[2] Lecture 12-Control Of Blood Flow Flashcards
Rapid changes in local vasodilation/vasoconstriction
Acute control of local blood flow
Two basic theories of acute control of local blood flow:
- Vasodilator theory
2. oxygen (nutrient) lack theory
Increase in sizes/ number of vessels
Occurs over a period of days, weeks, or months.
Long-term control of local blood flow
Increased metabolism = decreased O2 availability
Formation of vasodilator [adenosine, CO2, Adenosine P compounds, histamine, K+ ions H+ ions]
Vasodilator theory
Decreased O2 = blood vessel relaxation
[vasodilation]
Oxygen [nutrient] lack theory
Cyclical opening and closing of precapillary sphincters
Vasomotion
What controls the number of precapillary sphincters open at any given time?
Roughly proportional to nutritional[O2] req’ments f tissues.
Tissue blood flow blocked [s to hrs or more]
When unblocked, blood flow increases 4-7x normal
Reactive hyperemia
When any tissue becomes active rate of blood flow increases
Active hyperemia
When there is a higher rate of metabolism, what happens to blood flow rate
Increased blood flow
When arterial oxygenation desats, what happens to blood flow?
Blood flow increases
Rapid increase in arterial pressure leads to increased blood flow
W/in minutes, blood flow returns to normal even with elevated pressure
What term would be used to describe this phenomenon
Autoregulation
2 theories/views to explain autoregulation:
Metabolic/myogenic theory
Increase in blood flow leads to:
Too much O2 or nutrients leads to:
Washes out vasodilators
Metabolic theory of autoregulation
Stretching of blood vessels leads to reactive vasculature constriction
Myogenic theory of autoregulation
Range that autoregulation typically operates at:
75 mmHg to 175 mm Hg
Higher arterial pressure has what effect on blood flow:
Increases blood flow [w/ higher arterial pressure]
What is the kidneys role in ACUTE blood flow control
Involves the macula densa / juxtaglomerular apparatus
Tubuloglomerular feedback
[CO2] increase and/or [H+] increase leads to:
Cerebral vessel dilation leads to:
Washing out of excess CO2/H+
Acute blood flow control mechanism: Brain
Blood flow linked to body temperature
Sympathetic nerves via CNS
(3ml/min/100g tissue->7-8 L/min for entire body)
Acute blood flow control mechanism: skin
What type of endothelial cells can help control blood flow to tissue?
Healthy Endothelial cells
Sequence of Helathy endothelial cell blood flow control mechanism:
Endothelial cell->Nitric Oxide->cGTP becomes cGMP in vascular smooth muscle->activation of protein kinases->VASODILATION
What happens in damaged endothelial cells?
Damages cells-> endothelin->vasoconstriction
21 AA peptide; effective in nanogram quantities
Endothelin-potent!
If endothelial cells aren’t healthy, they can’t do what?
