L2 Glomerular Filtration Flashcards
As blood flows through the glomerular capillaries, about ____% of the plasma volume is forced across the capillary wall by the pressure difference between the ____ ____ and ____ ____. The glomeruli filter approximately ____ liters per day however only a small fraction of the filtrate (____-____ litres) is excreted as urine.
As blood flows through the glomerular capillaries, about 20% of the plasma volume is forced across the capillary wall by the pressure difference between the capillary lumen and Bowman’s space. The glomeruli filter approximately 180 liters per day however only a small fraction of the filtrate (0.6-2.5 litres) is excreted as urine.
Filtration Fraction = ?
what does it depend on?
Glomerular Filtration Rate GFR / Renal Plasma Flow RPF
Depends on :
- magnitude of GFR
- plasma composition
- condition of the glomerular capillaries
the glomerular capillary wall GCW is made up of …
the space between glomerular capillary loops is filled by …
the glomerular capillary wall GCW is made up of the glomerular basement membrane, endothelial, epithelial (podocytes - made up of visceral and parietal epithelial cells)
the space between glomerular capillary loops is filled by mesangial cells and mesangial matrix
epithelial cells (podocytes) characteristics
visceral epithelial cells :
- synthesis of matrix components
- maintenance of capillary wall permeability
- clean filtration barrier
parietal epithelial cells
- line Bowman’s capsule
- continuous with epithelium of renal tubule
endothelial cells characteristics
- synthesis of matrix components
- have fenestrations - only restrict RBCs
mesangial cells characteristics
- contain contractile elements + receptors for angiotensin II (causes contraction) and other factors that regulate renal hemodynamics :
- situated at branch points to control flow into different branches of the glomerular capillaries
- contribute to synthesis of matrix components
- can change phenotype to become phagocytic
what separates different adjacent foot
processes of podocytes?
slit diaphragm (modified tight junctions)
filtration pore in center of slit diaphragm
what do endothelial, epithelial and visceral cells synthesize?
- type IV collagen
- laminin
- heparan sulfate proteoglycan
- fibronectin (cell attachment protein)
type IV collagen characteristics
- backbone of the GB, main molecular sieve
- distinct from interstitial collagens I, II, and III
- triple helical, three domains
- creates mesh-like framework that epithelial cells sit on
laminin characteristics
- cross-shaped attachment protein: anchors cells to GBM collagen
- interacts with ECM
- concentrated in lamina rare externa and rara interna
heparan sulfate proteoglycan characteristics
- electronegative barrier
- anionic sites of the GBM → SO42- confers (-) charge to BM → repels (-) proteins (ex. albumin)
- contains O-linked or N-linked carbohydrates
- consists of core protein and glycosaminoglycan
- distributed throughout the GBM but concentrated in lamina rara externa and interna
fibronectin characteristics
cell attachment protein
what are the characteristics of passage of molecules < 10 000 MW and of macromolecules (10 000 - 60 000 MW) by glomerular endothelial cells?
molecules < 10 000 MW freely pass
macromolecules slightly restricted
- (-) molecules (anionic dextrane sulfate) : only penetrate into proximal layer of GBM (lamina rara interna), (-) slower than neutral molecules of the same size
- (+) (cationic dextrane sulfate) or neutral : permeability enhanced, but passage restricted at GBM, (+) faster than neutral molecules of the same size
- remainder : restricted by glomerular epithelial cells at filtration slit diaphragm
what’s the effect of injury of only glomerular epithelial cells (not the GBM)?
↑↑ glomerular permeability since blood → endothelial cells → GBM → epithelial cells (podocytes) → Bowman’s space
Glomerular Filtration Rate = ?
what’s proteinuria?
too much protein makes it into Bowman’s space and gets excreted
(usually: a large amount of protein is filtered everyday, but majority of it gets retained in the plasma)
what’s the consequence of build up of immune complexes and how does the body compensate?
