microcirculation - u-szeged.hu › edu › pharmuk › notesph › circ2bw.pdf · capillary...

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Page 1 Microcirculation Microcirculation Microcirculation Microcirculation 1. 1. Structure Structure 2. 2. Diameter: 5 Diameter: 5-8 μm 8 μm 3. 3. Transit time: 1 Transit time: 1-2 sec 2 sec 4. 4. Role, Krogh cylinder Role, Krogh cylinder 5. 5. Types of capillaries (about 46 Types of capillaries (about 46 milliard, 4.6* 10 milliard, 4.6* 10 10 10 ), ), 6. 6. Starling Starling-filtration law filtration law Capillary Capillary structure structure Capillary Capillary structure structure 1. 1. Endothel Endothel cell cell 2. 2. Basement Basement membrane membrane (reticular reticular fiber) fiber) 3. 3. Pericyte Pericyte Intercellular Intercellular cleft cleft: most : most water water-soluble soluble substances substances diffuse diffuse through through the the capillary capillary membrane membrane along along the the clefts clefts.

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Page 1: Microcirculation - u-szeged.hu › edu › pharmuk › notesph › circ2bw.pdf · Capillary hydrostatic pressure ( Pc) Interstitial hydrostatic pressure ( Pi) (skin:) (skin:-2 mmHg,

Page 1

MicrocirculationMicrocirculationMicrocirculationMicrocirculation

1.1. StructureStructure

2.2. Diameter: 5Diameter: 5--8 µm8 µm

3.3. Transit time: 1Transit time: 1--2 sec2 sec

4.4. Role, Krogh cylinderRole, Krogh cylinder

5.5. Types of capillaries (about 46 Types of capillaries (about 46

milliard, 4.6* 10milliard, 4.6* 101010), ),

6.6. StarlingStarling--filtration lawfiltration law

CapillaryCapillary structurestructureCapillaryCapillary structurestructure

1.1. EndothelEndothel cellcell2.2. BasementBasement membranemembrane ((reticularreticular fiber)fiber)3.3. PericytePericyteIntercellularIntercellular cleftcleft: most : most waterwater--solublesoluble

substancessubstances diffusediffuse throughthrough thethe capillarycapillarymembranemembrane alongalong thethe cleftsclefts..

Page 2: Microcirculation - u-szeged.hu › edu › pharmuk › notesph › circ2bw.pdf · Capillary hydrostatic pressure ( Pc) Interstitial hydrostatic pressure ( Pi) (skin:) (skin:-2 mmHg,

Page 2

Capillary system

Precapillary sphincter (control)

AV-shunt

Postcapillary venule

Opened capillary: 10-30 %

Changeable permeability

ArteriesVein

Venule

Arteriole

Precapillary sphincters

Metarteriole

Capillaries

Small venule

Arteriovenous

bypasss

MicrocirculationMicrocirculationPrecapillary

sphincters

Page 3: Microcirculation - u-szeged.hu › edu › pharmuk › notesph › circ2bw.pdf · Capillary hydrostatic pressure ( Pc) Interstitial hydrostatic pressure ( Pi) (skin:) (skin:-2 mmHg,

Page 3

METARTERIOLES AND PRECAPILLARY SPHINCTERS

Venule

Capillaries

Arteriole

Precapillarysphinctersrelaxed

Precapillary sphincters constricted

Page 4: Microcirculation - u-szeged.hu › edu › pharmuk › notesph › circ2bw.pdf · Capillary hydrostatic pressure ( Pc) Interstitial hydrostatic pressure ( Pi) (skin:) (skin:-2 mmHg,

Page 4

Two capillary beds in series.

