Renal Physiology Flashcards
The kidney makes: ______________________, _______________________, such as _____________________ and ____________________ in the active form
Renin
Hormones
Erythropoietin
Vit D
Once urine is formed and exiting the medulla, it enters the ___________ calyx then the ___________ calyx and further into the renal ______________ and finally to the ureter
minor
major
pelvis
As the interlobar artery flows up the renal pyramid, it then runs parallel across the medulla and cortex where the artery is now termed , _________________ artery. These artery then run perpendicular up into the medulla and are now termed: _________________ artery. The _____________ arteriole branch off of the interlobar artery
Arcuate artery
Interlobar artery
afferent
The ______________ comprise 90% of the total glomeruli of the kidney and are located in the outer 2/3 of the cortex. The remaining 10% are termed: _____________
Cortical glomeruli
Juxtamedullary glomeruli
The peritubular capillaries are found:
They surround the _________________ and ___________________ ________________
Entirely in the cortex
Proximal and distal tubules
What are some differences of the juxtamedullary glomeruli?
1.) Deep within the cortex, proximal to the medulla
2.) The efferent arteriole from the glomeruli form the vasa recta that are vital to concentrating urine
3.) The vasa recta stretch deep into the medulla
The glomerular capillary is surrounded by:
Bowman’s capsule
Bowman’s capsule is formed by epithelial cells which then stretches on to form the:
Proximal tubule
The glomerulus has capillary ___________. When filtration occurs, the ______________ and ________________ ________________ of the plasma are forced across the capillary wall known as filtration.
loops
water
small solutes
T/F: The glomerulus itself cannot contract since it is comprised of capillary loops
False, in the central core of the glomerulus there is mesangial cell that can contract
List some functions of the mesangial cell
Contractile
Synthesizes products
Role in phagocytosis and immunity
In the glomerular capillary loop, there is a layer of endothelial cells. These cells like on a basement membrane that is proximal to Bowman’s capsule. Outside of the basement membrane exists the huge cell type:
Podocyte
What do podocytes do?
Within Bowman’s capsule inside the glomerular filtrate that give rise to “footlike projections” that surround the basement membrane of glomerular capillary.
What does fenestrated mean?
With perforations
What is the basement membrane within the glomerulus made of?
Gel layer that is supported by a matrix
T/F: Only the juxtamedullary glomeruli have a loop of Henle extending into the medulla
False, both have a loop of Henle extending into the medulla. The JMG extends much deeper into the medulla
What is the macula densa?
The portion of the thick ascending loop of Henle that is making contact with the afferent arteriole of the glomerulus
Where do you find the peritubular capillaries? Where do you find the vasa recta capillary network?
1.) surrounding the tubules of the superficial glomeruli
2.) Vasa recta ascending and descending run parallel to the loop of Henle of the juxtamedullary glomeruli
What is the Juxtaglomerular apparatus comprised of?
Macula densa + extraglomerular mesangium + terminal portion of the afferent arteriole
The thick ascending loop of Henle contacts with the afferent arteriole. What specialized cell type are going to communicate with the terminal portion of the afferent arteriole?
Cells termed macula densa communicate with extraglomerular mesangial cells
What two things are being communicated between the macula densa and mesangial cells at the Juxtaglomerular apparatus?
1.) Communicate to influence vascular tone if the afferent arteriole
2.) Communicate to influence granular cells that are at the top of the glomerulus underneath the afferent arteriole
Where are granular cells? What do they do? What is their structure type?
1.) Cells near the top portion of the glomerulus
2.) They synthesize renin and release
3.) specialized smooth muscle
What is the term for the side of epithelial cells that faces the tubule lumen?
Luminal or apical surface
What connects the epithelial cells lining the nephron tubules?
Tight junctions
What is the term for the epithelial cells that are facing the interstitial fluid of the nephron?
