FINAL EXAM - Lecture 6 Flashcards
Most drugs we will use, will affect which arteriole?
Afferent arteriole
ANG II binds to what receptors and where?
AT1 in the proximal tubule
What happens once the ANG II binds to AT1?
Increases Na/K ATPase pump, increases sodium being removed from the cell into the interstitium.
This lowers sodium inside cell, which will increase sodium absorption from tubular lumen via the NHE pump (NA and H exchanger)
Reabsorption into interstitium for HCO3- is also increased via Na+/HCO3- co-transporter
What is the main pump/channel affected in proximal tubule by ANG II binding?
NHE pump (1Na+ for 1 H+)
Which pump does ANG II directly affect?
Increased activity of Na+/K+ ATPase pump
Some literature will say it also increases NHE, but not sure thats the case.
Routes for ions to go in the proximal tubule?
Transcellular and paracellular
Transcellular
Going through a transporter or channel through cell wall
Paracellular
Ions going in between cells. Some parts of kidney, it is really tight and not much can fit. Other parts, it’s more open.
BBB is extremely tight.*
Most popular ions that get dragged through paracellular route at proximal tubule
Cl-. It’s due to Na+ being a very common secondary active transporter (Transcellular), and Cl- wants to follow the Na+, so it follows through the paracellular route
Parts with really really tight junctions? (less paracellular route)
Parts where water is impermeable (ascending parts)
Bulk flow
Tons of reabsorption happening in the peritubular capillaries from proximal tubule
How does water get reabsorbed in proximal tubule to peritubular capillaries?
Has to follow other “stuff”. The more concentrated renal interstitium, the more water it can absorb.
Role of urea in renal interstitium
Helps us reabsorb water in proximal tubule
If we are super dehydrated, the odds are that our renal interstitium will have a ____ amount of ____
High;water.
To promote reabsorption
Feature of cells on luminal side of proximal tubular cells
Border will be brush like, increases surface area by 20x. Gives us lots of area for transporters.
Membrane potentials for tubular epithelial cells
-70mV
What’s the gradient cells generally use to get inside tubular epithelial cells?
Electrochemical
Proximal Tubular lumen “charge” and what causes itr
Around -3mV, due to solutes such as K+, Cl-, and Na+. Typically lots of chloride, thats why it’s negative.
Concentration of Na+ as it moves through tubule
Stays the same, follows water reabsorption.
What is chlorides concentration throughout the tubule?
Slightly becomes more concentrated as it goes, typically needs a higher concentration to be absorbed. So it has to wait until it becomes more concentrated, to be reabsorbed. Not much reabsorption in first half, mostly in second half.
How much protein is filtered each day in grams?
1.8g
How much protein gets reabsorbed?
1.7g
How much protein gets excreted a day?
100mg
How does protein get reabsorbed?
Endocytosis (or Pinocytosis). The tubular cell will grab it (remember, brush border) and pull it apart into amino acids, and allow it to reabsorb with other amino acids.
What is pinocytosis?
Pulling something inside the cell (endocytosis) and pulling it apart
If we have extra protein that get filtered, how do they reabsorb them?
They dont. You just lose proteins. This contributes to lost blood proteins and why septic patients will become hypovolemic from losing intracellular volume.
Where does the pinocytic process occur?
Only in proximal tubule
Proteins that are more often found getting filtered
Growth hormone, microproteins (peptides, string of amino acids). Albumin is much more rare because of how big it is.
How do protons get into proximal tubule?
Secretion via the NHE.
The single most pathway for reabsorption of Na+ in proximal tubule is
NHE
After the proton is dumped into tubular lumen, what happens to it?
It combines with bicarbonate in the tubule to form H2CO3/Carbonic Acid.
What happens once carbonic acid is formed in tubule?
Dissolved into CO2 and H2O.
What happens once carbonic acid is dissolved into CO2 and H2O?
H2O easily gets reabsorbed into tubular cells through osmotic pathways, and CO2 is a gas so it diffuses across
What does Carbonic Anhydrase in proximal tubule?
Speeds up the process of breaking apart Carbonic acid into CO2 and H2O.
How does HCO3- get into tubular lumen?
Filtered
Where is Carbonic anhydrase specifically in tubular lumen?
