A&P final Flashcards
Where in the kidney do we secrete the compounds that the body needs to get rid of like organic compound transporters?
in the PCT
Why does the PCT have a really high metabolic rate?
It needs energy to reabsorb and secrete everything that it does
Which part of the loop of Henle do we have 20% of our water that was originally filtered be reabsorbed?
Thin descending limb
By the time the water that was filtered at the glomerular capillaries makes it to the end of the thin descending limb of Henle, what percent of it is reabsorbed?
~85%
2/3 + 20% = ~85
the ascending limb of the loop of Henle is relatively ______ to water
impermeable
The regulation of exactly how much water we hold on to happens where in the kidney?
The collecting duct and distal tubule
The Thick Ascending Limb is where we reabsorb what? (vague)
lots of stuff, primarily ions
What percent of the ions or electrolytes that are filtered get reabsorbed in the Thick ascending limb?
25%
2/3 of the ions/electrolytes that are filtered get reabsorbed in the PCT + 25% get reabsorbed in thick ascending limb.
Which cells decide what happens to the rest of it?
principal cells in the last part of the tubule
Where are principal cells found?
late part of distal tubule and pretty much all of the collecting duct
Water regulation in the late part of the tubular system is dependent on
How much Vasopressin/ADH floating around
Vasopressin/ADH allows us to
fine tune the amount of water we are reabsorbing
Which two portions of the tubule have a high metabolic rate?
PCT and thick ascending limb
In the distal tubule, which transporter does the heavy lifting in regards to getting Ca++ reabsorbed from the tubular lumen?
Na+/Ca++ exchanger
The secondary pumps are the Ca++ ATPase pumps
The electrochemical gradient that the Na+/Ca++ pump depends on is formed from the
Na+/K+ pump
This keeps Na+ concentrations low in the cell and bc of that Na+ wants to come into the cell from the interstitium
One of the things we can do to make the Na+/Ca++ pump spin faster is to
block Na+ entry from the tubular fluid from entering the cell
How does sodium get into the distal tubule cell?
Though a simple Na+/Cl- pump on the luminal side of the cell, then it is pumped out by the Na+/K+ pump and then brought back into the cell via the Na+/Ca++ exchanger.
If we block the Na+/Cl- pump in the distal tubule with a ________ (drug) then
thiazide diuretic
Then it should speed up the cycling of the Na+/Ca++ exchanger which would increase the amount of Ca++ that gets reabsorbed.
What kidney drug is prescribed for osteoporosis and why?
thiazide diuretic
It speeds up the Na+/Ca++ exchanger which helps them reabsorb more Ca++
if you are on a thiazide diuretic, then which supplement do you have to be mindful of?
Ca++ supplements
Prevention of kidney stones can include ____(drug). why
thiazide diuretics.
Stones are made from crystalized Ca++.
This drug is not good for removing stones that are already formed but can be good for prevention
When you think of principal cells think of
Aldosterone
The more aldosterone we have the more ____ we reabsorb
Na+
Aldosterone is a
mineralocorticoid. It helps us manage and maintain our electrolyte balance
What makes aldosterone levels rise?
low blood pressure or low sodium
Having a lot of aldosterone has what effect on K+?
It decreases K+
works by:
aldosterone binding to intracellular aldosterone receptors which speeds up the Na+/K+ pump on the ISF side of the cell. Na+ goes into the ISF and K+ goes into the cell.
We have channels on the tubule side of the cell that is going to allow K+ out into the tubule and Na+ into the cell.
This means we have a bunch of Na+ moving towards the renal ISF (reabsorption) and a bunch of K+ moving towards the tubule (secretion)
Aldosterone (probably) increases the number of K+ channels and (definitely) increases the number of Na+ channels found on the tubule side of the cell. The more channels we have the more/faster the ion movement is going to be.
How does K+ get into the tubule from the tubular cells in the distal tubule?
Through a channel that stays open NOT A PUMP.
Despite this, this process is still called secretion because it is relying on the Na+/K+ pump
Lots of aldosterone = lots of K+ ______ in the distal tubule
secretion
What does the aldosterone do directly in the distal tubule?
- speeds up Na+/K+ pump
- Enhances the number of Na+ channels in the cell wall
- Likely also plays a role in how many open potassium channels we have in the tubule side of the wall as well. (not as well ironed out)
What are the two types of K+ channels that operate in the principal cells?
ROMK (renal outer medullary K+ Channel)
BK (Big K+ channels)
How do the ROMK and BK channels work?
