Lecture 4: Histology and Biology of the Vascular System Flashcards
What is the gradient of blood flow?
Blood flow in the vasculature flows along a pressure gradient that gradually DECREASES
Cross section of aorta = 3 cm^2 …. SMALL
Cross section of capillary bed = 3000 cm^2 … LARGE
Where is blood flow fastest? Slowest?
Aorta
Gets slower as the individual vessels become progressively smaller but cross section gets collectively bigger
What is responsible for macrocirculation?
Arteries
Veins
What is responsible for microcirculation?
Arterioles
Capillaries
Venules
What is a tunica?
Coat or layer (intima, media, adventitia)
Applies to arteries/veins but not capillaries, which only have intima
Are lymphatics a circuit?
No, they are one way
In general, what is present in the tunica intima?
- ENDOTHELIAL CELLS
- basal lamina
- subendothelial loose connective tissue
- Internal elastic lamina (arteries and veins ONLY)
In general, what is present in the tunica media?
- Smooth muscle cells
- Elastic fibers (elastic art > musc art > veins)
- collagen
In general what is present in the tunica adventitia?
- External elastic lamina (arteries only)
- Smooth muscle cells (esp. larger veins)
- Loos connective tissue
- vasa vasorum
- nerves (nervi vascularis)
What is the source of basal lamina?
Whatever cell that it is attached to (ie endothelial cells)
What is the source of the internal elastic lamina?
Smooth muscle cells
What are the similarities between arteries and veins? Differences?
Similarities
i. have similar intima
ii. predominantely differentiated by features of media
iii. lesser differences in their adventitia
Differences
Arteries tend to have THICKER walls, relative to their luminal diameter than do corresponding veins
What is the only vessel that has external elastic lamina?
Arteries
What are elastic arteries? What is it composed of?
Helps propel blood during cardiac diastole to dampen difference between systolic and diastolic arterial pressure
Example: aorta and primary branches
Elastic fibers allow aorta to expand during systole, storing energy, which can then propel arterial blood downstream during ventricular diastole
“snap” back of fibers to relaxed means closure of A-V valves
What is the vasa vasorum?
A network of small blood vessels that supply the walls of large blood vessels
Vessels of vessels
What is the function of MUSCULAR arteries?
Control regional blood flow as needed
Regulated by varying luminal diameter and resistance to flow by contraction/relaxation
Controlled by autonomic nervous system and endothelium
What are the key characteristics of small arteries/arterioles?
Major determinant of arterial RESISTANCE to blood flow and therefore arterial blood pressure
Controls flow to microvascular bed
If you want to control local blood flow and BP, you turn to the arterioles ninja
How are the small arteries/arterioles regulated?
- autonomic nervous system
- angiotensin II
- endothelial factors
i. NO
ii. endothelin
iii. Prostacyclin - chemical environment including O2, CO2, pH, etc.
At what point do the vessels stop having 3 layers?
Capillaries
What are the characteristics of the capillaries?
Responsible for fluid, gas, electrolyte and small molecule exchange between blood and tissues
Comprised of very thin endothelial cells with a basal lamina
Pericytes may surround capillaries
Lacks media and adventitia!
What are pericytes?
Contractile cells that wrap around endothelial cells of capillaries
Aka Rouget or mural cells
What are the mechanisms of exchange between capillary lumen and extravascular space?
- Passive diffusion across the membranes and cytoplasm
- Active transport across membranes via pinocytic vesicles (w/ or w/o receptors)
- Passage between adjacent endothelial cells
What is the function of venules?
Controls permeability and leukocyte emigration
What are the key characteristics of venules?
Capacitance vessels readily distend and can store variable volume of blood
Site of egress of inflammatory cells from blood to tissues
What are the function of venous valves?
Endothelial covered semi-lunar flaps of INTIMA that protrude into venous lumen in direction of forward flow
What are the key characteristics of veins?
