Lecture 11/15: Renal Physiology Cont'd Flashcards
Final
What does it mean when creatinine clearance is reduced?
Renal function is reduced
How does chronic HTN above MAP of 150 effect the kidney?
AA will try to constrict but only to an extent –> increased RBF –> increased pressure in GC –> increase GFR –> increases UO
The GC is most effected by this
What are the 2 things in the kidney effected by HTN?
GC: Primary; prolonged high pressure = scarring; effects podocytes efficiency; widens fenestrations
AA: prolonged constriction = stiffening & prevents dilation when needed (BP drops)
T/F: increasing GFR will increase Reabsorption rate
F
You will reabsorb the same amount which is 124 ml/min
You will EXCRETE MORE
What happens to Reabsorption when GFR is decreased? why?
Reabsorption is increased
-fluids moving slowing thru the nephron
-more time in nephron = more time for reabsorption
What happens in the kidney when BP is decreased?
AA dilates –> GFR decreases –> reabsorption increases –> UO decreases
**MD senses… juxta releases renin –> constricts EA
Most vasoconstrictors, except ANG II, constricts ______ more than _______
AA
EA
T/F: ANG II constricts the AA & EA both equally
F
Constricts both, but constricts EA more
Prostaglandins preferentially dilate the ______ more
AA
NSAIDs preferentially vasoconstrict the ______ more. How?
AA
By inhibiting prostaglandins
T/F: There is reabsorption happening at every segment of the nephron
T
How much is reabsorbed at the PCT?
2/3
65%
Where is the MD located?
TAL
How does the MD work? Explain for low & high GFR
Acts as a sensor that counts Na+ & Cl- molecules as they pass by
Can detect a higher/lower number of Na/Cl and gauges GFR
Low: More ions are reabsorbed –> less ions make it to MD –> MD dectects that GFR is low –> juxta cells release renin –> ANG II increases –> EA constrict –> Pressure in GC increases –> GFR increases
High: normal ions are reabsorbed –> more ions make it to MD –> MD dectects that GFR is high –> juxta cells decrease release renin –> ANG II decreased –> EA relax –> Pressure in GC decreases –> GFR decreases
In addition to constricting to EA & AA, what other effects do ANG II have?
Increases Na reabsorption in PCT
This increases water reabsorption –> increase fluid volume –> increases BP
Describe the pathology if you had an increase in reabsorption of Na+ in the nephron. What could cause this? What is the Tx for this?
GFR could be normal, you’re just reabsorbing more more Na+
Less Na+ molecules at MD –> MD thinks GFR is low –> Juxta cells release Renin –> increase ANG II –> EA constricts –> Pressure in GC increases –> GFR increases (even tho it was fine)
This is bad. Creates high pressure at the GC which can destroy the GC –> destroys the nephron.
Causes: THE DIABETES!!!!
-Excess sugar intake causes the excess Na intake as well via the SGLT transporters in the PCT
Tx: ACE inhibitors (-prils)
ARBs (-sartan)
All of _____ & _______ should be filtered and reabsorbed at the proximal tubule if WNL
Glucose
Amino acids
What is the concentration of Na+ in the tubular cells?
14
What is the charge inside of the tubular cell?
-70 mV
Describe the amino acid transporter
1 Amino acid & 1 Na+
Cotransporter
-Located in PCT
-Apical side
What happens if you constant consume a high amount of amino acids?
Kidneys could be destroyed
Na+ reabsorption is increased with amino acids –> GFR is normal but Na+ at MD decreased –> Juxta releases Renin/ANGII
This causes pressure in the GC to increase which increases GFR more than needed
This is the same pathology as Diabetes
What is the main pathology in uncontrolled glucose (DM)?
Hyperfiltration of the GC
This causes damage to the GC which can ultimately destroy the Nephron putting strain on other nephrons –> this shortens the lifespan of the other nephrons
What food items are high in amino acids?