Secrete NO for vasodilation
Hormones for vasoconstriction:
NEVA
Norepinephrine
Epinephrine
Vasopressin
Angiotensin II
WHich hormone typically acts to increase total peripheral resistance
Angiotensin II
Which hormone is a very powerful vasoconstrictor; major function is to control body fluid volume
ADH- vasopressin
Hormones that result in vasodilation:
Bradykinins
Histamine
Hormone that cause vasodilation and increased capillary permeability:
Bradykinin
Hormone that is a powerful vasodilator derived from mast cells and basophils
Histamine
Innervates all vessels except capillaries
Primarily results in vasoconstriction
Sympathetic system
What vessels do sympathetic innervation not apply to:
Capillaries;
Arteries, arterioles,
venules, veins do apply
Vasomotor center in brain has 2 components:
Vasoconstrictor and vaso dilator
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
Vasoconstrictor area of vasomotor center of Brain
Partial state of contraction of blood vessels
Vasomotor tone
Bilateral in the anterolateral portions of the medulla
Inhibits activity in vasoconstrictor area
Vasodilator area of vasomotor center of Brain
Part of the medulla
Receives signals via: vagus nerve and glossopharyngeal nerves
Sensory area vasomotor center of Brain
Cranial nerve X
Vagus nerve
Cranial nerve IX
Glossopharyngeal nerve
Controlled by higher nervous centers than medulla (3)
Reticular substance (RAS)
Hypothalamus
Cerebral cortex
Continual firing of vasoconstrictor area:
Vasoconstrictor tone
Partial state of blood vessel contraction:
Vasomotor tone
Inhibit vasoconstrictor center/ stimulate vasodilator center
Baroreceptor
Chemosensitive cells that are more important in resp control
Carotid bodies
Aortic arch baroreceptor vs. carotid baroreceptor:
Carotid: >60 mm Hg
Aortic: >30 mm Hg
How does the baroreceptor signal travel to glossopharyngeal nerve (CN IX)
Herings nerves ***
Completely define and state How to decrease the continual firing of the vasoconstrictor area? *
The vasodilator area negatively impacts vasoconstrictor to decrease firing…so,
The vasoconstrictor is always active but in HTN states, the vasodilator area will kick on to compensate for the elevated BP..this is only activated by CN IX from hering’s nerves from carotid baraprecptors
What 2 hormones come from Adrenal medulla?
Epinephrine and norepinephrine
3 simultaneous changes during rapid neural control of arterial pressure:
Constriction of most systemic arteries
Constriction of veins
Increased HR
Within seconds
Rapid response
What is increased BP during exercise accompanied w/?
Vasodilation
Alarm rxn
Fight or flight
Spinal anesthesia and norepinephrine chart:
Anesthesia dropped pressure and norepinephrine increased pressure
Located in carotid and aortic sinus:
Baroreceptors
Stimulated by a pressure drop >60 mm Hg
Carotid sinus
Stimulated by a pressure drop > 30 mm Hg:
Aortic sinus
Besides the carotid and aortic sinus, what are the 2 others involved in detecting low pressure?
Vagus nerve (CN X)
Glossopharyngeal nerve (CN IX) via hering’s nerves [carotid baroreceptors]
What are other baroreceptors?
Reticular substance (RAS)
hypothalamus
Cerebral cortex
What are the signals from baroreceptors:
- inhibit vasoconstrictor
- excite vasodilator
- increase/decrease arterial pressure
What is primary function of baroreceptors:
To reduce the minute-by-minute variation in arterial pressure `
Graph depicting clamping carotid arteries:
Pressure increased b/c there was no longer barorecptor control
What is the necessity for baroreceptors:
Maintaining pressures at a steady rate
Located in carotid bodies in bifurcation of the common carotid and in aortic bodies
Chemoreceptors
Chemosenesitive means sensitive to what chemicals?
Lack of O2,
Increase in CO2,
Increase in H+ ion
Chemoreceptors pass through what nerves? (2)
Vagus and hering’s
Chemoreceptors play an important role in:
Respiratory control
Located in the atria and pulmonary arteries and play an important role in minimizing arterial pressure changes in response to changes in blood volume
Low pressure receptors
Increase in atrial stretch results in:
-reflex dilation of kidney afferent arterioles:
Increase FLuid loss(urine excretion) ad decrease blood volume
-increase in HR
-Signals to hypothalamus-drop [ADH]
-atrial natriuretic peptide (ANP)-kidneys:decrease Na+ reabsorption and increase GFR
-basically stop keeping fluid, pee it out including Na+
Arterial pressure =
CO x Total peripheral resistance
Arterial pressure rises when TPR is:
Increased
Normal functioning kidneys return the arterial pressure back to normal w/in a day or 2 by 2 means:
Pressure dieresis and
Pressure Natriuresis
Increased amt. of Na+ lost in urine
Natriuresis
Increased urine output
Diuresis
CO can be increased or decreased by certain conditions. What’re the 2 that cause decrease CO
Removal of limbs
And
Hypothyroidism…
Everything else has sympathetic effect
With many conditions causing increased pressure, what compensatory mechanism helps to bring back to norm?
