MICRO CIRCULATION
•Microcirculation is the blood flow through blood vessels smaller than 100 µm (i.e. arterioles, capillaries, and venules).
• Function: Transport of cells, oxygen and other substances to or from the tissues and helps in regulation of body temperature
Microcirculation depends of two main forces
1) Capillary hydrostatic pressure
2) Capillary osmotic pressure
CAPILLARY HYDROSTATIC PRESSURE
• This pressure drives fluid out of the capillary (i.e., filtration), and is highest at the arteriolar end of the capillary and lowest at the venular end.
• Depending upon the organ, the pressure may drop along the length of the capillary (axial pressure gradient) by 15-30 mmHg.
• The axial gradient favors filtration at the arteriolar end (where PC is greatest) and reabsorption at the venular end of the capillary (where PC is the lowest).
• The average capillary hydrostatic pressure is determined by arterial and venous pressures (PA and PV), and by the ratio of post-to- precapillary resistances (RV/RA). PC is more sensitive to changes in PV than by changes in PA.
CAPILLARY OSMOTIC PRESSURE
• Osmotic pressure is the hydrostatic pressure produced by a solution in a space divided by a differentially permeable membrane due to a differential in the concentrations of solute.
• Because the capillary barrier is readily permeable to ions, the osmotic pressure within the capillary is principally determined by plasma proteins that are relatively impermeable.
• Therefore, instead of speaking of “osmotic" pressure, this pressure is referred to as the "oncotic".
• Albumin generates about 70% of the oncotic pressure. This pressure is typically 25-30 mmHg.
• The oncotic pressure increases along the length of the capillary, particularly in capillaries having high net filtration (e.g., in renal glomerular capillaries), because the filtering fluid leaves behind proteins leading to an increase in protein concentration.
ENDOTHELIUM
• The endothelium (0.5 μm) is the layer of thin specialized epithelium, comprised of a single layer of flat cells that line the interior surface of blood vessels, forming an interface between circulating blood in the lumen and the rest of the vessel wall.
•Space between cells 6-7 nm (little bit less than albumin) Endothelial cells line the entire circulatory system, from the heart (endocardium) to the smallest capillary. Both blood and lymphatic capillaries are composed of a single layer of endothelial cells
FUNCTIONS OF ENDOTHELIUM
• vasoconstriction and vasodilation, and hence the control of blood pressure
• blood clotting (thrombosis & fibrinolysis)
•formation of new blood vessels (angiogenesis)
• inflammation and swelling (oedema)
• transit of white blood cells
• Pathology
•Atherosclerosis (patients with diabetes mellitus, hypertension and hyperlipidemia)
ARTERIOLES
• An arteriole is a small diameter (<20 μm, up to 5-9 μm) blood vessel that extends and branches out from an artery and leads to capillaries.
• Arterioles have thin muscular walls (usually only one to two layers of smooth muscle) and are the primary site of vascular resistance.
• In a healthy vascular system the endothelium, inner lining of arterioles and other blood vessels, is smooth and relaxed.
• This healthy condition is promoted by the production of nitric oxide in the endothelium.
• The mean blood pressure in the arteries supplying the body is a result of the interaction between the cardiac output (the volume of blood the heart is pumping per minute) and the vascular resistance, usually termed total peripheral resistance.
• Any pathology which constricts blood flow, such as stenosis, will increase total peripheral resistance and lead to hypertension.
TOTAL PERIPHERAL RESISTANCE
• Total peripheral resistance refers to the cumulative resistance of the thousands of arterioles in the body, or the lungs, respectively.
• It is approximately equal to the resistance of the arterioles, since the arterioles are the chief resistance vessels in the body.
TOTAL PERIPHERAL RESISTANCE FORMULA
• Total Peripheral Resistance = Mean Arterial Pressure / Cardiac Output.
• The total peripheral resistance of healthy lung arterioles is typically about 0.15 to 0.20 that of the body, so pulmonary artery mean blood pressure are typically about 0.15 to 0.20 of aortic mean blood pressures.
CAPILLARIES
• Capillaries, are the smallest of a body's blood vessels, measuring 5-10 μm .
• They connect arteries and veins, and most closely interact with tissues.
• Capillaries have walls composed of a single layer of cells, the endothelium.
• This layer is so thin that molecules such as oxygen, water and lipids can pass through them by diffusion and enter the tissues.
• Waste products such as carbon dioxide and urea can diffuse back into the blood to be carried away for removal from the body.
• Capillary permeability can be increased by the release of certain cytokines.
• The "capillary bed" is the network of capillaries supplying an organ.
• The more metabolically active the cells, the more capillaries it will require to supply nutrients.
• The capillary bed usually carries no more than 25% of the amount of blood it could contain, although this amount can be increased through autoregulation(i.e. active muscle cells) by inducing relaxation of smooth muscle.
• Any signaling molecules they release (such as endothelin for constriction and Nitric oxide for dilation) act on the smooth muscle cells in the walls of nearby, larger vessels, e.g. arterioles.
