Urinary System Flashcards
1
Q
How is ion content of urine adjusted?
A
Aldosterone
2
Q
What does freely filtered mean? What is freely filtered?
A
There is the same concentration in filtrate and plasma.
E.g. Fluids and small solutes
3
Q
What is the kidney functions?
A
- excretion of metabolic products
- excretion of foreign substances
- homeostasis of cell volume
- regulation of blood pressure
- secretion of hormones
4
Q
What is the glomerular filtration rate?
A
GFR = the amount of fluid filtered from the glomeruli into the bowman capsule per unit of time - sum of filtration rate of all functioning nephrons
ml/min
Ultrafiltration coefficient is the membrane permeability and surface area
5
Q
What is normal GFR?
A
Around 120 ml/min
6
Q
What is renal tubular acidosis?
A
It is caused by hyperchloremic metabolic acidosis where there is an inability to acidity urine below 5.5 pH leading to impaired growth and hypokalaemia.
- causes acidosis because it proton-ATPase pump fails. Protons diffuse into cell but not into filtrate leading to tubule acidosis
7
Q
What is bartter syndrome?
A
It is a defect in the thick ascending limb of Henle leading to excessive electrolyte secretion, premature birth, polyhydramnios, severe salt loss, hypokalaemia and moderate metabolic alkalosis
- effects Na/K/Cl transporter.
Tubular fluid has high osmotic pressure as salts are reabsorbed so water is not reabsorbed
8
Q
What is fanconi syndrome?
A
Increased secretion of low molecular weight proteins, uric acid, phosphate, glucose and bicarbonate. Disease of proximal tubules associated with renal tubular acidosis
- caused by dent’s disease which is acidification of endoso even preventing protein reabsorption
9
Q
What equations can be used to calculate GFR?
A
GFR = net ultrafiltration pressure x ultrafiltration coefficient
-ultrafiltration pressure = hydrostatic pressure in capilleries - hydrostatic pressure in tubule - osmotic pressure in capilleries
GFR = RPF x filtration fraction
ml/min
10
Q
What are the main components of the urinary system?
A
Kidenys, ureters, bladder and urethra
11
Q
What muscles are posteriorly associated with the kidneys?
A
psoas Major muscle, Quadratus lumborum muscle and Transversus abdominus
12
Q
Describe the blood supply to the kidneys.
A
Renal arteries are short branches directly from the abdominal aorta. Renal veins drain into the inferior vena cava
13
Q
Describe the structure of the kidney
A
The kidney is surrounded by a dense fibrous capsule.
The medulla is straited due to arrangement of tubules and micro-vessels. The kidney is multilobular
Urine is expelled from each lobe cdrains through it’s own renal papilla into minor calyx ➡️ these fuse to form renal pelvis which becomes the ureter
14
Q
How is urine transported from the kidneys to the bladder?
A
Urine is transported through the ureters to the bladder. The fluid is moved by peristalsis and when the bladder fill the ureters are closed off at the ureterovesical valve. The ureters enter the bladder at the ischial spinal level
15
Q
Where are 3 common sites for ureteric contraction (and kidney stone trapping)?
A
- pelviureteric junction: where the renal pelvis becomes ureter (most common)
- where ureter crosses pelvic brim
- where ureter transverses bladder
16
Q
What cell type lines the urinary tract? How are they adapted to their function?
A
UROTHELIUM (transitional epithelium)
- 3 layers, slow turnover, large luminal cells with tight junctions and thick apical plasma membrane leading to low permeability
- pleater borders of urothelial cells allows unfolding and flattening as bladder fills
17
Q
What holds the urethra in place?
A
pubovesical ligament
18
Q
At what volume does bladder contraction begin to be initiated?
