Patent Publication Number: US-6219567-B1

Title: Monitoring of total ammoniacal concentration in blood

Description:
CROSS-REFERENCE TO RELATED APPLICATIONS 
     STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH 
     Not applicable. 
     BACKGROUND OF THE INVENTION 
     Ammoniacal levels (often referred to as “ammonia”) are found normally in the body and ordinarily are not harmful, yet in increased concentration become toxic. Hyperammonemia is the clinical condition associated with increased plasma ammoniac levels which manifests itself in vomiting, lethargy, confusion, and coma. Prognosis for patients suffering from hyperammonemia depends on prompt detection and aggressive treatment. Once it has been recognized that a patient is suffering from hyperammonemia, there are alternatives available for lowering the level of ammoniac component present in the blood. If undetected or untreated, however, continuing hyperammonemia may result in severe brain damage or death. 
     Hyperammonemia is not a diagnosis, rather it is a condition which may result from one of any number of underlying causes which range from inherited abnormalities, to acquired diseases, to inducement during the course of treatment for other illnesses. The normal ammoniacal concentration ranges from 15 to 35 μmol/liter in adults and 20 to 50 μmol/liter in children. A patient may experience a symptomatic range including vomiting, loss of muscle coordination, irritability and hyperactivity at 100 or above μmol/liter, vomiting and lethargy at 200 μmol/liter, and coma at or above 300 μmol/liter. While these ammoniacal concentration levels may seem high, being double to six times the normal levels in a healthy adult, ammoniacal concentration levels for inherited disorders have been reported being over 1000 μmol/liter to as much as 4000 μmol/liter. 
     The highest levels of ammoniacal concentration are reported in cases of transient hyperammonemia where concentration may rise to 2000 to 4000 μmol/liter, nearly 100 times greater than normal. This occurs with one type of transient hyperammonemia whose cause, while still uncertain, has been linked to transient abnormalities of the urea cycle, delayed development of an affecting enzyme outside the urea cycle, tissue hypoxia or poor perfusion through the liver. Another type of transient hyperammonemia involves ammoniacal concentration levels which are approximately twice the normal level, but which generally decreases to normal without treatment. 
     Inherited disorders of the urea cycle also may cause hyperammonemia in both adults and children, although the most severely affected are present in the neonatal period. If there is a deficiency in one of the urea cycle enzymes, inadequate urea will be formed and nitrogen, in the form of an ammoniacal concentration, will accumulate in all cells of the body. Congenital deficiencies of each of the five enzymes in the urea cycle have been identified. In children, high levels of ammoniac concentration often will manifest itself as a catastrophic illness known as hyperammonemic coma. Morbidity has been associated with the duration of hyperammonemic coma rather than with the specific enzyme deficiency causing the level of ammoniacal concentration elevation. 
     Another inherited disorder associated with hyperammonemia is organic acidemias, which is a defect in the metabolism of amino acids and fatty acids. A metabolic crisis may be precipitated by excessive protein intake, intercurrent infections, incorrect diet or incorrect medications. For more information on hyperammonemia caused by inherited disorders, see: 
     1. Ballard, R. A., et al. “Transient Hyperammonemia of the Preterm Infant.” New England Journal of Medicine. 1978; 299: 920-925. 
     2. Batshaw, M. L., et al. “Treatment of urea Cycle Disorders.” Enzyme. 1987; 38: 242-250. 
     3. Leonard, J. V. “Hyperammonemia in Childhood.” Clayton, B. E., ed. Chemical Pathology and the Sick Child Oxford: Blackwell, 1984: 96-119. 
     In addition to inherent abnormalities, hyperammonemia may be caused by acquired diseases or conditions. The leading cause of hyperammonemia in adults is intrinsic liver disease. Acute liver disease being caused by viral hepatitis, drug overdose, reaction to anesthetic agents or medications, and obstruction of bile duct, while the most common causes of chronic liver disease in adults include cirrhosis, infection, excessive protein intake, diuresis, and sedative drugs. Renal failure can precipitate or exacerbate hepatic encephalopathy by excessive production of ammonia. Other diseases or conditions, such as leukemia, urinary tract infections, congestive heart failure, physical trauma to the liver or kidneys, or disseminated herpes simplex infection also may cause hyperammonemia. 
     A final category of causes for hyperammonemia is inducement during treatment for other illnesses. Sodium valproate is an anti-epileptic agent used to control generalized seizures and other refractory types of seizures which has been reported to cause high levels of ammoniacal concentration in the blood. Hemodialysis may lower ammoniacal concentration levels in patients with hepatic encephalopathy, however, the opposite may be found during hemodialysis with sorbent-based low-volume dialysate regeneration systems. With these systems, urea is converted to ammoniacal components which then are absorbed by a cationic exchange resin. If the absorption rate of the resin is exceeded, these components continue to be converted but diffuses from the dialysate into the patient. Hyperammonemia is also a risk during transurethral resection of the prostate using glycine irrigant due to the metabolic decomposition of glycine into ammoniacal components. Heart and lung transplantation may be accompanied by hyperammonemia, which if not promptly and aggressively treated, can be a life threatening complication. 
     While the foregoing is not an exhaustive list of potential causes of hyperammonemia, these examples illustrate the wide variety of sources of increased ammoniacal concentration levels and the seriousness of the resulting condition. Fortunately, once a hyperammonemic episode has been identified, a number of intervention alternatives are available to lower ammonia levels. For example, in urea cycle disorders these include limiting nitrogen intake, improving the quality of protein ingested, supplying deficient metabolites, providing alternate pathways for waste nitrogen excretion and removal of nitrogen, i.e., by peritoneal dialysis or hemodialysis. Cases of acute hyperammonemia may require mannitol infusions to control intracranial pressure. With ammoniacal concentration levels decreased to within acceptable bounds, the underlying cause may be addressed. 
     Several conventional methods currently are available to measure the ammoniacal concentration level present in a patient. Most of these require some form of separation process before analysis. Ammonia gas and ammonium ion are separated from their matrix either by absorption onto a resin or by conversion to ammonia using alkali followed by gaseous diffusion. The ammonia gas concentration may then be quantified colorimetrically or by an ion-specific electrode. Alternatively, enzymatic methods are available which involve the formation of reaction product, proportional to the presence of ammonium ion, which is measured spectrophotometrically or fluorimetrically. While these methods may measure ammoniacal concentration levels with a certain degree of accuracy if performed properly, there are several documented sources of error which may affect the accuracy of the ammonia measurement. One source of error with existing enzyme techniques is that ammonia, as a combination of the gaseous and ionic state, is generated by the deamination of endogenous amino acids in the sample as soon as the blood is withdrawn. Delays greater than 15 minutes before centrifuging of the sample have been reported as causing a clinically significant increase in measured ammoniacal concentrations. Other sources of error include variations in test strip or reagent consistency used to indicate analyte, inconsistencies in indicator sensing means, variations in homogeneity of ammonia distribution in the blood sample, and variation due to the background levels of ammonia gas in the laboratory environment at the time of actual specimen assay. For discussion of current ammoniacal concentration measurement techniques and devices, see: 
     4. Burtis, C. A. and E. R. Ashwood, eds.  Teitz Textbook of Clinical Chemistry  (second edition). Philadelphia: W. B. Saunders Company, 1994. pp. 1487-1489. 
     5. losefoshn, M. “Ektachem Multilayer Dry-Film Assay for Ammonia Evaluation.” Clinical Chemistry. 1985; 31 (12): 2012-2014. 
     6. Quiles, R., et al. “Continuous flow assay of Ammonia in Plasma Using Immobilized Enzymes.” Analytica Chimica Acta 1994; 294 (1): 43-47. 
     Even assuming an accurate measurement, the time and expense associated with these types of analysis limit their repeatability during a given time period. The assay process can take 30 minutes or more once the sample is introduced into the analyzer. The expense involved with each blood sample includes the cost for the ammoniacal concentration assay as well as hospital staff time and expenses associated with withdrawing a blood sample, centrifuging the blood sample in a refrigerated centrifuge, and transporting the blood sample to the hospital&#39;s laboratory for assay. Given that these procedures are relatively expensive and labor intensive, blood ammoniacal concentration measurements are necessarily performed on an infrequent basis, typically several times per day. As such, trending, which would indicate the necessity for intervention where a patient&#39;s ammoniacal concentration level begins to rise but before a dangerous condition is reached, is not possible. 
     In view of the problems associated with existing blood ammoniacal concentration measurement techniques, a need exists for an approach which is more accurate, less expensive, and less time-consuming. Such an approach could consequently be performed more frequently allowing the practitioner to monitor trends in a patient&#39;s ammoniacal level and to provide more timely diagnosis and treatment. 
     BRIEF SUMMARY OF THE INVENTION 
     The present invention is addressed to a system and method for monitoring total ammoniacal concentration (TAC) in blood. Utilizing either catheter borne or bypass containing sensors, the system employs a controller to obtain TAC values at highly desired relatively short measurement frequency intervals. In general, the sensors of the system are configured and controlled to measure the value of a select ammoniacal component, either ammonia gas (NH 3 ) or the ammonium ion (NH 4   + ). A preferred sensor structure employs fiberoptic technology to repeatedly measure ammonia concentration. Utilizing the measured pH level in the blood, those ammonia component concentration values then are converted to TAC using the Henderson-Hasselbalch relationship. The value of blood pH may be acquired separately or may be monitored simultaneously with the monitoring of the ammonia component, using for example, fiberoptic technology in conjunction with the sensing function. 
     The relatively higher TAC measurement frequency permits the use of moving average filtering employing a predetermined number, n, of measurement values in a first in-last out queue of values which is averaged. These filtered TAC values are associated with the real time occurrence of each of the noted first measurements and are submitted to memory as well as to a display function. The processor driven controller further provides a graphics developed trend readout, plotting TAC with real time of measurement. Responding to input supplied by the practitioner, the controller provides an alarm output when measured total ammoniacal concentration equals or exceeds a designated threshold. This controller function further performs rate-of-rise of TAC values and will respond to a practitioner input threshold for such rate-of-rise values to provide an alarm. Also, the processing function of the controller will provide a warning output as a visual cue indicating the occurrence of a rising TAC level from one measurement to a next. 
     A further feature of the invention is to provide a method for monitoring the ammoniacal concentration in blood within the vascular system contained bloodstream of the body, such system directing blood exhibiting a given pH value along given path directions and extending to peripheral regions of such body without the immediate region of the heart, comprising the steps of: 
     (a) providing a catheter assembly having a proximal end region, a measurement region spaced therefrom extending to a tip, having a first sensor channel extending from the proximal region to the measurement region, an ammoniacal component sensor supported by the first sensor channel, having an ammoniacal component responsive forward assembly at the measurement region contactable with flowing blood within the bloodstream, the sensor assembly being controllable to provide ammoniacal sensor outputs at the proximal end region; 
     (b) providing a controller actuable to control the ammoniacal component sensor assembly to derive the ammoniacal sensor outputs over a sequence of measurement intervals, and responsive to the ammoniacal sensor outputs to derive a sequence of total ammoniacal concentration values over a measurement period and deriving display signals corresponding with that sequence of values; 
     (c) providing a display assembly responsive to the display signals to derive a visibly perceptible information output corresponding therewith; 
     (d) positioning the catheter assembly measurement region within the bloodstream and preferably at one of the peripheral regions however, the catheter may be of a variety having components located within the heart; and 
     (e) actuating the controller to derive the display signals and effect derivation of the perceptible information output. 
     Other objects of the invention will, in part, be obvious and will, in part, appear hereinafter. The invention, accordingly, comprises the system and method possessing the construction, combination of elements, arrangement of parts and steps which are exemplified in the following detail description. 
     For a fuller understanding of the nature and objects of the invention, reference should be made to the following detailed* description taken in connection with the accompanying drawings. 
    
