What is blood flow?
Amount of blood flowing through a tissue in a given time (ml/min)
Tissues usually regulate their own blood flow according to their own metabolic & functional needs
Why the blood flow is Vital?
Why not simply allow a very Large blood flow all the time through every tissue of the body?
To do this would require many times more blood flow than the heart can pump
What does blood flow regulation depend on?
tissue’s requirement
Blood flow to each tissue usually is
regulated at the minimal level that
will supply the tissue’s requirement
▪ No more , No less
Which organs have the highest/lowest percentage of cardiac output?
Highest-kidneys=22 // liver=27
Lowest-adrenal glands=0.5
What is the 2 Mechanisms of Blood Flow Control?
Acute/Long term
How Acute Mechanism control blood flow?
Achieved by rapid changes in local vasodilation or vasoconstriction
blood flow.of the
1-arterioles,
2-metarterioles,
3- precapillary sphincters,
occurring within seconds to minutes.
▪ To provide very rapid maintenance of appropriate local tissue
Acute control divided into 2 type.. and give ex of each
Intrinsic
Ex:
1- Myogenic regulation
2- Local chemical agents (Tissue metabolites – Endothelial products – Oxygen concentration)
3-Local temperature
Extrinsic
1-Neural (Autonomic)
▪2-Humoral (circulating hormones)
How Long term Mechanisms control the blood flow? Give ex
Due to ↑ and ↓ in the physical size and numbers of actual blood
vessels supplying the tissues.
Controlled changes in flow over a period of days, weeks, or even
months. ▪ Provide even better control of the flow in proportion to the needs
of the tissues.
1-Angiogenesis(the development of new blood vessels.)
2–Vascular remodeling
Acute Control of Local Blood Flow:(intrinsic):
Effect of tissue metabolism on local blood flow . . . ?
Effect of oxygen availability on local blood flow . . . ?
The Two major theories???
Increase in tissue metabolism leads to increase in blood flow.
Decrease in oxygen availability to tissues increase tissue blood flow.
Two major theories
1. Vasodilator theory
2. Oxygen lack or(demand) theory
Intrinsic : Local Agents – Tissue Metabolites
Dose all active cells release metabolites ?
What happen if there is an Increased in metabolite concentration?
1- yes
2-Increased metabolite concentration leads to
local arteriolar smooth muscle relaxation
- Vasodilatation increases local blood flow ▪
-Metabolites washed away ▪
- Metabolite concentration decreases ▪
- Vasodilation reverses and blood flow returns to
normal
Intrinsic : Local Agents – Oxygen response to what?
Response to hypoxia in systemic circulation is vasodilation
Intrinsic : Local Agents – Oxyge
Explain the Mechanism of systemic vasodilation?how can control blood flow??
– Hypoxia leads to drop in ATP availability in smooth muscle –K
ATP
-K atp channels open ( K+ efflux leading to hyperpolarization)
– Smooth muscle relaxation
Explain Mechanism of pulmonary vasoconstriction?
Endothelial factor increases smooth muscle sensitivity to Ca2+
(((vasoconstriction in respond to hypoxia Only in pulmonary not systemic))))
When Tissue Oxygen Conc. Can effect Blood Flow?
1- At high altitude
2-Carbon monoxide poisoning
• Poisons the ability of Hb to transport O 2
3-Pneumonia (dec O2 exch)
4- Cyanide poisoning
• Poisons ability of the tissues to use O2
Vasodilator Theory for Blood Flow Control
Where vasodilator substances form?
What is the cases that need vasodilator substances??
1-There is formation of vasodilator substances in the tissue cells and act
on pre-capillary sphincters, metarterioles, and arterioles.
2-
i. Greater rate of metabolism
ii. Less availability of O 2
iii. Nutrients to tissue ↓
What is the relationship between sphincters opening and requirements of the tissue for nutrition.
The number of precapillary sphincters that are open at any given time is roughly proportional to the requirements of thetissue for nutrition.
▪ Which metabolites cause vasodilation?
Increased local concentration of:
–1-Adenosine (cardiac muscle)
2– Carbon dioxide (skin, brain)
3– Potassium ions (skeletal muscle, brain)
4– Hydrogen ions (brain)
5– Histamine (injured tissue)
• Low local concentrations of Nutrients
1-glucose
2-thiamine
3-niacin
4- riboflavin
• Increased local temperature(direct vasodilator effect)
Oxygen Demand Theory for Local Blood Flow Control
What is the Role of Oxygen in Acute Local Blood Flow Regulation?
