A&P final Flashcards
What percent of PAH is removed from the blood as it passes through the kidneys?
90%
Despite the fact that angiotensin II would constrict the afferent arteriole by itself, the afferent arteriole will actually relax d/t
the effect of Nitric oxide mediated relaxation being the stronger force
If you vasodilate both the efferent and afferent arteriole you would expect ______ blood flow and ________ filtration
increased blood flow
decreased pressure d/t efferent constriction and increased pressure d/t afferent constriction could lead to possibly no difference in filtration.
Angiotensin II type 1 receptors are found in the _______ and respond to____.
What is the result of this?
in the PCT
angiotensin II
increases the rate of the Na+/K+ pump which therefore increases other pumps that rely on it.
Na+/K+ pump primarily speeds up which pump in the PCT?
secondarily speeds up?
Na+ Hydrogen Exchanger
The reabsorption process for bicarb via the Na+/HCO3- pump. This is done because of the Na+/H+ (Na+ Hydrogen) pumping out Hydrogen and making the cell more negative. This should push HCO3- out of the cell.
slide 14 pic
What kind of transporter is the Na+/HCO3- pumps?
Symporter
secondary active transporter
What is the primary driver for the Na+/HCO3- pump?
HCO3-
Some texts say that the Angiotensin II type 1 receptors directly effects which pumps?
the Na+/K+ pump (has a lot of science to back this)
the Na+/HCO3- pump (Smidt says this is possible but not as much science to prove it so probably relies more on the Na+/H+ pump)
How does the Na+/K+ pump effect the Na+/HCO3-pump?
if affects the Na+/H+ pump
proton leaving makes HCO3-want to leave
Pathway between the cells are called______. In the PCT these spaces are wide or narrow?
What is it called when something is reabsorbed through this route?
tight junction
Wide
Paracellular reabsorption
What is transcellular reabsorption?
When a substance moves through a transporter or channel in the cell wall
Through which pathway does a lot of substances get “dragged”?
paracellular route
d/t a massive amount of fluid flowing between cells
What is the most common ion that gets “dragged” through the cells via paracellular reabsorption in the PCT?
Why is this?
Cl-
Because there is a lot of movement of Na+ and where a positively charged Na+ goes, Cl- likes to follow
What is the transcellular route for water called?
aquaporin
The places in the kidney that are impermeable to water have what kind of tight junctions? Are there aquaporins in these areas?
very tight junctions
They probably don’t have aquaporins in them either
what is bulk flow?
reabsorption d/t the pushing and pulling forces that are in the capillaries and ISF.
10mmHg in the peritubular capillaries
Are there water pumps in the body?
No! The only pump we don’t have. Water moves via osmosis
what is urea?
A waste product that the body uses to help create a concentrated renal ISF so that we reabsorb water via osmosis
If we are in the desert for a couple of days, what is our urine going to look like and why?
Very concentrated! The body creates more urea to increase reabsorption of water so that the body is conserving water.
The transcellular path is driven by what kind of diffusion?
active diffusion
Passive diffusion is driven by what kind of diffusion?
passive diffusion
What is the purpose of the brush boarder on the lumanal side of the tubule and where is it really prevalent at?
Increase surface area by 20X to put more transporters on the cell wall.
PCT
The cells in the kidney has a resting membrane potential of_____.
This helps us to pull in which ion?
-70mV
Na+
Na+ is pulled into the cells in the kidney via what kind of gradient?
electrochemical gradient
part of the driving force for our secondary active transporters.
The tubular lumen has a charge associated with it as a product of
whatever ions are left over in the tubule (Na+, K+, Cl-)
If there is a lot of Cl- then the charge will be negative.
What is the charge of the proximal tubule lumen?
-3mV
probably d/t Cl-
Why doesn’t Na build up?
water is reabsorbed at about the same clip
Chlorides reabsorption along the length of the proximal tubule increases d/t what?
Slide 5
Which part of the PCT does most of the Cl- reabsorption happen?
The concentration of Cl- building up in the PCT
plus
CL- following Na+’s positive charge
The second part of the PCT
Are proteins like albumin and growth hormone unfilterable?
NO, they do get filtered, just at very very small rates.
Who’s job is it to filter the proteins that get filtered?
