TRANS Chapter Title: Local and Humoral Control of Tissue Blood Flow

Reference: Guyton & Hall Textbook of Medical Physiology

Local Control of Blood Flow in Response to Tissue Needs vasodilation

Specific tissue needs for blood flow: Delivery of oxygen to the ▪  BF =  carbon dioxide, lactic acid, and potassium ions
tissues. ▪ Adenosine:
1. Delivery of oxygen to tissues ▪ Important local vasodilator
2. Delivery of nutrients (glucose, amino 
acids, and fatty acids) ▪ Leaks out of the heart muscle cells to cause coronary
3. Removal of carbon dioxide. vasodilation
4. Removal of hydrogen ions. ▪ Provide coronary blood flow to supply the increased
5. Maintenance of proper concentrations of other ions in the nutrient demands of the active heart.
tissues. ▪  heart’s metabolism → causes  O2 utilization followed
6. Transport of various hormones and other substances to the by:
different tissues. 
 ▪  O2 concentration
▪ Degradation of adenosine triphosphate (ATP)
Variations in Blood Flow ▪ ATP  release of adenosine
▪ OXYGEN LACK THEORY (Nutrient lack theory)
▪ Absence of adequate oxygen = blood vessels would relax and
naturally dilate.
▪ Increased utilization of oxygen = decrease availability of
oxygen causes local vasodilation.
▪ Vasomotion - cyclical oopeningg and closing of precapillary
and metaarteriole sphincters.
▪ Enough O2 = muscle contract; sphincter close
▪  O2 = muscle relax; sphincter open
▪ Other Nutrients that Control Local Blood Flow
▪ Lack of glucose = tissue vasodilation
▪ Vitamin B deficiency disease (beriberi)
▪ Thiamine, niacin, and riboflavin
▪ Necessary for oxygen-induced phosphorylation

Acute “Metabolic” Control of Local Blood Flow

▪ Reactive Hyperemia:
o Block and unblock of blood flow in tissues results to 4-7x  in
blood flow for few seconds to hours depending on the duration
Muscle (heavy exercise): of the blockage.
▪ Metabolic activity 60x  and blood flow 20x  o Lack of flow sets into motion all of those factors that cause
▪ 16,000 ml/min in the body’s total muscle vascular bed vasodilation.
▪ 80 ml/min/100 g of muscle ▪ Active Hyperemia:
o Increase in local metabolism causes cells to devour tissue fluid
Mechanisms of Blood Flow Control: nutrients rapidly and also to release large quantities of
▪ ACUTE CONTROL: vasodilator substances to dilate the local blood vessels and,
▪ Occurs within seconds to minutes increase local blood flow.
▪ Provide very rapid maintenance of blood flow o The active tissue receives the additional nutrients required to
▪ Achieved by local vasodilation or vasoconstriction (arterioles, sustain its new level of function.
metarterioles, and precapillary sphincters). o Active hyperemia (skeletal muscle): 20x  local muscle blood
▪ Factors causing acute change in blood flow: flow during exercise
▪ Rate of tissue metabolism
▪  metabolism of up to 8x normal (skeletal muscle) =  “Metabolic” and “Myogenic” Mechanisms
BF 4x ▪ Autoregulation:
▪ Oxygen availability o Rapid increase in arterial pressure causes an immediate rise in
▪  tissue O2 =  BF blood flow.
▪ Causes of  O2: o But the blood flow returns almost to the normal level, even
▪ High altitude though the arterial pressure is kept elevated.
▪ Pneumonia ▪ Solid “acute” curve:
▪ Carbon monoxide poisoning o 70-175 mmHg srterial pressures – 20-30%  blood flow even
▪ Cyanide poisoning = 7x  though the arterial pressure increases 150%.
Basic theories for regulation of local blood flow: ▪ Mechanism of Autoregulation:
▪ VASODILATOR THEORY o Metabolic theory
▪  rate of metabolism or  availability of oxygen =  rate ▪ When arterial pressure increases, excess O2 and nutrients
of formation of vasodilator substances are provided to tissues and “washes out” the vasodilators
▪ Adenosine, carbon dioxide, adenosine phosphate compounds, released by tissues.
histamine, potassium ions, and hydrogen ions. ▪ Excess nutrients and decreased vasodilators causes the
▪  oxygen = adenosine and lactic acid release → blood vessels to constrict and the flow to return nearly to