Oxygen required to cause vascular muscle contraction.
What happen if there is absence of adequate oxygen?
blood vessels simply relax and therefore naturally dilate.
What can cause local vasodilation.??
Increased utilization of oxygen in the tissues as a result of increased metabolism could decrease the availability of oxygen to the smooth muscle fibers in the local blood vessels causing local vasodilation.
Acute "Metabolic" control of local blood flow
Define Hyperemia ?
Increase in Blood Flow
What is the different b/w Active Hyperemia and Reactive Hyperemia??
Active Hyperemia: Increase in blood flow during a period of increased
activity
Reactive Hyperemia: Increase in blood flow after a period of
occlusion(blook) of flow
Give ex to each Active Hyperemia and Reactive Hyperemia??
▪ When any tissue becomes highly active, the rate of blood flow to the tissue increases.such as an
1-exercising muscle,
2-a GI gland during hypersecretory period
3- the brain during rapid mental activity
▪ 20-folds increase of blood flow to skeletal muscle during intense exercise
▪ When the blood supply to tissue is blocked for a few seconds to as long
an hour or more and than is unblocked, blood flow through the tissues
usually increases immediately to four to seven times.
▪ Lack of flow sets into motion all of those factors that cause vasodilation.
What is the role of Nutrients in Control of Local Blood Flow (Nutrient Demand Theory)
-When there is Lack of Glucose – local tissue vasodilation ▪ Deficiency of Amino acids and Fatty acid give similar effect
-Vitamin Deficiency
Role of Nutrients in Control of Local Blood Flow (Nutrient Demand Theory)
Give an ex about Vitamin Deficiency:
Beri Beri in which the patient has deficiencies of Vitamin B substances
(Thiamine, Niacin and Riboflavin)
▪ In their deficiency tissues become unable to take oxygen, decreased peripheral resistance causing vasodilatation.
▪ Peripheral Blood flow increases twofold to threefold.
What is the meaning of Autoregulation.?
The capacity of the tissues to regulate their own blood
In any tissue of the body, acute ↑ in B.P. causes
blood flow to ↑ .. BUT .. within less than 1 min
returns back to normal.
Within what range blood flow remain auto regulated?
B/w B.P. 70-175 mmHg
What is the 2 theory autoregulation ?
1. Metabolic theory of Autoregulation
2. Myogenic theory of Autoregulation
Define Metabolic Theory?
when BP Increases, the excess blood flow provides more O2 and nutrients to the tissue.
▪ Excess O2 cause blood vessels to constrict and the flow return back to normal despite increase pressure.
Define Myogenic Theory ?
Smooth muscles respond to stretch by contracting
▪ When high arterial pressure stretches the vessel, reactive vascular
constriction results, which reduces blood flow nearly back to normal.
What is the mechanism of Myogenic Theory ?
▪ Stretch-induced depolarization of vascular myocytes
– Stretch-sensitive ion channels
▪ Leads to opening of L-type Ca2+ channels
– Increases in intracellular [Ca2+]
– Contraction of myocytes
How can blood pressure effect Myogenic Mechanism?
When B.P. ↑ there is ↑ stretch of small blood vessels causes reactive
vascular constriction of the smooth muscle that reduces blood flow
nearly back to normal.
▪ When B.P. ↓ the degree of stretch of the vessel is less → smooth
muscle relaxes → reducing vascular resistance and helping to return
flow toward normal.
Special Mechanisms for Acute Blood Flow Control????
In Kidneys - Tubuloglomerular feedback mechanism
In brain tissue:
Skin blood flow
When microcirculation or microvascular B.F. increases endothelium derived
relaxing factor (nitric oxide) is released which causes dilation of larger B.V.
True or false
Long-term Regulation of Blood Flow More effective than acute mechanism
True
When we can consider long term regulation is more important than acute?
More important when the long-term metabolic demands of a tissue
changes.
Long-term local blood flow regulation occurs by changing the ……..
the degree of vascularity of tissues (size and number of vessels) within a few weeks to match the need of the tissue.