A
300-400 ml
19
Q
Describe the micturation reflex (allows for urination)
A
Trigone stretch is detected by pelvic splanchic nerves of parasympathetic nervous system ➡️ increase stretch increases impulses to PNS nerves ➡️ detrusor muscle stimulated to contract and internal uretral sphincter to open
sympathetic innervation by hypogastric plexus.
cerebral cortex allows voluntary control component ➡️ motor neurones to external uretral sphincter contract, inhibition of this allows relaxation and urine to flow.
information is relayed by pontine-micturition centre in the brain
20
Q
What are the main constituents of a nephron
A
Glomerulus (capillary bed involving an afferent arteriole and an efferent arteriole) ➡️ Bowman’s capsule ➡️ proximal convoluted tubule ➡️ loop of Henle ➡️ distal convoluted tubule ➡️ collecting duct
21
Q
How is the Bowman’s capsule and glomerulus specialised to perform ultrafiltration?
A
Occurs in the renal corpuscle comprising of glomerulus, podocytes and bowman’s capsule.
- High pressure in glomerulus as afferent is larger than efferent (pressure gradient) & blood pressure from aorta
- Fenestrated capillary endothelium and specialised basal lamina allow for filtration (only small substances)
- Podocytes have feet like projections that wrap around the capillaries and allow further blood filtration (only things that can pass through the slits created)
All the above contribute to ultrafiltration where ions and molecules
22
Q
What epithelium lines the proximal convoluted tubule?
How are they specialised?
A
cuboidal epithelium
Tight junctions making them water impermeable, but aquaporins allow H2O reabsorption. Lots of mitochondria for active transport. Brush border on apical surface to increase surface area for exchange
23
Q
What is the function of the proximal convoluted tubule?
A
reabsorption of substances from the filtrate
24
Q
What substances are reabsorbed by the proximal convoluted tubule? How are they reabsorbed?
A
- sodium
- water & anions (follow sodium)
- glucose via Na+/glucose co-transporter
- amino acids via Na+/amino acid co-transporter
- protein uptake by endocytosis
25
How does the epithelium lining the ascending and descending loops of henle differ?
descending = simple squamous
| ascending limb: cuboidal epithelium
26
Where is the juxtaglomerular apparatus found and what does it do?
located at the distal convoluted tubule and has endocrine function. detection of low BP or low sodium content leads to renin secretion
- receive BP information from juxtaglomerular cells of afferent arteriole
- information about sodium from macula densa cells on distal convoluted tubule
27
What is primary urine?
A clear fluid (ultrafiltrate), completely free of blood and porteins, is produced containing electrolytes and small solutes via the process of ultrafiltration
28
What are normal values for renal blood flow, renal plasma flow and filtration fraction?
Renal blood flow = around 1L/min
Renal plasma flow = around 0.6 L/min
filtration fraction = around 0.2
29
What clinical events might effect GFR and what might their effect be?
severe haemorrhage ➡️ decreased GFR due to low BP
obstruction in nephron tubule ➡️ decreased GFR as hydrostatic pressure in tubule increases
reduced plasma protein concentration ➡️ increased GFR (due to increased osmotic pressure)
small changes to blood pressure does not effect GFR due to autoregulation
30
How does autoregulation ensure fluid and solute excretion remain reasonably constant in the kidney?
Myogenic mechanism: contraction of smooth muscle when it's stretched
e.g. increase BP ➡️ stretching ➡️ contraction of arteriole ➡️ vessel resistance increases ➡️ blood flow reduced and GFR remains constance
- contract arterioles ➡️ decrease GFR
- dilate arterioles ➡️ increase GFR
tubuloglomerular feedback: sodium concentration is detected by macula densa cells which can control renin-angiotensin systenm
31
What is clearance? what is the equation and units for clearance?
Clearances is the number of litres of plasma that are completely cleared of the substance per unit time
clearance (ml/min) = concentration in urine x urine production rate/ concentration in plasma
32
When does GFR = clearance? Give example molecules
When a molecule is freely filtered and neither reabsorbed or secreted then the GFR = clearance
Inulin (plant polysaccharide)
Creatinine
33
What is the renal plasma flow?
The volume of blood plasma delivered to the kidneys per unit time
ml/min
34
What molecule can be used to measure renal plasma flow and why?
PAH (para aminohippurate) is used because it is filtered and actively secreted by kidney in one pass so is equal to the RPF
value gives 625ml/min
35
how much more water and salt so we consume than what we need to replace?
