Renal Structure and Function

Question 1

What are renal arteries? What is the ureter? What is the urethra?

Answer 1

• Renal arteries are branches of abdominal aorta: tube carrying urine to bladder is URETER; tube carrying urine from bladder to outside world is URETHRA, (don’t confuse ureter with urethra)

Question 2

What does the main renal artery divide into?

Answer 2

• The main renal artery divides into interlobar vessels and then these divide into small arcuate (arch shaped) arteries in the renal cortex.

Question 3

Where does urine drain into before the ureter?

Answer 3

Urine drains into the calyxes which then fuse to form the renal pelvis which reduces down into the ureter

Question 4

What is the glomerulus? How does blood travel through it?

Answer 4

• The arcuate arteries terminate in a little clump of capillaries in the cortex called a glomerulus; each little black blob in the diagram above represents a glomerulus
• Blood enters the glomerulus of each nephron in the afferent arteriole and leaves in the efferent arteriole.
• About 20% of the blood plasma is filtered through the glomerulus and enters the capsular space which empties into the proximal tubule.

Question 5

What is the difference between afferent and efferent arterioles?

Answer 5

• Afferent arterioles have larger diameters than efferent arterioles, so there is considerable drop in pressure between afferent and efferent arteriole.
• This is the filtration pressure forcing fluid through the endothelium of the capillaries into the capsular space

Question 6

What is the filtration fraction?

Answer 6

• The proportion of plasma filtered into Bowman’s capsule is the ‘filtration fraction’. It is normally ~20%.
• A greater filtration fraction would render the blood in the efferent arteriole too viscous as it would have too high a haematocrit

Question 7

What are the characteristics of capillaries in the glomerulus?

Answer 7

• The capillaries in the glomerulus are fenestrated (have gaps between the endothelial cells) and are covered on the outside (capsule side) with an extra layer of cells called podocytes.
• The podocytes have slits between them; these slits form the filtration mechanism.
• The slits between the podocytes are too small normally to allow proteins to pass through, but ions like sodium chloride and bicarbonate pass easily
• The slits can become inflamed and enlarged in renal disease, enabling more solutes (mainly proteins) to enter the urine; proteinuria may be a sign of inflammation in the glomerulus.

Question 8

How is filtration of water controlled in a healthy individual?

Answer 8

• The filtration of water into the capsule and proximal tubule is controlled in a healthy individual by the constriction or relaxation of the afferent arteriole.
• Normally this is adjusted so that a physical pressure of about 55 mm Hg is present in the glomerular capillaries.
• Starling’s principle applies. The net filtration pressure is the sum of a physical (hydrostatic) pressure in the capillaries of about 55 mm Hg minus an osmotic pressure due to proteins of about 30 mm Hg.
• The physical pressure of fluid in the capsule is about 15mm Hg, and the osmotic pressure is nearly zero (no proteins) so the normal net filtration pressure is about (55-30-15) =10 mmHg.

Question 9

Where does fluid pass to from Bowman’s capsule? What happens to the fluid from there?

Answer 9

• Fluid passes from Bowman’s capsule into the proximal tubule (1). Here filtered materials can be reabsorbed into the peritubular capillaries (2).
• Material can also be transported out of the capillaries and secreted into the tubular fluid (3).
• The amount of a material (eg glucose) excreted (4) is the amount filtered plus the amount secreted minus the amount reabsorbed

Question 10

Where is about 2/3 of all the water filtered in the glomerulus reabsorbed? What are the characteristics of this structure that allow for absorption?

Answer 10

• About 2/3 of all the water filtered in the glomerulus is reabsorbed in the proximal tubule.
• The tubule is lined with epithelial cells.
• The basal membranes of the cells (i.e. the layer not in contact with filtered fluid) contain sodium pumps which extrude sodium into the interstitial fluid.
• Sodium channels exist in the luminal (inner) membrane of the cells and so sodium passes out of the lumen into the cells down its concentration gradient.
• This sodium influx carries glucose with it.
• Water is reabsorbed down an osmotic gradient generated by the sodium pumps from the lumen into the cells and then out into the interstitial fluid

Question 11

Where does fluid go after passing out of the proximal convoluted tubule fluid?

Answer 11

• Fluid passes out of the proximal convoluted tubule fluid and enters the ‘Loop of Henle’. (see later lecture)
• After the loop it enters the distal convoluted tubule.
• The distal convoluted tubule returns to the junction where the afferent and efferent arterioles meet the glomerulus.
• This meeting of afferent and efferent arteiroles and distal tubule is called the juxtaglomerular apparatus.
• Finally the distal tubule enters the collecting duct. The collecting ducts drain into the ureter.
• The complete set of tubes, from Capsule to Collecting Duct, is known as a NEPHRON.
• Each kidney contains many tens of thousands of nephrons, all operating in parallel.

Question 12

How is filtration rate (glomerular filtration rate or GER) regulated in a healthy kidney?

Answer 12

• Filtration rate (glomerular filtration rate or GFR) in a healthy kidney is autoregulated by tubuloglomerular feedback and. it does not change over a wide range of blood pressures.
• Autoregulation of GFR means that renal blood flow also does not change over a wide range of blood pressures.
• As the renal blood flow is constant, and the metabolic rate of the kidney (i.e. its oxygen consumption) is constant, the pO2 in the kidney interstitium is a measure of the oxygen delivery to the kidney and thus oxygen carrying capacity of the blood.
• This is why erythropoietin releasing cells are in the kidney.

Question 13

How does tubuloglomerular feedback regulate the GFR?

