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
describe the relationship between GFR and creatinine
* 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
who will have naturally high GFR? how will this affect the eGFR?
muscular individuals | eGFR underestimates true GFR
27
who will have naturally low GFR? how will this affect the eGFR?
Malnourished individuals have low serum creatinine. i.e. eGFR overestimates true GFR
28
how can some drugs have an effect on creatinine?
Some drugs inhibit tubular secretion of creatinine (eg Trimethoprin), leading to a raised plasma creatinine even though GFR may be unchanged
29
what fills the gaps between the tubular cells?
tight junction – limits salt and water. Also maintains polarities
30
what do carrier proteins do?
take sodium, potassium, amino acids etc and into the tubular lumen and take it away so it isn’t secreted in the urine
31
what are the methods of passive solute transport?
o Passive diffusion - Down a concentration and electrochemical gradient o Carrier mediated (facilitated) diffusion  Carrier proteins  Selective o Diffusion through membrane channel
32
what are methods of active solute transport?
``` 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
what is primary active transport?
uses ATP as an energy source to dry movement
34
what is secondary active transport?
uses energy form non-ATP sources (ie electrochemical gradients)
35
what defects can occur in the proximal tubule and what can they lead to?
o Apical Na/cystine cotransporter  Cystinuria o Apical Na/glucose cotransporter  Renal glyocsuria o Basolateral Na/HCO3 cotr.  proximal RTA
36
what defect in the thick ascending loop of Henle can occur and what does this lead to?
o Apical Na/K/2CL co transport  Bartter type 1
37
what defect can occur in the distal tubule and what does this lead to?
Apical Na-Cl cotr.  Gitelman’s
38
describe the anatomy of the PCT
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
describe the function of the PCT?
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
what is the function of the loop of Henle
Aim of the LoH is to reduce the volume of water and solutes within the urine w/o changing the concentration  hypertonic medulla
41
why is the countercurrent mechanism needed?
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
what is actively transported out of the ascending loop of Henle?
Na+
43
what maintains the osmotic gradient?
countercurrent exchange by the vasa recta
44
how do loop diuretics work?
Loop diuretics inhibits the Na+/Cl-/K+ loop of Henle (e.g. furosemide) - inhibits sodium excretion --> less water gets out the tubule
45
how are solutes transported in the loop of henle?
water by osmosis
46
how are solutes transported in the ascending limb?
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
what does the distal nephron consist of?
o Distal tubule o Connecting tubule o Collecting duct (cortical and medullary)
48
what is the function of the distal nephron?
o K excretion o Regulation of sodium delivery to collecting duct o Urine acidification
49
what do thiazide diuretics targets?
NaCl transporter in the distal tubule
50
what determines the concentration of the urine?
ADH
51
what happens to the collecting tubule in the presence of ADH?
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
what is the renal threshold?
concentration of a substance dissolved in the blood above which the kidneys begin to remove it into the urine
53
what happens when the renal threshold is exceeded?
reabsorption of the substance by the proximal renal tubule is incomplete and some of the substance remains in the urine
54
what is the most common reason for the glucose renal threshold being exceeded?
diabetes
55
what happens to glucose at normal plasma glucose levels?
o All filtered glucose is reabsorbed | o No glucose is excreted
56
what is the glucose threshold?
10mmol/L
57
what happens when the glucose threshold is exceeded?
• Glucose appears in the urine when the amount of glucose exceeds the reabsorption capacity of the tubules – all glucose carriers are saturated
58
what is the transport maximum for glucose?
when the rate of glucose reabsorption reaches a constant maximal value
59
what does the glucose threshold depend on?
depends on the GFR | o Low GFR = higher threshold – filtering rate is reduced, decrease in glucose load  more glucose reabsorbed
60
what does glucose in the urine induce?
osmotic diuresis
61
what is osmotic diuresis?
if excess solute present in tubular fluid this will attract water and increases urine volume
62
why do diabetics feel thirsty?
• Increase in plasma osmolality bc of increasing water excretion