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sem 2 renal > structure and function of the renal tubule > Flashcards

structure and function of the renal tubule Flashcards

1
Q

reabsorption

A

when the direction of movement is from the tubular lumen into the peritubular capillary plasma

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2
Q

secretion

A

when the movement is in the opposite direction to reabsorption i.e. peritubular plasma into tubular lumen

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3
Q

for a substance to be reabsorbed from the tubule what must it first cross?

A

it must first cross the luminal membrane – diffuse through the cytosol – across the basolateral membrane and into the blood (transcellular transport). Vice versa for secretion

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4
Q

2 physiological processes involved in reabsorption

A

active and passive transfer

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5
Q

Active Transfer/Primary Active Transport:

A

Moving molecule/ion against conc gradient (low→high)

Operates against electrochemical gradient

Requires energy - driven by ATP

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6
Q

Passive Transfer:

A

Passive movement down concentration gradient (requires suitable route)

Active removal of one component - concentrates other components

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7
Q

Co-transport/Secondary Active Transport:

A

Movement of one substance down it’s concentration gradient - generates energy

Allows transport of another substance against it’s concentration gradient

Requires carrier protein

2 types: symport and anti-port

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8
Q

how do lipid substances, ions and natural substances move through the membrane?

A

lipid soluble substances move through lipid matrix

ions and neutral substances move through water filled protein channels

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9
Q

symport and antiport

A

Symport = transported species move in same direction e.g. Na+ - glucose

Antiport = transported species move in opposite directions e.g Na+ - H- antiport

If a substance is going down its concentration gradient passively, it can generate energy to take another substance either in the same direction (symport), or the other direction (antiport)

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10
Q

how does the co transport of sodium and glucose work?

A

because Na moves into the cell down it’s concentration gradient which creates lots of energy

this means it can pull other substances along with it - cotransport (a form of secondary active transport)

for Na to pull another substance with it needs a coupling mechanism – carrier protein

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11
Q

sodium glucose transport n tubule

A

high Na+ conc in tubular fluid, flows down its concentration gradient into cell

in this process it generates energy so it can take a molecule across its concentration gradient - glucose

Na+ and glucose move into the cell via the SGLUT-2 transporter

as glucose levels build up in the cell, it diffuses down its concentration gradient into blood via the GLUT-2 transporter

Na+ enters the blood via sodium potassium ATPase pump.

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12
Q

what other movement does the sodium potassium ATPase pump help with?

A

movement of other substances with sodium

amino acids reabsorbed (supporter)

also aids movement of H+ ions but an ANTIPORTER is used, so H+ ions are secreted into the tubular fluid and are excreted out in the urine makes the urine a bit acidic

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13
Q

a mutation in the gene that encodes for SGLUT 2 causes what?

A

get familial renal glycosuria – glucose in the urine

Patients don’t make SGLUT 2, so all the glucose that is filtered is just dumped into the urine and remains there

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14
Q

what are SGLUT 2 inhibitors are used to treat?

A

diabetes

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15
Q

name some techniques to investigate tubular function

A
  1. Clearance studies
  2. Micropuncture & Isolated Perfused Tubule
  3. Electrophysiological Analysis (look at notes)
    - Potential measurement
    - Patch clamping
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16
Q

Micropuncture

A

Direct sampling of tubular fluid in different parts of nephron

  1. puncture tubule
  2. inject viscous oil to block ends
  3. inject fluid for study
  4. sample and analyse
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17
Q

tubule can be divided into how many segments?

A

7

  1. PCT
  2. Thin Descending Limb, LoH
  3. Thin Ascending Limb, LoH
  4. Thick Ascending Limb, LoH
  5. Distal convoluted tubule (DCT)
  6. Collecting/Connecting tubule
  7. Medullary Collecting duct
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18
Q

throughout its length what is the nephron comprised of?

A

a single layer of epithelial cells resting on a basement membrane

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19
Q

2 Types of Nephron

A

Cortical nephron - 85%
Short LoH

Juxta-medullary nephron - 15%
Long LoH

they have different vascular systems

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20
Q

Juxta-medullary nephrons

A

long-reach loops that penetrate deep into the medulla - better at concentrating urine

long efferent arterioles extend from glomeruli to outer medulla and are divided into specialised capillaries called vasa recta - they extend downward into medulla and run in parallel with the LoH

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21
Q

the nephrons with the long LOH play a very crucial role in?

