Nephrotic Syndrome I Flashcards
Differentiate the following features of nephrotic and nephritic syndrome.
• Edema
• Proteinuria
• Urinary Sediment
NephrOtic:
• Edema - PROMINENT
• Proteinurea - in nephrotic rangeMore Severe
• INACTIVE urinary sediment
NephRITic:
• Edema - Mild
• Proteinurea
• ACTIVE urinary sediment with Dysmorphic RBCs and RBC casts
Differentiate the following features of nephrotic and nephritic syndrome.
• Blood Pressure
• Inflammatory?
• Serum Creatinine
NephrOtic:
• Blood Pressure - Normal
• NON-inflammatory condition
• Normal Serum Creatinine - possible slight elevation
NephRITic:
• Hypertension
• INFLAMMATORY
• Elevated Serum Creatinine
Differentiate the Key cells involved in nephrotic and nephritic syndrome.
NephrOtic:
• Visceral Epithelial Cell - PODOCYTE
NephRITic:
• Endothelial Cell
T or F: a urinary dipstick can be used to show proteinuria AND hematuria.
True
Comment on specificity of Hyaline casts.
Usually seen in CONCENTRATED urine with ANY renal pathology such as DEHYDRATION and use of DIURETICS, can be associated with PROTEINURIA too
When are White Cell Casts seen?
- Nephritic Syndrome
* UTI
When are RBC casts seen?
ONLY in glomerular Disease
When are granular Casts seen?
• ANY cause such as ACUTE TUBULAR NECROSIS
Which is in contact with the urine podocytes or epithelium?
Podocytes - these are the cells that are messed up in nephrotic syndrome
What are the 3 groups of Podocyte injury that can lead to nephrotic syndrome?
- Injury can happen in PODOCYTES
- Injury can happen in Immune complex deposition in subepithelial space (Under the Podocytes)
- Glomerular Capillary Wall Deposition Diseases
What are some injuries that can happen to podocytes?
• what syndrome does this cause?
- Minimal Change Disease
- Focal Segmental Glomerulosclerosis
Nephrotic Syndrome*
What is a disease that causes Injury by Immune complex deposition in subepithelial space (Under the Podocytes)?
• diseases caused?
Membranous Nephropathy
Nephrotic Syndrome*
What causes are some diseases of the glomerular capillary wall that lead to nephrotic syndrome?
Diseases:
• Amyloidosis
• Light Chain Deposition Disease
• Diabetic Nephropathy
What what are 3 groups of mechanisms that can lead to Nephritic syndrome?
- Subendothelial Space or Mesengial Immune complex formation and Complement Activation
- Antibodies Directed at the Glomerular Basement membrane
- Necrotizing Injury and Inflammation of the vascular and glomerular capillary wall
What are some diseases that cause Subendothelial Space or Mesengial Immune complex formation and Complement Activation?
• does this result in nephrotic or nephritic syndrome?
- Post-infectious Glomerulonephritis
- IgA nephropathy
- Lupus Nephritis
Nephritic Syndrome
What are some disease that cause production of Antibodies Directed at the Glomerular Basement membrane?
Anti-Glomerular Basement Disease (Goodpastures syndrome)
Nephritic Syndrome*
What are some disease that cause Necrotizing Injury and Inflammation of the vascular and glomerular capillary wall?
ANCA associated diseases
What is the glomerulus such a common place for immune complex deposition?
- High Plasma Flow Rate (~20% of CO goes to the kidney)
- High Intraglomerular Pressure
- High Glomerular Hydraulic Conductivity (permeability)
What determines the spectrum of glomerular disease caused by immune complexes?
- Nature of Antigen Involved (what its directed against)
* Site of Immune Complex Deposition
Where are immune deposits placed in Membranous Nephropathy?
• cause?
• Association?
SUBEPITHELIAL Deposits
Cause:
• Idiopathic
Associated with:
• Systemic Lupus Erythematous, Diabetes Mellitus, Hepatitis B, Drugs (gold, Penicillamine)
What is seen in the late course of membranous Nephropathy?
• Post-Infectious Glomerulonephritis
T or F: Anti-glomerular Basement membrane disease is usually Nephrotic with segmental Glomerulonephritis.
FALSE, is it usually NephrphRITic with CRESCENTRIC GN.
What disease often presents with macroscopic asymptomatic hematuria that presents intermittently?
• IgA nephropathy (nephritic syndrome)
What 3 diseases often present with large proteinuria?
- Membranous Nephropathy
- Minimal Change Disease
- Focal Segmental Glomerulosclerosis
What are some causes of rapidly progressive glomerulonephritis that can progress to renal failure in a period of days to weeks?
- ANCA vascultis
* Lupus nephritis
T or F: in hypertensive and diabetic nephropathy disease progression is fast.
False, disease progression is SLOW characterized by Proteinuria
What are 4 key features to look for in someone with nephrotic syndrome?
