13. Renal Function

Question 1

Label A-D

Answer 1

A: capsule (CT)

B: cortex

C: medullary pyramids

D: ureter

Question 2

Label A-C

Answer 2

A: arcuate vessels

B: interlobular arteries

C: interlobar vessels

Question 3

What is the path of renal arteries?

What are the 2 secondary capillary plexi providing blood to the kidney paryenchyma?

Answer 3

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

Question 4

Label A-H

Answer 4

A: afferent arteriole

B: DCT

C: macula densa

D: juxtaglomerular cell

E: efferent arteriole

F: bowman’s capsule

G: glomerulus

H: PCT

Question 5

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?

Answer 5

20%

glomerulus -> capsular space -> PCT

Afferent = larger diameter so pressure decreases between afferent and efferent. Creates filtration pressure forcing fluid through capillary endothelium -> capsular space.

Question 6

Describe glomerular capillaries.

What is proteinuria?

Answer 6

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

Question 7

Label A-D

Answer 7

A: podocyte cell body

B: fenestrations

C: foot processes of podocytes

D: filtration slits

E: cytoplasmic extensions of podocytes

Question 8

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?

Answer 8

Glomerulus -> PCT -> LoH (in medulla) -> DCT -> CD -> ureter (all = NEPHRON)

Excretion = filtration - reabsorption + secretion (in PCT, reabsortion and secretion to/from peritubular capillaries)

10mmHg

1.2L/min

Question 9

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?

Answer 9

1.2L/min and 120-125ml/min

680ml/min and 1ml/min

99%, 2/3 in PCT

Question 10

Describe how fluid is reabsorbed in the PCT

Answer 10

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.

Question 11

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

Answer 11

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)

Question 12

How does kidney damage affect GFR and RPF?

GFR is an important test of kidney health. What is the formula for clearance?

Answer 12

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

Question 13

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?

Answer 13

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

Question 14

Apart from GFR, what can creatinine clearance also be used to measure?

What is the substance used to measure clearance and hence RPF?

Answer 14

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.

Question 15

GFR is autoregulared - what does this mean, and thus what can be measured?

Hence what kinds of releasing cells are found in the kidney?

Answer 15

It (and RPF) doesn’t change over a wide range of BPs, thus pO₂ in interstitium - measure of O₂ carrying capacity of blood.

Erythropoietin

Question 16

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?

Answer 16

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

Question 17

What happens if Na⁺ concentration in the DCT is too low?

And if too high?

Answer 17

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

Question 18

Label D, 6, 7, 9 and 11

Answer 18

D: juxtaglomerular apparatus

6: granualar cells (juxtaglomerular cells)
7. macula densa
9. afferent arteriole
11: efferent arteriole

Question 19

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?

Answer 19

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)

Question 20

What 3 sensors is blood volume regulated by?

Answer 20

Neuronal volume sensors

Hormonal volume sensors

Osmotic sensors

Question 21

What are neuronal volume sensors?

What happens when venous return increases?

Answer 21

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.

Question 22

What are hormonal volume sensors?

What do they do in response to increased blood volume?

What is BNP?

Answer 22

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

Question 23

What are osmotic volume sensors?

Answer 23

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

Question 24

What happens when osmoreceptors detect high blood osmolarity?

Apart from osmoreceptors, what also modifies ADH release?

Answer 24

ADH released from pituitary -> decrease H₂O loss from urine -> thirst triggered (and vice versa)

Sympathetic arousal - fight or flight increases ADH

Question 25

Label A-D

Answer 25

A: pituitary stalk B: hypothalamus C: pituitary gland D: hypothalamus

Question 26

Label A and B. Where do they project to?

Answer 26

A: supraoptic nucleus B: paraventricular nucleus Project to post pituitary gland

Question 27

How does the kidney concentrate urine, and by how much? Describe the process of reabsorption from the PCT, down the LoH and to DCT.

Answer 27

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. **DCT:** 100mosmol/l

Question 28

What are the 2 Na⁺ Cl^- transport mechanisms?

Answer 28

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

Question 29

Give an example of a loop diuretic, and explain what they do.

Answer 29

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

Question 30

Where is the site of ADH in the kidney? What does ADH do?

Answer 30

Collecting duct. 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.

Question 31

Describe the urea cycle. What is the counter current multiplier mechanism?

Answer 31

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.

Question 32

Describe the counter current exchange mechanism of the vasa recta.

Answer 32

Preserves conc gradient despite blood flow through vasa recta. Blood enters at normal osmolatiry, gets concentrated in medulla, and dilute again as it leaves.

Question 33

Distinguish between the terms: water diuresis osmotic diuresis diabetes insipidus diabetes melluitus

Answer 33

**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.

Question 34

Describe the structure of the Bowman's capsule. Describe the structure of the glomerulus. What 3 things form the glomerular filtration barrier?

Answer 34

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