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Nephritis and Nephrosis
CLINICS ON OTHER S'UBJECTS NEPHRITIS AND NEPHROSIS LOWRAIN E. MCCREA, M.D., F.A.C.S., F.I.C.S. o EARL W. CLAWATER, JR., M.D.t AND HALSEY F. WARNER, M.D.t RENAL disease is of. considerable clinical importance to th~ entire medical profession because of the frequency with which it is encountered. Differentiation of the various types of renal disease is difficult in many instances owing to the apparent overlapping of symptoms, laboratory and physical findings. Evaluation and interpretation of reliable diagnostic and laboratory findings are always imperative for a clear understanding of the symptomatology presented by the patient. Confusion of nomenclature of the various conditions and the bewildering interpretation of clinical and pathological findings have existed for years. The confusion has existed between the clinician and pathologist and not infrequently between pathologist and pathologist, as to the fundamental causative factors and the clinicopathological picture presented by
MEDICAL
~ Clinical Professor, Temple University Medical School; Attending Urologist, Temple University and Philadelphia General Hospitals, Philadelphia. t Resident in Urology, Philadelphia General Hospital, Philadelphia. t Fellow, Department of Medicine, Temple University Hospital, Philadelphia.
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2. Nephrosis (degenerative) a. Lipoid (Epstein) b. Toxic-of pregnancy c. Heavy metals (mercury, etc.) d. Crush syndrome 3. Nephropathies-vascular basis a. Arteriolosclerotic nephrosclerosis b. Arteriosclerotic nephrosclerosis c. Orthostatic albuminuria d. Back pressure (passive congestion) SURGICAL
1. Obstructive lesions to urinary flow
A. Intrarenal a. In collecting tubules Post-transfusions hemoglobin reaction. b. In distal collecting tubules in crush syndrolne B. Extrarenal a. Ureter, bladder and urethra Resulting in: Pyelitis Pyelonephritis Atrophic pyelonephritis Infected hydronephrosis Pyonephrosis 2. Infections A. Nonspecific or pyogenic Route in invasion a. Hematogenous 1. Massive blood stream infection leading to miliary abscesses. 2. Infection following urinary stasis. b. Lymphogenous-ascending infections Localized infections of urinary tract. c. Retrograde Incompetent ureterovesical sphlDcter. B. Specific-tuberculosis
The term "nephritis" is used to connote a nonsuppurative inflammatory process primarily involving the glomeruli but capable of affecting the renal tubules secondarily to a minor degree. This nonsuppurative inHammatory process is not due to direct bacterial invasion, but rather to a reaction of the kidney elements to specific bacterial toxins, notably streptococcal. The resulting lesions in the kidney are noted bilaterally in the parenchyma because the bacterial toxin circulates in the blood stream. Since all the glomeruli do not function simultaneously, a varying degree of involvement and toxic reaction to the total number of glomeruli may be observed. It is a well established fact that such frequently ,.observed conditions as tonsillitis, scarlet fever, rheumatic fever, ery~ipelas and even the "common cold" predispose to the development of bephritis. The fundamental pathological changes to be found in nephritis or glomerulonephritis are threefold. The initial lesion is one of hemor-
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L. E. MCCREA, E. W. CLAWATER, JR., H. F. WARNER
rhage. Later changes are those of proliferation, degeneration and necrosis, and in the third or terminal stage of this process advanced sclerosis of the kidney elements becomes evident. THE ACUTE OR FIRST STAGE OF GLOMERULONEPHRITIS
The presence of acute diffuse glomerulonephritis becomes apparent when a child or young adult presents a marked puffiness around the eyes, edema of the extremities, a mild- degree of hypertension, and urine Date
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P.M. A.M. P.M. A.M. P.M. A.M. P.M. A.M. P.M. A.M. P.M. A.M. P.M. 8 12 48 12 4 8 12 4 8 12 4 8 12 4 8 12 4 8 12 48 12 ~ 8 12 <4 8 12 .. 8 12 .. 8 12 .. 8 12
Fig. 214.-Temperature chart. Acute glomerulonephritis. E. D., aged 7 years. Sore throat, fever, cervical adenopathy two weeks prior to admission. Persistent temperature of 100-104. Generalized convulsions morning of admission. Convulsions recurred every two to three hours for twenty hours. Physical examination: blood pressure 148/120, pharynx injected, tonsils hypertrophied; mentally disoriented; no edema; catheterized urine was reddish. brown; 4 plus albumin, many granular casts, many red and white blood cells. Hemoglobin 9 gmt Red blood count, 2.87; white blood count 39,000; blood urea nitrogen 23; carbon dioxide 46. 0
that is ~~smoky" in appearance. It is usual that such a s.eries of symptoms may follow an acute streptococcal infection of the tonsils, an attack of scarlet fever, rheumatic fever or erysipelas. Characteristically in this clinical picture there is a latent period, of varying length, between the predisposing infection and the onset of acute glomerulonephritis. These classical symptoms have been considered diagnostic, but additional symptoms such as nausea, vomiting, mild fever, malaise and anorexia often accompany the onset of glomerulonephritis. The urine described as "smoky" on examination, is found to be scanty in quantity and to
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contain red blood cells, blood casts, white blood cells, varying amounts of albumin and is usually rather concentrated. The specific gravity has been observed in instances to range from 1.022 to 1.026 gm. Oliguria and anuria are found commonly in the acute stage of glomerulonephritis (Fig. 214). The clinical picture presented by the patient does not always follow the classical pattern and it not infrequently occurs that differentiation from other pathological conditions is imperative. The differential diagnosis must include such problems as (1) orthostatic albuminuria; (2) the fever state with accompanying dehydration and albuminuria; and (3) surgical problems of renal pathology such as calculus, neoplasia, pyelonephritis and tuberculous infection. Orthostatic albuminuria in the tall angular adolescent is not accompanied by hematuria or the febrile state. Confusion is unlikely. The chronicity of a toxic, febrile dehydration state serves to differentiate this type of albuminuria from any acute process. 'A carefully elicited history and a meticulous physical examination will aid in establishing th'e origin of the extrinsic causes of hematuria. In instances of doubt in establishing an accurate diagnosis, intravenous urography may be considered the procedure of choice, for the purpose of demonstrating renal function or the' presence of obstructive uropathy. Cystoscopic examination with catheterization of individual ureters may be of value in those difficult cases with diminished urinary output and poor kidney function. It is imperative that the early recognition of the acute phase of glomerulonephritis be made and that accepted types of therapy be instituted to prevent the progression through the advanced phases of the pathological process. Despite rigorous enforcement of therapeutic criteria, the acute process may proceed into the subacute, and subsequently pass into the chronic stage. It has been estimated that this progression occurs in 26.8 to 32 per cent of all cases. Such progression of events may take place in a very short period of time. The development of the more advanced forIl) of glomerulonephritis, the degenerative or necrotic phase, may occur in two to three months in some instances. THE SUBACUTE OR SECOND STAGE OF GLOMERULONEPHRITIS
Symptoms of the sec.ond stage of progression include a marked albuminuria and a generalized edema of subcutaneous tissues and serous cavities. Hypertension becomes a very important symptom when associated with this stage of glomerulonephritis. There is a lowering of the total blood proteins through a marked and constant albuminuria. There is also nitrogenous retention. Some of the more constant urinary findings of the acute stage remain present during this stage of progression. It is not uncommon during the subacute stage that red blood cells, blood casts, hyaline casts and debris are observed on microscopic examination of the urine.
