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 V of a series of chapters from the new book “The Physiology of Transport Substances in the Blood (Sodium)”; preceeding and subsequent chapters have been/will be featured in recent past/upcoming issues of this Journal. This segment features Chapter Six].
I have presented above the mechanisms through which the transport of Na+ in the blood is made, from which the idea derived that the normal functioning and normal excitability are compatible with low chemical activity of Na+ within the method described above (218, 232, 233). In other words, Na+ is transported in a state of interaction with proteins. The process has been described in humans (Figure 21 and Table no.21.) and rats (figure 20 and table no. 23), in normal collectivities in the case of both species, this is a dominant distribution of about 75%.
Figure 21. The number of anionic sites (M 5HT) of heparin in school children in a normal collectivity (236).
Table No. 21. Detailed table with children of the two lots which include mechanisms for transport of Na in the blood (236)
6.1. Determining the health status in humans
6.1.1. General health status.
6.1.2. The mental health status.
22.214.171.124. Personal history.
126.96.36.199. Heredo - collateral history.
188.8.131.52. Socio – familiar background .
184.108.40.206. Preschool period. The appreciation of parents.
220.127.116.11. Investigations at school .
18.104.22.168. Clinical psychiatric examination.
Determining the chemical activity of blood sodium.
The classification of subjects.
The second batch in which the chemical activity of Na+ in the blood is very small being screened through interactions with proteins is composed of psychically normal subjects : children with neuropsychic disorders with brain lesion history. A last group is formed of children with various psychiatric disorders on puberty background without behavioral deviations.
Non excitabile function structures and mechanisms of transport of blood Na.
6.4.1. Total proteins and Na (flamfotometric) in the blood.
Table 22. Biological blood constants in humans in relation to the mechanism of transport of Na (224)
leucocytes hemoglb red cell group. hematocrit blood
glucose. protein mEq of sodium Na
4,187 6.311 13,33 35.72 0.87 5.7 151.1
(II) 4.05 6.750 12 56 34, 05 0 9 6.04 151.1 . 0.43 1.05 0.03 0.3 1.16
6.4.2. Respiratory function.
23 Spirometric static and dynamic data in
group I (Na in interaction with proteins) and II (Na transported as
F VE VO
CV CV% VEMS
IISD 541,6 21.4
11 301 2798
2194 2515 90
6.4.3.White blood cells.
6.4.4. Carbohydrate and lipid metabolism (224, 100).
6.4.5. Growth and Development ( Somatometric values , GH ).
(Na without chemical activity, with group II (children with abnormal behavior of constitutional type ) (224)
Group weight height pubis head chest abd pelvis biacr bithr
I 39.5 151 80 53.3 71.8 61 78.6 33.1 26.6
MSD 1 1.3 0.8 0.2 0.8 0.7 0.9 0.4 0.1
II 38 150.7 80.2 54 67.5 64.1 75.4 33.3 26.7
M 2.1 2.4 1.7 0.4 3.3 3.0 3.7 0.8 1.1
But the release of GH response to the test ladder requires a more detailed analysis that does not have in view the processes of Na transport in the blood but are present in children with organic injuries of the nervous system (Table nr.26), in history (36). In this case, low reactivity of GH (104, 105, 130, 162) in the ladder test can not be attributed to disturbance of the mechanisms of Na interaction - compounds polianionic plasma, which otherwise are not even present - but rather recognize postlesional effects.
Table 26: The GH blood concentrarion in children with normal transport of Na (Group I) and those with high activity chemical Na (Group II) and response to the test ladder (224)
before the effort after
Unlesional GroupII MSD 6 75 10 .05 P0.01
In conclusion , the function of tissue and non excitable organs presented here is not correlated with the transport of Na in the blood - the interaction with proteins or ionic state - its role is associated with general metabolic processes which have been discussed.
6.5. The function of the excitable structures and Na transport in the
blood of humans.
EEG serves as the most direct indicator of the state of vigilance and the cortico-cerebral excitability (45, 63, 78, 240). The analysis of cortico-cerebral electrical signals (45, 64, 105, 130) requires processing of signals obtained from recording selected according to intentional local activation , or in case of clinical investigations, imposed by the need of diagnostics, etc. Brain excitability investigation in children from the mentioned groups was made by one single parieto - occipital derivation ,(163) under standard conditions: (63 240) with open eyes in mental relaxation or in a mental effort (solving a test of attention), followed by activation of rate at the closing of eyes (fig.22). The records are postprandial and before conducting the school. EEG activity in humans (163, 164) shows variations in the frequency and amplitude as described. EEG signals are processed (164) as the F / V (frequency / voltage) (Figure 22, 23 and Table No. 27) which allows a statistical analysis and insurance between different epochs in the same subject or identical parts from different subjects: bioelectric activity in children with Na in the interaction with serum proteins and children with Na transport in ionic state.