    
     BRIEF DESCRIPTION OF THE DRAWINGS 
     FIG. 1 is a chart illustrating blood ammonia levels for normal ranges and ranges associated with various diseases; 
     FIG. 2 is a block diagram illustrating various sources, metabolism sites, and clearance pathways for ammoniacal products in the human body; 
     FIG. 3 is a stylized graph showing a rate-of-rise for endogenous total ammoniacal concentration (TAC) with respect to real time; 
     FIG. 4 is a pictorial view of a catheter employed with the system and method of the invention; 
     FIG. 5 is a partial sectional view of the forward end region of the catheter of FIG. 4; 
     FIG. 6 is a sectional view taken through the plane  6 — 6  in FIG. 5; 
     FIG. 7 is a schematic representation of a front end assembly of a concentration sensor employed with the invention; 
     FIG. 8 is a schematic representation of the front end assembly of a concentration sensor which may be employed with the invention; 
     FIG. 9 is a schematic representation of a membrane containing front end assembly of a concentration sensor which may be employed with the invention; 
     FIG. 10 is a schematic representation of a membrane containing front end assembly of a transmission-type concentration sensor which may be employed with the invention; 
     FIG. 11A is a schematic representation of a front end assembly of a concentration sensor which may be employed with the invention; 
     FIG. 11B is a schematic representation of the front end assembly of a concentration sensor which may be employed with the invention; 
     FIG. 12 is a schematic representation of a front end assembly of a concentration sensor which may be employed with the invention; 
     FIG. 13 is a schematic representation of a front end assembly for a concentration sensor which may be employed with the invention; 
     FIG. 14 is a schematic representation of a pH sensor which may be employed with the invention; 
     FIG. 15A is a schematic representation of optical components performing with a sensor according to the invention; 
     FIG. 15B is a sectional view taken through the plane  15 B- 15 D shown in FIG. 15A; 
     FIG. 16 is a pictorial view of a catheter incorporating a concentration sensor with non-optical technology; 
     FIG. 17 is a partial sectional view of the catheter of FIG. 16 taken through the plane  17 — 17  in FIG. 18; 
     FIG. 18 is a sectional view taken through the plane  18 — 18  in FIG. 17; 
     FIG. 19 is a partial sectional view of a catheter taken through the plane  19 — 19  shown in FIG. 20; 
     FIG. 20 is a sectional view taken through the plane  20 - 20  shown in FIG. 19; 
     FIG. 21 is a schematic diagram of a Schottky diode-based ammoniacal component concentration sensor; 
     FIG. 22 is a sectional view taken through the plane  22 — 22  shown in FIG. 21; 
     FIG. 23 is a sectional view taken through the plane  23 — 23  shown in FIG. 21; 
     FIG. 24 is a schematic representation of an acoustic wave-based ammoniacal concentration sensor; 
     FIG. 25 is a sectional view of a catheter of minimal dimension employed with the system and method of the invention; 
     FIG. 26 is sectional view taken through the plane  26 — 26  shown in FIG. 25; 
     FIG. 27 is a schematic sectional view of a vessel in which a catheter has been inserted; 
     FIG. 28 is an other sectional view of a vessel within which a catheter has been inserted; 
     FIG. 29 is a pictorial representation of a human arm with a catheter insertion according to the invention; 
     FIG. 30 is a pictorial representation of a human arm with the insertion of a pair of catheters of minimal dimension according to the invention; 
     FIG. 31 is a pictorial representation of a human arm with a bypass sampling arrangement for carrying out the monitoring procedure of the invention; 
     FIG. 32 is a pictorial representation of a system according to the invention; 
     FIG. 33 is a block schematic diagram of the controller arrangement of the invention; and 
     FIGS. 34A-34E combine as labeled thereon to provide a flow chart describing the operation of a controller employed with the invention. 
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
     The system and method of the invention looks to a relatively rapid succession of measurements of total ammoniac content in the blood over an extended measurement interval. The multiple measurement approach generally will be seen to employ a control arrangement wherein total ammoniacal concentration (C TAC ) is computed in conjunction with a processor driven controller. Relatively normal or asymptomatic ranges for this total ammoniac concentration have been the subject of prior investigation, as well as higher values associated with symptomatic conditions. Practitioners using the system will desire to determine baseline values for TAC which may be somewhat unique to the preexisting condition of the patient. Accordingly the system provides for a manual inputting of a threshold level for total ammoniac concentration, C th . Election by the clinical practitioner of appropriate thresholds for inputting to the system, will be carried out in cognizance of exhibited total concentration levels as well as reported symptomatic levels. Referring to FIG. 1, total ammoniacal concentration levels are charted in bar graph form. In the figure, a compilation is provided showing not only normal level ranges, but also, asymptomatic ranges to the highest levels heretofore reported in literature. Conditions, whether normal or otherwise, are shown as abbreviations developed with respect to the first letter of each word describing the condition. In Table 1 below, these abbreviations are listed in combination with their associated definitions. 
     
       
         
           
               
               
             
               
                 TABLE 1 
               
               
                   
               
             
            
               
                 NRFA 
                 NORMAL RANGE FOR ADULTS 
               
               
                 NRFC 
                 NORMAL RANGE FOR CHILDREN 
               
               
                 NRFN 
                 NORMAL RANGE FOR NEONATES 
               
               
                 NRDHE 
                 NORMAL RANGE DURING HEAVY EXEXCISE 
               
               
                 SRVWLOMCIAH 
                 SYMPTOMATIC RANGE WITH VOMITING, LOSS OF MUSCLE 
               
               
                   
                 COORDINATION, IRRITABILITY AND/OR HYPERACTIVITY 
               
               
                 SRWVAL 
                 SYMPTOMATIC RANGE WITH VOMITING AND LETHARGY 
               
               
                 CRTPSO 
                 COMATOSE, RESPONSIVE TO PAINFUL STIMULI ONLY 
               
               
                 IDOUC 
                 INHERITED DISORDERS OF UREA CYCLE 
               
               
                 OA 
                 ORGANIC ACIDEMIAS 
               
               
                 TH 
                 TRANSIENT HYPERAMMONEMIA 
               
               
                 PA 
                 PERINATAL ASPHYXIA 
               
               
                 INIH 
                 INTRAVENOUS NUTRITION INDUCED HYPERAMMONEMIA 
               
               
                 I 
                 INFECTON/SEPSIS 
               
               
                 LD 
                 LIVER DISEASE 
               
               
                 RF 
                 RENAL FAILURE 
               
               
                 SVI 
                 SODIUM VALPORATE THERAPY 
               
               
                 UTI 
                 URINARY TRACT INFECTIONS 
               
               
                 CHF 
                 CONGESTIVE HEART FAILURE 
               
               
                 HIH 
                 HEMODIALYSIS INDUCED HYPERAMMONEMIA 
               
               
                 L 
                 LEUKEMIA 
               
               
                 GUIH 
                 GLYCINE UPTAKE INDUCED HYPERAMMONEMIA 
               
               
                 OT 
                 ORGAN TRANSPLANT 
               
               
                   
               
            
           
         
       
     
