Kidneys

?
  • Created by: Sarah
  • Created on: 19-04-17 09:33
what is osmality?
concentration of ions and solutes
1 of 314
what would a high osmality be?
high ion and solute content
2 of 314
what is the other name for vasopressin?
anti diuretic hormone
3 of 314
what does vasopressin do?
conserve water
4 of 314
where is vasopressin made?
neurosecretory cells of hypothalamus
5 of 314
where is vasopressin stored?
nerve terminals (until ap)
6 of 314
what does vasopressin act on?
kidneys
7 of 314
what inhibis vasopressin?
excessive water intake, alcohol
8 of 314
what type of hormoneis aldosterone?
a mineralcorticoid
9 of 314
what does aldosterone do?
regulates K+, Na+ and body fluid volume
10 of 314
what is important in the principal cell on the apical membrane?
aquaporin 2
11 of 314
what receptor responds to vasopressin on the basolateral membrane?
V2
12 of 314
what happens when V2 is activated?
protein kinase A is activated which phosphorylates proteins on vesicles which cause them to fuse with membrane which are AQ2 water channels, more aquaporin 2 channels
13 of 314
what does adding more aquaporin 2 channels allow?
more water to be reabsorbed, fall in body fluid osmalility
14 of 314
what is diabetes insipidus?
you produce copious amounts of dilute urine, up to 23L a day
15 of 314
how is central DI treated?
nasal spray of vasopressin
16 of 314
what is central DI?
CNS- prob at hypothalamus ort pituitary gland no release of vasopressin not produced or secred
17 of 314
what is nephrogenic DI?
no response from kidney to vasopressin, eg mutations in V2 or AQ2
18 of 314
what is nephrogenic DI treatment?
as far as your concerned rn there's none
19 of 314
where is aldosterone released from?
adrenal gland from zona glomerulson
20 of 314
what is sodium regulated by?
only a minor change vasopressin steps in, or decrease aldosterone steps in
21 of 314
when is aldosterone released?
fall in ECF volume, decreased Na and increase in potassium
22 of 314
what does aldosterone act on?
distal tube and collecting duct
23 of 314
why does aldosterone cause to happen?
reabsorption of Na, reabsorption of water and secretion (excretion) of K+ and H+
24 of 314
what cells do aldosterone work on?
intercalated and principal cells
25 of 314
how does aldosterone enter the cell?
diffuses across the basolateral lipid membrane as its a steroid hormone
26 of 314
where is the receptor for aldosterone?
in the cytosol
27 of 314
what is the cytosolic receptor for aldosterone called?
mineralcorticoid receptor
28 of 314
what happens to the complex of receptor and aldosterone when aldosterone has binded?
moves to nucleus cell --> RNA transcritpion and protein synthesis (genomic pathway)
29 of 314
what does aldosterone cause the transcription of in the principal cell?
more Na/K ATPase, ENAC channel, ROMK channel, sodium hydrogen exchangers
30 of 314
what pathway does aldosterone activate in the principal cell?
genomic pathway
31 of 314
what does aldosterone do to the intercalacted cell?
more proton pumps on apical membrane are made
32 of 314
whats the net effects on plasma by aldsterone?
1) increase Na content 2) decrease H and K 3) increase ECF volume
33 of 314
what is difference between content and conc?
concentration number of moles per litre influences osmalility, content-total number of moles of Na in your body
34 of 314
does aldosterone regulate the concentration or content of Na?
content
35 of 314
what does aldosterone coordinate regulation with?
renin-angiotensin system
36 of 314
diseases caused by aldosterone?
liddles syndrome and pseduohypoaldosterone
37 of 314
whatis liddles syndrome?
really high bp (hypertension) caused by NA reabsorption by too many eNAC, excess sodium by principal cell but low aldosterone, mutation in eNAC can't pull out
38 of 314
what is pseudohypoaldosterone?
losing salt in urine, excrete Na that normally retained, aldosterone high but still lose Na, loss of response to aldosterone, prob with mineralocorticoid receptor
39 of 314
where is renin released from?
kidney structure called juxtaglomerular apparatus (JGA)
40 of 314
what does renin angiotensin regulate?
plasma Na + K, body fluid volume
41 of 314
why is it called the juxtaglomerular apparatus?
