Microcirculation and Regulation of blood flow

DR. Shafali Singh

Learning objectives • Define the microcirculation • Describe the four Starling forces, and explain for each, whether

they favor absorption or filtration • Explain how changes in Starling factors promote edema • Define autoregulation of blood flow. Describe how the theory of

metabolic regulation of blood flow accounts for active hyperemia and reactive hyperemia.

• Describe the contribution of myogenic tone to blood flow regulation.

• Identify the role of PO2 , PCO2 , pH, adenosine, and K+ in the metabolic control of blood flow to specific tissues.

• Understand the synthetic pathway for nitric oxide (EDRF, endothelial derived relaxing factor), including substrate and the interplay between endothelium and vascular smooth muscle

Transcapillary Exchange

• Solvent and solute move across the capillary endothelial wall by three processes:

1. Diffusion,2. Filtration, 3. Pinocytosis

For diffusion across a capillary wall, Fick's law can also be expressed as

CAPILLARY FILTRATION-Rate of filtration

• Q. At the arteriolar end of a capillary, Pc is 30 mm Hg, πc is 28 mm Hg, Pi is 0 mm Hg, and πi is 4 mm Hg. Will filtration or absorption occur?

• Q.At the venous end of the same capillary, Pc has decreased to 16 mm Hg, πc remains at 28 mm Hg, Pi is 0 mm Hg, and πi is 4 mm Hg. Will filtration or absorption occur?

Causes and Examples of Edema

Cause Examples↑ Pc Arteriolar dilation

Venous constrictionIncreased venous pressure

Heart failureExtracellular volume expansionStanding (edema in the dependent limbs)

↓ πc Decreased plasma protein concentrationSevere liver disease (failure to synthesize proteins)Protein malnutritionNephrotic syndrome (loss of protein in urine)

↑ Kf BurnInflammation (release of histamine; cytokines)

Lymph

a. Function of lymph• Normally, filtration of fluid out of the capillaries is slightly

greater than absorption of fluid into the capillaries. The excess filtered fluid is returned to the circulation via the lymph.

• Lymph also returns any filtered protein to the circulation.b. Unidirectional flow of lymph• One-way flap valves permit interstitial fluid to enter, but

not leave, the lymph vessels.• Flow through larger lymphatic vessels is also

unidirectional, and is aided by one-way valves and skeletal muscle contraction.

Microcirculation

• Circulation of blood through the smallest vessels of the body-arterioles, capillaries, and venules.

Vasoactive Role of the Capillary Endothelium

Local Control of  Blood Flow: • There are several examples of local control of

blood flow, including:

(1)Autoregulation(2)Active hyperemia (3)Reactive hyperemia

• Active hyperemia : blood flow to an organ is proportional to its metabolic activity. • When any tissue becomes highly active e.gAn exercising muscle,A gastrointestinal gland during a hypersecretory

period, Brain during rapid mental activity, • the rate of blood flow through the tissue

increases.

• Reactive hyperemia : increase in blood flow in response to or reacting to a prior period of decreased blood flow (arterial occlusion). 

MECHANISMS FOR CONTROL OF REGIONAL BLOOD FLOW

EXTRINSICINTRINSIC

Autoregulation

Myogenic Metabolic

Autonomic Nervous system

Intrinsic Regulation (Autoregulation)

• The control mechanisms regulating the arteriolar smooth muscle are entirely within the organ itself.

• No nerves or circulating substances are involved in autoregulation.

• Thus, the autonomic nervous system and circulating epinephrine have nothing to do with autoregulation.

• There are 2 main theories that attempt to explain autoregulation. Of them, the metabolic hypothesis has more support.

• Two basic mechanisms are proposed to explain the phenomena of autoregulation and active and reactive hyperemia:

• Metabolic hypothesis. • Myogenic hypothesis 

Intrinsic Regulation (Autoregulation)

Metabolic hypothesis• Tissue produces a vasodilatory metabolite that

regulates flow, e.g., adenosine in the coronary circulation

• A dilation of the arterioles is produced when the concentration of these metabolites increases in the tissue.

• The arterioles constrict if the tissue concentration of metabolites decreases.

Vasodilator Theory for Acute Local Blood Flow Regulation—

• Adenosine• Carbon dioxide, • Adenosine phosphate compounds,• Histamine• Potassium ions, • Hydrogen ions.

Oxygen Lack Theory for Local Blood Flow Control

• Autoregulation is the maintenance of a constant blood flow to an organ in the face of changing arterial pressure.