1. INTESTINES - LIVER

absorption – storage/processing/detoxication

2. INTRAGLOMERULAR – PERITUBULAR CAPILLARIES

filtration – reabsorption/secretion

3. HYPOTHALAMUS – ANTERIOR PITUITARY

neurohormone delivery for regulation of anterior pituitary

“PORTAL” CIRCULATION

StarlingStarling--filtrationfiltration lawlawStarlingStarling--filtrationfiltration lawlaw

Straling equation:Straling equation:

Jv: Jv: net fluid movement between compartments. net fluid movement between compartments. ([([PcPc − − PiPi] − σ[π] − σ[πcc − π− πii]) net driving force (effective filtration pressure)]) net driving force (effective filtration pressure)

Capillary hydrostatic pressure ( Capillary hydrostatic pressure ( PcPc ) ) Interstitial hydrostatic pressure ( Interstitial hydrostatic pressure ( PiPi ) (skin:) (skin:--2 mmHg, liver, kidney: +6 mmHg)2 mmHg, liver, kidney: +6 mmHg)Capillary oncotic pressure ( πCapillary oncotic pressure ( πcc ) ) Interstitial oncotic pressure ( πInterstitial oncotic pressure ( πii ) ) Filtration coefficient ( Filtration coefficient ( KfKf ): capillary surface and permeability): capillary surface and permeabilityReflection coefficient ( σ ) : protein content in the interstitium. 1= no protein Reflection coefficient ( σ ) : protein content in the interstitium. 1= no protein permeability; 0=high protein permeabilitypermeability; 0=high protein permeability

Permeability changes: histamine, bradikinin, serotonin, SPPermeability changes: histamine, bradikinin, serotonin, SP

Page 5: Microcirculation - u-szeged.hu › edu › pharmuk › notesph › circ2bw.pdf · Capillary hydrostatic pressure ( Pc) Interstitial hydrostatic pressure ( Pi) (skin:) (skin:-2 mmHg,

Page 5

Pressures (Hgmm)

Pc Pi σπc σπi Sum

Arterial end +35 -2 +28 +0.1 8.9

37.1-28

Venular end +15 -2 +28 +3 -8

20-28

STARLING (NEAR) EQUILIBRIUM

28.028.028.328.3TOTALTOTAL

28.028.0Plasma colloid osmotic pr.Plasma colloid osmotic pr.

8.08.0Interstitial colloid osmotic pr. Interstitial colloid osmotic pr.

3.03.0Negative interstitial pressureNegative interstitial pressure

17.317.3Mean capillary pressureMean capillary pressure

Absorption Absorption

forceforce

Filtration Filtration

forceforce

ForcesForces

BALANCE: 0.3 mmHg excess filtration force.

The excess fluid is taken up by the lymphatics.

Page 6: Microcirculation - u-szeged.hu › edu › pharmuk › notesph › circ2bw.pdf · Capillary hydrostatic pressure ( Pc) Interstitial hydrostatic pressure ( Pi) (skin:) (skin:-2 mmHg,

Page 6

Diffusion of fluid molecules and dissolved substances Diffusion of fluid molecules and dissolved substances

between the capillary and interstitial fluid spaces.between the capillary and interstitial fluid spaces.

Diffusion of fluid molecules and dissolved substances Diffusion of fluid molecules and dissolved substances

between the capillary and interstitial fluid spaces.between the capillary and interstitial fluid spaces.

Filtration: 24 l/day (0.3% CO)Filtration: 24 l/day (0.3% CO)

Reabsorption: 20.4 l/day (85%)Reabsorption: 20.4 l/day (85%)

Lymph: 3.6 l/day (15%)Lymph: 3.6 l/day (15%)

ARTERIOLES REGULATE BOTH ARTERIAL AND

INTRACAPILLARY PRESSURES

Arteriolar constriction:

- rise in arterial pressure

- drop in capillary press.

Arteriolar dilation:

- drop in arterial pressure

- rise in capillary press.

