Pathology of the Kidney PDF

7 Pathology of the Kidney LM 202 Dr. Hassan Kofahi The kidney The kidneys are bean-shaped organs that perform several important functions: Excretion of the waste products of metabolism. Regulation of body water and salt. Maintenance of acid balance. Secretion of...

7 Pathology of the Kidney LM 202 Dr. Hassan Kofahi The kidney The kidneys are bean-shaped organs that perform several important functions: Excretion of the waste products of metabolism. Regulation of body water and salt. Maintenance of acid balance. Secretion of a variety of hormones. The nephrons (shown in b & c) are the structural and functional units of the kidney. Diseases of the kidney Diseases of the kidney are divided according to their effect into: Diseases that affect the glomeruli. Diseases that affect the tubules. Diseases that affect the interstitium. Diseases that affect the blood vessels. Diseases that affect the glomeruli Glomerulus: structure The glomerulus consists of a network of capillaries surrounded by two layers of epithelium. The visceral epithelium: Part of the capillary wall Composed of podocytes. The parietal epithelium Encircles the urinary space (Bowman space). Glomerular capillaries consists of the following components: Endothelial cells: form a fenestrated endothelium (i.e., pores-containing endothelium) The glomerular basement membrane (GBM) Podocytes: cells that possess foot processes that wrap around the capillaries leaving filtration slits between them. Adjacent foot processes are bridged by a thin slit diaphragm composed mainly of the protein nephrin. Mesangial cells: reside between the capillaries, supports the glomerular tuft. Clinical Manifestations of Glomerular Diseases The clinical manifestations of glomerular disease can be grouped into two well-defined syndromes: Nephrotic syndrome Nephritic syndrome Nephrotic syndrome Characterized by the following: Proteinuria: Protein in the urine Hypoalbuminemia: Low albumin levels in the blood Generalized edema Hyperlipidemia: High levels of lipids in blood Lipiduria: lipids in urine Nephrotic syndrome is caused by an abnormality in the capillary walls of the glomeruli that results in increased permeability to plasma proteins. Nephrotic syndrome can be caused by several diseases including: Minimal change disease. Focal segmental glomerulosclerosis Systemic diseases including diabetes mellitus Nephritic syndrome Characterized by the following: Hematuria: red blood cells in urine Proteinuria: less severe than in nephrotic syndrome, with or without edema. Azotemia: an elevation of blood urea nitrogen and creatinine levels. Oliguria: low volume of urine Hypertension The nephritic syndrome is caused by inflammatory lesions of glomeruli. Inflammation causes injury to capillary walls allowing red blood cells to pass into the urine. Injury induces hemodynamic changes (vasoconstriction) that reduces the glomerular filtration rate (GFR). This results in oliguria, azotemia, fluid retention and hypertension. Mechanisms of Glomerular Injury and Disease Primary glomerular diseases: in these diseases, the kidney is the only (or the predominant) organ involved. Secondary glomerular diseases: the glomerular injury occurs secondary to systemic diseases. Most of the primary and many of the secondary glomerular diseases are immune-mediated. Minimal-Change Disease (MCD) One of the most common cause of nephrotic syndrome. Affects mostly the children (1-7 years old). Morphology: Light microscopy: glomeruli have normal appearance (hence the name “minimal change disease”). Electron microscopy: diffuse effacement or fusion of podocyte foot processes. The pathogenesis is unknown. Clinical features: Sudden development of nephrotic syndrome in a healthy child Renal function is preserved in most of the cases The majority of cases respond to treatment with corticosteroids. Focal Segmental Glomerulosclerosis (FSGS) Focal➔ only some of the glomeruli are involved (foci) Segmental➔ only part of each glomerulus is involved Glomerulosclerosis ➔ refers to scarring of the glomeruli FSGS is characterized by sclerosis of some (but not all) glomeruli that involves only a part of each affected glomerulus. FSGS causes nephrotic syndrome Responsible for 20%-30% of all cases of nephrotic syndrome. FSGS is one of the most common causes of nephrotic syndrome in adults. FSGS Types: Primary (idiopathic), Has no identifiable cause Secondary, occurs secondary to other conditions including: HIV infection Heroin abuse (heroin nephropathy) Others Pathogenesis: FSGS is initiated by an injury to podocytes. The cause of podocyte injury in FSGS is unknown. FSGS is poorly responsive to corticosteroid treatment, 50% of the cases develop end-stage renal disease within 10 years of diagnosis. Membranous Nephropathy (MN) Also known as membranous glomerulopathy Causes nephrotic syndrome Characterized by subepithelial deposits of immune complexes along the GBM. ❖Immune complex= antibody + antigen Morphology: Light microscope: diffuse thickening of the GBM Electron microscope: Podocytes show effacement of foot processes Subepithelial deposits separated from each other by spike-like protrusions of GBM (spike and dome pattern) MN Could be primary or secondary 80% of cases are primary and caused by autoantibodies against podocyte antigens. The remaining cases occur secondary to other conditions including infections or malignancies. Pathogeneses: Formation of subepithelial immune deposits activates