The cells that line the proximal tubule
_______ of protein are filtered each day in a healthy person with a normal kidney
1.8g
The PCT reabsorbs _______ of protein that gets filtered each day in a healthy person with a normal kidney
1.7g
__________ of protein is found in the normal urine per day
0.1g or 100mg
How do the cells of the PCT deal with the small amount of proteins that gets filtered each day?
endocytosis or pinocytosis
In the PCT cells, endocytosis happens by something(i.e. a protein) binding to the brush border. The cell builds a wall around it (swallowing it up) and then breaks it down into the component parts (amino acids) and reabsorbs these with the other amino acids that are already being reabsorbed.
If something spills proteins (sepsis) in the proximal tubule what happens?
it overwhelms the endocytosis/pinocytosis so we lose a lot of proteins in the urine.
endocytosis/pinocytosis is only found in the
PCT
So if they make their way past the PCT then they have to be flushed out or they get stuck there which can cause problems
What is a really small string of amino acids called? how many amino acids is this?
peptide
10-20
Why don’t we filter a lot of albumin?
It would have to be destroyed into amino acids to be reabsorbed which would be pointless
acid base regulation at the PCT is done by what?
Carbonic anhydrase which is linked to the Na/H exchanger
The Na/H exchanger is a form of
secretion. It actively pumps H into the tubule.
For every 1 proton that leaves the pct cell via the NHE pump _____ Na+ gets put ______ the cell
1
into the cell
what is the primary way that Na+ is reabsorbed in the PCT?
NHE pump
1 Na+ : 1 H+
Go through the carbonic anhydrase pathway in the PCT
NHE pumps 1 Na+ into the cell and 1H+ out into the renal tubule
H+ is paired with HCO3- and forms H2CO3
Carbonic anhydrase does an anhydrase process to break down H2CO3 into CO2 and H2O. Neither of these has any trouble being reabsorbed into the cell. H2O can be reabsorbed via “water pathways” and CO2 diffuses across the cell membrane into the cell.
(OR it can break it down in the other direction into H+ and HCO3-, but typically goes the other way)
Now in the cell: CO2 combines with H2O with the help of carbonic anhydrase. The carbonic acid that is formed can then be split again into bicarb and hydrogen.
This bicarb can drive the HCO3-Na pump.
The H+ can be secreted back into the tubule and be reused.
If there is no bicarb in the tubule when H gets secreted then it either is excreted by itself in the urine or in ammonia-> ammonium. This helps buffer our urine so it isn’t so painful.
Where is Carbonic Anhydrase found in the PCT?
tethered to the wall
wedged in the cell wall
inside of the cell
Carbonic anhydrase inhibitor uses and side effects
Used as a diuretic
Makes us have a problem reabsorbing HCO3- which leads to acidosis
How is bicarb balanced in the PCT?
By the carbonic anhydrase pathway and the production of new bicarb by glutamine. Glutamine is produced in the liver and is converted by the PCT cells into 2 bicarbs and 2 ammonium (NH4+)
What is one reason why people in liver failure can’t regulate acid/base well?
can’t produce enough glutamine to be turned into bicarb and ammonium.
Supplementing can be useful.
Acid/base processes in the rest of the tubular system follows what?
The PCT process. While it can occur in other parts of the tubule it happens the most in the PCT. He doesn’t care about the other places.
Important urinary buffers:
ammonium
phosphate(higher inside the cell than ECF) but the ECF phosphate is important in the urine
NaH2PO4
sodium phosphate
Where is Ca++ reabsorbed in the kidney?
Ca++ is reabsorbed through many places in the kidney, not just the PCT, and is done so through both the paracellular and transcellular routes as well as through Ca++ channels
a lot of the Ca++ that we reabsorb is d/t
the rest is
It being dragged between/through the cells with water. If water reabsorption increases typically so does Ca++ reabsorption
Why is it so easy for Ca++ to be dragged into the cells with water and through Ca++ channels?
The inside of the cell is negatively charged and there is a high concentration gradient for Ca++ to come into the cell.
Electrochemical gradient
What are the ways that Ca++ is removed into the renal interstitium?
Ca++ ATPase pump
3Na in /1Ca++ out exchanger
What gets filtered by the kidneys is partially affected by
acid base status
How might a Ca++ avoid being filtered?
