UREMIA

UREMIA (from Greek uron-urine and haima-blood), in the literal sense of the word urinemia, a pathological condition or clinical symptom complex observed in a number of diseases of the kidneys and urinary tracts. Nosologically, U. consequently is not an independent disease. The clinical picture of U. does not have a single symptom that is strictly specific to this pathological condition, and only the presence, along with uremic signs, of some lesion of the urinary excretory organs provides a basis for a firm conclusion about U. In the broad clinical understanding, U. represents a sum of pathological phenomena, different in their mechanism of development and apparently also in their causes of origin. Nevertheless, U. often dominates so much in the entire picture of the disease and determines its outcome, and often the fate of the patient, that it inevitably attracts attention. History of the doctrine of U. The term uremia belongs to the French clinician Piorry (1848). Piorry was not inclined to see the cause of the U. he described as a lesion of the kidneys or loss of their function, but explained it by the absorption of urine from the surface of the urinary tracts or through ulcers forming on the skin. Somewhat later, in the 1850s, simultaneously Frerichs in Germany and Bouchard in France described U. as a condition accompanying Bright's disease. Both of these outstanding clinicians considered U. to be a consequence of the retention in the body of toxic constituents of urine, with Frerichs inclined to consider ammonia salts (ammoniemia) as this poison, while Bouchard considered other unknown, biologically active toxic substances usually excreted in urine. Observations by the Englishman Wilson, who obtained a large amount of urea from the blood of a deceased uremic patient, also spoke in favor of retention. In contrast to the above retention theories of the origin of U., their contemporary Traube put forward to explain the origin of U. the importance of a violation of mechanical, rather more precisely hydrodynamic conditions in the cranial cavity. The cause of the main pathological symptoms from the central nervous system observed in U., according to Traube, is brain edema and increased intracranial pressure. However, pathologists (Cohnheim and others) accumulated many indisputable observations that in those who died from U., there was no edema of brain tissue. Clinical observations also multiplied in cases with complete anuria, in which, despite the retention in the body of urine or rather its constituents, U. did not occur. Such contradictory concepts of U., existing among the leading clinicians of the 19th century, were primarily due to the fact that several different pathological conditions were attributed to U. What was common to all types of U. was only that they were observed in patients with various kidney ailments and were accompanied by severe disturbances in the activity of the central nervous system. Over time, clinicians, based on the predominance in the clinical picture of U. of one symptom or another, distinguished many of its subspecies, such as: psychotic, eclamptic, epileptic, asthmatic, comatose, visceral, etc. In addition, it was universally recognized that some forms of U. arise acutely, while others develop insidiously and have a prolonged course. The task of subsequent researchers was to show that the acutely developing, convulsive state usually observed in acute nephritis and the severe state of intoxication developing in various forms of renal insufficiency represent completely different pathological phenomena not only from the external semiological side, but also in their genesis. The great merit of Vidal and his school (France), as well as G. Strauss and Volhard (Germany), is therefore the clear delimitation of true, so-called azotemic U. from a number of clinically "adjacent" forms called by these researchers chloruremias or eclamptic U., as well as from various convulsive states close to U., so-called pseudo-uremias. In the classification of U., the aforementioned modern clinicians were guided not only by the symptomatology of the main forms of U., but also attempted to pathogenetically delimit each separate form, clarifying the unique, special mechanism of its development. Azotemic U. (azotemia of French authors, true, "quiet" U. of German authors) is usually observed with complete or partial loss of kidney function, especially if renal insufficiency develops slowly. The symptoms characteristic of U. in this case appear gradually, insidiously, manifesting at first only by individual disturbances, mainly from the central