Urinary System

Question 1

the ________ and _________ functions of the kidneys are enabled by the filtration of large volumes of blood plasma followed by the selective ________ of required elements from the filtrate or the __________ of other materials into the filtrate. the kidneys are also responsible for the synthesis and release of a number of physiologically important compounds including ________ (during prolonged fasting), the hormone ______ (involved
in red blood cell production) and the enzyme ________ which plays a very important role in sodium homeostasis.

Answer 1

homeostatic
excretory
reabsorption
secretion
glucose
erythropoietin
renin

Question 2

the consequences of renal failure.

Answer 2

• An increase in blood pressure (hypertension) and pulmonary oedema due to an increase in fluid volume.
  
  • Cardiac arrhythmias due to potassium accumulation (hyperkalemia).
  • Acidosis due to accumulation of metabolites.
    Anaemia due to impaired erythropoietin synthesis

Question 3

Externally the kidneys appear as roughly oval–shaped organs
with an indentation in the medial surface called the _____ ______ through which the ureter, major blood vessels, lymphatic vessels and nerves enter. In an adult each kidney is around __ cm long, _ cm wide and _ cm thick.
The kidneys are positioned just above the ____ (around the level of the ___-__ vertebrae) between the peritoneum and musculature of the back. Because they are outside the peritoneum they are described as ________ and are fairly well protected from physical damage by the lower ____.

Answer 3

renal hilum
10
6
3
waist
T12-L3
retroperitoneal
ribs

Question 4

A frontal section through a kidney reveals three distinct layers:

* A superficial (outer) lighter-coloured layer known as the \_\_\_\_\_\_ \_\_\_\_.
*  A deeper darker coloured layer known as the \_\_\_\_\_ \_\_\_\_\_\_. 
 The renal medulla is characterised by cone-shaped \_\_\_\_\_\_ \_\_\_\_\_\_\_\_ that have their bases facing the renal cortex.
*  A single large cavity called the \_\_\_\_\_\_ \_\_\_\_\_\_ that collects urine and is continuous with the ureter. Each renal pyramid together with its adjacent cortical tissue forms a structural unit within the kidney known as a \_\_\_\_\_\_, there are usually around _ per kidney.

Answer 4

renal cortex
renal medulla
renal pyramids
renal pelvis
lobe
8

Question 5

The wall of the ureter consists of three major layers of tissue:

• An outer layer of connective tissue known as the _________.
• A middle layer made up primarily of smooth muscle and referred to as the ________.
• An inner _____ layer that consists of a lining of ________ _______ cells and its supporting _________ _____

Answer 5

adventitia
muscularis
mucosa
transitional epithelial
connective tissue

Question 6

The mechanism by which urine is transported along the length of the ureters:
The ureters penetrate the ________ wall of the bladder at an ______ angle. This angle turns out to be quite useful because as the bladder fills with urine this _______ the distal portion of the ureters and prevents ______ _____ of urine.
Urine does not rely on _____ to move along the length of the ureters but is propelled by _______ _____ produced by contractions of the smooth muscle in the ________ layer.
The magnitude and frequency of the peristaltic waves is directly proportional to the _______ of urine being produced.

Answer 6

posterior
oblique
compresses
back flow
gravity
peristaltic waves
muscularis
volume

Question 7

In the male, the urethra is the terminal portion of both the urinary and reproductive ductal system. It originates from the ______ portion of the urinary bladder, is approximately __ cm long and is divided up into three parts:
* ______ Urethra: The - cm portion which runs through the middle of the ______ gland where it fuses with the ________ ducts.
* _________ Urethra: A short portion at the base of the ______ gland.
* ______ Urethra: The major constituent of the urethra which runs through the _____.

Answer 7

inferior
20

Prostatic
2-3
prostate
ejaculatory

Membranous
prostate

Penile
penis

Question 8

In females, the urethra is approximately _ cm long, is located immediately behind the ____ ______ and has its _______ ______ between the vaginal opening and the _____.

Answer 8

4
pubic symphysis
external orifice
clitoris

Question 9

In both sexes the movement of urine along the urethra is regulated by two sphincters:
* The ________ urethral sphincter is located at the junction between the _______ and the ______. It consists of a specialised ______ of the _______ _____ and when closed prevents the movement of urine into the _______.
* The ________ urethral sphincter consists of _______ muscle surrounding the urethra as it penetrates the pelvic ______. As this sphincter contracts it _______ the urethra and prevents the flow of urine.

Answer 9

internal
bladder
urethra
thickening
detrusor muscle
urethra

external
skeletal
floor
compresses

Question 10

Despite their small size the kidneys receive around a quarter of the cardiac output (approximately _____ ml/min) through the renal ______ (which are branches of the abdominal aorta).
Just outside the kidney each renal artery divides to form _ segmental arteries and on entering the renal pelvis each of these divides to form a variable number of ______ _____ which, as the name suggests, supplies blood to a single lobe. These then divide into _______ arteries (which run between the renal ______) then divide to form _____ arteries that run around the bases of the renal pyramids. Branches of these radiate out to provide blood to the cortex so are known as ______ ______ arteries (and are sometime confusingly referred to as interlobular arteries).
Blood draining from the kidney follows a similar branching system of veins. Blood from the cortex flows into cortical radiate veins that fuse to forms the arcuate veins. The arcuate veins fuse to form the ______ veins than drain directly into the renal vein (as there are no lobar or segmental veins) and hence into the ______ _____ ____.

