Alterations in Renal Function, pg 1
Renal Structure
The kidneys are a pair of bean shaped organs that lie outside the peritoneal cavity between the T-12 and L-3. The right is
slightly lower than the left because the liver is in the way (the liver is HUGE). The kidney is made up of three layers, the
cortex, medulla and pelvis. The cortex is the outer layer, the medulla is where the nephrons are, and the pelvis is the very
inner part where urine collects. Note that the renal artery is second aorta off the heart (first is hepatic)...they get a large
blood supply and this is why urine output is an indicator of organ/tissue perfusion.
Renal Perfusion...a huge deal! Love to be flooded with fluid all the time!
• Kidneys are perfused with 1000 to 1300 ml of blood per minute
• This amounts to 20 – 25% of cardiac output (another 25% goes to hepatic). These two organs get a LOT of blood!
• Recall that GFT = glomerular filtration rate...it is the rate at which blood flow perfuses through the renal artery into the
filtration system of the kidney.
• A sufficient GFR is needed for removal of waste products (GFR= how much blood going into the kidneys and how much
filtration is going on) > or < 60 ml/min...what we watn to know is that GFR less than 60, then we have to start adjusting
meds and being careful about contrast dye...that means there is renal insufficiency.
• Feedback mechanisms are designed to keep GFR up despite changes in circulatory status. The body will sacrifice a lot
of things, but will not sacrifice the kidneys (the body will even sacrifice the brain in favor of the kidneys!)
• SNS maintains GFR. Recall that SNS is responsible for heart rate and vasodilation/vasodilation. Vasoconstriction
and tachycardia will keep kidneys perfused...these are SNS responses! If the body has a lowered perfusion state,
the kidneys will try to compensate (as in shock).
Micro Structure
• The working unit of the kidney is the nephron whose primary function is to filter blood. There are about 1 million in each
kidney. Each nephron consists of three parts:
• glomerulus for filtration (filters blood as it comes through the Juxtoglomerular Apparatus)
• tubular components (designed to equilibrate things like K, Na, glucose, etc...)
• Collecting duct (purpose of collecting filtrate and sending it to renal pelvis and out through ureter)
Kidney Function
• Filtration and removal of wastes (extra nutrients, glucose, etc...)
• Fluid and electrolyte balance
• Acid Base Balance (works to maintain that normal range of pH...a very narrow window! 7.40-7.45!
• RBC production (secrete erythropoietin to stim RBC production)
• Calcium absorption (kidneys do this, too!)
Glomerulus
The glomerulus is a compact tuft of capillaries encased in Bowman’s Capsule. It is essentially a series of membranes
allowing for filtration of blood that is entering the nephron. It is a high-pressure, semi-permeable capillary bed. So, for
adequate filtration to occur, there must be adequate blood volume in the intravascular space and adequate hydrostatic
pressure from the cardiac output and vascular resistance.
Alterations in these mechanisms occur in chronic diseases (diabetes, HTN, kidney disease). When damaged, they no
longer filter appropriately...so when your pt has long-term disease you need to look at kidney function...they will be spilling
sugar and protein (no longer filtering)...this is a sign of strain on the kidneys d/t DM and HTN. Tells us some of the
nephrons are damaged!
Glomerular Filtration Rate
• Measures the plasma volume that can be cleared of any given substance
• Used as an indicator of adequacy of renal function
• Altered by diseases that change plasma flow or permeability of membrane
• Normal GFR is 180 L per day. Minimum GFR is 60 mL / hour (will be on the chem panel <60 or > 60). If < 60 we
have to adjust meds and avoid contrast material.
• Tells us how well we can clear any given substance (a med, a nutrient, acid, etc...)
, Alterations in Renal Function, pg 2
Tubules of the Nephron:
The tubules are responsible for adjusting all the electrolytes to maintain homeostasis. (Reabsorption/Secretion) Ex: If
filtrate is delivered to G and filters out a bunch of Na, the filtrate goes out to the tubule and now the Na level in the body
has dropped a little bit, the tubule will send some of that Na back into circulation (reabsorption).