20-25% more
36
What two paths can molecules take when reabsorbed or excreted?
transcellular or paracellular
37
What facilitates waters movement transcellularly and paracellularly?
```
transcellular = aquaporins
paracellular = permeable tight junctions
```
38
What is the transport maxima? Give a situation where this is exceeded.
Transport maxima is the point at which a rise in solute concentration does not yield a rise in rate
E.g. in diabetics there is too much glucose in the filtrate to all be absorbed when in a hyperglycaemic state. So excess is lost in urine
39
What is actively reabsorbed in the proximal convoluted tubule?
glucose, amino acids, sodium, potassium, calcium, vitamin C and uric acid
40
Describe movement of substances in the proximal convoluted tubule
Water: moves via paracellular and transcellular pathways
Sodium: reabsorbed by antiporter which pumps protons into lumen (Na+/H+ antiporter)
Glucose and amino acids: co-transported into the cell with sodium (glucose/Na+ co-transporter and na+/amino acid co-transporter)
On basolateral membrane a Na+/K+ works to maintain gradient where by it pumps sodium out and potassium into bell. glucose and amino acids are transported out of the cell into the blood.
41
What happens to the protons pumped into lumen by Na+/H+ antiporter in the proximal convoluted tubule?
The excreted protons bind to bicarbonate ions in tubular fluid forming carbonic acid.
Carbonic anhydrase converts carbonic acid ➡️ H2O and CO2 which are reabsorbed into cell. Co2 is transported into blood to be excreted.
if there is excess CO2 cytoplasmic carbonic anhydrase will convert it into carbonic acid resulting in proton formation which can be excreted. in this case Na+/H+ antiporter used more so there is increased sodium reabsorption and urinary acidity increases
42
What substances are reabsorbed in the distal convoluted tubule?
Calcium is reabsorbed in the distal convoluted tubule through the apical membrane. It is transported into the blood by 3Na+/Ca2+ antiporter on the basolateral surface of the cell. (3 sodium in and 2 calcium out)
Sodium and chloride are reabsorbed via co-transporters on the apical membrane. Sodium is removed from the cell by Na+/Kt ATPase. Chloride enters blood through leak channels. the potassium also leaves cells through leak channels
43
What drugs inhibit the sodium-chloride symporter and what effect does this have?
Thiazides inhibit this pump
Sodium is removed from cell by K+/Na+ ATPase, but as the sodium-chloride symporter is blocked no sodium is entering the cell. The sodium-calcium channel becomes more active to move more sodium into the cell and as a result of this blood calcium concentration increases.
44
What is osmolarity? What is 1 osmole/L?
Osmolarity is a measure of the solute concentration in a solution
- depends on the number of dissolved solutes present and the greater the number the greater the osmolarity
1 osmole/L is 1 mole of dissolved solute per litre.
45
Why is it important to get rid of excess volume, water and salt?
excess water that is not removed may lead to oedema and blood pressure increase.
excess water that is not removed will lead to dilution of salts in the body and cell swelling.
excess salt in the body will cause the cells to shrink
46
What does the counter-current present in the loop of henle create?
a hyperosmolar extracellular fluid which enables the urine to be concentrated above normal plasma osmolarity
the gradient also allows reabsoprtion of water, for which we have no pumps, by osmosis
47
Describe what happens in the loop of henle.
The descending limb is water permeable and ascending limb is water impermeable. In the ascending limb salts are actively pumped into the interstitium ➡️ interstitial osmolarity increases. Water flows out of the descending limb into the interstitium to equilibrate the osmolarity.
UREA recycling: urea enters the bottom on the loop of henle causing osmolarity to increase even more than usual. It then reenters the filtrate via urea transporters and it cycles from here to the collecting duct where it can be recycled or excreted
48
How does medullary flow not eliminate the counter-current gradient created by the loop of Henle?
The blood supply to the medulla is via the vasa recta.
