renal system

The Renal System Dr. Mohammed Sami Saeed Ass. Prof./ Histopathologist

Normal

The kidneys function to:1. Excrete the waste products of metabolism.2. Regulate the body's concentration of water and salts.3. Maintain the appropriate acid-base balance of plasma.4. Serve as an endocrine organ secreting some hormones as  erythropoietin, renin and prostaglandins. Each human adult kidney weighs about 150 gm. Anatomically the ureter forms the pelvis which is divided into 2 or 3 major calyces, each one giving 3 or 4 minor calyces. The kidney is divided into the cortex 1.2-1.5 cm and medulla. The medulla consists of renal pyramids, the apices of which are called papillae, each related to a calyx.

Anatomy of the Kidney

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cotex

cortex
Medulla

Congenital Anomalies

About 10% of all people are born with potentially significant malformations of the urinary system. Congenital renal disease can be hereditary, but is most often the result of an acquired developmental defect that arises during gestation.

Congenital anomalies-cont

Agenesis of the kidney: Bilateral agenesis is incompatible with life, seen in stillborn. Unilateral type is uncommon. The opposite kidney is usually enlarged as a result of compensatory hypertrophy. Hypoplasia: Is failure of the kidney to develop to a normal size. This anomaly may occur bilaterally, resulting in renal failure in early childhood death. Unilateral cases are more common.


Congenital anomalies-cont
Ectopic Kidneys: These kidneys lie either just above the pelvic brim or within the pelvis. They are usually normal or slightly small in size. Because of their abnormal location, kinking or tortuoisity of the ureters may cause some obstruction to urinary outflow. Horseshoe kidneys: Fusion of upper or lower poles of the kidneys that is continuous across the midline anterior to the great vessels. This anomaly is common and is found in about 1:500 to 1000 autopsies. Ninety percent of the kidneys are fused at the lower poles.

Cystic Diseases Of The Kidney

They are heterogeneous group comprising hereditary, developmental and acquired disorders. They are important for several reasons; 1. They are reasonably common and often represent diagnostic problems for clinicians, radiologists and pathologists. 2. Some forms are major causes of chronic renal failure. 3. They can occasionally be confused with malignant tumors.  Classification; 1. Cystic renal dysplasia. 2. polycystic kidney disease a. Autosomal dominant (adult) type. b. Autosomal recessive (childhood) type.3. Medullary cystic disease. a. Medullary sponge kidney. b. Nephronophthisis. 4. Acquired (dialysis-associated) cystic disease. 5. Simple renal cyst.6. Renal cysts in hereditary malformation syndromes (e.g. Tuberous sclerosis).7. Glomerulocystic disease.8. Parasitic cysts (e.g. hydatid cyst).

Cystic Renal Dysplasia:

This sporadic disorder is due to an abnormality in metanephric differentiation,. Characterized histologically by the persistence in the kidney of abnormal structures, cartilage, undifferentiated mesenchyme and immature collecting ductules and by abnormal lobar organization. Most cases are associated with ureteropelvic obstruction, ureteral agenesis or atresia and other anomalies of the lower urinary tract. Dysplasia can be unilateral or bilateral and is almost always cystic. When unilateral, the dysplasia is discovered by the presence of flank mass. The function of the opposite kidney is normal

Autosomal Dominant (Adult) Polycystic Kidney Disease

It is characterized by multiple expanding cysts of both kidneys that ultimately destroy the renal parenchyma and cause renal failure. It affects roughly 1 of every 400 to 1000 live births and accounting for about 5-10% of cases of chronic renal failure requiring transplantation or dialysis. The mode of inheritance is autosomal dominance with high penetrance. The disease is universally bilateral.

The cysts initially involve only portions of the nephrones, so renal function is retained until about the 4th or 5th decade of life. gene mutation located on chromosome 16p (PKD1) and 4q (PKD2). Mutation of PKD1 accounts for about 85% of the cases and are associated with a more severe disease.

Morphologically

Grossly both kidneys are enlarged and may achieve enormous sizes, weights up to 4 kg for each kidney have been reported. The external surface appears to be composed solely of a mass of cysts, up to 3 to 4 cm in diameter, with no intervening parenchyma. The cysts may be filled with clear serous fluid or more usually with turbid red to brown, sometimes hemorrhagic fluid.

Clinically

Many of these patients remain asymptomatic until renal insufficiency occurs. In about 40% of cases, one to several cysts in the liver are present, which are usually asymptomatic and are derived from biliary epithelium. Cysts occur less frequently in the spleen, pancreas and lungs. Intracranial Berry aneurysms may be present and can cause death in about 4-10% of patients due to subarachnoid hemorrhage. Mitral valve prolapse occur in 20-25% of patients, but most are asymptomatic. About 40% of patients die of coronary or hypertensive heart disease, 25% of infection, 15% of ruptured Berry aneurysm or hypertensive intracranial hemorrhage.

Autosomal Recessive (Childhood) Polycystic Kidney Disease

Is rare anomaly. Perinatal, neonatal, infantile and juvenile types. The first 2 are the most common; the disease appears to be genetically homogeneous, being associated with a gene, PKHD1, that maps to chromosome region 6p2.

