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33 Cards in this Set

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How does cigarette smoking cause heart disease?
- Nicotine increases the amount of work that the heart has to do
- Chemicals from the cigarettes also attack and damage endothelium which is the first step in heart disease
→ makes it easier to get heart disease
Why is the arterial blood supply at such a high pressure compared with the venous blood supply?
- High pressure needed to overcome systemic resistance
- Also need to raise the blood to the level of the brain, requiring considerable force
What is the average stroke volume at rest?
About 70ml of blood per beat
What is the typical cardiac output at rest?
Approx. 5 litres of blood per minute
What are the roles of the systemic and pulmonary circulations?
- Systemic = flow serves to supply cells with their metabolic needs by exchange between the blood and the metabolising cells
- The pulmonary circulation has the role of acquiring oxygen and excreting carbon dioxide in appropriate amounts, by exchange between blood and the gas in the lungs.
How does the main part of exchange occur across capillaries?
Via diffusion
What factors will determine the rate of transfor of water and solute through the capillary wall and give the equation that combines these
1. The area (A) available for exchange - essentially the capillary density
2. Permeability (P)
→ How readily the substance moves through the endothelium
→ The path length to or from the metabolising cell.
3. The concentration gradient (Ci-Co) down which movement occurs

Summarised by Fick's Law:
J = P.A.(Ci-Co)
Describe how the permeability of the capillary wall may be determined by the nature of the molecules involved
Depends largely on the molecules involved:
- Lipid soluble molecules, which include O2 and CO2, diffuse easily through capillary cell membranes
- Hydrophilic molecules travel through pores, often through a paracelular route. The larger the molecule the greater the resistance to transfer
- Molecules whose molecular mass >60kD are not transferred and many plasma proteins are retained in the circulation - important in the equilibrium between plasma and the interstitial fluid
Describe how path length may be important in determining the rate of diffusion of molecules through the capillary walls
- Substances diffusing out of capillary beds must traverse a path through interstitial fluid between the capillary wall and the metabolising cell
- The length depends on the capillary density
- An increase length will mean that the molecules must travel further and thus may not reach necessary cells
- This is particularly important in oedema = increase volume of interstitial fluid jeopardises the supply of metabolites to cells and can cause necrosis
Give 2 factors that may affect the size of the gradient of molecules across the capillary wall
1. How rapidly the tissues are using the substances being delivered in the blood = metabolic rate
2. How rapidly the blood flows through the tissues = blood flow
Why is rate of flow of blood important in defining rate of capillary transfer?
- The rate of flow must be adjusted to optimise delivery to and removal of substances from tissues
- If the flow is too rapid, there may not be time for exchange
- If the flow is too slow, the concentration gradient will be dissipated as transfer will largely occur at the beginning of the capillary so that there will be no gradient further down the capillary
- For many small, highly diffusible substances, the gradient is dissipated along the whole length of the capillary
- Transfer then becomes flow limited
What is the most important factor in determining the rate of transfer in capillaries?
- Concentration gradient
→ the delivery of many metabolically important materials is limited by the rate of flow
→ Metabolic need is a major physiological mechanism for regulating flow and optimising transfer (i.e. maintain the right flow of blood for the prevailing level of metabolic activity)
- Generally, area, and for small molecules, diffusion resistance, are not limiting factors.
What are the 2 major roles of capillaries?
1. Permits the exchange of nutrients and metabolites between the blood stream and metabolising tissues by diffusion
2. Determines the equilibrium between the plasma and the interstitial fluid
What are the forces governing the development of the equilibrium of interstitial fluid and plasma across the capillary bed?
- Governed by Starling forces
- Loss of fluid from the plasma due to hydrostatic pressure is opposed by reabsorption of fluid into plasma, owing to colloid osmotic pressure (oncotic pressure)
- Hydrostatic pressure of the blood at the arteriolar end is 37 mmHg
- Hydrostatic pressure of the blood at the venous end is 17 mmHg
- Hydrostatic pressure of the interstitial fluid is 0 mmHg, so that hydrostatic pressure forces fluid out of the plasma across capillary walls
