Test 2 - Renal Physiology Flashcards
What is the most common cause of elevated plasma creatinine?
Dehydration
What does it mean to say that the kidney (like the heart and lungs) have reserve capacity?
This means that the kidney can do more work than it does at basal levels, Which means that filtering, reabsorptive and secretory function is not at its maximimal in the basal resting state; all can be increased.
This masks nephron loss to an extent.
What is meant by transport maximum?
There is a maximum rate at which nephron epithelium can remove substances from plasma and secrete them into filtrate. Similarly, there is a maximum rate at which nephron epithelium can reabsorb substances from filtrate.
What is the cause of transport maximum?
Transport is dependent on number/density of membrane transporters that allow for secretion or reabsorption.
Exceeding the transport maximum may occur in disease states and accumulation of substances in plasma may occur OR substances that should be reabsorbed are lost in urine.
What will happen if the rate of glucose getting filtered is greater than the rate of glucose getting reabsorbed?
You will see glucose in the urine.
TRUE/FALSE.
Rate of filtration is not variable.
FALSE.
The rate of filtration is variable and is dependent on GFR (flow) and concentration.
Amount/Time = Concentration x Flow
If concentration increases, more gets filtered.
Once Tmax is reached, the rate of excretion is ___ ( >, <, = ) the rate of filtration.
Equal to
Where does glucose get reabsorbed?
Proximal tubule ONLY.
This is also true for lactate, amino acids, VFAs, Ketones, glycerol, all organic molecules that cells obtain energy from.
TRUE/FALSE.
Tmax differes from one substance to another.
TRUE.
e.g. Tmax is high for glucose, but low for ketones. You only need to have a slight increase for it to appear in the urine.
TRUE/FALSE.
All cells have the same transport maximum.
FALSE.
Each cell has a different number of transporters. This difference accounts for the “splay” in the quantitative representation.
Once glucose passes the proximal tubule, can it be reabsorbed?
NO. It will not go to another nephron to get reabsorbed. It will be excreted.
Describe bovine glucose Tmax.
Bovine has low glucose Tmax. There is less plasma glucose to begin with because not a lot of glucose reabsorption is done in the GI tract. Virtually all roughage is acted on by microbes in the forestomachs to convert them into VFAs. This then undergoes gluconeogenesis. Therefore, the kidney does not have a lot of glucose transporters. Stress causes increase in glucose production.
THE USUAL SUSPECTS:
Urine Glucose
- Too much plasma glucose - Tmax will be exceeded
- Proximal Tubular Disease - Since this is the only place glucose gets reabsorbed
- Hemorrahge into the urinary tract
- Endocrine Problem:
a. Too much Hormones that increase glucose
b. Not enough insulin
What hormones increase plasma glucose?
What causes their increase?
Growth Hormone
Cortisol
Thyroid
Epinephrine
*Too much is a result of stress
In the graph, what is does it mean when the filtered and reabsorption graphs are superimposed?
During this time, the kidney can keep up. The amount being filtered is equal to the amount being absorbed.
When the reabsorption curve begins to deviate from the filtered curve, what is happening in the kidney?
Some nephrons are beginning to reach their transport maximum, while others are not. At the same time, there is a proportional increase in the amount of glucose excreted.
What do filtration, secretion, reabsorption and excretion measure?
Amount of a given substance per time in units mg/min.
GFR and clearance are expressed in units of ______ and measure _____.
ml/min
volume of plasma per time
The slope of the graph is a reflection of ______.
GFR
If the filtration curve were to increase its slope, what would this indicate? Decrease its slope?
An increase in slope would indicate an increase in GFR (it would lean more to the left). A decrease in slope would indicate a decrease in GFR (it would lean more to the right).
What does the amount of reabsorbtion depend on?
- The number of cells in the PCT that can reabsorb
- The number of transporters in each cell.
*Each of these is variable.
TRUE/FALSE.
When filtration = reabsorption of a particular substance, none is seen in the urine.
TRUE.
Only when filtration > reabsorption, is a substance excreted.
How does specific gravity relate to water balance as a whole?
