Urinary system

Introduction

The urinary tract comprises the kidneys, pelvicalyceal systems, ureters, bladder and urethra. The kidney is responsible for excretion of the waste products of metabolism, the waste products being excreted in the form of an aqueous solution called urine . Urine passes from the kidneys into the pelvicalyceal systems and thence via the ureters to the bladder, which acts as a reservoir. Urine is held in the bladder by a series of muscular sphincters until sufficient volume has accumulated. Relaxation of the sphincters and contraction of smooth muscle in the bladder wall allows the urine to be voided to the exterior through the urethra (micturition) at a convenient time.

The kidney

The kidney is divided into two main anatomical divisions, the cortex and medulla ( E-Fig. 15.1 H ). Disorders of the kidney may affect either of these zones, but diseases affecting one part will often have secondary effects on the other component. Disorders may arise from a wide range of pathological causes, many of which are common in other organ systems (e.g. infections, tumours, drug reactions, vascular disorders). However, the kidney is unusual in that it is much more prone to immunological disorders than most other organs. Vascular diseases such as hypertension, diabetes mellitus and vasculitis may also have profound effects on renal function. Disorders of the kidney can be conveniently divided into categories according to which structural component of the kidney is primarily affected:

Diseases of the glomerulus

Glomerular disorders arise from a variety of causes; the two major causes being immunological (including disorders confined to the kidney and some systemic diseases) and metabolic (the most important being diabetes mellitus). It is confusing to many students that there is not a direct one-to-one relationship between a particular mechanism of damage and a particular histological appearance and/or clinical syndrome. In fact, most causes of glomerular damage will give rise to one of several clinical presentations, summarised in Table 15.1 , along with the diseases with which they are most commonly associated. Acute and chronic renal failure are described above and may supervene in any of the above conditions. For example, an individual with a severe nephritic syndrome may progress quickly to acute renal failure or an individual with undiagnosed diabetes mellitus, who has had undetected proteinuria for some time, may first be diagnosed with chronic renal failure.

Glomerulonephritis

Most types of GN are caused by immune complex deposition in the glomerulus. This applies to primary GN , where the condition is confined to the kidney (e.g. membranous nephropathy , membranoproliferative GN ), and to diseases with a systemic component (e.g. Goodpasture’s syndrome , SLE , Henoch-Schönlein purpura ).

The site of immune complex deposition is dependent on the size of the complexes, which is in turn dependent on the type of antigen and on the class of immunoglobulin produced, i.e. the host response. The antigen may be either a normal component of the body (a self antigen as in Goodpasture’s) or an external antigen such as a bacterial product (as in post-streptococcal GN ). Immune complexes may be deposited from the circulating blood or may be formed in situ. In the latter situation, the complexes may involve intrinsic glomerular antigens (basement membrane components in Goodpasture’s) or antigens that have been deposited there from the circulation (e.g. DNA in the case of SLE). An important exception to this rule is minimal change nephropathy where the podocytes are thought to be damaged by a cell-mediated immune response, rather than by immune complex deposition.

Whatever the mechanism of damage to the glomerulus, the various immunological insults alter the structure and therefore the function of the glomerulus and ultimately of the nephron as a whole.

In response to damaging stimuli, the glomerulus appears to react in one or more of the following ways:

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  Swelling and/or proliferation of the normally flat endothelial cells lining the glomerular capillaries

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  Proliferation of the epithelial cells investing the outer surface of the glomerular capillary tuft (the podocytes ( E-Fig. 15.4 H ) and the cells lining Bowman’s capsule (crescent formation)

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  Thickening of glomerular basement membranes ( E-Fig. 15.5 H )

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  Proliferation of the cells of the mesangium and excessive production of acellular mesangial material

These reactions give rise to various histological patterns of GN, which can be identified by light microscopy. This is then put together with the immunofluorescence and electron microscopy findings, clinical history and other investigations to come to a definitive diagnosis. As in many other areas of histopathology, good communication between pathologists and clinicians is vital to arrive at an accurate diagnosis, which is essential for appropriate treatment.

