13) 04_Capillary Fluid Exchange.pdf

Capillary Fluid Exchange and Lymphatic system 2024 1 • Define capillary exchange by explaining diffusion, transcytosis and bulk flow • Describe the factors that are affecting capillary exchange • Define hydrostatic and osmotic pressures • Describe how to calculate net filtration pressure that det...

Capillary Fluid Exchange and Lymphatic system 2024 1 • Define capillary exchange by explaining diffusion, transcytosis and bulk flow • Describe the factors that are affecting capillary exchange • Define hydrostatic and osmotic pressures • Describe how to calculate net filtration pressure that determines the net flow of fluid across the capillary membrane by considering the four Starling forces • Define edema • Explain the four types of alteration in capillary exchange that result with edema by giving examples 2 • Describe the structure and the general features of the lymphatic system • Describe the features that are affecting lymphatic flow • Describe the importance of the lymphatic system in maintaining volume and protein concentration of interstitial fluid 3 Blood usually flows intermittently through the capillaries, turning on and off every few seconds or minutes. - intermittent contraction of the sphincters Vasomotion Guyton and Hall Textbook of Medical Physiology, 14th edition, 2021 4 5 Medical Physiology, 2e 2017 6 1 Continuous capillary. This is the most common form of capillary, with interendothelial junctions 10 to 15 nm wide (e.g., skeletal muscle). These clefts are absent in the blood-brain barrier, whose capillaries have narrow tight junctions. 2 Fenestrated capillary. the endothelial cells are thin and perforated with fenestrations. These capillaries most often surround epithelia (e.g., small intestine, exocrine glands). 3 Discontinuous capillary. In addition to fenestrae, these capillaries have large gaps. Discontinuous capillaries are found in sinusoids (e.g., liver). 7 Human Physiology: An Integrated Approach 6e Pearson Fenestrated capillaries {fenestra, window} have large pores (fenestrae) that allow high volumes of fluid to pass rapidly between the plasma and interstitial fluid 8 Substance exchange Gases such as O2 and CO2 are highly lipid soluble, and they cross the capillary wall by diffusing through the endothelial cells; diffusion is driven by the partial pressure gradient for the individual gas. The diffusion of water-soluble substances is limited to the aqueous clefts between endothelial cells or pores (fenestrae). Electrolytes, nutrients, and waste products of metabolism all diffuse between compartments. 9 Relative permeability of skeletal muscle* capillary pores to different-sized molecules • the permeability for glucose molecules is 0.6 times that for water molecules, • the permeability for albumin molecules is very slight—only one 1/1000 that for water molecules. *The capillaries in various tissues have extreme differences in their permeabilities. 10 • The proteins are the only dissolved constituents in the plasma and interstitial fluids that do not readily pass through the capillary membrane. • Transcytosis – transportation of protein and macro-molecules 11 Transportation of macromolecules Guyton and Hall Textbook of Medical Physiology, 14th edition. Transcytosis vesicles are small membrane invaginations, called caveolae, that are believed to play a role in transporting macromolecules across the cell membrane. Caveolae contain caveolins, which are proteins that interact with cholesterol and polymerize to form the caveolae. 12 • The caveolae appear to swallow small packets of plasma or extracellular fluid that contain plasma proteins. • Then these vesicles move slowly through the endothelial cell. Some of them may fuse to form vesicular channels all the way through the endothelial cell 13 Special Types of “Pores” Occur in the Capillaries of Certain Organs • In the brain, the junctions between the capillary endothelial cells are mainly “tight” junctions that allow only extremely small molecules to pass into or out of the brain tissues. • In the liver, the clefts between the capillary endothelial cells are wide open so that almost all dissolved substances (even plasma proteins) can pass. • In the glomerular capillaries of the kidney, small oval windows called fenestrae penetrate all the way through the middle of the endothelial cells so that very small molecular and ionic substances (but not the plasma proteins) can filter through the glomeruli. 14 BODY FLUID COMPARTMENTS BODY FLUIDS Extracellular fluid Intracellular fluid Interstitial fluid* (Tissue fluid) Blood plasma Transcellular fluid (cerebrospinal fluid and the fluids in the synovial, peritoneal, paricardial spaces) Interstital fluid: inter - between + stare - to stand. Fluid which surround most cells of the body 15 Structure of Interstitium The interstitial fluid is entrapped mainly among the proteoglycan filaments. This combination of proteoglycan filaments and fluid entrapped within them has the characteristics of the tissue gel. The amount of free fluid present in most normal tissues is usually less than 1%. But it may increase more than 50% in edema. Proteoglycan filaments are everywhere in the spaces between the collagen fiber bundles. Free fluid vesicles and small amounts of free fluid (<%1) in the form of rivulets occasionally also occur. 16 Unequal distribution of solutes in extracellular and intracellular fluid The composition of plasma and interstitial fluid are almost identical, except for proteins à Interstitial fluid is poor in protein 17 Fluid Filtration Across Capillaries • The hydrostatic pressure in the capillaries tends to force fluid and substances through the capillary pores into the interstitial spaces. • Osmotic pressure caused by the plasma proteins (called colloid osmotic pressure ) tends to cause fluid movement by osmosis from the interstitial spaces into the blood. • This osmotic pressure prevents significant loss of fluid volume from the blood into the interstitial spaces. 18 Hole's Human Anatomy and Physiology 11e Osmotic pressure, is a form of pressure exerted by proteins in blood plasma that usually tends to pull water into the circulatory system. Hydrostatic pressure: pressure of the fluid that it exerts on walls of its container. 19 Blood pressure Blood pressure is the force that blood exerts against the inner walls of blood vessels. Human Physiology: An Integrated Approach 6e Pearson Blood pressure rises and falls in a regular fashion, it is pulsatile. The pressure is highest in arteries and lowest in veins 20 Primary forces that determine whether fluid will move out of the blood into the interstitial fluid or in the opposite direction. 1. 2. 3. 4. The capillary hydrostatic pressure (Pc), which tends to force fluid outward through the capillary membrane The interstitial fluid hydrostatic pressure (Pif), which tends to force fluid inward through the capillary membrane when Pif is positive but outward when Pif is negative The capillary plasma colloid osmotic pressure (Πp), which tends to cause osmosis of fluid inward through the capillary membrane The interstitial fluid colloid osmotic pressure (Πif), which tends to cause osmosis of fluid outward through the capillary membrane 22 Starling Forces* Fluid movement across a capillary wall is driven by the Starling pressures across the wall. Guyton and Hall Textbook of Medical Physiology, 14th edition. If the sum of these forces—the net filtration pressure —is positive, there will be a net fluid filtration across the capillaries. If the sum of the Starling forces is negative, there will be a net fluid absorption from the interstitial spaces into the capillaries *Physiologist Ernest Starling first demonstrated their importance 23 • The rate of fluid filtration in a tissue is also determined by the number and size of the pores in each capillary, as well as the number of capillaries in which blood is flowing. • These factors are usually expressed together as the capillary filtration coefficient (K f ). The K f is therefore a measure of the capacity of the capillary membranes to filter water for a given NFP and is usually expressed as ml/min per mm Hg NFP. Kf of the average tissue is about 0.01 ml/min per mm Hg per 100 g of tissue. It varies more than 100-fold among the different tissues. 24 Hole's Human Anatomy and Physiology 11e At the arteriolar end of capillaries, the blood pressure is higher than the colloid osmotic pressure, so filtration predominates. At the venular end, the colloid osmotic pressure is unchanged, but the blood pressure has decreased, thus reabsorption predominate. Closed-ended vessels called lymphatic capillaries collect the excess fluid in the interstitial fluid and return it through lymphatic vessels to the venous circulation. 26 mmHg 35 25 Colloid osmotic pressure Hydrostatic pressure Filtration Absorption 27 Interstitial Fluid Pressure • interstitial fluid pressure in loose subcutaneous tissue is, in normal conditions, averaging about −3 mm Hg. • In some of these tissues (e.g. brain and kidney), the interstitial fluid pressures are positive. • In most natural cavities of the body, where there is free fluid in dynamic equilibrium with the surrounding interstitial fluids, the pressures that have been measured have been negative. – Intrapleural space: −8 mm Hg – Joint synovial spaces: −4 to −6 mm Hg – Epidural space: −4 to −6 mm Hg 28 Filtration is usually greater than absorption, and about 3 liters/day of fluid flow out of the capillary into the interstitial space. Restoring fluid lost from the capillaries to the circulatory system is one of the functions of the lymphatic system. 29 Lymphatic System • The lymphatics carry excess fluid, proteins, and large particles away from the tissue. Guyton and Hall Textbook of Medical Physiology, 14th edition. 30 Medical Physiology, 2e 2017 The initial lymphatics (terminal lymphatics) have many interendothelial junctions that behave like one-way microvalves, also called primary lymph valves. The walls of the larger collecting lymphatics are similar to those of small veins, consisting of endothelium and sparse smooth muscle. 31 Medical Physiology, 2e 2017 The large lymphatic vessels, like the veins, have secondary lymph valves that restrict retrograde movement of lymph. Lymph flow depends on waves of contraction of smooth muscle in the walls of the larger lymph vessels (lymphatic pump) and interstitial fluid pressure. 32 • About 100 ml/hr of lymph flows through the thoracic duct of a resting human, and approximately another 20 ml flows into the circulation each hour through other channels, making a total estimated lymph flow of about 120 ml/hr or 2 to 3 L/day. 33 • Increases in mean Pif cause an increase in lymph flow • Elevated capillary hydrostatic pressure • Decreased plasma colloid osmotic pressure • Increased interstitial fluid colloid osmotic pressure • Increased permeability of the capillaries Medical Physiology, 2e 2017 • Intermittent compression and relaxation of lymphatics occur during respiration, walking, and intestinal peristalsis … • As P lymph rises in the collecting lymphatic vessels, smooth muscle in the lymphatic walls actively contracts by an intrinsic myogenic mechanism 34 Lymph nodes are located along the path of the collecting lymphatics. The large lymphatics ultimately drain into the left and right subclavian veins. Guyton and Hall Textbook of Medical Physiology, 14th edition. The lymphatic system allows the one-way movement of interstitial fluid from the tissues into the circulation 35 Functions of the lymphatic system 1) 1. 2) 2. 3) 3. returning fluid and partly proteins filtered out of the capillariesfluid to the system, returning andcirculatory partly proteins filtered out of the picking uptofatthe absorbed at the small intestine and capillaries circulatory system, transferring to the circulatory system, picking up fatitabsorbed at the small intestine and serves as a filter to help capturesystem, and destroy foreign transferring it to the circulatory pathogens. serves as a f 36 Almost all tissues of the body have special lymph channels that drain excess fluid directly from the interstitial spaces Essentially all the lymph vessels from the lower part of the body empty into the thoracic duct, which in turn empties into the blood venous system at the juncture of the left internal jugular vein and left subclavian vein. Guyton and Hall Textbook of Medical Physiology, 14th edition. Lymph from the left side of the head, left arm, and parts of the chest region also enters the thoracic duct before it empties into the veins. 37 Lymph from the right side of the neck and head, right arm, and parts of the right thorax enters the right lymph duct (much smaller than the thoracic duct), which empties into circulation at the juncture of the right subclavian vein and internal jugular vein. 38 Brain lymphatics The central nervous system is previously believed to be devoid of lymphatic vessels. However, recent studies showed meningeal lymphatic vessels, and the glymphatic pathway for the ISF and cerebrospinal fluid drainage. Maps of the lymphatic system: old (left) and updated to reflect the new discovery. University of Virginia Health System. (https://www.nih.gov/news-events/nihresearch-matters/lymphatic-vessels-discovered-centralnervous-system) https://sitn.hms.harvard.edu/flash/2016 /how-a-newly-discovered-body-partchanges-our-understanding-of-the-brainand-the-immune-system/ 39 Formation of Lymph • Lymph is derived from interstitial fluid that flows into the lymphatics. Therefore, lymphatics has almost the same composition as the interstitial fluid. • The average protein concentration of the interstitial fluid is about 2 g/dl. Lymph formed in the liver has a protein concentration as high as 6 g/dl, and lymph formed in the intestines has a protein concentration as high as 3 to 4 g/dl. • Thus, lymph from all areas of the body, usually has a protein concentration of 3 to 5 g/dl. 40 Formation of Lymph • The lymphatic system is also important for the absorption of fats from the gastrointestinal tract. After a fatty meal, thoracic duct lymph sometimes contains as much as 1% to 2% fat. • Even large particles, such as bacteria, can push their way between the endothelial cells of the lymphatic capillaries and in this way enter the lymph. As the lymph passes through the lymph nodes, these particles are almost entirely removed and destroyed 41 Edema • Accumulation of abnormally large amounts of fluid in the tissues • In many cases, edema occurs mainly in the extracellular fluid compartment, but it can also involve intracellular fluid accumulation. • The conditions that may cause intracellular swelling: (1) hyponatremia, (2) depression of the metabolic systems of the tissues (3) lack of adequate nutrition to the cells. (4) Inflammation in tissue 42 Intracellular Edema • e.g., if blood flow becomes too low to maintain normal tissue metabolism, the cell membrane ionic pumps become depressed, and sodium ions that normally leak into the interior of the cell can no longer be pumped out of the cells. The excess intracellular sodium ions then cause osmosis of water into the cells. • In inflammation cell membrane permeability increases, allowing sodium and other ions to diffuse into the interior of the cell, with subsequent osmosis of water into the cells. 43 Extracellular Edema • Extracellular edema occurs when excess fluid accumulates in the extracellular spaces. • There are two general causes of extracellular edema: (1) abnormal leakage of fluid from the plasma to the interstitial spaces across the capillaries; (2) failure of the lymphatics to return fluid from the interstitium back into the blood, often called lymphedema. 44 • Edema results from alterations in capillary exchange – – – – Increased filtration pressure Decreased osmotic pressure gradient across capillary Increased capillary permeability Inadequate lymph flow 45 Ø Increased filtration pressure • Increased arterial pressure • Venular constriction • Increased venous pressure (heart failure, incompetent valves, venous obstruction, increased total ECF volume, effect of gravity, etc) Ø Decreased osmotic pressure gradient across capillary • Decreased plasma protein level (protein-deficient diet, ascites; liver disorders) • Accumulation of osmotically active substances (e.g. protein) in interstitial space 46 mmHg 35 25 Colloid osmotic pressure Hydrostatic pressure Filtration Absorption 47 Edema Caused by Heart Failure • In heart failure, the heart fails to pump blood normally from the veins into the arteries, which raises venous and capillary pressures, causing increased capillary filtration. • In addition, the arterial pressure tends to fall, causing decreased excretion of salt and water by the kidneys, which causes still more edema. • Also, blood flow to the kidneys is reduced in persons with heart failure, and this reduced blood flow stimulates secretion of renin, causing increased formation of angiotensin II and aldosterone, which both cause additional salt and water retention by the kidneys. 48 Pulmonary edema in heart failure • In patients with left-sided heart failure blood is pumped into the lungs normally by the right side of the heart but cannot escape easily from the pulmonary veins to the left side of the heart because this part of the heart has been greatly weakened. Consequently, all the pulmonary vascular pressures, including pulmonary capillary pressure, rise far above normal, causing serious and life-threatening pulmonary edema. • When untreated, fluid accumulation in the lungs can rapidly progress, causing death within a few hours. 49 Increased capillary permeability • inflammation • e.g. Histamine released in the inflammatory response makes capillary walls leakier and allows proteins to escape from the plasma into the interstitial fluid à local swelling 50 Lymphedema—Failure of the Lymph Vessels to Return Fluid and Protein to the Blood •infections of the lymph nodes •certain types of cancer or after surgery in which lymph vessels are removed or obstructed Edema can become especially severe because plasma proteins that leak into the interstitium have no other way to be removed. The rise in protein concentration raises the colloid osmotic pressure of the interstitial fluid, which draws even more fluid out of the capillaries. e.g. infection by filaria roundworms (elephantiasis) 51 Safety Factors That Normally Prevent Edema • Even though many disturbances can cause edema, the abnormality must usually be severe before serious edema develops. (1) low compliance of the interstitium when interstitial fluid pressure is in the negative pressure range; (2) the ability of lymph flow to increase 10- to 50-fold; (3) washdown of the interstitial fluid protein concentration, which reduces interstitial fluid colloid osmotic pressure as capillary filtration increases. 52