If we don’t need to get rid of a lot of K+ then the channels are sequestered inside the cell, waiting to be needed.
If we need to pick up K+ secretion then the ROMK channels get put in the cell wall to be used as extra pathways for K+ to move out of the cell. This is aldosterone mediated
If we have really high K+ excretion the BK channels also open up. This is aldosterone mediated
Those are in the cell wall all the time, it’s just a matter of if they’re open or closed. If we don’t need them they’re closed and if we have a ton of K+ we need to secrete they open.
POTASSIUM maintenance think
PRINCIPAL cells
What is another name of the Na+ channel that is found on the tubule side of the tubular cell in the Distal tubule?
Epithelial Na+ channel
ENaC
What do Amiloride and Triamterene do?
Block the ENaC pump in the distal tubule which indirectly slows down the K+ secretion by slowing down the Na+/K+ pump. This might be useful if you wanted to hang on to K+.
aldosterone receptor antagonist example:
spironolactone
spironolactone
Blocks the aldosterone receptor in the distal tubule which slows down the Na+/K+ pump which slows down K+ secretion and Na+ reabsorption
What are the K+ sparing diuretics?
Amiloride
Triamterene
spironolactone
A loop diuretic slows down reabsorption where in the kidney?
Thich Ascending Limb in the loop of Henle
Thiazide diuretics work in what part of the kidney?
just upstream of principal cells
Osmotic diuretics reabsorb water in which part of the kidney?
the early parts of the tubule
Anything that reduces NaCl reabsorbed upstream of principal cells have what effect on water reabsorption?
indirectly decreases water reabsorption or increases water leaving the body
K+ wasting diuretic.
Anything that reduces NaCl reabsorption before the principal cells leads to what effect in the later part of the tubule?
Means more will be reabsorbed in the later parts where there are principal cells which would increase K+ secretion
K+ wasting diuretic
Smidt says if you are on a K+ wasting diuretic but you want to conserve K+ then
you might be put on a small dose of a K+ sparing diuretic too to increase volume excretion but limit K+ wasting.
what is the most commonly prescribed diuretic combination?
Triamterene with Hydrochlorothiazide
Where does aldosterone come from?
zona glomerulosa- the most outside part of the adrenal gland
Layers of the adrenal cortex outside to inside:
zona glomerulosa
zona fasciculata
zona reticularis
Medulla
What do the zona fasciculata and zone reticularis produce?
- most of our cortisol (helps us even things out when we are under stress)
and androgens including androstenedione (an anabolic steroid that converts to sex hormones)
a small amount of estrogen from the zona fasciculata specifically.
If you have a crazy on the tumor zona fasciculata you would produce a lot of
estrogen
Where do catecholamines(epi/norepi) come from?
The deep inner part of the adrenal cortex called the Adrenal Medulla.
What is the ratio of epi to norepi that is released at the adrenal gland?
4epi : 1norepi
aldosterone secretion is sensitive to
K+ levels.
High potassium= high aldosterone
Low potassium = low aldosterone
angiotensin II binding to at1 receptors at the zona glomerulosa
What is the enzyme that produces aldosterone? Where in the body is this found?
aldosterone synthase
Found in the zona glomerulosa
aldosterone, cortisol and estrogen are derivatives of
cholesterol
What is the difference in the shape of aldosterone, cortisol and estrogen?
1 chemical modification to differentiate them from each other.
However they all look very similar to cholesterol and each other
If you have a buttload of extra cortisol, sometimes it interacts with aldosterone receptors. Why?
It structurally looks very similar to aldosterone
If you have someone with an ACTH lung tumor what would you expect to see?
increases cortisol levels that overwhelm the 11 beta hydroxy steroid dehydrogenase type 2 enzyme. Cortisol looks like aldosterone= cortisol binding to aldosterone receptors= HTN & hypokalemia
why don’t people like steroids?
they drive up bp by increasing cortisol which interacts with aldosterone receptors
cortisol is a
glucocorticoid. It helps provide glucose to the brain to help us make good decisions when we are under stress
Can cortisol cross through the cell wall easily?
Yes, it is a steroid compound so it has no problem.
What does 11β- HSD type 2 stand for?
11 beta hydroxy steroid dehydrogenase type 2
What is the one natural inhibitor of 11 beta hydroxy steroid dehydrogenase type 2?
Natural Chinese licorice
Can you use licorice candy to inhibit 11 beta hydroxy steroid dehydrogenase type 2?
No, that’s fake.
