The Physiology of Transport Substances in the Blood (Sodium)

   

By Professor Marcel Uluitu, M.D. Ph.D.

Spiru Haret University

Bucharest, Romania

 

Co-Authored by Diana Popa (Uluitu), M.D.

Department of Microbiology, Immunology and Molecular Genetics

University of Kentucky, Lexington, Kentucky, USA

 

[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].

 

 

Chapter 6

Physiology and Physiopathology of Sodium Transport in the Blood

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)

No.	Name	Personal antecedents which may influence the brain	Dificultăţi familiale				Type A questionnaire Attitude towards :					Woodworth-Matthews  test		Psychiatric conclusions		Activity of  serum cations   += free (not bound - = bound
			Educational excess	Disintegrated families	Lack of  supervision		School	Teachers	Own self	Family	Colleagues	balanced	Tendencies		Degree of  instability
	LOT I                                                                                                   1. NORMAL
1.	B.D.	-	-	-		-	0	0	0	0	0	+	-	Mentally normal	-	-
2.	B.C.	-	-	-		-	0	0	0	7	7	+	-	Mentally normal	-	-
3.	B.D.	-	-	+		-	0	0	0	0	0	-	High emotivity	Mentally normal	-	-
4.	B.G.	-	-	-		-	0	0	0	0	0	+	-	Mentally normal	-	-
5.	B.D.	-	-	-		-	0	0	0	0	0	+	-	Mentally normal	-	-
6.	C.G.	-	-	+		-	0	0	0	0	0	+	-	Mentally normal	-	-
7.	C.G.	-	-	-		-	0	0	0	0	0	-	Slightly impulsive and epileptical	Mentally normal	-	-
8.	C.F.	-	+	-		-	0	0	0	0	0	+	-		-	-
9.	C.C.	-	-	+		-	0	0	7	7	0	+	-		-	-
10.	C.R.	-	-	-		-	0	7	0	6	0	+	-		-	-
11.	D.A.	-	-	-		-	0	0	0	0	0	+	-	-	-	-
12.	D.G.	-	-	-		+	0	0	0	0	0	-	Depressive and  hypochondrical	-	-	-
13.	D.D.	-	-	-		-	0	0	0	0	0	-	Very slight emotivity	-	-	-
14.	G.A.	-	-	-		-	0	8	6	8	6	+	-	Mentally normal	-	-
15.	I.D.	-	-	-		-	0	0	0	0	0	-	Intense emotivity , depressive and hypochondrical	Mentally normal	-	-
16.	M.F.	-	-	-		-	0	0	7	7	0	+	-	Mentally normal	-	-
17.	N.B.	-	-	-		-	0	0	10	9	0	-	Very slight emotivity	Mentally normal	-	-
18.	P.G.	-	-	-		-	7	7	10	11	0	+	-	Mentally normal	-	-
19.	P.G.	-	-	-		-	0	0	0	0	0	+	-	Mentally normal	-	-
20.	R.A.	-	-	+		-	-	-	-	-	-	+	-	Mentally normal	-	-
21.	T.I.	-	-	-		-	0	0	0	0	0	+	-	Mentally normal	-	-
	2. “OTHER PSYCHIC DISTURBANCES”
22.	B.C.	-	+	-		-	-	-	-	-	-	+	-	Inhibiory type pubertary  disturbances	1	-
23.	C.A	-	-	-		+	11	11	8	9	0	-	Very slight emotivity	Mixed behavioral disturbances	1	-
24.	D.N.	-	-	+		-	-	-	-	-	-	-	Slightly schizoid , paranoic and depressive	Reactive depression in involution	0/1	-
25.	F.A.	-	-	+		-	0	0	0	9	0	+	-	Purbertary behavioral disturbances
26.	G.M.	-	-	-		-	0	10	14	12	0	-	Shlightly depressive , hypochondrical and unstable	Essential pubertary and reactive behavior	2	-
27.	M.M.	-	-	-		+	-	-	-	-	-	+	-	Slight pubertay disturbances due to social reasons	1	-
28.	M.M.	-	-	+		-	8	8	8	9	8	-	Obsessive	Essential instability with pubertary opposition elements	1/2	-
29.	M.D.	-	+	-		-	-	-	-	-	-	+	-	Slight behavioral disturbances , instability , reactive elements	1	-
30.	T.D.	-	-	+		-	-	-	-	-	-	-	Intensely reactive	Reactive behavioral disturbances	0/1	-
	3. TRAUMATIC
31.	M.A.	Trauma at birth . Reanimation with O2	-	-		-	0	7	11	11	9	-	Paranoic and schizoidal	Slight reactive depression. Microeffects	0/1	-
32.	M.P.	Effects of meningo-encephalitis	-	+		-	8	7	12	18	9	+	-	Slight instability. Organic behavioral disturbances	1	-
33.	N.A.	Forceps. Eye bleeding	-	-		-	-	-	-	-	-	-	Neurotic	Uşoară instabilitate. Dezinteres şcolar	0/1	-
34.	T.N.	Front-nasal trauma	-	-		+	7	12	9	15	7	-	High instability , and slightly emotive, depressive and hypochondrical	Tulburări mixte de comportament esenţiale şi reactive	2	-
	LOT II                                                                   CONSTITUTIONAL BEHAVIORAL DISTURBANCES
35.	A.D.	-	-	-		-	0	9	0	0	8	-	Emotivity combined with a slight depression	Essential instability. Choreic movements of fingers	2	+
36.	C.D.	-	-	-		-	0	0	0	0	0	+	-	Behavioral and personality disturbances	1/2	+
37.	D.A.	-	-	+		-	-	-	-	-	-	-	Instability, emotivity	-	-	+
38.	G.C.	-	-	+		-	0	0	6	17		-	Slight emotivity	Slight essential disturbances , anxiety , emotions	0/1	+
39.	G.M.	Brain traumatism with unconsciousness	-	-		-	0	7	10	8	0	-	Sligh paranoic and schizoidal forms	Mixed essential behavioral disturbances and lesional instability	2	+
40.	G.T.	-	-	+		-	-	-	-	-	-	-	Slight instability and emotivity	-	-	+
41.	S.M.	-	-	+		-	-	-	-	-	-	-	Instability	Essential reactive disturbances	2	+
42.	S.M.	-	-	+		-	0	12	9	15	0	-	Depressive, hypochondrical and instability	Essential and reactive behavioral disturbances	2	+

