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renal excretory function Flashcards

1
Q

what is a functional unit of the kidney?

A

nephron

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2
Q

what is the nephron made up of?

A

PCT, Loop of Henle, DCT and collecting duct

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3
Q

what are the main functions of the glomerular basement membrane?

A
  • Needed for the free movement of electrolytes and water

* Prevents big molecules from leaving the glomerulus – once gone they cant be taken back up

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4
Q

what are the 2 main cell types in the glomerulus basement membrane?

A

podocytes

endothelial cells

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5
Q

what is the difference between the function of endothelial cells and podocytes?

A

o Endothelial cells are not selective – anything can get through them
o Podocytes make up a podocyte slit diaphragm – selectively reabsorbs stuff

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6
Q

what is found in the gaps between podocytes?

A

o Between podocytes there are many anchoring proteins that restrict movement of proteins

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7
Q

how much plasma is filtered by the glomerulus each day?

A

180L

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8
Q

how much urine is produced by a person with normal renal function?

A

1-2L of urine

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9
Q

what factors determine the filtrate?

A 
•	Net filtration pressure
•	Podocyte slit pores
•	Size of molecule
•	Charge of molecule
o	-ve charge of GBM glycoproteins
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10
Q

what molecules can move through the glomerulus freely?

A

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

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11
Q

what is the GFR?

A

total amount of fluid that’s filtered through the glomerulus

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12
Q

what is the normal GFR?

A

120mL/min

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13
Q

what is the ideal substance for GFR?

A

o One that is completely filtered and none is reabsorbed (completely cleared)
o No naturally available substance exists

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14
Q

what is creatinine?

A

Breakdown product of creatine phosphate found in muscles

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15
Q

what is the issue with using creatinine for GFR?

A
  • Creatinine is freely filtered by the glomerulus
  • But it’s also actively secreted by the peritubular capillaries in small amounts
  • Means that creatinine clearance overestimates the actual GFR by 10-20%
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16
Q

why is creatinine used for GFR?

A
  • completely filtered by the glomerulus

- already at a steady state concentration in the blood

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17
Q

what is the formula for creatinine clearance?

A

(urine Cr conc x urine volume/min)/plasma Cr concentration

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18
Q

how do you measure clearance of a substance?

A
  1. Measure the concentration of the creatinine 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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19
Q

in what ways can you measure GFR?

A
  • creatinine clearance
  • nuclear medicine scan
  • estimated GFR
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20
Q

how is creatinine clearance measured?

A

24 hour urine collection

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21
Q

how does a nuclear medicine scan work?

A

when a radio-labelled compound is injected and its clearance is measured

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22
Q

when is a nuclear medicine scan done?

A
  • Done for kidney donors to make sure they have good kidney function
  • Also done when dosage needs to be done for chemotherapy
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23
Q

what factors need to be taken into account when using the MDRD equation?

A

CAGE

Creatinine
Age
Gender
Ethnicity

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24
Q

why do Afro-Caribbeans produce more creatinine?

A

have a higher muscle mass

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25
Q

describe the relationship between GFR and creatinine

A
  • GFR is more important than creatinine clearance bc its more sensitive– when there’s a small difference in serum creatinine there’s a big change in GFR
  • When creatinine goes from 400-600 there is a small change but at lower concs of creatinine there are high changes in GFR
26
Q

who will have naturally high GFR? how will this affect the eGFR?

A

muscular individuals

eGFR underestimates true GFR

27
Q

who will have naturally low GFR? how will this affect the eGFR?

A

Malnourished individuals have low serum creatinine. i.e. eGFR overestimates true GFR

28
Q

how can some drugs have an effect on creatinine?

A

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

29
Q

what fills the gaps between the tubular cells?

A

tight junction – limits salt and water. Also maintains polarities

30
Q

what do carrier proteins do?

A

take sodium, potassium, amino acids etc and into the tubular lumen and take it away so it isn’t secreted in the urine

31
Q

what are the methods of passive solute transport?