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L. E. MCCREA, E. W. CLAWATER, JR., H. F. WARNER
In addition, extrarenal changes associated with this stage of degeneration may be observed. The colloid osmotic pressure is lowered by a loss of total plasma proteins through the marked albuminuria. The .albumin ·fraction of the protein is lost more rapidly than the globulin fraction, resulting in a reversal of the normal albumin-globulin ratio. The retention of the larger globulin molecule is the mechanism whereby the colloid osmotic pressure is lowered. This protein derangement leads to furth,er chemical imbalance with a shift of the electrolytes and a retention of the sodium ion, and art actual water retention- occurs. This mechanism is known as. the edema of hypoproteinemia. Secondary anemia. is usually marked in the subacute stage. This type of anemia is caused by the constant loss of red blood cells through·the filter beds of the kidney, as· well as. seepage and· extravasation of the blood through an increasingly permeable,capillary network. It has also been considered by some investigators that there is an actual depression' of erythropoiesis. Hypertension may develop to such an extent as to playa definite role in.the loss of cardiac efficiency and the development of conge_stive failure. Nitrogen retention, as measured by the nonprotein. nitrogen values, becomes increased; but the blood urea nitrogen levels are usually found to be normal, or relatively so. The hypertension and the nitrogen retention are noted to be outstanding symptoms of renal impairment, and almost·without exception, contribute to an early death in the third or chronic phase of glomerulonephritis. THE TERMINAL OR TmRD STAGE OF GLOMERULONEPHRITIS
The third stage of this pathological progression of glomerulonephritis is marked by the symptomatology commensurate with extreme sclerosis of the renal arterioles. Renal failure is caused by the fibrosis and contraction -of the previously damaged areas. of the kidney into well defined scar tissue (Fig. 215). There is marked diminution in kidney function; development of severe degrees of hypertension, and excessive nitrogen retention occurs. The terminal stage ·is uremia, acidosis and congested cardiac failure. The progressive ravages of· this destructive process are gradual. It may also be said that the symptomatology is similarly insidious. It may be seen that considerable renal damage may have occurred with relatively few gross manifestations, until extensive parenchymal destruction and impending uremia is evident. Hypertension of severe degree is the outstanding symptom of the chronic stage. 'The systolic pressure usually rises to a level of about 200 mm. of mercury, while the diastolic pressure is persistently elevated above 100 mID. There are many theories for this elevation of blood pressure. The most logical theory states that an increase in the .blood pressure is necessary to force blood through a badly damaged filter process of the kidney. It is known that the total number of normal functioning
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glomeruli has been materially reduced by this sclerosing process. Com.. pensatory kidney function must be maintained by the remaining normal or partially damaged glomeruli. Ocular changes, even to the point of temporary blindness, are not uncommon. Urinary findings of the tertiary stage reveal a fixed specific gravity -due tolhe failure of the concentrating ability of the kidney. This inabil.. ity'is revealed by the Mosenthal or the Fishberg concentration tests. There is an increase in the quantity of urine excreted, and particularly an increase in the night volume. A marked albuminuria due to impaired filtration processes is always present. Microscopic examination of· the urine reveals a persistence of hyaline and granular casts admixed with
Fig. 215.-Glomerulonephritis.. J>hotoulicrograph showing sclerosis of glomeruli. This is' the microscopic picture presented in the final stage - of glomerulonephritis. -(Photomicrograph by Dr. Edwin S.Gault.)
- leukocytes and red blood cells. Secondary anemia is constant and is more apparent than in the preceding stages. Edema is constant through.. out the advancing progression. The edema increases due: to the constant lowering in the serum protein level and -to the adyancing renal failure. Uremia rapidly follows nitrogen retention and increases. in intensity with continueddehydfation and nutritionalloss. As the degree of uremia progre~s~s, acidosis increases desp~te rigorous therapy. TREATMENT OF GLOMERULONEPHRITIS
The treatment of glomerulonephritis -is divided according to the stage or-phase -present. In each sta.ge, therapy is directed toward relief. of symptoms and the. attempted establishment· {)f' normal renal funetion.
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L. E. MCCREA, E. W. CLAWATER, JR., H. F. WARNER
The essentials of the treatment of acute diffuse glomerulonephritis are absolute bed rest and adequate dietary intake. Bed rest should be maintained until there is complete absence of red blood cells in the urine, although it is a definitely known fact that microscopic hematuria may persist for months. Periorbital edema and hypertension usually tend to subside withiQ a few weeks after institution of bed rest. The dietary management should consist of a high protein, high carbohydrate regimen. Meat, cheese, eggs, milk and cream should be encouraged at every meal. A total caloric intake of 2200 to 2500 calories per day should be instituted if possible. Salt should be withheld since numerous investigators have shown that the sodium ion in the edema state is responsible for the binding of water in the intracellular spaces. Fluid intake should be increased to a total of 2000 to 2500 cc. daily. The regimen of a high protein, acid ash, salt-poor, hydration program appears to be the most efficacious. Supplemental vitamins should be given orally. The methods of treating oliguria and anuria accompanying the acute phase are neither specific nor satisfactory. Lower urinary tract obstruction should be ruled out by catheterization. Measures to increase the urinary output should be instituted whenever possible. The use of weak coffee, undiluted tea and fruit juices should be encouraged. The intravenous use of 50 per cent dextrose may temporarily increase urinary flow. Since marked anuria is thought to be caused by a swelling of the renal parenchyma against its outer capsule, it is considered that a decrease in blood flow through the glomerular filtration bed occurs. To combat this, surgical decapsulation, or splitting of the kidney capsule, has been advocated by some investigators. It is considered that decapsulation releases the intravenal pressure and permits an increase of the blood How through the filter. In our considered opinion such a procedure has not proved worthy of consideration. The treatment of chronic glomerulonephritis is equally nonspecific. Symptomatic relief is all that can be attempted. The edema of the third or chronic phase is considered to be due to a lowering of the total serum proteins with an increase in the globulin fraction and a lowering of the albumin fraction. This is manifest by a marked albuminuria. Correction of this discrepancy is the aim of the therapy davocated. A high protein diet is advised. A total of four or five grams of protein per kilogram of body weight is thought adequate. Dairy products, lean meats and eggs are suggested. Contrary to the popular conception, the sodium ion, rather than the harmless chloride ion, is responsible for the binding of water in intracellular spaces. In this phase of the disease, the use of salt is to be discouraged. Seasoning substitutes slIch as potassium chloride or salt-free mustard may be used. It has been demonstrated that the use .of strong diuretics is contra-
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. indicated. The use of xanthines is not recommended. Proper chemical and fluid balance is usually more effective. A charted record of the fluid intake and output of the patient is essential to proper management. The secondary anemia of this phase of glomerulonephritis has been found to respond very poorly to the usual hematinics such as iron and liver. Whole blood transfusions are preferred, although the result is only temporary. The terminal stage of chronic glomerulonephritis necessitated the use of such drugs as digitalis for the failing myocardium, aminophylline and ammonium chloride for pulmonary and hepatic congestion, and oral and parenteral measures such as increased fluid to combat the rapidly developing acidosis. It may be seen that acute glomerulonephritis, if untreated and uncontrolled, progresses through successive stages to almost complete fibrosis of the excretory elements of the kidney. Never at any time during the advancing degeneration and ultimate sclerosis is true evidence of pyogenic infection present. These negative findings are in contrast to the findings in the "surgical"or pyogenic infection of the kidney. Unlike glomerulonephritis, the pyogenic infection presents on inception the characteristics of infection. Destruction of the kidney occurs in each clinical entity yet, pathologically, a contrasting picture is presented. The end result of the advancing sclerosis process is much slower and often more insidious in glomerulonephritis than the suppurative process seen in pyogenic infection of the kidney. PYOGENIC INFECTIONS OF THE KIDNEY