early distal tubule is passing very close to its own glomerulus
42 of 314
what is macula densa cells?
looking at flow rate of tubule fluid, if different releases chemicals impact cells in the afferent arteriole brings blood to glomerulus
43 of 314
why is the afferent arteriole importnat?
afferent arteriole blood supply to glomerulus, source of renin, granular cells in wall of afferent arterioles, granules in these cells are renin
44 of 314
how do granular cells release renin?
by sympathetic nerve fibres stimulation OR by chemical signals from the maccula densa cells
45 of 314
what happens when granular cells are stimulated to release renin?
release renin into plasma, initiates renin angiotensin cascade system producing Angiotensin 2
46 of 314
how does the renin-angiotesin cascade work?
fall in ECF volume -> activation of sympa NS -> impacts tubular flow rate -> macula densa cells sigs to afferent arteriole ->
47 of 314
what does renin catalyse?
conversion of angiotensinogen to angiotensin 1
48 of 314
what happens to angiotensin 1?
converted to angiotensin 2 by ACE
49 of 314
where in the body is angiotensin 1 converted to angiotensin 2?
in the capillaries
50 of 314
where is most angiotensin 1 converted to angiotensin 2?
made in lungs because biggest density of capillaries
51 of 314
what does angiotensin 2 release?
aldosterone
52 of 314
where does aldosterone released from?
zona glomerulosa of adrenal gland
53 of 314
what does angiotensin 2 do?
release of aldosterone, vasoconstriction increase bp, inceease Na uptake increases ECF volume
54 of 314
why is ACE inhibitors used treatment for high bp to give low bp?
less angiotensin 2, less aldosterone and vasoconstriction --> ower blood pressure, less Na uptake
55 of 314
what happens in the integration system?
ingest salt, more Na absorbed from intestine and water out of ICF, ECFV increases, plasma osmalility plasma increases
56 of 314
whatis priority to regulate and why, osmalility or ecf ?
ecf volume as it influences blood pressure
57 of 314
why do males have more total body water than females?
females carry more body fat so water cant go where there's fat
58 of 314
how many Kg/L of water does an average 70kg person have?
42L or 42kg
59 of 314
what age catergory has more total body water?
infants
60 of 314
whats the 2 basic body cellular fluid?
intracellular fluid or extracellular fluid
61 of 314
what percentage of fluid is found intracellular?
62% (25-30L)
62 of 314
3 parts of extracellular fluid?
interstitial fluid
63 of 314
what is interstitial fluid?
fluid found outsde of cells but no role in circulation (CVS) fluid surrounds cell of body
64 of 314
what is transcellular fluid?
specialised fluid, specific locations like CSF or urine in bladder
65 of 314
largest componet of ECF? percent? number of litres?
Interstitial fluid, 11-12L 28%
66 of 314
what cation is higher outside the cell?
Na+(140)
67 of 314
what cation is low in the interstitial fluid?
K+ (5)
68 of 314
The intracellular fluid has a high concentration of potassium (K) but how many mmol?
148mmol
69 of 314
are there more chloride ions inside or outside the cell?
outside the cell(in interstitial fluid)
70 of 314
why is it important to have more potassium inside the cell?
so K channels open and K moves out of the cell depolarising cause ap, creates -ve ap
71 of 314
is protein concentration inside cell high or low?
high- 55
72 of 314
what are the kidneys a major route of?
excretion
73 of 314
how do we take in sodium?
diet (Salt)
74 of 314
how do we excrete sodium?
majority urine(140) but 10 in stool + sweat
75 of 314
intake 2.6L a day of water how much is excreted as urine?
1.5l/day
76 of 314
1.1l of water is excreted by what?
stool, sweat, respiration
77 of 314
how do we take in water?
food, metabolism and drink
78 of 314
the kidney runs from what to what?
12th thoracic to 3rd lumbar
79 of 314
where is the adrenal gland?
just above kidneys (releases aldosterone
80 of 314
what is renal agenisis?
complete inability to form the kidneys
81 of 314
how many people get renal agensis whats it asscoiated with?
1 in 2500, early miscarriage (not always kidneys not as important in baby in womb)
82 of 314
ectopic kidney?