Answer 10

1200
arteries
5
lobar arteries
interlobar
pyramids
arcuate
cortical radiate
interlobar
inferior vena cava.

Question 11

The major innervation of the kidneys is from the ________ division of the _______ nervous system. The ________ neurones innervate a number of structures within the kidney and play a number of important physiological roles.

Answer 11

sympathetic
autonomic
postganglionic

Question 12

Nephrons are the functional units of the kidney each of which has around . million of these microscopic structures involved in the processes of filtration, secretion and reabsorption that are fundamental to kidney physiology. Each nephron consists of two structures; a long continuous _____ made up of ______ cells and its associated ______ _____.

Answer 12

1.2
tubule
epithelial
blood supply

Question 13

Be able to draw a labelled diagram of a nephron’s tubule, label the component parts and appreciate where they are located within the thickness of the kidney

Question 14

The tubule of each nephron is a small diameter hollow structure made up of a ______ layer of ______ _____. Although its size varies along its length it is usually less than __ microns in diameter but can be up to __ mm in length. This relationship between diameter and length means that the tubule has a very high surface area:volume ratio which makes it well designed for regulating the movement of ______ and ______.

Answer 14

single
epithelial cells
55
65
fluid
solutes

Question 15

Each nephron receives its blood supply from a tiny branch of a ______ ______ _______ known as an ________ ______.

The afferent arteriole supplies blood to a dense network of capillaries called the ________ that sits inside the cup-shaped ________ capsule of the tubule.

The blood flows out of this capillary network into a vessel known as an ________ _______. The glomerular capsule and glomerulus are collectively known as the ________ _______.

Blood flowing out of the glomerulus into the efferent arteriole then enter a complex capillary network that is closely associated with the renal tubule and are therefore referred to as the _________ _______.

These capillaries eventually drain into the ________ ______ _____.

Answer 15

cortical radiate artery
afferent arteriole
glomerulus
glomerular
efferent arteriole
renal corpuscle
peritubular capillaries
cortical radiate veins

Question 16

the blood flow to a nephron

Answer 16

afferent arteriole – glomerulus – efferent arteriole – peritubular capillaries

Question 17

define renal capsule

Answer 17

thin membranous sheath that covers the outer surface of each kidney

Question 18

define capsular space

Answer 18

The slitlike space between the visceral and parietal layers of the capsule of the renal corpuscle

Question 19

define renal corpuscle

Answer 19

filtration unit of vertebrate nephrons, functional units of the kidney. It consists of a knot of capillaries (glomerulus) surrounded by a double-walled capsule (Bowman’s capsule) that opens into a tubule.

Question 20

The majority of nephrons have their renal corpuscles located in the outer portion of the cortex and a loop of Henle that only penetrates a short distance into the medulla. These are referred to as _______ ______ and constitute approximately __% of the population.

In the remaining __% of nephrons the renal corpuscles are located at the border of the cortex and medulla so have a ____ __ ____ that penetrates deep into the medulla. These are known as ________ ________.

Answer 20

cortical nephrons
85
15
loop of Henle
juxtamedullary nephrons

Question 21

• Associated with the wall of the tubule are a group of cells collectively referred to as the ______ ____.
  
  • Associated with the afferent arteriole are another group of cells known as ________ _____ and these are innervated by sympathetic postganglionic neurones.
    Together these cells are known as the ___________ ______. The juxtaglomerular cells secrete the enzyme ____ which plays a very important role in sodium homeostasis

Answer 21

macula densa
juxtaglomerular cells
juxtaglomerular apparatus
renin

Question 22

Be able to describe the basic renal process of glomerular filtration, tubular reabsorption and tubular secretion.

Answer 22

The first stage of the process is the movement of fluid and dissolved solutes from the capillaries of the glomerulus into the glomerular capsule. Because of its microscopic structure the renal corpuscle acts like a molecular sieve that allows fluids and small molecules (but not large molecules or cells) to move from the blood in the glomerulus into the glomerular capsule. This fluid is known as glomerular filtrate and the process is referred to as glomerular filtration.

The glomerular filtrate then moves along the length of the renal tubule during which some materials move back into the blood of the peritubular capillaries (a process known as tubular reabsorption) whilst others move from the peritubular capillaries into the renal tubule (tubular secretion).

Anything left in the filtrate flowing out of the collecting ducts leaves the body as urine and anything left in the peritubular capillaries is returned to the systemic circulation

Question 23

Understand the basic principles of membrane transport with particular emphasis on active transport, passive transport and osmosis.

Question 24

Be able to describe how the spaces between endothelial cells lining the walls of the glomerular capillaries and the epithelial cells forming the glomerular capsule combine to form a filtering membrane.

Answer 24

The endothelial cells of the glomerulus and the epithelial cells forming the wall of the glomerular capsule form what is often referred to as the filtering membrane.

