renal physiology

Question 1

Micturition
Describe the neurological pathways involved in normal micturition

Answer 1

● Sacral spinal reflex Mediated by S2, S3 and S4 nerve roots facilitated and
inhibited by hire centres, subject to voluntary control.
● First urge to void at 150ml.
● Marked fullness at 400 ml – sudden rise in intravesical pressure triggers reflex
contraction.
● Micturition reflex:
○ Stretch receptors in the bladder wall.
○ Afferent limb in pelvic nerves
○ Parasympathetic efferent fibres (via same pelvic nerves) mediate
contraction of detrusor muscle.
○ Pudendal nerve (S2, S3 and S4) permits voluntary contraction of perineal
muscles/external urethral sphincter, to slow or halt flow.
● Sympathetic nerves to the bladder play no role in micturition.

Question 2

Describe the muscles involved in micturition

Answer 2

● Bladder- smooth muscle arranged in spiral, longitudinal and circular bundles.
Circular bundle is called the detrusor muscle period contraction of detrusor is
responsible for involuntary emptying.
● External urethral sphincter - skeletal muscles of the membranous urethra.
Relaxes during micturition. This is voluntarily controlled
● Perineal muscles. Relaxes during nutrition. Also voluntarily controlled.
● In males, urine left in the urethra is expelled by several contractions of
bulbocavernosus muscle.
● Contraction of abdominal wall muscles aids expulsion of urine.

Question 3

List other factors that stimulate and inhibit micturition

Answer 3

Stimulants
● Stretch/pressure
● Higher centre input
● Parasympathetics
● Sympathetic inhibiting drug (Alpha blockers)
● Voluntary abdominal muscle contraction augments stream but does not initiate
micturition per se

Inhibitors
● Parasympathetic inhibitors (atropine)
● Higher centres
● Sympathomimetics

Question 4

Glucose handling
Describe how the kidney handles glucose

Answer 4

● Freely filtered in the glomerulus
● Reabsorbed in the early part of the PCT by secondary active transport
● Na dependent co transport via SGLT2 into cells then GLUT2 facilitated diffusion
into the interstitium
● Excreted in the urine if the renal threshold is exceeded

Question 5

What are the clinical consequences of glycosuria

Answer 5

● Osmotic diuresis
● Dehydration
● Electrolyte loss (Na, K)

Question 6

Sodium handling
Where does sodium reabsorption occur in the nephron?

Answer 6

Filtered by the glomerulus, 99% reabsorbed overall
● 60% reabsorbed in the PCT by Na-H exchange but also a range of
co-transporters (with glucose, AAs, lactate)
● 30% thick ascending limb of the loop of henle
● 7% in the DCT via NaCl cotransporter
● 3% via ENac channels in collecting ducts

Question 7

How is Na transported from the tubular cell into the interstitium?

Answer 7

By the Na/K ATPase active transport pump
Moves 3Na and 2K across the basolateral memnrabe

Question 8

Following high Na intake, what mechanisms are there to enhance Na excretion?

Answer 8

High Na intake causes ECF expansion (Na is the prime determinant of ECF volume)
This increase triggers various response mechanisms
● Stretch receptors in pulmonary veins inhibit sympathetic outflow to the kidneys
and decreased Na reabsorption
● Small increase in arterial pressure can cause pressure natriuresis
● Suppression of AT II formation, thereby r

Question 9

How does the kidney reduce Na secretion?

Answer 9

By reducing the GFR to reduce the amount filtered
Increasing tubular reabsorption via increase in adrenocortical hormones such as
aldosterone.

Question 10

How does aldosterone influence sodium handling?

Answer 10

Aldosterone acts on principal cells in collecting ducts to increase the number of
active epithelial sodium channels (ENaC)
● Upregulates and activated basolateral Na/K ATPase
● Increased tubular reabsorption of Na, and Cl follows.
● Secretion of K into lumen via exchange with Na
● Latent period of 10-30 minutes before the effect

Question 11

Hydrogen handling
Where does acidification of the urine occur?

Answer 11

Proximal and distal tubules and collecting ducts

Question 12

How is H+ secreted in each of those areas?

Answer 12

● PCT - Na/H exchange transporter. This pathway also involves the action of
carbonic anhydrase, which allows the recycling of H+ and absorption of one Na
and one HCO3 for every H+ secreted.
● DCT/CD - secretion of H+ is independent of Na.
○ ATP driven pump
○ Also H-K ATPase pump an anion exchanger.

Question 13

What is the limiting pH and where does it occur?

