Lecture 4: Renal Histology and Cell Biology Flashcards
What is the uriniferous tubule?
Term for nephron + collecting duct
How can you tell where the cortex is in relation to the medulla?
If you see glomeruli, that is where the cortex is
No glomeruli in medulla
What are the histological features of the glomerulus?
Purple balls with thin white space around it
What are the histological features of the tubules?
Defined as columns of tissue running parallel past the glomerulus down to medulla
Where does the nephron start?
Renal corpuscle
What is the renal corpuscle?
Bowman’s capsule + glomerulus of capillaries
What part of the nephron is responsible for acid base balance?
DCT
What is the medullary ray?
Center of each lobule
Contains tubules that are parallel to each other and oriented radially in cortex
The tubules in medullary rays are continuous with those in medulla
What is a lobule?
Comprises all glomeruli that contribute urine to the collecting ducts within a medullary ray
Radially running arteries and veins are located at borders of lobules
What portions of the nephron are located in the medullary ray?
- Proximal Thick descending LoH
- Distal thick ascending LoH
- Collecting Duct
What structures are NOT part of the medullary ray?
- Proximal convoluted tubule
- Distal convoluted tubule
- Glomerulus
- Artery, veins and lymphatics
What are the histological features
Of the PCT?
- brush border (microvilli)
- Cuboidal epithelium
- eosionophilic on PAS stain
- 3-4 nuclei, fuzzy luminal surface and mitochondria defined by deeper eosinophilic striations
What are the characteristics of EM of kidney?
PCT have extensive basal invaginations
Large mitochondria located between the basal invaginations
What is the difference between distal and proximal tubules histologically?
Proximal is pinker and has more cytoplasm
Distal = less pink and less cytoplasm (as seen above) = no brush border
What are the two domains of the cortex?
- medullary rays containing ascending, descending LoH and collecting ducts
- PCT, DCT and glomeruli
What forms the medulla?
- outer zone
i. thick ascending limbs
ii. LoH
iii. collecting ducts - inner zone:
i. LoH
ii. Collecting ducts
What are the two categories of nephrons?
- Those located in the outer cortex have short LoH
2. Juxtamedullary nephrons have long loops of Henle
Where does the connection between nephron and collecting ducts take place?
At the level of the medullary ray
What are the histological features of collecting tubules vs LoH in medullary kidney?
Collecting tubes have bigger endothelium and more cytoplasm
As seen below
What are the characteristics of the stellate interstitial cells?
They are adherent to both tubules and vessels
Are the site of prostaglandin synthesis
What is the site of prostaglandin synthesis?
Stellate interstitial cells
What artery leads to afferent artery?
Intralobular artery (IIu on picture) as stated in the notes Intralobular arteries branch off of interlobular arterioles at each renal corpuscle
What are the SEM features of podocytes?
Sits on capillary loop
Contains negatively charged cells
That repel negatively charged proteins
Like albumin
What do fenestrations do?
Block exit of cells but allow
Free flow of plasma
Basal lamina + podocytes = sieve to prevent
Molecules >70kD
What is the slit diaphragm?
The portion of the membrane that the “slits” arrows are pointing to in SEM above
Contains nephrin and regulates what gets filtered from blood
What are slit diaphragms composed of?
Elongated proteins that arise from the surface of the adjacent cell membranes
What is the function of nephrin?
Nephrin on one podocyte that can attach to the nephrin on another podocyte
Absence of nephrin = podocytes incapable of forming foot processes and slit diaphragms
-leads to proteinuria
Defect in nephrin = defect in actin cytoskleteon
What are the 3 components of the glomerular filtration barrier?
- endothelial cell
- podocyte
- glomerular basement membrane
How are podocytes connected to one another?
By the slit diaphragm and is also connected to basal lamina
What are the key characteristics of the glomerular basement membrane?
A type IV collagen
Rich in heparan moieties
Heparan = negative charge
Acts as a coarse filter restricting large molecules
Where are the mesengial cells located?
Between capillaries under the basal lamina but outside the capillary lumen
What is the specialized blood supply sequence only found in the kidney?
Arteriole capillary arteriole capillary vein sequence
Afferent arteriole glomerulus efferent arteriole vasa recta intermediate venules arcuate veins
What are the characteristics of the vasa recta?
Efferent arterioles of juxtamedullary glomeruli descend into the medulla and form the descending vasa recta which supplies adjacent capillary plexus
The capillary plexus is most dense in the inner stripe of the outer medulla
What is the significance of the vasa recta?
Allows one to create salt gradient in the loop of Henle
What is the countercurrent system?
The countercurrent system creates a gradually increasing hypertonicity of extracellular fluid
Geometry of loops of henle and vasa recta is essential
What are the two most unique cells in kidney (aside from mesangial cells)?
- cells that produce renin
2. cells that produce EPO
What are the two hormones the kidney secretes?
- Renin
- EPO
Also produces 1,25 vitamin D (calcitriol) but only contains the enzyme to convert calcidiol to calcitriol
What are the cells that produce the renin?
Components of the juxtaglomerular apparatus
Sit in afferent arteriole
Produced by juxtaglomerular cells (aka epithelioid cells)
What is the function of the macula densa?
Sense changes in salt concentration in the lumen of the distal convoluted tubule
Has Na-Cl-K symporter and Na-H antiporter on apical membrane
Releases PGE2 and NO in response to LOW DCT salt concentrations
PGE2 and NO are what ultimately stimulate JG cells to release renin
What are the three key players of in the juxtaglomerular apparatus?
JG cells
Macula densa
Lacis cells (polkissen cells,
or function unknown)
What are the 3 ways the renin granular cells (JG cells) are stimulated to produce renin?
- Beta-1 adrenergic innervation
- PGE2 and NO as secreted from macula densa (in response to elevated salt)
- Local baroreceptor which trigger stretch receptors in apical membrane of JG cell
- stretches membrane and makes Ca2+ permeable
- Increases levels of cAMP which leads to renin release
What are the two ways renin granular cells are antagonized?
- Angiotensin II
- Atrial natriuretic peptide (ANP…which makes sense because ANP is only released if atria is stretched to signify too much volume)
What is the stimulus for upregulation of EPO?
Low oxygen delivery to the kidney
Hypoxia Inducible Factor (HIF) activates transcription of EPO gene
What is the HIF?
Hypoxia inducible factor
A transcription factor that activates transcription of EPO gene
What cells produce EPO?
Renal Cortical interstitial cells
Sit in the interstitium!
What is the HIF pathway?
A universal system for sensing oxygen
-Normally, you get proline hydrogenation at the level of the
HIF-alpha
-In hypoxia, you do not get an addition of O2 to
hydroxylate the proline residue in the HIF-alpha
-This is how renal interstitial cells know when to secrete
EPO
No proline hydroxylation = EPO secretion
Under normal conditions, how is HIF activated?
HIF is constitutively hydroxylated by enzyme called PHD
Hydroxylation allows subsequent binding of different protein called VHL
VHL targets HIF for degradation
Under hypoxic conditions how is HIF activated?
Hydroxylation is arrested
HIF is stabilized and you get activation of HIF target genes such as that for EPO
Normal = no HIF Hypoxic = HIF = more EPO
What mutations can lead to polycythemia (increased red cell mass)?
In PHD2 and HIF-2 as well as ones on VHL
Patients behave as hypoxic
Key roles in oxygen sensing pathway for renin release
