The Kidney

Definitions

Azotemia – Increased BUN and creatinine, usually related to decreased GFR

Pre-renal azotemia – hypoperfusion of the kidneys

Post-renal azotemia – obstrution to urine flow

Uremia – azotemia plus other metabolic and endocrine alterations resulting from renal damage

Definitions

Nephritic syndrome – glomerular disease, hematuria, RBC casts, mild to moderate proteinuria, hypertension, oliguria, edema

Rapidly progressive glomerulonephritis- nephritic syndrome with rapid decline (hours to days) in GFR

Nephrotic syndrome – glomerular disease, proteniuria >3.5 gm per day, hypoalbuminenia, severe edema, hyperlipidemia, lipiduria, inreased risk of infection, inreased risk of thrombosis, renal vein thrombosis

Definitions

Acute renal failure – rapid and frequently reversible onset, oliguria or anuria and recent onset of azotemia

Chronic renal failure – Prolonged symptoms and signs of uremia

Definitions

Diminished renal reserve GFR 50% of normal,

Asymptomatic

Renal insufficiency GFR 20%-50% of normal, azotemia, anemia, hypertension, decreased concentrating ability leading to polyuria and nocturia

Chronic renal failure GFR < 20% of normal, volume and solute composition cannot be regulated, edema, metabolic acidosis, hyperkalemia, overt uremia

End-stage renal disease GFR < 5% of normal, terminal stage of uremia

Chronic Renal FailureFluid and Electrolyte Dehydration

Edema

Hyperkalemia

Metabolic acidosis

Calcium, Phosphate, Bone

Hyperphosphatemia

Hypocalcemia

Secondary hyperparathyroidism

Renal osteodystrophy

Hematologic Anemia

Bleeding diasthesis

Cardiopulmonary Hypertension

CHF

Cardiomyopathy

Pulmonary edema

Uremia pericarditis

Chronic Renal Failure

Gastrointestinal Nausea and Vomiting

Bleeding

Esophagitis, gastritis, colitis

Neuromuscular Myopathy

Peripheral neuropathy

Encephalopathy

Dermatologic Sallow color

Pruritus

Dermatitis

Glomerular Diseases

Acute Proliferative Glomerulonephritis- ( poststreptococcal)

1-4 weeks after a strep infection ( pharynx or skin)Most frequently -6-10 years of ageMalaise, fever, nausea, oligouria, hematuria, RBC casts, mild proteinuria, periorbital edema, mild to moderate hypertension

Immune complex mediated diseaseEnlarged, hypercellular glomeruliGranular depositsSerum complement is decrease. ASO and other anti-strep antibodies are

increasedEM – subepithelial humpsAdults tend to present with sudden hypertension and/or edema and elevated

BUN

Glomerular Diseases

Rapidly progressive ( crescentic ) GN-Rapid and progressive loss of renal functionFormation of crescents- proliferation of parietal cells, infiltration of WBCs into the urinary space, compress the glomerular tuft, obliterate Bowman capsuleRupture of the GBM

Type I anti-GBM, e.g. Goodpasture syndromeType II Immune complex, e.g. Post-infectious GNType III pauci-immune ANCA, e.g. Wegener

granulomatosis

Causes of Nephrotic Syndrome

Primary GlomerularMembranousMinimal-changeFocal segmental glomerulosclerosisMembrano-proliferativeOther – e.g. IgA nephropathy

SystemicDMAmyloidosisSLEDrugs- NSAIDs, penicillamine, heroinInfections – malaria, syphilis, HBV, HCV,HIVMalignant diseaseMisc – e.g. hereditary nephritis

Minimal Change Disease

Most frequent cause of nephrotic syndrome in children

Visceral epithelial cells- uniform and diffuse effaement of foot processes

Immunoflorescence is negative

Membranous Nephropathy

Common cause of nephrotic in adults

Diffuse, uniform thickening of the glomerular capillary wall

Granular immunoflorescence

Subepithelial deposits

Focal Segmental Glomerulosclerosis

Most common form of nephrotic syndrome in adults

Collapsing glomerulopathy – HIV associated

Loss of foot processes

Epithelial damage

Membranoproliferative GN

Alterations in the GBMProliferation of glomerular cellsLeukocyte infiltration

Also called mesangiocapillary GN

Type I Immune complexes and activation of both classical and alternative complement pathways, subendothelial deposits

Type II dense-deposit disease activation of the alternative complement pathway

IgA Nepropathy (Berger Disease)

