What is normal GFR?

  • 125ml/min in 70kg male, 10% less in female

What factors affect GFR?

  • Net filtration pressure
    • = hydrostatic pressure in capillaries and bowmans capsule AND colloid osmotic  pressure
    • Afferent – efferent pressure- under control of – autoregulation, sympathetic, AgtII, dobutamine, PGs, serum Na – renin
    • Pressure in bowmans capsule – renal obstruction
  • Capillary filtration coefficient
    • Relates to surface area and permeability of capillaries
    • Surface area controlled by mesagial cells under control of AgtII, ADH, NA, PGs ( constrict)
    • ANP, dopamine, cAMP, PGE2(relax)

Pass criteria

  • 3 to pass

As well as filtration, by what other means does the kidney regulate the composition of urine?

  • Secretion and resorption

Pass criteria:

  • 1 out of 2



Can you draw a nephron and describe the functions of each part.

  • Glomerulus – filtration
  • Afferent arteriole(contain juxtaglomerular cells – secrete renin) then capillary tuft then efferent arteriole encapsulate in bowmans capsule
  • PCT- resorption of most solute – Na, glucose, aa, reclaim HCO3
  • Desc limb of LOH – thin, water permeable
  • Thick Asc LOH – site of Na K 2 Cl – generates concentration gradient
  • DCT – site of Na K Cl pump
  • Proximal part is the macula densa forms juxtaglomerular apparatus –
  • CD- p cells – under control of ADH and aldosterone(water and Na resorption)
  • I cells – involved in H+ excretion


renal 1


How does vasopressin cause retention of water?

  • Increases permeability of CD, acting on V2 receptors
  • Insertion of protein water channels (aquaporin 2) in uminal membranes.
  • Water enters hypertonic interstitium
  • Urine becomes concentrated and volume decreases
  • Retention of water in excess of solute

What stimuli affect vasopressin secretion?

  • Factors increasing vasopressin secretion
    • Increased effective osmotic pressure of plasma
    • Decreased ECF volume
    • Pain, emotion, “stress”, exercise, standing
    • Nausea and vomiting
    • Clofibrate, carbamezepine, angiotensin 2
  • Factors decreasing vasopressin secretion
    • decreased effective osmotic pressure of plasma
    • increased ECF volume



How does the kidney handle potassium?

  • K+ filtered ~600meq/24hrs
  • Active K+ reabsorption in prox tubules ~560meq/24hrs
  • K+ secretion ~502meq/24hrs at distal tubule – amount proportionate to flow rate through distal tubules
  • Secretion – Electrical coupling to Na+ reab, thus H+ also

How do other ions affect potassium transport across the membranes in the nephron?
Prompt: How is potassium transported into and out of the tubules?

  • Collecting tubules Na reab’d, K excreted, electrical coupling  and passive K movement
  • Na reabsorbed in association with H secretion, K excretion decreased if Na low in distal tubule
  • Na/K 2Cl apical transporter/transport protein
  • 3Na/2K ATPase



What is a typical value for renal blood flow in an adult at rest?

  • ~25% of cardiac output or 1250 ml/min

What factors regulate renal blood flow?

  • Chemical:
    • Noradrenaline constricts interlobular and afferent arterioles.
    • Dopamine causes renal vasodilation.
    • Angiotensin II constricts efferent arterioles to a greater extent than the afferent arterioles.
    • Prostaglandins increase blood flow in the cortex and decrease blood flow in the medulla.
    • Acetylcholine produces renal vasodilation.
  • Neural:
    • Strong stimulation of the sympathetic nervous system produces renal vasoconstriction.
  • Autoregulation:
    • Direct contractile response of smooth muscle of afferent arteriole to stretch.
    • NO may be involved.
  • At low perfusion pressures angiotensin II plays a role in constricting efferent arterioles.



Please outline the structure of the Loop of Henle?

  • Thin/descending, Thick/ascending. Situated mostly in the renal medulla
  • Origin from PCT
  • Short (cortical) and long (juxta med.)loops
  • Macula densa at distal end, where joins DCT

Pass Criteria:

  • Must list 3 properties

What happens to electrolytes in the loop?

  • (Thin) Descending limb water permeable
  • Fluid becomes hypertonic as descends loop
  • (Thick) Asc limb impermeable to water, NaK Cl transported out, hypotonic at end, so K+ diffuses back
  • Active trans. ATPase

Explain the counter-current concentrating mechanism.

  • Gradient
  • Exchange (vasa recta)



What is a normal Glomerular Filtration Rate in humans?

  • 125 ml/min

What factors would cause a decrease in GFR?

  • Hydrostatic pressure
  • Renal blood flow
  • Capillary permeability
  • Plasma protein osmotic pressure
  • Size of capillary beds

Pass criteria:

  • 3 out of 5 to pass



What is the renal response to acidaemia?

  • Hydrogen ions actively secreted into the proximal tubule, thick ascending loop of Henle and distal tubules, facilitated the reabsorption of bicarbonate ions by forming the carbonic acid, which dissociates to form CO2 and water

Describe the buffer systems involved.

