Topic 3 - Hemodynamics of Glomerular Filtration Flashcards
Why does RBF exceed the metabolic needs of the kidney?
as an organ that regulates the size and composition of the ECF, it must ‘process’ a large quantity of blood
Why is there a lower partial pressure of oxygen in the outer and inner medulla compared to the cortex?
cortex provides lots of flow for filtration and reabsorption
in medulla:
- higher flow would wash out the osmotic gradient
- lower flow would increase the risk of papillary necrosis
What does it mean to have localization of renal vascular resistance (afferent and efferent arterioles)?
pressure profile
- renal a (100mmHg) -> glomerulus (50mmHg) -> renal v (12mmHg)
implications:
- high resistance sites as points of regulation
- afferent and efferent arterioles
- spatial separation of filtration and reabsorption sites
- two arteriole segments and two capilarry beds on either side
- at glomerulus: site strict for filtration
- at peritubular: site strict for uptake or reabsorption
- two arteriole segments and two capilarry beds on either side
Compare efferent and afferent artiole resistances
equal resistances:
- renal arteriole pressure = 100
- GFR = 20%
- Pgc = 60
- Peritubular cap pressure = 20
- Filtration fraction (FF) = GFR/RPF
increased afferent resistance:
- renal arteriole pressure = 100
- GFR = decreased;
- Pgc = 40
- peritubular cap pressure = 13
- FF = decreased GFR/decreasd RPF -> same FF = 20%
increased efferent resistance
- renal arteriole pressure = 100
- GFR = 70
- Pgc = 70
- peritubular cap pressure = 30
- increase FF = increase GFR/decrease RPF -> increased FF = 30%
What is net filtration pressure?
the algebraic sum of the magnitude of direction of forces of the glomerular capillary pressure and Bowman’s capsule hydrostatic pressure
hydrostatic pressure gradient
- glomerular capillary hydrostatic pressure (Pgc)
- Bowman’s space hydrostatic pressure (Pbs)
colloid osmotic (oncotic) pressure gradient
- glomerular capillary oncotic pressure (∏gc)
- Bowman’s space oncotic pressure (∏bs)
Pgc = 60mmHg
Pbs = -15mmHg
∏bs = -29mmHg
Net: 26mmHg
What is the filtration coefficient (Kf)?
Kf is a factor that accounts for surface area and the conductance of water
What are the dynamics of glomerular filtration?
What is the glomerular ultrafiltration equation?
GFR is the result of the same forces that cause filtration across any capillary wall
GFR = Kf * [(Pgc - Pbs) - (∏gc - ∏bs)]
Kf = glomerular ultrafiltration coefficient
- in disease states, Kf is often reduced either as a result of reduced area for filtration of individual glomerular capillaries or because of reduction in number of nephrons
How do changes in glomerular ultrafiltration equation predict changes in GFR?
glomerular hydrostatic pressure (Pgc)
- afferent arteriole resistance
- constriction -> decrease glomerular pressure
- dilation -> increase glomerular pressure
- efferent arteriole resistance
- constriction -> increase glomerular pressure
- dilation -> decrease glomerular pressure
- tubular pressure (Pbs)
- obstruction -> increase pressure in Bowman’s space -> decrease net filtration and decrease GFR
- colloid osmotic (aka oncotic) pressure (∏gc)
- hyper- or hypoalbuminemia
- hyper -> decrease GFR
- hypo -> increase GFR
- hyper- or hypoalbuminemia
- filtration coefficient (Kf)
- pathological damage to the glomerular membrane (permeability and/or area)
What is a reduction in GFR in disease states most often due to?
decreases in the ultrafiltration coefficient (Kf) because of loss of filtration surface area
GFR also changes in pathologic conditions because of changes in the hydrostatic pressure in the glomerular capillary (Pgc), oncotic pressure in the glomerular capillary, and hydrostatic pressure in Bowman’s space (Pbs)
How do changes in Kf affect GFR?
increased Kf -> increased GFR
- some drugs and hormones that dilate the glomerular arterioles also increase the Kf
decreased Kf -> decreased GFR
- some kidney diseases reduce the Kf by decreasing the number of filtering glomeruli (i.e. diminished surface area)
- drugs and hormones that constrict the glomerular arterioles decrease Kf
How do changes in Pgc affect GFR?
decreased renal perfusion -> decreased GFR because Pgc decreases
- reduction in Pgc is caused by
- a decline in renal arterial pressure
- an increase in afferent arteriolar resistance
- a decrease in efferent arteriolar resistance
How do changes in ∏gc affect GFR?