unusual location, 1 in 800
83 of 314
whats the problem with the kidney growing in the pelvic?
kindey stones and calcification
84 of 314
what is the horseshoe kidney?
kidneys fused at midline 1 in 1000
85 of 314
probs with horseshoe kidney?
kidney stone formation
86 of 314
what parts of the kidney have a very rich blood supply?
pelvis, calyx and ureter
87 of 314
what is the capsule?
tough fibrous layer, holds kidney together and protects kidney
88 of 314
what does the medullary rays drain into?
calyx (bottom of medullary rays = papilla)
89 of 314
what part of the kidney does the pelvis/ureter come out rom?
the hilus
90 of 314
whats the outermost part of the kidney?
cortex
91 of 314
innermost part of the kidney?
medulla
92 of 314
how many nephrons in each kidney?
1-1.5 million
93 of 314
what does medulla consist of?
loop of henle and collecting duct
94 of 314
what is in the cortex?
bowmans capsule, distal tubule, proximal tubule
95 of 314
how many nephrons drain into 1 collecting duct?
6
96 of 314
what does the bowmans capsule surround?
the glomerular capillary bed
97 of 314
where does the blood supply for the glomerulus come from?
renal artery--> afferent arteriole
98 of 314
what is ultarfiltrate?
filtrate from glomerulus thats in bowmans capsule plasma protein free
99 of 314
diameter of glomerulus?
200um
100 of 314
what happensto stuff thats not filtered out?
leaves kidney by efferent arteriole back to circulation
101 of 314
what is the gfr?
125ml/min
102 of 314
what are most nephrons?
superficial (85%)
103 of 314
what are juxtamedullary neurons?
glomerulus+ bc on border between cortex and medulla, LOH deep into medulla
104 of 314
what are juxtamedullary neurons?
ability to concentrate urine
105 of 314
whats renal failure?
fall in gfr, increase in urea and creatinine in plasma
106 of 314
what renal failures reversible?
acute
107 of 314
treatment for chronic renal failure?
dialysis or transport
108 of 314
what stays the same in acute renal failure but not chronic?
hameoglobin levels, renal size (decreases in chronic), peripheral neuropathy
109 of 314
whats peripheral neuropathy?
damage to sensory and motor nerves, lose sensation and motor movements
110 of 314
what renal failure progression involve?
thickening of glomerular membranes, damage to glomeruli, decrease in renal size and progressive scarring(glomerulosclerosis), tubular atrophy
111 of 314
whats the consequence of glomerular membrane thickening up?
more difficult to filter plasma
112 of 314
whats tubular atrophy?
nephrons start to die off
113 of 314
whats interstitial inflammation and fibrosis about?
expansion of fluid, inflammation puts pressure on nephrons so generates hydrostatic pressure damages them
114 of 314
what is the collective group of symptoms from renal failure progression called?
uraemia
115 of 314
what does renal failure look like on an ultrasound?
small and bright
116 of 314
why is not excrete excess salt and water a problem?
hypertension, hyperkaelmia (too much K in plasma) gives mild acidosis PH low impacts ability of excitable cells+ CVS
117 of 314
what does poor excretion of creatinine and urea result in?
anorexia, nausea and vomiting -> it is toxic
118 of 314
why does renal failure often result in leaking protein into urine?
due to breakdown of glomerular barrier
119 of 314
whats pericarditis?
inflammation of pericardium sack that surrounds the heart
120 of 314
why do you get peripheriphal neuropathy?
cretainine and neuropathy damage nerves
121 of 314
what does failure to produce erythropoitin cause?
lethargy and anaemia (less RBCs)
122 of 314
what does erythropoeitin do?
stimulates production of RBCs
123 of 314
wheres erythropoeitin made?
produced in kidney
124 of 314
faiilure to excrete plasma phosphate leads to what?
lower calcium in serum as phosphate combines with calcium and pecipitaet -> metastatic calfication
125 of 314
what does metastatic calcification do to your skin?
make it itch lots- pruritus
126 of 314
what does problems with phosphate and calcium give?
itichiness and bone disease
127 of 314
2 problems with bone disease?
osteomalacia (Soft pones) or osteoporosis (brittle bones)
128 of 314
what stage does anaemia become apparent?
