Glomerular Filtration & Renal Blood Flow Flashcards
Excretion Rate: Three renal processes
1.)Glomerular filtration From glomerular capillaries to Bowman’s capsule
2.)Tubular reabsorption:From renal tubules to
peritubular capillaries
3.) Tubular secretion From peritubular capillaries to renal tubules
Excretion =Filtration – Reabsorption + Secretion
why high filtration rate
llows rapid removal of waste products These substances depend on filtration for adequate
removal (i.e. not reabsorbed or secreted) Allows multiple passes of the blood volume through the kidneys each day
daily GFR
180 L/day versus 3 to 4 liters of plasma volume Allows complete filtering of plasma volume 6 times each day Allows rapid and precise control of body fluid volume and composition
filtration rate=
GFR / Renal Plasma Flow
≈ 20%
Each minute 20% of the plasma flowing through the kidneys is filtered
normal reabsorption daily
≈ 178.5 Liters/day (123 mls/minute)
Normal urine output daily
180 – 178.5 ≈ 1.5 Liters/day
Normal urine output per minute
125 -123 ≈ 2 mls/minute
glomerular Capillary Membrane is different from reg. capillaries how?
lters significantly more volume than normal capillaries – Thicker but more porous Three major layers (not 2) Endothelial cell layer Basement membrane layer Epithelial cell layer
Podocytes: surround outer surface of basement membrane
Endothelial layer
perforated by thousands of fenestrations (small holes)
Protein passage prevented by negative charge on surface of endothelial cells
Basement membrane
allows movement of water and small solutes
Protein passage prevented by proteoglycan mesh and negative charge
Epithelial layer
not continuous
Slit pores present between adjacent podocytes – allow free movement of water and small solutes
Negative charge of surrounding epithelial cells hinders protein filtration
Overall pore size approximately 8 nanometers (80 angstroms)
Filterability of 0.75 means
iltered 75% as quickly as water
Filtrate concentration < plasma concentration
Filterability of 1.0 means
freely filtered (at the same rate as water) Concentration in filtrate will equal plasma
Dextrans
Polysaccharidesthat can be made with specific charges. polycationic dextran more filterable than polyanionic because of repelling of negative charges from molecule and pore
In some renal diseases, the negative charge of basement membrane is lost before any histological changes are seen and will cause
appearance of albumin in urine is an early indicator
GFR=
Kf x Net filtration pressure. Kf is the glomerular capillary filtration coefficient. Net filtration pressure ≈ 10 mmHg
Promotes filtration
Glomerular hydrostatic pressure (60 mmHg)
Bowman’s capsule oncotic pressure (0 mmHg) (factor with disease)
Inhibits filtration
Glomerular oncotic pressure (32 mmHg) Bowman’s capsule hydrostatic pressure (18 mmHg)
Glomerular Capillary Filtration Coefficient
Affected by overall hydraulic conductivity and surface area of the glomerular capillaries
Not able to measure directly Kf = GFR / Net filtration pressure
Kf = 125 mls/min / 10 mmHg = 12.5 mls/min/mmHg Kf = 4.2 mls/min/mmHg/100 grams of tissue
Normal Kf other capillaries=
0.01 mls/min/mmHg/100 gm
Filtration Coefficient and GFR
Direct positive relationship
Usually not part of day-to-day control of GFR
Can be affected by disease Decreasing number of function glomerular capillaries
(decreased surface area)
Increasing thickness of membrane (decreased hydraulic conductivity)
Hypertension & diabetes mellitus
Factors Affecting GFR
Colloid Osmotic Pressure & Filtration Fraction Hydrostatic Pressure
Oncotic Pressure – Glomerulus
Increased glomerular oncotic pressure = Decreased GFR
Decreased glomerular oncotic pressure = Increased GFR
As blood passes through glomerulus plasma oncotic pressure will increase
≈ 20%
Approximately 20% of fluid is filtered producing increased [protein]
Plasma oncotic pressure ≈ 28 mmHg entering glomerulus
Glomerular oncotic pressure ≈ 36 mmHg as blood leaves glomerulus
[32 mmHg average]
Factors Affecting Glomerular Oncotic Pressure
Plasma protein concentration of arterial blood Increased plasma protein concentration will increase
glomerular oncotic pressure which will decrease GFR Fraction of plasma being filtered (filtration fraction)
Increased filtration fraction means more plasma is being filtered from each ml of blood in the glomerulus
As blood is concentrated the oncotic pressure of blood remaining in the glomerulus increases which will decrease GFR
Filtration Fraction and GFR
Filtration fraction = GFR / RBF
A decrease in RBF (no initial change in GFR) will increase the filtration fraction thus producing a decrease in GFR
Changing RBF with constant glomerular hydrostatic pressure thus has an effect on GFR
Increased RBF – Decreased Fraction – Decreased glomerular oncotic pressure – Increased GFR
HYDROSTATIC PRESSURE
Increased pressure = Increased GFR Decreased pressure = Decreased GFR
Primary means of controlling GFR Arterial pressure
Increased MAP = Increased GFR [Buffered by autoregulation of flow to keep consistent glomerular pressure]
Afferent arteriole resistance Efferent arteriole resistance
Afferent Arteriole Resistance
Increased constriction = Decreased pressure = Decreased GFR
Decreased constriction = Increased pressure = Increased GFR
As constriction increases, RBF also decreases. But GFR decreases at a faster rate
Efferent Arteriole Resistance initially
Increased constriction = Increased pressure = Increased GFR
Decreased constriction = Decreased pressure = Decreased GFR
But not as simple as it appears!!