Patterns of GN may be described as:

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  Diffuse: affecting all glomeruli

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  Focal: affecting some glomeruli

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  Global: the entire glomerulus is abnormal

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  Segmental: only part of the glomerulus is abnormal

We shall now consider some specific examples of GN, reviewing the typical histological and immunofluorescence patterns and their associated clinical presentations. As indicated in Table 15.1 , some diseases may present clinically in several different ways, with nephritic or nephritic features or even combinations of these.

For convenience, we shall begin with disorders which typically give rise to acute nephritic features ( acute diffuse proliferative GN ; Fig. 15.2 and necrotising GN ; Fig. 15.3 ) followed by those with mixed patterns of haematuria and proteinuria ( mesangial proliferative GN ; Fig. 15.4 and membranoproliferative GN ; Fig. 15.5 ) and then important causes of nephrotic syndrome ( membranous GN ; Fig. 15.6 , focal segmental glomerulosclerosis ; Fig. 15.7 and minimal change disease ; Fig. 15.8 ).

At the end of this section on glomerular diseases, we shall consider the typical changes of diabetes mellitus in the kidney ( Fig. 15.9 ) and the features of renal amyloidosis ( Fig. 15.10 ). It is worth bearing in mind that primary GN is a relatively rare disease, whilst diabetes and hypertension together account for the bulk of clinically important renal dysfunction in developed counties; in the developing world, toxins and infections are also very important factors in the burden of chronic renal disease.

Disorders of the renal tubules and interstitium

The tubules and interstitium may be primarily damaged as a result of hypovolaemic shock, by inorganic and organic toxins or as the result of infection. In hypovolaemic states and intoxication, tubular epithelial cells may exhibit marked cytoplasmic degenerative changes or frank necrosis leading to the pathological term acute tubular necrosis ( Fig. 15.12 ) and producing the clinical syndrome of acute renal failure. Tubular epithelial cells have considerable powers of recovery and regeneration and acute renal failure may be reversible under such circumstances if the patient can be sustained in the interim by dialysis and other supportive measures.

Another increasingly important cause of tubulo-interstitial disease is drug toxicity giving rise to interstitial nephritis ( Fig. 15.13 ). In this condition, a large number of drugs have been implicated including certain antibiotics, non-steroidal anti-inflammatory drugs, thiazide diuretics and proton pump inhibitors. Onset may be acute or chronic. There is a mixed inflammatory infiltrate in the interstitium in which eosinophils may be prominent. Tubular damage occurs and the condition may proceed to chronic renal failure.

Infections of the kidney include acute and chronic pyelonephritis and tuberculosis (see Ch. 5 ). Acute suppurative bacterial infections of the kidney ( pyelonephritis ) usually follow ascending infection from the lower urinary tract, particularly when there is obstruction to urinary outflow such as in benign prostatic hyperplasia or pressure from the fetus in pregnancy; in such cases, coliform organisms (such as Escherichia coli and Proteus species) are the most frequent infecting agents. Infection may also spread to the kidney by the haematogenous route during episodes of bacteraemia. Acute pyelonephritis may be complicated by the development of papillary necrosis ( Fig. 15.14 ) or pus accumulation in a dilated, obstructed pelvicalyceal system ( pyonephrosis ) . Acute pyelonephritis is illustrated in Fig. 15.11 . Tuberculous infection of the kidneys and lower urinary tract may also arise by similar routes of spread.

Patients with urinary reflux or obstruction are prone to develop recurrent pyelonephritis Repeated attacks lead to scarring and after many episodes the kidney becomes coarsely scarred, a phenomenon termed chronic pyelonephritis .

Vascular disorders

The kidney is especially vulnerable to the effects of arterial hypertension as illustrated in Figs 11.1 and 11.2 , and irreversible damage to nephrons may result either acutely from accelerated (malignant) hypertension or progressively over a period of years in benign (essential) hypertension.

Hypertensive nephrosclerosis resulting from benign (essential) hypertension is illustrated in Fig. 15.15 . Malignant or accelerated hypertension causes a different pattern of renal damage, similar to the changes seen in acute scleroderma , and may result in acute renal failure. In reality, hypertension cannot be neatly divided into essential and accelerated types; individuals who have had mild hypertension for many years may progress quite suddenly to very high blood pressures that put eyesight, kidneys and other organs at severe risk. This is especially the case where the individual has underlying renal disease that progresses. Other individuals may develop accelerated hypertension out of the blue.