Norm kidney function.
Increased CO
Increased sympathetic nerve activity
Increased Angiotensin II and aldosterone
Impairment of renal-pressure natiuresis mechanism
Inadequate secretion of salt and water
Primary HTN
90-95% of HTN
HTN of unk origin
Major factors:
Weight gain and sedentary life
Primary HTN
HTN second to another cause:
Secondary HTN
Ex of 2 HTN
Tumor affecting renin-secreting cells
Renal artery constriction
Carctation of aorta
Preeclampsia
Neurogenic HTN
Genetic causes
Renal causes of HTN:
Chronic renal disease Renal artery stenosis Renin-producing tumors Acute glomerulonephritis Polycystic disease Renal vasculitis
Endocrine causes of HTN:
cushing syndrome Exogenous hormones Pheochromocytoma Acromegaly Hypothyroidism Hyperthyroidism Pregnancy induced
CV causes of HTN:
Coarctation (narrowing) aorta Polyarteritis nodosa Increased intravascular volume Rigidity of aorta Increased CO
Neurological causes HTN:
Psychogenic
Increased ICP
Sleep apnea
Acute stress
Contributing factors to HTN:
Genetics Single-gene disorders that alter NA reabsorption in kidney Renin-angiotensin system Stress Smoking Physical inactivity Heavy consumption Na+
Factors in decreased peripheral resistance (vessel dilation) = decreased BP
Increased: production of NO, release of prostacyclin, release of kinins, atrionatriuretic peptide (ANP)
Decreased: neural factors [ß-adrenergic]
Factors resulting in decreased CO leading to decreased BP:
Decreased: blood volume, HR, contractility
Factors resulting in increased CO leading to increased BP:
Increased HR, contraction, blood volume
Factors resulting in increased peripheral resistance leading to increased BP
Increased: angiotensin II, catecholemines, thromboxane, neural factors (alpha-adrenergic)
Vasoconstrictors:
Angiotensin II
Catecholemines
Endothelin
Vasodilators
Kinins
Prostaglandins
NO
Lethal effects of chronic HTN:
Early heart failure/ CAD
Cerebral infarct
Kidney failure
Hardening of the arteries
Atherosclerosis
Major characteristic of atherosclerosis:
Presence of lesions w.in the intima of the vessel wall that produce into the vessel lumen.
Non-modifiable risk factors for atherosclerosis: (3)
Age [risk increased 40-60, death rate increases w/ each decade]
Gender [increases after menopause]
Genetics [mendelian disorders asso. W/ atherosclerosis]
Modifiable risk factors of atherosclerosis: (4)
Hyperlipidemia [high cholesterol-major risk factor-high levels of LDL]
HTN [increases risk of IHD by 60%][most important cause L ventricular hypertrophy]
Cig smoking
Diabetes
Other risk factors for Atherosclerosis:
Inflammation:
[linked w/ atherosclerotic plaque formation- CRP c reactive, synthesized by liver, play important role in opsonizing complement, inflammation correlated w/ high levels of LDL (not HDL)]
Hyperhomocytinemia [inborn error of metabolism, asso. W/ premature vascular disease]
Metabolic syndrome: asso. W/ insulin resistance [obesity,fasting hyperglycemia, increased lipid triglycerides, low HDL, HTN]
Other risk factors atherosclerosis:
Lipoprotein A
Factors affecting hemostasis
Lifestyle: lack of exercise, stressful lifestyle, obesity
Pathogensis of atherosclerotic Dz:
Results in intimate thickening after endothelial injury or dysfunction, may lead to formation of atheroma in presence of hyperlipidemia
Same factors cause atherosclerosis are r.t endothelial injury
Accumulation of lipoproteins in pathogenesis of atherosclerosis:
Result chronic hyperlipidemia
Lipoproteins accumulate in intima and are oxidized by O2 free radicals generated by macrophages or endothelial cells
Oxidized LDL:
Ingested by macrophages=foam cells, stimulate growth factors, cytokines, chemokines, is toxic to endothlial cells and smooth muscle cells
Ozxidzed LDL is ingested by macrophages which becomes:
Foam cells
Consists of a cap of smooth muscle cells, macrophages, foam cells, and other Extracellular components, overlying a necrotic center composed of cell debris, cholesterol, foam cells and Ca+
Atheroma
Common sites for arterial sites in atherosclerosis:
Lower abd aorta Coronary arteries Popliteal arteries Internal carotid arteries Circle of willis
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 inflammation response
Activated leukocytes and endothelial cells realease growth factors that promote smooth muscle cell proliferation
Short term control of pressures:
Via sympathetic NS:
Total PV resistance and c capacitance
Cardiac pumping ability
Long term control of pressures:
Via multiple Nervous and hormonal controls
And local controls in kidney that regulate Na and water excretion
More arterial pressure r/t urinary output?
