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
Signs/Symptoms of Cushing’s?
interWeight gain, muscle weakness, high blood pressure, fragile skin, increased body hair, and bone loss
This is all related to the overproduction of cortisol from the adrenal glands (zona glomerulosa)
What effect does potassium concentration have on aldosterone release?
As potassium levels increase, aldosterone release increases
This mechanism helps regulate potassium excretion.
What are the two types of intercalated cells in the distal tubule?
- Type A intercalated cells
- Type B intercalated cells
Type A cells secrete hydrogen ions, while Type B cells secrete bicarbonate.
Fill in the blank: Type A intercalated cells are responsible for _______.
secreting hydrogen ions via H+/K+ ATPase pump and/or strict H+ ATPase pump
They help eliminate excess acid from the body by putting A LOT of protons in the urine thanks to its ATP-dependent, proton specific, pump
What is/are the role(s) of Type B intercalated cells?
They “can” reabsorb protons nut their primary purpose is to secrete bicarbonate
They are involved in regulating acid-base balance.
What types of receptors do principal and intercalated cells have that respond to vasopressin?
V2 receptors
These receptors are involved in water reabsorption mechanisms.
How do V1 receptors differ from V2 receptors?
Both respond to ADH but V2 receptors are located in the nephron vs. the periphery. V1 receptors are primarily responsible for providing periphreal vessel squeeze to increase BP.
Effect of V2 receptor binding in principal cells?
V2 binding increases cAMP which will activate PKA that phosphorylates AQP-2s. This will move (sequester) aquaporin channels to lumen side (apical) of principal cell and begin reabsorbing H20.
What happens to aquaporin channels when vasopressin binds to its receptors?
Aquaporins are moved (sequestered) to the cell membrane surface on the apical (nephron lumen) side.
This allows increased water reabsorption in the kidneys.
What condition results from a problem with the kidney’s response to vasopressin?
Nephrogenic diabetes insipidus
This condition occurs when the kidney fails to respond to ADH, leading to excessive urination.
What is the only known natural inhibitor of the enzyme 11 beta HSD?
Licorice
Real licorice can inhibit this enzyme, leading to increased blood pressure and possibly hypokalemia.
How can real licorice affect blood pressure? What products have real licorice?
Licorice is the only known natural inhibitor of the enzyme 11 beta HSD, the enzyme responsible for cortisol destruction.
* Without this enzyme, excess cortisol will interact with aldosterone receptors in the principal cells causing sodium retention and an increase in BP
* The real chinese licorice candy and tobacco products (along with nicotene in them) contain natural licorice
True or False: The adrenal glands respond to angiotensin II by releasing aldosterone.
True
Angiotensin II stimulates aldosterone release, which helps regulate blood pressure.
How do principal cells primarily regulate potassium?
By secreting potassium
This is crucial for maintaining potassium homeostasis in the body.
What are the effects of elevated aldosterone levels?
- Increased sodium reabsorption
- Increased potassium secretion
These changes help regulate blood volume and pressure.
What is the primary role of the kidneys in acid-base balance?
To excrete excess acids or bases
This function is essential for maintaining pH homeostasis.
What is nephrogenic diabetes insipidus?
A condition where the kidneys do not respond properly to ADH
Nephrogenic diabetes insipidus indicates a problem with kidney function in response to vasopressin.
What does ADH stand for?
Antidiuretic hormone
ADH is also known as vasopressin.
How often would a person need to urinate if ADH were absent?
Every 45 minutes
This is due to the inability to retain water without ADH.
What condition is characterized by a problem with ADH secretion?
Central diabetes insipidus
This condition arises when there is an issue with the release of vasopressin from the brain.
What is a common cause of nephrogenic diabetes insipidus?
Lithium therapy
High doses of lithium can induce nephrogenic diabetes insipidus.
What is the typical urine output for a patient with nephrogenic diabetes insipidus induced by lithium?
About 20 liters a day
Patients will also experience very dilute urine, AS LOW AS 50mOsm.
What is the osmolarity limit for urine in nephrogenic diabetes insipidus?
Approximately 50 milli osmolar
This indicates extremely dilute urine.
What happens in the thick ascending limb of the loop of Henle?
Reabsorption of electrolytes without water
This segment is often referred to as the diluting segment and also has a high metabolic rate “because it does lots of stuff”
What effect does alcohol have on ADH?
Reduces ADH release and impairs kidney response to ADH
This leads to increased urine output.
What is the primary controller of ADH release?
Osmolarity
Changes in blood osmolarity are the most significant factors influencing ADH levels.
What two factors influence ADH release aside from osmolarity?
- Blood pressure
- Blood volume
Low blood pressure and low blood volume typically trigger increased ADH release.
What are osmoreceptors responsible for?
Sensing changes in blood osmolarity
They send feedback to the hypothalamus to regulate ADH release.
Where in the brain is ADH produced?
In the hypothalamus
* supraoptic nuclei produces 5/6 of ADH
* Paraventricular nuclei produces 1/6
What are the names of the two nuclei involved in ADH production?
- Supraoptic nucleus
- Paraventricular nucleus
The supraoptic nucleus produces about 5/6 of ADH, while the paraventricular nucleus produces about 1/6.
What is another name for the posterior pituitary gland and is the storage location for ADH?
Neurohypophysis
This is where ADH is stored and released into the bloodstream.
What is the anterior lobe of the pituitary gland also called?
Adenohypophysis
This term is important for understanding pituitary gland functions.
What happens to a cell placed in a hypotonic solution?
It swells due to water influx
* This typically leads to reduced ADH release.
Cell expansion causes slower action potentials which explains the decrease in ADH.
What occurs when a cell is placed in a hypertonic solution?
