The Physiology of Transport Substances in the Blood (Sodium)
By Professor Marcel Uluitu, M.D. Ph.D.
Co-Authored by Diana Popa (Uluitu), M.D.
Department of Microbiology, Immunology and Molecular Genetics
[Editor’s Note: This paper is presented as Part III of a series of chapters from the new book “The Physiology of Transport Substances in the Blood (Sodium)”; subsequent chapters will be featured in upcoming issues of this Journal. This segment features Section III (of three sections) of Chapter Two, Chapter Three and Chapter 4 (of six chapters)]
Chapter 2 (Section III):
The Blood-Vascular Space
2.8. Na transport in the blood.
Na chemical activity in the blood is conditioned by
its interaction with local components.
Na + heparin (H) = H-Na with an energy of interaction = E
H = H-5HT interaction with energy E
The determinations show that the chemical activity of
Na is lower than the reference value. This is consistent with normal nervous
excitability. The increase of the Na chemical activity is accompanied by
increased neuromuscular excitability: in rats by audiogenic seizures,
hypermotility, etc.In humans, they are expressed by behavior disorders of
constitutional type, EEG abnormalities, attention deficit disorders, disorders
of hemodynamic (see chapters of physiopathology). The interaction of Na with
proteins in the blood represents a barrier of energy in the way of Na motion as
a result of decrease of its chemical activity (218).
Na – proteins interaction in the blood has a
regulatory role for cation transport and also for mass transfer to endocellular
space of the excitable structure (218).
Unpolarizable Na induces protein conformational changes, increases the strength of anionic sites field (208, 166) and interacts with the water dipole. The intensity of these influences is reduced in the presence of other anions in solution and depends on the strength of the cationic field of hydrated Na.The loss of water molecules shortens ionic radius (Tab.9) (173, 126) and thus increases the energy of interaction. The energy of interaction is thus variable, it falls asymptotic to "0" from the center of ions towards periphery, defining in this manner a number of crystalline rays (120) of the ions.The charge of Na ions induces the increase of the energy of anionic sites of proteins and diminishing rays of interaction of the cation field. It interacts with all kinds of anions in blood (tb.11). The degree of interaction depends on the polarizability anions. The Na interaction with protein sites anion has decreased as a result of its chemical activity and its capacity to react with other anions. Proteins are the most important substances for the transport of Na. Proteins are amfoteric substances, have great plasticity and thereby enable the accommodation of various other ligands (191). Their capacity of transport depends on their nativity (Table 17). Interacting with metals they modify their charge by transferring electrons from the metal. The intensity of interaction of anionic sites of proteins with cations depends on other factors as well , such as (10) the number of coordination, the amino acid composition, polarizability of anino groups (Ling cit.16).
Strength sites is also influenced by internal neighboring groups, with variable polarity interacting through inductive forces, with intensity dependent on the square of the distance between them (120). The activity of proteins depends on the degree of dissociation of anionic sites, according to the theory of multiple equilibrium (112): it increases with the length of the polypeptide chain, with the pH of the solution and the intensity of the electrostatic forces (4, 20, 191). The affinity of proteins decreases by denaturation (233), the interest of coordination involving prototropic groups of the aminoacids residue aspartame, glutamic, histidine, treonine, cysteine, arginine. The charge density of the proteins , decisively influences the interaction with CATIONS. Its decrease diminishes the afinity for cations(166). The density of the charge of anionic sites induces the formation of a cationic cloud around them causing an unequal distribution of cations in the neighborhood (161). The selection for monovalent cations (20) depends on the charge density of the anionic electrostatic field and their degree of hydration (20,181,170). The amount of the charge density of the proteins influences inversely proportional the activity in solution of sodium (165.62).
