SM 189a/190a - Functional Renal Anatomy and Glomerular Filtration, Regulation Flashcards
Which of the following would tend to decrease GFR?
- An increase in hydrostatic pressure in the glomerular capillary
- A decrease in oncotic pressure in the glomerular capillary
- A decrease in total glomerular capillary surface area
c. A decrease in total glomerular capillary surface area
If solute delivery to the juxtaglomerular apparatus is too high, which cells respond?
What is the response?
- 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
What is the equation for clearance (kidney)?
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
c. Parietal epithelial cells (a.k.a. Bowman’s capsule)
What fraction of cardiac output goes through the kidney?
20%
If solute delivery to the juxtaglomerular apparatus is too low, which cells respond?
What is the response?
- 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
What are the requirements for the use of creatinine clearance for GFR?
- Renal function must be in steady-state
- No vigorous activity or muscle breakdown
- No protein loading
What is the function of the macula densa?
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)
Which macromolecules will filter through the glomerular permeability barrier more easily:
Positively charged, negatively charged, or neutral?
Why?
Positively charged
The glomerular basement membrane contains anionic glycosaminoglycans that repell negatively charged molecules
[smaller molecules filter more easily than large]
How do the Starling forces change from the affertent to efferent arterioles of the glomerulus?
- PGC remains constant, may drop slightly
- PBS remains constant
- πGC increases
- Fluid is leaving, protein concentration in the glomerular capillary increases
- πBS remains zero
Filtration stops when πGC increases to oppose PGC
What are mesangial cells?
Supporting cells of the glomerulus that help to maintain capillary structure
They can contract (contain actin and myosin)
Where in the kidney does filtration occur?
Glomerulus
(Located in the cortex)
Filtration = fluid going from capillaries to Bowman’s space; this is the ultrafiltrate that will eventually become urine
Does albumin filter into the urine?
Why or why not?
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)
What mechanisms affect LpS?
Mesangial cell contraction can decrease capillary surface area
Decreased surface area (S) = decreaed GFR
Lp remains constant
Which of the following statements about creatinine is FALSE?
- Creatinine is freely filtered by the glomerulus
- Creatinine is neither reabsorbed nor secreted by the tubules
- Creatinine is a clinically useful marker of GFR
- Cimetidine may increase the plasma creatinine concentration
b. Creatinine is neither reabsorbed nor secreted by the tubules
(I think this is right, but let me know if not!)
Where in the kidney does filtration take place?
Glomerulus
Filtration = movement from glomerular capillaries -> Bowman’s capsule
What is angiotensin II?
What are the effects?
Angiotensin II is a potent vasoconstrictor
- Kidney
- Vasoconstriction of the efferent arteriole
- -> Raises PGC and increases GFR in response to low Cl- delivery to the macula densa or beta-1 adrenergic stimulation
- Systemic
- Rise in blood pressure
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?
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
Describe the sequence of events that happens if renal blood flow increases
- PGC (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
- PGC decreases
- GFR returns to normal
- Macula densa senses return to normal, stops releasing ATP into the extracellular space
Which of the following statements is most consistent with tubuloglomerular feedback?
- increased NaCl delivery to the thick ascending limb causes increased proximal fluid reabsorption.
- decreased NaCl delivery to the thick ascending limb causes increased proximal fluid reabsorption.
- increased NaCl delivery to the thick ascending limb causes no change in proximal fluid reabsorption.
- increased NaCl delivery to the thick ascending limb causes decreased glomerular filtration rate
- increased NaCl delivery to the thick ascending limb causes increased glomerular filtration rate
D. increased NaCl delivery to the thick ascending limb causes decreased glomerular filtration rate
What is the equation for glomerular filtration rate (GFR)?
- 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
What are the major differences between cortical and juxtamedullary nephrons
-
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
Why doesn’t renal artery pressure have a large effect on GFR?
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
What is the role of renin secretion in autoregulation of GFR?
Renin secretion -> Angiotensin II production (via RAAs)
Active when renal arterial pressure is low
Responsible for raising glomerular capillary pressure to maintian GFR
What signals to the macula densa inhibit the release of renin?
- High Cl- delivery
- Angiotensin II (negative feedback)
- ANP
- Vasopressin
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?
Creatinine in the urine will be lower than expected
(Calculate the expected level using age, lean body mass, and plasma creatinine)
How would efferent arteriole dilation affect GFR?
Why?
Dilation of the efferent arteriole would decrease GFR
Dilation -> decreased pressure in the glomerulus -> PGC (hydrostatic pressure in the glomerular capillaries) ->
decreased GFR
Where in the RAA system do beta blockers act?
What do they do?
Beta-1 adrenergic stimulation causes renin release
Beta blockers prevent renin release, thus inhibiting the RAA system that produes Angiotensin II
Which cells make up the juxtaglomerular apparatus?
What do they do?
- 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
Angiotensin II constricts the [afferent/efferent] arteriole, resulting in [increased/decreased] GFR
Angiotensin II constricts the efferent** arteriole, resulting in **increased GFR
What trigger promotes signals from the macula densa that result in renin release?
- Low Cl- delivery
- Beta-1 adrenergic stimuli
- Catecholamines
- PTH
- Glucagon
What types of cells are found in the glomerulus?
- Endothelial cells
- Visceral epithelial cells (podocytes)
- Create slit diaphragms
- Parietal epithelial cells
- Make up the outer lining of Bowman’s Capsule
- Mesangial cells
How does creatinine clearance change as we age?
Creatine clearance decreases as we age
However, muscle mass also decreases as we age, so creatine production is lower as well
Where in the kidney are the glomeruli located?
The cortex
Cortical nephrons are in the mid-outer cortex
Juxtamedullary nephrons are right above the boundary between the cortex and the outer medullay
What is normal for GFR?
Male: ~125 mL/min, = 180 L/day
Female: ~95 mL/min = 137 L/day
What is reabsorption?
Where in the kidney does reabsorption take place?
Reabsorption is movement from tubular fluid -> peritubular capillaries
Reabsorption takes place throughout the kidney tubule, from the proximal convoluted tubule through the connecting duct
Describe the structure of the of the glomerular basement membrane
- 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)
What is Renin?
What does it do?
A proteolytic enzyme that cleaves Angiotensinogen to
Angiotensin I
The rate-limiting enzyme of the RAAs pathway
What is the difference between filtration and secretion in the kidney tubule?
Filtration: from glomerular capillaries -> Bowman’s capsule
Secretion: any substances moving from peritubular capillaries/interstitial space -> kidney tubule distal to Bowman’s casule
Describe the RAA system
Renin is the rate-limiting step
Why is oncotic pressure in Bowman’s space zero under normal conditions?
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
What are the 3 main mechanisms of autoregulation of GFR?
- 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
What is the major driver of glomerular filtration?
Hydrostatic pressure in the glomerular capillary
(Usually much higher than hydrostatic pressure in Bowman’s space)
What is the role of tubuloglomerular feedback in autoregulation of GFR?
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)