Where are people exposed to real Chinese licorice?
Flavoring in tobacco compounds, like smokeless tobacco
what is one reason why people who smoke have HTN?
A flavoring compound in tobacco is made of Chinese licorice which is a natural inhibitor of 11β- HSD type 2
Where are Angiotensin 1 receptors found?
blood vessels
kidneys
adrenal cortex
PIcture slide 37
The effect of plasma K+ concentration on how much aldosterone we are going to have around, and how much K+ excretion we are going to have as aldosterone levels increase.
picture slide 27 the blue chart at the bottom left.
aldosterone influences ______ secretion
K+
The more K+ we secrete in the distal tubule the more we
excrete
What is a great controller of blood potassium in the body?
Aldosterone level from the adrenal cortex working with the kidneys.
If you have healthy kidneys and adrenal glands it is almost impossible to have
hyperkalemia
What are the two types of cells found in the Distal tubule?
principal cells=potassium
intercalated cells= acid/base
What role do intercalated cells play in acid base regulation?
They secrete protons/hydrogen or reabsorb protons and secrete bicarb
The cells that secrete protons in the distal tubule are called
Type A intercalated cells
manage acid
The cells that reabsorb protons and secrete bicarb are called
Type B intercalated cells
manage base
Generally, which cells do people think about when you mention intercalated cells, and why?
type A
acidosis is way more common than alkalosis so the type a intercalated cells are usually the cells working to get rid of protons/H+
What are the two ways Type A intercalated cells secrete protons/H+? Which pump is stronger?
Strongest: H+ ATPase pump- burns 1 ATP to pump H+ into the tubule. This can move a lot of H+ compared to the second pump.
Hydrogen potassium ATPase- Exchanges H+ into the tubule for K+ into the cell
How do the kidney’s manage pH?
By getting rid of acid through type A intercalated cells, mostly from the proton ATPase but some through the H+/K+ATPase exchanger
Both intercalated and principal cells are sensitive to
vasopressin/ADH
Where are intercalated and principal cells found?
At the end of the distal tubule called the Distal convoluted tubule and the collecting duct
Besides K+ and acid/base management, intercalated and principal cells do what?
Help manage water balance
What is the receptor called that Vasopressin/ADH binds to in the distal tubule?
V2 receptor
If you have an agent that can selectively activate V2 receptors, where in the body would you see an effect?
The kidney, specifically the late distal tubule and collecting ducts
Where are V1 receptors found?
Out in the periphery on blood vessels that produce lots of squeeze and vascular resistance
When Vasopressin/ADH binds to receptors in the DCT/collecting tubule, what happens?
- cAMP increases
- which activates PKA
- PKA phosphorylates aquaporin-2 vesicles where aquaporin channels are built and ready to go.
- Aquaporin-2 channels are then moved to the tubule side of the cell where they allow water entry on the tubular side of the cell
Which isoform of aquaporin channels are completely dependent on vasopressin/ADH?
AQP-2
Where are AQP-3 and AQP-4 found? Are they dependent on vasopressin/ADH?
The renal ISF side of the distal convoluted and collecting duct
They are not dependent on vasopressin/ADH, they are in the cell wall at all times
if you have a problem at the kidney and/or how it responds to vasopressin/ADH(like maybe something is wrong with the PKA gene), then what will be the result?
you are going to have a problem getting the AQP-2 channels to the cell wall on the tubular side where they can be used for water reabsorption. This is called nephrogenic DI
What is keeping us from having to go to the bathroom every 45 minutes?
A constituent level of vasopressin/ADH binding to V2 channels in the DCT and collecting duct that are increasing cAMP which are activating PKA which are moving AQP-2 channels to the tubular side of the cell wall to help us reabsorb water.
If you have a problem with the secretion of Vasopressin/ADH this disorder is called
Diabetes insipidus
What is an example of something that causes nephrogenic DI?
High Lithium doses.
If your pt. is on lithium they will have what kind of urine?
producing about 20L a day and drinking a ton to try and replace it.
Very dilute, about 50mOsm
What is the lower limit of renal osmolarity?
50mOsm
What is the diluting segment of the kidney? Why is it called that?
The thick ascending limb of the loop of Henle
We are reabsorbing a lot of electrolytes but not reabsorbing water
Why is it that you have to urinate a lot and frequently after drinking alcohol?
Alcohol takes your vasopressin/ADH system offline.