  • Bicarbonate
  • Phosphate
  • Ammonia



What stimuli influence vasopressin (ADH) secretion?

Increased by

  • decreased ECF volume
  • increased effective plasma osmotic pressure
  • angiotensin II
  • nausea & vomiting; stress, exercise, clofibrate, carbamazepine;

Decreased by

  • increased ECF volume
  • decreased effective plasma osmotic pressure
  • alcohol

How does vasopressin exert its anti-diuretic effect?

  • It increases permeability of the collecting ducts to water resulting in renal retention of water.
  • Activation of V2 receptors, causing insertion of proteins called water channels (aquaporins) into apical (luminal) membranes of the principal cells of the collecting ducts



What is the normal renal blood flow?

  • 1250ml/min, 25% CO

How is renal blood flow regulated?

  • Neuroendocrine; NA constrictor, DA dilator, Angio2 constrictor, PG’s (incr cortical decrease medulla), ACH dilates
  • Autoregulation, probably vessel wall stretch reflex as occurs in denervated isolated vessels
  • Renal nerves



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

  • Spinal reflex facilitated and inhibited by higher centres
  • First urge to void at 150ml
  • Marked fullness at 400ml
  • During micturition, the Detruser muscle contracts and perineal muscles/external urethral sphincter relax
  • Parasympathetic( S2,3,4) afferents respond to stretch receptors in  bladder wall to initiate reflex contraction via parasympathetic efferents.
  • Pudendal nerve to External Urethral Sphicter causes relaxation.
  • Spinal reflex integrated in sacral portion of spinal cord
  • Sympathetic (L1,2,3) play no role in micturition but only in prevention. EUS and perineal muscles can be controlled voluntary for a period of time but eventually void reflex overcomes voluntary control

Pass criteria:

Spinal Reflex
Parasympathetic control
Voluntary Control



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)



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



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



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



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



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



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



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)



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.



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.



What factors affect filtration across the glomerular capillary bed?

  • Permeability and area of the glomerular capillary bed.
  • Hydrostatic pressures in the capillary and the tubule
  • Oncotic pressure in the plasma and the filtrate.

How can GFR be measured?

  • UxV / Px or concepts.



What is the renal response to respiratory acidosis?

  • Increased H+ secretion and HC03 – absorption.

What buffering systems are there for H+ in renal tubular fluid?

  • At least HC03 – and one of HPO/- or NH3 with explanation of buffering mechanism.



How does the renin-angiotensin system respond to hypotension?

  • With a drop in BP, renin is released from the JG cells and act on a renin substrate to form angiotensin I, which is converted to angiotensin II in the lung.
  • Angiotensin II causes vasoconstriction and decrease the excretion of both salt and water (long term effect).

What are the other effects of the renin-angiotensin system?

  • Salt and water retention
  • Stimulate aldosterone secretion
  • Faciliate the release of noradrenaline
  • Downgrade the baro-receptors
  • Increase the secretion of vasopressin



Describe the physiological characteristics of renal blood flow.

  • Renal blood flow is 25% of the cardiac output.
  • The glomerular capillary pressure is 40% of systemic arterial pressure.
  • The peritubular capillary network and renal veins are low pressure systems.
  • The renal cortex gets higher blood flow, but has low oxygen extraction (filtration).
  • Renal medulla gets less blood flow, but high oxygen extraction (osmolality) and sensitive to hypoxia

Pass criteria:

  • 3 out of 5

What are the factors that affect renal blood flow?

  • Decreased MAP – decreased baroreceptor firing – renal vasoconstriction – decreased RBF.
  • Exercise decreased RBF.
  • Pg ­ increased Rcbf decreased Rmbf.
  • Proteins ­increased RBF ­increased GCP.
  • Dopamine and ACh – vasodilatation – ­ increased RBF.
  • NA – vasoconstriction 1 > 2 constricts afferent arterioles and interlobular arteries decreased RBF.
  • Posture – lying to standing decreased RBF.
  • AgII constricts efferent arteriole increased perfusion pressure.

How can renal blood flow be calculated?

  • By determining clearance of PAH, its extraction ratio and the haematocrit



How does the kidney acidify the urine?

  • Secretion of hydrogen ions.
  • Binding of the hydrogen ions with buffers.
  • Secretion/absorption of bicarbonate ions.

Pass criteria

  • 2 out of 3

Is there a difference between the proximal and distal tubules?

  • PCT/DCT/CD secrete H+.
  • PCT via Na+/H+ exchange.
  • Na+/K+ATPase – Na+ from cell to interstitium.
  • DCT/CD H+ secretion ATP driven proton pump.

What factors increase acid secretion?

  • Factors which increase acid secretion
    • increased PCO2 ­ increased PaCO2 ­ increased aldosterone
    • decreased K+ increased CA concentration
    • increased K+, ­ decreased H+ secretion



What determines renal blood flow?