     For patients undergoing total ammoniacal content monitoring from a starting condition representing normality, the practitioner typically will elect a threshold under which the system provides an alarm somewhere between total ammoniac concentrations (TAC) of about 100 μmol/liter to about 150 μmol/liter. At blood ammoniacal levels between about 200 and 350 μmol/liter, the patient generally presents as asymptomatic as represented in the table. However, it should be observed that during normal heavy exercise, ammoniacal levels will elevate, for example, to levels above 100 μmol/liter. When patients present exhibiting total ammoniacal content levels well above these lower thresholds, then to avoid the irritation of a constantly published alarm, the threshold may be established at elevated levels. The system also will indicate a warning, for example, as may be generated by an amber illuminator indicating that the ammoniacal levels are increasing from measurement to measurement. Additionally, the system looks to an increase over a set threshold for rate-of-rise of total ammoniacal level to alert the practitioner with an appropriate alarm. 
     Advantage also may be taken of the relative rapidity of measurement of total ammoniacal content (TAC) by deriving real time based trending which may be visually represented in graphical format in a display readout which also, will provide real time and total ammoniacal content values in numeric form. To avoid distractive overly rapid numeric changes for TAC, the system preferably employees a moving average filtering approach wherein an inputted number, n, of successive TAC values are averaged and that average is updated with each measurement on a first in last out basis. Thus, readability of the numeric data is improved and any erratic readings are somewhat accommodated for. 
     The role of ammoniacal fluid in body physiology has been subject of extensive investigation. See, for example: Lockwood, A. H. et al., “The Dynamics of Ammonium Metabolism in Man—Effects of Liver Disease and Hyperammonenia,”  J. Clin. Inves.,  Vol. 63, pp 449-460, 1979. Under resting conditions, most blood ammoniac content is of dietary origin. Normal digestive processes generate ammoniacal concentration from ingested protein, while bacteria in the gastrointestinal track generates ammoniacal concentration by metabolizing protein products of dietary protein digestion and urea. An illustration of the major organs of ammonia/ammonium formation, utilization and circulation is presented in FIG.  2 . The figure includes representations of the various forms of nitrogenous compounds, e.g., ammonia gas (NH 3 ), ammonium ion (NH 4   + ) or related nitrogenous by-products. Ammonia/ammonium metabolically formed in a given organ of the body generally is widely distributed. In FIG. 2, the blood pool or blood system is represented at block  10 . Blood pool  10  is depicted supplying glutamine (GLN) to the gut or gastrointestinal tract as represented at arrows  12  and bock  14 . Ammonia/ammonium generated in the gut as at  14  from protein digestion and deamination of glutamine (GLN) enters the portal venous circulation as represented at arrow  16  and  18  and is involved in the liver function as represented at block  20 . The metabolic relationship of the blood pool or blood system  10  with the liver is represented by arrows  22 - 24 . Metabolic interaction with the kidney as at block  26  is represented at arrows  28  and  29 , while catabolic ammonium is excreted as represented at arrow  30  and block  32 . Transport to and from the brain with respect to the blood pool is represented at block  34  and arrows  36 - 38 . A similar metabolic interrelationship with respect to skeletal muscle is represented at block  40  and arrows  42  and  43 . Exercise induced hyperammonemia (EIH) will witness a transfer of ammonium ion into the blood supply as represented at arrow  44 . It may be observed that such relatively short excursions thus are readily tolerated by the body. See generally “Exercise-Induced Hyperammonemia: Peripheral and Central Effects,” Bannister, et al., Int.J. of Sports Medicine, Vol. 11, pp 5129-5142 (1990). Under conditions typical of patients in an intensive care unit, resting muscles take up ammonia/ammonium from the circulating blood wherein the substance enters into protein synthesis via ketoglutaric and glutamic acid. When the muscle begins working again, ammonia/ammonium is once again released from the muscle into the bloodstream. If additional ammonia/ammonium (in the form of ammonium salt solution) is injected into a peripheral vein, the added ammoniacal content is brought directly to tissue via the blood where it may be retained and eventually used for amino acid and protein synthesis. See: Furst, P. et al. “Nitrogen Balance After Intravenous and Oral Administration of Ammonia Salts in Man,”  Journal of Applied Physiology,  Vol. 26, No. 1, pp 13-22 (1969). 
     The availability to the practitioner of displayed trends in total ammoniacal concentration (TAC) in blood as well as the opportunity to establish thresholds both with respect to TAC level and threshold rates of elevation of TAC are of value in establishing a prompt treatment of such elevating TAC level conditions. Additionally, a warning (preferably non-audible) to the practitioner that such TAC levels are elevating is of value for achieving an early as possible treatment of excessive ammoniacal levels. These levels may rise at a relatively rapid pace. Looking to FIG. 3, an idealized curve  50  drawn from both literature and animal studies with respect to the introduction of ammoniacal levels is presented in conjunction with a similarly typical time of day representation. When the patient presents with such rapidly elevating TAC levels, the alarms and warnings will be generated. In this regard, the blood TAC threshold value, C th  is represented at dashed line  52  at a level of about 180 μmol/liter. The rate of increase of TAC level, for example, taken over time interval commencing at a time of day of about 1000 is represented at the curve region  54 . Such rate is determined as a division of the change in blood total ammoniacal concentration identified in simple form as “ΔC TAC ” is divided by the time interval “δt ROR ”. Where the rate-of-rise, as computed, exceeds a rate-of-rise inputted by the practitioner as a threshold, then an alarm is developed which may be either or both audible and visual in cuing extent. 
     The instrumentation employed for carrying out sequential measurements of total ammoniacal concentration in blood (TAC) may involve relatively short inline catheter structures carrying at least a sensor channel which incorporates a sensor responsive to one component of the ammoniacal concentration in blood. That component, for example, may be ammonia (NH 3 ) or ammonium (NH 4   + ). Because of variations in vascular system vessel cross-sectional sizes and the presence of branching and hydraulic impedance phenomena, the instrumentation also may employ devices insertable within the vascular system which are quite diminutive in diametric size, so as to present minimum impedance to bloodflow. Where, for example, neonate infants are involved, peripheral vascular diametric extent may be quite small necessitating such diminutive size. Further, the system looks to the utilization of its sensing capability with blood by-pass devices which may assume a variety of mechanical designs. Typically catheters will be employed in conjunction with the vascular system at a peripheral region of the body which is considered to be a region remotely disposed from the heart. In general, this type of interaction with the bloodstream or blood from the bloodstream may be considered to be less invasive. 
     Referring to FIG. 4, a catheter assembly is represented generally at  60 . Assembly  60  is configured for insertion within the bloodstream of the vascular system located in a peripheral region of the body. Such a region will, for example, be in a forearm radial artery or ulnar artery. Where excessive blood hydraulic impedance is encountered, the sensing components may be extended into the brachial artery. Having a body portion  66  intended for vascular positioning which is of somewhat short lengthwise extent, for example, five to ten inches, this portion extends from a base  62  within a relatively extended proximal region represented generally at  64  to a measurement region  68  extending, in turn to a tip  70 . Located within the measurement region  66  and, preferably, extending from tip  70 , are two fiberoptic channels (not shown) which extend to base  62  for further continuous communication with a fiberoptic cable  72  terminating in a fiberoptic connector  74 . Connector  74  is configured for insertion within a two channel fiberoptic input of a controller. Two additional or auxiliary channels may be provided within the structure  66  which terminate, for example, in a distal auxiliary port  76  and a proximal auxiliary port  78 . Distal auxiliary port  76  extends to a flexible tubular conduit  80  coupled in fluid transfer relationship with the channel at base  62 . Conduit  80 , terminates in a connector and valve assembly  82 . In similar fashion, the auxiliary channel extending to proximal port  78  in turn, leads to base  62  at which position it is connected in fluid transfer association with a conduit  84  terminating, in turn, at a connector and valve assembly  86 . These auxiliary channels may, for example, be employed for the purpose of withdrawing blood for sampling, for the infusion of irrigants, or delivery of medicants. 
     Referring to FIGS. 5 and 6, the structure of catheter  60  extending from its measurement region  68  is revealed in sectional fashion. Additionally, in the former figure, signal treating aspects of a controller function represented at  90  are depicted. In general, the body portion  66  of the catheter assembly  60  is formed of a medical grade polymeric material which is slightly flexible, permitting sufficient flexure for facile insertion through an introducer into a vascular vessel for contact of the measurement region  68  with the bloodstream. The polymeric body portion  66  is shown having an outer cylindrical surface  94 . Formed typically by extrusion through the body portion  66  is a first sensor channel  96  which extends from the base  62  (FIG. 4) to tip  70  and which serves to support an ammoniacal component sensor assembly represented in general at  98  and seen to be comprised of a fiberoptic strand  100  extending to an ammoniacal component responsive forward assembly represented generally at  102 . Assembly  102  includes the confronting face or tip surface  104  of the fiberoptic strand  100  which is seen to be extending slightly forwardly of the forward surface  106  of the body portion  66  of catheter  60 . Forward assembly  102  further includes a membrane  108  which, inter alia, forms a blood confronting surface of an ammoniacal component concentration reactor which may take a variety of configurations. For example, the elected ammoniacal component may be ammonia (NH 3 ) and the reactor may be selected to be a gaseous ammonia sensitive dye which may be captured by the membrane either by admixture therewith or by encapsulating the dye intermediate the membrane  108  rear face and the forward face  104  of the fiberoptic strand  100 . For the former approach, the dye is deposited upon the membrane surface for migrating into its pore structure. This approach has been observed to improve response time. With the above arrangement, the fiberoptic strand  100  functions as a transmission assembly for conveying a signal corresponding with the output condition of the reactor along the body portion  66  to connector  74 . (FIG.  4 ). 
     Positioned diametrically opposite the first sensor channel  96  is a second sensor channel  110  again extending from the forward surface  106  of body portion  66  to the base  62  (FIG.  4 ). Sensor channel  110  functions to support a pH sensor structure represented generally at  112 . Structure  112  includes a pH responsive forward assembly represented generally at  114  formed including the forward portion of a fiberoptic strand  116 , the forward face  118  of which is seen to protrude slightly from forward surface  106  of catheter body portion  66  at tip  70 . Forward assembly  114  of the sensor  112  may assume a variety of configurations for carrying out in vivo measurement of pH. In this regard, typically, a pH-sensitive indicator is immobilized on the face  118 . Light energy of a selected wavelength is guided along the fiberoptic strand  116  to excite the indicator which then fluoresces and resultant emission intensity is a function of the pH of blood within the bloodstream. To provide the forward assembly structure  114 , the face  118 , supporting the indicator is covered with a hydrogen ion permeable membrane represented at  120  which is impermeable to the other constituents of blood. 
     FIG. 6 reveals the distal auxiliary port  76  extending through the outer cylindrical surface  94  of the body portion  92 . Port  76  is in fluid transfer communication with an auxiliary channel  122  which extends to the base  62  and thence to a fluid transfer communication with conduit  80 . In similar fashion, the proximal auxiliary port  78  (FIG. 4) is in communication with auxiliary channel  124  which extends, in turn, to face  62  and thence to a fluid communication with conduit  84 . 
     FIG. 5, shows that the fiberoptic components of ammoniacal sensor assembly  98  and pH sensor assembly  112  extend to signal treatment components of a controller function, as represented in block form, at  124  and  126 . Cable  72  (FIG. 4) is symbolically represented by dual arrows  128  and  130 , the former extending from the ammoniacal sensor assembly  98  and the former from the pH sensor assembly  112 . The signal treatment function represented at block  124  includes a light source (LS) and transducing (T) network  132 , the interactive association with arrow  130  being represented by dual lines  134  and  135 . In similar fashion, arrow  128  is seen to be operationally associated with a light source (LS) and transducing (T) network  138 , the interactive operational association with arrow  128  being shown by lines  140  and  141 . For the fiberoptic embodiment shown, networks  132  and  138  function to interrogate the reactor components of forward assemblies  102  and  114  to provide an analog signal at outputs represented at respective lines  144  and  145 . These analog signals then are converted to digital form as represented at the analog-to-digital conversion block  126 . The resultant digital data then is submitted for processing as represented at arrow  146 . 
