The Renal System

Question 1

A key function of the kidneys is filtration. List some things that kidneys filter or regulate in the blood.

Answer 1

1. Kidneys regulate electrolyte (salt) balance in the blood, by inhibiting or promoting their absorption into the bloodstream. Many electrolytes are essential for the body’s function: K+ and Na+ essential for establishing membrane resting potential, Ca2+ generating an action potential, Cl- aiding in the formation of HCl in the stomach.
2. Regulating acid base balance. pH can greatly affect the affinity of haemoglobin for oxygen, and hence effect the transport of oxygen.
3. Excretion of waste products of metabolism; urea, water and ammonia.
4. Excretion of toxins and drugs.
5. Production of important hormones.
6. Maintenance of blood pressure via the reabsorption of water and production of hormones that controls how much substance is filtered out.

Question 2

Where are kidneys found in the body?

Answer 2

The kidneys are found just under the ribcage in the posterior part of the abdomen on either side of the spin. The left kidney is slightly higher than the right kidney due to the presence on the right side of the body.

On top of each kidney is an adrenal gland.

Question 3

What vessels lead into and out of the kidneys?

Answer 3

The aorta branches off into the renal artery, and the renal artery is the vessel that brings oxygenated blood into the kidneys. The oxygenated blood that is brought to the kidneys is the blood that is going to be filtered.

Going away from the kidneys is a tube called the ureter. The ureter holds components that was filtered out of the blood. The ureter carries these components to the bladder, and these contents leaves the body via the urethra.

The blood in the kidney that has been filtered is also deoxygenated. This deoxygenated (but filtered) blood travels through the renal vein, which eventually joins the inferior vena cava which reaches the heart.

Question 4

The kidney can be divided into two sections: renal cortex and renal medulla. What is the difference between these two sections?

Answer 4

Renal cortex and renal medulla refers to different regions of the kidneys. Renal cortex refers to the outlining regions of the kidneys.

On the other hand, the renal medulla refers to the center regions of the kidney.

These regions are important because a nephron is not just found in the cortex, or not just found in the medulla. Different areas of the nephrons can be found in the cortex and medulla.

Question 5

What areas of a nephron is found in the renal medulla? What areas of a nephron is found in the renal cortex?

Answer 5

Of a nephron, the renal corpuscle, afferent and efferent arteriole, PCT and DCT are found in the renal cortex.

The collecting ducts and loop of Henle is found in the renal medulla.

Question 6

The nephron can also be categorized into tubular and vascular components. What is the difference between the two?

Answer 6

Tubular components refers to the filtrate (the fluid that is filtered out after the blood passes through the renal corpuscle) and what structures it flows through in the nephron. E.g. PCT, loop of Henle, DCT, collecting duct.

Vascular components refers to blood vessels (NOT TUBES !!!) of the nephron that brings blood to the nephron and carries blood away. Such vascular components includes: afferent arteriole, efferent arteriole, glomerulus, peritubular capillaries and vasa recta. (Peritubular capillaries are vessels that surround the PCT and DCT and are there for reabsorption of water and ions back into the blood. The vasa recta are specialized capillaries that are around the loop of Henle, and they maintain an osmotic gradient in the medulla, but also for reabsorption).

Question 7

What is the renal capsule?

Answer 7

A coating that surrounds each kidney.

Question 8

Give a description of what the juxtaglomerular apparatus is.

Answer 8

The juxtaglomerular apparatus is a structure where a segment of the distal convoluted tubule (normally the initial segment) comes into contact with the afferent and efferent arteriole of the renal corpuscle.

There are two types of specialised cells present in this juxtaglomerular apparatus structure: macula densa cells and granular cells (juxtaglomerular cells).

Macula densa cells are epithelial cells that lines the walls of the distal convoluted tubule that comes into close contact with the afferent and efferent arteriole.

The granular cells are cells found in the wall of the afferent arteriole, and a bit of the efferent arteriole. Some granular cells may have secretory granules in their cytoplasm, that secretes a hormone called renin. The secretion of renin is essential in controlling blood volume and pressure.

Question 9

Describe the structure of the ureter, urinary bladder and urethra.

Answer 9

The ureters are two tubes that carries filtrate from the kidney to the bladder.

The bladder is the sac that holds our urine (the filtrate that just arrived from the kidneys). The bladder sac has walls made of smooth muscle, also known as detrusor muscle. During micturition, it is the contractor of the detrusor muscle (as well as other things) that causes the urine to be released.

The neck of the bladder then develops into a structure called the urethra, which is where the urine leaves the body (in males, the urethra extends into a penis).

At the top of the urethra (near the neck of the bladder), there is internal urethral sphincter. At the bottom of the urethra, there is also an external urethra sphincter. The contraction and relaxation of these sphincters leads to the release of urine.

Question 10

What is micturition?