ENDOTHELIN
• Endothelin is a 21-amino acid vasoconstricting peptide that plays a key part in vascular homeostasis and it is one of the strongest vasoconstrictors.
• In a healthy individual a delicate balance between vasoconstriction and vasodilation is maintained by endothelin, calcitonin (vasoconstrictors) and by nitric oxide, prostacyclin (vasodilators).
• Overproduction of endothelin can cause pulmonary artery hypertension.
NITRIC OXIDE
• The chemical compound nitric oxide is a gas with chemical formula NO.
• In the body, nitric oxide (the 'endothelium-derived relaxing factor', or 'EDRF') is synthesized from arginine and oxygen by various nitric oxide synthase (NOS) enzymes and by sequential reduction of inorganic nitrate.
FUNCTIONS OF NITRIC OXIDE (NO)
• The endothelium (inner lining) of blood vessels use nitric oxide to signal the surrounding smooth muscle to relax, thus dilating the artery and increasing blood flow.
• Nitric oxide is a key biological messenger, playing a role in a variety of biological processes (vessel dialatation, neurotransmission, penile erections, hair growth / loss).
•"Nitro" vasodialators such as nitroglyceric are converted to nitric oxide.
• Immune system: generated by macrophages, toxic to bacteria
CAPILLARY PRESSURES VALUES
•Middle pressure is about 25 mm Hg
•30-40 mm Hg by arterioles
•10-15 mm by venules
•Oncotic pressure is about 28 mm Hg
•19 mm Hg because of proteins
•9 mm Hg because of some cations
• As their are differences in capillary pressures by arterioles and venules.
• Venous end has lower pressure, but there is higher permeability - therefore 90 % of liquid that goes out at arterial end comes back at venous end.
•Increase of capillary pressure of 20 mmHg, increases filtration pressure and Lymphatic system is not able to accomodate the increase of IC liquid which results in oedemas.
PRESSURES IN THE ARTERIAL END OF CAPILLARY
• Pressures going out of the capillary:
Capillary pressure - 30mmHg
Pressure of interstitial fluid - 3mmHg
Oncotic pressure of ISF - 8mmHg
Total pressure outwards is - 41mmHg
• Pressures going into the capillary:
Oncotic pressure of plasma - 28mmHg
•Together 41-28=13 mmHg in direction out of the capillary (0.5 % of plasma)
PRESSURE IN THE VENOUS END OF CAPILLARY
• Pressures going out of the capillary:
Capillary pressure - 10mmHg . Pressure of interstitial fluid - 3mmHg
Oncotic pressure of ISF - 8mmHg
Total pressure going out - 21mmHg
• Pressures going into the capillary:
Oncotic pressure of plasma - 28mmHg
•Together 28-21=7 mmHg in direction into the capillary (0.5 % of plasma)
TYPES OF CAPILLARIES :
CONTINUOUS CAPILLARIES
Continuous capillaries have a sealed epithelium and only allow small molecules, water and ions to diffuse.
FENESTRATED CAPILLARIES
Fenestrated capillaries (as their name implies "fenster") have openings that allow larger molecules to diffuse.
SINUSOIDAL CAPILLARIES
Sinusoidal capillaries are special forms of fenestrated capillaries that have larger openings in the epithelium allowing RBCs and serum proteins to enter.
* One of the two major types of capillaries, found in muscle, skin, lung, central nervous system and other tissues, characterized by the presence of an uninterrupted endothelium and a continuous basal lamina, and by fine filaments and numerous pinocytotic vesicles.
* One of the two major types of capillaries, found in the intestinal mucosa, renal glomeruli, pancreas, endocrine glands and other tissues and characterized by the presence of circular fenestrae or pores that penetrate the endothelium;
• These pores may be closed by a very thin diaphragm.
SINUSOIDAL CAPILLARIES
• A sinusoid is a type of a capillary with a fenestrated endothelium.
• Located in: liver, lymphoid tissue, endocrine organs, and hematopoietic organs (bone marrow, spleen).
Their highly permeable in nature, which is due to larger inter-cellular clefts which allows small and medium-sized proteins such as albumin to enter and leave the blood stream.
•Some spaces are large enough for blood cells to pass.
•Liver sinusoids are equipped with Kupffer cells that can take up and destroy foreign material such as bacteria entering the sinusoids.
VENULES
• A venule is a small blood vessel that allows deoxygenated blood to return from the capillary beds to the larger blood vessels called veins.
•Venules have three layers:
➢ An inner endothelium composed of squamous epithelial cells that act as a membrane.
➢ A middle layer of muscle and elastic tissue. (poorly developed so that venules have thinner walls than arterioles)
➢ An outer layer of fibrous connective tissue.
LYMPHATIC SYSTEM
• The lymphatic system is a complex network of lymphoid organs, lymph nodes, lymph ducts, and lymph vessels that produce and transport lymph fluid from tissues into the circulatory system.
• The lymphatic system is a major component of the immune system.
FUNCTIONS OF LYMPHATIC SYSTEM
➢Removal of excess fluids from body tissues.
➢Absorption of fatty acids and subsequent transport of fat and chyle to the circulatory system.
