Renal 3 Flashcards
What is the effect of pumping Na/Cl/K out of the tubule into the iterstitium?
It concentrates the renal medulla
How does the countercurrent multiplier system affect the concentration gradient?
It amplifies the first effect of pumping Na/Cl/K into the interstitium to yield an even steeper concentration gradient
What solute does ADH add and what effect does this have?
It adds urea, which makes the concentration gradient steeper
What changes does ADH (vasopressin) respond to?
Increased osmolarity and decreased blood pressure (can be dangerous)
What does ADH cause?
Excretion of concentrated urine, which is negative free water clearance and diluting of the body fluids
What do RAAS and ANP respond to?
Changes in volume in the body, which cause changes in high and low blood pressure sensing systems
ADH flow chart
What is ADH release triggered by?
↑ osmolarity
↓ plasma volume
If you drink too much water and your blood becomes dilute, you need a ___ free water clearance
Positive
Overview of how an osmotic gradient is established
- You establish a gradient of osmolarity starting at the junction of the cortex and the medulla, where the extracellular fluid is around 300 mlOsm/L (standard)
- As you go further down into the medulla, towards the renal pelvis, where the collecting ducts empty, the concentration gradient gets steeper as you go down towards 600 or even 1,200 mlOsm/L
- Depending on how permeable water is in the collecting duct, there’ll be more or less water reabsorbed
How does the kidney maintain a standing gradient in the medulla?
- It’s a dynamic process that involves active transport of solutes in the tubule system and a constant flow of filtrate going through the system
- If you cut off blood flow through the kidney, this vertical gradient would diminish
- Isoosmotic fluid (blood plasma minus proteins) enters the proximal tubule
- As it goes down the descending limb, there is (active transport)?? of sodium, glucose, amino acids, and chloride is following
- Water is drawn out osmotically
- The further down the loop of Henle (at the turn), the greater the concentration of solutes, so water will come out constantly, all the way down
- What we end up with at the lumen of the tubule at the bottom is hyperosmotic fluid. It’s lost some solutes, but it’s lost more water because of this gradient
- In the ascending limb, water is IMpermeable
- Solutes are actively transported
- Therefore, the concentration of the filtrate gets more dilute
- What comes out of the top of the ascending limb is a filtrate that is more dilute than 300 (it is hypoosmotic, more dilute than plasma)
- If you do not let water come back into the body, and leave the excess dilute filtrate unimpacted by the gradient, the urine will go out very dilute
- If water is not permeable in the ascending limb, water will enter the bladder very dilute
Countercurrent multiplier system
Step 1: Thick Ascending Limb of Loop of Henle to make filtrate more dilute and concentrate interstitial fluid
- Na/K/2Cl pump (active transport out of filtrate into interstitial fluid
- impermeable to H2O so filtrate gets dilute and interstitial fluid gets concentrated
Step 2 Loop of Henle and Vasa Recta
Multiply this effect to create a large, standing, vertical osmotic gradient in renal medulla
- ascending limb activity concentrates filtrate in descending limb
- higher concentration of Na, K and Cl increases flux of these ions in thick ascending limb
- direction of loop and transport generates and maintains vertical gradient
Step 3 ADH allows urea to be more permable in lower renal medulla. Adding another solute increases the concentration
The more concentrated the filtrate going through the ascending limb, the ___ active transport there will be
More
22 mins?
Countercurrent multiplier system
Another way to demonstrate countercurrent system
Urea’s role in establishing a vertical osmotic gradient
- ADH increases permeability of urea in collecting duct and loop of Henle at the very lower end of the renal medulla.
- Some urea is kept inside the kidney to further concentrate extracellular fluid
Presence vs. absence of ADH
In the absence of ADH, is urea recycled?
No
What does ADH do with respect to aquaporins?
- ADH works through a second messenger system to insert existing proteins (aquaporin-2) into the apical membrane of endothelial cells in the collecting duct (triggers exocytosis of vesicles containing aquaporins)
- The existing osmotic gradient draws water back into the body
- This system is fast to turn on and off as it inserts or removes proteins that already exist
- In the absence of ADH, there is endocytosis of the vesicles)
What is the other mechanism that removes the aquaporins in the absence of ADH?
ADH and low blood pressure
ADH is also secreted in response to low blood pressure in systemic arteries and atria (to get volume back into the body to increase MCFP)
Graph showing concentration/osmolarity in the renal medulla interstitium (outside the tubule) with and without ADH
Graph showing concentration of filtrate of nephron with/without ADH
Flow chart about ADH release
- ## Yellow ovals at top show factors that stimulate ADH release
How does having a blood osmolarity greater than 280 mOsm trigger ADH release?
- There are hypothalamic osmoreceptors (neurons in the hypothalamus that are sensitive to stretching)
- If a cell is in a hypertonic solution (high osmolarity), it will lose water and shrink
- The shrinking of the cell membrane of that neuron regulates the number of APs it fires. When it shrinks, it fires MORE
- Those neurons will regulate what happens in the hypothalamus, and triggers the release of ADH from the posterior pituitary
RAAS (renin angiotensin aldosterone system)
- We have a circulating level of angiotensinogen in the blood (the source is the liver)
- It is not a signalling molecule - it needs to be enzymatically digested to be converted to angiotensin 1
- How much of it being activated depends on how much renin is being secreted by the kidneys
Is angiotensin 1 a signalling molecule?