     The type of sensor technology employed with the ammoniacal concentration monitoring may vary somewhat and is generally selected with respect to the ammoniacal component, i.e., ammonia gas (NH 3 ) or ammonium ion (NH 4   + ) being monitored. The system and methodology of the invention may be employed with catheters, certain of which may be of very minimal outer diametric extent to avoid undue blood hydraulic impedance, and also may perform in an ex vivo fashion. In the latter regard, a bypassing approach may be employed not only with respect to ameliorating the noted hydraulic effect but also may be used in conjunction with pre-established bypass related modalities such as in dialysis procedures where hyperammonemia may present itself or in such modalities as heart bypass procedures wherein organ failure may be manifested in elevation of ammoniacal levels. The forward assemblies of the sensor systems should be located within the blood being evaluated in a manner optimizing their performance. Thus, where the sensors are employed with catheters, such devices should be in an orientation wherein their principal sensing surface confronts the direction of bloodflow as opposed to being in an orientation where blood flows over their rearward portion and a tip located sensing surface. The later kind of orientation in the bloodstream tends to develop depletion regions at a forward sensing surface. Where measurement occurs ex vivo and is carried out in conjunction with flowing blood, the same geometry of bloodflow and sensor association is preferred. Positioning the forward assembly sensing tip or face in less than desired orientations has been found to extend the interval required to achieve measurement value equilibrium. In general, the optical sensors include: direct spectrometric sensors; indirect spectrometric sensors; transmission spectrometric sensors; transmission/reflective spectrometric sensors; colorimetric sensors; and fluorometric sensors. Such sensors are described in conjunction with schematic representations of them in the figures to follow. 
     Considering initially the direct spectrometric sensors, reference is made to FIGS. 7 and 8. In FIG. 7, the forward assembly of one such ammoniacal component concentration sensor is revealed. This sensor, for example, directly measures the ammonia gas component of the blood. With this arrangement an optical fiber  150  is employed. Fiberoptic component  150  is mounted within a sensor channel, for example, as represented at  96  in FIGS. 5 and 6. Component  150  is surrounded along its lengthwise extent by a sheath  152 . Tip or forward face  154  of component  150  is coated with a very thin, optically transparent coating  156 . Coating  156  is an anti-coagulant such as heparin which functions to reduce the possibility of deposits such as fibrin or blood coatings over the tip  154 . The embodiment of FIG. 7 is one wherein there is a simultaneous transmission of light at one or more predetermined wavelengths and reflectance reception of that light. In this regard, the bloodstream is schematically represented in general at  158 . The ammonia gas (NH 3 ) component of the bloodstream is analyzed with the instant embodiment and particles of that gas are represented at  160 . For the preferred embodiment wherein ammonia gas is the elected ammoniacal component, analysis is made by light transmission to and reflectance from the ammonia gas particles  160 . Light transmission is schematically represented in the figure as wave arrows  162 , while reacting reflectance or reflections are represented by the wave arrows  164 . This latter reflective illumination as represented by the arrows  164  will exhibit a spectrum which is characteristic of the ammonia component and the intensity of the spectral portions thereof will be related to the concentration of ammonia  160  within blood  158 . As noted above, it is preferred that the face  154  of the forward assembly  102  confront the direction of bloodflow as represented by arrow  166 . In general, the diameter of the fiberoptic component  150  will be in a range from about 50 to 1000 microns, and preferably falls at a range of about 100 to 500 microns for conventional catheter applications. A typical diameter for the latter applications will be about 250 microns. 
     The transmission and reception of investigatory light at one or more predetermined wavelengths also may be carried out using two or more fiber components. In one approach, two fiber components are positioned in immediate adjacency. Alternately, one fiberoptic component may provide a transmission aspect while a group of such fiber components surmounting a central transmission fiber component carries out the opposite or reception function. In such an arrangement, the transmitted light and reflected or emitted light are advantageously separated during their transmission to and from the blood. In FIG. 8, the forward sensor assembly is again represented at  102 . The fiberoptic assemblies employed with the optical sensor may be singular fibers which are typically formed of plastic or when formed of glass, typically are provided as bundles or multiple strands of glass. In the instant figure, two optical fibers are schematically represented at  170  and  172 . The lengthwise extent of each of these fibers is enclosed within a sheath as represented, respectively at  174  and  176 . Tip surfaces or faces of respective fibers  170  and  172  are configured such that tip surface or face  178  is slightly canted inwardly as is the opposite surface or face  180 . Tip surfaces  178  and  180  additionally may be coated as respectively represented at  182  and  184 , with an optically transparent anti-coagulant such as heparin. The overall diameter of the transmission/reflection separated assembly will be selected as the same as the overall diameter of the single fiber arrangement of FIG.  7 . In the instant figure, the bloodstream is represented in general at  186 , and the ammoniacal component, ammonia gas (NH 3 ), is represented for instance, at  188 . With the arrangement shown, light of one or more wavelengths is transmitted through fiber assembly  170  as represented by the transmission wave arrows  190 . Resultant reflection, as represented by the transmission wave arrows  192 , is collected and transmitted by fiberoptic assembly  172  for analysis. With this sensing forward structure, the transmitted light and reflected light are advantageously separated during their transmission to and from the bloodstream or blood  186 . In general, this enables a more accurate quantitative measurement of spectral intensity and in turn, a more accurate measurement of the concentration of ammonia (NH 3 ) as represented at  188 . It may be noted, by way of example, that the direct measurement arrangement of FIGS. 7 and 8 may be used to measure both ammonia (NH 3 ) concentration as well as the oxygen saturation level of the blood. Particularly for the catheter form of embodiments, the tip surfaces of the forward assemblies and their associated coatings preferably are oriented to directly confront the direction of flowing blood in the bloodstream as represented by arrow  194 . This generally reduces the interval required to evoke a valid measurement and assures an appropriate contact of the bloodflow against the forward faces of the sensor forward assemblies. 
     Now considering indirect spectrometric sensor technology, reference is made to FIGS. 9,  10 ,  11 A and  11 B. In FIG. 9, the forward assembly of the sensor, as represented generally at  102  includes a fiberoptic transmission/reception assembly  200  which extends to a tip surface or face  202 . Positioned over the tip surface  202  is a cap-shaped membrane  204  having a forward inner surface portion  206  which is spaced from tip surface  202  to define a gap  208 . A peripheral inner surface  210  of membrane  204  is sealed to the outer surface  212  of fiberoptic assembly  200  to assure the integrity of the gap  208 . The outer surface  214  of membrane  204  is in contact with blood or flowing blood of the bloodstream represented generally at  216 . As before, the ammoniacal component preferred for measurement is ammonia gas (NH 3 ), particles of which are represented in exemplary fashion at  218 . Membrane  204  is structured to contain microscopic pores and functions to minimize or block the ingress of water and other liquid components within the blood  216  while permitting the ammoniacal component of interest, for example, ammonia gas, to rapidly defuse across it due to a developed concentration gradient. In effect, a fluid space is developed at the gap  208  containing the measured ammoniacal component as represented at  218 ′. With the arrangement, an equilibrium develops between the ammoniacal component  218 ′ and the component as at  218 . One or more wavelengths of light, as represented by the transmission wave arrows  220  are transmitted into gap  208  and reflections from the ammoniacal components such as ammonia gas  218 ′ as are represented by reflection wave arrows  222 , then may be analyzed. The intensity of the reflected light is represented by these arrows  222  and the concentration of the ammoniacal component is correlatable with the intensity of the light at one or more wavelengths. Light transmitted as represented at arrows  220  may be of specific wavelengths or a spectrum of wavelengths may be employed. The advantage of this sensor structuring resides in the simplification of spectral analysis, inasmuch as the species of interest has been separated from other blood-carrying species. The membrane  204  as well as the membrane employed with other embodiments of the invention may be provided as a Teflon barrier, for example, manufactured by W. L. Gore &amp; Associates, Inc., of Elkton, Md. These membranes contain microscopic pores whose size, for the ammonia ammoniacal component, preferably are the range from 0.02 to 3 microns. The overall thickness of the membrane  204  will be in the range of from 1 to 500 microns and, preferably, in the range of 10 to 50 microns. The hydrophobic nature of the Teflon material serves to minimize ingress of water and other liquid components within surrounding blood. As before, it is preferred that the forward face or outer sensing surface of the forward assembly  102  confront the direction of flow of the bloodstream  216 , such direction being represented by arrow  224 . For catheter applications of the system, this calls for positioning the measurement region of the catheter at its tip in confronting relationship with the direction of bloodflow. 
     A transmission spectrometric sensor is illustrated in FIG. 10, forward assembly  102  of the sensor being schematically revealed for this configuration. In the figure, the fiberoptic assembly is seen to have a generally U-shaped configuration with a light transmission leg  230  and a return leg  232 . With the configuration, there is, as in the case of FIG. 9, a gap  234  defined between the end face  236  of transmission leg  230  and the end face  238  of return leg  232 . A surmounting membrane  240 , which may be of cylindrical shape, is positioned across the gap  234  and sealed against the outer surfaces  242  and  244  of respective legs  230  and  232 . As before, the membrane  240  is configured having microscopic pores which permit the ingress of the elected ammoniacal component from the blood or bloodstream. In this regard, such blood or bloodstream is represented in general at  246  and the ammoniacal component, for example, ammonia gas (NH 3 ) is represented symbolically, for example, at  248 . The sensor forward assembly  102  being so configured, when it is immersed within the blood or bloodstream  246 , a concentration gradient builds between such blood  246  and the gap  234  to provide for the migration of the ammoniacal component such as ammonia gas into the gap, such migrated ammonia gas being represented within the gap at  248 ′. Light having one or more wavelengths is transmitted toward the gap  234 , as represented by transmission wave arrow  250  to be selectively attenuated by the ammonia gas  248 ′. The thus attenuated light then is returned for analysis, as represented by wave arrows  252 . Such analysis quantifies the concentration of ammonia gas in the gap  234  and, hence, in the blood or bloodstream  246 . As in the case of FIG. 9, this arrangement has the advantage of isolating the ammoniacal component of interest to simplify analysis. No blood directional arrows are shown in the instant figure, inasmuch as the forward assembly  102  may be used in longitudinally directed bloodflows moving in forward or rearward directions with respect to it as well in bypass systems wherein blood movement may be transverse to the longitudinal axis of the sensor. 
     Schematic representations of transmission/reflectance spectrometric sensors are provided in FIGS. 11A and 11B. Looking to FIG. 11A, the forward assembly  102  for this embodiment is seen to comprise an optical fiber assembly  258  having a surface  260  and extending to a tip surface or face  262 . Spaced from the surface  262  is a polymeric end piece  264  having an inwardly disposed surface  266  which supports a light reflector provided as a coating or the like as seen at  268 . The edge surface  270  of end piece  264  is dimensioned in correspondence with the side surface  260  of the assembly  258 . 