Because of the large number of nephrons the total surface area of the filtering membrane of the kidneys is over 1 m2 and the cells that form it have a number of structural specialisations that assist in its role as a molecular sieve:

Between adjacent endothelial cells lining the walls of the glomerular capillaries there are tiny gaps that make these capillaries around 50 times more permeable than other capillaries in the body. The term ‘fenestra’ is Latin for window so this is often referred to as a fenestrated endothelium.
The epithelial cells forming the glomerular capsule are known as podocytes as they have foot-like processes that adhere to the capillaries. Although these processes enable a strong attachment between the glomerular capsule and the glomerulus there are spaces between them known as filtration slits.

Question 25

The filtering membrane offers very little resistance to substances up to _ nm in diameter. Molecules of - nm in diameter become increasing restricted and above that the filtering membrane acts as an effective barrier. Consequently the fluid that reaches the lumen of the glomerular capsule contains small molecules at concentrations virtually the same as those found in plasma, but virtually no ______ or substances that are bound to plasma proteins (such as calcium and some hormones).

Answer 25

3
3-9
restricted
small
plasma
proteins

Question 26

Understand what glomerular filtration rate is and why it is such an important determinant of renal function.

Answer 26

he rate at which fluid moves into the glomerular capsule is termed the glomerular filtration rate

Question 27

Be able to describe the difference between hydrostatic pressure and oncotic pressure and know the typical values of these in healthy humans

Answer 27

Hydrostatic Pressure: This is the pressure exerted by a fluid (in this case, blood) against a surface. In the context of the kidneys, it refers to the pressure of the blood in the glomerular capillaries. In this case, it’s around 45 mmHg. This pressure tends to push fluid out of the capillaries and into the glomerular capsule.

Oncotic Pressure: This is the osmotic pressure caused by the presence of proteins in a fluid. In the kidneys, it’s mainly due to proteins in the blood. Because the filtering membrane of the nephron allows water to pass through but not proteins, the presence of proteins creates an osmotic pressure. In the glomerular capillaries, the oncotic pressure is around 25 mmHg, while in the tubules (where there are no proteins), it’s effectively zero. This pressure tends to pull water back into the capillaries from the tubules.

So, in summary:

Hydrostatic pressure pushes fluid out of the glomerular capillaries into the glomerular capsule.
Oncotic pressure pulls water back into the glomerular capillaries from the tubules

Question 28

Be able to calculate net filtration pressure and understand how it can be altered by severe malnutrition and kidney stones.

Answer 28

In severe malnutrition plasma protein levels can fall quite dramatically and this decreases plasma oncotic pressure and results in increased GFR.
Blockage of the ureter by kidney stones or an invasive tumour can increase tubular hydrostatic pressure and results in decreased GFR.

Question 29

Understand the basis for using creatinine and inulin to calculate glomerular filtration rate.

Answer 29

Theoretically, one of the best substances for the measurement of GFR is the polysaccharide inulin because it is completely filtered and neither secreted nor reabsorbed by the tubule. Following injection inulin becomes distributed evenly thoughout the plasma and if you measure its plasma concentration, urine concentration and urine flow rate you can calculate glomerular filtration rate.
The problem with inulin is that it isn’t found naturally in the body so must be administered by a continuous intravenous infusion to obtain the steady-state plasma concentrations required to measure GFR. Creatinine however is a naturally occurring metabolite that is produced at fairly constant rate by skeletal muscle. As it is freely filtered it is often used in more routine measure of GFR.

Question 30

Explain why glomerular filtration rate remains remarkably constant despite changes in mean systemic blood pressure.

Answer 30

When you measure renal blood flow and GFR these remain remarkably constant despite changes in systemic blood pressure over the range 90 – 200 mmHg. Interestingly you see exactly the same effect in isolated kidneys which means that neither the nervous system nor hormones are responsible. This means that the control must be intrinsic to the kidneys which is why it is referred to as autoregulation.
Autoregulation of renal blood flow and GFR in the face of changes in systemic blood pressure is thought to be due to two mechanisms:
Myogenic regulation
- when pressure in the afferent arterioles increases, the wall of the arteriole stretches
- the smooth muscle in the wall contracts causing constriction and reduced blood flow to the glomerular capillaries
- if systemic blood pressure decreases, the force exerted on the smooth muscle in the afferent arterioles is reduced and the smooth muscle relaxes which causes arteriole dilation and an increase in blood flow

Tubular Glomerular Feedback
- the juxtaglomerular apparatus is a specialised microscopic structure located where the afferent arteriole comes into very close apposition to the distal convoluted tubule of the same nephron
- Tubular glomerular feedback involves the juxtaglomerular apparatus detecting the rate at which filtrate flows into the distal convoluted tubule and automatically adjusting GFR to keep this constant.
- the macula densa cells in the distal convoluted tubule are sensitive to sodium chloride. If GFR increases the flow rate in the tubule increases which delivers more sodium chloride to the distal convoluted tubule. Detection of the increase in sodium chloride triggers the release of local chemical mediators from the macula densa which causes constriction of the afferent arteriole and dilation of the efferent arteriole

Question 31

Understand that tubular epithelial cells are connected by tight junctions with lateral spaces behind them, have a luminal and basolateral surface and that material can move by either transcellular or paracellular routes.