The main issue is to decipher the mechanisms of Na transport in the blood. The data presented so far do not suggest an individualized transporter but present a general process in which blood proteins , or a multitude of anionic groups with which Na can interact , are involved. The type of binding, as well , is not identified, being represented by interactions that have been discussed at length. These are weak interactions that have an influence mainly by their number and type , rather than by their strength. Therefore the equilibrium of the three compartments does not depend only upon the gradient of the cation but also on the distribution of anionic groups between compartments. On the other hand the existence of olygoenergetic bonds ( weaker than between 5HT and heparin, taken as a reference value in the method used by us in this research ) enables us to underline some physicochemical properties of Na-proteins interaction. Sodium involved in various complex interactions, is in equilibrium with its free form, chemically active, as demonstrated by the method of competition and it is compatible with the functional manifestations of the excitable tissues. Increased chemical activity in humans and rats is accompanied by cerebral hyperexcitability .There are no data available to explain, among other things, the transfer mechanism of Na to the level of the excitable membranes, or the blocking of ionic channels by using toxins.
Na interacts with any kind of anions from the blood ( table 11 )
Method of determining the Na activity in blood serum. (Method of competition
5HT / Na for anionic sites of heparin)
Principle of method.
For dynamic dialysis the competition is determined between Na cations and serotonin (5HT) for the anionic sites of polyanion heparin (H).
Their affinity for heparin is different and can be
described by equations:
Eq. 1: Na
(mM)+ H(mg) Na-H with
interaction energy = E
5HT (g)+H(mg ) HT-H with
interaction energy = E
Since EE we have:
Eq 3: 5HT
+ Na + H Na-H + 5HT Eq.3 is valid for any solution that contains
the active chemical Na, and interacts with other substances with EE. In the presence of blood serum, the above equations are
written as follows:
+ Na + H + 5HT Na -H + 5HT + sn. Na is of exogenous origin.
Eq.6: denatured serum (sd)+ 5HT + H Na-H + 5HT. Na has endogenous blood origin. Dialysis allows to obtain the necessary values to calculate and to identify the heparin anionic sites.
126.96.36.199. Dialysis cell. (Figure 4).
The dialysis cell is made of a balloon with round bottom (1), with a polished neck in which a glass tube is mounted(4), polished as well (3), with the outer end open , where reactants are being introduced into the cellophane bag(2). This may be replaced by a rubber stopper pierced by a glass tube. The neck of the balloon has an orifice (5) where the solution of 0.25 M sucrose is inserted in which the cellophane bag is immersed. The system is equipped with a device for fixation on the agitator (6).
188.8.131.52. Preparation of the equipment.
A prerequisite is to avoid contact with ions of other source or ion exchangers, detergents. For this purpose glassware is abundantly flushed with double distilled water, dried and siliconed . Ion exchangers will not be used because fine particles of them can remain in water and modify the reactivity of proteins and the interaction with Na. The same steps are required in the preparation of cellophane bags. Solutions are to be prepared only with distilled water.
Reagents: heparin, serotonin, sucrose, NaCl, water.
2.9.4. Technical procedure.
184.108.40.206. Characterization of the dialysis bags
220.127.116.11. Measurement of the dialysis coefficient
Eq. 7 (C - C) / (C- C = e where :
C - C = concentration rate at 5HT EVRY "t" =
The calculation of diffusion coefficient "D"
depending on the concentration of heparin (Table 15, Fig 5) and under the
influence of Na (Table 16 and Figure 6).
Eq. 8 (C-C) / (C - C) =e of Ficks law leads to the conclusion that the process
of diffusion depends only on the nature and physical-chemical status of the diffusible
substance, 5HT (18). "D" is used to calculate 5HT-free running ,
diffusible in the mixture of reactances in the bag.
Figure 6. Dynamics of the 5HT dialysis in the bag , in the presence of 0,5 mg of heparin and of variable quantities of Na and in the absence of it(232).
2.9.5. Determination Na/5HT competition for anionic
sites of heparin.
Diffusion coefficient (D) in the presence of variable amounts of Na (232).
