Renal Physiology Flashcards
What is clearance?
A general concept that describes the rate at which substances are removed from plasma
Define renal clearance
The volume of plasma completely cleared of a substance by the kidneys per unit time
The higher the renal clearance, the ____ plasma that is cleared of the substance.
more
How do you calculate renal clearance?
C = ([U]x × V) / [P]x
where…
C = Clearance
[U]x = Urine concentration of substance X
V = Urine flow rate per minute
[P]x = Plasma concentration of substance X
Renal clearance is the ratio of what 2 things?
urinary excretion to plasma concentration
Renal clearance of a substance increases as the urinary excretion _____.
increases
What is the renal clearance of albumin? Explain why
Approximately zero, because normally, albumin is not filtered across the glomerular capillaries
What is the renal clearance of glucose? Explain why
Approximately zero, because glucose is filtered and then completely reabsorbed back into the bloodstream
What is the renal clearance of Na+, urea, phosphate, and Cl-? Explain why
Higher than zero, because they are filtered and partially reabsorbed
Which substances have the highest renal clearance rates? Explain why
Organic acids such as para-aminohippuric acid (PAH), because they are both filtered and secreted.
What is the only substance whose clearance is exactly equal to the glomerular filtration rate (GFR)?
Inulin
Describe how inulin’s clearance rate is equal to the GFR?
Because it is freely filtered across the glomerular capillaries, but once it is filtered, it is neither reabsorbed nor secreted. Therefore, the amount of inulin filtered will be exactly equal to the amount of inulin excreted
What is inulin referred to as?
a glomerular marker
What is the clearance ratio?
The ratio between the clearance of any substance and the clearance of inulin
Under what circumstances will the clearance ratio equal 1.0?
When the clearance of substance x is equal to the clearance of inulin. Therefore, substance x is also a glomerular marker
Under what circumstances will the clearance ratio be less than 1.0?
When the clearance of substance x is lower than the clearance of inulin. So, substance x is either not filtered or it is filtered and subsequently reabsorbed.
Which substances will produce a clearance ratio less than 1.0?
- Albumin
- Na+
- Cl-
- Bicrobonate
- Phosphate
- Urea
- Glucose
- Amino Acids
Under what circumstances will the clearance ratio be greater than 1.0?
When the clearance of substance x is higher than the clearance of inulin. So, substance x is filtered and secreted
Which substances will produce a clearance ratio greater than 1.0?
- organic acids and bases
- K+
What percentage of the cardiac output do the kidneys receive?
about 25%
Renal blood flow = __ L/min
1.25
Renal blood flow is _____ proportional to the pressure gradient and _____ proportional to the resistance.
directly
inversely
What 3 things cause vasoconstriction of the afferent and efferent renal arterioles?
- Sympathetic nervous system
- Angiotensin II
- Endothelin
Sympathetic nerve activity causes a _____ in both renal blood flow and glomerular filtration rate.
decrease
Sympathetic nerve activity causes vasoconstriction of which arteriole?
The afferent
Angiotensin II causes vasoconstriction of which arteriole?
Both afferent and efferent
Angiotensin II constricts both arterioles, _____ resistance, and ______ blood flow
increases
decreases
Which arteriole is more sensitive to angiotensin II?
the efferent arteriole
High levels of angiotensin II produce a(n) ______ in GFR by constricting both the efferent arterioles
increase
Low levels of angiotensin II produce a(n) ______ in GFR by constricting both the afferent and efferent arterioles
decrease
What 4 things cause vasodilation of the afferent and efferent renal arterioles?
- prostaglandins
- nitric oxide
- bradykinin
- dopamine
What do prostaglandins modulate?
The vasoconstriction produced by the sympathetic nervous system and angiotensin II
At ___ levels dopamine causes vasoconstriction
low
What is the range in which renal arterial pressure is autoregulated?
80 to 200 mm Hg
*important to note that RBF is kept constant
When will renal blood flow begin to decrease?
When renal arterial pressure decreases to less than 80 mm Hg
What occurs in order to maintain constant blood flow in the face of changing arterial pressure?
The resistance of the afferent arterioles varies
Why can we conclude that the autonomic nervous system is not involved in the mechanism of autoreguation?
A denervated (transplanted) kidney autoregulates as well as any intact kideny
What are the 2 major theories explaining renal autoregulation?
- myogenic mechanism
- tubuloglomerular feedback
What does the myogenic response state?
That increased arterial pressure stretches the blood vessels, which causes reflex contraction of smooth muscle in the blood vessel walls and consequently increased resistance to blood flow
How does the myogenic hypothesis explain autoregulation of renal blood flow?
1) Increases in renal arterial pressure stretch the walls of the afferent arterioles, which respond by contracting.
2) Afferent arteriolar contraction leads to increased afferent arteriolar resistance.
