent Nitric Oxide to work properly, lead to the production of a peptide called endothelin,
- Which leads to vasoconstriction
- May wanna read this chapter for reals.
- And also, see slide 18


Describe Humoral Circulation Controls for Vasoconstriction

- Norepinephrine
- Epinephrine
- Angiotensin II - Normally acts to increase total peripheral resistance
- Vasopressin - aka = ADH; very powerful vasoconstrictor; major function is to control body fluid volume


Describe Humoral Circulation Control for Vasodilation

- Bradykinins - Causes both vasodilation and increased capillary permeability.
- Histamine - Powerful vasodilator derived from mast cells and basophils)


What is the purpose of the sympathetic system?

- Innervates all vessels except capillaries
- Primarily results in vasoconstriction
- See Slides 22, 23


Where is the vasoconstrictor and the vasodilator area of the brain located

* Vasoconstrictor area:
- Anterolateral portions of upper medulla
- Transmits continuous signals to blood vessels:
-- Continual firing results in sympathetic vasoconstrictor tone.
-- Partial state of contraction of blood vessels = vasomotor tone.
* Vasodilator area:
- Bilateral in the anterolateral portions of lower medulla
- Inhibits activity in vasoconstrictor area


Where is the vasomotor sensory and the higher nervous control centers of the brain located?

* Sensory area:
- Bilateral in tractus solitarius in posterolateral portion of medulla
- Receives signals via:
-- Vagusnerves (CN X)
-- Glossopharyngeal nerves (CN IX)
* Controlled by higher nervous centers:
- Reticular substance (RAS)
- Hypothalamus
- Cerebral cortex

See Slides 26, 27


What is the adrenal medulla

Secretes epinephrine and norepinephrine


What occurs during neural rapid control of arterial pressure?

- Simultaneous changes:
-- Constriction of most systemic arteries
-- Constriction of veins
-- Increased heart rate
- Rapid response (within seconds)
- Increased blood pressure during exercise (accompanied by vasodilation)
- Alarm reaction (fight or flight)

- See Slide 30


Where are baroreceptors located

* Located in carotid sinuses and aortic sinus:
- Stimulated by low arterial pressures:
-- Carotid sinuses are stimulated by pressure > 60 mm Hg
-- Aortic sinus is stimulated by pressure > 30 mm Hg
-- Vagus nerves (CN X)
- Glossopharyngeal nerves (CN IX) via small Herring’s nerves (carotid baroreceptors)
- Reticular substance (RAS)
- Hypothalamus
- Cerebral cortex


Describe the signals from baroreceptors

- Inhibit vasoconstrictor center
- Excite vasodilator center
- Signals cause either increase or decrease in arterial pressure.
- Primary function is to reduce the minute-by-minute variation in arterial pressure.
- See Slides 34-38


Describe Chemoreceptors

- Located in carotid bodies in bifurcation of the common carotids and in aortic bodies.
- Chemosensitive cells sensitive to lack of oxygen, carbon dioxide excess, and hydrogen ion excess.
- Signals pass through Herring’s nerves and vagus nerves.
- Play a more important role in respiratory control.


Describe atrial reflexes

- Low pressure receptors are located in the atria and pulmonary arteries and play an important role in minimizing arterial pressure changes in response to changes in blood volume.
- Increase in atrial stretch results in:
- Reflex dilation of kidney afferent arterioles
- Increases kidney fluid loss
- Decreases blood volume
- Increase in heart rate (via CN X to medulla)
- Signals to hypothalamus to reduce [ADH]
- Atrial natriuretic peptide (ANP) -> Kidneys
- Peptide in Kidneys Increase GFR, and Decrease Sodium Reabsorption


Describe arterial pressure relationship with kidneys

* Arterial pressure = cardiac output X total peripheral resistance
- Arterial pressure rises when total peripheral resistance is acutely increased.
- Normal functioning kidneys return the arterial pressure back to normal within a day or two:
-- Pressure diuresis
-- Pressure natriuresis

- See Slide 42


What are the 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
* Primary (essential hypertension):
- Hypertension of unknown origin
- 90 –95% of hypertension
- Major factors include:
-- Weight gain, characterized by: Increased cardiac output, Increased sympathetic nerve activity, Increased antiotensin II and aldosterone levels, and Impaired renal-pressure natriuresis mechanism
--Sedentary life style


Describe secondary hypertension

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


What are renal-based causes of hypertension?

- Chronic renal disease
- Renal artery stenosis
- Renin-producing tumors
- Acute glomerulonephritis
- Polycystic disease
- Renal vasculitis


What are endocrine-based causes of hypertension?

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


What are cardiovascular-based causes of hypertension

- Coarctation of the aorta
- Polyarteritis nodosa
- Increased intravascular volume
- Rigidity of the aorta
- Increased cardiac output


What are neurological-based causes of hypertension?

- Psychogenic
- Increased intracranial pressure
- Sleep apnea
- Acute stress


What are contributing factors to hypertension

- Genetic factors (Essential hypertension is a complex multifactorial disorder)
- Other single-gene disorders that alter sodium reabsorption by the kidneys
- Genetic variants in the renin-angiotensin system
- Stress
- Obesity
- Smoking
- Physical inactivity
- Heavy consumption of salt


What are Factors resulting in decreased peripheral resistance (vessel dilation) leading to decreased blood pressure

- Increased production of nitric oxide
- Increased release of prostacyclin
- Increased release of kinins
- Increase in atrionatriuretic peptide (ANP)
- Decreased neural factors (β-adrenergic)


What are Factors resulting in decreased cardiac output leading to decreased blood pressure

- Decreased blood volume
- Decreased heart rate
- Decreased contractility


What are hypertension factors resulting in increased cardiac output leading to increased blood pressure

- Increased heart rate
- Increased contraction
- Increased blood volume (due to aldosterone)


What are hypertension factors resulting in increased peripheral resistance leading to increased blood pressure

- Increased angiotensin II
- Increased catecholamines
- Increased thromboxane
- Increased neural factors (α-adrenergic)


List examples of humoral vasoconstrictors and vasodilators.

