Acute:

*acts within seconds or minutes

*special phenomena: reactive hyperemia, active hyperemia and autoregulation

*constriction or relaxation of the arterioles, metarterioles and precapillary sphincters based on rate of metabolism in the local tissue or changes of oxygen availability

Chronic:

*acts within days or weeks

*results in changes of physical sizes and numbers of the blood vessels supplying the tissues

*Based on the needs of the body as a whole

*mainly through autonomic nervous system and other neural reflexes

*The local increase of the blood flow to a tissue when this tissue become active (e.g. muscle during exercise)

Mechanism:

Active tissue -> increase local metabolism -> use up more nutrients and release more vasodilator substances (adenosine, NO, CO2, K+) -> increase blood flow e.g. intense exercise -> ↑ muscle blood flow 20 fold

*Transient increase in blood flow (4-7 times normal) after a brief period of arterial occlusion (ischemia)

Mechanism: Temporary blood occlusion -> oxygen deficiency and increase vasodilators in local tissue -> vasodilation and increase blood flow

ex - ischemia of the LV occurs during systole

- during tachycardia ischemia can occur as well

*the intrinsic ability of an organ to maintain a constant blood flow despite changes in perfusion pressure

Mechanism:

1) Metabolic theory

2) Myogenic theory

Mechanisms:

a) Vasodilator theory: increase tissues metabolites -> relax vascular smooth muscle -> increase blood flow

CO2, increased adenosine, increased lactic acid increased H+ (decreased pH), increased K+, increased osmolarity

b) O2 lack theory: precapillary sphincters and metarterioles open and close cyclically several times/min (vasomotion) based on availability of O2 and others nutrients

decreased O2, decreased nutrients -> relaxation -> increase blood flow

1- Cerebral circulation

2- Coronary circulation

3- Renal circulation

4- Circulation of skeletal muscle during exercise

Vasoconstrictor agents:

Norepenephrine (NE) and epeniphrine -> sympathetic stimulation -> alpha1 receptor in blood vessels -> vasoconstriction beta1 receptors in the heart -> increased heart rate and contractility

Endothelin -> vasoconstriction

Angiotensin II -> vasoconstriction in small arterioles

Serotonin -> vasoconstriction in response to vessel damage (migraine)

Vasopressin or ADH -> vasoconstriction in small vessels increased [Ca2+] -> stimulate smooth muscle contraction

Stimulators

*angiotensin II

*catecholamines

*growth factors

*hypoxia

*insulin

*oxidized LDL

*HDL

*shear stress

*thrombin

Inhibitors

*NO

*ANP

*PGE2

*Prostacyclin

Nitric oxide (NO) -> vasodilation

Bradykinin: among others kinins family cause vasodilation of blood vessels

Histamine: release mainly from mast cells in damaged tissues and basophils in the blood -> vasodilation of blood vessels

Ions and other substances: increased [K+] inhibit smooth muscle contraction -> vasodilation increased [Mg+] increased [H+] increased CO2

Causes: Increase long-term metabolic demand (overactive tissues for a long period of time)

Effects: Formation of new blood vessels to keep up with the metabolic demand

Mechanisms: Deficiency of tissue O2 and other nutrients -> formation of angiogenic factors such as: *Vascular Endothelial Growth Factor (VEGF) *Fibroblast growth factor

*Angiogenin

Predominantly neural Arteries, arterioles, and veins are innerved by:

α1 adrenergic receptors -> vasoconstriction

β2 adrenergic receptors -> vasodilation

Muscarinic cholinergic receptors are located on the endothelial cells -> vasodilation of adjacent smooth muscle (NO mediated)

Humoral control: Examples include adrenal medullary catecholamines, angiotensin II, and ADH. Blood volume control includes aldosterone, ANP, erythropoietin

Reflexes: Combination of neural and humoral mechanisms

Reflexes includes:

*Arterial baroreceptor reflex.

*Volume reflexes - atrial stretch receptors mediating HR. ADH, ANP.

*Chemoreceptor reflex (central and peripheral). *Central ischemic response and Cushing’s reflex.

*The various tissues and organs have different blood flow requirements, e.g. skin and kidneys need blood flow both for tissue nutrition and an excretion function (heat and urine).

*Blood flow control differs in different tissues and organs, e.g. in brain and heart there is minimal sympathetic vasoconstriction and potent local control.

*Blood volume can be shunted from some tissues and organs to others, e.g. liver and splanchnic blood volume can be mobilized by sympathetic vasoconstriction in exercise.

Blood flow: depends on metabolic demands.

*At rest, 750 ml/min, 15-20% of blood flow for 40-50% of body mass.

*During exercise, 20L/min, 80-90% of greatly increased cardiac output.