 

 

 

           6.1. Determining the health status in humans

 
Determining the health status in humans was carried out with means that are refer to the physical and mental status. It is necessary to detect subclinical manifestations as well , when normal school collectivities are studied(1).

          6.1.1. General health status.

This was investigated by clinical examinations on medical instruments, laboratory tests, medical records at the school medical rooms, psychological examinations, psychic pathology etc.

 

          6.1.2. The mental health status.

 
The investigations on Mental Health made use of multiple methods for showing some known factors involved in the origin  of psychic disorders (19).

 

             6.1.2.1. Personal history.
Prenatal and postnatal periods.

 

 

             6.1.2.2. Heredo - collateral history.

 

 

 

             6.1.2.3. Socio – familiar background .
Educational opportunities in the family, family conditions, population density per room.

 

             6.1.2.4. Preschool period. The appreciation of parents.

Evaluation of parents on : psychomotor development up to school age, evaluation of parents on behaviour in the family, the quantity and quality of sleep, phobias, parents’ opinion  about child’s friends, relations with parents.

 

             6.1.2.5. Investigations at school .
Educational results  , opinion of teachers about the  child, relations with the teachers, complex process of behavioral integration.

 

 

 

 

             6.1.2.6. Clinical psychiatric examination.
Clinical examination and psychiatric test for assessing the balance between the processes of excitation and inhibition.

 

 

           6.2. Determining the chemical activity of blood sodium.

 

 

           6.3. The classification of subjects.
Results of tests presented above (Table 21) on 44 subjects of 12 years for both sexes show a group (1) of 8 children with high chemical activity, it is homogeneous, all having constitutional type behavioral disorders.

 

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.

The formation of the two lots, with Na⁺ transported in the ionic state with high chemical activity and a second group to which the chemical activity of Na⁺ is unsignificant (141, 60) was also  made at rats , by selection of animals from normal  collectivity , estimating the response to acoustic stimulation (109, 132, 19, 59, 192, 60).

