Circulatory and vascular system

• What are the 6 types of blood vessels?

  Elastic conducting arteries

  Muscular distributing arteries

  Arterioles

  Capillaries

  Venues

  Veins
• What are the three layers of a blood vessel?

  Tunica externa: connective tissue (collagen+elastin), nerves, fibroplasts, adipocytes, control of collapse, vasa-vasorum in some large vessel.

  Tunica media: Smooth muscle with connective tissue (strengthens the vessel), internal/external elastic lamina, sympathetic innervation, for blood pressure control.

  Tunica Intima: Thin, single layer, tight junctions to prevent leaks, releases vasoactive substances.
• What are the function of large arteries?

  Elastic, absorbs pressure generated by cardiac contractions to reduce peak systolic pressure and for better flow, narrow lumen, thick muscular wall, dilates in regulated manner.
• What are the function of small arteries?

  Resistance vessels, limited elasticity, contains smooth muscle, regulates blood pressure and flow through capillaries, diameter regulated by mediators released by inner lining endothelial cells.
• What are the two types of inner lining endothelial cells?

  Vasodilators: histamine, nitric oxide, prostaglandins, bdrakinin and adenosine.

  Vasoconstrictors: endothelia, thromboxane, noradrenalin (alpha), adrenalin (alpha).
• Factors of veins:

  Venules; narrow diameter and no tunica media

  Medium diameter veins; thin tunica media, few smooth muscle cells

  Larger diameter veins; thicker tunica externa; thicker tunica media

  Larger veins; valves for one way flow, muscle contraction aids venous return, varicose veins ate formed because of dysfunctional valves.
• What is the role of the arterioles when regulating blood flow?

  Tissue blood flow controlled by vasoconstriction/dilation of small arteries supplying the tissue

  Arterioles and their pre capillary sphincters control blood flow

  Smooth muscle contraction/relaxation of precapillary sphincter is regulated by a range of local (metabolic) and extrinsic (neural) mechanisms
• Parts of capillaries and its functions?

  Endothelium: single cell layer, controls fluid movement

  Continuous capillaries (most common)

  Finest rated capillaries (permeable/leaky)

  Discontinuous capillaries (completely breakdown, restart again) (sinusoids in lover/bone/spleen)
• Explain the blood flow in capillaries?

  Flow is slow allowing better gas and nutrient exchange

  Net loss of fluid to interstitial fluid (high pressure, blood leaks) leading to a fall in blood pressure

  Plasma proteins generate osmotic pressure

  Fluids form urine in the kidney and lymph elsewhere
• What is lymphatic vessels?

  Plasma-like fluid that leak from arterial ends of capillaries due to blood pressure

  Lymph capillaries are found in all tissues except CNS, bone marrow and epidermis

  Fluid enter tiny lymph capillaries and is returned to blood to prevent edema and help maintain normal blood volume and pressure

  Lymphatic fluid (WBC, no RBC)

  Lymph flows by lymph nodes, to the subclavian vein.
• What influences the vascular smooth muscle (myogenic tone)

  Local- endothelium derived substances (vasodilations nitric oxide, prostacyclin)

  (Vasoconstrictors endothelin thromboxane), substances released from surrounding tissue/cells

  Hormones-Adrenaline, acetylcholine, histamine, angiotensin

  Intracellular free calcium

  External factors like muscles squeezing blood vessels
• How does smooth muscle contract?

  Intracellular Ca2+ increases which initiates contraction

  Ca2+ combines with acid protein (calmodulin)

  Ca2+/Cal complex activates Myosin light chain kinase → phosphorylates 20 kDA light chain of myosin (the interaction is a regulated process, maintains smooth muscle tone)

  Light chain phosphates reverses the binding of myosin with actin → smooth muscle relaxation
• Flow chart of how smooth muscle relaxation works?

  Agonist (removed)

  Receptor (blocked)

  Reduces Ca2+ /Calmodulin

  MLCKinase enzyme (gets blocked)breaks Myosin into Myosin P is broken down

  MLCPhospotase enzyme (gets blocked) Myosin P back into Myosin

  Myosin P + Actin ——> Actin-Myosin P
• What is the most potent vasoconstrictor?

  The most potent vasoconstrictor (peptide)

  Formed from Big E in endothelial cells- cleaved by ET converting enzyme (ECE)

  Triggered by agonists (noradren, thrombin, AVP) stimulate receptor + hypoxia or ischaemia
• What are the three isoform?

  ET-1, ET-2, ET-3

  Stimulated by endotoxin, various cytokine and growth factors, adrenaline, hypoxia, low shear stress

  Inhibited by NO, PGE2, PG1, high shear stress

  Endothelin binds to two receptors ETa/ETb

  (G-protein coupled, ETa expressed on vsmc→vasoconstriction, ETa receptor antagonist used in treating pulmonary hypertension)
• What’s another highly potent vasoconstrictor?

  Angiotensin II

  Constricts cutaneous, splanchnic and renal vasculature

  Renin acts on angiotensinogen → and 1

  ACE converts ang 1 →ang 2

  Ang 2 actions are mediated via AT1 receptors
• How does Ca2+ and vascular relaxation work?

  Induced by:

  CAMP (cyclic adenosine mono phosphate)- stimulated PKA opens K (ATP) channels

  CGMP (cyclic guanosine mono phosphate)- stimulates PKG open K(ATP)/K Ca channels

  Both inhibits Ca 2+ influx via VOCCs

  Stimulates:

  SERCA (SR)

  PMCA (plasma membrane)

  Reduce sensitivity of contractile apparatus

  Increases MLC P sensitivity → less force

  Decreases MLC K

  CAMP + CGMP stimulates PKG (inhibits cross-bridge formation)