The Urinary System

Part II

Dr. Khan, MD, MCPS,

DTCD
PA 5402
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Diabetic Glomerulosclerosis
• It is seen in both type of diabetes.
• Glomerulosclerosis is a part of
diabetic vasculopathy.
• Involves small vessels throughout
the body.
• The earliest lesions of diabetic
glomerulosclerosis are glomerular
enlargement.
• Decline in the numbers of
podocytes.
• Mild mesangial hypercellularity Microscopic view of glomerulus shows
may be present. Nodular Glomerulosclerosis( nodules of
pink hyaline material). Can have diffuse
• It is called Nodular (Kimmelsteil Glomerulosclerosis
Wilson disease)
Diabetic Kidney Disease
Clinical:
• Microalbinuria is seen in early stages
• After 10-15 years nephrotic syndrome
will develop.
• Progresses to diffuse with chronic
renal failure.
• End-stage kidney disease in 30% of
patients
• Accounts for 20% of patient deaths
Others
• Pyelonephritis
• Papillary necrosis
Microscopic view of glomerulus
• Strict control can postpone these
shows Nodular Glomerulosclerosis.
They can also have Diffuse
Glomerulosclerosis
Diabetic Glomerulosclerosis

• This is a PAS stain of nodular glomerulosclerosis (Kimmelstiel-Wilson disease) in

a patient with long-standing diabetes mellitus.
• Note also the markedly thickened arteriole at the lower right which is typical for
the hyaline arteriolosclerosis that is seen in diabetic kidneys as well.
Acute Proliferative Glomerulonephritis
(Post streptococcal or Post infective or APPGN):
• The exact cause is unknown.
• Deposition of immune complexes like in Autoimmune
complexes
• Classified into the following
• Exogenous:
• Glomerulonephritis that follows certain bacterial Group-A Beta-
hemolytic (streptococcal), Staph. Endocarditis, viral (Mumps,
Hepatitis B,C or HIV Inf.), parasitic (Plasmodium falciparum
malaria), and spirochetal (Treponema pallidum)
• Endogenous:
• SLE
Acute Proliferative Glomerulonephritis
(Post streptococcal or Post infective or APPGN):

• The glomerulus of a
patient who developed
glomerulonephritis after
streptococcal infection.
• The glomerular lesions
usually consist of
leukocytic infiltration
(exudation) into glomeruli
(contains numerous
neutrophils).
Acute Proliferative Glomerulonephritis
(Post streptococcal or Post infective or APPGN):

• Accumulation of numerous
sub epithelial immune
complexes as humplike
structures is a characteristic
feature.
• Frequently, proliferation of
mesangial cells and a
thickened mesangial matrix
result in widening of the stalk.
Acute Proliferative Glomerulonephritis
(Post streptococcal or Post infective or APPGN):

Sign/Symptoms:
• Age: Most common between 6-10 year.
• Smoky or Cocoa-colored urine (Proteins + RBCs).
• The nephritic syndrome begins with oliguria, hematuria,
facial edema and hypertension.
• The diagnosis depends on serologic evidence of
increasing antibody titers to streptococcal antigens.
• Like ASO titer may be high.
• Serum complement levels are low.
Prognosis:
• 95% recover
Rapid proliferative glomerulonephritis (RPGN)

• A Syndrome with severe glomerular

injury.
• Rapid and progressive loss of renal
function (acute renal failure-death?).
• Oliguria (Anuria).
• Most important- “Crescent” formation
in glomeruli.
• “Crescent” refers to shape of the lesion
• Normal architecture of glomerulus is
lost – appears solid, hyper-cellular,
and surrounded by inflammatory
infiltrates
Crescentic (rapidly progressive) glomerulonephritis

• A variety of different pathogenic

mechanisms cause crescent
formation by disrupting
glomerular capillary walls.

• This allows plasma constituents

into Bowman's space, including
coagulation factors and
inflammatory mediators.

• Fibrin forms, and there is

proliferation of parietal epithelial
cells and influx of
macrophages, resulting in
crescent formation.
Rapid proliferative glomerulonephritis (RPGN) (Cresentric form)

• Primary Kidney disorders or Secondary systemic

disorders.
• Most are Immunologic.
• Anti-BM antibodies: In this type of injury,
antibodies are directed against fixed antigens in
the GBM.
• Immune complex mediated.
• Anti-neutrophil cytoplasmic antibodies (ANCAs)
are a group of autoantibodies, mainly of the IgG
type can cause crescentic glomerulonephritis.
• Many instances of anti-GBM antibody GN are
characterized by very severe glomerular damage
with crescents and the development of the
clinical syndrome of rapidly progressive GN.
• Sometimes the anti-GBM antibodies cross-react
with basement membranes of lung alveoli,
resulting in simultaneous lung and kidney lesions
(this is called as Goodpasture syndrome).
Crescent (Half-Moon) Formation
Anti GBM GLOMERUNEPHRITIS
•Antibody-mediated
glomerulonephritis.

