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Metabolism 2 > Renal Excretory function > Flashcards

Renal Excretory function Flashcards

1
Q

what is the glomerulus made up of

A
  • endothelium of capillaries - these are fenestrated
  • basement membrane
  • epithelium of the bowman capsule that contains podocytes (these have gaps between them)
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2
Q

what are the factors that determine the filtrate

A
  • Net filtration pressure
  • Podocyte slit pores
  • Size of molecular
  • Charge of molecule
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3
Q

what is allowed to diffuse through the glomerulus

A

– Water
– Electrolytes eg Na, K, Cl, phosphate, glucose
– Urea, amino acids

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4
Q

what is the molecular weight cut off by the basement membrane

A

– MW cut off of 5200 daltons
– MW of albumin is 69,000 daltons - therefore albumin is usually not in the urine as it cannot get through the basenent membrane

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5
Q

what is the difference between the afferent and efferent blood vessels

A
  • afferent has a larger diameter than efferent

- afferent brings blood in whereas efferent removes the blood

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6
Q

what is the filtration fraction

A

it is normally 20%
- this is the proportion of the blood plasma that is filtered through glomerulus into the bowman capsule which enters in the proximal tubule

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7
Q

What happens to podocytes in renal disease

A
  • in renal disease - the podocytes become inflamed and enlarged therefore the gaps between them get larger which enables more solutes to enter the urine
  • proteinuria is therefore a sign of glomerular inflammation
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8
Q

what is the normal physical pressure in the glomerular capillaries and wha tis the net pressure

A

= normal physical pressure is 55mmHg

= net pressure 10mmHg

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9
Q

define the glomerular filtration rate

A
  • this is the total amount of fluid filtered through all the glomeruli in both kidneys
  • usually 120-125 ml/min
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10
Q

what is the renal plasma flow

A
  • 680 ml/min
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11
Q

what is used clinically to assess the health of the kidney

A

GFR

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12
Q

how do you measure GFR

A
  • Measured by clearance (of creatine)
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13
Q

what is clearance

A

it is the effective volume of plasma completely cleared of a substance per minute

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14
Q

write dow the formula for clearance

A

clearance = urine concentration x urinve volume/ plasma concentration

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15
Q

what do you need to measure the clearance of a substance

A
  1. measure the concentration of the creatine in the plasma
    2, collect urine for a fixed period to get the urine flow (ml/min)
    3, measure the concentration of creatinine in the collected urine
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16
Q

if 100% blood component is filtered through the glomerulus ..

A
  • this means that material goes into the proximal tubule at the same rate as the water in the plasma, therefore the clearance of the substance will be the same as the glomerular filtration rate which is 125 ml/min
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17
Q

if 100% of the blood component is filtered through the glomerulus and all of it is reabsorbed ..

A
  • no blood will be cleared of the material

- clearance is o

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18
Q

that 100 % of the material is filtered and in addition all of the material in the efferent arteriolar blood is secreted into the urine

A
  • renal venous blood will have no material in it and all the blood passing through the kidney will have been cleared of the material
  • the clearance will then equal the renal plasma flow
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19
Q

what can clearance be equal to

A

Not removed at all by kidney: Clearance = zero

Removed at same rate as water passes through glomeruli: Clearance = GFR

Completely removed from blood passing through kidney: Clearance = RPF

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20
Q

what do you use to measure clearance

A
  • inulin - completely filtered from the plasma and is not reabsorbed, have to iV inulin over a period of hours until you reach a steady plasma concentration - not clinically practical as it takes too long
  • Clinically use creatinine to measure GFR, produced naturally by the Body and is filtered by the glomerulus and is also secreted by the peritubular capillaries in the small amounts, it is already at a steady state concentration in the blood so it takes much shorter to measure
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21
Q

what does the secretion of creatinine by the peritubular capillaries do

A
  • means that the creatinine clearance overestimates the GFR by 10-20%
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22
Q

how do you measure eGFR

A

MDRD

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23
Q

what is the equation of MDRD

A

eGFR (ml/min per 1.73m2) = 185 x creatine/88.4)-1.154 x age-0.203 x (0.742 if female)x 1.210 if black

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24
Q

what do you need for MDRD

A

CAGE

  • creatine
  • age
  • sex(gender)
  • ethnicity
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25
Q

why is eGFR more important

than creatine for measreuemtn

A

eGFR is more important than creatine as you want to known what happens when someone develops acute kidney injury as this can result in small changes in serum creatine but big changes in eGFR

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26
Q

what does the creatinine levels also depend on

A

Muscle mass - increase in muscle mass increase in the amount of creatine
Body size - means more muscle mass
Sex and race

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27
Q

what are the 3 structures of the juxtaglomerular apparatus

A
  • afferent arteriole
  • efferent arteriole
  • distal tubule
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28
Q

what lines the wall of the distal tubules

A
  • macula densa
29
Q

what are macula densa

A
  • sodium sensors

- release local chemicals which modulate the contraction of smooth muscle around the afferent arteriole

30
Q

why does a low sodium level indicate a low GFR

A

Sodium is removed (by reuptake) from the proximal tubule at a fixed rate.
If the flow is slow (low GFR) , more sodium has been removed by time the fluid has reached the end of the tubule and the remaining concentration will be low . Conversely, if the flow is fast (high GFR) , more sodium is flowing past the uptake sites than they can manage, so the concentration remains high.