  • Systemic blood pressure
  • Renal vascular resistance, which is in turn influenced by:
    • Catecholamines (nerves & systemic)
    • Angiotensin II (JG cells -> renin)
    • Prostaglandins
  • Control systems:
    • Renal autoregulation (myogenic- stretch response, vasodilator metabolites, ? NO, ?prostaglandins)
    • JG apparatus
    • Renal sympathetic nerves

What are the consequences of a sustained reduction of renal blood flow?

  • Renal blood flow maintained MBP >70
  • Medulla is vulnerable to hypoxia (high MR)
  • ATN
  • Uraemia



What is THIRST, and what causes it?

  • An appetite, under hypothalamic control
  • Increased plasma osmolality
    • osmoreceptors in anterior hypothalamus
  • Hypovolaemia
    • Renin-angiotensin system
    • Baroreceptors in heart and blood vessels
  • Prandial
    • Learned or habit response
    • Osmolality & GI hormone effects
  • Psychogenic
  • Dry pharyngeal mucous membranes

What are the actions of vasopressin (ADH), and what influences secretion of this hormone?


  • Retention of water by kidney (collecting duct permeability), thus decreasing blood osmolality
  • V2 receptors -> insertion of aquaporin-2 (water channel proteins stored in endosomes) into cell membranes
  • Decreased cardiac output (via area postrema)
  • Vasoconstriction via V1 receptors
  • Glycogenolysis
  • ACTH secretion from ant pituitary


  • Osmolality
  • ECF volume (low pressure receptors in great veins, atria and pulmonary vessels, high pressure receptors in carotid sinuses and aortic arch)
  • Increased secretion with high osmolality &/or low ECF Volume, and visa versa
  • Pain, nausea, surgical stress and some emotions increase secretion
  • Alcohol decreases secretion



What happens to potassium as it passes through a nephron?

  • Freely filtered
  • 67% reabsorbed prox tub (with Na + H2O)
  • 20% reabsorbed asc limb (with Na and Cl)
  • Distal tubule reabsorbs or secretes (H/K/ATPase)
  • Reabsorbed in alpha intercalated cells
  • Secretion by principal cells
  • Diet, aldosterone, A/B, lumen ions, diuretics

How does potassium handling by the kidney change in response to changes in pH?

  • H and K are exchanged
  • Acidosis decreases K excretion
  • H makes K move into circulation, less for excretion
  • Alkalosis increases K excretion

How does aldosterone increase K secretion?

  • Increased Na entry into cells
  • Increased pumping out of Na by Na-K pump
  • Increased K uptake into principal cells
  • Increased K conc inc secretion driving force
  • Also inc luminal membrane K channels



What general mechanisms are involved in renal tubular reabsorption and secretion?

Mechanisms involved in re-absorption and secretion include endocytosis, passive diffusion and facilitated diffusion and active transport.

2 of Bold to Pass

How is Sodium reabsorped in the various parts of the nephron?

No sodium transport in Thin descending Loop of Henle.
In rest of system, sodium moves by co-transport, exchange or down concentration gradient.

Sodium pumped out of cell by Active Sodium-Cl-Potassium pump in basolateral membrane.
60% in PCT by Sodium-Hydrogen exchange.
30% in thick ascending Limb via Sodium —Potassium co-transport.
7% in DCT via Sodium-Chloride exchange

Site                                                        Apical Transporter                          Function

Proximal tubule                                                Na/        CT                                           Na uptake,          uptake

Na /P, CT                                             Na- uptake, Pt uptak

Na’         CT                                           Na’ uptake,         .. uptake

Na/lactate CT                                     Na uptake, lactate uptake

Na/H exchanger                               Na’ uptake. H extrusi

CI base exchanger                           Cl uptake
Thick ascending limb                       Na-K-2Cl CT                                        Na- uptake, H uptake, K uptake

Na/H exchanger                               Na’ uptake, H extrusio

K channels                                          K extrusion (recycling)


Distal convoluted tubule               CT                                                           Na uptake, Cl uptake


Collecting duct                                  Na.”. channel (ENaC)                      Na uptake
Pass: Bold to pass, demonstrating reasonable understanding of different processes



Describe the renal response to metabolic acidosis.
Prompts: (i) What prevents FT secretion stopping when urine pH falls to 4.5? (ii) Can you name any of the buffers that operate?

  • Renal mechanisms operate to compensate for metabolic acidosis and return the serum
  • pH towards normal
  • Anions that replace HCO3-are filtered at the glomerulus along with corresponding
  • cations (mainly Na-)
  • Renal tubule cells secrete 11-. into tubular fluid in exchange for Na’ and HCO3-
  • Buffering in the urine gives greater capacity to this system (otherwise limiting pH of
  • 4.5 would stop futher H secretion)
  • Buffering systems include: Bicarbonate, Phosphate, Ammonia

Pass: Compensatory mechanisms identified
Must know H- secreted into tubular fluid in exchange for Na_
Must know about buffering and give two buffers



How is H+ ion secreted in the proximal tubule of the kidney?