It might be hanging around albumin and/or other things that have a negative charge. If the Ca++ isn’t freely floating around in the blood then it can’t be filtered
What is the PTH glands?
Little nodules on the sides of the thyroid glands that monitors the Ca++ levels in the ECF which mirrors the levels in the blood.
When the PTH thinks Ca++ is low it:
- Encourages Vit. D3 activation -increases the amount of Ca++ we are able to reabsorb from the diet
- Increases Ca++ reabsorption. Occurs through increased number of Ca++ channels
- Stimulates bone breakdown (osteoclasts do this)which liberates Ca++ and phosphate
- Decreased activity of osteoblasts
Bone is a hardened ______
calcium salt
bones are our_______ long term storage place in the body
calcium
If you are chronically hypocalcic you would have_______. Why?
porous bones- osteoporosis
Because the PTH is pulling the Ca++ from the bones to raise blood levels
What is a short term Ca++ storage space?
SR
How do osteoblasts build bone?
Putting phosphate and Ca++ together.
If we have high ca++ levels in the blood then PTH levels should be _____, osteoclasts should be _____ and osteoblasts should be ______
PTH should be low
osteoclasts should be low
osteoblasts should be high
the increased Ca++ is used to rebuild bone
handling of organic compounds in the PCT is done by:
Organic Anion and Cation Transporters (OATs and OCTs)
Endogenous organic Cations:
ACh
choline
creatinine
dopamine
epinephrine
histamine
serotonin
norepinephrine
Endogenous organic Anions:
bile salts
hippurates
urate
prostaglandins
oxalate
Fatty acids
Exogenous organic anions:
PCN
furosemide
salicylates (ASA)
sulfonamides
acetazolamide
chlorothiazide
endogenous organic Cations:
isoproterenol
atropine
morphine
procaine
quinine
tetraethylammonium
How do PCT cells get rid of organic cations?
proton dependent antiporter systems. Proton moves one way and organic cation moves other way.
How are organic cations removed from the body?
- Cation has to get into the PCT cell- came from the renal interstitium d/t it leaking out of the peritubular capillaries. The PCT cell sees it and pulls it into the cell.
- It is then removed on the other side into the tubule via the Proton/Cation antiporter. 1 H+ goes in and “some” cation goes into the cell
How are organic anions removed from the body?
- αKG (compound floating around) is brought into the cell with 3 Na+. This concentrates the αKG inside the cell
- αKG is exchanged back out of the cell for some amount of organic anion
- Now that the organic anion is inside the cell an unnamed facilitated transporter transports it into the tubule
The first person to take PCN was in the year
1942
How were the cation and anion removal systems discovered?
WWII
When crazy things happen in the world, priorities change. In WWII the focus was on how to keep injured military folks alive.
PCN was a new thing. (Discovered 2 decades before WWII)
Someone noticed that there was some bacteria in a petri dish and that when this mold/fungus was there too, staph couldn’t grow. Not sure why there was fungus in the petri dish, perhaps bad hygiene in the lab?
what were the methods of production of PCN back then?
grow a bunch of mold
kill the mold
find the PCN
select it
concentrate it into a drug people can take
Blood levels of PCN would drop faster than what they wanted to which was a problem bc there wasn’t a lot of PCN. Only other “abx” like thing was like salt. What did this problem lead to discovering?
If they gave a synthetic Hippurate with the PCN, the PCN would stick around longer bc they use the same transporters. The Hippurates competitively inhibit the transporters that normally remove PCN.
If you overwhelm the transporters with Hippurates the body will remove the one thing in highest concentration, so Hippurates, leaving the PCN in the body
If you don’t know how much of something is reabsorbed in the PCT, can’t remember the kinetics or whatever, odd are that the answer is
2/3 !
Pretty much 2/3 of everything gets reabsorbed in the PCT
The deeper you go in the tubule the more _____ the renal ISF is
concentrated
Why is water reabsorbed as you go farther into descending thin limb of the loop of Henle?
It’s more concentrated in the renal ISF. Concentration gradient pulls water out into the ISF.
How much water is reabsorbed in the PCT?
Where is majority of the water that is left over going to be reabsorbed?
