The Circulatory System: Blood Vessels and Circulation

**Hormonal control

**1. Angiotensin II: a very strong vasoconstrictor, enzyme required for synthesis is angiotensin converting enzyme, (made in lungs) e.g. ACE inhibitors 2. Aldosterone: "salt retaining hormone"; promotes sodium retention by the kidneys; increase water retention->increased blood volume->increased bp 3. Atrial naturetic peptide: secreted by the heart antagonizes aldosterone, increases sodium loss thereby decreasing blood volume, also works as a vasodilator 4. Antidiuretic hormone: promotes water retention, at pathologically high concentrations may act as a vasoconstrictor (vasopressin) 5. Epinephrine/norepinephrine: adrenal and sympathetic catecholamines bind to alpha receptors on the smooth muscles of blood vessels, also stimulates increased heart rate, and force of contraction resulting in increased bp, in the coronary system work on beta adrenergic receptors resulting in vasodilation

Special Circulatory Routes: Lungs

**Reminder: In the pulmonary circuit arteries carry oxygen poor blood, and veins carry oxygen rich blood** - BP in the pulmonary circuit is lower than in the systemic circuit, therefore - Blood flows more slowly through the pulmonary capillaries; resulting in greater time for gas exchange - Oncotic pressure overrides hydrostatic pressure, so capillaries are engaged in reabsorption - Clinically: a backup of blood in the pulmonary circuit results in increased capillary hydrostatic pressure, resulting in pulmonary edema, congestion, and hypoxemia - Pulmonary arteries constrict in response to hypoxemia, resulting in redirection of blood flow to other parts of the lungs which are better ventilated blood to lung - pick up O2, drop off CO2 Tissues - autoregulate to a point

Special Circulatory Routes: Brain

- Blood flow to the brain must remain consistent - Oxygen deprivation of a few seconds results in loss of consciousness - The brain regulates its own blood supply in response to changes in BP and chemistry - The main chemical stimulus for cerebral autoregulation is pH - MAP below 60 mm Hg results in syncope; and greater than 160 mm Hg causes cerebral edema - Extreme hypercapnia (↑CO2) depresses neural activity - Hyperventilation induces hypocapnia (↓CO2) which leads to cerebral vasoconstriction, ischemia (death of tissues), dizziness, and syncope - Clinical Situations: transient ischemic attacks (TIAs) may result from spasms of diseased cerebral arteries; while a stroke or cerebrovascular accident (CVA) is the sudden death of brain tissue caused by ischemia If MAP goes too high, risk of cerebral edema

Special Circulatory Routes: Skeletal Muscles

- Skeletal muscles receive a highly variable blood flow - Arterioles dilate in response to epinephrine & norepinephrine - Precapillary sphincters dilate in response to lactic acid, CO2, and adenosine

Blood Vessel: Tunica media

- the middle layer - usually the thickest, consists of smooth muscle, collagen, and elastic fibers - principle function is to provide strength and prevent the vessel from rupturing -vasomotor changes (changes in diameter of the blood vessel brought about by smooth muscle) vasodilation/vasoconstriction

**Responses to Circulatory Shock

1. Compensated shock: several homeostatic mechanisms bring about spontaneous recovery: Hypotension is corrected by activation of the baroreflex and production of angiotensin II both which counteract shock by stimulating vasoconstriction 2. Decompensated shock: results inactivation of several life-threatening positive feedback loops Poor cardiac output results in myocardial ischemia and infarction, which further weakens the heart and reduces output Slow circulation of blood can lead to disseminated intravascular coagulation Venous return continues to deteriorate Ischemia and acidosis of the brainstem depresses the vasomotor and cardiac centers causing loss of muscle tone, further vasodilation, further drop in BP, and cardiac output Approximately 50% of individuals who go into decompensated shock die

Movement through Capillary Walls

1. Diffusion: the most important mechanism of exchange; solute must be able to pass through the cell membrane 2. Transcytosis: process by which endothelial cells pick up material on one side of the plasma membrane by pinocytosis or receptor-mediated endocytosis, and transport the vesicles across the cell, and release on the other side by exocytosis 3/4. Filtration & Reabsorption: Hydrostatic pressure: the physical force exerted against a surface Capillaries reabsorb approximately 85% of the fluid they filter Clinical condition: Edema: accumulation of excess fluid in a tissue Three fundamental causes: Increased capillary filtration: Reduced capillary reabsorption: Obstructed lymphatic drainage:

