Module 4: Renal: Nephrotic Disorders Flashcards Preview

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Flashcards in Module 4: Renal: Nephrotic Disorders Deck (39):

First lets review the basics of renal. What is nephrotic disease and the 5 key components?

Damage is more toward the epithelial side (urinary side) so you get more than 3.5g protein per day
1. Massive Proteinuria
2. Anasarca (generalized edema because your losing oncotic pressure)
3. Hypoalbuminemia because your losing albumin
4. Lipoproteins (transport lipids -- leads to athersclerosis)
5. Leads to lipiduria (oval fat bodies in the urine)


What is nephrin in the Glomerular basement membrane.

Protein that is negatively charges so it repels other proteins but in most of the nephrotic syndromes there is damage to the nephrin


Now for Nephritic Syndrome, what are some features?

Damage is more toward the endothelial side (blood vessel side)
1. Hematuria (RBC casts taking the shape of tubules)
2. Proteinuria (less than 3.5g)
3. Periorbital edema (Not anasarca because less protein)
4. Oliguria
5. Hypertension
6. Azotemia


What is the key prognostic factor for both nephritic and nephrotic syndrome?

Degree of protein loss
--hence why nephrotic is usually worse
--note that albumin is the smallest protein (20-40nm)


First lets cover the nephrotic disorders. First one to discuss in minimal change disease. What are some features in children?

Most common cause of nephrotic syndrome in children due to leukemia, solid malignancies, vaccines, viral infections, and NSAIDS.
--really good prognosis in kids because they respond to steroids


What are some features of minimal change disease in adults?

Associated with Hodgkin's Lymphoma
--worse prognosis and usually progresses to FSGS (doesn't respond to steroids)


For both kids and adults what is the pathogenesis, in minimal change disease?

Autoimmune destruction of BM by T cells -- leads to selective proteinuria (lose albumin so this indicates that just with this loss the destruction of the layers is small)


What is the presentation for minimal change disease?

Foamy Urine (massive proteinuria)
Generalized Edema
Weight gain (edema)


What investigations are done for minimal change disease?

Urine: lipids, proteins, oval fat bodies on microscopy/fatty casts and greater than 3.5 g/day protein (because all your losing is albumin no other protein)
Blood: hypoalbuminemia and hyperlipidemia


Renal Biopsy is the most accurate diagnosis test. Explain what you see on LM, IF and EM

LM: normal (use silver and PAS to see foot processes)
IF: normal
EM: diffuse effacement of foot processes of the podocyte


What complications are seen in adults with minimal change disease?

End stage renal disease --- uremia --- bleeding because platelets do not degranulate (in uremic environment), pericarditis, puritis, encephalopathy, ARDS and gastritis


What complications are seen in children?

Good prognosis


What complications are seen in both kids and children?

Hypercoaguable state
--loss of antithrombin III = DVT and PE
--Renal vein thrombosis = left sided varicocele in males (bag of worms)
--atherosclerosis (MI, stroke, and Ulcers/Gangrene)


Next nephrotic disease is Focal Segmental Glomerulosclerosis, what are some features?

Worst prognosis of all renal diseases (b/c it does not respond to steroids)
--only seen in adults
--Most common intrinsic renal disease that leads to nephrotic syndrome but most common systemic disease that leads to nephrotic syndrome is DM.


What is the etiology for FSGS?

Often idiopathic or secondary (Anything that decreases the mass of the kidney) to:
Heroin Abuse
Morbid Obesity
African Americans
Chronic Renal Disease
Subtotal Nephrectomy
Congenital Unilateral Renal Agenesis


What is the pathogenesis for FSGS?

Decreased renal mass --- compensatory hyperfiltration -- intraglomerular HTN and Hyperfiltration injury --- non selective proteinuria (so losing immunoglobins and albumin)
--basically you have damage to one part of the kidney so the other kidney is compensating


What is the presentation for FSGS?

Foamy urine


What do you see in the blood and urine in patients with FSGS?

Blood: hyperlipidemia and hypoalbuminemia
Urine: lipiduria (oval fat bodies/fat cell casts)
proteinuria greater than 3.5g/day (non selective so losing globulins and albumins)
--microscopic hematuria


What do you see on renal biopsy for patients with FSGS?

LM--PAS stain : segmental hyalinosis of some glomeruli (so basically the glomerulus is fibrosed focally not globally)
EM: Patchy effacement of foot processes of podocytes
IF: negative or non specific IgM and C3


What conditions can progress to FSGS?

IgA neuropathy
Alports Syndrome (nephritic syndrome)
Minimal Change disease
Chronic Kidney Disease
Subtotal nephrectomy
Berger's Disease ( nephritic syndrome)


What are the complications of FSGS?