It reduces the amount of Vasopressin/ADH that is released from brain and impairs the kidney from being able to respond to the little ADH that was there
Water levels in the body are controlled via
vasopressin/ADH
If we need to get rid of water we drop our vasopressin/ADH levels
If we are in a desert and need to conserve water our vasopressin/ADH levels are going to be very high
If someone has a head injury and they start dumping a lot of urine, what do you suspect is the cause?
They have damaged their hypothalamus and are not releasing vasopressin/ADH anymore.
This would be a bad cause of Diabetes Insipidus
What are the sensors in the body that trigger Vasopressin/ADH release or no release?
- Primary: Osmolarity- salty blood triggers more release of Vasopressin/ADH to dilute out the blood
- Arterial bp- low arterial bp triggers more release of Vasopressin/ADH to help increase blood volume and therefore blood pressure.
- Blood volume- low blood volume triggers more release of Vasopressin/ADH to help increase blood volume
Where are our blood volume sensors?
Low pressure side of the circulation: large veins, atria of heart
Where are our blood pressure sensors?
Baroreceptors look at the high pressure side of the circulation
What are osmoreceptors? Where are they found?
specialized cells in the hypothalamus that sense changes in osmolarity
Osmoreceptor send information to
2 nuclei in the brain:
1. supraoptic nucleus (above the eye)
2. paraventricular nuclei (on the sides of the 3rd ventricle)
If we have a bad bacterial infection what does the hypothalamus do?
Increases body temp to try and kill the bacteria
If we have really salty blood the hypothalamus releases
vasopressin/ADH
What are collections of cell bodies in the CNS called?
Nuclei
How much vasopressin/ADH is released by the supraoptic nuclei?
5/6 or 83.33%
How much vasopressin/ADH is released by the paraventricular nuclei?
1/6 or 16.67%
Para means
to the side of
Which ventricle is the paraventricular nuclei situated next to?
3rd ventricle
How does vasopressin/ADH get into the bloodstream?
Produced in the hypothalamus
sent through “pathways” to the posterior pituitary gland aka neurohypophysis which is surrounded by a lot of blood vessels.
What is another name for the posterior lobe of the pituitary gland?
neurohypophysis
What is another name for the anterior lobe of the pituitary gland?
adenohypophysis
How does the body handle changes in osmolarity: think of the cell as an osmoreceptor and the solution as our blood.
- If you put a cell in a solution that the has same osmolarity(isotonic), what happens?
- If you put a cell in a hypertonic solution what happens?
- If you put a cell in a hypotonic solution what happens?
- The volume of the cell isn’t going to change
- Water is going to move into the cell until the osmolarity is equal to the solution. This slows the rate of action potentials that are being sent to the 2 vasopressin/ADH production areas which reduces Vasopressin/ADH in the pituitary gland and therefore reduces it in the body to get rid of water
- Water is going to leave the cell until the concentration is equal to the solution. Increase Vasopressin/ADH in the pituitary gland This increases the rate of action potentials that are being sent to the 2 vasopressin/ADH production areas which increases Vasopressin/ADH in the pituitary gland and therefore increases it in the body to retain water
Explain the effect of vasopressin/ADH
picture
Vasopressin/ADH produces a wide variation of osmolarity of urine
In the proximal tubule we are reabsorbing 2/3 of EVERYTHING- not picky on electrolytes besides making sure to keep most of the amino acids and glucose, and it is really porous to water. So here the osmolarity of the urine should be isotonic with the blood
In the loop of Henle-deep parts are concentrated with urea and electrolytes so as the blood moves deeper into the kidney and water leaves the tubule, the solutes left behind in the urine are concentrated. When the tubule is permeable to water(descending limb), the urine will have the same osmolarity as the environment in the ISF of the kidney, as the urine moves into the ascending limb and early part of the distal tubule the renal ISF becomes more dilute and we are now impermeable to water but permeable to NaCl. Therefore NaCl leaves the urine and is reabsorbed into the ISF making the urine more dilute. this is the diluting segment
Late part of distal tubule: completely dependent on ADH.
Lots of ADH= lots of water is reabsorbed so very concentrated urine. 1200mOsm
Really low levels of ADH: the urine is already dilute from the diluting segment. If we are reabsorbing electrolytes still but not reabsorbing any water d/t no ADH moving APQ-2 channels to the cell wall then the urine is very dilute. 50mOsm
What role does Vasopressin/ADH play in the loop of Henle?
It plays a role in how much urea we reabsorb from the tubular fluid.
Urea is small and freely filterable at the glomerular capillaries.