- Impermeance of plasma proteins generates an oncotic pressure of 25 mmHg, which draws fluid back into the capillaries from the interstitial spaces
- The filtration pressure = hydrostatic pressure - oncotic pressure
- At the arterial end, the hydrostatic pressure is greater that the oncotic pressure, and there is net filtration
- At the veonus end, the oncotic pressure is greater than the hydrostatic pressure, and there is net reabsorption
- In the middle an equilibrium is met where these are balanced
Give 3 different causes that may disrupt the equilibrium between the interstitial fluid and the plasma
1. Increase in hydrostatic pressure will force fluid into the interstitial space. Oedema will result if there is an accumulation of fluid in this space
2. In liver disease, renal disease or severe starvation, plasma protein levels fall, decreasing oncotic pressure. This will also drive fluid into the interstitium , leading to oedema
- Capillaries become more permeable to protein when damaged, causing a decrease in oncotic pressure, leading to oedema e.g. in the swelling of a sprained joint
Describe capillary transport mechanisms
- Exchange of solutes generally occurs by diffusion down concentration gradients
- Processes involved include:
→ diffusion through the endothelial cell membrane = lipid-soluble substances e.g. O2 and CO2
→ Diffusion through the pores and fenestrations in the cell membrane = water soluble substances e.g. water, glucose, amino acids
→ Active transport by transcytotic vesicles = some proteins
Describe the distribution of blood flow to the brain, heart, kidney, gut, skeletal muscle and skin
- Brain = the metabolic needs of the brain are constant and can be met by a flow of 0.5ml/min/g. The brain is extremely intolerant of flow interruption
- Heart = at rest the heart needs 0.9ml/min/g but if it has to work hard this can increase four-fold. The heart is extremely intolerant of inadequate flow
- Kidney = requires a high constant blood flow to maintain its function, though most flow is not nutritive
- Gut (and liver) = at rest receives 1ml/min/g. Digestion of a meal generates a substantial increase in flow. Short term flow reduction tolerable
- Skeletal muscle = metabolic needs very variable. At rest flow needs ~0.03ml/min/g, which may rise up to 6.0ml/min/g in exercise, but this may not reach metabolic needs. Muscles can survive a degree of anabolic metabolism.
- Skin = not metabolically very active and may be supported by 0.03ml/min/g, though flow may increase to 0.1ml/min/g for thermoregulation
Describe the 3 aims of the cardiovascular system
1. Deliver between 5 and 25 l/min of blood to the body
2. Maintain a blood flow of 750 ml/min to the brain at all times
3. Maintain blood flow to the heart and kidney at all times
Describe 4 ways in which the cardiovascular system can carry out its specifications
1. Needs a pump to create flow = the heart. Two sides of the heart must put out the same volume of blood, virtually beat for beat
2. Distribution vessels = arteries. High arterial pressure and low venous pressure allows distributions
3. Flow control = the output of the pump (the cardiac output) must be distributed by restricting flow to those parts of the body which are easy to perfuse so as to drive blood to those, often vulnerable, parts which are not so easy to get blood to. Flow control is via resistance vessels:
- arterioles and arteries, which can be altered by metabolic factors, and neural and humoral factors
- Precapillary sphincters, which can shut down or open parts of the capillary bed and therefore alter the effective density
4. The ability to cope with changes in the cardiac output = requires capacitance in the system - a store of blood that can be called upon to cope with temporary imbalances between the amount of blood returning to the heart and the amount it is required to pump out. This store is in the veins.
Describe the distribution of blood volume in the body
Blood volume is ~5L. Distrubuted as:
- 11% in the arteries and arterioles
- 5% in the capillaries
- 17% in the heart and lungs
- 67% in the veins
What are the 4 classifications of blood vessels and name the blood vessels in each type
1. Conductance
- Low resistance vessels
- Large arteries with predominantly elastic walls to smooth out pulsatile flow
- Role is delivering blood to more distal vessels, although they may have a small resistance role

2. Resistance
- Terminal arteries and arterioles
- Act to control local blood flow
- Muscular walls
- Dilation of these vessels lowers resistance and increases blood flow
- Constriction of these vessels increases resistance and decreases blood flow
- Influence exchange vessels by governing the flow that reaches them

3. Exchange
- Capillaries
- Thin walled for exchange
- Optimises their function, which is to allow rapid transfer between blood and tissues
- Also contribute some resistance to flow

