38: Renal Hemodynamics, Blood Flow

A decreased GFR slows the flow rate in the loop of Henle, causing increased reabsorption of sodium and chloride ions, thereby reducing concentration of sodium and chloride at the macula densa cells. What two effects occur as this decrease in sodium chloride concentration initiates a signal from the macula densa?

(1) It decreases resistance to blood flow in the afferent arterioles, which raises glomerular hydrostatic pressure and helps return GFR toward normal, and (2) it increases renin release from the juxtaglomerular cells. Renin catalyzes the formation of angiotensin I to angiotensin II. Finally, the angiotensin II constricts the efferent arterioles, thereby increasing glomerular hydrostatic pressure and helping to return GFR toward normal.

What two components of feedback control GFR?

(1) an afferent arteriolar feedback mechanism and (2) an efferent arteriolar feedback mechanism.

What two factors influence the glomerular capillary colloid osmotic pressure?

(1) The arterial plasma colloid osmotic pressure and (2) the fraction of plasma filtered by the glomerular capillaries or the filtration fraction.

Angiotension II Blockage

Impairs GFR & renal blood flow autoregulation.

Filterability

A filterability of 1.0 means that the substance is filtered as freely as water, whereas a filterability of 0.75 means that the substance is filtered only 75 percent as rapidly as water. Note that electrolytes such as sodium and small organic compounds such as glucose are freely filtered.

How does a high protein diet affect GFR?

A high protein diet causes an increase in plasma protein and in renal circulation at the glomerular capillary. This causes an increase in the oncotic pressure and an increase in filtration fraction and decrease in GFR. This can be alleviated by vasodilation of the afferent arteriole so that blood flows at a higher rate across the glomerular capillary and oncotic pressure will go back down.

Why do changes in renal blood flow can influence GFR independently of changes in glomerular hydrostatic pressure?

A reduction in renal plasma flow with no initial change in GFR would tend to increase the filtration fraction, which would raise the glomerular capillary colloid osmotic pressure and tend to reduce the GFR. In summary, even with a constant glomerular hydrostatic pressure, a greater rate of blood flow into the glomerulus tends to increase the GFR and a lower rate of blood flow into the glomerulus tends to decrease the GFR.

Efferent arterioles are highly sensitive to what hormone?

Angiotensin II, which preferentially constricts efferent arterioles and raise glomerular hydrostatic pressure while reducing renal blood flow. Increased angiotensin II formation usually occurs in circumstances associated with decreased arterial pressure, low sodium diet or volume depletion, which tend to decrease GFR. In these circumstances, this helps prevent decreases in glomerular hydrostatic pressure and GFR; at the same time, though, the reduction in renal blood flow caused by efferent arteriolar constriction contributes to decreased flow through the peritubular capillaries, which in turn increases reabsorption of sodium and water, which increases blood volume and blood pressure. Increased angiotensin II levels also maintain normal excretion of metabolic waste products such as urea and creatinine that depend on glomerular filtration for their excretion.

NSAIDS

Blocks vasodilation effects because they inhibit prostaglandin synthesis and may cause reduction in the GFR.

Inflammatory cytokines

Can alter the size of the gaps between the podocytes or reduce negative charges along the membrane, which allows proteins to pass thru causing proteinuria.

What diseases gradually reduce Kf and how?

Chronic, uncontrolled hypertension and diabetes mellitus gradually reduce Kf by increasing the thickness of the glomerular capillary basement membrane (thereby reducing the surface area for filtration) and, eventually, by damaging the capillaries so severely that there is loss of capillary function, leading to decreased GFR. Obesity and glomerulonephritis are also diseases that can reduce GFR.

Norepinephrine, Epinephrine, and Endothelin

Constrict Renal Blood Vessels and Decrease GFR. Plasma endothelin levels are increased in with vascular injury, such as toxemia of pregnancy, acute renal failure, and chronic uremia.

How does constriction of the efferent arterioles affect glomerular hydrostatic pressure and GFR?

Constriction of the efferent arterioles increases the resistance to outflow from the glomerular capillaries. This raises glomerular hydrostatic pressure, and as long as the increase in efferent resistance does not reduce renal blood flow too much, GFR increases slightly. However, because efferent arteriolar constriction also reduces renal blood flow; filtration fraction and glomerular colloid osmotic pressure increase as efferent arteriolar resistance increases

Why do some patients with hypertension or atherosclerosis may have increased renal constriction and elevated blood pressure?

Damage of the vascular endothelium and impaired nitric oxide production may contribute to increased renal vasoconstriction and elevated blood pressure.