moderate
129 of 314
when do you get early bone disease?
mild
130 of 314
when does uraemic syndrome and serum biochemistry become mild?
when its moderate
131 of 314
whats the biggest cause of renal failure?
gloerulonephritis (infection)
132 of 314
whats other risks for chronic renal failure?
hypertension and diabetes mellitus
133 of 314
whats most common inherited renal failure?
polycystic kidney disease
134 of 314
why do intercalated cells switch between alpha and beta?
depends on the acid basis state of the body
135 of 314
what is the late DT, connecting tubules and CD for?
concentration of urine, reabsorption of Na+H2O and secretion of K+H
136 of 314
what is the connecting tubules for?
connects DT and CD, same structure as DT
137 of 314
what part of the nephron determines how much potassium you have in your urine?
DT + CD
138 of 314
what 2 cells are in the DT + CD?
1) principals cells 2) intercalated cells
139 of 314
what are principal cells mainly important for?
reabsorbing water and Na, secreting K and H
140 of 314
what is the intercalated cells important for?
acid basis of body, H secretion and absorption, bicarbonate secretion and absorption
141 of 314
intercalated cells maintain what?
bicarbonate and hydrogen ions
142 of 314
what does eNAC stand for?
epithelium sodium channel
143 of 314
what is on the apical membrane of the principal cell?
enac, romk and aqp2
144 of 314
what does it mean that AQP3 and AP4 are constitutively activated?
not regulated by hormones if theres an osmotic gradient water will move down them
145 of 314
what is the rate limiting step of water uptake by the principal cell?
whether AQP2 is in the membrane or not
146 of 314
what is ROMK important for?
how much potassium you excrete in your urine, lots of K in urine, lots of K across apical membrane by ROMK
147 of 314
what determines how K is secreted?
num of ROMK channels and how often they are open,but Na movement
148 of 314
why is sodium movement important in how much K is secreted
theres a strong link between how much Na is taken up by ENaC and potassium is excreted by ROMK, more Na taken up by ENaC = more K secreted by ROMK
149 of 314
if you upregulate Na uptake in principal cells what is also upregulated?
potassium secretion
150 of 314
what do patients with barter ands giltemans have a problem with the prinicpal cell?
hypokalemia, upstream of CD theres a reduction in Na reabsorption ->Na load hits late DT+CT+CD
151 of 314
barters affects what part of the nephron?
thick ascending limb (red in Na reabsorption)
152 of 314
Gitelmans affects what part of the nephron?
early DT (red in Na reabsorption)
153 of 314
why is there a bigger drive force for Na by ENac in the principal cell?
barters and giltemans sodium is not reabsorbed before in the nephron, sodium load so more influx of Na through enac
154 of 314
what do you have more uptake by of in barters and giltemans?
more sodium uptake by enac
155 of 314
why is more uptake by enac a problem?
more uptake of na by enac means more secretion of K by ROMK, K goes in urine get hypokalemia
156 of 314
what are principal cell diseases?
diabetes insipidus (AQ2), liddles syndrome, pseudohypoaldesterosim
157 of 314
what happens in diabetes insipidus?
lots of urine as can't absorb water problem with AQP2
158 of 314
liddles syndrome happens as a result of failure of what?
ENaC
159 of 314
what is pseudohypoaldosteronism a result ofthe failure of what?
ENaC or the mineralcorticoid receptor
160 of 314
what does blocks enac?
amiloride
161 of 314
what is amiloride (diuretic used to reduce)?
high blood pressure
162 of 314
how does amiloride treat high bp?
blocks enac -> less Na taken up -> less water absorbed -> ECF volume reduce
163 of 314
what does amiloride spare?
potassium
164 of 314
what intercalated cells do you have more of if you have a diet high in protein?
alpha intercalated cells
165 of 314
why do you have more alpha IC cells with a high protein diet?
excess of acid in body need to secrete acid in urine
166 of 314
what are alpha IC cells?
acid secreting cells
167 of 314
what do alpha IC cells absrb?
bicarbonate
168 of 314
where does the bicarbonate that is absorbed by alpha ICs come from?