Peritubular or basolateral
Where are the Na+/K+ ATPase transporters found in the epithelial cells of the tubule
On the peritubular/basolateral side only so that sodium can only be reabsorbed back into the body
Why is the proximal tubule have a brush border?
Active site of reabsorption
Name the two types of cells found in the cortical collecting duct
1.) Principal cell
2.) Intercalated cell
T/F: Like most organ systems, the parasympathetic and sympathetic play a significant innervation role in the renal system
False, controlled by sympathetic. NO significant parasympathetic innervation
Glomerular filtration rate is normally very high. The normal is approx:
80-200 ml per minute
What are the 6 requirements of a substance to be used to measure GFR
1.) Freely filtered at the glomerulus so it will reach the tubule
2.) Not reabsorbed in the tubule
3.) Not secreted in the tubule
4.) Not metabolized
5.) Not toxic
6.) Not effect on the kidney
When determining if a substance is appropriate to use for GFR calculation, the amount filtered must be equal to the:
Amount excreted in the urine
(If freely filtered) Rate of filtration of substance X =
Plasma concentration x (Px) * GFR
Rate of excretion of substance X =
Urine concentration of X * urine flow rate (v)
Why is inulin used to measure GFR?
Because it cannot cross the cell wall of the tubule
If you have concentration of urine and plasma, what is the equation to calculate GFR?
GFR = ( [Ux]/[Px] ) * v
where Ux is urine concentration of substance X
Px is plasma concentration of substance X
v is urine flow rate
What is an endogenous substance that can be used to measure GFR? What is the drawback to this substtance?
Creatinine is freely filtered and not reabsorbed made in skeletal muscle
Drawback: there is some tubule secretion downstream from glomerulus so there is a little bit more creatinine cleared than is filtered at the glomerulus
What endogenous substance is typically used to measure GFR?
Creatinine
Creatine production matches creatinine excretion. Therefore, if GFR halves, what happens to plasma concentration Creatinine?
Its plasma concentration doubles
The higher the plasma creatinine, the:
lower the GFR
Why must creatinine measurement be adjusted when calculating GFR?
It can be affected in the setting of pregnancy, muscle wasting disease, and aging
What are three additional factors to consider when calculating eGFR from creatinine clearance?
Age, body weight in Kg, and sex
What is the clearance equation?
Cx = ( [Ux] / [Px] ) * V
C clearance substance X
U concentration of substance X
Plasma concentration of substance X
urine flow
Define clearance of a substance
A volume of plasma from which all of the substance is removed per unit time
T/F: Urinary clearance is the same as renal clearance
True
What is the equation for final urinary excretion of a substance?
[Ux] V = filtered x - reabsorbed x + secreted x
What is fractional clearance?
Method used to evaluate how the kidney handles a particular substance compared to how the substance is filtered
Compare the clearance to inulin, such that if clearance is the same of substance X compared to inulin, then it is considered freely filtered
If clearance substance X is < clearance inulin, what does this tell you?
There is reabsorption
Is clearance of substance X greater than or less than inulin clearance when there is secretion of substance X
Clearance substance X is greater than clearance inulin = substance X secretion
_______________ and _________________ are two examples of substances that are entirely (or almost entirely) reabsorbed and filtered by the kidney
Glucose (entirely reabsorbed normally)
Phosphate (mostly reabsorbed)
What is the normal plasma glucose?
100 mg/dL
What happens when the filtered load of the glomerulus is overloaded?
The substance is excreted through the urine
What is the expected fractional clearance of glucose? How would it compare to the fractional clearance of inluin?
Fractional clearance glucose is 0.0
Is lower to inulin because all of the glucose is reabsorbed rather than entirely excreted
What is the fractional clearance of phosphate?
0.2
Where is phosphate absorbed? What is its absorption coupled to?
Absorbed at the proximal tubule and coupled to sodium absorption
Why is fractional clearance of phosphate greater than factional clearance of glucose?
Because the reabsorptive capacity of phosphate is lower in the proximal tubule
What does phosphate’s fractional clearance of 0.2 actually mean?