It is a measure of how well the kidney is reabsorbing.
It is a measure of the density of urine in regards to all of the solutes present.
If an animal is dehydrated, you expect the kidney to _____ (increase, decrease, not change) water reabsorption at the PCT.
Increase
During dehydration, does the amount of waste molecule excreted in the urine change?
NO. The same amount of waste moleucles is filtered. The change is the concentration of waste that is excreted since the nephron is sent the message to increase it’s reabsorption.
If the osmolarity of plasma is 300 mOsm, what will the osmolarity be in Bowman’s Space?
300 mOsm
If the osmolarity of plasma is 300 mOsm, what will the osmolarity be in the renal vein?
290 mOsm
If the osmolarity of plasma is 300 mOsm, what will the osmolarity be of waste leaving?
310 mOsm
TRUE/FALSE
During dehydration, the animal is filtering the same volume and solute as prehydration status.
TRUE.
The animal is maintaining GFR (or at least trying to), and so the amount of plasma getting filtered remains the same, with the same amount of waste.
The osmolarity of plasma entering the lungs is _____ ( >, <, = ) the osmolarity of plasma leaving the lungs.
Less than.
This is due to the fact that water is lost during exhalation, concentrating the plasma.
What causes a greater release of ADH, a 10% drop in blood pressure or a 10% increase in osmolarity?
Increase in osmolarity. This will elicit a stronger signal to the kidney to reabsorb water.
What is the osmolarity that you don’t usually see animals exceed? What animals are the exception?
330 mOsm
Camels
TRUE/FALSE.
All osmolytes are freely filterable.
FALSE.
All except the 1mmol of protein are filterable.
What are the main non-protein nitrogen substances found in plasma?
Creatinine and Urea
What does specific gravity test?
Water reabsorption of the kidney.
What is the main route of nitrogen removal?
Urine
Who is putting urea into the blood stream?
LIVER ONLY
Who is putting creatinine into the blood stream?
Cardiac and skeletal muscle
What is the GI tract’s contribution to concentration of solutes and water?
It is putting water into (and taking it out of) plasma.
It puts solutes into the plasma (including amino acids to synthesize creatine).
If you’re going to use amino acids for reasons other than making protein, does nitrogen need to be removed?
Yes, it is done so as urea thanks to the liver.
If liver cells are being lost, then urea levels are _____.
Decreasing
During liver disease, what is happening to unwanted amino groups?
They are being turned into ammonia, giving the animal the smell of ammonia.
What causes the variability in creatinine concentration in plasma?
%body mass that is skeletal muscle.
African americans have more
Geriatrics have less because muscle decreases with age.
Do creatinine and urea exist in the same concentration in plasma?
NO. They are filtered at the same time and in the same volume of water.
How long does it take for all plasma to get filtered?
20-25 minutes
What are the two factors contributing to urine concentration? Which is the most significant contributor?
Water reabsorption and secretion of solute
Water reabsorption is the most significant.
By reabsorbing 99% of water, a substance is being concentrated _____ times.
100
If Substance X is secreted in the same amount that it was filtered, then 99% of water is reabsorbed. How concentrated is Substance X?
200 times more than its original concentration
What substances control urea reabsorption?
ADH and Cortisol
TRUE/FALSE.
There are ports available for creatinine reabsorption.
FALSE.
There are only unidirectional ports for its secretion from plasma to filtrate.
If urine osmolarity is ______ ( >, <, = ) plasma osmolarity, then the kidney is trying to decrease plasma osmolarity. When should this be seen?
Greater than
Most of the time because the animal is mostly in a state of dehydration (and therefore high plasma osmolarity).
When will USG =1?
NEVER. There is always waste in urine.
What is the USG range in bowman’s space?
What is this dependent on?
1.008-1.012
This depends on the animal’s hydration status.
Define isosthenuria.
When an animal excretes a urine with an osmolality/SG that is essentially identical to that of Bowman’s space - the kidney did nothing to the urine.
Is isosthenuria an acceptable finding?
NO. This means that the kidney is not concentrating the urine/doing anything. The only time this is OK is when we have given the animal a lot of fluids.