With low distal tubule sodium, the macula densa cells release local chemical factors which relax the smooth muscle in the afferent arteriole, thus increasing the filtration pressure and increasing GFR. Conversely, if the sodium level is too high, the macula densa cells release chemical factors which constrict the the afferent arteriole, decrease filtration pressure and reduce GFR.

31
Q

name a drug that inhibits tubular secretion of creatinine

A

Some drugs inhibit tubular secretion of creatinine (eg Trimethoprin), leading to a raised plasma creatinine even though GFR may be unchanged

32
Q

what is apical and basolateral

A

Apical – this is facing the tubules

Basolateral is facing the peritubular capillary and interstitial

33
Q

are there gaps between tubular cells

A

There are no gaps between tubular cells unless they are tight junction this restricts flow from the tubular lumen to the intersititum

34
Q

what do the tight junction do

A

limits water and solute and movement between cells, they maintain polarity and allow different transport proteins in the basolateral versus the apical

35
Q

what are the mechanisms of solute transport and give examples

A

• Passive
– Passive diffusion
• Down a concentration and electrochemical gradient
– Carrier mediated (facilitated) diffusion
• Carrier proteins
• Selective
– Diffusion through membrane channel

•	Active
–	Movement of solutes against an electrochemical gradient
–	Dependent on ATP
–	Examples
•	Sodium pump ( Na-K ATPase)
•	H+-ATPase (distal nephron)
•	Ca +2 -ATPase
36
Q

describe how proximal convoluted tubule does trnaposrt

A
  • Most important part is the sodium potassium ATPase on the basolateral membrane
  • this pumps 3 sodium into the interssitum and 2 potassium into the tubular cell - this requires ATP to work therefore it is primary active transport
  • This drives everything else that happens within the tubular lumen, tubular cells and insterisititum
  • This maintains different concentrations intracellular and extraceullar - low sodium inside the cell, whereas high potassium inside the tubular cell
  • Glomerulus pumps everything into the tubular lumen therefore the sodium concentration in the tubular lumen is high compared to the intracellular tubular cell due to the Sodium potassium ATPase
  • Therefore the sodium, phopshate, glucose and amino acids pass along a gradient into the tubular cells this is seocndary active transport as this is due to the sodium and potassium ATPase
  • Urea on the other hand oves passively diffusion
37
Q

what happens if there is mutation in the sodium potassium ATPase on the basolateral membrane

A

you die - don’t survive

38
Q

what active transport does the sodium potassium ATPase work by

A

primary active transport

39
Q

what happens if there are defects in the apical sodium/cysteine cotransporter

A

cystinuira

– Autosome recessive. Abnormal cystine excretion – resulting in recurrent cystine renal stones

40
Q

what happens if there are defects in the apical Na/glucose cotransporter

A

renal glycosuria

  • abnormal urinary glucose loss.
  • Happens despite normal/low blood glucose
41
Q

what happens if there is a defect in the basolateral sodium bicarbonate

A

proximal renal tubular acidosis
Type 2 renal tubular acidosis. A classic course would be Fanconi’s syndrome (along with glycosuria, amino aciduria, phosphaturia, glycosuria, bicarbonaturia)

42
Q

what happens if there is a defect with the apical Na/Cl/K in the thick ascending loop

A

• Bartter’s type 1
mimic of the effects of furosemide.

causes

  • Hypokalaemia,
  • metabolic alkalosis,
  • hypocalcaemia,
  • hypomagnasaemia
43
Q

what happens if there is a defect in the apical sodium chloride con transporter in the distal tubule

A

• Gitelman’s:
- Mimic of thiazide use.

causes

  • Hypokalaemia,
  • metabolic alkalosis,
  • hypomagnasaemia,
  • hypercalcaemia
44
Q

name some proximal tubule defects

A
  • Apical Na/cysteine cotransorpter = cystinuria
  • Apical Na/glucose cotransporter = renal glycosuria
  • Basolateral Na/HCO3 = proximal RTA
45
Q

what does the proximal tubule have that increases its surface area

A

– Apical brush border (microvilli), this causes a Large surface area

46
Q

what is the function of the proximal tubule

A

– Bulk of reabsorption of solutes – up to 80%
– Water – up to 65%
– Amino acids, low molecular weight proteins – up to 100%

