SM_189a-190a: Functional Renal Anatomy and Glomerular Filtration, Regulation and Measurement of Glomerular Filtration Flashcards
Cortex of the kidney is a dense array of small capillary structures forming the ______
Cortex of the kidney is a dense array of small capillary structures forming the glomerulus
(only the cortex contains glomeruli)
Medulla of kidney has dense packing of ______
Medulla of kidney has dense packing of renal tubules
Glomerular capillary is fed by ______ and drained by ______
Glomerular capillary is fed by afferent arteriole and drained by efferent arteriole
(two capillary beds in series)
Efferent arteriole feeds blood into _______
Efferent arteriole feeds blood into peritubular capillaries
There are two types of nephrons: ______ and _______
There are two types of nephrons: cortical nephrons and juxtamedullary nephrons
- Cortical nephrons: glomerulus is in outer or middle zone of cortex
- Juxtamedullary nephrons: glomerulus at edge of cortex close to medulla, has long loops of Henle to retain solute and concentrate urine
The four kidney functions are ______, ______, ______, and ______
The four kidney functions are filtration, reabsorption, secretion, and excretion
- Filtration: pressure forces ultrafiltrate of blood into Bowman’s space
- Reabsorption: fluid and solutes transported from tubular fluid to peritubular capillaries
- Secretion: fluid and solutes transported out of peritubular capillaries into tubular fluid
- Excretion: getting rid of filtrate
What is the formula for renal excretion?
Excretion = Filtration - Reabsorption + Secretion
(only a small part of what is filtered is excreted – a lot is reabsorbed)
In the macula densa in the thick ascending limb, tubular fluid can elicit signals to _____
In the macula densa in the thick ascending limb, tubular fluid can elicit signals to modulate filtration
(thick ascending limb has many mitochondria)
Describe the histology of the glomerulus
Glomerulus histology
- Endothelial cells with large nuclei
- Visceral epithelial cells sit upon capillary loops
- Parietal epithelial cells are in Bowman’s capsule
- Mesangial cells maintain capillary structure (supporting structure)
- Macula densa is thick walled epithelial tube with specialized tubular epithelial cells that can communicate signals to modulate glomerular filtration
Glomerular capillary endothelium is ______ to allow for filtration
Glomerular capillary endothelium is fenestrated to allow for filtration
_____ create the outer boundary of the glomerular capillary
Podocytes create the outer boundary of the glomerular capillary
Glomerular permeability barrier is composed of three layers: _____, _____, and _____
Glomerular permeability barrier is composed of three layers: fenestrated capillary endothelium, glomerular basement membrane, and podocyte foot processes
(blood cells too large to pass through, albumin too charged to pass through)
Glomerular basement membrane is made of _____, _____, _____, and _____
Glomerular basement membrane is made of anionic glycosaminoglycans, type IV collagen, laminin, and fibronectin
Matrix of glomerular permeability barrier is negatively charged, so ______ are not filtered effectively
Matrix of glomerular permeability barrier is negatively charged, so negatively charged molecules are not filtered effectively
Glomerular filtration is based on _____ and _____
Glomerular filtration is based on size and charge
_____ charged molecules are better filtered by the glomerulus than _____ charged molecules
Positively charged molecules are better filtered by the glomerulus than negatively charged molecules
(albumin is not normally filted because negatively charged)
Surface membrane of podocytes is studded with _____, which repel _____
Surface membrane of podocytes is studded with negatively charged proteins, which repel negatively charged molecules
Describe the molecular structure of the slit diaphragm
What is the equation for GFR?
