12.1 - The Genitourinary System Flashcards
What path does urine take through the kidney?
Urine flows from medulla –> minor calyx –> major calyx –> ureter
What are the functions of the kidney?
- excretion of metabolic products e.g. urea, uric acid, creatinine
- excretion of foreign substances e.g. drugs
- homeostasis of body fluids, electrolytes and acid-base balance
- regulates blood pressure
- secretes hormones e.g. erythropoietin, renin
Describe the renal blood supply to the kidneys.
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 functions of peritubular capillaries?
- provide oxygen and nutrients to nephron
- help in reabsorption of substances along nephron and take it to circulatory system
- help in secretion of substances into tubular fluid e.g. drugs
What are the different parts of the bladder and urethra?
- detrusor muscle
- trigone
- internal sphincter
- external sphincter
- bulbourethral gland
What is the function of the detrusor muscle?
Contracts to build pressure in the urinary bladder to support urination
What is the function of the trigone?
Stretching of this triangular region to its limit signals the brain about the need for urination
What is the function of the internal sphincter?
Involuntary control to prevent urination
What is the function of the external sphincter?
Voluntary control to prevent urination
What is the function of the bulbourethral gland?
Produces thick lubricant which is added to watery semen to promote sperm survival
Which areas of the kidney nephron are rich in mitochondria and what does this mean?
- PCT epithelial cells, thick ascending loop of Henle (LOH), DCT epithelial cells, intercalated cells of the collecting duct
- because a lot of active transport of substances occurs here e.g. reabsorption of salts
Which areas of the kidney nephron have a low density of mitochondria and what does this mean?
- epithelial cells of thin descending and ascending LOH, principal cells of collecting duct
- there is a lot of passive reabsorption of substances happening so they do not need as much mitochondria
What are the two types of nephrons and what is the difference between them?
- superficial nephrons and juxtamedullary nephrons
- superficial - glomerulus is closer to outer cortex and tubules are short and only extend into outer medulla
- juxtamedullary - glomerulus is closer to inner cortex/outer medulla and tubules are longer and extend into inner medulla
- 10:1 ratio of superficial to juxtamedullary nephrons
Why is the cortex of kidney granular but medulla has a striated appearance?
- 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 –> striated look
Where is the juxtaglomerular apparatus located?
Where DCT and efferent + afferent arterioles are
What makes up the juxtaglomerular apparatus?
- macula densa cells (in distal convoluted tubule)
- extraglomerular mesangial cells
- juxtaglomerular cells (sit on afferent arteriole)
What are the two functions of the juxtaglomerular apparatus?
- GFR regulation through tubulo-glomerular feedback mechanism
- renin secretion for regulating blood pressure
What are the four main renal processes?
- glomerular filtration
- reabsorption - from filtrate/tubular fluid –> blood
- secretion - from blood –> filtrate/tubular fluid
- excretion
What is the overall process of filtration at the nephron?
- 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 (fluid–>blood) and secretion of substances 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.
- passive process where fluid is driven through the semipermeable glomerular capillaries into the Bowman’s capsule space by the hydrostatic pressure of the heart
- the filtration barrier (size and charge dependent) is highly permeable to fluids and small solutes, but impermeable to cells and proteins
Describe the structure of the basement membrane.
- 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 - most of our plasma proteins are negatively charged (e.g. albumin) so cannot pass through (repelled)
- slit diaphragm allows thin and porous water + small solutes to pass
- slits
- epithelial podocytes make up lining of Bowman’s capsule
What two pressures participate in glomerular filtration?
- hydrostatic pressure - ‘pushing’ - fluid exerts this pressure, solute&fluid molecules shoved out of capillary
- oncotic pressure - ‘pulling’ - solute (e.g. proteins) exert this pressure, fluid molecules drawn in across a semipermeable membrane
- IF and blood both have both types of pressure, but IF pressures are much less
What is net ultrafiltration pressure (Puf)?