Leads to ESRD and uremia: does not respond to steroids
Hyperlipidemia: atherosclerotic complications
Hypercoaguable states: loss of antithrombin III, protein C and protein S in the urine
Recurrent Infections: loss of immunoglobulins and complement
50% will have recurrence of this


The next nephrotic disorder is Membranous Glomerulopathy, what are some features?

Nephrotic Syndrome in adults with non selective proteinuria
--most common etiology: idiopathic (dx of exclusion)
--Secondary causes: SLE, Hep B, Malaria, Syphilis, Leukemia/Lymphoma, Lithium (bipolar patients), NSAIDS, Penicilamine (immunosuppressants: wilson's and RA), Gold Salts (immunosuppressants), Mercury poisoning and Captopriol (ace inhibitor for HTN)


How do patients with Membranous Glomerulopathy present?

Foamy urine
Anasarca (pleural effusion and pericardial effusions)
HTN (nephritic syndrome symptom)


What is seen in the urine and blood of patients with Membranous Glomerulopathy?

Urine: Lipiduria = oval fat bodies/ fat cell casts
proteinuria greater than 3.5 g/day
microscopic hematuria (nephritic syndrome symptom)
Blood: hyperlipidemia and hypoalbuminemia


What is seen on renal biopsy in patients with Membranous Glomerulopathy?

LM (PAS): diffuse global thickening of the GBM with no hypercellularity
--need to differentiate it from MPGN (see thickening and hypercellularity)
Silver stain: thickening and spikes domes
IF : fine, granular subepithelial deposits of IgG and C3
EM: subepithelial immune complex deposits with alternating spikes and domes


What are the complications for Membranous Glomerulopathy?

Hypercoagulability (leads to ischemic heart disease)
Renal Failure
--better prognosis than FSGS but worse than minimal change disease


What is are poor prognosis indicators?

greater than 50 y.o
greater than 10 gm proteinuria


Other etiologies of nephrotic syndrome is Amyloidosis, explain AL in terms on nephrotic syndrome

AL (primary) amyloidosis
--precursor protein = light chain
--can occur alone or in association with multiple myeloma


Explain AA in terms on nephrotic syndrome ?

AA (secondary) amyloidosis
--precursor protein = apolipoprotein produced by liver as an acute phase reactant in response to long standing infection/inflammtion
--RA, Bechet syndrome, Crohn's disease, osteomyelitis, TB, renal cell carcinoma, and Hodgkin's


What is seen on LM and EM in Amyloidosis?

LM: nodular, amorphous hyaline material in the mesangium and capillary loops ---narrowing of the capillary lumen
Congo red stain: positive with polarizable apple green biefringence
EM: subendothelial and mesangial fibrils


What is the presentation for patients with Amyloidosis?

Proteinuria and edema (nephrotic syndrome)
--electrolyte abnormalities
--heart: CM/CHF, arrhythmias, heart block
--GI: hepatomegaly, malabsorption, bleeding
--Neuro: ischemic stroke, neuropathy, orthostatic hypotension
--Skin: easy bruising and purpura


What is the prognosis for Amyloid?

Very poor prognosis
--many patients die of end organ failure from amyloid deposition


Another cause for nephrotic syndrome is due to Diabetic nephropathy, what are some features?

The leading cause of end stage renal disease in USA
--seen in 25-40% of type 1 and type 2 diabetics


What is the pathogenesis for Diabetic nephropathy?

Kidney disease is a result of adverse effects of systemic hyperglycemia:
--normal kidney transplanted into patients with diabetes developed diabetic lesions
---kidneys from patient with DM that were inadvertently transplanted into non- diabetic ERSD patients resolved their diabetic lesions
--therefore strong evidence that exposure to the diabetic milieu and not an intrinsic defect in the kidneys result in development of diabetic nephropathy.


What structures does hyperglycemia damage in the kidney?

Glomerulus and Arterioles
this gives you diabetic nephropathy


What are the earliest lesions in diabetic nephropathy?

Expansion of mesangial matrix and thickening of GBM


What are the later lesions in diabetic nephropathy?

Diffuse Global Glomerulosclerosis with:
--diffuse increase in mesangial matrix and diffuse thickening of GBM
--Kimmelstiel-Wilson nodules (nodules contain lipids and fibrin)
---fibrin cap and capsular drop (plasma proteins)
--ischemia: causes tubular atrophy and interstitial fibrosis
--hyaline arteriolosclerosis


What is the clinical outcome of diabetic nephropathy?

Initially hyperglycemia leads to hyperfiltration and increased glomerular hydrostatic pressure
--after 7 to 13 years of disease: microalbuminuria appears
--after 10-20 years: macroalbuminuria
--after ward there is persistent and progressive proteinuria, HTN, highly variable decline in GFR


What is the pathogenesis for membranous glomerulus?

IgG4 antibodies act against phospholipase A2 (PLA2) receptors and deposit in the subepithelium --- causes podocytes to be displaced and lay down additional basement membrane.

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