Lecture 11/18: Renal Physiology Cont'd Flashcards
Final
T/F: MD relaxes both the AA & EA
T
Selective to AA though
___% of PAH is left in plasma
10%
Describe how a selective vs Nonselective vasoconstrictor/dilator can effect GFR
Selective: Will effective either the AA or EA more and we can better gauge how GFR will change
Nonselective: You dont know which one is effected more therefore you cant determine how GFR will be exactly effected
Most pressers/dilators are selective to the _____
AA
Describe the Angiotensin II Type 1 Receptors
AT1
AT1-R binds to ANGII
-Proximal Tubule
-Apical & Basolateral
Speeds up the cycling of Na/K Atpase pump
-Ultimately results in increased reabsorption of Na+ (and water) and Bicarb by speeding up the NHE pump
Describe the Sodium-Hydrogen Exchanger pump
NHE
1 Na+ in (tubular cell)
1 H+ out (urine)
-Important in acid/base regulation
-SECRETES a proton into tubular lumen
-Major role in Na reabsorption
-Proximal Tubule
-Apical
Affected by AT1-R; Speeds up based on Na/K ATPase Na+ gradient on basolateral
Describe the Sodium-Potassium ATPase pump
Na+/K+ ATPase
3 Na out (Renal ISF)
2 K in (Tubular cell)
-Proximal Tubule
-Basolateral
-Sped up by AT1-R
-Speeds up the NHE
Describe the Sodium-Bicarb Symporter
Co-transporter
1 Na+ & THREE (3) Bicarbs in renal ISF
-Proximal Tubule
-Basolateral
Affected by AT1-R; Sped up by the NHE
What pumps do AT1 affect?
This is the ANGII receptor
- Na/K ATPase <– primary
- NHE
- Sodium-Bicarb symporter
What are the routes of reabsorption in the PT?
- Paracellular pathways via osmosis
- Trancellular pathways via transporter/channels in the cell wall
- Aquaporins (specialized trancellular pathway for water) via osmosis
Describe water reabsorption in the PT
- Aquaporins
- Transcellular pathway: Na+ influenced
- Paracellular: dragged with other ions
Describe how chloride is reabsorbed in the PT
Paracellular
This is heavily Na+ influenced
Na+ is reabsorbed via the transcellular route (pumps in the cell wall) and pumps positive charges into the renal ISF. These positive charges attract the negative charges on Cl-
Also increased glucose & amino acids influence Na reabsorption
If you have diabetes, what 2 ions will you see an increased reabsorption in? What will this cause?
Increase reabsorption of Na (SGLT) & Cl (paracellular route)
This causes a decrease in Na and Cl at the MD –> thinks GFR is low –> releases renin/ANGII –> EA constricts to increase GFR……. you know this
What is osmosis?
Passive movement of water from an area of lower osmolarity to a higher osmolarity to equalize osmolarity
What is bulk flow?
The process of reabsorption at the PT cap based on the starling capillary forces
Remember NFP = -10 & NRP = 10
This is a high pressure so lots of reabsorption
What is a big portion of the concentrated renal ISF? What is this?
Urea
A waste product that assists in concentrating the renal ISF to assist with reabsorption and osmosis
If you’re dehydrated, you would expect your renal ISF to be _________. Why?
Very concentrated
Body is trying very hard to conserve water (prevent body from excreting it)
______ assists with osmosis
urea
What is the brush border?
Brush-looking structure that increases surface area by 20-fold
Increases room for transporters for reabsorption
Located on the apical/luminal side
T/F: Tubular cells are electrically excitable
T
What is the charge in the tubular lumen in the Proximal tubule? What attributes to this?
-3 mV
Excess Cl-
T/F: Cl- builds up in the PCT. Why?
T
Cl- reabsorption lags behind Na+
What part of the PCT is Cl- most absorbed in?
2nd half
What happens when proteins are filtered at the GC?
A small amount of SMALL proteins can be filtered
Reabsorbed at the PCT ONLY
-1.8g/day filtered
-1.7g/day reabsorbed via endocytosis (pinocytosis) <– this is the max amount
-0.1g/day excreted (this is normal)
After protein is filtered the brush border grabs the protein –> endocytosis –> degrades to amino acids –> reabsorbs
What is the max amount of protein that can be reabsorbed?
1.7g/day
T/F: pinocytosis of proteins can happen in the PCT and DCT
F
only in the PCT; if it doesnt happen here the protein will be excreted or stuck in tube causing damage
About how much protein do we filter per day? Excrete?
1.8g/day
0.1g/day
What is the driving forces behind Na reabsorption in the PCT?
