Renal Blood Flow & Glomerular Filtration Rate

increases -plasma spends more time in the glomerular capillaries

If renal blood flow decreases, filtration fraction _________________.

Renal blood flow decreases Glomerular capillary hydrostatic pressure decreases -> NFP decreases -> GFR decreases

Describe how renal blood flow, NFP, and GFR change as the afferent arteriolar resistance increases.

Renal blood flow decreases Glomerular capillary hydrostatic pressure increases -> NFP increases -> GFR increases

Describe how renal blood flow, NFP, and GFR change as the efferent arteriolar resistance increases.

Renal blood flow markedly decreases Afferent arteriole end -glomerular capillary hydrostatic pressure stays constant -> NFP stays constant -> GFR stays constant Efferent arteriole end -because the renal blood flow is markedly decreased, plasma spends more time in the glomerular capillaries, leading to more ultrafiltrate being formed -as a result, the oncotic pressure of plasma in the glomerular capillaries at the efferent arteriole end increases even more (plasma is even more concentrated) -because the oncotic pressure of plasma opposes filtration, NFP decreases, and hence, GFR decreases

Describe how renal blood flow, NFP, and GFR change as the resistance of both the afferent arteriole and efferent arteriole increases.

Small changes around normal arterial pressure (i.e. small changes in NFP and GFR) result in parallel changes in afferent and efferent arteriolar resistance. Large increases in arterial pressure result in large increases of afferent arteriolar resistance and no change or even dilation of the efferent arteriole. This differential response of the afferent and efferent arterioles at high blood pressures appears to be due to the distribution of vasoconstrictor A1 receptors and vasodilator A2 receptors.

Describe the difference between the effect of the tubulo-glomerular feedback on afferent arterioles and the effect on efferent arterioles.

Intrinsic property of vascular smooth muscle to contract in response to pressure-induced stretching, increasing vascular resistance -if perfusion pressure increases, the arteriole smooth muscle stretches, causing an influx of calcium into the smooth muscle cells -as a result, the smooth muscle cells contract Important mechanism at the level of protection -very fast -responds very quickly -very sensitive to the pulsatile nature of blood pressure

Describe the myogenic response.

High rate of blood flow with increased glomerular capillary hydrostatic pressure leads to increased glomerular filtration rate and flow through the distal tubule, which causes the macula densa of the JGA to release ATP that is converted to adenosine, which is a vasoconstrictor of the afferent and efferent arterioles (through A1 receptors)

Describe the tubulo-glomerular feedback.

During a massive sympathetic outflow to the kidney, the kidney becomes ischemic because there is a massive constriction of the renal arterioles, and renal blood flow massively decreases. As a result, the tissue starts producing and releasing prostaglandins and nitric oxide. Prostaglandins have a vasodilatory effect on the afferent and efferent arterioles, balancing and protecting against the effects of renal sympathetic nerve activity (norepinephrine), epinephrine, and angiotensin II.

Explain the mechanism of extrinsic humoral control of RBF by prostaglandins.

Renin (from kidney) converts angiotensinogen (from liver) into angiotensin I. Angiotensin converting enzyme (mainly in pulmonary capillaries) converts angiotensin I into angiotensin II. Angiotensin II constricts and increases the afferent and efferent arteriolar resistance, which results in a decrease of RBF, a small decrease of GFR, and an increase of FF.

Explain the mechanism of extrinsic humoral control of RBF by renin.

Epinephrine released from the adrenal medulla increases the afferent and efferent arteriolar resistance. Due to the same reason as the mechanism of extrinsic neural control of RBF, there is a small decrease in GFR with an increase in filtration fraction.

Explain the mechanism of extrinsic humoral control of RBF by the adrenal medulla.

Renal sympathetic nerves release norepinephrine (at the afferent and efferent arterioles) that increase the afferent and efferent arteriolar resistance. This results in a small increase in glomerular capillary hydrostatic pressure that favors filtration and increases GFR. However, because the renal blood flow is markedly decreased, plasma spends more time in the glomerular capillaries, leading to more ultrafiltrate being formed. As a result, the oncotic pressure of plasma in the glomerular capillaries at the efferent arteriole end increases even more (plasma is even more concentrated). Because the oncotic pressure of plasma opposes filtration, NFP decreases, and hence, GFR decreases.

Explain the mechanism of extrinsic neural control of RBF.

1. A decrease in arterial pressure causes a decrease in the stretching of the afferent arteriole (where the JGC are located), which in turn causes the release of renin via intrarenal baroreceptors. 2. Decrease in arterial pressure -> decrease in GFR -> decrease in rate of fluid delivery to the macula densa -> decrease in Na and Cl concentrations in the macula densa cells -> decrease in reabsorption of Na and Cl by macula densa cells -> increase in renin secretion

Explain the two mechanisms by which the JGC release renin.

