Renal 1. Organization of the Urinary System Flashcards
What are the two main regions of the capsule around the kidney?
- Renal Cortex - outer portion
* Renal Medulla - inner portion
• Nephrons are where main action takes place, make urine, 2 types:
1) cortical nephron: located in renal cortex (80-90%)
2) juxamedullary nephron: big parts of then extends to renal medulla region (10%)
Nephron: composed of two parts -
the renal corpuscle and renal tubule
Renal tubule segments:
proximal convoluted tubule, Loop of Henle
Renal corpuscle:
Glomerulus + Bowman’s capsule
Flow of fluid through a Cortical Nephron
Globular (bowmans) capsule —> proximal consulates tubule —> descending loop of Henley —>
ascending loop of henle —>
distal consulates tubule (drains into collecting duct)
Flow of fluid through a medullary nephron
Globular (bowmans) capsule —> proximal consulates tubule —> descending loop of Henley —> thin ascending loop of henle —> ascending loop of henle —> distal consulates tubule (drains into collecting duct)
Where does blood enter and exit the nephron?
Blood enters via the Afferent arteriole and exits through the Efferent arteriole
How does blood enter the KIDNEY?
How does blood leave the KIDNEY?
Renal artery (enter) Renal vein (leave)
From the afferent arteriole, where does the blood flow after?
From afferent arteriole, flows into capillary network called glomerulus, then goes back into another arteriole (efferent exterior), this efferent arteriole turns into peritubular capillaries (tightly coupled with blood supply, important for putting things in and out of blood)
• Vasa-recta:
specific to medullary nephrons, referred to tight coupling of the nephron with surrounding blood supply
Which nephrons contain the vasa recta?
Medullary nephrons
• Granular cells
tightly coupled with afferent arteriole, important for blood pressure regulation. Sensitive to stretch.
High blood flow = with high blood pressure = granular cells stretch = sets cascade of events that reduces in blood pressure.
• Macula densa cells:
very sentive to amounts of salt that’s inside the tubule, not inside the blood.
High blood pressure = filter out a lot of salt out of blood into the glomerulus, and gets into distal tubule as it leaves glomerulus
Macula densa senses high salt =
high blood pressure = tries not to increase blood pressure.
Macula densa senses low salt =
low blood pressure = communicates with granular cells that produce renin, renin increases blood pressure. (Renin cascade)
What is the relationship between salt level in the blood and blood pressure?
They are direct.
- low salt = low blood pressure
- high salt = high blood pressure
Granular cells are coupled with ?
Afferent arteriole
What’s the relationship between blood pressure and blood flow?
They they direct.
- high blood pressure = high blood flow
- low blood pressure = low blood flow
The three cell types that regulate GFR are
- granular
- macula densa,
- mesengial
A decrease in the GFR flowing past the macula densa →
decreases sodium deliver to macula densa → increase renin secretion
What is the order blood flows through the different types of tubules in the medullary nephron?
proximal consulates tubule PCT—> THIN descending limb —> THIN ascending limb —> THICK ascending limb —> distal consulates tubul DCT —> cortical collecting tubul CCT —> connecting tubule —> initial collecting tubule (ICT) —> collecting duct
contrast the thin descending limp, the thick ascending limp is very important for
water balance (reapportion of water and blood pressure)
What kind of nerve fibre is connected where in the nephron, what does it do?
Granular cells Innervated by sympathetic nerve fibers which can change the resistance of the afferent arteriole
• Release renin which controls afferent arteriole resistance
Does the kidney connect do parasympathetic or sympathetic nerve fibres?
Only connects to sympathetic nerves.
What’s the sympathetic nerve role
Regulation of blood pressure
Blood enters the glomularus via the
Afferent arteriole, 20% of the blood gets filtered into the bowman capsule in the form of plasma, then leaves through the efferent arteriole
Are are the three ways the Glomulerus Filters the blood?
1) fenestrated (pores) of glomerular endothelial cells
2) basement membrane (basal lamina of glomerulus)
3) slit membrane between pedicels
Fenestration (pore) of the glomerular endothelial cells
Prevents filteration of blood cells
(like RBC, albium, Hb & other large mol.) Blood plasma passes through !
