Renal Pathophysiology: Common Disorders and Etiology

1. Renal pathophysiology Mehtap KAÇAR KOÇAK MD, PhD YEDİTEPE UNIVERSITY, FACULTY OF MEDICINE

2. ALTERATIONS OF RENAL AND URINARY TRACT FUNCTION • 1- URINARY TRACT INFECTION • - Cystitis, • - Acute Pyelonephritis, • - Chronic Pyelonephritis. • 2- GLOMERULAR DISORDERS • - Glomerulonephritis, • - Nephrotic syndrome. • 3- TUBULOINTERSTITIAL DISORDERS • - Acute interstitial nephritis, • - Chronic tubulointersititial nephritis. • 4- RENAL FAILURE: • - Acute renal failure, • - Chronic renal failure. • 5- URINARY TRACT OBSTRUCTION: • - Obstructive disorders (Kidney stones, neurogenic bladder) • - Tumors (Renal tumors, Bladder tumors) • 6- HYPERTENSION AND KIDNEY

3. 1- URINARY TRACT INFECTIONS

4. Urinary Tract Infections (UTI) • Very common • Urine is excellent medium for microorganismal growth • Escherichia coli • Most are ascending • Perineal cavity  mucosa  bladder  ureters  kidneys

5. UTI—Etiology • Females more anatomically vulnerable • Short urethra • Proximity to anus • Frequent irritation to tissues • Tampons, bubble bath, sexual activity • Older males with prostatic hypertrophy and retention of urine prone to UTI

6. UTI—Etiology • Incontinence • Bladder retention of urine • Obstruction of urine flow • Congenital abnormality • Pregnancy, scar tissue, kidney stones, vesicourethral reflux • Urine does not flow freely • Decreased host resistance (immunosuppression) • Impaired blood supply to bladder (aging) • Diabetes mellitus

8. Cystitis • Bladder wall and urethra inflamed, red, swollen • Decreased bladder capacity

9. The Signs and Symptoms of Cystitis • Pain in lower abdomen • Dysuria, frequency, urgency • Inflammation of bladder wall irritated by urine • Systemic signs of infection • Cloudy urine with unusual odor • Urinalysis indicates bacteria (+100,000/mL), pyuria, microscopic hematuria

10. Acute Pyelonephritis • Affects cortex with sparing of glomeruli and vessels. • One or both kidneys involved • Infection from ureter  renal pelvis  medullary tissue (tubules and interstitial) • Purulent exudate fills kidney pelvis and calyces • Abscess and necrosis seen in medulla • May extend through cortex to capsule • Severe may compress renal artery and vein and • obstruct urine flow to ureter • Bilateral obstruction results in acute renal failure • Recurrent chronic infection • Can lead to fibrous tissue over calyx • Loss of tubule function

11. Symptoms of acute pyelonephritis: • Signs of cystitis • Pain • Dull aching in lower back • Results from renal capsule stretching • Urinalysis • Similar to cystitis • Except urinary cast • Leukocytes or renal epithelial cells present • Involvement of renal tubule • White cell casts in urine are pathognomonic.

12. Chronic Pyelonephritis • Chronic pyelonephritis is a persistent or recurrent autoimmune infection of the kidney with inflammation and scarring of the kidney. • One or both kidneys may be involved. • The specific cause of chronic pyelonephritis is more difficult to determine, and controversy surrounds the criteria for constituting the diagnosis. • Recurrent infections from acute pyelonephritis may be associated with chronic pyelonephritis. • Generally, chronic pyelonephritis is more likely to occur in patients who have renal infections associated with some type of obstructive pathologic condition. (renal stones, vesicouretheral reflux)

13. Pathophysiology of Chronic Pyelonephritis • Chronic urinary tract obstruction prevents elimination of bacteria in the normal flow of urine, resulting in progressive inflammation that causes fibrosis and scarring. • The renal pelvis and calyces become dilated and blunted. • The lesions of chronic pyelonephritis are sometimes termed “chronic interstitial nephritis” because the inflammation and fibrosis are located in the interstitial spaces between the tubules.

14. 2- GLOMERULAR DİSORDERS

15. GLOMERULAR DİSORDERS • Disorders resulting in glomerular disease fall into five categories: • 1- Acute glomerulonephritis, • 2- Rapidly progressive glomerulonephritis, • 3- Chronic glomerulonephritis, • 4- Nephrotic syndrome, • 5- Asymptomatic urinary abnormalities.

16. Glomerulonephritis • Glomerulonephritis is an inflammation of the glomerulus that can be caused by a variety of factors including • immunologic abnormalities, • effects of drugs or toxins, • vascular disorders, and • systemic diseases. • Immunologic alterations are most frequently responsible for glomerular injury.

20. Acute Glomerulonephritis • Causes of acute glomerulonephritis: • 1- Infectious diseases: • - Poststreptococcal g.n., • - Nonstreptococcal postinfectious g.n. • 2- Multisystem diseases (e.g. SLE, vasculitis) • 3- Primary glomerular diseases (IgA nephropathy, mesangiocapillary gn)

21. Acute Glomerulonephritis • This diseases occurs typically in the setting of infectious diseases, classically pharyngeal or cutaneous infections with certain “nephritogenic” strains of group A beta-hemolytic streptococci. • It is characterized by acute inflammatory changes due to immune deposits in a subepithelial location. These contain large amounts of C3 and smaller amounts of IgG.