Medications for lowering BP

1. Essential hypertension: the most common form of hypertension, which is poorly understood and is a complex process 2. Blood pressure is proportional to cardiac output and total peripheral resistance a. Increased activity of the sympathoadrenal system may contribute to elevated blood pressure b. May interact with sodium from salt to raise blood pressure 3. Medication include drugs that are: a. Diuretics: act on kidney to reduce the amount of water reabsorbed, results in lower blood volume and therefore lowers blood pressure b. Beta-blockers: block the beta 1 adrenergic receptors in the heart, thus epinephrine and norepinephrine have less stimulatory effect on the cardiac rate; lower cardiac rate, lower cardiac output and thus reduce blood pressure (stage fright) c. Alpha-blockers and -stimulators: some stimulate the alpha 1-adrenergic receptors in the brain, which reduces the activation of the sympathoadrenal system; others block the alpha-2 adrenergic receptors in vascular smooth muscle, preventing sympathetic axons from stimulating vasoconstriction; vasodilation lowers total peripheral resistance, thus lowers blood pressure d. Calcium channel blockers: block the calcium channels in the plasma membrane of smooth muscle cells, reducing their ability to contract, resulting in arterioles dilating, lowering peripheral resistance and thus blood pressure e. ACE (angiotensin-converting enzyme)inhibitors and ARBs (angiotensin receptor blockers): you get weak ACE inhibitors reduce the production of angiotensin II from angiotensin I; thereby reducing the ability of angiotensin II to stimulate vasoconstriction, ARBs allow angiotensin II to be produced but block its interaction on receptors; results in arteriole dilation, leading to lower peripheral resistance and thus lower blood pressure reduces the ability of angiotensin II to stimulate aldosterone secretion from the adrenal cortex; leads kidneys to reabsorb less sodium and therefore less water, higher urine excretion; causing less blood volume and therefore less blood pressure (doesn't let Angiotensin I change to Angiotensin II)

Physical Activity on Venous Return

1. Exercises increases venous return a. Increased heart rate b. Increased cardiac output c. Increased blood pressure d. Blood vessels and coronary arteries dilate e. Respiratory rate increase, improves the action of the thoracic pump f. Increased skeletal muscle activity, results in increased venous return 2. Venous pooling: accumulation of blood that occurs when the venous pressure is not high enough to override the weight of the blood and return it to the heart 3. Syncope: fainting

Venous Return Methods

1. Pressure gradient: pressure generated by the heart is the most important force in venous flow a. Central Venous Pressure: the pressure at the point where the venae cavae enter the heart 2. Gravity: (feet higher than heart) 3. Skeletal muscle pump: contracting muscles squeeze the blood out of the veins (squeezing veins) 4. Thoracic (respiratory) pump: the internal pressure of the thoracic cavity decreases, and blood flows in 5. Cardiac suction: during ventricular systole the tendinous cords pull the AV valve cusps downward, expanding the atrial space and thereby creating a slight suction chest wall expands - pressure down inside - things flow in

Capillary beds

Approx 3/4 of body's capillaries are shut down at any given time Brain monitors and shifts blood to area that needs it - metabolic needs

**BP and Flow Regulation: Local control

Autoregulation: ability of tissue to control their own blood supply Responds to accumulation of metabolites **Vasoactive chemicals: histamine, bradykinin, prostaglandins stimulate vasodilation prostacyclin and nitric oxide are also vasodilators (allows more blood flow), endothelins vasoconstrictors **Reactive hyperemia: an increase in the normal level of flow Angiogenesis: growth of new blood vessels

Abdominal Aorta & Major Branches Zoomed

Celiac Trunk - very short Superior - gastric Left - Splenic Right - Hepatic

Capillaries

Composed of only endothelium and a basement membrane This is where the greatest exchange of nutrients, wastes, hormones, and leukocytes can occur Three types of capillaries - Continuous capillaries, Fenestrated capillaries, Sinusoid capillaries

