Vascular Physiology Flashcards
What are the different types of blood vessels?
Aorta and Pulmonary artery Arteries Arterioles Capillaries Venules Veins
Describe the features of blood flow hydraulics
Blood flow will always be from an area of high pressure down to an area of low pressure.
As blood flows from the arteries, it goes down a pressure gradient.
As we get down to the veins and the venules we have a very low pressure.
What is the normal blood pressure in the different blood vessels?
Aortic pressure 120mmHg
Systemic pressure varies between 120-80mmHg
Pulmonary pressure varies between 25-10mmHg
Pressure in veins is virtually zero
Describe the structure of blood vessel walls
All vessels except capillaries have three layers:
- Tunica Intima- endothelial cells (barrier and secretions) on connective tissue basal lamina
- Tunica media- smooth muscle cells (circular- contraction) in elastin and collagen fibres
Internal and external elastic laminae = sheets of elastin at boundaries
- Tunica adventitia/ externa- connective tissue sheath to hold the vessel in place.
Large vessels have vasa vasorum- own vessels in adventitia; and sensory nerve fibres
What are the two different types of arteries?
Elastic arteries
Conduit or muscular arteries
Give examples of elastic arteries
Pulmonary artery
Aorta
Iliac artery
Describe the structural features of elastic arteries
1-2 cm diameter
Very distensible walls
Rich in elastin- protein more extensible than rubber
Expand to receive stroke volume
Recoil to produce continuous flow
Collagen in media to prevent over distension
Give examples of muscular arteries
Popliteal, radial, cerebral, coronary
Describe the structural features of muscular arteries
0.1-1cm Thick tunica media Lots of smooth muscle Low resistance Prevent vessel collapse at bends Rich autonomic nerve supply Contract or relax to regulate flow
Describe the features of arterioles
Resistance vessels
Large fall in pressure
Describe the functional features of elastic arteries
They are elastic and they recoil when they receive the flow of blood out of the heart.
Blood gets ejected into the aorta, the force of the blood causes the wall to expand.
As the pressure falls in the blood vessel, we will then see the recoil of that stretched artery. It acts as a pump in itself. It squeezes the blood into one part of the artery into the next.
Elastic arteries are able to expand as they have the protein elastin. There are lots of elastin fibres present in the artery walls.
The collagen fibres give them strength.
Describe the functional features of arterioles
These contain a large amount of smooth muscle, which gives them the capacity to have a lot of control to how the blood flow is directed through particular organs.
They supply the organs directly with blood.
They have a good nerve supply for control and so the blood flow can be regulated.
They are simpler structures compared to the arteries.
Describe the features of terminal arterioles
The terminal arterioles directly feed the capillaries.
Some are able to take part in gas exchange.
When the terminal arteriole is constricted, it will stop blood flow going through that particular capillary bed.
The reason that you get this vasomotion is because of the relaxation and constriction of the terminal arterioles.
Some terminal arteriole have a little muscle at the end of them called a pre capillary sphincter.
What blood vessels are capable of gas exchange
Terminal arterioles- oxygen Continuous capillaries Fenestrated capillaries Discontinuous capillaries Pericytic venules- fluid exchange
Where is the main area of gaseous exchange?
The main area of exchange in the capillaries.
The continuous capillaries is the typical capillary.
Discontinuous capillaries are in specialised tissues.
Depending on which capillaries are present depends on how much exchange can take place in each muscle.
What are the structural features of the capillaries?
4-7mm diameter Numerous- cells never more than 10-20mm Single layer of endothelial cells on basal lamina (connective tissue) Rapid diffusion Very large cross sectional area Modest resistance to flow for small size Slow velocity for exchange
What are the functional features of the capillaries?
There are millions of capillaries in our bodies.
Substances can be taken into the endothelial cell.
As well as substances passing from the blood into the tissues, we get substances moving in the opposite direction, from the tissues into the bloodstream.
The blood flow goes through the capillaries very slowly, this gives plenty of chances for the exchange to take place.