• Tubular Reabsorption
• Filtrate returned to the blood supply
• Tubular Secretion
• Substances secreted into tubules to be excreted
• 4 segments
• Proximal Convoluted Tubule
• Loop of Henle (important...the loop where things like Lasix work to Increase urine output “Loop Diuretics”)
• Distal Convoluted Tubule
• Collecting tubule
Tubular reabsorption is accomplished in the proximal convoluted tubules of the kidneys. Reabsorption occurs as a result of
active transport and passive transport. Tubular secretion is the process by which substances like K, H and abx are
secreted into the tubules to be excreted in the final stage of urine formation. The final concentration of dilution of urine
occurs in the distal tubules and collecting ducts that lead to the bladder. The volume of urine excreted should be about
1500 mL per day. Less tahn 400 mL per day is considered renal failure.
Urine Formation: A Three step process (body constantly makes adjustments throughout)
• Filtration : filters out excess potassium, H+ ions, Calcium, glucose, Phosporous etc.
• Reabsorption: calls back electrolytes that are needed
• Secretion: sent through to the collecting ducts to be emptied into the ureter and bladder
Elimination Function of the Kidney
Every substance has its own clearance rate (glucose, K, meds, etc...). Two conditions that can increase renal blood flow
and GFR (so we can get rid of those)
• Elevated protein content in the blood
• Elevated glucose content in the blood (ex: polyuria in DM is the body trying to get rid of sugar..does this via
vasoconstricion/HTN...explains why DM can cause HTN!)
Urea Elimination
Urea is the end product of protein metabolism (eat chicken, liver metabolizes it and the byproduct is urea...when you eat a
lot of protein the urea is going to be high, when liver not working, urea will be low). A normal adult produces 25 – 30 g/ day
of urea. Urea in the blood increases with high protein diet, muscle breakdown, GI bleeding (if bleeding into stomach,
stomach digests that and sends it to liver to be metabolized), and dehydration.
The kidneys filter and reabsorb to maintain a normal BUN of 8-20. During dehydration, BUN may go up due to a decreased
GFR and decreased clearance of BUN. Note that BUN decreases with malnutrition and liver failure as the body no longer
metabolizes proteins efficiently and urea is not formed.
Drug Elimination
Drugs are selectively filtered in the glomerulus...they can be reabsorbed or secreted as well (can be sent out and pulled
back in). Drugs that are not bound to plasma proteins are filtered (they leave very quickly...fat soluble ones don’t get
filtered out so you have to watch toxic levels of ADEK). Other drugs are detox’d in the LIVER.
Fluid / Electrolyte Balances.
In addition to being adjusted during filtration/secretion stage...are also affected by hormones: aldosterone, anti-diuretic
hormone and atrial naturetic peptide (ANP). Baroceptors and chemoreceptors detect changes and initiate the secretion of
the hormones.
, Alterations in Renal Function, pg 3
Aldosterone
Aldosterone is secreted by the Adrenal gland (it is a hormone) in response to fluid deficits...it prompts sodium reabsorption
(where sodium goes, so goes water...where Na goes, K goes in the opposite direction.) So it hangs on to Na and Water,
but gets rid of K (secretes it into collecting tubule). If we don’t have enough Aldosterone, then no Na is reabsorbed and we
lose a lot of water in the kidneys. We secrete Aldosterone when we need to retain water.
What happens when Na is low? decreased mentation, confusion, hallucinations and then twitching all the way to seizures.
Not really a factor of how low Na is, but how FAST it dropped. Some pt can live with a low sodium...if it gradually dropped
off then they may be asymptomatic. When it drops FAST, this causes substantial fluid shifts leading to swollen brain. (ex:
Wee Wii contest) And what happens when K too low? Scary changes in contractility.
Anti Diuretic Hormone
ADH is produced/triggered by the hypothalamus and secreted by the posterior pituitary. It enhances the ability of water to
follow sodium as it is excreted or reabsorbed. The release of ADH is stimulated by baroreceptors and osmoreceptors that
sit in the carotids. (Note that if the carotids get lined with plaque, then these receptors have a hard time doing their job.)
When a baroreceptor senses low pressure, it stimulates production of ADH so that the body hangs on to fluid. When the
osmoreceptor sense the blood is too concentrated (high osmolarity), it inhibits production of ADH. What is going to happen
to urine output with ADH release? It goes down!
Atrial Naturetic Peptide
ANP is synthesized in the muscle cells of the atrium (BNP is synthesized in walls of ventricle). It is released when the atria
is stretched, →
• Vasodilation of afferent and efferent arterioles
• Increased renal blood flow
• Increased GFR (wants to get rid of fluid when preload is too high...this happens with CHF to help compensate)
• Inhibits Aldosterone and ADH at the same time (aldosterone conserves water, ADH conserves water)
We can measure BNP and this sometimes tells us if pt is in congestive heart failure. (will be elevated with CHF.)