Flow vs Perfusion

Flow: the amount of blood flowing through an organ, tissue, or blood vessel in a given amount of time, expressed as mL/min. Perfusion: the flow per given volume or mass of tissue, expressed as mL/min/g

BP and Flow Regulation: Neural Control

Neural control: vessels are controlled by the autonomic system, located in the vasomotor center which is located in the medulla oblongata Sympathetic control: over most blood vessels results in vasoconstriction (to organs), however in skeletal and cardiac muscle results in vasodilation the vasomotor center is an integrating center for three autonomic reflexes 1. Baroreflex: an autonomic negative feedback response to changes in blood pressure (always monitoring BP) ; detected by baroreceptors; important in short term regulation; e.g. Clinical Situation: Immediately after stopping exercise, the baroreceptors will stimulate the cardio-inhibitory center, and inhibit the vasomotor center and BP will go does 2. Chemoreflex: autonomic response to changes in blood chemistry, pH and CO2/O2 concentrations, detected by sensors in the aortic and carotid regions; stimulation of receptors results in vasoconstriction, also stimulate breathing 3. Medullary ischemic reflex: autonomic response to a drop in perfusion of the brain; send impulses via sympathetic nerves to cause widespread vasoconstriction and increase the heart rate as well as force of contraction (shuts down everything not necessary - sacrifice arm/leg to protect brain)

Capillaries: Continuous

Occurs in most tissues held together by tight junctions forma continuous tube, surrounded by a basal lamina, the endothelia cells are separated by narrow intercellular clefts which all small solutes (glucose) to pass through some continuous capillaries are surrounded by pericytes which may help regulate blood flow The continuous capillaries of the brain lack intercellular clefts

Inferior Vena Cava and Tributaries

Pregnancy compresses inferior vena cava can have problems with blood flow to heart - backup system that drains into azygose and hemiazygos

Vasomotion

Purposes: 1. Generalized raising or lowering of BP 2. Selectively modifying the perfusion of a particular organ and rerouting the blood from one region of the body to another If you are sitting/relaxing vs exercising your body will reduce or increase blood flow

Arterial Sense Organs

Sensory structures in the walls of certain vessels that monitor blood pressure and chemistry Transmit information to brainstem that serves to regulate heart rate, vasomotion, and respiration Needs info from outside for brain to gain info 1. Carotid sinuses: are baroreceptors (pressure sensors); located in the internal carotid artery just distal to the bifurcation Monitors blood pressure - signaling brainstem Decreased heart rate and vessel dilation in response to high blood pressure 2. Carotid bodies: are chemoreceptors; located near the branch of the common carotid arteries; monitor changes in blood composition Mainly transmit signals to the brainstem respiratory centers used to stabilize blood pH, CO2 and O2 3. Aortic bodies: are chemoreceptors; located in the aortic arch; same function as carotid bodies *know where baroreceptors and chemoreceptors are located

**Circulatory Routes

Simplest and most common is: Heart-> arteries-> capillaries-> veins->heart **1. Portal system: blood flows through two consecutive capillary networks before returning to the heart (Blood vessels do not actively transport blood - but can regulate their diameter by contraction of the muscular layer. These result in alteration to the blood flow to the target tissues are determined by the autonomic NS and endocrine system) **2. Anastomosis: point where two blood vessels merge/meet 3. Arteriovenous anastomosis: blood flows directly from an artery into a vein 4. Venous anastomosis: the most common type; one vein empties directly into another vein 5. Arterial anastomosis: two arteries merge and provide collateral circulation routes of blood supply to tissues

Veins

Sometimes called capacitance vessels; relatively thin walled, flaccid, and expand easily At rest ~54% of the blood is found in the systemic veins Veins can be categorized into 5 types 1. Postcapillary venules: smallest of the veins, consist of tunica interna with a few fibroblasts around it; are more porous than capillaries, leukocytes immigrate through the venule walls 2. Muscular venules: have a tunica media and a thin tunica externa 3. Medium veins: tunica media is thinner than in arterioles; many of the medium veins have the presence of venous valves 4. Venous sinuses: veins with especially thin walls, e.g. coronary sinus and the dural sinuses 5. Large veins: relatively thin tunica media; tunica externa is the thickest, e.g. vena cava, pulmonary veins