nervous system and general nutrition of the patient. The typical clinical picture of azotemic U. with all its manifestations occurs significantly later, after prolonged renal insufficiency. From a practical point of view, it is more appropriate to consider azotemic U. not only the essentially "terminal" forms, but also those "minor" signs of it that pathophysiologically have a common genesis with true U. These suburemic states, which are sometimes precursors of true U., are also practically extremely important because they are reversible. With such an expansion of the concept of azotemic U., its frequency sharply increases, and the clinical picture becomes much more diverse. From a clinical point of view, azotemic U. should be characterized as severe auto-intoxication with a sharply expressed complex of neuropsychiatric symptoms, which in general play the most important role in the picture of azotemic U. Subjectively, patients complain only of weakness, persistent headache, bad taste and bitterness in the mouth, nausea, and sometimes skin itching. The patient is lethargic, apathetic, and as if stunned. The reaction to external stimuli (sound, light) is slowed and inconsistent, patients are sleepy, although their sleep is interrupted and superficial. Often consciousness in uremic patients is confused or clouded. Voluntary movements are markedly slowed, and at the same time there are hyperkinesia and muscle twitching in individual groups of striated muscles. With azotemic U., these relatively small twitchings and restlessness, as a rule, are limited to the motor disorders and do not reach the degree of large clonic-tonic type convulsions. The pupils are constricted and react sluggishly to light. Uremic intoxication affects to a greater or lesser extent, along with the nervous system, also other organs and systems. The skin is pale, dry, and covered with scratches, and sometimes also with crystalline scales of urea and uric acid excreted in large quantities by the sweat glands. On the skin and mucous membranes, one can often see multiple hemorrhages resembling the picture of hemorrhagic diathesis in leukemia or sepsis. The pallor of the skin is due primarily to the sharp spasm of small arteries and capillaries, usually present in U. At the same time, it is necessary to take into account the presence of true progressive hypochromic anemia, which increases as the duration of U. increases. In rare cases, necrotic ulcers of significant size form on the skin. Breathing is also very disturbed in azotemic U., and in severe forms it is also very typical. The depth of breathing is sharply increased, while the frequency is little changed, which creates the impression of deep breathing during sleep (so-called large Kussmaul breathing). In far-advanced cases, breathing becomes arrhythmic and approaches the Cheyne-Stokes type (see Cheyne-Stokes breathing). The disturbance of breathing is not associated with any changes in the lungs and should in fact be attributed to the intoxication of the central nervous system, in particular the respiratory center in the medulla oblongata. From the side of the digestive organs, there is a whole range of pathological phenomena on the mucous membranes (from the oral cavity to the large intestine); they are connected with the excretion by the digestive organs of toxic products formed and circulating in the body of the uremic patient, and subsequent autoinfection. Such "excretory" origin, for example, uremic stomatitis, persistent, agonizing, and often progressive. In a similar way, uremic pharyngitis, esophagitis, gastritis, and especially colitis, which usually takes a severe hemorrhagic character, also arise. Persistent vomiting and especially diarrhea, often with blood admixtures, indicate ulcers and inflammatory processes on the mucous membranes of the digestive tract. In late and at the same time severe cases of azotemic U., the appearance of inflammatory phenomena on the serous membranes is characteristic. Uremic fibrinous, sero-fibrinous, sometimes hemorrhagic pericarditis is particularly typical, often so extensive that a rough friction noise of the pericardium can be heard over the entire anterior surface of the chest. Pleuritis, which is less common in U., also belongs here. Finally, to the toxic, aseptic inflammations observed in U. should be included the sometimes fresh uremic endocarditis, clinically difficult to diagnose, as well as interstitial myocarditis. In addition, in U., focal necrobiotic changes are noted in the myocardium, resembling foci of fatty degeneration, or myomalacia, especially in the left ventricle.

