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Basophilic Leucocytes: Structure, Function and Role in Disease

1975; Elsevier BV; Volume: 4; Issue: 3 Linguagem: Inglês

10.1016/s0308-2261(21)00099-0

1558-1977

Harold F. Dvorak, Ann M. Dvořàk,

Lipid metabolism and disorders

The vascular and skeletal networks are fundamental systems spanning the entire body volume. They are critical for life and their dysfunction leads to health challenges that worsen with ageing. Globally, the dominant cause of death is from cardiovascular disease (stroke, cardiac, vascular) with one-third of deaths attributed directly. Identification of disease states relies on clinical imaging and monitoring predetermined risk factors or known biomarkers. They create significant spatial and temporal challenges for direct measurement. Classification of small geometric and morphological changes is time-consuming and costly. Disease also slowly progresses over years but catastrophic physiological events such as plaque rupture, thrombus blockage and bone fracture can occur suddenly. Modelling of key elements of these systems at different scales can greatly expand our understanding of healthy physiological function and dysfunction, as well as causal factors that influence the progression of diseased states. Particle-based models provide specific advantages for representing multiphase heterogeneous biological flows and material evolution for intra-body processes. This knowledge can support better clinical diagnostics for vulnerable disease states and guide improved intervention strategies. Example applications of such modelling which are explored in this chapter include the following:•microcirculation flow of plasma and deformation of red blood cells which provides a mechanistic explanation of the Fahraeus–Lindqvist effect;•rolling adhesion of deformable white blood cells along a vascular wall based on adhesion kinetics and tether formation/rupture;•single-phase arterial flow in a clinical carotid bifurcation geometry with potential for prototyping virtual surgery scenarios;•a simple model of thrombin-induced coagulation of fibrin gel in a capillary flow that allows identification of key limiting factors for clot growth;•rupture of vulnerable large plaque whose dynamics are shown to depend on cap thickness and elasticity and nature of the initial damage. This provides novel insights into the role of intravascular haemorrhage and inflation, as well as iteration of multiple rupture/remodelling events that drive the stepwise growth of large plaques; and•bone remodelling using stress level-dependent conversion of marrow to bone linking cortical pore structure to age-related osteoporosis.