→ barrier becomes less permeable → build up phagocytosed by mesangial cells
how does glomerular filtration vary? key Starling Forces
hydrostatic pressure:
↳ ~constant along glomerular capillaries (low resistance in capillary bed)
↳ ↓ sharply after efferent arteriole → promotes reabsorption in peritubular capillaries
vascular resistance:
↳ Afferent + efferent arterioles = high resistance
↳ Glomerular capillaries = low resistance → blood flows easily
oncotic pressure (πGC):
↳ ↑ progressively along capillary as fluid is filtered out
↳ Protein concentration ↑ → πGC ↑ → opposes filtration
net ultrafiltration pressure (NFP):
↳ NFP = (PGC - PBS - πGC)
↳ ↓ along capillary length
↳ → may ≈ 0 near efferent end (filtration slows or stops)
how is Glomerular Filtration Rate modulated?
↑ GFR → ↑ Cl⁻ sensed in macula densa of cTALh → ↑ ATP release → constriction of afferent arteriole → ↓ GFR
↓ GFR → ↓ Cl⁻ sensed in macula densa of cTALh → ↓ ATP release → dilation of afferent arteriole → ↑ GFR
macula densa cells of distal tubule immediately adjacent to vascular pole of glomerulus of same nephron
what’s clearance? formula? what does it measure? what is most often used?
minimum volume of plasma from which the kidney could, in one minute’s time, remove all substance
clearance mL/min = [X]u x Vu / [X]p
= [X] in urine (mg/mL) x urine flow rate (mL/min) / [X] in plasma (mg/mL)
Indirect measurement that allows estimation of GFR, RPF (renal plasma flow), and tubular transport functions. While practical and widely used, it doesn’t provide information on the location of transport within the nephron or whether it is passive or active.
Most often with inulin since it freely passes and it’s not absorbed or secreted.
Creatinine is an indicator of renal failure because its steady-state concentration in plasma varies directly with GFR.
which is filtered/ reabsorbed/ secreted: inulin, glucose and amino acids, PAH, potassium
- inulin: filtered
- glucose and amino acids: filtered, reabsorbed
- PAH: filtered, secreted (can be used to measure renal plasma flow, since the more flow there is, the more secretion and subsequent excretion there will be)
- K+ potassium: filtered, reabsorbed (in proximal tubule), secreted (depending on K+ balance)
clearance reabsorption and secretion
how do we define the amount of freely filterable substances filtered per unit time?
amount filtered per unit time = GFR x [X]plasma
Practice question
A creatinine clearance test is performed in an 80-kg man. The following results are obtained (dL= 100mL): Pcr = 3.5 mg/dL , 24-h urine volume = 800 mL, Ucr = 125 mg/dL. Calculate the creatinine clearance.
20 mL/min
Practice question
The concentration of calcium in Bowman’s capsule is 3 mM, whereas its plasma concentration is 5 mM. How do you explain this?
The calcium ion is small, but approximately 40% is bound to proteins and so is not filterable.
Practice question
The concentration of glucose in plasma is 100 mg/100 mL and the GFR is 125 mL/min. How much glucose is filtered per minute?
125 mg/min. The amount of any substance filtered per unit time is given by the product of the GFR and the filterable plasma concentration of the substance, in this case, 125 mL/min x 100 mg/100 mL.
Practice question
A protein has a molecular weight of 20,000 and a plasma concentration of 100 mg/L. The GFR is 100 L/day. How much of this protein is filtered per day?
No exact value can be calculated from these data because the concentration of the protein in the glomerular filtrate is not known. The molecular weight is high enough that there would be some “sieving”, but low enough so that the restriction would not be total.
Practice question
An increase in the plasma concentration of inulin causes which of the following in the renal clearance of inulin:
a) Increase
b) Decrease
c) No change
No change. When PIn increases, there is no change in CIn because inulin is freely filtered and neither reabsorbed nor secreted, therefore UIn rises by an identical amount. Thus the mass of inulin filtered and excreted increases, but the volume of plasma supplying this inulin, i.e., completely cleared of inulin, is unaltered.
Practice question
Calculate the urea clearance of a patient who produces 1440 ml of urine in one day and has urea concentrations of 2050 mg/100 ml and 25 mg/100 ml in urine and plasma, respectively.
82 mL/min
