Lecture 4: Renal Histology and Cell Biology

Question 1

What is the uriniferous tubule?

Answer 1

Term for nephron + collecting duct

Question 2

How can you tell where the cortex is in relation to the medulla?

Answer 2

If you see glomeruli, that is where the cortex is

No glomeruli in medulla

Question 3

What are the histological features of the glomerulus?

Answer 3

Purple balls with thin white space around it

Question 4

What are the histological features of the tubules?

Answer 4

Defined as columns of tissue running parallel past the glomerulus down to medulla

Question 5

Where does the nephron start?

Answer 5

Renal corpuscle

Question 6

What is the renal corpuscle?

Answer 6

Bowman’s capsule + glomerulus of capillaries

Question 7

What part of the nephron is responsible for acid base balance?

Answer 7

DCT

Question 8

What is the medullary ray?

Answer 8

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

Question 9

What is a lobule?

Answer 9

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

Question 10

What portions of the nephron are located in the medullary ray?

Answer 10

1. Proximal Thick descending LoH
2. Distal thick ascending LoH
3. Collecting Duct

Question 11

What structures are NOT part of the medullary ray?

Answer 11

1. Proximal convoluted tubule
2. Distal convoluted tubule
3. Glomerulus
4. Artery, veins and lymphatics

Question 12

What are the histological features

Of the PCT?

Answer 12

1. brush border (microvilli)
2. Cuboidal epithelium
3. eosionophilic on PAS stain
4. 3-4 nuclei, fuzzy luminal surface and mitochondria defined by deeper eosinophilic striations

Question 13

What are the characteristics of EM of kidney?

Answer 13

PCT have extensive basal invaginations

Large mitochondria located between the basal invaginations

Question 14

What is the difference between distal and proximal tubules histologically?

Answer 14

Proximal is pinker and has more cytoplasm

Distal = less pink and less cytoplasm (as seen above) = no brush border

Question 15

What are the two domains of the cortex?

Answer 15

1. medullary rays containing ascending, descending LoH and collecting ducts
2. PCT, DCT and glomeruli

Question 16

What forms the medulla?

Answer 16

1. outer zone
   i. thick ascending limbs
   ii. LoH
   iii. collecting ducts
2. inner zone:
   i. LoH
   ii. Collecting ducts

Question 17

What are the two categories of nephrons?

Answer 17

1. Those located in the outer cortex have short LoH

2. Juxtamedullary nephrons have long loops of Henle

Question 18

Where does the connection between nephron and collecting ducts take place?

Answer 18

At the level of the medullary ray

Question 19

What are the histological features of collecting tubules vs LoH in medullary kidney?

Answer 19

Collecting tubes have bigger endothelium and more cytoplasm

As seen below

Question 20

What are the characteristics of the stellate interstitial cells?

Answer 20

They are adherent to both tubules and vessels

Are the site of prostaglandin synthesis

Question 21

What is the site of prostaglandin synthesis?

Answer 21

Stellate interstitial cells

Question 22

What artery leads to afferent artery?

Answer 22

Intralobular artery (IIu on picture) as stated in the notes
Intralobular arteries branch off of interlobular arterioles at each renal corpuscle

Question 23

What are the SEM features of podocytes?

Answer 23

Sits on capillary loop
Contains negatively charged cells
That repel negatively charged proteins
Like albumin

Question 24

What do fenestrations do?

Answer 24

Block exit of cells but allow
Free flow of plasma
Basal lamina + podocytes = sieve to prevent
Molecules >70kD

Question 25

What is the slit diaphragm?

Answer 25

The portion of the membrane that the “slits” arrows are pointing to in SEM above Contains nephrin and regulates what gets filtered from blood

Question 26

What are slit diaphragms composed of?

Answer 26

Elongated proteins that arise from the surface of the adjacent cell membranes

Question 27

What is the function of nephrin?

Answer 27

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

Question 28

What are the 3 components of the glomerular filtration barrier?

Answer 28

1. endothelial cell 2. podocyte 3. glomerular basement membrane

Question 29

How are podocytes connected to one another?

Answer 29

By the slit diaphragm and is also connected to basal lamina

Question 30

What are the key characteristics of the glomerular basement membrane?

Answer 30

A type IV collagen Rich in heparan moieties Heparan = negative charge Acts as a coarse filter restricting large molecules

Question 31

Where are the mesengial cells located?

Answer 31

Between capillaries under the basal lamina but outside the capillary lumen

Question 32

What is the specialized blood supply sequence only found in the kidney?

Answer 32

Arteriole  capillary  arteriole  capillary  vein sequence Afferent arteriole  glomerulus  efferent arteriole  vasa recta  intermediate venules  arcuate veins

Question 33

What are the characteristics of the vasa recta?

Answer 33

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

Question 34

What is the significance of the vasa recta?

Answer 34

Allows one to create salt gradient in the loop of Henle

Question 35

What is the countercurrent system?

Answer 35

The countercurrent system creates a gradually increasing hypertonicity of extracellular fluid Geometry of loops of henle and vasa recta is essential

Question 36

What are the two most unique cells in kidney (aside from mesangial cells)?

Answer 36

1. cells that produce renin | 2. cells that produce EPO

Question 37

What are the two hormones the kidney secretes?

Answer 37

1. Renin 2. EPO Also produces 1,25 vitamin D (calcitriol) but only contains the enzyme to convert calcidiol to calcitriol

Question 38

What are the cells that produce the renin?

Answer 38

Components of the juxtaglomerular apparatus Sit in afferent arteriole Produced by juxtaglomerular cells (aka epithelioid cells)

Question 39

What is the function of the macula densa?

Answer 39

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

Question 40

What are the three key players of in the juxtaglomerular apparatus?

Answer 40

JG cells Macula densa Lacis cells (polkissen cells, or function unknown)

Question 41

What are the 3 ways the renin granular cells (JG cells) are stimulated to produce renin?

Answer 41

1. Beta-1 adrenergic innervation 2. PGE2 and NO as secreted from macula densa (in response to elevated salt) 3. 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

Question 42

What are the two ways renin granular cells are antagonized?

Answer 42

1. Angiotensin II 2. Atrial natriuretic peptide (ANP…which makes sense because ANP is only released if atria is stretched to signify too much volume)

Question 43

What is the stimulus for upregulation of EPO?

Answer 43

Low oxygen delivery to the kidney | Hypoxia Inducible Factor (HIF) activates transcription of EPO gene

Question 44

What is the HIF?

Answer 44

Hypoxia inducible factor | A transcription factor that activates transcription of EPO gene

Question 45

What cells produce EPO?

Answer 45

Renal Cortical interstitial cells | Sit in the interstitium!

Question 46

What is the HIF pathway?

Answer 46

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

Question 47

Under normal conditions, how is HIF activated?

Answer 47

HIF is constitutively hydroxylated by enzyme called PHD Hydroxylation allows subsequent binding of different protein called VHL VHL targets HIF for degradation

Question 48

Under hypoxic conditions how is HIF activated?

Answer 48

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 ```

Question 49

What mutations can lead to polycythemia (increased red cell mass)?

Answer 49

In PHD2 and HIF-2 as well as ones on VHL Patients behave as hypoxic Key roles in oxygen sensing pathway for renin release