SM 189a/190a - Functional Renal Anatomy and Glomerular Filtration, Regulation

Question 1

Which of the following would tend to decrease GFR?

1. An increase in hydrostatic pressure in the glomerular capillary
2. A decrease in oncotic pressure in the glomerular capillary
3. A decrease in total glomerular capillary surface area

Answer 1

c. A decrease in total glomerular capillary surface area

Question 2

If solute delivery to the juxtaglomerular apparatus is too high, which cells respond?

What is the response?

Answer 2

• Macula densa senses increase in solute (Na+) delivery
• Macula densa releases adenosine
• Adenosine causes extraglomerular mesangial cells to contract and cause vasocaonstriction of the afferent arteriole

Question 3

What is the equation for clearance (kidney)?

Answer 3

Question 4

Which of the following is NOT a component of the glomerular permeability barrier?

a. Visceral epithelial cells (a.k.a. podocytes)
b. Glomerular basement membrane
c. Parietal epithelial cells (a.k.a. Bowman’s capsule)
d. Negatively charged glycosaminoglycans
e. Glomerular capillary endothelial cells

Answer 4

c. Parietal epithelial cells (a.k.a. Bowman’s capsule)

Question 5

What fraction of cardiac output goes through the kidney?

Answer 5

20%

Question 6

If solute delivery to the juxtaglomerular apparatus is too low, which cells respond?

What is the response?

Answer 6

• Macula densa senses decrease in solute (Cl-) delivery and/or flow
• Signals to the granular cells in the wall of the afferent arteriole
• Granular cells release renin
• Renin secretion -> Increased Angiotensin II production
• Angiotensin II ->
  
  • Increased Na/H exchange
  • Constriction of the efferent arteriole
  • Aldosterone secretion -> Na+ reabsorption

Question 7

What are the requirements for the use of creatinine clearance for GFR?

Answer 7

• Renal function must be in steady-state
• No vigorous activity or muscle breakdown
• No protein loading

Question 8

What is the function of the macula densa?

Answer 8

The macula densa…

• Senses changes in solute concentration and tubular flow
• Communicates to granular cells in wall of afferent arteriole if solute (Cl-) delivery and flow are low
  
  • ​-> Granular cells release renin
• Communicates to extraglomerular mesangial cells of solute (Na+) delivery and flow are high
  
  • -> Mesangial cells contract, causing constriction of the afferent arteriole (tubuloglomerular feedback)

Question 9

Which macromolecules will filter through the glomerular permeability barrier more easily:
Positively charged, negatively charged, or neutral?

Why?

Answer 9

Positively charged

The glomerular basement membrane contains anionic glycosaminoglycans that repell negatively charged molecules

[smaller molecules filter more easily than large]

Question 10

How do the Starling forces change from the affertent to efferent arterioles of the glomerulus?

Answer 10

• P_GC remains constant, may drop slightly
• P_BS remains constant
• π_GC increases
  
  • Fluid is leaving, protein concentration in the glomerular capillary increases
• π_BS remains zero

Filtration stops when πGC increases to oppose PGC

Question 11

What are mesangial cells?

Answer 11

Supporting cells of the glomerulus that help to maintain capillary structure

They can contract (contain actin and myosin)

Question 12

Where in the kidney does filtration occur?

Answer 12

Glomerulus

(Located in the cortex)

Filtration = fluid going from capillaries to Bowman’s space; this is the ultrafiltrate that will eventually become urine

Question 13

Does albumin filter into the urine?

Why or why not?

Answer 13

Albumin does not filter into the urine

It is large and negatively charged - it cannot get through the glomerular permeability barrier

(Fenestrated endothelium, GBM, Foot processes of podocytes)

Question 14

What mechanisms affect LpS?

Answer 14

Mesangial cell contraction can decrease capillary surface area

Decreased surface area (S) = decreaed GFR

Lp remains constant

Question 15

Which of the following statements about creatinine is FALSE?

1. Creatinine is freely filtered by the glomerulus
2. Creatinine is neither reabsorbed nor secreted by the tubules
3. Creatinine is a clinically useful marker of GFR
4. Cimetidine may increase the plasma creatinine concentration

Answer 15

b. Creatinine is neither reabsorbed nor secreted by the tubules

(I think this is right, but let me know if not!)