3) This increase resistance then balances the increase in arterial pressure
4) RBF is kept constant
How does tubuloglomerular feedback explain autoregulation of renal blood flow?
1) Increases in arterial pressure increases both RBF and GFR
2) The increase in GFR results in increased delivery of solute and water to the macula densa region of early distal tubule, which senses some component of the increased delivery load
3) The macula densa responds to the increased delivery load by secreting a vasoactive substance that constricts afferent arterioles
4) Local vasoconstriction of afferent arterioles then reduces RBF and GFR back to normal
What is the first step in the formation of urine?
Glomerular filtration
As the renal blood flow enters the glomerular capillaries, a portion of that blood is filtered into Bowman’s space, what is this filtered fluid called?
ultrafiltrate
What does the ultrafiltrate contain? What does it not contain?
It contains water and all of the small solutes of blood, but it does not contain proteins and blood cells
What forces are responsible for glomerular filtration?
Starling forces
What 2 things do the characteristics of the glomerular capillary wall determine?
- what is filtered into Bowman’s space
- how much is filtered into Bowman’s space
What are the 3 layers of the glomerular capillary wall?
- endothelium
- basement membrane
- epithelium
What is filtered across the endothelium?
Fluid, dissolved solutes, and plasma proteins
What are the 3 layers of the basement membrane?
- lamina rara interna
- lamina densa
- lamina rara externa
Which layer of the glomerular capillary wall constitutes the most significant barrier of the glomerular capillary?
the basement membrane, followed by the epithelium
The epithelial cell layer consists of specialized cells called what?
podocytes
In addition to size barriers what is another feature of the glomerular barrier?
the presence of negatively charged glycoproteins
Where are these negatively charged glycoproteins present?
- on the endothelium
- on the lamina rara interna and externa of the basement membrane
- on the podocytes and foot processes
- on the filtration slits of the epithelium
What is the consequence of these fixed negative charges?
they add an electrostatic component to filtration
Positively charged solutes will be attracted to the negative charges on the barrier and be _____ readily filtered.
more
Negatively charged solutes will be attracted to the positive charges on the barrier and be _____ readily filtered.
less
What are the 4 Starling pressures?
- capillary hydrostatic pressure
- capillary oncotic pressure
- interstitial hydrostatic pressure
- interstitial oncotic pressure
What is the oncotic pressure of Bowman’s space analogous to? What is the typical value of this? Explain why…
analogous interstitial fluid, which is considered zero, since filtration of protein is negligible
What is the Starling equation?
GFR = Kf [(PGC - PBS) - πGC]
= filtration coefficient [(hydrostatic pressure in the glomerular capillary - hydrostatic pressure in Bowman’s space) - oncotic pressure in glomerular capillary]
What are the 2 factors that contribute to Kf (the filtration coefficient)?
- Water permeability per unit of surface area
- Total surface area
The filtration coefficient for glomerular capillaries is much _____ than the filtration coefficient for systemic capillaries
greater (by as much as 100-fold)
What is the consequence of an this extremely high glomerular filtration coefficient?
More fluid is filtered from glomerular capillaries than from other capillaries
Which Starling force favors filtration?
hydrostatic pressure in the glomerular capillaries
P(GC)
Which Starling forces oppose filtration?
- hydrostatic pressure in the Bowman’s space
P(GB) - oncotic pressure in the glomerular capillaries
pi(GC)
In other words, GFR is the product of what 2 things?
- Kf
- the net ultrafiltration rate
Therefore, the net ultrafiltration rate equals what?
The sum of the 3 Starling pressures (omitting the oncotic pressure in Bowman’s space)
For glomerular capillaries, the net ultrafiltration pressure always favors _____.
filtration
At the beginning of the glomerular capillary (right after the afferent arteriole) net ultrafiltration pressure strongly favors ______.
filtration
At the end of the glomerular capillary what does net ultrafiltration equal? What state is filtration in at this point?
zero
a state of filtration equilibrium
What causes filtration equilibrium to occur?
By the end the glomerular capillaries, the oncotic pressure of glomerular capillary blood has increased to the point where the net ultrafiltration pressure becomes zero
What 3 things cause a decrease in glomerular filtration rate?
- constriction of afferent arteriole
- increased plasma protein concentration
- constriction of the ureter
What 2 things cause a increase in glomerular filtration rate?
