L7- Nephrotic Syndrome Flashcards
list the signs and symptoms that characterize nephrotic syndrome
- heavy proteinuria (>3.5g/day)
- hypoalbuminemia
- edema
- hyperlipidemia, lipuria
- normal complement levels
describe how hypoalbuminemia occurs in nephrotic syndrome and what it leads to in terms of clinical presentation
1) glomerular membrane damage –> proteinuria / albumin loss –> hypoalbuminemia
2a) hypoalbuminemia => dec oncotic pressure + dec GFR (–> RAAS activation –> fluid retention) => edema
2b) hypoalbuminemia => inc plasma protein synthesis in liver => inc lipoproteins => hyperlipidemia
list the common nephrotic renal diseases (and their categories)
Immunoglobulin deposition: membranous nephropathy
No immunoglobulin deposition: minimal change disease, FSGS, diabetic nephropathy, amyloidosis
minimal change disease is mostly common in (1) and is usually caused by (2) and is possibly seen in (3) and (4) conditions
1- children (15% in adults)
2- idiopathic
3- lymphoma
4- renal cell carcinoma
what is the reason minimal change disease and FSGS are suspected to linked to circulating glomerular permeability factors
rapid recurrence of disease after renal transplantation into patients with the disease
(50% w/ FSGS)
minimal change disease as a result of (1) injury causing (2); there is no (3) or (4) involved although there may be involvement of (5) because treatment with (6) resolves symptoms
1- glomerular epipthelial cells / podocytes
2- inc glomerular permeability –> massive proteinuria
3- immune complex deposition
4- inflammatory injury
5- immune system
6- steroid therapy (immune suppressors)
effacement of foot processes = …..
flattening, therefore more likely to break from basement membrane (rara externa) and less likely to prevent protein filtration
describe the microscopic changes observed in minimal change disease
LM: normal
IF: no IG deposits
EM**: fusion of foot processes with their effacement and detachment from basement membrane
On physical exam in minimal change disease, BP pressure is (high/normal/low) and (2) is very evident. On labs, serum shows (3) and urine shows (4).
-normal BP
-edema (periorbital, pedal)
Labs: low albumin, normal creatinine
Urine: proteinuria, bland urine sediment
Minimal change disease is treated with (1) and usually has a (good/bad) prognosis although (3) frequently occurs and there (is/is not) a tendency to progress to CRF/ESRD.
1- 8 wks steroids
2- good: >90% children have complete remission (1/3 no relapse, 1/3 few, 1/3 frequent), usually relapses in adults
3- relapse after stopping steroids
4- no progression to CRF/ESRD
define the components of FSGS
- Focal: affects few/some glomeruli
- Segmental: affects segment/part of glomerulus
- Glomerulo: affects glomeruli
- Sclerosis: scarring
FSGS is often a primary disease with (1) as its cause, but it can be a secondary disease to the following: (2).
1- idiopathic
2- HIV, obesity, chronic reflux nephropathy, heroin use, malignancies (lymphoma)
describe the pathogenesis of secondary FSGS
‘renal ablation glomerulopathy’
1) i) reduction in renal mass (due to renal disease), ii) partial nephrectomy, iii) glomerularnephritis, iv) congenital unilateral renal agenesis/aplasia
2) compensatory hypertrophy + hyperfiltation of remaining glomeruli to maintain GFR
3) intraglomerular HTN + hyperfiltration injury
4) FSGS
describe the microscopic changes observed in FSGS
LM: FSGS
IF: negative OR non-specific granular deposits of IgM/C3
EM: patchy foot process fusion and effacement
The initial presenting feature of FSGS is (1) that will progress into (2). Many patients also have (3) and (4). There (is/is not) a tendency to progress into CRF/ESRD.
1- asymptomatic proteinuria
2- nephrotic syndrome (massive proteinuria, microscopic hematuria)
3/4- HTN, renal insufficiency
5- it will progress to ESRD n 5-20 yrs
membranous nephropathy is usually caused by (1) via (2) or (3) [include examples for each]
1- idiopathic
2- endogenous Ags: DNA (SLE/tumors)
3- exogenous Ags: Hep B, syphilis, malaria, captopril, mercury, gold, penicillamine
describe the process of immunoglobulin deposition in membranous nephropathy
1) Ab-Ag reaction
2) complement activation
3) C5b-C9 (MAC) insert onto podocyte membrane
4a) direct damage to cytoskeleton => podocyte detachment
4b) stimulation of epithelial / mesangial cells + protease, oxidant, CK release => GBM growth / thickening
5) GFM damage, inc permeability, massive proteinuria
[subepithelial deposition]`
what are the two theories of immune complex deposition in membranous nephropathy
(localized to sub-epithelial zone) in situ (favored theory, Heymann Nephritis): IC formation in the kidney / glomerulus
circulating: IC formation in blood
describe the microscopic changes observed in membranous nephropathy
- LM: diffuse GBM thickening (little inc in cellularity)
- IF: fine IgG/C3 subepithelial deposits
- EM: subepithelial IC deposits, GBM spikes indicating proliferation / growth
Patients with membranous nephropathy present with (1). At the 20 year follow up they can develop into (2), (3), or (4) [include % chance]. It is worse in patients that are/have (5).
