Circulatory systemWilliam Harvey• Heart- pump• Arteries- efferenttransport, pulsedampener• Capillaries- exchange• Veins – afferent transport• Lymphatics- return ofextracellular fluid to bloodvascular systemAndreas VesaliusDe Humani Corporis Fabrica, 1543
An Anatomical DisputationOn The Movement Of TheHeart And Blood InAnimals) -William Harvey,1628http://www.rcplondon.ac.uk/heritage/harvey/exhib_harvey_demotu.htm
Demonstration of venous valves byWilliam Harvey.•When the upper arm is bandaged,valves show up as ‘bumps’•If a finger is pressed along the vein inthe direction leading from the heart,the vein is emptied of blood•Valves prevent blood from flowing‘backwards’ away from the hearthttp://www.rcplondon.ac.uk/heritage/harvey/exhib_harvey_demotu.htm
William Harvey’s discovery• Old view- blood produced in liver, Galen, A.D.190.• Harvey, 1628 How is the heart involved in circulation? How does blood circulate throughout the body?• Demonstrated that heart pumps during systole• Left side of heart pumps to body, right to lungs• Blood recirculates• Marcello Malpighi• Discovered capillarieshttp://www.rcplondon.ac.uk/heritage/harvey/exhib_harvey_demotu.htm
Organization of blood vessel• Tunica intima Endothelial cells Subendothelial layer Internal elastic membrane (disappears duringvasodilation)• Tunica media Smooth muscle Elastic fibers Collagen type III• Tunica adventitia Collagen fibers Vasa vasorum
Figure 11—11.Cross sections ofsmall arteries. A:The elastic laminais not stained and isseen as a pallidlamina of scallopedappearance justbelow theendothelium(arrowhead).Mediummagnification. B: Asmall artery with adistinctly stainedinternal elasticlamina(arrowhead). Froma preparation of thelate GeorgeGomori. Lowmagnification.
Figure 11—9. Crosssection through a smallartery and itsaccompanying muscularvein. Because ofvasodilatation, thearteriole is unusuallyfilled with blood. At thisstage the internal elasticlamina is notdistinguished. Manyother small arterialbranches and capillariescan be seen in thesurrounding connectivetissue. Pararosaniline—toluidine blue (PT) stain.Medium magnification.
Capillaries• Single endothelial cell layer• Endothelial cells rolled into tubes• Endothelial cells held together by tightjunctions, gap junctions- these determinethe extent of the capillary permeability• Venules are the leakiest vessels• Pericytes- mesenchymal cells thatsurround endothelial cells, contain actin,myosin, tropomyosin
Capillary formation from endotheiial cells in vitro.Folkman J, Haudenschild C. Angiogenesis in vitro. Nature. 1980 288(5791):551-6
angiogenesis• Formation of new blood vessels• vascular endothelial growth factor(VEGF)Shortage of oxygen causes increase levels ofhypoxia-inducible factor 1 (HIF-1)HIF-1 stimulates transcription of VEGFVEGF acts on endothelial cells
© 2002 by Bruce Alberts, Alexander Johnson, Julian Lewis, Martin Raff, Keith Roberts, and Peter Walter.
Four types of capillaries• Continuous capillaries Muscle, skin, exocrine glands No pores or fenestrae Pinocytotic vessels (except in CNS)
Figure 11—14. Electron micrograph of a transverse section of a continuous capillary.Note the nucleus (N) and the junctions between neighboring cells (arrowheads).Numerous pinocytotic vesicles are evident (small arrows).
Four types of capillaries• Fenestrated capillariesLarge pores (80 nm)Pores covered by an operculum that is thinnerthan plasma membraneBasal lamina is continuousGI tract, kidney, endocrine gland
Figure 11—15. A fenestrated capillary in the kidney. Arrows indicatefenestrae closed by diaphragms.
Figure 11—16. Schematic representation of a longitudinal view of a fenestratedcapillary showing its hydrophilic transporting system represented by pinocytoticvesicles (1) and fenestrae (2). Observe that fenestrae are obliterated by diaphragms(arrows) whose chemical composition is still unknown. N, nucleus; BM, basementmembrane.
Four types of capillaries• Special fenestrated capillariesNo operculum over poresKidney glomerulus• Sinusoidal capillariesLarge diameterDesigned for slow exchangeFenestrated, basal lamina is discontinuouspituitary, liver, spleen, bone marrow
http://education.vetmed.vt.edu/Curriculum/VM8054/Labs/Lab12b/IMAGES/URL27.jpgSpecialfenestratedcapillary inglomerulus ofnephron
Factors affecting microcirculation• Tightness of the intercellular junctionscapillarypermeabilityChemicals such as histamine and bradykinincan loosen these junctions• Biochemical modulation ofvasoconstriction and vasodilation
Methylxanthines• Eg. Caffeine• Block phosphodiesterase activity, increasecAMP Only occurs at very high levels of caffeine• Block adenosine receptors Most physiologically relevant• Can alter cerebral blood flow Adenosine dilates cerebral and coronary bloodvessels• Direct effects on brain motor pathways
CaffeineadenosineCaffeine•Binds to adenosine receptors and blocks them•Binds to phosphodiesterase and prevents it from converting cAMP to ATPhttp://www.bmrb.wisc.edu/metabolomics/standards/caffeine/lit/9684.png
Cyclic AMPPhosphodiesterase breaksPhosphate ester bonds in cAMPATPAMP
Athero- and arteriosclerosis• Arteriosclerosis Hardening of the arterial walls regardless of the cause• Atherosclerosis Development of lipid deposits in and around T. intima Kills one-half of all Americans• 2/3- coronary artery thrombosis• 1/3- thrombosis in other arteries
Stress and heart attacks• Med War. 1993 Jan-Mar;9(1):40-4.Related Articles, LinksAcute cardiac effects of 'SCUD' missile attacks on a civilian population.Hart J, Weingarten MA, Druckman A, Feldman Z, Shay A.Hasharon Hospital, Golda Medical Center, Petah-Tiqva, Israel.The 'SCUD' raids on Israel during the Gulf War afforded a rare opportunity to examine the effect of massacute fear on the cardiac health of the general population. Press reports suggested an alarming rise incardiac deaths during the first missile raids. In order to ascertain this statement, we examined theEmergency Room records of a community hospital in the affected area and all the death certificates inthe local region. The periods studied were from 1 January to 28 February 1991, and the equivalentweeks in 1990. The Emergency Room records showed that there was an increased rate of cardiaccomplaints throughout the war, most marked during the first week. However, this was not accompaniedby an increased cardiac mortality, either in the hospital or in the region as a whole, except during the firstweek. A similar increase in cardiac mortality occurred during the same week the previous year. Theincreased incidence of acute cardiac events during the first week of the war was probably a coincidence,and not a direct consequence of mass fear. Panic, occasioned by press reports, may have led to a lowerthreshold of referral which persisted throughout the war.
Heart• Endocardium Analagous to tunica intima and continuous with it Subendocardium• Blood vessels, Purkinje fibers• Myocardium Similar to tunica medium Impulse conducting cells, ie. Purkinje cells Contracting cells• Epicardium Visceral pericardium