The Genitourinary System Flashcards
What path does urine take through the kidney
Urine flows from cortex into medulla into minor calyx then major calyx then out of ureter
What 5 functions does the kidney perform?
1) Excretion of metabolic products e.g. urea, uric acid and creatinine
2) Excretion of foreign substances e.g. drugs
3) Homeostasis of body fluids, electrolytes & acid-base balance
4) Regulates blood pressure
5) Secretes hormones e.g. erythropoietin, renin
Describe the blood supply to the kidney and what arteries + veins etc it’s divided into
Renal artery → segmental artery → interlobar artery → arcuate artery → interlobular artery → afferent arteriole → glomerular capillaries → efferent arteriole → peritubular capillaries → interlobular vein → arcuate vein → interlobar vein → renal vein
- What are the 3 functions of peritubular capillaries?
1) provide oxygen and nutrients to nephron
2) help in reabsorption of substances along nephron and take it to circulatory system
3) help in secretion of substances into tubular fluid e.g. drugs
Detrusor muscle
Contracts to build pressure in the urinary bladder to support urination
Trigone function
Stretching of this triangular region to its limit signals the brain about the need for urination
Internal sphincter
Involuntary control to prevent urination
External sphincter
Voluntary control to prevent urination
Bulbourethral gland function?
Produces thick lubricant which is added to watery semen to promote sperm survival
Which areas of the are rich in mitochondria and what does this mean?
PCT epithelial cells, thick ascending LOH epithelial cells, DCT epithelial cells and intercalated cells of collecting duct
They are rich in mitochondria because a lot of active transport of substances happens in them
- Which areas of nephron have a low density of mitochondria & what does this mean?
Epithelial cells of thin ascending + descending LOH, principal cells of collecting duct
There is a lot of passive reabsorption of substances happening which is why they don’t need as many mitochondria
Which cells of the collecting duct are rich in mitochondria?
Intercalated cells
Which cells of the collecting duct have low density of mitochondria?
Principal cells
Which part of the nephron is permeable to water (i.e. lets water out)?
Thin descending LOH
Which part of the nephron is impedance to water
Think and thick ascending LOH
- Which part of the nephron is responsible for the majority of water reabsorption?
Proximal CT
What are the 2 type of nephrons and what is the anatomical difference between them?
Superficial nephrons and juxtamedullary nephrons
Superficial- glomerulus is closer to outer cortex and tubules are short, LOH only extend into outer medulla
Juxtamedullary- glomerulus is closer to inner cortex/outer medulla and tubules are longer and Loop of Henle extend into inner medulla
There is 10:1 ratio of superficial to juxtamedullary nephrons
Why is cortex of kidney granular but medulla has striated appearance?
Because in cortex we have Bowman’s capsule and PCT + DCT which make it look granular whereas tubules of LOH and collecting duct go through medulla which give it striated look
Where is juxtaglomerular apparatus located
Where DCT and efferent and afferent arterioles are
What makes up the juxtaglomerular apparatus
- Macula densa cells (in DCT)
- Extraglomerular mesangial cells
- Juxtaglomerular cells (sit on afferent arteriole)
- What are the 2 function of the juxtaglomerular apparatus?
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- Glomerular filtration rate (GFR) regulation through tubulo-glomerular feedback mechanism
- Renin secretion for regulating blood pressure
What is the overall process of filtration at nephrons, (what are the 4 different renal processes)?
Afferent arteriole brings blood into glomerular capillaries where glomerular filtration happens and then goes into efferent arteriole which forms peritubular capillaries
Reabsorption of certain substances into blood, and secretion of substances from blood into tubular fluid happens at peritubular capillaries.
There is also excretion of different substances
Different substances undergo a different combination of these 4 renal processes
Describe the process of glomerular filtration (i.e is it an active process or a passive process & what pressure drives glomerular filtration)
- It’s a passive process where fluid is driven through semipermeable glomerular capillaries into the Bowman’s capsule space by hydrostatic pressure of the heart
- The size and charge dependent filtration barrier is highly permeable to fluids and small solutes but impermeable to cells and proteins
Describe Function of basement layers
capillary endothelium has 70nm fenestrae and allows water, ions and small proteins to pass
Glomerular basement membrane is second layer and is lined with negatively charged proteins (so repels negatively charged proteins from passing through)- most of our plasma proteins are negatively charged like albumin so can’t pass through
Epithelial podocytes make up lining of Bowman’s capsule
What substances can pass through the fenestrae?