Secondary active transport (The renal tubular cells secrete H* into the tubular fluid in exchange for Na*; and for each H* secreted, one Na* and one HCO3 are added to the blood)

Linked to Na+/K+ ATPase

Outline the buffer systems that act to bind H+ ion in the tubular fluid.

3 systems — HCO3, HPO4, NH3
Major role of carbonic anhydrase/HCO3 system

Pass: 2 of 3 – must have bicarbonate

What is the importance of H+ buffering systems in the urine?

Limiting pH (-4.5) would rapidly be reached unless free H+ is buffered



Describe the counter-current mechanism in the kidney.
Prompt: What is the role of the vasta recta?

renal 3
a) Countercurrent multipliers in the LOH through active transport of Na (& Cr) out of its thick ascending limb. Water moves out of the thin descending limb, with inflow of tubular fluid from the PCT. This increases the interstitial osmolarity. This results in hypotonic fluid flows into DCT, isotonic fluid flows into the asc thick LOH. The final result is a gradient conc from the top to the bottom of the LOH & a gradient hyperosmolarity in the medulla interstitium.

b)Vasta recta as countercurrent exchangers in the kidney in which NaCI & urea diffuse out of the asc limb of the vessel & into the desc limb, while water diffuses out of the desc into the ascending limb of the vascular loop. As a result the solute remains in the medulla pyramid & maintain the interstitial conc.


renal 4



Where does sodium reabsorption occur in the nephron?

a)            All parts of the nephron except thin part of the LoH (+Specify at least two of:)
b)            60% PCT primarily by Na+-H+ exchange but also a range of cotransport (glc, Pi, AA, lactate)
c)            30% thick ascending limb of LoH (Na’-2CI–K-cotransporter)
d)            7% DCT LoH (Na+-C1- cotransporter)
e)            3% collecting ducts through Na+ channels (ENaC)

Pass: Bold

What are the mechanisms of sodium re-absorption in the nephron?

Na/K ATPase active transport. Moves (by gradient thus generated) across apical membranes from tubular lumen into cell via cotransport & exchanger proteins. Driven by active transport by Na-K ATPase (3Na/2K) from tubular cell into interstitium (mainly into lateral interstitial spaced)

Pass: Bold



Please describe how the urinary bladder empties.
Prompt : Could you describe the relationship between pressure and volume in the bladder as it relates to bladder emptying?

  1. Smooth muscle of the bladder is arranged in spiral, longitudinal, and circular bundles
  2. Contraction of the circular muscle, (detrusor muscle), is mainly responsible for emptying the bladder during urination **
  3. Micturition is fundamentally a spinal reflex facilitated and inhibited by higher brain centers and, like defecation, subject to voluntary facilitation and inhibition **
  4. Urine enters the bladder without producing much increase in intravesical pressure until the viscus is well filled
  5. The bladder muscle has the property of plasticity; when it is stretched, the tension initially produced is not maintained
  6. The curve shows an initial slight rise in pressure when the first increments in volume are produced; a long, nearly flat segment as further increments are produced; and a sudden, sharp rise in pressure as the micturition reflex is triggered
  7. The first urge to void is felt at a bladder volume of about 150 mL, and a marked sense of fullness at about 400 mL.
  8. The flatness of segment Ib is a manifestation of the law of Laplace which states that the pressure in a spherical viscus is equal to twice the wall tension divided by the radius. In the case of the bladder, the tension increases as the organ fills, but so does the radius. Therefore, the pressure increase is slight until the organ is relatively full
  9. During micturition, the perineal muscles and external urethral sphincter are relaxed; the detrusor muscle contracts; and urine passes out through the urethra. **
  10. The mechanism by which voluntary urination is initiated remains unsettled. One of the initial events is relaxation of the muscles of the pelvic floor, and this may cause a sufficient downward tug on the detrusor muscle to initiate its contraction.
  11. The perineal muscles and external sphincter can be contracted voluntarily, preventing urine from passing down the urethra or interrupting the flow once urination has begun.

Pass: 2, 3, 9 and basic understanding the process in an organised fashion

Describe the reflex control associated with voiding.

  1. The bladder smooth muscle has some inherent contractile activity; however, when its nerve supply is intact, stretch receptors in the bladder wall initiate a reflex contraction that has a lower threshold than the inherent contractile response of the muscle.
  2. Fibers in the pelvic nerves are the afferent limb of the voiding reflex, and the parasympathetic fibers to the bladder that constitute the efferent limb also travel in these nerves.
  3. The reflex is integrated in the sacral portion of the spinal cord.
  4. In the adult, the volume of urine in the bladder that normally initiates a reflex contraction is about 300-400 mL.
  5. The sympathetic nerves to the bladder play no part in micturition,
  6. They do mediate the contraction of the bladder muscle that prevents semen from entering the bladder during ejaculation

Pass: Parasympathethetic reflex, Sacral portion of cord, Vol to trigger 300 —400MIS




Describe water handling in the collecting ducts of the kidneys.
Prompt : How does vasopressin affect water handling in the collecting ducts?

