Urinary System Flashcards
1
Q
How are the homeostatic and excretory function of the kidneys enabled?
A
Filtration of large volumes of blood plasma followed by the selective reabsorption of required elements from the filtrate or the secretion of other materials into the filtrate
2
Q
Failure of the kidneys is characterised by a number of pathological changes. Name them
A
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.
3
Q
As well as these important roles in the maintenance of the volume and composition of body fluids the kidneys are also responsible for the synthesis and release of a number of physiologically important compounds. Name them
A
Glucose (during prolonged fasting)
The hormone erythropoietin (involved in red blood cell production)
The enzyme renin
4
Q
On average how much urine is excreted per day?
A
1000 - 2000 ml.day-1
5
Q
What is the structure of the kidneys where the ureter, major blood vessels, lymphatic vessels and nerves enter?
A
Renal hilum
6
Q
What is the superficial (outer) lighter-coloured layer of the kidney called?
A
Renal cortex
7
Q
What is the deeper dark coloured layer of a kidney and what does it consist of?
A
Renal medulla that is characterised by cone shaped renal pyramids
8
Q
What is the single large cavity that collects urine and is continuous with the ureter in a kidney?
A
Renal pelvis
9
Q
What is a ‘lobe’ when referred to kidneys?
A
Each renal pyramid together with it’s adjacent cortical tissue. Around 8 per kidney
10
Q
What are the 3 major layers of the ureters and what are they made of?
A
An outer layer of connective tissue known as the adventitia
A middle layer made up primarily of smooth muscle and referred to as the muscularis
An inner mucosa layer that consists of a lining of transitional epithelial cells and its supporting connective tissue
11
Q
Where does the ureters penetrate the bladder? How does this help with urine storage?
A
Posterior wall at oblique angle because as the bladder fills with urine, this compresses the distal portion of the ureters and prevents back flow of urine
12
Q
How does the ureters transport urine to the bladder?
A
Peristaltic waves produced by contractions of the smooth muscle in the muscularis layer
13
Q
What are the folds in the urinary bladder and how do they change?
A
Rugae. As it fills it extends upwards, the walls are stretched and as it reaches its limit of 800 – 1000 ml the rugae disappear.
14
Q
What are the 3 major layers of the ureters and what are they made of? What is its function?
A
An outer layer of connective tissue known as the adventitia.
The middle muscularis layer made up of three fairly thick layers of smooth muscle and sometimes referred to collectively as the detrusor muscle.
An inner mucosa layer made up of a lining of transitional epithelial cells and its supporting connective tissue.
Ureters transport urine from kidneys to bladder. Smooth muscle contraction of muscularis layer causes peristaltic waves that propel urine across ureters
15
Q
The triangular area defined by the openings of the ureters and urethra is known as? Why is this region clinically important?
A
Trigone. It is often the site of persistent bacterial infections of the urinary tract.
16
Q
What are the 3 parts of the male urethra and what is its total length approximately?
A
Prostatic Urethra: The 2-3 cm portion which runs through the middle of the prostate gland where it fuses with the ejaculatory ducts
Membranous Urethra: A short portion at the base of the prostate gland
Penile Urethra: The major constituent of the urethra which runs through the penis
Approx 20cm
17
Q
How long is the female urethra and where is it located?
A
The urethra is approximately 4 cm long, is located immediately behind the pubic symphysis and has its external orifice between the vaginal opening and the clitoris.
18
Q
What are the 2 sphincters that regulate the movement of urine along the urethra?
A
The internal urethral sphincter 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.
The external urethral sphincter consists of skeletal muscle surrounding the urethra as it penetrates the pelvic floor. As this sphincter contracts it compresses the urethra and prevents the flow of urine.
19
Q
How much cardiac output does the kidneys receive?
A
1/4 of total output (approximately 1200 ml/min) through the renal arteries (which are branches of the abdominal aorta).
20
Q
How is blood supplied to the cortex of kidneys?
A
Just outside the kidney each renal artery divides to form 5 segmental arteries and on entering the renal pelvis each of these divides to form a variable number of lobar arteries which, as the name suggests, supplies blood to a single lobe. These then divide into interlobar arteries (which run between the renal pyramids) then divide to form arcuate 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 cortical radiate arteries
21
Q
How does blood drain from the kidneys?
