Transcript 13 Renal Clearance overview

Renal Physiology
PART ONE
Renal Physiology
overview
PART TWO
Renal Physiology
details
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Role of the kidney in maintaining water,
electrolytes, and pH balance
 Plasma leaks out of the capillaries in the
glomerulus. The kidneys return the nutrients to
the plasma, while removing the waste products.
This also maintains the pH balance.
 Under the direction of aldosterone, they keep
the balance between electrolytes, especially
sodium and potassium.
 This keeps the plasma volume constant to
maintain BP.
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Role of Kidneys
 The kidneys can adjust blood volume, composition, and
pressure
 BLOOD VOLUME
 Adjusts the volume of water lost in urine by
responding to ADH
 BLOOD COMPOSITION
 Releasing erythropoietin (increases RBC production)
 BLOOD PRESSURE
 Releasing renin (increases blood pressure)
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Sympathetic Nervous
System Effect on Kidneys
Changes in glomerular blood flow and
pressure
The stimulation of renin release from the
juxtaglomerular apparatus
Changes in water and sodium
reabsorption by the nephron
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Hypothalamus
 The hypothalamus monitors the concentration of water in the
plasma.
 If the plasma is too concentrated (high osmotic pressure), it means
there are many electrolytes and not enough water inside the blood
vessels (the person is dehydrated, and blood pressure will drop).
 Since water goes to the area that has the most particles (particles
SUCK water!), water will be drawn out of the nearby cells, which
will cause them to shrink.
 If the plasma is too dilute (low osmotic pressure), it means there is
too much water and too few electrolytes inside the blood vessels
(the person is over-hydrated, and blood pressure will rise).
 Water will be drawn out of the blood vessels to enter the nearby
cells (causing them to swell) or the space between them (interstitial
space).
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Hypothalamus and Adrenal Gland
 When a person is dehydrated and has low blood pressure, the
hypothalamus will sense that the osmotic pressure of the plasma is
too high (above homeostatic levels; plasma is too concentrated: too
many electrolytes and not enough water is in the plasma), it tells
the pituitary gland to release ADH (antidiuretic hormone) to cause
the kidneys to retain additional water to dilute the plasma. This will
make the low blood pressure go back up.
 The adrenal cortex will also release aldosterone, which causes
sodium ions to be reabsorbed by the kidneys, and water will follow.
This will also increase the plasma volume (which will dilute it), and
also help the low blood pressure to go back up.
 If the osmotic pressure is too low (plasma is too dilute: too much
water and not enough electrolytes in the plasma), ADH and
aldosterone are not released, and excess water will pass out of the
body as urine. This will make the high blood pressure go back
down.
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Quiz Yourself
 What does it mean when the osmotic pressure is too
high? Too low?
 What are the causes of each of these situations?
 How does the body compensate for each of these
situations?
 What does it mean when the plasma is too dilute? Too
concentrated?
 What are the causes of each of these situations?
 How does the body compensate for each of these
situations?
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pH Imbalances
Many things can alter the pH of the blood
Beverages we drink
Acids produced by metabolism
Breathing rate
Vomiting (loss of acid)
Diarrhea (loss of base)
pH imbalances are dangerous because
many enzymes only function within a
narrow pH range.
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Renal Physiology
Basic Mechanisms
of Urine Formation
1) Glomerular filtration
2) Tubular reabsorption
3) Tubular secretion
4) Excretion
How do we determine
these rates?
Master formula
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Glomerular Filtration
 The capillaries in the glomerulus contain many
holes, called fenestrations. As blood passes
through the glomerulus, the plasma passes
through the fenestrations. Proteins and other
large substances do not cross through; they
stay in the bloodstream.
 The filtered plasma leaves the bloodstream in
this way, and enters the glomerular capsule,
and then enters the proximal convoluted tubule.
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Glomerular Filtration
 In a sprinkler hose, the higher the water pressure, the faster the water squirts
through its holes. The same process is also true for the glomerulus.
 The blood pressure inside the glomerulus affects how fast the fluid can filter through
the fenestrations. Therefore, blood pressure affects the glomerular filtration rate
(GFR). The higher the blood pressure, the higher the GFR.
 The pre-capillary sphincters can also control how much pressure is in the glomerulus,
much like the cold water faucet controls the pressure in a hose.
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Glomerular Filtration
 GFR is used as a measure of kidney function.
 Normal GFR is 125 ml per minute for both kidneys
combined.
 That means 7.5 liters per hour, or 180 liters per day.
 That is 45 gallons of filtrate produced per day!
 Of course, most of that is reabsorbed.
 Average urine output is about 1.2 liters per day.