There blood vessels branch off from efferent arteriole so they have lost some fluid to nephron. Due to their permeability in the descending limb water will diffuse out and solutes in, while in the ascending limb water will diffuse in and solutes out ➡️ leading to no net change in the water content and salt content of the interstitium
➡️ oxygen and nutrients are delivered and gradient is maintained
49
What is diabetes insipidus?
caused by:
- no/insufficient production of vasopressin (ADH)
- no detection of vasopressin
- no response to vasopressin
leads to urinating large quantities of urine and unremitting thirst
50
What artery leads to the afferent arteriole of the glomerulus?
arcuate artery
51
When a substance (not made in body) is intially injected why may there is initial rapid excretion (log graph) which slows to a steady linear relationship?
rapid loss is due to diffusion of the substance down the concentration gradient into the extracellular fluid from blood plasma and it then being lost through the kidney
52
What is absorbed and secreted by the proximal convoluted tubule?
ABSORBED: all glucose, amino acids and oligiopeptides. 90% bicarbonet, 65% sodium, Cl-, K+ and water, 50% urea
SECRETED: protons, urate, NH4+, drugs (e.g. penicillin)
53
What is absorbed and secreted by the descending loop of henle?
25% of water is reabsorbed, no solutes
| nothing secreted
54
What is absorbed and secreted in the thin ascending limb of the loop of Henle?
REABSORBED: 5% of sodium, Cl- and no water
| nothing secreted
55
What is absorbed and secreted in the thick ascending limb of the loop of Henle?
REABSORBED: 25% of sodium,Cl- and no water
| nothing secreted
56
What is absorbed and secreted in the distal convoluted tubule?
REABSORBED: 5% sodium and chloride
| nothing secreted
57
What is absorbed and secreted in the late distal tubule and collecting duct?
REABSORBED: 5% sodium, Cl-, bicarbonate, water (under ADH control)
SECRETED: protons and potassium
58
What is absorbed and secreted in the medullary collecting duct only?
REABSORBED: urea (under ADH control)
| nothing is secreted
59
What might be present in a urine sample from a patient in renal failure?
High haemoglobin, protein, nitrites, proteinuria/haematuria
60
Girl admitted wtih dehydration. She has been tired over the last few months and losing weight. On examination there was evidence of dehydration, pulse - 115bpm, BP = 95/55 mmHg and breath smelled of acetone.
what might her urine sample show?
High ketones, glucose and specific gravity. Low pH
61
What might be found in the urine of a patient who is jaundiced?
bilirubin
62
What are the 4 components allowing generation of hyperosmolar environment?
- counter current mechanism
- descending loop impermeable to salt but permeable to water
- ascending loop impermeable to water but permeable to salt
- Na+/K+ ATPase activity in ascending loop
- urea permeability at the bottom of the loop and collecting duct
63
Describe ion transport in the ascending loop of Henle naming specific ion transporters.
The ascending limb is impermeable to water.
APICAL: Na+/k+/Cl- triple transporter (symporter) is found on the apical membrane and transports 1 Na+, 1 K+ & 2 Cl- into the cell from the tubular fluid. Some of the potassium returns to filtrate via potassium leak channels on the apical membrane.
BASOLATERAL MEMBRANE: Na+/K+ ATPase more 3 sodium out and 2 potassium in on the basolateral membrane (sodium entering blood). Chloride and potassium leak channels are present so both of these ions leave the cell ➡️ blood. K+/Cl- co-transporter is present moving both these ions into the blood.
64
What do loop diuretics block and what are they used to treat?
Loop diuretics block the triple Na+/K+/Cl- symporter in the ascending loop of henle. This prevents water following the salts so more water is retained in the tubule leading to the diuretic effect.
these are used to treat hypertension
65
Describe ion transport in the distal convoluted tubule naming specific ion transporters.
APICAL MEMBRANE: Na+/Cl- symporter moves sodium and chloride into the cell. Calcium moves in via passive diffusion via leak channels.
BASOLATERAL: Na+/K+ ATPase channels to maintain sodium gradient. Chloride leak channels allow chloride to move out of the cell into the blood. 3Na+/Ca2+ anti-porter moves sodium in and calcium out into the blood.