GFR = LpS (∆P – ∆π)
Lp: glomerular capillary wall permeability
S: total glomerular capillary surface area
∆P: hydrostatic pressure gradient across the glomerular capillary
∆π: oncotic pressure gradient across the glomerular capillary
Oncotic pressure is _______, with the general effect of _______
Oncotic pressure is exerted by proteins that are resitricted to one side of a fenestrated vascular barrier, with the general effect of opposing filtration and promoting retention of fluid within a vascular space
Gradient of pressures favors ______, particularly because ______ is greater inside glomerulus
Gradient of pressures favors filtration, particularly because hydrostatic pressure is greater inside glomerulus
______ is the main determinant of filtration
Hydrostatic pressure is the main determinant of filtration
∆P = ____ – ____
∆P = PGC – PBS
PGC: hydrostatic pressure in the glomerular capillary
PBS: hydrostatic pressure in Bowman’s space
∆π = ____ – ____
∆π = πGC – πBS
πGC: oncotic pressure of fluid in glomerular capillary (equal to plasma)
π<span>BS</span>: oncotic pressure of fluid in Bowman’s space (usually zero)
πBS is usually ____ because ____
πBS is usually zero because unfilterable plasma proteins will not be in Bowman’s space
_____ pressure favors filtration, while _____ pressure opposes filtration
Hydrostatic pressure favors filtration, while oncotic pressure opposes filtration
Hydrostatic pressure is ____ along the glomerular capillary, but oncotic pressure ______
Hydrostatic pressure is constant along the glomerular capillary, but oncotic pressure rises along glomerular capillary
(concentration of unfilterable proteins increases along length of glomerular capillary)
Filtration equilibrium is when ______
Filtration equilibrium is when filtration ceases because hydrostatic and oncotic pressure are equal in magnitude and opposite in direction
Normal GFR is ______
Normal GFR is 125 mL/min (180 L/day)
Describe the mechanism affecting LpS
Mechanism affecting LpS
- Mesangial cell contraction affects capillary surface area (S)
Describe the mechanisms affected ∆P
Mechanisms affecting ∆P: modulation of PGC
- Renal artery pressure
- Afferent arteriole (pre-glomerular capillary) tone including intrinsic myogenic reflex, vasoconstrictors, and vasodilators
- Efferent arteriole (post-glomerular capillary) tone: vasoconstrictors, vasodilators
Describe modulation of PGC via changing afferent arteriole tone
Modulation of PGC via changing afferent arteriole tone
- Intrinsic myogenic reflex
- Vasoconstrictors (adenosine, ATP, catecholamines, PGF2alpha, TXA2)
- Vasodilators (nitric oxide, PGI2, bradykinin)
Describe modulation of PGC via changing efferent arteriole tone
Modulation of PGC via changing efferent arteriole tone
- Vasoconstrictors (angiotensin II, catecholamines)
- Vasodilators (adenosine)
Constricting the afferent arteriole causes ______, which ______ GFR
Constricting the afferent arteriole causes hydrostatic pressure to decrease, which decreases GFR
Constricting the efferent arteriole creates ______, which ______ GFR
Constricting the efferent arteriole creates back pressure, which raises GFR
Adenosine ______ afferent arteriole and ______ efferent arteriole, which ______ GFR
Adenosine constricts afferent arteriole and dilates efferent arteriole, which decreases GFR
RBF decreases when ______ and increases when ______
RBF decreases when there is a constriction and increases when there is a dilatation
Mechanisms for autoregulation of GFR are ______, ______, and ______
Mechanisms for autoregulation of GFR are myogenic reflex of the afferent arteriole, tubuloglomerular feedback, and angiotensin II
Systemic blood pressure is _____ in determining GFR
Systemic blood pressure is not important in determining GFR
Relationship between RBF or GFR and arterial pressure ______ at physiologically relevant arterial pressures
Relationship between RBF or GFR and arterial pressure levels off at physiologically relevant arterial pressures
Myogenic reflex is intrinsic to the ______
Myogenic reflex is intrinsic to the afferent arteriole
(first line defense)
Tubuloglomerular feedback is responsible for plateauing RBF and GFR at _____ end of physiological blood pressure
Tubuloglomerular feedback is responsible for plateauing RBF and GFR at high end of physiological blood pressure
Angiotensin II is responsible for ______ GFR when arterial blood pressure is on low end of physiological BP range
Angiotensin II is responsible for increasing GFR when arterial blood pressure is on low end of physiological BP range
Juxtaglomerular appratus includes three cell types: _____, _____, and _____
Juxtaglomerular appratus includes three cell types: macula densa, granular cells, and extraglomerular mesangial cells
(tubuloglomerular feedback and renin secretion are the mechanisms for this)