Blood volume: 700ml-1L, 15-20% of total.

Control: (dual control) only in arteries

Neural control (during REST)

*α1 adrenergic - considerable constriction.

*beta2 adrenergic - dilation, particularly with epinephrine.

*Sympathetic cholinergic dilation (minor role if any) *No parasympathetic

Local control (very important with EXERCISE) Increase local metabolites

Extravascular compression: Most important with isometric contraction. Milking action on veins with rhythmic contractions.

*Blood flow:

Resting, 1,000ml/min via hepatic portal vein, 500 ml/min via hepatic artery. 20% of cardiac output, 25% of body mass. Minimal, 300 ml/min. Important for uptake of nutrients from GI.

*Blood volume: 20-25%of blood volume at rest, 10-15% with baroreflex response.

*Control:

Sympathetic - α1 predominates. No cholinergic. Local - intrinsic basal tone in intestine. Hormones important.

*Extravascular compression: Important in exercise, aids venous return.

*Blood flow: ~ 200 ml/min at rest and ~ 1 L/min maximal 4-5% of cardiac output at rest and during exercise. Tied very closely to cardiac function.

*Blood volume: Not an important reservoir.

*Control: Neural - only for fine tuning

Local - metabolic (dominant factor) and intrinsic basal tone (some) - AUTOREGULATION

*Extraction of oxygen - very high 65-75% at rest and ~ 90% during max. exercise Coronary veins have lowest PO2 level at rest

*Extravascular compression: phasic flow

*in both arteries there is a high increase in blood flow during diastole

*during systole there is contraction of the ventricles which compresses the subendocardial arterial plexus

*the high increase in blood flow is due to reactive hyperemia

*left coronary has a higher increase in blood flow than the right because the left side of the heart needs more blood

*Blood flow:

Overall brain metabolic activity does not change very much and blood flow is relatively constant. Resting, 12-15% of resting cardiac output, 2.5% of body mass. Overall can increase by 40%, doubling in some areas, and decrease by 20%. Brain death - decrease flow, "hot nose" sign

*Blood volume: small variation, skull limitation, not an important volume reservoir. 1,400g, 75 ml blood, 75 ml CSF.

*Control:

Neural: minor functional importance.

Sympathetic and parasympathetic innervation.

Both α1 and β2 receptors.

NPY is a powerful vasoconstrictor (protects against sudden increases in arterial pressure),

5HT is a powerful vasoconstrictor (vasospasm with subarachnoid hemorrhage).

Parasympathetic function unknown.

Local: predominates - PCO2 very important. May be an important myogenic component to autoregulation. increases PC02, decreased pH -> increased blood flow

*Extravascular compression: Very important in pathological conditions - hemorrhage, increased intracranial pressure, cerebral edema.

*Blood flow: 5% of cardiac output at rest, <0.5% in the cold. ~ 200- 600 ml/min at rest, may be > 5L/min in extremely hot environment.

*Blood volume: Fairly large capacity, mostly in venous plexus. Increase by 40% with sympathectomy, decrease by 50% with maximum sympathetic tone.

*Control:

Neural tone dominates. α1 adrenergic receptors. Sympathetic cholinergic stimulation of sweat glands - bradykinin causes secondary vasodilation.

Local: intrinsic basal tone. Temperature also has a direct effect.

*Normal body temperature set point - 37°C or 98.6°F

*Temperature-regulated center is located in anterior hypothalamus.

*Generating-heat and dissipating-heat mechanisms maintain the balance between environmental and body temperatures

*These mechanisms act if the core temperature is above or below the set point temperature

Generating-heat Mechanisms: (core temperature is below the set point temperature)

1- Thyroid hormones: thermogenic hormone Stimulates Na+-K+ATPase, increased O2 consumption, increased metabolic rate, increased heat production

2- Sympathetic nervous system:

a) Stimulates metabolic rate and heat production via beta receptor in brown fat,

b) stimulates alpha1 receptors -> vasoconstriction -> reduces heat loss

3- Shivering: most potent mechanism of heat production

Dissipating-heat Mechanisms (core temperature is above the set point temperature)

1- decrease sympathetic activity in skin blood vessels

2- increase sympathetic cholinergic stimulation to the sweat glands

*Increase the hypothalamic set point temperature via pyrogens

*Mechanism:

Pyrogen -> increase interlukin-1 -> increase prostaglandins in ant. hypothalamus -> increase set point temperature

*Treatment: inhibiting prostaglandins synthesis by inhibiting cyclooxygenase enzyme (e.g. aspirin)

*Massive increase in the following in skeletal muscle:  a) metabolic rate

b) O2 consumption

c) heat production

*Heat-dissipating mechanisms can not keep up

*Caused by inhalation anesthetics