The "surgical kidney" is the kidney of focal suppuration. There are five phases, each a progression to the other: (1) pyelitis, (2) pyelonephritis, (3) atrophic pyelonephritis, (4) infected hydronephrosis, and (5) pyonephrosis. It may be seen that infection, if permitted to remain and progress, tends to produc~ one common end, destruction of the kidney. The Bacillus coli is the most frequent offending organism. According to Kidd, the organism is responsible for approximately 98 per cent of the infections of the kidney. The Staphylococcus aureus or albus or the streptococcus is the infecting organism in approximately 2 per cent. T~e Bacillus proteus may on rare occasions be the infecting organism. There are three primary modes of entry of these bacteria into the kidney: (1) hematogenous, (2) lymphogenous, and (3) urogenous. 1. The hematogenous route is the most frequent route by which bacteria enter the kidney, and is the result of the direct implantation of bacteria from far distant foci of infection. These foci may be infected teeth, tonsils, sinuses, the skin, gall bladder or intestine. Bacteremia due to the Bacillus coli not infrequently accompanies colitis or appendicitis. Bacteremia may also follow the passage of a urethral instrument in the presence of a similar infection in the lower urinary tract. 2. Infection of the kidney by the lymphogenous route may occur. It is believed
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L. E. MCCREA, E. W. CLAWAlTER, JR., H. F. WARNER
by some investigators that infection traversing primarily the lower lymphatics is carried through the thoracic duct into the general circulation and then to the kidney rather than directly up the lymphatics surrounding the individual ureter. It is considered possible for the infection to traverse the periureteral lymphatics and invade the kidney. This periureteral route is believed to be the method of spread of the so-called "ascending infections." 3. The urogenous or retrograde route of the spread of infection occurs within the ureteral lumen. The retrograde ascension to the kidney is considered to be due to vesico-ureteral reflex caused by an incompetent ureterovesicle sphincter. Neurogenic dysfunction of the bladder, congenital anomalous obstruction of the lower urinary tract, or malignant infiltration of the trigone produce obstruction which may result in this reflux.
The secondary factors favoring infection of the kidney are obstruction and trauma which result in stasis to the urinary How. Obstruction may occur at any point in the urinary tract from the tip of the urethral meatus
. /:CIO~ . Obstruction
Infection
CYCLE OF
StaSiS
URINARY TRACT INfECTION
LoUlered Mucosal ~ Ischemia of Resistance the Mucosa Fig. 216.-Diagram illustrating the vicious cycle of urinary tract infection following obstructive uropathy.
to the collecting tubules within the kidney. Obstruction as a causative factor in kidney infection is generally recognized as producing a vicious cycle: obstruction-statis-ischemia of the mucosa-lowered mucosal resistance-infection (Fig. 216). It is believed that the ischemia produced by stasis in the urinary tract is always a predisposing factor to infection. Trauma to the kidney, regardless of its nature, is an accessory factor in the production of infection. This trauma may be the result of a direct blow to the kidney, obstructive uropathy, the passage of a calculus, bacterial toxins or chemical toxins which are excreted by the kidney. The trauma results in a lowering of local resistance which creates a favorable area for bacterial invasion. It is obvious that infection is the basis of focal suppuration of the kidney. Pyelitis, if permitted to continue unhampered and untreated, will progress through successive stages of infection until destruction of the kidney results and pyonephrosis occurs.
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PYELITIS
Pyelitis, per se, is a doubtful pathological or clinical entity. The term denotes an acute or chronic inflammatory process limited in its extent to the renal pelvis. It has not been proved conclusively in the majority of instances that the infection is present without coexisting medullary or cortical involvement. It is a well established fact that the disease is present with a minimal involvement of the renal parenchyma. In the hematogenous and in the lymphogenous routes of extension, the infection originates in the renal parenchyma and rapidly extends to the pelvis. In the retrograde route of extension, the renal pelvis is primarily involved and this involvement is followed by rapid spread to the parenchyma. Pathologically the renal pelvis in pyelitis shows a hyperemic injected mucosa irregularly studded with petechial hemorrhages. There is also an exudate composed of cellular debris and pus cells loosely held together by a network of fibrin. The mucous membrane is thickened and contains dilated capillaries and is infiltrated with polymorphonuclear leukocytes. This coexists with minute cortical abscesses or linear infiltrations of polymorphonuclear leukocytes and round cells in the stroma between the tubules of the pyramids. This is in reality the earliest stage of pyelonephritis and cannot be differentiated clinically from pyelitis. . PYELONEPHRITIS
The second phase of focal suppuration is pyelonephritis. Pyelonephritis may be acute or chronic. In the acute hematogenous type the renal cortex shows the major involvement while the pelvis shows minimal change. Pathologically the cut surface of the kidney is studded with varying sized areas of hemorrhage or small raised nodules which have a yellowish center surrounded by an intensely red areola. There are also wedge-shaped areas, dark red in color, mottled with areas of suppuration. These areas are caused by venous thrombosis along the path of spread of the infection and are known as B7ewer's septic infarcts. At the time of inception of the acute ascending lymphogenous type, the renal pelvis sho\vs a greater involvement than does the parenchyma. The mucous membrane of the renal pelvis mirrors the infection approximately twenty-four hours earlier than the remainder of the ki;dney. The mucous membrane of the pelvis is edematous, injected, and is studded with petechial hemorrhages. The process in the kidney shows minute abscesses and multiple minute hemorrhages lying on the pyramids between the tubules or located in the cortex. It is possible for the cortical abscesses to coalesce and form a renal carbuncle or to rupture through the capsule and cause a perinephritic abscess. Perinephritic abscess usually follows the staphylococcic infections of the kidney. The clinical picture of acute pyelonephritis is one of a sudden onset of sharp, stabbing pain at the costovertebral angle associated with chills
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L. E. MCCREA, E. W. CLAWATER, JR., H. F. WARNER
and fever (Fig. 217). The patient may complain of generalized malaise, and occasionally of nausea and vomiting. Within seventy-two to ninetysix hours this syndrome may be associated with the secondary symptoms of bladder infection such as urgency, frequency and pyuria. Examination of the urine shows a normal specific gravity, an acid pH, mild albuminuria, many pus cells, a few red blood cells and numerous bacteria. Bacteriological examination of the urine shows B. coli to be the most frequent causative organism. The albuminuria is due to the abnormal constituents present in the urine such as pus and red blood cells. The red blood cells are present due to the hemorrhage from the mucous .oat. A.M. P.M. A.tl1~ P.M. A.M. P.M. A.'''. P.M. A.M. P.M. A.M. P.M. A.M. P.M~ .. 8 12 48 12 .. 8 12 .. 8 12 4 8 12 .. 8 12 .. 8 12 .. 8 12 .. 8 12 .. 8 12 .. 8 12 .. 8 12 .. 8 12 .. 8 12
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Fig. 217.-Temperature chart. Acute pyelonephritis. M. S., aged 39. Sudden chills, fever, pain at costovertebral angle. Urine culture revealed B. coli. Catheterized urine: few red blood cells, innumerable pus cells.
