kidney as a regulator, excretor and producer Flashcards
(112 cards)
1
Q
what are the roles of the kidney?
A
excretor
producer
regulator
2
Q
what does the kidney produce?
A
erythropoietin
vitamin D
3
Q
Erythropoietin (EPO)
A
secreted by the kidney
4
Q
what produces EPO?
A
peritubular cells of kidney
5
Q
what causes EPO production?
A
fall in oxygen level in renal tissues
6
Q
what does EPO do?
A
stimulates precursors in bone marrow and their differentiation to RBCs
7
Q
untreated chronic kidney disease
A
likely to cause anaemia due to EPO deficiency
hypocalcaemia
8
Q
formation of vitamin D
A
skin and UV light
cholecalciferol produced from dietary precursors
converted to 25-hydroxycholecalciferol in liver
converted to 1,25-dihydroxycholecalciferol in kidney
9
Q
what does vitamin D do?
A
raises serum calcium by:
promotes GI absorption
decreasing renal excretion - increased reabsorption
stimulating bone reabsorption
10
Q
overall renal function
A
high volume filtration - majority is reabsorbed
multiple mechanisms for selective, adjustable reabsorption or secretion
variable intercellular junctions act as selective barriers to passage of small molecules
11
Q
tubular cells
A
tight junction between tubular cells - selective and variable barrier to small molecules
12
Q
capillaries
A
capillary wall junctions allow easy movement of ions and water
13
Q
Na+/K+ ATPase
A
pump
maintains the low Na+ concentration intracellularly
it is the main active process in Na+ reabsorption
14
Q
passive conductance
A
water and K+ can leave the tubular cells passively into the interstitial fluid and capillary
15
Q
tight junctions
A
fusion of adjacent cell membranes to crease a barrier to passage of water and dissolved particles
the extent is variable
16
Q
variable tight junctions in kidney
A
PCT - loose/ leaky
DCT - tight
CD - very tight
17
Q
standard capillary tight junctions
A
large gaps between cells allowing water and electrolytes to pass easily
18
Q
afferent arteriole
A
goes into glomerulus
19
Q
efferent arteriole
A
goes out of the glomerulus - takes the blood out
20
Q
order of nephron structure
A
glomerulus PCT Loop of Henle DCT collecting duct
21
Q
what does the glomerulus do?
A
produces filtrate
120ml/min
22
Q
how does the glomerulus work?
A
high pressure filtration of blood
podocytes covering the ball of glomerular capillaries have filtration channels which are negatively charged and so cations and uncharged particles can more easily move through
23
Q
podocytes
A
loss
24
Q
proteins
A
most cannot get through the glomerulus - small ones can. Albumin is the cut off, so if albumin is present there may be pathology
25
what is filtered through the glomerulus?
```
glucose
Na+
HCO3-
water
other ions
```
26
loss of filtrate
leads to a rise in oncotic pressure in efferent arteriole which is useful to increase reabsorption as it increases the gradients
27
what influences filtration?
hydrostatic pressure gradient pushing water out
oncotic pressure gradient pushing in
net filtration pressure - 14mmHg out into bowman's capsule
28
filtration fraction
the proportion of plasma that goes through the kidney - that becomes filtrate - 15-20%
29
glomerular filtration rate (GFR)
useful measure of renal function as this is generally what is affected by pathology
30
marker of GFR
readily filtered
| not metabolised, reabsorbed or secreted
31
how to measure GFR?
rate of filtration = rate of excretion (mg/min)
| filtrate flow x filtrate concentration
32
calculate GFR
filtrate flow x filtrate concentration = urine flow x urine concentration
GFR = filtrate flow
the others can be measured
filtrate conc = plasma conc
33
what are the GFR markers?