Nitric oxide

Derived from endothelium, this decreases renal vascular resistance and increase GFR

Glomerular colloid osmotic (oncotic) pressure

Determined by proteins that are not filtered at this glomerulus which opposes filtration.

Autoregulation in kidneys

Feedback mechanisms intrinsic to the kidneys normally keep the renal blood flow and GFR relatively constant, despite marked changes in arterial blood pressure.

Bowman's capsule hydrostatic pressure

Fluid in the Bowman's space exerts a pressure on the capillary working against filtration.

What factor is a major determinant of GFR?

Glomerular hydrostatic pressure. Factors that influence hydrostatic pressure are arterial pressure, afferent & efferent arteriole resistance. Increases in arterial pressure do not dramatically change the glomerular hydrostatic pressure because of autoregulation, so GFR is maintained with arterial pressure between 80-120 mmHg. So, under normal conditions GFR does not change.

prostaglandins (PGE2 and PGI2) and bradykinin

Hormones that cause vasodilation and increase renal blood flow and GFR, opposed vasoconstriction in afferent arterioles. Afferent arterioles are protected from angiotensin II-mediated constriction due to release of vasodilators, since vasodilators counteract the vasoconstrictor effects of angiotensin II in these blood vessels.

What is the role of vascular smooth muscle?

In the afferent arteriole, vascular smooth muscle cells are responsive to stretch. An increase in volume at the afferent arteriole causes a stretch and calcium influx to cause vasoconstriction. This prevents increases in GFR & renal blood flow.

What is good autoregulation?

Increase in arterial pressure above 120, with increase in reabsorption, urine volume is minimally increased.

Increased sympathetic nerve activity stimulates what secretion?

Increased sympathetic nerve activity stimulates renin secretion (enzyme necessary for angiotensin II). Angiotensin II will override sympathetic activity until GFR is normal, so then sympathetic activity returns to normal and blood pressure returns to normal. If sympathetic activity remains high, then BP does not return to normal and angiotensin II remains high to try to return BP back to normal.

How can we increase filtration fraction?

Increasing efferent arteriole resistance is a way to increase filtration fraction by reducing renal blood flow and allowing blood to have more time to filter at the glomerulus; this subsequently increases colloid osmotic pressure and thus decreasing GFR. Increasing the filtration fraction concentrates the plasma proteins and raises the glomerular colloid osmotic pressure.

How does increasing the Bowman's capsule hydrostatic pressure affect GFR?

It decreases GFR, even though this is not the primary regulator for GFR. Obstruction of the urinary tract causes Bowman's capsule pressure to increase markedly, causing serious reduction of GFR.

How does increasing the glomerular capillary colloid osmotic (oncotic) pressure affect GFR?

It decreases GFR. As blood passes from the afferent arteriole, plasma protein concentration increases about 20 percent, because 20% of fluid in the capillary filters into Bowman's capsule, thus concentrating the glomerular plasma proteins that are not filtered. So, glomerular capillary colloid osmotic pressure begins at 28 mmHg, then increases to 36 mmHg by the time the blood reaches the efferent arteriole. The average pressure is 32 mmHg.

What obstructions can raise Bowman's capsule hydrostatic pressure?

Kidney stones (uric acid or calcium crystals) that lodge in the urinary tract, often in the ureter, obstruct outflow of the urinary tract and raise Bowman's capsule pressure.

What is hydronephrosis? What causes it?

Kidney stones that obstruct the outflow of the urinary tract and raise the Bowman's capsule hydrostatic pressure can also reduce the GFR and cause distention and dilation of the renal pelvis and calyces. This can damage or destroy the kidney unless obstruction is relieved.

Renal sympathetic nerves

Most important in reducing GFR by constricting renal arterioles and decreasing renal blood flow. There is more sympathetic innervation along the afferent arteriole, than efferent arteriole.

Plasma Filtration

Plasma volume is filtered 60 times per day. Glomerular filtrate composition is about the same as plasma, except for large proteins. About 20% of plasma is filtered, this is the filtration fraction. 99% of what gets filtered gets reabsorbed.

How does an increased resistance of afferent arterioles affect glomerular hydrostatic pressure and GFR?

Reduces glomerular hydrostatic pressure, lowers renal blood flow and decreases the GFR. Conversely, dilation of the afferent arterioles increases both glomerular hydrostatic pressure and GFR.

Why would glomerular hydrostatic pressure be low in kidney disease?

Since obstruction or stenosis in the renal artery leads to reduced blood flow thru the kidney and low glomerular pressure leads to a decrease in GFR.

