Loop of Henle, Distal Tubule and Collecting Duct

Question 1

What are the 2 key functionally distinct components of the Loop of Henle?

Answer 1

1. Descending Limb (cortex –> medulla)

2. Thick Ascending Limb (medulla –> cortex)

Question 2

What is the key function of the thick ascending limb?

Answer 2

To create a hyperosmolar interstitial space in the medulla to drive water loss from the descending limb and cortical collecting duct

Question 3

What is the descending limb permeable to?

Answer 3

Water, not NaCl

Question 4

Does water leave or enter the descending limb?

Answer 4

Leave the filtrate because of osmotic force

Question 5

What happens to the water once it has left the descending limb?

Answer 5

Gets removed by the vasa recta

Question 6

What is the permeability of the thick ascending limb (TAL)?

Answer 6

permeable to NaCl, impermeable to water

Question 7

What does TAL do?

Answer 7

Actively transports Na+ into the medullary interstitium, and other ions follow (e.g. Cl-)

Question 8

What is the osmotic pressure difference between the luminal side and interstitial side called?

Answer 8

Transverse gradient

Question 9

What is the transverse gradient?

Answer 9

200mOsm/kg H2O

Question 10

What is the primary active transport process in the TAL?

Answer 10

Na+/K+-ATPase on the basal cell membrane

Question 11

What transporter is used by the TAL to move ions into the cell?

Answer 11

NKCC2 (Na+K+2Cl- transporter) on the apical membrane

Question 12

What is the systematic name of the gene for NKCC2?

Answer 12

SLC12A1

Question 13

What type of transporter is NKCC2?

Answer 13

Cation coupled chloride transporter

Question 14

What is K+ recycling important for?

Answer 14

To ensure that the NKCC2 transporter can maintain its role of transporting large quantities of Na+ and Cl-
Na+ conc is much higher, so K+ needs to be recycled

Question 15

What drugs inhibit the transporter NKCC2?

Answer 15

Loop diuretics

Question 16

Examples of loop diuretics?

Answer 16

Furosemide, bumetanide, piretanide

Question 17

What are the uses of furosemide?

Answer 17

cardiac failure, renal failure

Question 18

What are the side effects of furosemide?

Answer 18

K+ loss (& subsequent hypokalaemia)
Hypovolaemia
Mild metabolic alkalosis
Los of Mg2+ and Ca2+

Question 19

What is the permeability of the thin ascending limb?

Answer 19

Impermeable to water, permeable to Na+ so allows Na+ to passively move out into th emedullary interstitial fluid

Question 20

What is Bartter’s syndrome?

Answer 20

Impairment of the transport processes in TAL

Question 21

What transporter is used for Na+ absorption in the distal tubule?

Answer 21

Na+-Cl- transporter

Question 22

What drugs block Na+ absorption in the distal tubule?

Answer 22

Thiazides and thiazide-like drugs

Question 23

Examples of thiazides?

Answer 23

bendroflumethiazide, hydrochlorothiazide

Question 24

Examples of thiazide-like drugs?

Answer 24

indapamide

Question 25

What are the uses of thiazides and thiazide-like drugs?

Answer 25

antihypertensive

Question 26

What are the side-effects of thiazides and thiazide-like drugs?

Answer 26

Increased uric acid Hyperglycaemia Hyponatraemia

Question 27

What is the permeability of the collecting tube?

Answer 27

impermeable to urea and NaCl, sodium permeability controlled by ENaC, water permeability is regulated by ADH

Question 28

What channel is used for water entry into the cell?

Answer 28

AQP2

Question 29

What channel is used for water entry into interstitial space?

Answer 29

AQP3

Question 30

What effect does aldosterone have on the channels in the collecting tubule?

Answer 30

Aldosterone stimulates synthesis of ENaC, K+ channels and Na+/K+-ATPase

Question 31

What is aldosterone important for?

Answer 31

K+ output regulation, Na+ & water retention

Question 32

What drug blocks the effect of aldosterone?

Answer 32

Spironolactone

Question 33

What are the uses of spironolactone

Answer 33

heart failure (K+ sparing diuretic)

Question 34

What are the side effects of spironolactone?