A

concentrating and diluting urine

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22
Q

Proximal Convoluted Tubule

A

directly adjacent to Bowman’s capsule

high capacity for reabsorption

special cellular characteristics:

  • highly metabolic, numerous mitochondria for active transport
  • extensive brush border on luminal side –> large SA area for rapid exchange
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23
Q

what are located in the luminal and basolateral membranes of the PCT

A

enzymatic and protein carriers, primary and secondary active transport systems, which together with its permeability characteristics make the PCT the major site of reabsorption of the glomerular filtrate

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24
Q

PCT - lysosomal enzymes

A

Glomerular filtrate is protein free but some small proteins (<60kD) get through

These proteins are taken up into the cell by endocytosis → degraded by lysosomal enzymes into amino acids and simple sugars, and reabsorbed into plasma

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25
Q

by the end of the early PCT whats been absorbed?

A

essentially all of the glucose and amino acids and much of the HCO3- have been reabsorbed

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26
Q

HCO3- is preferentially absorbed relative to what?

A

Cl-

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27
Q

where does Cl- concentration rise, and what is the effect of this?

A

the concentration of Cl- rises in the tubular fluid, establishing a Cl- concentration gradient from lumen to peritubular fluid

as Cl- moves passively down its concentration gradient the lumen acquires a positive electric charge relative to the peritubular fluid

Na+ moves passively along the gradient with Cl-

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28
Q

Fanconi’s Syndrome

A

all proximal tubule reabsorptive mechanisms are defective, so glucose, AA, Na+, K+ etc. are all found in the urine

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29
Q

how does the H2O reabsorption occur in the PCT?

A

Water is reabsorbed by osmosis – as the various substances are driven across they will pull water across

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30
Q

3 functionally distinct segments of the LoH:

A

Thin descending limb
Thin ascending limb
-thin epithelial cells, no brush border, few mitochondria & low metabolic activity

Thick ascending limb
-thick epithelial cells, extensive lateral intercellular folding, few microvilli, many mitochondria, high metabolic activity

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31
Q

the LoH has a critical role in what?

A

concentrating/diluting urine »adjusting rate of water secretion/absorption by creating an osmotic gradient in the medulla (tissue around the LoH)

so water is pulled out of the LoH by osmosis

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32
Q

what part of the LoH is permeable to water?

A

only the descending limb is permeable to water – the ascending limb (both thick and thin parts) is impermeable to water, but very active in reabsorbing sodium

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33
Q

what are loop diuretics and where do they act?

A

act at the thick ascending limb of the LoH to inhibit sodium, chloride and potassium reabsorption

they cause 20% of filtered Na to be excreted, by blocking Na-transport out of LoH

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34
Q

diuretics

A

allow you to pee out out increased amount of fluid for whatever reason

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35
Q

what does the LoH create?

A

an osmolarity gradient in medullary intersititum

36
Q

how does the LoH create a medullary osmotic gradient?

A

Solutes accumulate in the renal medullary interstitium

A high solute concentration/high osmotic pressure is generated and maintained in the medullary interstitium and the tubular fluid becomes hypotonic

37
Q

as we descend down into the medulla from the cortical region what happens?

A

we are creating a gradient around the LoH

38
Q

as the collecting duct traverses the medulla what happens?

A

the urine gets more concentrated because water leaves duct by osmosis

39
Q

why is the movement in the LoH called counter current?

A

because the 2 limbs are parallel to each other but the fluid in the 2 limbs are moving in opposite directions to each other (down and then up)

40
Q

what is the fluid leaving the LoH like compared to how it entered?

A

the fluid leaving is hypo-osmotic in comparison to how it entered and the plasma

41
Q

ascending limb

A

thin ascending limb permeable to Na & Cl

on the thick ascending limb side you have lots of sodium-potassium chloride transporters. Pump NaCl out of tubular fluid– accumulation in the intersititial tissue spaces around the LOH and in the medulla

42
Q

the accumulation of solutes around in LoH and in the medulla creates what?

A

the osmotic gradient

43
Q

what is the effect of the ascending limb causing this osmotic gradient?