Why is the capillary endothelium fenestrated and negatively charged?

So the plasma proteins cannot be filtered (plasma proteins like albumin are negatively charged and are repelled by the endothelium). Therefore, positively charged substance are filtered more freely than negative and neutral particles. Even though positive substance are filtered more easily, the size of particles also affect filterability.

How do starling forces play a role in glomerular filtration?

The GFR is determined by (1) the balance of hydrostatic and colloid osmotic forces acting across the capillary membrane and (2) the capillary filtration coefficient (Kf). GFR=Kf x Net filtration pressure. Normally, GFR = 125 ml/min. Kf is a filtration coefficient which is important in determining GFR. Kf = 12.5 ml/min/mmHg, or 4.2 ml/min per mmHg/100 gm. Kf = hydraulic conductivity x surface area of glomerular capillaries.

What are the 3 layers of the glomerular capillary membrane?

The capillary endothelium is where the blood supply first enters, then particles move from the endothelium and across a basement membrane, then filtered material travels between podocytes.

Bowman's capsule colloid osmotic pressure

The colloid pressure of the proteins in Bowman's capsule promotes filtration is essentially zero.

filtration fraction=GFR/renal plasma flow

The filtration fraction can be increased either by raising the GFR or by reducing renal plasma flow.

What is the role of the juxtaglomerular complex in feedback?

The juxtaglomerular complex consists of macula densa cells in the initial portion of the distal tubule and juxtaglomerular cells in the walls of the afferent and efferent arterioles. Decreased Macula Densa Sodium Chloride Causes Dilation of Afferent Arterioles and Increased Renin Release.

What determines renal blood flow (RBF)?

The pressure gradient across the renal vasculature, divided by the total renal vascular resistance. Renal artery pressure is about equal to systemic arterial pressure, and renal vein pressure averages about 3 to 4 mm Hg under most conditions. Most of the renal vascular resistance resides in three major segments: interlobular arteries, afferent arterioles, and efferent arterioles. Resistance of these vessels is controlled by the sympathetic nervous system, hormones, and local internal renal control mechanisms.

What happens if the constriction of efferent arterioles is severe?

The rise in colloid osmotic (oncotic) pressure exceeds the increase in glomerular capillary hydrostatic pressure which leads to a decreased GFR. The curve for the resistance in the efferent arteriole is biphasic. Once the efferent resistance is 3-4x normal, GFR decreases.

What is net filtration pressure?

The sum of all the forces acting at the glomerular capillary bed to produce filtrate, which is 10 mmHg.

What happens during severe hemorrhage?

There is a decrease in blood volume and decrease in blood pressure. In this case there is increased sympathetic innervation for norepinephrine release and epinephrine release from adrenal medulla to the afferent arteriole, causing constriction to decrease in renal blood flow. This will decrease GFR.

tubuloglomerular feedback

This feedback helps ensure a relatively constant delivery of sodium chloride to the distal tubule and helps prevent fluctuations in renal excretion.

What is the role of vasodilators?

To decrease vascular resistance and increase GFR.

What is the role of vasoconstrictors?

To increase vascular resistance and decrease GFR

What other conditions can increase the Bowman's capsule hydrostatic pressure and cause decrease GFR?

Tubular necrosis, prostate hypertrophy or prostate cancer

Microalbuminuria

Urine excretion of between 30-150 mg albumin a day. This can be caused by early diabetes, hypertension and glomerular hyperfiltration. Diabetic patients with microalbuminuria are 10-20 times fold more likely to develop persistent proteinuria.

Glomerular hydrostatic pressure

Usually in the 50-60 mmHg range, this is the largest force (primary regulator) that will determine GFR and promotes filtration.

What is poor autoregulation?

When renal artery pressure rises above 120, this causes a slight increase in GFR but no change in reabsorption and urine volume increases causing pressure diuresis.

Does oxygen and nutrients delivered to the kidneys normally exceeds their metabolic needs?

Yes, a large fraction of the oxygen consumed by the kidneys is related to the high rate of active sodium reabsorption by the renal tubules. If renal blood flow and GFR are reduced and less sodium is filtered, less sodium is reabsorbed, and less oxygen is consumed. Therefore, renal oxygen consumption varies in proportion to renal tubular sodium reabsorption. This residual oxygen consumption reflects the basic metabolic needs of the renal cells.

What are other examples of prostaglandin-blocks that lower GFR?

liver cirrhosis, hypoperfusion, sepsis or heart failure

What can test the urine for protein and glucose?

standard urinary dipstick