Week 1 PBL

Question 1

What are the four types of nephrotic syndrome

Answer 1

1. minimal change disease
2. membranous glomerulonephropathy
3. focal segmental glomerulosclerosis
4. membranoproliferative glomerulonephritis

Question 2

what is the most frequent cause of nephrotic syndrome in children

Answer 2

minimal change disease

Question 3

what is minimal change disease

Answer 3

• glomeruli appear normal (no electron dense deposits) but visceral epithelial cells show uniform and diffuse effacement of foot processes (replaced by rim of cytoplasm showing vacuolization, swelling, and villous hyperplasia)
• visceral epithelial injury leading to cytokine release may result in loss of the glomerular charge barrier, detachment of epithelium, loss of granular polyanions
• may follow prophylactic immunization or respiratory infection
• usually dramatically responsive to corticosteroids and immunosuppression

Question 4

what are two distinguishing features of minimal change disease

Answer 4

1. diffuse effacement of foot processes of epithelial cells in glomeruli that appear virtually normal by light microscopy–principle lesion is in the VISCERAL EPITHELIAL CELLS
2. dramatic response to corticosteroid therapy

Question 5

What is membranous glomerulonephropathy

Answer 5

type of nephrotic syndrome

ELECTRON DENSE DEPOSITS (contain immunoglobins) on subepithelial side of basement membrane leading to diffuse thickening of capillary wall

may result from tumors, lupus, gold, mercury, captopril, penicillamine, Hep B, syphilis, schistosomiasis, malaria, diabetes mellitus, thyroiditis

• complement activation leading to the MAC makes the BM more leaky
• a form of chronic immune complex-mediated disease–in the primary form, the resulting nephrotic syndrome is considered an autoimmune disease linked to susceptibility genes and cause by antibodies to a renal autoantigen

Question 6

What is the most common cause of nephrotic syndrome in adults?

Answer 6

membranous glomerulonephropathy

Question 7

how does the glomerular capillary wall become so leaky in membranous glomerulonephropathy?

Answer 7

• neutrophils, monocytes, or platelets in glomeruli and the virtually uniform presence of complement, and experimental work suggests a direct action of C5b-C9, the pathway leading to the formation of the MEMBRANE ATTACK COMPLEX
• C5b-C9 causes activation of glomerular epithelial and mesangial cells, inducing them to liberate proteases and oxidants, which cause capillary wall injurt and increased protein leakage

Question 8

do membranous glomerulonephropathy and focal segmental glomerulosclerosis respond well to corticosteroid therapy?

Answer 8

no

Question 9

what is focal segmental glomerulosclerosis

Answer 9

sclerosis of some but not all glomeruli

idiopathic–may follow renal mass loss such as in advanced renal endstage disease, HIV, heroin use

may progress to glomerulonephritis and 50% of patients end up in end stage renal disease

IgM and complement are deposited in the sclerotic segment as well as HYALINE masses with lipoid drops

basement membrane collapses, increase in mesangial matrix, denudation of epithelium from BM

Question 10

how does focal segmental glomerulosclerosis differ from minimal change disease?

Answer 10

high degree of hematuria
decreased GFR
hypotension

Question 11

how does focal segmental glomerulosclerosis prevalence differ between children and adults

Answer 11

equally prevalent

Question 12

what does it mean by “focal” and “segmental” glomerulosclerosis

Answer 12

focal = because it is characterized by sclerosis of some but not all glomeruli

segmental = because in the affected glomeruli, only a portion of the capillary is involved

Question 13

how do the clinical signs of focal segmental glomerulosclerosis differ from minimal change disease

Answer 13

in FSG there is?

1. there is higher incidence of hematuria, reduced GFR and hypertension
2. proteinuria is often more nonselective
3. there is poor response to corticosteroid therapy
4. there is progression to chronic glomerulosclerosis
5. immunofluorescence microscopy may show nonspecific deposition (trapping) of IgM and C3 in the sclerotic segment

Question 14

what is membranoproliferative glomerulonephritis?

Answer 14

IDIOPATHIC

type 1 - subendothelial electron dense deposits (immune complexes)

type 2 - deposition of dense material that changes the lamina dense of the BM into irregular ribbon-like electron dense structures

poorly responsive to corticosterois

changes in BM and proliferation of glomerular cells (which also become large and hypercellular), proliferating mesangial cells, leukkocytes infiltration

Question 15

what are three distinguishing characteristics of membranoproliferative glomerulonephropathy?

Answer 15

alterations in the basement membrane
proliferation of glomerular cells
leukocyte infiltration

**proliferation is predominantly in the mesangium

Question 16

Distinguish between nephrotic and nephritic syndrome

Answer 16

Nephritic = PHAROH 
Proteinuria (mild-moderate)
Hypertension
Azotemia
RBC casts
Oliguria
Hematuria 

Nephrotic = PECH
Proteinuria (>3.5g/day)
Edema
Cholesterolemia 
Hypoproteinemia

Question 17

Why are corticosteroids administered in physiologic doses?

Answer 17

to replace deficient endogenous hormones

Question 18

why are glucocorticoids administered in pharmacologic (larger) doses

Answer 18

decrease inflammation

Question 19

What is the first step in treatment of idiopathic nephrotic syndrome in which kidney biopsy is not initially indicated?

Answer 19

trial of corticosteroids

Question 20

are steroids immunosuppresive

Answer 20

yes

Question 21

side effects of corticosteroid treatment

Answer 21

hyperglycemia
weight gain and severe swelling
psychiatric symptoms (mania, depression, cognitive dysfunction)
gastric and duodenal bleeding
infections and immunosuppresion
skin effects
eyes
MSK (muscle wasting)
adipose redistribution (buffalo hump)
skeletal effects (osteoporosis)
cushings
adrenal suppression

Question 22

what is prednisone

Answer 22

corticosteroid

glucocorticoid activity as well as anti-inflammatory and immunosuppresant activity

Question 23

indications for prednisone treatment for nephrotic disease

Answer 23

• mainstay of treatment for minimal change disease in children and adults
• used commonly in membranous glomerulonephropahy and FSGS initially but with less consistent results
• may hasten remission in membranous nephropathy

Question 24

precautions with prednisone use

Answer 24

• long term use or doses greater than physiologic amounts may lead to clinically relevent suppression of the pituitary-adrenal axis, suppression of linear growth in pediatric patients or hypercorticoidism (Cushings)
• may cause immunosuppression
• contraindicated in patients with active TB
• use with caution in patients with hypothyroidism, diabetes, cirrhosis, peptic ulcer, ulcerative colitis, osteoporosis, glaucoma, myasthenia gravis, recent MI, psych disorders, epilepsy or thromboembolic disorders