Glomerular Filtration

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Kidney Physiology FNM L:075

What is the renal blood flow

1200 mL/min

What percentage of the total resting cardiac output is renal blood flow?

25% of cardiac output.

Which organ has the highest blood flow per unit mass?

Kidneys

Why do the kidneys have such high blood flow?

To supply fluid for filtration.

Why do the kidneys have the lowest a-v oxygen difference of any organ?

Because their blood flow is so high - so the amount of O2 uptake is relatively small compared to the amount of blood flowing through.

What substances pass from the glomerular capillaries to Bowman's space?

All molecules and ions apart from proteins.

What is the osmolality of the glomerular filtrate compared with the plasma?

About the same.

What are the three components that make up the barrier between the glomerular capillaries and Bowman's space?

1) Fenestrated endothelial cells of glomerular capillaries
2) Basement membrane
3) Podocytes (epithelial cells of Bowman's capsule membrane)

What is the charge of the basement membrane?

Negatively charged.

What is the structure of podocytes?

They extend thing foot processes (pedicels) over the basement membrane that interdigitates with other food processes forming gaps; filtration slits.

What is thought to be the major filter of what gets through to Bowman's space?

Podocytes filtration slits.

Which factors determine glomerular filterability?

Molecular weight
Electrical charge

How does molecular weight affect glomerular filterability?

Low molecular weight substances are freely filtered while large molecules are severely restricted.

How does electrical charge affect glomerular filterability?

Neutral molecules and cations are filtered more readily than anions.

Why do neutral molecules and cations have a higher filterability than anions?

Because anions (have a negative charge) and are repelled by the negatively charged basement membrane.

What is the name given to the forces that cause glomerular filtrations

Starling's forces.

What are the forces that cause glomerular filtration? (4)

1) Hydrostatic pressure of glomerular capillaries
2) Oncotic pressure of glomerular capillaries
3) Hydrostatic pressure of Bowman's space
4) Oncotic pressure of Bowman's space

What is the value of the oncotic pressure in Bowman's space?

Zero

Why is the oncotic pressure in Bowman's space zero?

Because hardly any protein is filtered out of the glomerular capillaries.

What does the hydrostatic pressure of the glomerular capillaries act to do?

Force plasma out of the capillaries.

What does oncotic pressure in the glomerular capillaries do?

Opposes the hydrostatic pressure of the capillaries.

Which other force, apart from the oncotic pressure in the glomerular capillaries, opposes the hydrostatic pressure in the capillaries?

The pressure within Bowman's capsule (capsular pressure).

What does the pressure within Bowman's capsule provide the force for?

It provides the force required to propel filtrate through nephron.

What is the equation for net filtration pressure across the glomerular membranes?

Net filtration = net hydrostatic pressure - net oncotic pressure

What is approximate value for glomerular hydrostatic pressure?

45mmHg

What is the approximate value for the pressure in Bowman's capsular space?

10mmHg

Hence, what is the approximate value for the net hydrostatic pressure difference?

35mmHg

What is the approximate value for the oncotic pressure in the glomerular capillary plasma (near the afferent arteriole end)?

25mmHg

Does the oncotic pressure in the glomerular capillary plasma change along the length of the glomerular capillary and if so, why?

Yes it does. More fluid leaks from the glomerular capillary causing the oncotic pressure to increase.

What affect does increased oncotic pressure along the length of the glomerular capillary have on the net filtration pressure?

Increasing oncotic pressure means that net filtration pressure decreases along the length of the glomerular capillary.

Does the hydrostatic pressure in the glomerular capillary change along the length of the capillary, and why?

No. Because the resistant vessels keep the hydrostatic pressure high (higher than systemic capillaries).

What is the approximate value of pressure in Bowman's capsule?

10mmHg

Does the pressure in Bowman's capsule change?

No.

What is the rate of glomerular filtration directly related to?

Net ultrafiltration pressure.