20% of the filtered phosphate is excreted while the remaining 80% is absorbed
What is the fractional clearance of water?
0.01
What is the approx. amount of water being filtered at the glomerulus per minute?
~120 mL/min
Water reabsorption is ___________________ along the nephron
Passively
How does the changing concentration of inulin in the kidney relate to water reabsorption?
The plasma concentration of inulin is going to be less than what is excreted. This is because as inulin travels down the tubule, water is being reabsorbed which makes the concentration of inulin greater
Urine to plasma concentration (U/Pin) ratio of:
1 means:
U/Pin ratio of 1 means there is equal plasma concentration of inulin compared to urine [inulin]. If there was water absorption then the urine concentration would be high. Thus NO water reabsorption
Urine to plasma concentration (U/Pin) ratio of:
2 means:
Why?
U/P in ratio of 2 means the urine [inulin] is greater than plasma [inulin], thus some water is reabsorbed since the urine concentration is higher as the inulin traveled down the tubule. More specifically, 50% of water is reabsorbed
Urine to plasma concentration (U/Pin) ratio of:
100 means:
Why?
U/ Pin ratio of 100 means almost all of the water is reabsorbed since the urine [inulin] is much much greater than the plasma [inulin]
In normal humans, 99% of water is reabsorbed and 1% is excreted
Define free water of the body
Solute free, pure (distilled) water
What is free water clearance?
Comparing the volume of free water leaving the body compared to solute
What is the question to calculate free water clearance?
Clearance H20 = V - C osm
V is urine flow rate (Total amount of water leaving body)
C osm is osmolar clearance
C osm = U [osmolar] / P [osmolar] * V
What is the difference between tonicity and osmolarity?
Osmolarity can describe the state of solution vs cell and vice versa
Tonicity describes the state of the solution ONLY
What does it mean physiologically if there is positive free water clearance?
This means the urine flow rate, V, is greater than osmolar clearance. Such that the urine being excreted is hypo-osmotic and dilute
What does it mean if there is negative free water clearance?
Means the osmolar clearance is greater than urine flow rate, V. Thus the excreted urine is hyper-osmotic and more concentrated compared to plasma
What is the fractional clearance of urea?
~ 0.2 - 0.6
Urea is a _______________ product of ___________________ metabolism. Made in the __________________ and released into circulation for excretion by the kidney.
Waste
protein
liver
Urea is small and thus: _____________ _____________ into the tubule. And cross the tubule wall via:
Thus the, the MORE water absorption =
Freely filtered
Passive movement across the tubule wall down its concentration gradient
the more water absorption means more urea reabsorption since the leaving of H20 concentrates the urine creating a concentration gradient
Normally urea excretion and fractional clearance of urea are both low due to:
This means the blood urea nitrogen is:
Large water reabsorption which urea follows
High
What does comparing the plasma creatinine and BUN allow us to do clinically?
Determine dehydration VS kidney disease
If both go up this means GFR is falled = CKD
BUN up only = dehydration
The comparison of plasma creatinine and BUN can indicate difference between dehydration and CKD, why?
Creatinine is an endogenous substance that can be used to calculate GFR
BUN indicates the amount of water being excreted/reabsorbed because urea excretion is opposite BUN. Urea excretion and fractional clearance correlates to water absorption/excretion.
If BUN and creatinine levels go up what does this indicate and why?
CKD
Because creatinine filtration is supposed to match excretion under normal GFR. If creatinine levels go up, then the GFR went down
If BUN only goes up, what does this indicate and why?
Dehydration
This is because urea effectively follows water absorption/excretion
If urea is up, then water absorption is up due to the body needing to hydrate itself with water available
Urea is _________________ in the PCT and inner medullary collecting duct. Urea can be ________________ into the thin ascending loop of Henle.
Reabsorbed
Secreted
Clearance of urea is always <, >, or = to the clearance of inulin. Why?
