Renal Blood Flow & Glomerular Ultrafiltration Flashcards
discuss perfursion and oxygen consumption of renal vasculature and why this is important
- despite small size, kidneys get 20% of cardiac output. they have the the highest blood flow of all major tissues. in other worse, kidneys are over-purfused for their metabolic needs
- kidneys second highest oxygen consumption (second to cardiac tissue)
- kidney needs high flow/high O2 extraction to drive the Na/K ATPase that establishes Na+ gradient (drives secondary active transport)
relationship between O2 consumption and Na reabsorption in nephron
Na/K ATPase represents about 90% of oxygen consumption
“arrangement” of glomerular & peritbular capillaries and what type of fluid movement occurs at each
glomerular and peritubular capillaries are arranged “in series”: afferent - glomerulus - efferent - peritubular capillaries
- glomerular capillaries … specialized for filtration (PG >πG)
- peritubular capillaries that are specialized for reabsorption (PC < πC )
effect of arterial pressure renal function
- Autoregulation - the ability to maintain a relatively constant blood flow despite changes in arterial pressure - key in maintaining constant flow across 80-140 mmHg. this keeps RBF (plasma passing thru glomerular capillaries/min) and GFR (amount of fluid filtered out of glomular capillaries/min) constant
- however - increase in arterial pressure markedly increases urine production: called pressure diuresis
role of autoregulation in renal function
an intrinsic property of renal vasculature - maintains constant flow in the face of changes in MAP, keeping RBF/GFR relatively constant
- GFR is “secondary to RBF” - meaning that an increase/decrease in GFR is due to/matches a change in RBF
effect of metabolic vasoregulation in kidney
NOT an important control mechanism
- role of myogenic vasoconstriction in renal function
- what parts of the nephron are involved?
myogenic vasoconstriction = type of autoregulation
- changes in pressure - percieved as “stretch” - cause a reflexive change in vessel radius (increased stretch causes vasoconstriction, decreased stretch causes vasodilation) to alter resistance such that wall tension remains relatively constant (T = Pr / h)
- maintaining wall tension protects arteries
- called “intra renal” baroreceptor
myogenic vasoconstriction regulates wall tension in:
- afferent arteriole
- to a lesser degree, interlobular arteries
tubuloglomular filtration
- involves what components of the nephron?
- when/how does it play a role in renal function?
- permitted by the macula densa: cells in distal nephron (DCT) adjacent to the glomerulus
- cells located at point in the tubules at which 85% of the tubular filtrate has alreadly been reabsorbed
- the macula densa detects
- tubular flow
- NaCl concentration
- then releases mediators accordingly
- in response to increased tubular flow/[NaCl] –> ADP release
- this vasoconstricts afferent –> decreased GFR
- this decreases renin release –> decreased Na+ reabsorption
- in response to decreased tubular flow/ [NaCl] –> NO, prostaglandin release
- this vasodilates afferent –> increased GFR
- this increases renin release –> increase Na+ reabsorption
- in response to increased tubular flow/[NaCl] –> ADP release
extrinsic control of kidney function
- what subsets of of regulation constitutesextrinsic control?
- what are the key roles of extrinsic control?
- what is the authority of extrinsic control relative to extrinsic control?
- can override intrinsic control
- is a much bigger player than metabolic vasoregulation (in contrast to the heart)
- involved both neural and hormonal control
-
neural role is key in a hypovolemic state.
- symapathetics constrict the afferent arterioles, which:
- limits flow to the kidney, and redirects it to the rest of the body
- decreases both GFR and RBF –> promoting reabsorption –> retention of blood volume
- symapathetics constrict the afferent arterioles, which:
-
neural role is key in a hypovolemic state.
- what molecules play a role in humoral control of RBF and GFR?
- what type of control is humoral control?
humoral control is a type of “extrinsic” control
Vasoconstrictors:
• Circulating catecholamines
• Angiotensin II
- ADH
- Adenosine
Vasodilators:
• Prostaglandins (PGE2, Prostacyclin)
Kinins
- ATP
- NO
discuss the relationship between vasoconstrictors and vasodilators in modulating renal blood flow
- in hypovolemic states, an increase in SNS outflow induces vasoconstrictor release - most notably, angiotensin II. Ang II constricts the afferent and efferent arterioles, which will:
- decreased RBF
- decrease GFR (though to a lesser degree than RBF)
- these same vasoconstrictors stimulate release of vasodilatory prostaglandins (PGE2 and PGI2) that blunt/modulate vasoconstrictor effects of catecholamines/Ang II and prevent excess vasoconstriction that might reduce RBF too much
- this prevents ischemia and other renal damage
this chart shows the effects of administering indomethacin, which blocks prostaglandins, in a hypovolemic state. RBF drops dramatically without prostaglandin modulation.
dicuss the components of the “glomular filtration barrier”.
which component serves as the _limiting elemen_t to filtration?