carbonate that has been produced by metabolism inside the cell, newly generated bicarboante
169 of 314
what is on the apical membrane of alpha IC?
hydrogen pump (ATPase)- a primary active transport protein
170 of 314
what is on the basolateral membrane of the alpha IC cell?
chloride bicarbonate exchanger that is coupled with a chloride channel
171 of 314
what does the chloride bicarbonate exchanger do?
pumps bicarbonate outside the cell (into PERITUBULAR CAPILLARIES) for exchange with Cl tinto cell that is then recycled through the Cl channel
172 of 314
where is chloride recycled in the alpha IC cell?
across the basolateral membrane
173 of 314
what is the chloride bicarbonate exchanger called?
AE1 = anion exchanger 1
174 of 314
what condition is asscoiated with mutations in AE1?
distal renal tubular acidosis
175 of 314
features of distal renal tubular acidosis?
genetically inherited, nephrocalinosis, metabolic acidis and nephrolithiasis
176 of 314
what is nephrocalcinosis?
having problems with calicum precipitation in tubular fluid therefore kidney stones (H, phosphate and Ca)
177 of 314
what is metabolic acidosis in distal renal tubular acidosis?
prob with IC cells in last part of nephron, can't maintain normal body PH, it is too low- acidic
178 of 314
what is nephrolithiasis?
increase in urine flow rate
179 of 314
what happens to AE1 in distal renal tubular acidosis?
the AE1 protein is mistargeted, AE1 is puts on apical and BL M when should only be on BL, it works well, gain of function mutation
180 of 314
what does AE1 being mistargeted to the apical membrane have a problem with and why?
bicarbonate that would have been absorbed is now secreted into tubular fluid, lose bicarbonate cant maintain plasma bicarbonate have acidosis
181 of 314
how is the beta IC different from alpha IC?
all transporters and channels are on opposite side except Cl channe stays on BL M
182 of 314
what are beta IC for?
absorption of H+CL and secretion of bicarbonate
183 of 314
when do you have more beta ICs?
when body PH is too high (alkaline) alkalosis
184 of 314
difference in function of alpha and beta regards to PH of body?
Alpha- make body less acidic, beta- make body more acidic
185 of 314
where is AE1 on beta IC cells?
apical M
186 of 314
what is the permbeality of the medullary CD?
high water permeability and urea permeability in presence of V, low Na permeability
187 of 314
where is most (70%) of Na reabsorbed?
proximal tubule
188 of 314
how much Na is reabsorbed by the ascending limb in the loop of henle?
20%
189 of 314
where is he site for regulation for Na handling in kidney? why?
DT&CD as it is what aldosterone works on
190 of 314
how much sodium that is filtered is reabsorbed?
99%, only 1% excreted
191 of 314
where does most water reabsorption happen (70%)?
PT
192 of 314
where does the hormone vasopressin work?
DT+CD how much water we reabsorb
193 of 314
how much water that is filtered is excreted?
1%
194 of 314
where is potassium lost? percent?
most PT 80%, loop 20%
195 of 314
difference between what aldosterone and V Is regulating?
aldosterone = Na, V = water
196 of 314
secretion of H+?
PT (NHE3), principal and alpha IC cell
197 of 314
where is H reabsorbed?
beta intercalated cells
198 of 314
what secretes bicarbonate?
Beta IC cells
199 of 314
what reabsorbs bicarbonate?
alpha IC cell, PT and principal
200 of 314
approximately how long does acute renal failure last?
approx
201 of 314
what is acute renal failure definition?
fall in GFR over a period of hours/days
202 of 314
what are causes of acute renal failure causes?
pre-renal/renal/post-renal
203 of 314
what is a post-renal cause of acute renal failure?
major block in urinary system, urine backs up puts pressure on kidney
204 of 314
probs with acute renal failure?
salt+water retention, urea and creatinine toxic in body, impaired fluid+electrolyte homeostasis
205 of 314
what can be a treatment for acute renal failure?
treat the cause, may need dialysis
206 of 314
general symptoms of acute renal failure?
hypervolaemia (expansion of ECF vol), hyperkalaemia, acidosis, high urea/creatinine
207 of 314
what is hypovolamia?
expansion of ECF volume
208 of 314
what is oliguria?
a very low urine flow rate
209 of 314
