Renal Physiology III b

Question 1

• Understand the factors that affect renal handling of potassium and secretion.

Answer 1

A

Question 2

*Understand the renal handling of other ions (Ca, Mg, and Phosphate)

Answer 2

A

Question 3

*Understand the renal handling of cations, anions and peptides

Answer 3

A

Question 4

Describe the regulation of potassium distribution. Where is K+ mostly found and why? How much of K is contained in ECF/

Answer 4

About 98% total body K+ is found INTRACELLULARLY due to Na/K+ ATPASE pump
K+ found within cells as this pump actively transports potassium into cell.
Because the amount of K+ in ECF is so SMALL, even small changes into or out of cells can produce Large changes in extracellular potassium concentration.

Question 5

Explain why it is important to maintain extracellular concentration of potassium relatively constant? What are the main variables for extracellular potassium?

Answer 5

It is important to maintain extracellular concentration of potassium relatively constant because of Role of K+ in Nerve and Muscle excitability.
Extracellular potassium is a function of variables:
1. Total amount of K+ in the body
2. Distribution of K+ between the extracellular and intracellular fluid compartments
1st variable: function of amount of K+ ingested and excreted.

Question 6

What is the range of extracellular potassium concentration in the blood?

Answer 6

range Extracellular K+ concentration in blood: 3.5 to 5.7 millimolar (small amount)

Question 7

Define how sodium concentration and K+ concentration are regulated.

Answer 7

Sodium is regulated by reabsorptive process,
the amount of K+ in body is regulated by a Net SECRETORY process.
Most of the potassium is reabsorbed in proximal tubule, 20% reabsorbed in thick ascending limb via Na/K+ 2 Cl- co transporter.

Question 8

Where is K+ mostly reabsorbed? What is another location potassium is reabsorbed and how? What occurs when there is increasesd K+ in blood?

Answer 8

Most of Potaassium is reabsorbed in the proximal tubule
20% K+ is reabsorbed in THICK ASCENDING limb via Na/K+ 2 Cl- co-transporter. Variability of how potassium is handled in nephron is through secretion
increased K+ potassium in blood, increase aldosterone, which increases potassium secretion. Increase dietary K+, increase K+ secretion.

Question 9

What process occurs with K+ in thick ascending loop of henle and distal tubule/collecting duct? Which cells are more prevalent (alpha-intercalating disk or principle cells)?

Answer 9

K+ reabsorption is reabsorbed in Thick ascending loop of Henle as well as in alpha-Intercalated disk (distal convoluted tubule)
Principle cells- where K+ SECRETION occurs in collecting duct, where MOST REGULATION of K+ occurs.
Principle cells are MORE PREVALENT than alpha-intercalated cells.

Question 10

Where is K+ most regulated?

Answer 10

K+ is most regulated in PRINCIPLE cells of Collecting duct.

Question 11

What are the factors that affect regulation of K+ secertion?

Answer 11

Factors affecting Regulation of K+ secretion:

1. plasma K+ concentration
2. Aldosterone
3. Flow of Tubular fluid
4. Diuretics
5. Acid-base Balance

Question 12

Explain how plasma K+ concentration regulates K+ secretion?

Answer 12

Plasma K+ concentration:
When there is a high potassium diet ingested, it causes plasma potassium to increase which drives the uptake of potassium (from blood to inside cell) via Na-K-ATPase which drives potassium into tubular lumen (pee out K+)

Question 13

How does K+ intake affect aldosterone release?

Answer 13

High Potassium INCREASES Aldosterone release from adrenal cortex.
High potassium intake (diet) will increase plasma K+ concentration which increases aldosterone plasma aldosterone and INCREASES K+ SECRETION by principal cells of cortical collecting ducts.
Due to high K+ secretion you will have HIGHER K+ EXCRETION.
Anything that increases aldosterone release, will have impact on increasing K+ secretion and excretion.

Question 14

What will have a great impact on K+ secretion and excretion?