Answer 31

• the walls of the peritubular capillaries are highly permeable and most materials moving between the interstitial space and the lumen of the capillaries do so by simple diffusion
• Movement across the tubular epithelial cells however is more complex and in some instances highly regulated.
• the cells are usually held together by specialised tight junctions with narrow intercellular spaces known as lateral spaces behind them
• Absorption or secretion can involve substances moving through the tubular epithelial cells (transcellular route) or between them (paracellular route)
• When a substance moves by the transcellular route it has to cross two plasma membranes. To simplify things when describing these we refer to the one closest to the lumen the luminal membrane and the one facing the interstitial space the basolateral membrane.
  -Movement across the tubular epithelial membrane by the transcellular route normally involves active transport across one membrane and diffusion across the other. Movement through the tubular epithelial membrane by the paracellular route is normally mediated by diffusion.

Question 32

Appreciate that whilst the reabsorption of some physiologically-important substances is very carefully regulated by the kidney, the reabsorption of others is not.

Answer 32

• glucose and amino acids are not controlled
• sodium and water is very carefully controlled

Question 33

Understand the mechanisms by which sodium moves across the luminal and basolateral membrane during tubular reabsorption.

Answer 33

• Na+ simply diffuse across the luminal membrane -> tubular epithelial cells through Na+ channels down their concentration gradient
• inside the tubular cells, Na+ is actively transported across the basolateral membrane against its concentration gradient by a sodium-potassium exchange pump powdered by the hydrolysis of ATP
• most of Na+ pumped into the lateral spaces
• Na+ reaches interstitial space and moves into the pertibular capillary by diffusion
• 70% reabsorption by proximal convoluted tubule, 30% by loop of Henle and distal convoluted tubule

Question 34

Understand that osmolarity is the driving force for the reabsorption of water and be able to describe the routes by which water can move across the wall of the tubule.

Answer 34

• The movement of sodium (and other solutes) out of the tubule and into the interstitial space on the other side of the tubular epithelial cells reduces the osmolarity of the tubular fluid and increases the osmolarity of the interstitial fluid.
• this difference in osmolarity across the tubular membrane means that there is a higher concentration of water in the tubular fluid than the interstitial space. Consequently water will flow from the tubular fluid into the interstitial fluid by osmosis.
• Water can move through the tubular epithelial cells by the transcellular route because of the presence of water channels (aquaporins) in both the luminal and basolateral membranes. In addition water can take the paracellular route by leaking through the tight junctions that hold adjacent epithelial cells together.

Question 35

Be able to describe the mechanism by which glucose is reabsorbed in the proximal convoluted tubule.

Answer 35

• just about completely absorbed & occurs almost entirely in the proximal convoluted tubule
• Glucose is transported across the luminal membrane by active transport using a transporter that moves both glucose and sodium into the cell simultaneously.
• form of active transport known as cotransport where the driving force for the movement of one of the molecules is the concentration gradient created by the active transport of the other.
• Once it is inside the cell glucose moves across the basolateral membrane by facilitated diffusion and then diffuses into the peritubular capillaries via the interstitial fluid space.

Question 36

Be able to describe the mechanism by which amino acids are reabsorbed.

Answer 36

Like glucose, amino acids are small enough to be freely filtered at the glomerulus so are found in the filtrate at the same concentration as in plasma.
And just like glucose, amino acids are reabsorbed by cotransport with sodium across the luminal membrane using the sodium concentration gradient as the driving force. Because of the diversity in their structure there is a different carrier for each of the major amino acids.
Once the amino acids are inside the cell they then move across the basolateral membrane by facilitated diffusion and subsequently diffuse into the peritubular capillaries.

Question 37

Know what urea is and why it is reabsorbed.

Answer 37

• waste product produced by metabolism of protein and is small enough to be freely filtered by the glomerulus so is present in tubular fluid at the same concentration as plasma.
• Although urea is a waste product about 50% of it is actually reabsorbed by the proximal convoluted tubule. This occurs because the reabsorption of water and other solutes (described above) causes an increase in the urea concentration in the filtrate.

Question 38

Understand the concept of transport maximum and the consequences of it being exceeded in people with diabetes mellitus.

Answer 38

Once all of the proteins are saturated no more substance can be transported and the maximum rate of transport has been achieved. This point is referred to as the transport maximum (Tm) for that substance.
Of course the Tm for physiologically important substances is usually very high (and rarely exceeded) but when it is these substances are eliminated from the body in urine. For example the Tm of glucose in an adult is around about 375 mg/min which ensures that virtually all of the filtered glucose is reabsorbed. In individuals with poorly controlled diabetes however the plasma glucose levels are so high that the amount of glucose in the filtrate exceeds the Tm and large amounts of glucose begin to appear in the urine.

Question 39

Understand the physiological significance of tubular secretion and the types of substances that end up in the urine as a consequence of this process.

Answer 39

• potassium - due to secretion by the distal convoluted tubule and upper parts of the collecting duct
• hydrogen ions - important in maintaining control of the pH of the blood (7.3-7.4)
• urea, ammonium ions and creatinine as well as some drugs (e.g. penicillin and aspirin) are eliminated from the body by secretion into the tubule.

Question 40

Appreciate that maintaining plasma osmolarity in the face of huge variations in fluid volume and electrolyte concentration in our diet requires the production of urine that can vary in osmolarity from 50 – 1400 mOsm/L.