why is oliguria caused in acute renal failure?
low GFR
210 of 314
what does high urea/creatinine cause in renal failure?
vommiting, nausea, impaired mental function
211 of 314
why is hyperkalemia such a big problem in acute renal failure?
causes heart excitability, tachycardia, increase in heart rate
212 of 314
why is acidosis a problem in acute renal failure?
impacts on eletrically excitable cells, causes depression of activity on CNS neurons (this+heart biggest killer of acute)
213 of 314
why would you have hypovalemia instead of the usual hypervalemia in acute renal failure?
because of an accident bleeding lowers the ECF
214 of 314
what does minimal urinary output suggest and why?
acute renal failure as fall in GFR
215 of 314
what is a pre-renal cause?
hypotension, less to filter, gfr drops, poor perfusion of kidneys
216 of 314
what is a renal cause?
rhabdomyolysis (relase of myoglobin from muscleas crushing injury)- toxic on kidney tubules, gives high K (no secretion +released from damaged cells = tachycardia) low bicarbonate gives acidosis
217 of 314
highest cation inside cell?
potassium, important in crushing injury as release from damaged cells
218 of 314
how do we mop up hydrogen ions?
H combine with bicarbonate so bicarbonate going down shows acidosis
219 of 314
why is an IV saline given?
to treat hyperkalemia + help increase blood vol back to normal, bicarbonate back to normal, minimises acidosis
220 of 314
why would you not give a massive volume of IV to a normal acute renal failure case?
patients already have expansion of ECF vol dont want to make hypertension worse
221 of 314
what does the cotransporter SGT1 and SGLT2 use?
sodium and glucose across the cell
222 of 314
what do cotransporters in the principal cell that use Na use to bring things in?
the sodium gradient
223 of 314
what proteins are on the apical membrane of the principal cell (PT))?
SGLT1, SGLT2, NaPiII, Na amino acid cotransporter, NHE3 (sodium hydrogen exchanger)
224 of 314
how much Na and H2o Does the PT reabsorb?
70%
225 of 314
how much glucose and aa does the PT reabsorb?
100%
226 of 314
where are other Napi proteins found?
intestine and kindyes
227 of 314
how much bicarbonate does the PT reabsorb?
90%
228 of 314
how is water reabsorbed?
water follows sodium- paracellular water reabsorption
229 of 314
anything that disrupts sodium reabsorption distrupts what else?
water reabsorption
230 of 314
what cotransporters are there on the apical m of the principal cell int the PT?
SGLT1+2, NapiII, glucose and amino acid cotransporter
231 of 314
what happens in NapiII YOUNG knockout mouse?
phosphate cant be reabsorbed across PT goes from 2.1 normal to 1.65 in KO of phosphate in plasma
232 of 314
If you take KO NaPiiII OLDER mouse what happens to plasma phosphate levels?
plasma phosphate levels normal able to adapt + upreg other mechanisms, show compensation
233 of 314
what is the impact of not being able to absorb phosphate on young mice?
on bones- abnormal skeletal dev, size of bones are smaller and less dense so cant form bone, brittle or soft bones
234 of 314
how many aa is SGL1 made of?
664
235 of 314
how many amino acids is SGLT2 have?
672
236 of 314
what is both SGLT1 and SGLT2?
monomer, 14 TM
237 of 314
What disease does SGLT2 mutations (21) give?
familial renal glycosuria (glycosuria = high glucose in urine)
238 of 314
how much glucose do you normally reabsorb?
100%
239 of 314
features of familal renal glycosuria?
increased urinary flucose, no general tubule damage, normal plasma glucose, no long term effects
240 of 314
what do carriers of famililal glycosuria have?
slightly abnormally high glucose in urine
241 of 314
what is wrong with the mutations in SGLT2?
some of the protein is missing, deletion mutaton P324...347X
242 of 314
what happens with carbonic acid and the NHE3?
uses sodium gradient to bring Na in and exchanges for H out, H leaves combines with bicarbonate thats been filtered forms carbonic acid disocciates by carbonic anhydrase to co2 + water, carbonic anhydrase is on extracellular surface of apical m,
243 of 314
what happens to the Co2 and water from disociation of carbonic acid extracellularly?
