Pathophys and Clinical Nephrotic Syndrome Flashcards

1
Q

What is the upper limit of normal protein excretion per day?

A

100 mg per day, with an average concentration of 7 mg/dl

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2
Q

What is the breakdown of normal protein in urine?

A

plasma protein (50%) and tissue origin protein (50%)

plasma protein is mostly albumin

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3
Q

Define postural proteinuria

A

Postural proteinuria is observed only when the subject assumes an upright or lordotic position. It may be associated with mild glomerular histological abnormalities, but there is no evidence linking this finding with significant renal disease.

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4
Q

Define persistent proteinuria?

A

Persistent proteinuria is present when several urine collections obtained with the subject supine at rest contain detectable protein.

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5
Q

What shape is the permselectivity curve that defines fractional clearance of a solute?

A

sigmoidal - upper limit is 56 angstroms in size

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6
Q

What is steric hindrance?

A

size selective permeability

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7
Q

How does convection lead to macromolecule movement across a barrier?

A

dragged across by increased filtration

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8
Q

How does diffusion lead to macromolecule movement across a barrier?

A

down a concentration gradient

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9
Q

A patient who has strong perfusion of fluid through the glomerular filter may pass more protein by: convection or diffusion?

A

convection

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10
Q

a patient who is dehydrated may filter more protein by: diffusion or convection?

A

diffusion because dehydration concentrates the plasma proteins.

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11
Q

Where is urumucoid protein (tamm horsfall protein) added to the urine?

A

the distal tubule

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12
Q

Define primary nephrotic syndrome

A

persistent proteinuria caused by selective mechanisms that affect handling of protein

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13
Q

What are examples of nephrotic diseases caused by decreased tubular REABSORPTION of protein?

A
Fanconi syndrome
Dent disease 
tubulointerstitial nephritis 
drugs 
toxins
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14
Q

What processes would cause overflow proteinuria in the setting of normal renal function?

A

repeated albumin infusions or blood transfusions; myeloma,leukemia

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15
Q

What are the four findings that define nephrotic syndrome?

A
  1. proteinuria
  2. hypoproteinemia/hypoalbuminemia
  3. edema
  4. hypercholesterolemia
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16
Q

What is the cut off for hypoalbuminemia?

A

serum albumin of less than 2 gm/dl

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17
Q

What is nephritis?

A

Nephritis may show

varied symptoms, but basically is a pathologic diagnosis denoting renal inflammation.

18
Q

What is nephrosis?

A

Nephrosis characterizes the symptom complex described above and does not invoke any particular disease process.

19
Q
Low serum albumin 
peripheral edema 
decreased intravascular volume 
significant edema 
sometimes HTN 
normal heart and pleural fluid on CXR

These are traits of: nephrotic syndrome or nephritis?

A

nephrotic syndrome

20
Q
renal inflammation 
decreased GFR
increased intravascular volume 
mild edema 
HTN 
cardiomegaly/pulmonary edema 

These are traits of: nephrotic syndrome or nephritis?

A

nephritis (symptomatic)

21
Q

Can albuminuria in nephrosis occur without filter damage?

A

yes. Since it may occur in the absence of disruption of the glomerular filter (e.g., in minimal change disease), such
loss may not be caused by obvious physical damage to
that filter.

22
Q

Does overall macromolecular clearance increase in nephrosis?

A

Not necessarily.

Importantly, even if overall macromolecular clearance is decreased, if the relative clearance of albumin increases, the consequences could be clinically significant

23
Q

Do patients with severe fanconi or dent disease develop nephrotic syndrome?

A

no

24
Q

What is the mechanism for nephrotic proteinuria?

A

The latticework of the epithelial slit diaphragm is comprised of a number of molecules that bridge between the podocyte foot- processes of adjacent cells. Principal among these is nephrin, which has homotypic protein-protein interactions that create the interdigitating “fingers” of the slit diaphragm (see Figure 4), along with other molecules. Importantly, these molecules are further anchored in the cell by intracellular molecules such as actin. Interaction with the actin cytoskeleton maintains the slit diaphragm and slit pore structural integrity.

In nephrotic syndrome, when the actin cytoskeleton is disrupted, this disrupts the anchorage of the slit- diaphragm molecules, changing their interaction and the structure of the slit pore. That event causes a sufficient increase in the slit pore size to increase the amount of albumin that transits the glomerular filter. As a secondary event, the loss of cytoskeletal integrity also leads to podocyte effacement, disrupting streaming potential. The resulting loss of charge selectivity serves as an amplifying or maintenance factor in albuminuria.

25
Q

Why would nephrotic patients with less albumin develop edema?

A

According to
the balance of Starling forces at the capillary wall, the difference between hydrostatic and
oncotic pressure at the beginning of the capillary
permits perfusion of all cells, whereas a shift in that
balance permits reabsorption of extravasated fluid at
the end of the capillary. In this model, nephrotic
patients have less albumin and therefore less impetus
for the return of fluid to the vascular space. This sets
up a vicious cycle in which
fluid is lost, decreasing venous return to the heart. As
a result, perfusion pressure drops and the kidney,
responding appropriately to an abnormal stimulus,
produces renin.