Answer 40

• The osmolarity of plasma for example is maintained within 5 mOsm/L of its normal value (around 290 mOsm/L)
• Thus when dietary intake of water exceeds that which is required to maintain the osmolarity of the plasma, less water is reabsorbed, resulting in more water being eliminated and dilute urine being produced as a consequence.
• Similarly when fluid intake is less than required to maintain plasma osmolarity, more water is reabsorbed, less water is eliminated and concentrated urine is produced.

Question 41

Be able to describe the physiological mechanisms by which dilute and concentrated urine are produced.

Answer 41

A. Dilute Urine Production
- All the nephron has to do is reabsorb solute from a portion of the tubule that is impermeable to water
- If the solutes are removed and water can’t follow, the osmolarity of the tubular fluid decreases which results in the production of dilute urine.

• When increased water loss is required to maintain plasma osmolarity, the terminal portions of the nephron (ascending loop of Henle, distal convoluted tubule and collecting duct) reabsorb Na+, Cl- and other solutes.
• In this state, these portions of the tubule are essentially impermeable to water so it cannot follow the solutes and consequently the osmolarity of the tubular fluid decreases.
• As a result of this solute reabsorption the tubular fluid flowing into the renal pelvis can be as low as 50 mOsm/L and the urine is dilute.

B. Concentrated Urine Production
- Reducing water loss requires the production of urine which is more concentrated than plasma
- water can only move across membranes passively (i.e. down its concentration gradient). Consequently to get water out of the tubule (and thus concentrate the urine) it has to pass through a region of the kidney where the osmolarity of the interstitial space is much higher than the tubular fluid.

Fortunately this is exactly what you find if you measure the osmotic pressure at different depths of the medulla. The osmolarity of the interstitial fluid at the cortical-medullary boundary is around 300 mOsm/L and this gradually increases to about 1400 mOsm/L at the tip of the loops of Henle. This is referred to as the medullary osmotic gradient and is the key to the production of highly concentrated urine.

Let’s not worry too much about how this osmotic gradient is produced but just accept that it is there. Because of the removal of sodium and other solutes by the ascending limb of the loop of Henle (described above) the osmolarity of the tubular fluid flowing into the distal convoluted tubule is very low (around 100 mOsm/L).

As we saw in the previous section, the membrane of the collecting duct is normally impermeable to water. However when conservation of water is required, the permeability of the collecting duct to water increases. As the osmolarity of the interstitial fluid is higher than the fluid in the collecting duct, water is able to move out of the collecting duct down its concentration by osmosis.

This reabsorption of water of course causes the osmolarity of the fluid to increase as it flows along the collecting duct. But because of the medullary osmotic gradient, the osmolarity of the adjacent interstitial space also increases, so water will continue to be reabsorbed along the length of the collecting duct.

This reabsorption of water back into the interstitial space will continue until the tubular fluid has the same osmolarity as the deepest parts of the medulla or it flows out of the collecting duct into the renal pelvis. Through this mechanism water reabsorption is maximised and the urine becomes concentrated.

Water which has moved from the tubule to the interstitial space diffuses into the adjacent peritibular capillaries and is returned to the systemic circulation.

How much water is reabsorbed depends upon just how permeable the collecting duct becomes and this is very precisely regulated by the control systems we will discuss in the next section. However what the medullary osmotic gradient does permit is the production of urine which has a much higher osmolarity thant plasma. In fact during serious dehydration, when the water permeability of the collecting ducts is at its highest, the osmolarity of the urine can become as high as the interstitial fluid in the deeper regions of the medulla (1400 mOsm/L).

Question 42

Understand why water balance is important and how the osmolarity of plasma is modified by changes in fluid intake.

Answer 42

• the maintenance of water balance is a very important physiological function of the urinary system
• changes in fluid intake (or fluid loss) have an immediate and direct effect on the osmolarity of extracellular fluid
• increasing water intake decreases the osmolarity of plasma whilst dehydration increases it
• Consequently water balance is regulated through the control of plasma osmolarity

Question 43

Know what the neurones responsible for monitoring plasma osmolarity are called, where they are located and where they project to.

Answer 43

Changes in plasma osmolarity resulting from changes in water balance are detected by neurones in the brain know as osmoreceptors. These neurones are located in the supraoptic and paraventricular nuclei of the hypothalamus and respond to very small changes (as little as 3 mOsm/L) in the osmolarity of the blood flowing past them.

Question 44

Be able to explain the physiological mechanisms responsible for restoring water balance in a dehydrated subject.

