AP 20 Nov 24’ Lecture 32 Flashcards
What percentage of filtered water and electrolytes is reabsorbed in the proximal tubule?
65%
The proximal tubule also has a high metabolic rate due to extensive reabsorption.
What is the role of the thin descending limb of the loop of Henle?
Reabsorbs 20% of the initially filtered water
This brings the total water reabsorption to 85%.
What percentage of electrolytes is reabsorbed in the thick ascending limb of the loop of Henle?
25%
The thick ascending limb is relatively impermeable to water but has many channels for ion absorbption. Approximately 2/3 of ions are absorbed in the PCT
Which cells in the distal tubule and collecting duct play a crucial role in electrolyte reabsorption?
Principal cells
These cells determine the final amount of electrolytes reabsorbed or secreted.
How does ADH influence water reabsorption?
Fine-tunes the amount of water reabsorbed
Higher ADH levels lead to increased water reabsorption.
Only signaling compound that’s capable of influencing water reabsorption without simultaneously influencing some type of salt reabsorption.
ADH
What mechanism facilitates calcium reabsorption in the distal tubule?
Sodium-calcium exchanger (NCX). Considered a heavy lifter by Dr. Schmidt regarding the amount of calcium it can put into the renal interstitium.
Calcium ATPase pumps also assist but are secondary.
What is the effect of thiazide diuretics on calcium reabsorption?
Increases calcium reabsorption
* Thiazide diuretics are used to treat osteoporosis and prevent kidney stones.
Cafeful consideration must be taken into account with patients on high calcium diets in order to prevent hypercalcemia as blocking sodium entry from DCT will drop sodium in the principle cells and will speed up the NCX because the cell needs to get more sodium in.
What occurs when more sodium reabsorption is allowed in principal cells?
Potassium will be indirectly wasted
What role does aldosterone play in electrolyte balance?
Increases sodium reabsorption and reduces potassium excretion
It acts on principal cells to enhance sodium channels.
What are the functions of intercalated cells in the distal tubule?
Handle acid-base balance
Type A cells secrete hydrogen; Type B cells reabsorb bicarbonate.
What condition occurs when the kidney fails to respond to ADH?
Nephrogenic diabetes insipidus
Often due to issues with the protein kinase A gene.
What influences the release of ADH?
Blood osmolarity, blood pressure, and blood volume
Low blood volume and low pressure increase ADH release.
What is the ideal urine osmolarity under normal conditions?
Around 600 mOsmol/kg
Actual values may vary based on individual fluid intake and diet.
What is the role of urea transporters in the collecting duct?
Aid in water reabsorption and concentration
Urea is essential for creating a concentrated renal interstitium.
True or False: ADH affects electrolyte reabsorption.
True, just indirectly
ADH primarily regulates water reabsorption in the DCT and Collecting Duct. A change in water concentration will change the tubule solute concentrations and, depending on where in the nephron we are referencing, this can drastically affect the amount of electrolytes reabsorbed, such as sodium in the DCT.
Fill in the blank: Aldosterone receptors in principal cells enhance _______ channels.
Sodium
More sodium channels lead to increased sodium reabsorption.
What happens to urinary flow rate when blood osmolarity is restored?
Increases until balance is restored
After restoration, flow rate returns to original state.
What effect do drugs like alcohol and caffeine have on ADH release?
Reduce ADH release
Increased blood osmolarity and low blood volume stimulate ADH release.
What primary electrolyte should be monitored in patients on thiazide diuretics? Why?
Calcium intake
* Inhibition of the NaCl Co-Transporter will drop sodium in the principle cells and will speed up the NCX because the cell needs to get more sodium in.
Excessive calcium can lead to complications, particularly in the context of kidney stone formation.
How can thiazide diuretics help in preventing kidney stones?
By reducing calcium in tubular urine
By inhibiting the NaCl Co-transporter, thiazides indirectly speed up the NCX pump on the interstitial side of the principal cell which will decrease urinary calcium excretion. This may lower the risk of calcium-based kidney stones but the calcium reabsorption increase is not drastic enough to remove a kidney stone that is already present.
What is the primary function of aldosterone in principal cells?
Increases sodium reabsorption
* Aldosterone is a mineralocorticoid that helps maintain electrolyte balance by promoting sodium retention.
* When the kidney identifies lower Na reabsorption, it will signal for more aldosterone to release via RAAS
Renin is produced and secreted by juxtaglomerular cells
Cortisol is a __corticoid
Aldosterone is a __corticoid
Glucocorticoid
Mineral corticoid
Both are produced in the zon glomerulosa
What effect does aldosterone have on potassium levels?