A
Blood from the cortex flows into cortical radiate veins that fuse to forms the arcuate veins. The arcuate veins fuse to form the interlobar veins than drain directly into the renal vein (as there are no lobar or segmental veins) and hence into the inferior vena cava.
22
Q
What is the major innervation of the kidneys?
A
the sympathetic division of the autonomic nervous system. The postganglionic neurones innervate a number of structures within the kidney
23
Q
What are nephrons?
A
functional units of the kidney each of which has around 1.2 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 tubule made up of epithelial cells and its associated blood supply.
24
Q
How is the tubule well designed for regulating the movement of fluid and solutes?
A
the tubule has a very high surface area:volume ratio
25
Where does filtration take place and where filtrate enters the tubule?
glomerular (or Bowman’s) capsule
26
What structure comes before the loop of Henle in filtration?
Proximal convoluted tubule
27
How does diameter of loop of Henle change?
Gets smaller toward the deeper portions of the loop (at descending and ascending limbs)
28
What structure is often closely associated with the glomerular capsule in the cortex?
distal convoluted tubule
29
What is the function of a collecting duct in tubule?
filtrate flows into the collecting duct which is known as the cortical collecting duct as it passes through the cortex and the medullary collecting duct as it passes through the medulla. The collecting ducts from a number of nephrons fuse and eventually drain into the cavity of the renal pelvis.
30
Where do nephrons receive blood supply from?
tiny branch of a cortical radiate artery known as an afferent arteriole.
31
Where do afferent arterioles supply blood to?
dense network of capillaries called the glomerulus that sits inside the cup-shaped glomerular capsule of the tubule
32
Where does blood from the glomerulus flow to?
efferent arteriole
33
What is the renal corpuscle?
The glomerular capsule and glomerulus
34
Where does blood from the efferent arterioles flow to?
enter a complex capillary network that is closely associated with the renal tubule and are therefore referred to as the peritubular capillaries
35
What do peritubular capillaries drain into?
cortical radiate veins
36
What is the difference between cortical and juxtamedullary nephrons?
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 cortical nephrons and constitute approximately 85% of the population.
In the remaining 15% of nephrons the renal corpuscles are located at the border of the cortex and medulla so have a loop of Henle that penetrates deep into the medulla. These are known as juxtamedullary nephrons.
37
What are the 2 specialised groups of cells where loop of Henle becomes the distal convoluted tubule and the tubule comes in very close apposition to both the afferent and efferent arteriole? What do these cells form and what do they secrete?
Associated with the wall of the tubule are a group of cells (green in the diagram opposite) collectively referred to as the macula densa.
Associated with the afferent arteriole are another group of cells known as juxtaglomerular cells (yellow in the diagram opposite) and these are innervated by sympathetic postganglionic neurones.
Together the macula densa and juxtaglomerular cells are known as the juxtaglomerular apparatus. The juxtaglomerular cells secrete the enzyme renin
38
What is the basic renal process steps?
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.
We can now begin to see how these three basic renal process enable the kidneys to maintain homeostasis of body fluids despite the highly variably nature of fluid and dietary intake. By regulating which substances are filtered, reabsorbed and/or secreted the kidney can control the amount of different substances that are eliminated as urine and therefore the levels that are retained by the body.
39
How do kidneys deal with harmful elevated fluid volume?
decreasing tubular reabsorption of water. If the same amount of fluid is undergoing tubular filtration but there is a reduced tubular reabsorption then more urine will be produced.
40
How does the movement of materials across the walls of the tubule and its associated capillary networks play a very important role in renal function?
If a substance is reabsorbed (i.e. moves from the renal tubule back into the blood stream) then it has to move into and then out of the epithelial cell forming the wall of the tubule and then into and out of the endothelial cells forming the wall of the peritubular capillaries. This means that the substance has to traverse 4 cell membranes as well as the connective tissue layers that support these membranes
41
What is glomerular filtration?
movement of water and solutes from the plasma in the capillary network of the glomerulus into the lumen of the glomerular capsule
42
What is the filtering membrane?
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
43
What is a fenestrated endothelium?
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.
44
What are podocytes and what are filtration slits?
