Exam 3 Lecture: Glomerular Filtration Flashcards
What is the function of fenestrated capillaries?
hold back red blood cells and larger plasma proteins bigger than the size of albumin
What is albumin?
the most common protein found in blood
What are the fenestrated capillaries covered in and what do they do?
covered in laminin and fibronectin which repel negatively charged molecules
What is in the lamina rara and what does it do?
laminin, fibronectin, heparan sulphate and they repel negatively charged molecules
What type of proteins do the lamina densa filter?
collagenous proteins for less than 2nm
What is the slit diaphragm made out of?
protein - mostly nephrin
What does the slit diaphragm filter based on?
size - they have small pores
What do the supporting podocytes of the slit diaphragm filter based on?
the basis of charge as they are covered in negative charge
How easy is it for a neutral protein to cross the filtration barrier?
it depends on the size, since their charge is 0, that is not a factor, but the bigger they are the harder it is for them to cross the barrier
How easy is it for a catatonic protein to cross the filtration barrier?
it is still size dependent, but catatonic proteins have an easier time crossing the filtration barrier because the negative charge of the filtration barrier does not repel them very well
How easy is it for anionic proteins to cross the filtration barrier?
it is also size dependent, but anionic proteins also have a difficult time crossing the barrier because the negative charge of the filtration barrier will repel them away
If proteins get through the filtration barrier, what must happen to them?
they must be reabsorbed or passed in the urine
If proteins are not filtered, what happens?
the kidney cannot regulate serum protein concentration
What drives fluid movement out of the capillaries of the glomerulus??
hydrostatic and oncotic pressures
What has the biggest influence on fluid movement?
hydrostatic pressure
In what direction does capillary hydrostatic pressure push?
Pc, pushes out of the capillary
What is Pc generated by?
the resistance difference of afferent/efferent arterioles
What direction does bowman’s space hydrostastic pressure push?
Pbs, pushes into the capillary
Which hydrostatic pressure is bigger?
the capillary hydrostatic pressure - therefore the net effect of hydrostatic pressure is to push plasma out of the glomerulus
What is oncotic pressure?
osmotic pressure caused by colloids (plasma proteins)
Where is the protein concentration in the capillaries the highest?
in Bowman’s space
In what direction does oncotic capillary pressure push?
in
In what direction does bowman’s space oncotic pressure push?
in, but it is negligible
What are the starling’s forces?
the forces of hydrostatic and oncotic pressure: Capillary hydrostatic pressure, bowman’s space hydrostatic pressure, capillary oncotic pressure and bowman’s space oncotic pressure
What determines whether a fluid moves into or out of the capillary?
the balance of the starlings forces
What is the largest Starling’s force?
Pc
What is the biggest determinant of GFR?
Pc
What s the easiest way for the kidney to modulate GFR?
keep a handle on Pc
If it is easier for blood to enter the glomerulus than leave it, what will this do to the Pc and GFR?
increase the Pc and increase the GFR
If it is easier for blood to leave the glomerulus than enter it, what will this do to the Pc and GFR?
reduce the Pc and reduce GFR
Constriction of afferent and dilation of efferent equals…
decreased Pc therefore decreased GFR
Relaxation of afferent and constriction of efferent equals…
increased Pc therefore increased GFR
Usually, what does disease affect in relation to GFR?
it usually decreases GFR
What does schistosomiasis do to GFR?
it decreases it and results in renal failure
How does schistosomiasis reduce GFR?
causes antigens to collect in the filtration apparatus initiating a war at the glomerulus, shredding the filtration apparatus
What does decreased plasma protein levels lead to?
a decrease in capillary oncotic pressure, and increase the GFR; happens during liver impairment
What do uroliths or plugs lead to?
increased hydrostatic pressure in bowman’s space which inhibits GFR
What signifies ‘good’ renal clearance?
if a substance is freely filtered, not reabsorbed or secreted by the tubules and passed in the urine
What signifies ‘bad’ renal clearance?
if the substance gets caught in the filtration apparatus, or is reabsorbed in the tubules and returned to the blood
How is clinical evaluation of renal function measured?
by monitoring creatinine or BUN
What does high levels of creatinine signify?
Low GFR, less is getting cleared through filtration
What is the purpose of autoregulation?
To offset the consequences that a change in BP can do to the kidney and keep it functioning properly
What can a spike in BP cause in the absence of autoregulation?
increase the amount of blood flowing down the afferent arteriole and slamming into the glomeruli causing damage
What does autoregulation control?
blood flow into the glomeruli to prevent changes to the GFR despite the changes in systemic blood pressure
What is the range of BP that the kidney can autoregulate for?
80-180 mmHg
What are the two mechanisms of autoregulation?
the myogenic mechanism and tubulohlomerular feedback
Where does the myogenic mechanism occur?
in the afferent arteriole
When blood pressure has increased, what does the myogenic mechanism do in order to fix the problem?
vasoconstriction of the afferent arteriole and decreased blood flow
When blood pressure has decreased, what does the myogenic mechanism do in order to fix the problem?
vasodilation of the afferent arteriole and increased blood flow
Which mechanism of autoregulation is the fastest?
the myogenic mechanism
What is the only thing that the myogenic mechanism senses?
changes in BP
What is the sensor for tubuloglomerular feedback?
the fluid in the distal tubule
What is the trigger for tubuloglomerular feedback?
Fluctuations in BP change GFR meaning distal tubule fluid composition is altered; ion concentration is the trigger
What would the ion levels resemble in the distal tubule if GFR were high?
they would also be high
What would the ion levels resemble in the distal tubule if GFR were low?
they would be low
What are ion levels in the distal tubule fluid sensed by?
the macula densa
What component of autoregulation is tubuloglomerular feedback considered?
the regulatory component
Explain the Renin-Angiotensin system.
- Angiotensionogen is made in the liver, then meets Renin in the afferent arterioles
- Renin converts Angiotensionogen into Angiotensin I
- Angiotensin I is converted into Angiotensin II via a converting enzyme in the lungs
What are the functions of angiotensin II?
- systemic arteriolar vasoconstriction to increase blood pressure
- Increase aldosterone secretion
- promotes ADH secretion
- Increases tubular NaCl uptake
How does the tubuloglonerular feedback mechanism work in response to high blood pressure?
- High ion levels are sensed by NKCC2 on the apical surface of the macula densa
- ATP and/or adenosine is relased by the macula densa
- ATP/adenosine activate receptors on extraglomerular mesangial cells
- Increased intracellular Ca causes the afferent tubule to contract, and the juxtaglomerular cells do not release renin
How does the tubuloglomerular feedback mechanism work in response to low blood pressure?
- Low ion levels are sensed
- Macula densa releases PGE2
- PGE2 causes arteriole vasodilation and JG releases renin
- Angiotensin II increases causing systemic vasoconstriction (prefers to contract the efferent arteriole) PGE2 production increases
What do NSAID’s do to tubuloglomerular feedback?
they inhibit prostaglandin production, there is no vasodilation and GFR is not normalized
What is the most important autoregulation mechanism?
the myogenic mechanism because it protects against injury where as tubuloglomerular feedback just focuses on GFR and homeostasis