47
Q

what is the aim of the loop of Henle

A
  • to reduce the amount of water present in the urine
48
Q

how does the loop of Henle work

A
  • descending loop of Henle is permeable to water and solutes so they can move in and out
  • thick ascending loop of Henle is impermeable to water but can do active transport of sodium
  1. Fluid flows from the proximal tubule down into the thin descending loop of Henle
    • as the fluid descends in the tubule it becomes more concentration because it is in equilibrium with the high concentration in the extracellular fluid in the renal medulla
  3. this then goes up into the thick part of the ascending limb
  4. the thick part is impermeable to water but it has membrane pumps that move sodium and chloride ions out into the extracellular space by active transport
  5. this maintains the high extracellular fluid concentration in the renal medulla
  6. when the fluid leaves the loop of Henle it enters the distal tubule
  7. the fluid entering the distal tubule is more dilute than the plasma due to the removal of sodium and chloride
49
Q

how much water does the loop of Henle reabsorb

A
  • Important in reabsorbing 30% of water that enters the loop of Henle
50
Q

what is the difference in osmolaitiy in the ascending and descending loops of heel

A

There is therefore a difference in osmolality in the ascending and descending loops of around 200 mOsm at any one time

51
Q

as the urine travels up the ascending loop of Henle it …

A

As the urine travels up the TALH, it reaches the same concentration that it was at the point where it enters the loop. Thus, urine volume is decreased but solutes are preserved

52
Q

why do we have a counter current mechanism

A

– Filtrate that leaves the proximal tubule is iso-osmolar to plasma
– In the event of excess water overload, excretion of urine is required that is hypo-osmolar to plasma (i.e dilute urine)
– In the event of water restriction, hyper-osmotic urine excretion is required (concentrated urine)

53
Q

what provides the counter current mechanism

A
  • the vasa recta provide a countercurrent exchange mechanism to preserve the concentration gradient despite a blood flow through the vasa recta capillaries
54
Q

the longer the loop of Henle…

A

The longer the loop of Henle the greater the countercurrnet multiplier system therefore the more water reabsorbed and a more concentrated urine

55
Q

describe what solutes are transporter in the ascending limb

A

– Secondary active transport of Na, K and Cl in thick ascending limb
– Paracellular transport of Na, Ca and Mg down a electrochemical gradient

56
Q

what does the distal nephron consist of

A

– Distal tubule
– Connecting tubule
– Collecting duct (cortical and medullary)

57
Q

what is the function of the distal nephron

A

– K excretion
– Regulation of sodium delivery to collecting duct
– Urine acidification

58
Q

what happens to the collecting duct in the presence of ADH

A

– Aquaporins become permeable to water
– Passage of water from collecting tubule to interstitium down a concentration gradient
– Production of concentrated urine

59
Q

what determines the concentration of the urine in the collecting duct

A

ADH

60
Q

what happens if there is a defect of ADH secretion

A

– A deficit of ADH secretion leads to copious dilute urine i.e Diabetes insipidus

61
Q

what is the renal threshold

A
  • Renal threshold is the concentration of a substance dissolved in the blood above which the kidneys begin to remove it into the urine.
  • When the renal threshold of a substance is exceeded, reabsorption of the substance by the proximal renal tubule is incomplete and some of the substance remains in the urine.
62
Q

describe what the renal absorption of glucose is like when glucose is normal versus when it is high

A

At normal plasma glucose levels, eg 5.0 mmol/L ………
• all filtered glucose is reabsorbed
• no glucose is excreted.

At a plasma glucose level of about 10 mmol/L ……….
• glucose appears in urine (glycosuria)
• this plasma concentration is called the glucose threshold

63
Q

what is the glucose threshold

A

10 mmol/L

64
Q

why does glucose appear in the urien

A
  • Glucose appears in urine because the amount of glucose exceeds the reabsorption capacity of the tubules – all the glucose carriers are saturated.
  • The rate of glucose reabsorption reaches a constant maximal value called the transport maximum for glucose (TmG)
  • The glucose threshold of about 10 mmol/L is not fixed as it depends, for example, on the GFR.
  • A low GFR leads to an elevated threshold - filtering rate reduced, decrease in glucose load \ more glucose reabsorbed
65
Q

how does GFR effect the renal threshold of glucose

A
  • The glucose threshold of about 10 mmol/L is not fixed as it depends, for example, on the GFR.
  • A low GFR leads to an elevated threshold - filtering rate reduced, decrease in glucose load \ more glucose reabsorbed
66
Q

what are the side effects of glucose present in the urine

A

osmotic diuresis

67
Q

what is osmotic diuresis

A

: if excess solute present in tubular fluid this will attract water and increases urine volume (water balance lecture)

68
Q

what does increase plasma omsolaity lead to

A

Thirst sensation

Metabolism 2 (40 decks)

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