efferent arteriole resistance as constriction increase
As constriction increases, RBF will decrease while glomerular pressure increases
INITIALLY the change in glomerular pressure has more effect than the decrease in RBF which produces an overall increase in GFR.
[Increase in glomerular pressure greater than decrease in RBF]
BUT as constriction continues to increase the change in filtration fraction begins to play a role:
Filtration fraction increases (decreased blood flow, increased GFR) which results in higher glomerular colloid oncotic pressure which decreases GFR
When effect of the increase in glomerular oncotic pressure exceeds the effect of the increase in hydrostatic pressure, the GFR will decrease
Hydrostatic Pressure – Bowman’s Capsule
Increased hydrostatic pressure = Decreased GFR Decreased hydrostatic pressure = Increase GFR
Normally does not play a primary role in controlling GFR
Obstruction of urinary tract
Could produce big increase in pressure with big decrease in GFR
decrease in Kf (glomerular filtration coefficient) will cause
decrease in GFR. possibly caused by renal disease, diabetes mellitus, hypertension
increase in PB (Bowman’s hydrostatic pressure) will cause
decrease in GFR. caused by urinary tract obstruction (kidney stones)
increase in sigma G (glomerular capillary colloid osmotic pressure) will cause
decrease in GFR. caused by a decrease in BF or an increase in proteins
decrease in PG (glomerular hydrostatic pressure) will cause
decrease in GFR
decrease in AP
decrease in PG but only has small effect due to autoregulation
decrease in RE
decrease in PG. drugs that block angiotensin 2 formation
increase in RA
decrease in PG. increased sympathetic activity. vasoconstrictor hormones like nore, epi, or endothelin
Regulation of RBF closely linked to
control of GFR and excretion
RBF provides flow for
basic metabolic needs of kidneys and excess flow for plasma filtration
Renal O2 consumption is
2x that of the brain BUT blood flow is 7x
Most of O2 consumed supports
sodium reabsorption – consumption directly related to rate of sodium reabsorption
Determinants of RBF
(Renal artery pressure – Renal vein pressure) / Total renal resistance
Arterial ≈ 100 mmHg; Venous ≈ 4 mmHg
Percentage of renal vascular resistance
Afferent arterial ≈ 26% Efferent arterial ≈ 43% Interlobar, arcuate, interlobular arteries ≈ 16%
Account for 85% total renal resistance
Resistance of these three areas controlled
by sympathetic
nervous system, hormones, local control within kidneys
Increased resistance tends to reduce RBF
Decreased resistance tends to increase RBF (assume no change in arterial or venous pressures)
Flow Distribution Within Kidney
98 to 99% goes to renal cortex
1 to 2% goes to renal medulla via the vasa recta Key part of ability to concentrate urine
Effect of Sympathetic Activation
All vessels receive sympathetic innervation Strong activation – Constriction
Decrease RBF and GFR Mild to moderate activation (moderate decrease in
BP with corresponding baroreceptor response) Little effect on RBF or GFR
Most important when body faced with life threatening problem
Severe hemorrhage Healthy normal person – very little effect
Hormonal Effect on Epi, Norepi, Endothelin
Epinephrine and norepinephrine Effect similar to effect of sympathetic nervous system
Endothelin
Released by damaged vascular endothelial cells of kidneys and other tissue – play role in hemostasis??
