1. Khairat Battah, MD The University of Jordan Faculty of medicine, pathology department

2.  Diseases of the kidney are as complex as its structure, but their study is facilitated by dividing them into those that affect its four components: 1. Glomeruli 2. Tubules 3. interstitium 4. blood vessels

3.  Glomerular diseases are often immunologically mediated.  Tubular and interstitial disorders are more likely to be caused by toxic or infectious agents.  Whatever the origin, there is a tendency for chronic renal disease ultimately to damage all four components of the kidney, culminating in end-stage kidney disease.

4.  Azotemia is an elevation of blood urea nitrogen and creatinine levels and usually reflects a decreased glomerular filtration rate (GFR).  Uremia : when azotemia gives rise to clinical manifestations and systemic biochemical abnormalities.

5.  Major renal syndromes:  Nephritic syndrome results from glomerular injury  Nephrotic syndrome is a glomerular syndrome  Asymptomatic hematuria or non- nephrotic proteinuria, or a combination of these two, is usually a manifestation of subtle or mild glomerular abnormalities.

6.  Rapidly progressive glomerulonephritis is associated with severe glomerular injury and results in loss of renal function in a few days or weeks.  Acute kidney injury

7.  Chronic kidney disease.  Urinary tract infection  Nephrolithiasis (renal stones) is manifested by renal colic, hematuria.

8. A. Nephrotic syndrome :  In all there is a derangement in the capillary walls of the glomeruli that results in increased permeability to plasma proteins.  This allows protein to escape from the plasma into the glomerular filtrate

9. Characterized by 1. Massive proteinuria, with daily protein loss in the urine of 3.5 g or more in adults 2. Hypoalbuminemia, with plasma albumin levels less than 3 g/dL 3. Generalized edema, is the most obvious clinical manifestation 4. Hyperlipidemia and lipiduria.

10. - The relative frequencies of the several causes of the nephrotic syndrome vary according to age: a. In children 1 to 7 years of age, the nephrotic syndrome is almost always caused by a lesion primary to the kidney, b. Whereas among adults it often is due to renal manifestations of a systemic disease. The most frequent systemic causes of the nephrotic syndrome in adults are diabetes, amylodosis and systemic lupus erythematosus.

11. 1.Minimal-change disease : is the most frequent cause of nephrotic syndrome in children; and is manifested by selective proteinuria for albumin. - The glomeruli have a normal appearance by light microscopy but show diffuse effacement of podocyte foot processes when viewed with the electron microscope- - -The prognosis for children with this disorder is good. - More than 90% of children respond to a short course of corticosteroid therapy. - Less than 5% develop chronic kidney disease after 25 years.

12. 2. Focal segmental glomerulosclerosis Characterized histologically by sclerosis affecting some but not all glomeruli (focal ) and involving only segments of each affected glomerulus (segmental ) a. Primary injury by unknown mechanisms b. Secondary to other forms of GN, heroin abuse, HIV infection. Note:- The incidence of hematuria and hypertension is higher in persons with FSGS than in those with minimal-change disease; The associated proteinuria is nonselective The response to corticosteroid therapy is poor. At least 50% of patients with FSGS develop end-stage kidney disease within 10 years of diagnosis.

13. 3.Membranous Nephropathy : -Is a slowly progressive disease, most common between 30 and 60 years of age -Well-developed cases show diffuse thickening of the capillary wall. - In about 85% of cases, membranous nephropathy is primary - In the remainder it occurs secondary to : 1. Infections (chronic hepatitis B, syphilis, schistosomiasis, malaria) 2. Lung and colon carcinomas 3. Exposure to inorganic salts (gold, mercury) and Drugs (penicillamine, captopril, nonsteroidal anti-inflammatory agents)

14. B) The Nephritic Syndrome: characterized by a. Hematuria, b. Oliguria with azotemia c. Proteinuria, d. and hypertension.

15. 1. Acute postinfectious glomerulonephritis - Typically occurs after streptococcal infection in children and young adults - The classic case of poststreptococcal GN develops in a child 1 to 4 weeks after they recover from a group A streptococcal infection. - Most affected children recover ; the prognosis is worse in adults.

