Download MBBS Nephrotic Syndrome Lecture PPT

Download MBBS (Bachelor of Medicine and Bachelor of Surgery) Latest Nephrotic Syndrome Lecture PPT


DEFINITION

? According to ISKDC (International Study of

Kidney Disease in Children) it is defined as

1. Massive proteinuria - 40 mg/m2/hr (50 mg /

kg / d or 3.5 gm/day)

2. Hypoalbuminemia ( < 2.5g/dl)
3. Hypercholesterolemia ( >220 mg/dL)
With or without
4. Edema


Nephrotic syndrome is a clinical complex

characterized by a number of renal and extra renal
features, most prominent of which are

? Proteinuria (in practice > 3.0 to 3.5gm/24hrs),
? Hypoalbuminemia,
? Edema,
? Hypertension
? Hyperlipidemia,
? Lipiduria and
? Hypercoagulabilty.



Classification

Nephrotic syndrome can be

?Primary, being a disease specific to the

kidneys,

?Secondary, being a renal manifestation of a

systemic general illness
Primary causes

Primary causes include-
? Minimal-change nephropathy (70-90% children

and 10- 15% in adult)

?Focal segmental glomerulosclerosis (FSGS)(15%

in adult)

? Membranous nephropathy (30% in adult)
?Mesangial proliferative glomerulonephritis .
? Rapidly progressive glomerulonephritis
Secondary causes

Secondary causes include-
?Diabetes mellitus
? Lupus erythematosus
? Amyloidosis and paraproteinemias
? Viral infections (eg, hepatitis B, hepatitis C,

HIV )

? Preeclampsia


?Nephrotic syndrome is 15 times more common

in children

? Most cases in children are due to minimal-

change disease.

? In adults, the most common form is

membranous glomerulonephritis, followed by
FSGS.

? Diabetic nephropathy is emerging as a major

cause of nephrotic syndrome








? In a healthy individual, less
than 0.1% of pl. albumin may
traverse the glomerular filtration

barrier.





?Glomerular capillaries are lined
by a fenestrated endothelium
that sits on the glomerular
basement membrane

?Which in turn is covered by
glomerular

epithelium,

or

podocytes, which envelops the
capillaries

with

cellular

extensions called foot processes.

?In between the foot processes are the filtration slits.
?These 3 structures are the glomerular filtration barrier








- Idiopathic, Drugs, Malignancy, especially

Hodgkin's lymphoma,

- Hepatitis C, autoimmune disease (SLE), and

diseases of intraglomerular coagulation


Pathophysiology of NS
Pathophysiology of proteinuria

? The glomerular structural changes that may cause

proteinuria are damage to the endothelial surface, the

glomerular basement membrane, or the podocytes.

? Glomerular

haemodynamics

(Intraglomerular

hypertension

and

hyperfiltration)

can

alter

Glomerular permeabiality.

? Selectivity of proteinuria- Excretion of relatively

low M.W. protein (Albumin or transferrin) is known

as selective proteinuria while if excretion is

predominately high M.W. protein (IgG, IgM or 2

macroglobulin) it is nonselective proteinuria
? It is



also related to relative damage of Glomerular filter.

? If there is predominantly loss of charge selectivity

selective proteinuria.

? If there is predominantly loss of size selectivity

nonselective proteinuria

? A clearance of IgG > 20% of transferrin or albumin

represents nonselective proteinuria and < 10% is

selective proteinuria.

? Proteinuira leaking through damaged glomeruli are

toxic to renal tubules.

? So every attempts should be made to prevent and

reduce proteinuria irrespective of serum protein level or

basic disease
Hypoalbunemia

? It is due to both the proteinuria and due to the

increase renal catabolism (in tubules).

? In fact hepatic albumin synthesis is increased from

145?9mg/kg/day to 213?17mg/kg/day in nephrotic
patients.


Pathogenesis of edema



Metabolic consequences of proteinuria

? Metabolic consequences of the nephrotic

syndrome include the following:

Infection
Hyperlipidemia and atherosclerosis
Hypocalcemia and bone abnormalities
Hypercoagulability
Hypovolemia
Infection in Nephrotic Syndrome

Proposed explanations include the following:
?Urinary immunoglobulin losses
?Edema fluid acting as a culture medium
?Protein deficiency
? Decreased bactericidal activity of the leukocytes
?Immunosuppressive therapy
?Urinary loss of a complement factor (properdin

factor B) that opsonizes certain bacteria
Hyperlipedemia

? Due to increase hepatic lipoprotein synthesis that is

triggered by reduced oncotic pressure.

? Defective lipid catabolism has also important role.
? LDL and cholesterol are increased in majority of

patients whereas VLDL and triglyceride tends to rise
in patients with severe disease.

? It increases the relative risk for MI 5.5 fold and

coronary death 2.8 fold.

? It also increases progression of renal disease
Hypercoagulability

v Multifactorial in origin
v Increase urinary loss of antithrombin III.
v Altered levels and/or activity of protein C & S.
v Hyperfibronogenemia due to increase hepatic

synthesis.

v Impaired fibrinolysis due to decrease plasminogen.
v Increase platelet aggregability ? relative immobility

- haemoconcentragtion from hypovolemia. ?
hyperlipidemia

v Alteration in endothelial function
Hypocalcemia

? Hypocalcemia is common in the nephrotic syndrome,

but rather than being a true hypocalcemia, it is usually
caused by a low serum albumin level.