Water ions and small proteins
What substances can pass through the slit diaphragm of the glomerular basement membrane?
Water and small solutes only
What 2 pressures are participating in glomerular filtration?
1) Hydrostatic pressure- pushing- fluid exerts this pressure and solute and fluid molecules are pushed out of capillary
2) Oncotic pressure- pulling- solute (e.g. proteins) exert this pressure and fluid molecules drawn in across a semipermeable membrane
Interstitial fluid (IF) and blood both have both pressures but IF pressures are much less
How do you calculate the net ultrafiltration pressure (Puf)?
Puf = HPgc - HPbw - πgc
Puf - Net ultrafiltration pressure
HPgc - hydrostatic pressure in glomerular capillaries
HPbw - hydrostatic presure in bowman’s capsule
πgc - Oncotic pressure of plasma proteins in glomerular capillaries
There is virtually no oncotic pressure in bowman’s capsule due to large proteins/cells not being able to get through into the capsule so the small proteins exert such a small oncotic pressure it’s basically 0
- What is the glomerular filtration rate (GFR) and what are its units?
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- Amount of fluid filtered from glomeruli into Bowman’s capsule per unit time (mL/min)
- It is the sum of all functioning nephrons in both kidneys
How is it calculated?
GFR = ultrafiltration pressure x ultrafiltration coefficient
Any changes in filtration forces or Kf will result in GFR imbalances
What is Kf? (2 things)
Ultrafiltration coefficient- the membrane permeability and surface area available for filtration
Tumours, infection etc can reduce SA or membrane permeability
What is normal GFR?
For male adults is 90-140 mL/min
For female adults is 80-125 mL/min
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What does a fall in GFR indicate?
It is the cardinal feature of renal disease, with a build up of excretory products in the plasma
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What two mechanisms js GFR regulated
Myogenic mechanism
Tubulo glomerular feedback
Describe the myogenic mechanism used to regulate the GFR when arterial pressure is high
Happens in response to an increase in arterial pressure
1) Arterial pressure increases
2) This causes afferent arteriole to stretch
3) Soon as stretching happens, smooth muscle in afferent arteriole contracts
4) This causes vessel resistance to rise
5) This reduces (rate of) blood flow
6) GFR stays the same
- Describe the tubulo-glomerular feedback mechanism used to regulate the GFR
In response to change in GFR
1) Increase/decrease in GFR
2) Increased/decreased NaCl in Loop of Henle
3) This change is detected by macula densa
4) Macula densa sends signal in the form of increased/decreased ATP & adenosine discharge to afferent arteriole
5) Afferent arteriole receives signal and constricts/dilates- changes blood flow
6) GFR stabilises
NOTE; non-lecture info which is very important: The macula densa cells will also inhibit renin release/stimulate renin release in response to Increased/decreased NaCl in Loop of Henle
What is renal clearance?
Number of litres of plasma that are completely cleared of the substance per unit time
It’s only concerned with excretory role of the kidneys i.e. rate of removal of a substance from the blood and excretion through urine
What is renal clearance useful in
In the calculation of GFR, renal plasma flow (RPF) and to understand the excretory route of a substance (e.g. is it only filtered, combination of filtration and secretion etc)
What is renal clearance of a substance and what’s the formula for it, and what are its units?
C x P = U x V therefore C = (U x V)/P
The extent to which that substance is cleared from the blood
mL/min
If C = 50mL/min for a substance this means 50mL of plasma has been cleared of that substance per minute
What is a freely filtered particle’s renal clearance like? (how does conc. of substance change from afferent to efferent arteriole)
If a molecule is freely filtered and neither reabsorbed nor secreted in nephron then amount filtered = amount excreted
Thus GFR = renal clearance of the molecule
(this doesn’t mean all of the molecule is filtered and so the conc of it will stay the same between afferent and efferent arterioles)
FREELY FILTERED DOESN’T MEAN NONE IS REABSORBED/SECRETED
What is meant if a substance is freely filtered?