Table 16. M anionic sites depending on the concentration of
0.175 0.25 0.375
0.5 0.75 1,o
M anionic 0,0136 0, 02 0 041 0,0603 0,0747 0,0899
1 mg heparin, 60 g serotonin, complex salt in 0.25 M sucrose, the final amount
of 2.0 ml , are being introduced into the dialysis bag. The bag is
immersed in the 58 ml dialysis solution,
sucrose 0.25 M. The dialysis cell thus
prepared is fixed on the stirring device (Fig 4) and introduced into the bath with a temperature
of 200,1 C and stirred with a frequency of 80 cycle / min. At
baseline in the bag there are two forms of serotonin: one free, dialyzable and
other bonded, in interaction with the anionic sites of heparin. While 5HT free
running is difusing outside the bag , the
equilibrium between the bonded and the free forms left in the bag is
disturbed , initiating thus defixation processes (Fig. 6) which maintains the concentration rate of the free form. The reaction continues
until an equilibrium is reached between
the interaction energy 5HT-heparin and
the strength of dialysis induced by the
concentration rate (Fig 6). To determine the parameters of interaction ligand -
heparin (number of anionic sites of heparin and the association constant ligand - heparin) the free and bonded serotonin quantity is determined during
dialysis, at intervals of 5 minutes, until the equilibrium dialysis is reached
. The calculation of the two forms of 5HT is by Eq.9.
Eq.9: dC/dt = - DC that:
C = total concentration of the ligand (free + bound) of the
bag every "t" = 5 min.
equation is not satisfactory because the time interval of 5 minutes is very short and gives large errors
especially when the absolute diffusion and the variation of concentrations
outside the bag are small (120) close to the equilibrium of dialysis, when
processes of defixation are small as compared to those of diffusion of ligand.
Therefore the form of successive approximation of eq. 9 is recommended.
Eq. 10: C = (v + v) /vx C/1 –e in which
C = concentration of the free ligand from the bag at "t" = 0
corresponding to each point of determination.
11: C = C - C
12: C = C - C
C : is the initial amount of serotonine. Eq 10 allows highlighting decomplexation processes that characterize multiple equilibriums of the polyanion with small ions by the graphical representation of the equation 13:
Eq.13 v + v / vx C = f(1-e) (Fig 7)
Non linear graph indicates the presence of defixation
The calculation of the association constant 5HT / heparin and of the number of
The equation of multiple equilibriums is used for this
purpose . (Eq 14).
: C= (nK-Ce / 1+KC + e) which for a small number of sites can be written as Scatchard’s Eg (181),(Eq. 15)
: C/C = nK -KC where
n = number (M) anionic sites
Information is thus obtained about the influence of small cations that compete for 5HT anionic sites of heparin, when they are free in solution and about the interaction energy equal or bigger than E2 (Fig. 7). (Tb.16) shows the number of anionic sites at different concentrations of heparin and the existence of defixation processes.
18.104.22.168. Determination of the 5HT – Na competition.
Heparin (0.5 mg / ml) 5 HT (30 g / ml) and variable
amounts of NaCl in sucrose 0.25 M are introduced into the dislysis bag. Further
the above mentioned protocol is to be
observed. Fig. (6, 7 and GT 17) show the displacement of 5HT by Na+
in the heparin complex , the curves getting closer to those obtained for
determination of diffusion coefficient (Fig.5). In Figure 11 the semi
logarithmic strait line represents a
constant of exchange. The dependence of competitiveness processes Na+ / 5HT depending on the amount
of active chemical Na+ can be noticed.