1- nephrotic syndrome, microscopic hematuria (50%), HTN
2- spontaneous remission (25%)
3- persistant proteinuria, stable or loss of renal function (50%)
4- ESRD, renal vein thrombosis (25%)
5- males, >50 y/o, >10g proteinuria
1 cause of ESRD in USA is…..
diabetic nephropathy (1/3 of all ESRD patients)
-seen in 25-40% of type 1/2 diabetics
what is the main evidence that diabetic nephropathy results from systemic effects
(mainly systemic hyperglycemia)
1) normal kidney into diabetic patient => diabetic lesions
2) diabetic kidney into normal patient => resolution of diabetic lesions
list the 5 general effects of hyperglycemia that starts the pathogenesis of diabetic nephropathy
- non-enzymatic glycosalation
- advanced glycosylation products
- inc GFs (TGF-β)
- activation of CKs
- O2 species formation
Hyperglycemia has many effects in the blood that will lead to: -increased (1) causing (2) -(3) changes leading to GBM thickening -(4) hemodynamic changes all of which result in (5)
1/2- inc matrix formation –> mesangium expansion
3- inc type IV collagen, inc fibronectin, dec proteoglycan heparin sulfate
4- hyperfiltration, inc glomerular capillary pressure, glomerular hypertrophy
5- glomeruloscelerosis
describe the initial and later presentation of diabetic nephropathy (microscopically)
Early lesions: mesangial matrix expansion, GBM thickening
Later lesions: diffuse global glomerulosclerosis: Kimmelstiel-Wilson nodules, plasma proteins, ischemia, hyaline atherosclerosis
describe the progression of clinical changes in diabetic nephropathy
- initially: inc GFR + inc glomerular hydrostatic pressure
- 7-13 yrs: microalbuminuria
- 10-20 yrs: macroalbuminuria
- lastly: persistent/progressive proteinuria, HTN, GFR decline (1-24 ml/min/yr)
Amyloidosis most commonly affects the (1) part of the (2) organ. This is usually the result of primary amyloidosis caused by (3) which occurs alone or in association with (4). It can also be from secondary amyloidosis, which results from (5).
1/2- glomerulus, kidney
3- AL (abnormal light chain from Ig via abnormal plasma cell clone)
4- multiple myeloma
5- AR (serum amyloid via inc plasma protein synthesis in liver during chronic inflammation / long-standing infection)
list other related diseases resulting from secondary amyloidosis besides renal deposition
- RA
- Behcet syndrome
- Crohn’s
- osteomyelitis
- tuberculosis
- renal cell carcinoma
- Hodgkin’s disease
describe the microscopic changes observed in amyloidosis nephropathy
- LM: nodular, amorphous hyaline material in mesangium / capillary loops –> narrowing of capillary lumens
- Congo Red: ‘salmon pink’ on LM, ‘apple-green’ under polarized light
- EM: subendothelial / mesangial fibrils
describe the renal symptoms of amyloidosis
- proteinuria, edema, nephrotic syndrome
- 50% have renal insufficiency (at time of Dx)
- electrolyte abnormalities (Fanconi’s syndrome)
describe the non-renal / systemic presentation of amyloidosis
- Heart: cardiomyopathy, CHF, arrhythmias, heart block
- GI: hepatomegaly, malabsorption, bleeding
- Neuro: ischemic stroke, neuropathy, orthostatic hypotension
- Skin: easily bruised, purpura
prognosis of amyloidosis (by years since Dx)
- very poor prognosis
- 1 yr, 51% survival
- 5 yr, 16% survival
- 10 yr, 5% survival
(1) is the main complication of nephrotic syndrome, more common in (2). (3) results from urinary loss of (4), (5) causing increased plasma protein synthesis in the liver including (6), and increased blood viscosity due to (7). (8) dysfunction also contributes due to proinflammatory CKs.
1- thrombosis, thromboembolism (venous, deep/renal vein --> possible PE OR arterial --> coronary, cerebral, periphery thrombosis) 2- membranous nephropathy 3- hypercoagulability 4- antithrombin-III 5- hypoalbuminemia 6- coagulation factors 7- intravascular volume depletion 8- endothelial dysfunction