Answer 14

Anything that INCREASES Aldosterone release, will have impact on increasing K+ secretion and excretion.
so, HIGH levels of Angiotensin II, you will get hypokalemia, due to high Ang II leading to high Aldosterone and high level of K+ secretion (so less K+ in bloodstream)

Question 15

What is hypokalemia?

Answer 15

Hypokalemia- occurs when there is a decrease in K+ in body due to having high Aldosterone and high level of K+ secretion/excretion.
heart failure can lead to this also, as an increase renin, lead to increase in ang II, aldosterone- lead to hypokalemia (decrease in potassium) as well

Question 16

What occurs when you decrease plasma volume?

Answer 16

Decrease plasma volume, increase renin secretion, increase plasma renin, increase plasma Ang II and cause increase in Aldosterone, which increases tubular reabsorption of sodium and hence decreasing sodium excretion.
At the same time, when you increase plasma K you increase plasma aldosterone and increase Tubular Secretion of K+ leading to Increase in Potassium excretion.

Question 17

What happens when you increase flow rate to cortical collecting duct?

Answer 17

When you increase flow rate to cortical collecting duct INCREASES K+ secretion in cortical collecting tubule. This is because flow rate ( more fluid moving per unit time) , tends to dilute the K+ concentration in luminal fluid and so enhances K+ gradient for secretion.
you’ll have more time to dilute K+ and have more K+ secretion.
INCREASE Flow Rate ALWAYS increases K+ Secretion, leading to high K+ Excretion

Question 18

What can cause in increase in flow rate?

Answer 18

DIURETICS cause an INCREASE in flow rate.
Diuretics will cause increase fluid flow through nephron tubule, which will increase potassium secretion and excretion. This can often cause Hypokalemia (loss of K in body)
Can also think; As you increase flow rate, more Na+ is reabsorbed, so more K+ can be secreted).

Question 19

how are Na, K+ and flow rate connected?

Answer 19

Increase flow rate, Increase Na+ that can be reabsorbed, so more K+ can be secreted)

Question 20

What happens when you are given a Thiazide diuretic

Answer 20

If a loop of Henle diuretic or Thiazide diuretic (works on distal convoluted tubule) is given, it cause increased fluid delivery or increased flow to cortical collecting duct, which increase potassium secretion and hence excretion.
This Thiazide diuretic will cause a Decreased Na+ reabsorption. which will increase Na Delivery to collecting duct principal cells. This will cause enhanced Na reabsorption, but still increased K+ secretion.

Question 21

Describe effect of acid-base changes on K+ secretion

Answer 21

Alkalosis (decrease in H+ ion in blood) will INCREASE potassium concentration in Principal cells of cortical collecting duct (alkalosis can increase activity of Na+/K ATPASE pump) which INCREASES K+ SECRETION and K+ Excretion. This later leads to K+ Depletion.

Question 22

How does alkalosis increase K+ concentration in cortical collecting duct?

Answer 22

Alkalosis will increase the activity of Na+/K+ ATPASE pump, driving more K+ into the cell, ultimately driving more K+ secretion and excretion

Question 23

What causes increase in flow rate, and what occurs as a result?

Answer 23

Diuretics increase flow rate. Increase in flow rate ALWAYS increases K+ secretion and excretion.

Question 24

What happens when you eat a High Sodium diet?

Answer 24

Eating a High sodium diet, you will have High sodium will increase Extracellular fluid volume, which increases GFR. Increase GFR will increase Fluid delivery to macula densa, which will decrease Renin, which decreases Aldosterone. Decrease in Aldosterone will Decrease K+ secretion by cortical collecting ducts and leads to Unchanged K+ secretion and excretion.
In another scenario: High sodium diet can increase GFR and lead to increase in Fluid delivery to the cortical collecting ducts, which increases K+ secretion, and these factors balance to form unchanged K+ Secretion and excretion.

Question 25

What is the main factor that does not change K+ secretion?

Answer 25

Eating a High-Sodium Diet will NOT change K+ secretion

Question 26

Describe what occurs during Renal Calcium regulation? how might calcium function during hypokalcemia.