- NHE
- SGLT
- Amino acid/Na cotransporter
What is the enzyme associate with bicarb formation?
Carbonic Anhydrase
Describe the bicarb process
Proton secreted into tubular lumen from NHE pump –> Bicarb forms with it to make carbonic acid –> carbonic acid (H2CO3) + carbonic anhydrase –> Water + CO2
These can freely diffuse across the cell via osmosis/passive diffusion. Once in the cell:
Water + CO2 + Carbonic Anhydrase –> Carbonic Acid (H2CO3) –> Bicarb + H+
-Bicarb is reabsorbed via the Na-Bicarb Symporter
-H+ is used by the NHE again for the process to start again :)
What happens to bicarb if you decrease Na intake?
Decreases
this can cause mild acid/base imbalances –> acidosis
Bicarb formation is dependent on what pump?
NHE
Where is CA (carbonic anhydrase) located? What does it do?
-Tethered to the walls & in between cells in the PCT
-Breaks down Carbonic Acid H2CO3 to water and CO2
-Tubular cells
-promotes formation of carbonic acid from water and CO2
What happens to protons if there’s no bicard in the tubular lumen?
-Protons attach to the excess ammonia in the urine –> forms Ammonium
-Dont want free protons in urine = pain
-Ammonium helps buffer Cl-
Describe how CA inhibitors work
Inhibit CA in the PCT –> indirectly slows down the NHE pump (Decrease in protons to spin pump) –> less Na reabsorbed & less bicarb reabsorbed
Results: Diuretic effects
-acidosis
Where is glutamine produced?
Liver
What does Glutamine do?
PCT
-inside tubular cells
in combination with Proximal Tubular cell … Produces NEW bicarb:
– 2 HCO3 and 2 ammonium
What is a common side effect we see in people with liver failure?
acid/base imbalances
unable to produce sufficient glutamine –> not able to produce new bicarb or ammonium
What are the urinary buffers?
-Ammonia/Ammoniun
-NaHPO4- (Sodium phosphate) –> NaH2PO4
-Bicarb
Describe the Ammonium pump
SECRETES 1 NH4 into tubular lumen for 1 Na reabsorbed into tubular cells
-PCT
-apical
How is Calcium reabsorbed in the PCT?
- Paracellular: dragged with water/ions
- Trancellular:
-Apical: Ca++ ion channel
-Basolateral: Ca++ ATPase & NCX
Explain how Ca++ plays a role in acid/base balance
-If you are more acidotic there are more protons in your blood. Those protons will attach to albumin in the blood because they have opposit changes. Causing more free Ca++ to be in the blood. –> More Ca++ able to be filtered
-Alkalotic –> more Ca++ binding to albumin –> less Ca++ filtered
What detects low Ca++ levels in the blood?
Parathyroid gland
How does the parathyroid gland regulate Ca++ levels?
They sense Ca++ is low & release
Parathyroid hormone (PTH)
- Increases Vit D activation –> increases the amount of Ca++ absorbed from diet
- Increases Ca++ reabsorption in kidneys –> increases # of Ca++ channel
- Stiumlates bone breakdown via osteoclasts –> uses Ca++ store
- Inhibits activity of osteoblasts –> prevents Ca++ being used to build new bone
Our long term Ca++ stores are ______ & short term is _______
Bone
Sarcoplasmic Reticulim
Differentiate between Osteoblast & osteoclasts
Blasts = bone builder; increases bone density
clasts = break down bone
What is bone made of?
Calcium
Phosphate
What is a common disorder we see in people who are chronically hypocalcemic? What does this put them at risk of? What is the Tx for this?
Osteoporosis
Bone fractures
Tx: Vitamin C with Activated Vitamin D
What is an Antiporter?
Pump that secretes organic compounds into the Proximal tubule to be excreted
Location: PT only
Apical/Tubular Lumen
What are your endogenous Organic Cations?
Think neurotransmitters mostly
Ach
Creatine
choline
dopamine
epi
histamine
serotonin
NE
What are your exogenous organic cations?
Think heart drugs
isoproteranol
atropine
procaine
quinine
tetraethylammonium (TEA)
TEE
What are the endogenous organic anions?
Bile salts
hippurates
prostaglandins
urate (uric acid)
oxalate
What are the exogenous organic anions?
Abx & Diuretics
Furosemide
Penicillin
Salicyclates (ASA)
sulfonamides
acetazolamide
chlorothiazide
How are Organic cations secreted?
An H-Dependent antiporter
-Secreted the organic cation into the PCT
-Reabsorbs a proton
Organic Anions antiporters involve ________
Alpha-Ketoglutarate
How are Organic anions secreted?