16. 2. IgA nephropathy, - Is the most common nephropathy worldwide - It is also a common cause of recurrent hematuria - Begins as an episode of gross hematuria that occurs within 1 or 2 days of a nonspecific upper respiratory tract infection - It commonly affects children and young adults and has a variable course

17. 3. Rapidly progressive glomerulonephritis (RPGN ) - Is associated with severe glomerular injury and results in loss of renal function in a few days or weeks. RPGN is commonly associated with severe glomerular injury with necrosis and GBM breaks and subsequent proliferation of parietal epithelium (crescents).  RPGN may occur with A) autoantibodies to the GBM develop in anti-GBM antibody mediated cresent GN. B) immune complex deposition. C) pauci-immune, associated with antineutrophil cytoplasmic antibodies (ANCA)

18. - The onset of RPGN is much like that of the nephritic syndrome, except that the oliguria and azotemia are more pronounced. - Proteinuria sometimes approaching nephrotic range may occur. - Some affected persons become anuric and require long-term dialysis or transplantation.

19.  The prognosis can be roughly related to the fraction of involved glomeruli: Patients in whom crescents are present in less than 80% of the glomeruli have a better prognosis than those in whom the percentages of crescents are higher. - Plasma exchange is of benefit in those with anti-GBM antibody GN and Goodpasture disease, as well as in some patients with ANCA-related pauci-immune crescentic GN.

20. Is dominated by oliguria or anuria (no urine flow), and recent onset of azotemia.  It can result from A) glomerular injury (such as rapidly progessive glomerulonephritis) B) interstitial injury, vascular injury (such as thrombotic microangiopathy), or acute tubular injury.

21.  Characterized by prolonged symptoms and signs of uremia.  It is the result of progressive scarring in the kidney from any cause and may culminate in end-stage kidney disease, requiring dialysis or transplantation.

23. - A group of inflammatory diseases of the kidney that involve the interstitium and tubules.

24. It is a suppurative inflammation of the kidney  Caused by bacterial infection  It is an important manifestation of urinary tract infection which means involvement of the lower(cystitis, prostatitis, urethritis) or upper (pyelonephritis) urinary tract, or both.

25. The principal causative organisms is E.coli. There are two routes by which bacteria can reach the kidneys A) Through blood stream B) From lower urinary tract (ascending infection). Ascending Infection is the most important and common route by which the bacteria reach the kidney

26.  The onset of acute pyelonephritis is sudden with pain at costovertebral angle and systemic evidence of infection such as chills, fever and weakness  Urinary findings include pyuria and bacteriuria  Also there is dysuria, frequency and urgency

27.  Urinary obstruction, either congenital or acquired  Instrumentation of the urinary tract, most commonly catheterization  Vesicoureteral reflux.  Pregnancy..  Patient's sex and age. After the first year of life (when congenital anomalies in males commonly become evident) and as far as around age 40 years, infections are much more frequent in females. With increasing age, the incidence in males rises as a result of the development of prostatic hyperplasia and frequent instrumentation.  Preexisting renal lesions, causing intrarenal scarring and obstruction  Diabetes mellitus  Immunosuppression and immunodeficiency.

28.  A morphologic entity in which predominantly interstitial inflammation and scarring of the renal parenchyma are associated with grossly visible scarring and deformity of the pelvicalyceal system  It is an important cause of chronic renal failure.  It can be divided into two forms: chronic obstructive pyelonephritis and chronic reflux–associated pyelonephritis.

29.  Most commonly due to synthetic penicillins like methicillin and ampicillin and other antibiotics like rifampin and also complicates diueritics like thiazides.  The clinical disease begins about 15 days after exposure to the drug and is characterized by fever, eosinophilia and rash (hypersensitivity reaction) in about 25% of the individuals  Renal findings include hematuria, minimal or no proteinuria and leukocyturia.

30.  A rising serum creatinine or acute renal failure develop in about 50% of cases especially in elderly people.  The onset of nephropathy is not dose related, and recurrence of hypersensitivity occur after re-exposure to the same or a cross-reactive drug  It is important to recognize drug-induced renal failure because withdrawal of the drug is followed by recovery.

31.  Individuals who consume large quantities of analgesics may develop chronic interstitial nephritis, often associated with renal papillary necrosis.  Aspirin, acetaminophen, caffeine, and codeine for long periods. Aspirin and acetaminophen are the major culprits.  Papillary necrosis is the initial event, and the interstitial nephritis in the overlying renal parenchyma is a secondary phenomenon.

