Editing Circulatory lecture notes

*continued here from [[Cardiovascular lectures]] on 02/17/10.

==Vasculature==
*We will not cover all the circulatory routes.
**Don't read pages 748-767.

===Circulation===
*Arteries away, veins to; capillaries in between.
*Capillaries are site of exchange because of permeability and thin wall.

===Vasculature - control mechanisms===
*All vessels except capillaries have:
**smooth muscle cells so they can undergo constriction or dilation
**innervation that can control the constriction / dilation in response to the autonomic nervous system.
*Veins, in general, have much larger diameters.
*The artery has some layers.
**Throughout these layers are elastic fibers.
**The endothelial cells that line the inside of the artery are bunched up so they can expand outward and then spring back forward.
*Veins have some layers
**These include the outer and inner layers of smooth muscle.
**There are no elastic fibers.

*All three arteries, veins, and capillaries have:
**An endothelial layer, a basement membrane (on which the endothelial layer sits).

*Arteries and veins both have:
**Smooth muscle (except that arteries have larger layers of smooth muscle).

*Only arteries have:
**Two elastic layers between the smooth muscle and the basement membrane.
***These are important for handling pressure.

*Only the veins have:
**One way valves.

*In the arterioles, the smooth muscle layer has become very thin.

*Veins progress from capillaries as small venules, medium sized venuoles, and veins.

*When you have an increased stroke volume, it is handled by the expansion of the arteries.
**As you lose expansion ability (via disease or age), then the whole system pressure is increased, including backward pressure.  This will cause problems with the afterload.

*Blood pressure measurement:
**Close off artery.
**Release pressure until you hear a sound, this is systolic pressure.
**Release more until you hear nothing, this is the diastolic pressure.

====Arterial system====
*Nature of the wall changes:
**Elasticity decreases, muscle decreases.
*Next level is known as the muscular or distributing arteries.
**These can change how much blood gets to the muscles.
**Uses vasoconstriction / dilation.

=====Fluid dynamics=====
*Resistance to flow is inversely proportional to the radius raised to the fourth power.
*Flow is proportional to the pressure divided by the resistance.
*Flow is proportional to the pressure times the resistance raised to the fourth power.
*Take home: change the radius a little, change the resistance and flow a lot (in opposite directions).

=====Arterioles=====
*Smallest of these is a single smooth muscle cells surrounding the endothelial lining of the vessel.
*Not much bigger than the capillary, but can still change diameter.
*There are both neuronal control and small molecule control that can change arteriole flow.
*This is where diameter changes will help to direct blood away from the skin if cold.

*There are arteriole systems that can bypass the capillaries.  When closed it will increase the pressure in the capillaries.

====Capillaries====
*Very thin wall, with a basement membrane.
*Very small diameter.
*Not all capillaries are the same.
*Water, O2, Co2 just diffuse.
*There are intercellular clefts and pinocytic vesicles which can be used to move stuff across the membrane.
*You can move things across the endothelial membranes.
*You can move stuff through fenestrations; these are areas of membrane that do not have cytoplasm behind them that are adjacent to the endothelial cells.  Think of them as a window into the extracellular space.
*Some capillaries don't let much through, like those in the brain.
*Some capillaries let lots thorugh, like the kidney and the intestinal tract.
**There will be more endo and exo cytosis.
**There will be fenestrations.
*There are some like the liver, bone, and lymphoid capillaries that have to move stuff.
*There are three classes:
**Continuous: no fenestrations, in the brain
**Fenestrated: in the intestinal tract and kidney,
**Sinusoid: liver, bone marrow, lymphoid tissue.

====Venous system====
*While there is smooth muscle, there is much less control.
*There are thinner walls.
*There is less pressure.
*61% of the blood in an at rest, healthy person, is found in the systemic venous system.
**Only 18% in systemic arterial system.
 
*We'll finish vasculature next time.

*stopped here on 02/17/10.
*started here on 02/22/10.

===Physiology of circulation===

====Control mechanisms====
*These are the key to physiology.

=====General control=====
*Pressure causes movement.
*ARterial blood pressure is what we measure.
*Hydrostatic pressure is in the capillary beds.
*Venous pressure rarely matters.
*Resistance is the force that opposes movement.
**Vascular resistance is a function of vessel length and diameter.
***As we gain weight, there is longer length and therefore more resistance.
**Viscocity of the blood can aslo affect resistance.
***The number of RBCs, the amount of protein, etc. can affect viscosity.
**Lastly, turbulence can change resistance.
***This only becomes an isusue when we're talking about disease states and are therefore not smooth on the inside (because of plaque, for example).
*The capillaries account for much more total cross-sectional area than the aorta.
*The blood pressure is highest closest to the heart.
*The velocity of the blood is inversely proportional to the cross-sectional area.
*Cardiac output is MABP / R (mean alteriol blood pressure over resistance).
**The MABP is not just the average of systolic and diastolic.
**It is the diastolic + 1/3rd of the difference between systolic and diastolic pressures.
*So, if the cardiac output rises to to increased stroke volume or HR, then the BP also rises.