- glomerular capillaries
- have a fenestrated endothelium with a pore size of 500-1000A
- have a basement membrane domposed of Type IV collagen, laminin, proteoglycans with a pore size of 70-100 A
- this is the limiting element
- mesangial cells
- contactile cells in between between capillaries at capillary loop ends. by contracting/relaxing, they can modify pore size
- thus, they can modify Kf (surface area)
- contactile cells in between between capillaries at capillary loop ends. by contracting/relaxing, they can modify pore size
- Bowman’s capsule
- the visceral layer is made of podocytes with various size processes that interdigate to produce “slits” pf about 250 A
what is the “effective pore size” of the glomerular filtration barrier?
about 50 Angstroms. this is the largest size molecule that can get filtered from the blood
ultrafiltration of the glomerulus
- characterize this movement of solutes/fluid
- what plasma components typically do/do not get filtered and why?
- filtration at the glomerulus is considered to be “buolk flow”
- what gets filtered:
- solutes with the following characteristics:
- MW =/
- effective radius of =/
- neutral or positive charge
- this includes:
- water
- urea
- glucose
- inulin
- many cations
- solutes with the following characteristics:
- what does NOT get filtered:
- proteins that are too large and/or have a negative charge
- this includes
- MOST proteins (eg, albumin)
- substances bound to protein (eg, 50% of Ca++)
- many hormones and drugs
- formed elements
what are the two primary determinants of glomerular capilllary barrier permeability?
- size and number of pores in the glomerular barrier
- the presence of fixed negative charges on the basement membrane
- netatively charged glycooproteins repell negatively charged plasma proteins, thus limiting their filtration
- this creatres a preferential filtration for cations and neutrally charged solutes
explain the relative filtration of neutral, cationic, and anionic solutes across the glomerulus
- filtration of cations > neutral solutes > anions
- this is due to the negatively charged glycoproteins on the basement membrane of glomerular capillaries
how do starling force’s at the glomerulus drive fluid movement?
- discuss the values of hydrostatic/ oncotic pressures of capillaries/bowman’s capsule and why their discrepencies are important.
- write out the “effective” net starling forces that determine fluid movement
- Kf (filtration coefficient):
- higher in glomerular capillaries than in systemic circurclation due to an increase in surface area
- Pg (glomular hydrostatic pressure): 45-60 mmHg
- larger than systemic circulation due to constriction of efferent arteriole.
- also larger than Pb and πg, which drives fluid into bowman’s capsule.
- Pb (bowman’s capsule hydrostatic pressure): 10 mmhg
- much less than Pg.
- though this pressure doesn’t significantly counter hydrostatic pressure in the capillaries, it is enough to drive fluid from Bowman’s capulse into the proximal tuuble
- much less than Pg.
- πg (glomular oncotic pressure) 25-33
- increases from afferent to efferent end due to fluid leaving capillaries.
- much less than Pg
- πb (bowman’s capsule oncotic pressure): 0mmHg
- this is because the glomerulus is impermeable to plasma proteins, and there will be none in Bowman’s capsule
GFR is determined by these net forces.
since Pg is so much higher than Pb and π, fluid moves into the filtrate.
contrast hydrostatic pressures at the glomerulus to that of systemic circulation, and what this means
- systemic circulation: the hydrostatic pressures at the artertiole/venous end of a capillary vary tremendously.
- thus, at the the venous end, reabsorption occurs.
- glomerulus: the hydrostatic pressures at the afferent arteriole & efferent arteriole are almost the same
- almost all filtration occurs at the afferent end
- no reabsorption occurs at the efferent end
how does a hypervolemic state influence movement at the peritubular capillaries?
- in a hypervolemic state, SNS outflow decreases, and the afferent/efferent arterioles vasodilate.
- this increases RBF and to a lesser degree, GFR.
- filtration fraction (GFR/RBF) decreases, and less fluid/solutes end up the tubules relative to the capillaries.
- in the peritubular capillares, hydrostatic pressure increases/oncotic pressure decreases.
- starling forces do NOT favor reabsorption into the peritublar capillaries.
- in fact, the pressure balances in the peritubular capillaries can drive a back-leak of water/solute into the proximal tubule
- “back-leak” = movement through leaky paracellular junctions
- this increases RBF and to a lesser degree, GFR.
how does isolated constriction of the efferent arteriole affect GFR?
how does isolated constriction of the afferent arteriole effect GFR?
how does isolated dilation of the efferent arteriole effect GFR?
how does isolated dilation of the afferent arteriole affect GFR?
- how does constriction of both the afferent/efferent arteriole effect GFR and RBF?
- constriction of both arteries lowers blood flow
- constriction of the afferent arteriole significantly lowers GFR, while constriction of the efferent actually increases GFR
- overall, constriction of them together
- drops RBF
- drops GFR, but less than RBF
how does RBF,GFR and filtration fraction change in a hypovolemic/hypervolemic state?
- hypovolemic states (↓↓RPF, ↓GFR). FF increases.
- hypervolemic states (↑↑RPF, ↑GFR). FF decreases.