- HPgc = hydrostatic pressure in glomerular capillaries
- HPbw = hydrostatic pressure in Bowman’s capsule
- pi(gc) = oncotic pressure of plasma proteins in glomerular capillaries
- virtually no osmotic pressure in Bowman’s capsule due to large proteins/cells not being able to get through
- Puf = HPgc - HPbw - pi(gc)
What is glomerular filtration rate (GFR)?
- amount of fluid filtered from glomeruli into Bowman’s capsule per unit time (mL/min)
- sum of all functioning nephrons in both kidneys
- GFR = Puf x Kf
- Puf = ultrafiltration pressure
- Kf = ultrafitration coefficient (membrane permeability and surface area available for filtration)
- changes in filtration forces / Kf will result in GFR imbalances
What is normal GFR?
- male adults: 90-140 mL/min
- female adults: 80-125 mL/min
What does a fall in GFR indicate?
It is the cardinal feature of all renal disease, with a build up of excretory products in the plasma
What are the two mechanisms through which GFR is regulated?
- myogenic mechanism
- tubulo-glomerular feedback mechanism
How does the myogenic mechanism work?
- happens to an increase in arterial pressure
- arterial pressure increases
- afferent arteriole stretches
- arteriole contracts
- vessel resistance rises
- blood flow reduces
- GFR stays the same
How does the tubulo-glomerular feedback mechanism work?
- in response to change in GFR
- increase/decrease in GFR
- increased/decreased NaCl in Loop of Henle
- this change is detected by macula densa
- macula densa sends signal in the form of increased/decreased ATP & adenosine discharged to afferent arteriole
- afferent arteriole receives signal and constricts/dilates - changes blood flow
- GFR stabilises
What is renal clearance?
- number of litres of plasma that are completely cleared of the substance per unit time
- only concerned with the excretory role played by the kidneys i.e. rate of removal of a substance from the blood and excretion through urine
What is renal clearance of a substance and what is the formula for it?
- the extent to which that substance is cleared from the blood e.g. if C = 50mL/min –> 50mL of plasma has been cleared of that substance per minute
- C x P = U x V
- C = (U x V) / P mL/min
- C = renal clearance
- U = concentration of substance in urine
- V = rate of urine production
- P = concentration of substance in plasma
What is the concept of renal clearance useful in?
- in the calculation of GFR
- renal plasma flow (RPF)
- to understand the excretory route of a substance (e.g. is it only filtered, combination of filtration and secretion etc)
What is a freely filtered particle’s renal clearance like?
- if a molecule is freely filtered and neither reabsorbed nor secreted in the nephron, then the amount filtered = amount excreted
- thus GFR = renal clearance of the molecule
What is the ideal molecule for measuring GFR?
- inulin - a plant polysaccharide which is freely filtered and not reabsorbed/secreted
- not toxic and measurable in urine and plasma
- however not found in mammals so needs to be transfused
What is the commonly used molecule for measuring GFR?
- creatinine - 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 of high plasma creatine
Why is creatinine not a perfect molecule?
- 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 GFR calculations
- the method for measuring creatinine also measures the concentrations of ‘non-creatinine chromogens’
What is renal plasma flow (RPF)?
Volume of blood reaching the kidney per unit time
What happens if the total amount of a molecule entering the kidney = amount excreted?
Renal clearance = RPF
What molecule is used to work out renal plasma flow?
- PAH (para aminohippurate) 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 concentration
- rate of PAH excretion through urine: V x urine PAH concentration
- 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 value ranges 0.15-0.2 = 15-20% of plasma has been filtered
- FF = GFR/RPF
What are the three types of passive transport?
- diffusion
- osmosis
- electrical gradient difference - charged ions can go to the side of a membrane with the opposite charge
What are the two types of active transport?
- primary active transport e.g. Na+K+ATPase pump which uses energy from 1 ATP to move 2 K+ ions into cell and 3 Na+ ions out of cell
- endocytosis is also primary active e.g. small proteins reabsorbed in PCT
- secondary active/coupled transport - movement of one 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 its gradient –> glucose moves against its own)
- e.g. antiporters like Na+H+ antiporter
How are substances transported in renal tubules?