22.214.171.124. The influence of native blood serum on the 5HT/heparin complex.
Collecting blood serum has to be made under the
conditions necessary to preserve the native state of macromolecular components
of the plasma. The blood is collected in tubes prepared as above. The blood is
collected through free flowing to avoid foaming. To store 15-20 minutes at room
temperature. Avoid low temperatures between 0 and 8C because they induce severe changes to serum reactivity
macromolecules. It is centrifuged for 10 minutes at 2000 rpm. Blood serum is
separated in an other tube by free flowing, and the clot is discarded. The
content of protein, total electrolytes (by flam photometry) and chemical
activity of serum cations , of which 95% is Na+ , are determined in
To determine the chemical activity of Na+ ,
0.15 ml serum, heparin and serotonin in the quantities mentioned above are to
be introduced into the cellophane bag. The data obtained from the dialysis of the serotonin in the bag are represented
reactants present n n n pK pK pK
0.5 mg heparin (H) -
- 0 06 -
Figure 9. - The influence of denaturizing upon the reaction 5HT-protein, as compared with native blood serum ( native serum ● 0.15 ml; ○ denatured serum 0.15 ml, "x" 0.15 ml native serum, and Na 37 μEq) (232)
126.96.36.199. The influence of denatured blood serum upon the interaction
The denaturizing of the serum is made by vigorously shaking the tube , thus avoiding the addition of other chemicals. 0.15 ml of this serum is used instead of native serum. Further , the above steps will be followed. The results of dialysis 5HT (Fig.9) show that serotonin values are similar to those obtained when the ligand is the only reagent in the bag, not interacting with heparin.
Figure 10. Representation of the number of sets of sites with high affinity for serotonin. Every set is identified by pK under the image of each set in various combinations, including native and denaturized blood serum (232).
188.8.131.52.The influence of exogenous Na on 5HT/heparină interaction
in the presence of native serum.
184.108.40.206. Determination and identification of the
number of anionic sites of heparin in the presence of blood serum.
This is done by graphical representation of Eq. (15)
by Scatchard (Fig 11, Tab 17).In the presence of denatured serum , heparin
does not interact with 5HT and a
straight line, parallel to the abscise ,is obtained(Fig.12). The subtraction
point by point of the two curves (Fig.12) can also be used.
Figure 11.The graphic calculation of the number of anionic sites in the native and denatured blood serum (232).
Figure12.Direct and semi logarithmic representation of decrease in the
number of anionic sites with affinity for 5Ht under the influence of variable
quantities of Na (232)
Figure 14. Graph equation CF = f(CL), where CF = 5HT bonded on sites anionics; CL = free 5HT (1) = native serum containing 10 mg% protein + serotonin (2) = native serum containing 10 mg% proteins + 0.5 mg heparin+ 5HT (3) = native serum with 10 mg% proteins + 0.5mg heparin + serotonin + 0.15 M NaCl (4) = difference point by point between curve 2 and curve 1 representing μM serotonin fixed on the anionic sites in the environment. (232).
In conclusion, the method allows the determination of plasma Na+ activity and its interaction with proteins , as related to the reference value of the interaction of 5HT with the heparin polyanion.
The cells of any tissue are held together by occlusive junctions, which anchor the cytoskeleton on the fundamental substance , the extra cellular matrix. The distribution of the fundamental substance is uneven. In some tissues it is hard to identify , like in epithelial tissues, poorly represented in the brain and spinal cord and in very large quantities in bone and connective tissue (33, 66, 73, 111). The matrix is composed of a variety of proteins and polysaccharides locally secreted and assembled into a network in close contact with the surface of the producing cells. With all this variety of distribution and structure, there is communication between all its departments and they, remarkably maintain the essential aspects of the tissue of origin (92, 171). Quantitative and structural variations of the matrix satisfy the requirements of the function of each tissue ( calcified forms in bones, transparent ones in the cornea, etc.). The pericellular matrix , rich in carbohydrates , is organized as a network.
The matrix and the cytoskeleton are intimately associated (116). Macromolecules from the matrix, in their turn , orientate the cytoskeleton. In the area of separation between an epithelium and the connective tissue (5),the matrix structures intself as a thin and hard baseline membrane , which plays an important role in controlling the cellular compartment, in the development , proliferation, shape and function of the cell (55).
The role of ECM.