This fact apparently indicates the presence of angiospastic phenomena also in the internal organs. Excretory (with subsequent autoinfection) lesions in U. are described along the respiratory tract (necrotic tracheitis, laryngitis, bronchitis), the reproductive system (endometritis, vaginitis), etc. The ammonia smell, perceived upon the opening of most organs (especially the intestines, respiratory system), is very characteristic. In azotemic U., the changes in the blood and excretes are extremely great; the chemical shifts in the blood, urine, and saliva are so profound and specific that they even gave rise to designating this form as 'azotemic.' In essence, the matter is not about a simple accumulation of nitrogenous waste products in the organs and tissue fluids, but about significantly deeper changes in their chemical composition. The osmotic pressure in the blood plasma is sharply elevated, which is reflected in a lowering of its freezing point to -0.7-0.72°. Such a drop in the cryoscopic index (see Cryoscopy) is due to the accumulation in the blood of uremics of large amounts of substances, which under physiological conditions are removed from the body by the kidneys (first of all NaCl, then urea, creatinine, uric acid, amino acids). In addition, the blood contains a number of aromatic organic acids, formed in uremics due to intensified tissue breakdown. It deserves attention that the degree of accumulation of individual substances in the blood is uneven and also varies among different uremics. In cases where U. developed relatively rapidly, the amount of residual nitrogen in the blood serum is usually extremely elevated (150-300 mg% and more). The increase in residual nitrogen in this case occurs primarily at the expense of urea nitrogen, which normally constitutes 50-60% of the non-protein nitrogen of the serum. In most patients, however, in whom azotemic U. developed slowly, insidiously, the increase in residual nitrogen is not so significant (70-150-200 mg%). Upon closer study of the blood composition, the amounts of the most complex nitrogenous waste products—creatinine, uric acid, and especially indoxan, which is usually found in the blood serum only in traces—are found to be significantly increased. The chemical changes in the blood are to a large extent a consequence of the insufficient excretory function of the kidneys. Therefore, regardless of the nature of the kidney disease that caused U., the urine excreted by uremics shows regular changes: it is as a rule light, straw-colored, poor in pigment; its specific gravity is low (1.006-1.012) and extremely constant. This can be detected without resorting to complex functional studies, simply by determining the specific gravity in a series of separate portions of urine collected over 24 hours. Corresponding to the low specific gravity of urine, the content of non-protein residual nitrogen and table salt in it is also sharply reduced. In particular, the amount of urea in the 24-hour urine sometimes falls to negligible amounts (1-2 g per day). Anbar's constant (see), which reflects the ratio of urea in the blood and urine, is thus particularly sharply altered in azotemic U.: the absolute value of the constant increases to 0.15-0.2 and more. In the initial stages of U., the decrease in the nitrogen- and salt-excretory function of the kidneys is partially compensated by abundant urination—the so-called forced or compensatory polyuria. However, as the functional capacity of the kidneys decreases, a decrease in the amount of urine excreted is also observed. The onset of uremic phenomena in a number of individual cases coincides only with the onset of oliguria or even anuria. The insufficiency of the excretory function of the kidneys is reflected in a sharp change in the composition of saliva and sweat as well. The saliva of uremics is rich in residual nitrogen; for this reason, the breath of uremics smells of urea or ammonia. Sweat is also so saturated with urea that the latter often precipitates in the form of crystals on the skin. Parenchymatous organs and endocrine glands are likewise affected by uremic intoxication, however clinically this does not manifest itself in any particularly sharp or characteristic symptoms. It deserves attention that the liver is often enlarged, however, if urobilin was previously detected in the urine, it disappears with the onset of U. An objective sign of impaired liver function can be considered the accumulation in the blood of aromatic acids (phenols, oxy- and dioxyphenols) and other acidic metabolic products, which in azotemic uremics are formed by the liver in excessive amounts and moreover are difficult to excrete by the kidneys. An objective expression of these metabolic disorders is the observed decrease in the alkaline reserve of the blood, resp. the accumulation of acid valences in the blood and tissues during U.