  1. The collecting ducts (CD) have two portions: a cortical portion and a medullary portion
  2. Changes in osmolality and volume in the CDs depend on amount of vasopressin acting on ducts
  3. This antidiuretic hormone from the post pituitary gland increases the permeability of CDs to H2O
  4. Key to action of vasopressin on the CDs is aquaporin-2. Unlike other aquaporins, this is stored in vesicles in cytoplasm of principal cells.
  5. Vasopressin causes rapid insertion of these vesicles into apical membrane of cells. Effect is mediated via the vasopressin V2 receptor, cyclic AMP, protein kinase A, and a molecular motor, one of the dyneins
  6. In presence of enough vasopressin to produce maximal antidiuresis, H2O moves out of hypotonic fluid entering cortical CDs into interstitium of cortex, and the tubular fluid becomes isotonic
  7. As much as 10% of the filtered H2O is removed
  8. When vasopressin is absent, the collecting duct epithelium is relatively impermeable to water and the fluid therefore remains hypotonic, and large amounts flow into renal pelvis.


Pass: 2, 3, 6

What is an osmotic diuresis?
Prompt: Describe how it occurs.
Prompt: Can you give me an example.

  1. Presence of large quantities of unreabsorbed solutes in renal tubules causes an increase in urine volume called osmotic diuresis.
  2. Solutes that are not reabsorbed in the proximal tubules exert an appreciable osmotic effect as volume of tubular fluid decreases, and their concentration increases
  3. Therefore, they “hold water in the tubules”
  4. Concentration gradient against which Na+ can be pumped out of proximal tubules is limited. Normally, movement of H2O out of proximal tubule prevents any appreciable gradient from developing, but Na+ concentration in fluid decreases when H2O reabsorption is decreasing, because of presence in tubular fluid of increased amounts of unreabsorbable solutes. Limiting concentration gradient is reached, and further proximal reabsorption of Na+ is prevented; more Na+ remains in tubule, and H2O stays with it
  5. The result is that loop of Henle is presented with a greatly increased volume of isotonic fluid.
  6. This fluid has a decreased Na+ concentration, but total amount of Na+ reaching the loop per unit time is increased
  7. In loop, reabsorption of water and Na+ is decreased, because the medullary hypertonicity is decreased. The decreasing is due primarily to decreased reabsorption of Na+, K+, and Cl in the ascending limb of loop because limiting concentration gradient for Na+ reabsorption is reached. More fluid passes through the distal tubule, and because of the decreased, in osmotic gradient along the medullary pyramids, less water is reabsorbed in collecting ducts. Result is a marked increase in urine volume and excretion of Na+ and other electrolytes.
  8. Osmotic diuresis is produced by administration of compounds such as mannitol and related polysaccharides that are filtered but not reabsorbed. It is also produced by naturally occurring substances when present in amounts exceeding the capacity of the tubules to reabsorb them. E.g. diabetes mellitus, glucose that remains in tubules when filtered load exceeds TmG causes polyuria. Osmotic diuresis can also be produced by infusion of large amounts of sodium chloride or urea.

Pass: 1, 2, 3



Describe a method for measuring the glomerular filtration rate.
Prompt: Describe the properties of a suitable substance and give an example.

Measure excretion of a substance which is freely filtered through the glomeruli neither secreted nor reabsorbed by the tubules.

Non toxic, not metablised

Eg Inulin, NB Endogenous Creatinine has limitations


Ux is the conc of X in the urine

P is the urine flow per unit time

Px is the arterial plasma level of X.

If X is not metabolized in the tissues then the peripheral venous plasma level can be substituted for the arterial plasma level.

Pass: 3 of 5 bold, one example, definition or description and basic formula

What is normal GFR and what are the factors which affect it?

125m1/min in normal 70 kg male, 10% less

for women, and correlates with surface area.

Factors RBF, Systemic BP, Ureteric obstruction, compression by oedema within renal capsule, Plasma proteins, Permeability changes, Filtration surface area

Pass: Value (100-150) and three factors



What are the major physiological factors affecting sodium excretion from the kidney?
Prompt: How does the kidney regulate sodium excretion?


1.            Amount filtered versus amount reabsorbed, therefore

2.            ECF,

3.            GFR,

4.            Na intake,

5.            hormonal e.g. aldosterone, angiotensin and K and H excretion

4 to pass

What are the major physiological factors affecting potassium excretion from the kidney?
Prompt: How does the kidney regulate potassium excretion?

1.            K is reabsorbed in PTs and secreted in distal tubule,

2.            Amount secreted relates to tubular flow,

3.            Na excretion or reabsorption,

4.            K intake

2 to pass



Describe how water is reabsorbed in the different parts of the nephron.

I.             60-70% in the Proximal tubule

2.            15% in the loop of Henle

3.            5% in the distal tubule

4.            Up to 10% in the collecting duct depending on the presence of antidiuretic hormone.

Pass: Need to understand that water is reabsorbed in different parts and the role of vasopressin in the collecting duct.

What hormonal factor influences water excretion?
Prompt: What does vasopressin do?