A

water moves out of the descending limb by osmosis, so as you move down the descending limb the osmolarity increases because water is leaving, therefore all the stuff in there gets more concentrated (hairpin bend is where its most concentrated)

44
Q

the ascending limb is impermeable to what?

A

H2O

45
Q

what is the relevance of the ascending limb being impermeable to H2O?

A

water remains in there but salts are pumped out, so the osmolarity changes and when the fluid leaves it is hypo-osmotic in comparison to how it entered and the plasma

46
Q

the thick ascending LoH reabsorbs how much of the filtered Na?

A

25%

47
Q

how does the thick ascending LoH limb reabsorb the Na, K and Cl-?

A

Sodium (Na+), potassium (K+) and chloride (Cl−) ions are reabsorbed by active transport

via Na:K:2Cl cotransporter (symporter)

48
Q

how do the Na, K and Cl move from the cell to the peritubular capillary when the ascending limb actively reabsorbs them?

A

Na is transported actively via Na-K-ATPase

K and Cl cross into the peritubular fluid passively.

49
Q

what inhibits the Na:K:2Cl transporter, and what does this result in?

A

loop diuretics, results in inhibition of net NaCl reabsorption and increased excretion of these ions along with water

50
Q

what do the loop diuretics do?

A

disrupt reabsorption of the ions, preventing the generation of the medullary osmotic gradient

without such a concentrated medulla, water has less of an osmotic driving force to leave the collecting duct system, ultimately resulting in increased urine production.

51
Q

As K+ and Cl- move transcellularly across into the capillary, what happens?

A

they will build up a bit along the surrounding areas – this contributes to the formation of the medullary osmotic gradient

52
Q

what does the vasa recta do?

A

delivers O2 and nutrients to cells of the loop of Henle

53
Q

the vasa recta is permeable to both H2O and salts - what is the problem with this?

A

could disrupt the salt gradient established by the loop of Henle
-it avoids them by acting as a counter-current multiplier system

54
Q

vasa recta and counter current

A

As the vasa recta descends into the renal medulla, water diffuses out into the surrounding fluids, and salts diffuse in. When the vasa recta ascends, the reverse occurs.

As a result, the concentration of salts in the vasa recta is always about the same, and the salt gradient established by the loop of Henle remains in place.

55
Q

if blood flow increases in the vasa recta what happens?

A

solutes are washed out of the medulla and its interstitial osmolality is decreased

56
Q

why is medullary blood flow in the vasa recta slow?

A

because it is sufficient to supply the metabolic needs of the tissue, but minimize solute loss from the medullary interstitium

-got to be at a certain sufficient rate that it will keep the gradient maintained but also deliver sufficient nutrients to keep the surrounding tissues of the LOH alive.

57
Q

Distal Convoluted Tubule

2 parts

A 
1st part (macula densa) linked to juxtaglomerular complex
-comes in close contact with the afferent and efferent arteriole and becomes specialized to form the macula densa

Provides feedback control of GFR & tubular fluid flow in the same nephron

2nd part is very convoluted

58
Q

Connecting Tubule

A

Connects end of DCT to collecting duct – mainly in outer cortex

59
Q

Functions of DCT

A
  • Solute reabsorption continues, w/out H2O reabsorption
  • High Na+,K+-ATPase activity in basolateral membrane
  • Very low H2O permeability
  • Further dilution of tubular fluid
  • ADH can exert actions
  • Role to play in acid-base balance via secretion of NH3
60
Q

does ADH work in the DCT or PCT?

A

DCT

61
Q

what happens to tubular fluid in its passage through the distal convoluted tubule?

A

it’s further diluted

62
Q

the joining of collecting tubules form what?

A

Collecting Ducts

-cuboidal epithelia, very few mitochondria

63
Q

what 2 types of cells make up the collecting duct

A

Intercalated cells
-involved in acidification of urine and acid-base balance

Principal cells
-role to play in Na balance and ECF volume regulation

64
Q

function of collecting duct

A
  • Final site for processing urine
  • Made very permeable to H2O by ADH
  • Also permeable to urea

-the last 2 contribute o the counter-current mechanism

65
Q

where is ADH made and stored?

A

made in hypothalamus, stored in pituitary gland

66
Q

single effect of ADH?