Means they can be found in the ultrafiltrate and plasma at same concentration
E.g for substance X
Conc of X in plasma = conc of X in glomerular filtrate
What is one ideal molecule used to measure GFR using this concept?
- Inulin- a plant polysaccharide which is freely filtered and not reabsorbed/secreted
- Isn’t toxic and is measurable in urine and plasma
However not found in mammals so needs to be transfused
Not given orally as we don’t have enzymes to digest it
What is the commonly used molecule for measuring GFR using this concept?
- Creatinine- a waste product from creatine in muscle metabolism
- Amount of creatinine released is fairly constant
- If renal function is stable, creatinine amount in urine is stable
- Is freely filtered and not reabsorbed/metabolised by kidneys
What might indicate renal failure?
Low creatinine clearance or high plasma creatinine levels
Not a perfect molecule as It is freely filtered and not reabsorbed but a small amount is secreted into the nephron
However the process for estimating creatinine in blood and urine can account for that to allow for GFR calculations
Clearance ratio formula:
conc of substance/conc of inulin
If it =1 that means that it is freely filtered, if greater than 1 then must be freely filtered and actively secreted, if less than 1 it is either not freely filtered or freely filtered with some reabsorbed.
Renal plasma flow
Volume of blood reaching kidney per unit time
What happens if the total amount of a molecule entering the kidney = amount excreted?
Then the renal clearance of this molecule is RPF
PAH (para aminohippurate) is used as all the PAH is removed from the plasma passing through the kidney through filtration and secretion
Rate of PAH entering kidney per min: RPF x Plasma PAH conc
Rate of PAH excretion through urine: V x Urine PAH conc
Since RPF x Ppah = V x Upah, this can be rearranged to RPF = V x Upah/Ppah
Why is PAH clearance not used clinically when renal disease is suspected?
Since PAH is both filtered and secreted, if PAH clearance isn’t normal we don’t know if that’s because of impaired RPF or impaired secretory process
What is filtration fraction?
The ratio of the amount of plasma which is filtered and which arrives via afferent arteriole
Normal range is 0.15-0.2 which means 15-20% of plasma has been filtered
- If in 1 person the arterial plasma inulin conc is 1 mmol/L and 20% of renal plasma is filtered, what is the plasma inulin conc in:
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- Efferent arteriole?1 mmol/L
- Renal vein0.8 mmol/L because the 0.2 mmol of inulin that leaves to go into the nephron takes 0.2 mmol of water with it and this water is reabsorbed back into the renal vein to dilute it from 1 mmol/L in the efferent arteriole to 0.8 mmol/L in the renal vein
2 types of transport
Passive eg diffusion,osmosis,electrical gradient difference
Active 1) Primary active e.g. sodium-potassium ATPase pump which uses energy from 1 ATP to move 2 K+ ions into cell and 3 Na+ ions out of cell
2) Secondary active/coupled transport- movement of 1 solute along its electrochemical gradient provides energy for the other solute to move against it
e.g. symporters like sodium-glucose symporter (Na+ moves down electrochem grad but glucose moves against its own)
antiporters like sodium-hydrogen antiporter
- In the epithelial cell layer of the renal tubules, how does water follow the transcellular pathway?
It is transported from tubular fluid → Epithelial cells → blood via aquaporins in the epithelial cells
How does transcellular Na+ reabsorption occur in the renal tubules?
3Na+ is transported from epithelial cells into blood via Na+/K+ ATPase
This creates a concn. gradient for Na+ as it is lower in the epithelial cell so Na+ from the tubular fluid diffuses into cell
2 K+ is transported from blood into epithelial cells via Na+/K+ ATPase so this is an active transport as ATP is used
- What is meant by the paracellular pathway in the renal tubules?
Substances such as water, Ca2+, K+, Cl- and urea are transported through the tight junctions between the epithelial cells
What substances are reabsorbed at PCT? (6)
100% glucose
100% amino acids
67% Na+
67% Cl-
67% water
50% urea
80% HCO3-
What substances are secreted at PCT?
- Drugs
- Ammonia
- Bile salts
- Prostaglandins
- Vitamins (folate and ascorbate)
What are the steps through which sodium and bicarbonate are reabsorbed?