* Vasoconstrictors:
- Angiotensin II
- Catecholamines
- Endothelin
* Vasodilators:
- Kinins
- Prostaglandins
- Nitric oxide


What are the lethal effects of chronic hypertension?

- Early heart failure and coronary artery disease
- Cerebral infarct
- Kidney failure


What are characteristics of atherosclerosis

- Atherosclerosis is a type of arteriosclerosis (“hardening of the arteries”).
- The major characteristic of atherosclerosis is the presence of lesions within the intima of the vessel wall that protrude into the vessel lumen.


What are non-modifiable (constitutional) risk factors of atherosclerosis?

* Age:
- Risk increases between the ages of 40 and 60.
- Death rates from ischemic heart disease increase with each decade.
* Gender:
- Uncommon in premenopausal women without other risk factors
- Increases after menopause and eventually exceeds that of men
* Genetics:
- Some Mendelian disorders associated with atherosclerosis but mostly multifactorial


What are modifiable risk factors of atherosclerosis?

* 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


What are other risk factors of atherosclerosis?

* Inflammation
* Hyperhomocystinemia
* Metabolic Syndrome
* Lipoprotein(a)
* Factors affecting Hemostasis
* Lifestyle (Including Lack of Exercise, Competitive/Stressful lifestyle, and Obesity)


How does inflammation contribute as a risk factor to atherosclerosis?

- Intimately linked with atherosclerotic plaque formation
- C-reactive protein (CRP) is a major marker for inflammation.
- Synthesized by liver
- Plays important role in opsonizing bacteria and activating complement
- Correlated with high levels of LDL (carries cholesterol to peripheral tissues) as opposed to HDL (carries cholesterol to liver)


How does hyperhomocystinemia contribute as a risk factor to atherosclerosis?

- Inborn error of metabolism
- Associated with premature vascular disease


How does metabolic syndrome contribute as a risk factor to atherosclerosis?

- Associated with insulin resistance:
- Characteristics:
-- Obesity (esp. abdominal fat)
-- Insulin resistance
-- Fasting hyperglycemia
-- Increased lipid triglycerides
-- Decreased HDL levels
-- Hypertension


What factors can cause endothelial injury or dysfunction?

- Results in intimal thickening
- May lead to formation of atheroma in presence of hyperlipidemia
- Factors related to endothelial dysfunction:
-- Hypertension
-- Hyperlipidemia
-- Cigarette smoke
-- Homocysteine
-- Infectious agents
-- Hemodynamic disturbances
-- Hypercholesterolemia


What can cause an accumulation of lipoproteins? (Especially LDL)

- Result of chronic hyperlipidemia (esp. hypercholesterolemia)
- Lipoproteins accumulate in the intima and are oxidized by oxygen free radicals generated by macrophages or endothelial cells.
- Oxidized LDL is ingested by macrophages which become foam cells.
- Oxidized LDL stimulates release of growth factors, cytokines, and chemokines.
- Oxidized LDL is toxic to endothelial cells and smooth muscle cells.


What factors are associated with monocyte adhesion to the 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


How is smooth muscle proliferation linked as a risk factor to atherosclerosis?

- Intimal smooth muscle cell proliferation and extracellular matrix deposition converts a fatty streak into a mature atheroma.


What is the morphology of atheroma?

An atheroma consists of a cap of smooth muscle cells, macrophages, foam cells (converted macrophages), and other extracellular components, overlying a necrotic center composed of cell debris, cholesterol, foam cells, and calcium.


What are the developmental stages of atherosclerosis?

- Earliest lesions are fatty streaks:
-- Note these are also seen in all children older than 10.
- Atherosclerotic plaques impinge on the lumen of the artery and grossly appear white or yellow.
- Plaques progressively enlarge due to cell death and degeneration and synthesis/degradation of extracellular matrix.
- Plaques often undergo calcification.
- Plaques may rupture, ulcerate, or erode.


What are the most common arterial sites for atherosclerosis?

Ranked from Most Involved to Least:
- Lower abdominal aorta
- Coronary arteries
- Popliteal arteries
- Internal carotid arteries
- Circle of Willis

- See Slide 68


What are short-term and long-term controls of arterial pressure?

* Short term control of arterial pressure:
- Via sympathetic nervous system effects on:
-- Total peripheral vascular resistance and capacitance
-- Cardiac pumping ability
* Long term control of arterial pressure:
- Via multiple nervous and hormonal controls
- Via local controls in kidney that regulate:
-- Salt and water excretion

- See Slide 70, 71


What is the relation of arterial pressure and kidney output?

- As arterial pressure goes up, urine output goes up, causing pressure diuresis
- As arterial pressure goes up, sodium output goes up, causing pressure natriuresis
- Return of the arterial pressure always back to the equilibrium point = Near Infinite Feedback Gain Principle.
- Primary determinants of the long-term arterial pressure level:
-- Degree of pressure shift of the renal output curve for water/salt
-- Level of water/salt intake

* SEE SLIDES 73-76


Define Chronic Hypertension

- One’s 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 (250/130)
- See Slide 79-80


What are the lethal effects of chronic hypertension?

- Early heart failure
- Coronary heart disease
- Heart attack
- Cerebral infarct
- Destruction of kidney areas->kidney failure->uremia->death


See Slides 83-88

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