- Found within thinnest layer
if blood comes in urine = problem with
Fenestration as its job is to filter out blood cells and prevent then form goin into urine
What’s a reason the fenestrated pores in glomerular endothelial cells would allow blood to pass?
pores stretched due to high blood pressure = blood passes through tubule = goes into urine
Basement membrane
Prevents filtration of larger proteins.
Membrane is (-) charged, so repels any (-) charged molecules like ions, and attracts (+) charges ions and modules. Anything with (-) wont pass the membrane and is filtered
Slit membrane between pedicels
Prevents filteration of medium sized protiens.
What are pedicels and how do they help in filtration of medium sized molecules through the glomerulus?
Pedicels are projections that are created by podocytes, which are part of glomerulus.
These projection have slits between them (play role in filtration). Podocytes and slit membrane both have a (-) charge = only allow the passage of (+) charged ions, no (-) charges pass.
3 basic renal functions
1) filtration
2) reabsorption
3) secretion
Filtration:
Blood comes in through the afferent arteriole, goes into the glomerulus and then a certain amount of plasma contianing all ions is filter out of the blood ( 20% of it )
Where do all the filtered plasma and other contents o the blood go once filtered by the glomerulus?
It flows down the tubule (20% of all the ions and plasma will have been filtered)
In this tubule where the filtrate flows down, what occurs?
Reabsorption and secretions process occur in the tubule where all the filtrate is flowing down, so things are still being put in and out.
• Reabsorption:
After blood passes the glomerulus, continues down the efferent arteriole, there are still undersiables in the blood within the tubule, these undesirables are removed from the tubule and into the afferent capillary through REABSORPTION, putting it back into the blood.
In terms of reabsorption, what happens to glucose?
glucose in the glomulerus is freely filterable, so it all goes into the blood through reabsorption once its passes through glomerulus. That’s why there’s no glucose in urine.
If glucose in urine = problem with
reabsorption.
Glucose clearance is
0
• Secretion:
for the components that dont get filtered by glomerulus, and continue down the efferent and shouldn’t be in the blood, they will be secreted into the tubule (into the urine).
How does reabsorption occur?
Through the proximal tubule, substances can pass through the membrane via either the tight junctions (paracellular) or through transcellular transport. They are selectively permeable.
• Intercalated cells:
important for acid base balance.
• principal cells:
important for water regulation
Clearance measurements compare the
rate at which the glomeruli filter a substance (water or a solute) with the rate at which the kidneys excrete it into the urine
Renal clearance is the
“virtual” volume of plasma from which a substance is completely removed by the kidney in a given amount of time (usually a minute).
Measurements of renal clearance indicate/evaluate
renal function
Renal clearance is used clinically to estimate what?
estimate:
- Renal Plasma Flow (RPF)
- Glomerular Filtration Rate (GFR)
Renal Plasma Flow indicates/estimates
cardiovascular systems ability to provide blood flow to the kidneys.
Glomerular Flow Rate (GFR) indicates/estimates
Kidney function
• Clearance of any substance is proportional to
The (conc. of substance X in the urine)X (how much urine is produced / min).
Or proportional to: ———> [Cx * V]
• Clearance is inversely proportional to the
amount of substance X staying inside of the plasma. Or [ Px]
• If you have more substance staying inside of the plasma then you do leaving the plasma, clearance will be
lowerm
• If you have less substance staying inside of the plasma then you do leaving the plasma, clearance will be
Higher
PAH is filtered and secreted, therfore is would be a good marker for measuring what?
For renal plasma flow
Afferent arterial blood flows with a certain amount of PAH. 20% of that PAH is filtered out of the blood through the glomerulus and goes into the tubule = ~ 12ml/min filtering out of the blood plasma and into the tubule. The remaining 80% or 48ml/min actually is
secreted back into the tubule, so that all of the PAH infused into this person per min is ending up in the urin.
NORMAL RENAL PLASMA FLOW IS
600-700 ml/min.
For PAH, we know 20% is filtered, what happens to the other 80% that was not filtered by the glomerulus?
The remaining 80% in the efferent arteriole is secreted back into the tubule and end up in the urin.
So even tho 20% is filtered + 80% is not = 100% still ends up in the urine.
What kind of marker would be used for measuring GFR?
A substance that is 100% filtered and 0% secreted or reabsorbed.
• Glomerular filtration rate is the volume of fluid
filtered from the glomerulus into the Bowman’s space per unit time.