Answer 13

The limiting pH is 4.5 because this is the maximal gradient that can be achieved across
the tubules. It occurs in the collecting duct. Possible due to buffers (bicarb, phosphate,
ammonia)

Question 14

In metabolic acidosis, describe the buffer systems in the urine that allow excretion
of large amounts of H+

Answer 14

BICARB: HCO3- forms CO2 and H2O
PHOSPHATE: HPO42- forms H2PO4-
AMMONIA: NH3 forms NH4+ (ammoniA = A goes first, them AmmoniUM)

Question 15

What happens to glutamine synthesis in chronic metabolic acidosis?

Answer 15

Glutamine synthesis increased in the liver to provide the kidneys with enough ammonia
to form buffer

Question 16

K handling
How do the kidneys deal with potassium?

Answer 16

Freely filtered at the glomerulus (600mmol/day)
● Actively reabsorbed in the PCT (over 90% resorbed)
● Also reabsorbed in the Na/K/2Cl co-transporter
● Secreted in the DCT - rate proportional to flow
● Secreted in CD in response to aldosterone, which increased K secretion
● Total secretion is low (approx 90mmol per 24hrs) but varies with flow and
aldosterone

Question 17

Explain K transport in the collecting duct

Answer 17

*H-K ATPase in the cells of collecting ducts reabsorbs K in exchange for H
*So, if H secretion is increased, K excretion is decreased.

Question 18

How does aldosterone increase potassium secretion in the urine?

Answer 18

● Aldosterone secretion is triggered by hyperkalaemia
● Acts at the DCT and collecting ducts
● Stimulates the Na/K APT pump at the basolateral surface of the principle cells.
● 2K enters in exchange for 3 Na into the bloodstream
● Causes K channels to form at the apical surface of the principle cells
● Higher intracellular K concentration means that K enters the tubular lumen
● This causes Na channels to form at the apical surface of the principle cells
● Na enters the principal cells from the tubular lumen and gets to the bloodstream
via Na/K ATP pump.

Question 19

How do hydrogen ions influence K transport in the nephron?

Answer 19

It is coupled. If H secretion is increased then K excretion is decreased as K is
reabsorbed in exchange for H+

Question 20

Urea handling
What is the role of urea in the countercurrent mechanism?

Answer 20

*Contributes to the osmotic gradient in the medullary pyramids
*Enhances the ability of the kidney to concentrate urine

Question 21

How does the kidney handle urea?

Answer 21

● Facilitated diffusion out of the late PCT
● Secreted in the loop of henle
● Reabsorbed in the collecting ducts
● 40% of filtered urea can be found in the urine
● The amount of urea depends on the amount filtered, which is influenced by
dietary protein

Question 22

How does urea reach the interstitium?

Answer 22

Transported via 4 different urea transporters (facilitated diffusion)

Question 23

Renal blood flow
What is the normal renal blood flow?

Answer 23

1.2 - 1.3 litres per minute or 25% of cardiac output.

Question 24

Describe the factors which determine renal blood flow

Answer 24

● Perfusion pressure (systemic MAP)
● Renal arterial effects
○ local constriction from Na, Ang II
○ dilation from ACh, PGs,
dopamine
*Renal nerves (sympathetic nerves constrict and decrease RBF)
● Autoregulation (myogenic, NO, Ang II)
● Regional differences between the cortex and medulla

Question 25

How can renal blood flow be measured?

Answer 25

Fick Principle (the amount of a substance taken up per unit time divided by
arterio-venous concentration difference)
● Para-amino hippuric acid (PAH) is used to measure renal blood flow. It is both
filtered and secreted, meaning 90% of it is cleared from circulation by the kidney
and only small amounts remain in the renal vein.
● So, if we know the concentration in the plasma, and concentration in the urine
and the urine flow rate we can use that to calculate the renal blood flow.
● This is done by using the formula for clearance - UV/P - U is the Urine
concentration, V is the volume of urine collected in minutes and P is the plasma
concentration.
● The clearance of PAH from the circulation is equal to the effective renal plasma
flow. The ERPF from the calculation is only 90% of the actual flow, because we
know that when we measure the PAH in the urine, we are only getting 90% of it,
because 10% flows back out into the renal vein.
● The actual renal plasma flow is calculated by dividing the effective renal plasma
flow by 0.9 to reflect the fact that what we have calculated is only 90%
● In order to calculate whole blood flow we need to think about what else is in
blood aside from the plasma, particularly RBCs. So, the renal whole blood flow is
the actual renal plasma flow divided by 1-HCT.

Question 26

How do blood flow and oxygen extraction vary in different parts of the kidney?