Tend to have thinner walls, esp media, and larger lumen compared to arteries
Have less muscle and elastic fibers in media
More easily stretched so can be capacitance (or
Storage) vessels for blood volume
have SEMILUNAR valves that prevent backflow
What are the three kinds of capillaries?
- Continuous capillaries
- Fenestrated capillaries
- Discontinuous capillaries
What are continuous capillaries?
Lined by complete layer of endothelial cells with tight junctions and COMPLETE basal lamina
Transport takes place across the endothelial cells by diffusion or via pinocytotic vesciles
Most COMMON type of capillary
What are fenestrated capillaries?
Endothelial cells with pores w/ or w/o a diaphragm
Basal lamina is CONTINUOUS
Pore diaphragm fenestrated capillaries in gall bladder, intestine, endocrine and renal tubules
NO DIAPHRAGMS in fenestra are seen in RENAL GLOMERULI
What are discontinuous capillaries?
Incomplete endothelial lining + basal lamina Holes in cytoplasm and basal lamina E.g. sinusoids in spleen Most permeable capillary structures Guarded by Kupfer cells in the liver
Where do you see discontinuous capillaries?
Liver
Spleen
What are sinusoids?
Larger diameter capillaries with sinuous (sinusoidal) profiles
Associated with DISCONTINUOUS ENDOTHELIUM
e.g. liver sinusoids
What are the exceptions to the usual microcirculation?
- Portal ARTERIAL circulation
e. g. renal circulation (2 sets of capillaries) - Portal VENOUS circulation
e. g. hepatic portal and hypophyseal portal - Hypothalamic/anterior pituitary
What is the purpose of different aspects of macro/microcirculation?
Elastic arteries = CONDUCTANCE (propels blood during ventricular diastole)
Muscular arteries = regional distribution of blood flow
Small arteries/arterioles = RESISTANCE (BP and local blood flow)
Capillaries = exchange
Venules = immune cell migration
Veins = CAPACITANCE (accommodate increased intravascular volume
What are the four key features of vascular endothelial biology and function? (Starred)
- Anti-thrombotic/prothrombotic properties
- Exchange of fluids, gases and solutes, etc.
- Modulation of inflammatory cell migration
- Modulation of vascular smooth muscle contractility
How do endothelial cells act to induce thrombosis?
- reduced prostacyclin and thrombomodulin
- increased von Willebrand factor (factor VIII) exposure
Endothelials cells become prothrombotic with stasis (lack of movement of legs, etc.)
What is factor VIII?
Von willebrand factor
Where are vWF synthesized? Stored?
Endothelial cells
Stored in cytoplasm by Weibel-Palade bodies (W-P bodies)
What is Prostacyclin?
A prostaglandin produced in the walls of blood vessels that acts as a VASODILATOR and INHIBITS platelet aggregation
What is thrombomodulin?
Integral membrane protein that is a cofactor of thrombin
REDUCES coagulation by turning thrombin into an anticoagulant enzyme
What modulates inflammatory cell migration?
Expresses E-selectins and ICAMs (immunoglobulin cell adhesion molecules) that latch onto to circulating leukocytes
What modulates vascular smooth muscle contractility?
Endothelial cells produce molecules that can either vasodilate or vasoconstrict Vasodilators i. NO ii. Prostacyclin iii. endothelin (if it acts INDIRECTLY) Vasoconstrictors i. endothelin (if it acts DIRECTLY)
What are key features of vascular smooth muscle?
Always in a constant state of tension
Requires very little motion
Classified as a tonic smooth muscle
Depends on constant sympathetic stimulation
Can proliferate and MIGRATE into the intima in response to stimuli
What are the differences between smooth and skeletal muscle?
Smooth muscle has NO sarcomeres, no T tubules and no Troponin
Multiple triggers of contraction
Functions can be modulated
Can proliferate and migrate
Actin-myosin linkage for smooth muscle can maintain tension with little expenditure of energy, LATCH STATE
Thin filaments are attached to DENSE BODIES in either the cytoplasm of plasma membranes
-attachment to dense bodies mediated by desmin and vimentin
What are dense bodies of smooth muscle?
