2/11/1999

Pathology II

Kidney Section

· Recall kidney information from Physiology II (what we just took the test on)

· Diabetics are more susceptible to kidney/bladder infections for 2 reasons

high blood glucose
increased blood pressure

Kidney Disease

· glomeruli-vulnerable to immune-mediated disorders

· tubules-sensitive to toxic or infectious agents

· interstitium-same as above

· blood vessels

· all chronic renal diseases ultimately destroys all components—end-stage contracted kidneys

· functional reserve is large-much damage before impairment is evident

Clinical Manifestations of Renal Disease

· azotemia—increased BUN, increased creatinine levels---due to decreased GFR

· Prerenal azotemia-hypoperfusion of kidney, impairs renal function in absence of parenchymal damage

· Postrenal azotemia—obstruction of urine flow below kidney

· Uremia-more extensive renal failure-CNS symptoms, neuropathies, cardiovascular involvement, intense pruritus

Includes:

· Azotemia

· Metabolic acidosis (decreased excretion of fixed acids)

· Anemia (decreased erythropoietin production)

· Hypocalcemia (decreased formation 1,25-dihydroxycholecalciferol)

· Hyperkalemia (decreased K+ excretion)

Major Renal Syndromes

1. Acute nephritic syndrome-hematuria, proteinuria, hypertension—classic presentation of proststreptococcal glomerulonephritis (GN)

2. Nephrotic syndrome—heavy proteinuria, hypoalbuminemia, sever edema, hyperlipidemia, lipiduria

3. Asymptomatic hematuria or proteinuria-subtle or mild glomerular abnormalities

4. Acute renal failure-olioguria, anuria, azotemia-glomerular or interstitial injury or acute tubular necrosis

5. Chronic renal failure-prolonged uremia-end result of all chronic renal disease

6. Urinary tract infection –bacteriuria, pyuria-kidney

7. Kidney stones

Glomerular Diseases

Major site of renal problems leading to renal failure

Glomerular filtration:

· High permeability to water

· Impermeable to large molecules

· Primary glomerular disease-only kidney is involved

· Secondary –result of systemic disease

Antibody-mediated

· Theses immune mechanisms underlie most cases of GN

1. circulating immune complexes

· innocent by-stander —ag originates elsewhere

· ag-ab complexes formed in circulating and trapped in glomeruli

· endogenous, i.e. SLE

· exogenous

· bacterial – strep

· viral—hepatitis B

· parasitic—Plasmodium flaciparum (malaria)

· spirochetal – Treponemia palladium

2. Immune Complex—In Situ

Ab react direct w/fixed or planted ag in glomerulus

· Anti-glomerular basement membrane nephritis (anti-GBM)

· Ab directly bind along GBM and crate “linear pattern” seen immunofluorescense techniques

· Autoimmune—Good Pasture’s (lung and kidney)

· Heymann’s nephritis-granular pattern of complex deposition along the GBM in the visceral epithelium-sikmoal elastin to membranous

Other Mechanisms of Glomerular Injury

· Cell-mediated immune reactions-sensitized T cells, formed during cell-mediated immune reaction—glomerular injury

· Epithelial cell injury-toxins

· Renal ablation glomerulopathy-when loss of nephrons (any reason) reduces GFR to 30-50% of normal-hypertrophy of remaining glomeruli occurs. Hemodynamic changes, increased load, etc. Cause widespread glomerulosclerosis. Vicious cycle of further damage and reduction in nephron mass

Glomerular Syndromes and Disorders

Conditions that Present w/Nephrotic Syndrome

Nephrotic Syndrome

· Loss filtration barrier, increase perm to plasma protein

· Massive proteinuria-daily loss > 3.5 gm

· Hypalbuminemia (drop in osmotic P)

· Generalized edema

· Common causes

· Children—lipid nephrosis

· Adults-systemic disease (SLE, diabetes, amyloidosis

1. Minimal Change Disease (Lipoid Nephrosis)

· Relatively benign-children ages 2-3yrs

· Diffuse loss of visceral epithelial foot processes

Pathogenesis

· Epithelial cell injury-an immune defect causes production of substance causes damage