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
45
How does the filtering membrane offer resistance to molecules of different sizes?
The filtering membrane offers very little resistance to substances up to 3 nm in diameter. Molecules of 3-9 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 proteins or substances that are bound to plasma proteins (such as calcium and some hormones).
46
What is glomerular filtration rate? What is main driving force for this?
The rate at which fluid moves into the glomerular capsule which is an important determinant of renal function. Filtration is a passive and fairly non-selective process. The major driving force for the movement of substances from the capillaries of the glomerulus and the lumen of the glomerular capsule is the difference in fluid pressure (known as hydrostatic pressure) between these two compartments.
47
Why is hydrostatic pressure in the glomerular capillaries (45mmHg) much higher than the capillaries that supply other tissues?
Afferent arterioles have a larger diameter than other arterioles (and consequently a lower resistance).
Glomerular capillaries are relatively short so the pressure doesn’t drop significantly along their length.
Efferent arterioles have a smaller diameter than the afferent arterioles (and consequently a higher resistance).
The hydrostatic pressure of the fluid in the glomerular capsule is only 10 mmHg so there is a pressure difference of around 35 mmHg that is responsible for the movement of materials from the capillary into the glomerular capsule.
48
What is the cause of oncotic pressure in the glomerular capillaries?
The filtering membrane of the nephron is just such a membrane as it is freely permeable to water but not proteins. The presence of proteins in the capillaries but not the tubular fluid means there is an osmotic pressure that results in the movement of water from the tubule back into the capillaries. As this osmotic pressure is due almost entirely to proteins that are too large to fit through the filtering membrane it is known as the oncotic pressure.
The oncotic pressure of the beginning of the glomerular capillary network is around 25 mmHg while it is effectively zero in the tubule (where there are no proteins). Consequently there is an osmotic pressure gradient of around 25 mmHg driving the movement of water out of the tubule and into the capillaries.
49
What is net filtration pressure? What is the formula?
The difference between the hydrostatic pressure and the osmotic pressure gradients across the filtering membrane. Determines glomerular filtration rate
NFP= (HPg - HPt) - (OPg - OPt)
HPg = hydrostatic pressure inside the glomerular capillaries.
HPt = hydrostatic pressure inside the glomerular capsule.
OPg = oncotic pressure inside the glomerular capillaries.
Opt = oncotic pressure inside the glomerular capsule.
NFP = net filtration pressure.
50
What pathological conditions have a marked effect on GFR?
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
51
What is glomerular filtration rate formula? How is it determined?
GFR can be calculated by the administration of a marker to the blood and then measuring the amount of the marker that appears in the urine. If the marker substance is small enough to freely cross the filtering membrane then it will have the same concentration in the glomerular filtrate as in the plasma. If the substance is neither reabsorbed nor secreted by the tubule then the rate at which the substance appears in the urine must be the same as the rate at which it is filtered.
GFR= [U]x x V / [P]x
[P]x = Concentration of the marker substance X in the plasma (mg/ml)
[U]x = Concentration of the marker substance X in the urine (mg/ml)
V = urine flow rate (ml/min)
GFR = glomerular filtration rate (ml/min)
52
What are the two most common marker substances used to calculate GFR and why?
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. However there are two problems with using creatinine to measure GFR:
Unlike inulin a small amount of creatinine is secreted into the tubular fluid which would mean that there is more creatinine in the urine than is filtered. This will tend to overestimate GFR.
The techniques used to measure creatinine tend to overestimate its concentration in plasma which will tend to underestimate GFR.
Fortunately these two sources of error cancel each other out and measurements of GFR with creatinine are usually remarkably similar to those obtained with inulin.
52
How is glomerular filtration rate controlled? What two mechanisms are responsible for this?
Autoregulation
Myogenic Regulation:
When pressure in the afferent arterioles increases (due to an increase in systemic blood pressure) this causes the wall of the arteriole to stretch. In response to this stretch the smooth muscle in the wall of the arteriole contracts causing constriction of the arteriole and reduced blood flow to the glomerular capillaries.
Similarly if systemic blood pressure decreases the force exerted on the smooth muscle in the afferent arterioles is reduced and the smooth muscle relaxes. This relaxation results in arteriole dilation and an increase in the blood flow to the glomerular capillaries.