First of all , it physically stabilizes the parenchyma tissue, which it is part of .It has multiple biochemical , informational , physical-chemical , metabolical etc. influences. It maintains a constant character of cellular environment and protects the parenchyma from variations in the blood composition , temporarily stores substances until they are eliminated or included into the cell function. It mediates and modulates exchanges of substance between the vascular and endocelular spaces : electrolytes, fatty acids, oxygen, carbon dioxide, etc. It modulates the activity of (140) of the compounds from cell environment, optimizing the intake of substances in the cell. It has structures which analyze the composition of intercellular matrix and of the endocellular medium. It participates in the direct intercellular communication. The matrix releases soluble factors under cell influences, with response from the cells themselves. There are complex relations of interdependence between the parenchyma cells and ECM : mechanical, biochemical, information embryo genetic, immunological, transportation, etc. Between the cells and the components of ECM there are connections of adherence and molecular interaction.
3.3. The chemical composition of ECM. (156).
Collagen and hialuronan are structural, abundant components of the connective tissue. These are counterbalanced by the network of collagen(162). Hialuronan surrounds the neuron leaving a perineuronal space. Glycosaminoglycan controls bivalent ions (238). So does heparansulfat (209, 210). Glucuronic acid combined with condroitinsulfate is also a good absorber of shocks. Condroitinsulfate is very rich in negative groups and works as an ions exchanger. (2) Proteoglicans (glycosylate glycoprotein) are constituted of multi sulphurated gags (68), as covalently connected chains on which many gag chains are fixed like proteins on a protein core , usually a glycoprotein (156). They are extremely heterogeneous. They have negative electrical charge given by fragments of sulfated sugars (162). Glycoproteins from the proteoglicans structure are components of matrix, in interaction with cells. When they have hialuronan in their structure, they induce the cell membrane. For many types of cells they act as real receptors (116). They are able to transmit biochemical, hormonal, metabolic, etc signals which influence the intracellular processes. They are connected to the cytoskeleton. They are the so-called "mosaic proteins” , spread in the body, some very specialized when they are included in the constitution of the base membrane. Due to the ability of gelatin extra cell pericellular matrix, cavities of various sizes and with different charges are formed serving to select the cells and molecules. They play a role in chemical intercell signaling.
They regulate the activity of other proteins such as protease
inhibitors and proteolytic inhibitors by immobilizing protease in the production place, limiting
the sphere of action by steric blocking
or by creating reserves of proteins, by protection against proteolize. They may increase or
decrease the concentration of proteins by presentation of receptors on the
surface of the cell. They may be associated with the fibrous matrix proteins
(collagen or protein from the network of basal lamina). They interact with
other proteins in ECM as elastin, collagen, fibronectin, laminin, etc.. As
polyanions , they are in interaction with cations and cationic groups. It is
hydrophilic and permits the turgescence of tissues.They are components of
plasmatic membranes. They participate in
cell adhesion and intercellular relationships. The fibronectin binds the cell
with the matrix (5). At the ends there are carboxylic groups. It is also
present in blood plasma, where it participates in the process of blood
From the electronomicroscopic point of view there have been shown physical connections - head to head between filaments of fibronectin in the ECM and the intracell actin filaments . The molecule has three fields on the α chains: cellular, membrane and extracellular having aspartic acid residues of which compete in the binding of bivalent intracellular cations. Collagen is the major protein of ECM, secreted by the cells of connective tissue.
They are fibrous proteins, twisted in the triple helix rich in proline and glycine. The triple helix (25) originates in the hydrogen bondings between OH groups of hydroxylizin and hydroxyprolin. In the brain ECM there is the type IV collagen . The type IV molecule forms a network included in the composition of lamina base.
The characteristics of matrix molecules suggest that they control the function of tissues in which they are located. In the excitable tissues, proteins have intensely negative charge and interact with cations.
The ECM interactions are mediated by some matrix receptors (molecules on the cell surface which bind themselves to the matrix components). In fact it is not possible to specify the place where the membrane component ends and where the membrane matrix starts. The last binding between them is made through a transmembrane protein which binds the matrix to the citoskeleton. The most important receptors on the cell membrane are very specialized integrins (laminine, entactine, tensine, etc...), which are binding to the matrix proteins (collagen) (116).