Arteries - 3 classes

Sometimes called resistance vessels, because they have a relatively strong, resilient tissue structure that resists high blood pressure 1. Conducting ( elastic/large) vessels: are the largest, e.g. aorta, common carotid arteries, and subclavian arteries, pulmonary trunk, and common iliac arteries, Have a layer of elastic tissue, internal elastic lamina, at the border between the interna & media Elastic lamina at the border between media and externa expand with systole and recoil during diastole, (Dicrotic notch) which lessens fluctuations in blood pressure

Arteries: 3 classes

Sometimes called resistance vessels, because they have a relatively strong, resilient tissue structure that resists high blood pressure 2. Distributing ( muscular/medium) arteries: distribute blood to organs e.g. brachial, femoral, renal, and splenic arteries composed of approximately 40 layers smooth muscle;

Arteries: 3 classes

Sometimes called resistance vessels, because they have a relatively strong, resilient tissue structure that resists high blood pressure 3. Resistance (small) arteries: a. Arterioles: smallest arteries Control amount of blood to various organs Thicker tunica media in proportion to their lumen than larger arteries and very little tunic externa b. Metarterioles: Short vessels that link arterioles to capillaries Muscle cells form a precapillary sphincters about entrance to capillary Constriction of these sphincters reduces or shuts off blood flow through their respective capillaries Diverts blood to other tissues

Blood Vessels

Systemic Circuit: Arteries (R) -- arterioles (R) -- capillaries (R/B) -- venules (B) -- veins (B) -- superior and inferior vena cava (B) Pulmonary circuit: Arteries (B) -- arterioles (B) -- capillaries (B/R) -- venules (R) -- veins (R) -- Lt. Atrium (R) Exchange of gases/nutrients/wastes (O2, CO2), distribution of hormones/other substances happen in capillaries

Hepatic Portal System

The principle veins of the hepatic portal system (purple on models) are (formed by the union of): Hepatic portal vein Gastric Vein Splenic Vein Inferior Vena Cava Superior Vena Cava

Blood Vessels

Tubes through which blood is transported to and from within the body. Three types: 1. arteries (blood away from the heart) 2. capillaries (exchange of gases, nutrients/wastes, water, and chemicals take place between the blood and tissues), 3. veins (blood back to the heart).

Regulation of Blood Pressure and Flow

Vasomotion is a quick and powerful way to alter blood pressure and flow There are three major mechanisms for controlling vasomotion Local control Neural control Hormonal control

**Blood Vessel: Tunica externa

a.k.a. tunica adventitia - the outer layer - consists of loose connective tissue that often merges with that of neighboring blood vessels, nerves, or other organs ** contains the vasa vasorum; small vessels that supply (perfuse) blood to at least the outer half of the larger vessels - very tough/high pressure (coronary system of blood vessels - too thick for nutrients to diffuse through) - Blood from the lumen is thought to nourish the inner half of the vessel by diffusion

Blood Vessel: Tunica interna

a.k.a. tunica interna - lines the lumen of the vessels - composed of simple squamous epithelium (endothelium - same as endocardium) , overlying a basement membrane and a sparse layer of loose connective tissue (low pressure) - Acts as a selectively permeable barrier - Secrete chemicals that stimulate dilation or constriction of the vessel - Normally repels blood cells and platelets that may adhere to it and form a clot - When tissue around a vessel is inflamed, the endothelial cells produce cell adhesion molecules that induce leukocytes to adhere to the surface - Causes leukocytes to congregate in tissues where their defensive actions are needed

Capillaries: Sinusoids

aka discontinuous capillaries irregular blood filled spaces in the liver, bone marrow, spleen, etc.; the endothelial cells are separated by wide gaps which allows for proteins and other molecules synthesized by the liver to enter the circulation found in the liver, bone marrow, lymph organs

