Week 1 Renal Intro Flashcards
1
Q
6 Functions of the kidney
A
- Filtration of blood,
- Detoxification (incl drugs),
- Regulation of blood pressure,
- Regulation of blood pH,
- Regulation of haematopoiesis
- Making vitamin D
2
Q
Does the kindey work by filtering out toxins?
A
No
There are infinate ammount of toxins including new ones that will appear, selectively binding to and excreteing these would be evolutionarily wrong.
Intead we know the handful of molecules that we do want to keep.
The kindney works by filtering all molecules from the blood. Placing into a holding cell (the nephron) and then selectively recovering the molecules we want.
3
Q
What is the size of molecules that can get through the kidney’s filter?
What deos this means for the pressure required?
A
Anything above 4nm or 40A gets filtered entirely.
Anything less than 1.8nm or 18A is completely free flowing.
This is very fine therefore we need a high pressure to force these molecules through.
4
Q
What is the name of the kidney’s finest filter?
A
Slit diaphragm
5
Q
What does the slit diaphragm look like?
What is the name of the molecules that make it up?
A
You have cells over the capillaries called foot processes, these look like interlocked fingers.
Between the fingers you have the slit diaphragm.
This consists of chains of overlapping nephrin molecules. The points at which they don’t overlaps are the pores that allow molecules through.
6
Q
How does osmotic pressure impact that pressure required to push molecules through the filter?
A
On the blood side there are more molecules in total such as large protiens and RBC.
This will create an osmotic pressure that will want to draw water back through the filter in order to even out the concentrations.
This therefore increases the pressure required to pass molecules through the filter even more.
7
Q
Why does the pressure need to be right?
A
If it’s too low stuff won’t filter, if it’s too high the filter can get damaged
8
Q
Basic anatomy of a nephron?
A
Blood enters via an afferent arteriole into the glomerulus where molecules are filtered out.
It then leaves via the efferent arteriole and follows the tubule where it recovers what it needs.
9
Q
Anatomically what is the filter of the kidney called?
A
Glomerulus
10
Q
How are does is filtration pressure in the glomerulus controlled?
A
If the afferent arteriole (entering, this blood affects the filter) is restricted then capillary pressure is reduced and filtration reduces.
If the efferent arteriole (leaving, this blood if effected by the filter) is restricted then capillary pressure is increased and filtration increases
11
Q
How does the slit diaphragm remove small particles that get clogged?
A
Through pinocytosis and the creating of visticles.
However some things are too big for pinocytosis then we need further filters.
12
Q
What is the corsest of the glomerular’s filters?
A
These are fenestrae.
Fenestrae are holes in the endothelium of the glomerulus.
These are apprix 100nm and prevent large proteins.
13
Q
What is the medium corse glomerular filter?
A
This is the glomerular basement membrane.
This prevent proteines bigger than albumin from ever getting through along with charged particles.
14
Q
What is the overal anatomy of a renal corpuscle + glomerulus?
Draw it out
A
Don’t have to include all these things.
However definately include:
Afferent/efferent arterioles
Endothelium
GBM
Podocytes
Bowman’s space
Proximal tubule
Parietal epithelium
15
Q
Order the three golmerular filters in order of fineness
A
Finest
- Slit diaphragm
- Gomerular basement membrane
- Fenestrae in the endothelium
Corsest
16
Q
How are the three glomerular filters cleaned?
A
Endothelium:
Cleaned by blood flow and phagocytes
GBM:
Renewed by mesangial cells
Slit diaphragm:
Cleaned by pinocytosis by podocytes
17
Q
Where do the glomerular capillaries lie within a renal corpuscle?
A
18
Q
In real anatomy what is a renal corpuscle and what is a glomerulus?
A
Glomerulus: The capillaries plus the podocytes, the inner part that does the filtering
Renal corpuscle: The whole contained filter unit including the bowman’s space and parietal epithelium
However the renal corpsuscle is commonly miss reffered to as the glomerulus and you won’t be missunderstood if you use it.
19
Q
How many nephron’s does one human have?