membrane of the renal pelvis, and are usually microscopic in amount. In the acute stage there is a leukocytosis. Renal function tests such as phenolsulfonphthalein are of no material value as such tests are not sufficiently sensitive. Intravenous urography may be of considerable aid and is not contraindicated at any stage of the disease. It is valuable in determining the presence or absence of obstructive uropathy. While a grossly normal urogram does not exclude the presence of acute inflammation, an abnormal urogram which shows blunting and distortion of the calices is of marked value in diagnosing chronic pyelonephritis. Valuable information as to kidney function and the presence of congenital anomalies is
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also obtained by intravenous urography. Intravenous urography is always done before cystoscopic examination or retrograde pyelography is attempted. Cystoscopic procedures are never done in the acute stage of pyelonephritis. Much valuable information may be obtained from cystoscopic examination and/or ureteral catheterization in the subacute stage after the fever 'and generalized symptoms have subsided. Catheterization of the ureter reveals the presence or absence of any obstructive factors. The urine obtained from the catheter may be studied for bacterial growth. Individual kidney function is obtained by the use of indigo car.. mine or phenolsulfonphthalein. The acute infection either subsides leaving very little residual or develops into the chronic stage which may be followed by acute exacerbations of chills, fever, pyuria, slight tenderness in the costovertebral angle arid low-grade lumbar pain. Chronic pyelonephritis either heals or may progress into the stage of atrophic pyelonephritis. ATROPHIC PYELONEPHRITIS
Atrophic pyelonephritis may be defined as a contracted, scarred kid.. ney resulting from infection and abscess formation in the absence of obstruction. The kidney is usually reduced to one third or one fourth its normal size. There is usually marked scar formation, as the capsule is markedly thickened and fibrous. Atrophic pyelonephritis is usually unilateral. The clinical picture is that of acute pyelonephritis which subsided. It is usual that a sense of heaviness in the lumbar area is experienced and intermittent pyuria is noted by the patient. Hematuria does not occur, although albuminuria may be present. The urine usually shows a culture of B. coli or a mixed infection on bacteriological exam.. ination. Intravenous urogram reveals a diminution or a complete lack of function on the affected side. When visualized, the renal pelvis and calices are usually contracted and irregular. The kidney is usually decreased in size. INFECTED HYDRONEPHROSIS
Infected hydronephrosis begins as a diffuse pyelonephritis with dilatation of the pelvis and calices. As the condition advances, secondary pressure atrophy occurs, resulting in cessation of excretory function.AIn infected hydronephrosis the parenchyma is compressed but not destroyed, the abolished- function resulting from pressure atrophy. Throughout this compressed parenchyma, a diffuse pyelonephritis'may be seen on microscopic examination. The condition tends to follow any variety of obstructive uropathy, particularly those obstructive factors affecting the ureter. If the obstruction to the ureter is complete, pyuria does not occur. Intermittent or constant pyuria, and bacilluria ate usually present. There may be occasional hematuria. If the condition is
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L. E. MCCREA, E. W. CLAWATER, JR., H.
}i'.
WARNER
bilateral and extensive, there may be retention of nitrogenous waste products in the blood. Frequency, urgency, dysuria and nocturia are generally present due to an associated cystitis. There is diminution in the per~entage excretion of phenolsulfonphthalein. Intravenous' urography reveals eith~r anonfunctioning kidney or hydronephrosis. Cystoscopic exarriina~ion reveals the degree .of cystitis, if present, and· the presenC'e or absenceo£ obstructive uropathy. Retrograde pyelography demonstrates a hydronephrotic kidney. TIle ·condition if. permitted to progress' gradually passes to the, terminal phase 6f kidney destructionpyonephrosis. . PYONEPHROSIS
The pyonephrotic kidney is the final stage of progress~ve destruction ~esulting from in~ec~on. Th:ekidney 'in pyonephrosis becomes a func-
Fig. 218.-Pyonephrosis. Retrograde pyelogram showing complete destructiQD of Ule kidney. Note the shaggy appearance outlined by the radiopaque medium. This is the picture presented in the ·'end stage. of uncontrolled pyogenic renal infection. ' '
tionless, distended, thin-walled bag filled with thick, creamy pus. Clini-, cally· the patient .may complain of backache, tenderness in the loin, recurrent attacks of chills and fever following acute attacks of pain. There may be recurrent .symptoms of cystitis. Urine examination reveals
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pyuria and bacilluria. Hematuria seldom occurs. The pyonephrotic kidney shows a reduced or complete lack of function as shown by phenolsu~fonphthalein and indigo carmine excretion.Urographic studies show . loss of form and contour of the pelvis and calices which is considered . ,·typical of pyonephrotiqdestruction .( Fig. 218).. The management of the ':':surgical" or infected _kidney is _primarily directed toward the elimination of the disease in its early phase before the sequ~nce of events leading to total destruction of the renal parenchyma occurs. The early management is directed to· eradication of all foci of infection, removal of obstructive factors and the institution of normal urinary drainage. Since the Bacillus coli is the pri~ary offend~ ing organism, alkalinization of the urine by· potassium citrate and soda .bicarbonate is indicated to create a medium unfavorable to itsgrQwth. 1£ the offending organism is the staphylococcus or streptococcus, suI.. fonamide and/or penicillin therapy is-the treatment of choice. AciQi6.ca~ tion of the urine with sodium acid phosphate or, ammonium chlQride is indicated in those infections caused by the BacUluspr<;>teus. Streptomycin,although unproven, holds great promise ·in the· treatment of the gram-negative bacillae. _An adequ~te fluid and dietary regimen should be- maintained. In the -later phases of the disease; -therapy should be directed toward improvem·ent of the patienfs general condition, and the surgical removal of the -diseased kidney. Adv~ncing kidney. disease whethef -described asglomerulonephrltis Of· pyogenic infection has a common goal-destruction of the kidney. It is imperative that early recognition and institution of treatment be inaugurated to check or eradicate the 'constant trend and advancing tendency to kidney destrn,ctlon so characteristic of each condition.