—Finally, the general thermoregulation is also deeply disturbed in azotemic uremia. Despite tissue breakdown and often multiple inflammatory foci (colitis, pericarditis, etc.), in patients with uremia, body temperature as a rule is not only not elevated, but is sharply reduced compared to the lowest limit of normal. A temperature of 35-34° is not uncommon in azotemic uremics. E T I O L O G Y and pathogenesis. The cause of azotemic U. is primarily renal insufficiency. Many clinicians (Vidal, Rosenberg, Strauss) assert that without a decrease in the excretory function of the kidneys, uremia cannot develop at all, just as the accompanying azotemia cannot. These researchers therefore consider it an invariable sign accompanying any azotemic U. the low specific gravity (resp. dry residue) of the urine' and the accumulation of nitrogenous waste products in the blood. Clinically, renal insufficiency is not a consequence of any one disease, therefore azotemic U. develops in the most diverse kidney ailments accompanied by a sharp drop in renal activity. Most often, azotemic U. occurs in the final stage of chronic diffuse nephritis and diffuse arteriolosclerosis of the kidneys, i.e., in primary and secondary shrunken kidney. In these cases, the impairment of individual kidney functions occurs gradually, and likewise slowly, insidiously, do the individual symptoms of U. develop and increase, reaching a pronounced degree at a certain moment. However, also in other chronic bilateral kidney diseases (e.g. cystic degenerations, pyonephroses and tuberculosis of the kidneys), in case the pathological process involves the greater part of the renal tissue, with loss of its function, a uremic picture develops. True, in these cases U. manifests itself as if suddenly, by a leap, sometimes even unexpectedly for the observing physician. However, upon careful questioning, it is possible to retrospectively detect the appearance in the pre-uremic period of a large number of minor symptoms, the so-called suburemia. There is no doubt that azotemic uremia can also arise in more acute processes occurring in the kidneys, as well as in extrarenal diseases, e.g. in prolonged renal colic or acute hydronephrosis with anuria, in hypertrophy of the prostate gland and a number of diseases of the bladder with retention of urine (tumors, chronic cystitis, etc.), in obstructions, kinks of the ureters or their reflex spasm. The pathogenesis of azotemic U., despite extremely thorough and comprehensive study of U. to this day, has not found a generally accepted and fully convincing explanation. Since Wilson discovered large amounts of urea in the blood of uremics, it was most natural to genetically connect U. with poisoning of the body by urea. Proponents of this view are especially French authors (Vidal and his school), who conducted various experiments on animals and healthy people with the administration of large amounts of urea. The phenomena observed in urea poisoning (diarrhea, convulsions, apathy, loss of appetite and finally death) greatly resembled the clinic of azotemic U., however, to obtain all these pathological symptoms, it was necessary to administer very large amounts of urea (5.3-8.0 g per 1 kg of weight) and to bring the urea content in the blood to 5-6.6 g per 1 liter. In these experimental azotemias, there was therefore such a saturation of the body with urea as is usually not observed in the clinic of U. Other clinicians are therefore not inclined to attribute to urea the role of a causal factor in the origin of U. Even less can U. be caused by the accumulating in the bodies of patients uric acid, creatinine, or indoxan, the absolute amount of which is significantly less than that of urea. The accumulation of all the above-mentioned nitrogenous substances in the blood should therefore be attributed only the value of an important accompanying phenomenon in U. From this viewpoint, the azotemia of uremics has only the role of an important diagnostic symptom, but by no means a pathogenetic factor of U. On the other hand, the similarity of the final phase of azotemic U. with the coma observed in diabetics led to the assumption of the unity of their genesis. Thus arose the doctrine of the acidotic origin of the coma of uremics and U. in general.

The assumption that uremia is caused by a single specific poison is supported primarily by the presence, even in the pre-uremic phase, of a clear delay in the excretion of acidic valences by the kidneys; a decrease in the alkaline reserve of the blood, poor excretion of anions by the kidneys—all this was cited as proof of true acidosis in uremia. Becher, who discovered in the blood of uremic patients substances of the aromatic series (phenols and their derivatives)—products of decomposition, or rather, of protein putrefaction—insists on their importance in the development of uremia. Becher was able to show that phenolic derivatives possess very poisonous properties, similar to the organic acids of the fatty series (acetoacetic and β-oxymethyl acids), found in the blood and tissues in diabetic coma. Finally, Chrometska, Andrews, and others discovered in the serum of uremic patients, after precipitating its proteins with lead acetate, substances that kill mice, causing paralysis and convulsions. Chrometska considers this substance identical to tyramine and attributes to it the role of the main uremic poison. The mentioned changes in the blood and tissues, the variety of clinical symptoms in U., and finally its severe outcome indicate profound self-poisoning of the uremic patient's body. However, this autointoxication is hardly caused by any single specific poison; on the contrary, based on our current knowledge of the pathogenesis of U., it can be thought that true or azotemic uremia is the result of the most complex disturbances of protein and mineral metabolism arising from renal insufficiency. Its danger was properly assessed