     Light reflecting surface  268  is spaced from tip surface  262  a distance defining a gap  272  and a cylindrical membrane  274  is seen to surround and further define gap  272 . In this regard, the membrane  274  is sealed to side surfaces  260  and  270 . Forward assembly  102  is immersed in the blood or bloodstream represented in general at  276 . The ammonia (NH 3 ) ammoniacal component is represented within the bloodstream  276 , for example, at  278 . With the arrangement, a concentration gradient is developed between the bloodstream or blood  276  and the gap  272 . The microstructure of the membrane  274  permits a migration of the ammoniacal component of interest, for example, ammonia, into the gap as represented at  278 ′. Light is transmitted along the assembly as represented by the wave transmission arrows as at  280 , whereupon it is reflected from the light reflecting surface  268  and returned as represented by wave transmission arrow  282 . The interaction of this light in crossing the gap  272  then is analyzed to develop values for the concentration of the ammoniacal component such as ammonia. The sensor configuration of this embodiment is particularly suited for employment within the sampling chambers of blood bypass systems where blood is flowing transversely to the longitudinal axis of a fiberoptic assembly  258 . 
     Referring to FIG. 11B, an alternative structuring of the transmission/reflectance spectrometric sensor is revealed. The forward assembly  102  is seen to be structured incorporating a fiberoptic assembly  288  having a side surface  290  and extending to a tip surface or face  292 . Positioned over the forward end of the fiberoptic assembly  288  is a cap-configured membrane represented generally at  294  having an inwardly disposed surface  296  and a peripheral, cylindrically-shaped inward surface  298 . Supported by the inwardly-disposed surface  298  is a light-reflecting component present as a coating and shown at  300 . The peripheral inward surface  298  of the membrane  294  is sealed to the side surface  290  of fiberoptic assembly  288  to define a gap  302 . Outwardly disposed surface  304  of membrane  294  is immersed in blood or a bloodstream as represented in general at  306 . As before, the membrane  294  is configured having microscopic pores permitting the migration of the analyte component such as ammonia represented at  308  into the gap  302  by virtue of the evolution of a concentration gradient between the gap  302  and blood represented at bloodstream  306 . Other components of the blood essentially are blocked from movement into the gap  302 . Ammoniacal component or ammonia which will have migrated into the gap  302  is represented at  308 ′. Analysis of concentration of the ammoniacal component for ammonia  308 ′, which is equilibrated with the corresponding concentration of ammonia  308 , is made by directing light at one or more wavelengths across the gap  302  as represented by transmission wave arrows  310 . This light interacts with the ammonia or component  308 ′ and is reflected from the reflector component or coating  300  to return for analysis as represented by wave transmission arrows  312 . 
     With the sensor geometry shown and where the sensor is positioned within a peripheral region of the vascular system, it is desirable that the forward surface  304  be positioned so as to confront the direction of flow of the bloodstream as represented at arrow  314 . In other applications such as blood bypass applications, a transversely directed bloodflow or a temporarily quiescent blood quantity may be engaged with the surface  304  to permit appropriate measurement. 
     Referring to FIG. 12, a forward assembly  102  is illustrated schematically which has a structure common to both colorimetric and fluorometric sensors. The sensor arrangement includes a fiberoptic assembly  320  which extends to a tip surface or face  322  and is surrounded by a sheath  324 . Mounted over the sheath  324  and fiberoptic assembly  320  is a cap-shaped membrane  326  having an inwardly-disposed surface  328  and an inwardly-peripherally-disposed surface  330 . Surface  330  is sealed to the outer surface of sheath  324  in a manner spacing the inward surface  328  from the tip surface or face  322  a distance defining a gap  332 . Located within this gap  332  is a reactor  334  which, for the structure shown, may be an analyte component responsive dye for the preferred colorimetric version of the sensor, or a reactor which fluoresces under light stimulation. The outward surface  336  of membrane  326  is immersed in blood or flowing blood of a bloodstream as represented in general at  338  and containing an ammoniacal component such as ammonia as represented, for example, at  340 . For the preferred embodiment of the invention, wherein ammonia (NH 3 ) is the component of interest, and an ammonia-sensitive dye is employed for the reactor  334 , the membrane  326  is configured having microscopic pores through which the ammonia  340  may migrate and chemically react with the dye-defined reactor  334 . This will result in a change in coloration of the dye-defined reactor  334  which may be analyzed by colorimetric procedures. Accordingly, the reactor  334  is seen stimulated by light at one or more wavelengths as represented by the light wave transmission arrow  342 . The resultant light reflected from the reactor dye is represented at transmission arrow  344 . As before, it is preferred that for catheter based usage wherein the sensor forward assembly  102  is positioned within a vessel of the vascular system of the body, it be located to confront the direction of flow of the bloodstream as represented by arrow  346 . 
     Referring to FIG. 13, a preferred arrangement for the forward assembly  102 , particularly with respect to the sensing of the ammoniacal component ammonia (NH 3 ) is revealed. The sensor arrangement includes a fiberoptic assembly  350  which extends to a tip surface or face  352  and is surrounded by a sheath  354 . Mounted over the sheath  354  and face  352  is a cap-shaped membrane represented generally at  356  having an inwardly-disposed surface  358  which is in intimate contact with the forward face  352  of the fiberoptic assembly  350 . Surface  358  is sealed to the outer surface of sheath  354 . In this regard, the membrane may be provided as a coating over the tip region  360  of fiberoptic assembly  350 . The reactor of the sensor forward assembly  102  may be a dye or the like which is responsive to the ammoniacal component and which is incorporated within the membrane  356 . In this regard, the reactor may be, for example, a dye which changes color with respect to the concentration of ammonia within a bloodstream  362  as represented, for example, at  364 . Membrane  356  may be provided for example, as a silicone perthiorinated urethane, cellulose acetate butyrate or methymethacrylate polymer matrix incorporating a dye. The outward surface  366  of membrane  356  is shown immersed in flowing blood of the bloodstream  362  in a manner wherein it confronts the direction of flow of that bloodstream as represented at arrow  368 . The ammonia affected reactor dye incorporated within the membrane  356  will respond to the migration of ammonia thereinto to evoke a change in coloration which may be analyzed, inter alia, by colorimetric procedures. Accordingly, the dye-containing membrane  356  is seen to be interrogated by light at one or more wavelengths as represented by light transmission arrow  370 . The resultant light reflected from the reactor dye or the like as integrated within the matrix of membrane  356  is represented at transmission arrow  372 . 
     A system utilizing ammonia as the ammoniacal component and an ammonia sensitive dye as the reactor  334  which is incorporated in a membrane  356  is a preferred embodiment of the invention. Of the ammonia dyes available for use as such reactor, bromocreosol green, excited at wavelengths in a first band of 380 to 480 nm; in a second band of 520 to 680 nm; and in a third band of 700 to 900 nm; chlorophenol red excited at wavelengths in a first band of 380 to 420 nm; in a second band of 520 to 620 nm; and in a third band of 650 to 900 nm; bromophenol blue excited at wavelengths in a first band of 380 to 440 nm; in a second band of 520 to 640 nm; and in a third band of 700 to 900 nm; m-creosol purple; thymol blue; and congo red may also be considered. The light wavelengths for stimulation for interrogation conventionally are generated by light emitting diodes (LEDs) and the wavelengths utilized are based upon the wavelengths corresponding to the peak absorption intensity and wavelengths which are insensitive to changes in the ammonia concentration. If a plastic fiberoptic assembly is used, the preferred third wavelength is about 700 nm. If a glass fiberoptic light transmitting assembly is used, the preferred third wavelength of those cited above is within the range specified. Dyes serving as a reactor quite rapidly reach an equilibrium with the ammoniacal component under analysis. The intensity normalized reflectance of the responding wavelength of light  372  is utilized to quantitate the concentration of ammoniacal component (e.g., ammonia). 
     Where the reactor is provided as an ammoniacal component-sensitive fluorescent material upon excitation by light wavelengths, the level or intensity of fluorescence or the rate of quenching when a stimulation source is extinguished is correlated with the concentration of the ammoniacal component at hand. 
     Where the ammoniacal component is ammonia, as is preferred, in order to derive the value of total ammoniacal concentration, the value of the corresponding pH of the blood is utilized in a straight forward computation to find a total ammoniacal concentration. In general, the Henderson-Hasselbalch relationship is resorted to. pH may be measured with a variety of techniques using reactors which are chemical or ion selective electrode-based. A pH sensitive dye is employed in connection with the embodiment described in conjunction with FIGS. 4-6. Looking to FIG. 14, the front end assembly  114  represented generally in FIG. 5 is revealed in schematic fashion but at an enhanced level of detail. In the figure, fiberoptic strand  116  as it is present at the forward assembly  114  again is represented. The outer cylindrical surface  380  of strand  116  is covered with a sheath  382  and the tip surface or face  384  of the fiberoptic strand  116  is coated with a pH sensitive dye which is applied as a porous coating and is represented at  386 . Sealingly positioned over the tip surface or face  384  and the dye or pH reactor  386  is a hydrogen ion permeable membrane represented generally at  388  which is cap-shaped having a cylindrical side component  390  sealed to the sheath  382 . The inner forward surface  392  of membrane  388  is spaced from the dye layer or pH reactor  386  to accommodate a medium  394  whose pH is in equilibrium with the pH of the blood within which this forward assembly  114  is immersed. The pH sensitive dye or the like is interrogated by light at one or more wavelengths to determine the value of pH of the blood. For the present embodiment, the forward assembly  114  of the pH sensor is at the tip  70  of the catheter  60  (FIG.  4 ). It may perform at other locations, for example, adjacent one of the injectate ports  68  or  78 . Additionally, for catheter structures of minimal size as described later herein, forward assembly  114  may be incorporated within a separate catheter or a separate support structure within an ex vivo sampling chamber of a bypass based system. 
     Optical sensors for the measurement of pH, particularly in connection with the in vivo measurement of pH of the blood are described, for example, in U.S. Pat. No. 5,607,644 by Olstein, et al, entitled “Optical Sensor for the Measurement of pH in a Fluid, and Related Sensing Compositions and Methods” issued Mar. 4, 1997. Additionally, description of such pH sensors is provided in the following publication: 
     Zhang, et al, “Evaluation of Fluorescent Dyes for In Vivo pH Measurement”, Medical &amp; Biological Engineering &amp; Computing, March 1994, pp 224-227. 
     These references describe, in particular, fluorescing pH analysis techniques. 
     Referring to FIGS. 15A and 15B, the light source and transducing function described that at  132  in FIG. 5, representing a component of the signal treatment system of the invention is revealed in more detail. This light source and transducing function also may be utilized for the function of that figure represented at block  138  as employed for carrying out pH analysis. The particular assembly disclosed may be utilized with the colorimetric approach to ammoniacal component evaluation wherein the reactor is a component-sensitive dye, for example, being sensitive to ammonia (NH 3 ). In FIG. 15A, the fiberoptic connector  72  described in conjunction with FIGS. 4 and 5 and, in particular, incorporating the transmission component  130  described in the latter figure is seen extending to a step-down chamber  400 . Through utilization of this chamber  400 , a singular fiberoptic strand or assembly  130  is positioned in light exchange relationship with an assemblage of seven fiberoptic components or channels represented generally at  402 . The discrete fiberoptic components of the assemblage  402  include: a fiberoptic component  404  which transmits light at a wavelength, for example, of 450 nm from an LED source  406 ; a transmitting fiberoptic component or strand  408  which transmits light at a wavelength, for example, of 615 nm from an LED source  410 ; and a fiberoptic strand or component  412  which carries light, for example at a wavelength of 700 nm from an LED source  414 . Reference fiberoptic components  416 ,  418  and  420  transmit light from respective sources  406 ,  410  and  414  to a photodiode reference function represented at block  422 . Light returning from impingement upon the ammoniacal component sensitive dye is collected or gathered and transmitted by core gathering fiberoptic components  424 - 427 . Optical components  424 - 427  are directed to a combining input at a photodiode sensor represented at block  428 . 