Acid Base Balance (HCO3, Phosphate, Ammonia)
• North American diet results in 40 – 80 mMol of H+ ions each day
• The kidney is the only pathway for eliminating H+ ions
• The ability of the kidneys to excrete H+ ions depends on buffers
• HCO3 - bicarbonate (H ions binds with bicarb in urine filtrate...forms CO2 and H20)
• HPO4 - phosphate (phosphate ions are metabolic end products that bind with H and are excreted)
• NH3 - ammonia (a byproduct of liver fxn...if liver not working well, ammonia will build up)
• Ex: Lactulose is given as a laxative...look at labs and you’ll often see that liver enzymes will be elevated, so
lactulose is given to get rid of ammonia that is building up....so a double-whammy.
• When H ions bind up with something like bicarb, sometimes the body will send a lot of CO2 back into the system,
and the CO2 goes into the lungs and we get rid of it that way. This explains how the body attempts to compensate
for acid/base balance.
• Recall that potassium tends to be high when the body is acidotic. This is because when acidosis occurs, the
kidneys will increase the excretion of H and decrease the elimination of potassium so there is a resultant increase in
serum potassium levels. Secondly, the H will be forced into the cells and the K will come out of the cells in
exchange (both are cations so an exchange MUST take place to maintain the electrical properties of the cell).
• So, in summary...H that is formed in the body is sent to the kidneys to be excreted. The kidneys excrete some of it
by linking it up with phosphate and ammonia and sending it away. The rest of it binds with HCO3 to form carbonic
anhydrase, then reabsorbs it and sends it to the lungs, where carbonic anhydrase (H2CO3) is broken down to H20
and Co2 and then lungs then blows it off. EXCEPT for when the lungs cannot do their job (hypoventilation,
decreased perfusion, COPD, pneumonia, etc...)
Endocrine Function of Kidney: Renin – Angiotensin, Erythropoietin, Vitamin D
Renin - Angiotensin (secreted by kidney when GFR is low)
Renin plays an important role in BP regulation. It is stored in the Juxtaglomerular cells (JG cells)
Renal Structure
The kidneys are a pair of bean shaped organs that lie outside the peritoneal cavity between the T-12 and L-3. The right is
slightly lower than the left because the liver is in the way (the liver is HUGE). The kidney is made up of three layers, the
cortex, medulla and pelvis. The cortex is the outer layer, the medulla is where the nephrons are, and the pelvis is the very
inner part where urine collects. Note that the renal artery is second aorta off the heart (first is hepatic)...they get a large
blood supply and this is why urine output is an indicator of organ/tissue perfusion.
Renal Perfusion...a huge deal! Love to be flooded with fluid all the time!
• Kidneys are perfused with 1000 to 1300 ml of blood per minute
• This amounts to 20 – 25% of cardiac output (another 25% goes to hepatic). These two organs get a LOT of blood!
• Recall that GFT = glomerular filtration rate...it is the rate at which blood flow perfuses through the renal artery into the
filtration system of the kidney.
• A sufficient GFR is needed for removal of waste products (GFR= how much blood going into the kidneys and how much
filtration is going on) > or < 60 ml/min...what we watn to know is that GFR less than 60, then we have to start adjusting
meds and being careful about contrast dye...that means there is renal insufficiency.
• Feedback mechanisms are designed to keep GFR up despite changes in circulatory status. The body will sacrifice a lot
of things, but will not sacrifice the kidneys (the body will even sacrifice the brain in favor of the kidneys!)
• SNS maintains GFR. Recall that SNS is responsible for heart rate and vasodilation/vasodilation. Vasoconstriction
and tachycardia will keep kidneys perfused...these are SNS responses! If the body has a lowered perfusion state,
the kidneys will try to compensate (as in shock).
Micro Structure
• The working unit of the kidney is the nephron whose primary function is to filter blood. There are about 1 million in each
kidney. Each nephron consists of three parts:
• glomerulus for filtration (filters blood as it comes through the Juxtoglomerular Apparatus)
• tubular components (designed to equilibrate things like K, Na, glucose, etc...)
• Collecting duct (purpose of collecting filtrate and sending it to renal pelvis and out through ureter)
Kidney Function
• Filtration and removal of wastes (extra nutrients, glucose, etc...)