IgA deposits in the mesangial regions

Frequent cause of recurrent gross or microscopic hematuria

Probably the most common cause of GN worldwide

Henoch-Schonlein purpura

Secondary- liver disease and gluten enteropathy

Alport Syndrome

Hereditary nephritisHematuria with progression to chronic renal

failureNerve deafnessVarious eye disorders ( e.g. lens dislocation)Abnormalities of alpha chains in type IV

collagen

Benign Familial Hematuria

Hereditary nephritis

Asymptomatic hematuria

Diffuse thinning of the GBM

Renal function is normal

Prognosis is excellent

Lupus Nephritis

Type I – No renal involvement ( mild mesangial)

Type II – Mesangial form – granular mesangial deposits of immunoglobulin and complement

Type III – Focal-proliferative -

Type IV – Diffuse proliferative ( most severe) - crescentic

Type V – Membranous – thickening of GBM

Diabetic Glomerular Nephropathy

Widespread thickening of the GBM

Diffuse increase in mesangial matrix- expansion of the mesangium correlates with measures of deteriorating renal function

Nodular glomerulosclerosis – Kimmelsteil- Wilson disease

Tubular and Interstitial Diseases

AKI ( ATN)Acute diminution of renal failure,

and often morphologic evidence of tubular injury

Most common cause of Acute renal failure

Tubular injury and persistent and severe disturbances in blood flow

Causes – Ischemia, direct toxic injury, acute tubulointerstitial nephritis, urinary obstruction

Initiation, maintenance, recovery phases

Tubulointerstitial nephritis

Causes- infections, toxins, metabolic diseases, physical factors, neoplasms, Immunologic reactions,vascular diseases, miscellaneous

Pyelonephritis and UTI

Lower track – frequency, urgency, pyuria, dysuria, hematuria,Upper track ( pyelo) – fever leukocytosis, CVA tenderness, WBC casts

in urinepatchy interstitial suppurative inflammation, intratubular aggregates ofn neutrophils, tubular necrosis, Papillary necrosis, pyonephrosis, perinephric abscess, pyelonephritic scar-inflammation, fibrosis, deformation of underlying calyx and pelvis

E. Coli most commonAscending infection VUR, obstruction, instrumentation, pregnancy, preexisting renal

lesions, DM, immunosuppression

Vascular Diseases

Benign nephrosclerosis- hyaline arteriosclerosis

Malignant nephrosclerosis – fibrinoid necrosis and onion-skinning

Renal artery stenosis – most common cause is atherosclerosis, fibromuscular dysplasia

Renal infarction – white – end-organ

Thrombotic Microangiopathies

Microangiopathic hemolytic anemiaThrombocytopeniaRenal failure ( in many cases)Thrombotic lesions in capillaries and arteriolesEndothelial injuryPlatelet aggregationTypical ( epidemic, classic, diarrhea-positive) HUS- Shiga-like toxins,

E. coli 0157:H7Atypical ( non-epidemic, diarrhea-negative) HUS- genetic mutations in

complement-regulatory factors, antiphospholipid syndrome, postpartum, vascular diseases, drugs, irradiation

Thrombotic Thrombocytopenia Purpura – ADAMTS13, CNS involvement dominant

Cystic Diseases

Adult polycystic kidney disease – AD, CRF later in life, berry aneurysms, hepatic cysts,MVP and other valvular lesions

Childhood polycytic kidney disease- AR, Death in infancy or childhood, hepatic fibrosis

Urinary Tract Obstruction

Common causes: Congenital anomaliesUrinary calculiBPHTumorsInflammationSloughed papillae or blood clotsPregnancyUterine prolapse and cystoceleFunctional disorders – neurogenic bladderHydronephrosis – Dilation of the renal pelvis and calyces associated with

progressive atrophy of the kidney due to obstruction to the outflow of urineObstruction also triggers an interstitial inflammatory reaction, leading eventually

to interstitial fibrosis

Urolithiasis

Calcium stones- oxalate and/or phosphate

Triple stones – magnesium ammonium phosphate, infections, staghorn calculi

Uric acid stones

Cystine

Tumors

Renal cell carcinoma – adenocarcinoma. Smoking, obesity, unopposed estrogen,Asbestos, petroleum products, heavy metalsCRF, acquired cystic disease, tuberous sclerosisvon Hippel-LindauClear cell- 70-80%CVA pain, palpable mass, hematuriaParaneoplastic syndromes, widespread metastases before local signs and symptoms