Tethered/wedged into cell wall
Once there is H2O and CO2 in tubular cell, what happens?
Carbonic anhydrase will catalyze them back into carbonic acid.
Once carbonic acid is formed inside tubular cell, what happens? Where does each compound end up?
It dissociates into H+ and HCO3-, which will allow HCO3- to be reabsorbed, and allows the proton to go back out into tubular lumen.
If there is excess H+ in tubular lumen with no bicarbonate and it cant form carbonic acid, what happens?
It will be secreted, or it will combine to ammonia to form ammonium (NH4+). Free protons are painful to excrete, it would burn.
If we were to inhibit carbonic anhydrase, what would happen?
The NHE wouldn’t cycle as fast (less carbonic dissociation in tubular cell), and we would also have a problem with reabsorbing bicarb and excrete it (less carbonic acid dissociation in lumen), causing acidosis.
Original use for Carbonic anhydrase inhibitors?
Weak dirutic, since it would slow down the reabsorption of Na+. Less reabsorption of sodium, less reabsorption of water.
How is bicarb able to be balanced in the tubular cells?
Production of bicarb, through glutamine.
Where is glutamine produced?
In the liver
What happens to glutamine in the kidney, and where?
MOSTLY In the proximal tubular cells, glutamine is split into 2HCO3-, and 2NH4+.
How does the ammonium made from glutamine breakdown leave the proximal tubular cells?
NH4+/Na+ exchanger
If you have a liver failure pt, they produce less ____ and it causes _____
Glutamine, and it causes acid/base issues since it makes 2HCO3- and 2NH4+
Another buffer of protons in the tubular lumen other than Ammonium?
NaHPO4 binds H+ to form NaH2PO4
How does calcium get reabsorbed?
Both paracellular and Transcellular.
How does calcium reabsorb when it’s paracellularly?
Just dragged along with water and other ions.
How does calcium get reabsorbed Transcellularly?
Electrochemically because tubular cells are negatively charged and have a low amount of calcium. It’s just a channel, no other ions or ATP involved.
How does calcium exit the proximal tubular cells and get into renal interstitial fluid?
Ca++ ATPase pump and 3Na+/Ca++ exchanger.
What dictates how much calcium is filtered?
Depends on your acid base balance. Remember, calcium binds to albumin, so if there’s more H+ binding to albumin, then there will be more free floating Ca++, and more will get filtered.
What controls calcium levels?
Parathyroid gland (on side of thyroid gland)
How does parathyroid gland know when to increase calcium?
Monitors calcium levels in extracellular fluid, and it should mirror Ca++ levels in blood.
How does parathyroid gland increase calcium?
When it think its low, it will increase secretion of parathyroid hormone, which will increase Vitamin D3 activation by picking up more calcium from dietary intake, and it increases calcium reabsorption in the intestines. PTH also increases renal Ca++ reabsorption, by increasing amount of Ca++ Transcellular channels.
Lastly, PTH stimulates bone breakdown.
What breaks down bones?
Osteoclasts
What are the ions that form bones?
Phosphate and calcium fused together tightly.
What do osteoclasts do?
Liberates calcium from the bones, which in the process will liberate phosphate.
Bones are the storage place for calcium in the body.
What is a result of chronic hypocalcemia?
Osteoporosis, since your body is using your bones as a source of calcium.
What does increased PTH cause a decreased amount of? And what do those things do?
Osteoblasts. They build bones or increase bone density by taking calcium and phosphate and fusing them together.
Therefore, PTH breaks bones down AND decreases bone building.
If we have high levels of calcium in our blood, what is the result of osteoclasts and osteoblasts?
Decreased osteoclasts, and increased osteoblasts.
There are 2 categories of organic compounds, which are ______ and how are they removed from the blood?
Organic cations and organic anions; via secretion
Both organic cations and anions have 2 subcategories, which are
Endogenous and exogenous
What are organic anions dependent on for secretion transport?
Na+
What are organic cations dependent on for secretion transport?
H+
How did cation get into renal interstitium before it gets secreted to lumen?
Leaked out of peritubular capillaries, because they are porous.
How does cation get from renal interstitium to lumen?
Proton cation antiporter (1 H+ for 1 cation)
How does anion get into renal interstitium?