Morphology

· Glomeruli appear normal

· Proximal convoluted tubules laden w/ lipoproteins, due to reabsorption having passed through diseased glomeruli-old name “lipoid nephrosis”

· Foot processes on the visceral epithelium (podocytes) are affected

HI AMY JUST WANTED TO SEE IF YOU WOULD NOTICE, MARK

Clinical Course

· Insidious onset nephrotic syndrome in healthy child

· Good prognosis-90% of cases respond to corticosteroids

· <5% develop chronic renal failure after 25 yrs

2. Membranous Glomerulonephritis

· Slowly progressive disease-ages 30-50 yrs

· Granular pattern of immunoglobulin-containing deposits along GBM

· “spike and dome” pattern-early in disorder, formed by small protrusions of GBM matrix b/w deposits

Clinical Course

· insidious onset nephrotic syndrome

· not responsive to corticosteroids

· variable course

· 60%-persistent proteinuria

· 40% progressive w/ renal failure

3. Focal Segmental Glomerulosclerosis

· Sclerosis affecting some glomeruli and only segments of each glomerulus

· 4 settings

1. HIV nephropathy, heroin addiction nephropathy

2. Secondary to other forms of GN

3. Component of renal ablation nephropathy

4. Primary (idiopathic) disease-1-% of cases

Pathogenesis

· Unknown-characteristic disruption of visceral epi cells (focal and segmental)

· Probably a circulating mediator is cause of damage

Clinical Course

· Poor response to corticosteroids

· Spontaneous remissions are unlikely

· 50% progress to renal failure in 10 yrs

4. Membranoproliferative Glomerulonephritis (MPGN)

· Alterations in basement membrane and mesangium w/proliferation of glomerular cells

· Thickened basement membrane-split by mesangial cell process-“tramtrack” appearance

· 2 Major types

MPSN I (2/3) –chronic immune complex rxn—subendothelial deposits
MPGN II-“dense-deposit disease”-intramembranous deposits of unknown material

Clinical Course

Nephrotic syndrome-initial presentation

Prognosis is poor

Conditions Causing Nephritis Syndrome

Nephritic syndrome-clinical complex of acute onset

Primary features

1. hematuria w/RBC casts in urine

2. oliguria

3. hypertension

1. Acute Proliferative Glomerulonephrits

· Frequent form-exogenous or endogenous ag

· May follow infection: strep, staph, mumps, measles, chickenpox, hepatitis B

· Classic poststrep GN-in child

Clinical Course

· Abrupt onset

· Gross hematuria-urine appears smoky-brown

· Complete recovery in children >99%

· Adult cases 15% to 50% become chronic

2. Rapidly Progressive (Cresecentic )

· Not a specific form – a clinicopathologic syndrome

· Immunologically-mediated severe glomerular injury

· Rapid loss of renal fxn-severe oliguria-renal failure (wks-to-months)

· Cresents-proliferation of parietal epithelial cells of Bownam’s capsule and infiltrate-will obliterate space and compress glomeruli

· Prognosis bad

Type I RPGN

· Idiopathic

· Goodpasture’s syndrome

Type II

Idiophatic

SLE

· Post infection

· Henoch-Schonlein purpura

Type III

· Idiopathic

· Wegener’s granulmatosis

· Polyarteritis

3. IgA Nephropathy (Berger’s Disease)

· Children and adults-1-2 days after URI, hematuria subsides in few days, then recurs every few months

· One the most common causes of recurrent microscopic or gross hematuria and the most common glomerular disease worldwide

· Pathogenic hallmark is deposition of IgA in mesangium

· Could be variety of Henoch-Schonlein purpura although Berger’s is only renal

4. Hereditary

Chronic Glomerulonephritis

· Acute outcome of disease already described

· Important cause of end-stage renal disease

· 30-50% require chronic hemodialysis or transplant

Diseases Affecting Tubules and Interstitium