MEDICAL
~ Clinical Professor, Temple University Medical School; Attending Urologist, Temple University and Philadelphia General Hospitals, Philadelphia. t Resident in Urology, Philadelphia General Hospital, Philadelphia. t Fellow, Department of Medicine, Temple University Hospital, Philadelphia.
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2. Nephrosis (degenerative) a. Lipoid (Epstein) b. Toxic-of pregnancy c. Heavy metals (mercury, etc.) d. Crush syndrome 3. Nephropathies-vascular basis a. Arteriolosclerotic nephrosclerosis b. Arteriosclerotic nephrosclerosis c. Orthostatic albuminuria d. Back pressure (passive congestion) SURGICAL
1. Obstructive lesions to urinary flow
A. Intrarenal a. In collecting tubules Post-transfusions hemoglobin reaction. b. In distal collecting tubules in crush syndrolne B. Extrarenal a. Ureter, bladder and urethra Resulting in: Pyelitis Pyelonephritis Atrophic pyelonephritis Infected hydronephrosis Pyonephrosis 2. Infections A. Nonspecific or pyogenic Route in invasion a. Hematogenous 1. Massive blood stream infection leading to miliary abscesses. 2. Infection following urinary stasis. b. Lymphogenous-ascending infections Localized infections of urinary tract. c. Retrograde Incompetent ureterovesical sphlDcter. B. Specific-tuberculosis
The term "nephritis" is used to connote a nonsuppurative inflammatory process primarily involving the glomeruli but capable of affecting the renal tubules secondarily to a minor degree. This nonsuppurative inHammatory process is not due to direct bacterial invasion, but rather to a reaction of the kidney elements to specific bacterial toxins, notably streptococcal. The resulting lesions in the kidney are noted bilaterally in the parenchyma because the bacterial toxin circulates in the blood stream. Since all the glomeruli do not function simultaneously, a varying degree of involvement and toxic reaction to the total number of glomeruli may be observed. It is a well established fact that such frequently ,.observed conditions as tonsillitis, scarlet fever, rheumatic fever, ery~ipelas and even the "common cold" predispose to the development of bephritis. The fundamental pathological changes to be found in nephritis or glomerulonephritis are threefold. The initial lesion is one of hemor-
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L. E. MCCREA, E. W. CLAWATER, JR., H. F. WARNER
rhage. Later changes are those of proliferation, degeneration and necrosis, and in the third or terminal stage of this process advanced sclerosis of the kidney elements becomes evident. THE ACUTE OR FIRST STAGE OF GLOMERULONEPHRITIS
The presence of acute diffuse glomerulonephritis becomes apparent when a child or young adult presents a marked puffiness around the eyes, edema of the extremities, a mild- degree of hypertension, and urine Date
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12 -11-46
12. .... 12-46
P.M. A.M. P.M. A.M. P.M. A.M. P.M. A.M. P.M. A.M. P.M. A.M. P.M. 8 12 48 12 4 8 12 4 8 12 4 8 12 4 8 12 4 8 12 48 12 ~ 8 12 <4 8 12 .. 8 12 .. 8 12 .. 8 12
Fig. 214.-Temperature chart. Acute glomerulonephritis. E. D., aged 7 years. Sore throat, fever, cervical adenopathy two weeks prior to admission. Persistent temperature of 100-104. Generalized convulsions morning of admission. Convulsions recurred every two to three hours for twenty hours. Physical examination: blood pressure 148/120, pharynx injected, tonsils hypertrophied; mentally disoriented; no edema; catheterized urine was reddish. brown; 4 plus albumin, many granular casts, many red and white blood cells. Hemoglobin 9 gmt Red blood count, 2.87; white blood count 39,000; blood urea nitrogen 23; carbon dioxide 46. 0
that is ~~smoky" in appearance. It is usual that such a s.eries of symptoms may follow an acute streptococcal infection of the tonsils, an attack of scarlet fever, rheumatic fever or erysipelas. Characteristically in this clinical picture there is a latent period, of varying length, between the predisposing infection and the onset of acute glomerulonephritis. These classical symptoms have been considered diagnostic, but additional symptoms such as nausea, vomiting, mild fever, malaise and anorexia often accompany the onset of glomerulonephritis. The urine described as "smoky" on examination, is found to be scanty in quantity and to
NEPHRITIS AND NEPHROSIS
1507
contain red blood cells, blood casts, white blood cells, varying amounts of albumin and is usually rather concentrated. The specific gravity has been observed in instances to range from 1.022 to 1.026 gm. Oliguria and anuria are found commonly in the acute stage of glomerulonephritis (Fig. 214). The clinical picture presented by the patient does not always follow the classical pattern and it not infrequently occurs that differentiation from other pathological conditions is imperative. The differential diagnosis must include such problems as (1) orthostatic albuminuria; (2) the fever state with accompanying dehydration and albuminuria; and (3) surgical problems of renal pathology such as calculus, neoplasia, pyelonephritis and tuberculous infection. Orthostatic albuminuria in the tall angular adolescent is not accompanied by hematuria or the febrile state. Confusion is unlikely. The chronicity of a toxic, febrile dehydration state serves to differentiate this type of albuminuria from any acute process. 'A carefully elicited history and a meticulous physical examination will aid in establishing th'e origin of the extrinsic causes of hematuria. In instances of doubt in establishing an accurate diagnosis, intravenous urography may be considered the procedure of choice, for the purpose of demonstrating renal function or the' presence of obstructive uropathy. Cystoscopic examination with catheterization of individual ureters may be of value in those difficult cases with diminished urinary output and poor kidney function. It is imperative that the early recognition of the acute phase of glomerulonephritis be made and that accepted types of therapy be instituted to prevent the progression through the advanced phases of the pathological process. Despite rigorous enforcement of therapeutic criteria, the acute process may proceed into the subacute, and subsequently pass into the chronic stage. It has been estimated that this progression occurs in 26.8 to 32 per cent of all cases. Such progression of events may take place in a very short period of time. The development of the more advanced forIl) of glomerulonephritis, the degenerative or necrotic phase, may occur in two to three months in some instances. THE SUBACUTE OR SECOND STAGE OF GLOMERULONEPHRITIS
Symptoms of the sec.ond stage of progression include a marked albuminuria and a generalized edema of subcutaneous tissues and serous cavities. Hypertension becomes a very important symptom when associated with this stage of glomerulonephritis. There is a lowering of the total blood proteins through a marked and constant albuminuria. There is also nitrogenous retention. Some of the more constant urinary findings of the acute stage remain present during this stage of progression. It is not uncommon during the subacute stage that red blood cells, blood casts, hyaline casts and debris are observed on microscopic examination of the urine.