A
1’000’000
If born to a healthy mother
50’000-100’000
If born to a starving mother
20
Q
Fill in the following values:
Blood flow to kidneys L / min
Plasma flow to kidneys L /min (assuming normal haematocrit of 0.45)
Rate of filtration through glomeruli L /min
A
Blood flow to kidneys - 1.2L / min
Plasma flow to kidneys – 0.66L /min (assuming normal haematocrit of 0.45)
Rate of filtration through glomeruli (summed across all) = 0.13L /min
-> 20% of plasma is removed as filtrate.
Most of this however is recovered again hence why you don’t pee everything
21
Q
Describe the relationship between GFR and plasma creatinine?
A
As GFR decreases creatinine builds up in the plasma
22
Q
Why is creatinine useful for measuring GFR?
A
Because unlike urea creatine is not reabsorbed in the tubule as all.
Therefore the filtration rate of creatinine will equal the excretion rate of creatinine and from this GFR can be measured
23
Q
What is the basic equation for GFR?
A
24
Q
Fill out the following
A
25
What is the different in a cross section of a distal vs proximal tubule?
Proximal tubules have microvilli, distal tubules don't
26
What types of channels are present in the nephron epithelia?
Primary Active Transporters (Na+/K+ ATPase and H+ ATPase). These are the only ones that use energy.
Solute Carrier Family (SLC) proteins – about 300 – many are co-transporters powered by established conc gradients (eg in Na+).
Aquaporins (Water channels)
Ion Channels
Protein endocytosis receptors (catch proteines and gobble them up)
27
The active transporter Na+/K+ ATPase will have what effect on K+ and Na+ inside of the epithelial cell?
High Na+ outside
High K+ inside
28
What does Na+/H+ exchanger SLC9A3 mean?
This import Na+ from the urinary space and exchanges a proton
We are not expected to know the names of every SLC proteins.
However would be asked to interpret what Na+/H+ exchanger means
29
What does a Sodium chloride co-transporter SLC12A3 mean?
30
How is glucose recovered?
How does this lead to "sweet" urine in diabetes mellitus?
Most is recovered using SLC5A2 at a Na+:glucose = 1:1ratio.
Once urine concentrations are really low it is done at a more costly Na+:glucose = 2:1ratio.
Overall the Na+ is finite therefore once plasma glucose and therefore filtrate glucose concentrations become too high this is overwhelmed and the urine ends up with high glucose.
Note: diabetes means polyurea, mellitus means sweet
31
What are OCTs?
Organic cation transporters
These are passive and follow a gradient intot he epithelial cell.
They are used to excrete cations into the urine which are too charged to get through the GBM.
32
What is the method by which organic cations are excreted from plasma into urine?
They go from plasma in the epithelial cells via OCTs.
They are then pumped into the urine via a proton anti porter (MATE anti porter) and an ATP pump.
The protons gradient is acheived by and Na+/H+ antiporter.
33
Examples of organic cations which are excreted via the OCT system?
* tetraethylammonium (TEA)
* 1-methyl-4-phenylpyridinium (MPP)
* endogenous amines, such as dopamine
* therapeutic drugs, such as cimetidine and morphine
* cationic xenobiotics, such as antihistamines
In sum:
Amines
34
What are OATs?
Like OCT but for anions
35
How do the OATs work for methotrexate, furosemide and penicillin
They work by exchanging OAs for α-ketoglutarate which is then imported using sodium.
36
Examples of OATs using passive transport the whole way
37
Why is a build up of methotrexate, furosemide and penicillin dangerous for the proximal tubule whereas amines aren't?
Because these OATs use an active pump to pull the OAs in but have passive drift out therefore if the drift is weak this can cause build up to toxic levels with the epithelial cell.
Where OCTs use passive drift into the epithelial cell but actively pump out therefore concentrations will rarely ge to toxic levels
38
What does probenicid do?
Blocks the OAT/α-ketoglutarate antiporter.
Can be used alongside OAs to prevent toxic buildup in the kidney but also if you want to decrease their metabolism if a drug is particularly expensive.
39
How is phosphate recovered?