This reflex contraction or relaxation in response to the degree of stretch is an intrinsic property of the smooth muscle cells and as we can see keeps the pressure in the glomerular capillaries remarkably consistent despite fluctuations in systemic blood pressure.
Tubular Glomerular Feedback:
As we have seen previously 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.
Exactly how this regulation works remains speculative. One theory is that 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. This of course will result in a reduction of glomerular capillary hydrostatic pressure causing a drop in GFR.
53
Where are substances transferred to to be reabsorbed? How much substances are reabsorbed?
peritubular capillaries
about 99% of the glomerular filtrate is reabsorbed by the renal tubules and returned to the blood. On the other hand reabsorption of waste products such as urea is relatively incomplete so they end up in the urine.
Whether a substance is reabsorbed or secreted it has to traverse the tubular epithelial cells, the peritubular capillary endothelial cells and the interstitial space between them
54
How do substances move through the tubular epithelial cells?
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.
55
How does sodium reabsorption occur?
Sodium ions simply diffuse across the luminal membrane into the tubular epithelial cells through sodium channels. This is possible because the intracellular sodium concentration is lower than that of the filtrate so sodium is simply flowing down its concentration gradient.
Once inside the tubular cells sodium is actively transported across the basolateral membrane against its concentration gradient by a sodium-potassium exchange pump powered by the hydrolysis of ATP.
Significantly there appears to be a high concentration of these pumps located at the ends of the cells meaning most of the sodium is pumped into the lateral spaces. As well as moving sodium across the basolateral membrane the sodium-potassium exchange pump keeps the intracellular sodium concentration low enough for diffusion to occur across the luminal membrane as described above.
Finally the sodium reaches the interstitial space and eventually moves into the peritubular capillary by diffusion.
The proximal convoluted tubule is responsible for around 70% of sodium reabsorption with the remaining 30% occurring in the loop of Henle and distal convoluted tubule.
56
How does water reabsorption occur?
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. The osmolarity of the lateral spaces increases most dramatically as a lot of sodium is pumped into them (see above) and they tend to be long and narrow which restricts the dilution of the solutes through mixing with the rest of the interstitial fluid.
As we know from our consideration of osmosis 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.
57
How does amino acid reabsorption occur?
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.
58
How does urea reabsorption occur?
Urea is a 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.
This means that there is a concentration gradient across the tubular epithelium which provides the driving force for the diffusion of urea through both the luminal and basolateral membrane into the interstitial space and subsequently into the peritubular capillaries.
59
How does glucose reabsorption occur?
glucose is just about completely reabsorbed and this 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. This is an example of a 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. In this case it is the active transport of sodium across the basolateral membrane (described above) that creates the low intracellular sodium concentration that provides the gradient that stimulates the movement of sodium into the cell across the luminal membrane. (Yes it may take a couple of readings to get your head around that sentence). As glucose binds to the same transporter as sodium the glucose is effectively dragged along as sodium flows into the cell down its concentration gradient.
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.
60
What is transport maximum (Tm)?
a lot of reabsorption involves active transport where the substance being transported binds to a membrane protein. Because of this the rate at which any substance that moves across a membrane by active transport is limited by the number of membrane proteins involved in its transport. Once all of the proteins are saturated no more substance can be transported and the maximum rate of transport has been achieved.
61
Describe tubular secretion. Where are substances secreted from? Where do they flow to? Name 2 important substances that are secreted
Failure to reabsorb substances from the tubular filtrate is one way the kidney can eliminate unwanted substances from the plasma. Another mechanism is the secretion of such substances from the peritubular capillaries into the filtrate. These substances subsequently flow out through the collecting duct and are excreted in urine. With the exception of K+ (see below) the proximal convoluted tubule is the major site of secretion
Two very important secreted substances are:
(i) Potassium.
Potassium is almost completely reabsorbed by the proximal convoluted tubule and loop of Henle so all of the potassium that appears in urine is due to secretion by the distal convoluted tubule and upper parts of the collecting duct. This process is very carefully controlled and it is the major mechanism of potassium homeostasis.
(ii) Hydrogen Ions.
