Comprehensive notes on renal system

1. Regulation of Urine
Concentration and Volume
E. ANOKYE KUMI

2. One crucial renal function is to keep solute concentration of
the body fluids constant
✓ the kidneys keep the solute load of body fluids constant at
about 300 mOsm (osmotic concentration of blood plasma)
by regulating urine concentration and volume
✓ the kidneys accomplish this feat using countercurrent
mechanisms
✓ the countercurrent mechanisms are:
➢ countercurrent multiplier
➢ countercurrent exchanger

3. ✓ Glomerular filtrate has same osmolarity as blood 300
mOsm/liter
✓ Fluid leaving PCT is isotonic to plasma
✓ When dilute urine is being formed, the osmolarity of fluid
increases as it goes down the descending loop of Henle,
decreases as it goes up the ascending limb, and
decreases still more as it flows through the rest of the
nephron and collecting duct

4. Countercurrent system
A countercurrent exists when fluids flow in opposite
directions in tubes that are parallel and in close proximity for
some distance
Countercurrent multiplier
A countercurrent multiplier system is a mechanism that
expends energy to create a concentration gradient.
The interaction between the flow of filtrate through the
ascending and descending limbs of the long loops of Henle
of juxtamedullary nephrons

5. Copyright 2009, John Wiley & Sons, Inc.
✓Osmolarity of interstitial fluid of
renal medulla becomes greater,
more water is reabsorbed from
tubular fluid so fluid become
more concentrated
✓Water cannot leave in thick
portion of ascending limb but
solutes leave making fluid more
dilute than blood plasma
✓Additional solutes but not much
water leaves in DCT
✓Low ADH makes late DCT and
collecting duct have low water
permeability

6. Copyright 2009, John Wiley & Sons, Inc.
Countercurrent multiplication
✓Process by which a progressively increasing osmotic
gradient is formed as a result of countercurrent flow
✓Long loops of Henle of juxtamedullary nephrons function as
countercurrent multiplier
✓Symporters in thick ascending limb of loop of Henle cause
build up of Na+ and Cl- in renal medulla, cells impermeable to
water
✓Countercurrent flow establishes gradient as reabsorbed Na+
and Cl- become increasingly concentrated
✓Cells in collecting duct reabsorb more water and urea
✓Urea recycling causes a buildup of urea in the renal medulla
✓Long loop of Henle establishes gradient by countercurrent
multiplication

7. ✓ the descending limb of the loop of Henle is relatively
impermeable to solutes but freely permeable to water
✓ water passes osmotically out of the filtrate all along this
limb into the elevated medullary interstitial fluid
✓ the filtrate osmotically reaches its highest point (1200
mOsm) at the bend of the loop
✓ the ascending limb is impermeable to water but permeable
to solutes
✓ Na+ and Cl- concentration entering the ascending limb is
very high compared to the interstitial fluid

8. ✓ Na+ and Cl- reabsorption in the ascending limb is both
passive (mostly in the thin segment) and active (via the Na+-
K+-2Cl--cotransporter in the thick segment)
✓ as fluid travels up the ascending limb, it becomes less and
less concentrated because Na+ and Cl- are pumped out
✓ at the DCT it is hypotonic (100 mOsm) to blood plasma and
cortical interstitial fluid
✓ urea also contributes to the medullary osmotic gradient
✓ urea enters the thin ascending limb of the loop of Henle by
facilitated diffusion

9. ✓ water reabsorption from the cortical collecting duct leaves
behind urea in the tubular fluid
✓ urea is transported out of the inner medullary
collecting duct into the interstitial fluid by
facilitated diffusion
✓ ADH enhances urea transport in the medullary collecting duct

13. Countercurrent Exchange
✓Process by which solutes and water are passively
exchanged between blood of the vasa recta and interstitial
fluid of the renal medulla as a result of countercurrent flow
✓Vasa recta is a countercurrent exchanger
✓Osmolarity of blood leaving vasa recta is only slightly
higher than blood entering
✓Provides oxygen and nutrients to medulla without washing
out or diminishing gradient
✓Vasa recta maintains gradient by countercurrent exchange

14. Countercurrent exchanger
The flow of blood through the ascending and descending
portions of the the vasa recta vessels
✓ the vasa recta brings nutrient and oxygen to the tubules within
the medulla
✓ helps maintain medullary hyperosmolality
✓ it is freely permeable to both solute and water throughout the
length
✓ blood entering the descending limb of vasa recta is ~
300mOsm/L and blood leaving the ascending limb of vasa
recta is ~ 325mOsm/L