Using a Na+ co-transporter
40
How is bicarb recovered?
Bicarb combines with a proton where it can become CO2. This can then pass the cell membrane freely where it can then bicarb again.
The proton is pumped back out.
The bicarb is then brought out of the cell and into the plasma using a Na+ co transporter.
This system means we can recover bicarb without changing the pH of the urine as H+ stays the same conc.
41
What are the backups to the bicarb recovery if the body is in acidosis?
Phosphate can pick up extra protons as can ammonia if phosphate gets overwhelmed.
42
90% of acid base correction is done automatically in the proximal tuble. The remaining 10% is done via homeostatic feedback in the collecting duct.
What are the names of the cells here that make your body more acidic and more alkaline?
These type A cells throw H+ out of the body (make the body more alkaline)
These type B cells throw H+ back into the body (make the body more acidic)
hint: type A personalities could cope with the stress with alkoholism
43
How is water recovered in the proximal tuble?
By removing salts from the urine it becomes more diluted than the blood therefore water is passively recovered through aquaporins via osmosis.
44
How is calcium recovered in the proximal tubule?
Once the salts are recovered actively the water follows via aquaporins.
This then leaves a high concentration of calcium which will also passively recover via gaps in the tight junction betwen epithelial cells
45
How is protein recovered in the proximal tubule?
Big proteins shouldn't of made it through the glomeruler but small ones such a albumin do.
These are recovered using protein endocytosis receptors such as Megalin
46
Once urine has left the proximal convoluted tubule how much has been recovered and what has happened to the concentration and acid/base balance?
65% has been recovered.
However because this has been solute recovery with water naturally following the concentration gradient the concentration stays the same and is roughly iso-osmotic
There has been some automatic acid/base correction however this is mostly active in extreme circumstances and the pH should be more or less the same.
47
What is the mechanism of recovery in the loop of henle?
Thick ascending limb has active transport of sodium and chlorine into the tissue outside the tubule causing it to become hypertonic.
The thin descending limb contain aquaporins only and so water is drawn out into the hypertonic space.
This causes the filtrate to become hypertonic thus ions naturally move out in the thin ascending limb where there are channels for ions only.
48
How much has been recovered after the loop of henle?
An additonal 10% of water and 25% of NaCl.
65% of both in proximal convoluted tubule therefore after loop of henle we have:
75% of water recovered and 90% of NaCl.
49
How does the Sodium chloride co-transporter SLC12A2 work in the thick ascending limb?
50
How does blood flow in the medulla area prevent the hypertonacity from just washing away?
It also loops down and up with the loop of henle but in the opposite direction.
The effect of this is that as blood travels down past the hypertonic ascending limb it becomes more hypertonic, however as this then travels back up again past the less hypertonic descending limb water is drawn in and thus the space remains hypertonic.
51
What is the name of the vessel that passed around the loop of henle?
Vasa recta
52
What is the name os the part of the kidney that contains most of the loops of henle thus all working together to create a hypertonic space?
Renlal medulla
53
What happens in the distal convoluted tubule?
What is the final ammounts recovered after the distal tubule?
There is some further salt recovery but no water recovery.
The final amounts extracts is:
95% solutes
75% water
54
What happens in the collecting duct?
How much is recovered by the end of it?
This begins with rather dilute filtrate.
There is some further salt extraction (2-5%)
The collecting duct contains aquaporins which are regulated by vassopressin. So the ammount of water recovered can vary depending on needs is anything up to 24% (99% total).
In the proximal collecting duct we are in the cortex so some water can leave but only to point of equilibrium with plasma (0.29).
The distal collecting duct passes through the hypertonic medulla therefore much more water may leave here.
55
What can happen to urea in the collecting duct during dehydration?
In cases of extreme dehydration vassopressin can begin to release some of the concentrated urea in the collecting duct into the medullary space thus increasing the hypertonicity even further resulting in even more water recovery.
Basically you recover more water at the expense of urea excretion.
56
What is a renal pyrimid?
One unit of kindney which is a collection of corpsucles and nephrons all leading to one collecting duct.
