Intro into the Glomerulus

Question 1

The job of the glomerulus is to?

Answer 1

1. Allow ultra-filtrate into Bowman’s space (water, electrolytes, glucose and AA);
2. Prevent proteins and RBC

Question 2

Pathology of glomerulus occur when ______ and ______ are present

Answer 2

proteinuria and hematuria

Question 3

What are the 3 components of the glomerular filtration barrier?

Answer 3

1. Capillary endothelium
2. BM
3. Podocytes (epithelial cells)

Question 4

Describe the components of the glomerular filtration barrier.

Answer 4

1. -Capillary endothelium is the 1st barrier to filtration: fenestrated, only allowing small molecules (~40nm) molecules to pass; does not allow RBCS, white cells or platelets
2. -BM: negative charged molecules made up of proteins like type 4 collagen and heparin sulfate (- charged); repels (-) molecules, like albumin; only ~4nm can pass
3. -Podocytes (epithelial cells): have foot processes that wrap around capillaries and form slits to filter PROTEINS
   
   • Largely responsible for making GBM
   • Injury => proteinuria

Question 5

Albumin is the major protein in the blood; small (~3.6nm) and can fit through all size barriers. Thus, what prevents filtration of it?

Answer 5

(-) charged BM

Question 6

Glomerular diseases are caused by___________________=> cause RBCS and protein (esp albumin) in urine, which should not be there.

Answer 6

Breakdown of the filtration barrier

Question 7

How can we measure blood in the urine?

Answer 7

1. UA dipstick- tests for heme, which has peroxidase activity
2. Microscopy

Question 8

Glomerular bleeding forms what?

Answer 8

• red cell casts (bunch), dysmorphic RBCS, acanthocytes (spikey RBC), proteinuria,
• clots are generally not seen

Question 9

How can we measure proteins in the urine?

Answer 9

1. UA dipstick- tests for albumin, thus, tells us if we have a glomerular disease

• Often 4+ if a glomerular disease
• Affected by amount of urine

2. Urine protein-to-creatinine level (spot urine test);

• Take the 1st or 2nd morning urine sample test after avoid excercise;
• NL ratio is less than 0.2 mg/mg);

3. 24 hour urine collection

• GOLD STANDARD, gives you grams/day or protein excretion;
• NL is less than 150 mg/day

Question 10

Glomerular diseases occur on a spectrum. Describe the 3 findings in each nephritic syndromes and nephrotic syndromes.

Answer 10

• Nephritic syndrome: Hematuria (RBC casts), azotremia, mild proteinuria and HTN
  
  • Proteinuria is less then 3.5g/day
• Nephrotic syndrome: Severe proteinuria (hypoalbumenemia), hyperlipidemia and lipiduria
  
  • Proteinuria is more than 3.5g/day (less in children)
  • Hypoalbuminemia is plasma levels less than 3gm/dL
  • 4+ on dipstick

Question 11

Major determinant of whether a disease leads to nephritic or nephrotic syndrome is the what?

Answer 11

SITE of glomerular injury

Question 12

Damage to what part of the glomerulus leads to nephritic syndrome?

​Does inflammation occur?​

Answer 12

• Endothelial/mesangial cells, with an influx of inflammatory cells that damage the entire glomeruli (nephritis) ==>
  
  • ​ Filtration barrier to RBC and proteins are lost.

Question 13

Damage to what part of the glomerulus causes nephrotic syndrome?

Does inflammation occur?

Answer 13

• Podocytes (epithelial cells) ONLY=> protein loss only
  
  • Filtration barrier to RBC: intract
  • Podocytes are separated from the blood by the GBM.
  • Thus, injury does not lead to inflammation.

Question 14

Nephritic syndrome is often an __________ process that damages the __________, thus, damaging the filtration barrier ______________.

• _______ onset dominated by acute onset of grossly visible __________, _______, ________.

Answer 14

• Inflammatory
• Entire glomerulus
• To RBC and proteins
• Acute
• Hematuria, mild proteinuria and HTN

Question 15

Describe the processes that occur in the body when a patient has nephritic syndrome

Answer 15

• Damage to the entire filtratration barrier causes: hematuria (dysmorphic RBCs/RBC clasts) and mild proteinuria (less than 3.5 g/day).
  
  • ↓ GFR =>
    
    • Azotremia (↑ in BUN/Cr)
    • Oliguria
    • ↑ hydrostatic pressure causes HTN and edema

Question 16

Describe the processes that occur in the body when a patient has nephrotic syndrome

Answer 16

• Damage to protein filtration barrier causes:
  
  1. Frothy urine d/t ↑ proteins in the urine (>3.5 g/day)
  2. ↓ in albumin
     
     • ↑ liver activity to make more => hyperlipidemia & and fatty casts/oval bodies in urine (lipiduria)
     • Severe edema occurs via 2 mechanisms:
       
       • ​↓ plasma oncotic pressure
       • ↓ ECV and GFR => + RAAS => Na/H20 retention => worsening edema
  3. ↓ of immunoglobulins => more prone to infection
  4. ↓ in antithrombin 3 => pt is in hypercoagulable state

Question 17

What is the classic presentation of a patient with nephritic syndrome?

Answer 17

1. Dark urine (RBCs)
2. Swelling and fatigue (d/t uremia)
3. <3.5g/day proteinuria

Question 18

What is the classic presentation of a patient with nephrotic syndrome?

Answer 18

• Frothy urine d/t proteinuria (>3.5 grams/day)
• Swelling of ankles/around eyes (periorbital edema), often mistaken for an allergic reaction
• Serum total cholesteral (>300mg/dl; mainly LDL)

Question 19

In nephrotic syndrome, lipids are present in the urine.

What is unique about them?

Answer 19

• Organized in fatty casts and can be enclosed by plasma membrane of degenerative epithelial cells (oval fat bodies)
• Under polarized light, fat droplets look like a maltese cross.

Question 20

How can we DX nephrotic vs. nephritic syndromes?

Answer 20

1. Light microscopy
2. Immunofluorescence
3. Electron microscopy: used to look at BM, podocytes

Question 21

What are the major causes of nephritic syndrome?

Answer 21

1. Post-streptococcal diffuse proliferative glomerulonephritis
2. Berger’s IgA nephropathy
3. Diffuse (acute) proliferative glomerulonephritis
4. RPGN
5. Alport Syndrome
6. Membranoproliferative glomerulonephritis

Question 22

What are the major causes of nephrotic syndrome?

Answer 22

1. Minimal change disease: d/t cytokines
2. Focal segmental glomerulosclerosis (FSGS): d/t podocyte damage
3. Membranous nephropathy: d/t immune complexes
4. Diabetic: glucose
5. Amyloidosis
6. Membranoproliferative glomerulonephritis