Answer 26

● Cortical flow is high and oxygen extraction is low
● Medullary blood flow is low and oxygen extraction is high because there is a lot of
metabolic work done.
● This means the medulla is more vulnerable to hypoxic damage if flow is
compromised.

Question 27

8. Counter current mechanism
   How does the countercurrent mechanism enable the kidney to concentrate urine?

Answer 27

● The “countercurrent mechanism” refers to a system in which the inflow runs
parallel to, counter to and in close proximity to the outflow for some distance.
● Concentrating mechanism depends on maintaining a gradient of increasing
osmolality along medullary pyramids
● 2 parts in this system:
○ Gradient is produced by the countercurrent multipliers in the loop of Henle
○ and maintained by the vasa recta acting as countercurrent exchangers
● Countercurrent Multiplier:
○ Isotonic fluid flows from the PCT and enters the medulla in the lumen of
tubules.
○ Water moves out of the thin descending limb of the LoH (highly
permeable to water via aquaporin 1)
○ The luminal fluid becomes hypertonic, to equilibrate with the interstitium
○ When flowing back up the thick ascending limb of the loop of Henle, there
is active transport of Na and Cl out of the lumen which is not permeable to
water
○ The fluid flowing into the DCT is hypotonic
○ Water moves out of collecting duct (into the hypertonic interstitium of the
medullary pyramids) under the influence of ADH
● The vasa recta acts as a countercurrent exchanger
○ Water diffuses out of the descending limb and into the ascending limb of
the vascular loop.
○ Na, Cl and urea diffuse out of the ascending limb and into the descending
limb.
○ As a result, the solute remains in the medullary pyramid, maintaining the
interstitial concentration.

Question 28

GFR
What is the definition of glomerular filtration rate

Answer 28

Amount of fluid (plasma filtrate) filtered by the glomerulus per unit time

Question 29

What is the normal GFR?

Answer 29

125ml/minute or 180L in 24 hours in a normal adult

Question 30

List some factors that affect GFR

Answer 30

● Overall surface of the capillary bed within the glomerulus - Regulated by
mesangial cells that can contract, located between the basal lamina and
endothelium.
● Permeability of glomerular capillaries
○ More permeable than those found elsewhere in the circulation
● Hydrostatic pressure gradients
○ Afferent arterial pressure (renal artery blood flow) This is kept stable
through autoregulation between 90-220mmHg
○ Systemic BP may be proportional to GFR if outside autoregulation range
○ Afferent or efferent arteriolar constriction and the resulting renal blood
flow
○ Hydrostatic pressure in Bowman’s capsule (i.e. ureteric obstruction)
● Osmotic pressure gradients
○ oncotic from plasma protein concentration
○ Intrarenal interstitial pressure from obstruction or oedema
● Number of functioning renal corpuscles
○ Age
○ Atrophy
○ Nephrectomy
○ Parenchymal disease

Question 31

Describe a method for measuring the GFR

Answer 31

Measure the excretion of a substance which is freely filtered through the glomerulus and
neither secreted nor absorbed by the tubules. Must also be non toxic and not
metabolised. Example: Inulin.
Again, we can use the clearance equation UV/P
Where;
U is the urine concentration of inulin
V is the urine flow in ml/min
P is the arterial plasma level of inulin
The resulting value or the “clearance” rate is the GFR
It can be easy to confuse PAH and Inulin calculations and what you use for which
equation but if you remember that only about 20% of plasma inulin is filtered by the
kidney then you know that concentration in the renal vein will still be pretty high so it’s
not useful for calculating renal blood flow. Whereas, PAH is almost completely eliminated
by the kidney through filtration and secretion, so the AV difference will be high, and the
fact that it’s secreted by the kidney makes PAH unsuitable to be used to calculate GFR.

Question 32

Water Handling & Thirst
Describe how water is reabsorbed in the different parts of the nephron

Answer 32

● 60-70% in the proximal tubule
● 15% in the loop of henle
● 5% in the distal tubule
● Up to 10% in the collecting duct depending on the presence of ADH or
vasopressin

Question 33

What is thirst, what causes it?

Answer 33

● An appetite, under hypothalamic control
● Increased plasma osmolarity
● Hypovolaemia
● Prandial response - habitual
● Psychogenic
● Response to dry mucous membranes

Question 34

What are the physiological effects of dehydration?

Answer 34

Water loss lowers the ECF and ICF leading to low BP, tachycardia, increased ADH,
decreased urine output, decreased GFR, activation of the renin-angiotensin system,
increase in thirst.

