2. PYELONEPHRITIS AND URINARY TRACT INFECTION

3. Definition Pyelonephritis is a renal disorder affecting the tubules, interstitium, and renal pelvis It occurs in two forms. 1- Acute pyelonephritis is caused by bacterial infection associated with urinary tract infection. 2- Chronic pyelonephritis is caused by: A- bacterial infection (blood) B- other factors (vesicoureteral reflux, obstruction) C- Bacterial infection of the lower urinary tract(asend infection)

4. Etiology and Pathogenesis The most common causes are: 1- Bacterial such as Escherichia coli, followed by Proteus, Klebsiella, and Enterobacter. 2- In immunocompromised persons, with transplanted organs, 3- viruses such as Polyomavirus, cytomegalovirus, and adenovirus Routes of infection There are two routes (1 ) through the bloodstream (hematogenous infection) through distant foci (seticemia or infective endocarditis -less common ) (2 ) from the lower urinary tract (ascending infection)-more common

5. . Schematic representation of pathways of renal infection.

6. Normal human bladder urine are sterile: (a number of steps must occur for renal infection to occur) 1- ascending the colonized coliform bacteria present in distal urethra - Introduction of bactera From the urethra to the bladder,is common with: A- female (short short urthera) and hormonal changes ( adherence of bacteria) to the mucosa, and urethral trauma during sexual intercourse B - during urethral catheterization or other instrumentation. C- Urinary tract obstruction and stasis of urine and patient cannot evacuate all urine (bacteria multiply on residual volume of urine) with benign prostatic hypertrophy, tumors, or calculi, or with neurogenic bladder dysfunction caused by diabetes or spinal cord injury. D- Vesicoureteral reflux (VUR): ( congenital or acquired. ) E- Intrarenal reflux( ureteral to kidney ) &Reflux can be demonstrated radiographically by a voiding cystourethrogram

7. Vesicoureteral reflux demonstrated by a voiding cystourethrogram. Dye injected into the bladder refluxes into both dilated ureters, filling the pelvis and calyces.

8. ACUTE PYELONEPHRITIS IT is an acute suppurative inflammation of the kidney caused by bacterial and sometimes viral (e.g., polyomavirus) &infection, whether hematogenous or ascending and associated with vesicoureteral reflux.

9. Morphology NE One or both kidneys show discrete focal abscesses which extend to large wedge shaped areas of suppuration. Histology: 1- patchy interstitial suppurative inflammation 2- Then,intratubular aggregates of neutrophils,and tubular necrosis. (2)- The distribution of these lesions is haphazard, but in pyelonephritis associated with reflux, damage occurs in the lower and upper poles.

10. Acute pyelonephritis. Cortical surface shows grayish white areas of inflammation and abscess formation.

11. Acute pyelonephritis marked by an acute neutrophilic exudate within tubules and interstitial inflammation.

12. complications of acute pyelonephritis. (1)-Papillary necrosis (diabetics and in those with urinary tract obstruction). (2)- Pyonephrosis: The suppurative exudate is unable to drain and thus fills the renal pelvis, calyces, and ureter with pus. (3) - Perinephric abscess : is an extension of suppurative inflammation through the renal capsule into the perinephric tissue. After the acute phase of pyelonephritis, healing occurs: 1- The inflammatory foci are replaced by irregular scars (fibrous depressions on the cortical surface). 2- Such scars are characterized microscopically by: tubular atrophy, interstitial fibrosis, and a lymphocytic infiltrate

13. Papillary necrosis. Areas of pale- gray necrosis involve the papillae (arrows).

14. Clinical Features When acute pyelonephritis is clinically apparent: 1- Sudden onset 2- pain at the costovertebral with fever and malaise(indicate infection). 3- bladder and urethral irritation, such as dysuria, frequency, and urgency. 4- Laboratory : The urine contains: A- pyuria from the inflammatory infiltrate.(dead cells) B-leukocyte casts, typically rich in neutrophils (pus casts), indicates renal involvement, because casts are formed only in tubules.. 5- Uncomplicated cases follows a benign course, and the symptoms disappear within a few days after appropriate antibiotic therapy.,

15. CHRONIC PYELONEPHRITIS AND REFLUX NEPHROPATHY Chronic tubulointerstitial inflammation and renal scarring with pathologic involvement of the calyces and pelvis. Chronic pyelonephritis divided into 1- chronic reflux-associated 2-chronic obstructive.