Answer 44

In response to an increase in the osmolarity of the extracellular fluid surrounding osmoreceptors these neurones shrink which triggers an increase in the frequency of action potentials travelling long their axons.
Some of these neurones have axons that project out of the hypothalamus to other parts of the brain and are responsible for initiating the sensation of thirst.
Other osmoreceptors have axons that project into the posterior pituitary gland and secrete antidiuretic hormone (ADH; also known as vasopressin) into the blood stream.
The major effects of ADH in the kidney are mediated by its binding to V2 receptors on the basolateral membrane of the epithelial cells forming the wall of the collecting ducts.
Through a fairly complex intracellular cascade this binding results in the insertion of more aquaporins (water channels) into the luminal membrane which increases the permeability of the collecting duct to water.
Because of the existence of the medullary osmotic gradient (described in the previous module) water flows out of the collecting duct down its concentration gradient into the interstitial fluid and then into the adjacent peritubular capillaries. By increasing the number of aquaporins ADH increases the permeability of the collecting duct to water so enhances water reabsorption.
A secondary effect of ADH is to increase the permeability of the collecting duct to urea through expression of a specific urea transporter. Thus in the presence of ADH more urea is recycled into the medulla which increases the medullary osmotic gradient that also enhances water reabsorption.
So in response to increased circulating levels of ADH there is increased water reabsorption by the kidney and consequently the production of concentrated urine. This decrease in the excretion of water together with the increased fluid intake associated with the sensation of thirst reverses the increase in osmolarity and restores water balance.

Question 45

Be able to explain the physiological mechanisms responsible for the restoration of water balance in a subject who has consumed 3 litres of tap water.

Answer 45

As there is a small but significant level of ADH secretion at normal plasma osmolarity (290 mOsm/L) ADH can also help regulate fluid balance in response to increased fluid intake.
In response to a dramatic decease in plasma osmolarity (produced for example by the consumption of 3 litres of ice-cold foaming Coopers Sparkling Ale) plasma osmolarity will drop.
As a consequence osmoreceptor activity will decline, circulating levels of ADH will drop and the permeability of the collecting ducts to water (and urea) will decrease. As a result less water reabsorption occurs, there will be an increase in the volume of dilute urine produced and water balance will be restored.

Question 46

Understand why sodium homeostasis is important for the maintenance of health.

Answer 46

With a plasma concentration of 135 - 145 mmol/L, sodium is the major solute present in extracellular fluid and plays an important role in the function of the excitable tissues found in the nervous, cardiovascular and musculoskeletal systems. In addition sodium is the single most important determinant of plasma fluid volume. If plasma sodium levels fall, less water is required to maintain the osmolarity of the plasma so water is eliminated, plasma fluid volume will decrease and blood pressure falls. On the other hand, if plasma sodium increases, more water is required to maintain the osmolarity so water is conserved and blood pressure increases. Given these very important physiological roles it is perhaps not surprising then that the homeostatic regulation of sodium is essential for the maintenance of health.

Question 47

Understand that plasma sodium levels cannot be determined directly but are detected indirectly by the changes in blood pressure.

Question 48

Be able to describe the physiological processes that are responsible for the control of sodium reabsorption in response to low and elevated levels of plasma sodium levels.

Answer 48

• baroreceptors provide a very good (although indirect) measure of plasma sodium
• The key step in the control of sodium reabsorption is the secretion of the enzyme renin by the juxtaglomerular cells associated with the afferent arteriole in the juxtaglomerular apparatus.
• In response to sodium depletion, renin secretion increases and this triggers a cascade of events that leads to increased sodium reabsorption and hence decreased sodium excretion
• (i) Renin released by the juxtaglomerular cells diffuses into the bloodstream and converts angiotensinogen (a large plasma protein secreted by the liver) into a smaller polypeptide called angiotensin I.
  (ii) Angiotensin I is then converted to angiotensin II by angiotensin converting enzyme (ACE) located on the luminal surface of capillary endothelial cells.
  (iii) Angiotensin II in turn stimulates the release of the steroid hormone aldosterone from the zona glomerulosa cells of the adrenal cortex.
  (iv) Aldosterone stimulates the synthesis of the proteins required to build sodium channels and the sodium-potassium exchange pump in the tubular epithelial cells of the distal convoluted tubule and the cortical portion of the collecting ducts.
  (v) This results in greatly enhanced transport of sodium out of these portions of the tubule and enhanced reabsorption of sodium by the kidney.
• in response to elevated plasma sodium the whole thing works in reverse as renin secretion decreases with the end result being a decrease in aldosterone secretion and a decrease in reabsorption leading to increased sodium excretion.
• the renin-angiotensin system.

Question 49

Appreciate the important role that secretion of renin plays in the control of sodium reabsorption and be able to describe the physiological processes that regulate renin secretion.
(ii) Intrarenal Baroreceptors
The juxtaglomerular cells within the kidney are closely associated with the afferent arteriole and are very sensitive to the _____ _ ________ in these blood vessels. When plasma volume decreases there is a decrease in renal blood pressure which reduces the degree to which the juxtaglomerular cells are stretched. In response to reduced stretch these cells release more renin. Because they respond to changes in blood pressure within the kidney these juxtaglomerular cells act as ________ ________.

Answer 49

degree of stretch
intrarenal baroreceptors

Question 49

Appreciate the important role that secretion of renin plays in the control of sodium reabsorption and be able to describe the physiological processes that regulate renin secretion.
(i) Systemic Baroreceptors
In response to declining plasma volume there is a drop in venous pressure, atrial pressure and arterial blood pressure that are detected by ______, ____ and _____ _________. This information is relayed to the medullary cardiovascular control centres which respond reflexly by increasing activity in ____ _______ ______ innervating the juxtaglomerular cells of the kidney. These cells respond by increasing the release of renin.