57
What is the side effect of having all of these long blood vessels passing by eachother in the kidney?
Just like the effect with tonicity in the vasa recta or a bad heating system or the penguin's feet there is oxygen exchange betweent he arteries and viens passing close to each other.
This take oxygen out of the arteries and into the viens thus the kidney is particularly sensitive to ischemia.
58
Summary of what is recovered at different stages and the tonicity of the filtrate at:
Proximal tubule
Decsending limb of loop of henle
Acsending limb of loop of henle
Distal tubule
Proximal collecting duct
Distal collecting duct
Proximal tubule: salts and water, equilibrium
Decsending limb of loop of henle: water only, hypertonic
Acsending limb of loop of henle: salt only, hypotonic
Distal tubule: more salt, hypotonic
Proximal collecting duct: water only, equilibrium
Distal collecting duct: more water and urea in extreme cases. Can become hypertonic.
59
What are the 5 things that can be controlled with regards to the kidneys?
60
Three ways to control blood flow into kidneys. Which two are responsible for maintaining a stable filtration rate?
The systemic blood pressure can vary widely. Hence the constriction of the arterioles is the fine tuning that allows a constant filtration rate over a w ide range of sytemic blood pressures.
61
Two mechanisms of glomerula blood flow homeostasis. Acute and chronic.
1. Direct pressure sensing in the afferent arteriole – the myogenic mechanism. Acute, useful when sprinting for example.
2. Monitoring the performance of the nephron - tubuloglomerular feedback. Chronic
62
Why is the tuboglomerular feedback done individually by each nephron and not systemic
Because if one nephron gets damaged this would then influence the whole kidney. Whereas if it done nephron by nephron then the blood flow can be appropriate for the state of each nephron.
63
What is the macula densa?
The area of the nephron where the distal tuble makes contact with the glomerulus in order to feedback nephron performance to the arterioles.
64
How does the macula densa work?
65
What do juxtraglomerula cells do globally and locally?
Globally they release renin
Locally they release adenosine to constrict afferent glomerula arterioles
66
What inhibits juxtaglomerula cells from releasing renin?
Macula densa secreting NaCl
Baroreceptors detecting raised glomerular bp
67
What are the three actions of angiotensin II which directly increase BP?
* Increased sympathetic activity
* Ateriolar vasoconstriction
* Tubular Na+Cl- reabsorption
68
What is the mechanism by which angiotensin II causes Na+Cl- reabsorption?
It promotes the Na+/H+ exchanger
69
How does aldosterone work on the kidney?
It is a steroid hormone so it acts on gene expression in the nucleus.
It increases expression Na+ uniporters and Na+K+ transporters recovering more Na+.
It also increases expression of H+ ATPase H+ exporters.
There is more K+ being brought into the cell because of the Na+K+ increase therefore more is exported via passive channels. There is also less H+ being directed toward the H+K+ trnasporter so less K+ being recovered. The result is less K+ recovered.
70
After encouraging the release the aldosterone what is the second non-direct way in which angiotensin II contributes to blood pressure?
Acts on the posterior pituitary to release vasopressin
71
Where does vasopressin act in the kidney?
It acts on the collecting duct cells
72
How does vasopressin influence the collecting duct cells?
Collecting duct cells decide how much aquaporin to put in the membrane or store in vacuoles. Vasopressin encourages more aquaporin to translate tot he membrane
73
Describe an additional effect of sympathetic activation on the RAAS that act directly on the glomerulus?
Renal nerves release noradrenaline with constricts both glomerular efferent and afferent arterioles, the efferent constricting results in decreased flow but increased pressure to drive perfusion. Noradrenaline also directly promotes renin release.
74
How does ANP come into play regarding blood pressure?
ANP (from the heart) (atrial natruietic peptide) blocks the Na+ re-uptake channel in collecting ducts and causes more sodium loss.
ANP is released is released as blood pressure rises so acts as a safeguard against runaway BP
75
How does PTH act on the kidneys to increase calcium absorption?