1508
L. E. MCCREA, E. W. CLAWATER, JR., H. F. WARNER
In addition, extrarenal changes associated with this stage of degeneration may be observed. The colloid osmotic pressure is lowered by a loss of total plasma proteins through the marked albuminuria. The .albumin ·fraction of the protein is lost more rapidly than the globulin fraction, resulting in a reversal of the normal albumin-globulin ratio. The retention of the larger globulin molecule is the mechanism whereby the colloid osmotic pressure is lowered. This protein derangement leads to furth,er chemical imbalance with a shift of the electrolytes and a retention of the sodium ion, and art actual water retention- occurs. This mechanism is known as. the edema of hypoproteinemia. Secondary anemia. is usually marked in the subacute stage. This type of anemia is caused by the constant loss of red blood cells through·the filter beds of the kidney, as· well as. seepage and· extravasation of the blood through an increasingly permeable,capillary network. It has also been considered by some investigators that there is an actual depression' of erythropoiesis. Hypertension may develop to such an extent as to playa definite role in.the loss of cardiac efficiency and the development of conge_stive failure. Nitrogen retention, as measured by the nonprotein. nitrogen values, becomes increased; but the blood urea nitrogen levels are usually found to be normal, or relatively so. The hypertension and the nitrogen retention are noted to be outstanding symptoms of renal impairment, and almost·without exception, contribute to an early death in the third or chronic phase of glomerulonephritis. THE TERMINAL OR TmRD STAGE OF GLOMERULONEPHRITIS
The third stage of this pathological progression of glomerulonephritis is marked by the symptomatology commensurate with extreme sclerosis of the renal arterioles. Renal failure is caused by the fibrosis and contraction -of the previously damaged areas. of the kidney into well defined scar tissue (Fig. 215). There is marked diminution in kidney function; development of severe degrees of hypertension, and excessive nitrogen retention occurs. The terminal stage ·is uremia, acidosis and congested cardiac failure. The progressive ravages of· this destructive process are gradual. It may also be said that the symptomatology is similarly insidious. It may be seen that considerable renal damage may have occurred with relatively few gross manifestations, until extensive parenchymal destruction and impending uremia is evident. Hypertension of severe degree is the outstanding symptom of the chronic stage. 'The systolic pressure usually rises to a level of about 200 mm. of mercury, while the diastolic pressure is persistently elevated above 100 mID. There are many theories for this elevation of blood pressure. The most logical theory states that an increase in the .blood pressure is necessary to force blood through a badly damaged filter process of the kidney. It is known that the total number of normal functioning
NEPHRITIS AND NEPHROSIS
1509
glomeruli has been materially reduced by this sclerosing process. Com.. pensatory kidney function must be maintained by the remaining normal or partially damaged glomeruli. Ocular changes, even to the point of temporary blindness, are not uncommon. Urinary findings of the tertiary stage reveal a fixed specific gravity -due tolhe failure of the concentrating ability of the kidney. This inabil.. ity'is revealed by the Mosenthal or the Fishberg concentration tests. There is an increase in the quantity of urine excreted, and particularly an increase in the night volume. A marked albuminuria due to impaired filtration processes is always present. Microscopic examination of· the urine reveals a persistence of hyaline and granular casts admixed with
Fig. 215.-Glomerulonephritis.. J>hotoulicrograph showing sclerosis of glomeruli. This is' the microscopic picture presented in the final stage - of glomerulonephritis. -(Photomicrograph by Dr. Edwin S.Gault.)
- leukocytes and red blood cells. Secondary anemia is constant and is more apparent than in the preceding stages. Edema is constant through.. out the advancing progression. The edema increases due: to the constant lowering in the serum protein level and -to the adyancing renal failure. Uremia rapidly follows nitrogen retention and increases. in intensity with continueddehydfation and nutritionalloss. As the degree of uremia progre~s~s, acidosis increases desp~te rigorous therapy. TREATMENT OF GLOMERULONEPHRITIS
The treatment of glomerulonephritis -is divided according to the stage or-phase -present. In each sta.ge, therapy is directed toward relief. of symptoms and the. attempted establishment· {)f' normal renal funetion.
1510
L. E. MCCREA, E. W. CLAWATER, JR., H. F. WARNER
The essentials of the treatment of acute diffuse glomerulonephritis are absolute bed rest and adequate dietary intake. Bed rest should be maintained until there is complete absence of red blood cells in the urine, although it is a definitely known fact that microscopic hematuria may persist for months. Periorbital edema and hypertension usually tend to subside withiQ a few weeks after institution of bed rest. The dietary management should consist of a high protein, high carbohydrate regimen. Meat, cheese, eggs, milk and cream should be encouraged at every meal. A total caloric intake of 2200 to 2500 calories per day should be instituted if possible. Salt should be withheld since numerous investigators have shown that the sodium ion in the edema state is responsible for the binding of water in the intracellular spaces. Fluid intake should be increased to a total of 2000 to 2500 cc. daily. The regimen of a high protein, acid ash, salt-poor, hydration program appears to be the most efficacious. Supplemental vitamins should be given orally. The methods of treating oliguria and anuria accompanying the acute phase are neither specific nor satisfactory. Lower urinary tract obstruction should be ruled out by catheterization. Measures to increase the urinary output should be instituted whenever possible. The use of weak coffee, undiluted tea and fruit juices should be encouraged. The intravenous use of 50 per cent dextrose may temporarily increase urinary flow. Since marked anuria is thought to be caused by a swelling of the renal parenchyma against its outer capsule, it is considered that a decrease in blood flow through the glomerular filtration bed occurs. To combat this, surgical decapsulation, or splitting of the kidney capsule, has been advocated by some investigators. It is considered that decapsulation releases the intravenal pressure and permits an increase of the blood How through the filter. In our considered opinion such a procedure has not proved worthy of consideration. The treatment of chronic glomerulonephritis is equally nonspecific. Symptomatic relief is all that can be attempted. The edema of the third or chronic phase is considered to be due to a lowering of the total serum proteins with an increase in the globulin fraction and a lowering of the albumin fraction. This is manifest by a marked albuminuria. Correction of this discrepancy is the aim of the therapy davocated. A high protein diet is advised. A total of four or five grams of protein per kilogram of body weight is thought adequate. Dairy products, lean meats and eggs are suggested. Contrary to the popular conception, the sodium ion, rather than the harmless chloride ion, is responsible for the binding of water in intracellular spaces. In this phase of the disease, the use of salt is to be discouraged. Seasoning substitutes slIch as potassium chloride or salt-free mustard may be used. It has been demonstrated that the use .of strong diuretics is contra-
NEPHRITIS AND NEPHROSIS
1511