• Fluid and electrolyte balance
• Acid Base Balance (works to maintain that normal range of pH...a very narrow window! 7.40-7.45!
• RBC production (secrete erythropoietin to stim RBC production)
• Calcium absorption (kidneys do this, too!)
Glomerulus
The glomerulus is a compact tuft of capillaries encased in Bowman’s Capsule. It is essentially a series of membranes
allowing for filtration of blood that is entering the nephron. It is a high-pressure, semi-permeable capillary bed. So, for
adequate filtration to occur, there must be adequate blood volume in the intravascular space and adequate hydrostatic
pressure from the cardiac output and vascular resistance.
Alterations in these mechanisms occur in chronic diseases (diabetes, HTN, kidney disease). When damaged, they no
longer filter appropriately...so when your pt has long-term disease you need to look at kidney function...they will be spilling
sugar and protein (no longer filtering)...this is a sign of strain on the kidneys d/t DM and HTN. Tells us some of the
nephrons are damaged!
Glomerular Filtration Rate
• Measures the plasma volume that can be cleared of any given substance
• Used as an indicator of adequacy of renal function
• Altered by diseases that change plasma flow or permeability of membrane
• Normal GFR is 180 L per day. Minimum GFR is 60 mL / hour (will be on the chem panel <60 or > 60). If < 60 we
have to adjust meds and avoid contrast material.
• Tells us how well we can clear any given substance (a med, a nutrient, acid, etc...)
, Alterations in Renal Function, pg 2
Tubules of the Nephron:
The tubules are responsible for adjusting all the electrolytes to maintain homeostasis. (Reabsorption/Secretion) Ex: If
filtrate is delivered to G and filters out a bunch of Na, the filtrate goes out to the tubule and now the Na level in the body
has dropped a little bit, the tubule will send some of that Na back into circulation (reabsorption).
• Tubular Reabsorption
• Filtrate returned to the blood supply
• Tubular Secretion
• Substances secreted into tubules to be excreted
• 4 segments
• Proximal Convoluted Tubule
• Loop of Henle (important...the loop where things like Lasix work to Increase urine output “Loop Diuretics”)
• Distal Convoluted Tubule
• Collecting tubule
Tubular reabsorption is accomplished in the proximal convoluted tubules of the kidneys. Reabsorption occurs as a result of
active transport and passive transport. Tubular secretion is the process by which substances like K, H and abx are
secreted into the tubules to be excreted in the final stage of urine formation. The final concentration of dilution of urine
occurs in the distal tubules and collecting ducts that lead to the bladder. The volume of urine excreted should be about
1500 mL per day. Less tahn 400 mL per day is considered renal failure.
Urine Formation: A Three step process (body constantly makes adjustments throughout)
• Filtration : filters out excess potassium, H+ ions, Calcium, glucose, Phosporous etc.
• Reabsorption: calls back electrolytes that are needed
• Secretion: sent through to the collecting ducts to be emptied into the ureter and bladder
Elimination Function of the Kidney
Every substance has its own clearance rate (glucose, K, meds, etc...). Two conditions that can increase renal blood flow
and GFR (so we can get rid of those)
• Elevated protein content in the blood
• Elevated glucose content in the blood (ex: polyuria in DM is the body trying to get rid of sugar..does this via
vasoconstricion/HTN...explains why DM can cause HTN!)
Urea Elimination
Urea is the end product of protein metabolism (eat chicken, liver metabolizes it and the byproduct is urea...when you eat a
lot of protein the urea is going to be high, when liver not working, urea will be low). A normal adult produces 25 – 30 g/ day
of urea. Urea in the blood increases with high protein diet, muscle breakdown, GI bleeding (if bleeding into stomach,
stomach digests that and sends it to liver to be metabolized), and dehydration.
The kidneys filter and reabsorb to maintain a normal BUN of 8-20. During dehydration, BUN may go up due to a decreased
GFR and decreased clearance of BUN. Note that BUN decreases with malnutrition and liver failure as the body no longer
metabolizes proteins efficiently and urea is not formed.
Drug Elimination
Drugs are selectively filtered in the glomerulus...they can be reabsorbed or secreted as well (can be sent out and pulled
back in). Drugs that are not bound to plasma proteins are filtered (they leave very quickly...fat soluble ones don’t get
filtered out so you have to watch toxic levels of ADEK). Other drugs are detox’d in the LIVER.
