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module 104 - theme 3 > formation of urine > Flashcards

formation of urine Flashcards

1
Q

what are the 5 stages of urine formation?

A

1) glomerulus: filtration of blood
2) proximal tubule: reabsorption of filtrate, secretion into tubule
3) loop of Henle: concentration of urine
4) distal tubule: modification of urine
5) collecting duct: final modification of urine

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2
Q

what is the force of filtration?

A
  • blood pressure

- differing diameter of afferent and efferent arterioles

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3
Q

what is the glomerular filtration rate?

A

125mL/min

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4
Q

what is the normal plasma volume?

A

2-3L

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5
Q

what are the 2 factors filtration are dependent on?

A

1) blood pressure

2) renal blood flow

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6
Q

where does the filtrate have to pass through?

A

1) pores in the glomerular capillary endothelium
2) the basement membrane of the Bowman’s capsule
3) epithelial cells of Bowman’s capsule via filtration slits into capsular space

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7
Q

what are the characteristics of glomerular filtrate rate?

A
  • this is the rate at which filtrate is produced in the kidneys
  • it remains constant even when systemic BP changed
  • this involved a regulatory mechanism known as auto regulation of renal blood blow
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8
Q

how is renal blood flow autoregulated?

A
  • renal blood flow subject to auto regulation over broad range of systemic BPs
  • autoregulation persists in denervated kidneys and isolated perfusion kidneys so it isn’t a neuronal, hormonal response but instead a local effect
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9
Q

what are the 2 hypothesis of auto regulation of renal blood flow?

A

1) myogenic: autoregulation is due to response of renal arterioles to stretch
2) metabolic: renal metabolites modulate afferent and efferent arteriolar contraction and dilation

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10
Q

how do changes in GFR alter the systemic blood pressure?

A

1) a drop in filtration pressure causes a drop in GFR
2) lower GFR means less Na+ enters the proximal tubule
3) the macula densa senses a change in tubular Na+ levels
4) this stimulates juxtaglomerular cells to release renin into the blood
5) renin release leads to generation of angiotensin II
6) Ang II is a vasoconstrictor which causes BP to increase
7) increased BP causes filtration pressure to increase and GFR returns to normal

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11
Q

what happens when glomerular filtrate enters the proximal tubule?

A

60-70% of filtered water, Na+, HCO3-, Cl-, K+ and urea are reabsorbed from the PT

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12
Q

what is almost completely reabsorbed in the proximal tubule?

A
  • glucose
  • amino acids
  • small amounts of filtered proteins
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13
Q

how does Na+/K+/ATPase drive reabsorption?

A
  • Na+/K+/ATPase pumps out Na_ from cells into the blood against chemical and electrical gradients
  • this process requires energy in the form of ATP
  • accompanied by entry of K+ ions which rapidly diffuses out of cell
  • the ratio of transport is 3 Na+ leaving cell: 2 K+ entering cell
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14
Q

how is sodium reabsorbed from the proximal tubule?

A
  • PT cells have a low intracellular Na+ concentration due to action of the Na+/K+/ATPase
  • Cl- follows Na+ by facilitated diffusion
  • phosphate and sulphate are also co-transported with Na+
  • PT cells have an overall negative charge due to the presence of intracellular proteins
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15
Q

how is water reabsorbed from the proximal tubule?

A
  • 60-70% filtered water reabsorbed in the PT: active transport of Na+ out of the PT cells is the driving force
  • movement of solutes reduces osmolarity of tubular fluid and increases osmolarity of interstitial fluid
  • a net flow of water from tubule lumen to lateral spaces occurs by transcellular and paracellular routes
  • transcellular routes involve aquaporin channel locates on apical and basolateral surfaces
  • there is no active water reabsorption along nephron: it occurs by osmosis and it follows sodium
  • PT is highly permeable to water
  • water flow from tubule to lateral spaces occurs by paracellular and transcqallular routes
  • transcellular routes involve aquaporins: specific water channels located in cell membranes
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16
Q

how many aquaporins have been identified?

A

13 (6 in the kidney)

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17
Q

where is aquaporin 1 found?