 

           6.4. Non excitabile function structures and mechanisms of transport of blood Na.
An important parameter is to compare the response of non excitable cells to those  excitable at physiological stimuli. Non excitabile cells have also polarized membranes (MP) by the participation of potential K⁺, but without AP. At their polarization , Na⁺ has a contribution of 1%. Below there is a  comparision of  parameters of non excitable organs in subject  groups  with sodium ionic activity to those where Na⁺ linked to proteins is inactive.

 

            6.4.1. Total proteins and Na (flamfotometric) in the blood.
The values of total blood sodium (flamfotometric) and plasma protein levels (Table no. 22) shows no differences between the two groups: (I) without any chemical activity of blood Na⁺, (II) with transport in the ionic state.

 

         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
                        
group     RBC   WBC   hgl       hcr         gly        prot     Na mEq
          mil   mii  

(I)                            4,187 6.311 13,33    35.72       0.87    5.7  151.1           
             0,13       0.33         0.01     0.15     1.27      

(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.

It is illustrated by red blood cell number, hematocrit, globular values (tabel.22), chest development (27), spirometry (25). These do not indicate differences between lots formed on the basis of transport mechanisms of Na. Both groups present values of respiratory function corresponding to age (Table 23).

 

           Table 23 Spirometric static and dynamic data in  group I (Na in interaction with proteins) and II (Na transported as ions) (224).
  

  Group   Vt    F     VE    VO    CV    CV%    VEMS    VEMS%     VIMS
  ISD   592   18,4   10    310  2958   2199   2617      89     2778
           28    07     05    10    95     33     72       1       92

  IISD  541,6  21.4   11     301  2798  2194   2515      90      2614
           45.8   1.7    0.8    10.8 193    59.4  154,4     1 6     175

 

 

 

 

          6.4.3.White blood cells.
Similar situation is found on line leucocyte (Table No 22 )

 

 

 

           6.4.4. Carbohydrate and lipid metabolism (224, 100).

 
Glucose values (Table No.22) of insulinemy and response after a standard effort (Table no. 24) - test of  pancreas reactivity - shows that the transport mechanisms of Na  are not important for regulating carbohydrate metabolism for both groups (224), which range within normal values (138). There have been established no differences in terms of triglycerides, cholesterol, phospholipids and serum lipase in children with psychiatric disorders (100).

 

          6.4.5. Growth and Development ( Somatometric  values , GH ).

 
Somatic parameters analysis values (Table nr.25), the level and reactivity to an effort to standard growth hormone (Table nr.26) shows that between these two groups there are no quantitative differences in the development of these functions , as there is  no excitable tissue in the sense discussed above.

      Table 25 Comparison of somatometric indices of children in group I

 

(Na without chemical activity, with group II (children with abnormal behavior of constitutional type ) (224)

                                     circumferences          diameter    

  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 effort
         unlesional    6 9 0 7                                                        11 6 1 1 P 0, 01
      I                    I
        lesional     4 2 0 9                                                7 03 1, 07 P = insignificant.
     II unlesional   6 75 0, 81                                        10 05 1 34 P 0, 02

 

                      before the effort        after effort
       unlesional  MSD      6.9                  11 6   Po.o1  Grouo I                       0.7                   ].]
     lesional     MSD        4 2                  7 03  P=ansignif                                ]                             1.09                 1.07
 

Unlesional  GroupII   MSD    6 75                 10 .05   P0.01
                              0.81                  1.34  

 

             

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.

The functional level of excitable tissue has been  measured at the same two groups for both species. (Table No. 22, 25, 26) (Figure No. 21 and table No. 21): (1) subjects in which Na is transported by intreaction with blood proteins (without chemical activity) and (2) Na having chemical activity on the couple reactance heparin / serotonin.A problem raised is represented by the need  to determine  parameters of excitability in both species . In humans , the great variety of living and genetic  conditions  , (127) influences the development , while the somato-psychic state of health  requires verification of the components of the studied batch with the means mentioned (26), and other methods to provide additionally  data regarding  excitability. From the examination of table no.21 it results that the group  of examined children contains two subgroups. A subgroup includes children who have Na with significant chemical activity, which accompanies abnormal behavior constituti (1) some intensity clinic, which accompanies constitutional behavior disorders , some of clinical intensity , which are accompanied by educational disorders and by unbalance of inhibition processes and excitation. Another subgroup, where  no  chemical activity of serum Na is detected , is non homogenous. Some of them present postlesional psychic disturbances (95, 96). A second subgroup with abnormal type prepubertary disorders, but not behavioral, and a third group of mentally normal children. These data are supplemented by the resuls of  EEG examinations , psychic aptitudes , etc.and establishment of some neuro-endocrine mechanisms where Na  is involved  to maintain the homeostasis of circulation.

