The Integrative Five-Fluid Circulation System in the Human Body

Abstract

Water is the key medium to transport numerous constituents and to provide a platform for physiological processes to take place in the living organisms in general; it also participates actively in many of these processes. In humans, there are different vehicles to contain water and its constituents. Our objective is to find out whether there is an overall water-base circulation system in the human body by analyzing the updated findings of different research groups on the physiological functions of various seemingly isolated fluid systems. By 1963, there were five separate fluid systems discovered in mammalians: (i) The Primo Vasculature Fluid (PVF) with protein precursors and micro cells held in the Primo Vasculature System (PVS). (ii) Blood with its constituents held in the cardio vasculature. (iii) Extracranial interstitial fluid (ISF) whose vehicle had a very irregular structure-the interstitium all over the body. (iv) The cerebrospinal fluid had been considered to be within the brain ventricles and spinal canal. (v) The extra-cranial lymphatic system which drained ISF, and had been known to join the subclavian vein. Fluid (i) was first reported in 1963 and fluids (ii) to (v) have been known for many decades, but the failure to detect a lymphatic system inside the skull has also been a mystery for many decades. The intra-cranial ISF (which we name as BISF) has drawn little attention, apart from discussing the mechanism of the blood-brain-barrier. During the past decade, there has been direct evidence indicating that CSF and BISF are actually mixed. After that, the intracranial lymphatic system was discovered and confirmed in animal models only slightly over one year back, and we called such fluid as glymphatic-fluid. After reviewing the stated "classical" five fluid systems together with the new findings in Sections 2 -7, we propose, for the first time, that the PVF, the blood, ISF, a mixture of CSF-BISF, and a mixture of glymphatic-fluid and lymph form an integrative circulation system in water base in the human and other mammalian bodies, as schematically represented in the last section. In this paper, we point out the positive correlation of chronic neuro degenerative diseases such as Alzheimer's disease, Parkinson's diseases and the insufficient brain wastes clearance by the glymphatic system. We also discuss the role played by the venous vessels as part of such clearance in upright posture. Moreover, simple non-invasive maneuver techniques are introduced here, as one example of enhancement of glymphatic fluid flow out of the skull to join the lymphatic system. A series of questions are raised in Section 8, the answers to which would help us to understand the transition from physio-to pathological states in the development of many diseases. Detailed analysis of this paper leads us to consider that research in understanding this integrative circulation system is only at the infancy stage, and fluid dynamics investigation seems to be the plausible modality of approach in the near future.

Manifestation of Pathological States of Numerous Diseases in the Largest Organ of the Human Body: (I) Basics and the Diseases of Tendon

“…The stated communications include the transportation of molecules and various forms of energy signals (such as mechanical, sound, electrical signals). In particular, the IF is responsible for the following main processes: 1) Exchange of O 2 and CO 2 in muscles and organ cells; 2) Provision and re-absorption of nutrients to organ cells; 3) Transportation of metabolic debris and harmful cells to the peripheral lymphatic system via the flow of the IF to the lymphatic collecting ducts; 4) Supplying shear forces (acting as signals) during durotaxis/chemotaxis [10] of fibroblasts, chondrocytes, osteocytes, osteoblasts, mesenchymal stem cells and stem cells in the CT, including those in the hair-follicles, for tissue homeostasis as well as repairs/turnover of the CTIF system, cartilages and bones; 5) Provide a medium for the migration of International Journal of Clinical Medicine leucocytes from the blood vessels to the CTIF during inflammation; 6) It has been discovered only in the recent few years that a lymphatic system in the brain exists-called glymphatic system and the fluid is named the glymphatic fluid (see review of [11]). This fluid is a mixture of the classical cerebrospinal fluid flowing in the subarachnoid space and the brain interstitial fluid in the brain parenchyma.…”

“…GAG with binding water molecules builds a jelly-like IF as the ground substance of the fascia, and the IF, together with other fluids forms an integrative five-fluid system [11]. The fibroblasts are the most important, and most abundant cells in the largest organ of the body.…”

“…The concept of the CTIF system being a dynamic microenvironment for stem cell niche has been introduced [35]. The six main functions of the ground substance, or interstitial fluid have been stated in Section (1.3), and also described in more details in our previous work [11]. This fascia organ therefore also forms the largest communication network of the body.…”

“…details are described in [11]. If the mechanical tension of the collagen network is "properly high", the fibroblasts are in the activated state, stretching to form cell-cell connection, and there is a good communication network.…”

“…In the above statement, it has been assumed that the flow rate of IF into the lymphatic system remains constant. Moreover, it has recently been discovered that a lymphatic system inside the skull exists, and the "glymphatic lymph", which is a mixture of the classical cerebrospinal fluid and the interstitial fluid in the brain parenchyma, will flow from the brain via sheaths of nerve fibers, sheaths and inside the collagen layers of blood vessels to join the IF of the neck and peripheral lymphatic vessels (see Fig.3, 4, 6, 7, 8 and 10 of [11]). The fluids inside the body form a complicated circulation system.…”