Involves an intermediary alpha-ketoglutarator which is a compound that floats around in plasma.
aKG enters tubular cell from plasma via 3Na+ with 1 aKG, which drives up intracellular concentration of aKG, and then aKG is exchanged back into the plasma with 1 anion into the tubular cell.
How does organic anion get into lumen from interstitium?
Facilitated transporter.
How were organic secretion systems discovered?
During WW2, penicillin was a relatively new thing (2 decades old, someone discovered mold in petri dash, and the fungus mold produced penicillin and was killing bacteria in petri dishes).
They discovered penicillin blood levels were dropping fast, and since it was difficult to produce, this was bad.
They then discovered if they administered it with hippurates, they were using the same transport process for secretion. So, they used hippurates as a competitive inhibitor, to keep penicillins from being cleared so quickly.
As a rule of thumb, how much “stuff” is reabsorbed at the proximal tubule?
2/3rds.
The deeper/lower you go in the thin descending loop of henle, the more ________ the interstitium is. And what primarily occurs here?
Concentrated. Water absorption occurs here, not much ion reabsorption.
How much water is reabsorbed in the proximal tubule, and how much in thin descending limb?
66%; most of the rest, and then the distal tubule fine tunes the remaining amount of water reabsorption.
The more superficial you are in the nephron, the less ______ the renal interstitium is.
Concentrated
What is reabsorped in thin ascending loop of henle?
Na and Cl are reabsorbed, driven by ATP. It does it in relatively small amounts. Water is not very permeable here.
Thick ascending loop of henle as a large ______
Paracellular space for lots of cationic reabsorption. Na, K, Mg, Ca
Charge of tubular lumen in thick ascending loop of henle?
+8mV
What forces the Na, K, Mg and Ca to be reabsorbed through the paracellular route in the TAL?
K+ leaking out of the tubular cells into the tubular lumen, creating a positive charge in the lumen. This especially forces the divalent ions, Ca and Mg, since the lumen is positive now.
What exchanger was in the proximal tubule cell wall, and is also in the TAL cell wall?
NHE
What special pump is in the TAL cell wall from the tubular lumen to the tubular cell?
Big pump that moves 4 ions, 1 Na+, 1 K+, and 2 Cl- into the cell.
A portion of the K+ that gets pumped in, is leaked back out into the lumen.
What is most responsible for all of the stuff in renal interstitium in TAL?
The Na/K/2Cl pump
How do loop diuretics work and which drugs are they?
It blocks the big pump, which will dilute the renal interstitium, which results in loss of ability to reabsorb water via osmosis.
Furosemide, Ethacrynic acid, bumetanide
Renal interstitium is always more concentrated in the
Deep/lower parts
Max concentration of renal interstitium?
1200
What is the max concentration osmolarity of urine?
- The renal interstitium at end of tubule is reflective of the osmolarity of urine
Water permeability in the distal tubule is dictated by
ADH
Lizards in the desert are able to survive longer because
Their kidneys interstitium has a way higher max osmolarity of 3000, so it can reabsorb much water and excrete less.
If the renal interstitium osmolarity is 600 at the bottom of the loop of henle, what’s the max urine osmolarity it can be before it’s excreted into the ureters?
600
The higher the renal interstitium osmolarity, the more
Water reabsorption
Most of our calcium is being reabsorbed at
Proximal tubule
Where else can calcium be reabsorbed, and how?
PTH stimulation, increases luminar calcium channels.
How is calcium reabsorbed into the interstitium in the distal tubule?
Na+/Ca++ exchanger, and also a Ca++ ATPase
what else, other than calcium, is reabsorbed from lumen in distal tubule?
NaCl
What do thiazides do?
Inhibit NaCl pump in distal tubule
The distal tubule is also sensitive to ___ and _____.
ADH and Aldo
Aldo sensitive cells are called
Principal cells
Principal cells and intercalated cells are also sensitive to
ADH
How do principal cells work?
They have aldosterone receptors INSIDE the cell
Aldosterone is what kind of derivative?
Cholesterol
Aldosterone has no kind of problem getting inside of the cell wall, thats why its receptors are inside, because its a
Cholesterol
What happens when aldosterone binds to its receptor inside the cell in the distal tubule cell wall?
They speed up K+ secretion into tubule, and, increases sodium reabsorption from the tubule.