Ratio (F / V) (64, 240) is an integrative size of EEG segments. Its value is a sensitive indicator for brain activity in humans (163, 164, 240, 241). High values of the ratio (F / V) is observed when on the EEG route there prevails the rate . Alteration of values F / V is an important indicator of the overall level of activation (240). The ratio value allows comparison with the basic status of tensional status . From the statistical analysis of EEG data obtained from children (Table No. 27) and (Figures 22, 23) show that the "normallly psychic" children with normal behavior in which transport of Na in the blood is in a bound form , the values of the (F / V) ratio decrease significantly upon the closing of eyes, while children with Na+ wth chemical activity in the blood, with constitutional disturbance behavior record a deficit . The installation of rhythm (Table no.27, Figure No. 23), describes the deficit for these subjects (140). The deficit is not found in the other two subgroups of children: postlesional and endocrino - puberty (Table No. 27). It is to be noticed that this deficit is to be found particularly in children with somatogenic abnormal behavior where Na+ is screened in the blood (104, 105, 130, 162) . This calls for a regulating role transport for Na+ transport in the blood, in interaction with proteins, on brain excitability, the bound transport of Na+ being compatible with the normal excitability of the brain. The increased chemical activity of Na+ blood is accompanied by nervous hyperexcitability. Thus the response of the body to the sensory stimulation can advocate for the phyisiology of the blood transporter of Na+.
Table no. 27 The ratio F / V of the EEG in different conditions in children studied (236)
Figure 22.Cerebral bioelectric activity in a 12-years child with (1) eyes open and (2) with eyes closed (236)
Figure 23. Variation in the ratio F / V (frequency / amplitude) of EEG in a normal psychic subject with Na transport in interaction with serum proteins. 1 = eyes open mind at rest; 2 = eyes closed; 3 = eyes open, effort to resolve a test of attention, 4 = eyes closed. The immediate installation of rhythm α upon reopening the eyes is to be noticed (236)
Changes in the F / V (frequency / amplitude) of EEG in a child with hyperactive syndrome with seric Na transport in a
Determining the mental aptitudes, in centiles, in
conjunction with Na+ seric
activity suggests the influence the
latter has on intrinsic cerebral excitability on socio-intellectual and
adjustive performances . Importance has been given to the processes of
concentrated and distributive (90) attention, to imeediate auditive memory for
words (24), psycho-neurotic tendencies
(90), a type A questionnaire for
determining the overall image of the child adapteded to the population of
In children with disturbances of constitutional type behavior concentrated attention is affected , as well as in children with behavior of somatogen type disturbances (1) , thus the targeting attention deficit compared with mentally healthy subjects with blood Na screened is showing a deficit .The disturbance of concentrated attention is accompanied by hyperactivity. As regards the quantity of concentrated attention, this is only showing deficit in children with somatogenic behavior (95, 96, 104, 105) , with neuronal affections, inexistent in children with constitutional behavior disturbances.
The total distributive attention shows a deficit only
in children with somatogenic disturbances (Figure no. 25). Children with behavioral disorders of
constitutional type present a very good distributive attention.
Figure 25. The quality and quantity of attention in children investigated in relation to the mechanism of transport of serum Na (236)
Immediate auditory memory and intelligence have
complex producing mechanisms ,
insufficiently known. They are dependent on the processes of attention
and on the neuronal capacitaty to store information and especially the
ability to extract and to reproduce (1). In this context, mentally normal
children , with mechanisms for the transport of Na+ normal, have the
coefficients of memory close to 100, while the other categories of groups are
located below the value of 50 centiles.
Intelligence does not show differences between groups formed by the mechanisms of transport of Na in the blood.
Distribution of mass blood in the vascular bed is determined by the occasional functional level of certain organs and apparatus: postprandial digestion activity, physical effort of various types and intensities, the body position (clino-ortostatism), the action of external factors on the body (positive acceleration), mode of exposure to heat sources, etc.
Adjusting mechanisms are multiple and complex, nervous and humoral. The dissociation of these mechanisms and evaluation of every one of them is difficult, the most relevant parameters being the cardiovascular hemodynamics and hydroelectrolitics, but the most important being the sodium.From among cardiohemodynamic parameters,the most representative are: heart frequency, systolic and diastolic blood pressure during clinostatism and after passing to ortostatism, pulse pressure, index of ventricular work (Figure 26).