Rises in venous pressure

greatly increase intra-

capillary pressure.Blo

od p

ress

ure

(mm

Hg)

Vasocontriction

VasodilationNormal tone

Page 7: Microcirculation - u-szeged.hu › edu › pharmuk › notesph › circ2bw.pdf · Capillary hydrostatic pressure ( Pc) Interstitial hydrostatic pressure ( Pi) (skin:) (skin:-2 mmHg,

Page 7

Venous valves of the leg.

Venous circulationVenous circulationVenous circulationVenous circulation

StructureStructure

smooth musclesmooth muscle

collagen fibercollagen fiber

valvesvalves

Low pressureLow pressure

Blood reservoirBlood reservoir

VENOUS COMPLIANCE

VE

NO

US

VO

LU

ME

VENOUS PRESSURE

Sympatheticstimulation

• Relatively high compliance but:

• Compliance varies with filling

• Sympathetic activation decreases compliance

Page 8: Microcirculation - u-szeged.hu › edu › pharmuk › notesph › circ2bw.pdf · Capillary hydrostatic pressure ( Pc) Interstitial hydrostatic pressure ( Pi) (skin:) (skin:-2 mmHg,

Page 8

FactorsFactors enhancingenhancing venousvenous circulationcirculationFactorsFactors enhancingenhancing venousvenous circulationcirculation

1.1. HeartHeart pumppump functionfunction

2.2. SkeletalSkeletal musclemuscle contractioncontraction

3.3. PulsationPulsation of of arteriesarteries

4.4. SmoothSmooth musclemuscle contractioncontraction in in thethe vesselvessel wallwall ((myogenicmyogenic; ;

sympatheticsympathetic: : αα1; 1; humoralhumoral factorsfactors: : endothelinendothelin))

5.5. NegativeNegative intrathoracalintrathoracal pressurepressure

6.6. PositivePositive intraabdominalintraabdominal pressurepressure

7.7. ValvesValves ((butbut no no valvesvalves: : smallsmall veinsveins, , greatgreat veinsveins, , brainbrain, ,

visceraviscera))

8.8. GravitationGravitation ((aboveabove thethe heartheart), (), (inhibitsinhibits belowbelow thethe heartheart))

EffectEffect of of gravitationalgravitational pressurepressure onon thethe venousvenous pressurespressures throughoutthroughout

thethe body in body in thethe standing standing personperson. .

StandingStanding: 500 ml : 500 ml intointo thethe leg leg veinsveins

CentralCentral venousvenous pressurepressure: : 00--2 2 mmHgmmHg; ; ↓↓ => => hypovolemiahypovolemia

Page 9: Microcirculation - u-szeged.hu › edu › pharmuk › notesph › circ2bw.pdf · Capillary hydrostatic pressure ( Pc) Interstitial hydrostatic pressure ( Pi) (skin:) (skin:-2 mmHg,

Page 9

RoleRole of of musclemuscle contrationcontration and and venousvenous valvevalveRoleRole of of musclemuscle contrationcontration and and venousvenous valvevalve

ZártZárt

ZártZárt

NyitottNyitott

Effect of respiration on the venous circulationEffect of respiration on the venous circulationEffect of respiration on the venous circulationEffect of respiration on the venous circulation

Page 10: Microcirculation - u-szeged.hu › edu › pharmuk › notesph › circ2bw.pdf · Capillary hydrostatic pressure ( Pc) Interstitial hydrostatic pressure ( Pi) (skin:) (skin:-2 mmHg,

Page 10

Blood reservoirsBlood reservoirsBlood reservoirsBlood reservoirs

1.1. Venous systemVenous system

2.2. Pulmonary blood vesselsPulmonary blood vessels

3.3. Heart (increased ejection)Heart (increased ejection)

Specific reservoirs:Specific reservoirs:

1.1. Skin venous plexus (300Skin venous plexus (300--500 ml)500 ml)

2.2. Large abdominal veins (300 ml)Large abdominal veins (300 ml)

3.3. Liver (200Liver (200--300 ml)300 ml)

4.4. Spleen (150 ml)Spleen (150 ml)

Lymphatic systemLymphatic systemLymphatic systemLymphatic system

Structure of the interstitium. Structure of the interstitium. Proteoglycan filaments are everywhere in the spaces between the collagen fiber bundles. Proteoglycan filaments are everywhere in the spaces between the collagen fiber bundles. Free Free

fluid vesiclesfluid vesicles and small amounts of and small amounts of free fluidfree fluid in the form of rivulets.in the form of rivulets.

