296 ın Chapter 4. Pathophysiology of kidneys and urinary system ( I. Hul´ ) moderate and asymptomatic proteinuria. Even be- fore proteinuria appears carbohydrate intolerance is almost in all cases present. The glomerular ﬁltration 4.10 Infections of the urinary rate is normal or increased. tract When the proteinuria appears during the diabetes, glomerular ﬁltration begins to decrease. Very exact regulation of glucose level in peripheral blood can sig- niﬁcantly delay the appearence of diabetic nephropa- In most cases of urinary system infections is bac- thy. teriuria present. Bacteriuria is a condition where in the midstream urine more than 105 bacteria are 4.9.6 Hereditary glomerulopathies found. Less amount of bacteria may also indicate in- fection if the urine was obtained by catheterization or 126.96.36.199 Alport’s syndrome (hereditrary by suprapubic aspiration. Bacteriuria however, migt nephritis with deafness) be absent in some cases, thought the urinary system Pathogenesis of this condition is not known ex- infection is evident. This situation may occur follow- actly. There is a disorder of glycoprotein, non- ing or during the antibiotic treatment, during high collagenous components of glomerular and tubular urea concentration in urine and when the pH of urine capillary basement membrane synthesis. The clini- is low. cal manifestation is haematuria and proteinuria. The microscopic picture shows commonly focal and dif- 4.10.1 Cystitis, acute pyelonephritis, fuse glomerular proliferation with segmental sclero- urethritis sis. Various types of microbes might be the underlying 188.8.131.52 Fabry’s disease (hereditary dystopic cause of these diseases. Ninety per cent of acute lipidosis) urinary tract infections are caused by Escherichia coli. Further Gram-negative microbes, as Proteus, is an inherited disorder of glycosphingolipid meta- Klebsiella, Enterobacter and Pseudomonas may be bolism with accumation of trihexosylceramide in the responsible for urinary infections. They participate tissues of eye, skin, cardiovascular system and kid- in nosocomial infections. Among the Gram-positive neys. In glomeruli, tubules and in renal interstitium cocci the enterococci and staphylococcus saprophyti- typical foam cells are found with lipid vacuoles and cus occur most commonly. The viral infections may excentric location of nucleus. Clinical manifestation be the cause of cystitis and pyelonephritis. of disease are: haematuria and proteinuria with pro- Under physiological circumstances the urinary gressive development, resulting in renal failure. tract cannot be settled by micro-organisms. The urine dispose of direct antibacterial eﬀects. The high 184.108.40.206 Congenital nephrotic syndrome urea content and the high osmolarity of urine kill di- rectly the pathogenic germs. The prostatic secretion is a fatal hereditary disease, inherited as an auto- has also antibacterial activity. The polymorphonu- somal recessive trait, manifested by nephrotic syn- clear leucocytes in the urinary bladder wall also have drome in ﬁrst weeks of life. The synthesis of glomeru- a protective function. lar and tubular basement membrane components is Favorable conditions for infection arise if obstruc- pathologically altered. Large amount of proteins tion occurs. Tumors of urinary tract, urinary cal- cross the impaired basement membrane. The pro- culosis and hypertrophy of prostata may lead to hy- teinuria of non-selective type is very massive. The dronephrosis and urinary tract infections. In these disease leads to renal failure. Concomitant infection cases the concomitant infection accelerates the renal is commonly fatal. tissue destruction. Vesicoureteral reﬂux facilitates sometimes the de- velopment of infection. The reﬂux of urine may at- 4.10. Infections of the urinary tract 297 tain ureters or even renal pelvis. Reﬂux occurs most function. Patients with chronic pyelonephritis have commonly in anatomic aberrations. a history of frequent, repeated urinary outﬂow tract Renal disturbances raise the possibility of infec- infections with impaired renal functions. Their urine tions appearence. It is not known if renal hyper- contains pus, leucocyte casts and bacteria. Alter- tension accelerates the infection occurence. The dia- ations of renal pelves can be detected by excretion betic nephropathy has, however, a very close relation urography. In other cases this ﬁnding can be absent to the urinary tract infections. During the diabetic in spite of chronic pyelonephritis presence. nephropathy the chronic pyelonephritis occurs most Kidneys are of uneven magnitude, with irregu- frequently and necrosing papillitis is easily develop- lar, rugged surface. The pathologic process be- ing. Renal papillae and medulla are very receptive gins usually in renal interstitium, in medullar re- to pathogenic microorganisms. gion and in renal papillae. Fibrous tissue, lympho- Infections of urinary tract can clinically occur as cytes and plasma cells replace completely the inter- strictly deﬁned diseases. Bacteriuria per se occurs stitium and the tubules. In the interstitium, mainly also in completely asymptomatic patients. Cystitis in the medulla renis are foci of inﬂammation. In some has a rather strict clinical symptomatology. Acute tubules leucocyte casts occur, in others large amount pyelonephritis may include the symptomes of the cys- of eosinophilic material and colloid casts are found. titis and further signs as fever attacks, nausea, vom- These tubules are dilated. Proliferative arteritis may iting, diarhea and tachycardia. Leucocyte casts and be present. None of these alterations is pathognomic purulent matter are found in urine. Bacteriuria and for chronic pyelonephritis. The ﬁnding in kidneys de- pyuria may persist longtime. Haematuria is present scribed above may appear during diabetic nephropa- only at the beginning of disease. During urethral thy and many diﬀerent nephropathies. syndrome dysuric troubles are dominant. Infections The chronic pyelonephritis does not have any typ- of urinary tract in hospitalized patients occur namely ical clinical manifestation. Systemic arterial hyper- in connection with catheterization. tension is commonly found stimulating the search for the underlying cause. Patient usually visits the 4.10.2 Prostatitis doctor only when