32.  chronic renal failure, hypertension, and anemia.  The anemia results in part from damage to red cells by phenacetin metabolites(acetaminophin).  Cessation of analgesic intake may stabilize or even improve renal function.  A complication of analgesic abuse is the increased incidence of transitional-cell carcinoma of the renal pelvis or bladder in persons who survive the renal failure

33.  Characterized morphologically by damaged tubules and clinically by acute suppression of renal function and is the most common cause of acute renal failure  In acute renal failure, urine flow falls within 24 hours to less than 400 ml per day

34. Acute tubular necrosis is a reversible renal lesion that arises in a variety of clinical settings a. Ischemic type develop in cases of shock (severe trauma to acute pancreatitis to septicemia, have in common a period of inadequate blood flow to the peripheral organs, often in the setting of marked hypotension) b. Nephrotoxic is caused by a variety of toxins like mercury and and drugs like gentamicin and also radiographic contrast materials.

35. - The clinical course of ischemic ATI initially is dominated by the inciting medical, surgical or obstetric event. - Affected patients often present with manifestations of acute kidney injury, including oliguria and decreased GFR - During acute kidney injury, the clinical picture is dominated by electrolyte abnormalities, acidosis and the signs and symptoms of uremia and fluid overload

36.  With supportive care, patients who do not die from the underlying precipitating problem have a good chance of recovering renal function unless kidney disease was present at the time of the acute insult.  In those with preexisting kidney disease complete recovery is less certain, and progression over time to end-stage renal disease is unfortunately too frequent.

37.  Many types of benign and malignant tumors occur in the urinary tract. The most common malignant tumor of the kidney is renal cell carcinoma, followed in frequency by nephroblastoma (Wilms tumor) and by primary tumors of the calyces and pelvis.  Tumors of the lower urinary tract are about twice as common as renal cell carcinomas

38.  Derived from the renal tubular epithelium, and hence they are located predominantly in the cortex.  Men are affected about twice as commonly as women.  The risk of developing these tumors is higher in smokers, hypertensive or obese patients, and those who have had occupational exposure to cadmium.  The risk of developing renal cell cancer is increased 30-fold in individuals who develop acquired polycystic disease as a complication of chronic dialysis.

39. Clear Cell Carcinomas  The most common type.  The majority of them are sporadic, they also occur in familial forms or in association with von Hippel-Lindau (VHL) disease. Papillary Renal Cell Carcinomas  These tumors are frequently multifocal and bilateral and appear as early-stage tumors.

40. Chromophobe Renal Carcinomas  These are the least common, representing 5% of all renal cell carcinomas. They arise from intercalated cells of collecting ducts

41.  The symptoms vary, but the most frequent presenting manifestation is hematuria, occurring in more than 50% of cases.  Less commonly produce flank pain and a palpable mass.  Extra-renal effects are fever and polycythemia  Polycythemia results from elaboration of erythropoietin by the cancer cells (paraneoplastic syndrome).

42.  It is the third most common organ cancer in children younger than the age of 10 years.  May arise sporadically or be familial, with the susceptibility to tumorigenesis inherited as an autosomal dominant trait

43.  The entire urinary collecting system from renal pelvis to urethra is lined with transitional epithelium, so its epithelial tumors assume similar morphologic patterns.  May cause urinary outflow obstruction.  Urothelial (transitional) cell carcinomas range from papillary to flat, noninvasive to invasive, and low grade to high grade.  Occasionally, these cancers show foci of squamous cell differentiation, but only 5% of bladder cancers are true squamous cell carcinomas

44.  Painless hematuria is the dominant clinical presentation of all these tumors  They affect men about three times as frequently as women and usually develop between the ages of 50 and 70 years.  Cigarette smoking, chronic cystitis, schistosomiasis of the bladder, and certain drugs (cyclophosphamide) are also believed to induce higher rates of this cancer.  Although most occur in persons with no known history of exposure to industrial solvents, bladder tumors are 50 times more common in those exposed to β-naphthylamine.

45.  The clinical significance of bladder tumors depends on their histologic grade and differentiation and, most importantly, on the depth of invasion of the lesion.  Except for the clearly benign papillomas, all tend stubbornly to recur after removal.  Lesions that invade the ureteral or urethral orifices cause urinary tract obstruction