even by Bouchard (see above), who wrote about seven poisons excreted by the urine and retained in the body in uremia. Recognition of azotemic uremia in pronounced cases presents no difficulties. Persistent vomiting, headaches, the typical color of the skin, characteristic lethargy, a uremic odor from the mouth, scratches on the skin, diarrhea, sometimes with blood, excretion of light-colored urine, clouded consciousness, drowsiness, pinpoint pupils, and finally, the often audible dry friction of the pericardium even without anamnestic data and without laboratory studies, as a rule, make it possible to make a diagnosis. The presence of bilateral kidney disease or lesions of the urinary system in the anamnesis supports the diagnosis of U. The basis for a firm conclusion about true azotemic uremia, along with the mentioned clinical picture, is also the presence of azotemia (elevation in the blood of residual nitrogen, uric acid, indican), as well as the low specific gravity of urine when the kidneys lose their concentrating function (see Kidneys, functional diagnosis). It must be emphasized that unconsciousness, or rather, comatous state, is observed only in the latest period of azotemic uremia and is not characteristic of it. Grand mal seizures are by no means typical for uncomplicated, 'pure' forms of azotemic uremia; only small, fine twitchings are usually observed. Many of the symptoms mentioned can already be found in the so-called pre-uremic stage and should serve as the basis for early recognition and active treatment. The prognosis in azotemic uremia is determined by the underlying disease and is therefore usually unfavorable. Exceptions are individual cases where azotemic uremia complicates acute nephritis, which ends in recovery, or such a disease of the urinary tract in which difficulty in urination can be eliminated. The treatment of azotemic uremia consists of a series of measures that can be grouped into two categories. With some therapeutic methods, an attempt is made to quickly remove toxic metabolic products from the body or neutralize them, to lower blood pressure as much as possible, and finally, to eliminate, if possible, the primary cause that caused U. (removal of a stone or prostate, emptying the renal pelvis and bladder, etc.). On the other hand, with longer-term and systematic treatment, mainly of a dietary nature, an attempt is made to protect the patient from self-poisoning, from the retention of toxic metabolic products in the body, especially of protein origin. The first group includes repeated large bloodlettings followed by the subcutaneous injection of a glucose solution (5%) and intravenously (20% - 200.0), and the administration of large quantities of saline laxatives. In the presence of pronounced pre-comatose and comatose symptoms, the administration of alkaline salts to neutralize acids, for example, sodium citrate, sodium bicarbonate with an enema or intravenously, is also indicated. As for table salt, its maximum restriction is highly indicated both to spare the functionally insufficient kidneys and, especially, to lower blood pressure. By means of long-term diathermy or X-ray therapy of the kidney area, it is sometimes possible to achieve increased diuresis and unloading of the body from waste products. However, it must be taken into account that all the mentioned methods, at best, lead to the elimination of 'major' uremic symptoms, but almost never eliminate renal insufficiency and the associated self-poisoning. That is why at the first signs of decreased kidney function and the appearance of autointoxication, the patient's protein diet should be sharply restricted to 25 g of protein per day with the aim of reducing the amount of nitrogenous and acidic metabolic products formed. At the same time, it is necessary to administer to the patient a sufficient amount of carbohydrate-vegetable food to cover his minimal caloric needs. Otherwise, due to tissue starvation, the body's own tissue proteins undergo breakdown. Therefore, the best food products for patients in the suburemic period are fruits and vegetables, glucose, cream, sour cream. To prevent intestinal protein putrefaction, it is recommended to prescribe soured milk or kefir, as well as charcoal to absorb putrefactive products. The amount of allowed fluid is determined by the concentrating function of the kidneys. In patients with a sharp decrease in concentrating ability and forced polyuria, restriction of fluid intake is associated with the danger of waste retention in the body. In persistent oliguria, fluid intake should also be partially restricted. Somewhat separate is the clinical form of the disease accompanied by azotemia but occurring in people with normal kidney function. In such cases, the increase in residual nitrogen in the blood, resp. the development of the disease, occurs parallel to the loss of large amounts of table salt by the body (chloropenia) and is causally dependent on it. Blum, who first described this form, designated it as azotemia from lack of salt (azotemie par manque du sel), while some simply call it chloropenic azotemia. The course of the condition resembles azotemic uremia, but it is obviously not identical to it, as it is characterized by comparative mildness and reversibility of the phenomena and a less severe course. Such chloropenic azotemic states can be recognized by the low chlorine content in