If GFR stays constant, that means that NFP has to stay constant, and hence, glomerular capillary hydrostatic pressure has to stay constant. At this point, because renal arterial pressure is so high, the vasodilator A2 receptors on the efferent arteriole get activated. This dilation of the efferent arteriole causes the glomerular capillary hydrostatic pressure to stay constant (and hence, NFP and GFR) even though the renal arterial pressure is high.

Explain why does GFR stay constant at high renal arterial pressure even though RBF increases.

Using a substance that has constant plasma concentration, is freely filtered, and is NOT reabsorbed, secreted, or metabolized in the kidney -therefore, the rate that it appears in the urine = the rate of filtration in the kidney

How is GFR measured?

GFR/RPF

How is filtration fraction calculated?

increases

If glomerular capillary hydrostatic pressure increases, NFP ________________.

1. Maintain RBF and GFR constant at high or low arterial pressure 2. Match GFR ("function") to flow -allows the tubules to continue to function and not be deprived of fluid 3. Protects glomerulus from hypertension

Mention the three effects of autoregulation at the level of the kidney.

greater

The higher the arterial pressure and the lower the resistance, the ____________ the renal blood flow.

sympathetic -there are sympathetic nerve fibers that innervate both the afferent and efferent arteriole, as well as throughout the cortex

The kidney is innervated by the __________________ nervous system.

True (R ~ 1/r^4)

True or False: A very small change in arteriole radius produces a very large change in blood flow resistance.

True -autoregulatory zone still present

True or False: Autoregulatory mechanisms are still in place even during the effects of renal sympathetic nerve activity (norepinephrine), epinephrine, and angiotensin II.

True -e.g. increase or decrease in sympathetic outflow to arterioles

True or False: Extrinsic mechanisms are part of the whole animal's systemic homeostatic mechanisms.

True

True or False: If NFP stays constant, then GFR stays constant.

True

True or False: If RBF changes, then filtration fraction will also change.

True

True or False: Neural activation not only affects vasculature, but also tubular function.

True -the effects on GFR are much smaller than the effects on RBF

True or False: The extrinsic control mechanisms, because they constrict both the afferent and efferent arterioles, have mild effects on GFR (mild decrease), but not to the same magnitude as their effect on RBF.

True

True or False: The kidneys are capable of controlling GFR and RBF by mechanisms that are entirely within the kidneys.

True -large swings in systolic pressure cause this myogenic response to become additive because the muscle is not recovering as quickly as it is responding -hence, with each beat there is a greater response, and eventually, a maintained response

True or False: The myogenic response has a relatively long lag time of recovery.

True

True or False: The neural and humoral (by the adrenal medulla) extrinsic control mechanisms of RBF are redundant.

True

True or False: The signal that comes from the distal tubule that causes the JGC to release renin is unknown.

True

True or False: There is a point where, if glomerular capillary hydrostatic pressure is decreased enough, no filtration is taking place at the end of the glomerular capillary just before the efferent arteriole.

Intrinsic/"autoregulatory" and extrinsic (hormonal and neural) mechanisms that alter renal blood flow resistance

What are the determinants of renal blood flow?

1. Myogenic response 2. Tubulo-glomerular feedback

What are the two autoregulatory mechanisms of RBF?

Arterial blood pressure and resistance

What are the two determinants of renal blood flow?

Afferent arteriole and efferent arteriole (resistances are added because they are in series)

What are the two sites of blood flow resistance in the glomerulus?

How much of plasma being delivered to the afferent arteriole is being converted into ultrafiltrate (efficiency of producing ultrafiltrate)

What does the filtration fraction represent?

Specifically protect and regulate functions of the kidney

What is the function of the autoregulatory mechanisms that alter renal blood flow resistance?

Increase in arterial pressure -> increase in afferent arteriolar resistance -> only a small increase in RBF, glomerular capillary hydrostatic pressure, NFP, and GFR

What is the net effect of myogenic autoregulation?

0.20 -20% of plasma is being converted to ultrafiltrate

What is the normal value of filtration fraction?

Glomerular capillary hydrostatic pressure

What is the primary force determining filtration, and therefore, NFP?

As RPF increases, plasma is spending less time in the glomerular capillaries, and there is less time for filtration. Therefore, less filtrate is produced per unit of plasma, causing a decrease in filtration fraction.

What is the relationship between RPF and filtration fraction?

PAH (para-aminohippurate) -foreign chemical, non-toxic -freely filterable -fully secreted by renal tubules -NO reabsorption

Which substance can be used to measure RBF and RPF?

Inulin -oligosaccharide of fructose Creatinine -metabolic product of muscle creatine

Which substances can be used to measure GFR?