What would we think if an animal’s USG was 1.013?
It is slightly higher than what is found in Bowman’s space but this could be due to protein secretion. The jury is still out.
What would we think if an animal’s USG was 1.048?
That animal’s got damn good kidneys.
Is USG an accurate measurement of urine osmolarity?
NO. It is a good estimate though. A precise measurement of osmolarity found that one value of USG amongst 3 different dogs had 3 different osmolarities varying about 100 mOSm.
What is the range of mOsm urine for USG 1.008-1.012?
286-290 mOsm
Why does plasma osmolality increase in a dehydrated animal?
Solutes are continuously being deposited into plasma while plasma volume is decreasing.
What would also be seen in addition to isosthenuria?
Since the kidney is not concentrating the urine, the blood volume would be decreasing. USG would also be decreasing. However, plasma urea and creatinine begin to increase. You may think that the animal is dehydrated due to increased urea and creatinine, but it could be due to the fact that the kidney is not concentrating the urine.
Define what is meant by azotemia.
Accumulation of non-protein nitrogen molecules. An animal is azotemic if plasma urea and/or creatinine are greater than normal.
Azotemia is not considered a disease state.
When waste products accumulate such that toxic effects manifest, this is known as _____.
Uremia
What is the main cause of azotemia?
Dehydration
Define prerenal azotemia and some examples of causes.
This is azotemia caused by derangements “in front of” the kindey.
First though = dehydration. Same amount of NPNs just decreased volume. (Diarrhea, excess salivation due to choking)
Failing heart - unable to pump blood effectively and urea/creatinine are still being deposited into the bloood without efficient delivery to the kidneys.
Animal is hemorrhaging into the GI tract = high protein diet due to hemoglobin.
Define renal azotemia and some causes.
Azotemia that results from lack of filters at the kidney.
Edema/interstitial nephritis would decrease the lumen diameter and increase hydrostatic pressure in bowman’s space, leading to decreased GFR.
Kidney disease
Tumor in the renal pelvis
Define post-renal azotemia and some causes.
Azotemia caused by dysfunction downstream from the kidney.
Post-renal obstruction
D. renale
bladder bursts into the peritoneum (animal becomes azotemic when urea and creatinine diffuse across the peritoneal membrane, which they can).
Tumor - transitional epithelial carcinoma
Congenital issues - angles of ureters entering the bladder is wrong and the flow is altered.
TRUE/FALSE.
It is possible to have more than one azotemic condition.
TRUE.
If something is neither secreted nor reabsorbed, this means that ______.
There are no transporters present across the length of the membrane.
TRUE/FALSE.
Tight junctions are impermeable to substances in filtrate and interstitium.
FALSE.
They allow things through with varying constituency. Different proteins can be put into the membrane. Out of all the tight junctions, the ones in the PCT are the leakiest. They also allow water and electroyte movement between cells.
TRUE/FALSE.
The PCT secretes urea.
FALSE.
Urea is secreted by the LOH. The PCT reabsorbs it and the LOH brings it back to its original concentration.
Throughout the nephron, urea’s concentration continues to ______ (increase, decrease, stay the same, vary).
Increase.
Although it is reabsorbed, a greater amount of water is reabsorbed relative to urea.
Although urea is a waste molecule, why does it get reabsorbed?
It gets reabsorbed in order to use it as an osmolyte and further concentrate the urine.
TRUE/FALSE.
There are glucose transporters throughout the nephron.
FALSE.
The PCT is the ONLY place with glucose transporters.
Approximately _____ % of osmolyte and water get reabsorbed at the PCT.
65%-80% depending on the animal’s hydration status.
What are the two ways substances move through tight junction?
- Solvent Drag
- Diffusion
Describe how solvent drag works.
Because water is polar, it attracts anything that is electrically charged such as sodium, chloride, potassium. Together, they travel through the tight junctions.
Describe diffusion of substance X through a tight junction when substance X does not have transporters in the membrane and is freely filterable.
