blood flow (Cardiovascular physiology) physiology of blood vessels (blood pressure)

1. Local blood flow (Local control of blood flow)
© Prof. Dr. Rashid Mahmood 1
Prof. Dr. Rashid Mahmood
1. What are some of the specific needs of the tissues for blood flow?
2. Why not simply allow a very large blood flow all the time through
every tissue of the body, always enough to supply the tissue's
needs whether the activity of the tissue is little or great?
3. How blood flow to each tissue usually is regulated at the minimal
level that will supply the tissue's requirements- no more, no less?

2. © Prof. Dr. Rashid Mahmood 2
Introduction

3. Specific needs of the tissues for
blood flow?
© Prof. Dr. Rashid Mahmood 3
1. Delivery of oxygen to the tissues
2. Delivery of other nutrients, such as glucose,
amino acids, and fatty acids
3. Removal of carbon dioxide from the tissues
4. Removal of hydrogen ions from the tissues
5. Maintenance of proper concentrations of
other ions in the tissues, and
6. Transport of various hormones and other
substances to the different tissues
By controlling local blood flow in an exact way, the tissues
almost never suffer from oxygen and nutritional deficiency,
and yet the workload on the heart is kept at a minimum

4. Variations in Blood Flow in
Different Tissues and Organs
© Prof. Dr. Rashid Mahmood 4

5. Objectives
Goal/Aim: To understand the importance and
mechanism of Mechanism of Blood Flow Control
Specific Objectives: At the end of the lesson
student will be able to :
List the regulatory mechanisms of local control of
blood flow
Describe different factors involved in Acute control
of blood flow
Describe different factors involved in Long term of
control of blood flow
Describe the Humoral & Nervous control of local
circulation © Prof. Dr. Rashid Mahmood 5

6. Lesson content
Acute control of blood flow
Auto regulation
Hyperemia
Vasoconstriction
Vasodilation
Long term control
↑tissue vascularity
Collateral blood vessels
Humoral control
Nervous control© Prof. Dr. Rashid Mahmood 6

7. Objectives
Goal/Aim: To understand the importance and
mechanism of Mechanism of Blood Flow Control
Specific Objectives: At the end of the lesson
student will be able to :
1. List the regulatory mechanisms of local control of
blood flow
2. Describe different factors involved in Acute control
of blood flow
3. Describe different factors involved in Long term of
control of blood flow
4. Describe the Humoral & Nervous control of local
circulation
© Prof. Dr. Rashid Mahmood 7

8. Control of Blood Flow
Local Humoral Nervous
Acute
Long-
term
Special Areas
1.Kidney
2.Brain
3.Skin
4.Muscles
Endocrines
1.Epinephrine
2.Norepinephrine
3.Angiotensin I
4.ADH
Chemical factors
1.Prostaglandins
2.Bradykinin
3.Histamine
4.CO2
5.Osmolarity
Ions
1.H+
2.K+
3.Ca++
4.Mg++
5.Na+
© Prof. Dr. Rashid Mahmood 8
Endothelium-
Derived Factors
Sympathetic
Para-sympathetic

9. Objectives
Goal/Aim: To understand the importance and
mechanism of Mechanism of Blood Flow Control
Specific Objectives: At the end of the lesson
student will be able to :
 List the regulatory mechanisms of local control of
blood flow
2. Describe different factors involved in Acute control
of blood flow
3. Describe different factors involved in Long term of
control of blood flow
4. Describe the Humoral & Nervous control of local
circulation
© Prof. Dr. Rashid Mahmood 9

10. Acute Control of Blood Flow
↑ metabolism
1.Adenosine
compounds
2.Lactic acid
3.CO2
4.K+
5.H+
↓ O2
1.Adenosine
2.↑ demand
↓ nutrition
1.Glucose
2.Amino
acids
Autoregulation of blood Flow
during Changes in BP
Metabolic
theory
Myogenic
theory
© Prof. Dr. Rashid Mahmood 10
1. vasodilator theory
2. Oxygen lack theory
Roll of other nutrients
(Nutrient lack theory)
Metabolic Requirements

11. Blood flow is directly proportional to metabolic rate
© Prof. Dr. Rashid Mahmood 11
Acute Control of Blood Flow
1. Vasodilator theory
↑ metabolism
1.Adenosine
compounds
2.Lactic acid
3.CO2
4.K+
5.H+

12. © Prof. Dr. Rashid Mahmood 12
2. Oxygen lack theory(Nutrient lack theory)
Acute Control of Blood Flow
↓ O2
1.Adenosine
2.↑ demand
↓ nutrition
1.Glucose
2.Amino
acids

