Blood flow heterogeneity in the pulmonary and systemic circulations can cause significant reductions in oxygen transport, particularly under conditions of high oxygen demand such as exercise.  Heterogeneity in the microcirculation arises from both intrinsic factors and extrinsic factors.  Intrinsic factors include the structural heterogeneity of microcirculatory networks that arise in part due to geometric constraints and the stochastic nature of angiogenesis, and the resultant variations in blood flow and hematocrit.  Extrinsic factors include variations in oxygen supply and demand.  Various mechanisms of compensating for this heterogeneity to improve oxygen uptake and utilization have evolved, and include short-term mechanisms such as flow regulation and long-term mechanisms such as structural adaptation.  Quantitative modeling suggests that the matching of blood flow to ventilation in the lung and to metabolism in the systemic circulation is imperative for maintaining oxygen transport, particularly under conditions of high oxygen demand. Impairment of flow regulation under pathophysiological conditions can lead to low blood oxygen levels and organ failure, even under conditions of adequate overall tissue perfusion, suggesting new therapeutic approaches.

https://www.mayoclinic.org/biographies/roy-tuhin-k-m-d-ph-d/bio-20054451