Once water gets reabsorbed, the concentration of Substance X in filtrate increases. This allows a concentratation gradient to build up and allows it to diffuse through the tight junctions.
What part of the nephron absorbs the most water/osmolyte?
Proximal tubule - doesn’t matter how hydrated you are.
If an animal is overly hydrated, how much water does the PCT reabsorb?
50% of what got filtered
What are the only two organic molecules that the PCT does not reabsorb ALL of?
Urea and uromodulin.
TRUE/FALSE.
The PCT alters filtrate osmolarity.
FALSE.
The PCT absorbs the same amount of osmolyte and water and does not alter the osmolarity at ALL.
The osmolarity of filtrate leaving the PCT is ____ (>, <, =) the osmolarity in bowman’s space/plasma.
Equal to.
Who alters the osmolarity of the filtrate?
Loop of Henle
By the time the filtrate reaches the end of the descending limb of the loop of henle, it is _____. Explain.
Hyperosmotic.
It reabsorbed ~20% of water and did not let water follow.
By the time the filtrate reaches the end of the ascending limb of the loop of henle, it is _____. Explain.
Hyposmotic
When would an animal have to create hyposmotic urine?
When it is overhydrated.
What signal is sent when salt touches the tongue?
ADH to conserve water.
What can we assume if the USG is 1.008?
The ascending limb of the LOH is working. We know this because this is the part the makes urine hyposmotic.
Does the DCT alter the osmolarity of urine?
NO. It absorbs solute and water at the same rate.
TRUE/FALSE.
Reabsorption of osmolytes and water is variable at the collecting duct.
TRUE.
This is dependent on the presence of messages such as ANP and aldosterone.
How do aquaporins vary in the medullary collecting duct?
From virtually none to plenty depending on the animal’s hydration status.
In what part(s) of the nephron are aquaporins present all the time?
PCT
Descending Loop of Henle
DCT
What part of the nephron completely lacks aquaporins?
Ascending limb of the Loop of Henle
TRUE/FALSE.
ADH and Aldosterone concentrations increase simultaneously.
TRUE.
At the medullary collecting duct, Aldosterone wants to reabsorb more sodium & ADH adds aquaporins to allow water to follow.
The medullary interestitium is ________ ALL OF THE TIME.
Hyperosmotic
Most of the time an animal is dehydrated and its [ADH] ______ ( <, >, =) [ANP].
Greater than
The animal wants to conserve water. ANP increases water loss.
What percentage of the osmolyte (and water) has been reabsorbed by the time urine is excreted?
99.80%
At the end of the PCT, what happens to the concentration of substances that are not reabsorbed?
Increases
By the end of the LOH, ___% of water and osmolyte has been reabsorbed.
85
What does PU/PD mean?
Polyuric/polydipsic animal. This means that the animal is urinating and drinking too much. It could be a problem with the kidney or the brain.
TRUE/FALSE.
If urea is not being produced at its normal rate, this could lead to increased urination and a PU/PD animal.
TRUE.
Urea is used as an osmolyte.
Cortisol ____ (increases/decreases) urea reabsorption for use as an osmolyte.
Decreases
How would an animal’s urine production change when put on steroids?
It would increase because urea would not be reabsorbed. Tell the owner to put more water out for the pet.
Urea that is reabsorbed at the medullary collecting duct is secreted in the _____.
Descending Limb of the Loop of Henle
What two ways does cortisol decrease water reabsorption?
- Decreases reabsorption at the medullary colelcting duct.
- Makes it more difficult for the brain to secrete ADH.
What are examples of drugs that act like cortisol to stop itching?
Prednisone, prednisolone, dexamethasone.
When is urea at it’s highest concentration?
When it reaches the Collecting duct.
What is cortisol’s action on urea reabsorption?
It blocks urea transporters at the medullary collecting duct.
How does the descending Loop of Henle reabsorb water?
It does so passively, through osmosis.
______ is the driving engine for vitually all reabsorbing and secretory properties.
Na/K ATPase
Where is Na/K ATPase found?
On the basolateral membrane in every cell.
TRUE/FALSE.
Cells are uniform in the protein distribution.
