Microcirculation Faculty of Medicine, Masaryk University 1 Microcirculation Microcirculatory function is the main prerequisite for adequate tissue oxygenation and thus organ function. The microcirculation is formed by the smallest blood vessels (<100 μm diameter), and consists of arterioles, capillaries, and venules. Its purpose 1) provides access for oxygenated blood to the tissues and appropriate return of volume; 2) maintains global tissue flood flow, even in the face of changes in central blood pressure 3) ensures adequate immunological function and, 4) links local blood flow to local metabolic needs The main cell types endothelial cells smooth muscle cells (mostly in arterioles), circulating blood cells Microcirculation The structure and function of the microcirculation is highly heterogeneous in different organ systems Main determinants of capillary blood flow driving pressure, arteriolar tone, hemorheology capillary patency Transport of substances through capillary membrane At arterial end of capillary the difference in hydrostatic pressures is higher than the difference in osmotic pressures which causes filtration. At arterial end of capillary the difference in hydrostatic pressures is lower than the difference in osmotic pressures which cause reabsorbtion. 4/9/2020 5 Regulation of blood supply Vasodilatation NO – produced in the endothelium by constitutive (eNOS) and inducible (iNOS) synthase prostacyclins catecholamines histamine bradykinin pO2, pCO2 ,pH cGMP, cAMP Vasoconstriction Endothelin ATII ADH Catecholamines Ca2+ a) short-term regulation Special mechanisms Kidney Tubuloglomerular feedback Brain Vasodilation as a response to elevated pCO2 in CSF Skin Blood flow control is linked to the control of body temperature Lungs hypoxia – vasoconstriction 8 Large vessels Mainly NO Regulation of blood supply b) Long-term regulation Days, months or years Mechanisms The blood vessels supplying the tissues increase their a. physical sizes b. Numbers Angiogenesis (buds from existing vessels) vs. vasculogenesis (de novo) 9 Important for tissues with high metabolic requirements Mechanisms 1.Increase of vascularity Examples: scar tissue tumours Slow process in terminally differentiated tissues 2.Development of collateral circulation from already existing vessels When the flow is blocked, other collateral vessels open Dilation in the acute phase (neurogenic and metabolic factors) Remodelation and enlargement in the long term 10 Neovascularisation The lymphatic system 13 Lymphatic circulation The interstitial fluid enters lymphatic capillaries through loose junctions between endothelial cells. Lymph flow back to the thoracic duct is promoted by contraction of smooth muscle in wall of lymphatic vessels & contraction of surrounding skeletal muscle (lymphatic pump) Lymph carry proteins that cannot pass the capillary wall – necessary for maintaining the circulating protein concentration (failure leads to death within 24 hours) Lymphatic drainage is also the main way of lipid absorption in GIT Pathogens are eliminated in the lymphatic nodes Lymph flow Is increased when the fluid filtration from the capillaries to the interstitium is increased a) Elevated capillary hydrostatic pressure b) Decreased capillary oncotic pressure c) Increased interstitial oncotic pressure d) Increased capillary permeability -Lymphatic pump generates the negative hydrostatic pressure in the interstitium -When the interstitial pressure is permanently elevated to +1 - +2 mmHg, a compression of larger lymphatic vessels may occur 16 Lymphatic pump A. intrinsic Contraction of vessel wall following its dilation Generates pressure between 50 – 100 mmHg 17 B. extrinsic Intermittent compression from outside During exercise, the lymphatic flow increases up to 30-fold Oedema Cellular (cytotoxic) oedema – fluid collection in the cells usually caused by ischemia → ionic pumps failure → ↑ cellular osmolarity most important inside the skull Interstitial oedema – fluid collection in the interstitium local vs. systemic causes – see further Effusion – fluid collection in body cavities Starling forces Actually pressures, or pressure gradients F = A . K . [(Pv – Pt) – σ(πv – πt)], where: F…filtration A…filtration area K…membrane permeability coefficient (for water) σ…membrane reflection coefficient (for proteins) The pressure gradient is directed outside at the arterial end and inside at the venous end of a capillary Exception: glomerular capillaries (high hydrostatic pressure – cave shock) Pulmonary capillaries – filtration slightly prevails all along the capillary (low both hydrostatic and oncotic pressure gradient) The flow from the capillary little exceeds the reabsorption – lymphatic drainage Causes of interstitial oedemas and effusions Higher capillary hydrostatic pressure hypervolemia hyperperfusion ↓ venous return Lower plasma oncotic pressure Increased capillary wall permeability Obstruction of the lymphatic vessels Hypervolemia - etiology Capillary hyperperfusion and oedema Oedema during hypertensive crisis – important in brain circulation Oedema as a side effect of vasodilation treatment Odemas in venous diseases ↑hydrostatic pressure at the venous end of