Morphology

The kidneys are enlarged and have a smooth external surface. On cut section, numerous small cysts in the cortex and medulla give the kidney a sponge-like appearance. The cysts are perpendicular to the cortico-medullary junction. The disease is invariably bilateral. In almost all cases, the liver has cysts with portal fibrosis as well as proliferation of portal bile ducts. Clinical Features; serious manifestations are usually present at birth, and the young infant might succumb rapidly to renal failure. Patients, who survive infancy, may develop congenital hepatic fibrosis. In older children, the hepatic picture predominates, in form of portal hypertension

Cystic Disease Of Renal Medulla:1/ Medullary Sponge Kidney

It should be restricted to lesions consisting of multiple cystic dilations of the collecting ducts in the medulla. The condition occurs in adults and is usually discovered radiologically, either as an incidental finding or sometimes in relation to secondary complications. The latter include calcifications within the dilated ducts, hematuria, infection and urinary calculi. Renal function is usually normal. Unless is there is superimposed pyelonephritis, cortical scarring is absent. The pathogenesis is unknown.

Acquired (Dialysis-Associated) Cystic Disease

The kidneys of patients on chronic dialysis, sometimes exhibit numerous cortical and medullary cysts. The cysts measure 0.5-2cm, contain clear fluid, are lined by either hyperplastic or flattened tubular epithelium and often contain calcium oxalate crystals. They probably form as a result of tubular obstruction due to interstitial fibrosis or by oxalate crystals.

Acquired (Dialysis-Associated) Cystic Disease

Most are asymptomatic, but sometimes the bleeding inside the cysts cause hematuria. The most ominous complication is the development of renal cell carcinoma in the walls of these cysts in about 7% of patients during 10 years period.

Simple Cysts

These occur as single or multiple, usually cortical. The size range from 1-10cm or more. They are translucent and filled with clear fluid. They are lined by a single layer of cuboidal or flattened epithelium. They are common postmortem findings. On occasion, hemorrhage into them may cause sudden pain, and calcification may be visible radiologically. The main importance of these cysts is in their differentiation from kidney tumors.

Glomerular Diseases:

They constitute some of the major problems in nephrology; in fact they are the most common causes of chronic renal failure in humans. Clinical manifestations; they are clustered into 5 major syndromes. 1. Acute nephritic syndrome. 2. The nephrotic syndrome 3. Asymptomatic hematuria &/or proteinuria, 4. Acute renal failure. 5. Chronic renal failure.

Schematic Representation of a Glomerular Lobe

Histologic alterations
There are 5 basic tissue reactions 1. Increased glomerular cellularity a. Proliferation of mesangial or endothelial cells. b. Leukocyte infiltration, including neutrophils, monocytes, and, in some diseases, lymphocytes. c. Formation of crescents. 2. Basement membrane thickening, best seen in sections stained with (PAS). By EM, it can be resolved as one of 2 alteration;

a. Deposition of amorphous electron dense material, of immune complexes, on the endothelial or epithelial side of basement membrane, or within the GBM itself. b. Thickening of the BM proper, as occurs in diabetic glomerulosclerosis. Hyalinization and sclerosis, made up of plasma proteins and collagen material deposited exracellularly. Additional alterations include; accumulation of lipids, fibrin or other metabolic materials. Intraglomerular vascular thrombosis The histologic changes can be further subdivided into;1. Diffuse 2. Focal. 3. Global. 4. Segmental. 5. Mesangial

Localization of immune complexes in the Glomerulus

1. Subepithelial humps, 2. Epimembranous deposits, 3. Subendothelial deposits, 4. Mesangial deposits, 5. Basement membrane. EN, endothelium; EP, epithelium; LD, lamina densa; LRE, lamina rara externa; LRI, lamina rara interna; MC, mesangial cell; MM, mesangial matrix.

Pathogenesis

Although little is known about etiologic agents and triggering events, it is clear that immune mechanisms underlie most forms of primary glomerulopathies, and many of the secondary forms. I. Immune-mediated mechanisms; 1. Ab-mediated, a. Insitu immune complex deposition, Fixed intrinsic antigens Planted antigens (exogenous as infectious agent or drug and endogenous as DNA, immunoglobulins) b. Circulating immune complex deposition Endogenous Ag (DNA, tumor) Exogenous Ag (infectious products) c. Cytotoxic Ab

Pathogenesis-cont

2. Cell-mediated. 3. Activation of alternative complement pathway. II. Non-immune mechanism (adaptive changes secondary to renal ablation). The 2 major histologic characteristics of such changes are;1. Focal segmental Glomerulosclerosis.2. Tubulointerstitial fibrosis

GLOMERULAR DISEASES

Primary GlomerulonephritisAcute diffuse proliferative GNRapidly progressive GNMembranous GNLipoid nephrosis (minimal change disease)Focal segmental glomerulosclerosisMembranoproliferative GNIgA NephropathyChronic GNSecondary (Systemic) DiseasesSystemic lupus erythematosusDiabetes mellitusAmyloidosisGoodpasture’s syndromePolyarteritis nodosaWagener’s granulomatosisHenoch-Scholein purpuraBacterial endocarditis . Hereditary Disorders Alport’s syndrome Fabry’s disease


Clinical Presentations of GN