4. Capacitance
- Thin walled and low-resistance
- Venules and veins
- Variable reservoir of blood volume and contain almost 2/3 of the volume
- Innervated by venoconstrictor fibres which, when stimulated, can displace blood back to the heart
Describe the basic structure of a blood vessel
1. Lumen
2. Tunica intima:
- Endothelium
- Supporting connective tissue (arterial disease develops here due to endothelial damage)
3. Tunica media
- Elastic tissue = alters resistance and stretch
- Smooth muscle = regulates width of the lumen
4. Tunica adventitia
- Principally collagen
Describe a typical elastic artery
- Walls expand slightly with each heartbeat
- Large amount of elastic and muscular tissue throughout the tunica media
- Media thicker than the adventitia
Describe the histology of a muscular artery
- Has a prominent muscular tunica media, with an internal and external elastic laminae
- Less resistant to stretch as less elastic tissue
Describe a typical atheroma
- If the endothelium is damaged an athethromatous plaque may develop in the tunica intima
- The tunica intima may grow so thick that a thrombus may be caused. This may break off and cause a heart attack, stroke or pulmonary embolism
Describe factors involved in the vasoconstriction and vasodilation of arteries and arterioles
- Local metabolites (including O2 and CO2)
- Nervous action - sympathetic nerve fibres
- Circulating vasoactive hormones
- factors secreted by endothelial cells
- mechanical factors e.g. stretch of vessel wall
Name 3 ways that flow can be reduced to the capillary bed
1. Constriction of metarterioles
2. Use precapillary sphincters to close off parts of the bed
3. Arteriovenous anastomoses = not capillaries as have smooth muscle and do not take part in gaseous exchange. Very important in temperature regulation, as shunts the blood straight into the venous system without any loss of resistance to flow
Describe the histology of capillaries
- Most capillaries are thin walled, with a single layer (sometimes 2 layers) of endothelial cells on a basement membrane
- No tunica media so no smooth muscle nor elastic tissue
- The arrangement of endothelial cells determines the permeability of capillaries
- Surrounding periocytes may have a muscular function, and may be involved in angiogenesis
Describe the classification of capillaries
1. Continuous
→ endothelial cells joined via tight junctions
→ prevents the leakage of proteins
→ found in most tissues
2. Fenestrated
→ Found in exocrine glands
→ Large windows which are covered by a mesh of fibres so that molecules larger than 70kD cannot get through
→ Capillaries more permeable to water, but prevents leakage of proteins
3. Discontinous
→ No joining of cells
→ Intracellular gaps/pores
→ Found particularly in the liver and spleen where proteins are secreted into the blood

Note: Endothelial cells junctions in the brain have a complex arrangement of fibres so that they are only permeable to hydrophilic molecules. This comprises the blood-brain barrier, which tightly controls the neuronal environment
Describe the molecules that are transferred through capillary walls
- Transfer occurs by way of cellular and paracellular routes
- O2 and CO2 readily transferred through the cells
- Water, glucose and electrolytes principally through paracellular routes = intercellular junctions, fenestrae in fenestrated capillaries
- Protein transfer is limited = intercellular gaps in discontinuous capillaries or cellular transfer in vesicles
How to lymphatics help regulate extracellular fluid?
- Lymphatics act by mopping up any excess filtrate and returning it to the main circulatory system (LSV). They also carry foreign antigens from the blood to cells of the immune system located in the lymph nodes
- Lymphatics start as blind ended sacs = terminal lymphatics which are found around capillary beds
- Terminal lymphatics have large endothelial cell junctions anre so they are permeable to plasma proteins and other large molecules
- Lymph capillaries join together to form collecting vessels, which may contain valves to prevent backflow. They also have smooth muscle in their walls
- Afferent vessels drain into lymph nodes, where the fluid is presented to the immune system and some lymph may enter the blood
- Efferent vessels leave the lymph node and enter the cisterna chyli, which acts as a reservoir for chylomicrons from the gut
- Eventually the lymph drains into the large thoracic duct, draining into the LSV
Describe the structure of veins and venules
- Veins and venules have a very thin tunica media, but a larger tunica adventitia than arteries and arterioles
- Post-capillary venules have no tunica media, similar to capillaries
- Like muscular arteries, small and medium-sized veins have internal and external elastic layers on either side of a muscular layer, which makes up the tunica media. Large veins have a larger amount of both elastic tissue and smooth muscle
- Veins contain valves, which aid in the transport of blood back to the heart
How are large blood vessels and nerves supplied with blood?
- Larger vessels need their own blood supply as nutrients are unable to diffuse across the many layers of cells, and deoxygenated blood is already low in nutrients. Instead they are supplied with small vessels called vasa vasorum
- Similarly, nerves are supplied by small vessels called vasa nervorum. In certain conditions, such as diabetes, these vessels are targeted, causing damaged nerves and neuropathy. The neuropathy then predisposes to subsequent joint damage and ulceration