the blood and urine. They are relatively easily treated by the intravenous administration of hypertonic solutions of table salt (10% NaCl solution - 30-50 cm³) or a saline drip enema (500 cm³ of physiological solution). Eclamptic uremia, or rather eclampsia of Bright's disease, represents a clinically extremely bright and at the same time clearly defined state, sharply differing from azotemic uremia. Many clinicians are not inclined to associate this symptom complex, which undoubtedly has its own pathogenesis, with kidney disease and therefore classify eclamptic uremia in the group of so-called pseudo-uremias. Such a definition is justified insofar as the occurrence of eclamptic uremia is not associated with insufficiency or loss of known kidney functions. Eclampsia of Bright's disease usually develops in patients with acute diffuse glomerulonephritis or during an exacerbation of its chronic forms, and exclusively in the edematous stage of the disease. CLINICAL PICTURE. Eclamptic uremia, unlike azotemic uremia, usually develops acutely, in the form of externally very severe eclamptic coma seizures. Without any precursors or after a brief but agonizing headache, following a cry or loud sigh, a violent picture of an eclamptic seizure rapidly develops. As if an electric current were passing through the patient's body, and all muscles come into a state of tonic convulsions for a short time; the patient's body, his musculature, is tensed to the utmost, and only small twitchings here and there indicate the frequent and strong contractions of the muscles. Tonic convulsions are soon replaced (after 1-3 minutes) by sharp clonic twitchings. The patient thrashes about, is 'thrown' from side to side, the eyeballs are deviated, the tongue is drawn in and often bitten. A foamy fluid is excreted from the mouth, the pupils are widely dilated and do not react to light. Consciousness is usually completely clouded. The convulsive state lasts about 5-30 minutes, followed by a short period (from several minutes to an hour or more) of relative rest, when the patient is in deep sopor or comatose sleep.

In some cases, immediately following the convulsive period, in others only after a stuporous sleep, the patient 'wakes up,' i.e., opens his eyes and with great difficulty orients himself to his surroundings. Stupor, difficulty of movement and speech, and indifference to surroundings persist for many more hours. Sometimes, after the cessation of the convulsive seizure, on the contrary, there is motor restlessness and psych. excitement, which can be characterized as an uremic submaniacal state: the patient is noisy, incoherently shouts words, or continuously complains of violence, cries, and attempts to jump up from the bed. Such excitement can last for a day or more and ceases only after active therapeutic intervention. Subsequently, as a rule, retrograde amnesia is found, which brings renal eclampsia closer to clinically similar eclampsia of pregnancy. The described seizure of eclamptic U. is only rarely single. Usually, on the same day, a second convulsive seizure occurs, very similar to the first. The number of seizures varies and can range from 2 to 50 (or more) per day. As their number increases, the seizures become weaker in intensity and shorter in duration; in rare cases, their intensity gradually increases. Uremic convulsive seizures usually end within the first or second day, and their cessation occurs as unexpectedly as their onset, in some cases even without any external influence. Physical examination of internal organs does not, in eclamptic U., reveal anything characteristic. The pulse is as a rule slowed (50 or fewer beats per minute) and tense. Blood pressure is sharply elevated. Pressure in the spinal canal likewise reaches high figures. The increase in spinal and intracranial pressure can be so great that when examining the fundus of the eye, a picture of choked disk is found. In the blood in eclamptic U., only minor pathological deviations can be noted: the amount of nitrogenous waste in the blood serum is normal or slightly elevated, while chlorides are present in smaller quantities, rarely in normal amounts. Indeed, hypochloremia (of serum) is often apparent and is associated with the transition of the chloride ion into red blood cells. The pathogenesis of eclamptic U. remains to this day not fully clarified. It can only be considered proven that eclamptic U. often arises without any symptoms of renal insufficiency. Thus, there is obviously no reason to connect the onset of eclampsia with urinary retention and the formation of nephrolysins, as Ascoli thought, or guanidine derivatives (Weber), especially since a picture similar to eclamptic U. and its individual equivalents can be experimentally obtained by changing intracranial pressure and cerebral circulation. In old experiments with the ligation of the four cerebral arteries, Kussmaul and Tenner were able to observe the main symptoms of the eclamptic seizure—convulsions and coma. The same was observed by Landois with artificial obstruction of the outflow from cerebral veins, and by Leiden with increased intracranial pressure. All these experiments, along with the focal symptoms of deficit observed in eclamptic U. (hemianopia and prot.),^; gave many modern authors reason to connect eclamptic U. with angiospasm, resp. acute oxygen starvation of certain areas of the central nervous