W04: RENAL PHYSIOLOGY

Question 1

Define the functions of the kidney.

Answer 1

Filtration and excretion of substances from blood plasma / cardiac output

Question 2

Describe the mechanisms of glomerular filtration, tubular reabsorbtion and secretion, and handling of solutes and water by the kidneys.

Answer 2

1. GLOMERULAR FILTRATION governed by glomerular capillary pressure and autoregulation
2. TUBULAR REABSORPTION facilitated by carrier mediated transport systems and utilisation of Tm
   * Tm = capacity d/t saturation. Exceeded = substrate enters urine
3. ACTIVE SECRETION of protein-bound substances from the peritubular caps to the proximal tubule. Via Tm-limited carriers.

Question 3

List the three basic renal processes.

Answer 3

1. FILTRATION which forms @ glomerular capillaries to produce protein-free filtrate of plasma
2. REABSORPTION regaining substances body needs while excreting substances body doesnt need or via active secretion
3. TUBULAR SECRETION substances from PERITUBULAR CAP. TO TUBULE LUMEN providing 2º route into tubule

Question 4

Explain why normally only filtration occurs at the glomerular capillaries.

Answer 4

Due to Pglom.cap.&raquo_space; π

Pressure here is higher as the AFFERENT ARTEIROLE is short and wide = little resistance to flow = blood has high hydrostatic pressure
+ narrow efferent arterioles = HIGH POST CAPILLARY RESISTANCE exceeds oncotic. pressure (π)

*autoregulation effective over a range of 60-130mmHg
if P falls = dilatation and vice versa
*autoregulation is intrinsic and independent of hormones and nerves

Question 5

Explain why normally only reabsorption occurs at the peritubular capillaries.

Answer 5

Within the efferent arteriole, resistance is offered along its entire length, there is a large P drop so that hydrostatic pressure is very low, ie PPC  15mmHg thus FACILITATING REABSORPTION INTO THE NEPHRON with ONCOTIC FORCES FAVOURED (π)

π is high d/t remaining proteins plus large volume lost as well

Question 6

List some of the factors which can influence glomerular filtration.

Answer 6

Pgc dependent on arteriolar diameters (aff. and eff) subject to:

• SYMPATHETIC VC NERVES = constriction, greater sens of afferent
• CIRCULATING CATECHOLAMINES = afferent primarily constricted
• Angiotensin II = constriction of efferent at [low], both at [high]

Question 7

Explain what is meant by the renal plasma threshold for glucose.

Answer 7

= 10mmoles/l (glucose)
Threshold is when SATURATION OCCURS, and where Tm occurs when looking at transport rate.

• governed by limited number of carriers
• Tm is set high to ensure optimum reabs. in non diabetic [glucose]

Question 8

Explain the significance of the active reabsorption of Na+ ions at the proximal tubule.

Answer 8

Majority of reabs occurs in PROXIMAL TUBULE via ACTIVE TRANSPORT (not by Tm) thereby creating a ▲Na+ across tubule wall

passive from lumen driven by active transport:
tubule (high) | epithelial (low) | ISF (high)

proximal tubule membrane unique numerous microvilli allow the permeability of sodium ions.

*Cl- follow ▲elec. = H20 follows, out of the tubule
= thereby concentrating the substances left in the tubule

Question 9

Describe the way in which K+ ions are handled by the kidney.

Answer 9

Thanks to the active transport of Na+ and the osmotic consequences, ⇧[K] (tub. lumen) facilitating passive solute diffusion.

Question 10

Describe the essential features of the loops of Henle which enable them to act as countercurrent multipliers.

Answer 10

ASCNEDING LIMB actively co-transports Na+ and Cl- OUT OF TUBULE into ISF but is IMPERMEABLE TO H20 = diluting filtrate

meanwhile

DESCENDING LIMB is freely permeable to H20 but impermeable to NaCl = H20 moves out (remember LOOP) to equate osmolarity

H20 moves to interstitium and draws NaCl further in (ascending)
H20 is then reabs into the vasa recta

1) concentration increases down descending and bends
2) concentrated fluid delivered to ascending
3) concentration decreases upon ascent

200mOsm difference between ascending and interstitium

Question 11

Explain the crucial importance of maintaining K+ homeostasis.

Answer 11

K+ is a MAJOR CATION = ECF[K+] = ~4mmols/l

⇧5.5mm = hyperkalaemia = ventricular fib.