Question 16

Where in the kidney does filtration take place?

Answer 16

Glomerulus

Filtration = movement from glomerular capillaries -> Bowman’s capsule

Question 17

What is angiotensin II?

What are the effects?

Answer 17

Angiotensin II is a potent vasoconstrictor

• Kidney
  
  • Vasoconstriction of the efferent arteriole
  • -> Raises P_GC and increases GFR in response to low Cl- delivery to the macula densa or beta-1 adrenergic stimulation
• Systemic
  
  • Rise in blood pressure

Question 18

What is the basis for the structural difference between the thin and thick ascending loop of Henle?

What does this tell us about their functions?

Answer 18

The thick ascending limb is thick because the walls are full of mitochondria

The mitochondria in the thick ascending limb generate ATP that fuels active transport of NaCl into the medulla to increase osmolality in the medullay, which drives the countercurrent multiplier

Question 19

Describe the sequence of events that happens if renal blood flow increases

Answer 19

• P_GC (Hydrostatic pressure in the glomerular capillary) increases
• GFR increases
• Macula densa senses increased NaCl in the ultrafiltrate
• Macula densa releases ATP into extracellular space
• ATP is converted to adenosine
• Adenosine activates mesangial cells to contract, causing vasoconstriction of the afferent arteriole
• P_GC decreases
• GFR returns to normal
• Macula densa senses return to normal, stops releasing ATP into the extracellular space

Question 20

Which of the following statements is most consistent with tubuloglomerular feedback?

1. increased NaCl delivery to the thick ascending limb causes increased proximal fluid reabsorption.
2. decreased NaCl delivery to the thick ascending limb causes increased proximal fluid reabsorption.
3. increased NaCl delivery to the thick ascending limb causes no change in proximal fluid reabsorption.
4. increased NaCl delivery to the thick ascending limb causes decreased glomerular filtration rate
5. increased NaCl delivery to the thick ascending limb causes increased glomerular filtration rate

Answer 20

D. increased NaCl delivery to the thick ascending limb causes decreased glomerular filtration rate

Question 21

What is the equation for glomerular filtration rate (GFR)?

Answer 21

• Δπ = π inside of the glomerular capillary
  
  • Oncotic pressure inside of Bowman’s space is zero
• Hydrostatic pressure in the glomular is the driver of glomerular filtration

Question 22

What are the major differences between cortical and juxtamedullary nephrons

Answer 22

• Location
  
  • Cortical: mid-outer cortex
  • Juxtamedullary: boundary of cortex and outer medulla
• Loop of Henle​
  
  • Cortical: short
  • Juxtamedullary: long
• Function
  
  • ​Cortical: recieve 95% of filtrate
  • Juxtamedullary: establish high osmolarity in the inner medulla -> countercurrent multiplier
• Abundance
  
  • Cortical: more abunant
  • Juxtamedullary: less abundant

Question 23

Why doesn’t renal artery pressure have a large effect on GFR?

Answer 23

The afferent arteriole that leads into the glomerulus “protects” the glomerular capillary bed from changes in renal artery pressure

The affernet arteriole is under control of the intrinsic myogenic reflex, vasoconstrictors, and vasodilators

Question 24

What is the role of renin secretion in autoregulation of GFR?

Answer 24

Renin secretion -> Angiotensin II production (via RAAs)

Active when renal arterial pressure is low

Responsible for raising glomerular capillary pressure to maintian GFR

Question 25

What signals to the macula densa inhibit the release of renin?

Answer 25

* **High Cl- delivery** * **Angiotensin II (negative feedback)** * ANP * Vasopressin

Question 26

If a patient is doing a 24h collection to measure creatinine clearance, what will yo use if the patient did not collect all of their urine?

Answer 26

Creatinine in the urine will be lower than expected (Calculate the expected level using age, lean body mass, and plasma creatinine)

Question 27

How would efferent arteriole dilation affect GFR? Why?

Answer 27

Dilation of the efferent arteriole would decrease GFR Dilation -\> decreased pressure in the glomerulus -\> P_GC (hydrostatic pressure in the glomerular capillaries) -\> decreased GFR

Question 28

Where in the RAA system do beta blockers act? What do they do?