system. These clinicians also supported their assumptions with the well-known fact: before a seizure of U., the already elevated blood pressure sharply increases to very high figures. Along with this, many clinicians (Vidal, Folgard, Strauss, Lichtwitz) still continue to uphold and justify the old doctrine of Traube on cerebral edema as the pathogenetic mechanism of eclamptic U. The occurrence of seizures in edematous subjects, high pressure in the spinal canal in renal eclampsia, the beneficial therapeutic effect of lumbar puncture, the possibility of explaining all symptoms by changes in intracranial pressure—all this speaks in favor of Traube's hydrodynamic theory. In the same sense, many pathological-anatomical data could be used, where in the brain, examined in situ, a sharp decrease in the cavities of the cerebral ventricles was noted. In cases of death from eclamptic U., focal hemorrhages into the brain substance are also observed, differing little from those in eclamptic seizures of any origin (eclampsia, whooping cough, etc.). Further research must show whether in U. there is only edema of the brain membranes and intercellular substance (Hirnoedem) or whether eclamptic U. can also arise with intracellular swelling of the brain cells themselves (Hirnschwellung). Even greater difficulties are presented by clarifying the mechanism of the periodicity of seizures in eclamptic U.: what is the reason for the alternation of severe U. attacks with intermediate periods of almost normal consciousness and satisfactory condition of patients? It is completely obvious that the gross anatomical-physiological changes in the body, against which the uremic seizure occurs (kidney damage, hypertension, oliguria), existed long before the onset of eclamptic convulsions. Thus, for the onset, resp. cessation, of an eclamptic seizure, as with other seizures, e.g., epilepsy or migraine, some additional mechanism is required, the accumulation or potentiation of irritation with its discharge. In this sense, there are attempts to interpret eclamptic U. as an acute discharge of a sensitized organism, in other words, to consider the uremic seizure, like an attack of bronchial asthma or migraine, as an allergic reaction (French authors, Lichtwitz). However, it must be emphasized that to date no convincing data in favor of such an interpretation of the uremic seizure has been presented, except for far-reaching clinical analogies. Recognition of eclamptic U. presents no difficulties. The acute onset of the seizure, clonic-tonic convulsions, dilated pupils in the presence of glomerulone^ritis with edema in the patient allow the nature of the suffering to be determined without error. Clinically similar eclampsia of pregnancy differs from eclamptic U. not only in the causal factor, i.e., the presence of pregnancy, but also in its pathogenesis. In eclampsia of pregnancy, signs of increased blood breakdown (hematin, increased bilirubin) can be found in the patient's blood serum, which usually does not occur in U. Sometimes a picture similar to U. has to be observed in epileptics. However, the semiotics of the epileptic seizure (biting of the tongue, involuntary urination and defecation, absence of true coma) is somewhat different from that in eclamptic U. The anamnesis and accompanying clinical picture are of course completely different. Treatment of eclamptic U. can be extremely effective. Indeed, cases are well known where a suddenly occurring eclamptic seizure also suddenly stops and does not recur without any therapeutic intervention. Nevertheless, active intervention to stop the uremic seizure is indicated for a number of reasons; first, a delay or recurrence of the seizure threatens the patient with a number of complications, of which the most serious are focal changes in the brain and aspiration pneumonias. Among therapeutic measures, lumbar puncture and bloodletting should be given first place. The latter is especially indicated in the presence of high blood pressure, which as a rule is observed in patients with eclamptic U. In these cases, bloodletting must be abundant (400-600 cm³). Often one bloodletting is sufficient to stop the U. seizure; however, in many patients the seizures recur, which necessitates resorting to therapeutic lumbar puncture. The release of spinal fluid in uremics should be done slowly with caution, under control of pressure in the spinal canal; a rapid drop in pressure in the presence of edema in the brain is a known danger to the patient. The mechanism of action of bloodletting and lumbar puncture cannot and should not be reduced to a simple mechanical unloading of the circulation, resp. intracranial pressure. Both of these interventions entail a series of shifts in the water-salt exchange between blood and tissues, in the state of tissue swelling, etc. (See also Bloodletting, Lumbar Puncture.) In the same sense, injections of small amounts of hypertonic glucose solutions and especially magnesium sulfate have a beneficial effect on the course of eclamptic U. The latter also has a specific antispasmodic effect. Finally, to prevent the recurrence of seizures of eclamptic U., a dehydrating dietary regimen in the form of a dry diet or even complete fasting is extremely valuable. Such nutrition promotes a more rapid increase in diuresis, resp. eliminates one of the main factors contributing to the onset of uremic seizures.