the complement on the surface of podocytes. Activation of complement causes podocyte injury and proteinuria. Clinical features Affects mainly the adults (30-60 years). Fails to respond to corticosteroid. Poststreptococcal Glomerulonephritis (PSGN) Develop in children (or rarely in adults) 2-4 weeks after recovery from an infection with certain strains of group A streptococci (Nephritogenic strains). Pathogenesis: PSGN is an immune complex disease Immune complexes (host antibodies + bacterial antigens) deposit in the GBM. Deposition of immune complexes induces a strong inflammatory reaction that causes acute injury to the glomeruli. PSGN: clinical features Acute nephritic syndrome Edema Hypertension Mild to moderate azotemia Hematuria: the urine appear dark-brown in color (cola color) Recovery occurs in most of the children 15-50% of affected adults develop chronic renal disease years after the infection. IgA Nephropathy One of the most common causes of recurrent gross or microscopic hematuria. Caused by the deposition of IgA-anti IgA immune complexes in the mesangium (mesangial cells). Pathogenesis: Abnormally glycosylated IgA1 plays a central role in the pathogenesis. Abnormally glycosylated IgA1 elicit an immune response against it. Autoantibodies bind to the abnormally glycosylated IgA1, forming immune complexes that deposit in the mesangium. Deposition of the immune complexes in the mesangium induces inflammation which causes injury to the glomerulus leading to the release of red blood cells into the urine. IgA Nephropathy: clinical features Usually, affects children and young adults. Begins as an episode of hematuria that occurs within 1 or 2 days of a nonspecific upper respiratory tract infection or, less commonly, gastrointestinal or urinary tract infection. The hematuria lasts for several days and then subsides, but it recurs periodically, usually after an upper respiratory tract infection. 25%-50% of the cases progress to end stage renal disease in a period of 20 years. Diseases that affect the tubules and interstitium Acute Pyelonephritis A common suppurative inflammation of the kidney and the renal pelvis. Caused by bacterial infection. The principal causative organisms are enteric gram-negative bacilli (E.coli, Klebsiella, Proteus, etc..) Routes of infection: Bacteria reach the kidneys from the lower urinary tract (ascending infection). Through the bloodstream (hematogenous infection) ➔less common.  Acute Pyelonephritis: clinical features Females are more affected than males. The risk increases with catheterization Symptoms: Pain at the costovertebral angle Chills, fever, nausea and malaise Dysuria (painful urination), frequency, and urgency. Turbid urine. The disease is usually unilateral (affect only one kidney). CYSTIC DISEASES OF THE KIDNEY Simple cysts Fluid-filled sacs that grow in the kidney Occur as a single or multiple cysts, 1-5 cm in size Rarely, massive cysts as large as 10 cm in diameter are encountered. Usually, confined to the cortex Very common, occurs in 25% of adults over the age of 40. Usually, asymptomatic and have no clinical significance. Occasionally, produce symptoms such as fever and pain. Adults Polycystic Kidney Disease (PKD) An inherited disorder, occurs in 1 of every 500-1000 individuals. Characterized by multiple expanding cysts that form in both kidneys. As a result, kidneys enlarge and lose function with time. PKD accounts for 10% of cases of chronic kidney disease. Clinical features: Usually, does not produce symptoms until the age of 40. Symptoms: Pain Hypertension Intermittent gross hematuria Infections Can lead to renal failure Urinary Outflow Obstruction Renal Stones (Urolithiasis) Calcium Oxalate Urolithiasis is the formation of stones in the urinary collecting system. Most commonly occur in the kidneys. Symptomatic renal stones are more common in men than in women. 11% of men and 5.6% of women developed symptomatic kidney stones at some point in their life. Struvite Have a strong familial tendency. Types of stones: Calcium oxalate or calcium oxalate mixed with calcium phosphate: 80% of the cases. Uric Acid Struvite (Magnesium ammonium phosphate): 10% of the cases. Uric acid stones: 6-7% of the cases Cysteine stones: 1-2% of the cases. Other rare types Cysteine Urolithiasis: Pathogenesis Kidney stones form when solutes precipitate out of the urine. The exact cause of most kidney stones is not clear. Predisposing conditions: Increased urinary concentration of the stone’s constituent so that it exceeds the solubility in urine (supersaturation). 50% of patients who develop calcium stones have hypercalciuria caused mainly by excessive absorption of the calcium in the gut. Gout disease causes a high uric acid level in the urine and as a result, increases the possibility of uric acid stone formation. Change in the pH of the urine. Struvite stones almost always occur in individuals with a persistently alkaline urine resulting from urinary tract infections. Persistently acidic urine of pH < 5.5 favors formation of uric acid stones. Bacterial infections: Changes the pH of urine The bacteria act as nidi for the formation of stones. Urolithiasis: clinical features In some cases, stones may not cause any symptoms. When the stones pass into the ureter, it may cause: Severe pain known as renal colic. In many cases, may cause gross hematuria. Obstruction of the renal flow, ulceration and bleeding, caused by stones, predispose the patient to bacterial infections.