. indicated. The use of xanthines is not recommended. Proper chemical and fluid balance is usually more effective. A charted record of the fluid intake and output of the patient is essential to proper management. The secondary anemia of this phase of glomerulonephritis has been found to respond very poorly to the usual hematinics such as iron and liver. Whole blood transfusions are preferred, although the result is only temporary. The terminal stage of chronic glomerulonephritis necessitated the use of such drugs as digitalis for the failing myocardium, aminophylline and ammonium chloride for pulmonary and hepatic congestion, and oral and parenteral measures such as increased fluid to combat the rapidly developing acidosis. It may be seen that acute glomerulonephritis, if untreated and uncontrolled, progresses through successive stages to almost complete fibrosis of the excretory elements of the kidney. Never at any time during the advancing degeneration and ultimate sclerosis is true evidence of pyogenic infection present. These negative findings are in contrast to the findings in the "surgical"or pyogenic infection of the kidney. Unlike glomerulonephritis, the pyogenic infection presents on inception the characteristics of infection. Destruction of the kidney occurs in each clinical entity yet, pathologically, a contrasting picture is presented. The end result of the advancing sclerosis process is much slower and often more insidious in glomerulonephritis than the suppurative process seen in pyogenic infection of the kidney. PYOGENIC INFECTIONS OF THE KIDNEY
The "surgical kidney" is the kidney of focal suppuration. There are five phases, each a progression to the other: (1) pyelitis, (2) pyelonephritis, (3) atrophic pyelonephritis, (4) infected hydronephrosis, and (5) pyonephrosis. It may be seen that infection, if permitted to remain and progress, tends to produc~ one common end, destruction of the kidney. The Bacillus coli is the most frequent offending organism. According to Kidd, the organism is responsible for approximately 98 per cent of the infections of the kidney. The Staphylococcus aureus or albus or the streptococcus is the infecting organism in approximately 2 per cent. T~e Bacillus proteus may on rare occasions be the infecting organism. There are three primary modes of entry of these bacteria into the kidney: (1) hematogenous, (2) lymphogenous, and (3) urogenous. 1. The hematogenous route is the most frequent route by which bacteria enter the kidney, and is the result of the direct implantation of bacteria from far distant foci of infection. These foci may be infected teeth, tonsils, sinuses, the skin, gall bladder or intestine. Bacteremia due to the Bacillus coli not infrequently accompanies colitis or appendicitis. Bacteremia may also follow the passage of a urethral instrument in the presence of a similar infection in the lower urinary tract. 2. Infection of the kidney by the lymphogenous route may occur. It is believed
1512
L. E. MCCREA, E. W. CLAWAlTER, JR., H. F. WARNER
by some investigators that infection traversing primarily the lower lymphatics is carried through the thoracic duct into the general circulation and then to the kidney rather than directly up the lymphatics surrounding the individual ureter. It is considered possible for the infection to traverse the periureteral lymphatics and invade the kidney. This periureteral route is believed to be the method of spread of the so-called "ascending infections." 3. The urogenous or retrograde route of the spread of infection occurs within the ureteral lumen. The retrograde ascension to the kidney is considered to be due to vesico-ureteral reflex caused by an incompetent ureterovesicle sphincter. Neurogenic dysfunction of the bladder, congenital anomalous obstruction of the lower urinary tract, or malignant infiltration of the trigone produce obstruction which may result in this reflux.
The secondary factors favoring infection of the kidney are obstruction and trauma which result in stasis to the urinary How. Obstruction may occur at any point in the urinary tract from the tip of the urethral meatus
. /:CIO~ . Obstruction
Infection
CYCLE OF
StaSiS
URINARY TRACT INfECTION
LoUlered Mucosal ~ Ischemia of Resistance the Mucosa Fig. 216.-Diagram illustrating the vicious cycle of urinary tract infection following obstructive uropathy.
to the collecting tubules within the kidney. Obstruction as a causative factor in kidney infection is generally recognized as producing a vicious cycle: obstruction-statis-ischemia of the mucosa-lowered mucosal resistance-infection (Fig. 216). It is believed that the ischemia produced by stasis in the urinary tract is always a predisposing factor to infection. Trauma to the kidney, regardless of its nature, is an accessory factor in the production of infection. This trauma may be the result of a direct blow to the kidney, obstructive uropathy, the passage of a calculus, bacterial toxins or chemical toxins which are excreted by the kidney. The trauma results in a lowering of local resistance which creates a favorable area for bacterial invasion. It is obvious that infection is the basis of focal suppuration of the kidney. Pyelitis, if permitted to continue unhampered and untreated, will progress through successive stages of infection until destruction of the kidney results and pyonephrosis occurs.
NEPHRITIS AND NEPHROSIS
1513
PYELITIS
Pyelitis, per se, is a doubtful pathological or clinical entity. The term denotes an acute or chronic inflammatory process limited in its extent to the renal pelvis. It has not been proved conclusively in the majority of instances that the infection is present without coexisting medullary or cortical involvement. It is a well established fact that the disease is present with a minimal involvement of the renal parenchyma. In the hematogenous and in the lymphogenous routes of extension, the infection originates in the renal parenchyma and rapidly extends to the pelvis. In the retrograde route of extension, the renal pelvis is primarily involved and this involvement is followed by rapid spread to the parenchyma. Pathologically the renal pelvis in pyelitis shows a hyperemic injected mucosa irregularly studded with petechial hemorrhages. There is also an exudate composed of cellular debris and pus cells loosely held together by a network of fibrin. The mucous membrane is thickened and contains dilated capillaries and is infiltrated with polymorphonuclear leukocytes. This coexists with minute cortical abscesses or linear infiltrations of polymorphonuclear leukocytes and round cells in the stroma between the tubules of the pyramids. This is in reality the earliest stage of pyelonephritis and cannot be differentiated clinically from pyelitis. . PYELONEPHRITIS
The second phase of focal suppuration is pyelonephritis. Pyelonephritis may be acute or chronic. In the acute hematogenous type the renal cortex shows the major involvement while the pelvis shows minimal change. Pathologically the cut surface of the kidney is studded with varying sized areas of hemorrhage or small raised nodules which have a yellowish center surrounded by an intensely red areola. There are also wedge-shaped areas, dark red in color, mottled with areas of suppuration. These areas are caused by venous thrombosis along the path of spread of the infection and are known as B7ewer's septic infarcts. At the time of inception of the acute ascending lymphogenous type, the renal pelvis sho\vs a greater involvement than does the parenchyma. The mucous membrane of the renal pelvis mirrors the infection approximately twenty-four hours earlier than the remainder of the ki;dney. The mucous membrane of the pelvis is edematous, injected, and is studded with petechial hemorrhages. The process in the kidney shows minute abscesses and multiple minute hemorrhages lying on the pyramids between the tubules or located in the cortex. It is possible for the cortical abscesses to coalesce and form a renal carbuncle or to rupture through the capsule and cause a perinephritic abscess. Perinephritic abscess usually follows the staphylococcic infections of the kidney. The clinical picture of acute pyelonephritis is one of a sudden onset of sharp, stabbing pain at the costovertebral angle associated with chills
1514
L. E. MCCREA, E. W. CLAWATER, JR., H. F. WARNER
and fever (Fig. 217). The patient may complain of generalized malaise, and occasionally of nausea and vomiting. Within seventy-two to ninetysix hours this syndrome may be associated with the secondary symptoms of bladder infection such as urgency, frequency and pyuria. Examination of the urine shows a normal specific gravity, an acid pH, mild albuminuria, many pus cells, a few red blood cells and numerous bacteria. Bacteriological examination of the urine shows B. coli to be the most frequent causative organism. The albuminuria is due to the abnormal constituents present in the urine such as pus and red blood cells. The red blood cells are present due to the hemorrhage from the mucous .oat. A.M. P.M. A.tl1~ P.M. A.M. P.M. A.'''. P.M. A.M. P.M. A.M. P.M. A.M. P.M~ .. 8 12 48 12 .. 8 12 .. 8 12 4 8 12 .. 8 12 .. 8 12 .. 8 12 .. 8 12 .. 8 12 .. 8 12 .. 8 12 .. 8 12 .. 8 12
lio",
108° 106° 104° '~
.