Question 35

Explain how thirst works to restore fluid status

Answer 35

● As plasma oncotic pressure rises, it is sensed by the osmoreceptors in the
anterior hypothalamus.
● This triggers a release of vasopressin (ADH) from the posterior pituitary
● Vasopressin acts on the V2 receptor to trigger insertion of aquaporin channels
into the luminal membrane of the renal collecting tubules. Aquaporins are usually
stored in the cytoplasm of principal cells.
● Insertion of these allows more water to return to the body

Question 36

What factors other than rising osmotic pressure increase vasopressin secretion?

Answer 36

Decreased ECF volume, emotion, surgical stress, nausea, vomiting, standing,
angiotensin II, medications.

Question 37

Describe the effects of a rapid infusion of 1000ml of normal saline to a dehydrated
person (2016)

Answer 37

● Increased Cl and acidosis
● Increased baroreceptor firing
● Decreased HR
● Increased BP
● Increased urine output
● Decreased RAAS

Question 38

What is an alternative physiological fluid?

Answer 38

Hartmanns or plasmalyte

Question 39

RAAS
What conditions lead to activation of the renin-angiotensin system?

Answer 39

Activated in response to a decrease in BP/ECF or increased sympathetic activity. I.e.
hypotension, haemorrhage, dehydration, cardiac failure, cirrhosis, Na depression,
diuretics, pain, fear

Question 40

Explain how hypotension activates the renin-angiotensin system

Answer 40

● Hypotension leads to reduced perfusion pressure of the afferent glomerular
arteriole, stimulating release of renin by the juxtaglomerular cells.
● Renin converts angiotensinogen to angiotensin I.
● Angiotensin-converting enzyme converts angiotensin I to angiotensin II.
● Angiotensin II acts on the adrenal cortex’s zona glomerulosa cells to release
aldosterone.
● Aldosterone acts on the renal distal tubules to retain Na+ and water, thus in
intravascular volume.
● Angiotensin II is also a potent arteriolar constrictor and contributes to a rise in
blood pressure.

Question 41

What physiological factors are involved in regulating renin secretion?

Answer 41

● Intrarenal baroreceptors - an increase of afferent arteriolar pressure at the JG
cells causes a decrease in renin secretion and vise versa.
● The amount of Na and Cl entering the distal tubules in the macula densa -
increased resorption causes a decrease in renin secretion.
● Increase in sympathetic nervous system - stimulates renin
● Vasopressin can decrease renin
● Angiotensin II provides inhibitory feedback to JG cells

Question 42

Angiotensin
Describe the factors influencing angiotensin II production

Answer 42

Angiotensin II is the effector protein in the renin-angiotensin system
So, the factors which increase renin secretion also increase the activity of angiotensin II
These are:
● Increased sympathetic activity
● Increased circulating catecholamines
● Prostaglandins

Factors which decrease renin and therefore decrease ATII
● Increased Na and Cl reabsorption across macula densa
● Increased afferent arteriolar pressure
● Vasopressin

Question 43

What are the physiological effects of angiotensin II?

Answer 43

● Arteriolar constriction
● Direct effects on the adrenal cortex to increase aldosterone
● Can enhance noradrenaline release
● Contraction of mesangial cells
● Direct action on renal tubules to reabsorb Na+
● Acts on the brain to decrease sensitivity of baroreceptor reflex
● Acts on the brain to increase water intake and increase release of vasopressin
and ACTH

Question 44

Impaired renal function
What are the physiological consequences of impaired renal function?

Answer 44

● Proteinuria (predominantly albuminuria) due to the increased permeability of
glomerular capillaries
● Uremia - the accumulation of breakdown products of protein metabolism resulting
in symptoms of uremia
● Acidosis - failure to excrete products of digestion and metabolism with the urine
maximally acidified. The total amount of H+ that can be secreted can be reduced
do to impaired renal tubular production of ammonium (NH4). The exception to
this is renal tubular acidosis where there is an impaiored ability to acidify the
urine.
● Hyperkalaemia from H+/K+ exchange.
● Abnormal handling and excess retention of Na - 3 mechanisms
○ Acute GN - reduction in the amount of Na filtered
○ Nephrotic syndrome - increased aldosterone causing salt retention. Low
plasma proteins cause fluid shift from plasma to interstitium.
○ Volume overload

Question 45

Why does the kidney lose the ability to concentrate urine in a patient with
impaired renal function?

Answer 45

In advanced kidney disease osmolality is fixed at pasma level indicating loss of ability to
concentrate or dilute the urine
This is due to
● Disruption of countercurrent mechanism
● Loss of functioning nephrons causing positive feedback that increases filtration
on the remaining nephrons, which eventually causes more damage to remaining
nephrons