Session 3: GFR and Filtration Flashcards

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1
Q

Basic functions of the kidneys.

A

Regulation and control of concentrations of key substances in the ECF. Excretion of waste products. Synthesis of renin, EPO and prostaglandins. Activation of vitamin D, catabolism of insulin and PTH + calcitonin.

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2
Q

What does the kidney filter?

A

The extra cellular fluid which includes interstitial fluid and the plasma of the blood.

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3
Q

How much ECF does the kidney filter?

A

180L/day

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4
Q

Where does the main filtration occur?

A

In the glomerulus of a nephron in the kidney into Bowman’s capsule.

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5
Q

What is being filtered?

A

Most water Almost all of the salts Almost all of the glucose Almost all of the urea

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6
Q

What is not being filtered?

A

Proteins and large molecules.

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7
Q

What is ultra-filtrate?

A

It is more or less plasma but without the proteins and large molecules. It is what has been filtered into Bowman’s capsule.

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8
Q

How much of the ultra-filtrate will be recovered and reabsorbed into system circulation?

A

99% water 99% sodium and chloride ions 100% bicarbonate 100% glucose and amino acids

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9
Q

How much fluid is excreted by the kidneys daily?

A

Around 1.5L of urine per day

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10
Q

What is osmolality?

A

Solute per kilogram of solvent Measured in milliosmoles

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11
Q

What is osmolarity?

A

Number of osmoles of solute per litre

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12
Q

What is the glomerulus?

A

A small tuft of capillaries which are specialised and have fenestrations in order for increased permeability.

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13
Q

What is the specialised basement membrane of the glomerulus? What is its purpose?

A

It is an acellular glycoprotein membrane which has a negative charge. It provides further selectivity to ions.

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14
Q

What are podocytes?

A

Specialised type of epithelial cells which directly invest the glomerular capillaries.

They are critical for selectivity of glomerular filtration.

The podocytes contact the glomerular capillaries’ basement membrane using thin outpouchings known as foot processes.

The narrow area between adjacent foot processes forms an extremely thin slit which is sometimes termed the slit diaphragm.

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15
Q

After the podocytes where will the ultra-filtrate go?

A

Into the Bowman’s space which is between the glomerular capillaries and the Bowman’s capsule. After this it will go into Bowman’s capsule.

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16
Q

What is Bowman’s capsule?

A

A layer of epithelial cells that surrounds the glomerular capillaries and is continuous with the epithelium of the proximal convoluted tubule.

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17
Q

Where can the glomerulus be found?

A

Only in the cortex of the kidney.

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18
Q

What is glomerular filtrate rate? (GFR)

A

How much filtration of ECF (ml) occurs per min.

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19
Q

What is a normal GFR?

A

90-125 ml/min

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20
Q

What is renal plasma flow?

A

The amount of plasma (ml) that flows through the glomerulus every minute.

21
Q

What is a normal renal plasma flow?

A

800 ml/min

22
Q

What is filtration fraction?

A

A normal GFR does not add up to the renal plasma flow.

125 ml/min as a normal GFR could be vs a renal plasma flow of 800 ml/min means that only around 20% of the ECF that passes through the glomerulus is being filtrated at any point in time.

23
Q

Why is filtrate fraction important?

A

FF = GPR/RPF

This means that 80% of the blood arriving will exit via the efferent arteriole without being filtered.

This is also important because if 100% would be filtered at any point in time you would end up without plasma.

24
Q

What are filtration slits?

A

Spaces between podocytes which become selective towards molecules

25
Q

Why are the filtration slits important?

A

Because they are definitive in size. Anything bigger than the diameter of the filtration slits will not fit through and enter the proximal convoluted tubule.

This is also relevant regarding the fenestrations of the glomerular capillaries.

26
Q

What happens if the basement membrane of the glomerular capillaries’ (filtration barrier) charge is lost?

A

This means that proteins are more readily filtered, especially anions (negative). Increase in filtration of anions.

This is a condition called proteinuria.

27
Q

There are three pressures which regulate GFR.

Which are they? Explain them.

A

Hydrostatic pressure in the capillary called Pgc

Hydrostatic pressure in the Bowman’s capsule called Pbc

Oncotic pressure difference between the capillary and tubular lumen called πgc.

28
Q

Give a formula of net filtration pressure.

A

Pgc - (Pbc + πgc)

29
Q

How does the πbc differ between the afferent and efferent arterioles?

A

The oncotic pressure in the glomerulus at the efferent end is higher than at the afferent. This is because a lot of water has been lost and the protein concentration is higher in the efferent end.

30
Q

What is tubular reabsorption?

A

The recovery process of the majority of all water and substances reabsorbed by the kidney into systemic circulation.