Vasopressin increases the permeability of the collecting duct to water & allow water to be reabsorbed.



What factors control glomerular filtration?

Mention average 125m1/min or 0.16-0.2 of RPF and its derivation Ui x V/ Pi= Ci= GFR for inulin; Creatinine Clearance is approximation
Control of GFR depends on

  1. size of capillary bed,
  2. permeability of capills,
  3. hydrostatic pressure,
  4. oncotic pressure.

These influenced by changes in RBF, MAP, [plasma proteins], effective surface area, changes in pressure across                Bowman’s capsule – eg  ureteric obstruction, renal oedema. Glomerular                capills are 50x permeable as skeletal.

Need 3 of 4 to pass



Describe how respiration compensates for acid-base changes.

CO2 + H2O = H2CO3 = H + HCO3. Rapid responder.
Respiratory Centre responds to H, mainly at peripheral chemoreceptors, also transferred to CSF by CO2.
Metabolic acidosis —> inc ventilation, dec CO2 -> dec H, dec HCO3 (`base deficit’).
Metabolic alkalosis —> dec ventilation, inc CO2 -> inc H, inc HCO3 (‘base excess’). In reality often no compensation.

Davenport Diagram.

What clinical conditions might cause metabolic acidosis? / metabolic alkalosis?

– DKA; hypoxia -> lactic acid
– Vomiting ->loss of acid.



Describe the structure of the Loop of Henle.

Thin descending, thin ascending, thick ascending limbs. Cortical nephrons with short loops (85%) & juxtamedullary nephrons with long loops into medullary pyramids (15%).

Describe the function of the Loop of Henle.

Counter current multiplier: maintains gradient of osmolality; requires vasa recta as countercurrent exchangers Thin descending: high permeability to water; it moves out of tubule into interstitium Thin ascending: high permeability to NaCI; it moves out of tubule into interstitium Thick ascending: active transport Na, K, CI, from tubule to interstitium; impermeable to H2O



Describe the control renal blood flow.

Chemical: Noradrenaline constricts interlobular and afferent arterioles. Angiotensin 11 constricts efferent arterioles > afferent arterioles. Dopamine (made in kidney) vasodilates. Acetylcholine vasodilates. Prostaglandins inc. bl flow in cortex, dec. bl flow in medulla.

Neural: SNS -> dec bl flow. Fall of BP, vasoconstrictor response includes renal bl flow.

– Autoregulation: contractile response of smooth muscle of afferent arteriole to stretch (BP). NO may be involved. Angiotensin 11 plays a role in constricting efferent arterioles, maintaining GFR,



What are the major buffers of blood? How do they work?

Proteins, albumin; Haemoglobin; histidine residues = x6 proteins; Deoxygenated Hb better than Hb02; Carbonic Acid-Bicarb system, fast with carbonic anhydrase; lib deoxygenated; Hb histidine residues; proteins anions
What are the major buffers in cells?

Hproteins = H+ and Protein- ; H2PO4 = 2H+ and HPO4 –
Describe the Henderson-Hasselbalch equation.

pH = .pK + log [A-] / [HA]. Most effective when [A-] / [HA] = 1, so pH — pK



Explain how hypotension activates the renin-angiotensin system.

  • Hypotension leads to reduced perfusion pressure of the afferent glomerular arteriole, stimulating release of renin by the juxtaglomerular cells

Pass Criteria:

  • Bold to pass

How does the renin-angiotensin system contribute to the restoration of the blood volume?

  • Renin converts angiotensinogen to angiotensin I
  • Angiotensin converting enzyme converts angiotensin I to angiotensin II
  • Angiotensin II acts on the adrenal cortex’s zona glomerulosa cells to release aldosterone
  • Aldosterone acts on the renal distal tubules to retain Na and water, thus increases intravascular volume. Angiotensin II also a potent arteriolar constrictor and contribuets to a rise in blood pressure.

Pass Criteria:

  • 4/5 bold to pass

What other factors increase renin secretion?

  • Renin (protease) release is stimulated by increases in:
    • Catecholamines
    • Sympathetic activity through renal nerves
    • Prostaglandins
    • Low sodium states – cardiac failure, liver failure, sodium depletion

Pass Criteria:

  • 1/3 bold to pass



Describe the renal response to acidosis.

PROMPT – Describe the role of buffers in the kidney.

  • Aims to return serum pH to normal by increasing H+ excretion
  • Kidney retains HCO3 by actively secreting H+
  • Renal tubule cells excrete carbonic anhydrase converting CO2 to H+ and HCO3, then tubule cells secrete H+ in exchange for Na+
  • Amount of secreted H+ limited by urinary pH >4.5 (limiting pH)
  • Buffering in tubular fluid pH with HCO2, HPO4 and NH3 allows greater H+ secretion

Pass Criteria:

  • Must know that H+ actively secreted into tubular fluid in exchange for Na
  • Must know about buffering and name 2 buffers



Describe how the kidney responds to metabolic acidosis.