24. Chronic Glomerulonephritis • Chronic glomerulonephritis includes a variety of glomerular diseases, each with a progressive course leading to chronic renal failure. • Two types of immune mechanism commonly contribute to glomerular injury: • 1- deposition of circulating soluble antigen-antibody complexes, • 2- formation of antibodies specific for the anti-glomerular basement membrane (anti-GMB antibodies).

26. Symptoms of glomerulonephritis • Back pain • Stretching renal capsule • Dark, cloudy urine • Hematuria • Oliguria • Facial edema, then generalized • Low osmotic pressure of blood (due to proteinuria) • Salt, water retention • Generalized signs of inflammation • Increased blood pressure

27. Characteristics of common glomerular diseases at presentation

28. Nephrotic Syndrome • Is not a disease but a group of signs and symptoms seen in patients with • heavy proteinuria • presents with edema • Proteinuria (particularly albuminuria) usually > 3.5g / 24hrs (>0.05g / kg / 24hrs in children) • Hypoalbuminemia (serum albumin < 30g/l) • other features: hyperlipidaemia, and hypercoaguable state

29. Pathophysiology of Nephrotic Syndrome • proteinuria: due to an increase in glomerular permeability • hypoalbuminuria: occurs when liver synthesis cannot keep up with urine losses • edema mechanism is complex and still in dispute: primary salt and water retention associated with reduced renal function as well as reduced plasma oncotic pressure are primary factors (overfill and underfill) • minimal change disease fits the underfill theory best • hyperlipidaemia: increased liver synthesis • hypercoagulation: increased fibrinogen and loss of antithrombin III

32. Primary glomerular diseases commonly causing the nephrotic syndrome: • minimal change disease • focal and segmental glomerulosclerosis • membranous glomerulonephritis • proliferative glomerulonephritis (various histology and less common cause) • membranoproliferative (mesangiocapillary) • focal proliferative • diffuse proliferative • mesangial proliferative

33. Other causes of the nephrotic syndrome: • Systemic diseases • diabetes mellitus • amyloidosis • SLE and other connective tissue diseases • HIV/Aids • nephrotoxins • nsaids • mercury poisoning • penicillamine • gold salts

34. Allergies • bee sting • pollens • poison ivy • Circulatory effects • congestive cardiac failure • constrictive pericarditis • renal vein thrombosis (cause or result?) • Neoplastic • leukaemia • solid tumours

36. 3- TUBULOINTERSTITIAL DISORDERS

37. Interstitial Nephritis • A disorder of the interstitium and tubules

38. Causes of interstitial nephritis • Drugs • Infection • Autoimmune • Metabolic • Radiation • Neoplastic infiltration • Mechanical

39. Drug Toxicity(hypersensitivity) • penicillins • sulphonamides (cotrimoxazole) • rifampicin • thiazides • frusemide • omeprazole

40. Drug toxicity(direct toxicity) • aminoglycosides • amphotericin B • heavy metals (e.g lead, mercury) • analgesics (especially NSAIDS)

41. Bacterial infection • bacterial infection of the renal parenchyma causes interstitial nephritis. • infection without anatomical abnormality seldom produces permanent damage. • obstruction (stones, prostate etc) in combination with infection can cause progressive disease. • tuberculosis causes extensive destruction from granulomata, fibrosis and caseation.

42. systemic lupus erythematosus transplant rejection immunological metabolic • deposition of : • calcium salts • uric acid

43. Infiltration in neoplastic and other diseases • lymphoma and leukaemias • myeloma • Bence-Jones protein (light chains from malignant plasma cell clone) causes interstitial nephritis, tubular obstruction(cast nephropathy) and amyloid deposition • called myeloma kidney • sarcoidosis

44. mechanical causes of interstitial nephritis • reflux nephropathy • calculi • ureteric fibrosis • prostatic hypertrophy • urethral stenosis • tumours

45. Functional Consequences of Tubulointerstitial Disease

46. pathophysiolgical changes in interstitial nephritis • hypertension (50%) • proteinuria (~1-2 g/24hrs) • reduced urinary concentrating ability • salt wasting • renal tubular acidosis

47. 4- RENAL FAILURE

48. Overview • Chronic renal failure • Presentation and progression of chronic renal failure • Common causes of chronic renal failure • Possible physiological targets for treatment of chronic renal failure • Differences between chronic and acute renal failure • Pathology of acute renal failure

49. Chronic renal failure Chronic renal failure is a chronic progressive disease that presents by an ongoing loss of kidney function and performance This process has normally a duration of several years leading to end-stage renal failure In this stage dialysis or kidney transplantation become obligatory! Between 1 April 2004 and 31 March 2005 in the UK 1,783 patients received a kidney transplant* currently close to 18,000 people on dialysis* (with an ~5% annual increase) *Transplant UK

50. Chronic renal failure Presentation • Asymptomatic serum biochemical abnormality • Asymptomatic proteinuria/haematuria • Hypertension • Oedema • Symptomatic primary disease • Symptomatic uraemia • Complications of chronic renal failure