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How many L of blood are filtered by glomeruli? How many are excreted in urine?

only a small fraction of the filtrate (0.6-2.5 litres) is excreted as urine


What is the FF? Is it a fixed number? What influences the FF?

The exact proportion between glomerular filtration rate (GFR) and the renal plasma flow (RPF) rate is not fixed but may vary depending on the magnitude of GFR, the composition of the blood and the condition of the glomerular capillary. The ratio of GFR/RPF is called the filtration fraction (FF).


Explain Rudolf Heidenhain's view of GF and what experiment he did to think this.

- Thought renal tubules secrete (things that are not needed by body)
- Experiment: Took rabbits and injected dyes indigo kurmin – taken up by renal tubules cells. When dissecting kidneys, he realized dyes went primarily in cells of proximal tubules at the beginning, and then in lumen of tubules later.


Explain Carl Ludwig's view of GF.

- Thought everything should be explainable in mechanistic terms using the laws of physics
- Said that kidneys must filter a large volume and then reabsorb the volume. But pretty inefficient?
- Would need to filter 70L of fluid per day to get rid of the amount of urea we have in our urine. But nature would never make something so inefficient…
- Truth: Urea is actually reabsorbed by renal tubules, so need to filter 180L per day!


Does every species have glomeruli in their kidneys?

No, some fishes don't have glomeruli but have a tubule


What is the glomerular capillary wall made of? (3)

From the inside out:
- Endothelial cells
- The glomerular basement membrane (GBM)
- Visceral epithelial cells


Name the 3 cellular components of the glomerulus

1. Epithelial cells (podocytes)
2. Endothelial cells (blood vessels)
3. Mesengial cells (pericytes)


Name 2 functions of podocytes.

a. Synthesis of matrix components (in mesengium)
b. Maintenance of capillary wall permeability


Name 1 function of the epithelial cells of the glomerulus.

a. Synthesis of matrix components (which go to basement membrane)


Name 3 functions of pericytes.

a. Contain contractile elements and receptors for angiotensin II and other factors that regulate renal hemodynamics (thus they contract when stimulated by those different agonists)
b. Contribute to the synthesis of matrix components (which go to mesengium)
c. Have capacity for phagocytosis (cleaning function)

Strategically situated at the branchpoints of the capillaries – control diameter of capillary through contraction --> regulates blood flow; increases and decreases surface area


What is a fenestra

spaces between endothelial layer which allow most small solutes to go through


How many layers does the glomerular barrier have? what are they?

Glomerular barrier (basement membrane) is tri-layered
1. lamina rara externa,
2. lamina interna
3. lamina densa


What is a slit diaphragm

Tight junctions in the glomerular epithelium (visceral epithelium) are specialized for filtration.
They have a pore in the center which discriminates molecules that can go through in terms of size. Smaller than albumin molecules; thus prevents filtration of big proteins
Epithelial cells have slit diaphragm and endothelial cells have fenestra.


What synthesizes the components of the GBM and the mesengial matrix?

The epithelial, endothelial, and mesangial cells.


Name 4 components of the GBM and mesengial matrix

- Type IV collagen (backbone of the GBM, and main molecular sieve)
- laminin (anchors cells to GBM collagen)
- fibronectin (cell attachment protein)
- heparan sulfate proteoglycan (electronegative barrier)


What is type IV collagen? What is its structure? Function?

o distinct from interstitial collagens I, II and III
o triple helical, three domains
o Structural support; forms 2D mesh
o Pressure in glomerular barrier is 10x higher than blood everywhere else. Type 4 collagen allows structural support for higher pressures


What is laminin? What is its function? Where is it located?

o Attachment protein
o Concentrated in lamina rara interna and externa
o Important connection for podocytes to GBM


What is heparan sulfate proteoglycan ? What is its function? Where is it located?

o Anionic site of the GBM
o Consists of core protein and glycosaminoglycan
o Polypeptide with many sugar groups on them (which are modified to have sulfate – negatively charge)
o Confers charge to whole barrier. Thus the barrier selects not only on the size but also on the charge. We mostly want to avoid filtering negatively charged molecules.
o Distributed throughout the GBM but concentrated in the lamina rara interna and externa
o N-linked and O-linked glycosylation


Solutes up to molecular weights of ___ pass quite freely through the glomerulus for filtration

10,000 Da


Name 7 examples of molecules that go easily through the glomerulus. Name 4 examples of molecules that don't. Name 1 exception to the rule.