- Used to look at the health of the kidney
What is normal healthy GFR
• ~ 125 mL/minute or 180L/day
Criteria for Ideal Marker:
- Substance must be freely filterable in the glomeruli.
- Substance must be neither reabsorbed nor secreted by the renal tubules.
- Substance must not be synthesized, broken down, or accumulated by the kidney.
- Substance must be physiologically inert (not toxic and without effect on renal function).
What were the two substances given as good examples for marker to GFR ?
Inulin and creatinine
For creatinine the glomerular filtration rate is inversely proportional to the
plasma concentration of the substance
Creatinine gives a GFR of
125 ml/min (normal)
• if you had a condition where a problem in the kidneys caused a decrease in GFR, the amount of creatinine staying in the plasma
doesn’t change. This means that the kidneys have a buffer zone that allows them to withstand a decrease in GFR and still function normally.
At what point does GFR have to decrease for creatinine to begin rising in the plasma sue to insufficient filtration
(ie poor GFR)
Around the 60 ml/min creatinine begins rising due to shitty filtration = indicates problem in kidney function.
• net renal processing:
majority being reabsorbed or major secreted.
• If the clearance of a substance X is greater than the glomerular filtration rate of 125 millilitres per minute, substance X is being
secreted
• If the clearance of substance X is less than the glomerular filtration rate of 125 millilitres per minute, substance X is being
reabsorbed
Any substance that has a clearance rate lower then 125 is gonna be _____ and above 125 is gonna be ______
Any substance that has a clearance rate lower then 125 is gonna be reabsorbed and above 125 is gonna be secreted
What is the net renal processing of inulin ?
What is the net renal processing of glucose ?
None
Reabsorption
Between renal plasma flow and renal blood flow, which one is always smaller?
Renal plasma flow will always be less then renal blood flow.
RPF normal level is
625 ml/min, and about 20% (125 ml/min) of it is filtered in glomerulus.
• Renal blood flow ( RBF ) is the
volume of blood delivered to the kidneys per unit time.
• Renal plasma flow ( RPF ) is the
volume of plasma delivered to the kidneys per unit time
What Determines the Filterability of Solutes Across the Glomerular Filtration Barrier
Molecular Size, Electrical Charge, and Shape of the molecule
Heavier molecules will have a filtrate of
Less the one, meaning its harder to filter.
Why cant Hb or albumin be used for GFR measment?
To large in size.
The more (+) charge the molecule is, the greater
filter ability it will have since the basement membrane carries a (-). A (-) molecule would just be repels and would never be able to pass through, having lower filter ability.
Even if 2 molecules were the same size, between a (+) and (-) charged mol, which would have greater filter ability
The (+)
Removing the (-) charge on molecule would do what to the filtration of anions?
It would increase.
Nephrotoxic serum nephritis
Pathological condition that removes (-) form the basement membrane. This would cause things that should be in urine (like albumin to be in urine) = BAD = insufficient filter ability
Glomerular ultrafiltration rate depends on
net starling forces
Starling forces show that there are
forces working in both directions. It’s the net force that determines how much or how easily something can get into the tubule.
What are the four starling forces ?
1) Glomerular capillary hydrostatic pressure (PGC)
2) Bowman’s space hydrostatic pressure (PBS)
3) Glomerular capillary oncotic pressure (πGC)
4) Bowman’s space oncotic pressure (πBS)
Of the four factors, the most intuitive one is the
glomerulus capillary hydrostatic pressure (PGC)
Which of the startling forces favour filtration?
1) Glomerular capillary hydrostatic pressure (PGC)
And
4) Bowman’s space oncotic pressure (πBC)
Which starling forces impede filtration?
2) Bowman’s space hydrostatic pressure (PBC)
And
3) Glomerular capillary oncotic pressure (πGC)
As blood flows into the glomerulus, the
pressure in there increases causing it to filter out into the tubule. Normal PGC is 60 mmHg (favouring filtration)
What are the normal numbers for each of the starling forces
1) Glomerular capillary hydrostatic pressure (PGC) = 60 mmHg
2) Bowman’s space hydrostatic pressure (PBC) = 15 mmHg
3) Glomerular capillary oncotic pressure (πGC) = 29mmHg
4) Bowman’s space oncotic pressure (πBS)
= 0 mmHg
Besides the PGC and PBC, we also have non intuitive factors which are called
protein pressure oncotic pressure, which is measured by the PI symbol.
protein pressure oncotic pressure are used to measure increases in protein in the blood pressure because
its pulling fluid into the blood, an increase in blood volume you can increase blood pressure.