====Blood flow in capillaries====
*By the time the blood gets to the capillaries the blood pressure is very low.
*This is important b/c they are so thin they cannot take high pressure (like the 120 mm/hg as in the heart).
*They are meant for exchange, not pressure.
*There are two opposing forces: hydrostolic pressure (blood pressure) and osmotic pressure.
**The hydrostolic blood pressure wants to force fluid forward and / or outward.
**The osmotic pressure keeps fluid in the veseel, however, because of the concentration of proteins in the blood.
*Fluid can move out because of the thin walls.
*On the arteriole end of the capillariy, the blood pressure is greater than the contradicting osmotic force so fluid is lost.
*Then, on the venous system, this is reversed such that fluid is gained back.
*Blood loses 24 ish liters and gains 20, the other four go through the lymphatic system.
*What happens when these are unbalanced?  Edema!
**So if BP increases beyond the counter force of osmotic pressure, you get peripheral adema: swelling of the ankles, etc.
**You can also decrease the amount of blood protein content (in something like liver disease) and thus have decreased osmotic force and therefore the bp is more effective at forcing fluids out and edema occurs.
**If you have increased permeability of capillaries (because of infections, inflammation, etc.).  This is more localized.
**You can also increase the extracellular fluid of the blood (by retention of ions at the kidney, for example) which will increase osmotic pressure and result in higher blood volume and thus extra pressure because of the increased volume.  So we're looking for the shift one way or the other: edema or ...
**You can also block the lymph vessels.  This will result in edema in the area.  This will result in higher returns at the venous side, but not enough to relieve the edema.

====Extremes====
*A drastic decrease in volume and thus bp decrease and thus hydrostatic pressure decreases.  Therefore, there is less pressure pushing things out of the blood stream and the patient will retain fluids, which is good!
*In dehydration, the patient has lost fluids through sweating (let's say).  So they have the same number of plasma proteins and so the BCOP (blood coloital osmotic pressure) increases and therefore less fluid is lost to the intracellular area.

====Veins====
*Veins are low pressure.
*They need some help to move blood back to heart.
*We have to auxillary pumps: respiratory pump, muscular pump.
*Muscular pump:
**Veins have one-way valve.
**When muscle flexes, it squeezes the vein and blood can only go toward heart because of valves.
*Respiratory pump
**During inspiration, the diaphragm is moving and the skeletal muscles are contracting.
**These keep the blood moving.

====Homeostatic control of blood pressure====
*BP is dependent on resistance and cardiac output and blood volume.
*Cardiac output = blood pressure / peripheral resistance.
*So blood pressure = cardiac output * peripheral resistance.
*Remember that CO is controlled by stroke volume and heart rate.
*Blood viscocity does not change on an acute basis, really.
**You can add RBCs or water (via salt).
*You don't change blood vessel length in acute situations.
*You can, however, change blood vessel diameter acutely.
**Recall that the resistance is inversely proportional to the fourth power of the radius.

=====Regulation of peripheral resistance=====
*Important for temp regulation.
*Important for shunting toward GI tract after a meal.
*Important for stress and danger, getting blood to the heart, brain, and skeletal muscle.
*Peripheral resistance can be regulated in three ways: autoregulation, neuronal regulation, and endocrine regulation.

======Autoregulation======
*These are mechanisms that the vessel itself generates.
*Warming a vessel will dilate it, cooling it will vasoconstrict.
*Endothelin is released to constrict the vessel in low flow.
**NO is the opposite, it causes dilations in response to high blood flow.
*Inflammatory chemicals, which are likely to come from blood that is inside the vessels (like histamine).  These can change the permeability of the vessels.
*Metabolic processes can generate both dilators and constrictors.
**Lactic acid is a dilator which makes sense because the muscles need to get that lactic acid out of there and to get oxygen to the muscle.
**K+ and H+ also cause dilation.  These, too, make sense because they are like acids and metabolic processes generate acids which means there is work going on and that oxygen is needed.
**Prostaglandins are vasoconstrictors.
***This makes sense because they are released in inflammatiion / clotting.
*Response to oxygen:
**When oxygen levels are low, the systemic vessels will dilate to slow blood down so the oxygen can be dumped off at the tissues.
**When oxygen levels are low, the pulmonary vessels will constrict to increase ''blood velocity'' in order to absorb oxygen from the air at a faster rate.

======Neural controls======
*The cardiovascular center in the brain stem both positively and negatively affects cardiac output.
*This exact same area can also control the cardiovascular system.
*There are lots of receptors yielding input for the neural control system:
**Baroreceptors, higher brain centers, chemoreceptors, and propriocenters.
*The major affect on peripheral constriction is the sympathetic system.
*Smooth muscle and peripheral tissue are vasoconstricted:
**Mostly veins in order to release the resevoired blood.
*The sympathetic system vasoconstrics only the veins, the periphery, and the ... not the heart or brain.
*In skeletal muscle, heart, and brain, sympathetic causes dilation of arteries.