- paracellular pathway lets some substances pass between epithelial cells
- transcellular pathway lets other things pass across cells like water through aquaporins
- transcellular Na+ reabsorption occurs through sodium-potassium pump - pumps Na+ into blood so [Na+] in epithelial cell decreases –> Na+ from tubular fluid diffuses into cell
What substances are reabsorbed at PCT?
- 50% urea
- 67% Na+
- 67% Cl-
- 67% H2O
- 80% HCO3-
- 100% glucose
- 100% amino acids
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?
- sodium-potassium pump creates low [Na+] in epithelial cell
- CO2 diffuses from tubular fluid into epithelial cell
- CO2 combines with water by action of carbonic anhydrase to form H+ and HCO3-
- H+ leaves cell into tubular fluid via sodium-hydrogen antiporter and is excreted from body - antiporter uses energy from Na+ diffusing into epithelial cell (due to low Na+ in cell due to pump) to transport H+ out into tubular fluid
- HCO3- leaves cell through sodium-bicarbonate symporter into blood = both reabsorbed
What does angiotensin II do during the process of sodium and bicarbonate reabsorption?
Regulates Na+ reabsorption by increasing Na+H+ antiporters
What are the steps through which glucose is reabsorbed?
- sodium-potassium pump creates low [Na+] in epithelial cell
- SGLT2 sodium-glucose symporter brings Na+ and glucose into cell from tubular fluid
- GLUT2 glucose transporter reabsorbs glucose back into blood
What are the descending and ascending limbs permeable to?
- descending limb permeable to water but impermeable to salts = water out, more concentrated as you go down
- ascending limb impermeable to water but permeable to salts = salts out, less concentrated as you go up
What happens as fluid passes through the Loop of Henle?
- fluid goes down thin descending limb where water passively moves out but Na+ and Cl- are impermeable so cannot leave
- by bottom, the fluid is hyperosmolar due to low water and high salt concentration
- as it goes up thin ascending limb, it is impermeable to water but permeable to salts so Na+ and Cl- passively leave
- 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 put of tube in step 1)
- at the top, the fluid has become hypo-osmolar
What substances are reabsorbed at Loop of Henle?
- 25% Na+
- 25% Cl-
- 15% water
What happens at thick ascending limb cells?
- sodium-potassium pump transports 2K+ into cell and 3Na+ out into blood
- Na+K+2Cl- symporter absorbs Na+, K+ and 2Cl- into the cell
- potassium-chlorine symporter reabsorbs K+ and Cl- into blood
- through paracellular pathways some cations like Na+, Ca2+, K+ and Mg2+ are reabsorbed too
What happens in the early part of the distal convoluted tubule?
Na+, Cl- and Ca2+ is reabsorbed
How is Na+ and Cl- reabsorbed at early DCT?
- more Na+ and Cl- gets reabsorbed into blood which makes fluid more hypo-osmolar (same thing as thick ascending limb of LOH)
- no water channels so no water is reabsorbed
- sodium-potassium pump transports 2K+ in and 3Na+ out
- Na+Cl- symporter brings in Na+ and Cl-
- K+Cl- symporter moves both K+ and Cl- into blood
How is Ca2+ reabsorbed in early DCT?
- Ca2+ comes through channels from tubular fluid into epithelial cell
- Na+Ca2+ antiporter sends Ca2+ into blood (Na+ in down conc grad due to Na+K+ATPase) and Ca2+ ATPase pump also pumps Ca2+ back into blood
What do principal cells do (in the late part of DCT and collecting duct)?
- Na+ reabsorption and K+ secretion (they correct hyperkalaemia)
- water is also reabsorbed through aquaporin channels
What does aldosterone do?
Regulates Na+ reabsorption by increasing apical Na+ channels and basolateral Na+K+ATPase pumps
What does anti-diuretic hormone do?
Regulates water reabsorption by increasing apical aquaporins
What are the two types of intercalated cell (in the late part of DCT and collecting duct)?
- alpha-intercalated cells - pumps/secretes H+ into tubular fluid and conserves/reabsorbs bicarbonate (treat acidosis)
- beta-intercalated cells - secretes bicarbonate into tubular fluid and conserves/reabsorbs H+ (forms minority of operation but needed in alkalosis)
