Session 3

Question 1

What is the difference between a superficial nephron and a juxtamedullary nephron?

Answer 1

Superficial nephrons only penetrate the outer medulla and they have no thin descending limb of the loop of Henle. In juxtamedullary nephrons the thin loop of Henle penetrates into the inner medulla and there is a long descending thin limb of the loop of Henle.

Question 2

How do cortical nephrons build up pressure for filtration?

Answer 2

Much narrower afferent arteriole than efferent arteriole to increase preload into the kidney and therefore increases filtration pressure.

Question 3

What types of nephron form vasa recta?

Answer 3

Juxtamedullary nephrons.

Question 4

What types of nephron form peritubular capillaries?

Answer 4

Cortical nephrons.

Question 5

How many segmental arteries are usually found in a kidney?

Answer 5

5

Question 6

Describe the main features of peritubular capillaries.

Answer 6

Arise from efferent arterioles; each peritubular capillary network surrounds the PCT and is only associated with one nephron.

Question 7

Is oncotic pressure in blood in the efferent articles higher or lower than in the afferent, why?

Answer 7

Higher, albumin levels are higher in comparison to the afferent arteriole due to filtration in the glomerulus.

Question 8

What does the end product of filtration in the glomerulus resemble?

Answer 8

Blood plasma but without the large proteins and cells present.

Question 9

What forces are involved in filtering plasma at the kidneys?

Answer 9

• Hydrostatic pressure in the capillary
• Hydrostatic pressure in the Bowman’s capsule
• Oncotic pressure difference between the capillary and tubular lumen

Question 10

What forms the filtration barrier in the kidneys?

Answer 10

Capillary endothelium, basement membrane, podocyte layer.

Question 11

How are negatively charged proteins prevented from moving across the filtration barrier in the kidneys?

Answer 11

Basement membrane contains glycoproteins which have a negative charge, any proteins with a negative charge are repelled from movement across the membrane.

Question 12

What is the purpose of filtration slits in the filtration barrier of the kidney?

Answer 12

To prevent large molecules and cells from getting through; insulin is the largest molecule which can fit through the slits normally.

Question 13

How is filtration in the kidneys regulated?

Answer 13

Autoregulation via the myogenic response; autoregulation via tubular glomerular feedback.

Question 14

Describe the myogenic response in the kidneys.

Answer 14

If blood pressure increases, smooth muscle cells respond to an increase in force created by the increased pressure by contracting more, less blood can move into the capillaries so hydrostatic pressure remains constant and GFR remains unchanged. Mechanism can maintain GFR when BP is within physiological limits.

Question 15

Describe autoregulation via tubular glomerular feedback.

Answer 15

When GFR changes, tubular flow also changes so a different amount of NaCl reaches the distal tubule. Different [NaCl] is detected by the macula densa cells via concentration-dependent salt uptake through NaK2Cl channels and chemical signals are sent to the afferent arteriole to increase/decrease GFR. Adenosine and prostaglandins can also be released by the juxtaglomerular apparatus to cause vasodilation of the efferent/afferent arterioles.

Question 16

What effect does adenosine have on the kidneys?

Answer 16

Causes vasodilation of the efferent arteriole.

Question 17

What effect do prostaglandins have on the kidneys?

Answer 17

Cause vasodilation of the afferent arteriole.

Question 18

When is tubular glomerular feedback utilised?

Answer 18

In acute changes in tubular flow.

Question 19

Describe resorption in the proximal convoluted tubule of the kidney.

Answer 19

Isosmotic and driven by sodium uptake. All glucose and half of urea is usually reabsorbed here.

Question 20

Why is 50% of urea reabsorbed in the PCT?

Answer 20

To allow regulation of osmolarity of urine.

Question 21

How is sodium moved across the basolateral membrane in the kidney tubules?

Answer 21

Actively via 3Na-2K-ATPase.

Question 22

How does sodium move across the apical membrane in the kidney tubules?

Answer 22

Passively along its concentration gradient through a variety of transporters.

Question 23

Which transporters allow sodium movement across the apical membrane in the PCT of kidney tubules?

Answer 23

Na-H antiporter and Na-Glucose symporter (SGLUT).

Question 24

Which transporters allow sodium movement across the apical membrane in the loop of Henle of kidney tubules?

Answer 24

Na-K-2Cl symporter.

Question 25

Which transporters allow sodium movement across the apical membrane in the early distal tubule of kidney tubules?

Answer 25

Na-Cl symporter.

Question 26

Which transporters allow sodium movement across the apical membrane in the late distal tubule and collecting duct of kidney tubules?

Answer 26

ENaC.

Question 27

What happens if plasma glucose concentration is above the transport maximum for SGLUT?

Answer 27

Some glucose will spill into the urine, water will follow the glucose so the patient will present with polyuria and glucosuria.