Answer 10

The process where urine is expelled from the body.

Question 11

Describe the contraction and relaxation of sphincters in the urethra and detrusor muscle in the bladder during the storage phase (a relaxed bladder).

Answer 11

During the storage phase, the internal urethral sphincter is passively contracted by the sympathetic nervous system.

The external sphincter is actively and consciously contracted by us (under the control of somatic nervous system). There is a motor neuron from the CNS that is constantly firing action potentials to this sphincter to make it remain contracted (hence closing the urethra).

This causes the urethra to stay closed, preventing urine from escaping the bladder.

It is also important to note that the detrusor muscle in the bladder is relaxed.

Question 12

Which sphincter in the urethra is controlled by the parasympathetic system, and which is controlled by the somatic nervous system?

Answer 12

The parasympathetic nervous system controls the internal urethral sphincter (the one near the neck of the bladder).

The external urethra sphincter is under somatic control, meaning we consciously contract or relax these sphincters ourselves.

Question 13

How does the contraction and relaxation of sphincters and muscles change during micturition?

Answer 13

Firstly, when a lot of urine fills the bladder, the bladder stretches to hold more urine. When the bladder stretched, the stretch receptors within the bladder wall generates an action potential to send to the CNS.

The generation of the action potential notifies the CNS, and two things occur:

1) The parasympathetic neurons to the detrusor muscles in the bladder fire action potentials. This causes the detrusor muscle to contract. pushing urine out of the bladder as well as passively opening the internal sphincter.

2) The motor neuron that normally fires action potentials to the external sphincter stops firing these action potentials. This causes the external sphincter to stop contracting, and instead relaxes.

Overall, 3 things occur: the detrusor muscle contracts, the internal sphincter relaxes & opens, and the external sphincter also relaxes and opens.

Question 14

What three basic processes take place in the nephron?

Answer 14

Filtration, reabsorption and secretion.

Question 15

Of the blood that reaches the glomerulus in the kidneys, how much is filtered?

Answer 15

20% of the blood that reaches the glomerulus is filtered.
The other 80% carries on into the efferent arteriole and becomes blood vessels that wraps around the nephron.

Question 16

Outline what the glomerular membrane is composed of and how it forms filtrate.

Answer 16

Remember, when we are talking about a glomerular membrane, it is referring to the membrane between a glomerular capillary and the Bowman’s capsule.

So, the first layer is the capillary endothelial layer, which is basically the normal layer of endothelium cells you would have lining a capillary. The gaps between these endothelium cells are called fenestrations, and this causes the layer to be highly permeable to water and solutes.

The next layer is called the basement membrane. The basement membrane is composed of collagen proteins, which is negatively charged. This prevents negatively charged plasma proteins from also being filtered; the negative charged collagen proteins repels the negatively charged plasma proteins.

The last layer is the epithelial cells that line the glomerulus, which can also be referred to as podocytes. These podocytes have special extensions (almost octopus shaped, or the shape of a hair claw) that wraps around the glomerular capillary. The gaps between these podocytes are called slit pores. These slit pores only allows molecules to pass that are smaller than 60 kD.

This shows that the membranes that pass the glomerular membrane is dependent on their size, charge and shape.

Question 17

What components of the blood normally forms filtrate in the Bowman’s capsule, and what components stay in the blood and carry on to the efferent arteriole?

Answer 17

Small molecules like water, ions, urea, amino acids and glucose form filtrate.

Large molecules like erythrocytes, white blood cells and other plasma proteins stay in the blood and carry on to the efferent arteriole.

Question 18

What components determines the net filtration pressure?

Answer 18

Three components determines the net filtration pressure: hydrostatic pressure of glomerular capillaries, osmotic pressure (net osmotic pressure if from Bowman’s capsule to capillaries) and capsule hydrostatic pressure.

Net filtration pressure = Hydrostatic pressure in glomerular capillaries - osmotic pressure - hydrostatic pressure in Bowmans capsules (also called capsule fluid pressure)

Question 19

How is hydrostatic pressure generated in the glomerular capillaries?

Answer 19

The decrease in lumen size when the blood travels from the afferent arteriole to the glomerular capillaries causes an increase in the flow of blood; increase in blood pressure; increase in hydrostatic pressure.

The increased hydrostatic pressure forces more small molecules like water, ions and more out of the glomerular capillaries into the Bowman’s capsule.

Question 20

What is the net movement of osmotic pressure in the renal corpuscle, and does it oppose or favour filtration?

Answer 20

When blood arrives at the glomerular capillaries (from the afferent arterioles), the hydrostatic pressure causes water as well as other molecules to move into the Bowman’s capsule.

With water leaving the glomerular capillaries, the concentration of plasma proteins, erythrocytes and white blood cells increases, which in turn decreases the water potential.

