Renal Physiology

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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
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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 waste products are left, such
  as urea, ammonia, and bilirubin.

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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
Filtrate arriving from Bowmans Capsule
Tubular Cells
Lumen of Tubule
Peritubular Capillaries

• 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 (NSAIDs).
• 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 ApparatusAlters 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 bladders 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.