Answer 28

Beta-1 adrenergic stimulation causes renin release Beta blockers prevent renin release, thus inhibiting the RAA system that produes Angiotensin II

Question 29

Which cells make up the juxtaglomerular apparatus? What do they do?

Answer 29

* Macula densa * Senses Na+ delivery and flow through the renal tubule * Signals to respond to changes * If Na+ delivery is high, signals mesangial cells to contract the afferent arteriole * If Na+ delivery is low, signals granular cells to release renin * Extraglomerular mesangial cells * Contract to constrict the afferent arteriole if Na+ delivery to the macula densa is too high * Granular cells * Release renin if Na+ delivery to the macula densa is too low

Question 30

Angiotensin II constricts the _[afferent/efferent]_ arteriole, resulting in _[increased/decreased]_ GFR

Answer 30

Angiotensin II constricts the **_efferent**_ arteriole, resulting in _**increased_** GFR

Question 31

What trigger promotes signals from the macula densa that result in renin release?

Answer 31

* **Low Cl- delivery** * **Beta-1 adrenergic stimuli** * Catecholamines * PTH * Glucagon

Question 32

What types of cells are found in the glomerulus?

Answer 32

* Endothelial cells * Visceral epithelial cells (podocytes) * Create slit diaphragms * Parietal epithelial cells * Make up the outer lining of Bowman's Capsule * Mesangial cells

Question 33

How does creatinine clearance change as we age?

Answer 33

Creatine clearance decreases as we age However, muscle mass also decreases as we age, so creatine production is lower as well

Question 34

Where in the kidney are the glomeruli located?

Answer 34

The cortex **Cortical nephron**s are in the mid-outer cortex **Juxtamedullary nephrons** are right above the boundary between the cortex and the outer medullay

Question 35

What is normal for GFR?

Answer 35

Male: ~125 mL/min, = 180 L/day Female: ~95 mL/min = 137 L/day

Question 36

What is reabsorption? Where in the kidney does reabsorption take place?

Answer 36

**Reabsorption** is movement from **tubular fluid -\> peritubular capillaries** Reabsorption takes place throughout the kidney tubule, from the proximal convoluted tubule through the connecting duct

Question 37

Describe the structure of the of the glomerular basement membrane

Answer 37

* Anionic glycosaminoglycans * Type IV collagen * Laminin * Fibronectin The GBM is negatively charged (negatively charged plasma proteins (ex: albumin) cannot easily filter out of the glomerular capillaries)

Question 38

What is Renin? What does it do?

Answer 38

A proteolytic enzyme that cleaves Angiotensinogen to Angiotensin I The rate-limiting enzyme of the RAAs pathway

Question 39

What is the difference between filtration and secretion in the kidney tubule?

Answer 39

**Filtration**: from glomerular capillaries -\> Bowman's capsule **Secretion**: any substances moving from peritubular capillaries/interstitial space -\> kidney tubule distal to Bowman's casule

Question 40

Describe the RAA system

Answer 40

Renin is the rate-limiting step

Question 41

Why is oncotic pressure in Bowman’s space zero under normal conditions?

Answer 41

Oncotic pressure is exerted by large plasma proteins that are stuck on one side of a membrane. Plasma proteins cannot get out of the glomerular capillary into Bowman’s space – they are, by definition, undfilterable. Therefore, the oncotic pressure inside of Bowman's capsule is zero

Question 42

What are the 3 main mechanisms of autoregulation of GFR?

Answer 42

* Myogenic reflex * First line of defense * Protects the kidney from fluctuations in systemic blood pressure * Tubuloglomerular feedback * Active when renal arterial pressure is **high** * Responsible for **preventing increases** **in glomerular capillary pressure** * Renin secretion (-\> Angiotensin II) * Active when renal arterial pressure is **low** * Responsible for **raising glomerular capillary pressure** to maintian GFR

Question 43

What is the major driver of glomerular filtration?

Answer 43

Hydrostatic pressure in the glomerular capillary (Usually much higher than hydrostatic pressure in Bowman’s space)

Question 44

What is the role of tubuloglomerular feedback in autoregulation of GFR?

Answer 44

Active when renal arterial pressure is high Responsible for preventing increases in glomerular capillary pressure (Macula densa releases adenosine, causing mesangial cells to contract, which constricts the afferent arteriole)