So there is a decreased water potential in the glomerular capillaries, and increased water potential in the Bowman’s capsule (as water was just filtered into this space). This water potential gradient means water is more likely to move from Bowman’s capsule to the glomerular capillaries.

Hence, the overall colloid osmotic pressure would be from Bowman’s capsule to the glomerular capillaries, which is in the opposite direction to the movement of the filtrate. Therefore, this colloid osmotic pressure opposes filtration.

Question 21

Capsule fluid pressure can be referred to as hydrostatic pressure in the Bowman’s capsule, and is also a factor in determining the glomerular filtration rate. How is hydrostatic pressure built up in the Bowman’s capsule, and does this pressure oppose or favour filtration?

Answer 21

When fluid is filtered from the glomerular capillaries and enter the Bowman’s capsule, it starts to accumulate. The accumulation of filtrate increases pressure because the fluid is in an almost closed space (due to the Bowman’s capsule being a cup-like structure) and has no place to escape other than entering the renal tubule.

There is also some resistance to flow of filtrate into the PCT due to the decrease in space/lumen size of the PCT compared to the Bowman’s capsule. Hence, there is a small force causing filtrate to remain in the Bowman’s capsule, and the accumulation of filtrate generates a capsule fluid pressure (hydrostatic pressure in Bowman’s capsule).

The hydrostatic pressure in the Bowman’s capsule can cause some filtrate to re-enter the glomerular capillaries. This opposes the direction of filtration, which means capsule fluid pressure opposes filtration.

Question 22

Briefly state the net movement of pressures across the glomerular membrane.

Answer 22

The net hydrostatic pressure of glomerular capillaries is from the capillaries to the Bowman’s capsule (filtrate is pushed into Bowman’s capsule).

The net colloid osmotic pressure is from Bowman’s capsule into glomerular capillaries.

The next capsule fluid pressure if from Bowman’s capsule into glomerular capillaries.

So, colloid osmotic pressure and capsule fluid pressure works against the hydrostatic pressure of glomerular capillaries.

Question 23

What is the net filtration pressure if:
Hydrostatic pressure of glomerular capillary= 55 mm Hg
Colloid osmotic pressure= 30 mm Hg
Capsule fluid pressure= 15 mm Hg

Answer 23

Net filtration pressure= 55 - 30 -15
Net filtration pressure= 10 mm Hg

Question 24

What is glomerular filtration rate?

Answer 24

The amount of fluid that filters into the Bowman’s capsule per unit time. Average GFR is 125ml/min or 180L/day.

Question 25

What are some important information needed in calculating glomerular filtration rate?

Answer 25

Cardiac output- how much blood is pumped by the heart per minute? Normally, approximately 5 L is pumped by the heart per minute; 5L/min.

It is then important to know, that of this 5L (or accurate cardiac output of patient), 20% goes to the kidney. So 50 x 0.2 = 1 L.
This means 1L of blood goes to the kidneys.

Of that 1 L, 375 mL are proteins that cannot be filtered due to their size and charge. The remaining 625 mL is plasma.

As said before, 20% of the total blood plasma in the glomerulus that could potentially be filtered is actually filtered (the remaining 80% of plasma leaves via the efferent arteriole). Therefore:
625 mL x 0.2 = 125 ml/min.
GFR= 125 ml/min
This figure can be changed into L per day, which gives 180 L/ day.

Question 26

What formula can be used to indirectly estimate glomerular filtration rate, and why may we use this formula?

Answer 26

Estimated glomerular filtration rate:
(Urine conc x urine flow) / plasma conc

We use this formula rather than directly measuring glomerular filtration rate, because measuring it directly is difficult. We would have to know the volume of blood that arrives at the kidneys, the concentration in the afferent arteriole, and then then concentration after filtration; these are difficult to measure directly.

Question 27

The glomerular filtration rate of patients can be estimated, but what must be put in the system of patients for the GFR to be calculated?

Answer 27

By injecting a substance into the patient’s system, we can take a blood sample to look at the plasma concentration of this sample. Then we can take the urine concentration of this sample, to help us deduct how much was filtered out (an estimate).

A good example substance that can be injected in inulin. After glomerular filtration, no inulin is reabsorbed back into the blood or excreted by the kidney. so the rate of excretion is directly proportional to the rate of filtration of water and solutes across the glomerular membrane.

Creatinine is another substance measured to determine eGFR used by the NHS. However, as it is secreted by the renal tubules, it is a bit less accurate than using inulin.
However, the NHS does use creatinine for more practical reasons. Creatinine is a naturally occurring waste product of muscle metabolism that can be measured (blood plasma and urine concentration), however, inulin needs to be administered intravenously to measure eGFR.
Additionally, insulin requires specialised tests which involves collecting urine samples over a specific time period.

Question 28

What is myogenic feedback? What part of the nephron does it target and why does it occur?