Page 11: Microcirculation - u-szeged.hu › edu › pharmuk › notesph › circ2bw.pdf · Capillary hydrostatic pressure ( Pc) Interstitial hydrostatic pressure ( Pi) (skin:) (skin:-2 mmHg,

Page 11

Arteriole

Net

filtration Net

absorption

Venule

Lymph vessels

LYMPHATIC CAPILLARIES ARE PART OF THE

MICROCIRCULATION

StructureStructure of of thethe lymphaticlymphatic

capillariescapillaries

StructureStructure of of thethe lymphaticlymphatic

capillariescapillaries

Capillaries terminate blind.

EndothelEndothel cellscells

No No fenestrationfenestration, no , no basementbasement membranemembrane, no , no

pericytepericyte, no , no tighttight intercellularintercellular connectionconnection

Capillary endothelial cells form valves.

LargeLarge permeabilitypermeability: it : it permitspermits passagepassage of of

substancessubstances of of highhigh molecularmolecular weightweight intointo thethe

lymphlymph. .

Page 12: Microcirculation - u-szeged.hu › edu › pharmuk › notesph › circ2bw.pdf · Capillary hydrostatic pressure ( Pc) Interstitial hydrostatic pressure ( Pi) (skin:) (skin:-2 mmHg,

Page 12

Lymphatic circulationLymphatic circulationLymphatic circulationLymphatic circulation

Right lymphatic ductRight lymphatic duct

Thoracic ductThoracic duct

Right and left subclavian veinsRight and left subclavian veins

LymphoidLymphoid folliclefollicleLymphoidLymphoid folliclefollicle

Functional structures of the spleen

Page 13: Microcirculation - u-szeged.hu › edu › pharmuk › notesph › circ2bw.pdf · Capillary hydrostatic pressure ( Pc) Interstitial hydrostatic pressure ( Pi) (skin:) (skin:-2 mmHg,

Page 13

LYMPHATIC SYSTEM

Functions:

1. Drainage of interstitial proteins: fundamental, vital function!

2. Return of excess filtrate.

3. Absorption of lipids.

4. Hosting lymphocytes.

Functional characteristics:

•Vessels contain valves.

• Smooth muscle displays

intrinsic pumping activity

FactorsFactors enhancingenhancing lymphaticlymphatic circulationcirculationFactorsFactors enhancingenhancing lymphaticlymphatic circulationcirculation

1.1. HeartHeart pumppump functionfunction

2.2. SkeletalSkeletal musclemuscle contractioncontraction

3.3. PulsationPulsation of of arteriesarteries

4.4. SpontaneousSpontaneous smoothsmooth musclemuscle contractioncontraction inin thethe vesselvessel wallwall

5.5. NegativeNegative intrathoracalintrathoracal pressurepressure

6.6. PositivePositive intraabdominalintraabdominal pressurepressure

7.7. ValvesValves

8.8. GravitationGravitation ((aboveabove thethe heartheart), (), (inhibitsinhibits belowbelow thethe heartheart))

Page 14: Microcirculation - u-szeged.hu › edu › pharmuk › notesph › circ2bw.pdf · Capillary hydrostatic pressure ( Pc) Interstitial hydrostatic pressure ( Pi) (skin:) (skin:-2 mmHg,

Page 14

Relation between interstitial fluid pressure and lymph Relation between interstitial fluid pressure and lymph

flow. flow.

Relation between interstitial fluid pressure and lymph Relation between interstitial fluid pressure and lymph

flow. flow.