Q11

Discuss how and where H+ is secreted in the kidney?
Prompt: How is Bicarbonate involved?

  • Active secretion H+ ( H+/Na+ co transport- 2ary active secretion), allows reuptake of HCO3- from C anhydrase brush border_- H20/ CO2- Bic then into interstitium with Na via Na/K ATPase)
  • Bic in cell transferred to Interstitium along gdt_
  • In DCT/ Coll ducts- Principle cells/ Aldo- have H+ ATPAse channels + H/K ATPAse linked to Bic/ Cl- exchanger in BM

Pass Criteria:

  • 2 different mechanisms PLUS Bicarbonate

renal 2

What is the limiting pH of urine and how is this limitation dealt with?

  • pH 4.5 maximal acidity urine
  • much > acidity required excreted
  • 3 major BUFFER systems
    • H2CO3 (proximal)
    • NH4+(throughout)
    • HPO4 (distal)

Q12

Describe how sodium is handled in the glomerulus and the PCT.

  • Most Filtered out with solutes/ AAs  (90%)
  • Most (60%) Na-H counter-transport,
  • Bicarbonate is main anion reabsorbed with Na
  • Absolutely depends on Na K ATP ase ( Basement M)/
  • C Anhydrase-tub cell to generate H+/ Bic
  • Small co-transport with nutrients /anions/ Cl latter part
  • Approx 60%

Pass Criteria:

  • Good candidates will volunteer Na resorbtion through out except TALH, 60/30/7/3 % – all Na excretion last 3%

List the mechanisms that effect Na reabsorption.

  1. Tubulo-glom – Macula Densa, increased Na increased adenos/ Ca, aff vasocon
  2. Glomer/tub balance- > filtered = > resorbed (good capacity)- mainly oncotic p in eff capillaries
  3. Humeral
    • Aldosterone- distal CT / ENaC, K+/H+
    • PGE2 – pron Na K ATP ase block/ Ca ++ >
    • Ouabain endog- ATP ase block effect
    • Endothelin and IL-1 cause natriuresis (prob > PGE2)
    • ANP-increased cGMP – less ENaC
    • Angio 2- renal ACE increased circ Ang 1 + renal – increased PCT > reabs

Q13

Describe how anti-diuretic hormone/ Vasopressin acts on the kidney.

  • ADH binds to G-receptor,
  • V2 activates adenylate cyclase.
  • Increased IC c-AMP -> migration of IC  endosomes.
  • H20 channels (aquaporin2) inserted into  luminal membrane
  • Increased water permeability, with increased water reabsorption

Pass Criteria:

  • Must list 3 properties

What factors influence ADH secretion?

  • Table 39-1. Summary of stimuli affecting vasopressin secretion
  • Vasopressin Secretion Increased
    • Osmotic P of plasma increased 285mmol
    • Decreased ECF
    • Pain, emotion, “stress,” exercise
    • Nausea and vomiting
    • Standing
    • Clofibrate, carbamazepine
    • Angiotensin II
  • Vasopressin Secretion Decreased
    • osmotic P of plasma decreased
    • Increased ECF volume
    • Alcohol

Pass Criteria:

  • Must mention thick ascending limb of loop of Henle and reduced resorption of Na and Cl

Q14

Describe the physiologic process of Micturition.
Prompt: What are the nerves and muscles involved?

  • A spinal reflex inhibited and facilitated by higher centres
    • Intravesical pressure rises only after 400mls urine in bladder
    • Anatomy: Detrusor m, int and ext urethral sphincters
    • During micturition Detrusor contracts, and perineal muscles and EUS relax
  • Nerve Supply: Parasympathetic (S 2,3,4,)
    • via pelvic nn (afferent and efferents) to/from detrusor (efferent contraction) and pudendal nn to EUS (relaxation)
  • Nerve Supply: Sympathetic (L1,2,3)
    • Hypogastric nn via Inf Mesenteric Ganglion play no role in active micturition per se but role in prevention. (cause contraction of bladder muscle to prevent reflux of semen into bladder during ejaculation)
  • Initiation – remains unsettled, pelvic floor muscle relaxation  initiates. Perineal muscles and EUS  can be contracted voluntarily for prolonged periods. Bladder SM has intrinsic contractile activity Post urination, female urethra empties by gravity.
  • Male expels by contraction of bulbocavernosus m

List other factors that stimulate and inhibit micturition.
Prompt: What is the effect of autonomic agents on micturition?

  • Stimulants
    • Stretch/pressure (intravesical volume > 400mls)
    • Higher centre input
    • Parasympathetics (eg organophosphates)
    • Sympathetic inhibiting drug( eg a-blockers)
    • Voluntary abdominal muscle contraction augments stream but does not initiate micturition per se
  • Inhibitors
    • Parasympathetic inhibitors (atropine)
    • Higher centres
    • Sympathomimetics

Q15

Describe how the nephron handles potassium.