 

 

          6.5.1. Electroencephalography activity.

 

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)

	OE (ochi deschişi, prima secvenţă)		CE (ochi închişi, secvenţa a 2-a)	OE-CE	TEST (efort psihic de atenţie concentrată)		CEt (ochi închişi după efort psihic)	TEST- CEt
NORMALI	444.13±18.30	P<0.05	263.40±24.12	180.70±14.70	541.50±17.00	P<0.05	263.30±17.90	212.50±17.90
CONSTITUŢIONALI	422.50±34.40	P<0.01	308.80±54.50	113.70±29.50	416.70±33.50	P<0.01	284.80±33.60	131.80±10.20
Semnificaţiile faţă de normali				P<0.05				P<0.02
LEZIONALI	433.00±35.40	P=N	347.50±80.00	85.50±51.60	449.25±24.20	P=N	316.00±75.20	133.25±69.20
Semnificaţiile faţă de normali				P<0.05				P=N
ALTE TULBURĂRI PSIHICE	398.30±13.50	P<0.01	231.30±13.30	167.00±19.80	424.90±27.00	P<0.01	237.00±13.10	185.00±28.30
Semnificaţiile faţă de normali				P=N				P=N

 

       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)

 

 

      Figure 24 Changes in the F / V (frequency / amplitude) of EEG in a child with  hyperactive syndrome  with seric Na transport in a free state. 1 = eyes open mind at rest ; 2 = eyes closed; 3 = eyes open, effort to resolve a test of attention, 4 = eyes closed. The delayed installation of the α rhythm upon closing of the  eyes is to be noiced (236)

 

 

       6.5.2. Psychic funtions.

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 Romania (98 ). Correlation of Na⁺ seric activity (Fig. 25) with the state of the psychic aptitudes shows the coincidence with the neuropsychic clinic examination (table No. 21; Figure 21).

 

 

       6.5.2.1. Concentrated attention.

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.

 

 

       6.5.2.2. Distributive attention.

 

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)

 

          

 

 

6.5.2.3. Memory.

 

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.
                                               
       

 

        6.5.2.4. Intelligence.

Intelligence does not show differences between groups formed by the mechanisms of transport of Na in the blood.

 

 

 

      6.5.3. Cardiohemodynamic function.

 

        6.5.3.1. General

 

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.

In these conditions, the maintenance of circulatory homeostasis takes place through keeping an optimum ratio between the blood volume of vessels and that which is provided by the adequate irrigation of each tissue.

 

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).

 

 

         6.5.3.2. 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)

 

 

          6.5.3.3. 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.

 

 

 

       6.5.3.4. The evolution of hemodynamic parameters after the change of posture (Fig. 26, 27)

 

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 electrocorticography (ECG).

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.
Determinig the chemical activity of Na⁺ in blood shows its absence in normal animals, nonsensitive to noise, but it is present, in accordance with the intensity of functional manifestations, in hyperexcitable animals (Table No. 28).

 

 

 

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 

 

         calm                       3 1 1,04
        agitated                    2,74 1,69       P = 0, 52
      convulsions                   2,14 0,72       P = 0, 024
agitated + convulsions              2,42 1, 26      P = 0, 086

The absence of chemical activity of Nations or its reduction is therefore compatible with calm behavior during acoustic stimulation in rats.

Figure 30. Elimination of Na according to the ingestion (mEq / 24h)of sodium in normal rats and in rats susceptible to acoustic convulsions (225)

 

 

        6.6.3. Motor activity.

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)

      Table 29.Total motor activity of the two groups recorded during free behavior in the cage. (227, 230, 229, 223)
                      references (with Na bound), calm during stimulation) 353.87 149.5
                      animals hypersensitive to noise (Na in the ionic state, convulsions) 517.41 264.8
                      P = 0 .001.