1) Sodium-potassium pump creates low Na+ conc in epithelial cell
2) CO2 diffuses from tubular fluid into epithelial cell
3) CO2 combines with water by action of carbonic anhydrase produces H+ and HCO3-
4) H+ leaves cell into tubular fluid via sodium-hydrogen antiporter and is excreted from body
5) The antiporter uses the energy from Na+ diffusing into epithelial cell to transport H+ out into tubular fluid
6) Bicarbonate (HCO3-) leaves cell through sodium-bicarbonate symporter into blood
How does Angiotensin II regulate the Na+ reabsorbed?
Regulates Na+ reabsorption by increasing sodium-hydrogen antiporters
What are the steps through which glucose is reabsorbed?
1) Sodium-potassium pump creates low Na+ conc in epithelial cell
2) SGLT2 sodium-glucose symporter brings Na+ and glucose into cell from tubular fluid
3) GLUT2 glucose transporter reabsorbs glucose back into blood
What happens as fluid passes through loop of henle
1) Fluid goes down thin descending limb where water passively moves out but Na+ and Cl- are impermeable so can’t leave
2) By the bottom of the loop the fluid is hyperosmolar due to having low water and high salt conc
3) As it goes up thin ascending limb it’s impermeable to water but permeable to salts so Na+ and Cl- passively leave
4) Fluid enters thick ascending limb where Na+ and Cl- are actively pumped out (this + passive movement of salts in thin ascending limb create salty conditions in medulla which draw water out of tube in step 1)
5) At the top the fluid has become hypo-osmolar
What substances are reabsorbed?
- 25% Na+
- 25% Cl-
- 15% water
- What happens at thick ascending limb cells? (describe the steps of Na+ and Cl- reabsorption + K+ moving into the blood from tubular fluid)
1) Sodium-potassium pump (2 K+ into cell, 3 Na+ out and into blood)
2) Na-K-2Cl symporter absorbs these into cell
3) Potassium-chlorine symporter reabsorbs K+ and Cl- into blood
Through paracellular pathways some cations like Na+, Ca2+, K+ and Mg2+ are reabsorbed too
Na+/K+ ATPase creates concn. gradient with low conc. in the epithelial cell
Na+/K+/2Cl- symporter transports these ions from the tubular fluid into the epithelial cell
K+ is recycled back out into the tubular fluid, through K+ ion channel
K+/Cl- symporter allows reabsorption of these ions back into the blood from the epithelial cell
What happens in early part of DCT?
Na+, Cl- and Ca2+ is reabsorbed
How is sodium and chlorine reabsorbed in DCT
More Na+ and Cl- gets reabsorbed into blood which makes fluid more hypo-osmolar (same thing as thick ascending limb of LOH)
1) Sodium-potassium pump makes sodium leave cell enters the blood
2) Na+ Cl- symporter does its ting and brings in Na+ Cl- into cell,
3) K+ Cl- symporter does its ting and moves K+ Cl- into blood
There are no water channels so no water is reabsorbed
How is calcium reabsorbed in DCT
1) Ca2+ comes through channels from tubular fluid into epithelial cell
2) Na+ Ca2+ antiporter sends Ca2+ into blood and Ca2+ ATPase pump pumps Ca2+ back into blood
What happens in late part of DCT (distal DCT) and collecting duct?
Intercalated cells maintain acid base homeostasis
Principal cells allow sodium reabsorption and potassium excretion
What do the principal cells do (2 things)? + which 2 hormones are present here
- Na+ reabsorption and K+ secretion (they correct hyperkalaemia)
- Water reabsorption through aquaporin channels
What does aldosterone do in last part of DCT
Regulates Na+ reabsorption by increasing apical Na+ channels and basolateral sodium-potassium ATPase pumps
What does ADH do here in last part of DCT
Regulates water reabsorption by increasing apical aquaporins
Alpha intercalated cells- what do they do?
Pumps (secretes) H+ into tubular fluid and conserves (reabsorbs) bicarbonate in blood
Alpha secretes Acid to correct acidosis
Beta intercalated cells- what do they do?
Secretes bicarbonate into tubular fluid and conserves H+
Form minority of operation but is needed in alkalosis
Beta secretes bicarbonate/base to correct alkalosis