13. © Prof. Dr. Rashid Mahmood 13

14. Vasomotion
© Prof. Dr. Rashid Mahmood 14
Mechanism of Vasodilator theory and
Oxygen lack theory

15. Vasomotion
© Prof. Dr. Rashid Mahmood 15

16. Local feedback control of blood flow
(Control of precapillary sphincter)
© Prof. Dr. Rashid Mahmood 16

17. Assessment Q. 1
Name the two theories that explain
the Acute Control of Blood Flow in
order to meet the Metabolic
Requirements of the tissues.
© Prof. Dr. Rashid Mahmood 17
vasodilator theory
Oxygen lack theory

18. Hyperemia (↑ blood flow)
1. Reactive Hyperemia
When blood flow is
stopped for some
time
2. Active hYperemia
During active
metabolism
© Prof. Dr. Rashid Mahmood 18
Special Examples of “Acute Metabolic Control of Local Blood Flow”

19. Endothelium-Derived Factors
Endothelium-Derived Relaxing Factor
(EDRF) (Nitric Oxide) (NO)
Endothelium-Derived Constricting
Factor (Endothelin)
© Prof. Dr. Rashid Mahmood 19

20. Endothelium-Derived Relaxing
Factor (EDRF) (Nitric Oxide) (NO)
Released from healthy endothelial
cells in response to many physical
and chemical stimuli
Acts on larger vessels
© Prof. Dr. Rashid Mahmood 20

21. Mechanism of Synthesis of
Nitric Oxide
© Prof. Dr. Rashid Mahmood
21
1
2
3
4
5
6
7

22. © Prof. Dr. Rashid Mahmood 22
Shear stress NO cGMP
Relaxation
PDE-5
Degradation of cGMP
Chronic Hypertension Atherosclerosis
Damage to endothelial cells
-ve No
relaxation
Tissue damage

23. Endothelium-Derived
Constricting Factor (Endothelin)
A powerful vasoconstrictor
Released by damaged Endothelium e.g.
Crushing, and
Chemical injury
Function:
Prevention of bleeding
© Prof. Dr. Rashid Mahmood 23

24. Autoregulation of blood flow
Very quick
response
BP rise 75 to 170
causes only 30%
increase in Blood
flow
Two Mechanisms
(Theories)
1. Metabolic
mechanism
2. Myogenic
mechanism
© Prof. Dr. Rashid Mahmood 24

25. Summary of Mechanisms of
vasodilation in acute local control
Small vessels
Vasomotion
(pre-capillary
sphincter)
Metabolic
factors (micro
vessels)
Large vessels
EDRF(endothelial
derived relaxing
factor)
(nitric oxide)
© Prof. Dr. Rashid Mahmood 25

26. Assessment Q. 2
What is the effect of Chronic
Hypertension on release of Nitric
Oxide by the endothelial cells?
© Prof. Dr. Rashid Mahmood 26
Decreased secretion due to damage to
endothelial cells, as Nitric Oxide is released by
normal endothelium.

27. Objectives
Goal/Aim: To understand the importance and
mechanism of Mechanism of Blood Flow Control
Specific Objectives: At the end of the lesson
student will be able to :
 List the regulatory mechanisms of local control of
blood flow
 Describe different factors involved in Acute control
of blood flow
3. Describe different factors involved in Long term of
control of blood flow
4. Describe the Humoral & Nervous control of local
circulation
© Prof. Dr. Rashid Mahmood 27

28. Long-term control
Collateral Blood Vessels
↑Tissue Vascularity
Angiogenesis
Angiogenesis factors
released FROM
1.Ischemic tissues
2.Growing tissues
3.↑ Metabolism
Angiogenesis factors
include
1.VEGF (Vasculo-
Endothelial Growth Factor)
2.FGF (Fibroblast Growth
Factor)
3.Angiogenin
© Prof. Dr. Rashid Mahmood 28
Vascular Remodeling

29. Angiogenesis
Physical reconstruction of tissue
vasculature
Within days
Rapid in new growth tissues, like
neonates
Oxygen deficiency is a strong
stimulant
© Prof. Dr. Rashid Mahmood 29

30. Disappearance of blood vessels
when not in use
Angiostatin
Endostatin
Steroid hormones (Clinical use)
© Prof. Dr. Rashid Mahmood 30

31. © Prof. Dr. Rashid Mahmood 31
Vascular
Remodeling

32. Special phenomena of Long-Term
Local Blood Flow Regulation
© Prof. Dr. Rashid Mahmood 32
Vascularity Is Determined by Maximum
Blood Flow Need, Not by Average Need
after extra vascularity does develop, the extra blood vessels
normally remain mainly vasoconstricted unless required
Development of Collateral Circulation

33. Assessment Q. 3
Name any TWO Angiogenesis
factors.
© Prof. Dr. Rashid Mahmood 33
1. VEGF (Vasculo-Endothelial Growth Factor)
2. FGF (Fibroblast Growth Factor)
3. Angiogenin