In tubuloglomerular feedback, macula densa senses ______ and sends signals via ______ and ______ to afferent arteriole smooth muscles to constrict
In tubuloglomerular feedback, macula densa senses solute concentration and sends signal via adenosine and renin to afferent arteriole smooth muscles to constrict
(granular cells contain renin)
As perfusion rises, GFR ______
As perfusion rises, GFR decreases (tubuloglomerular feedback)
As delivery of solute (mainly NaCl) to tubule increases, GFR ______
As delivery of solute (mainly NaCl) to tubule increases, GFR decreases (tubuloglomerular feedback)
Describe what happens via tubuloglomerular feedback if RBF increases
RBF increases
- Hydrostatic pressure in afferent arteriole and glomerular capillaries increases
- GFR increases
- NaCl delivery to macula densa increases
- Macula densa releases adenosine or ATP
- Afferent arteriole constricts
- Hydrostatic pressure in afferent arteriole decreases
- GFR returns to normal
- NaCl to macula densa decreases
When NaCl delivery to macula densa increases, macula densa enacts ______
When NaCl delivery to macula densa increases, macula densa enacts tubuloglomerular feedback
(high NaCl delivery is a proxy for high GFR)
When NaCl delivery to macula densa decreases, macula densa stimulates _____
When NaCl delivery to macula densa decreases, macula densa stimulates release of renin from wall of afferent arteriole
(low NaCl delivery is proxy for low GFR)
(renin released in response to PGE2, which is generated by COX-2)
Macula densa control of renin secretion depends on [ion]
Macula densa control of renin secretion depends on Cl–
Describe modulators of renin release
Describe the effect of angiotensin II on GFR
Locally produces angiotensin II in kidney
- Efferent arteriole constricts
- Back pressure raises GFR
Describe strategies to decrease GFR and subsequently decrease blood pressure
Strategies to decrease GFR and subsequently decrease blood pressure
- Beta-1 adrenergic receptor selective blocker: stops renin secretion
- ACE inhibitor
- ARB
(renin secretion can be driven by macula densa or beta-1 adrenergic receptor on cells of the wall of the afferent arteriole)
If patient takes an ACE inhibitor or ARB when their BP has fallen to the lower end of the physiological range, autoregulation of GFR is ______
If patient takes an ACE inhibitor or ARB when their BP has fallen to the lower end of the physiological range, autoregulation of GFR is unavailable
(cannot raise GFR through angiotensin II-dependent mechanism)
Renal clearance is _______
Renal clearance is equivalent volume of plasma that is completely cleared of a substance per unit time
Cs = (Us * V) / Ps
What is the equation for renal clearance?
Cs = (Us * V) / Ps
Cs: clearnace of “s”
Us: urine concentration of “s”
V: urine flow rate (mL/min)
Ps: plasma concentration of “s”
(Us * V): urinary excretion rate of “s”
Describe the criteria for GFR to equal clearance of a substance
GFR will equal clearance of a substance if the substance is
- Freely filtered by the glomerulus
- Not reabsorbed by the tubules
- Not secreted by the tubules
- Not metabolized by the kidney
- Not excreted by extra-renal routes
- Can be measured in plasma and urine
_____ is a poly-fructose used traditionally as a marker of GFR
Inulin is a poly-fructose used traditionally as a marker of GFR
(not used clinically anymore)
____ is the most widely used GFR marker
Creatinine is the most widely used GFR marker
(creatinine comes from protein metabolism, muscle breakdown, and dietary supplements)
Describe the requirements for measurement of creatinine clearance
Requirements for measurement of creatinine clearance
- Renal function must be in steady state
- No vigorous activity or muscle breakdown
- No protein loading
Describe the procedure for measurement of creatinine clearance
Procedure for measurement of creatinine clearance
- Timed urine collection (24 h)
- Serum creatinine level
- Measure urine volume and creatinine level
If kidney function abruptly changes, creatinine level ______
If kidney function abruptly changes, creatinine level reaches a new steady state reflecting what the GFR is
- Creatinine production does not change
- Creatinine excretion dips then comes back to normal
- Plasma [creatinine] increases
Normal creatinine production is ______ in males
Normal creatinine production is 20-25 mg/kg in males
The lower the plasma creatinine, the ______ GFR is
The lower the plasma creatinine, the closer to normal GFR is
(as person ages plasma creatinine may stay constant while GFR decreases)
______ is an empiric formula for predicting CCr from serum Cr levels, age, and weight
Cockroft-Gault formula is an empiric formula for predicting CCr from serum Cr levels, age, and weight
(correct by 0.85 for women, use caution in cirrhosis and muscle wasting)
