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All lectures from the course Kidney: Bench to Bedside
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Kidney: bench to bedsideLecture 1 - glomerulus – 10 november ’21
1. In which part of the kidney glomeruli can be detected → cortex
2. Which of the following is absent in urine of healthy individuals → glucose
3. Which of the following segments is involved in the tubulo-glomerular feedback system? →
Macula Densa (the macula densa cells measure the pressure (amount of salt) so then it
knows if hormones need to be released and it makes sure that there is a constant flow of
pre-urine. It acts on the pressure, too much pressure the macula densa senses to the
arterioles)
4. What is the charge of the glomerular basement membrane → negative, is must be negative
because then the proteins cannot pass and will be filtrated.
5. Which of the following renal disease is characterised by the presence of red blood cells in the
urine? → nephritis
6. Which of the following substances increases the oncotic pressure in the glomerulus? →
albumin (oncotic pressure is depended on the molecules that are present in the glomerulus,
higher pressure when there is a high concentration of molecules)
7. The renal handling of which substance is essential for volume regulation? → sodium
8. Where are the baroreceptors located ? → carotid sinus
9. What happens to the volume of the intracellular and extracellular fluid compartments during
an isotonic infusion? → ICF volume remains the same, ECF volume increases
10. Which of the following diuretics is considered potassium-sparing? → amiloride
11. Insulin results in the cellular uptake of which ion? → potassium
a. Na+ is about 140 mM in the body and K+ is about 5mM, it is important to keep these
concentrations constant.
12. What is the function of Henle’s loop ? → urine concentration
13. Which of the following hormones regulates the osmolarity of the blood? → vasopressin
(anti-diuretic hormone)
14. Which of the following substances are secreted in the proximal tubule? → ammonium
15. What is the effect of metabolic acidosis on the breathing rate? → breathing rate will be
increased
a. H2O + CO2 → H2CO3 → H+ + HCO3-
i. The CO2 is coming from the lungs and H+ from the kidney. If there is more of
the H+ then there will be more of the CO2 formed and thus the breathing
rate will be increased.
1
, From the picture above you can see that the
glomerulus and all the convoluted tubule
structures are laying in the cortex. The OSOM
and ISOM are both part of the medulla. In the outer (OSOM) you have the thick tubules, where in the
inner ones the thin tubules are. Many nephrons go to one collecting duct, you see two branching but
there will be many more (the branches should all be in the cortex and not in the inner medulla part.
The glomerulus: the afferent will bring the blood in and the efferent
the blood out. So the blood goes to the capillaries, then it via filtration
barrier is comes in the bowman’s space and then leaves the
glomerulus into the proximal tubule.
*you go from one arteriole to another, normally you go from one
arteriole to a vein, but in the glomerulus the blood stays oxygen rich.
What is important for the Glomerular Filtration Rate (GFR):
- Afferent/efferent arteriole
- Osmotic pressure → concentration of molecules in bowman’s space
and in the capillary network
- Tubule-glomerular feedback → regulating for example the blood
pressure
- Hormones → for example angiotensin/adrenaline that can regulate the blood pressure
Clearance= filtration + absorption – secretion = excretion
Creatinine is a waste product that comes from the muscle.
Between the podocytes the finest filtration takes place.
The endothelium is already important, because then all
the large part are already taken out. If you do not have
this filtration with first the endothelium then it will be
clothed immediately, so therefore there is a layered
system in the filtration barrier.
The slit diaphragm is in between the podocytes. The
endothelial cells have a kind of sugar layer, the
glycocalyx, this keeps mainly the larger proteins out
which prevents clothing of the filter, it is negative charged. There are diseases where the glycocalyx is
disturbed and then the filtration is disturbed as well.
There is junctions between pedicles of the podocytes; takes care of filtering, connecting to
cytoskeleton and plasticity of podocytes. Signalling function: calcium, mechanosensation, cell polarity
and endocytosis.
There are forces in the glomerulus; there is the starling forces. The opposing forces are hydrostatic
pressure and oncotic pressure. It is regulated by afferent and efferent arterioles.
2
, The aim of autoregulation is to keep GFR stable
during changes in the systemic blood pressure.
There is myogenic mechanism, which is the
contraction and dilation of afferent arteriole. And
there is the tubule-glomerular feedback; this is by
sensing via macula densa and signalling to
afferent arteriole.
So autoregulation, despite the blood pressure is
getting low, the flow in the nephron is constant.
By classification of chronic kidney disease the doctors look at the GFR, but also at how much albumin
is in the urine (proteinuria) (if there is (a lot of) albumin in the urine, then this is a sign that the
filtration barrier is broken).
CKD: diabetis;
- Microvascular damage; loss of glomeruli
- Hyperfiltration
- Inflammation of the kidney
Glomerular diseases:
- Nephrotic syndrome
o Initial defect = podocyte (loose
complete podocytes)
o Proteinuria
o Several causes
- Nephritis
o Defect= endothelium
o Inflammation → if the
endothelium is defect, then more
inflammatory cells are attracted
to the basement membrane,
more and more cytokines will go
to the place and then there will be an inflammation in the glomerulus.
o Proteinuria/hematuria (blood in urine)
Lecture 2 – Tubule – 10 november ’21
Volume is regulated by sodium, and osmolarity is regulated by water transport.
- Control of body fluid volume → i.e. Renin-angiotensin-aldosterone system to control NaCl
excretion
- Control of body fluid osmolality → i.e. vasopressin secretion to control water excretion
So in the tubule is the only place where volume and osmolality are regulated separately, in other
cells in the body water always follows sodium.
3
, In the proximal tubule and the thick ascending limb there is mostly paracellular transport, whereas in
the more distal parts there is mostly transcellular transport.
Proximal tubule: it consists out of three different segments (S1, S2, S3). It has a very large surface
area of the apical membrane, that is because then there is more transport capacity. Further it is a
leaky epithelium, so therefore lot of paracellular transport. There is bulk and iso-osmotic transport,
this means that if you measure the osmolarity of the pro-urine at the beginning of the proximal
tubule and at the end then this will be exactly the same.
- 60% Cl- absorption, 65% Na+/K+/Ca2+/H2O, 90% HCO3-, 100% glucose/amino acids and
100% proteins by endocytosis via megalin/cubulin receptors.
Fanconi syndrome → mutation of
proximal tubule, in the cubulin,
megalin or ClC-5 causes all the same
disease.
This is in the proximal tubule, the S1 segment. There is
only glucose reabsorption in the proximal tubule, it is
done via a cotransporter. Dapagliflozin blocks the
reabsorption of glucose, so glucose will be in the urine,
this is a medicine for diabetes and thus glucose
lowering effect.
There is the thin limb of Henle’s loop, this has a descending and ascending part.
- Descending → there is no NaCl transport and it is highly permeable for H2O
- Ascending → there is active NaCl transport, and it is not permeable for H2O
This counter current mechanism for urine concentration in the collecting duct, and this a relatively
cheap to do a lot of transport, because you have a high osmotic concentration in the medulla (the
deeper in the medulla the higher the concentration). If there is a permeability of the water to go out,
4
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