- constriction of the efferent arteriole
- decreased plasma protein concentration
Changes in the hydrostatic pressure in the glomerular capillaries are produced by what?
changes in the resistance of the afferent and efferent arterioles
When there is constriction of the afferent arteriole both RPF and GFR ____. Explain why
Decreases, because as less blood flows into the glomerular capillary the hydrostatic pressure in the glomerular capillaries decreases, reducing net ultrafiltration pressure
So the effects of the sympathetic nervous system and high levels of angiotensin II ______ RPF and GFR.
decrease
When there is constriction of the efferent arteriole RPF _____, but GFR ____. Explain why
decreases
increases
Because there is an increase in the resistance to blood leaving the glomerular capillary, causing hydrostatic pressure in the glomerular capillaries and net ultrafiltraton pressure to increase
So the effects of low levels of angiotensin II _______ RPF and ______ GFR.
decrease
Changes in the oncotic pressure in glomerular capillary are produced by what?
changes in plasma protein concentration
Increases in plasma protein concentration produce _____ in oncotic pressure in glomerular capillary.
increases
Changes in the hydrostatic pressure in Bowman’s space are produced by what?
by obstructing urine flow
How is GFR measured?
by the clearance of a glomerular marker, inulin
What are the 3 characteristics of a glomerular marker?
- Freely filtered
- Cannot be reabsorbed or secreted
- Cannot alter GFR when infused
Describe the equation in which both GFR and inulin are equal to
GFR = [U]inulin × V˙ / [P]inulin = C(inulin)
[U]inulin = urine concentration of inulin V˙ = urine flow rate [P]inulin = plasma concentration of inulin
What is another marker for glomerular filtration rate?
creatinine
*important to note it is not a perfect marker like inulin
What is the advantage of using creatinine over inulin as a glomerular marker?
It is an endogenous substance therefore, it does not need to be infused in order to measure GFR
The filtration fraction expresses the relationship between what 2 things?
- glomerular filtration rate (GFR)
- renal plasma flow (RPF)
What does the filtration fraction equal?
= GFR/RPF
What is the normal value of the filtration factor? What does this number represent?
0.20 or 20%
20% of the RPF is filtered, and 80% is not filtered
The sum of what 3 processes equal excretion?
- filtered load
- reabsorption
- secretion
Filtration is fluid movement from the what structure in what structure?
From the glomerular capillary into Bowman’s space
Reabsorption is fluid movement from where to where?
From the glomerular filtrate into the peritubular capillary
Secretion is fluid movement from where to where?
From the peritubular capillary into the glomerular filtrate
The amount of a substance excreted per unit time is referred to as what?
excretion
How do you calculate the filtered load?
Multiply GFR by the plasma concentration of substance x
= GFR x [P]x
How do you calculate the excretion rate?
Multiply urine flow rate by the urine concentration of substance x
= V˙ x [U]x
How do you calculate the rate of net reabsorption or net secretion?
Subtract excretion rate minus the filtered load
If the filtered load is greater than the excretion rate, there has been net _______ of the substance
reabsorption
If the filtered load is less than the excretion rate, there has been net _______ of the substance
secretion
Glucose is filtered across what structure? It is then reabsorbed by what structure?
- filtered across the glomerular capillaries
- reabsorbed by the epithelial cells of the proximal convoluted tubule
Describe the 2 steps involved in reabsorbing glucose from tubular fluid into peritubular capillary blood
1) glucose moves from tubular fluid into the cell on the Na+-glucose contransporter in the luminal membrane, which is an uphill process
2) glucose is transported from the cell into peritubular capillary blood by facilitated diffusion
How is the Na+ gradient maintained?
by the Na+ - K+ ATPase in the peritubular membrane
What depicts the relationship between plasma glucose concentration and glucose reabsorption?
The glucose titration curve
As the plasma glucose concentration is increases, the filtered load ______linearly
increases
At plasma glucose concentrations less than ___ mg/dL, all of the filtered glucose can be reabsorbed. During this time reabsorption _____ filtration.
200
equals
What happens to the glucose titration curve when plasma concentrations rise above 200 mg/dL? Why?
The reabsorption curve bends, because some of the filtered glucose is not reabsorbed
At what plasma concentration level are Na+ - glucose contransports completely saturated? What happens to the curve at this point?
350 mg/dL
Reabsorption levels off
At plasma concentration levels less than 200 mg/dL what does excretion equal? Why?
Zero, because all of the filtered glucose is reabsorbed and none is excreted
At plasma concentration levels more than 200 mg/dL but less than 350 mg/dL what does excretion equal? Why?
The amount of glucose that is not reabsorbed, although most is
What is the plasma concentration at which glucose is first excreted in the urine called?
threshold
Threshold occurs at a ____ plasma concentration than T(m)
lower
When does the curve for excretion increase linearly? Explain why
When plasma concentration levels reach greater than 350 mg/dL, because all carriers are fully saturated
Describe the phenomenon of splay
The T(m) for glucose is approached gradually, rather than sharply.
_____ is the portion of the titration curve where reabsorption is approaching saturation, but it is not fully saturated.
Splay
What is the significance of splay?
Glucose is excreted in the urine before reabsorption levels off at the T(m) value
What are the 2 explanations for splay?
- low affinity of the Na+-glucose cotransporter
- heterogeneity of nephrons