Top: Antiglomerular basement

membrane (GBM) antibodies
cause glomerulonephritis by
binding in situ to basement
membrane antigens.
•This activates complement and
recruits inflammatory cells.

Middle: Immune complexes that

deposit from the circulation also
activate complement and recruit
inflammatory cells.

Bottom: Antineutrophil
cytoplasmic antibodies (ANCA)
cause inflammation by activation
IgA Nephropathy (Berger Disease)
• IgA nephropathy is one of the most common causes of recurrent microscopic
or gross hematuria
• This condition usually affects children and young adults.
• Begins as an episode of gross hematuria that occurs within 1 or 2 days of a
nonspecific upper respiratory tract infection.
• Often associated with loin pain.
• The pathogenic hallmark is the deposition of IgA in the mesangium.
• IgA nephropathy to be a localized variant of Henoch-Schönlein purpura.
• Henoch-Schönlein purpura is a systemic syndrome involving the skin (purpuric
rash), gastrointestinal tract (abdominal pain), joints (arthritis), and kidneys.
Morphology:
• The glomeruli may be normal
• May show mesangial widening
• Segmental inflammation confined to some glomeruli (focal proliferative GN);
• Diffuse mesangial proliferation (mesangio-proliferative).
IgA Nephropathy
Things you must know

Common!
Child with hematuria after URI
IgA in mesangium
Variable prognosis
Summary of clinical features of the glomerunephritis
Signs of Glomerulonephritis
• sign and symptoms like
anemia , high blood
pressure or reduce
kidney functions develop
Diagnosis
The main way to confirm the
diagnosis of
glomerulonephritis is via
kidney biopsy.
Other test include:
• Urine analysis
• Protein test,
• Ceatinine test,
• Acid /Concentration test
Nephrotic Syndrome:
• The most important of the primary glomerular
lesions that characteristically lead to the nephrotic
syndrome are:
• Focal and segmental glomerulosclerosis (FSGS)
• Minimal-change disease (MCD).
• The latter is more important in children and former in the
adult.
Nephrotic Syndrome:
Nephrotic syndrome

Diabetes mellitus‡
Amyloidosis‡
Systemic lupus erythematosus
Ingestion of drugs (gold, penicillamine, "street heroin")

Infections (malaria, syphilis, hepatitis B, HIV)

Malignancy (carcinoma, melanoma)

Miscellaneous (bee-sting allergy, hereditary nephritis)

Pathophysiology of the Nephrotic Syndrome:
Nephrotic Syndrome:
Outcome:
• Massive Proteinuria.
• Hypoalbuminemia-Anasarca.
• Low gamma globulins.
• Hyperlipidemia/Lipiduria.
• Loss of antithrombin(anticoagulant), and loss of anti-plasmin activity-
(Outcome: Thrombotic and thromboembolic complications).
Q:
What is the etiology of Nephrotic syndrome in children vs. adults?

A: In children, primary renal disease accounts for 95% of

the cases, the most common cause being minimal
change disease.

By comparison, primary renal diseases are responsible

for only 60% of cases in adults; membranous
glomerulonephritis is the most common primary renal
disease in adults.
Acute Nephritic syndrome
Acute Glomerulonephritis:
• Also known as:
• Acute Nephritis
• Acute Nephritic syndrome
• Seen in- Primary conditions (Acute
proliferative post streptococal
glomerunephritis (APPGN), Rapid
proliferative glomerulonephritis
(RPGN)
• Secondary conditions:
Immunologically-mediated like SLE.
Poststreptococcal GN. A, Glomerular hypercellularity is caused
by intracapillary leukocytes and proliferation of intrinsic
glomerular cells. Note the red cell casts in the tubules. B, Typical
electron-dense subepithelial "hump" (arrow) and
intramembranous deposits. BM, basement membrane; CL,
capillary lumen; E, endothelial cell; Ep, visceral epithelial cells
(podocytes).
Clinical features of Acute Nephritic syndrome

• Hematuria, RBC Casts (Urine).

• Azotemia (A stage before Uremia).
• Oliguria (Reduced Urine output).
• Hypertension.
• Mild-moderate Proteinuria.
• Periorbital edema.
• Sometimes acute renal failure (RPGN).
• Serum anti-streptolysin O antibody titers are elevated in
poststreptococcal cases.
• In adults, 15% to 50% of individuals develop end-stage
renal disease.
Post-Infectious Glomerulonephritis
Things you must know

• Child after strep throat.