Answer 34

Gynaecomastia, menstrual disorders, testicular atrophy, hyperkalaemia

Question 35

Where does ADH have an effect on urea permeability?

Answer 35

Medullary collecting duct, but NOT cortical collecting tubule

Question 36

Which parts of the nephron are urea permeable?

Answer 36

Loop of Henle, medullary collecting duct

Question 37

What happens to urea in the medullary collecting duct?

Answer 37

Urea moves out due to increased urea concentration

Question 38

What effect does ADH have on urea permeability?

Answer 38

Increase

Question 39

How does ADH increase urea permeability?

Answer 39

increase the expression of UT-A1 (urea transporter A1)

Question 40

What does the urea in the medullary interstitial fluid do?

Answer 40

Increase the osmotic pressure in the medulla, and aids water reabsorption in the medulla

Question 41

What transporter is used for urea reabsorption in the loop of Henle?

Answer 41

UT-A2

Question 42

Where is ADH synthesised?

Answer 42

Hypothalamus

Question 43

Where is ADH released from?

Answer 43

The terminals of the hypothalamic neurones found within the posterior pituitary

Question 44

Where does ADH act in?

Answer 44

distal tubule and collecting tubule

Question 45

How does ADH affect urine concentration?

Answer 45

Increases water permeability by increasing AQP2

Question 46

How does ADH affect osmolality in the nephron?

Answer 46

High osmolality i.e. concentrated urine

Question 47

What happens to the osmolality in the nephron with no ADH?

Answer 47

60mOsm

Question 48

What happens to the osmolality in the nephron with maximum ADH?

Answer 48

1400mOsm

Question 49

What happens to the flow rate in the nephron with no ADH?

Answer 49

17ml/min

Question 50

What happens to the flow rate in the nephron with maximum ADH?

Answer 50

0.1ml/min

Question 51

What is the normal urine volume?

Answer 51

1.5L/day

Question 52

What is the urine volume with absence of ADH?

Answer 52

25L/day

Question 53

Where is aldosterone synthesised?

Answer 53

Zona glomerulosa of the adrenal gland

Question 54

What happens with urea production in the presence of selective protein starvation?

Answer 54

Urea production low, so the kidney has a lower capacity to concentrate urine

Question 55

What urea transporter is regulated by ADH?

Answer 55

UT-A1

Question 56

What adaptation enables medullary cells to survive in high osmolarity?

Answer 56

Accumulation of organic osmolytes within the cells

Question 57

What are examples of organic osmolytes in the medullary cells?

Answer 57

Sorbitol, inositol, glycerophosphorylcholine, bwetaine

Question 58

What is Diabetes Insipidus?

Answer 58

Loss of ADH secretion or a low in sensitivity of the kidney to ADH

Question 59

What are the consequences of diabetes insipidus?

Answer 59

Unable to produce concentrated urine, leading to polyuria (with low osmolality), dehydration, hypovolaemia This would cause polydipsia (drinking too much) If fluid intake inadequate, they become hypernatraemic

Question 60

What are the two forms of diabetes insipidus?

Answer 60

Central and Nephrogenic

Question 61

What are the causes of central diabetes insipidus?

Answer 61

head injury, tumours, infection

Question 62

What is an example of an ADH analogue?

Answer 62

Desmopressin

Question 63

How can central diabetes insipidus be managed?

Answer 63

Give desmopressin | Thiazide diuretics

Question 64

What are the causes of nephrogenic diabetes insipidus?

Answer 64

Toxicity (e.g. Lithium), Hypercalcaemia, genetic (mutations in either V2 or AQP2)

Question 65

Treatments for nephrogenic diabetes insipidus?

Answer 65

NOT wit desmopressin Thiazide diuretic Low salt diet

Question 66

What does SIADH stand for?

Answer 66

Syndromes in Inappropriate ADH

Question 67

What are symptoms of SIADH related to?

Answer 67

Inappropriately high ADH

Question 68

What is a common cause of SIADH?

Answer 68

Head injury

Question 69

What are the treatments for SIADH?

Answer 69

Fluid restrction, give urea