It promotes formation of Ca2+ uptake channels and inhibits sodium/phosphate co transporters so there is less phosphate to mop up calcium and make bone leaving more free calcium
76
What are the two mechanisms by which vitamin D enables calcium uptake in the kidney
It allows for the creation of calbindin inside the kidney cells, which enables calcium to collect inside the cells without causing signals. It is also nessecary for the transporter that allows calcium to leave the cells into the blood.
77
How does the Na+/H+ antiporter respond to pH?
The lower the pH the more active it becomes thus eliminateing H+ in urine and bringing pH back up.
78
Where does the majority of potassium absorption occur? How is it regulated?
90% occurs early on in the nephron and is unregulated
79
Two mechanisms by which aldosterone cause K+ loss?
1. Primarily enhances Na+/K+ antiporters
2. In intercalted-alpha collecting duct cells it uprugulates H+ATPase pumps, this lowers the ammount of cellular H+ available for H+/K+ antiporters thus less K+ is absorbed
80
Give a summary of the collecting duct cell types?
81
In addition to aldosterone what are the 3 other ways potassium is regulated?
1. More extracellular potassium results in more potasium flowing from the ECF into principle cells
2. Low K+ diet causes the excretory K+ uniporter to get recycled and therefore there are less
3. High K+ diet causes excretory channel to accumulate
82
What is the relationship between acidosis/alkalosis and hyper/hypokalaemia
1. Acute acidosis results in hyperkalaemia - hint, bananas like acidic soil
2. Acute alkalosis results in hypokalaemia
3. Chronic acidosis results in hypokalaemia due to inefficient sodium uptake in the proximal tubule therefore more of everything gets flushed out including potassium.
83
How do loop diuretics work?
They block SLC12 A2 which prevents salt recovery in the loop of henle. This in turn prevents water recovery in the loop of henle also
84
What is a surprising blood pressure side effect of loop diuretics?
They also inhibit Na+ uptake in the macula densa, if the macula densa senses low Na+ then it thinks BP is low and ramps up prostaglandins -> renin etc.
So although they are diuretics they actually increase BP
85
What is the loop diuretic side effect that relates to calcium?
With less salt recovery there is also less calcium recovery.
Hypocalcaemia isn't so much of an issue as you can give more calcium.
The problem is increased calcium in the urine can result in kidney and bladder stones
86
Side effect of loop diuretics relating to potassium?
Less Na+ recovery in the LOH means more Na+ in the collecting duct therefore more sodium exchange with potassium in principle cells hence hypokalaemia
87
How do thiazide diuretics work?
They block Na/Cl uptake in the distal tubule and therefore water resorption in distal tubule
88
How do the side effects compare to loop diuretics?
1. Decreases BP instead of raises
2. Doesn't result in hypercalcuria therefore no kidney/bladder stones
3. Still get some hypokalaemia
89
How do potassium sparing diuretics work? What is their drawback?
They block sodium uptake in the principle cells in the collecting duct.
This is where the issues with potassium occur hence by blocking this potassium is spared.
Drawback is only 2-5% of NaCl is recovered here so the effect is quite small.
90
How does spironolactone work?
Blocks aldosterone hence works on the same part as potassium sparing diuretics
91
Side effect of spironolactone?
Is similar to oestrogen so acts on oestrogen receptors
92
How do carbonic anhydrase inhibitors work?
More bicarb in lumen, resists egress of water osmotically
93
Summary of where each diuretic acts
94
Bartter's syndrome impairs SLC12A2.
What do you think the effect is going to be?
a) Loss of Na+, K+, H2O, hypocalcuria
b) Loss of Na+ K+, much H2O; hypercalcuria
c) Na+ loss, K+ retention, high aldosterone
d) Diabetes insipidus (polyuria, polydipsia)
e) Volume expansion (body), hypertension
b) Loss of Na+ K+, much H2O; hypercalcuria
Will act in the same way as a loop diuretic
95
Gitelman's syndrome impaires SLC12A3
What do you think the effect is going to be?