16. 1-REFLUX NEPHROPATHY It is common form of chronic pyelonephritic scarring. It occurs early in childhood from: 1- superimposition of a urinary infection on congenital vesicoureteral reflux and intrarenal reflux(congental). 2-Reflux may be unilateral or bilateral: cause scarring and atrophy of one kidney or involve both, leading to chronic renal insufficiency.

17. 2-CHRONIC OBSTRUCTIVE PYELONEPHRITIS It is recurrent infections superimposed on diffuse or localized obstructive lesions lead to: 1- recurrent bouts of renal inflammation and scarring (the obstruction also share in parenchymal atrophy). 11- The obstruction is : 1-bilateral (anomaly of posterior urethral valves) 2-unilateral ( in ureter with calculi or anomalies)

18. Morphology (1)-NE Presence of scares which are: &-coarse, discrete, corticomedullary scars overlying dilated, blunted, or deformed calyces, and flattening of the papillae. (11) -The microscopic changes: involve tubules and interstitium. 1-The tubules show atrophy in some areas and hypertrophy or dilation in others. Dilated tubules with flattened epithelium(filled with colloid casts (thyroidization). 2-Interstitium show interstitial inflammation and fibrosis in the cortex and medulla. 3- In active infection there may be neutrophils in the interstitium and pus casts in the tubules.

19. Typical coarse scars of chronic pyelonephritis associated with vesicoureteral reflux. The scars are usually polar and are associated with underlying blunted calyces.

20. Low-power view showing a corticomedullary renal scar with an underlying dilated deformed calyx. Note the thyroidization of tubules in the cortex.

21. Clinical Features (1)-Chronic obstructive pyelonephritis may be: & insidious onset or back pain, fever, frequent pyuria, and bacteriuria. (11)-Chronic pyelonephritis associated with reflux may be: & (commonly with silent onset). These patients come to medical attention late because 1-the gradual onset of renal insufficiency 2- hypertension 3- the discovery of pyuria or bacteriuria on routine examination.

22. VASCULAR DISEASES of the kidney

23. BENIGN NEPHROSCLEROSIS Benign nephrosclerosis is : renal pathology associated with sclerosis 1- affects renal arterioles and small arteries (vessels with thickened walls narrowed lumens.). 2- This cause focal ischemia of parenchyma supplied by affected vessels 3-The parenchymal effects include glomerulosclerosis and chronic tubulointersititial injury, producing a reduction in functional renal mass. 4- Hypertension and diabetes mellitus, increase its incidence and severity of the lesions.

24. Pathogenesis Two processes cause arterial lesions: 1- Medial and intimal thickening (fibrosis of media and thicken intema) as a response to: A- hemodynamic changes, B- Aging C-genetic defects D- combination of these 2- Hyaline deposition in arterioles, caused by: A- Partly by extravasation of plasma proteins through injured endothelium B- partly by increased deposition of basement membrane matrix

25. Morphology NE The kidneys are normal or moderately reduced in size (due to cortical scarring and shrinking) On histologic examination there is: 1- narrowing of the lumens of arterioles and small arteries, (by thickening their walls (hyaline arteriolosclerosis). 2-subcapsular scars with sclerotic glomeruli and tubular dropout(preserved parenchyma in between) 3-the interlobular and arcuate arteries show medial hypertrophy, reduplication of the elastic lamina, and increased myofibroblastic tissue in the intima, which combine to narrow the lumen( called fibroelastic hyperplasia) 5- there is patchy ischemic atrophy(due to vascular narrowing ), consists of (1) foci of tubular atrophy and interstitial fibrosis (2) a variety of glomerular alterations(collapse of the GBM, deposition of collagen within the Bowman space, periglomerular fibrosis, and total sclerosis of glomeruli.

26. . Benign nephrosclerosis illustrating the fine, leathery granularity of the surface.

27. Hyaline arteriolosclerosis. High-power view of two arterioles with hyaline deposition, marked thickening of the walls, and a narrowed lumen.