The integrins binding is weak but their value is given by their number. Integrins are composed of two subunits and bind themselves to transmembrane protein matrix. Their intracellular domains are NH2- terminals, while the matrix ends are COOH-terminals.The extracellular domain matrix interacts with bivalent cations. On a cell there are several types of integrines. Their function is very diverse. In order to have the cell to bind to the matrix, integrines interact with the cytoskeleton through protein intracell, actine and fibronectine (162).
The organization and the chemical composition show features that ensure optimal environment for the neuron. It is composed of the capillary space, the cellular neuron and the glia and by the extracellular matrix with varying sizes (73). The neurons of the central nervous system are multipolar, excitable cells. They respond to chemical stimuli, transmiting excitation to other neurons and to the effectors. At the level of the synapses, the stimulus is transmitted by means of chemical mediators. Stimuli are encoded and stored as memory or used by conjugation with other stimuli in mental processes, etc.. Neurons are constituted of the pericarion and of extensions (dendrites and axon). The neurons in the brain are associated in nuclei. Association neurons are entirely situated (including the processes) in the brain tissue.
The exchange between these two areas is done through various mechanisms: diffusion, active transport, electrostatic interaction, endocitosis, exocytosis, selective transport imposed by that barrier. Astrocytes play key roles in the energy distribution of substances in the blood, (128) mediate glucose intake as a first barrier to nerve cells. Perisynaptic processes incorporate glutamate during synaptic activity in somato-sensorial areas. Glutamate is incorporated by astrocites through a mechanism dependent on Na in the proportion of three cations for a molecule of glutamate / 128).
Na in the extracellular medium achieves an electrochemical gradient, so that glutamate is recycled within the glia. The astrocyte participating in the synapse function and reincorporation of the neurotransmitter, vesicle fusion ,as well as its local catabolization. The astrocyte also has a secretory activity. The products secreted by astrocytes together with the secretion of the endothelial cells are constituents of the blood-brain barrier. The secretion of the astrocyte maintains the characteristic of the blood-brain barrier and of intercell junction . In culture, the astrocyte secretes laminine, fibronectine, chondroitinsulphate, collagen. The collagen stimulates endothelial cells maturation. They in turn stimulate the growth of astrocytes. So, with the mixed secretion of the two cell types the functionality of the blood-brain barrier is ensured. The network formed by the " vascular astrocyte processes" also plays a mechanic role by absorbtion of vascular pulsations, which are no longer transmitted to the neuron.
Figure nr.15. The diagram represents the astrocyte role in angiogenesis and functional hyperaemia. Glutamate release (1) of neuronal presynaptic that binds to receptors on astrocyte, activating phospholipase and diglycerol lipase (2) to release arahidonic acid from astrocytes (3). The conversion of arahidonic acid to epoxygenase under the influence of cytochrome C450 2C11 (4). This increases output K + ,which prevents hyperpolarisation (5) and vascular dilatation. At the same time it increases Ca2 + intracellularly and stimulates both mitogenesis and angiogenesis. (187)
3.4.3. Cerebrospinal fluid (CSF) (174).
Chemical composition ,by comparison to blood - CSF
Water % 99
93 99 93
3.4.4. Lymphatic system
The lymphatic system is one of the ways of communication between the three areas: Intravascular,interstitial and endocelular. Lymphatic capillaries begin in the interstitial space, and through lymphatic vessels carry to the interstitial fluid vessels the result of capillary filtration, secreted and enriched with compounds produced at cellular level and metabolytes.It is absent at brain level.