*Baroreceptors:
**Found in carotid arteries, in the aorta, in many of the major vessels.
**They sense the blood pressure.
**If bp goes up, there is feedback to the cardiovascular center which causes vasodilation of the vessels.  This makes sense because dilating will decrease blood pressure.  The heart rate and contractile force can also be decreased in order to decrease bp.
**If bp goes down, the cardiac output center can constrict blood vessls and increase heart rate / contractile force.  This is done by 
***stimulating the vasomotor centers which are trying to constrict the vessels
***stimulating the cardioacceleratory centers
***inhibiting the cardiovascular control function to allow the heart rate to increase.
**Some baroreceptors are set up to allow for individual responses to bp changes.
***For example, the carotid sinus reflex controls bp to the brain, even while the rest of the body is going for a fast run or what not.
***The aortic reflex is systemic.
***The atrial (right heart) reflex response to venous blood return (venous BP) and thus makes the heart pump faster and with more contractility to avoid a backlog of blood.
**These are all short term and only meant for acute changes.

*Chemoreceptors:
**Sense changes to gasses and pH in blood and cerebrospinal fluid.
**When stimulated, they cause vasoconstriction.
**Chemoreceptors have systemic effects, including the pulmonary branc, not just local.
**Found mostly in arteries.
**Also affects respiratory rate.

*Higher brain centers:
**Anxiety, fear, temperature, exercise can all change either vasodilation or cardiac output.

*Hormonal control:
**The endocrine controls act directly on vascular smooth muscle or on the vasomotor area.
**There is lots of overlap of neural and endo control because the two systems use similar molecules.
**Neural control didn't change blood volume but endocrine system can.
**Adrenal medulary hormones:
***Epi, norepi: vasoconstrictive, except for skeletal and cardiac muscle.
***ADH, AVP: produced by hypothalamus, released by posterior pit, released in response to decreased blood volume or increases in osmotic concentration.  If levels are high enough, it will cause vasoconstriction.  It stimulates the kidney to retain water.
***Renin-angiotensisn-aldosterone axis: when blood volume falls, renin is released which increases angiotensin II.  Angiotensin II is vasoconstrictive and causes the release of aldosterone (long lasting steroid) and ADH (fast acting protein) which increase salt and water retention by the kidney.  Aldosterone and ADH work on calcium and sodium channels (though I don't know which one is which).  ADH also yields thirst.
***EPO: causes increase in RBC, which increases viscosity, so we must consider this when thinking about how to regulate BP.
***ANF (atrial naturetic factor / peptide): this is the exact opposite of ADH.  It is a peptide hormone.  This hormone is released by the cardiac atria upon increased pressure (particularly atrial return).  The immediate affect is vasodilation.  Long term, ANH causes the kidneys to excrete salt and water.
***Alcohol: immediate depresses vasomotor center which promotes vasodilation and gives you a flushed look.  It also inhibits ADH and thus makes you have to go the bathroom.
 On Friday, go over the related pictures.

*Illustration of changes in blood pumping rate and where all the blood gets directed and in what amounts.

=====Exercise=====
*Muscle activity is increased so blood gets moved there.
*Breathing rate has increased to get more oxygen but also increased venous return because the respiratory return is going fast.
*Frank Starling's principle is in effect: more blood comes in, more blood gets pumped.
*There is also increased heart rate in response to low oxygen..

=====Blood loss=====
*In the short term, the baroreceptors will cause peripheral vasoconstriction and increase the heart rate.
*The stress of losing blood stimulates the sympathetic nervous system which increases vasomotor tone and increases vaosconstriction.
*Epi and norepi will be released t increase CO and vasoconcstritno.
*ADH will be released which iwll cause vasoconstriction.
*Now for the longer term:
**Aldosterone will get become active and cause retention of fluid via salte and water of kidney.
**Thirst will go up because of ADH.
**EPO will be released to increase RBCs.

====Circulatory shock=====
*Shock is when you cannot maintain normal flow through the system.
*Hypovolemic shock is a low blood volume, caused by vomiting, diahhrea, blood loss, etc.
*Vascular shock: an infection or reaction is causing dilation in vasculature such that blood pressure is low.
*Cardiogenic shock: the heart isn't pumping well.
*Orthostatic intolerance: under zero G force, body fluids shift to upper body, activate baroreceptors  which trigger fluid loss because they think there is too much bp.  When back to normal G force, blood rushes to lower limbs and is inadequate at the brain because the body has shed blood volume.

====Alterations in blood pressure====
*Hypotension: a chronic low blood pressure.  Can be caused by:
**starvation (low protein in blood)
***This makes sense because you won't generate proteins and the viscocity of the blood will decrease.
**Addison's disease (inadequate adrenal cortex funcion)
***This makes sense because it won't make aldosterone so you can't regulate blood volume.
**Hypothyroidism (this will cause an increased metabolic rate)
 Why would this cause hypotension?
**Orthostatic hypotension:
***Blood is not flowing correctly, perhaps still in the peripheral.
*Circulatory shock: talked about it already.
**It is found more often in older people.
*Hypertension
**Acute: fever, exercise, fear
**Chronic: affects 28% of adult Americans.
***Over age of 50, 55% of people have chronic hypertension.

*done with cardiovascular system.
*We'll do CF next.

*stopped here on 02/22/10.