Answer 49

venous, atrial and arterial baroreceptors
renal sympathetic neurones

Question 49

Urine leaving the kidney is transported along the length of the ureters by ______ _____ produced by the contraction of the smooth muscle of the _______ _____. These waves travel the length of the ureters approximately _ times per minute and ensure that the urine reaches the bladder whether you are lying down, standing on you head or living in zero gravity in the International Space Station

Answer 49

peristaltic waves
muscularis layer
5

Question 49

Appreciate the important role that secretion of renin plays in the control of sodium reabsorption and be able to describe the physiological processes that regulate renin secretion.
(iii) Macula Densa
The macula densa is part of the juxtaglomerular apparatus and is associated with the ______ _______ ______. The cells of the macula densa are sensitive to ______ levels in the tubular fluid as well as tubular ____ ___:
- If sodium intake is ____, less is filtered by the glomerulus so less is detected by the macula densa
- If renal blood pressure is _______ then glomerular filtration rate is reduced so less fluid enters the tubule and tubular flow rate is reduced.
In response to low tubular sodium concentration and reduced tubular flow detected by the macula densa the juxtaglomerular cells increase ____ secretion.

Answer 49

distal convoluted tubule
sodium
flow rate
low
decreased
renin

Question 50

Normally hydrated humans produce urine at about _ mL.min-1 and this is stored in the bladder until it is convenient and/or socially-acceptable to dispose of it. Because of its ______ shape and its ability to _____ (due to the presence of the rugae) the _____ in the bladder doesn’t increase markedly as the bladder begins to fill.

Answer 50

1
spherical
distend
pressure

Question 51

Like the ureters the bladder is lined by _______ epithelium. This type of epithelium is only found in the urinary system as a couple of very useful features:
- The _____ shaped cells on its surface allow it to tolerate a lot of _______ without leaking.
- It is a ________ epithelium so consists of multiple layers of cells piled on top of each other. Because of this it essentially _______ so there is no reabsorption of salts or water.

Answer 51

transitional
dome
stretching
stratified
impermeable

Question 52

Understand the functional significance of the detrusor muscle, internal urethral sphincter and external urethral sphincter in micturition.

Answer 52

The muscularis layer of the bladder is made up of three fairly thick layers of smooth muscle that are sometimes referred to collectively as the detrusor muscle. Contraction of this muscle is regulated by the parasympathetic division of the autonomic nervous system
and is responsible for the generation of the quite high forces inside the bladder during micturition (see dotted line in above graph).
The wall also contains sensory neurones that are sensitive to its tension.
These stretch receptors relay information about the fullness of the bladder to the central nervous system.
In both sexes the movement of urine from the bladder into the urethra is regulated by the internal urethral sphincter which is located at the junction between the bladder and the urethra.
It consists of a specialised thickening of the detrusor muscle and when closed prevents the movement of urine into the urethra. This sphincter is under the control of the parasympathetic division of the autonomic nervous system so is NOT under voluntary control.
Movement of urine along the urethra is regulated by the external urethral sphincter made up of skeletal muscle surrounding the urethra as it penetrates the pelvic floor.
This sphincter is fairly near the external urethral orifice in women and just below the prostate gland in men. As this sphincter contracts it compresses the urethra and prevents the flow of urine. Being skeletal muscle the external urethral sphincter IS under voluntary control and is innervated by somatic motoneurones.

Question 53

Be able to describe the elements that cooperate in order to regulate the filling phase of micturition

Answer 53

As the bladder starts to fill the stretch receptors in the wall of the bladder begin to signal this to the spinal cord and brain.
These stretch receptors excite an interneurone in the spinal cord
which in turn activates the parasympathetic neurones innervating the detrusor muscle (causing it to contract) and the internal sphincter (encouraging its opening).
This simple spinal reflex is known as the micturition reflex.
If bladder emptying isn’t appropriate then this reflex is consciously inhibited
by a descending pathway from the brain.
In addition we make a conscious effort to keep the external sphincter closed through a descending pathway that increases activity in the somatic motoneurones that innervate them.
As the bladder increases in volume it becomes increasingly more difficult to override the micturition reflex and at around 600 ml bladder fullness starts to cause pain and emptying difficult to stop.

Question 54

Be able to describe the elements that cooperate in order to regulate the emptying phase of micturition

Answer 54

In order to initiate emptying, the inhibitory influence of the brain over the micturition reflex is consciously removed
As a result the parasympathetic activity to the detrusor muscle and the internal urethral sphincter increases.
This causes the wall of the bladder to contract and the internal urethral sphincter to open.
At the same time the descending activation of the somatic motoneurones innervating the external urethral sphincter is reduced so the sphincter opens.
With a dramatic increase in pressure and the opening of both sphincters urine is forced out of the bladder through the urethra.
The movement of urine in the urethra is detected by another population of sensory neurones known as flow receptors. Activity in these flow receptors signals that micturition has started and provides a positive feedback loop to the brain and spinal cord that increases detrusor muscle contraction and sphincter opening and results in a marked increase in urine flow.
Because of this positive feedback loop once emptying has started it normally continues until the bladder is empty (although it can be stopped by the voluntary contraction of external sphincter if you are standing beside what you thought was a quiet stretch of the New England Highway in the middle of the night and a police car appears out of nowhere).

Question 55

Understand some of the causes of urinary incontinence.