     Looking to FIG. 15B, a cross-section of the assemblage  402  is provided. The gathering component  424  is seen centrally disposed within the assemblage  402 , while remaining gathering components  425 - 427  are disposed symmetrically about it. Transmitting fiberoptic components  404 ,  408  and  412  have the same diameters and are seen to be symmetrically disposed about the centrally located collecting component  424 . With this arrangement, about 11% of the source light from sources  406 ,  410  and  414  is transmitted to the associated reactor and about 44% of the light reflected from the reactor is transmitted to the photodiode detector  428 . 
     Ammoniacal concentration monitoring systems may be configured using technologies other than those which are optically based. Where such alternate approaches are utilized, some modification of the design of a catheter-based embodiment is undertaken. Referring to FIG. 16, a catheter is shown at  434  being structured with a concentration sensor which is non-optical in design. Catheter  434  may employ a variety of ammoniacal concentration sensor technologies, for example, sensors based on amperometry and voltometry as well as Schottky diode-based technologies and acoustic-wave based technologies. Catheter  434  includes a base component  436  from which extends a catheter body  438  configured for positioning within a vessel of a vascular system. Body  438  incorporates a measurement region  440  which extends to a tip  442 . Base  436  is located within a proximal region represented generally at  444  which includes a communication cable  446 . Spaced rearwardly from the tip  442  is a distal auxiliary port  448  and, still further rearwardly positioned is a second or proximal auxiliary port  450 . Ports  448  and  450  are optional within the catheter  434  and may be employed for deriving, for example, blood samples, introducing medicants or the like. The forward assembly of the ammoniacal concentration component sensor is represented generally at  452  within the measurement region  440  and preferably is located adjacent tip  442 . For most implementations of this form of forward assembly  452 , a membrane of the nature discussed above is employed. Catheter  434  is dimensioned having a principal cross-sectional dimension or outer diameter which is as minimal as practical to avoid blood hydraulic impedance phenomena. A membrane  454  covers a sensor assembly adjacent the tip  442 . This sensor assembly is electrically associated with the proximal region  444  via cable  446  and is seen to extend to electrical leads  456  and  458  terminating, in turn, at respective electrical connectors  460  and  462 . Communication with auxiliary port distal  448  is provided by a channel extending through the body portion  438  to base  436 . From that location, a flexible conduit  464  is seen to extend to a connector and valve assembly  466 . In similar fashion, the proximal port  450  is in fluid communication with a channel extending through the body portion  438  to base  436 . At base  436 , this channel is coupled in fluid transfer communication with a flexible conduit  468  extending to a connector and valve assembly  470 . 
     Referring to FIGS. 17 and 18, the structure of catheter  434  at its forward assembly  452  is revealed. At forward assembly  452 , the polymeric body portion  438  is configured of reduced diameter to accommodate for the sensor structure associated with the earlier described membrane  454 . FIG. 18 reveals this reduced cylindrical outer diametric surface  480  which additionally is configured to form three channels or lumens  482 ,  483  and  484 . Channel  483  is revealed in FIG.  18 . Channels  482  and  483  communicate with respective auxiliary ports  448  and  450 . These channels are plugged with a cylindrically-shaped tip plug  486  forming the outer tip  442  of catheter  434 . The ammoniacal component sensor is represented generally at  488  and, being formed in conjunction with membrane  454 , is structured as an ion-specific electrode-based device. Membrane  454  is provided as a microporus, hydrophobic polymer such as the earlier described Teflon or polytetrafluoroethylene. Membrane  454  is semi-permeable to the ion of interest, in the present embodiment that ion is the ammonium ion (NH 4   + ). FIG. 18 reveals that the cylindrical body surface  480  at the sensor assembly  488  forms the inner wall of an electrolyte retaining chamber or gap  490 , the outer wall of that gap or chamber  490  being the membrane  454 . Within the gap  490  is an electrolyte or electrically conducting liquid  492 . Where the sensor  488  is configured for detecting the noted ammonium ion component, the electrolyte liquid  492  may be a solution containing, for example, 0.1 molar ammonium chloride. That liquid  492  reaches equilibrium with blood carried ammonium ion flow across the membrane  454  to change or alter the pH of the solution or liquid  492 . For the ammonium ion component, the higher the concentration of ammonium ion in the blood stream passing over the membrane  454 , a corresponding effect will be observed in the ammonium ion concentration in liquid  492 . Ion selective electrodes are employed to measure this ion concentration within liquid  492 . In this regard, the cylindrical surface  480  is coated at the forward assembly  452  with a pH electrode which may be implemented as a glass electrode selective to the hydrogen ion. Such an electrode is shown at  494 . Electrode  494  may be a glass comprising silicon dioxide, lithium oxide and calcium oxide in the ratio 68:25:7. Note in FIG. 17 that electrode  494  extends from an annular shoulder  496  formed in body portion  438  adjacent tip  442  to an edge or termination at  590 , and is connected to an electrical lead  502  extending within channel  484 . A cylindrically-shaped reference electrode  504  completes the forward assembly  452 . This second electrode  504  may be provided as a metallic coating, for example, silver/silver chloride. Electrode  504  is spaced from the glass electrode  494  but remains operationally associated therewith within the electrolyte containing cavity or gap  490 . Electrode  504  is connected to a lead  506  which also extends through the channel  484 . Sensor  488  may perform in either a potentiometric mode wherein voltage across the reference and glass electrodes is determined, or may operate in an amperometric mode wherein the current flow between these two electrodes is evaluated during the application of a d.c. voltage difference. 
     Referring to FIGS. 19 and 20, sections of the catheter  434  adjacent the proximal auxiliary port  450  are revealed. In the figure, catheter body portion  438  is seen to have an enlarged diameter as compared with its diametric extent at the sensor  488 . FIG. 19 reveals auxiliary channel or lumen  483  as it extends to the port  450 . In this regard, while the channel  483  extends essentially the length of the catheter  434 , fluid is restricted to outflow from the port  450  by a plug  508  just forward of the port. FIG. 20 reveals the electrical leads  502  and  506  extending within the electrical lead channel  484 . These leads become a component of the cable  446  at base  436  and further evolve as the leads  456  and  458  leading to respective connectors  460  and  462  (FIG.  16 ). 
     Now looking to the utilization of Schottky diode-based ammoniacal sensor assemblies, reference is made to FIGS. 21-23. In these figures, the sensor assembly is represented in schematic fashion. Looking to FIG. 21, the measurement region  516  of a catheter  518  of a variety described in connection with FIGS. 4 and 16 is seen to incorporate a front end assembly  520  which employs the technology based upon the interaction of planar Schottky barrier diodes with an ammoniacal component. In this embodiment, the sensor assembly  520  is mounted upon, for example, a wall  522 . Sensor  520  is formed having two metal electrodes configured in spaced relationship and in an interdigitated geometry. These electrodes are provided as a gold electrode  524  configured in conjunction with an aluminum electrode  526 . Gold electrode  524  creates an ohmic contact and aluminum electrode  526  creates a Schottky barrier contact with a conducting polymer layer  528 . For example, a p-doped semiconductor such as P30T may be employed (poly (3-Octylthiophene)). The conducting polymer  528  exhibits an electrical conductivity which is correlatable with the concentration of the ammoniacal component at hand. The conducting polymer employed may be substituted polypyrroles, polythiothenes, or polyanillianes. Not shown in the drawings is an ammoniacal component permeable membrane as discussed earlier herein which covers the active sensor components. As before, the outer surface of such a membrane is in contact with flowing blood of the bloodstream. See generally: 
     Assadi, A et al., Interaction of Planar Polymer Schottky Barrier Diodes with Gaseous Substances”, Sensors and Actuators, Vol  20 , pp  71 - 77  (1994). 
     Now considering ammoniacal component sensors which are acoustic wave-based, reference is made to FIG.  24 . In the figure, the sensor forward assembly as it would be mounted in the manner of the sensor of FIGS. 21-23 is depicted schematically at  530 . The sensing principle of such acoustic sensors is based upon the detection of changes of wave velocity and attenuation caused by perturbations at the surface of the material in which the wave propagates. If an acoustic wave delay line is placed in an oscillator loop as the frequency-determining element, velocity shift causes a shift in the delay time of the wave. This results in a shift of the oscillation frequency. In the figure, an interdigitated transmission transducer is shown at  532  spaced from a reception transducer  534 . Sound reflectance from the ammoniacal component being investigated is represented by the arrow  536 . Transducers  532  and  534  are connected in a delay line oscillator circuit. The latter circuit includes an oscillator amplifier  538  having an input at line,  540  and an output at line  542 . Transducers  532  and  534  are incorporated within a feedback path or delay line, transducer  532  being coupled via lines  544  and  546  to line  542  and transducer  534  being coupled via lines  548  and  550  to line  540 . Accordingly, the output of the amplifier  538  is fed back by the delay line incorporating the transducers where A (ω) represents amplifier gain and B (ω) represents delay line losses. The transducers as well as the oscillator circuit may be multi-layer devices constructed using conventional integrated circuit manufacturing methods employing silicon, (base) silicon dioxide, aluminum, and zinc oxide (surface). See generally the following publication: 
     Velekoop, et al., “Integrated-Circuit-Compatible Design and Technology of Acoustic-Wave-Based Microsensors”, Sensors and Actuators, Vol 44, pp 249-263 (1994) 
     In the practice of accessing the vessels of the vascular system to carry out ammoniacal component monitoring according to the invention, a variety of vessel sizes and vessel conditions will be encountered by the practitioner. In this regard, a catheter of conventional diametric extent may evoke a hydraulic impedance in the vessel carrying blood to the extent that the vascular system may divert the bloodflow or bloodstream to a branch vessel. Further in this regard, particularly where infants such as neonates are the subject of ammoniacal component monitoring, the vessels themselves may be so small as to call for a catheter structure of very minimal principal cross-sectional dimension, for example, exhibiting a diameter in a range of about 0.010 inch to 0.060 inch. In this regard, a catheter can be developed which is quite similar to a hypodermic needle wherein the central channel supports a singular fiberoptic strand to carry out monitoring. Where the ammoniacal component is gaseous ammonia, two such catheters may be employed, one to measure pH and the other to measure the component ammonia gas, the forward end assemblies of such optical devices being structured in the manner described above, for example, in connection with FIGS. 13 and 14. Looking to FIGS. 25 and 26, a catheter structure of such minimized shaft diameter is revealed generally at  560 . Catheter  560  includes a rigid shaft  562  extending from a base shown generally at  564  to a pointed tip  566 . Configured in similar fashion as a hypodermic needle, the shaft  562  incorporates a cylindrical channel  568  as defined by its inner, curved surface  570  (FIG.  26 ). Base  564  includes a cap-shaped cylindrical hub  572  the internal cavity  574  of which is enclosed by a cover member  576 . Member  576  includes a circular opening  578  which extends to an aligned circular opening within a sealing gland or seal  580 . Seal  580  may be formed of silicone rubber. Extending through the assembly is a fiberoptic strand  582 , the forward tip  584  of which is covered with a membrane-based reactor structure  586  which is configured as described in connection with the above-noted figures. Catheters as at  560  may have overall lengths within a range of about 1.0 inch to 6.0 inch and perform with fiberoptic strands of diameter within a range of about 0.005 inch to 0.040 inch. 