103°
~
=
::I
i102°
&
!
1'-101°
:~
:
1 -
1000 99° Normal
98°
:~
qr
Fig. 217.-Temperature chart. Acute pyelonephritis. M. S., aged 39. Sudden chills, fever, pain at costovertebral angle. Urine culture revealed B. coli. Catheterized urine: few red blood cells, innumerable pus cells.
membrane of the renal pelvis, and are usually microscopic in amount. In the acute stage there is a leukocytosis. Renal function tests such as phenolsulfonphthalein are of no material value as such tests are not sufficiently sensitive. Intravenous urography may be of considerable aid and is not contraindicated at any stage of the disease. It is valuable in determining the presence or absence of obstructive uropathy. While a grossly normal urogram does not exclude the presence of acute inflammation, an abnormal urogram which shows blunting and distortion of the calices is of marked value in diagnosing chronic pyelonephritis. Valuable information as to kidney function and the presence of congenital anomalies is
NEPIllUTIS AND NEPHROSIS
1515
also obtained by intravenous urography. Intravenous urography is always done before cystoscopic examination or retrograde pyelography is attempted. Cystoscopic procedures are never done in the acute stage of pyelonephritis. Much valuable information may be obtained from cystoscopic examination and/or ureteral catheterization in the subacute stage after the fever 'and generalized symptoms have subsided. Catheterization of the ureter reveals the presence or absence of any obstructive factors. The urine obtained from the catheter may be studied for bacterial growth. Individual kidney function is obtained by the use of indigo car.. mine or phenolsulfonphthalein. The acute infection either subsides leaving very little residual or develops into the chronic stage which may be followed by acute exacerbations of chills, fever, pyuria, slight tenderness in the costovertebral angle arid low-grade lumbar pain. Chronic pyelonephritis either heals or may progress into the stage of atrophic pyelonephritis. ATROPHIC PYELONEPHRITIS
Atrophic pyelonephritis may be defined as a contracted, scarred kid.. ney resulting from infection and abscess formation in the absence of obstruction. The kidney is usually reduced to one third or one fourth its normal size. There is usually marked scar formation, as the capsule is markedly thickened and fibrous. Atrophic pyelonephritis is usually unilateral. The clinical picture is that of acute pyelonephritis which subsided. It is usual that a sense of heaviness in the lumbar area is experienced and intermittent pyuria is noted by the patient. Hematuria does not occur, although albuminuria may be present. The urine usually shows a culture of B. coli or a mixed infection on bacteriological exam.. ination. Intravenous urogram reveals a diminution or a complete lack of function on the affected side. When visualized, the renal pelvis and calices are usually contracted and irregular. The kidney is usually decreased in size. INFECTED HYDRONEPHROSIS
Infected hydronephrosis begins as a diffuse pyelonephritis with dilatation of the pelvis and calices. As the condition advances, secondary pressure atrophy occurs, resulting in cessation of excretory function.AIn infected hydronephrosis the parenchyma is compressed but not destroyed, the abolished- function resulting from pressure atrophy. Throughout this compressed parenchyma, a diffuse pyelonephritis'may be seen on microscopic examination. The condition tends to follow any variety of obstructive uropathy, particularly those obstructive factors affecting the ureter. If the obstruction to the ureter is complete, pyuria does not occur. Intermittent or constant pyuria, and bacilluria ate usually present. There may be occasional hematuria. If the condition is
1516
L. E. MCCREA, E. W. CLAWATER, JR., H.
}i'.
WARNER
bilateral and extensive, there may be retention of nitrogenous waste products in the blood. Frequency, urgency, dysuria and nocturia are generally present due to an associated cystitis. There is diminution in the per~entage excretion of phenolsulfonphthalein. Intravenous' urography reveals eith~r anonfunctioning kidney or hydronephrosis. Cystoscopic exarriina~ion reveals the degree .of cystitis, if present, and· the presenC'e or absenceo£ obstructive uropathy. Retrograde pyelography demonstrates a hydronephrotic kidney. TIle ·condition if. permitted to progress' gradually passes to the, terminal phase 6f kidney destructionpyonephrosis. . PYONEPHROSIS
The pyonephrotic kidney is the final stage of progress~ve destruction ~esulting from in~ec~on. Th:ekidney 'in pyonephrosis becomes a func-
Fig. 218.-Pyonephrosis. Retrograde pyelogram showing complete destructiQD of Ule kidney. Note the shaggy appearance outlined by the radiopaque medium. This is the picture presented in the ·'end stage. of uncontrolled pyogenic renal infection. ' '
tionless, distended, thin-walled bag filled with thick, creamy pus. Clini-, cally· the patient .may complain of backache, tenderness in the loin, recurrent attacks of chills and fever following acute attacks of pain. There may be recurrent .symptoms of cystitis. Urine examination reveals
NEPHRITIS AND NEPHROSIS
1517
pyuria and bacilluria. Hematuria seldom occurs. The pyonephrotic kidney shows a reduced or complete lack of function as shown by phenolsu~fonphthalein and indigo carmine excretion.Urographic studies show . loss of form and contour of the pelvis and calices which is considered . ,·typical of pyonephrotiqdestruction .( Fig. 218).. The management of the ':':surgical" or infected _kidney is _primarily directed toward the elimination of the disease in its early phase before the sequ~nce of events leading to total destruction of the renal parenchyma occurs. The early management is directed to· eradication of all foci of infection, removal of obstructive factors and the institution of normal urinary drainage. Since the Bacillus coli is the pri~ary offend~ ing organism, alkalinization of the urine by· potassium citrate and soda .bicarbonate is indicated to create a medium unfavorable to itsgrQwth. 1£ the offending organism is the staphylococcus or streptococcus, suI.. fonamide and/or penicillin therapy is-the treatment of choice. AciQi6.ca~ tion of the urine with sodium acid phosphate or, ammonium chlQride is indicated in those infections caused by the BacUluspr<;>teus. Streptomycin,although unproven, holds great promise ·in the· treatment of the gram-negative bacillae. _An adequ~te fluid and dietary regimen should be- maintained. In the -later phases of the disease; -therapy should be directed toward improvem·ent of the patienfs general condition, and the surgical removal of the -diseased kidney. Adv~ncing kidney. disease whethef -described asglomerulonephrltis Of· pyogenic infection has a common goal-destruction of the kidney. It is imperative that early recognition and institution of treatment be inaugurated to check or eradicate the 'constant trend and advancing tendency to kidney destrn,ctlon so characteristic of each condition.