Increases potassium secretion via big potassium (BK) channel opening and renal outer medullary potassium (ROMK)
- BK channels are always present on the tubular (basolateral) side of the principal cell but remain closed unless we need to really really really excrete a high amount of potassium
- ROMK channels are sequestered to the surface of the basolateral side when needed before BK channels are required to open
- Both channels are aldosterone-mediated
Because Aldosterone speeds up the Na/K ATPase pump, it promotes the excretion of potassium into the nephron (DCT) by increasing intracellular potassium concentration while facilitating sodium reabsorption. Don’t forget eNac sodium channels and open potassium (ROM-K) channels on the tubular (apical) side
What is the role of the sodium-potassium pump in principal cells (Besides exchanging 3 ICF sodium for 2 ECF potassium)?
The Na/K ATPase pump is the driving force behind the electrical gradient for Calcium entry into the cell from the DCT. Without it, the NCX would have a difficult time managing the calcium transport into the renal interstitium.
*The faster the Na/K pump spins, the more Ca we hold onto.
This pump is crucial for maintaining electrolyte balance and is influenced by aldosterone levels.
What happens to potassium channels in principal cells when potassium levels are high?
ROM K channels are expressed in the cell wall
* This increases the pathways for potassium secretion when needed.
Even though there are no K pumps in tubular cells, K being pushed into urine is still called secretion
What are the two types of potassium channels found in principal cells?
ROM K channels and BK channels
ROM K channels are regulated by aldosterone, while BK channels are always present but controlled by their opening.
True or False: Aldosterone directly pumps potassium into the tubule.
False
Potassium moves through channels rather than being actively pumped into the tubule.
What do diuretics that work upstream of principal cells typically affect?
Sodium and chloride reabsorption
These diuretics lead to increased sodium delivery to principal cells, affecting potassium excretion.
Fill in the blank: Aldosterone is produced in the __________ of the adrenal glands.
zona glomerulosa
This outermost layer is responsible for producing aldosterone, which responds to potassium levels.
Primary production location for Aldosterone and other androgens/cortisol?
Zona glomerulosa in the adrenal galnd
What happens when aldosterone receptors are blocked? What drugs block these?
Primary aldosterone receptor antagonist discussed is Aldactone (Spiranolactone)
Blocking aldosterone receptors slow the Na/K pump.
* This will slow Na absorption and inevitably slow the secretion of K
Aldosterone receptor antagonists block the binding site (receptor), not the production of aldosterone itself.
What is the relationship between renin-angiotensin system and aldosterone secretion?
Angiotensin II stimulates aldosterone release from the zona glomerulosa of the adrenal gland.
The renin-angiotensin-aldosterone system regulates blood pressure and fluid balance.
What type of drugs can block sodium channels (Not NaCl Transporters) in principal cells?
K sparing diuretics Amiloride and triamterene
* Blocking sodium entry to principal cells will drop sodium concentrations and will speed up the NCX because the cell needs to get more sodium in. This will increase Ca reabsorption.
These drugs are often used in diuretic therapy to reduce potassium secretion.
What is the effect of blocking aldosterone receptors?
Reduces sodium reabsorption and potassium secretion
Drugs like spironolactone are aldosterone antagonists that have these effects.
What do potassium-sparing diuretics do?
Reduce potassium secretion
They help maintain potassium levels while promoting diuresis.
What is the typical ratio of epinephrine to norepinephrine released by the adrenal medulla?
4 to 1
The adrenal medulla releases more epinephrine than norepinephrine.
What enzyme is crucial for the synthesis of aldosterone?
Aldosterone synthase
This enzyme is present in the zona glomerulosa of the adrenal gland where aldosterone is produced.
What determines the production of hormones in different parts of the adrenal glands?
Presence of specific enzymes
Each region of the adrenal glands has different enzymes that dictate hormone output.
What are the main hormones derived from cholesterol?
Aldosterone, cortisol, and androgens
These are produced in the zona glomerulosa of the adrenal gland
These hormones are known as steroid hormones due to their cholesterol origins.
Key hormone discussed that is from the adrenals (previous lectures said it was what baseball players used to dope and increase strength)
Androstenedione is produced within the zona fasciculata in adrenal gland (and technically gonadal region)
What is the primary function of cortisol?
To help balance glucose levels during stress
Cortisol is classified as a glucocorticoid.
What is the primary function of aldosterone?
To maintain electrolyte balance
Aldosterone is classified as a mineralocorticoid.
What is the enzyme that degrades cortisol in principal cells?
11 beta HSD type 2
This enzyme helps prevent cortisol from interacting with aldosterone receptors.
True or False: High levels of cortisol can lead to hypertension.
True
*Extra cortisol can also interact with aldosterone receptors (ACTH Lump Tumor)
Excess cortisol can activate aldosterone receptors, contributing to high blood pressure.
How does 11 beta HSD type II interact with cortisol? How can this enzyme help with an ACTH secreting tumor such as a lump tumor in the lungs?
It basically destroys or dehydrogenates it.
* 11 beta HSD type II is specific for cortisol so this will help with Cushing’s symptoms