What factors affect net ultrafiltration and hence affect rate of filtration? (3)

1) Hydrostatic pressure in glomerular capillaries
2) Pressure in Bowman's space
3) Oncotic pressure in glomerular capillary

Would an increase or decrease in hydrostatic pressure in glomerular capillaries increase filtration rate?

Increase in glomerular capillary hydrostatic pressure would increase filtration rate.

Would an increase or decrease in pressure in Bowman's capsule increase filtration rate?

Decrease in pressure in Bowman's capsule would increase filtration rate.

Would an increase or decrease in oncotic pressure in glomerular capillaries increase filtration rate?

A decrease in oncotic pressure would increase filtration rate.

What might cause an increase in the pressure in Bowman's capsule?

Blockage of a urethra leading to back pressure.

What additional factor affects net filtration rate (apart from starling's forces)?

Renal plasma flow.

What affect does renal plasma flow have on rate of filtration?

Increased renal plasma flow increases the filtration rate.

What is total glomerular filtration rate (GFR)?

The sum of filtration rates of all the nephrons.

What is the single best way of assessing kidney function quantitively?

Glomerular filtration rate (GFR)

How can GFR be measured?

By measuring the excretion rate of a substance e.g. inulin, that is freely filtered, not reabsorbed and not secreted.

How can GFR be calculated?

(urine concentration of substance x urine flow rate)/

Due to all the properties of substances such as inulin that are used to measure GFR, what will the amount of the substance excreted per minute be equivalent to?

The amount of substance filtered per minute.

What substance is commonly used to measure GFR?

Inulin

What is a typical value for GFR?

120ml/min
180 L/day

What is the filtration fraction?

The percentage of plasma arriving at the glomerulus that is filtered.

What is the name of the mechanism that is intrinsic to kidneys and that keeps renal blood flow stable between a certain range?

Autoregulation.

Between which range of arterial systemic blood pressure does autoregulation operate?

Around 90-180 mmHg.

What is the way in which autoregulation keeps renal blood flow stable?

Increased blood pressure results in increased vascular resistance which ensure the blood flow remains the same.

Which part of the glomerulus responds to changes in blood pressure and why?

Afferent arteriole responds to the changes so that pressure change is not transmitted to the glomerulus.

What are the main mechanisms why which autoregulation is thought to occur?

1) Myogenic mechanism
2) Tubuloglomerular feedback
3) Metabolic hypothesis

How does autoregulation occur by the myogenic mechanism?

Increased blood pressure increases stretch in afferent arteriole, this opens non-specific cation channels leading to depolarisation. Calcium channels open causing afferent arterioles to contract.

What is the tubuloglomerular feedback mechanism of autoregulation?

Increased blood pressure causes increased filtration which results in increase NaCl deliver to Macula densa cells which release ATP that has a local paracrine affect resulting in vasoconstriction of afferent arterioles.

Where are macula densa cells present?

Juxta-glomerular apparatus.

What is the metabolic hypothesis of autoregulation?

Renal tissue metabolites maintain a degree of vasodilation, increased perfusion pressure results in increased blood flow and leaching of these metabolites. Hence, there is a decrease in vasodilation (vasoconstriction).

Other than renal tissue metabolites, what else may act as vasodilators?

Humoral factors derived from vascular endothelium e.g. NO.

What things can override autoregulation of renal blood flow?

Nerves
Hormones e.g. angiotensin II

What affect does sympathetic nerve activity have on renal blood flow?

It causes afferent and (to some degree) efferent arteriolar constriction.

What affect affect does adrenaline have on renal blood flow?

Similar affect to sympathetic nerves - afferent arteriolar constriction.

What affect does the hormone angiotensin II have on renal blood flow?

It causes vasoconstriction, particularly of efferent arterioles.

Which locally produced substances cause vasodilation when released under conditions such as haemorrhage?

Prostaglandins and nitric oxide.

What do prostaglandins and nitric oxide protect kidneys from?

Renal ischaemia.

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