A

abundant distribution in proximal tubule. also other parts of tubule where water is reabsorbed

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18
Q

where is aquaporin 2 found?

A

present in the collecting duct on apical surface

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19
Q

what controls the expression of aquaporin 2?

A

anti diuretic hormone (ADH)

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20
Q

where are aquaporins 3 and 4 found?

A

present in basolateral surface of tubular cells involved in water reabsorption

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21
Q

what 4 things are reabsorbed other than water in the proximal tubule?

A
  • potassium
  • urea
  • amino acids
  • proteins
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22
Q

how much of potassium is reabsorbed in the proximal tubule?

A

70% of filtered K+ is reabsorbed in the PT, mostly passively via tight junctions

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23
Q

how much of urea is reabsorbed in the proximal tubule?

A

40-50% filtered urea is reabsorbed passively in the PT down its concentration gradient

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24
Q

where are amino acids reabsorbed in the proximal tubule?

A
  • 7 independent transport processes for reabsorption of AAs from the PT: depends on type of AA
  • high Tm for transport so that as much as possible is reabsorbed from PT
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25
Q

where are proteins reabsorbed in the proximal tubule?

A

reabsorbed from the PT via receptor-mediated endocytosis

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26
Q

how is protein reabsorbed from the proximal tubule?

A
  • small amounts of protein pass into filtrate via the glomerulus
  • these are reabsorbed by pinocytosis
  • vesicles transported into cell, degraded by lysosome and amino acids returned to blood
  • only limited transport capacity (low Tm)
  • proteinuria is a sign of glomerular damage and impending renal failure
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27
Q

how does secretion into the proximal tubule work?

A
  • some endogenous substances and drugs cannot be filtered at the glomerulus which may be due to their size or protein binding
  • specialised pumps in the PT can transport compounds from the plasma into the nephron
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28
Q

how is PAH secreted into the proximal tubule?

A
  • para-amino hippurate (PAH) is secreted into PT from blood
  • not an endogenous compound so PAH can be used as a tool to measure tubular secretion
  • transported into PT cells from blood with alpha-ketoglutarate or other di/tri carboxylates
  • transported out of PT cells in exchange for another anion present in the PT lumen
29
Q

what happens in the loop of Henle?

A
  • tubular fluid is further modified

- the aim here is to recover fluid and solutes from the glomerular

30
Q

what are the 2 stages that occur in the loop of Henle?

A

1) extraction of water in the descending limb

2) extraction of Na+ and Cl- in the ascending limp

31
Q

which type of nephrons is the processes that occur in the loop of Henle more important in?

A

juxtamedullary nephrons because the loop of Henle is longer

32
Q

what are the cells like in the thin descending limb of the loop of Henle?

A

cells are flat, no active transport of salts

33
Q

what happens in the thin descending limb of the loop of Henle?

A
  • freely permeable to water via aquaporin-1 channels

- some passive movement of water via tight junctions

34
Q

what happens in the thick ascending limb of the loop of Henle?

A
  • tubular wall is impermeable to water
  • has specialised Na+/K+/2Cl- as co-transport
  • transport: Na+, K+, Cl- reabsorbed but no water
35
Q

what happens in the loop of Henle?

A
  • fluid entering LOH from the proximal tube is isotonic
  • water reabsorbed out of descending LOH
  • by the tip of the LOH, the filtrate is hypertonic
  • solutes are then pumped out of the ascending LOH
  • by the end of the LOH, the filtrate entering the distal tubule is hypotonic
36
Q

how can the concentration of the filtrate vary from isotonic to hypertonic over a short distance in the medulla?

A

countercurrent multiplication

37
Q

what happens with the countercurrent multiplication?

A
  • creates large osmotic gradient within medulla
  • facilitated by Na+/K+/2Cl- transport in ascending limb of LOH
  • permits passive reabsorption of water from tubular fluid in descending LOH
38
Q

how does urea play a part in the countercurrent multiplication?