Fluid / Electrolyte Balances.
In addition to being adjusted during filtration/secretion stage...are also affected by hormones: aldosterone, anti-diuretic
hormone and atrial naturetic peptide (ANP). Baroceptors and chemoreceptors detect changes and initiate the secretion of
the hormones.
, Alterations in Renal Function, pg 3
Aldosterone
Aldosterone is secreted by the Adrenal gland (it is a hormone) in response to fluid deficits...it prompts sodium reabsorption
(where sodium goes, so goes water...where Na goes, K goes in the opposite direction.) So it hangs on to Na and Water,
but gets rid of K (secretes it into collecting tubule). If we don’t have enough Aldosterone, then no Na is reabsorbed and we
lose a lot of water in the kidneys. We secrete Aldosterone when we need to retain water.
What happens when Na is low? decreased mentation, confusion, hallucinations and then twitching all the way to seizures.
Not really a factor of how low Na is, but how FAST it dropped. Some pt can live with a low sodium...if it gradually dropped
off then they may be asymptomatic. When it drops FAST, this causes substantial fluid shifts leading to swollen brain. (ex:
Wee Wii contest) And what happens when K too low? Scary changes in contractility.
Anti Diuretic Hormone
ADH is produced/triggered by the hypothalamus and secreted by the posterior pituitary. It enhances the ability of water to
follow sodium as it is excreted or reabsorbed. The release of ADH is stimulated by baroreceptors and osmoreceptors that
sit in the carotids. (Note that if the carotids get lined with plaque, then these receptors have a hard time doing their job.)
When a baroreceptor senses low pressure, it stimulates production of ADH so that the body hangs on to fluid. When the
osmoreceptor sense the blood is too concentrated (high osmolarity), it inhibits production of ADH. What is going to happen
to urine output with ADH release? It goes down!
Atrial Naturetic Peptide
ANP is synthesized in the muscle cells of the atrium (BNP is synthesized in walls of ventricle). It is released when the atria
is stretched, →
• Vasodilation of afferent and efferent arterioles
• Increased renal blood flow
• Increased GFR (wants to get rid of fluid when preload is too high...this happens with CHF to help compensate)
• Inhibits Aldosterone and ADH at the same time (aldosterone conserves water, ADH conserves water)
We can measure BNP and this sometimes tells us if pt is in congestive heart failure. (will be elevated with CHF.)
Acid Base Balance (HCO3, Phosphate, Ammonia)
• North American diet results in 40 – 80 mMol of H+ ions each day
• The kidney is the only pathway for eliminating H+ ions
• The ability of the kidneys to excrete H+ ions depends on buffers
• HCO3 - bicarbonate (H ions binds with bicarb in urine filtrate...forms CO2 and H20)
• HPO4 - phosphate (phosphate ions are metabolic end products that bind with H and are excreted)
• NH3 - ammonia (a byproduct of liver fxn...if liver not working well, ammonia will build up)
• Ex: Lactulose is given as a laxative...look at labs and you’ll often see that liver enzymes will be elevated, so
lactulose is given to get rid of ammonia that is building up....so a double-whammy.
• When H ions bind up with something like bicarb, sometimes the body will send a lot of CO2 back into the system,
and the CO2 goes into the lungs and we get rid of it that way. This explains how the body attempts to compensate
for acid/base balance.
• Recall that potassium tends to be high when the body is acidotic. This is because when acidosis occurs, the
kidneys will increase the excretion of H and decrease the elimination of potassium so there is a resultant increase in
serum potassium levels. Secondly, the H will be forced into the cells and the K will come out of the cells in
exchange (both are cations so an exchange MUST take place to maintain the electrical properties of the cell).
• So, in summary...H that is formed in the body is sent to the kidneys to be excreted. The kidneys excrete some of it
by linking it up with phosphate and ammonia and sending it away. The rest of it binds with HCO3 to form carbonic
anhydrase, then reabsorbs it and sends it to the lungs, where carbonic anhydrase (H2CO3) is broken down to H20
and Co2 and then lungs then blows it off. EXCEPT for when the lungs cannot do their job (hypoventilation,
decreased perfusion, COPD, pneumonia, etc...)
Endocrine Function of Kidney: Renin – Angiotensin, Erythropoietin, Vitamin D
Renin - Angiotensin (secreted by kidney when GFR is low)
Renin plays an important role in BP regulation. It is stored in the Juxtaglomerular cells (JG cells)