⇩3.5mm = hypokalaemia = hyperpolarisation = cardiac arrythmias

After filtered, K+ reabs @ proximal tubule
+K+ secretion regulated by ALDOSTERONE

⇧K+ excretion induces negative feedback on aldosterone

Question 12

Significance of Tm

Answer 12

Tm is used to regulate certain substances

when set low = achieve early saturation = excretion thus ensuring plasma regulation

Question 13

Significance of proximal tubule and urea

Answer 13

only moderately permeable to urea therefore only around 50% reabs = remainder stay in the tubule

+tubule is impermeable to inulin and mannitol

Question 14

Passive Na transport across the tubule

Answer 14

SGLT cotransporter (Tm) facilitates transport if [Na] high. and where [Glc] low.

GLUT protein and NaKATPase on basolateral membrane

Question 15

Tubule relationship with drugs and pollutants

Answer 15

Naturally non-polar thus easily reabsorbed alongside osmotic forces
BUT
They become polar compounds and massively reducing permeability = excretion

Question 16

Action of FRUSEMIDE on LoH

Answer 16

Inhibit the active transport of NaCl @ ascending LoH preventing horizontal osmol. gr.

= 300mOsm. everywhere ensuring isotonic concentrations of urine in Patients.

Question 17

Significance of the countercurrent multiplier

Answer 17

Establishes horizontal gradient allowing concentration and eventual redilution of fluid
+~20% initial filtrate loss
+fluid entering distal tubule more dilute (from 300mOsm to 100mOsm)

= concentrating of medullary interstitium
= hypotonic fluid to distal convoluted tubule

Question 18

Significance of the Vasa Recta

Answer 18

Peritubular capillaries of the juxtamedullary nephrons act as countercurrent exchangers.

Hairpin arrangement prevents carrying away NaCl and consequently abolishing the horizontal gr.

instead equilibrates solutes but doesn’t draw water

1) provide O2 for medulla
2) removes volume from interstitium

Question 19

ADH & its Secretion

Answer 19

1º by plasma osmolarity = ⇧when osmotic pressure = ⇧ADH-secreting neurone discharge rate
therefore ⇧ADH release from posterior pit.

Osmoreceptors; neuronal discharge in the ant. hypo. and detect changes in cell stretch (d/t h20 loss/gain)

osmolarity changes induce vast increases/decreases in ADH = high gain system and very sensitive

2º ECF VOLUME affects ADH secretion

Question 20

ADH Action @ Tubule

Answer 20

Binds to membrane receptor

actives cAMP

Cell inserts AQP2 water pores in apical membrane

Ensuring water absorbed by osmosis in the blood

= ⇧permeability(H2O) @collecting duct

Question 21

ADH effect on urine

Answer 21

insertion of aquaporin in CD = permeable to water

ADH(+) = production of concentrated urine

ADH(++) = small volume of highly conc. urine via equilibration at each level
*observed in water deficit and retention

ADH(-) = impermeable to H2O thus LARGE VOL OF DILUTE URINE compensating for H2O excess.
d/t impermeability of H20 down the CD, remains hypotonic

Question 22

Role of urea

Answer 22

with ADH(+), urea is concentrated along the CD and then moves out down the conc. gr towards the medullary tip and REABS.

amplified in ADH(++) and urea moves out from CD into interstitiium reinforcing interstitial gr. in thin LoH
= uraemia occurs (⇧urea => goes to vasa recta)

Question 23

ECF volume effects on ADH + pressure receptors significance

Answer 23

⇧ECF vol = ⇩[ADH] and vice versa

• low pressure R located in atria and great veins = detect circulatory ‘fullness’
• high pressure R located in carotid and aortic arch baroreceptors
• haemorrhage
• volume expansion

Question 24

Other stimuli affecting ADH

Answer 24

(+): pain, emotion, stress, exercise, nicotine, morphine
*
*truamatic sx inductes ADH secretion thus H2O intake to be monitored

(-) alcohol suppresses ADH

Question 25

DIABETES INSIPIDUS

Answer 25

ADH deficiency d/t hypothalamic areas compromise = CENTRAL DIABETES INSIPIDUS

or CD insensitive to ADH = PERIPHERAL D. INSIPIDUS
*often 2º to hypercalcaemia or hypokalaemia so resolves when ions corrected

> ADH Tx