It shrinks as water leaves the cell
* This situation typically results in increased ADH release.
Cell shrinking causes faster action potentials which explains the increase in ADH.
How do osmoreceptors respond to swelling?
They decrease the rate of action potentials
Because these osmoreceptors are located in the hypothalamus, this reduces the release of ADH.
How do osmoreceptors respond to shrinkage?
They increase the rate of action potentials
This results in increased release of ADH.
What is the osmolarity of tubular fluid in the proximal tubule compared to plasma?
About the same as plasma osmolarity
This is due to the reabsorption of water along with solutes.
What do proximal tubules primarily reabsorb?
Amino acids and glucose, along with water
Proximal tubules are not very selective and allow water to follow the absorbed solutes.
What is the expected osmolarity in the proximal tubules compared to plasma?
About the same as osmolarity of plasma
This occurs because water follows the salts reabsorbed in the loop of Henle.
What happens to solutes as blood moves deeper into the kidney?
Solutes become concentrated as water leaves
This occurs in the descending thin limb of the loop of Henle.
What effect does the ascending loop of Henle have on tubular osmolarity?
Reduces tubular osmolarity
This is due to reabsorption of salts without reabsorbing water.
What is the role of ADH in urine concentration?
Determines the osmolarity beyond the early distal tubule
High levels of ADH lead to concentrated urine, while low levels lead to dilute urine.
How does ADH affect urinary osmolarity?
High ADH leads to urinary osmolarity around 1200; low ADH leads to around 50
This illustrates the dramatic effect of ADH on urine concentration.
What is the primary function of urea in the kidney?
Helps with water reabsorption
Urea is reabsorbed along with water and contributes to the osmolarity of the renal interstitium.
What type of transporters are present in the collecting duct related to urea?
Urea transporters (isoform 1 and 3)
These transporters help conserve urea in the body.
What is the relationship between urea and water reabsorption?
Urea helps draw water through aquaporins
The presence of urea in the renal interstitium increases water reabsorption efficiency.
What is unique about aquaporin 3 and 4 receptors?
AQP-3 and AQP-4 are located on interstitial (basolateral) side of principal cells all the time to move H20 into renal interstitium
*AQP-2 need ADH to move to the apical side of the cell and let more water in
What does anti-diuresis mean?
Retention of fluids and electrolytes
This is the opposite of diuresis, which refers to the loss of fluids.
What factors can decrease ADH release?
Reduction in plasma osmolarity (salty blood needs more water), high blood pressure, high blood volume
Alcohol and clonidine are also known to reduce ADH release.
What factors can increase ADH release?
Increased blood osmolarity, low blood pressure, nausea (vomiting decreases body fluid amount)
Morphine and nicotine can also drive up ADH release.
What is the primary controller for plasma osmolarity?
ADH (Antidiuretic Hormone)
ADH is the only compound that can influence water reabsorption without affecting salt reabsorption.
What happens when ADH is removed from the system?
Blood osmolarity can fluctuate significantly with small changes in sodium intake
This can lead to imbalances and potential health issues.
What is the effect of low sodium intake on blood osmolarity?
It should not significantly affect blood osmolarity if ADH is functioning properly
ADH helps maintain osmolarity despite sodium intake variations.
What is the role of angiotensin II in thirst regulation?
Increases thirst sensation
This is part of the body’s response to low blood volume or low blood pressure.
What happens to thirst levels when blood volume is high?
Thirst typically decreases
This is a natural response to prevent overhydration.
What is the consequence of a high potassium intake if the aldosterone system is functional?
Blood potassium concentration is effectively regulated
Issues arise in cases of renal failure or when aldosterone is blocked.
What factors prevent potassium problems in the body?
Functioning adrenals and kidneys
If the adrenals and kidneys are working properly, potassium levels are usually well-regulated.
What is the MOA of Triamterene?
Inhibition of epithelial sodium channel (ENaC) on luminal (apical) side of principal cells.
* Blocking these ENaC channels will increase sodium excretion, cause diuresis, and reduce the amount of potassium wasted.
What is the effect of high doses of spironolactone or triamterene on potassium control?
They interfere with potassium control centers
These medications can lead to increased potassium levels if not monitored.
What happens to blood osmolarity after drinking one liter of distilled water?
Produces a small reduction
This reduction affects ADH levels, leading to increased urine output.
What is the expected change in ADH levels after drinking distilled water?
ADH levels are reduced
Reduced ADH leads to increased urinary flow rate.
What is the typical urinary flow rate in normal conditions?
1 ml per minute
This rate can significantly increase after consuming large amounts of water.
What is the body’s response to excess water intake?
Increase in urinary flow rate
This process helps eliminate excess water without disturbing electrolyte balance.
What happens to urine osmolarity when excess water is excreted?
Urine osmolarity drops
This occurs as water reabsorption decreases, allowing for the excretion of excess water.
What is the normal urine osmolarity under ideal conditions?
About 600
This value can vary based on individual fluid intake and dietary habits.
True or False: The body can efficiently manage excess fluid intake without disrupting electrolyte levels.
True
The body has mechanisms to handle excess water while maintaining electrolyte balance.
What is the teacher’s proposed solution for class scheduling conflicts next semester?
Move class to Friday afternoon
This change aims to reduce student stress from overlapping exams and lectures.
How did the teacher assess the impact of the current class schedule on students?
By reviewing the exam schedule
The teacher noticed potential conflicts with student exam schedules.
What is the teacher’s stance on attendance for Friday classes?
Expecting full attendance
The teacher plans to closely monitor attendance on Fridays.
Fill in the blank: The urinary flow rate increases to eliminate excess _______.
water
This is part of the body’s homeostatic regulation.