Answer 28

Myogenic feedback is a mechanism that ensures a constant flow of blood into the kidneys, more specifically a constant flow of blood into the renal corpuscle. This mechanism is triggered when there is a change in blood pressure in the afferent arteriole; here we have myogenic feedback to have a constant flow of blood (constant blood pressure), and hence a constant GFR.

Hence, the myogenic feedback mechanism targets the afferent arteriole, more specifically the smooth muscle of the afferent arteriole.

Myogenic feedback also occurs in other organs to have a constant flow of blood; constant blood pressure.

Question 29

How is the myogenic feedback mechanism carried out at the renal corpuscle if there is an increase in blood pressure?

Answer 29

When there is an increase in blood pressure, the walls of the afferent arteriole will stretches.

To counteract this, the smooth muscle in the afferent arteriole contracts; vasoconstriction occurs. With a decrease in lumen size, there is a decrease in blood flow and hence a decreased blood pressure. As there is a decreased blood pressure in the afferent arteriole, there is a decreased blood pressure in the glomerular capillaries, decreasing the GFR.

Question 30

How is the myogenic feedback mechanism carried out at the renal corpuscle if there is an decrease in blood pressure?

Answer 30

If there is a decrease in blood pressure in the afferent arteriole, the smooth muscle of the arteriole relaxes; vasodilation occurs.

This increases the lumen size of the afferent arteriole, which leads to an increased blood flow in the afferent arteriole and glomerular capillaries- this increases GFR.

Question 31

What is tubuloglomerular feedback? What parts of the nephron does it occur and target? How is it different to myogenic feedback?

Answer 31

Tubuloglomerular feedback is another mechanism that occurs in the nephron to ensure a constant GFR by creating a constant blood pressure in the kidneys.

This feedback mechanism involved the distal convoluted tubule, macula densa cells, afferent arteriole and glomerulus.

Myogenic feedback only involves the afferent arteriole and any changes that occur affects the glomerulus. However, in tubuloglomerular feedback, as well as the afferent arteriole and glomerulus being involved, the DCT and macula densa cells are also involved.
In myogenic feedback, the mechanism is triggered by deviations in blood pressure in the afferent arteriole. However, in tubuloglomerular feedback, the mechanism is triggered by changes in blood pressure (blood flow) through the DCT.

Question 32

How is the tubuloglomerular feedback mechanism carried out if there is an increase in GFR?

Answer 32

If there is an increase in GFR, there is an increased pressure in the glomerular capillaries, which is brought about by an increased blood pressure in the afferent arteriole.

When there is an increased in GFR, more filtrate is formed. For this mechanism specifically, we focus by saying because of more filtrate, there is an increased blood flow through the DCT (note that increased blood flow occurs through whole nephron).

When there is an increased blood flow through DCT, the macula densa cells (epithelial cells of DCT wall) notices it and (paracrine) signals the afferent arteriole.

The signaling causes the afferent arteriole to constrict. The vasoconstriction of afferent arteriole leads to a decreased blood pressure, and hence decreases GFR.

Question 33

How is the tubuloglomerular feedback mechanism carried out if there is an decrease in GFR?

Answer 33

A decrease in GFR means there is a decreased blood pressure in afferent arteriole; it also means less filtrate is formed. As less filtrate is formed, there is a decreased blood flow through the whole nephron, but for this mechanism, we can focus by saying there is a decreased flow through the DCT.

The macula densa cells in the DCT picks up on this decreased blood flow through the DCT, and paracrine signals the afferent arteriole to dilate.

The vasodilation of the afferent arteriole allows more blood flow, hence leading to an increased blood pressure. An increased blood pressure in the afferent arteriole leads to an increased GFR.

Question 34

How does the macula densa cells know if there is an increased or decreased blood flow in the DCT?

Answer 34

The macula densa cells are sensitive to NaCl, and hence is able to detect a deviation in sodium chloride concentration in the filtrate.

In the normal functioning of a nephron, the loop of Henle and PCT is where NaCl is reabsorbed. If there is a decrease in flow of filtrate in the nephron, it means the filtrate can remain in the PCT and loop of Henle (as well as other nephron structures) for a longer period of time; this gives more chance for reabsorption of NaCl. Hence, when the filtrate reaches the DCT (after flowing through PCT and loop of Henle), there would be an abnormal decrease in NaCl.
This decrease in NaCl is what the macula densa cells detect, and then they carry out necessary actions to increase the flow of filtrate.

The same goes for an increase in blood pressure- increased blood pressure in the afferent arteriole leads to an increased flow of filtrate in the nephrons. The filtrate spends significantly less time in PCT and loop of Henle, and so there is less chance of reabsorption of NaCl at these places. Hence, when the filtrate reaches the DCT, there is abnormally high concentration of NaCl.

Question 35

When if the Renin-Angiotensin-Aldosterone System (RAAS) activated?