CO2 dffuses across cell, H2O moves into aquaporin on apical m, under influence of intracelullar carbonic anhydrase forms carbonic acid which dissociates to H and bicarbonate H goes again through NHE3, Na bicarbonate transporter HCO3leaves
244 of 314
why do we need bicarbonate anyway?
to maintain body fluid PH
245 of 314
How did they show we need bicarbonate to maintain body fluid PH?
NHE3 KO mice
246 of 314
what happened in an NHE3 KO mice?
cant reabsorb bicarbonate , 24.2mmol usually but 21.1 mmol in ko HCO3, plasma PH 7.33 --> 7.27 have acidosis ave a lower bp
247 of 314
what does NHE3 KO cause?
acidosis
248 of 314
what are the 2 basic systems of secretion in the PT?
transport proteins involved transport 1) organic cations 3) organic aninos by transport proteins
249 of 314
what do transporters on the basolateral mm allow?
rapid removal oand removal of plasma protein bound substances
250 of 314
what is a problem with secretion across the PT?
foreign compounds like drugs (penicillin+chemotherapy) , higher penicillin dose as some is lost by PT
251 of 314
what is the loop of henle for?
ability to concentrate urine, reabsorbs Na, Cl+H2O, Ca+Mg, site of action for loop diuretics
252 of 314
what species can concetrate their urine why?
us, birds and mammals as we're the only ones with a loop of henle
253 of 314
where is the site of action for loop diuretics?
loop of henle
254 of 314
what is the thin descending limb permeable to?
water but not sodium and chloride
255 of 314
what is the thin then thick ascending limb permeable to?
only sodium, cl, ca and mg, NOT water
256 of 314
what part of theloop of henle is really important for sodium and chloride handling?
thick ascending limb
257 of 314
what does NKC22 stand for?
sodium potassium 2 chloride co transport protein num 2
258 of 314
what does NKCC2 need to function?
1 sodium, 1 potassium and 2 chloride
259 of 314
what is on the basapical m of the thick ascending limb?
NKCC2 and ROMK
260 of 314
where does the chloride that enters the thick ascending limb go?
leaves the cell through CLCK
261 of 314
what is bartinin?
a beta or accesory subunit, CLCK only work properly when baritnin is present
262 of 314
how is potassium recycled across the apical membrane in the thick ascending limb?
enters the cell through NKCC2 leaves through a potassium transporter ROMK back to where it came from
263 of 314
what does ROMK stand for?
rat outer medullary potassium channel
264 of 314
what is another name for ROMK?
Kir1.1
265 of 314
what happens wih K at the end of the PT?
at end of PT there is insufficient potassium in tubule fluid to support the function of NKCC2
266 of 314
absence of romk (kir11)
not enough K in tubule fluid to reabsorb by Na and chloride, drives reabsorbs reabsorption of water in kidney
267 of 314
ability to concentrate urine depends on what?
thick ascending limb proteins- NKCC2, CLCK (+bartin) + ROMK (kir1.1)
268 of 314
net reabsorption of sodium and chloride dirives absortpion of what?
calcium and magnesium
269 of 314
what kind of transport does mg and ca take across the thick ascending limb?
paracellular- between cells
270 of 314
what is barrters syndrome?
recessive disease (inherited)
271 of 314
what hapens in bartters syndrome?
salt wasting (too much NaCl in urine) polyuria, water follows NaCl- so hypotension, hypokalemia(2ndary effect from CD) metabolic alkaloisis (high PH cos CD) hypercalciuria (ca follows NaCl) nephrocalcinosis (kidney stones as calcium in urine)
272 of 314
what can be mutated in bartters syndrome?
NKCC2, CLCK bartinin (stops cNKCC2 working cl accumulates in cell), ROMK (KIR1.1)
273 of 314
what happens in ROMK (KIR1.1) KO in thick ascending limb?
excrete Na+Cl in urine (salt wasting), produce more urine-polyuria =both same as humans but humans alkalosis, animals- acidosis, Ph+ K not different in mouse by hypokalemia in umans
274 of 314
what is fractional excretion?
how much is filtered 100%- everything filtered excreted
275 of 314
how do you work out fractional excretion?
amount in urine/amount filtered
276 of 314
what happens if you get a fractional excretion of more than 100%?
excreted more than you filtered, you secreted some too
277 of 314
less than 100% fractional excretion?