     Animal testing carried out in conjunction with fiberoptic-based catheters according to the invention have shown that improved sensor response is achieved where the catheter is inserted within a vessel of the vascular system in a manner wherein the sensing tip employed with fiberoptic-types of sensors, be in a confrontational orientation with respect to bloodflow. Where the tip of such catheter sensor structures is located within a blood carrying vessel in a manner wherein blood passes over it from what may be considered a rearward location, the surface of the sensors will encounter a more or less quiescent or back flowing blood. Looking to FIG. 27, the wall of a vessel such as an artery is shown at  590 . Within the interior of the vessel wall  590  there is schematically illustrated a catheter  592  incorporating a fiberoptic strand  594  having a sensing assembly  596  at its tip. Bloodstream flow is represented in the drawing by the arrows as at  598  and  600 . Note that the bloodflow arrows at  600  adjacent the sensor  596  illustrate the noted quiescent or back flow association with sensor  596 . Where such an arrangement is at hand, the interval required to derive a sensor output is more extended than when the catheter is positioned in a confronting orientation with respect to bloodflow. Such an orientation is revealed in FIG.  28 . In the figure, catheter  592  reappears with tip  596  in a confrontational orientation with respect to the flow of the bloodstream as represented at arrows  598 . Note that in the vicinity of the sensor  596 , the blood directly confronts the surface of the sensor. With such an orientation for the catheter  592 , the response time for achieving a readout from sensor  596  is substantially improved. 
     In a typical application, the ammoniacal concentration monitoring according to the invention is carried out with catheters which preferably are located in a peripheral region of the vascular system of the body. The term “peripheral” as used herein is intended to refer to those portions of this vascular system which are beyond or without the region of the heart. While monitoring of neonates typically will be carried out with the noted catheters of minimal dimension and utilizing, for example, an umbilical vein or artery, the catheter utilization for normal adults will typically involve a peripherally located artery such as the brachial, radial or ulnar arteries, the latter two residing in the forearm. As noted above, where blood hydraulic impedance becomes problematic, the catheter may be extended from a branch artery, i.e., into the brachial artery. Looking at FIG. 29, arterial, in-line employment of a catheter assembly according to the invention is illustrated. In the figure, the brachial artery is represented at  602  branching to the ulnar artery at  604  and the radial artery at  606 . A catheter assembly, for example, as described in conjunction with FIG. 4 is shown generally at  608  positioned within the radial artery  606 . In this regard, the catheter is located within and extending from an introducer  610  which is positioned within the artery  606 . The catheter assembly measurement region  611  extends from the introducer  610  within the artery  606  in an orientation confronting the direction of bloodflow as above discussed. Auxiliary channels of the catheter assembly  608  extend to conduits  612  and  614  terminating in respective connector and valve assemblies  616  and  618 . The fiberoptic components of the catheter assembly  608  are seen to extend via a cable  620  to an optical connector  622 . Catheter assembly  608  will incorporate, for example, both a pH sensing channel and an ammonia gas sensing channel. Where blood flow in the radial artery  606  may encounter excessive impedance evoked by the presence of the introducer  610  and catheter assembly  608 , the vascular system or body may react to evoke a hydraulic diversion toward the ulnar artery  604 . For such conditions, minimally dimensioned catheter structures as described in connection with FIGS. 25 and 26 may be employed. Alternatively, measurement region  611  may be inserted until it resides in brachial artery  602  which avoids blood hydraulic diversion in the parallel bronches represented by the radial and ulnar arteries. Looking to FIG. 30, the arm  600  again is reproduced with the earlier identifying vascular system vessel numerical identification as in FIG. 29. A minimally sized catheter assembly  624  is shown inserted within the radial artery  606  without utilization of an introducer (e.g., through the utilization of what, in effect, is a hypodermic needle as shown in FIG.  25 ), the sensor component being located at its tip  626  positioned within the artery  606 . The catheter assembly  624  will be of a single channel variety in keeping with its minimization of size and will provide an output from its sensor at fiber cable  628  which terminates in an optical connector  630 . Positioned downstream within the radial artery  606  is another catheter assembly  632  which, as in the case of assembly  624  is positioned within the artery  606  without utilization of an introducer, the hypodermic needle-shaped catheter body being represented at  634  extending to a sensor supporting tip  636 . The single channel optical output is directed along cable  638  which is seen to extend to an optical connector  640 . With the arrangement shown, where the ammoniacal component monitored is ammonia gas, one of the catheter assemblies, for example that at  624 , is utilized to derive a pH valuation, while the second catheter, for example that at assembly  632  is utilized to monitor the ammonia component. 
     The monitoring system and method of the invention also may be employed with sampling techniques wherein a catheter is not utilized. For example, the monitoring system and method may be carried out with a variety of blood bypassing systems or assemblies such as a hand actuated blood sample collecting system; a cardiac bypass system; or a hemodialysis system. Referring to FIG. 31, the former approach is illustrated. In the figure, arm  600  again is reproduced along with arterial vessels  602 ,  604  and  606 . A blood bypass assembly is represented in general at  650 . The bypass assembly includes a hypodermic needle or the like  652 , which has been positioned such that its tip extends within the radial artery  606 . A conduit  654  extends to a valve represented at symbol  656  which is coupled to a hypodermic syringe  658  utilized for flushing purposes in conjunction with a flushing fluid input at conduit  660 . Valve  656  additionally is coupled to conduit  662  which extends to a sampling chamber  664 . From the chamber  664 , a conduit  666  incorporating a valve  668  extends to a sampling syringe or pump  670 . A flushing drain conduit  672  is coupled to valve  668 . Sampling chamber  664  is accessed, for the instant embodiment, by a fiberoptic based pH sensor having an output cable  674  extending to an optical connector  676 . Also communicating with the sampling chamber  674  is a fiberoptic based ammonia sensor having an output cable  678  extending to an optical connector  680 . For the arrangement at hand, the syringe  670  is actuated by the practitioner to draw a sample of blood into sampling chamber  664 . As the blood enters chamber  664  it is monitored for ammonia concentration and pH level and the resultant values are submitted to a controller (not shown) via connectors  676  and  680 . Following monitoring, the syringe  670  again may be actuated to return the sample of blood to the radial artery  606  via the hypodermic needle  652 . It may be desirable from time to time to flush such bypass systems. For such an arrangement, the syringe  658  withdraws a quantity of flushing liquid from conduit  660  with appropriate manipulation of valve  656  to cut off fluid communication with conduit  654 . The syringe  658  then is actuated to pump the flushing liquid through conduit  662  and sampling chamber  664 . Valve  668  is manipulated such that the flushing liquid will drain through conduit  672  and the input to pumping syringe  670  is blocked. 
     A pictorial representation of the overall system of the invention for monitoring ammoniacal concentration is presented in FIG.  32 . In the figure, the system, represented generally at  690 , includes a monitoring catheter assembly represented generally at  692  which is seen having a cylindrical body portion  694  and a measurement region  696  extending to a tip  698 . Auxiliary ports  700  and  702  are provided with the assembly  692  for the purpose of withdrawing samples for blood assays or introducing medicants or the like. The catheter body  694  extends to a base  704  having a conduit  706  communicating with distal auxiliary port  700  and a hypodermic syringe  708 . Similarly, a conduit  710  extends from base  704  and is in fluid transfer communication with distal auxiliary port  702  and a syringe  712 . Monitoring readouts from a fiberoptic based ammonia sensor and a fiberoptic based pH sensor are conveyed via an elongate cable  714  and optical connector  716  to an appropriate input of a controller represented generally at  718 . Controller  718  is mounted upon a conventional IV pole or stand represented generally at  720 . The controller  718  includes an array of keys represented generally at  722  which are utilized for entering or inputting control parameters such as the type of sensor utilized, total ammoniacal concentration level threshold; real time information; total ammoniacal concentration rate-of-rise threshold and pH value where no sensor is employed for that measurement. Below the key array  722  is an array of connectors represented generally at  724  which may provide for a separate pH signal input, a dual pH and ammoniacal component sensor input as provided from connector  716 ; amprometric, potentiametric and acoustic system inputs as derived from the particular sensing system employed. A display is shown at  726  having a total ammoniacal content (trend) readout with respect to real time as shown at  728 . Displayed with the graphics or curve  728  is a threshold level visual cue  730 . A permanent record may be printed with the system via a printing assembly  732  providing a strip-type paper readout  734 . A serial input/output port  736  is mounted upon the upper surface of the controller  718 . The controller  718  also may supply aural cues to the practitioner indicating an alarm condition. Visual cuing is provided, for example, by light emitting diodes (LEDs) three of which are shown at  738 ,  740  and  742 . Diode  738  may be, for example, of an amber or yellow color indicating a warning that total ammoniacal concentration is rising from one display interval to the next. Diode  740  provides a red coloration output to indicate an alarm condition such as the meeting or exceeding of an inputted threshold value. Diode  742  provides a visual output, for example, in the red color of the spectrum where the rate of rise of total ammoniacal concentration exceeds a rate-of-rise threshold. 
     Referring to FIG. 33, a block diagram is provided illustrating the overall system  750  of the invention. In the figure, the controller function again is identified at  718  and now represented by a boundary. Video display  726  is represented symbolically, printer  732  is represented symbolically and the LED warning and alarm outputs again are represented with the same numeration at blocks  738 ,  740  and  742 . Controller  718  is microprocessor driven and the microprocessing or software functions of it are represented within a dashed boundary  752 . 
     FIG. 33 is configured in accordance with the preferred arrangement of the invention wherein the ammoniacal component monitored is ammonia gas (NH 3 ), an election which further requires the value of pH of the blood. Preferably, this pH value is monitored within the vascular system of the body in adjacency with the ammonia monitoring function. Recall that the embodiment of FIG. 4 provides a catheter with each such parameter being monitored within distinct channels of the instrument. The bloodstream of the patient is represented in the drawing within dashed boundary  754 , a pH sensor function being represented at block  756  and an ammonia sensor being represented at block  748 . A fiberoptic based approach is preferred for these sensing functions and the fiberoptic interaction for the functions at blocks  756  and  748  is represented by dual directional arrows shown respectively at  760  and  762 . The fiberoptic input represented at arrow  760  is directed to a pH sensor light source and transducer function as represented at block  764 . The pH related analog signal evoked from this function at block  764  is directed as represented at arrow  766  to an analog-to-digital conversion function represented at block  768 . The resultant digitized pH value then, as represented at arrow  770  is introduced to the microprocessor function  752  and a software program under processor control carries out a ratiometric analysis to obtain pH level as represented at block  772 . 
     Correspondingly, the ammonia sensor function  748  is implemented with an ammonia sensor light source and transducer function as represented at block  774 . Light intensity related analog signals corresponding with ammonia concentration, then, as represented at arrow  776  are digitized as represented at block  778 . Resultant digital signals, having been converted at the analog-to-digital function block  778  are then directed to the processing function as represented at arrow  780 . Arrow  780  is seen to be directed to the software algorithm function represented at block  782  wherein a ratiometric analysis is carried out to obtain ammonia levels. The pH level or value and ammonia level concentration value, then, as represented at respective arrows  784  and  786  are directed to an algorithm-based system which functions to calculate total ammoniacal concentration. 
     Total ammoniacal concentration in blood may be computed by applying the well known Henderson-Hasselbalch equation with respect to the equilibrated ammonia gas-ammonium ion (NH 3 )−(NH 4   + ) system. See generally in this regard: 
     Hindfelt, D., “The Distribution of Ammonia Between Extracellular and Intracellular Compartments of the Rat Brain”, Clinical Science and Molecular Medicine, Vol 48, pp 33-37, (1975). 
     The relative distribution of ammonia gas (NH 3 ) and ammonium ion (NH 4   + ) in solution is given by that Henderson-Hasselbalch equation as follows:              pH   -     pK   a     +     log          [       C   a          (     NH   3     )       ]       [       C   a     (     NH   4   +     ]                   (   1   )                         
     This equation can be restated in terms of the unknown C a (NH 4   + ) as follows: 
     