Exchanges Between Capillaries and Interstices
4.1.1. Endothelial capillary.
4.2. The blood-brain barrier (BBB).
The endothelium has the role of endothelial barrier to substances in the blood, the selective membrane for substances in both spaces ,through transcellular mechanisms.The basement lamina itself forms a barrier between capillary and neuron, is located between astrocyte and endothelium, acting as a filter . Thickness : 40 -120 nm. By means of electronic microscopy it is possible to see that it is made up of 2 distinct layers: (5): lamina lucida (lamina rara) adjacent to the plasma portion of the endothelial cells and of lamina densa, an electrono – dense layer. A third layer is further described, lamina fibroreticulata, binding the basement lamina to connective tissue. Basement lamina is a filtrable structure, polarizes the cell, influences the endothelial cell metabolism, organizes proteins on the adjacent plasma membrane etc. It plays a role in synaptic reconstruction, guided nerve regeneration in time, etc. In the constitution of BBB there is found collagen type IV, heparansulphate laminine, fibronectin. Between neurons and astrocyte, the barrier is richer in proteoglicans. Collagen type IV is flexible and forms networks, stabilized by disulphuric bridges . The membrane also contains agricans secreted by neurons surrounding the synapsis. Maintaining the brain function requires a certain extracellular ionic strength, especially metabolic conditions, neurotransmitters, growth factors, etc. between certain limits of variation maintained by the BBB. It accumulates (174) catabolites, ions (specialy K) for their removal, into the membrane endothelia there is found a large amount of Na,K-ATPaze. In the astrocyte endings there is a high density of channels K (73). At the level of synapsis there are accumulated , during the nervous pathways activity (sensory, and of multiple neural circuits ), neurotransmitters which are inactivated by removal or local metabolisation. From among these, (128) for example , glutamate that is inactivated by reuptake in astrocytes perisynapsis with the help of transporters and glial electrochemical gradients of Na (172).The thus enabled transportation represents a key signal for coupling neuronal activity with activation of glycolysis in the astrocyte. The transport of solvates from the blood into the brain is done either by specific transporters, or in a transendothelial way , by plexus choroides. BBB provides the necessary amino acids in the extraneuronal environment and protects neurons by large fluctuations in the content of Na (174).The change of BBB permeability allows brain penetration of the same substances that are not transporters, (5) such as lipophilic molecules, hydrophobic , according to the partition coefficient and they reach the brain extra cellular space. The barrier allows the passage of substances also due to the concentration gradient. The size of molecules and their steric configuration together with the above mentioned factors conditions the BBB function.
4.2.1. Adjusting the BBB function.
4.2.2. Cerebral territories without BBB.
4.3.1. Renal functional unit.
The structure of renal vessels. The glomerular capillaries are in large contact with the space encapsulation. In the cytoplasm of endothelial cells there are perforations of 0.1 on the internal face and perforations of 100 in the baseline membrane, through which the plasma passes into the capillary lumen, through filtration. The efferent glomerular vessels are relatively permeable and also for the molecules of albumin size. The blood circulation in the area of the thin loop of Henle is upwards, in counter current with the uriniferous tube. This vessel has a fenestrated epithelium up to the return of the vasa recta. The interstice between capillary and tubes consists of some wider and some narrow areas. At the level of the proximal contort tube , the space is represented by the merger of the membranes of the tubes and capillaries. Endothelial capillaries present fenestrations of 0.05, through which the tubular content passes directly into the blood vessels. Here there take place resorption processes for approx. 74% of the glomerular filtrate. Otherwise the space is wide. The size of the interstice is increasing toward the deep kidney regions. Interstice contains many mucopolisacharides rich in proteins and anionic sites with high basicity , which can be modified through changes in loading with water, Na+, or under hormonal influences. In rats with diabetes insipidus , the basicity of proteins is increased in the medulla. ADH increases the number of anionic charges, arresting more and more Na+ , with or without water. The interstice also contains some serum proteins , brought here by vascular fenestration, mostly albumins . These , together with the basic proteins , are important in Na+ reabsorption.
