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 Myogenic theory:
▪ Initiated by stretch-induced vascular depolarization.
▪ High arterial pressure → stretches vessel wall → causes
reactive vascular constriction that reduces blood flow
nearly back to normal.
▪ Low arterial pressures → degree of stretch is less →
smooth muscle relaxes → reducing vascular resistance and
helping to return flow toward normal.
▪ Inherent to vascular smooth muscle; can occur in the
absence of neural or hormonal influences.
▪ Most pronounced in arterioles but can also be observed
in arteries, venules, veins, and even lymphatic vessels.
▪ Prevents excessive stretch of blood vessel when blood
pressure is increased.
Special Mechanisms Specific Tissues
▪ Kidneys:
o Tubuloglomerular feedback
▪ Macula densa – detects fluid composition in distal tubule;
causes constriction of afferent arterioles to reduce blood
flow and GFR.
▪ Brain:
o Increase in O2 and Co2 dilates cerebral vessels to wash out
excess CO2 or Hydrogen ion.
o Important because the level of excitability of the brain itself is
highly dependent on exact control of both CO2 concentration
and hydrogen ion concentration.
▪ Skin:
o Regulation of body temperature.
o Controlled largely by CNS through the sympathetic nerves.
o Skin blood flow:
o 3 ml/min/100 g of tissue in cool weather
o 7-8L/min in hot weather
ENDOTHELIAL-DERIVED RELAXING OR CONSTRICTING
FACTORS
▪ Nitric Oxide (NO)
o Vasodilator; most important of the endothelial-derived
relaxing factors.
o Lipophilic gas released in response to chemical and physical
stimuli; acts locally
o Half-life in blood: 6 secs.
o Nitric oxide synthase (NOS) enzymes
▪ Synthesize NO from arginine and oxygen and by reduction
of inorganic nitrate.
o Activates:
▪ Soluble guanylate cyclases:
• Converts cyclic guanosine triphosphate (cGTP) to cyclic
guanosine monophosphate (cGMP)
▪ cGMP-dependent protein kinase (PKG)
• Cause the blood vessels to relax
▪ Initiated by: Shear stress in endothelial wall
▪ Stimulated by: angiotensin II
▪ Chronic hypertension or atherosclerosis causes impaired NO
synthesis resulting to excessive vasoconstriction and worsening
of the hypertension and endothelial damage.
▪ Angina pectoris, Severe chest pain: nitroglycin, amyl nitrates
▪ cGMP specific phosphodiesterase-5 (PDE-5) inhibitor:
o prolong the actions of NO to cause vasodilation
o Used to treat erectile dysfunction.
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o Penile erection:
▪ Caused by parasympathetic nerve impulses through pelvic
nerves to the penis
▪ Neurotransmitters: acetylcholine and NO
▪ ENDOTHELIN
• Powerful vasoconstrictor released from damaged
endothelium
• Initiated by: damage to the endothelium
• Helps to prevent extensive bleeding from arteries.
• Drugs that block endothelin receptors have been used to treat
pulmonary hypertension.
▪ LONG-TERM CONTROL:
▪ Slow; over a period of days, weeks, or even months.
▪ Provide better control in proportion to the needs of the tissues.
▪ Due to an increase or decrease in the physical sizes and
numbers of actual blood vessels supplying the tissues.
▪ Important when metabolic demands of a tissue change.
MECHANISM OF LONG-TERM CONTROL:
Change in “Tissue Vascularity” or “Angiogenesis”
▪  metabolism in tissue for a prolonged period =  vascularity
▪  metabolism =  vascularity
▪ Therefore, the time required for long-term regulation to take
Role of Oxygen
▪ Retrolental fibroplasia
▪ Excess oxygen causes almost immediate cessation of new
vascular growth in the retina – when oxygen is lowered there
is tissue overgrowth that the retinal vessels grow out from the
retina into the eye’s vitreous humor and eventually cause
blindness
Vascular Endothelial Growth Factor or “Angiogenic
Factors”
▪ Increase growth of new blood vessels:
o Vascular endothelial growth factor (VEGF)
o Fibroblast growth factor
o Angiogenin
▪ Dissolution of vascular cells and disappearance of vessels:
o Peptides - block the growth of new blood vessels
▪ Angiostatin - a fragment of the protein plasminogen;
naturally occurring inhibitor of angiogenesis.
▪ Endostatin - derived from the breakdown of collagen type
XVII.
Development of Collateral Circulation
▪ Blockage of artery results to the development of a new vascular
channel around the blockage to allows partial resupply of blood
to the affected tissue.
HUMORAL CONTROL OF THE CIRCULATION
Vasoconstrictor Agents
▪ Norepinephrine and Epinephrine
o Vasoconstrictor hormone; Sympathetic stimulation
o Excites the heart and contracts the veins and arterioles via:
▪ Direct nerve stimulation
▪ Indirect effects of norepinephrine and/or epinephrine in
circulating blood
▪ Angiotensin II
o Vasoconstrictor; one millionth of a gram can increase the
arterial pressure 50 mm Hg or more.
o Effect: constrict small arterioles
o Plays an integral role in the regulation of arterial pressure
2
 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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