4/5 - Nephron Function

Question 1

Starling forces?

Answer 1

Govern the movement of water and solutes between the plasma and ISF. Hydrostatic pressure forces water and solutes out of the blood while plasma proteins are not filtered and exert oncotic pressure inwards. In normal capillaries there is a small outwards fluid shift that is controlled by the lymphatics.

Question 2

The glomerulus?

Answer 2

• very leaky capillary tuft due to fenestrated epithelium

- located between 2 arterioles

Question 3

How much of the plasma volume in the glomerular capillaries is filtereD?

Answer 3

20%

Question 4

What is the normal GFR for both kidneys?

Answer 4

125ml/min

Question 5

How is GFR primarily regulated?

Answer 5

Changes in glomerular hydrostatic pressure and so BF to the glomerular capillaries. For the kidneys to tightly regulate ECF osmolality and pH GFR needs to be constant.

Question 6

How does renal autoregulation work?

Answer 6

• changes in systemic BP should change GFR but usually doesn’t
• works to maintain constant pressure and BF in the glomerulus and so constant GFR over a range of systemic BPs (MAP of 80-160)
• renal autoregulation involves fb mechanisms that cause dilation/constriction of the afferent arteriole or constriction of the efferent arteriole

Question 7

LOH?

Answer 7

Important in production of dilute or conc urine

Question 8

How can the medulla be divided?

Answer 8

Outer medulla and inner medullary. Boundary is where the short loop nephrons (superficial ones) end

Question 9

Thiazide diuretics?

Answer 9

Block the NaCl cotransporters in the early distal convoluted tubule

Question 10

Furosemide diuretics?

Answer 10

Block the NKCC2 channels in the Thick Ascending Limb. Promotes urine output and salt excretion

Question 11

2 primary cell types in the late distal convoluted tubule, connecting tubule and collecting duct

Answer 11

Principal cells and intercalated cells

Question 12

Principal cells?

Answer 12

Reabsorb na and secrete k

Question 13

Potential side effect of thiazide diuretics?

Answer 13

Block the na/cl cotransporter is early distal conv tubule. Means more na arrives at the ENac channel in the late distal tubule causing more K+ to be secreted by the ROMK channel causing hypokalaemia which can cause ventricular arrhythmias

Question 14

What is the target of K+ sparing diuretics

Answer 14

ENaC i.e. amiloride. Others work by the inhibition of aldosterone

Question 15

What does aldosterone do

Answer 15

Steroid hormone released by the adrenal cortex. Binds receptor and enters nucleus of principal cells to increase activity of existing ENaC channels in late distal conv tubule and increases transcription of ENaC and Na/K ATPases so increases Na abs and K+ secretion

Question 16

How does spirolactone work

Answer 16

Inhibits aldosterone so is a weak K+ sparing diuretic

Question 17

Intercalated cells?

Answer 17

Important for acid base balance and K+ absorption. Usually secrete H+ via H atpase and H/K ATPase. Some of the H+ is used to reabsorb the little HCO that wasnt reabsorbed in the prox tubule but some is also freely secreted into the urine and so is a way to rid the body of acid.
Means pH is dropped as H+ is being secreted like in proximal tubule BUT some is being secreted WITHOUT HCO3- reabsorption

Question 18

How is new HCO3- generated in the intercalated cells?

Answer 18

Some CO2 and H20 is generated by metabolism

Question 19

Diffusion trapping

Answer 19

pH can only drop to 4.5 which is not sufficient to secrete all dietary H+ - therefore NH4+ is formed and trapped in the lumen and is another way to void acid. (ammonia forms ammonium ion)

Question 20

What happens to the water in the late distal conv tubule, connecting tubule and CORTICAL collecting duct?

Answer 20

Depends on the level of ADH (anti-diuretic hormone). Causes aquaporin water channels to be inserted in the apical membrane causing water to be absorbed (conc urine - 300mOsm). Made by the hypothal and released by the posterior pituitary in response to changes in osmol and BP. The channel insertion/response is rapid.