15. ✓ as the blood descends through the descending limb of vasa
recta, water diffuses out and NaCl diffuses in to equilibrate
with the increasing osmolarity of medullary interstitial fluid
(ISF) from top to bottom established by the countercurrent
multiplier
✓ as the blood ascends through the ascending limb of vasa
recta, water diffuses in and NaCl diffuses out to equilibrate
with the decreasing osmolarity of medullary interstitial fluid
(ISF) from bottom to top
✓ this countercurrent flow of blood preserves the high solute
concentration of the medullary ISF

16. ✓ excess water is kept out of the medulla since it tends to
"short-circuit" the loop by leaving the dilute incoming plasma
and flowing into the more concentrated plasma leaving the
medulla
✓ in addition, most of the solute (NaCl and urea) deposited in
the medulla by the loop of Henle recycles from the
ascending to the descending vasa recta and is trapped in
the medulla

20. Role of Antidiuretic hormone (ADH) in urine concentration
and volume
✓ ADH, also known as vasopressin, is produced in the
hypothalamus and delivered to the posterior pituitary for
storage and release
✓ the most important effect of ADH is to conserve body water by
reducing the loss of water in urine
✓ it stimulates water reabsorbtion by stimulating insertion of
aquaporins into the luminal membrane of principal cells of the
collecting duct
✓ it works via the cAMP pathway

21. ✓ it is secreted in response to increasing osmolarity in the
blood
✓ this is sensed by osmoreceptors in the hypothalamus which
stimulate the posterior pituitary into releasing ADH
✓ absence of ADH results in large amount of dilute urine
produced (or diabetes insipidus)
✓ ADH secretion is also stimulated by angiotensin II

23. Diuresis
• Increased loss of body water to urine
• Water diuresis – decreased osmolarity of plasma and/ or increased
blood volume leading to decrease in anti diuretic hormone (ADH)
levels. Urine output increases
• Osmotic diuresis – osmotically active substances (e.g., glucose)
within renal tubule. Urine output increases

24. Diuretics
A diuretic is an agent that increases urine output and therefore
decreases water conservation by the body.
Diuretics primarily work by inhibiting sodium reabsorption by the
renal tubule. They act at various segments of the renal tubule.
✓ they increase urine output via different mechanisms
✓ an osmotic diuretic is a substance that is not reabsorbed and that
carries water out with it
eg. high blood glucose of a diabetes mellitus patient
✓ alcohol acts by inhibiting ADH secretion.
✓ Xanthines such as caffeine and theophylline act by inhibiting Na+
reabsorption and the obligatory water reabsorption that normally
follows

25. ✓ lasix inhibits the Na+-K+-2Cl- cotransporter in the medullary thick
ascending limb of the loop of Henle
✓ diuretics are used to treat hypertension, congestive heart failure, and
fluid retention associated with menstruation

26. Renal clearance (RC)
✓ Clearance is a general concept that describes the rate at which substances are
removed (or cleared) from plasma.
✓ Renal Clearance refers to the volume of plasma that is cleared of a specific
substance in a given time, usually 1 minute.
✓ Renal clearance of a substance refers to the how quickly a particular
substance is removed from the plasma by the kidney and excreted in urine
✓ Substances with the highest renal clearances may be completely removed on a
single pass of blood through the kidneys; substances with the lowest renal
clearances are not removed at all.
✓ renal clearance is a net result of glomerular filtration, active tubular secretion
and tubular reabsorption

27. ✓ Clearance studies are widely used to assess
o glomerular filtration rate
o renal blood flow
o study the excretion of various substances by the kidney.
✓ it is a measurement that allows one to analyze the activity of the kidney
✓ the renal clearance rate (RC) of any substance, in ml/min is
calculated from the equation:
RC = UV/P
where U = concentration of the substance in
urine (mg/ml)
V = rate of urine formation (ml/min)
P = concentration of the substance in
plasma (mg/ml)
UV = excretion rate

28. Clearance of Various Substances
• Renal clearance can be calculated for any substance. Depending on the
characteristics of the substance and its renal handling, renal clearance
can vary from zero to greater than 600 mL/min.
• For example, renal clearance of albumin is approximately zero
because, normally, albumin is not filtered across the glomerular
capillaries.
• The renal clearance of glucose is also zero. Glucose is filtered and then
completely reabsorbed back into the bloodstream.