Answer 55

• Paraplegics - damaged spinal cord
• babies or poorly coordinated children - easily overpowered by the micturition reflex
• natural child-birth - stretching of the pelvic floor can result in weakening of the external sphincter resulting in postpartum urinary incontinence

Question 56

If the glomerular hydrostatic pressure is 45 mmHg, the pressure in the glomerular capsule is 11 mmHg and plasma colloid osmotic pressure is 7 mmHg, then the net filtration pressure from capillary to capsular space is which of the following?

Answer 56

27 mmHg

Question 57

Which of the following structures involved in micturition are innervated by parasympathetic neurones?

1. The internal urethral sphincter
2. The detrusor muscle.
3. The external urethral sphincter

Answer 57

1 and 2

Question 58

In the following list, which components are parts of the juxtaglomerular apparatus?

Afferent arteriole.
Macula densa.
Peritubular capillaries.
Collecting duct.

Answer 58

Afferent arteriole.
Macula densa.

Question 59

Glucose is not found in the urine of a healthy person for which of the following reasons?

Answer 59

it is fully reabsorbed

Question 60

Which of the following is the correct sequence of blood vessels through which blood moves after it leaves the renal artery?

Answer 60

segmental arteries - lobar arteries - interlobar arteries - arcuate arteries

Question 61

Which of the following is the correct order through which blood flows in a nephron?

Answer 61

afferent arteriole – glomerulus – efferent arteriole – peritubular capillaries

Question 62

Which of the following statements is FALSE?
juxtamedullary nephrons constitute approximately 15% of the total population of nephrons
the renal corpuscles of juxtamedullary nephrons are located deep within the medulla
cortical nephrons constitute approximately 85% of the total population of nephrons
cortical nephrons have a loop of Henle that is only penetrates a short distance into the medulla
cortical nephrons have their renal corpuscles located in the outer portion of the cortex

Answer 62

the renal corpuscles of juxtamedullary nephrons are located deep within the medulla

Question 63

Which of the following is NOT a consequence of renal failure?
pulmonary oedema
anaemia
acidosis
hypotension
cardiac arrhythmias

Answer 63

hypotension

Question 64

Which of the following is the correct sequence of structures through which tubular fluid flows in a nephron?

glomerulus – distal convoluted tubule – loop of Henle – proximal convoluted tubule
glomerulus – proximal convoluted tubule – loop of Henle – distal convoluted tubule
glomerular capsule – proximal convoluted tubule – loop of Henle – distal convoluted tubule
glomerulus – distal convoluted tubule – loop of Henle – proximal convoluted tubule
glomerular capsule – distal convoluted tubule – loop of Henle – proximal convoluted tubule

Answer 64

glomerular capsule – proximal convoluted tubule – loop of Henle – distal convoluted tubule

Question 65

Which of the following is/are functions of the urinary system?

1. regulation of the volume of extracellular fluid.
2. elimination of metabolic waste products.
3. synthesis of glucose during prolonged fasting.

Answer 65

all

Question 66

The macula densa cells respond to which of the following?

changes in pressure in the tubule
changes in levels of antidiuretic hormone
changes in blood pressure
changes in composition of the tubular fluid
changes in levels of aldosterone

Answer 66

changes in composition of the tubular fluid

Question 67

Which of the following statements is CORRECT?

antidiuretic hormone release is stimulated by a low osmolarity of extracellular fluid
the ingestion of a large volume of water inhibits the release of antidiuretic hormone
water reabsorption is under the control of the anterior pituitary gland
antidiuretic hormone acts on the kidney proximal tubules
antidiuretic hormone is released when venous return to the atria is increased

Answer 67

the ingestion of a large volume of water inhibits the release of antidiuretic hormone

Question 68

In a nephron the macula densa is part of which of the following structures?

Answer 68

distal convoluted tubule

Question 69

When a substance is reabsorbed from the proximal convoluted tubule into the peritubular capillaries how many cells does it have to traverse?

Answer 69

2

Question 70

Which of the following is/are involved in the reducing water loss in response to dehydration?

The production of urine that has a lower osmolarity than plasma.
The cortical osmotic gradient.
An increase in the permeability of the collecting duct to water.

Answer 70

An increase in the permeability of the collecting duct to water.

Question 71

Which of the following structures is/are part of a renal corpuscle?

1. glomerulus.
2. glomerular capsule.
3. distal convoluted tubule.

Answer 71

1 and 2

Question 72

The sodium-potassium exchange pump powered by the hydrolysis of ATP that plays an important role in tubular reabsorption

is located on which of the following?

Answer 72

basolateral membrane of tubular cells

Question 73

In a normal healthy individual, what would happen to glomerular filtration rate (GFR) if mean systemic blood pressure DECREASED from 90 to 70 mmHg?

Answer 73

GFR wouldn’t change

Question 74

Which of the following statements is FALSE?
Glucose is almost completely reabsorbed from the tubule.
The reabsorption of sodium is very carefully regulated to maintain salt balance.
The reabsorption of water is very carefully regulated by the kidney.
Amino acids are almost completely reabsorbed from the tubule and returned to the blood stream.
The kidney carefully regulates the reabsorption of glucose to control blood glucose levels.

Answer 74

The kidney carefully regulates the reabsorption of glucose to control blood glucose levels.