C urea < C inulin because all plasma inulin should be excreted while plasma urea will be reabsorbed following flow of water
The para-aminohippuric acid fractional clearance is:
What does this mean
~ 5.0
Means the PAAH is secreted into the tubule
Why is plasma clearance of PAAH (para-aminohippuric acid) equal to the renal plasma flow rate?
Because, all PAAH from the plasma is secreted into the tubule for secretion = the volume is corresponding to the amount of plasma flowing through the kidney
Why is creatinine fractional clearance greater than clearance inulin?
Because while they are both freely filtered and entirely excreted, there is some tubular secretion of creatinine into the urine which raises the fractional clearance
Inulin and _____________ are perfect markers for GFR calculation but are not clinically used because they are not endogenous
Iothalamate
Describe the concentration of sodium and potassium in the intracellular and extracellular compartments
What maintains this composition?
INTRAcellular: High K+, Low Na+
EXTRAcellular: High Na+, Low K+
Na/K ATPase
Describe the concentration of protein inside the cell, in the interstitium, and within the plasma
INTRAcellular: 30 g/dl
Interstitium: 1 g/dl
Plasma: 7 g/dl
How much Na is reabsorbed?
The majority of it, 99%
Where are the ONLY two places that Na+ transport does NOT occur?
Descending loop of Henle and Thin ascending loop of Henle
Where does bulk reabsorption of sodium occur?
In the proximal tubule
What stimulates sodium reabsorption in the PCT?
What inhibits sodium reabsorption in the PCT (minor role)?
Stimulate: alpha-adrenergic nerves & ANG II
Inhibited: Atrial naturetic peptide and nitric oxide
How many “Stages” of sodium transport exist in the proximal tubule?
2
Describe sodium transport at the Early proximal tubule
The NHE3 major transporter
1.) The cell generates a H+ inside the cell and exchanges this ion for a Na+ from the tubule lumen
2.) Electrically neutral exchange
3.) Na+ is removed and put back into the body (interstitum) via Na+//K+ ATPase
What is the primary absorptive mechanism of sodium at the early PCT?
Na+ - H+ Exchange aka NHE3
Where does the NHE3 transporter exist? What type of transport occurs here?
At the early PCT
Uses secondary active transport using the energy generated from the Na+/K+ transporter on the apical side of the tubule
In the early PCT, what is significant about the H+ ion secretion?
The H+ drives bicarbonate reabsorption
T/F: The early PCT only reabsorbs sodium via NHE3 transporters
False, sodium transport also coupled to glucose, amino acid, phosphate, and lactate absorption
Describe the movement of Chloride in the early PCT
Leaks through channels into the interstitium
Describe the movement of H20 and sodium at the early PCT
Iso-osmotic. Water follows sodium transport
Why does solute concentration fall moving down the PCT?
Because it’s all been absorbed early in the PCT
Describe solute movement at the late PCT
1.) H ion + waste anions form H anion and are reabsorbed
2.) The anion breaks apart in the cell to release a H+ and anion
3.) Outward moving H+ couples with Na+ exchange while anion couples with Cl- exchange, thus Na+ and Cl- going into the cell
4.) The concentrated Cl- tubular fluid drives Cl-/Na+ down its concentration via paracellular diffusion into the peritubular capillary
Describe sodium movement at the Loop of Henle
Nothing in descending or ascending thin loop of Henle
Thick ascending loop of Henle, 25% Na sodium reabsorbed
What stimulates sodium reabsorption at the loop of Henle?
What inhibits sodium reabsorption?
Stimulate: alpha adrenergic nerve, Angiotensin II
Inhibit: prostaglandin
List the two transporters responsible for sodium exchange in the thick ascending loop of Henle
1.) NHE3, minor contributor
2.) Sodium potassium 2 Cl- Co-transporter (major transporter)
What is the abbreviation for the sodium potassium, 2 chloride co-transporter present in the TALH
NKCC2 transporter
What drives the NKCC2 co-transporter in the TALH?