Higher pressure. = higher urinary output
SMooth muscle proliferation
Intima smooth muscle cell proliferation and ECM deposition converts a fatty streak into a mature atheroma.
Earliest detection atherosclerosis:
Fatty streaks- these are also seen al all children older than 10.
Developmental stages of atherosclerosis:
Fatty streaks
Atherosclerotic plaques impinge on lumen of artery grossly appear yellow/white
Plaques progressively enlarge d/t cell death and degeneration and synthesis/degradation of ECM
Plaques often undergo calcification and may rupture, ulcerated, or erode.
Kidney compensation for increasing blood volume:
Output to compensate for increased volume
Increase in arterial pressure=
Increased urine and Na+ output
Terms for increased urine output and Na+ output
Pressure diuresis and natriuresis
Return of the arterial pressure always back to the equilibrium point=
Near infinite feedback gain principle
PRimary determinants of long term arterial pressure level:
Degree of pressure shift of renal output curve for water/ salt
Level of water/salt intake
Ways to increase arterial pressure:
Increase intake of salt and water
Retain water and salt- norm output and high arterial pressure
Increased salt intake causes only small changes in arterial pressure
Chronic renal output
Increased salt intake causes larger changes in arterial pressure
Acute renal output
Feedback mechanism of extracellular fluid volume increases arterial pressure
NEgative feedback mechanism: increased blood volume=increased CO= higher arterial pressure=increased urine output (negatively affects the increased blood volume)
One’s mean arterial pressure is > the upper range of accepted norm measure
Chronic HTN
Norm arterial pressure
90 mm Hg (110/70)
Hypertensive arterial measure
110 mm Hg (135/90)
Severe HTN arterial:
150/170[mean arterial pressure] / 250/130
Lethal effects of Chronic HTN:
Early heart failure Coronary heart disease MI Cerebral infarct Destruction of areas of kidney-kidney failure-uremia-death
Ex of vasoconstrictor:
Renin-angiotensin mechanism
Role of renin-angiotensin mechanism
To increase BP if it goes low
Effects of Renin-angiotensin:
Retention of salt and water and vasoconstriction
= increased arterial pressure
Angiotensinogen is produced in what organ
Liver
Precursor to angiotensin I
Angiotensinogen
What converts Angiotensin I to II?
Angiotensin converting enzyme
ACE enzyme comes from:
Many tissues including the lungs
Angiotensin II acts on:
Kidney [Na and water reabsorption]
Adrenal gland [by means of aldosterone]
Higher the arterial pressure=
Higher the urinary output
2 results of increased arterial pressure:
Pressure diuresis and natriuresis
Return to arterial pressure always back to the equilibrium point
Near infinite feedback gain principle
Why is here an initial decrease in TPR after adding fluid w/ Na+?
Barorecptor mechanisms- recalculation
What can assist if half blood volume is drained?
Renin-angiotensin system compensates by increasing arterial pressure