Tubular secretion of H+ is important in maintaining control of the pH of the blood. When the pH of the blood starts to drop, more hydrogen ions are secreted and if the blood should become too alkaline, secretion of H+ is reduced. In maintaining the pH of the blood within its normal limits of 7.3–7.4, the secretion of H+ can result in urine with a pH as low as 4.5 or as high as 8.5.
In addition metabolic waste products such as 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.
62
Which of the following is NOT a consequence of renal failure?
a) pulmonary odema
b) cardiac arrhythmias
c) hypotension
d) acidosis
e)anaemia
c
63
What is the correct sequence of blood vessels through which blood moves after it leaves the renal artery?
Segmental arteries -> lobar arteries -> interlobar arteries -> arcuate arteries
64
Which of the following components are NOT part of the juxtaglomerular apparatus?
a) afferent arteriole
b) macula densa
c) juxtaglomerular cells
d) efferent arteriole
e) collecting duct
e
65
What is the correct order of structures that blood supplying a nephron flows through?
afferent arteriole -> glomerulus -> efferent arteriole -> peritubular capillaries
66
What is the osmolarity of plasma?
around 290 mOsm/L and maintained within 5 mOsm/L of its normal value
67
What is the osmolarity of urine?
can vary from 50 – 1400 mOsm/L
68
How is concentrated urine made?
Concentrated- fluid intake is less than required to maintain plasma osmolarity, more water is reabsorbed, less water is eliminated
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 peritubular capillaries and is returned to the systemic circulation.
69
How is dilute urine made?
Dilute- 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.
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.
70
What is the medullary osmotic gradient?
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.
Permit the production of urine which has a much higher osmolarity than 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).
71
What % of total body weight is water?
55%
72
What are sources of water loss?
Water loss occurs in small amounts through our lungs (during breathing), skin (whilst sweating) and digestive tract (in faeces) but it is the kidneys, through their production of urine, that are the major sources of water loss
73
What effect does water intake have on the osmolarity of plasma?
increasing water intake decreases the osmolarity of plasma whilst dehydration increases it
74
What are osmoreceptors?
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.
75
What happens when there is an increase in plasma osmolarity?
Osmoreceptors 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 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.
76
What happens when there is a decrease in plasma osmolarity?
In response to drinking a lot of water, 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.
77
What are the major roles of sodium?
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.
78
What detects changes in plasma sodium?
detected indirectly by the changes in cardiovascular pressures detected by the baroreceptors
79
How is sodium reabsorption controlled (renin-angiotensin system)
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.
And of course 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.
80
What 3 main inputs to the juxtaglomerular cells regulate the secretion of renin?
(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 venous, atrial and arterial baroreceptors. This information is relayed to the medullary cardiovascular control centres which respond reflexly by increasing activity in renal sympathetic neurones innervating the juxtaglomerular cells of the kidney. These cells respond by increasing the release of renin.
(ii) Intrarenal Baroreceptors
The juxtaglomerular cells within the kidney are closely associated with the afferent arteriole and are very sensitive to the degree of stretch 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 intrarenal baroreceptors.
(iii) Macula Densa
The macula densa is part of the juxtaglomerular apparatus and is associated with the distal convoluted tubule. The cells of the macula densa are sensitive to sodium levels in the tubular fluid as well as tubular flow rate:
-If sodium intake is low, less is filtered by the glomerulus so less is detected by the macula densa.
-If renal blood pressure is decreased 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 renin secretion.
81
How much urine is produced per minute?
1 mL.min-1
82
What is the lining of the bladder? Why is this useful?
The bladder is lined by transitional epithelium. This type of epithelium is only found in the urinary system as a couple of very useful features:
-The dome shaped cells on its surface allow it to tolerate a lot of stretching without leaking.
-It is a stratified epithelium so consists of multiple layers of cells piled on top of each other. Because of this it essentially impermeable so there is no reabsorption of salts or water.
83
What is the muscularis layer of the bladder made of? What does it do?
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 (urination)
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.
84
What permits movement of urine from bladder to urethra? Is this voluntary or involuntary?
Internal urethral sphincter. This sphincter is under the control of the parasympathetic division of the autonomic nervous system so is NOT under voluntary control.
85
What regulates movement of urine along urethra? Is this voluntary or involuntary?