Figure 26. Cardio-vascular parameters in clino and ortostatism in groups I and II of children mentioned (224).
22.214.171.124. Mechanisms for regulating cardiac and vascular functions.
The response capacity of the heart and vessels to action of disturbing factors also depends on the nature of transport of Na+ in the blood. The parameters mentioned show differences between subjects where serum Na transport is in the form of binding comparatively to those in which it is transported in the ionic state (Table No. 21, Figure 21). The existence of free ionic Na+ in serum is accompanied by lower values of the parameters mentioned in clinostatism (noted "0" in fig 26, 27).
By passing to passive ortostatism by means of an
automatic tilting table there is induced an accumulation of blood in the lower
region of the body,thus producing variations of parameters recorded minute by
minute, for 10 minutes, to get the full picture of the effort of adjusting.
Figure 27. Cardio-vascular parameters normalized, during the changing posture of the groups I and II (224)
126.96.36.199. Compensation of hemodynamics.
The regulation of hemodynamics during posture change to ortostatism has two phases: first phase of six minutes from posture change includes rapid intervention mechanisms of the autonomic sympathetic nervous system to modify the diameter vessels, followed by the shifting of blood toward the heart (224): a second phase is slow, with long duration and is intensified by the humoral system renin-angiotensin-aldosterone-sodium, and natriuretic polypeptides with action on vascular muscles. Their release depends on Na+ action at kidney level. In addition, retention of Na under endocrine control, results in the restoration of mass blood circulating. This phase begins after the six minutes change of posture, in ortostatism.
The evolution of hemodynamic parameters after the change of posture (Fig. 26,
This period highlights the differences between the two groups of children, formed on the basis of different mechanisms of the transport of blood Na+ with reference to the regulation of cardiohemodynamic function. (fig, 26, table No. 25). In the group containing the subjects having serum Na transport in the ionic state there is noted a trend for maintaining the distribution of the blood through an increased mass heart rate , with arterial blood pressure showing a deficit in the first six minutes of ortostatism. In minutes 9-10 the deficit also invoves the diastolic pressure, expressing the disturbances in the humoral renin-angiotensin-aldosterone-Na mechanism and in the natriuretic peptides (148).
The picture obtained is similar to that induced by the
Na+ loading of the organism (230, 231, 232, 236). Moreover, research
on humans in outer space has demonstrated that
compensation of hemodynamics and of psychiatric disorders can be
obtained by the administration of water and Na+ (38, 76, 187, 247.
148). The addition of hormons, steroids and antidiuretics substantially
restores hemodynamic parameters (76, 146, 186).
6.6. Excitable systems function in rats.
6.6.1. The influence of hypersaline regimen on
In rats there has been studied (223) the influence of
hypersaline chronic regimen compared to a group maintained at hyposaline
regimen, by recording bioelectric cerebrocortical activity . The two groups
were kept, from intrauterine life until the age of 6-8 months with a different
intake of NaCl: both groups received an identical diet, normal, but one group
received for drinking physiological
solution ( hipersaline ) and another group received distilled water. In both
groups there was recorded the electrocorticography. There were used silver
electrodes , chronically implanted on the cortex, in the parieto-occipital region(223). Animals
prepared in this way were placed in individual
soundproof cages , obscured,but
having a 6-W bulb mounted for
light stimulation (197)or for recording in a light-up conditions.
Electrocorticography processing by determining the F / V (164)ratio is
inadequate, even though upon a simple
inspection clear changes are noticeable (Figure 28). Probably, in rats,
sensory stimulation induces conjugated variations of ECG potentials in frequency
and amplitude, resulting in a constant value of the ratio F / V. The ECG
processing in this case is done by applying Fourier transformant (223, 237),
with general applicability (figure 29) .
Figure 28.The electrocorticographic activity (ECG) in rats: A = chronically hypersaline regimen; B = chronically hyposaline regimen; 1 = reference, recording in the dark; 2 = stimulation by noise on dark background (223)
Figure 29. Comparing average ECG of rats consuming chronic hypersaline solution with the rats having a hyposaline one (223) (Fourier transformant).
6.6.2.The chemical activity of blood sodium,
correlated with the neuromuscular excitability in rats.
The auditory stimulation is the preferred method to form the groups of rats by selection of animals susceptible to audiogenic convulsions. For this purpose , every single animal is placed in a cage (236) covered with a transparent lid through which is monitored rat behavior during auditory stimulation. The noise is generated by an electric bell placed under the cage.