A

o Passive diffusion - Down a concentration and electrochemical gradient
o Carrier mediated (facilitated) diffusion
 Carrier proteins
 Selective
o Diffusion through membrane channel

32
Q

what are methods of active solute transport?

A 
o	Movement of solutes against an electrochemical gradient
o	Dependent on ATP
o	Examples
	Sodium pump ( Na-K ATPase)
	H+-ATPase (distal nephron)
	Ca +2 -ATPase
33
Q

what is primary active transport?

A

uses ATP as an energy source to dry movement

34
Q

what is secondary active transport?

A

uses energy form non-ATP sources (ie electrochemical gradients)

35
Q

what defects can occur in the proximal tubule and what can they lead to?

A

o Apical Na/cystine cotransporter  Cystinuria
o Apical Na/glucose cotransporter  Renal glyocsuria
o Basolateral Na/HCO3 cotr.  proximal RTA

36
Q

what defect in the thick ascending loop of Henle can occur and what does this lead to?

A

o Apical Na/K/2CL co transport  Bartter type 1

37
Q

what defect can occur in the distal tubule and what does this lead to?

A

Apical Na-Cl cotr.  Gitelman’s

38
Q

describe the anatomy of the PCT

A

o Apical brush border (microvilli), Large surface area for absorption
o Dense levels of mitochondria reflects ATP needs of active
o 1st 2/3 - Proximal convoluted tubule
o Final 3rd - proximal straight tubule

39
Q

describe the function of the PCT?

A

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

40
Q

what is the function of the loop of Henle

A

Aim of the LoH is to reduce the volume of water and solutes within the urine w/o changing the concentration  hypertonic medulla

41
Q

why is the countercurrent mechanism needed?

A

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

42
Q

what is actively transported out of the ascending loop of Henle?

A

Na+

43
Q

what maintains the osmotic gradient?

A

countercurrent exchange by the vasa recta

44
Q

how do loop diuretics work?

A

Loop diuretics inhibits the Na+/Cl-/K+ loop of Henle (e.g. furosemide) - inhibits sodium excretion –> less water gets out the tubule

45
Q

how are solutes transported in the loop of henle?

A

water by osmosis

46
Q

how are solutes transported in the ascending limb?

A

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

47
Q

what does the distal nephron consist of?

A

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

48
Q

what is the function of the distal nephron?

A

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

49
Q

what do thiazide diuretics targets?

A

NaCl transporter in the distal tubule

50
Q

what determines the concentration of the urine?

A

ADH

51
Q

what happens to the collecting tubule in the presence of ADH?

A

o Aquaporins become permeable to water
o Passage of water from collecting tubule to interstitium down a concentration gradient
o Production of concentrated urine
o A deficit of ADH secretion leads to copious dilute urine i.e Diabetes insipidus

52
Q

what is the renal threshold?

A

concentration of a substance dissolved in the blood above which the kidneys begin to remove it into the urine

53
Q

what happens when the renal threshold is exceeded?

A

reabsorption of the substance by the proximal renal tubule is incomplete and some of the substance remains in the urine

54
Q

what is the most common reason for the glucose renal threshold being exceeded?

A

diabetes

55
Q

what happens to glucose at normal plasma glucose levels?

A

o All filtered glucose is reabsorbed

o No glucose is excreted

56
Q

what is the glucose threshold?

A

10mmol/L

57
Q

what happens when the glucose threshold is exceeded?

A

• Glucose appears in the urine when the amount of glucose exceeds the reabsorption capacity of the tubules – all glucose carriers are saturated

58
Q

what is the transport maximum for glucose?

A

when the rate of glucose reabsorption reaches a constant maximal value

59
Q

what does the glucose threshold depend on?

A

depends on the GFR

o Low GFR = higher threshold – filtering rate is reduced, decrease in glucose load  more glucose reabsorbed

60
Q

what does glucose in the urine induce?

A

osmotic diuresis

61
Q

what is osmotic diuresis?

A

if excess solute present in tubular fluid this will attract water and increases urine volume

62
Q

why do diabetics feel thirsty?

A

• Increase in plasma osmolality bc of increasing water excretion

m2 (24 decks)

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