- E.g. small ions like Na, K and Cl- pass very easily (v. small) – relative concentration in filtrate vs. plasma is 1.0 --> no selection
- Urea, glucose, sucrose, polyethylene glycol --> relatively small too

- E.g. lysozyme, myoglobin, lactoglobulin, albumin
- Exception: Bence jone protein since it is secreted as a 22kDa protein and then forms a dimer in the urine
- Serum albumin has extremely low permeability because important for oncotic pressure of plasma


Name 2 molecules that are nor filtered because of charge. Name a molecule that passes easier than neutral molecules of the same size.

-: plasma protein and sulfated dextrans

+: diethylaminoethyl (DEAE) dextrans


Where are molecules restricted to pass in the glomerulus?

there is little if any restriction to the passage of macromolecules by glomerular endothelial cells. Negatively charged macromolecules penetrate only into the proximal layer of the GBM. For neutral and cationic molecules, permeability is progressively enhanced, but passage of most of these molecules is restricted at the GBM. The remainder are restricted by the glomerular epithelial cells at the filtration slit diaphragms. However, it should be noted that in experimental models, injury of only glomerular epithelial cells (with no damage of the GBM) leads to a marked increase in glomerular permeability.


What is membraneous glomerulopathy?

We make antibodies against basement membrane components --> can clog up GBM, and mesangial cells can have trouble keeping up with phagocytic needs.


What are the 2 starling forces (forces driving filtration)?

1. Hydrostatic pressure (~40-50 mmHg)
o Difference between BP and pressure within Bowman’s space

2. Colloid osmotic pressure (~15-30 mmHg)
o Due to proteins in plasma

--> Net pressure ~ 15 mmHg (45-30)


What factors are considered in the GFR calculation?

GFR = KF x PUF = KF (PGC -PT -(pi)GC)

KF = ultrafiltration coefficient; includes factors of hydraulic permeability and surface area for filtration
PUF = net ultrafiltration capillary

PT = hydraulic pressure in bowman's space
piGC = oncotic pressure in the glomerular capillary plasma


How do the hydrostatic and colloid osmotic pressures change during filtration?

Whereas the hydrostatic pressures in the capillary and in Bowman's space remain virtually constant, the plasma oncotic pressure increases as a direct consequence of ultrafiltration.


How does glomerular capillary hydrostatic pressure stay constant throughout the capillary length?

Capillaries have large cross-sectional areas compared to the afferent arteriole, so relatively little resistance = no pressure drop


Describe the pressure changes when going from the afferent arteriole to the efferent arteriole

Afferent arterioles and efferent arterioles create a hydrostatic pressure drop by creating a resistance point.
Bowman’s capsule doesn’t empty immediately so it can create some sort of back pressure. So, the hydrostatic pressure shown in the image is P (in lumen) – P (in Bowman’s capsule)
The net hydrostatic pressure stays relatively constant through capillaries (as Ludwig had guessed), then pressure drops after resistance in entry of efferent arteriole.
Oncotic pressure starts low then increases gradually. Doesn’t reach equilibrium (we’re not sure)
Everything reverses in efferent arteriole: High oncotic P but low hydrostatic P.


Name 2 pathways that can influence GFR.

1. elevating blood pressure above the autoregulatory range.
2. an intrarenal mechanism that senses correlates of flow through the distal tubule acts to reduce the filtration rate of the same nephron - the so-called "tubulo- glomerular feedback" mechanism. The macula densa cells of the distal tubule are thought to be the sensing site in the feedback pathway, since they are immediately adjacent to the vascular pole of the glomerulus of the same nephron.


What is clearance?

How much of a substance can be removed from the plasma in a given period of time (often 1 minute)
Measure of renal function