Answer 13

• Tubuloglomerular feedback regulates the GFR by the regulating the degree of constriction in the smooth muscle of the afferent arteriole;
• The constrictor tone in the afferent arterioles is lower than that in the efferents, producing a filtration pressure in the glomerulus.
• If the afferent arterioles constrict, this lowers the filtration pressure and thus GFR
• Conversely if the afferents relax, this raises filtration pressure and GFR

Question 14

What is the mechanism of tubuloglomerular feedback?

Answer 14

• The sodium concentration in the distal tubule regulates the release of ATP by the macula densa cells.
• The ATP is converted to adenosine and diffuses to the afferent arteriolar smooth muscle where it acts on type A1 adenosine receptors to increase the intracellular calcium concentration in the muscle and makes it contract.
• If the sodium concentration in the distal tubule is too low, indicating a low GFR, less adenosine is produced and the muscle relaxes, increasing GFR.
• If the concentration is too high then more adenosine is produced and the muscle constricts, reducing GFR.
• The macula densa cells also tonically produce prostaglandin PGE2. which acts on juxtaglomerular cells to stimulate renin release
• More prostaglandin and thus more renin is produced when sodium levels are low.

Question 15

What is the single most important measure of kidney function, and how is it measured?

Answer 15

• The Glomerular Filtration Rate (GFR) is the single most important measure of kidney function; we need to know how to measure it.
• GFR is measured by the CLEARANCE of a selected material. Clearance is measured in units of litres/minute. It is the effective volume of plasma completely ‘cleared’ of a substance per minute.

Question 16

What are the three classes of clearance in glomerular filtration?

Answer 16

• For a substance in arterial blood entering the kidney: three possible classes of clearance
• Class 1: Not removed at all by kidney:
• Clearance = zero
• Class 2: Removed at same rate as water passes through glomeruli and not secreted or reabsorbed:
• Clearance = glomerular filtration rate
• Class 3: Completely removed from blood passing through kidney: Clearance = renal plasma flow
• Clinical note: If kidneys are damaged, generally GFR will decrease although renal plasma flow may be normal.

Question 17

How is clearance measured? What is the formula and method?

Answer 17

• The formula is
• Clearance = (urine concentration/plasma concentration) x urine flow
• C= ([U] / [P]) x [V]
• Where [U]= urine conc. [P] = plasma conc. V= vol. of urine per minute. (so long as concentration units are same, it does not matter what they are)
• To measure clearance of a substance you therefore have to
  1) measure the concentration of the substance in the plasma
  2) collect urine for a fixed period to get the urine flow (ml/min)
  3) measure the concentration of the substance in the collected urine

Question 18

What is the gold standard for measuring GFR? How is it measured? How is this done in clinical practice? How does this affect the estimation?

Answer 18

• The ‘gold standard’ for measuring GFR is the clearance of INULIN. Inulin (not insulin!) is a polysaccharide derived from jerusalem artichokes.
• It is completely filtered from the plasma and not reabsorbed.
• BUT inulin does not occur naturally in plasma!
• So to measure inulin clearance you have to infuse inulin i.v. over a period of hours, to reach a steady plasma concentration.
• This makes measurement of GFR by inulin clearance impractical except in specialised kidney research units.
• In clinical practice, creatinine clearance is used to measure GFR. Creatinine is produced naturally by the body (creatinine is a break-down product of creatine phosphate, which is found in muscle). It is freely filtered by the glomerulus, but also actively secreted into the urinein small amounts.
• This secretion means that creatinine clearance overestimates actual GFR by 10-20%. This margin of error is acceptable considering the ease with which creatinine clearance is measured. Unlike precise GFR measurements involving constant infusions of inulin, creatinine is normally already at a steady-state concentration in the blood and so measuring creatinine clearance is much less cumbersome.
• Commonly a 24 hour urine collection is undertaken, from empty-bladder one morning to the contents of the bladder the following morning, with a blood test for creatinine then taken.
• N.B. Don’t confuse creatinine with creatine! Creatinine is the product of creatine metabolism

Question 19

What can clearance be used to measure? How? What substances may be involved?

Answer 19

Clearance can be used to measure RENAL BLOOD FLOW
- If all of a particular substance is filtered along with water and in addition all of the material in the efferent arteriolar blood is secreted into the urine, then the renal venous blood will have NO material in it. i.e. All the blood passing through the kidney will have been cleared of the material.
- The clearance will then equal the renal plasma flow
- PAH (para-amino-hippuric acid) is such a substance. To measure renal plasma flow, PAH is infused until a steady concentration in (arterial) blood is reached. Urine is collected for 24 hours and urine flow and PAH concentration measured.
- Example:
o Conc. of PAH in plasma: 0.02 mg/ml
o Conc. of PAH in urine: 14.0 mg/ml
o Urine flow 0.9 ml/min
o Clearance PAH = RPF = (14.0 x 0.9)/0.02 = 630 ml/min
o Haematocrit = 45% therefore renal blood flow =630 x (100/45) = 1.4 l/min

Question 20

Summarise clearance.

Answer 20

• Clearance of a substance Cs = [Us]V/[Ps]
• [Us] = urine conc. of substance s, [Ps] = plasma conc.
• V= vol. of urine litres per minute. Clearance measured as volume (ml) /min Clearance of creatinine normally used clinically as creatinine already present in blood. Clearance of creatinine slightly overestimates GFR
• Normal creatinine clearances:
  o women 88-128 mL/min:
  o men 97 to 137* mL/min
  o (*equals about 90ml/min/1.73 m2).
• Clearance of PAH (para-amin-hippuric acid) measures renal plasma flow (RPF) because all PAH is secreted into blood, therefore all blood passing through kidney is ‘cleared’ of PAH.
• Normal RPF (both kidneys) 600-700 ml/min