a) Loss of Na+, K+, H2O, hypocalcuria
b) Loss of Na+ K+, much H2O; hypercalcuria
c) Na+ loss, K+ retention, high aldosterone
d) Diabetes insipidus (polyuria, polydipsia)
e) Volume expansion (body), hypertension
a) Loss of Na+, K+, H2O, hypocalcuria
Same effect as a thiazide diuretic
96
Liddle's syndrome results in a hyperactive ASC (=ENaC)
What do you think the effect is going to be?
a) Loss of Na+, K+, H2O, hypocalcuria
b) Loss of Na+ K+, much H2O; hypercalcuria
c) Na+ loss, K+ retention, high aldosterone
d) Diabetes insipidus (polyuria, polydipsia)
e) Volume expansion (body), hypertension
e) Volume expansion (body), hypertension
Opposite effect of a K sparing diuretic.
Can be treated with a K sparing diuretic
97
Pseudohypoaldosteronism is due to an inactive ASC (=ENaC)
What do you think the effect is going to be?
a) Loss of Na+, K+, H2O, hypocalcuria
b) Loss of Na+ K+, much H2O; hypercalcuria
c) Na+ loss, K+ retention, high aldosterone
d) Diabetes insipidus (polyuria, polydipsia)
e) Volume expansion (body), hypertension
c) Na+ loss, K+ retention, high aldosterone
This mimics the effects of hypoaldosteronism and aldosterone is produced in response to this. However it can't work as the transporter it acts on is defective.
98
There is such things as inactivating mutations of aquaporins.
What do you think the effect is going to be?
a) Loss of Na+, K+, H2O, hypocalcuria
b) Loss of Na+ K+, much H2O; hypercalcuria
c) Na+ loss, K+ retention, high aldosterone
d) Diabetes insipidus (polyuria, polydipsia)
e) Volume expansion (body), hypertension
d) Diabetes insipidus (polyuria, polydipsia)
The opposite effect of vasopressin
99
In someone with Addison's what do you think the effect is going to be?
a) Loss of Na+, hyperK+, hypovolaemia
b) Loss of Na+ K+, H2O; hypercalcuria
c) Whole body hypo-osmolarity
d) Diabetes insipidus (polyuria, polydipsia)
e) Volume expansion (body), hypertension
a) Loss of Na+, hyperK+, hypovolaemia
Can't make aldosterone therefore same effect as giving someone a potassium sparing diuretic
100
What do you think the effect is psychogenic polydipsia?
a) Loss of Na+, K+, hypovolaemia
b) Loss of Na+ K+, H2O; hypercalcuria
c) Whole body hypo-osmolarity
c) Whole body hypo-osmolarity
101
What does renal agenesis mean?
Lack of formation of a kidney.
Bilateral - rare and fatal after birth
Unilateral - 1/500, doesn't cause any problems really
102
How is renal agenesis diagnosed?
Ultrasound
Used to be diagnosed at birth and a baby would have flat features as the amniotic cavity contains no urine the foetus gets pressed against the uterine wall.
This is called potter's facies
103
What is the most common form of congenital kidney disease?
Autosomal dominant polycystic kidney disease.
Caused by kidney cells not being able to detect direction of urine flow therefore growing in all directions.
Normally becomes detectable in people in their 30s and leads to end stage kidney disease by the time they are 60.
Sometimes appears at birth depending exactly what gene is affected.
104
What can be a problematic version of a duplex ureta?
If they connect pre bladder it's fine (right)
However sometimes they skip the bladder and connect to the urethra resulting in constant dribbling urine and frequent infections (left) (is operable).
105
What is a pelvic kidney?
When is it a problem?
This is where one of the kidneys remains in the pelvis instead of in the lumbar region.
Normally this isn't a problem however if someone becomes pregnant the kidney can become crushed by the foetus.
106
What is a horseshoe kidney?
When might a horseshoe kidney become a problem?
When two kidneys fuse together.
Again becomes a problem is childbirth when competing for space.
107
What is a congenital abnormality of Cloacal Development?
This is when the correct positioning of Rathke and Tourneaux folds fails.
Results in various scenarios where the rectum is connected to the urethra or uterus resulting in infections.
In med it can also result in hypospadia where the tip of the urethra is on the base of the penis.