an inverse relationship exists between the ∏gc and the GFR
- alterations in the ∏gc result from changes in protein synthesis outside the kidneys
- protein loss in the urine caused by some renal diseases can lead to a decrease in the plasma protein concentration and thus a decrease in the ∏gc
How do changes in the Pbs affect GFR?
an increased Pbs reduces the GFR
- acute obstruction of the urinary tract (e.g. a kidney stone occluding the ureter) increases the Pbs
decreased Pbs enhances the GFR
A decrease in GFR but no change in FF is due to?
change in afferent arteriole resistance
A decrease in GFR and an increase in FF is due to
predominant effect on efferent side
How are GFR and RBF regulated?
intrinsic regulation - autoregulation
- over a wide range of blood pressure (80-190), the renal blood flow and glomerular filtration rate are relatively constant
- despite this change in pressure, adjustments are made to keep renal blood flow and the GFR constant
How is GFR and RBF regulated over a wide range of arterial blood pressure?
the fact that both GFR and RBF are autoregulated (i.e. no change in filtration fraction[FF]), indicate that the resistance changes that maintain this constancy is occurring in the afferent arteriole
How does autoregulation occur?
every single nephron has its distal tubule return back to the glomerulus origin - feedback signal
- increase in GFR = more fluid will be filtered in the tubule
- increase in NaCl delivery to the loop of Henle
- more NaCl delivered, more is generated; more fluid and more NaCl
- arrive at macula densa segment and generates a signal by the juxtaglomerular apparatus
What are some main features of tubuloglomerular (TG) feedback?
increase delivery of Na+ to loop of Henle causes more Na+ to be reabsorbed, utilizing ATP for active transport
- hydrolysis of ATP for transport energy, forms ADP, AMP, and adenosine
adenosine acts to constrict the afferent arteriole and reduce GFR towards normal
- adenosine associated with the increase transport, sends a signal, causes constriction of the afferent arteriole, which brings back GFR to the control level
What happens in the juxtaglomerular apparatus?
made up of granular cells containing renin
- increase delivery of NaCl
- NaCl pumped across macula densa cell utilizing ATP
- formation, the hydrolysis of ATP leads to formation of adenosine
- adenosine is released and causes a vasoconstriction of the juxtaglomerular cells (and increase renin release)
How is the renal autoregulated extrinsically via the renin-angiotensin system (RAS)?
Angiotensin II - constricts both afferent and efferent arteriole, but predominates on the afferent arteriole
- Ang II has an overall effect to minimize renal blood fluid and sodium losses and to maintain arterial blood pressure
- exerts powerful renal vascular effects, which elicit decreases in RBF and to a lesser degree in GFR
- usually an increase in filtration fraction
- ACE inhibitors block the effect on the efferent arteriole and often result in a decrease in GFR
How is the renal autoregulated extrinsically via endothelial factors?
Nitric oxide - vasodilates both afferent and efferent arteriole
- endothelial cells respond to various physical stimuli (shear stress) and hormonal agents (e.g. thrombin, bradykinin) to release vasoactive factors
- NO is formed constitutively and diffuses out of the cell into adjoining cells
- through stimulation of soluble guanylate cyclase and increased cGMP levels in smooth muscle cell, NO exerts powerful vasodilator actions
How is the renal autoregulated extrinsically via paracrine factors?
Prostaglandins - vasodilation of afferent and efferent arterioles
- while prostaglandins are not major determinants of resting renal vascular tone under normal states of hydration and sodium balance, they do exert protective effects in response to vasoconstrictor stimuli, hypovolemic states, or hypotensive episodes
- when the kidney is under the sustained influence of vasoconstrictor stimuli such as elevated catecholamine levels, increased renal nerve activation, and increased activity of the renin angiotensin system, activation of the PG production helps counteract the vasoconstrictive effects of these stimuli
What are the effects on Angiotensin II?
