Renal Systems (Na+ Regulation (Leaky Epithelia:
Paracellular Cl and Na…
Renal pH Regulation:
- Acidosis = increase arterial H+
- Alkalosis = decrease arterial H+
- Acidosis: increase HCO3 reabsorption in the kidney
- Alkalosis: secretion of HCO3 in CCT of the kidney
- Acidosis (diarrhoea): increase ventilation
- Alkalosis (vomiting): decrease ventilation OR secretion of HCO3 in CCT
- 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
- Paracellular Cl and Na absorption establishes water gradient and rives trans and paracellular water absorption.
- 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.
- Diuretic drug in CCT
- Only transcellular reabsorption here
- ENaC is inhibited, induces mild diuresis.
- 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
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)
- Regulated by the kidneys
- Detectors: osmoreceptors in the brain and baroreceptors in the arteries and heart
- Antihypertensive drugs e.g. diuretics
- Regulation is mainly by heart and arteries, BUT depends on blood volume.
- Antihypertensive drugs e.g. Ca antagonists, B blockers.
Of filtered load:
- Intake of sodium is matched by output via the kidney.
- PCT = 66%
- TAL = 25%
- DCT = 5%
- CCT = 5%
- Tight epithelium
- Transcellular re-absorption
- Regulated by hormones (aldosterone)
- Amiloride (diuretic) inhibits ENaC, induces very mild diuresis
- Tight epithelium
- Only transcellular re-absorption
- Diuretics (thiazides) inhibit NCC, induce mild diuresis.
- 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.
- Trans and paracellular
- Provides gradient for nutrient absorption
- Isotonic re-absorption (equal water and sodium)
- 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)
"The amount of substance filtered per time"
- Plasma [S] x GFR = Filtered Load
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.
- Indicator for kidney function
- Even one healthy kidney can manage to keep plasma creatinine at a suitable level
Clearance = Volume of plasma that is cleared from a substance per time.
Us: Concentration in urine
Vu: Urine volume per time
Ps: Concentration in plasma
Vp: Plasma volume per time
Criteria for GFR determining substance:
- Freely filtered
- Not re-absorbed
- Not secreted
- Not metabolised
- Not toxic
- Inulin (exogenous)
- Creatinine (endogenous metabolite)
- Glomerular capillary blood pressure 60mmHg
- Fluid pressure in Bowmans space 15mmHg
- Osmotic forced to album protein in plasma 29mmHg
- Filtration = favoured
- Capillary and endothelium (fenestrated, charged)
- Basement membrane (three layers)
- Epithelial podocyte (slit diaphragm)
- Size: low molecular mass substances are freely filtered, large substances are not filtered.
- 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.
- Facilitated via filtration, secretion, re-absorption of ions, solutes or metabolites.
- Look: gold, red, brown, blue
- Smell: like fruits (ketosis) or rotten (infection/tumor)
- 1.5L water per day
- 95-98% water
- H+, NH3+
- Na+, K+
- Smell = Unremarkable
- pH = Diet dependent, V = 7.2, M = 4.8