- Edema
- Proteinuria
- Hypoalbuminemia
- Hypercholesterolemia
***How can all 4 common features of Nephrotic Syndrome be accounted for?
PROTEINURIA leads to protein loss (hypoalbuminemia) and EDEMA from reduced colloidal pressure in capillaries.
• In response to LOW plasma protein the LIVER kicks up ALL PROTEIN PRODUCTION leading to increased CHOLESTEROL (hypercholestolemia)
Lipoproteinlipase levels are also reduced leading to increased VLDL
What are some common urinary sediments in Nephrotic Syndrome?
- Oval Fat Bodies
* Maltese Cross
T or F: Xanthelasma is a characteristic of nephritic syndrome.
FALSE, this is subcutaneous fat deposits around the eyes are associated with Nephrotic Syndrome
NOTE: Hematuria, Proteinuria, Edema, and HTN can occur in both nephritic and nephrotic syndrome.
NOTE: Hematuria, Proteinuria, Edema, and HTN can occur in both nephritic and nephrotic syndrome.
T or F: Nephrotic syndrome is more associated with inflammation.
FALSE, NEPHRITIC SYNDROME is most associated with inflammation
What determines if something gets through the glomerulus?
- Charge
- Size
- Shape
NOTE: Uncharged molecules less than 1.8 nm filter freely through the glomerulus, Molecules greater than 4 nm are completely restricted
Charge Restriction prevents albumin from passing through
NOTE: Uncharged molecules less than 1.8 nm filter freely through the glomerulus, Molecules greater than 4 nm are completely restricted
What structure provides the main size barrier across the glomerulus?
• Charge Barrier?
Size Barrier:
• Lamina Densa of the Glomerular Basement Membrane and Slit Diaphragm
Charge Barrier:
• Lamina rara interna and on Fenestrated Capillary Endothelium
Assuming equal radius, rank the following on fractional clearance through glomerulus.
• Neutral, Anionic, Cationic
Greatest Clearance:
Cationic
Neutral
Anionic - Least
T or F: Beta-2 microglobulins are typically restricted from coming through the basement membrane
FALSE, these usually pass freely through
What happens to most proteins that make it through the glomerulus?
PROXIMAL TUBULE epithelial cells ENDOCYTOSE (via receptor mediated endocytosis) proteins into vesicles and HYDROLYZE them into AMINO ACIDS
Amino Acids are released out of the BASOLATERLAL side of the tubular cell to re-enter circulation
Why do people with hypertension tend to have more protein in their urine?
• The amount of protein that enters Bowman’s space is proportional to the pressure in the Glomerulus
Compare the size of proteins excreted by patients with normal kidney function and those with nephrotic syndrome.
•People with Nephrotic Syndrome tend to secrete Fewer Small Protein ans MORE LARGE PROTEINS
*This is due to loss of surface area at the expense of gaining big ass hone in the glomerulus
*Note: People with Nephrotic Syndrome also secrete more IgG
What protein does the urine dipstick measure?
ALBUMIN
Compare Proteinuria due to tubular dysfunction vs. Glomerular Dysfunction.
Tubular - Secondary to Tubulointerstitial Disease - LOW MOLECULAR WT. PROTs.
Glomerular - any type of Glomerulonephritis - ALBUMIN is dominant
SO URINE DIPSTICK LOOKS FOR GLOMERULAR DYSFUNCTION
What is the normal amount of protein to be excreted daily by the kidneys?
• amt of Albumin?
• amt Tamm-Horsfall mucoprotein?
• Upper Limit of Normal?
40-80 mg/day
- 30mg/day is Albumin
- 30 - 50 mg/day is Tamm-Horsfall Mucoprotein
Upper limit of Normal= 150 mg/day
How high is albumin if the dipstick changes color?
300 to 500 mg/day (10 to 15x the normal level)
Since we can’t quantify the total amount of protein excreted in a day, what do we typically quantify?
• what is the normal amt for this?
Ratio of Albumin to Creatinine
Normal: less than 0.15
What is the most important predictor of how will someone’s nephrotic syndrome is under control?
• Proteinuria
What two angles do we attack nephrotic syndrome at?
Supportive Measures
Disease Modifiers
What are some supportive measures used in nephrotic syndrome?
Supportive Measures:
• CONTROL HTN - low NaCl diet, ACE I’s, Angiotensin Receptor Blockers
What are some disease modifiers used in nephrotic syndrome?
Disease Modifiers:
- Steriod
- Immunosuppressive Drugs - Cyclophosphamide, Cyclosporin, Mycophenolate Mofeitil, Tacrolimus
If someone has a spot urine protien creatinine of 10.8, about how much protein are they pissing out per day?
• ~10 grams/day
T or F: both BUN and Creatinine are typically elevated in Renal Failure
True
How does treatment of Secondary Nephrotic Sydrome differ from that of primary?
• Secondary Nephrotic Syndrome requires treatment of the ROOT CAUSE
What is microalbuminuria?
- Microalbuminuria = 30-300 mg/day excretion of albumin
* This amount Can’t be detected by the dipstick