A
  • active transport of NaCl contributes 600-1000mOsm…the remainder is due to urea
  • urea freely filtered at glomerulus
  • some reabsorption in proximal tubule, but LOH and distal tubule relatively impermeable to urea
  • urea can diffuse out of collecting duct into medulla down its concentration gradient
  • this adds to the osmolarity of medullary interstitium
39
Q

how does the distal tubule further adjust the urine?

A
  • active reabsorption and secretion of solutes takes place here
  • sodium and chloride ions are actively reabsorbed from the tubular fluid
  • this is in exchange for potassium or hydrogen ions which are secreted into the tubular fluid
40
Q

how is the distal tubule involved in urine formation?

A
  • the distal tubule performs further adjustment of urine
  • Na+ and Cl- exchanged for K+ throughout the DT
  • Na+ exchanged for K+ in the late DT and early collecting duct
  • Na+ exchanged for H+ in DT and early collecting duct
41
Q

what cells help the exchange of Na+ for K+ in the late distal tubule and early collecting duct?

A

principle cells

42
Q

what are principle cells sensitive to?

A

aldosterone

43
Q

what cells help the exchange of Na+ for H+ in the distal tubule and early collecting duct?

A

intercalated cells

44
Q

what type of intercalated cells are there?

A

alpha and beta intercalated cells

45
Q

what type of exchange forms part of the renin-angiotensin aldosterone system (RAAS)?

A

exchange of Na+ for K+ in the late DT and early collecting duct using principle cells

46
Q

how does the collecting duct help in the formation of urine?

A
  • the collecting duct is relatively impermeable to movement of water and solutes
  • however, the permeability of the collecting duct can be considerable increased the action of ADH
47
Q

what is the most important hormone that regulates water balance?

A

ADH

48
Q

what is the molecular weight of ADH?

A

just over 1000

49
Q

what is another name of ADH

A

vasopressin of 8-arginine-vasopressin

50
Q

what is the plasma half life of ADH?

A

10-15 mins

51
Q

where does ADH act?

A

acts on vasopressin V2 receptors on basal membrane of principle cells in DT and collecting duct cells leading to activation of intracellular water channels

52
Q

what are the 2 types of ADH?

A
  • maximal circulating ADH

- no circulating ADH

53
Q

what is the function of maximal circulating ADH?

A
  • collecting duct becomes permeable to water due to maximal AQP2 insertion so water reabsorption occurs
  • reabsorbs up to 66% of the water entering the collecting duct
  • delivery of fluid to the collecting duct is low
  • urine volume can be reduced to 300mL/day
54
Q

what is the function of no circulating ADH?

A
  • reabsorption of water occurs at various sites in the nephron as described previously
  • however the collecting duct wall becomes impermeable to water due to no AQP2 so a large volume of water is excreted
  • lack of ADH: diabetes insipidus
55
Q

how do you treat diabetes insipidus?

A

synthetic ADH

56
Q

what are the 2 main types of diabetes insipidus?

A

nephrogenic and neurogenic

57
Q

what is nephorgenic diabetes insipidus?

A

due to inability of kidney to response normally to AHD

58
Q

what is neurogenic diabetes insipidus?

A

due to lack of ADH production by the brain

59
Q

what is the treatment for nephrogenic diabetes insipidus?

A

chlortalidone, indomethacin

60
Q

what is the treatment of neurogenic diabetes insipidus?

A

desmopressin, vasopressin, carbamazepine

61
Q

what is SIADH?

A

syndrome of inappropriate ADH

- excessive ADH

62
Q

what can SIADH lead to?

A

hypomatraeia and possibly fluid overload

63
Q

what is the treatment for SIADH?

A

V2 receptor blockers

64
Q

where is ADH synthesised

A

in the hypothalamus

65
Q

where is ADH stored and released?

A

posterior pituitary gland

66
Q

what agents increased ADH release?

A
  • nicotine
  • ether
  • morphine
  • barbiturates

(anti-diuretic action)

67
Q

which agent inhibits ADH release?

A
  • alcohol

diuretic action

68
Q

what happens to all the water and solutes reabsorbed from the tubule?

A

it is all taken back into the peritubular vessels and vasa recta surrounding the tubule

module 104 - theme 3 (13 decks)

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