Most of the animals (225, 117, 229) remain calm, or
even inspect the enclosure, to establish
the origin of the noise. Other animals are hypersensitive, expressed by
hypermotricity, a state of panic, convulsions, opisthotonus followed by a state
of weariness and sometimes death.
Table nr28. Variation of the number of anionic sites of heparin, as HT g / 1 mg heparin, in the presence of rats blood serum with various types of response to acustic stimulation (227)
behavior g 5HT/mg heparin
3 1 1,04
The absence of chemical activity of Nations or its
reduction is therefore compatible with calm behavior during acoustic
stimulation in rats.
Animals susceptible to audiogenic seizures are hyperactive not only during acoustic
stimulation, but they have also free behavior in the cage (No table. 29) or
motivated behavior (table No. 30)
It can be noticed that the animals in which blood serum Na+ is transported freely present a significantly more intense activity than normally excitable animals, in agreement with the behavior induced by acoustic stimulation.
No. 30. Motivated motric activity (for distilled water and physiological
solution)at their free choice,in groups of animals with normal excitability and
hyperexcitable animals (227)
normoexcitable 191,6186,15 162,2580,57 hyperexcitable 266,56146,19 250,85136,92
p 0,01 p
From the tables it results that the intensity of normal motor behavior is compatible only when blood Na+ is transported in interaction with proteins, without chemical activity for anionic grups of heparin, while the chemical activity of cation is accompanied by hyperexcitability, expressed by intense motor activity, comparable to that induced by a chronic hypoproteic regimen (192, 193, 194).
6.6.4. Hemodynamic compensation.
Rats exposed to disturbances of hemodynamics through hypergravitation (angular acceleration = G + 5) (76) in centrifuges for small animals, repeatedly , (224) is followed by changes of hemodynamic and Na+ homeostasis. In rats with normal excitability to noise and blood transport of Na+ in the interaction with proteins, the centrifugation induces the decrease of elimination of renal Na+ (148) from the ingested fraction (Figure no. 31). In rats whose Na+ is transported in ionic state, with susceptibility to audiogenic seizures (228) , exposure to hipergravitation increase is followed by renal loss of sodium, which expresses an inadaptable reaction (Fig. 31) (229, 186, 149).
Figure 31 The influence of repeated exposure to hypergravitation (+5 G) upon the elimination of renal Na in the normoexcitable rats and in rats , susceptible to audiogenic seizures and with Na in the ionic state in the blood. (Δ-normal before centrifugation;-x – normal after centrifugation, ¤ - rats susceptible to convulsions before centrifugation; - ○ susceptible to convulsions after centrifugation ) (229).
Mineralocorticoid function in connexion with the transport mechanisms of blood
Na and of age.
Investigation of the mineralocortcoid function is also done by determining a synthetic indicator of the function, the value of the ratio urinary Na / K. Researches conducted on the same two groups, normals adults , and another group of animals susceptible to audiogene convulsions (Tab No. 26 and Fig. 32) (230, 229, 223, 227).
Figure 33. Hydroelectrolitic metabolism in rats related to age and to the mechanisms of Na+ transport in the blood serum (230).
6.6.6. Hydroelectrolytic balance as referred to the Na transport mechanisms.
Table 31. Consumption of distilled water (ml/24 hours) and saline solution (ml/24 hours) in the two groups of rats (227) :
groups distilled water saline solution P(same group)
reference 12,436,75 10,768,56 P 0,18
convulsion 11,395,82 15,859,31 P 0,126
P(between groups) 0,57 0,034
The animals with Na+ ionic state transport
consume more liquids than the normal ones (Table 32)
Table 32. Total liquids (distilled water + saline) in normal and spasmodic rats (ml/24 hours) (220).
groups ( ml/24 h)
The same picture is presented by the renal elimination of Na+ (Figure 30) (242). Hyperexcitable animals with Na+ transport in ionic state lose a larger amount of Na+ corresponding to that ingested as intrinsic motivation , on choice. Data presented in tables 31 and 32 show that in both groups of animals there is no motivation for liquid in free access conditions to both vessels. However, animals susceptible to audiogenous convulsions, with higher Na+ serum activity than the reference system show significantly increased preference for the solution of NaCl as compared with normal animals, as well as for the distilled water vessel , thus compensating the mentioned renal losses (Fig. 30). In these animals there is an unbalanced matabolism of sodium by which motivational processes are stimulated as well.
[The Final Summary and the Bibliography will be featured in the upcoming
May-June 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