Steak
pre-workout
protein shakes
T/F: Glucose & amino acids can be absorbed in many places in the nephron
F
What happens if Glucose is not reabsorbed in the PCT?
It will not be reabsorbed anywhere else. It will be excreted
What is the tubular lumen?
The inside of the tubular structure (nephron)
The ______ side of the tubular cell touches the nephron & the _______ side of the cell touches the renal ISF
Apical
Basolateral
Describe the SGLT transporters
SGLT2: S1 Segment-Early PCT
-1Na/1Glucose
-High efficiency/low affinity
-GLUT2
SGLT1: S2/S3 Segments-Later in PCT
-2Na/1Glucose
-High affinity/low efficiency
-GLUT1
-Requires more energy (extra Na+ bc more dilute fluid & harder to pull out glucose)
-S3 segment has very few pumps
-Located in PCT
-Apical side
-Secondary Active transport
-dependent on Na+ electrochemical gradient (Na+ = 14 & -70mV inside cell)
Describe the GLUT transporter
Transfers glucose out of PCT brought in from SGLT transporters
-Located in PCT
-Basolateral side
-No energy required
-Gradient created by SGLT transporters by increasing glucose in tubular cell
GLUT2 = SGLT2
GLUT1 = SGLT1
What should the glucose concentration be at the end of the PCT?
0
T/F: Glucose concentration in the tubule should be the same as plasma glucose concentration
T
What are the 3 segments of the Proximal tubule?
S1: early part of PCT
S2: later part
S3: Last part
What portion of glucose is absorbed in each section of the Proximal tubule?
S1 = 90%
S2 - 10%
What is filtered load?
Amount of solute thats been filtered
Plasma concentration x GFR
What is the threshold for glucose? What does this mean?
Threshold: Between 101-199 mg/dL
This is where glucose will start showing up in the urine
SGLT1 transporters will start to miss excess glucose
What happens when you glucose transporters become saturated?
This is called Transport Maximum
For every extra glucose that is filtered, that extra glucose will show up in the urine
pathology: Reabsorption pumps become saturated bc they cannot do conformational changed fast enough.
What is glucose transport max? What does this mean?
300 mg/dL
Any higher sugar than this:
-The excretion line will become line
-1 extra glucose filtered = 1 extra glucose excreted
What does the MD primarily monitor? Why is this important?
Na+
More sensitive to changes due to high glucose (diabetes) and amino acids
What is the rate limiting step in ANG II?
Renin
It’s the rate limiting step in formation of ANG II bc its the rate limiting step to formation of ANG I
What is the process to get to ANG II?
Angiotensinogen (produced in the liver) + renin = ANG I + Angiotensin Converting Enzyme-ACE (produced in the lungs) = ANG II
What is a side effect of ACE inhibitors?
Bad cough/chest congestion
Inhibits ACE which is an enzyme produced in the lungs
When GFR is low, and what does the MD cells DIRECTLY do?
Releases Nitric oxide –> relaxes AA –> Increases RBF –> Increases GC pressure –> Increase GFR
When GFR is low, what are the 3 arms that are effected?
- Juxta with Renin/ANG II –> EA constricts
- MD with NO –> Dilates AA
- ANG II –> Na/Water reabsorption at PCT
MD release ______ on the ________ causing vasodilation
Nitric Oxide
AA
T/F: ANGII constricts both the AA & EA
T
Just constricts the EA more
What does ANGII do?
- Constricts EA to increase GFR
- Increase Na/Water reabsorption at PCT to increase blood volume
What adverse effects do we expect to see with excess glucose in the urine? What type of medications can cause this? What are these medications used for?
Excess glucose in downstream anatomy = breading ground for infection
-Ex) urethra: UTI
Also excess glucose build up can trigger an immune reaction (Glycocaylx damage)
Medication: SGLT inhibitors & GLP agonist
-Both are for DM but are commonly used for weight loss
What was very rare/expensive 2000 years ago & was used as a perservative?
Salt
Why was salt expensive 2000 years ago?
It was difficult to extract
