The Microcirculation

The microcirculation

Regulation of blood flow through tissues –

Not all capillaries are open at any given time

Regulatory area

The microcirculation

Regulation of blood flow through tissues –

Primary arteriolesInnervated-sympathetic

Secondary & tertiary arteriolesLess smooth muscle, sparselyinnervated

Terminal arterioles Capillaries

precapillary sphincter – at the start of capillary

The microcirculation

Blood flow is directly proportional to the metabolic demands and other needs of the tissues

For example, Blood flow through –Brain – 14%, 700ml/min, 50ml/min/100gHeart – 4%, 200ml/min, 70ml/min/100gKidneys – 22%, 1100ml/min, 360ml/min/100gLiver – 27%, 1350ml/min, 95ml/min/100gThyroid – 6%, 50ml/min, 160ml/min/100g

The microcirculation

Blood flow through tissues - 2 phases of regulation

Acute regulation/control Long term regulation

Acute control is achieved by local constriction or dilatation of arterioles, metarterioles, precapillary sphincters

The microcirculation - regulation

The microcirculation - acute regulation

Long term increase to a growing tissue/ tissue with increased demands over a period of days weeks due to generation of new vessels Angiogenesis – growth of new vessels Angiogenic factors – endothelial cell growth

factor, fibroblast growth factor, angiogenin

Collateral circulation Block in an artery/vein – development of a

new vascular channel allowing partial re-supply of blood to the affected tissue

The microcirculation – long term regulation

Exchange vessels There is a free exchange of water,

electrolytes, and small molecules between the intravascular and extravascular compartments of the body

The primary site of this exchange is capillaries and small post-capillary venules (sometimes grouped together and called "exchange vessels").

The exchange vessels

The exchange vessels

Capillaries Small exchange vessels (6-10 µ) composed of

highly attenuated (very thin) endothelial cells surrounded by basement membrane – no smooth muscle.

The exchange vessels

Capillaries

Three structural types

The exchange vessels

Capillaries - structural types Continuous (found in muscle, skin, lung,

central nervous system) – basement membrane is continuous and intercellular clefts are tight (i.e., have tight junctions); these capillaries have the lowest permeability

Fenestrated (found in exocrine glands, renal glomeruli, intestinal mucosa) – perforations (fenestrae) in endothelium result in relatively high permeability

Discontinuous (found in liver, spleen, bone marrow) – large intercellular gaps and gaps in basement membrane result in extremely high permeability

The exchange vessels

Capillaries Large surface area and relatively high

permeability (especially at intercellular clefts) to fluid and macromolecules make capillaries the primary site of exchange for fluid, electrolytes, gases, and macromolecules

In some organs, precapillary sphincters (a circular band of smooth muscle at entrance to capillary) can regulate the number of perfused capillaries

The exchange vessels

Venules Small exchange vessels (10-50 µ) composed

of endothelial cells surrounded by basement membrane (smallest postcapillary venules) and smooth muscle (larger venules)

Fluid and macromolecular exchange occur most prominently at venular junctions

Sympathetic innervation of larger venules can alter venular tone which plays a role in regulating capillary hydrostatic pressure

Fluid exchange

Capillary ExchangeExchange of fluid across the capillary is dependent on

four forces

1. Hydrostatic pressure in the capillary

2. Hydrostatic pressure in the interstitial tissue

3. Oncotic pressure in the capillary

4. Oncotic pressure in the interstitial tissue

Favouring fluid movement out of capillary – HPc, OPt

Favouring fluid movement into capillary – HPt, OPc

Main pressures – HPc, OPc

Fluid exchange

Starling Forces

The pressures that influence capillary exchange

Net driving force (net filtration pressure) is the arithmetic sum of all pressures

Fluid exchange

Capillary Exchange – (Systemic circulation)Pressures at the arterial and venous end of capillary (mmHg)

HPc 35 15

HPt 3 3

OPc 25 27

OPt 7 7

Arterial Venous

NFP + 14 - 8

Fluid exchange

Capillary Exchange The exchange of fluid across a capillary is

determined by hydrostatic and oncotic pressure gradients

Properties of of the capillary wall also influence fluid exchange - permeability and surface area of the capillaries

These relationships can be summarized by the following equation:JV = KF A [(PC – PT) – (pC - pT)][where, JV = rate of fluid movement, KF = capillary filtration constant, A = surface area for exchange, PC and PT = capillary and tissue hydrostatic pressures, and pC and pT = capillary and tissue oncotic pressures]

Fluid exchange

Capillary Exchange –Under normal conditions more fluid is filtered into the IF than reabsorbed Small amount of proteins is also filtered The excess of fluid and proteins are taken up by the lymphatics and returned to the veins

Fluid exchange

Terminal Lymphatics Composed of endothelium with intercellular gaps

surrounded by highly permeable basement membrane and are similar in size to venules – terminal lymphatics terminate as blind sacs

Larger lymphatics also have smooth muscle cells. Spontaneous and stretch-activated vasomotion is

present which serves to "pump" lymph Sympathetic nerves can modulate vasomotion and

cause contraction One-way valves direct lymph away from the tissue

and eventually back into the systemic circulation via the thoracic duct and subclavian veins (2-4 liters/day returned)

Fluid exchange

Mechanisms of fluid exchange

Fluid, electrolytes, gases, small and large molecular weight substances can transverse the capillary endothelium by several different mechanisms

Diffusuion – gases, lipid soluble substancesBulk flow – fluid and electrolytes

through pores Vesicular transport – macromolecules Active transport – not a major mechanism

Abnormalities of fluid exchange

Excess fluid accumulation in interstitial fluid

May occur due to a disturbance in the factors that influence filtration / reabsorption process

This condition is called ‘oedema’

Oedema

How do we know that there is increased interstitial fluid?

Swelling

Pitting (pitting oedema)

Abnormalities of fluid exchange

Mechanisms of oedema

Disturbances in Starling forces Increased capillary hydrostatic pressure Decreased plasma oncotic pressure (other two forces are insignificant)

Increased  capillary permeability

Lymphatic obstruction