Describe the features of continuous capillaries
These are your general type of capillary.
Found in muscle, skin, lung, fat, connective tissue, nervous system
Circumference of 1-3 endothelial cells on basement membrane
Diffusion distance is very small
Pericytes envelop the capillary (provides nourishment to the endothelial cells)
Describe the features of fenestrated capillaries
Higher permeability
Specialist areas of fluid exchange
Renal glomerulus and tubules, glands, intestinal mucosa
Endothelium perforated by fenestrae or windows
Allow molecules to 0.1mm of extravascular space
Bridged by extremely thin membrane- fenestral diaphragm sandwiched between basement membrane and glycocalyx
Major pathway of water and metabolite transport
Signals (e.g. VEGF) induce fenestration
Describe the features of discontinuous (or sinusoidal) capillaries
Large gaps over 100nm wide Discontinuity in underlying basal lamina Permeable to plasma proteins Allow red cells to migrate between blood and tissues Bone marrow, spleen, liver
What is an arteriovenous anastomosis?
A vessel that shunts blood from an artery to a vein in order to bypass a capillary.
Describe the features of arteriovenous anastomoses?
Present in skin and nasal mucosa Wide shunt vessels 20-135µm Connect arterioles to venules Bypass capillaries Thick muscular walls Rich nervous innervation Temperature regulation
Describe the features of venules and veins
50- 200mm Venules
Thin wall with thin media
Limb veins have semilunar valves to prevent backflow of blood
Large central veins and and veins of head and neck have no valves
Low resistance
Low pressure 10-15 mmHg
Large number
Veins contain about 2/3 of blood volume- capacitance vessels
Distend or collapse easily- ‘reservoirs’
Vasoconstrictor nerve fibres to control reservoirs
What are the different types of vascular circuit?
Parallel circuits
- Most organ supplies arise separately from aorta
- Prevents loss of pressure
Series circuits
- Portal systems in series
- Get flow ‘second hand’ to transport substances
- Oxygen may be reduced
- Eg. Liver, kidney, brain
What is angiogenesis?
Capillary growth
When does angiogenesis occur?
Occurs in Prenatal and Postnatal development
How is angiogenesis measured?
Measured by incorporation of radioactive thymidine into DNA of endothelial cells using autoradiography
Capillary sprouts/ capillaries in stained tissue sections or electronmicrographs
When is angiogenesis seen in adult tissue?
Skeletal muscle following training
Skeletal muscle following chronic stimulation
Cardiac muscle following training
Cardiac muscle following bradycardial pacing (artificial slowing of heart)
High altitude exposure
Female reproductive system
When is angiogenesis seen in pathological conditions?
Healing of wounds and tissue regeneration
Vascular growth in diabetes mellitus
Vascular growth in psoriasis
Tumours
Retrolental Fibroplasia (disorganised growth of blood vessels) in the retina of premature babies
What are the different types of angiogenesis?
Sprouting angiogenesis
Longitudinal angiogenesis
Intussusepction
What occurs during sprouting angiogenesis?
Dissolving of basement membrane (membrane surrounding vessel) by proteases
Migration of endothelial cells into area outside of vessel
Modification of extracellular matrix
Mitosis (division) of endothelial cells at tip of sprout
Develop lumen
Under the control of growth factors
What occurs during longitudinal division?
Endothelial cells extend a ridge along lumen of existing vessels
Internally divide the vessel in two
Retain the initial orientation
What occurs during intussusception?
Pillar like structure invades from the outside surface
Recruits vessel wall cells and extracellular matrix plug
Invagination creates a hole in capillary
Main form during development
What growth factors are involved in angiogenesis?
Vascular Endothelial Growth Factor Placental Growth Factor - (involved in pathological angiogenesis) Angiopoietins - (modulate vessel development and remodelling) Nitric oxide Basic fibroblast growth factor (bFGF) Platelet derived growth factors Angiotensin II Monocyte chemotactic protein-1 Integrins Matrix metalloproteinases
What are the features of VEGF?