No, it requires a second enzyme to be cleaved into angiotensin 2
What enzyme cleaves angiotensin 1 into angiotensin 2?
Angiotensin converting enzyme (ACE)
How does angiotensin 2 interact with the adrenal cortex?
It causes it to release aldosterone into the bloodstream, which goes into the kidney and causes isoosmotic reabsorption of sodium, chloride, and water
Effect of aldosterone on kidney reabsorption
Causes isoosmotic reabsorption of sodium, chloride, and water
What are the three stimuli that affect juxtaglomerular cells?
- Sympathetic neurons
- Change in renal bood pressure (renal pressure sensation)
- Flow of chloride in distal tubule, affecting macula densa cells, which regulate renin release from juxtaglomerular cells
RAAS flow chart
What cells is renin released from?
Juxtaglomerular cells
Chloride ions and renin release
- The number of chloride ions zipping past the macula densa cells in the distal tubule
- The distal tubule swings by the afferent and efferent arteriole in the glomerular capillary bed and that distal tubule at that point has macula densa cells that perform a paracrine function
- If chloride ion flow rate in the distal tubule decreases, the macula densa cells release paracrine signalling molecules that stimulate the release of renin from juxtaglomerular cells
Why is a decrease in the flow of chloride ions in the distal tubule indicative of decreased plasma volume?
- When plasma volume goes down, there’s a decrease in the GFR, so a lower pressure in the capillary bed
- This can be caused by a decreased BP
What does angiotensin 2 do?
One of the pathways is the adrenal cortex, which triggers aldosterone release
- An increase in plasma levels of aldosterone in the cortical collecting ducts increases sodium and water reabsorption in proportionate amounts (isoosmotic)
How does a drop in plasma volume and blood pressure cause secretion of renin?
- Decreased blood pressure causes increased activity of the sympathetic neurons, which directly causes release of renin because the afferent and efferent arterioles are innervated by a sympathetic fiber
- These can synapse onto juxtaglomerular cells and trigger renin release
- This is a good way of increasing blood volume to increase blood pressure
Arterial pressure effect on renin
A decreased arterial pressure in the renal artery causes a direct effect on the juxtaglomerular cells –> renin release (like renal baroreceptor)
ANP
- Complementary signaling system for the RAAS system
- When plasma volume goes down, the RAAS system goes on
- The ANP system turns OFF
- When plasma volume (pressure) goes up), ANP goes ON
Plasma volume and ANP flow chart
Effects of ANP
- ANP inhibits the release of aldosterone in the kidney
- Dilates the afferent arteriole and constricts the efferent, boosting GFR, pushing more filtrate out into the tubule, giving you a bigger urine flow rate
- This gets rid of sodium, chloride, and water (volume)
Flowchart with angiotensin II
- Angiotensin II is one of the most potent vasoconstrictors- causes vasoconstriction of precap sphincter muscles throughout the body, increasing BP
- More sympathetic, less parasympathetic
- In the hypothalamus, increases ADH release
- Triggers thirst
Micro scale of aldosterone action
- Aldosterone acts through regulation of transcription
- This system is slow to turn on and slow to turn off as it depends on changing levels of protein synthesis
Aldosterone comes from the ___
Adrenal cortex
Receptors for aldosterone
- Not on the surface, like for ADH (peptide)
- They’re cytosolic receptors (aldosterone is a steroid hormone)
Responsiveness of aldosterone effect vs. ADH
A little slower because it involves extra steps (going into nucleus and regulating transcription and translation of proteins)
What types of proteins does aldosterone trigger the synthesis of?
- New channels in the membrane for things like sodium and potassium
- New pumps in the basolateral membrane that pump molecules like sodium and potassium
- New proteins that modulate the existing channels and pumps to up-regulate them
What is the result of the protein synthesis triggered by aldosterone?
- Sodium is absorbed more aggressively
- Chloride follows electrically, and water follows by osmosis
- You have isoosmotic reabsorption of sodium, chloride, and water
- You lose potassium as a consequence (you can also use this system to regulate potassium levels
ANP (atrial natriuretic peptide) flow chart
Handling of a salt load
- You ingest a lot of salt, but there’s no change in the volume of your blood
- Triggers changes in kidney, behavior (drink more fluid), and if chronically elevated, can have an effect on blood pressure
Angiotensin II
- Triggered by low BP
- Triggers release of aldosterone from adrenal cortex
- Vasoconstriction
- More sympathetic stimulation, increases BP
- Increased ADH, thirst (hypothalamus)
- Increased sodium and water retention
Aldosterone
- Slower effect than ADH
- Causes release of ADH
- Acts through transcription (steroid hormone)
- Isoosmotic reabsorption of Na+, Cl-, H2O (chloride follows sodium electrically)
- K+ lost as consequence