  • Renal tubule cells secrete H+ into tubular fluid in exchange for Na+
  • HCO3- is actively reabsorbed into the peritubular capillary (for each H+ secreted, 1 Na+ and 1 HCO3- are added into blood).

Pass Criteria:

  • Bold to pass

What substances act as urinary buffers for the excretion of H+?

  • NH3 forms NH4+
  • HCO3 forms CO2 and H2O
  • HPO42- forms H2PO4

Pass Criteria:

  • 2 of 3

How else can the body compensate for a metabolic acidosis?

PROMPT – What other major system is involved in acidosis compensation?

  • The respiratory system responds by increasing ventilation which results in a decrease in PCO2 which causes increase in pH (this is a rapid response)

Pass Criteria:

  • Bold to pass



What is normal Glomerular Filtration Rate (GFR)?

  • 125mL/min in normal adult 180L/24h/10% lower in women

Pass Criteria:

  • Approximate value

What factors control GFR?

PROMPT – What agents, mediators and clinical factors affect GFR?

  • Hydrostatic pressure/osmotic pressure gradient
  • Size & permeability of capillary bed (mesangial cell contraction/relaxation & loss of renal tissue)
  • K in Starling Forces = GF coefficient = mesangial cell
    • Increase – ANP, Dopamine, PGE2, cAMP
    • Decrease – Endothelins, AGII, vasopressin, norepinephrine, PAD, PGF2, leukotrienes Ca/D4, histamine TxA2
  • Clinical
    • Systemic BP
    • Parenchymal oedema
    • Ureteric obstruction
    • After-efferent arteriolar constriction
    • Plasma proteins

Pass Criteria:

  • 2 of 4 bold
  • Role of mesangial cells
  • 2 vaso active agents
  • 2 clinical examples



What is the renal response to dehydration?

  • Renin release, converts angiotensinogen to AT1
  • ACE converts AT1 to AT2
  • AT2 increases aldosterone synthesis, vasoconstriction of afferent arteriole
  • Aldosterone – sodium and water retention

Pass Criteria:

  • Need details re secretion i.e. reduced pressure at JG cells of renin and actions of A-2

What is the role of vasopressin in dehydration?

  • Promotes water resorption in collecting duct via aquaporins insertion.
  • Vasoconstriction

Pass Criteria:

  • Bold to pass



What is normal Glomerular Filtration Rate (GFR) and what factors regulate it?

PROMPT  – How does it change?

PROMPT – Identify two clinical factors that alter Starling Forces

  • Normal GFR = 125mLs/min (180L/24hours). 10% lower in females.
  • Controlled by Starling Forces i.e. GFR = K(PGC-PT)-(?GC-?T)
    • PGC = mean hydrostatic pressure in glomerular capillaries
    • PT = mean hydrostatic pressure in tubule
    • ?GC = osmotic pressure of plasma in glomerular capillaries
    • ?T = osmotic pressure of filtrate in tubule
    • K = GF coefficient; altered by mesangial cell contraction (-> dec area for filtration)
      • Contraction = Angio II, ADH, NA, PAF, TxA2, hsitamine
      • Relaxation – ANP, dopamine, cAMP, PgE2
  • GFR changes along glomerular capillaries with Starling forces dropping from 15 mmHg to 0.
  • Clinical factors altering Starling Forces
    • Alterations in renal blood flow
    • Systemic BP
    • Ureteric obstruction
    • Renal parenchymal oedema
    • Changes in plasma protein concentration
    • Changes in K as above

Pass Criteria:

  • a) approximate value for GFR
  • b) Identify Starling Forces involved
  • c) Identify central role of mesangial cells and two factors which change their degree of contraction
  • d) Identify two clinical factors that alter Starling Forces

How do the kidneys deal with Potassium?

  • Freely filtered at glomerulus (600 mmol/d)
  • Actively reabsorbed in proximal convoluted tubule (560 mmol/d)
  • Secreted in distal tubule – rate proportional to flow
  • Secreted in collecting ducts – aldosterone exreted = 90 mmol/d
  • Total secreted load average 50mmol/d but varies with renal tubular flow and aldosterone level

Pass Criteria:

  • a) freely filtered at glomerulus
  • b) largely reabsorbed in PCT
  • c) Sites of distal secretion plus influence of aldosterone




What percentage of cardiac output goes to the kidneys?

  • Renal blood flow = 1.2-1.3L/min or approx 25% cardiac output (adult)

Pass Criteria:

  • Renal blood flow 

How is renal blood flow regulated?

PROMPT – What other mechanisms are there?

  • Substances/Chemicals
    • Norepinephrine (noradrenaline)
      • constricts renal vessels
      • Stimulates renal nerves to increase renin secretion
    • Dopamine – renal vasodilatation
    • Angiotensin II – arteriolar constrictor
    • PG – increased cortex flow, decreased medulla flow
    • Acetylcholine – vasodilatation
    • High protein – increased b/flow
  • Renal Nerves
    • Stimulation nerves = increased renin secretion, increased JG sensitivity, increased sodium resorption, renal vasoconstriction
    • Strong stimulation sympathetic – decreased flow
    • Fall in BP = vasoconstriction
  • Autoregulation
    • Renal vascular resistance varies with pressure to keep renal blood flow fairly constant
    • Present in denervated kidney, but not if drugs that paralyse vascular smooth muscle
    • Factors = direct contractile response, NO, angiotensin II

Pass Criteria:

  • 3/6 substances plus nerve or auto – with example 

How can renal blood flow be measured?