FALSE
Cells exhibit polarity and proteins can move since it is a fluid mosaic model.
What parts of the nephron actively move solute?
PCT
Ascending Loop of Henle
DCT
Collecting Duct
Which side of the membrane is known as the brush border membrane?
Luminal side
TRUE/FALSE.
Paracellular movement is occuring all of the time.
FALSE.
Paracellular movement only occurs if the cell is working to move things in the first place.
On what membrane do sodium leak channels exist?
Brush border membrane.
How are intracellular concentrations maintained when sodium is leaking in and potassium is leaking out?
Through the work of Na/K ATPase
What are some substances carried through sodium symports?
Chloride
Phosphate
Glucose
Creatinine
Lactate
Ketones
Amino Acids
What is the concentration of bicarbonate in the blood?
24 mmol = 1/12 plasma osmolarity
What is the importance of bicarbonate?
It is 1/12 of the osmolarity
It acts as a buffer for protons. Holds onto calcium ions in case it gets too high or too low.
Is HCO3- freely filterable? What is its pattern of reabsorption?
Yes. Its reabsorption depends on the animal’s acid/base status. Increased absorption of HCO3- would be a result of increased acidity.
TRUE/FALSE.
Bicarbonate ions are reabsorbed through ports.
FALSE.
It is reabsorbed by being converted back to CO2 and allowing it to diffuse into the cell. Once it diffuses in, the cell converts it back to bicarbonate.
What is bicarbonate reabsorption dependent on?
- CO2 production. The more CO2 that is produced, the more that gets reabsorbed.
- The number of ports on the basolateral membrane.
TRUE/FALSE.
It is more common to be more acidic.
TRUE.
What organs are the most important acid/base regulators?
Lungs (#1) & Kidneys
How is proton removed from the cell?
Through sodium symports.
What happens to an animal’s acid base status when its blood pressure lowers?
It becomes more acidic
How does Angiotensin II lower acidity?
It increases Na/H antiports on the luminal membrane of PCT cells.
TRUE/FALSE.
Potassium ports exist in the PCT.
FALSE.
How is potassium reabsorbed?
Since potassium is freely filterable and cannot get through the membrane, water that moves through aquaporins increases potassium concentration. This creates a concentration gradient allowing it to diffuse through tight junctions. It also gets reabsorbed through solvent drag.
There are ______ (more, less, the same amount of) substances that need to be secreted than reabsorbed.
More
Does each substance that needs to be secreted have a different symport?
No. Similar substances can travel through the same symport. For example, all negatively charged amino acids can go through a symport.
How is water reabsorption controlled?
By controlling the amount of solute in the interstitium. This causes osmotic pressure and the reason for water to move.
Does solute just sit in the interstitium?
No, it is carried away by the vasa recta.
Why is the interstitium always hyperosmotic?
Because of the solute that the ascending limb is putting into it.
How do diuretics work?
They block solute reabsorption at the A. LOH. These will cause the interstitium to become less hyperosmotic and osmotic pressure will decrease, which would decrease water reabsorption. This increases urine volume and decreases its osmolarity. A drug that does this can KILL YOU. E.g. Lasix.
Why is it important to block solute reabsorption at the A.LOH?
At the PCT, other important substances are being reabsorbed.
Describe how lasix works.
It is a loop diuretic. It blocks the reabsorption of sodium, potassium and chloride at in the ascending limb. These cells have a Na/K/2Cl Symport that is blocked. The longer lasix is given, the closer the animal is getting to isosthenuria.
What is another way a diuretic can work other than as a loop diuretic?
By blocking carbonic anhydrase.
Bicarbonnate will not be reabsorbed, which attracts sodium and will lose water.
Where do the most powerful diuretics work?
A.LOH
What is an osmotic diuretic?
A substance put in filtrate that does not have any ports to get reabsorbed. This increases the osmolyte in urine and decreases osmotic pressure for water to become reabsorbed. One such is mannitol.
What part of the nephron do you suspect to be damaged if you see isosthenuria?
A. LOH
What part of the nephron do you suspect to be damaged if you see hyposthenuria?