 

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.

 

 

 

        Table 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)

        steps to:        distilled water      physiological solution

            

 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).

 

 

 

         6.6.5. 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).

The ratio of urinary Na and K concentration (Na / K) is different in the two groups (Fig 32). The value is significantly higher in animals with chemical activity of Na⁺, expressing a functional lower level of the mineralocorticoid system (Fig.32). The ratio Na / K is significantly different in these animals and after repeated centrifugation (+5G for 30 min x 5 times), while in the normoexcitable animals the value of ratio is decreasing. It expresses the differences of the systems involved in regulating the balance of the increased hydrosalin (78). There has been noted  differences between the two groups regarding the mineralocorticoid activity (Fig 33) (230). In adults, the value of the ratio Na / K is significantly higher in animals susceptible to  audiogene convulsions ,  having therefore less   mineralocorticoid activity than normoexcitable animals. The differences between the two groups is emphasized with age. In normal animals, age induces diminution of the mineralocorticoid activity (Fig 33), also known (63, 212, 199, 67, 241), due to senility process of involution (5, 190, 199, 212), between 17 and 27 months age and decreased secretion of aldosterone. In the animal with Na⁺ sanguin transported in active chemical  state ,  the ratio Na / K decreases (Fig 33) to values comparable to those in the  normoexcitable adult animal, which suggests an improvement in mineralocorticoid activity. A picture in the mirror over the normoexcitable animal is carried out (Fig 33). This evolution of mineralocorticoid activity can recognize different causes.

Reduction of the concentration capacity of Na⁺ at the kidney level (Fig.33) having as a result the increase of the circulant Na⁺ and the decrease of K⁺ elimination, that stimulates aldosterone secretion (78,105,216). Another mechanism could recognize an up-regulation process  maintained by the low concentration level of aldosterone in the blood (63) in this group of  animals. Genetic factors could also be incriminated (190) in the carrier protein synthesis, but it is known that protein malnutrition is accompanied by increased content of corticosteron in the  blood in rats (129, 189) concomitant with the increase of the  fighting behavior.

Figure 32. Variation of the ratio urinary Na / K acc. to  mEq Na⁺ ingested by normoexcitable animals and by those with Na⁺ transport in ionic state (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.

Analysis of brain activity decodification also includes the estimation of hydroelectrolytic homeostasis in the two groups of rats: normal, with absent chemical activity of Na , and the group susceptible to audiogenous convulsions with Na⁺ transport in ionic state. Hypersensible animals consume significantly more saline solution  than normal animals (Table no. 31) in freely motivated behavior, than distilled water. (227)

 

 

       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)                       

 

       reference                                       24,039,3

 

  hypersensitive                                   27,236,9

 

 P                                                                 0,063            

                                                                                      

 

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 Physiology School (Medical School) Cluj-Napoca, in Romania. He continued his scientific activity in Physiology in Bucharest at the Institute of Physiology and Pathophysiology Daniel Danielopolu until 2004, at which time he retired as Director of the Institute; he had held this position since 1990. His research work includes studies of the central nervous system physiology relating to the transmission of information in the nervous centers; cerebral excitability, using methods, in their evolution, from the determination on reactive isolated organ, to the most complex physical and chemical methods, in the present. In his research of chemical mediation he studied acetylcholine, serotonin, and their connection with the cerebral metabolism.

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 Romanian Academy of Medical Sciences.

 

Dr. Diana Popa (Uluitu) is a researcher in the Department of Microbiology, Immunology and Molecular Genetics at the University of Kentucky in Lexington, Kentucky, USA. She attended Medical School at Vasile Goldis University in Arad, Romania, and graduated in 1998; during summer breaks at medical school she volunteered at the Institute of Physiology D. Danielopopu in the physiology and microbiology laboratories as well as in the clinic. After completing medical school and a one year internship, she worked as a Research Assistant at the Danielopopu Institute for three years before coming to the University of Kentucky. In addition to her medical thesis, which focused on the actions of Lithium on the central nervous system, since coming to the United States she has published numerous additional papers relating to Lithium and other substances. In continuing her on-going studies, Dr. Popa is currently pursuing a Master’s degree in Public Health at the University of Kentucky.