34. Objectives
Goal/Aim: To understand the importance and
mechanism of Mechanism of Blood Flow Control
Specific Objectives: At the end of the lesson
student will be able to :
 List the regulatory mechanisms of local control of
blood flow
 Describe different factors involved in Acute control
of blood flow
 Describe different factors involved in Long term of
control of blood flow
4. Describe the Humoral & Nervous control of local
circulation
© Prof. Dr. Rashid Mahmood 34

35. Humoral Control of the
Circulation
Vasoconstrictor
Agents
Norepinephrine
and Epinephrine
Angiotensin II, &
Vasopressin
Vasodilator
Agents
Bradykinin
Histamine
Effects:
arteriolar dilation
↑ capillary
permeability
– Edema
© Prof. Dr. Rashid Mahmood 35

36. Bradykinin (a Kinin)
© Prof. Dr. Rashid Mahmood 36
inactive kallikrein
kallikrein
1. maceration of the blood
2. tissue inflammation
3. chemical or physical effects
alpha2-globulin
Releases
kallidin bradykinin
tissue enzymes

37. Inactivation of bradykinin
In few minutes
By carboxypeptidase or by
Converting Enzyme
© Prof. Dr. Rashid Mahmood 37

38. Histamine
Produced in almost every tissue
Produced by
Damage
Inflammation, and
Allergic reaction
Derived from
mast cells , and
basophils
© Prof. Dr. Rashid Mahmood 38

39. Nervous Control of Local Blood
Flow
Sympathetic:
Vasoconstriction
Exceptions:
– Coronary vessels
– Some vasodilator fibers to skeletal
muscles
Parasympathetic Stimulation:
Vasodilation
Indirect effect© Prof. Dr. Rashid Mahmood 39

40. Core knowledge Points (1/2)
1. local blood flow in an exact way, the
tissues almost never suffer from
oxygen and nutritional deficiency
2. Blood flow is directly proportional to
metabolic rate
3. Blood flow to the tissues is
automatically regulated in spite of
changes in blood pressure, within
physiological limits (Autoregulation)
4. Regulatory mechanisms include Local,
Humoral, & Nervous mechanisms© Prof. Dr. Rashid Mahmood 40

41. Core knowledge Points (2/2)
5. Different multiple factors are involved in
Acute control of blood flow, and Long term
control
6. Endothelium-Derived Relaxing and
contracting Factors play a key role in
autoregulation
7. Humoral control of local circulation
involves certain Endocrines , Ions, and
Chemical factors
8. Nervous control of blood flow involves
Sympathetic, and to some extent Para-
sympathetic nervous system
© Prof. Dr. Rashid Mahmood 41

42. Control of Blood Flow (Take Home Points)
1. Local
i. Acute
a. Control by tissue metabolism
I. Vasodilator theory
II. Oxygen lack theory (Nutrient lack theory)
III. Special Examples of Acute metabolic Control
a. Reactive Hyperemia
b. Active Hyperemia
b. Autoregulation of blood flow during changes in arterial Pressure
I. Metabolic mechanism
II. Myogenic mechanism
ii. Endothelium-Derived Factors
iii. Long-term
a. Change in Tissue vascularity
b. Collateral Circulation
c. Vascular Remodeling
iv. Special Areas (Kidney, Brain, Skin, Muscles)
2. Humoral
i. Endocrines
ii. Ions
iii. Chemical factors
3. Nervous
i. Sympathetic
ii. Para-sympathetic
42

43. Learning Resources
Guyton and Hall (Text book of physiology), 13th
Edition
Ganong (Text book of physiology), 24th Edition
Berne & Levy Principles of Physiology (Koeppen
BM), 6th Edition
Human Physiology Stuart Fox, 13th Edition
Human Physiology : from cells to system with
Power Lecture DVD Lauralee Sherwood, 9th
edition
Internet
© Prof. Dr. Rashid Mahmood
43

44. Next topic:
Regulation of blood pressure –I
Prior knowledge required for next lecture
Overview of the Circulation; Medical Physics
of Pressure, Flow, and Resistance
Vascular Distensibility and Functions of the
Arterial and Venous Systems
Local and Humoral Control of Blood Flow by
the Tissues
Nervous Regulation of the Circulation
Basic Physiology of autonomic nervous
system © Prof. Dr. Rashid Mahmood
44

45. World Book and Copyright Day (also known
as International Day of the Book)
(April 23rd
)
The things I want to know are in books; my
best friend is the man who’ll get me a book
to read (Abraham Lincoln)
The book you don’t read won’t help (Jim
Rohn)
I read a lot of obscure books and it is nice
to open a book (Bill Gates)
Finishing a good book is like leaving a
good friend (William Feather)
© Prof. Dr. Rashid Mahmood 45

46. Assessment Q. 4
1. What is the effect of Bradykinin and
Histamine on blood vessels in
addition to arteriolar dilation?
2. When the World Book and Copyright
Day is celebrated each year?
© Prof. Dr. Rashid Mahmood 46
Thanks
Questions/ Comments/Feedback
rashid.mahmood@rmi.edu.pk,
drrashid62@gmail.com