A: capsule (CT)
C: medullary pyramids
A: arcuate vessels
B: interlobular arteries
C: interlobar vessels
What is the path of renal arteries?
What are the 2 secondary capillary plexi providing blood to the kidney paryenchyma?
Renal artery -> interlobar vessels -> arcuate arteries -> terminate in glomeruli in BC. Plasma filters from glomerular capillaries into space of capsule.
1. vasa recta -> to medulla and loops back on itself, provides blood and helps generate high osmotic ressure in medulla
2. cortical capillary network - allow material exchange between blood and cortical tubules
A: afferent arteriole
C: macula densa
D: juxtaglomerular cell
E: efferent arteriole
F: bowman's capsule
What is the filtration fraction of blood plasma filtered through glomerulus?
What is the path?
What is the difference between the afferent and efferent arterioles, and what does this create?
glomerulus -> capsular space -> PCT
Afferent = larger diameter so pressure decreases between afferent and efferent. Creates filtration pressure forcing fluid through capillary endothelium -> capsular space.
Describe glomerular capillaries.
What is proteinuria?
Fenestrated and covered on outside with extra layer of podocytes which have slits between them (filtration mechanism).
Renal disease: slits become inflamed and enlarged enabling more solutes to enter urine - mainly proteins = proteinuria
A: podocyte cell body
C: foot processes of podocytes
D: filtration slits
E: cytoplasmic extensions of podocytes
What is the path of fluid from the afferent arteriole?
What is the formula for excretion from the kidney?
What is the average net filtration pressure?
Glomerulus -> PCT -> LoH (in medulla) -> DCT -> CD -> ureter (all = NEPHRON)
Excretion = filtration - reabsorption + secretion (in PCT, reabsortion and secretion to/from peritubular capillaries)
What is the average kidney outflow and glomerular filtration rate?
What is average renal plasma flow and urine flow?
How much filtered fluid is reabsorbed, and where is most of it reabsorbed?
1.2L/min and 120-125ml/min
680ml/min and 1ml/min
99%, 2/3 in PCT
Describe how fluid is reabsorbed in the PCT
Na+ pumps in basal membrane move Na+ -> interstitial fluid. Na+ channels in luminal membrane so Na+ passes lumen -> cells down its conc gradient, carries glucose with it.
H2O reabsorbed down osmotic gradient, lumen -> cells -> intersitiual fluid.
What is glomerular filtration rate (GFR) for both kidneys and how is it measured?
What happens to clearance if substance in blood is:
a) not removed at all by kidney
b) removed at same rate as H2O passes through glomeruli
c) completely removed from the blood passing through the kidney
Effective volume of plasma completely 'cleared' of a substance/min (usually 120-125ml/min), measured by clearance of a selected material in L/min.
a) clearance = 0
b) clearance = GFR
c) clearance = RPF (renal plasma flow)
How does kidney damage affect GFR and RPF?
GFR is an important test of kidney health. What is the formula for clearance?
Normally GFR decreases but RPF may be normal.
Clearance = ([U]/[P]) x [V]
where U = urine conc, P = plasma conc and V = urine vol/min
What is the gold standard for measuring GFR and why is it not used much?
What is used clinically to measure GFR, and why is this an overestimate?
What are normal creatinine clearance levels for a male and female?
Inulin Clearance: Completely filtered from blood plasma. But need inulin IV over hours to get stready plasma conc.
Creatinine used clinically - break down prod of creatine phosphate in muscle, freely filtered by glomerulus. Creatinine normally already at steady state conc in blood so easier to measure than inulin.
It is also actively secreted by peritubular capillaries in small amounts - this secretion means creatinine clearance overestimates actual GFR by 10-20%.
NB: normally 24 hr urine collection and blood test for creatinine
Male: 88-128ml/min Female: 97-137ml/min
Apart from GFR, what can creatinine clearance also be used to measure?
What is the substance used to measure clearance and hence RPF?
RPF - if substance in blood completely removed from blood passing through kidney, clearance - RPF.
PAH (para-amino-hippuric acid). Infused until steady blood conc measured and urine collected for 24hrs.
GFR is autoregulared - what does this mean, and thus what can be measured?
Hence what kinds of releasing cells are found in the kidney?
It (and RPF) doesn't change over a wide range of BPs, thus pO2 in interstitium - measure of O2 carrying capacity of blood.
What is GFR regulated by?
Is constrictor tone higher in efferent or afferent arterioles?
What decreases filtration pressure and GFR?
What increases filtration pressure and GFR?
Balance of SM constriction in afferent and efferent arterioles (so maintains GFR despite changes in systemic BP).
Efferent = creates filtration pressure.
Afferents constrict and efferents relax
Afferents relax and efferents constrict
What happens if Na+ concentration in the DCT is too low?
And if too high?
If Na+ too low = GFR too low -> detected by cells in macula densa of juxtaglomerular apparatus (where DCT folds back and contacts glomerlus where afferent and efferent enter) -> cells in MD release local chemical factors -> relax SM in afferent -> increases filtration pressure -> increases GFR.
If GFR too high -> MD chemical factors constrict afferent arteriole -> decreases filtration pressure and GFR
Label D, 6, 7, 9 and 11
D: juxtaglomerular apparatus
6: granualar cells (juxtaglomerular cells)
7. macula densa
9. afferent arteriole
11: efferent arteriole
Define osmotic pressure.
What 2 system processes happen to control blood volume if e.g. you give blood?
What percentage of blood is in capillaries and veins?
Tendancy of solution to take in water by osmosis. NB: osmol = unit defining osmotic strenth of solution - blood plasma osmolatity = 300mOsm.
BP control system: Sypathetic NS causes immediated vasoconstriction to compensate for vol decrease. Blood vol control system: urine flow decreases and thirst increases to compensate.