creatinine
| cystatin C - more accurate but more difficult to measure
34
creatinine
product of muscle metabolism
minor tubular secretion - overestimation slightly
has to be measured at resting state
35
cystatin C
small protein produced by most cells
| no tubular secretion
36
Inulin
plant extract - has to be infused so not natural
37
GFR =
UFR x urine conc/ plasma conc
| UFR = urine flow rate
38
GFR is
inversely proportional to plasma concentration of creatinine in a steady state
39
creatinine variability
normally production is constant but age and race influence this
older = less production
black people = larger production
need to be factored in when measuring GFR using creatinine
40
detection of early kidney damage
GFR has to fall substantially before a noticeable rise in plasma creatinine is seen so difficult to detect early damage
severity is based on creatinine levels (5 stages)
41
stage 5 renal impariment
renal failure - need dialysis
42
what is autoregulation?
keeping the flow constant despite pressure changes
43
what needs autoregulation in the kidney?
renal blood flow
glomerular filtration rate
both have mechanisms
44
MAP for kidney
70-160mmHg
45
drop in afferent blood pressure
fall in renal blood flow via efferent arteriole and GFR
46
Autoregulation 1
to maintain renal blood flow
| afferent arteriole dilates which improves renal blood and lowers pressure
47
Autoregulation 2
to maintain GFR
efferent arteriole constricts
improves GFR but at a lower renal blood flow
filtration fraction increases
48
mechanisms of autoregulation
myogenic
| tubulo-glomerular feedback
49
tubulo-glomerular feedback
adenosine
angiotensin II
PGE2
50
Adenosine
produced in hydrated state
constricts afferent arteriole
reduces GFR
inhibits renin release
51
what switches off adenosine?
reduced filtrate flow
52
Angiotensin II
produced from RAAS
constricts efferent arteriole selectively to maintain glomerular capillary pressure and raise GFR
beware of inhibition of this in BP treatment (ARBs and ACEi) in hypovolaemia as kidneys are not protected by autoregulation
53
when is PGE2 released?
produced in DCT in response to decreased filtrate flow
54
what does PGE2 do?
dilates afferent arteriole to maintain renal blood flow
cytoprotective to tubule
antagonises vasopressin
beware of NSAIDs in hypovolaemia/ hypotension - loss of autoregulation 2
55
PCT main role
conservation of the majority of the useful filtrate components
56
what happens in the PCT?
reabsorption of Na+
and same amount of water
HCO3- reabsorption and glucose reabsorption completely
57
fluid composition after PCT
Na+ conc same as plasma due to reabsorption of water and sodium in equal amounts
no glucose
no HCO3-
58
how is Na+ reabsorbed in the PCT?
antiporter - H+/Na+ - 1 for 1 exchange
| Na+/ glucose symporter
59
antiporter H+/Na+
1 H+ secreted and 1 Na+ reabsorbed with HCO3- from acid/ base buffering
60
Na+/ glucose symporter
cotransport of Na+ and glucose into tubular cell
| Na+ into blood by Na+/K+ pump
61
leaky junctions
allows passage of water into blood from tubule lumen
| follows Na+
62
Cl- reabsorption
water follows sodium reabsorption
increases tubular conc of Cl- so it can then be reabsorbed down a conc gradient via para-cellular route
makes charge in tubular lumen - creating an electrochemical gradient which drives sodium reabsorption
63
paracellular router
between tubular cells - cell junctions
64
glucose reabsorption
transport maximum = 2mmol/min
| if GFR and glucose conc in blood increases glucose will be excreted into the urine
65
exceeding transport maximum (Tm)
glycosuria and osmotic diuresis
66
role of Loop of Henle
producing hypotonic tubular fluid and hypertonic interstitial fluid
some reabsorption of Na+, K+, Cl-
67
how does the loop of henle work?
selective permeabilities to ions and water in ascending and descending limbs
countercurrent multiplier
68
ascending limb of LoH
impermeable to water
| permeable to ions
69
what happens in ascending limb
Na+, Cl-, K+ ions pumped out
water unable to leave
water cannot escape due to very tight cell junctions
70
cortex
as ions are lost and water retained tubular fluid becomes more dilute and cortex medullary fluid/ interstitial fluid more concentrated
71
how are Na+/ K+/ Cl- reabsorbed?