Various forms of vasculitis may also affect the kidney, including polyarteritis nodosa (see Fig. 11.6 ) and those associated with antineutrophil cytoplasmic antibody (ANCA) such as granulomatosis with polyangiitis (previously known as Wegener’s granulomatosis) and microscopic polyarteritis (see Fig.11.7 ).

Small infarcts of the renal cortex are common in patients with the above vascular disorders. They are usually seen as incidental findings in kidneys removed for other reasons (e.g. tumours). The infarcts are usually seen as wedge-shaped pale scars with the base abutting the renal capsule, although they may be seen in any stage of infarction (see Fig. 10.1 ). In kidneys with extensive infarcts, the cortical surface is pitted and the kidney is shrunken. In rare cases, abrupt interruption to the blood supply, such as renal artery thrombosis, may lead to renal cortical infarction where the entire renal cortex undergoes coagulative necrosis. The renal medulla is much more resistant to ischaemia.

Tumours of the kidney

A range of benign and malignant tumours occurs in the kidney and many are unique to the kidney. Benign tumours include papillary adenoma , a fairly common incidental finding in nephrectomy specimens, oncocytoma , illustrated in Fig. 15.17 , and angiomyolipoma , shown in Fig. 15.18 .

The most common and important malignant renal tumour in adults is renal cell carcinoma. Several subtypes are recognised and some of the more common variants are illustrated in Fig. 15.19 . One of its important methods of spread is by venous invasion, typically giving rise to ‘cannon ball’ lung metastases and often bone metastases.

Our understanding of renal tumour pathology has been transformed in recent years by the use of new molecular techniques. Classification is now based upon a combination of histological appearances, immunohistochemical findings and the presence of typical genetic changes in certain tumour types. For example, papillary renal cell carcinomas typically show gains of chromosomes 7 and/or 17, as well as loss of the Y chromosome. These new investigative techniques have also revealed a range of rare but important hereditary renal cell carcinomas.

The kidney is the site of an important malignant tumour of children, nephroblastoma or Wilms’ tumour ( Fig. 15.20 ); this is an example of a ‘small round blue cell tumour’ and is of embryological origin.

Diseases of the lower urinary tract

The most important disorders of the lower urinary tract are infection and neoplasia. Infections are common, but usually remain confined to the bladder (cystitis) ; ascending spread into the ureters and pelvicalyceal systems may result in renal parenchymal involvement (acute pyelonephritis) as shown in Fig. 15.11 . Persistent or repeated infection in the urinary tract predisposes to the development of urinary stones (calculi) , particularly in the bladder and pelvicalyceal systems. Infections of the urethra (urethritis) are commonly sexually transmitted, often involving the organisms N. gonorrhoeae and Chlamydia .

The pelvicalyceal system, ureters and bladder are lined by a specialised epithelium known as transitional epithelium (urothelium) ( E-Fig. 15.11 H ). Malignant tumours of the urothelium, known as transitional cell or urothelial carcinomas ( Fig. 15.22 ), are common and are of particular interest because of the possible role of chemical carcinogens such as aniline dyes in their pathogenesis. Urothelial carcinomas may be either invasive or non-invasive. Most of the deeply invasive tumours are high-grade carcinomas. Malignant tumours are probably preceded by the development of urothelial dysplasia and carcinoma in situ ( Fig. 15.21 ). Benign tumours include transitional cell papillomas and inverted papillomas .

Classification and grading of transitional cell neoplasms is complex and continues to evolve. The traditional WHO 1973 system recognised benign papillomas as well as transitional cell carcinomas of grades 1, 2 and 3. This system has some limitations as the criteria for these categories are not very well defined and a large proportion of tumours tend to be classified as grade 2. Also, some tumours that are now known to behave in a benign fashion are classified as grade 1 carcinomas. The newer WHO/ISUP 2004 system uses the term papillary urothelial neoplasm of low malignant potential (PUNLMP) for these very low grade tumours with likely benign behaviour and it splits the remaining malignant tumours into low grade and high grade groups. The two systems do not directly correspond. Despite the limitations described above, the old 1973 WHO classification remains in widespread use as a validated and reproducible system, but now it is used alongside the newer WHO/ISUP 2004 system as these are thought to provide the best prognostic information when applied in conjunction. This is illustrated in Table 15.2 .