Vascular Endothelial Growth Factor (VEGF) is the most important growth factor
Involved in activity and pathological induced angiogenesis
Produced by endothelial cells, perivascular cells, and tissue cells eg skeletal muscle
Number of isoforms A-D: most potent is VEGF-A
Acts on endothelial cell receptor tyrosine kinases
Stimulates endothelial cell and smooth muscle cell proliferation and migration
What are the features of Nitric Oxide?
Mediates the effects of VEGF
Activation of VEGF receptors causes production of Nitric oxide
Nitric oxide thought to cause VEGF production
Nitric oxide produced in response to exercise thought to contribute towards angiogenesis
Which have more capillaries, slowly contracting postural muscles, or fast muscles?
Slowly contracting postural muscles
How can fast muscles be turned into slow muscles?
Long term stimulation of fast muscles at frequencies of slow muscles causes them to change to slow muscles:
Fast muscles of rabbits or rats stimulated at 10Hz for 8 hrs/day
Capillary growth seen after four days
After 28 days capillary density was doubled
Capillary sprouts occurs at bends
Loops of capillaries formed
How does blood flow affect capillary growth?
Increasing blood flow produces capillary growth
What is seen when a muscle undergoes training or long term stimulation?
More growth of capillaries is seen in the vicinity of fast glycolytic fibres
Why is more growth of capillaries is seen in the vicinity of fast glycolytic fibres in a muscle when it undergoes training or long term stimulation?
The velocity of blood flow increases more during contractions fast muscles than in the slow muscles.
There is more growth of capillaries closer to the fast glycolytic fibres since the velocity of blood flow increases more in these areas than close to the slow oxidative fibres.
How does ligation of the iliac artery affect capillary growth?
Ligation of iliac artery to restrict flow prevents capillary growth in skeletal muscle
How do mechanical factors affect angiogenesis?
Growth depends upon the tension to which blood vessels are subjected
Sprouting occurs at bends where there is more force
In tissue cultured endothelial cells if ‘contact inhibition’ is removed they proliferate
Stretching of cells produces proteases to digest basement membrane so sprout can form
Also intracellular signals used in proliferation- calcium, cAMP, growth factors
Thought that high shear stress (force of flow against vessel wall) produces high tension and produces the stimulus for growth
How do metabolic factors affect angiogenesis?
Thought that hypoxia (low oxygen) may be a stimulus for angiogenesis
Exercise induced angiogenesis is increased if blood flow is limited
Hypoxia-inducible factor (HIF) produced by intracellular degradation in low oxygen levels
HIF activates genes to cause capillary growth
May act through growth factors (eg.VEGF)
How does capillary growth differ in the heart?
Training induced capillary growth in the heart in younger individuals
Young rats treadmill trained show increased capillaries
Older rats treadmill trained show no increase
Athletic animals (hare, wild rats) have higher capillary density than sedentary animals (rabbit, domestic rat) but lower heart rate:
- Rabbits- bradycardial pacing to halve heart rate
- After 4 weeks show increased capillaries
- No other heart change apparent
Can also be used in hypertrophied hearts
What factors involved in the heart can affect vessel growth?
Bradycardia prolongs diastole duration to increase blood flow in coronary circulation
- Produces larger capillary diameters in diastole
- Wall tension is increased for longer
- Stretching of basement membrane produces endothelial distortion
- Bradycardia increases blood flow
Vasodilators given over long term led to capillary growth
Drugs increasing contraction force lead to capillary growth through disruption of basement membrane
Growth factors have been identified in heart
What is angiotherapy?
Use of angiogenic factors to initiate vessel growth
What are the applications for angiotherapy?
Treatment for:
- Peripheral vascular disease
- Coronary heart disease
Stem cell therapy- endothelial progenitor cells to encourage new vessel growth
Anti-angiogenic therapy in cancer- e.g inhibition of VEGF by Avastin improves survival in colorectal, breast and lung cancer when combined with chemotherapy