onluy some reabsrobed of what filtered
278 of 314
how do you compare WT and KO mice in ROMK ascending limb?
compare see if differences in fractional excretion = tubule defect (impacts tubule and ion)
279 of 314
why is mouse KO ROMK not perfect model?
animals have an acidosis, humans-alkalosis, no difff in K in mouse but hypokalemia in humans
280 of 314
what do loop diuretics do?
make you wee more, inhibit Na reabsorption therefore inhibit water reabsorption
281 of 314
what loop diuretics are there?
furosemide and bumetanide
282 of 314
where do loop diuretics work?
thick ascending limb
283 of 314
what protein does furosemide and bumetanide work on?
NKCC2- binds to pro stops it working, block NKC22 block reabsorption of Na+Cl o salt waste+polyuria but gets rid of excess fluid
284 of 314
What is loop diuretics used to treat?
high bp particularly as result of oedma, get rid of excess fluid
285 of 314
what are the side effects from loop diuretics?
side effects like barrters- hypokalemia,high Ca in urine, increased kindey stone formation
286 of 314
what is the early DT for?
reabsorption of Na and Cl, rebasorption of Mg
287 of 314
what parts is the DT tubule split into?
early and late
288 of 314
what diuretics in the early DT sensitive to?
thiazide diuretics
289 of 314
what do diuretics do?
inhibit sodium reabsorption therefore water resabsorption
290 of 314
what diuretics is the early DT sensitive to?
thiazide diuretics
291 of 314
what does the early DT reabsorb?
Na+Cl + Mg
292 of 314
what channels aids the net reabsorption of sodium in the early DT?
NCC and sodium potassium ATPase
293 of 314
what proteins are on the basolateral membrane in the early DT?
CLCK (bartin) and sodium-potassium ATPase
294 of 314
what protein do we not knw about in the early DT?
mg reabsorption pathway
295 of 314
what kind of disease is giltemans?
recessive
296 of 314
what are the symptoms of giltemans syndrome?
salt wasting and polyuria (bartters), hypotension (bartters), hypokalemia (bartters), metabolic alkalosis (bartters), Hypocalciuria
297 of 314
what is the difference between bartters and giltemans?
bartters- high calcium hypercalcuria (thick ascending limb), giltemans- hypocalcuria (early DT)
298 of 314
what is giltemmans caused by?
mutation in NCC (brings Na and Cl into the cell)
299 of 314
whats difference about the amount of calcium in the early DT?
absorb more calcium than expected in early DT
300 of 314
where are NCC proteins?
mutations are scattered throughout the NCC protein
301 of 314
why are xenopus oocytes used in expression studies?
inject RNA they will make the protein of interest
302 of 314
what was the functional analysis done on NCC on xenopus oocytes?
absence of NCC or presence NCC or presence mutant NCC, see how much sodium 22 goes into oocyte
303 of 314
what mutations did they do to NCC
GV (glycine 627 valine) + AG(arginine 935 Glutamine)
304 of 314
what happened in these mutations?
less sodium reabsorbed
305 of 314
what are the NCC mutations called? why?
trafficking mutations- NCC does not get to early DT
306 of 314
example of a thiazide diuretic?
clorothiazide
307 of 314
what do thiazide diuretics target (early DT)?
NCC
308 of 314
what do thiazide diuretics used to treat?
high blood pressure
309 of 314
what side effects does thiazide diuretics give?
giltelmans syndrome
310 of 314
where is the problem in the kidney with giltelmans?
early DT
311 of 314
where is the prob that gives bartters?
loop of henle
312 of 314
what happens to the carriers of bartters and giltelmans?
carriers have a lower bp, hypotension when young portects against hypertension!
313 of 314
what do principal cells do?
sodium, water reabsorption, k+ + H+ secretion
314 of 314

Other cards in this set

Card 2

Front

what would a high osmality be?

Back

high ion and solute content

Card 3

Front

what is the other name for vasopressin?

Back

Preview of the front of card 3

Card 4

Front

what does vasopressin do?

Back

Preview of the front of card 4

Card 5

Front

where is vasopressin made?

Back

Preview of the front of card 5
View more cards

Comments

No comments have yet been made

Similar Biology resources:

See all Biology resources »See all Physiology resources »