What is the overall net force / glomerular filtration pressure ?
16 mmHg
• In a healthy person, the filtrate in Bowman’s space does not contain
proteins
• Therefore theres no osmotic force due to the presence of proteins in Bowman’s space
Is there fluid movement due to osmosis form the glomerulus to the bowman’s capsule
No fluid movement due to osmosis from the glomerulus to Bowman’s
Why is πBS = 0
Because there is no protein in the filtrate in the bowman’s space. No protein = no fluid movement = no osmotic force = bowman’s space oncotic pressure is 0
Positive filtration pressure pushes filtered fluid/water containing the substances into
Bowman’s space
• The positive filtration pressure pushes the
protein-free filtrate from the plasma out of the glomerulus into Bowman’s space
What factor would contribute to an increase in the glomerular filtration rate?
• High blood pressure = increase glomerular filtration rate
What factor would contribute to a decrease in the glomerular filtration rate?
• An increase in the protein conc in the plasma would increase the protein content in the glomerular capillaries, decreasing the glomerular filtration rate
What Controls Both Glomerular Plasma Flow and Glomerular Filtration Rate?
Changes in resistance for Afferent and Efferent Arteriolar
4 scenarios that can alter the glomerular filtration rate:
1) Increase resistance in Afferent
2) Decrease resistance in Afferent
3) Increase resistance in Efferent
4) Decrease resistance in Efferent
- Constrict Afferent arteriole →
PGC, or the hydrostatic pressure of the glomerular capillary, will decrease → decrease GFR
- Dilate Afferent arteriole →
increase in blood flow into the afferent arteriole → increase in the hydrostatic pressure → increase GFR
- Dilate efferent arteriole →
decreases resistance → renal blood will drain rapidly → decrease in the capillary hydrostatic pressure → decrease GFR
- Constrict efferent arteriole →
volume of blood builds up in the glomerular capillaries → increase hydrostatic pressure in the glomerular capillaries → increase GFR
So an increase in relative arteriolar resistance will cause for a :
- decrease in renal plasma flow (RPF) form 600-700 down to ~200.
- Decrease in glomerular capillary pressure (blue) from ~60 down to ~40. Based on starling forces, if this goes down, then filtration goes down.
- Decrease in GFR which is normally at 25.
This indicates kidney function, in this case wouldn’t be good
Constriction of only Afferent arteriole will cause for GFR to decrease because
Both glomerular capillary pressure and renal plasma flow decrease
When donating a kidney, in order to do the job of two kidneys it needs to self regulate so that it has more blood flow going to one kidney. So therefore the afferent will
vasodilate to decrease resistance so that it gets more renal plasma flow and more pressure and able to filter more to make up for the lost kidney.
Two kinds of autoregulation:
- Myogenic regulation
- Tubulomerular regulation
For both, the stimulus is an increase in blood pressure.
Explain the tubuloglomerular feedback system mechanism
[stimulus] —>
Increase in MAP (mean arteriole pressure) = Increase in blood pressure in the Afferent arteriole = Increases Glomerular capillary pressure = increases in Glomerular filtration pressure - increases GFR = salt levels rise which macula densa detected = increases blood flow = increases paracrine section (Adenosine)
Paracrine secretion has negative feedback response on increasing constriction of the Afferent arteriole = increases resistance = decreases glomerular capillary pressure = decreases GFR back to normal !!!
Adenosine:
usually a vasodilator, BUT in the kidneys its a VASOCONSTRICTOR. Used in tubuloglomerular feedback
Constricts the vessels to increases resistance = decrease GCP back to normals)
Explain the Myenteric pathway
Increase in MAP (mean arteriole pressure) = increases blood pressure in afferent = —-> acts on 2 pathways
—>. 1) increases Glomerular capillary pressure = increases Glomerular filtration pressure = increases GFR (BAD!)
—-> 2) stretch of arteriolar smooth muscle = increases constriction of afferent = increases resistance = decrease in Glomerular capillary pressure (this one has (-) feedback effect on the increase of glomerular capillary pressure mentioned in the first pathway.) = fixes the elevated level of GFR back to normal !!
glomerulus + Bowman’s capsule =
the renal corpuscle