- A pump takes 3 Na+ & 1 AlphaKG into the renal ISF from the PT cap
- That is able to spin the pump that brings in 1 organic anion from the PT cap to the Renal ISF & takes out 1 AlphaKG from the renal ISF
- Now the antiporter is able to pump the organic anion into the PCT to be excreted
How does penicillin stay in the system longer?
Adding a synthetic hippurate
This creates competitive inhibition with the antiporters, making penicillin stay in the system longer
Explain the history of penicillin
Mold was producing PCN and stopping the growth of bacteria
Discovered prior to WWII –> Used during during WWII
PCN was leaving the body rapidly –> added hippurate
As a rule of thumb, if we dont know how much of something gets reabsorbed at the PCT, its _____
2/3
The majority of the loop of henle is _____
thin
Describe the Thin Descending Limb
-Fluid is descending into an area w/ a more concentrated renal ISF
-Tubular fluid is becoming more concentrated as well
Water reabsorption via AQP1 channels
Impermeable to ions
Where is the hairpin turn?
Between the descending and ascending loop of henle
Describe the thin ascending limb in the loop of Henle
-Fluid is ascending into an area w/ a more dilute renal ISF
-Tubular fluid is becoming more dilute as well
Na+/Cl- ATPase (reabsorbs 1Na & 1Cl)
Impermeable to water
____% of ions filtered are reabsorbed ath the thick ascending loop of henle
25%
T/F: TAL is permeable to water
F
What is the charge in the TAL? What causes this charge? What is the result of this charge?
+8 mV
cause: Leak K+ causing a positive charge
result: Causes cations to leave the TAL via the paracellular route
Which ions are pushed harder via diffusion in the paracellular route? Why?
Mg++
Ca++
They both have a double charge and want to leave even more away from the positive charge
Where does acid/base balance happen in the nephron?
TAL
PCT
Late DCT
Collecting tubule
What pumps do the TAL have that are neccesary for acid/base balance?
Na/K ATPase
NHE
Describe the NKCC2 transporter
1 Na+, 1 K+, 2 Cl- cotransporter
TAL
Apical
The ______ plays an important role, along with urea, in concentrating the renal ISF
TAL
Where do loop diuretics work? What is the MOA.
TAL
inhibit the NKCC2 pump –> This causes the renal ISF to become less concentrated –> losing the ability to reabsorb water –> excrete more urine
T/F: Animals that live in the desert can concentrate their renal ISF higher than 1200
T
This allows them to reabsorb more water so their body wont excrete it.
T/F: urine can be a little more concentrated than the renal ISF
F
Urine can only be as concentrated as the renal ISF, not higher
What are 3 examples of loop diuretics?
Furosemide
Ethacrynic acid
bumetanide
What helps preserve the osmotic gradient in the loop of henle?
countercurrent blood flow in allows for exchange of solutes & water with distruption of osmotic gradient
This is the reason why 1 side is impermeable to water and the other is impermeable to ions
Where does PTH influence Ca reabsorption ini the nephron?
PCT
DCT
What are the pumps associated with Ca++ reabsorption in the DCT?
apical:
-Ca++ ion channel
-NCC
Basolateral:
Ca++ ATPase
NCX
Na/K ATPase
The NCX exchanges ___ Na+ ____ the cell for ____ Ca++ _____ the cell
3 Na+ in the cell
1 Ca++ out the cell (renal ISF)
Basolateral
PTH increase Ca++ ion channels on the _____ side of the cell
Apical
What pump drives Na reabsorption in the DCT?
NCC (1Na/1Cl)
Where do Thiazide diuretics work? What is the MOA.
In the DCT
They inhibit the NCC pump –> More Na+ in the tubular lumen & more Ca++ in the renal ISF
Results: More Na+ in the tubular lumen –> less water reabsorption –> more water excreted
–Increased Ca++ reabsorbed into the renal ISF
What medication can help osteoporosis or preventing kidney stones? Why?
Thiazide diuretics
Increases reabsorption of Ca++ by inhibiting the NCC pump in the DCT
T/F: Thiazide diuretics can get rid of kidney stones
F
Can only help prevent
The DCT is also sensitive to ______ & ________
ADH
Aldosterone (Aldo)
Aldo =
Aldosterone
Which cells are sensitive to Aldo?
Intercalated & principal cells in the DCT
Which cells are sensitive to ADH?
Intercalated cells in the DCT
How does Aldo-R work in the DCT?
Speeds up the Na/K ATPase pump which –>
- Increase K+ secretion
- Increase Na+ reabsorption
Where are Aldo-R located? Why?
Inside intercalated and principal cells
Aldo is a cholesterol derivative therefore can cross membranes freely