As it moves down the PCT some urea is reabsorbed d/t it being dragged out of the tubule with water.
Half is left in the tubule about midway down the thin descending limb
This half follows the path of the tubule until the collecting duct.
If there is a lot of vasopressin/ADH the collecting duct it has a lots of AQP channels and urea transporters in the cell wall that help us to reabsorb urea. If we reabsorb urea and water then we increase blood volume and are left with concentrated urine.
What is one of the major components of the renal interstitium?
Urea. This is what makes the renal ISF as concentrated as it is
-also has-
proteins
electrolytes
What are the urea transporter isoforms that get placed in the cell wall d/t an increase in ADH
UT-A1
UT-A3
“urea transporter”
If we are in a state of antidiuresis what kind of transporters will we have in the collecting duct?
We would need to hanging on to as much electrolytes and water as possible so lots of UT-A3, UT-A1 and AQP-2
What is the primary controller of
blood plasma osmolarity?
vasopressin/ADH
What is the only signaling compound able to influence water reabsorption without simultaneously influencing salt reabsorption?
vasopressin/ADH
picture slide 44
It doesn’t matter if we have a low sodium intake (30mEq/day) to high sodium intake(180mEq/day), it doesn’t mess with osmolarity that much if you have normal Vasopressin/ADH present.
Why does caffeine make you urinate?
It decreases vasopressin/ADH release
If you remove vasopressin/ADH and have a wide variety of salt intake 30mEq/day-180mEq/day, what would you expect your blood osmolarity to look like?
Picture slide 44
It would have a huge range from ~137mEq/L-151mEq/L
What are the thirst controllers related to decreased thirst?
Decreased plasma osmolarity
(overhydrated, Na+ levels drop)
Increase in blood volume (sensed from atria)
Increased BP (sensed from high pressure baroreceptors)
Decreased in angiotensin II
Gastric distention (full belly)
What are the thirst controllers related to increased thirst?
Increased plasma osmolarity (dehydrated, Na+ levels are high)
Low blood volume or low blood pressure (sensed from high and low pressure sensors)
Increase in angiotensin II
Dryness in the mouth or lips
What are the vasopressin/ADH controllers related to decreased vasopressin/ADH?
Decreased plasma osmolarity
Increased blood volume
Increased blood pressure
drugs:
Alcohol
Clonidine
Haloperidol (common)
What are the vasopressin/ADH controllers related to increased vasopressin/ADH?
Increase blood osmolarity
Decreased blood volume
Increased blood pressure
Nausea(losing fluid or anticipating losing fluids)
drugs:
Morphine
Nicotine
picture slide 47
When we have changes in potassium intake, as long as we have a functional aldosterone system the body regulates potassium very well.
However, when you block the aldosterone system you can have a wide range of K+ levels.
What meds block the aldosterone system?
Spironolactone
Triamterene
picture slide 56
The subject drinks 1 liter of distilled water.
It takes a bit to absorb but when it does, it produces a small reduction in blood osmolarity that is going to decrease vasopressin/ADH levels.
This makes urinary flow rate go way up. It should be 1mL/min but in this scenario, 30 mins later, urine production rate increases as a function of getting rid of the excess water. It doesn’t really do anything with the body’s electrolytes (there might be a small increase in excretion as a function of water pulling a few electrolytes out with it but the majority of what is lost is just water). The flow rate stays high until balance is restored .
Though we only see a small change in the blood osmolarity, we would see massive amount of change in the urine osmolarity as it becomes very dilute to get rid of the excess water.
What is the only scenario Smidt can think of that makes the body have a hard time regulating K+ levels?
renal failure
How long does it take for the healthy body to get rid of 1 liter of distilled water we drank?
a couple of hours.
urine osmolarity under ideal conditions
600mOsml
what percent of water and electrolytes that get filtered get reabsorbed in the PCT?
65%
The last 15% of water that is left after it goes through the thin descending limb must be dealt with where in the kidney?
Distal tubule and collecting duct
The thick ascending limb reabsorbs what percent of the electrolytes that were filtered?
25%
As water reabsorption decreases, what happens to urine osmolarity?
urine osmolarity drops
The body tends to have more cortisol in the principal cells than aldosterone receptors in normal circumstance, much less when we are stressed and secreting extra cortisol. How does the body regulate cortisol interacting with aldosterone receptors and not have really high bp all the time?
Inside of the principal cell is an enzyme called 11β- HSD type 2 that floats around and degrades/destroys cortisol within the cell.