 That means you need to drink 1.2 liters of fluid per day
(remember that caffeine and alcohol are diuretics, so
you need more than that to compensate if you drink
those beverages). You need to drink more (about 2
liters per day) if you are getting a cold or flu.
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Altering GFR
Several different mechanisms can change
the diameter of the afferent and efferent
arterioles to alter the GFR:
Hormonal (hormones)
Autonomic (nervous system)
Autoregulation or local (smooth muscle
sphincters around the arterioles or
capillaries near the glomerulus)
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Remember the route the fluid takes:
Glomerulus 
Proximal convoluted tubule (PCT) 
Descending limb of LOH 
Ascending limb of LOH 
Convoluted tubule 
Collecting duct
Tubular Reabsorption
 This is the process by which substance in the renal tubules are
transferred back into the bloodstream. Reabsorption is the removal
of water and solute molecules from filtrate after it enters the renal
tubules.
 Fluid goes from the glomerulus to the proximal convoluted tubule
(PCT), down the loop of Henle and back up, then into the distal
convoluted tubule (DCT), and into the collecting duct.
 In the PCT, the nutrients are reabsorbed. If there are more
nutrients than can be reabsorbed (such as excess sugar), it will be
excreted in the urine.
 When the nutrients in the PCT are reabsorbed, the inside of the
tubule will have more water and less nutrients. Since water goes to
the area that has a higher concentration of particles (osmosis),
water will also leave the tubules; this occurs in the DCT.
 By the time the fluid has reached the collecting duct, nothing but
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waste products are left, such as urea, ammonia, and bilirubin.
Tubular Reabsorption
 Capillaries follow the renal
tubules and wrap around them.
 The straight capillaries that travel
longitudinally next to the tubules
are called vasa recta, and the
capillaries that wrap around the
tubule are called peritubular
capillaries.
 There is a space between the
capillaries and the tube, called
the peritubular space.
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Tubular
Reabsorption
Tubular
Cells
Peritubular
Capillaries
Filtrate arriving from
Bowman’s Capsule
Lumen of
Tubule
 The peritubular capillaries are nearby, and the particle
concentration is low inside of them. Therefore, the particles in the
peritubular space (high concentration of particles) will leave that
space and enter into the peritubular capillaries by osmosis.
 That is how the nutrients are reabsorbed from the tubules back into
the bloodstream.
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Tubular Reabsorption
 The ascending limb of the Loop of Henle and the DCT are
impermeable unless hormones cause substances to be moved
through their walls.
 If the blood is low in sodium, (after excessive sweating),
aldosterone (from the adrenal cortex) will cause more sodium to be
pumped out of the tubule and into the peritubular space. The
sodium will then enter the capillaries.
 Since water follows where salt goes, whenever the body needs
more water (such as dehydration), ADH is released (from the
neurohypophysis = posterior pituitary). ADH is also called
vasopressin.
 Aldosterone and ADH will increase blood volume, increasing blood
pressure.
 These two hormones begin their action in the ascending limb and
continue to work in the DCT.
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Tubular Secretion
 Some substances are unable to filter through
the glomerulus, but are not wanted by the
body.
 Examples are pollutants like pesticides, and
many drugs, such as penicillin and non-steroidal
anti-inflammatory drugs (NSAID’s).
 As blood passes through the peritubular
capillaries, those substances are moved from
the capillaries directly into the PCT and DCT.
 This is called tubular secretion.
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Juxtaglomerular Apparatus
 The distal end of the
renal tubule passes
next to the
glomerulus to form
the juxtaglomerular
apparatus (juxta
means “next to”).
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Juxtaglomerular Apparatus:
Alters BP and GFR
 Macula densa
 Juxtaglomerular
cells
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Juxtaglomerular Apparatus
 If blood pressure is
too low, the macula
densa releases
adenosine, which
causes
vasoconstriction
of the afferent
arteriole. This will
slow the GFR, so
less water is lost,
and blood
pressure
increases.
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Juxtaglomerular Apparatus
 If blood pressure is
too high, the
macula densa
stops releasing
adenosine, which
allows the sphincters
to relax.
 This will increase
GFR so more water
is lost, and blood
pressure
decreases.
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Juxtaglomerular Apparatus
 Juxtaglomerular
cells secrete renin if
the blood pressure is
still too low after
adenosine has caused
vasoconstriction.
 Renin causes more
sodium to be
reabsorbed, and water
follows, so blood
volume increases, so
blood pressure
increases.
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Autoregulation
 The nephron can alter the blood pressure and flow into the
glomerulus by autoregulation.
 The JGA senses the blood pressure going into the glomerulus and
the flow rate of the fluid going through the renal tubule. If the GFR
is too low, the JGA will cause the pre-capillary sphincters on the
nearby arterioles to relax, increasing blood pressure, like turning up
the faucet on a hose.