What is the most important stimulus for regulating tissue vascularity?
Oxygen
How can Angiogenic factors promote new vessel growth ??
by causing new vessels to sprout
from other small vessels.
Give an example of Angiogenic factors
.Vascular endothelial growth factor (VEGF)
▪ Fibroblast growth factor
▪ Platelet derived growth factor (PDGF)
▪ Angiogenin
What is the phenomena of long-term local blood flow regulation?
Development of Collateral Circulation
Define Development of Collateral Circulation?
When an artery or vein is blocked in any tissue of the body, a new vascular channel usually develops around the blockage and allows at least partial re supply of blood to affected tissue.
Humoral Control of the Circulation
Extrinsic : Circulating agents at physiological concentrations
Give ex of Vasoconstrictor agents?
i. Norepinephrine and Epinephrine
ii. Angiotensin II
iii. Vasopressin (ADH)
iv. Endothelin
Give an ex of Vasodilator Agents..
i. Bradykinin
ii. Histamine
iii. Serotonin
iv. Prostaglandins
v. Nitric oxide
Norepinephrine and Epinephrine
Increase in sympathetic tone → …….
Decrease in sympathetic tone → ……..
Increase in sympathetic tone → vasoconstriction
Decrease in sympathetic tone → vasodilation
T or F
Norepinephrine is more powerful vasoconstrictor than epinephrine.
What is the effect of sympathetic stimulation in epin and norepinephrine during stress or exercise??
During sympathetic stimulation e.g. in stress or exercise, norepinephrine
and epinephrine are released at nerve endings.
Sympathetic nerves also stimulates adrenal medullae which secrete both
norepinephrine & epinephrine.
Effect is ↑ excitability of heart and vasoconstriction of arterioles and
veins
Angiotensin II is Powerful vasodilator
False
Angiotensin II is Powerful vasoconstrictor
Where is the main effect of Angiotensin II ?
Main effect is on arterioles
What is the effect of angiotensin in arterials??
increases Total peripheral resistance so→ B.P. ↑
Endothelin consider as powerful vasoconstriction in……
damaged blood vessels
Where endothelin present??
present in endothelial cells of all blood vessels
In which case endothelin release??
when there is damage or crushing injury to blood vessels
Vasopressin (Antidiuretic hormone) More powerful vasoconstrictor than angiotensin II
Complete
Vasopressin (Antidiuretic hormone)Formed in the ……, transported and stored in the ……..
Formed in the hypothalamus, transported and stored in the posterior
pituitary gland
Why vasopressin called as anti diuretic hormone?.
hormone (ADH) is a hormone that helps your kidneys manage the amount of water in your body
Cause it responsible of Reabsorption of water from the renal tubules back into blood to control body fluid volume.
▪ Volume of urine is decreases hence called Antidiuretic hormone
What is the benefit of bradykinin??
Bradykinin causes both arteriolar
dilation and increases capillary
permeability → edema
▪ Bradykinin also helps to regulate
blood flow in the skin, in salivary
and GI glands.
What is the cases that require histamine release??
Histamine is released in almost every tissue of the body if the tissue becomes damaged or inflamed or is the subject of an allergic reaction.
from which cell histamine released?.
Derived from mast cells in the damaged tissues and basophils in the blood
What is the role of histamine in allergic reaction?.
Cause arteriolar dilation and increase capillary permeability=leaking of fluid =edema
increasing of which ion can cause vasoconstriction?.
↑ in Ca++ conc.→ stimulate smooth muscle contraction → Vasoconstriction
increasing of which ion can cause vasodilation?
↑ in K+ ion → inhibit smooth muscle contraction → Vasodilation
. ↑ in Mg++ ion → inhibit smooth muscle contraction → Powerful Vasodilation
What is the effect of decrease and increase of H ion con?.
↑ in H+ (acidosis or ↓ in pH) → dilation of the arterioles
▪ ↓ in H+ (alkalosis or ↑ in pH) → arteriolar constriction
How b f control when there is high con of co2??
Causes moderate vasodilation in most tissues but marked vasodilation in the-brain.
▪ CO2 in the blood also has an extremely powerful indirect effect on vasomotor center → sympathetic stimulation → vasoconstriction throughout the body
Anions (acetate and citrate) cause mild degrees of vasodilation.
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