ACE inhibitors
- block the effects of endogenous Ang II in various conditions such as hypertension, congestive heart failure, and diabetes
Enhanced Ang II activity:
- inhibition of RAS increases RBF while GFR eiter does not change or decreases (predominant effect on the efferent arteriole)
Under most conditions, blockade of the renin angiotensin system causes decreases in both pre- and postglomerular resistances
What happens when PG production is blocked?
blocked by cyclooxygenase inhibitors
- the unopposed actions of the co-existing vasoconstrictor agents are manifested by greater reduction in RBF and renal function
- thus, PGs take on a greater regulatory role in pathophysiological situations that compromise renal hemodynamics
- blockade of PG with nonsteroidal anti-inflammatory drugs, leave unopposed the vasoconstrictor influence of elevated levels of AngII and catecholamines and decrease RBF, GFR, and sodium excretion**
**most important clinically relevant info related to PGs
How is the renal autoregulated extrinsically via renal sympathetic nerves?
circulating catecholamines - constricts afferent arterioles predominantly
- renal blood flow is markedly influenced by the extrinsic stimuli - trauma, hemorrhage, pain, and exercise
- elicit increases in sympathetic nervous system activity to the kidney, which directly increases renal vascular resistance
- results in marked renal vasoconstriction mediated by alpha-adrenoreceptors, leading to decreased in both RBF and GFR, increases in renin release, and increases in proximal tubular sodium reabsorption
- renal circulation subject to influences by the adrenal medulla, which releases epinephrine systemically in response to many stress conditions
- smooth muscle-containing vessels of all sizes, from the main renal arteries to afferent and efferent arterioles, respond to exogenous norepinephrine and epinephrine
- afferent arterioles are more sensitive that efferent arterioles to the vasoconstrictive effect of norepinephrine
Which of the following statements about glomerular filtration is NOT true?
a. the hydrostatic pressure drop across the glomerular capillary bed is small
b. the oncotic pressure in capillary blood increases as blood flows through the glomerular capillary
c. increasing glomerular blood flow tends to increase glomerular filtration rate
d. the filtration coefficient (Kf) of the glomerular capillaries is similar to that of most other capillary beds
e. contraction of mesangial cells may decrease the GFR by reducing Kf
d.
Kf for glomerular capillaries is much greater than that of any other capillary bed
Which of the following statements about glomerular filtration is NOT true?
a. the capillary filtration coefficient of glomerular capillaries is 50 to 100 times greater than that of most other capillary beds
b. the net filtration pressure is equal to the hydrostatic pressure in the glomerular capillary minus the hydrostatic pressure in Bowman’s space
c. increasing plasma flow rate in a glomerulus should tend to increase the overall rate of glomerular filtration in that glomerulus
d. the net filtration pressure at the end of the glomerular capillary bed closest to the efferent arteriole is about 10mmHg
e. the net filtration pressure diminishes as blood flows along the glomerular capillaries
b.
the net filtration pressure is the hydrostatic pressure in the glomerular capillary minus that in Bowman’s space minus the oncotic pressure of te blood in the glomerular capillary
Constriction causes a decrease in renal blood flow and an increase in glomerular filtration:
a. renal artery
b. afferent arteriole
c. glomerular capillary
d. efferent arteriole
e. peritubular capillary
d. constriction of the efferent arteriole increases glomerular pressure and GFR and decreases overall renal blood flow
All of the following alter glomerular filtration rate EXCEPT:
a. sympathetic stimulation
b. decreased vascular tone in the kidney
c. change in mean arterial blood pressure from 100 to 120mmHg
d. vasoconstriction of efferent arterioles
e. epinephrine
c. renal autoregulation of GFR (and RBF) maintains a relatively constant GFR within the autoregulatory range of BP
- filtration across the glomerular basement depends on the difference between glomerular hydrostatic pressure and the sum of Bowman’s capsule hydrostatic pressure and the plasma protein osmotic pressure
- because of the autoregulator change (constriction) of the afferent arteriole, hydrostatic pressure does not change, even though mean arteriole pressure does
Which of the following elevates the filtration fraction?
a. dilation of the afferent arteriole
b. an increase in the ultrafiltration coefficient of the glomerulus
c. dilation of the efferent arteriole
d. a marked rise in arterial pressure
e. an increase in tubular pressure
b. an increase in filtration fraction is caused by an increase in GFR without a similar increase in renal plasma flow
- an increase in the ultrafiltration coeffecient increases GFR without increasing renal plasma flow
- C and E: decrease net filtration pressure and thus decrease GFR and filtration coefficient
- an increase in arterial pressure would have little effect on the filtration fraction since bowth GFR and renal blood flow are autoregulated (not D)
- afferent arteriolar dilation will increase both GFR and renal blood flow and probably have little effect on the filtration fraction (not A)
Increases in both glomerular filtration rate and renal blood flow are caused by:
a. decrease in the surface area available for filtration
b. constriction of the efferent arterioles in the kidney
c. increase in renal sympathetic nervous system activity
d. increase in colloid oncotic pressure of arterial plasma
e. dilation of the afferent arterioles in the kidney
e. only dilation of the afferent arterioles results in increased renal blood flow and GFR
What are the putative events in the tubuloglomerular feedback hypothesis of renal autoregulations? (DTF = distal tubule flow; MD = macula densa; JG = juxtaglomerular apparatus; AR = afferent arteriole resistance; ER = efferent arteriole resistance)
a. ↓DTF -> MD response -> ↑AR -> ↓GFR
b. ↑DTF -> ↑trenin -> ↑aldosterone -> ↓GFR
c. ↑DTF -> MD response -> ↑AR -> ↓GFR
d. ↑DTF -> JG response -> ↑AR -> ↓GFR
c. an increase in distal tubular delivery of fluid is sensed by the macula densa, which causes an increase in afferent arteriole resistance, which decreases the GFR back to its normal level
Which of the following acts to decrease GFR and renal blood flow below normals?