Concentration increased during toxemia of pregnancy, acute renal failure, chronic uremia
Powerful vasoconstrictor
Hormonal Effect of Angiotensin II
Potent vasoconstrictor that is normally circulating and is produced locally
All renal vessels contain receptors but preglomerular vessels show weak if any response because of simultaneous release of vasodilators such as nitric oxide and prostaglandins
Strong effect on efferent arterial producing increased glomerular pressure AND decreased renal blood flow
Helps reduce decrease in GFR during times of decreased MAP and/or volume depletion
Enhanced tubular reabsorption because of decreased flow thru peritubular capillaries
Hormonal Effect of Nitric Oxid
Renal endothelial cells release a basal level that helps maintain dilation of renal vessels
Giving nitric oxide inhibitor Increases renal vascular resistance Decreases GFR & urinary excretion of sodium
If continued will result in an increase in MAP due to the increased sodium levels
Hormonal Effect of Bradykinin & Prostaglandins
Potent vasodilators
Tend to increase RBF and GFR
Do not appear to have major impact during normal conditions
May dampen effect of sympathetic nerves and angiotensin II
May help prevent excessive decreases in RBF and GFR
Inhibited by administration of nonsteroidal anti- inflammatory agents
Autoregulation of RBF & GFR
Mechanisms are intrinsic to the kidneys Function without systemic or neural influence
Purpose is to maintain NORMAL GFR and allow control of renal excretion of water and solutes
Prevents big changes in water / solute excretion with normal changes in blood pressure
Decreasing MAP to 75 mmHg or increasing to 160 mmHg results in a small change in GFR (<10% change)
RBF not as well controlled as GFR
What Would Happen If No Autoregulation
Increased MAP 100 to 125 mmHg GFR would go from 180 L/day to 225 L/day
If reabsorption then remained constant: 225 – 178.5 = 46.5 L/day of urine output Would quickly deplete the circulating blood volume
Large increase in urine output prevented by
Autoregulation
Changes in tubular reabsorption Adaptive tubular mechanisms that produce increase in reabsorption
with an increase in GFR Glomerulotubular balance
But urine output and solute excretion DOES increase with an increase in MAP
Pressure diuresis and pressure natriuresis
Tubuloglomerular Feedback Mechanism
Links autoregulation of GFR and RBF to the amount of NaCl entering the distal tubule
Regulates RBF and GFR in parallel
GFR regulation rather than RBF regulation plays larger role in maintaining constant delivery of NaCl to distal tubule
Components Afferent arteriole feedback mechanism Efferent arteriole feedback mechanism Juxtaglomerular complex
Juxtaglomerular Complex - Structure
Macula densa cells
Epithelial cells located initial part of distal tubule
In contact with portions of afferent & efferent arterioles
Contain secretory Golgi apparatus Sense changes in NaCl
concentration in the tubular fluid
Juxtaglomerular cells
Surround afferent arteriole where it enters the glomerulus
Surround efferent arteriole where it leaves glomerulus
In contact with portion of distal tubule that contains macula densa
Major storage site for renin
Juxtaglomerular Complex - Operation
Believed that macula densa monitors amount of volume delivered to distal tubule via NaCl concentration
As GFR decreases Flow rate through Loop Henle also decreases Reabsorption of Na+ and Cl- in loop increases Concentration Na+ and Cl- at macula densa decreases Decreased concentration elicits response from macula densa
Response from macula densa has two effects
Dilationofafferentarteriole
Results in an increase in glomerular hydrostatic pressure
Stimulation of increased renin release from juxtaglomerular cells
Results in an increased constriction of efferent arteriole which produces an increase in glomerular hydrostatic pressure
Prevents major changes in GFR between MAPs of 75 to 160 mmHg
Myogenic Autoregulation
An increase in MAP will cause an increase in smooth muscle contraction especially of small arterioles
MAP increases which cause the vessel walls to stretch thus increasing wall tension. The increased stretch results in movement of additional calcium into the smooth muscle cells which increases the overall level of contraction
Not sure how important this mechanism is for the kidneys, but it has been shown that the afferent arterioles show a strong myogenic response to sudden increase in arterial pressure
Result of increased afferent constriction is a reduction in RBF (due to increased resistance) and a decrease in GFR (due to decreased glomerular hydrostatic pressure)
Problems With Juxtaglomerular Feedback
eedback mechanism designed to maintain consistent delivery of NaCl to the distal tubule
Any problem that increases NaCl reabsorption in the proximal tubule will trigger the feedback mechanism
High protein intake
Higher than normal amino acid concentration in the blood – Sodium and amino acid reabsorption linked, so an increase in amino acid reabsorption results in an increase in sodium reabsorption and stimulation of the feedback mechanism (20 to 30% increase in GFR 1 to 2 hours after eating a high-protein meal
Increase in blood glucose
Again, glucose reabsorption tied to sodium reabsorption – As concentration of glucose in the blood increases, glucose and sodium reabsorption also increase thus stimulating the feedback mechanism which ultimately results in an increase in GFR