ROMK channels
Potassium channels that allow K+ to flow down its concentration gradient into the tubular lumen
How does Na, K+, Cl- get into the interstitium?
Na+/K+ ATPase
K+/Cl- co-transporter
Both on the apical side
Other than supplying K+ in the TALH, what else is significant about the ROMK presence on the luminal cell side?
It creates a small + charge within the tubule lumen
What is special about the NKCC2 pump?
It is involved in signal transduction at the macula densa
T/F: The thick ascending limb is the site of sodium and water reabsorption
False, sodium reabsorption only. Always Impermeable to water!
How much sodium is reabsorbed by the distal tubule?
What stimulates this absorption?
What inhibits it?
~10%
Stimulated by: Aldosterone and Angiotensin II
Inhibited by: Atrial naturetic peptide and nitric oxide
What is the major controller of how much sodium is reabsorbed at the distal tubule and collecting duct?
Aldosterone
What transports sodium from the lumen in the distal tubule?
The NCC co transporter
What is special about the NCC transporter? Where is it located?
Thiazide sensitive
Distal tubule for sodium and Cl reabsorption
How does Aldosterone increase sodium reabsorption at the distal tubule?
Increases the number of NNC transporters in the luminal membrane
Also increases ATP to increase Na/K ATPase activity for more sodium to go back into the interstitium
Can even increase quantity of Na/K ATPase pumps
List the two different cell types of the collecting duct
1.) Principle
2.) Intercalated cell
Describe the movement of sodium and potassium in and out of the lumen in the principle cells of the collecting duct
1.) Sodium flows down its concentration gradient through epithelial sodium channels
2.) Potassium leaks out of the principle cell down its electrical concentration gradient to balance the negative charge that was established by reabsorption of Na+
What is the name of the epithelial sodium channels found in the collecting duct?
ENaC channel
T/F: Amiloride affects the number of ENaC channels in the principle cells of the collecting duct
False, Aldosterone influences the number of ENaC channels and causes channels to shuttle to the luminal membrane
Aside from reabsorbing sodium as needed for the body, what is significant about ENaC channels and the absorption of sodium from the collecting duct?
The + charged sodium being absorbed into the cell on a large scale creates a negative lumen charge that drives the flow of K+ out of the cell
T/F: Similar to its influence on sodium reabsorption in the principle cells of the collecting duct, Aldosterone also influences the movement of water in the collecting duct
False, water reabsorption is influenced by ADH
What diuretic inhibits the NKCC2 transporter? Thus, where is this diuretic acting?
Furosemide (Lasix)
Acting Thick ascending loop of Henle
What diuretics inhibit the NCC transporter? Thus, where is this diuretic acting?
Thiazides and Metolazone
Acting Distal tubule
What diuretics inhibit the ENaC transporter? Thus, where is this diuretic acting?
Amiloride and Triamterene
Collecting duct
What does Spironolactone inhibit? What further implications does this have?
Inhibits the actions of Aldosterone by inhibiting the actions of the mineralocorticoid receptors
Thus blocks reabsorption in the Distal tubule and Collecting duct
Describe how diuretics that act ahead of the collecting duct can cause hypokalemia and potassium wasting
If there is blocked sodium reabsorption ahead of the collecting duct, once filtrate reaches the collecting duct ENaC will attempt to compensate and reabsorb more Na+ here which will make the tubule lumen more negative and thus driving K+ out of the cell for excretion
Why is Amiloride considered a potassium sparing diuretic?
Because it blocks sodium reabsorption at the collecting duct, thus preventing the electrical concentration gradient formation to drive potassium out of the cell and into the lumen
Why does the sodium concentration in the ECF remain fairly constant even if sodium amount changes?
A change in sodium content reflects subsequent change in fluid volume to maintain concentration
In negative Na balance: Output > intake. Na ____________ occurs and ECF volume ____________. Which can lead to circulatory collapse and organ failure
Depletion
decreases/falls