glomerular syndromes pk

8/11/2019 Glomerular Syndromes PK

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Pathology of Common

GLOMERULAR SYNDROMES

Dr Purushotham krishnappa


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Objectives

To learn basic renal terminologies

Understand the common clinical featuresof common glomerular diseases Nephrotic syndrome

Nephritic syndrome

Rapidly progressive glomerulonephritis


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Basic terminology and concepts

Azotemia

Biochemical abnormality

Raised blood urea nitrogen and creatinineDecreased GFR

The cause may be:RenalExtrarenalPre-renal: hypoperfusion

Post-renal: obstruction


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Basic terminology and concepts

Uraemia

Azotaemia plusclinical signs and symptomsMetabolicEndocrineGastrointestinal uraemic gastroenteritis

Peripheral nerves peripheral neuropathyHeart uraemic fibrinous pericarditis.


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Clinical syndromes

Clinical syndromes are convenient starting pointstoidentify and evaluate kidney diseases.

Syndromes related to injury to the glomerular capillary

wall are quitespecificfor glomerular diseases.

Clinical presentations of diseases of tubules, interstitiumand blood vessels are less specific.

They often present as non-specific acute or chronicrenal insufficiency.


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Clinical syndromes

Point to remember:

Some diseases may have more than 1 clinicalpresentation with different syndromes or a mixture ofsyndromes, e.g. SLETherefore, clinical syndromes alone may not besufficient.

A renal biopsy - based diagnosis may be required.


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Clinical syndromes forglomerular diseases

1. Nephrotic syndrome

2. Acute nephritis3. Asymptomatic haematuria

4. Asymptomatic proteinuria.

5. Rapidly progressive glomerulonephritis6. Acute renal failure

7. Chronic renal failure


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Nephrotic Syndrome

1. Heavy proteinuria(Nephrotic range ismore than 3.5 gm /day)

2. Hypoalbuminaemia(less than 3 gm/dl)

3. Severe oedema-generalised4. Hyperlipidemia

Classic example: minimal change disease


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Causes of Nephrotic Syndrome

Primary Glomerular Disease

Membranous glomerulopathy - Adults Minimal change disease - Children Focal segmental glomerulosclerosis Membranoproliferative glomerulonephritides Other proliferative glomerulonephritis (focal, "pure mesangial," IgA

nephropathy)System ic Diseases

Diabetes mellitus Amyloidosis

Systemic lupus erythematosus Drugs (nonsteroidal anti-inflammatory, penicillamine, "street heroin") Infections (malaria, syphilis, hepatitis B and C, acquired

immunodeficiency syndrome) Malignant disease (carcinoma, lymphoma) Miscellaneous (bee-sting allergy, hereditary nephritis)


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Causes and conditions associatedwith nephrotic syndrome

Frequency:Children (unselected):

Minimal change disease 88%

Focal segmental glomerulosclerosis 5%Membranoproliferative glomerulonephritis 1%

Adults:

Minimal change 15%

Focal segmental glomerulosclerosis 35%

Membranous glomerulopathy 33%

Membranoproliferative glomerulonephritis 2%


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Nephrotic syndrome

Associated with a myriad of diseases.

A few forms of glomerular diseasesaccount of most of the cases of nephroticsyndrome.


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Hypoproteinemia

Albumin

Immunoglobulins

Metal binding proteins Erythropoietin urinary

loss

Transferrin Complement deficiency

Coagulation components


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Hyperlipidemia

Hypercholesterolemia

Hypertriglyceridemia

Low-density lipoproteins (LDL) Very low- density lipoproteins (VLDL)


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Mechanisms of Hyperlipidemia

Increased hepatic synthesis of LDL, VLDL andlipoprotein (a) in response to hypoalbuminemia

Urinary loss of HDL

Enzymatic changes with abnormal lipidbiosythesis and degradation


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Edema

Lower colloid osmotic pressure?

15mmHg H2Ocolloid osmotic pressure26 mmHg

Edema


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Diagnosis

Diagnosis:

NS?

Primary or secondary?Complications?


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Differential diagnosis

Primary Secondary

children minimal change allergic purpuranephritis

Teenager mesangial proliferative FSGSnephritis

Middle age mesengial capillary SLE LN

nephritisold age membranous myeloma,

amyloidosis

nephropathy


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Complications

Acute renal failure( ARF)

Hypoalbuminemia Hypovolemia pre-renal

azotemia

Dyslipidemia


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Treatment

Support care

Rest in bed; limitation of proteinintake(0.8-1.0g/kg/d); limitation of saltintake (


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Treatment

FSGS: sensitive to steroids in 30-50% ofpatients; slow response to therapy;steroids therapy (onset) for 3-4 months; if

not response until 6 month (resistant),then try cyclosporine.

Mesangial proliferative GN: no evidence

show that adults will response to steroids;aspirin


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Acute Nephritis

Acute onset Gross hematuria Hypertension Mild to moderate proteinuria

Classic example: acute post-s treptococcalglomerulonephr i t is


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Asymptomatic hematuria or

proteinuria

Haematuria

Subnephrotic proteinuria


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Rapidly Progressive

Glomerulonephritis

Characterised by:

Acute nephritis Proteinuria

Acute renal failure

Classic example: Crescentic glomerulonephritis


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Histologic Alteration of

glomerulus - 1

Hypercellularity

(proliferative)

Increase in number of cells

in glomerular tuft.Due to:

Cellular proliferation ofmesangial or endothelial

cells (endocapillary) Leukocyte infiltration

Crescent formation(extracapillary)


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glomerulus - 2Basement membranethickening

Thickening of capillary wall by lightmicroscopy

On electron microscopy -deposition of amorphous materialoften immune complexes onendothelial/epithelial side ofbasement membrane e.g.membranous g lomeru lopathy

OR Thickening of basement

membrane proper e.g diabet icg lomerulosc leros is


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glomerulus- 3

Hyalinisation or

sclerosis of

glomerulus

Amorphous substance plasma proteins

Collagen

Capillary luminaobliterated

End result of variousglomerular damage


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glomerulus

1. Hypercellularity (proliferative)

2. Basement membrane thickening

3. Hyalinisation or sclerosis ofglomerulus


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Glomerular Pathology

Terminology

Diffuse- all glomeruli affected

Global- the whole glomerulus affected

Focalonly a portion of glomeruli affected

Segmentalonly a part (segment) of each glomerulus affected

Mesangialmesangium affected.


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Summary of Glomerular SyndromesAcute nephritic syndrome Hematuria, azotemia, variable

proteinuria, oliguria, edema, andhypertension

Rapidly progressiveglomerulonephritis

Acute nephritis, proteinuria, andacute renal failure

Nephrotic syndrome >3.5 gm proteinuria,hypoalbuminemia, hyperlipidemia,lipiduria

Chronic renal failure Azotemia uremia progressing foryears

Asymptomatic hematuria orproteinuria

Glomerular hematuria; subnephroticproteinuria

glomerular syndromes pk

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