• Several organs exhibit autoregulation of blood flow, including the kidneys, brain, heart, and skeletal muscle.

• If BP falls compensatory vasodilation of the coronary arterioles decreases the resistance of the coronary vasculature  flow is maintained constant .

Intrinsic Regulation (Autoregulation)

Myogenic hypothesis• Increased perfusing pressure causes

stretch of the arteriolar wall and the surrounding smooth muscle.

• Because an inherent property of the smooth muscle is to contract when stretched, the arteriole radius decreases, and flow does not increase significantly.

• Blood flow in most cases is proportional to tissue metabolism.

• Blood flow is independent of nervous reflexes (e.g., carotid sinus) or circulating humoral factors.

• Autoregulating tissues include (tissues least affected by nervous reflexes):

Cerebral circulation Coronary circulation Skeletal muscle vasculature during exercise• Control of renal blood flow is also commonly referred

to as autoregulation even though it is partially controlled by neural and hormonal influences

Extrinsic Regulation

• These tissues are controlled by nervous and humoral factors originating outside the organ, e.g., resting skeletal muscle.

• The main mechanism controlling flow in resting skeletal muscle and all other major extrinsically regulated systemic circuits is tonic changes in sympathetic adrenergic activity, i.e., norepinephrine acting on α receptors, causing constriction.

• Generally, the parasympathetic system does not affect arterioles, and thus it has little or no influence on TPR (exception: the penis).

• Circulations with mainly extrinsic regulation (those most affected by nervous reflexes):

Cutaneous circulation Resting skeletal muscle

Control of Resting versus Exercising Muscle

Resting muscle• Flow is controlled mainly by increasing or decreasing sympathetic α -

adrenergic activity. But β2 receptors can contribute to the regulation of blood flow.

Exercising muscle• The increase in flow is mainly via vasodilatory metabolites, but this

cannot occur without a significant contribution via an increase in CO.• β2 activation via circulating epinephrine can contribute to the increase

in flow.• Sympathetic adrenergic nerves have no effect on flow in exercising

muscle. (α receptors become less responsive to norepinephrine.)• Thus, if there was an increase in sympathetic activity to an exercising

muscle, flow would not be altered significantly by α receptor-mediated effects.

Response to exercise

Muscle Blood Flow.

ml/100 g Muscle/min• Resting blood flow 3.6• Blood flow during maximal exercise 90

• Increase in flow results from intra-muscular vasodilation caused by the direct effects of increased muscle metabolism.

• Moderate increase in arterial blood pressure that occurs in exercise, usually about a 30 per cent increase.

• The increase in pressure not only forces more blood through the blood vessels but also stretches the walls of the arterioles and further reduces the vascular resistance.

Exercising skeletal muscle• Blood flow increases.• Vascular resistance decreases.• Capillary pressure increases.• Capillary filtration increases.• Lymph flow increases.• Venous PO2decreases and can reach

extremely low levels.• Extraction of oxygen increases.

Pulmonary response to exercise• A large increase in cardiac output means increased

volume pumped into the circuit.

• This will produce a rise in pulmonary pressures.

• Because of the passive, compliant nature of the circuit, the response to a rise in pressure is vessel dilation.

• This response leads to apical blood vessel recruitment.• The overall response is a large decrease in resistance.

Pulmonary Circuit• Blood flow (CO): large increase• Pulmonary arterial pressure: slight increase• Pulmonary vascular resistance: large decrease• Pulmonary blood volume: increase• Number of perfused capillaries: increase• Capillary surface area: increase, i.e., increased

rate of gas exchange

Q     Correct statements about the increase in 

pulmonary blood flow during vigorous exercise include which of the following?

a. The percentage of increase in flow is greater in the bases of the lungs than in the apices

b. The increase in flow is caused by a greater-than-fivefold increase in pulmonary arterial pressure

c. The increase in pulmonary blood flow is less than the increase in systemic blood flow

d. The increase in pulmonary blood flow is accommodated by dilation of pulmonary arterioles and capillaries

e. The increase in pulmonary blood flow is caused by sympathetic nerve stimulation of the pulmonary vasculature

Regional Circulations

• Blood flow to active organs like Heart, Skeletal muscle.

• Blood flow to inactive organs like Kidney, Skin, GIT

Regional Circulations

•Cutaneous blood flowInitial decrease, then an increase to dissipate heat•Coronary blood flowIncrease due to increase in volume work of the heart•Cerebral blood flowNo significant change (arterial CO2 remains 

unchanged)•Renal and GI blood flowAny change would be a decrease. This is more likely in 

the splanchnic circuit.