65% (constriction = SNS restores preload after hemorrhage)
What 3 sensors is blood volume regulated by?
Neuronal volume sensors
Hormonal volume sensors
What are neuronal volume sensors?
What happens when venous return increases?
Sensory nerve fibres in atria tissues and great veins, act as stretch receptors on carotid sinus and signal volume of blood returning to heart/min.
When venous return increases, they get more stretched, info carried up vagus nerve to brain -> NTS to obtain info on total blood vol -> hypothalamus.
What are hormonal volume sensors?
What do they do in response to increased blood volume?
What is BNP?
Specialised muscle cells in wall of R. atrium and inferior vena cava. Overstretching from increased preload can indicate excess blood volume.
Release ANP (atrial natriuretic peptide) which decreases Na+ reabsorption in DCT -> increased Na+ loss in urine (by osmosis) and also increased water loss -> reduced circulating blood vol and brings is back to normal.
brain-derived natriuretic peptide, released by these specialised muscle cells and other heart muscle cells, levels normally v low but increases when ventricles overstretched as in heart failure
What are osmotic volume sensors?
Supraoptic and paraventricular nuclei in the hypothalamus contain osmoreceptors that measure osmotic pressure of blood passing through (+ receive info from blood vol receptors via relays in NTS) -> send axons down pituitary stalk to secretory terminals on capillaries within posterior pituitary gland -> axons secrete ADH/vasopressin/AVP which inhibits H2O loss
What happens when osmoreceptors detect high blood osmolarity?
Apart from osmoreceptors, what also modifies ADH release?
ADH released from pituitary -> decrease H2O loss from urine -> thirst triggered (and vice versa)
Sympathetic arousal - fight or flight increases ADH
A: pituitary stalk
C: pituitary gland
Label A and B.
Where do they project to?
A: supraoptic nucleus B: paraventricular nucleus
Project to post pituitary gland
How does the kidney concentrate urine, and by how much?
Describe the process of reabsorption from the PCT, down the LoH and to DCT.
Can concentrate urine up to 4x plasma osmolarity (about 300mosmol/l) b/c kidney builds up conc gradient in medulla by LoH, reaching 1200mmol/lt at base. Its surrounded by vasa recta.
PCT: stays at 300mosmol/l b/c Na+ and H2O reabsorbed
Descending Limb: aquaporins allow H2O to leave channel b/c in equilibrium with high conc in extracellular fluid in renal medulla, so at base = v. concentrated
Thin part of ascending Limb: urea IN, NaCl OUT
Thick part of ascending Limb: impermeable to H2O, AT pumps move Na+ and Cl- to extra cellular space = maintains high extracellular fluid concs in medulla.
What are the 2 Na+ Cl- transport mechanisms?
1) K+ transporter: ATP dependant K+ channels (ROMK) moves K+ from cell -> lumen which generates +ve voltage (10mv) in tubular lumen (potential diff between lumen and inside cell = 80mv)
2) Na-K-Cl co-transporter channel (NKCC2): in luminal wall of epithelial cells, allows NaCl and K+ to move passively down conc gradient into cells, enhanced by ROMK +ve potential. Na+ actively transported from base of epithelial cells by Na+/K+ ATPase. Cl- moves out passively with Na+ -> renal medullary extracellular space
Give an example of a loop diuretic, and explain what they do.
Furosemide. Inhibit NKCC2 - block Na+ and Cl- transport from LoH = abolishes high conc in medulla - prevents formation of conc urine.
NB: similar NKCC2 in cochlea - SE= irreversible hearing loss, low BP with standing
Where is the site of ADH in the kidney?
What does ADH do?
ADH opens aquaporin channels in collecting duct so most H2O reabsorbed into conc extracellular fluid so prod small vol of conc urine (same osmolarity as renal medullary fluid). If no ADH = v dilute urine.
Describe the urea cycle.
What is the counter current multiplier mechanism?
Urea actively pumped from CD into interstitial fluid = increase solute conc in medulla, helps make more conc urine. Some passed to ascending limb = urea cycle! Some urea lost in urine.
The process of pumping out salt into the extracellular fluid around the LoH - concentrates urine.
Describe the counter current exchange mechanism of the vasa recta.
Preserves conc gradient despite blood flow through vasa recta. Blood enters at normal osmolatiry, gets concentrated in medulla, and dilute again as it leaves.
Distinguish between the terms:
Water diuresis: drinking too much water, blood becomes dilute, ADH release inhibited, high vol of dilute urine. If e.g. distruction of cells releasing ADH -> diabetes insipidus (constantly thirsty and prod lots urine)
Osmotic diuresis: glucose normally completely reabsorbed in PCT but if not due to excess glucose in blood, then glucose passing through CD provides osmotic force tending to pull H2O into the urine, opposing the osmotic force of the medulla (which tends to pull H2O out). Thus high vol of sugary urine = diabetes melluitus.
Describe the structure of the Bowman's capsule.
Describe the structure of the glomerulus.
What 3 things form the glomerular filtration barrier?
2 contiguous layers of epithelial cells with a space between them: Outer capsular epitehlium = simple squamous (parietal wall). Inner podocyte layer (visceral wall) forms part of filtration barrier. Podocytes have cytoplasmic extensions apposed to BM.
Capillary loops inside visceral layer of Bowman's capsule. Capillaries have fenestrated endothelium and is supported by mesangial cells which synthesise CT (mesangium), phagocytose particles, control glomerular blood flow by contracting/relaxing to make capillaries narrower/wider.
1. Podocyte layer of BC
2. Fenestrated endothelium of gomerulus
3. Thick, -ve BM shared between the 2 cellular components