the ﬁrst signs of renal failure ap- pear: fatigue, malaise, nausea, tendency to suﬀusion Prostatitis includes various types of inﬂammatory formation, anorexia, body weight loss, polyuria and processes comprising acute and chronic inﬂamma- nycturia. The progression of pyelonephritis is accom- tions caused by speciﬁc bacteria. Clinical manifes- panied with decreased glomerular ﬁltration rate an tations are: sacralgia, and peritoneal pains. Some- reduced renal blood ﬂow. The picture of uraemia is times testicular dyscomfort and moderate dysuria developing. Proteinuria raises to 2 g/day. The renal are experienced. In additions, microscopic pyuria ability to concentrate urine decreases. Presence of and haematuria are occasionally observed. bacteria, leucocytes, leucocyte casts in urine may be The underlying cause of acute prostatitis use to only intermittent. Renal biopsy can be completely be the Gram-negative bacterial ﬂora or Staphylococ- normal. cus pyogenes aureus. It is diﬃcult to diagnose the Chronic pyelonephritis need not cause dyscomfort chronic bacterial prostatitis, because the symptomes and troubles to patients until the renal functions do are often inapparent. In uric sediment excessive leu- not impair substantially. Hypertension makes the cocyte numbre may be found. The bacteriologic ex- prognosis of patient worse. During acute infection amination however, might be negative. Dysuric dis- or dehydration the renal functions may become es- orders appear when infection reaches urinary blad- sentially impaired. The impairment can result even der. in uraemia. At the beginning is the impairment usu- ally reversible. 4.10.3 Chronic pyelonephritis 4.10.4 Papillary necrosis This term indicates the condition developing follow- ing renal infections. It can occur under the inﬂu- Renal papillae play a very important role in the ence of predisposing factors as obstructions, vesi- pathogenesis of chronic interstitial nephritis. Renal coureteral reﬂux and disorders of urinary bladder papillae have high aﬃnity to bacterial infection. It is 298 ın Chapter 4. Pathophysiology of kidneys and urinary system ( I. Hul´ ) very probable that ﬁrst occurs the papillary damage that only some of these alterations might be caused and the chronic interstitial nephritis develops later. by infection. In tubulointerstitial disturbances are Papillae may be damaged during arthritis urica, and non-bacterial factors involved, as: exogenous toxins, diabetes mellitus. Relatively frequently the papillary immunologic and metabolic disorders. lesions occur during treatment with various drugs. Tubular disturbance is manifested by impaired Some substances attain just in papillae high concen- capability of concentration of the urine, by de- trations aﬀecting with toxic action papillae and the creased reabsorption of ﬁltered solutes, especially surrounding area. The eﬀect of phenacetin – a com- of amoinoacids, phosphates, sodium, chlorides and ponent of analgesic tablets is well known. It is not potassium. Tubular alterations appear at the begin- understood exactly which substances can damage re- ning separatly, later they become concomitant. The nal papillae. It is suggested however, that the uri- structural alterations lead to the progressively re- nary tract infections might cause papillary lesions. duced glomerular ﬁltration rate. Tubulointerstitial Papillary necrosis appears when the infection is damage causes secondary glomerular disturbances of retained in renal pyramids. Participation of a fur- glomeruli and their involution. ther factor is necessary to give rise to the papillary Kidneys have to excrete unnecessary substances, necrosis. These factors are often: diabetes mellitus, toxins or drugs from the body. This is why these sub- chronic alcoholism and blood vessel diseases. stances cummulate in urine. Various medicaments, Clinical manifestations of papillary necrosis are: the antibiotics above all, can damage the renal inter- back pains, abdominal pains, and fever. Acute renal stitium. failure with oliguria or anuria can occur occasionally. A sudden impairment of renal functions in patients with diabetes mellitus or with obstruction of ureters 4.11.1 Nephropathies signalizes almost in every case the papillary necrosis. If so, fever or pains are not present. 220.127.116.11 Phenacetin nephropathy (Analgesic nephropathy) It is known that in persons taking large amounts of analgesics lesions of renal interstitium and pap- illar necrosis frequently are developing. Especially 4.11 Tubulointerstitial phenacetin and acetylosalicylic acid can cause papil- renal diseases lary necrosis. Analgesic nephropathy is characterized by pap- illary necrosis and tubulointerstitial inﬂammation. The papillary necrosis occurs usually following A large group of diseases exists aﬀecting both the tubulointerstitial inﬂammation which causes kidneys simultaneously, in which morphologic alter- glomerular ﬁltration rate decrease. ations in interstitium and in tubules are present. Papillary damage following phenacetin intake is Also the functional disturbances are limited rather due to its metabolite acetaminophen. Its concen- exclusively to the tubules and interstitium. tration in papillae is ten times higher than in re- Glomeruli and the renal vessel system are usually nal cortex. High water intake reduces papillary ac- not involved. Interstitial edema prevails in acute etaminophen concentration and protects the papil- form of these diseases, associated often with corti- lae from necrosis. Acetylosalicylic acid inhibits the cal and medullar inﬁltration by polymorphonuclear synthesis of renal prostaglandins which are impor- leucocytes. Here are the foci of celullar necrosis. In tant vasodilating factors. Thus, the acetylosalicylic chronic forms more outstanding interstitial ﬁbrosis, acids acts simultanously by its toxic and by indirect mononuclear inﬂammatory inﬁltration with signs of vasoconstrictive eﬀects increasing so the possibility atrophy are observed. The tubular lumen is dilated of renal damage appearing. and the basement membranes are thickened. In past Analgesic nephropathy is developing usually if the was this morphologic ﬁnding considered to be the daily intake of phenacetin, lasting 1 to 3 years, is 1 picture of chronic pyelonephritis. We are aware now, to 2 g.