31
Q

There are three mechanisms of tubular reabsorption. Which?

A

Osmosis

Diffusion

Active transport

32
Q

Where is the majority of the volume of the glomerular filtrate solution reabsorbed?

A

In the proximal convoluted tubule.

This includes most of the water and all of the glucose

33
Q

Explain the sodium reabsorption and coupling with other substrates.

A

Most of the substrates are coupled with sodium via symporters on the apical membrane of PCT.

Glucose, amino acids, water solulbe vitamins, lactate, acetate and ketones are just some examples of substrates which are reabsorbed with the help of sodium.

These substrates then move on through the cells via diffusion and/or other transport processes.

The operation of these symporters located on the apical membrane is dependent on the action of the 3Na-2K-ATPase transporter located on the basolateral membrane.

34
Q

Explain tubular secretion.

A

Substances being added to the glomerular filtrate in the nephron tubule.

Removes excessive quantities of certain dissolved substances from the body.

Examples include H+ ions to regulate pH, potassium ions, ammonium ions, creatinine, urea and some hormones as well as drugs.

35
Q

How is GFR regulated?

A

It is mainly regulated through it’s hydrostatic pressure that is from the capillaries and pointed inwards to the Bowman’s capsule (Pgc).

36
Q

What is Pgc dependent on?

A

The arterial blood pressure.

37
Q

How is Pgc regulated if arterial blood pressure would rise or fall?

A

Most usually it is regulated by something called autoregulation where there is a range of blood pressure which autoregulation will effectively stabilise the GFR.

38
Q

There are two basic types of autoregulation of GFR.

Which?

A

Myogenic regulation

Tubuloglomerular feedback

39
Q

What is the autoregulatory range?

A

80-180 mmHg

40
Q

Explain myogenic regulation of GFR.

A

The arterial smooth muscle responds to increases and decreases in vascular wall tension.

This means that an increase in arterial blood pressure which leads to an increase in Pgc and also GFR has a response. There would be constriction of the afferent arteriole to lower the Pgc distal to the point of constriction. This also lowers GFR. However one could also dilate the efferent arteriole in order to balance things out.

This is a quick response which occurs after around 3-10 seconds.

41
Q

What is the tubuloglomerular feedback mechanism?

A

It’s a slower response which involves sodium and chloride concentrations at the macula densa. It controls renal arteriolar resistance.

42
Q

What is the macula densa?

A

Macula densa are cells which can be found in the distal convoluted tubule and proximal to the juxtaglomerular appartus and its granular cells. In the vicinity the glomerulus as well as EA and AA can be found.

43
Q

Explain the process of how the macula densa are involved in the regulation of resistance in the AA and EA.

A

When the amount of sodium increases in the lumen of the distal convoluted tubule this will be taken up into the macula densa via NKCC2 transporters. NKCC2 will also tranport Cl- and K+ ions.

The intracellular increase of Na+ and Cl- triggers release of ATP.

The ATP will leave the macula densa cells through exit channels and be converted into AMP and then into adenosine.

Adenosine will bind to A1 receptors on the extraglomerular mesangial cells in the afferent arteriole. Activation of G proteins and Gi causes inhibition of AC and Go which leads to an increase in intracellular calcium.

The calcium spreads rapidly to smooth muscles cells causing vasoconstriction of the afferent arteriole.

44
Q

Briefly explain the tubuloglomerular feedback mechanism.

A

Increase in Na+ and Cl- causes an intracellular response leading to vasoconstriction.

Also Na+ and Cl- inhibits renin release from JGA or granular cells. This leads to a drop in blood pressure as Angiotensin II will not work.

45
Q

Explain TGF response to a decrease in GFR.

A

Prostaglandin is released from macula densa leading to vasodilation of the afferent arteriole.

46
Q

Give examples of medications that can mess with the tubuloglomerular feedback.

A

NSAIDs inhibit prostaglandin. This means that the vasodilation of the kidneys via the TGF response will not work properly.

ACE-inhibitors block ACE in the lungs which means that angiotensin II will not be made. This renders the TGF response useless in the sense of sodium and chloride ions inhibiting renin release/not inhibiting.

47
Q

Explain neural regulation of GFR.

A

Sympathetic nerve fibres innervate AA and EA.

This is normally not heavily innervated and has no effect on GFR but in fight or flight, ischaemia or severe haemorrhage the nervous system can stimulate renal vessels to vasoconstrict.

Also parasympathetic NS releasing NO for endothelial cells can cause vasodilation.

48
Q

Explain the glomerotubular balance.

A

Reabsorption of sodium in the PCT is more or less always constant in its fraction.

Whether there is a high concetration of Na+ or low conc. it will always try to filter around 67% of the Na+ conc.