Collecting Duct
In the A.LOH, the membrane is _____ charged due to ______.
Positively
Potassium leak channels
What are tight junctions permeable to in the A. LOH?
Water and cations
** Very important for calcium reabsorption
What action is taken if an animal is hypocalcemic?
Calcium sensors in the basolateral membrane cause ports for calcium reabsorption to be put into tight junctions at the A. LOH and increase Na/K ATPase activity because as goes sodium, so does calcium.
THE USUAL SUSPECTS:
Increase Na/K ATPase Activity
**Also those who increase BP
Aldosterone
ADH
Angiotensin II
Epinephrine
Norepinephrine
What solute is the most important contributor to membrane potential?
Potassium and is a result of potassium leaking out
During abnormal changes in potassium concentrations, what portions of the nephron have obligate potassium reabsorption?
PCT - 67% - 80% (depending on hydration status)
A. LOH - 20%
Where is potassium reabsorption in the nephron variable depending on its concentration?
DCT
Cortical Collecting duct
What ion specifically do Loop diuretics waste?
Potassium
If giving Lasix, what should be your two concerns?
Dehydration & Hypokalemia
What are the 3 cell types of the distal nephron and which one is most abundant?
Principal cells (most abundant) a-intercalated cells B-intercalated cells
What are the transport components of a principal cell?
Basolateral Na/K ATPase
Na Uniport on the luminal membrane
K leak channels on the luminal membrane
Na/Cl Symports
What are the ways to alter reabsorption/secretion?
- Change activity of Na/K ATPase
- Change the number of Sodium Ports
- Change the number of Potassium Ports
What does aldosterone do?
A major stimulus for release is hyperkalemia and so it increases potassium secretory machinery. Increase Na/K ATPase activity (mainly), Increase K ports, increase Na ports.
Turning on Na reabsorptive machinery turns on K secretory machinery
Contributes to hyperosmotic interstitium
Acts on the ALOH, DCT, CCD and MCD (where principal and a-intercalated cells exist).
What are two big stimuli for Aldosterone secretion?
Hyperkalemia and RAAS system
TRUE/FALSE.
Na Uniports are only found in the distal nephron.
TRUE.
Why does potassium want to leave principal cells?
- The outside is negative due to tight junctions allowing through cations more easily than anions, so there is an accumulation of negative charge.
- Concentration gradient: There is more K inside the cell.
If an animal is normokalemic but experiences a drop in blood pressure. This would cause secretion of aldosterone, which increases K secretory machinery. How would K get reabsorbed if its concentration is normal?
Through the tight junctions. It will diffuse down its concentration gradient and be taken with solvent drag.
What happens if an animal is not producing enough aldosterone?
It is PU/PD and is usually in shock.
_____ is a distal nephron effector and acts to increase ___ reabsorption.
Aldosterone
Na
Addison’s Disease
An animal is not producing aldosterone, neither is cortisol.
What cells is water reabsorption attributable to in the nephron?
Principal cells
a/b intercalated cells are mainly dedicated to _____.
Acid/Base balance
TRUE/FALSE.
If an animal is hypotensive, it will become hypokalemic because aldosterone release will increase its secretory machinery.
FALSE.
Although it will be secreted, it will be reabsorbed through tight junctions.
What are the major stimuli for insulin release?
Too much potassium, glucose and amino acids
What cells does insulin communicate with during hyperkalemic situations?
Muscle cells to increase take up of potassium to eventually secrete it in the urine. Once muscle cells secrete it, this stimuluates aldosterone to tell principal cells to secrete it.
a-Intercalated cells pump ____ into interstitium and ____ into filtrate.
Bicarbonate
Proton
**Dedicated to alkalinizing plasma.
a-intercalated cells have additional ATPase. What are they?
H ATPase
H/K ATPase to make urine more acidic.
Acidemia.
WHO WE GONNA CALL?
PCT
a-intercalated cells
Elevated potassium also tells a-intercalated cells to stop secreting _____. WHY?
Proton
If proton is being secreted, it is decreasing negativity (attracting force for K).