Disorders of the central nervous system activity, very similar to attacks of U., especially eclamptic, are also observed in a number of local circulatory disorders of the brain. Such attacks are called pseudouremic, to emphasize their independence from kidney damage. Pseudouremic phenomena can occur both in chronic patients with Bright's disease and in persons suffering from heart, vascular diseases and in particular cerebral sclerosis. The occurrence of pseudouremic cerebral symptoms in such cases cannot be associated with renal insufficiency and obviously has a completely different genesis. Clinically, a pseudouremic attack manifests itself with a number of transient symptoms of loss from the cranial and motor nerves-aphasia, visual and auditory disorders, disorientation in space-, hemiparesis and hemiplegia. Attacks of violent clonic convulsions are also not uncommon, which are preceded by persistent dizziness and migraines. During an attack, a sharp increase in blood pressure (hypertensive crisis) is usually also observed; if the patient already had hypertension before the attack, it rapidly increases, and the blood pressure temporarily reaches very high figures (300 and more mm Hg). Hypertensive crises and loss of function of individual nerve centers, characteristic of pseudouremias, can recur, and sometimes pass into a persistent-irreversible form; then in essence a picture of an apoplectic stroke develops, only gradually progressing. Consciousness in pseudouremia, unlike an eclamptic seizure, is usually preserved; in individual cases, mental disorders and even transient psychotic states are observed. Along with the impairment of cortical function, bulbar symptoms are also not uncommon, of which the most important is the disturbance of respiration. The paroxysms of suffocation or pseudouremic asthma observed in these patients are very different from the large breathing of Kussmaul, which was described above in azotemic U. In some cases, suffocation occurs with movements and physical exertion, in others it manifests as nocturnal asthmatic attacks of cardiovascular type (see Cardiac asthma):-Finally, to the analogues of pseudouremic symptoms should also be included the occasionally observed intermittent claudication, paresthesias in the extremities (sometimes "dead fingers") and angiospasm in the retina (retinitis hypertonica angiospastica). The development of pseudouremic symptoms, however diverse they may be clinically, is ultimately apparently conditioned by a single mechanism. Disorders of blood supply, resp. angiospasm, in the area of the brain or peripheral vascular system-that is what underlies the mentioned focal losses and disorders of function. Angiospasm can be generalized and develop on the basis of existing hypertension, but it can obviously also be isolated, regional due to increased excitability of the neurovascular apparatus of individual areas (vascular crises of Paly). As a result of angiospasm, ischemia of certain areas develops, and its spread and duration determine the clinical picture (character of symptoms, persistence of phenomena, etc.). In some cases, repeated prolonged ischemias of cerebral vessels lead to the formation of white necrotic foci of softening, often the matter ends with the formation of multiple small hemorrhages and large hemorrhages into the brain.. One angiospasm and ischemia, of course, does not exhaust the pathogenesis of the complex clinical picture of pseudouremias. In the origin of the respiratory disorder in these patients, the weakness of the left heart, sometimes reaching great degrees, as well as acute disturbances of self-regulation within the cardiovascular system (perversions of vegetative reflexes) obviously play a significant role. One thing is certain, that the causal factors of a pseudouremic attack in both Bright's patients and patients with arteriosclerosis and essential hypertension should be sought not in the decrease in the excretory ability of the kidneys, but in vascular disorders, which among other things manifest themselves as an increase in blood pressure.-The treatment of a pseudouremic attack, which is a consequence of chronic suffering, should be twofold. First of all, one should quickly eliminate the angiospastic crisis by all available means, since one can never be sure that the acutely arisen symptoms will not take on a persistent character. For this purpose, complete physical and mental rest, vasodilators [diuretin, papaverine, luminal (0.015-0.05), Natr. nitros., saline laxatives, etc.], leeches, bloodletting are used. For long-term use, all methods that help reduce hypertension and decrease the excitability of vascular muscle are indicated: bromides, hot baths, choline preparations (acetylcholine), general d'Arsonval, achloride nutrition, etc.