 If that restores the desired filtration rate and flow, no further action
is needed. If not, the kidneys produce the enzyme renin, which
converts angiotensinogen into A-1. That makes the lungs produce
angiotensin converting enzyme (ACE), which turns A1 into A2,
which constricts blood vessels, and also causes the release of
aldosterone, raising the blood pressure.
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Hormonal Regulation
 If a person sweats from activity, eats very salty food, or has
diarrhea, it changes the sodium and water content of the plasma.
 Two hormones that affect the ascending limb of the Loop of Henle
are aldosterone and antidiuretic hormone (ADH).
 Adosterone is produced by the adrenal cortex and causes additional
sodium ions to be pumped our of the tubule and into the
bloodstream. Water comes with it by osmosis, and the blood
pressure increases.
 ADH is produced by the posterior pituitary gland and causes
retention of additional water from the DCT and collecting ducts.
Sodium is not included in this process, so the result is to dilute the
plasma during dehydration, when the plasma is becoming to
concentrated with particles.
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Erythropoietin
The kidneys also monitor the oxygen
content of the blood.
If O2 levels are low, the JGA releases
erythropoietin to stimulate the bone
marrow to produce more red blood cells.
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Neural Regulation
 The kidneys receive about 22% of the blood pumped
out of the heart, so that is a substantial quantity passing
through the kidneys at any given time.
 If there is a stressor and the sympathetic nervous
system causes us to go into fight or flight mode, the
skeletal muscles need to have a maximum amount of
blood flow.
 Neurons from the sympathetic nervous system innervate
the kidneys to decrease renal blood flow during critical
situations.
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Urine
 Urine contains ions such as sodium, chlorine, and potassium, as
well as suspended solids, known as sediments, such as cells,
mineral crystals, mucus threads, and sometimes bacteria.
 The pH of urine is normally 4.6-8
 A urinalysis can identify abnormal processes occurring in the body.
 Because urine is a waste product, its contents are influenced by the
foods and drinks we ingest.
 We may lose fluid elsewhere, such as through sweating or diarrhea,
which causes the urine to become more concentrated.
 Acids produced through metabolism can also change the pH of our
urine. Even changes in breathing rate can change the urine pH as
excess acids or bases are excreted to maintain normal plasma pH.
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Abnormal Urinalysis
 These substances should not be in the
urine. When they are, it is abnormal.






Glucose
Blood
Protein
Pus
Bilirubin
Ketones
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Causes of abnormal UA
Glucose: diabetes mellitus
Blood: bleeding in urinary tract from
infection or kidney stone
Protein: kidney disease, hypertension,
excessive exercise, pregnancy
Pus: bacterial infection in urinary tract
Bilirubin: liver malfunction
Ketones: excessive breakdown of lipids
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Micturition
 Urination is technically known as micturition.
 Once the volume in the urinary bladder exceeds 200 ml
stretch receptors in its walls send impulses to the brain,
indicating the need to eliminate.
 When you make the decision to urinate, the
parasympathetic nervous system stimulates the smooth
muscle in the urinary bladder’s internal sphincter to
contract.
 Remember, the internal sphincter is smooth muscle
(involuntary) and the external sphincter is skeletal
muscle (voluntary). Both must relax for urine to exit.
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Diuretics for hypertension and
congestive heart failure
 Diuretics decrease plasma volume. This group of drugs are thiazide
diuretics (such as Lasix). The inhibit the reabsorption of sodium and
potassium from the renal tubule, causing more water to pass out as
urine.
 Compared to sodium, the homeostatic range of potassium is quite
narrow.
 Lasix (Furosemide) inhibits reabsorption of potassium more than
other diuretics. Low blood levels of potassium are called
hypokalemia. It is important for someone on Lasix to take
potassium supplements or eat fruits or vegetables that have a lot of
potassium (such as cantaloupe).
 However, too much potassium from excessive supplements can
have fatal side effects.
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Diuretics
Furosemide (Lasix)
Mannitol
Spironolactone
Amiloride
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Homeostasis
 Maintaining the proper concentration of sodium and water is
critical.
 If the plasma is too concentrated with particles, nearby cells can
shrink and lose their function.
 If the plasma is too dilute, water can enter the nearby cells and
cause them to expand, also decreasing their function.
 This is especially dangerous in the brain.
 Studies have shown a close link between obesity, diabetes, and
kidney disease. Exercise helps maintain normal kidney function by
increasing blood flow, and it decreases the incidence of high blood
pressure. People receiving dialysis and those who have had kidney
transplants especially need to exercise.
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