➢Production of immune cells (such as lymphocytes, monocytes, and antibody producing cells called plasma)
LYMPH
• Lymph originates as blood plasma that leaks from the capillaries of the circulatory system, becoming interstitial fluid, and filling the space between individual cells of tissue.
• Plasma is forced out of the capillaries by hydrostatic pressure, and as it mixes with the interstitial fluid, the volume of fluid accumulates slowly.
• Most of the fluid is returned to the capillaries by osmosis (about 90% of the former plasma).
• The excess interstitial fluid is collected by the lymphatic system by diffusion into lymph capillaries, and is processed by lymph nodes prior to being returned to the circulatory system.
• Once within the lymphatic system the fluid is called lymph, and has almost the same composition as the original interstitial fluid.
LYMPH NODE
• A lymph node is an oval or kidney- shaped organ of the lymphatic system, distributed widely throughout the body including the armpit and stomach and linked by lymphatic vessels. Lymph nodes are major sites of B, T, and other immune cells.
• Lymph nodes are important for the proper functioning of the immune system, acting as filters for foreign particles and cancer cells. Lymph nodes do not deal with toxicity, which is primarily dealt with by the liver and kidneys.
CLINICAL SIGNIFICANCE OF LYMPH NODES
• They become inflamed or enlarged in various infections and diseases which may range from trivial throat infections, to life- threatening cancers.
• The condition of the lymph nodes is very important in cancer staging, which decides the treatment to be used, and determines the prognosis. When swollen, inflamed or enlarged, lymph nodes can be hard, firm or tender.
LYMPHATIC CIRCULATION
• The lymphatic system acts as a secondary circulatory system, except that it collaborates with white blood cells in lymph nodes to protect the body from being infected by cancer cells, fungi, viruses or bacteria.
• Unlike the circulatory system, the lymphatic system is not closed and has no central pump; the lymph moves slowly and under low pressure due to peristalsis, the operation of semilunar valves in the lymph veins, and the milking action of skeletal muscles.
• Like veins, lymph vessels have one-way, semilunar valves and depend mainly on the movement of skeletal muscles to squeeze fluid through them.
Rhythmic contraction of the vessel walls may also help draw fluid into the lymphatic capillaries.
• This fluid is then transported to progressively larger lymphatic vessels culminating in the right lymphatic duct (for lymph from the right upper body) and the thoracic duct (for the rest of the body);
• These ducts drain into the circulatory system at the right and left subclavian veins.
• The thoracic duct, is an important part of the lymphatic system—it is the largest lymphatic vessel in the body.
• It collects most of the lymph in the body (except that from the right arm and the right side of the chest, neck and head, which is collected by the right lymphatic duct) and drains into the systemic (blood) circulation.
• The thoracic duct drains into the left subclavian vein.
• In an adult, the thoracic duct transports up to 4 L of lymph per day. When the thoracic duct is blocked or damaged a large amount of lymph can quickly accumulate in the pleural cavity, this situation is called chylothorax.
FATTY ACID TRANSPORT SYSTEM
• Lymph vessels are present in the lining of the GIT.
• While most other nutrients absorbed by the small intestine are passed on to the portal venous system to drain, via the portal vein, into the liver for processing, fats are passed on to the lymphatic system, to be transported to the blood circulation via the thoracic duct.
• The enriched lymph originating in the lymphatics of the small intestine is called chyle.
• The nutrients that are released to the circulatory system are processed by the liver.
Lymphoid organs
• The thymus, spleen, lymph nodes, peyer's patches, tonsils, vermiform appendix, and red bone marrow are accessory lymphoid tissues that comprise the lymphoid organs.
• These organs contain a net that support circulating B- and T- lymphocytes and other immune cells like macrophages and dendritic cells.
• Another sub-component of the lymphatic system is the reticuloendothelial system.
• When micro-organisms invade the body or the body encounters other antigens, those are transported from the tissue to the lymph circulation. The lymph nodes filter the lymph fluid and remove foreign material, such as bacteria and cancer cells. Specialized cells called macrophages and dendritic cells phagocytose pathogens and present antigens to lymphocytes.
• When these pathogens are recognized, the lymph nodes enlarge and additional immune cells are produced to help fight the infection.
Thymus
• The thymus is an organ located in the upper anterior portion of the chest cavity.
• The thymus plays an important role in the development of the immune system in early life, and its cells form a part of the body's normal immune system.
• It is most active before puberty, after which it shrinks in size and activity in most individuals and is replaced with fat.
•Function: Production (maturation) of T cells.
SPLEEN
• The spleen is located in the upper left part of the abdomen, behind the stomach and just below the diaphragm.
• The spleen is the largest collection of lymphoid tissue in the body.
• It is regarded as one of the centres of activity of the reticuloendothelial system.
• Its absence leads to a predisposition to certain infections.
FUNCTIONS OF SPLEEN
➢Acts as Blood reservoir
➢Helps in destruction of old red blood cells
➢It even has some immune functions
➢Helps in blood cells production in embryogenesis
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