**Circulatory Shock

any state in which cardiac output is insufficient to meet the body's metabolic needs Your BP goes down rapidly - impaired flow to all organs (brain, heart - decreased flow) weak/unconscious, can't think clearly Your HR goes up (to try and increase CO) thready though Not enough blood going into heart - CO too low, blood going into coronary arteries also low gets worse and worse Two categories: 1. Cardiogenic shock: caused by inadequate pumping of the heart 2. Low venous return (LVR) shock: results in a low cardiac output when there is too little blood returning to the heart; there are three types of LVR shock: a. Hypovolemic shock: the most common form, produced by a loss of blood volume as a result of trauma, hemorrhage, bleeding ulcers, dehydration, dehydration is the major cause of death from heat exposure b. Obstructed venous return shock: occurs when any object compresses a vein and impedes it flow (completely blocked off) c. Venous pooling (vascular) shock: occurs when the body has a normal total blood volume, but too much of accumulates in the lower body d. Neurogenic shock: a form of venous pooling that results from widespread vasodilation Greatest amount of blood at one time is on venous side Combination of both venous pooling and hypovolemic shock combined 1. Septic shock: occurs when bacterial toxins trigger vasodilation and increased vascular permeability **2. Anaphylactic shock: results from exposure to an antigen to which a person is allergic ; the antigen-antibody complex results in release of histamine and subsequent vasodilation and increased capillary permeability (your body overshoots the mark, releases histamine - vasodilation, blood pooling - less back to heart and brain, ^ hr, but can't maintain)

Arteries

carry blood away from heart (efferent vessels) three layers - middle layer thicker for arteries

Veins

carry blood back to the heart (afferent vessels) three layers - middle layer thinner in veins

**Blood Pressure: Mean arterial pressure

diastolic pressure+1/3 pulse pressure (MAP = diastolic pressure + (PP (pulse pressure)/3) the difference between the mean arterial pressure and the pressure in the venous system drives the blood through the capillaries; influences the risk level for disorders such as edema, syncope, kidney failure, and aneurysm high MAP can result in cerebral edema (pressure on brain) low MAP can result in syncope (fainting or passing out)

Capillaries: Fenestrated

endothelial cells have filtration pores (fenestrations); these allow for rapid passage of molecules but retain rbc's, etc. e.g. kidneys, endocrine glands, small intestine

Capillary Exchange

refers to the two way movement of fluid Chemicals pass through the capillary wall by three routes Through the endothelial cell cytoplasm Intercellular clefts between the endothelial cells Filtration pores (fenestration) of the fenestrated capillaries

**Varicose Veins

results from the destruction of the valves present in the veins

Blood Pressure: Pulse Pressure

the difference between the systolic and diastolic pressure; measure of stress against the small arteries

Blood Pressure

the force blood exerts against a vessel wall Determined by: 1. Cardiac Output 2. Blood volume: regulated by the kidneys (blood/fluid volume); has greatest influence 3. Resistance to flow - how big is pipe - lumen gets thinner, more pressure to get blood through Two pressures are recorded with sphygmomanometer (expressed in mmHg) 1. Systolic pressure: 120-140 highest pressure in system 2. Diastolic pressure: 60-90 lowest pressure in system Hypertension (greater than 140/90)/Hypotension (less than 120/60) Arteriosclerosis (stiffness of arteries)/Atherosclerosis (lipid deposits in arterial walls) Cuff - all blood flow is cut off, 1st sound you hear is systolic, last sound you hear is diastolic

**Peripheral Resistance

the opposition to flow Factors affecting peripheral resistance include 1. Blood viscosity: lots of water - moves easier, less water - thick the most significant contributors are a. erythrocyte (how many RBC) count b. albumin concentration 2. Vessel length: the longer the length, the greater the resistance 3. Vessel radius: the greater the opening (lumen) the less resistance a. Vasoconstriction: the narrowing of a blood vessel b. Vasodilation: the widening of a blood vessel; e.g. a 3-fold increase in diameter, produces a 81-fold increase in flow

Hemodynamics

the physical principles of blood flow mainly based on pressure and resistance; e.g. the greater the pressure the greater the flow, & the greater the flow the greater the resistance

Capillaries

thin walled vessels that serve as a connection between the smallest arteries and smallest veins. Exchange of gasses and nutrients occur