Answer 26

Renal Calcium regulation:
Calcium is reabsorbed paracellularly down its electrochemical gradient (+ charge repels cations) in the Thick ascending limb of Loop of Henle.
In the distal tubule- Ca+ reabsorbed via calcium channels(in response to Parathyroid Hormone)
In response to hypocalcemia- the parathyroid hormone (PTH) is released acts to INCREASE Calcium reabsorption at level of distal tubule.
hypocalcemia- a decrease in blood calcium.
When this occurs, parathyroid hormone will be activated

Question 27

What hormone is activated during hypocalcemia?

Answer 27

Parathyroid hormone will be activated during hypocalcemia.

Question 28

What are the two different ways calcium is reabsorbed in renal system?

Answer 28

1. Thick Ascending limb of Loop of Henle: Calcium reabsorbed through Electrochemical gradient paracellularly
2. Distal Tubule- Calcium is reabsorbed via Calcium Channels (in response to PTH)

Question 29

Explain how Renal Phosphate is regulated? How much of phosphate is reabsorbed vs excreted. What regulates phosphate reabsorption?

Answer 29

Renal phosphate regulation:
Phosphate that is NOT bound to plasma proteins is Filtered across glomerular capillaries.
85% of Phosphate is REABSORBED in Proximal tubules.
15% is EXCRETED
PTH regulates reabsorption of Phosphate in the proximal tubule by INHIBITING Na+ phosphate cotransport, which decreases Phosphate reabsorption.

Question 30

What are the major roles of the Parathyroid Hormone?

Answer 30

Parathyroid Hormone:

1. Increases Calcium reabsorption in distal tubules (calcium channels)
2. Decreases Phosphate reabsorption in Proximal tubule

Question 31

Explain how Renal Mg is regulated. Where is Mg mostly reabsorbed? How is Mg reabsorbed?

Answer 31

Renal Mg:
Mg is mostly reabsorbed in the Thick Ascending Limb of Henle
There is 95% reabsorption of Mg: 30% in proximal tubules, 60% in Thick ascending limb (Highest), and 5% in distal tubule
Mg is reabsorbed Paracellularly down its Electrochemical gradient in Thick ascending limb of Loop of Henle (since Mg is Lumen Positive)

Question 32

How are proteins and peptides reabsorbed?

Answer 32

Small amount of proteins and peptides are reabsorbed.
These proteins bind to specific receptors and endocytosis occurs. Intracellular vesicles merge with Lysosomes whose enzymes degrade protein to LOW Molecular Weight fragments (amino acids). The end products then exit cells across membrane into interstitial fluid and are reabsorbed into Peritubular capillaries.

Question 33

Explain the process of secreting organic anions.

Answer 33

There is an active SECRETORY pathway for Organic ANIONS in proximal tubule, that has LOW specificity (a single kind of transporter is secretes all organic anions)

ex: PAH is actively transported into proximal tubular cell across basolateral membrane and resulting intracellular concentration provided gradient for facilitated diffusion of PAH across Luminal membrane into tubular membrane
* PAH moves from interstitial fluid to cell and exchanges with an anion to be secreted into cell.

Question 34

What is a main example of an organic anion secreted by proximal tubule? What happens when this secretory pathway is blocked? What is an example of one that blocks?

Answer 34

anions secreted by proximal tubule
1. Penicillin- secreted by organic ion pathway: LOW specificity
Block organic anion secretory pathway: Blood level of penicillin will rise.
Probenecid used to block secretory pathway
as this drug will compete with penicillin, so Less penicillin will be secreted and excreted. So blood levels of penicillin will rise (dangerous effects)

Question 35

Explain how renal system handles Organic cations.

Answer 35

Organic cations are transported across the basolateral membrane by facilitated diffusion mechanism. This mechanism is driven by Negative potential difference across Basolateral membrane .
Organic cation transport across luminal membrane is mediated by OC+ H+ ANTIPORTER. This antiporter is Nonspecific and other organic cations can compete with it.
hence organic cations will be secreted in exchange for H+.