  1. K+ is freely filtered at the glomerulus (~600 mEq/day).
  2. Most is reabsorbed by active transport in the proximal tubule (~560 mEq/day).
  3. K+ is then secreted by passive diffusion into the tubular fluid in the distal tubule.
  4. K+ is also generally passively secreted into the tubular fluid in the collecting ducts.
  5. The total K+ excretion is approximately equal to K+ intake (~90 mEq/day) and K+ balance is maintained.
  6. There is no direct exchange of  K+ for Na+ in the tubular fluid of the distal nephron.  However reabsorption of Na+ into the tubular cell tends to promote secretion of K+ (or H+) to maintain the potential difference across the apical membrane

Pass Criteria:

  • Bolded PLUS 1 iother

What factors influence this?

  1. The rate of  secretion of K+ is proportional to the rate of flow of tubular fluid through the distal nephron.  With rapid flow the concentration of K+ in the fluid remains lower and secretion continues.
  2. Increased delivery of Na+ to the collecting ducts promotes increased secretion of K+ (e.g. thiazide diuretics).
  3. Conversely decreased delivery of Na+ to the collecting ducts promotes decreased secretion of K+.
  4. Inhibition of K+ absorption in the proximal nephron (e.g. osmotic or loop diuretics) promotes excretion of K+.
  5. In the distal nephron K+ and H+ compete for secretion in association with reabsorption of Na+.  Therefore in acidosis when H+ excretion is increased, K+ secretion is decreased.
  6. Aldosterone increases reabsorption of Na+ in the collecting ducts and thereby promotes K+ secretion.

Pass criteria:

  • 2 of the 3 bolded

Q16

What is normal renal blood flow and how can it be measured?

  • Fick principle (amount of a substance taken up per unit time divided by arterio-venous concentration difference)
  • PAH (excreted, not metabolised or stored, doesn’t affect flow) is used to measure effective renal plasma flow (90% cleared)

ERPF = Clearance of PAH = UV/P = 630 mL/min

  • Actual renal plasma flow = ERPF/0.9 = 700 mL/min
  • Renal blood flow = RPF x 1/1-Hct (Hct = 0.45)
  • Renal blood flow = approx 1250 mL/min

Pass Criteria:

  • Must list 3 properties

How do blood flow and oxygen extraction vary in different parts of the kidney?

  • Cortical flow is high (5 mL/gm of tissue) and oxygen extraction is low
  • Medullary blood flow is low (2.5 mL/gm in outer cortex, 0.6 mL/gm in inner cortex) and oxygen extraction is higher (more metabolic work done)
  • Medulla is vulnerable to hypoxic damage if flow is reduced (low flow, high oxygen usage)

Pass Criteria:

  • 2 out of 3 bold

Q17

Describe the cell types in the glomerulus and their functions.
Prompt: What types of cells lie between blood and the capillary and filtrate in Bowman’s capsule?
Prompt: What are their functions?

  • Capillary endothelial cells
    • Afferent arteriole becomes a tuft of capillaries invaginated into Bowman’s capsule. Endothelium fenestrated with 70-90 nm pores. Separated from capsule epithelium by basal lamina
  • Epithelial cells of Bowman’s capsule
    • Podocytes possess pseudopodia that interdigitate to form 25 nm wide filtration slits over capillary endothelium. Each slit is closed by a thin membrane
    • Mesangial cells are stellate and lie between capillary endothelium and basal lamina. Involved in regulation of filtration, secretion of various substances and absorption of immune complexes

Pass criteria:

  • Need fenestrated capillary membrane
  • Need podocytes with pseudopodia forming filtration slits

What properties of substances in the blood prevent free passage across the glomerular membrane?

  • Larger diameter > 8 nm
  • Lack of neutrality (charged)

Pass criteria:

  • Need both points

Q18

What factors influence clearance of substances by the kidney?

  • Amount of substance excreted = amount filtered + net amount transferred
  • Changes in RBF and systemic
  • Active transport (primary and secondary)
  • Hormonal (aldosterone, angiotensin, endothelin)

Pass criteria:

  • At least 3

Explain the mechanism of tubuloglomerular feedback.

  • Increased rate of flow in LoH and DCT increases GFR and local Na+
  • Macula densa adenosine A1 receptors activated by increased Na+/K+ activity, causing increased Ca2+, vasoconstriction and decreased GFR
  • Percentage solute reabsorbed remains constant (glomerulotubular balance)

Q19

What are the buffer systems in blood?
Prompt: What binds to H+ in blood.

  • Especially carbonic acid / bicarbonate system
  • Plasma proteins (free carboxyl and amino groups)
  • Hb (imidazole groups of histidine residues)

Pass criteria:

  • Bold PLUS 1 other

Explain how carbonic acid / bicarbonate system works.

  • Draw equations
  • Highlight importance of carbonic anhydrase (increases speed of reaction) and where carbonic anhydrase is (intracellular)
  • Outline control by respiratory and renal systems.

Q20

How is the secretion of renin regulated?

  • Stimulatory:
    • Increased sympathetic nervous activity
    • Increased circulating catecholamines;
    • Prostaglandins
  • Inhibitory:
    • Increased Na+ and cr reabsorption across the macula densa;
    • Increased afferent arteriolar pressure;
    • Angiotensin II;
    • Vasopressin.

Pass criteria:

  • Three of the above
  • At least ONE from each

Describe the juxtaglomerular apparatus.

  • Afferent and efferent arterioles and tubule touch at one point
  • Macula dens a and juxtaglomerular cells.