A

conserve body water by reducing the loss of water in urine

67
Q

what triggers ADH release from the pituitary gland?

A

a change in plasma osmolarity (concentration of solutes in the blood), sensed by hypothalmic osmoreceptors

68
Q

what other receptors can regulate ADH secretion?

A

volume receptors and arterial baroreceptors

69
Q

how does ADH cause its effect?

A

binding of AVP to V2-receptors on peritubular capillary cell stimulates the synthesis of aquaporin-2 water channel proteins and promotes cAMP-dependent trafficking of aquaporin 2 water channels to the luminal membrane of principal cells allowing back diffusion of water down its concentration gradient

production of new aquaporin 2’s is also stimulated

70
Q

what does urea contribute to?

A

the medullary interstitial gradient

71
Q

how does the urea contribute to the medullary interstitial gradient?

A

Urea filters freely through glomerulus and passes down the tubule. Unlike cortical collecting tubule, the medullary collecting duct is permeable to urea.

As water is reabsorbed from the CD (say in the presence of ADH) the urea is concentrated so that it moves out of the CD and is absorbed into the surrounding capillaries and also into the intersitium of the medulla where it contributes to the osmotic gradient around the LoH.

72
Q

how are urea levels monitored?

A

BUN (blood urea nitrogen) test

if urea levels in the blood increase it shows that ADH has been activated and therefore patient is dehydrated

73
Q

what substances are reabsorbed from the CD regardless of ADH being present or not?

A

Na+ and Cl-

74
Q

what is the relevance of Na+ and Cl- being reabsorbed from the CD?

A

-maintains the medullary hyper-osmolarity, which facilitates the reabsorption of water in the presence of ADH

75
Q

In the absence of ADH what happens to the CD?

A

CD becomes impermeable to water and urea

Sodium reabsorption in the CD continues, the tubular fluid become progressively more dilute in its progress along the duct

the volume of urine excreted under these conditions is potentially very large

76
Q

4 major factors contributing to build up of solute concentration in renal medulla

A
  1. Active transport of Na+ and co-transport of K+ & Cl- out of thick ascending limb into medullary interstitium
  2. Active transport of ions from collecting ducts into medullary interstitium
  3. Facilitated diffusion of large amounts of urea from collecting ducts into medullary interstitium
  4. Very little diffusion of water from ascending limbs of tubules into medullary interstitium
77
Q

Polycystic Kidney Disease (PKD)

A

Genetic disorder characterised by growth of numerous cysts in kidney
-Each of the cysts contains urine – urine means the cysts could get infected over time

78
Q

glomerulonephritis (GN)

A

Inflammation of glomeruli of some or all of million nephrons in kidney

Can be primary or secondary to systemic disease like diabetes mellitus

Inherited diseases of the glomerular basement membrane

79
Q

Diseases of the tubules

A

obstruction (reducing glomerular filtration)

Impairment of transport functions (reducing water & solute reabsorption) eg. Fanconi’s syndrome

80
Q

Acquired Kidney Diseases - hypertension

A

Hypertension

Kidneys regulate ECF volume and hence influence blood pressure⇒compensatory mechanisms in response to high BP can lead to chronic kidney damage

81
Q

Acquired Kidney Diseases - Congestive Cardiac Failure

A

Fall in cardiac output⇒renal hypoperfusion⇒registered as hypovolaemia, compensation results in pulmonary oedema

82
Q

Acquired Kidney Diseases - Diabetic nephropathy

A

As a consequence of diabetes, filtering system of kidneys gets destroyed over time

83
Q

Lithium treatment results in what?

A

acquired nephrogenic diabetes insipidus

-due to reduction of AQP2 expression

84
Q

Diabetes insipidus (DI)

A

a condition characterized by excessive thirst and excretion of large amounts of severely diluted urine, with reduction of fluid intake having no effect on the concentration of the urine.

85
Q

name the different types of DI?

A

the different types of DI each have a different set of causes.

Central DI (CDI) - most common type in humans, neurological form that involves a deficiency of ADH/AVP.

Nephrogenic diabetes insipidus (NDI), due to kidney/nephron dysfunction caused by an insensitivity of the kidneys or nephrons to ADH.

sem 2 renal (10 decks)

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