Question 28

How is glucose reabsorbed in the PCT?

Answer 28

Moved across the apical membrane via SGLUT by using the sodium concentration gradient to power the pump. Moved across the basolateral membrane via facilitated diffusion into the peritubular capillaries.

Question 29

How are organic cations secreted in the kidney?

Answer 29

Cation enters tubular cells via passive carrier-mediated diffusion across the basolateral membrane using gradients set up by 3Na-2K-ATPase. Cation is secreted into the lumen via a H-OC exchanger driven by the H gradient from Na-H antiporters.

Question 30

What is the normal value of GFR in men and women?

Answer 30

Around 120 in men and 95 in women but decreases with age and varies with ethnicity, body size.

Question 31

How is GFR measured?

Answer 31

Measure a substance that isn’t altered as it travels through the nephron, e.g. creatinine or inulin.

Question 32

What is renal clearance?

Answer 32

The rate of elimination of a substance by the kidney and liver: GFR=Clearance=(UxV)/P

Question 33

What is eGFR?

Answer 33

An estimate of GFR used in clinical situations.

Question 34

What are cenobitic molecules?

Answer 34

Molecules which the body recognises as foreign.

Question 35

WHat relevance does clearance have on drug dosing?

Answer 35

Determines how long a drug will be therapeutically active, hence determines drug dosing regimes and the effectiveness of a drug.

Question 36

If the rate of removal of a drug is proportional to its free concentration in plasma, what does this imply about the pharmacokinetics of the drug?

Answer 36

It shows linear pharmacokinetics.

Question 37

What molecular factors affect the movement of drugs in and out of fluid and tissue compartments?

Answer 37

Lipophilicity; hydrophilicity; degree of binding to plasma proteins; degree of binding to tissue proteins.

Question 38

Why are tissue compartments modelled as one apparent fluid compartment?

Answer 38

Makes the model simple and tissue compartments usually have a very high capacity for drugs so they don’t behave like real fluid volumes.

Question 39

How is the apparent volume of distribution of a drug measured?

Answer 39

My measuring the actual plasma concentration of the drug and using it to calculate Vd.

Question 40

What does a high Vd imply?

Answer 40

A drug is lipophilic so leaves the plasma easily and therefore has a low clearance rate as little is available for excretion by the kidneys.

Question 41

What does a low Vd imply?

Answer 41

A drug is highly charged so is more confined to the plasma, therefore has a higher clearance rate as more drug is available for excretion by the kidneys.

Question 42

How are xenobiotics recognised by the liver?

Answer 42

Using phase I and phase II enzyme systems.

Question 43

What role does the liver have in removing xenobiotics?

Answer 43

Phase I and phase II enzyme systems recognise xenobiotics and act to increase their ionic charge so they become more readily excretable by the kidneys.

Question 44

What effect does decreased pH have on excretion of drugs?

Answer 44

Acidic urine allows acidic anions to become protonated and electrically neutral so they become more lipophilic and can diffuse back across the nephron more easily and less are excreted. It also makes weak bases more protonated so more is excreted in the urine.

Question 45

What effect does increased urinary pH have on the excretion of drugs?

Answer 45

Weak bases become deprotonated and electrically neutral so they become more lipophilic and less is excreted in the urine. It also prevents protonation of acidic anions so more will be excreted in the urine.

Question 46

Where are organic anion and cation transporters located in the kidneys?

Answer 46

In the PCT on both the apical and basolateral membranes.

Question 47

Which organic anion and cation transporters are found in the kidneys?

Answer 47

OAT and OCT transporters.

Question 48

How can half life of drugs be therapeutically increased in the kidneys?

Answer 48

By competitively binding to OATs and OCTs to reduce renal clearance of drugs.

Question 49

Problems with which systems can affect renal clearance?

Answer 49

Heart, renal or hepatic (HRH).

Question 50

How can cardiac problems affect clearance?

Answer 50

Reduced cardiac output causes a fall in GFR.

Question 51

How can renal problems cause reduced clearance?

Answer 51

Reduced renal vascular supply reduces GFR; renal failure/disease reduces clearance.

Question 52

How can liver problems impact on renal clearance?

Answer 52

Hepatic disease reduces drug metabolism by phase I and phase II enzyme responses so clearance reduces; in cirrhosis and hepatitis there is hyoalbunimea so increased availability of drugs normally bound to albumin and increased clearance of those drugs.

Question 53

Describe the features of inulin.

Answer 53

Fructose polysaccharide which is clinically inert so not broken down or altered. Inulin clearance=GFR.

Question 54

Why is inulin clearance not usually used to measure GFR?

Answer 54

It is expensive and cumbersome to measure so only used for experimental purposes.

Question 55

Are creatinine levels an over/underestimate of GFR? Why?

Answer 55

Usually 10-20% overestimate as around 10-20% of creatinine produced is secreted.