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TRANS Chapter Title: Local and Humoral Control of Tissue Blood Flow

Reference: Guyton & Hall Textbook of Medical Physiology

normal despite the increased pressure. o Penile erection:

o Myogenic theory: ▪ Caused by parasympathetic nerve impulses through pelvic
▪ Initiated by stretch-induced vascular depolarization. nerves to the penis
▪ High arterial pressure → stretches vessel wall → causes ▪ Neurotransmitters: acetylcholine and NO
reactive vascular constriction that reduces blood flow ▪ ENDOTHELIN
nearly back to normal. • Powerful vasoconstrictor released from damaged
▪ Low arterial pressures → degree of stretch is less → endothelium
smooth muscle relaxes → reducing vascular resistance and • Initiated by: damage to the endothelium
helping to return flow toward normal. • Helps to prevent extensive bleeding from arteries.
▪ Inherent to vascular smooth muscle; can occur in the • Drugs that block endothelin receptors have been used to treat
absence of neural or hormonal influences. pulmonary hypertension.
▪ Most pronounced in arterioles but can also be observed
in arteries, venules, veins, and even lymphatic vessels. ▪ LONG-TERM CONTROL:
▪ Prevents excessive stretch of blood vessel when blood ▪ Slow; over a period of days, weeks, or even months.
pressure is increased. ▪ Provide better control in proportion to the needs of the tissues.
▪ Due to an increase or decrease in the physical sizes and
Special Mechanisms Specific Tissues numbers of actual blood vessels supplying the tissues.
▪ Kidneys: ▪ Important when metabolic demands of a tissue change.
o Tubuloglomerular feedback
▪ Macula densa – detects fluid composition in distal tubule; MECHANISM OF LONG-TERM CONTROL:
causes constriction of afferent arterioles to reduce blood Change in “Tissue Vascularity” or “Angiogenesis”
flow and GFR. ▪  metabolism in tissue for a prolonged period =  vascularity
▪ Brain: ▪  metabolism =  vascularity
o Increase in O2 and Co2 dilates cerebral vessels to wash out ▪ Therefore, the time required for long-term regulation to take
excess CO2 or Hydrogen ion. Role of Oxygen
o Important because the level of excitability of the brain itself is ▪ Retrolental fibroplasia
highly dependent on exact control of both CO2 concentration ▪ Excess oxygen causes almost immediate cessation of new
and hydrogen ion concentration. vascular growth in the retina – when oxygen is lowered there
▪ Skin: is tissue overgrowth that the retinal vessels grow out from the
o Regulation of body temperature. retina into the eye’s vitreous humor and eventually cause
o Controlled largely by CNS through the sympathetic nerves. blindness
o Skin blood flow: Vascular Endothelial Growth Factor or “Angiogenic
o 3 ml/min/100 g of tissue in cool weather Factors”
o 7-8L/min in hot weather ▪ Increase growth of new blood vessels:
o Vascular endothelial growth factor (VEGF)
ENDOTHELIAL-DERIVED RELAXING OR CONSTRICTING o Fibroblast growth factor
FACTORS o Angiogenin
▪ Nitric Oxide (NO) ▪ Dissolution of vascular cells and disappearance of vessels:
o Vasodilator; most important of the endothelial-derived o Peptides - block the growth of new blood vessels
relaxing factors. ▪ Angiostatin - a fragment of the protein plasminogen;
o Lipophilic gas released in response to chemical and physical naturally occurring inhibitor of angiogenesis.
stimuli; acts locally ▪ Endostatin - derived from the breakdown of collagen type
o Half-life in blood: 6 secs. XVII.
o Nitric oxide synthase (NOS) enzymes Development of Collateral Circulation
▪ Synthesize NO from arginine and oxygen and by reduction ▪ Blockage of artery results to the development of a new vascular
of inorganic nitrate. channel around the blockage to allows partial resupply of blood
o Activates: to the affected tissue.
▪ Soluble guanylate cyclases:
• Converts cyclic guanosine triphosphate (cGTP) to cyclic HUMORAL CONTROL OF THE CIRCULATION
guanosine monophosphate (cGMP) Vasoconstrictor Agents
▪ cGMP-dependent protein kinase (PKG) ▪ Norepinephrine and Epinephrine
• Cause the blood vessels to relax o Vasoconstrictor hormone; Sympathetic stimulation
▪ Initiated by: Shear stress in endothelial wall o Excites the heart and contracts the veins and arterioles via:
▪ Stimulated by: angiotensin II ▪ Direct nerve stimulation
▪ Chronic hypertension or atherosclerosis causes impaired NO ▪ Indirect effects of norepinephrine and/or epinephrine in
synthesis resulting to excessive vasoconstriction and worsening circulating blood
of the hypertension and endothelial damage. ▪ Angiotensin II
▪ Angina pectoris, Severe chest pain: nitroglycin, amyl nitrates o Vasoconstrictor; one millionth of a gram can increase the
▪ cGMP specific phosphodiesterase-5 (PDE-5) inhibitor: arterial pressure 50 mm Hg or more.
o prolong the actions of NO to cause vasodilation o Effect: constrict small arterioles
o Used to treat erectile dysfunction. o Plays an integral role in the regulation of arterial pressure