28. Clinical Features patient with benign nepherosclerosis have: 1- moderate reductions in renal blood flow, 2- GFR is normal or only slightly reduced. Three groups of hypertensive patients with benign nephrosclerosis are at increased risk of developing renal failure: 1-people of African descent(increase sclerosis in black) 2- people with more severe blood pressure elevations(decreased R. blood flow) 3- persons with a second underlying disease, especially diabetes ( micro angiopsy -acute necrotizing papilities) Note be: &patients with the above groups enter renal insufficiency after prolonged benign hypertension, but & patient have developed malignant hypertension, enter renal failure more rapidly

29. MALIGNANT HYPERTENSION AND ACCELERATED NEPHROSCLEROSIS Malignant nephrosclerosis is associated with the malignant or accelerated phase of hypertension. It develop in 1-previously normotensive individuals 2- but often is superimposed on preexisting essential benign hypertension, 3-or an underlying chronic renal disease, particularly glomerulonephritis or reflux nephropathy. Malignant hypertension 1-uncommon(1%-5% from patients have elevated blood pressure) 2- its pure form usually affects younger individuals, and more in blacks men

30. Pathogenesis (1)-This initiated by vascular damage to the kidneys which causes: 1- increased permeability of the small vessels to fibrinogen and other plasma proteins, 2-endothelial injury, focal death of cells of the vascular wall, and platelet deposition. (2)-This leads to: 1-fibrinoid necrosis of arterioles and small arteries, 2-swelling of the vascular intima, 3-intravascular thrombosis. (4)-Mitogenic factors from platelets (PDGF), plasma, and other cells cause hyperplasia of intimal smooth muscle of vessels, resulting in the hyperplastic arteriolosclerosis (5)-Those (hyperplastic) with above reasons(sclerosis) cause typical of malignant hypertension and further narrowing of the lumens.

31. Morphology N/E Small, pinpoint petechial hemorrhages appear on the cortical surface from rupture of arterioles or glomerular capillaries (flea-bitten appearance). M/P Two histologic alterations in blood vessels happened: 1 Fibrinoid necrosis of arterioles ( eosinophilic granular change) 2- In the interlobular arteries and arterioles, there is: A- intimal thickening caused by concentrically arranged smooth muscle cells B- together with fine concentric layering of collagen &This alteration called onion-skinning because of its concentric appearance. & The arteriolar and arterial lesions cause narrowing of all vascular lumens, ischemic atrophy and infarction distal to the abnormal vessels.

32. Malignant hypertensio n. A, Fibrinoid necrosis of afferent arteriole B, Hyperplastic arteriolitis (onion-skinlesion) ).

33. Clinical Features & The full-blown syndrome of malignant hypertension is characterized by 1-systolic pressures greater than 200 mm Hg and diastolic pressures greater than 120 mm Hg, 2-papilledema, retinal hemorrhages, 3-Encephalopathy 4-cardiovascular abnormalities, 5-renal failure. &Most often is increased intracranial pressure which include : 1- headaches, 2-nausea, vomiting, 3- and visual impairments.

34. Obstructive lesions of the urinary tract

35. Hydronephrosis Hydronephrosis is dilation of the renal pelvis and calyces associated with progressive atrophy of the kidney due to obstruction to the outflow of urine.

36. . Hydronephrosis of the kidney, with marked dilation of the pelvis and calyces and thinning of the renal parenchyma.

37. Clinical Features 1-Unilateral complete or partial hydronephrosis may remain silent for long periods, since the(unaffected kidney maintain renal function). 2- polyuria and nocturia in bilateral partial obstruction due to inability to concentrate the urine(water normally absorbed in collecting tubules to concentrate urine & this not happened in the disease due high pressure in collecting tubules) 3- secondary renal calculi formation, 4- scarring and atrophy of the papilla and medulla due to. chronic tubulointerstitial nephritis 5-Hypertension is common in such patients. 6- oliguria or anuria and is incompatible with life due to Complete bilateral obstruction

38. UROLITHIASIS (RENAL CALCULI, STONES)

39. RENAL CALCULI, STONES 1-Renal Stones form at any level(mainly in kidney). 2-Affect men than women(20-30). Types four types of calculi: (1) calcium stones =about 70% (calcium oxalate or calcium oxalate mixed with calcium phosphate) (2) triple stones or struvite stones=15%( magnesium ammonium phosphate) (3)uric acid stones=5%-10% (4) 1% to 2% are made up of cystine.

40. Nephrolithiasis. A large stone impacted in the renal pelvis.

41. Urolithiasis:

42. Staghorn Calculus:

43. Clinical Features (1)- smaller stones: & are pass into the ureters, producing colic,, and ureteral obstruction. (2)- Larger stones: 1- cannot enter the ureters 2-remain silent within the renal pelvis(manifest themselves by hematuria). 3-predispose to superimposed infection, both by their obstructive nature and by the trauma they produce.