       
         C a (NH 4   + )=C a (NH 3 )/[10 exp(pH−pK a )]  (2) 
       
     
     where 
     C a (NH 4   + )=concentration of ammonium ions (NH 4   + ) in blood (micromole/liter) 
     C a (NH 3 )=measured concentration of ammonia gas (NH 3 ) in blood (micromole/liter) 
     pH=measured blood pH 
     pKa=pH level of solution above which all ammonia exists as a gas (NH 3 ) where pKa=9.15 (Hindfelt, ibid). 
     The total ammonia content of the blood, C a  (total) may be calculated as follows: 
     
       
         C a (total)=C a (NH 3 )+C a (NH 4   + )  (3) 
       
     
     The above computations are represented in FIG. 33 block  788 . Once these total values are obtained on a regular measurement interval basis, the system carries out a moving average filtering as represented by arrow  790  and block  792 . In this regard, in as much as the measurements of total ammoniacal concentration are carried out quite frequently with the system, an immediate display update of the numerical values or a graphical representation of those values may become distracting to the practitioner. Thus, the practitioner is afforded the opportunity of electing a number, n, of measurements which are compiled or queued in a first in, last out basis to provide a display both numerically and graphically which is “smooth” in its observable nature. The moving average filter is available for this purpose, inasmuch as very rapid excursions in ammoniacal concentration values will not occur in the realm of practical medical monitoring. Preferably, the display output  726  will provide a compilation of total ammoniacal concentration values as well as pH values in conjunction with that real time at which the filter values are developed. Accordingly, a real time clock function as represented at block  794  is incorporated with the system  718  and a time parameter, as represented at arrow  796  is combined with a pH value and the filtered total ammoniacal concentration value as represented at arrow  798  to provide a display update function as represented at block  800 . The display output from that update function, along with corresponding real time information is directed to the video display drive function as represented at arrow  802  and block  804 . Drive  804  then provides a video display as represented at arrow  806  and symbol  726 . A permanent record also is developed. As represented at arrow  808  and block  810  the real time, pH level and total ammoniacal concentration data also are directed to a printer drive and a paper record is created as represented at arrow  812  and symbol  732 . 
     The processing function  752  also carries out a variety of comparative functions generally associated with operator inputted threshold data. In this regard, the keypad function  722  is symbolically represented with the same numeration in the instant figure. That user inputted data, as represented at arrow  814  and block  816  will provide the value, n, for the number of measurements in a moving average filtering function, alarm limits with respect to the threshold for total ammoniacal concentration, the threshold for rates-of-rise of total ammoniacal concentration, a real time input, a sensor-type input, a display interval input and a pH value input where that parameter is not separately monitored. Such data, as represented at arrow  818  as well as the computer clock time function as represented at block  820  and arrow  822  is submitted to a comparative function wherein software provides a determination as to whether a threshold for total ammoniacal concentration has been equaled or exceeded and whether the rate-of-rise total ammoniacal concentration has exceeded a rate-of-rise threshold. This comparative function is represented at block  824  and performs in conjunction with the submitted total ammoniacal concentration values developed at block  788  as represented at arrow  826 . Where either of the noted two thresholds are exceeded, then the system provides an oral cue to the practitioner. As represented at arrow  828  an alarm signal is submitted to a driver network represented at block  830 , and as shown at arrow  832  and symbol  834 , an audible alarm cue is provided upon an excursion above the noted thresholds. Real time adjustments are submitted to time block  800  as represented by arrow  844 . The keypad input  722  provides for a resetting or acknowledgement function cutting off such alarms. As discussed in connection with FIG. 32, LED types of visual cuing also are provided. In this regard, as represented at arrow  836 , an alarm signal is directed to a driver network  838 , whereupon, as represented at arrows  840 - 842  leading to respective blocks  738 ,  740  and  742 , the driver network  838  provides, where appropriate, a visual warning cue showing a rising total ammoniacal concentration; a visual alarm threshold cue showing that the inputted threshold for total ammoniacal concentration has been equaled or exceeded; or a visual rate rise alarm indicating that the inputted rate-of-rise of total ammoniacal concentration threshold has been equaled or exceeded. 
     FIGS. 34A-34E combine as labeled thereon to present a flowchart describing the monitoring methodology of the invention. In the discourse to follow concerning that flowchart, a variety of system parameters are employed. These parameters are defined in the tabulation set forth in Table II below. 
     Table II 
     i=index 
     t=real time 
     t i =real time of measurement of pH 
     t l ′=real time of measurement of ammonia level in blood Ca(ti′) 
     t l ″=next previous real time 
     t ROR =elapsed time from start @ time  0  for rate-of-rise 
     δt ROR =time interval used for rate-of-rise calculation 
     t ret =elapsed time from start of each displayable measurement set (pH, TAC, rate-of-rise) 
     ET=elapsed time between display of rate of change of TAC 
     RT=elapsed time between displays of TAC 
     ΔT=display update interval 
     n=filter number 
     δ=interval between pH and TAC (variable) 
     C TAC (t i ′)=total ammoniacal concentration (TAC) calculated for real time t i ′ 
     {overscore (C)} TAC,n (t i )=filtered TAC (n values average taken at time of last TAC calculated i.e., at time t i    
     {overscore ({dot over (C)})} TAC (t i ′)=rate of change of TAC taken over interval, δt ROR                 C   _     .       TAC   ,   n            (     t   i   ′     )       =     {       [           C   _       TAC   ,   n            (     t   i   ′     )       -         C   _       TAC   ,   n            (     t   i   ′′′     )         ]       δ                   t   ROR         }                     
     where 
     t l ′″=t l ′−δt ROR    
     C th =Threshold for adverse effects 
     {dot over (C)} th =Rate of Rise Threshold 
     System start is represented at node  850  and arrow  852 . At startup, as represented at block  854 , conventional initialization activities are carried out, including the entry of any default parameters. Then, as represented at arrow  856  and block  858 , patient identification is entered at the keypad array  722 . As represented at arrow  860  and block  862 , the practitioner then enters the measurement display interval, ΔT, the homeostatic threshold for adverse effects (C th ); the rate-of-rise threshold, {overscore ({dot over (C)})} th ; the time interval for rate-of-rise calculation (δt ROR ) the number of values (n) for utilization with the moving average filter. Then, as represented at arrow  864  and block  866 , the real time, i.e., time of day and date is entered by the practitioner. As represented at arrow  868  and symbol  870 , the measurement function of the system then commences. As represented at arrow  872  and block  874  an index i, is said equal to one. Next, the parameter t rel  representing the elapsed time from the start of each displayable measurement is set to equal zero; the parameter t ROR  is set to equal zero. This parameter represents the time interval used for rate-of-rise calculation; and a parameter ET representing elapsed time, as well as the parameter RT representing the running time or relative elapsed time is started. The program then continues as represented at arrow  876  and block  878  wherein a query is posed as to whether a system stop command has been received. In the event that it has been received, then as represented at arrow  880  and node  882 , the program ends. In the event that no system stop command has been received, then as represented at arrow  884  and block  886 , the pH of the blood is measured at time, t i . In this regard, the system at hand is one wherein ammonia gas concentration is measured and combined with a corresponding pH measurement to derive total ammoniacal concentration. The program then continues as represented at arrow  888  and block  890  which provides for measuring the ammonia concentration at time t i ′ which is the real time of measurement of ammonia level in blood Ca (t i ′). The parameter, δ, represents the interval between measurement of pH and ammonia content. Following such measurement, as represented at arrow  892  and block  894 , total ammoniacal concentration in blood (TAC) is computed and that computation is assigned the real time t i ′. The resultant value is represented as: C TAC (t i ′). As represented at arrow  896  and block  898 , the system then sets the relative time, t rel  or elapsed time from the start of each displayable measurement as equal to the running time, RT, and the elapsed time from the start for determining rate-of-rise, t ROR  is set equal to elapsed time, ET, as provided as an elapsed time counter which, in general, is not reset. Then, as represented at arrow  900  and block  902 , a gate keeping function is carried out wherein a determination is made as to whether the index, i, is greater than or equal to the number of components elected for the moving average filtering function or, n. Where the value, n, is not reached, then as represented at arrows  904  and  906  and block  908 , the index, i, is incremented by one and, as represented at arrows  910  and  884 , the program returns to commence measuring blood pH again as set forth at block  886 . 
     In the event that the index counter indicates that a number, n, of measurements has been obtained, then as represented at arrow  912 , the computations represented at block  914  are carried out. In this regard, the moving average filtering approach utilizes, n, total ammoniacal concentration values to derive an average value. For each additional TAC measurement entered into the queue, from which the last oldest value is dropped. Additionally, the time assigned for the TAC value which is published at the display is the time, t i ′ of the most recent measurement which is entered into the queue. The value which is published or displayed is represented as: {overscore (C)} TAC,n (t i ′. Then, as represented at arrow  915  and block  916  the filtered total ammoniacal concentration (TAC) is recorded in memory and the program moves as represented at arrow  918  to the query posed at block  920  determining whether the elapsed time from the start of each displayable measurement t REL  is greater than ΔT or the display update interval. In the event that it is not equal to or greater than that value, then as represented at arrow  906 , the index, i, is incremented and the program loops to arrow  884 . Where the time interval for display is at hand, then as represented at arrow  922  and block  924 , the filtered or average total ammoniacal concentration in blood (TAC) and the pH measurement most recently taken are displayed at a real time, t i ′. As a correlative to this display of the numerical values, the system generates a real time graphics output displaying a time versus TAC value curve as well as an associated TAC level threshold. Additionally, a graphics display for pH is developed. This arrangement is represented at arrow  926  and block  928 . Correspondingly, a printed document or strip may be generated as represented at arrow  930  and block  932 . Next, as represented at arrow  934  and block  936 , a determination is made as to whether the computed and filtered total ammoniacal concentration assigned for the time, t i ′ has a value greater than the corresponding filtered TAC value at the next previous measurement time, t i ″. Where the contemporaneous value is greater, then a rise in TAC is at hand and, as represented at arrow  938  and block  940 , a visual warning cue is activated. This warning cue may be provided, as discussed above, as an illumination of an amber or yellow spectrum colored LED. In the event of a negative determination with respect to the query posed at block  936 , then as represented at arrow  942  and block  944 , any preexisting visual warning is deactivated and the program continues as represented at arrow  946 . Correspondingly, where the warning cue is activated as represented at block  940 , the program continues to arrow  946  as represented at arrow  948 . 
     The program then proceeds as represented at arrow  946  and block  950  wherein a determination is made to whether the filtered value for a total ammoniacal concentration as currently measured, {overscore (C)} TAC, n (t i ′) is greater than an inputted threshold value, C th . In the event that the threshold is exceeded, then as represented at arrow  952  and block  954  both visual and aural cues are activated to alert the practitioner. In the event that the threshold is not exceeded, then as represented at arrow  956  and block  958 , any threshold warning is deactivated. The program then continues as represented at arrow  960 . Where a warning activation has been developed as represented at block  954 , the program continues to arrow  960  as represented at arrow  962 . Arrow  960  leads to the query posed at block  964  determining whether the time elapsed from the start time, t ROR  is or equal to the time interval utilized for carrying out a rate-of-rise calculation with respect to TAC. In the event that the elapsed time has not reached that value, then the program proceeds as represented at arrows  966 ,  968  and block  970 . At block  970 , the elapsed time between displays of TAC, RT, is set to zero. The program then loops as represented at arrows  972  and  884 . 
     In the event of an affirmative response to the query posed at block  964 , then the time interval for calculating rate-of-rise of filtered TAC is at hand and, as represented at arrow  974  and block  976  the rate of change of total ammoniacal concentration during the period δt ROR  is computed, the resulting value being identified as: {dot over ({overscore (C)})} TAC,n (t i ′). As represented at arrow  978  and block  980  the program then records the rate of change of filtered total ammoniacal concentration in memory and continues as represented at arrow  982 . Arrow  982  leads to the display operation represented at block  984 . In this regard, the rate of change of the filtered total ammoniacal concentration is assigned a real time, t i ′ for the time of the last measurement of ammonia level and that value is numerically displayed and may be incorporated graphically in the display program, for example, as or the like. The latter approach is represented by dual arrow  986  and block  988 . Correspondingly, as represented at arrow  990  and block  992  a printout is provided showing this rate valuation. The program then continues as represented at arrow  994  and block  996 , where a query is posed as to whether the computed rate-of-change of filtered total ammoniacal content is greater than an inputted rate-of-rise threshold, C th . In the event that the threshold is exceeded, then as represented at arrow  998  and block  1000 , visual and aural alarm cues are activated. In this regard, an LED in the red spectrum is illuminated and a warning sound is provided. Where the inquiry as posed at block  996  indicates that no rate-of-rise threshold is exceeded, then as represented at arrow  1002  and block  1004  any rate-of-rise warning is deactivated and the program continues as represented at arrow  1006 . Where the rate-of-rise alarms have been activated as represented at block  1000 , the program then continues to this arrow  1006  as represented at arrow  1008 . Arrow  1006  leads to the instructions at block  1010  wherein the parameter ET or elapsed time between the displays of rate-of-change of filtered TAC is set to zero. The program then loops as represented at arrow  968 , block  970  and arrow  972  to arrow  884 . 
     Since certain changes may be made in the above system and method without departing from the scope of the invention herein involved, it is intended that all matter contained in the above description or shown in the accompanying drawings shall be interpreted as illustrative and not in a limiting sense.