a capillary Most often caused by venous valves insufficiency Deep venous thrombosis – asymmetric oedema Leg ulcers – most often of venous origin Increased filtration → increased capillary permeability → protein leak → „fibrin cuff“→ tissue ischemia → ulcer Heart failure and oedema Right-sided failure backward ↑ hydrostatic pressure at the venous and of systemic capillaries Oedemas in systemic circulation anasarca (systemic oedema) hepatomegaly, ascites forward Isolated is a rarity Leads into ↓ left ventricle preload → leftsided forward failure •Left-sided failure • backward • ↑hydrosta c pressure in pulmonary capillaries → pulmonary oedema • Respiratory failure, pleural effusion (transudate) • Pulmonary hypertension → secondary right-sided failure • forward • Systemic hypotension→ shock • Organ failure (liver, kidneys, GIT, brain) • Muscular weakness, fatigue, cachexia Pulmonary oedema and pleural effusion Pulmonary oedema: fluid accumulation in the lung tissue („swamp“) interstitial alveolar Both fluid filtration and resorption from/to pulmonary circulation Treatment: medication Pleural effusion: fluid between the parietal and visceral pleura („lake“) Fluid is filtrated mainly from the systemic circulation and reabsorbed mainly into the pulmonary circulation Treatment: medication or surgery In transudates, pulmonary oedema is often combined with pleural effusion X-ray Pulmonary oedema Bilateral pleural effusion Exudate vs. transudate Transudate ↓proteins ↓LD ↑glucose cells absent Etiology: 1) heart failure 2) hyperhydration 3) hypoproteinemia (liver failure, nephrotic syndrome) Exudate ↑proteins ↑LD ↓glucose cells present Etiology: 1) inflammation 2) tumour 3) Pulmonary embolism (results from local necrosis) 4) TBC Hypoproteinemia Normal blood protein level approx. 62 – 82 g/l Decrease: malnutrition (kwashiorkor) malabsorption liver failure nephrotic syndrome There is no pulmonary oedema (low both hydrostatic and oncotic pressure gradient in pulmonary capillaries)! Inflammation and oedema Mechanisms of endothelial permeability Transcellular transport vesiculo-vacuolar organelles (VVO) fenestrations (GIT, kidneys, endocrine glands) – with or without (glomerulus) a membrane Paracellular transport adherent junctions – formed mainly by cadherins dissolve when stimulated by: histamine bradykinin VEGF NO Tight junctions(esp. brain) – form a barrier Vascular mechanisms of inflammation Contraction of arterioles followed by vasodilation and increase in capillary permeability Vasoconstriction: endothelin, TXA2, PAF Vasodilation: iNOS, PGI2, bradykinin Cytokine production Lymphatic oedema Result of the impaired lymphatic drainage • Primary lymphatic oedema Idiopathic, a disorder of lymphatic system development Occurs usually during adolescence or early adulthood Sporadic or familiar occurrence • Secondary lymphatic oedema Secondary obstruction of lymphatic vessels (tumour, inflammation, trauma, iatrogenic – surgery radiation therapy, node extirpation) Filariasis in the tropics Oncologic diseases and their treatment in Europe Lymphatic oedema and tumours Mechanic compression of lymphatic vessels by a tumour Interstitial oedema around the tumour (inflammation, VEGF) → compression of lymphatic drainage Lymphatic node metastases „pitting and „non-pitting“ oedema In the low-protein oedema (heart failure, liver failure, nephrotic syndrome), a pit remains after pressing by a finger In high-protein oedema (lymphatic oedema, inflammation, chronic oedema), no pit is present Splanchnic circulation Precapillary sphincters Under normal circumstances, only some capillaries allow the blood passage When the precapillary sphincters open, more blood passes into the microcirculation The mechanism is present mainly in the splanchnic circulation Catecholamine-induced Changes in the Splanchnic Circulation Volumes and flows in the splanchnic region (normovolemic healthy male adult) blood volume of approximately 70 ml/kg body weight. splanchnic organs constitute 10% of the body weight, but contain 25% of the total blood volume. nearly two thirds of the splanchnic blood (i.e. > 800 ml) can be autotransfused into the systemic circulation within seconds. liver 300 - 400 ml intestine 300 - 400 ml spleen 100 ml splanchnic vasculature serves as an important blood reservoir for the circulatory system. Date of download: 3/21/2018 Copyright © 2018 American Society of Anesthesiologists. All rights reserved. From: Catecholamine-induced Changes in the Splanchnic Circulation Affecting Systemic Hemodynamics Anesthes. 2004;100(2):434-439. From: Catecholamine-induced Changes in the Splanchnic Circulation Affecting Systemic Hemodynamics Anesthes. 2004;100(2):434-439. Date of download: 3/21/2018 Copyright © 2018 American Society of Anesthesiologists. All rights reserved. From: Catecholamine-induced Changes in the Splanchnic Circulation Affecting Systemic Hemodynamics Anesthes. 2004;100(2):434-439. From: Catecholamine-induced Changes in the Splanchnic Circulation Affecting Systemic Hemodynamics Anesthes. 2004;100(2):434-439. Experiment Murine mesentery Adrenaline → arterial vasoconstriction (mainly α1 receptors) Histamine → arterial vasodilation (mainly H1 receptors)