Answer 35

Normally when there is a decrease in blood pressure, like a decrease in pressure in the afferent arteriole; granular cells (which secretes renin) is sensitive to the degree of stretch of the afferent arteriole.
The RAAS can also be activated by a decrease in mean arterial pressure (throughout the body?) which leads to a decrease in GFR. So, RAAS can also be activated by decreased GFR (which is detected by abnormal decrease in NaCl at the DCT).

Question 36

The RAAS system causes the formation of angiotensin II in the blood. How does this happen?

Answer 36

Firstly, renin (a protein) is secreted from the granular cells of the juxtaglomerular apparatus in the kidneys when there is a decrease in pressure.

Secondly, it is important to note that one of the plasma proteins always present in the blood is angiotensinogen, which is made by the liver (like most plasma proteins).

When renin (secreted from the kidneys) comes into contact with angiotensinogen, the renin converts angiotensinogen to a more active angiotensin I; now there is angiotensin I molecules present in the blood.

Another thing to note is that on the walls of blood capillaries around the body, there is an enzyme present called Angiotensin Converting Enzyme (ACE). ACE is present in the blood capillaries around the body, but is most abundant in the lung capillaries.

When the blood reaches the lungs, ACE converts the angiotensin I to angiotensin II. Now angiotensin II is the protein molecule that can bring about different changes to increase blood pressure in the body.

NOTE THAT: renin converts angiotensinogen to angiotensin I by cleaving off amino acids from angiotensinogen. ACE also converts angiotensin I to angiotensin II by cleaving off amino acids from angiotensin I.

Question 37

The RAAS results in the formation of angiotensin II. How does the formation of angiotensin II result in an increased blood pressure?

Answer 37

Angiotensin II stimulates the release of aldosterone from adrenal glands (adrenal cortex). Aldosterone functions by increasing reabsorption of NaCl at the PCT in the kidneys (reabsorption of NaCl creates a difference in osmolarity between blood and filtrate, causing higher re-absorption of water in loop of Henle). Reabsorption of NaCl and water leads to an increased blood pressure.

Angiotensin II also stimulates the release of ADH from the posterior pituitary gland (ADH made in the hypothalamus?). ADH stimulates an increased reabsorption of water into the blood at the DCT and collecting duct. More water in the blood increases the blood pressure.

Angiotensin II causes vasoconstriction of systemic arteries which increases mean arterial pressure.

Angiotensin II causes vasoconstriction of efferent arteriole. There is a resistance to flow of blood at the efferent arteriole, so blood remains in the glomerulus for a longer period of time, which allows more ultrafiltration to take place, increasing GFR.

Angiotensin II stimulates thirst center in hypothalamus, which could increase fluid intake; this will increase blood pressure.

Question 38

What in ANP? Where is it secreted from? What structures in the body does it act on?

Answer 38

ANP is atrial natriuretic peptide and has the structure of just a peptide (chain of amino acids), and this peptide serves as a hormone.

ANP is secreted from myocardium cells (muscular layer of heart) of the atria of heart. ANP is secreted from myocardium cells when there is a stretch in the myocardium (hence, a stretch in the atria) due to an increase in blood volume. Hence, it is also secreted when there is an increase in blood pressure in the body, because normally, with a high blood volume comes a high blood pressure.

ANP works on the kidneys, brain and adrenal cortex mainly.

Question 39

How does ANP work on the nephron to decrease blood pressure (and blood volume)?

Answer 39

The goal of ANP in the kidney is to increase sodium excretion. Increasing sodium excretion can be brought about by increasing glomerular filtration rate AND also decreasing sodium reabsorption into the blood.

ANP does this by vasodilation of the afferent arteriole and vasoconstriction of the efferent arteriole. With a larger lumen size of the afferent arteriole, more blood flows into the glomerulus. However, the blood is trapped in the glomerulus due to the decrease in lumen size of efferent arteriole which causes resistance to flow of blood (due to vasoconstriction of efferent arteriole). With more blood in the glomerulus, there is an increase in (hydrostatic) pressure, which increases the GFR.

With a higher GFR, more filtrate is being formed, which leads to an increased flow rate of the filtrate through the tubular components of the nephron. With the filtrate travelling faster, the filtrate spends less time in structures like PCT and loop of Henle, leaving less chance for Na to be reabsorbed in the body.

If less Na is reabsorbed in the body, more Na remains in the filtrate, which continues to the bladder to be excreted as urine.

With less Na in the blood, less water is reabsorbed. Because of these two facts, there is a smaller blood volume and hence, a decreased blood pressure.

ANP ALSO REDUCES THE SECRETION OF RENIN.

Question 40

What effect does have ANP have on the brain and adrenal cortex?

Answer 40

ANP inhibits the release of aldosterone from the adrenal cortex (as aldosterone functions to increase reabsorption of NaCl).