Composed of alpha actin Bodies that anchor THIN filaments of smooth muscle either in cytoplasm or plasma membranes Attachment set by intermediate filaments i. desmin ii. vimentin
What is the structure of myosin in smooth muscle?
Has 2 heads, each with actin binding site
Each side of myosin filament can bind to actin filament with OPPOSITE POLARITY
Higher proportion of Actin to myosin than in skeletal muscle
What is the latch state?
The state in smooth muscle in which there is tension maintained for a prolonged period with little energy expenditure
Does not require further stimulation
What is the significance of the lack of organized sarcomeres in smooth muscles?
Possibility of interaction of myosin with multiple actin of differing polarity and location allows vascular smooth muscle to undergo
i. greater degrees of contraction
ii. maintain maximal contractile force at multiple different lengths
Smooth muscle = side polarity while skeletal muscle = end polarity
What are the control mechanisms for contraction of vascular smooth muscle?
1. Increased intracellular calcium Derived from extracellular space or ER Increased calmodulin AP can open ENaC in plasma membrane to allow for influx of extracellular calcium 2. Can be triggered by chemical mediators such as i. norepinephrine ii. angiotensin II iii. endothelin iv. vasopressin v. thromboxane A2 Binding of chemical mediators activates phospholipase C and produces IP3 which then opens calcium channels 3. Can also be triggered by STRETCH
What is the MoA of smooth muscle contraction?
Phosphorylation of myosin by MLC KINASE
MLC kinase activated by increased Ca (which is activated by AP)
What is the MoA of smooth muscle relaxation?
Dephosphorylation of myosin by MLC PHOSPHATASE
How does smooth muscle relax?
1. reduction of intracellular calcium via ATP dependent Ca pumps
2. stimulation of GPCR to increase adenyl cyclase and cAMP which increase Ca efflux
3. At any given level of intracellular calcium, NO causes increased cGMP, which then increase phophotases
What is cGMP broken down by?
Phosphodiesterase
So more phosphodiesterase, less vasodilation
What is the structure of the myosin molecule?
- Regulatory light chain
- Essential light chain
- Head
What does calmodulin do?
Activates myosin light chain kinase
In context of smooth muscle
Ca-Calmodulin complex activates the light chain
What are the non-contractile functions of vascular smooth muscle?
- collagen secretion (type IV, I and III)
- elastin secretion (internal elastic fiber for instance)
- ECM components like proteoglycans and glycoproteins
- can contribute to the formation of the atherosclerotic plaque
What are the characteristics of lymphatics?
Delicate vascular structures that drain excess EXTRAcellular fluid out of tissues into systemic veins
One way flow (presence of valves) so it is not a circuit
No internal pump so depends on external compression
Where are lymphatics not found?
In the CNS, cartilage, bone, bone marrow, thymus, placenta, cornea, teeth and fingernails
What is the function of the lymphatics?
Drain extracellular fluid from most tissues and transport FATS
Also a CONDUIT for APCs and travel of LYMPHOCYTES to target tissue
What does chylous mean?
Description of the OPAQUE color seen in the usually clear lymph after a high fat meal
What is the course of lymphatics?
Extravascular space lymphatics lymph nodes thoracic duct and right lymphatic duct left and right brachiocephalic veins
What is contained in lymphatics?
Chylomicrons
Proteins
APCs
What are lymphangions?
Segments of the lymphatics that are divided by valves
What diseases may present in elastic/muscular arteries?
- Atherosclerosis
- aneurysms
- thromboemboli (systemic arterial, aortitis, arteritis)
What disease may present in small arteries and arterioles?
Arteritis (polyarteritis nodosa)
Arteriolosclerosis
Microvasculitis (Wegener granulomatosis)
What disease may present in capillaries?
Capillaritis (Goodpasture syndrome)
Microvasculitis
Role in acute inflammation
What disease may present in venules?
Microvasculitis
What disease may present in veins?
Varicose veins
Venous thrombosis
Thromboemboli
What disease may present in lymphatics?
Lymphedema