29. • Other substances such as Na+, urea, phosphate, and Cl− have
clearances that are higher than zero because they are filtered and
partially reabsorbed.
• Inulin, a fructose polymer, is a special case. Inulin is freely filtered
across the glomerular capillaries, but it is neither reabsorbed nor
secreted; therefore its clearance measures the GFR.
• Organic acids such as para-aminohippuric acid (PAH) and organic
bases such as morphine have the highest clearances of all substances
because they are both filtered and secreted.

30. Determination of Glomerular Filtration Rate
✓ inulin is used as a clearance standard to determine glomerular
filtration rate since it is not reabsorbed, stored, or secreted
✓ its clearance is equal to the glomerular filtration rate, the volume of
plasma filtered in one minute (125 ml/min)
✓ clinicians and medical doctors will measure the clearance of inulin
to determine whether the kidneys of their patients are filtering
properly
✓ a clearance value less than that of inulin means that the a substance
is reabsorbed
✓ if the RC is equal to inulin, there is no net reabsorption or secretion

31. ✓ if the RC is greater than that of inulin it means the tubule cells are
secreting the substance into the filtrate
✓ a RC of 0 means the substance is completely reabsorbed
✓ inulin is not an endogenous substance, thus it must be administered
to measure GFR
✓ the clearance of creatinine, an endogenous byproduct of muscle
metabolism, and a near-perfect glomerular marker is used to
measure GFR of creatinine which has an RC of 140 is often used to
give a rough estimation of the GFR instead of inulin since it is freely
filtered, not reabsorbed and slightly secreted
✓ although the amount of creatinine excreted in urine exceeds the
amount expected from filtration by about 10%, it provides a
reasonably accurate measure of GFR

32. Urine
A liquid waste produced by the kidneys, stored in the bladder and is
expelled from the body through the urethra
Urinalysis
✓ Analysis of the volume and physical, chemical and microscopic
properties of urine
✓ Water accounts for 95% of total urine volume
✓ Typical solutes are filtered and secreted substances that are not
reabsorbed
✓ If disease alters metabolism or kidney function, traces of
substances normally not present or normal constituents in
abnormal amounts may appear

33. Physical characteristics of Urine
Characteristics of the urine change, depending on influences such as
water intake, exercise, environmental temperature, nutrient intake,
and other factors
▪ Color
freshly voided urine is clear and pale to deep yellow due to
urochrome/urobilin, a pigment resulting from the destruction of
hemoglobin
✓ color may vary with diet, presence of bile pigments or blood,
drugs and vitamin supplements in urine
✓ cloudy urine may indicate a UTI

35. ▪ Odor
✓ fresh urine is slightly aromatic, but develops an ammonia odor if
allowed to stand, due to bacterial metabolism of urea
✓ some drugs and vegetables alter the usual odor of urine
✓ some diseases may alter the smell of urine eg urine of diabetics
may have a sweet or fruity odor because of its ketone content

36. ▪ pH
✓ normal pH is around 6.0
✓ changes in body metabolism or diet may cause the pH to vary
from 4.6 – 8, eg high protein diets result in more acidic urine,
but vegetarian diets generally result in more alkaline urine
▪ Specific gravity
This is the ratio of the mass of a substance to the mass of the same
volume of distilled water
✓ the specific gravity of normal urine ranges from 1.001 to 1.035

37. ▪ Turbidity
it is gauged subjectively and reported as clear, slightly cloudy,
cloudy, opaque or flocculant
✓ fresh urine is normally either clear or slightly cloudy
✓ excess turbidity results from the presence of suspended
particles in the urine
✓ common causes of abnormal turbidity include : increased
blood cells, numerous crystals, bacteria, lipiduria, mucus,
semen or fecal contamination

38. o Chemical composition
✓ about 95% of urine is water
✓ the remaining 5% consists of solutes
✓ normal solute constituents in order of decreasing concentration are
➢ urea 9.3 g/L
➢ chloride 1.87 g/L
➢ sodium 1.17 g/L
➢ potassium 0.750 g/L
➢ creatinine 0.670 g/L and
➢ other dissolved ions, inorganic and organic compounds
(proteins, hormones, metabolites)

39. ✓ unusually high concentrations of any solute, or the presence of
abnormal substances such as blood proteins, WBC (pus), or bile
pigments may indicate pathology

40. MICTURITION
• It is the act of emptying the urinary bladder
• When the bladder is filling with urine, sympathetic control
predominates. This sympathetic activity produces relaxation of the
detrusor muscle, via β2 receptors, and contraction of the internal
sphincter muscle, via α1 receptors.
• The external sphincter is simultaneously closed by trained voluntary
action. When the muscle wall is relaxed and the sphincters are closed,
the bladder can fill with urine.
• When the bladder is full, this fullness is sensed by mechanoreceptors
in the bladder wall, and afferent neurons transmit this information to
the spinal cord and then to the brain stem.