? Nonetheless, low bone density and abnormal bone

histology are reported in association with nephrotic
syndrome.

? This could be caused by urinary losses of vitamin D?

binding proteins, with consequent hypovitaminosis D
and, as a result, reduced intestinal calcium absorption
Hypovolemia

? Hypovolemia occurs when hypoalbuminemia

decreases the plasma oncotic pressure

? Resulting in a loss of plasma water into the

interstitium and causing a decrease in circulating
blood volume.

? Hypovolemia is generally observed only when the

patient's serum albumin level is less than 1.5 g/dL.

? Hypotension is a late feature
FUNCTIONAL CONSEQUENCE OF URINARY

LOSS OF PLASMA PROTEIN

? Thyroid binding globulins and thyroxin ? may lead to

hypothyroidism.

? Vit D binding protein ? osteomalacia, but rare
? Total calcium is also low due to low albumin level.

? Transferrin and erythropoietin and ? microcytic

hypochromic anaemia.

? ARF ? is rare in nephrotic syndrome. In whom it occur

patient are elderly of minimal changes disease / FGSS
Clinical Features

COMMON:
? Anorexia, irritability, abdominal pain, diarrhoea and genital

edema

? Frothy urine (high concentrations of protein)
? Edema may cause dyspnea (pleural effusion or laryngeal

edema),

? Chest discomfort (pericardial effusion), arthralgia

(hydrarthrosis), or abdominal pain (ascites or, in children,
mesenteric edema).

? Edema may obscure signs of muscle wasting and cause

parallel white lines in fingernail beds (Muehrcke's lines).

UNCOMMON:
? Hypertension, Gross hematuria







? Prolonged NS may result in

nutritional

deficiencies,

including

protein

malnutrition

? Myopathy
? Decreased total Ca+2, tetany
? Spontaneous peritonitis and

opportunistic infections

? Coagulation disorders, with

decreased

fibrinolytic

activity
Differential Diagnosis

? Heart failure

? Cirrhosis

? Glomerulonephritis

? Protein losing enteropathy

? PEM


INVESTIGATIONS
Urine Analysis

? Routine exam. : 3+ or 4 +

proteinuria

? 24 hour urine protein >3.0 gm or

40 mg/m2/hr

? Spot Urine protein/creatinine

ratio : > 2.0

? Urine protein selectivity
? Hyaline casts
? Microscopic hematuria in 20%


Proteinuria - Parameters


Hyaline Cast in urine


Blood

? S.Cholesterol ( > 250 mg/dL)
? S.Albumin (< 2.5 gm/dl)
? S. A/G ratio ? reversal
? S.Creatinine
? Bl. Urea
? S . C3 and C4 levels
? CBC : Increased Hb, Platelets, Hct
BLOOD

? Serum proteins -Total proteins decreased
? Serologic studies for infection and immune

abnormalities

OTHER INVESTIGATIONS:
? Renal ultrasonography
? Renal biopsy
? CXR: ? Pleural effusion
? Pulm edema - rare
MANAGEMENT

Specific treatment
? In minimal-change nephropathy, glucocorticosteroids, such

as prednisone, are used. Children who relapse may be treated

with rituximab

? In some lupus nephritis, prednisone and cyclophosphamide

are useful

? Secondary amyloidosis with nephrotic syndrome may

respond to antiinflammatory treatment of the primary disease.

? In membranous nephropathy, expectant management without

immunosuppression can be used for the first 6 months, in

patients at low risk for progression (ie, those with serum

creatinine level < 1.5 mg/dL).

? Patients with renal insufficiency (serum creatinine level > 1.5

mg/dL) are at greatest risk for the development of end-stage

renal disease and should receive immunosuppressive therapy.

[3
DIET AND ACTIVITY

? The diet in patients with nephrotic syndrome

should provide adequate energy (caloric) intake
and adequate protein (1-2 g/kg/d).

? A diet with no added salt will help to limit fluid

overload.

? Management of hyperlipidemia could be of some

importance if the nephrotic state is prolonged.

? Fluid restriction per se is not required.
? Ongoing activity, rather than bed rest, will reduce

the risk of blood clots
Acute Nephrotic Syndrome in Adults

? Diuretics will be needed; furosemide, spironolactone, and

even metolazone may be used. Volume depletion may
occur with diuretic use, which should be monitored.

? Anticoagulation has been advocated by some for use in

preventing thromboembolic complications,

? Hypolipidemic agents may be used, but if the nephrotic

syndrome cannot be controlled, the patient will have
persistent hyperlipidemia.

? ACE inhibitors and/or ARB are widely used. These may

reduce proteinuria by reducing the systemic blood
pressure, by reducing intraglomerular pressure, and also by
direct action on podocytes
Management

? Long-Term Monitoring- Follow-up care in

patients with nephrotic syndrome includes

? Immunization
? Treatment of relapses of steroid-responsive

nephrotic syndromes,

? Monitoring for steroid toxicity, and
? Monitoring of diuretic and angiotensin

antagonist regimens.


DIABETIC NEPHROPATHY

? The earliest morphologic

abnormalities

in

nephropathy are thickening

of the GBM and expansion

of mesangium.

? Composition of GBM is

altered with loss of heparan

sulfate moities.

? Prominent nodular matrix

expansion

(classical

Kimmelsteil-Wilson lesion)

are often found.



This post was last modified on 30 November 2021