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 arterioles Innervated-sympathetic precapillary sphincter – at the start of capillary Secondary & tertiary arterioles Less smooth muscle, sparsely innervated Terminal arterioles Capillaries

The microcirculation

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/100g Heart – 4%, 200ml/min, 70ml/min/100g Kidneys – 22%, 1100ml/min, 360ml/min/100g Liver – 27%, 1350ml/min, 95ml/min/100g Thyroid – 6%, 50ml/min, 160ml/min/100g

The microcirculation - regulation 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 - acute regulation

The microcirculation – long term 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 exchange vessels 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 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 Hydrostatic pressure in the capillary Capillary Exchange Exchange of fluid across the capillary is dependent on four forces Hydrostatic pressure in the capillary Hydrostatic pressure in the interstitial tissue Oncotic pressure in the capillary 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 NFP + 14 - 8 Arterial Venous

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 Bulk flow – fluid and electrolytes through pores 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 substances Bulk 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