66
Describe ion transport in the collecting duct naming specific ion transporters
APICAL: sodium moves in through channels. The amount of sodium absorbed is controlled by aldosterone. K+ leaks out into the filtrate. (above occurs in principle cells)
- in intercalculated cells protons are pumped into filtrate using ATP
BASLATERAL: in principle cells Na+/K+ ATPase exists as well as K+ leak channels.
- intercalculated cells: CL-/HCO3- anti-porter and chloride lead channels
some chloride ions can move through paracellular pathways
67
What mechanisms increase sodium reabsorption and where do they act in the kidney?
Increased sympathetic activity reduces GFR as afferent arteriole is constriction so the pressure gradient across glomerulus decreases. It also increases sodium reuptake in the PCT.
- additionally can influence JGA to release renin
Low tubular sodium will activate JGA and renin released
Angiotensin II increases sodium uptake in PCT. It also stimulates Aldosterone
Aldosterone increases sodium uptake in the DCT and collecting duct
68
What decreases sodium reabsorption and where does it act in the kidney?
Atrial naturietic peptide
| - acts at glomerulus, PCT, JGA and collecting duct
69
What does effects does aldosterone have?
increases sodium reabsorption, increases potassium secretion and increases proton secretion
70
How does aldosterone lead to sodium reabsorption?
it upregulates the expression of apical membrane sodium channels in the collecting duct. It also induces Na/K ATPase pump formation by acting as a transcription factor when in it's receptor-hormone complex
71
What three stimuli increase renin secretion?
- decrease in blood pressure
- decrease in fluid volume
- increase in beta1 - sympathetic activation
72
What does excess aldosterone result in?
hypokalaemic alkalosis
73
What happens in hypoaldosteronism? What symptoms may a patient present with?
Causes sodium reabsorption to decrease in the distal nephron so increased loss in urine.
ECF volume falls leading to dizziness, low blood pressure, salt craving and palpitations
74
What happens in hyperaldosteronism? What symptoms may a patient present with?
Sodium reabsorption increases so ECF will increase and as a result:
- hypertension, muscle weakness, polyuria and thirst
75
What is Liddle's syndrome?
Inherited condition of hypertension whic occurs because of a mutation in the aldosterone sodium channels. The channels are permanently activated leading to sodium retention and ECF volume increase and therefore hypertension.
76
How do diuretics work?
increase renal sodium excretion, thereby drawing water out and increasing urine volume
77
How do ACE inhibitors work?
They lower BP by preventing Angiotensin II formation which reduces aldosterone production
78
How do osmotic diuretics work?
they work in the PCT and descending limb of LOH. They increase osmotic pressure in the blood so less fluid leaves the tubule
79
How do carbonic anhydrase inhibitors work?
inhibit carbonic anhydrase enzyme. Protons are not formed so H+/Na+ antiporter doesn't work. sodium remains in tubule leading to a diuretic effect
80
Where do potassium sparing diuretics work? Name 2 and their mechanism?
they work in the DCT
Amiloride: blocks sodium channels
Spironolactone: aldosterone antagonist
81
What stimulates potassium secretion?
increased plasma potassium, increased aldosterone, increase tubular flow rate and increased plasma pH
82
What is hypokalaemia and what causes it?
It is low potassium and is a common electrolyte imbalance.
caused by diuretics, surreptitious vomiting, diarrhoea and genetic factors
83
What is hyperkalaemia and what causes it?
High potassium and commonly seen in inpatients, though less common than low potassium.
causes: potassium sparing diuretics, ACE inhibitors, seen in elderly
84
What happens when the kidneys stop working?
- Excretory function lost - accumulation of waste products
- homeostatic function lost - electrolyte disturbance, loss of acid-base control and volume homeostasis
- endocrine function lost
- glucose homeostasis via reabsorption glucose is disturbed
85
What causes lethargy and anorexia in patients with kidney disease?
accumulation of nitrogenous waste products, acidosis, hyponatraemia, volume depletion, anaemia, chronic neurological damage
86
explain the potential effects of kidney failure on salt and water balance.
most patients will present with difficulty excreting water and salt leading to retention and as a result hypertension, oedema and pulmonary oedema.