a. autoregulation
b. a small increase in efferent arteriolar resistance
c. prostaglandin E2
d. a decrease in afferent arteriole resistance
e. a high plasma catecholamine level
e. catecholamines cause constriction of both the afferent and efferent arterioles and thus tend to decrease blood flow and GFR
- autoregulation tends to prevent decreases in renal blood flow and GFR (not A)
- a small increase in efferent arteriole resistance would decrease renal blood flow but not GFR, which might increase slightly (not B)
- Prostaglandin E2 can be produced within the kidneys, but it is a vasodilator substance that tends to increase renal blood flow (not C)
- A decrease in afferent resistance increases both GFR and renal bloodflow (not D)
Which of the following statements about glomerular filtration is NOT true?
a. as blood flows through the glomerular capillaries, its hydrostatic pressure drops relatively little, but the plasma oncotic pressure rises significantly
b. anionic molecules are preferentially filtered over cationic molecules
c. the glomerular basement membrane and rectangular pores or slits in the membrane that bridges the processes of the podocytes may constitute the limiting barrier to large molecules
d. at low renal blodo flow rates, glomerular filtration rate may drop
e. a small fraction of plasma protein is filtered into Bowman’s space
b.
cationic molecules are preferentially filtered
- occurs because negatively charged carbohydrate residues on glycoproteins in the filtration barrier
- in certain renal diseases, the fixed negative charges are diminished
- as a result, a greater fraction of plasma proteins, which are predominantly anionic, is filtered
Kidney blood flow…
a. is normally approximately 10% of cardiac output
b. is approximately the same in all parts of the organ
c. not affected by the sympathetic nervous system
d. is far in excess of the metabolic needs of the kidney
e. is relatively constant and affected by few factors
d.
All of the following lead to a decrease in the filtration fraction EXCEPT:
a. increased ureteral pressure
b. increased efferent arteriolar resistance
c. increased plasma protein concentration
d. decreased glomerular capillary pressure
e. decreased filtration area
b.
Which of the following pressure changes leads to an increased GFR?
a. increased arterial plasma colloid osmotic pressure
b. increased glomerular capillary pressure
c. increased hydrostatic pressure in the renal interstitium
d. increased hydrostatic pressure in Bowman’s capsule
e. decreased net filtration pressure
b.
Under normal conditions the glomerular filtration rate is primarily regulated by:
a. glomerular capillary blood flow
b. glomerular capillary hydrostatic pressure
c. intracapsular hydrostatic pressure
d. plasma colloid osmotic pressure
e. colloid pressure of Bowman’s space
b.
The hydrostatic pressure in the efferent arteriole is best described as being:
a. less than that in the afferent arteriole
b. higher than the glomerular capillary pressure
c. less than the peritubular capillary pressure
d. equal to the glomerular capsular pressure
e. higher than the oncotic pressure in the glomerular capillary
a.
Autoregulation in the kidney is..
a. the constancy of urine flow rate despite large changes in arterial pressure
b. seldom intact during chronic renal failure
c. defined as the relative constancy of RBF and GFR over a large range of arterial pressures
d. maintained by the renal sympathetic nerves
e. a function of the permselectivity of the glomerular membrane
c.
Which of the following events would not be expected to decrease glomerular filtration rate?
a. urinary tract obstruction by renal stones
b. hypoalbuminemia (i.e. lower than normal serum albumin concentration)
c. decreased filtration coefficient (Kf) secondary to glomerular disease
d. hemorrhage accompanied by a significant decrease in arterial pressure
e. increased activity of the renal sympathetic nerves
b.
