1. The Microcirculation

2. The microcirculation Regulation of blood flow through tissues –
Not all capillaries are open at any given time
Regulatory area

3. 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

4. The microcirculation

5. 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

6. 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

7. The microcirculation - acute regulation

8. 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

9. 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").

10. 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.

11. The exchange vessels
Capillaries
Three structural types

12. 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

13. 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

14. 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

15. 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

16. Fluid exchange Starling Forces
The pressures that influence capillary exchange
Net driving force (net filtration pressure) is the arithmetic sum of all pressures

17. Fluid exchange
Capillary Exchange – (Systemic circulation)
Pressures at the arterial and venous end of capillary (mmHg)
HPc
HPt
OPc
OPt
NFP
+ 14
- 8
Arterial
Venous

18. 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]

19. 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

20. 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)

21. 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

22. 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’

23. Oedema How do we know that there is increased interstitial fluid?
Swelling
Pitting
(pitting oedema)

24. 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