• Immune complexes.
• Hypercellular glomeruli.
• Subepithelial humps.
Chronic Glomerulonephritis
• It is an important cause of end-stage renal
disease
• Require chronic hemodialysis or renal
transplantation.
• 20% of cases arise with no history of
symptomatic renal disease
• The kidneys are symmetrically contracted.
• Microscopically, scarring of the glomeruli,
sometimes to in the point of complete
sclerosis.
• There is also marked interstitial fibrosis,
associated with atrophy.
• Lymphocytic (and, rarely, plasma cell) Complete replacement of virtually all glomeruli
infiltrates are present in the fibrotic by blue-staining collagen. (Courtesy of Dr. M.
interstitial tissue. A. Venkatachalam, Department of Pathology,
University of Texas Health Sciences Center,
San Antonio, Texas.)
Clinical features of Chronic Glomerulonephritis
• S/S (of chronic renal failure) include:
Anemia
Hypertension
Proteinuria
High BUN
Progress to Uremia over the years
Most patients have cerebral and
cardiopulmonary complications
Glomerular diseases associated with Systemic diseases:

Most commonly seen in Systemic Lupus Erythematosus(SLE):

① Recurrent Acute nephritis with gross/microscopic hematuria.

② Four types of Nephritis in SLE depending on the
histopathology.
③ Nephrotic Syndrome with gross proteinuria.
④ Chronic renal failure.
⑤ S/S of Uremia like hypertension, anemia and other.
Pathogenesis of Autoimmune Glomerular Diseases
• Antibody-mediated glomerular injury.
• Injury can result either from the
deposition of circulating immune
complexes or from formation in situ of
complexes.
• They trapped in the glomeruli and
cause injury.
A. Deposition of circulating
immune complexes gives a
granular immunofluorescence
pattern.
B. Anti-GBM antibody GN is
characterized by a linear
immunofluorescence pattern.
C. Antibodies against some
glomerular components deposit
in a granular pattern.
Summary of specific form of primary or secondary
glomerulonephritis.
Acute Renal Failure
• Clinically Acute Suppression of renal function within 24 hours to
less than 400ml of Urine output.

Etiology:
• Conditions causing renal vessels obstructions- Polyarteritis
Nodosa, Malignant Hypertension, Hemolytic Uremic Synd.
• RPGN (Crescent in Bowman’s space)
• Conditions causing Acute Tubular Necrosis

• Secondary to destruction of tubules seen in:

• Drugs hypersensitivity acute tubulo-nephritis
• Massive Pyelonephritis
• DIC
• Shock
Urinary casts
• Urinary casts are composed of protein that has changed from the sol state into the gel state
and thus reflects the inside shape of the tubule in which it has condensed
• Several casts may be found in urine, and some of them have diagnostic value as follows:
• Hyaline casts. These clear translucent cylinders composed of protein only are normally found
in the urine.
• Fatty casts. These casts consist of a proteinaceous matrix and lipid droplets or cholesterol
crystals. They are found in nephrotic syndrome.
• RBC casts. These casts consist of a proteinaceous matrix studded with red fragmented RBCs.
They are typical of acute glomerulonephritis, in which they are usually admixed with
dysmorphic RBCs.
• WBC casts. These casts consist of a proteinaceous matrix intermixed with nucleated and
fragmented neutrophils. These casts are typically found in pyelonephritis and tubulointerstitial
nephritis.
Urinary casts continued…
• WBC casts. These casts consist of a proteinaceous matrix intermixed with nucleated and
fragmented neutrophils. These casts are typically found in pyelonephritis and tubulointerstitial
nephritis.
• Renal tubular casts. These casts consist of fragmented cytoplasm of tubular cells and are
usually dark brown.
• Granular casts. These casts are composed of cellular debris. Typically they are derived from
small granules.
• Waxy casts. These refractile casts have sharp outlines, and although there are no cellular
fragments in their matrix they are still readily visible. Waxy casts are a sign of chronic renal
failure.
• Broad casts. These bland or finely granular casts are wider than normal tubules.
CASE

70 year old patient with nausea and vomiting for 2 weeks.

 Dehydrated
 Oliguria
 Low urinary sodium
 No cast or red blood cells in urine

What is yours diagnosis?

Discussion
 Dehydration
 Pre renal cause
 Hypovolemic shock (bleeding, road accidents, severe burns,
severe diarrhea)
 Cardiovascular causes (edema)
 Nephrotic syndrome (anasarca)
 Cirrhosis of the liver
CASE
70 Year old patient with nausea and vomiting for 2 weeks.
 Oliguria
 High urinary sodium
 Granular RBC cast or red blood cells in urine

What is yours diagnosis?

Discussion
Infection
Glomerulonephritis
Renal cause