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 TRANS Chapter Title: Local and Humoral Control of Tissue Blood Flow

Reference: Guyton & Hall Textbook of Medical Physiology

o Normally acts on many of the arterioles of the body at the

same time to  total peripheral resistance →  arterial
pressure.
▪ Vasopressin (ADH)
o Vasoconstrictor; more powerful than angiotensin II
o Body’s most potent vascular constrictor substances
o Formed in nerve cells in the hypothalamus
o Transported downward by nerve axons to the posterior
pituitary gland, where it is secreted into the blood.
o Severe hemorrhage – 60mmHg  in arterial pressure
o Major function to  water reabsorption from renal tubules
back into the blood to help control body fluid volume.

Vasodilator Agents
▪ Bradykinin
o Powerful vasodilator; 1ug = 6x blood flow (local edema)
o Plays a normal role to help regulate blood flow in the skin,
salivary and gastrointestinal glands.
o Inactivated by: carboxypeptidase or converting enzyme,
o Kinins - small polypeptides that are split away by proteolytic
enzymes from alpha2-globulins in the plasma or tissue
fluids.
o Kallikrein:
▪ inactive form; activated by maceration of the blood, tissue
inflammation, or other similar chemical or physical effects on
the blood or tissues.
▪ Acts immediately on alpha2-globulin to release a kinin called
kallidin → converted by tissue enzymes into bradykinin.
▪ Destroyed by: powerful arteriolar dilation and increased
capillary permeability
▪ Histamine
o Powerful vasodilator on the arterioles.
o Increase capillary porosity → allowing leakage of both fluid
and plasma protein into the tissues.
o Released during tissue damage, inflammation and allergic
reaction.
o Derived from: mast cells (mostly) and basophils

Vascular Control by Ions and Other Chemical Factors

▪  calcium = vasoconstriction
▪  potassium = vasodilation
▪  magnesium = powerful vasodilation
▪  hydrogen ion (decrease in pH) = dilation of the arterioles
▪  hydrogen ion ( acidic pH) = arteriolar constriction
▪ Anions: acetate and citrate -- mild degrees of vasodilation
▪  carbon dioxide = moderate vasodilation (most tissues) to
marked vasodilation (brain)
o CO2 in blood: indirect effect to the sympathetic nervous
vasoconstrictor system--- widespread vasoconstriction
throughout the body.

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