Renal Systems

Urine

Normal:

  • 1.5L water per day
  • 95-98% water
  • Creatinine
  • Urea
  • H+, NH3+
  • Na+, K+
  • Drugs
  • Smell = Unremarkable
  • pH = Diet dependent, V = 7.2, M = 4.8

Pathologic:

  • Glucose
  • Protein
  • Blood
  • Haemoglobin
  • Leukocytes
  • Bacteria
  • Look: gold, red, brown, blue
  • Smell: like fruits (ketosis) or rotten (infection/tumor)

Final Urine:

  • Facilitated via filtration, secretion, re-absorption of ions, solutes or metabolites.

Filtration

  • Many substances are filtered at a constant rate at renal corpuscle, EXCEPT those bound to a protein.
  • Some need to be partly or entirely re-absorbed, others need to be entirely secreted e.g. PAH - represents many drugs.

Barrier:

  • Capillary and endothelium (fenestrated, charged)
  • Basement membrane (three layers)
  • Epithelial podocyte (slit diaphragm)

Exclusion Critera:

  • Size: low molecular mass substances are freely filtered, large substances are not filtered.
  • Charge

Forces
Favouring:

  • Glomerular capillary blood pressure 60mmHg

Opposing:

  • Fluid pressure in Bowmans space 15mmHg

  • Osmotic forced to album protein in plasma 29mmHg


  • Filtration = favoured

Clearance

Criteria for GFR determining substance:

  • Freely filtered
  • Not re-absorbed
  • Not secreted
  • Not metabolised
  • Not toxic

Suitable:

  • Inulin (exogenous)
  • Creatinine (endogenous metabolite)

Equation:
Clearance = Volume of plasma that is cleared from a substance per time.
Us xVu/Ps
Us: Concentration in urine
Vu: Urine volume per time
Ps: Concentration in plasma
Vp: Plasma volume per time

Creatinine or Inulin Clearance = GFR: 125mL/min

GFR:

  • Indicator for kidney function
  • Even one healthy kidney can manage to keep plasma creatinine at a suitable level

Clearance of PAH:

  • 600mL/min cleared from plasma in one perfusion round
  • C(PAH) = Renal Plasma Flow
  • RBF = RPF/(1-haematocrit) = 1.2L/min
  • PAH actively secreted by cascade of basolateral and apical transporters
  • PAH = model organic anion that does not exist in our body, but represents a wide range of drugs.

Filtered Load

"The amount of substance filtered per time"

  • Plasma [S] x GFR = Filtered Load

Reabsorption

Glucose:

  • Reabsorbed by 2 mechanisms; GLUTs and SGLTs
  • In early PCT, SGLT2 absorbs 90% of filtered glucose.
  • In late PCT, SGLT1 absorbs 10% of filtered glucose.
  • Transport can be saturated, results in excretion of excess glucose (diabetes mellitus)

Blood Pressure

  • Regulation is mainly by heart and arteries, BUT depends on blood volume.
  • Antihypertensive drugs e.g. Ca antagonists, B blockers.

Blood Volume

  • Regulated by the kidneys
  • Detectors: osmoreceptors in the brain and baroreceptors in the arteries and heart
  • Antihypertensive drugs e.g. diuretics

Na+:

  • Intake of sodium is matched by output via the kidney.

Of filtered load:

  • PCT = 66%
  • TAL = 25%
  • DCT = 5%
  • CCT = 5%

PCT:

  • Trans and paracellular
  • Provides gradient for nutrient absorption
  • Isotonic re-absorption (equal water and sodium)

TAL:

  • Semi-tight epithelium, 50:50 trans and para
  • Loop diuretics (furosemide) inhibit NKCC2, inhibit reabsorption - increase urination
  • Used to treat hypertension or oedema in lungs or legs: reduces volume.

DCT:

  • Tight epithelium
  • Only transcellular re-absorption
  • Diuretics (thiazides) inhibit NCC, induce mild diuresis.

CCT:

  • Tight epithelium
  • Transcellular re-absorption
  • Regulated by hormones (aldosterone)
  • Amiloride (diuretic) inhibits ENaC, induces very mild diuresis

Counter Current Multiplier System:

  • Key for maintaining a hyperosmotic interstitium.


  • TAL reabsorbs Na+ into interstitum via NKCC2

  • tDLH is leaky, facilitates water re-absorption via AQPs and paracellular pathway.
  • PCT : isotonic
  • tDLH : hypertonic
  • TAL : hypotonic
  • CD = hypertonic (during antidiuresis)

Na+ Regulation

Renin:

  • Low plasma volume increases renin release from JXA cells (low pressure receptors) due to low NaCl detection in the macula dense cells (chemoreceptors) AND increase in renal SNS activity.


  • Renin converts angiotensinogen to angiotensin I and ACE converts ATI to ATII.


  • AngiotensinII increases secretion of aldosterone from adrenal glands.


  • High plasma aldosterone increases Na+ and H2O reabsorption in the CCT

Amiloride:

  • Diuretic drug in CCT
  • Only transcellular reabsorption here
  • ENaC is inhibited, induces mild diuresis.

ANP:

  • Released when high plasma volume is detected
  • ANP decreases aldosterone secretion, increases GFR via afferent arteriole dilation and efferent constriction.
  • Overall reduces Na+ reabsorption and increases Na+ excretion = increases water excretion, decreases plasma volume.

Leaky Epithelia:

  • Paracellular Cl and Na absorption establishes water gradient and rives trans and paracellular water absorption.

Hormone Regulation

ADH/Vasopressin

  • Secreted via posterior pituitary gland
  • Inducer = low blood pressure sensed by baroreceptors
  • Inducer = high blood osmolarity sensed by osmoreceptors.
  • Increases CD permeability to water = increase absorption, increases plasma volume = increases blood pressure

Renal pH Regulation:

  • Acidosis = increase arterial H+
  • Alkalosis = decrease arterial H+

Respiratory:

  • Acidosis: increase HCO3 reabsorption in the kidney
  • Alkalosis: secretion of HCO3 in CCT of the kidney

Metabolic:

  • Acidosis (diarrhoea): increase ventilation
  • Alkalosis (vomiting): decrease ventilation OR secretion of HCO3 in CCT