Intro into the Glomerulus Flashcards
The job of the glomerulus is to?
- Allow ultra-filtrate into Bowman’s space (water, electrolytes, glucose and AA);
- Prevent proteins and RBC
Pathology of glomerulus occur when ______ and ______ are present
proteinuria and hematuria
What are the 3 components of the glomerular filtration barrier?
- Capillary endothelium
- BM
- Podocytes (epithelial cells)
Describe the components of the glomerular filtration barrier.
- -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
- -BM: negative charged molecules made up of proteins like type 4 collagen and heparin sulfate (- charged); repels (-) molecules, like albumin; only ~4nm can pass
-
-Podocytes (epithelial cells): have foot processes that wrap around capillaries and form slits to filter PROTEINS
- Largely responsible for making GBM
- Injury => proteinuria
Albumin is the major protein in the blood; small (~3.6nm) and can fit through all size barriers. Thus, what prevents filtration of it?
(-) charged BM
Glomerular diseases are caused by___________________=> cause RBCS and protein (esp albumin) in urine, which should not be there.
Breakdown of the filtration barrier
How can we measure blood in the urine?
- UA dipstick- tests for heme, which has peroxidase activity
- Microscopy
Glomerular bleeding forms what?
- red cell casts (bunch), dysmorphic RBCS, acanthocytes (spikey RBC), proteinuria,
- clots are generally not seen
How can we measure proteins in the urine?
- 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
- 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);
- 24 hour urine collection
- GOLD STANDARD, gives you grams/day or protein excretion;
- NL is less than 150 mg/day
Glomerular diseases occur on a spectrum. Describe the 3 findings in each nephritic syndromes and nephrotic syndromes.
-
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
Major determinant of whether a disease leads to nephritic or nephrotic syndrome is the what?
SITE of glomerular injury
Damage to what part of the glomerulus leads to nephritic syndrome?
Does inflammation occur?
-
Endothelial/mesangial cells, with an influx of inflammatory cells that damage the entire glomeruli (nephritis) ==>
- Filtration barrier to RBC and proteins are lost.
Damage to what part of the glomerulus causes nephrotic syndrome?
Does inflammation occur?
-
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.
Nephritic syndrome is often an __________ process that damages the __________, thus, damaging the filtration barrier ______________.
- _______ onset dominated by acute onset of grossly visible __________, _______, ________.
- Inflammatory
- Entire glomerulus
- To RBC and proteins
- Acute
- Hematuria, mild proteinuria and HTN
Describe the processes that occur in the body when a patient has nephritic syndrome
- 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
-
↓ GFR =>
Describe the processes that occur in the body when a patient has nephrotic syndrome
-
Damage to protein filtration barrier causes:
- Frothy urine d/t ↑ proteins in the urine (>3.5 g/day)
- ↓ 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
- ↓ of immunoglobulins => more prone to infection
- ↓ in antithrombin 3 => pt is in hypercoagulable state
What is the classic presentation of a patient with nephritic syndrome?
- Dark urine (RBCs)
- Swelling and fatigue (d/t uremia)
- <3.5g/day proteinuria
What is the classic presentation of a patient with nephrotic syndrome?
- 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)
In nephrotic syndrome, lipids are present in the urine.
What is unique about them?
- 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.
How can we DX nephrotic vs. nephritic syndromes?
- Light microscopy
- Immunofluorescence
- Electron microscopy: used to look at BM, podocytes
What are the major causes of nephritic syndrome?
- Post-streptococcal diffuse proliferative glomerulonephritis
- Berger’s IgA nephropathy
- Diffuse (acute) proliferative glomerulonephritis
- RPGN
- Alport Syndrome
- Membranoproliferative glomerulonephritis
What are the major causes of nephrotic syndrome?
- Minimal change disease: d/t cytokines
- Focal segmental glomerulosclerosis (FSGS): d/t podocyte damage
- Membranous nephropathy: d/t immune complexes
- Diabetic: glucose
- Amyloidosis
- Membranoproliferative glomerulonephritis