2/3
Simple water reabsorption in the descending thin limb of the Loop of Henle takes care of most of the rest of it. There is not a lot of ion transporters here so most of the movement is just water.
where is majority of filtered water going ot be reabsorbed?
early part of the tubule.
PCT and thin descending limb in the Loop of Henle
The Thin Ascending Limb is relatively ______ to water
impermeable
Why water is pretty much impermeable in the Thick ascending limb?
There is a NaCl transporter here that reabsorbs NaCl from the tubule fluid as it passes through the Thin Ascending Limb.
It uses ATP.
Does in relatively small amounts. Not a ton of salt reabsorbed this way but there is some.
what is permeable in the Thick Ascending Limb of Henle
Still relatively impermeable to water however there is lots of space for ions to be reabsorbed.
It is am important place for cation electrolytes to be reabsorbed from tubule
Cation electrolytes being reabsorbed in the thick ascending limb is driven by
K+ leaking back into the tubular fluid making the charge on the inside of the tubule positive 8mV This is the force that pushed the divalent cations Mg++ and Ca++ to be reabsorbed through the paracellular route. Some Na+ and K+ also get pushed into the cell.
What is the charge in the tubular fluid at the thick ascending limb?
8mV
What pumps/exchanger are found in the thick ascending limb of the Loop of Henle?
Na+/K+
Na+/H+ exchanger Means acid base is partially controlled here
NKCC2 (1Na+, 1K+, 2Cl-) from tubule into the Thick Ascending Limb
Which drugs work on the NKCC2 pump?
Loop: furosemide. Most powerful diuretic class
A lot of the reabsorption that happens in the thick ascending limb of the loop of Henle (NKCC2 pump) is responsible for
concentrating stuff in the renal interstitium
Some of it settles at the bottom which is why it is more concentrated as you go deeper in the nephron.
What is the most powerful diuretic class and why?
furosemide.
d/t renal interstitium becoming less concentrated as a result of those ions not being reabsorbed from the tubule. We lose the ability to reabsorb water when we take away that concentration gradient which means more water in the urine.
slide 29 This is a picture of the kidney doing what?
What kind of urine would you expect?
Kidney preserving water;
osmolarity of 1200 is about as concentrated as a renal interstitium can be d/t stuff reabsorbed at the thick ascending limb as well as urea.
If we have water permeability at the deep part of the collecting duct then we should have a really concentrated urine (about 1200).
This reflects someone trying to conserve water
Water reabsorption takes place/ can take place in the
collecting duct d/t ADH
What is the limitation of how much we can concentrate our urine?
The concentration of the renal interstitium
Lizard in the desert without much water can survive because
their kidneys can make their interstitium more concentrated than we can.
Osmolarity of 3,000
If renal ISF is 600 urine has an osmolarity of
600
If we were trying to get rid of water using a loop diuretic and we drop the renal ISF osmolality to 300 then the urine concentration would be
300
Distal tubule is another place where PTH can influence what?
Ca++ reabsorption by PTH increasing the number of Ca++ channels on the luminar side of the cell
Which pumps are usually found together?
Ca++ ATPase pump and the Na+/Ca++ exchanger
The Distal tubule is another place where we have simple reabsorption of _______
1Na+ for 1 Cl-
which drug class works on the distal tubule and how does it work?
Thiazides block the simple NaCl pump
Distal tubule is sensitive to which hormones?
ADH and aldosterone
aldosterone sensitive cells are called
principal cells
principal and intercalated cells are sensitive to ______
ADH
principal cells work via
aldosterone receptors found inside the cell speed up K+ secretion into the tubule while at the same time
increasing the amount of Na+ that is reabsorbed
aldosterone is a derivative of what? what does this tell us about their receptors?
cholesterol derivative
It explains why their receptors are found within the cell, because cholesterol shouldn’t have any problem getting into the cell.
What is similar to angiotensin II in how it works and how?
Aldosterone receptors
They speed up the Na/K+ pump and influence the number of channels that are in the tubular side of the cell
What is taken into account in the renal plasma flow formula that makes it different from the effective renal plasma flow formula that we need to know?
The difference in the arterial and venous concentrations of PAH
How does the PCT get rid of organic anions?
Na+ dependent process