41. • The micturition reflex is coordinated by centers in the midbrain, and now
parasympathetic control predominates. Parasympathetic activity produces
contraction of the detrusor muscle (to increase pressure and eject urine) and
relaxation of the internal sphincters.
• Simultaneously, the external sphincter is relaxed by a voluntary action.
• The sympathetic actions dominate for bladder filling, and the parasympathetic
actions dominate for bladder emptying.

43. ◆Innervation
✓ the bladder receives input from both the autonomic (sympathetic
and parasympathetic) and somatic arms of the nervous system
✓ the sympathetic nervous system communicates with the bladder
via the hypogastric nerve (T12 – L2), they innervate the;
o the detrusor muscle
o trigone region and
o internal urethral sphincter
✓ sympathetic stimulation relaxes the detrusor and contracts the
bladder neck at the internal sphincter via β and α receptors
respectively

44. ✓ the parasympathetic nervous system communicates with the bladder
via the pelvic nerve (S2-S4), they innervate the
o detrusor muscle
o trigone and
o internal urethral sphincter
✓ parasympathetic activity contracts the detrusor muscle and relaxes
the trigone and sphincter
✓ the somatic nervous supply gives voluntary control over
micturition. It innervates the external urethral sphincter, via the
pudendal nerve (S2-S4). The motor neurons are located in Onuf's
nucleus, in the ventral horn of the sacral spinal cord

45. ✓ in addition to the efferent nerves supplying the bladder, there are
sensory (afferent) nerves that report to the brain. They are found in
the bladder wall and signal the need to urinate when the bladder
becomes full.

47. ◆Control of micturition
The urinary bladder is controlled by reflex pathways in the spinal
cord and also by a supraspinal center
Bladder function can be thought of in two phases:
➢ filling and storage of urine
➢ emptying (voiding)
o Storage reflexes
occur during filling
✓ little or no increase in the intravesical pressure is observed,
despite large increases in urine

48. ✓ during filling low-level activity from bladder afferent fibers signals
distension via the pelvic nerve
✓ this in turn stimulates sympathetic outflow to the bladder neck and
wall via the hypogastric nerve
✓ this sympathetic stimulation relaxes the detrusor and contracts the
bladder neck at the internal sphincter
✓ afferent pelvic nerve impulses also stimulate the pudendal (somatic)
outflow to the external sphincter causing contraction and
maintenance of continence
✓ lower bladder volume primarily activate the pontine storage center,
which inhibit urination by suppressing the parasympathetic and
enhancing sympathetic output to the bladder

49. Voiding reflexes
Micturition is normally controlled by the micturition reflex
✓ mechanoreceptors in the bladder wall are excited by both stretch and
contraction of the muscles in the bladder wall
✓ as urine accumulates and distends the bladder, the mechanoreceptors
begin to discharge
✓ pressure in the urinary bladder is low during filling (5 to 10 cm
H2O), but it increases abruptly when micturition begins
✓ micturition can be triggered either reflexively or voluntarily

50. o Reflex micturition
✓ bladder afferent fibers excite neurons that project to the brainstem
and activate the micturition center in the rostral pons (Barrington's
center)
✓ ascending projections also inhibit sympathetic preganglionic
neurons that prevent voiding
✓ the ascending projection passes through the periaqueductal gray
matter before reaching the pontine micturition center where it
triggers micturition
✓ commands reach the sacral spinal cord through a reticulospinal
pathway

51. ✓ activity in the sympathetic projection to the bladder is inhibited
✓ pudendal nerves are also blocked
✓ these relax the internal and external sphincters and removes the
sympathetic inhibition of the parasympathetic receptors
✓ parasympathetic projections to the bladder are activated
✓ contraction of muscle in the wall of the bladder causes a vigorous
discharge of the mechanoreceptors that supply the bladder wall
and thereby further activates the supraspinal loop
✓ this results in complete emptying of the bladder
✓ the normal adult bladder can hold about 500 cc of urine
✓ after emptying, the bladder may still retain about 50 cc residual
volume

52. o Voluntary control
Normally, we are able to control where and when we void. This is
largely because the cerebrum is able to suppress the sacral micturition
reflex, especially the external sphincter which is voluntarily controlled
in response to afferent stimulation, the cerebrum becomes aware of
the need to void
✓ if it is appropriate, the cerebrum relaxes the external sphincter,
blocks sympathetic inhibition, the bladder contracts and urine is
expelled