ANP inhibits the release of ADH (vasopressin) from the posterior pituitary gland.

ANP also decreases the sympathetic output from the medulla oblongata.

Question 41

What are the overall effects of ANP?

Answer 41

> Increases Na excretion in the kidneys.
Decreases renin secretion in the kidneys.
Inhibits ADH release from brain.
Inhibits aldosterone release from adrenal cortex.
Decreases sympathetic output from medulla oblongata.

Question 42

Describe the structure between the tubules of the nephron and capillaries of the nephron.

Answer 42

If we start off with the tubules, we first have the lumen of the tubule. The epithelial cells that makes up the walls of the tubular components are called tubule cells.

Between the wall of the tubules and walls of blood capillaries is interstitial fluid.

Then we have the capillaries. The cells that lines the capillary walls are called endothelial cells. Then we have the lumen of the capillaries.

Question 43

Two different transports that can occur between a tubule and blood capillary are transcellular and paracellular. What is the difference between the two?

Answer 43

Transcellular transport is when a substance may move from the tubule to capillary by actually travelling through the epithelial cells that lines each structure. It would carry this out with the mechanisms of diffusion and active transport.

Paracellular transport is when substances moves from the tubule to blood capillary by travelling through the spaces between cells, also known as tight junctions.

Question 44

What mechanism is used to carry out the reabsorption of Na+ at the PCT?

Answer 44

Remember, when we are talking about reabsorption, we talk about the movement of substances from kidney lumen to capillary.

First note that there is some Na+ in the tubular cells (epithelial cells that lines the tubule). This Na+ is pumped out into the interstitial fluid using an Na+/K+ pump, while K+ is pumped into the tubular cells (via hydrolysis of ATP).

This causes there to be an accumulation of Na+ in the interstitial fluid (which then diffuses into surrounding blood capillaries, via diffusion?), but also a decrease in concentration of Na+ in the tubular cells.

So with high concentration of Na+ in the lumen of tubule and a low concentration of Na+ in tubular cells due to the work of the Na+/K+ pump, a concentration gradient has been established.

Now there is an increased diffusion of Na+ down this concentration gradient (from kidney lumen to tubular cells), via the Na+ channels.

The Na+ that enters the tubular cells are pumped out using an Na+/K+ pump and the cycle repeats itself.

Question 45

What % of energy is spent on reabsorption of Na+ in the kidneys?

Answer 45

80% of energy in the kidneys is spent on reabsorption of Na+

Question 46

Describe the mechanism for the reabsorption of glucose in the PCT of kidneys.

Answer 46

> Na+ in the tubular cells are pumped into interstitial fluid, using Na+/K+ pump (so K+ is simultaneously pumped into tubular cells from interstitial fluid).

> This causes a decrease in concentration of Na+ in the tubular cells. This establishes a concentration gradient, which makes Na+ in the PCT lumen to move into the PCT tubular cells.

> Na+ does move down the concentration gradient from PCT lumen to tubular cells via SGLT. This is co-transport in which glucose and Na+ is moving in the same direction to the tubular cells via diffusion.

> Now there is an increased glucose concentration in the tubular cells. Compared to the interstitial fluid, the tubular cells have a higher concentration of glucose. Hence, glucose easily diffuses down this gradient via a glucose transport protein (GLUT).

> The glucose is now in the interstitial fluid and can now diffuse into blood capillaries.

Question 47

Describe the mechanism in which bicarbonate ions are reabsorbed in the PCT.

Answer 47

> So, first we have bicarbonate ions in the filtrate.

> H+ is secreted from tubule cells into the PCT lumen. It does this by using a special transport protein; a Na+/H+ transporter. This means that while H+ diffuses into the PCT lumen, Na+ diffuses from PCT lumen into tubule cells.

> The H+ ions bonds with the bicarbonate ions in the filtrate to form carbonic acid. This carbonic acid then breaks down into carbon dioxide and water.

> The carbon dioxide produced in the PCT lumen then diffuses into the tubule cells.

> The carbon dioxide combines with water in the tubule cells to re-form carbonic acid. This carbonic acid dissociates into H+ and bicarbonate ions. The H+ can then diffuse back into the PCT lumen using the Na+/H+ transporter to start the process again. It is IMPORTANT to note that the H+ that diffuses from the tubular cells into PCT lumen at the start does not come from a fresh supply in the tubular cells. Instead, the same H+ ions that diffuses from tubular cells to PCT lumen comes back to the tubular cells (it does not come back in the form of H+, but the H+ is released at the end) through this mechanism, and is recycled to be used again.

> The bicarbonate ions produced in the tubular cells are transported into the interstitial fluid, which then moves to the blood.

Question 48

Describe the mechanism of water and electrolytes reabsorption in the PCT.

Answer 48

> Solutes are diffused and actively transported from PCT lumen to tubule cells and interstitial fluid.