  • Fick principle – subs taken up/unit time
  • PAH used to measure renal plasma flow
  • Renal blood flow using plasma flow and haematocrit

Pass Criteria:

  • One example 

Describe the differences in regional blood flow within the kidney.

  • AV O2 difference for kidney = 14mL
  • Cortical blood flow = 5mL/g/min
    • Little O2 consumption
  • Medulla blood flow low (outer = 2.5mL, inner = 0.6mL)
    • Maintenance of osmotic gradient

Pass Criteria:

  • One aspect of regional blood flow to pass



What are the major physiological features of acute intrinsic renal failure?

PROMPT – What happens to urine concentration?

  • Loss of urine concentrating and diluting capacity due to loss of countercurrent mechanism and nephron number. Polyuria -> Oliguria -> Anuria
  • Uraemia due to urea and creatinine and toxins (phenol and acids) build up.
  • Acidosis
  • Anaemia
  • Sodium retention and oedema and heart failure

Pass Criteria:

  • 3/5 bold

What are common findings in urinalysis of acute intrinsic renal failure?

  • Proteinuria
  • Leucocytes
  • Red cells
  • Casts

Pass Criteria:

  • 3 bold 

What are urinary casts?

  • Proteinaceous material precipitated in tubules washed into bladder

Pass Criteria:

  • Bold to pass



Describe the way the kidney handles glucose.

  1. Freely filtered at the glomerulus
  2. Resorbed in the early part of the PCT by secondary active transport
  3. Na dependent co-transportation (SGLT2 into cells then GLUT 2 facilitated diffusion into interstitial fluid).
  4. Excreted in the urine if renal threshold is exceeded.

Pass Criteria:

  • 1 & 2, plus understanding of 3 & 4

What are the potential consequences of glycosuria?

  • Osmotic diuresis – dehydration, electrolyte loss (Na, K)

Pass Criteria:

  • Understanding



What is normal renal blood flow?

  • Renal blood flow = approx 1250 mL/min

Pass Criteria:

  • Bold (accept 1000-1500)

What substances influence renal blood flow and how?

  • Noradrenaline
    • Constriction
  • Dopamine, ACh
    • Dilatation
  • Angiotensin II
    • Constricts afferent and efferent arterioles
  • PGs
    • Increase flow in cortex and decrease in medulla

Pass Criteria:

  • 2/5 substances + correct action

How can renal blood flow be measured?
Prompt: What substance can be used to measure renal plasma flow?

  1. Fick principle
    • Amount of a substance taken up per unit time divided by arterio-venous concentration difference
  2. PAH (or any substance that is excreted, not metabolised or stored, doesn’t affect flow)is used to measure effective renal plasma flow (90% cleared)
  3. Actual renal plasma flow = ERPF/0.9 = 700 mL/min
  4. Renal blood flow = RPF x 1/1-Hct   (Hct = 0.45)

Pass Criteria:

  • Concept/principle


What is the definition of the glomerular filtration rate?

  • The amount of fluid (plasma filtrate) filtered by the glomerulus per unit time

Pass Criteria:

  • Concept of filtration and time to pass

What is the normal GFR?

  • Usually 125 mL/min
  • 180 L/day
  • 10% less in women

Pass Criteria:

  • +/- 20% to pass
  • either per min or per day

What are the mesangial cells?
Prompt: Where are mesangial cells found? What do mesangial cells do?

Prompt: If “in nephron” stated – where in nephron?

  • Contractile cells that help to regulate GFR
  • Located between the basal lamina and the endothelium, in the glomerulus
  • Common between neighbouring capillaries, and in these locations the basal membrane forms a sheath share by both capillaries
  • Also secrete the extracellular matrix, take up immune complexes, and are involved in the progression of glomerular disease

Pass Criteria:

  • Bold to pass

What factors influence GFR?

  • Age
  • Afferent arterial (renal artery) pressure (however autoregulation keeps this stable between about 90-210 mmHg)
  • Afferent arteriolar pressure
  • Efferent arteriolar pressure
  • Efferent venous pressure
  • Intra-renal (interstitial) pressure (obstruction, oedema)
  • Oncotic pressure
  • Glomerular filtration fraction

Pass Criteria:

  • Any 3 to pass

What substances act on mesangial cells to change GFR?
Prompt: What substances act on mesangial cells to alter their function?

  • Glomerular filtration fraction (mesangial cell function) – influence by:
    • Increased
      • ANP, dopamine, PGE2, cAMP
    • Decreased
      • Noradrenaline, vasopressin, AII, PGF2, endothelins, TXA2, leukotrienes

Pass Criteria: