Microcirculation

Question 1

Anomalous viscosity

Answer 1

• indicated by the curvature at low flow rates, refers to the increase in viscosity at low flow rate
• at low flow rates blood appears to have a higher resistance than a faster flow rates due to formation of Rouleaux
• as blood flow increases, Rouleaux tend to break up, thereby decreasing the viscosity and the resistance, thus contributing to anomalous viscosity

Question 2

Hematocrit

Answer 2

• is the volume fraction of blood occupied by red blood cels
• the absolute and relative viscosities of blood increase with hematocrit
• when HCT increases from 40% to 60% as occurs in polycythemia- blood viscosity doubles, therefore the resistance to the flow of blood also doubles, and the heart must work harder to maintain normal cardiac output
• nearly one half of patients develop hypertension, treatment is effected by removing the excess red cell by phlebotomy in order to restore a normal hematocrit

Question 3

Blood viscosity

Answer 3

• apparent viscosity of blood also depends on the diameter of the tube through which the blood is flowing- Fahraeus-Lindqvist effect (tubes less than 0.3mm, so arterioles, capillaries, venules) the apparent viscosity of blood decreases
• the low blood viscosity in tubes of small diameter has been explained by axial streaming or the tendency of red cells to accumulate in the rapidly flowing axial lamina
• the formation of Rouleaux at low flow rates in the microcirculation increases blood viscosity thereby reducing the flow. However the Fahraeus-Lindqvist effect decreases viscosity in the microcirculation and facilitates flow

Question 4

Nonideal rheological effects

Answer 4

• formation of Rouleaux-chain like aggregates of red blood cells which form at low flow rates, as flow increases the Rouleaux tend to break up, decreasing the viscosity and the resistance, thus contributing to anomalous viscosity
• axial streaming; plasma skimming- altered hematocrits in small vessels result from this, the tendency of the cell free plasma to be skimmed off a branch point of microcirculation
• cellular deformability- the ability to bend
• Fahraeus-Lindqvist effect

Question 5

Microcirculatory circuit

Answer 5

• the structure and function of the microcirculation differs in different tissues
• nutritional source and waste removal in most vascular beds
• filtration in renal glomeruli
• thermoregulation in the skin

-the microcirculatory circuit extends from an arteriole to a venule. Arterioles are surrounded by a single layer of vascular smooth muscle cells; venules are surrounded by a discontinuous layer of vascular smooth muscle cells

Question 6

Small vessels effects show Fahraeus-Linqvist effect

Answer 6

• a Y shaped branching point, how the branch that heads off to the right recieves most of the flow, with the left branch receiving less total flow and many fewer erythrocytes
• the left branch has a variable flow rate, at times slowing down and almost reversing at one point
• the center column of red blood cells, the string of dark endothelial cell nuclei that outline the vessel wall and the clear plasma layer next to the wall that reduces blood viscosity at this level of blood viscosity
• this reduction in blood viscosity in small blood vessels is called the Fahraeus-Lindqvist effect after it discovers

Question 7

Three types of capillaries

Answer 7

• consist of a single layer of endothelial cells surrounded by a basement membrane, ranges from 4-10 microns, red cell deform as they pass through capillaries
• continuous capillaries- common with interendothelial junctions 10-15 nm wide as in skeletal muscle, the junctions are absent in brain capillaries which have narrow tight junctions that form the blood brain barrier
• fenestrated- surround exocrine glands or epithelial membranes such as small intestine, permit flow of fluid and solute across the capillary endothelial membrane
• discontinuous- found in liver sinusoids, have large gaps

Question 8

Cardiovascular transport

Answer 8

• substance are carried between organs within the cardiovascular system by convective transport carried along with the flow of blood
• the transport rate only depends on concentration of the substance and flow rate: transport rate of X = flow rate x concentration or X = Q x [C]
• only two methods to alter the rate at which a substance is carried to an organ- change the flow rate through the organ or change the arterial concentration
• tissue rate of utilization or production of substance x measured from transport rate in and out of the tissue. This is the Fick principle: transcapillary efflux rate (mass/time) = Q x ([Xarterial-Xvenous])
• if the transcapillary efflux rate of a substance is negative, then the tissue is producing it

Question 9

Fick’s first law of diffusion

Answer 9

• capillaries act as efficient exchange sites where most substances cross capillary walls by diffusion
• diffusion is tremendously powerful mechanism for material exchange over capillary distances: no cell is more than 10 um from one
• substances move from high to low concentrations
• four factors determine the diffusion rate of a substance between blood and interstitial fluid- concentration difference, surface area for exchange, diffusion distance, permeability of the capillary wall to the diffusing substance

Question 10

Osmotic pressure of solutions

Answer 10

• osmosis is the movement of water across a semipermeable membrane from a solution that is less concentrated to a solution that is more concentrated
• water flows from where its chemical potential is higher (in the dilute solution) to where its chemical potential is lower (the concentrated solution)
• chemical potential is a measure of the free energy of a solution; spontaneous processes always lower the total free energy of a system, and also act to equalize the free energy in the various compartments of a system
• the hydrostatic pressure that develops in the tube raises the chemical potential of the water in the solution
• the hydrostatic pressure that just suffices to stop the flow of water into the solution is defined to be the osmotic pressure

Question 11

Transcapillary fluid movement

Answer 11

• net shifts in fluid between capillary and interstitial compartments important for: maintenance of blood volume, interstitial fluid absorption, tissue edema formation, saliva production, sweat production, urine production
• fluid flows through transcapillary channels
• responds to pressure differences between compartments
• two types of pressure: hydrostatic, osmotic
• Capillary hydrostatic pressure (Pc) 25 mm Hg
• Interstitial fluid hydrostatic pressure (Pif) (~0 (-2) mm Hg)
• Capillary osmotic pressure (Pi c)
• Interstitial fluid osmotic pressure (Pi if)

Question 12

Starling equation

Answer 12

• fluid balance with a tissue (the absence of net transcapillary water movement) occurs when the bracketed term is 0
• equilibrium can be upset by alterations in any of the four pressure terms
• this equation sets the capillary filtration and reabsorption rates
• in most tissues, rapid net filtration is abnormal and causes tissue swelling
• water crosses the capillary membrane by the process of convection
• positive hydrostatic pressure difference- positive flow of water out of the capillaries into the interstitial fluid space
• negative hydrostatic pressure difference- negative flow of water into the capillaries from the interstitial fluid space

Question 13

Capillary Hydrostatic Pressure (Pc)

Answer 13

• Pc varies among different tissues
• higher Pc favors filtration
• in renal glomeruli, Pc is about 50 mm Hg, large enough to enable glomerular filtration
• in pulmonary capillaries, Pc is only 5-15 mm Hg, thereby preventing filtration and pulmonary edema
• Pc is influenced by gravity
• Pc is 35 mm Hg at arteriolar end and 15 mm Hg at venous end of capillaries

Question 14

Effect of arteriolar and venular constriction and dilation on capillary hydrostatic pressure

Answer 14

• normal, Arteriole- 60 mm Hg, Capillary 25 mm Hg, Venule- 15 mm Hg
• arterior dilation or venular constriction increase capillary hydrostatic pressure, arteriole- 60 mm Hg, Capillary 40 mm Hg, Venule 15 mm Hg
• arterior constriction or venular dilation decrease capillary hydrostatic pressure, arteriole- 60 mm Hg, Capillary 20 mm Hg, venule 15 mm Hg

Question 15

Capillary colloid osmotic pressure, Pi c

Answer 15

• total osmotic pressure of plasma is due both to salts and proteins. Higher concentration of protein in the plasma is the primary factor. Oncotic pressure is the portion of the solutions total osmotic pressure that is due to particles that do not move freely across the capillaries
• colloid osmotic pressure of plasma is due to proteins plus the excess salt caused by the Gibbs Donnan effect exerted by the proteins
• Pi c exerts a force that favors fluid adsorption
• about 2/3 of the colloid osmotic pressure is due to proteins- albumin, globulins, and fibrinogen
• the combined effects of the plasma proteins and the slight excess salt in the plasma together make the colloid osmotic pressure of the plasma about 25 mm Hg
• the salt concentration across the capillary membrane is about 0.5 mM greater in the plasma than in the interstitium due to the Gibbs-Donnan equilibrium

Question 16

Changes in interstitial fluid

Answer 16

• interstitium is made of both solid and liquid phases, and only a small fraction of the water is actually free to move
• difficult to measure Pif but in loose tissue it is negative while in rigid enclosed compartments (bone marrow and brain) and encapsulated organs (kidney) it is positive
• Pif is sensitive to the addition of fluids to the interstitial compartment, can lead to a disruption of the solid phase collagen fibers and the proteoglycan gel. This is especially true in loose subcutaneous tissue which can accommodate edema fluid

Question 17

Interstitial fluid hydrostatic pressure (pif)

Answer 17

• in loose tissues such as lung and subcutaneous tissue, Pif is typically slightly negative, about -2 mm Hg, exerting a force that drives fluid filtration
• in rigid enclosed compartments such as bone marrow or the brain, or in encapsulated tissues such as skeletal muscle or the kidney, Pif is positive at 1-3 mm Hg, exerting a force that drives fluid absorption

Question 18

Interstitial fluid osmotic pressure (Pi if)

Answer 18

• total body average Pi if is about 3 mm Hg, exerting a force that drives filtration
• interstitium contains a solid gel phase and a liquid phase
• solid gel phase consists of collegen fibers and proteoglycans
• water and solutes move by diffusion through the gel
• small additions of interstitial fluid raise Pif, thus opposing further filtration (low compliance system). However, with further additions some tissues such as loose subcutaneous tissue interstitium can accommodate large volume of edematous fluid without much rise in pressure (high compliance system)

Question 19

Starling forces along a capillary

Answer 19

• starling equation predicts filtration at the arteriolar end and absorption at the venular end of most capillary beds
• remember that Pc falls along the length of the capillary
• at the arteriolar end of a capillary, the hydrostatic pressure driving filtration exceeds the colloid osmotic pressure driving absorption; hence the net result is filtration
• fluid leaving the capillary at the proximal end contains plasma protein, resulting in a gradual increase in interstitial colloid osmotic pressure along the length of the capillary bed. The decreased capillary hydrostatic hydrostatic pressure of the plasma dominates, resulting in absorption at the venular end of the capillaries

Question 20

Net daily capillary filtration exceeds daily capillary absorption

Answer 20

• neglecting renal glomular filtration, the total capillary filtration is estimated to be about 20 L/day aat the arteriolar ends of capillary beds
• absorption at the venular ends of capillary beds is estimated at 16-18 L/day
• thus, a net filtration of about 2-4 L/day occurs from the plasma to the interstitium

Question 21

Lymph vessels

Answer 21

• the lymphatic system is a pathway for larger molecules to reenter the circulatory system
• initial lymphatics similar to capillaries but with primary one-way lymph valves
• collecting lymphatics similar to small veins with sparse smooth muscle with secondary lymph valves
• lymph nodes located along path of collecting lymphatics
• large collecting lymphatics drain into right and left subclavian veins
• lymph flow is 2-4 L/day

Question 22

Fluid and protein balance

Answer 22

• edema- excess salt and water in interstitial space
• caused by renal, cardiac, lung and hepatic disease
• left heart failure leads to pulmonary edema
• pulmonary hypertension also causes pulmonary edema
• right heart failure leads to edema in lower extremities and abdominal viscera
• fluid from the hepatic and intestinal capillaries may move from the interstitium into the peritoneal cavity, a condition called ascites
• plasma albumin is synthesized in the liver and secreted into the plasma, thus liver disease leads to hypoalbuminemia and peripheral edema
• SIADH (inappropriate secretion of antidiuretic hormone by certain lung tumors) leads to peripheral edema
• lymphatic blockage: maliginant neoplasms may cause local edema upstream of the sites of blockage