** this model has issues though - congenital hypoalbuminemia does not develop nephrotic syndrome

26
Q

WHy is hepatic synthesis of lipoprotein increased in nephrotic syndrome?

A

•Increased hepatic lipoprotein synthesis (probably related to viscosity) •Urinary loss of HDL and lecithin-cholesterol acyl transferase •Decreased lipoprotein lipase activity

27
Q

Do the lipid abnormalities in nephrotic syndrome respond to diet?

A

no - but yes to drugs

28
Q

What are some additional manifestations of nephrotic syndrome beyond the classic triad?

A
disordered hemostasis 
susceptibility to infection 
bone disease 
thyroid issues 
iron binding protein loss 
albumin changes in metabolism and buffering
29
Q

Why are nephrotic patients prone to developing clots?

A
  • Hemoconcentration from fluid extravasation. •Increased production of certain clotting factors.
  • Urinary loss of anticoagulant proteins. Antithrombin III is often referred to in the literature, but the most likely implicated factor is loss of free protein S.
  • Because of fluid excretion, hemoconcentration and loss of natural anticoagulants in the urine, the radicles of the renal vein are a likely site for coagulation to cause renal veinthrombosis. •When the ambient albumin concentration is decreased, platelets become hyperaggregable.
30
Q

Why are nephrotic syndrome patients more susceptible to infection?

A

loss of other proteins involved in:
•Immunoglobulin: in some cases this is sufficiently severe to make patients become
extremely susceptible to common organisms.
•Alternative complement pathway factors B and D are important opsonizing factors. Patients are particularly sensitive to infection with encapsulated organisms such as Pneumococcus. •Abdominal ascites is an excellent growth medium for bacteria.
•Patients with minimal change disease may be poorly responsive to immunizations. This may be a primary manifestation of the disease causing nephrosis rather than a direct manifestation of proteinuria.

31
Q

What kind of infections are nephrotic syndrome patients more susceptible to?

A

encapsulated organisms.

32
Q

how does ascites cause infection?

A

it’s a good medium for growing bacteria

33
Q

Why does osteopenia happen in nephrotic syndrome?

A

Patients with nephrotic syndrome lose Vitamin D-binding protein in their urine. In extreme
(unremitting) cases they may have little 1,25-(OH)2 vitamin D3 and virtually no 25-OH-D3. Corticosteroids used to treat the disease may exacerbate osteopenia. Vitamin D supplementation is often indicated in chronically nephrotic patients.

34
Q

When is the loss of thyroid binding globulin significant in nephrotic syndrome?

A

in Finnish type congenital nephrotic syndrome

35
Q

What part of the filter is most commonly affected in nephrotic syndrome?

A

the podocytes

36
Q

Minimal change disease, FSGS, diffuse mesangial sclerosis, collapsing glomerulopathy, and congenital nephrotic syndrome (finnish type) are all pathologies of what part of the kidney?

A

the podocytes

37
Q

In uncomplicated nephrotic syndrome, is renal function impaired?

A

no! this is an “appropriate” response to abnormal physiological circumstances that cause urinary protein loss

38
Q

An extremely edematous child is seen in the emergency ward for relapse of known minimal change nephrotic syndrome. What are the benefits and problems in treating the edema with furosemide?

A

Benefits:
-decreased fluid retention
-may interrupt the “vicious cycle” of nephrotic sodium retention
Problems:
-may be poorly effective if renal perfusion is poor
-dries out the vascular space, which may be “underfilled”
-may exacerbate hemoconcentration, predisposing to thrombosis -wastes total body potassium stores

39
Q

The most critical determinant of whether or not a molecule of effective Stokes radius = 40 Å is filtered by the glomerulus is:

a. Blood pressure
b. Hydration status
c. The endothelial glycocalyx
d. The lamina densa of the glomerular basement membrane
e. The epithelial slit pore

A

e - epithelial split pore

40
Q

A patient is admitted with facial and abdominal swelling. She has gained 5 kg in the past week and her urine shows 300 mg/dl albumin. Her serum albumin is 1.9 gm/dl. What steps should you take to evaluate her condition?

A
  • Check blood pressure
  • Full clinical history and physical exam for evidence of systemic illnesses
  • Evaluate urine for presence of blood, a possible indicator of underlying nephritis -Measure serum creatinine to evaluate kidney function.
  • Measure serum complements and anti-nuclear antibody to rule out inflammatory causes -Obtain daily weight and follow intake and output to monitor fluid balance
  • Consider vascular volume depletion in evaluating potential pharmacological diuresis
41
Q

A patient is admitted with facial and abdominal swelling. She has gained 5 kg in the past week and her urine shows 300 mg/dl albumin. Her serum albumin is 1.9 gm/dl. What potential complications might you anticipate as you treat the patient ?

A
  • Renal vein thrombosis -Excessive dehydration and shock -Infectious complications
  • Bone tissue loss
42
Q

Name four drugs or minerals that are bound to albumin and therefore are affected in nephrosis.

A
Drugs: -digoxin
-barbiturates
-some diuretics 
Minerals:
-iron -calcium -zinc