External urethral sphincter. Being skeletal muscle the external urethral sphincter IS under voluntary control and is innervated by somatic motoneurones
86
Describe the filling phase of the bladder
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). Known as 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
87
Describe the emptying phase of the bladder
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
88
Sodium potassium pump that plays a pivotal role in much of tubular reabsorption is located where?
Basolateral membrane of tubular cells
89
Why is glucose not found in urine normally?
It is fully reabsorbed
90
Macula densa responds to what?
Changes in composition of tubular fluid
91
Juxtaglomerular cells are closely associated with what structure?
Afferent arteriole
92
Which of the following statements is correct?
a) water reabsorption is under control of anterior pituitary gland
b) ingestion of large volume of water inhibits release of ADH
c) ADH is released when venous return to the atria is increased
d) ADH release is stimulated by low osmolarity of extracellular fluid
e) ADH acts on kidney proximal tubules
b
93
a) Calculate NFP if glomerular hydrostatic pressure is 45mmHg, hydrostatic pressure of glomerular capsule is 20mmHg and plasma oncotic pressure is 20mmHg
b) What would happen to NFP if plasma oncotic pressure is decreased to 10mmHg due to malnutrition. Explain why
a) NFP = (HPg - HPt) - (OPg - OPt)
= (45-20) - (20-0)
= 5mmHg
b) (45-20) - (10-0)
=15mmHg
NFP will increase due to decrease in plasma proteins
94
Explain why drugs that inhibit sodium-glucose cotransporters in the kidney can be effective in treating diabetes
Glucose small enough to move across filtration membrane. Normally is reabsorbed in proximal convoluted tubule. Reabsorption across luminal membrane of the tubule is enabled by glucose binding to membrane protein that also binds sodium.
Glucose then moves across basolateral membrane by facilitated diffusion. Patients with diabetes have elevated glucose levels so tubular fluid levels of glucose are also elevated. Inhibition of sodium-glucose cotransporters will mean less glucose is reabsorbed and more glucose will be excreted in urine (blood glucose levels decline)
95
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 what?
27mmHg
96
Which of the following statements is FALSE?
cortical nephrons have their renal corpuscles located in the outer portion of the cortex
juxtamedullary nephrons constitute approximately 15% of the total population of nephrons
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
the renal corpuscles of juxtamedullary nephrons are located deep within the medulla
the renal corpuscles of juxtamedullary nephrons are located deep within the medulla
97
When a substance is reabsorbed from the proximal convoluted tubule into the peritubular capillaries how many cells does it have to traverse?
2
98
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
1 and 2
99
Which of the following statements is FALSE?
The reabsorption of sodium is very carefully regulated to maintain salt balance.
Amino acids are almost completely reabsorbed from the tubule and returned to the blood stream.
Glucose is almost completely reabsorbed from the tubule.
The kidney carefully regulates the reabsorption of glucose to control blood glucose levels.
The reabsorption of water is very carefully regulated by the kidney.
The kidney carefully regulates the reabsorption of glucose to control blood glucose levels.
100
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.
All 3
101
In a normal healthy individual, what would happen to glomerular filtration rate (GFR) if mean systemic blood pressure DECREASED from 90 to 70 mmHg?
GFR wouldn't change
GFR would increase because of myogenic regulation
GFR would increase because of autoregulation
GFR would decrease because of myogenic regulation
GFR would decrease because of autoregulation
GFR wouldn’t change
102
In the following list, which components are parts of the juxtaglomerular apparatus?
Afferent arteriole.
Macula densa.
Peritubular capillaries.
Collecting duct.
Afferent arteriole and macula densa
103
In a nephron the macula densa is part of which of the following structures?
lobar artery
efferent arteriole
proximal convoluted tubule
loop of Henle
distal convoluted tubule
Distal convoluted tubule
104
Which of the following is/are involved in the reducing water loss in response to dehydration?
1)The production of urine that has a lower osmolarity than plasma.
2)The cortical osmotic gradient.
3) An increase in the permeability of the collecting duct to water.
3
105
Which of the following structures is/are part of a renal corpuscle?
1. glomerulus.
2. glomerular capsule.
3. distal convoluted tubule.
1 and 2
