Arterioles

Critical closing pressure Irreversible shock in severe haemorrhage Importance of rapid volume replacement
Preferred order Blood Plasma Plasma expanders Saline

Capillaries
Exchange Short,(750mm), small diameter,(6-8mm) but many in parallel 75-80% are closed at rest Thin-walled (Laplace) Good for exchange but some vulnerability Variations in structure from Brain capillaries to liver sinusoids

Lipid-soluble diffusion and carrier mediated diffusion allowed

Glucose (Not HCO3- or H+) Glial endfoot

Blood-Brain-Barrier
Mitochondrion

extra protection for the brain cells against false signals junctions between the endothelial cells are much tighter cells themselves have enhanced enzyme activity (to destroy possible neurotransmitters (like adrenaline and nor-adrenaline) before they can get across to send confusing signals

 astrocytes, connective tissue cells of the brain, send processes which reinforce the barrier Known as the blood-brain barrier (NB important in HIV, BSE ?)

Sinusoids
liver, spleen and bone marrow- capillary vessels replaced by sinusoids lined with endothelial cells, but large gaps between the individual cells most tissues require that their walls be impermeable to proteins, essential for normal tissue fluid balance with sinusoids there is almost free exchange of protein, some exchange of cells for other tissues the only way back for proteins is lymphatics (q.v.)

Flow in capillaries, a special sort of flow

Poiseuille's formula Flow = P.r4/8l Might expect very high resistance as r very small However Many in parallel Bolus flow

Flow of blood, or plasma, through tubes of varying diameter

Flow of blood through tubes of different diameter gives lower apparent viscosity as tubes get smaller

Viscosity
resistance to flow mostly due to friction between the molecules of the liquid itself. Fluid flow in most systems in the body is streamline flow. Viscosity is a measure of the friction between the molecules in a solution Reduce friction between layers and reduce apparent viscosity

Fahreas-Lindquist effect. Rbc smaller diameter

Streamline flow: each line represents the velocity of flow at that point in the stream

Bolus flow: with no possibility of a differential rate of flow developing

between layers flow is uniform across the

stream and frictional energy loss is minimal

than most capillaries Rbcs line up and single file through lumen Like a piston Push a column of plasma in front of them Whole column of fluid moves together so all layers moving at the same speed Only frictional energy loss is between the vessel wall and the outer layer of plasma

Flow in the body- does the FahreasLindquist effect matter?

Venules, veins and volumes

Distribution of blood volume
60

50

Percentage of volume

40

30 Series1 20

10

0 Large arteries Arterioles Capillaries Venules and small veins Vessels Large veins Heart Pulmonary circulation

Veins
Variable reservoir Role in changing pressure Control of cardiac output? Valves

Great veins
Venae cavae and (to a lesser extent) pulmonary veins are sense organs! Passivity ensures that pressure within them depends on their degree of filling Stretch receptors in their walls, vital for body fluid volume control More later in these lectures and in next term kidney lectures

Cardiac Performance in the intact animal

CO=O2 consumed/(PV-PA O2 concentrations)

Measure oxygen consumption

Measure oxygen concentration in pulmonary arterial blood

Measure oxygen concentration in pulmonary venous blood

Stewart-Hamilton indicator dilution method

Cardiac Output(litres/min) = (Q/Cmean) x 60/t

C mg/l

T secs

Flow meters
Electromagnetic or ultrasonic Placed round vessels Problem with aorta constant friction and erosion Ultrasonic better than electromagnetic Needs less tight fit Can be external to body

echocardiography is used to measure the radius of the aorta

flow = area x velocity

velocity of blood moving through aorta calculated by doppler effect

per minute = cardiac output

Pulse pressure measurement

The pressure rises when blood is forced into the aorta The aorta stretches The more stretched the aorta the greater the rise of systolic over diastolic pressure In young people 2ml of blood causes 1mm Hg rise in pressure So stroke volume is 2ml x pulse pressure Cardiac output is SV x HR

Cardiac Output in Vivo

Get bigger cardiac output than by Starling alone
Intact animal Human 12-15 litres/min, Dog 67 litres/min

Would involve bigger rises in pressure in filling vessels Must be other mechanisms involved

Extending the range of the heart

CO = SV x HR SV varies from 70-120ml HR from 60-180 bpm (max HR 220 - age in years, a VERY rough guide!) Starling has largely fixed heart rate Extrinsic factors can change rate and, to a lesser degree, stroke volume

Right and left vagal branches innervate the SA node, A.V node and atria ONLY

Superior Cervical Ganglion

Stellate Ganglion

Both right and left cervical chains., via stellate ganglion, supply atria, nodes and ventricles. Superior. Middle and Inferior cardiac nerves from stellate receive contributions from higher thoracic ganglia

Chronotropic Adrenaline or noradrenaline

effect
Faster rise in iCa

the major effect of nor-adrenaline on the rate is at the sino-atrial node where it increases intracellular cAMP causing the opening of calcium channels sodium, and other ions, leak in through these channels and depolarise the cell. There is an increase in iCa

Cardiac parasympathetic innervation

cardiac branches of the vagus, innervate mainly the atria with very few reaching either ventricle. effects of vagal stimulation are therefore confined to changes in rate

Slower decline in iK

Chronotropic Acetylcholine Muscarinic

Decreased iCa

mechanism seems to be by a decrease in cAMP causing a decrease in the calcium channel current, and by a G-protein linked increase in the potassium permeability of the pacemaker cells, This opposes the normal depolarisation and so slows the heart

Inotropic effect of sympathetic

The action of the noradrenaline is -receptor mediated. A number of consequences follow the generation of cAMP after the receptor and noradrenaline combine. What the changes all do is make a greater force of contraction happen faster, which is just what you want.

(Adr) NAdr

N Adr receptor

Three phosphorylation steps by NAdr Troponin I

Ca2+ channel Phospholamban

Ca pumps

Adenylate cyclase

 Starling effect and the catecholamine effect do not use the same pathways. Interact very effectively Produce a family of curves (Sarnoff)

Starling and nerves

HR 60 HR 180 CO

The nerves just multiply the Starling effect

RAP

CO

important all the curves are steep in the normal HR 120 low range of RAPs. Curve switching long before the plateau is HR 90 reached Stabilise RAP. HR 72 To stabilise RAP the sympathetic tone to the heart varies with activity HR 60 of the body. Heart is always on the steep part of a function curve RAP Starling mechanism can then always match the outputs of the ventricles