> This increases water potential of PCT lumen, but decreases water potential of tubule cells and interstitial fluid.

> Water moves down this water potential gradient using aquaporins and mechanism of osmosis.

> When water reaches the interstitial fluid, it diffuses into surrounding blood capillaries.

Question 49

What substances are secreted from the blood into PCT?

Answer 49

> Hydrogen ions
Nitrogenous waste products
Drugs; penicillin and morphine
Uric acid
Ammonium ions
Creatinine
Urea

Question 50

Describe the mechanism for reabsorption of water at the loop of Henle (the countercurrent multiplier mechanism).

Answer 50

Note that: filtrate enters loop of Henle via descending limb, and leaves loop of Henle via ascending limb.

> First, not that at the ascending limb, Na+, K+ and Cl- is pumped out of tubule (ATP required?) into the interstitial fluid, when then diffuses into the vasa recta.

> The direction of movement of fluid in the vasa recta and loop of Henle is in a counter-current fashion.

> This means that when Na+ and other ions diffuses into the vasa recta at the ascending limb of Henle, the blood is carried through the vasa recta to the descending limb region of the loop of Henle. Of course, at the same time filtrate moves from descending limb to ascending limb, and as it travels in the opposite direction to the blood (of the vasa recta), it is countercurrent.

> So, when Na+ and other ions diffuses into the vasa recta at the ascending limb, there is a decrease in osmolarity in the blood of the vasa recta. This blood is carried to the descending limb region of the loop of Henle, and due to the difference in osmolarity between the descending limb and vasa recta, water diffuses down the water potential gradient into the vasa recta.

IT IS IMPORTANT TO NOTE THAT THE DESCENDING LIMB OF THE LOOP OF HENLE IS THE ONLY REGION OF THE LOOP OF HENLE THAT IS PERMEABLE TO WATER. THIS MEANS THAT WATER IS ONLY CAPABLE OF DIFFUSING FROM THE LOOP OF HENLE TO THE VASA RECTA AT THE DESCENDING ARM.

Question 51

Talk about how osmolarity changes through the loop of Henle.

Answer 51

Going down the descending loop of Henle, the osmolarity increases. (Remember osmolarity is the concentration of solutes in a solution). Osmolarity increases because the descending limb is the region where water moves into the vasa recta. With less water at the descending limb and downwards towers the loop, the concentration of solutes in the filtrate increases which means the osmolarity also increases (and water potential decreases).

As we move up from the loop to the ascending loop of Henle, osmolarity decreases. This is because the ascending limb is the region where ions (like Na+, K+ and Cl-) is pumped out of the tubule into the vasa recta. With less solutes in the filtrate, the concentration of solutes decreases which decreases osmolarity (and water potential increases).

Question 52

Talk about how osmolarity changes through the vasa recta.

Answer 52

In the vasa recta at the ascending limb region, the osmolarity increases. This is because ions are being pumped in the vasa recta which increases the solute concentration of the blood (which decreases water potential).

However at the descending limb region, the osmolarity decreases. This is because the lowered water potential of the blood causes water to move into the vasa recta at the descending limb region.

With water entering the vasa recta at the descending limb region, the solute concentration in the blood of the vasa recta decreases, hence, the osmolarity decreases (and water potential increases).

Question 53

Why is the vasa recta and loop of Henle described as counter-current?

Answer 53

It is counter-current because the flow of fluids in the tubule and capillary are in opposite directions.

While filtrate moves from the descending limb to ascending limb, blood in the vasa recta moves from the ascending limb region to the descending limb region.

Question 54

What effect does aldosterone have on the kidney?

Answer 54

Aldosterone affects the DCT/collecting duct region of the nephron in the kidneys.

It targets this region to increase sodium absorption, while increasing potassium secretion.
The increased sodium absorption also leads to the indirect reabsorption of water and chloride ions (this is because with a higher reabsorption of Na+, there is a higher difference in osmolarity between tubules and the blood).

Question 55

Where does ADH target and what does it do? What can ADH also be referred as?

Answer 55

ADH can also be referred to vasopressin and it targets the DCT and collecting duct of the nephron in the kidneys.

ADH works to increase water reabsorption. As it is increasing water reabsorption, someone with a high ADH release will need the toilet less.
This is different to someone who is given diuretics; if they are given diuretics they need the toilet to pee more.

Question 56

What is the function of ANP (atrial natriuretic peptide)?

Answer 56

It decrease sodium and water reabsorption.

Question 57

What stimulates the release of aldosterone? What part of the nephron does aldosterone target?

Answer 57

Aldosterone is released as part of the RAAS when there is low blood pressure.

It is also released when there is a high concentration of K+ in the blood (hyperkalemia).

Aldosterone targets the collecting duct of the nephron. It is also secreted from the adrenal glands.