Question 21

What happens with water in the outer medulla collecting ducts?

Answer 21

Same thing - h20 extraction by osmosis using ADH regulated channels and the outer medulla salt gradient

Question 22

If you drink lots of water what happens to adh?

Answer 22

Reduced and so more is excreted whereelse if you infuse the same amount of normal saline osmol hasn’t changed so the level of ADH doesn’t change and there won’t be much of a change of urine output

Question 23

How is the conc gradient in the inner medulla established?

Answer 23

• gradient is made up of both NaCl and UREA
• when adh is high water is reabsorbed and as a result of this the conc of urea becomes very high in the cortical collecting duct
• adh increases both urea and h20 permeability of the inner medulla collecting ducts
• urea is then deposited in the interstitium and the water causes the conc of NaCl to drop
• NaCl then moves out of the tip and ascending limb into the interstium by osmosis

Question 24

What are the 2 theories for the conc gradients in the 2 different parts of the medulla?

Answer 24

1. Short loop countercurrent

2. Long loop passive hypothesis

Question 25

What can the osmol of the interstium reach?

Answer 25

2300 mOsmol

Question 26

How does the vasa recta influence the medullary conc gradient?

Answer 26

The counter current exchange by the vasa recta helps to preserve the osmotic gradient and carries water away that has been extracted

Question 27

What happens when adh is low?

Answer 27

- water is not reabsorbed in the distal nephron and cortical collecting duct so the conc of urea does not increase - the inner medulla is permeable to urea even when adh is low - if the conc of urea in the interstitium is greater than that in the collecting duct then the urea will diffuse out of the intersitum into the collecting duct and be excreted (wash out) - this means that as long as ADH is low then urea levels in the medulla will be low - when adh increases then urea is deposited in the medulla again

Question 28

Compare the inner medulla to the outer medulla

Answer 28

Outer: - the nacl gradient is formed by the countercurrent multiplication mechanism Inner: - nacl and urea gradient are formed by a passive mechanism that is dependent on high adh levels

Question 29

Summary of the proximal convoluted tubule

Answer 29

- reabsorbs 2/3 of water, inorganic ions, 90% of hco3- and 100% glucose and AAs - na coupled transport dominates - filtrate is isosmotic to plasma (300) as water follows the Na - the pH only slightly drops as most of the H+ is used to reabsorb HCO3- - some new HCO3- is made by glutamine metabolism

Question 30

LOH summary

Answer 30

- the thick ascending limb PUMPS out NaCl but is impermeable to water - countercurrent mechanism is established by short loops in the outer medulla (300-600 mOsm grad) - in the long loops when adh is high NaCl moves from the tip and acending thin limb into the inner medulla by osmosis, urea is deposited in the inner medulla by the collecting duct - the inner medulla conc gradient is established (600-1200 mOsm) and draws water in from the descending thin limb and collecting duct to concentrate the urine (taken away by vasa recta)

Question 31

Distal tubule summary

Answer 31

- the early distal tubule is impermeable to water and more nacl is absorbed (blocked by thiazide diuretics like Furosemide) - urea becomes concentrated

Question 32

Late distal tubule, connecting tubule and collecting duct summary

Answer 32

What happens here depends on ADH - no adh and is imperm to water, nacl continues to be reabsorbed by ENaC which is the target of K sparing diuretics and the urine stays dilute - in the presence of adh water is reabs and urine becomes conc. the intercalated cells secrete H+ where some is used to reabs hco3- while some is freely excreted

Question 33

Medullary collecting duct summary

Answer 33

- similar to cortical collecting ducts except in the presence of adh the tubule becoems more permeable to urea and it is deposited in the interstitum and NaCl moves via osmosis out of the thin descending limb to the interstitum - additional H+ is excreted via diffusion trapping