NKCC cotransporter into tubular cell
K+ passively diffuses into bloof
sodium potassium pump moves sodium into blood
72
descending limb of LoH
water permeable
| impermeable to Na+, K+ and Cl-
73
what happens at the bottom of the loop of Henle?
interstitial fluid very concentrated due to descending limb
74
countercurrent multiplier purpose
reabsorbed water and electrolytes need to be removed without disrupting the osmotic gradients
75
countercurrent flow
returning blood in contact with descending LoH and arriving blood in contact with ascending LoH
76
what happens in countercurrent multiplier?
electrolytes pass from ascending LoH to descending limb of vasa recta
water passes from descending LoH to ascending limb of vasa recta
77
blood flow around LoH
vasa recta
78
vasa recta
become hypermolar in medulla but returned to normal by the time they return to the blood supply
79
hypertonic environment in medulla
allows highly efficient water reabsorption in the collecting duct
80
DCT
final regulation of extent of Na+, K+ and H+ excreted in urine
81
what cells are involved in DCT?
principal
| intercalated
82
principal cells
reabsorb Na+
secrete K+
controlled by aldosterone
by ENaC
83
Intercalated cells
reabsorb K+
secrete H+
driven by ATPase
H+/K+ pump
84
fluid composition after DCT
determined by body volume state, acidosis and K+ conc
85
ENaC
epithelial sodium channel
86
what stimulates ENaC?
aldosterone
alkalosis
increased K+ conc
87
H+/K+ pump
active transport
secretes H+ and reabsorbs K+
involved in acid/ base balance
88
what stimulates the H+/K+ pump?
acidosis
| decreased K+ conc
89
main role of collecting duct
final regulation of water excretion - urine conc
90
how does collecting duct work?
normally impermeable to everything but becomes water permeable by insertion of aquaporins into luminal membrane
91
regulation of collecting duct
ADH
| controlled by osmoreceptors
92
aquaporins
trans-membrane proteins with narrow hour-glass shaped and charged walls
only allow water to pass through
without them water moves slowly by osmosis
93
types of aquaporins
more than 8
4 in kidney (1-4) - 3 constantly present and don't vary
AQP2 inserted in response to ADH so variable
94
AQP1
PCT
descending LoH
basal membrane
constant
95
AQP3
collecting duct basal membrane
| constant
96
AQP4
collecting duct basal membrane
| constant
97
AQP2
collecting duct
luminal membrane
inserted in response to ADH
variable water reabsorption
98
what allows AQP2 to work?
hypertonicity of interstitium
99
ADH
small polypeptide
| 3 types of receptors
100
ADH receptos
GPCR
V1a
V2
V3/ B1b
101
V1a receptor
peripheral circulation
| vasoconstriction
102
V2 receptor
collecting duct endothelium
AQP2 insertion
clotting factor release
103
V3/ V1b
CNS
| ACTH release
104
where is H+ secretion mainly done?
PCT and HCO3- reabsorption
| final urine acidity determined in DCT by intercalated cells
105
BP control in kidney
juxta-glomerular apparatus
106
juxta-glomerular apparatus location
between afferent arteriole and DCT allows input from both in terms of pressure supplying kidney and if Na+ flow is low in tubules
107
what does juxtaglomerular apparatus detect?
drop in kidney blood pressure
| drop in sodium conc of tubules by macula densa
108
macula densa
stores granules of renin
109
drop in Na+ or blood flow detected by juxtaglomerular apparatus
dilation of afferent arteriole by adenosine drop or PGE2 increase
releases renin from granular cells
110
renin release
triggered by sympathetic NS directly from B1 receptors as well
111
role of kidney in response to hypovolaemia
Drop in Na+/ flow/ BP detected by juxtaglomerular apparatus causing renin release
turns angiotensinogen into angiotensin I in plasma
ACE forms angiotensin II in lungs
112
what does angiotensin II do?
vasoconstriction
autoregulation in kidney
negative feedback
aldosterone release - sodium reabsorption
release of ADH - retains water and causes vasoconstriction
works with neural baroreceptors causing vasoconstriction, increased Heart rate and more renin release