HOWEVER patients with tubule-interstitial disorders or those whose kidneys have been damaged in the inner medulla area may present with salt and water loss. There is an inability to increase sodium reabsorption so they present with loss of volume so have low blood pressure
87
What are implications of hyperkalaemia?
It exacerbates acidosis leading to a shift of potassium from intracellular to extracellular to try and move protons into cells.
- this can cause cardiac arrhythmias (usually initial loss of p waves and bradycardia) which can result in arrest
- it can effect neurones and muscles (e.g paralysis)
88
What different changes on an ECG would you see in a patient with hyperkalaemia?
```
T waves peak
P wave disappears
bradycardia
broadening of QRS complex
sin wave
sin wave gradually flattens and end in arrest without intervention
```
89
How does kidney failure implicate endocrine systems?
- decreased erythropoietin so anaemia
- Low 1-25 vitamin D levels leads to poor intestinal calcium reabsorption leading in the short term to hypocalcaemia and in the long term to hyperpararthyroidism
90
What are problems and strengths associated with using the following to estimate renal function?
a) urea
b) creatinine
c) creatinine clearance
d) inulin clearance
e) radionuclide studies
f) estimated GFR
a) confounded by diet, catabolic state, GI bleeding, drugs, liver function (not useful)
b) creatinine is affected by muscle mass, age, race, gender
c) creatinine clearance leads to overestimation and creatinine is secreted into filtrate
d) inulin only used for research as laborious
e) radionuclide are reliable but expensive
f) estimated GFR calculates GFR from serum creatinine taking into account age, sex and ethnicity (other formulas can include weight and albumin)
- this is usually used
- unreliable is GFR >60ml and in very obese/thin patients
91
How is the proximal convoluted tubule involved in acid-base balance?
H+ combines with HCO3- in the lumen to form carbonic acid which is converted into CO2 and H2o (all catalysed by carbonic anhydrase)
CO2 diffuses into the luminal cell where cytoplasmic carbonic anhydrase catalyses the formation of carbonic acid (CO2 + water) which then dissociates forming a H+ and HCO3-.
On the apical membrane H+ ATPase and Na+/H+ exchanger moves protons into the filtrate
On the basolateral membrane Cl-/HCO3- exchanger and 3HCO3-/Na+ symporter moves bicarbonate into the blood.
3Na+/2K+ ATPase maintains gradient
92
How is the collecting duct of the kidney involved in acid-base balance?
The cells have both acid and bicarbonate secreting properties and their major character depends on blood pH.
ACID SECRETING:
luminal H+ and HCO3- forms CO2 and H2O via carbonic anhydrase. CO2 enters cell and carbonic anhydrase forms carbonic acid by combining it with water - the acid dissociates to H+ and HCO3-.
The protons are pumped out into the lumen by H+/K+ ATPase and H+ ATPase found on apical membrane.
Bicarbonate is moved across the basolateral membrane by HCO3-/Cl- exchanger
BICARBONATE SECRETING:
same as above so that CO2 moves in. Forms carbonic acid in cytoplasm and dissociates.
H+ ATPase pumps protons across basolateral membrane
HCO3-/Cl- exchanger moves bicarbonate into the filtrate to be excreted (across apical)
93
How can bicarbonate be generated in kidney cells?
Bicarbonate (HCO3-) can be formed via 2 pathways:
1) in the cytoplasm CO2 is reacted with water to form carbonic acid which dissociates to form H+ and HCO3- (via carbonic anhydrase)
the proton is pumped into the lumen via H+ ATPase. The proton may bind to phosphate to form dihydrogen phosphate ion.
The bicarbonate is pumped into blood across basolateral membrane by HCO3-/Cl- exchanger (AE1 transporter)
2. Glutamine is converted into 2NH4+ and 2HCO3-.
The NH4+ is pumped into the lumen via NH4+/Na+ exchanger. On the apical membrane Glucose and sodium are cotransported into the cell via SGLT-1 (helps maintain concentration gradient)
On the basolateral membrane Cl-/HCO3- exchanger moves bicarbonate into blood. Na+/K+ ATPase maintains gradient.