4.3.2. The mechanism of urine formation.
The endocrine factors have an important regulating role . Aldosterone acts at the level of the distal contort tube and of collector tubes. The inactivation of local protein synthesis and of Na.K.ATP is involved in the Na+ retention. DOCA acts in the same way as aldosterone, but weaker. The atrial natriuretic hormone (206) increases the glomerular filtration rate, diuresis and natriuresis , reduces the movement of signals through the point of departure in the atrial area. It acts at the level of distal portion contort and of the papillary membrane. Quinine , dopamine, prostaglandins also have action in the loss of Na, while angiotensin acts directly and indirectly by stimulating secretion of aldosterone : catecholamines act at proximal and distal contort level. ADH keeps water by acting at the level of contort distal portion and collecting tubes on the interstice space. The electrochemical interaction factors between Na - proteins act concurrently with oncotic factors, induced by proteins from the blood and the interstice, which control the tubular and peritubular reabsorbtion processes through their anionic groups.
220.127.116.11. Glomerular filtration (primary secretion of urine).
Increasing concentrations of protein in the efferent arteriole has a stabilizing role of blood flow. The glomerular flow decreases by clamping the aorta (97) and increases under experimental conditions, by increasing the concentration of protein (albumin) in the blood perfusion (5 - 7%) and intake of hypernatrium. The phenomenon is attributed to the increase of osmotic pressure over 55 mmHg. Protein increase above 10% leads to a non filtering kidney.
Plasma proteins influence the overall kidney function depending on its status. The increase of concentration of proteins in perfusion of the vasodilatated kidney with acetylcholine changes the effect in the loss on Na of the protein and decreases the elimination of Na+ and water. The non vasodilated kidney reacts in a variable mode to the increase of the proteic content of infused protein. Protein concentration level stabilizes the glomerular renal circulation and keeps under control the tubular level resorbtion . Patients with analbuminemy (177, 222), protein malnutrition (59, 141) and those with nefrotic syndrome, there is a simultaneous decrease of colloid-osmotic pressure and of fractional Na+ resorption. Increased protein keeps oxygen consumption response decay of glomerular filtration. Albumin increases from 2.5% to 5% and increases absolute resorption of Na+ and water. In the absence of albumin , the kidney eliminets however, 40 - 46% fraction of filtered water and Na+ , i.e only the minimal regulated fraction of oncotic pressure . Postglomerular decrease in the proteins produces volume expansion and kidney proximal reabsorbtion inhibition of Na+. The mechanisms by which proteins interfere in the regulation of Na+ reabsorbtion can be deciphered taking into account how communication between the three compartments takes place, a process in which oncotic pressure plays an important role. The proteins control reabsorption especially of Na+ (with their anionic charge). Between Na+ and polyanion protein there are interactions which also definie the fundamental mechanism of transport of Na+ in the blood (231, 232, 236). In addition to doubling the concentration of proteins in efferent arteriola and peritubular capillaries mention should be made of the richness of anionic groups of interstitial proteins: serum albumins passed through fenestration of capillaries , mucopolysaccharides rich in anionic groups.
Their numbers increases under the influence of increased quantities of Na+ crossing the interstice and from here into peritubular capillaries , through capillary baseline membrane. The increase of the number of substances removed, obtained by blood dilution, as well as the decrease of glomerular flow , diminishes excretion of sodium also because of the decrease of concentration of proteins from postglomerular territory. In Henle loop , the Na+ arrested by proteins, creates the hyperton enviromment necessary for water conservation.
18.104.22.168. Tubular reabsorption. The role of proteins.
[Chapter 5 will be featured in the upcoming January-February 2010 issue of this Journal.]
Professor Marcel Uluitu, M.D. Ph.D. began his
scientific activity in Physiology in 1953 at the
Professor Uluitu has also investigated cerebral tissue excitability, studying the structure modification of the protein macromolecules, and the physiological and pathopysiological processes in which are involved Sodium and Lithium. He implemented an original method for physical and chemical processes which involve the chemic active sodium, in normal processes and in the cerebral excitability dysfunctions, in human and in experimental model (animal). These results of this work gave him the chance to outline the chapter herein relating to the physiology of substances transport in the blood. This is based on the physical and chemical interaction between blood components.
His papers are included in the
collections of the U.S. National Library of Medicine and the U.S. National
Institute of Health. He is a member of the
Dr. Diana Popa (Uluitu) is a
researcher in the Department of Microbiology, Immunology and Molecular Genetics
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