Question 58

Describe the mechanism of how aldosterone works to increase sodium absorption and potassium secretion.

Answer 58

So, aldosterone targets the collecting duct of nephrons. When it reaches the collecting duct of kidneys (after travelling through the blood from the adrenal glands), it diffuses from the blood into the tubule cells of the collecting duct.

Once inside the tubule cells, it binds with a cytoplasmic receptor. The hormone-receptor complex formed initiates transcription and translation of proteins.

The proteins that are synthesised are specific because they are channels and pumps that will helps with the reabsorption of Na+.
So, one protein that is synthesised is the Na+ ion channel, and this will aid in Na+ moving from lumen of collecting duct to the tubule cells.
The second protein made is Na+/K+ pump. This aids in moving Na+ from tubule cells into the blood (while coming K+ from blood to tubule cells). Note that this step establishes a concentration gradient for Na+ to move from collecting duct to tubule cells via an Na+ ion channel.
The last protein made is a K+ ion channel. It aids in the movement of K+ ions from tubule cells to collecting duct to be secreted.

Question 59

Describe the trend in osmolarity down a collecting duct for a nephron that is being targeted with ADH, and a nephron that is not being targeted with ADH. Also state how the osmolarity in each collecting duct is linked to the concentration of urine.

Answer 59

For a nephron being targeted with ADH, the collecting duct becomes more permeable to water to allows more water to leave the kidney and enter surrounding blood capillaries. Hence, for a nephron being targeted with ADH, there will be an increasing osmolarity down the collecting duct. This is because if water is leaving the collecting duct, the concentration of solutes in the filtrate will increase, hence, increasing osmolarity.
This results in a low volume of concentrated urine being excreted (so ADH increases water reabsorption in the body, but creates concentrated urine).

For a nephron not being targeted with ADH, the osmolarity through the collecting duct should remain fairly the same (assuming Na+ is not being reabsorbed or K+ is not being secreted due to aldosterone) as water is not leaving so the concentration of solutes should remain fairly similar. This results in the

Question 60

Describe the mechanism in which ADH (vasopressin) increases water reabsorption in the nephron.

Answer 60

After ADH is released from the posterior pituitary gland, it travels through the blood and reaches the kidneys. When it has reached the collecting duct region, it diffuses from the blood into the tubule cells of the collecting duct.

Here, it binds to a membrane receptor of the tubule cells, and this activates cAMP within the tubule cell; here we can say cAMP acts as a secondary messenger.

When cAMP is activated, it stimulates vesicles containing aquaporins to move to the membrane of the tubule cells (membrane connecting tubule cell and interstitial fluid and membrane contacting tubule cell and collecting duct lumen).

The aquaporins are released from the vesicle and fuses with the membrane. The presence of aquaporins now allows water to move from the collecting duct lumen into the tubule cells, and from the tubule cells into the interstitial fluid (then into the blood).

Question 61

A disease called diabetes insipidus is where the kidneys stops conserving water, which can lead to dehydration and thirst. Regarding the kidney (and other related organ’s) structures and function, what can be possible causes to the disease?

Answer 61

Damage to hypothalamus, which is responsible for producing ADH. ADH increases water reabsorption to the blood.

Damage to posterior pituitary gland which releases ADH.

Low ADH.

Low response in nephrons to ADH.

Question 62

Compare the thickness of the ascending limb and descending limb of the loop of Henle.

Answer 62

The descending limb of the loop of Henle is relatively thin compared to the ascending limb (ascending limb is thicker).

Question 63

Describe the trend in osmolarity as we move from the renal cortex to renal medulla of the kidney.

Answer 63

As we move from the renal cortex to the renal medulla of the kidney, the osmolarity of the interstitial fluid increases.

Note that the interstitial fluid has the same trend in osmolarity throughout the kidney, but the osmolarity in the tubules and blood can vary depending on the level of absorption that is needed to meet with the body’s needs.

Question 64

What renal adaptations can some animals have to conserve water (like animals in the desert)?

Answer 64

NOTE: if an animal is conserving water, more water is reabsorbed into the blood, meaning less water ends up in the final filtrate (urine). If there is less water in the urine because most has been reabsorbed in the body, this means the urine is highly concentrated.

Some adaptations are:

Animals have an extremely long loop of Henle; higher surface area creates more chance for movement of water from tubule to blood.

Most loop of Henle’s are juxtamedullary type (this means the loop of Henle extends deep in the renal medulla). If loops of Henle are in the renal medulla, that means they are in an environment (interstitial fluid) of high osmolarity. This high osmolarity of interstitial fluid (and blood because ions in the interstitial fluid can simply diffuse into vasa recta) creates a steep water potential gradient, that allows water to easily move from tubule to vasa recta- this means more water is being conserved.

Another adaption is that animals may have a thicker renal medulla.

Question 65

Desert animals have to retain water more, so produces more concentrated urine.