Sodium & Acid Base

DCT bicarbonate, Aldosterone & BP, Aldo. secretion factors

DCT fluid

Hypotonic compared to plasma

• 25% filtered volume

• 5-10% NaCl filtrate

DCT role

• Na+ resorption → blood pressure

• K+ secretion (linked to Na+ regulation)

• HCO3- regeneration (buffer)

  • Respiratory system regulates acid (CO2)

• Ca2+ and Mg2+ excretion (linked to phosphates)

DCT filtration regulation (tubuloglomerular feedback)

• Cl- sensed by DCT macula densa

• High Cl- (too much in flitrate)

• afferent arteriole constriction (e dilation ) → high resistance, low flow → lower GFR

Early DCT

• Impermeable to water

• Na+ Cl- reabsorbed via cotransport → more dilute tubular fluid

• If high urine specific gravity → high urine concentration (e.g. diarrhoea when lots of water loss from ECF) → kidney working fluid

• If low urine specific gravity → low urine concentration → Na+ absorbed > H2O absorbed

  • Removing excess water → could be pathological (lack of ADH action)

  • Diabetes insipidus, Cushing’s

Late DCT

• Site of aldosterone action

  • Na+ resorption, K+ excretion

• Regeneration of HCO3- to buffer excess acid (acid base balance)

• Can make ammonia → increase acid secretion

  • Ionised ammonia trapped in DCT

    • Acts as buffer to attract more H+ into urine

• Site of PTH action → Ca2+ resorption

• No microvilli

Reason for filtration

• Avoid secretory processes for each waste product

• Organic acids (e.g. beta lactams) and bases actively secreted

Na+ homeostasis (kidney)

• Mammals evolve to conserve Na+

• Na+ regulation is response to change in blood pressure

  • Aldosterone: slow response → long term blood pressure

    • pressure natriuresis

  • Chronic → gradual BP change over a long time

  • Acute → small BP changes in short time

• Reducing blood pressure (plasma Na+) by small amount → greatly improves CV health

• Neurohormonal mechanisms → sympathetic, RAAS

Natriuretic system

(atrial naturetic peptide and BNP)

Response to lowered ECF/blood pressure → Na+ conservation

• Constrict afferent arteriole → decrease GFR

• Vasodilation → lowers MAP → lowers TPR → cGMP stimulation

• Inhibits RAAS

• Negative feedback (when natriuretic response too dominant) → RAAS inhibits natriuretic system

• High angiotensin 2 → high aldosterons secretion → high Na+ resorption

  • Higher blood pressure needed to achieve high GFR → achieves same level of Na+ excretion

Aldosterone

• Mineralocorticoid

• Zona glomerulosa

• Stilmulated by antiogensin 2 and hyperkalaemia

• Inhibited by ANP

• Increases epithelial Na+ channels expression (ENaC) apically

• Increases Na+/K+ ATPase expression basolaterally

  • Maintains Na+ concentration for facilitated diffusion (for ENaCs)

• Increases K+ channel expression (ROMK1) in apical membranes → increased K+ secretion into tubular lumen

Response to high ECF volume (BP)

• Excrete Na+

• High Cl- reaches macula densa

• Adenosine switches off renin → lowers aldosterone

• ANP → inhibits RAAS

  • ANP → diagnostic and prognostic markers of congestive heart failure

  • (pro)BNP → same for kidney failure

• Endogenous digitalis like factor

  • Inhibits Na+/K+ ATPase

  • Decreases Na+ concentration gradient

  • Less Na+ travels into ENaCs (cannot reach blood)→ less resorbed → less water resorbed

Cat hypertension

Older cats → less efficient kidney → less Na+ excretion → increased BP

Acid base regulation and kidney

• ECF = pH 7.4

• Intracellular fluid more acidic

• Haemoglobin buffer protects against pH change

• Most important buffers → bicarbonate and CO2

• pH = pKa + log[HCO3-]/pCO2

  • Hyperventilate → less CO2 → more alkaline

Alkaline plasma

• → regenerate less HCO3- in DCT, resorb + regenerate less HCO3 in PCT

Excess acid (lactic acid buildup) → bicarbonate regen

• H2O and CO2 in DCT epithelium → [carbonic anhydrase] → H2CO3

• Dissociation → H+ + HCO3- (within epithelium)

  • Basolateral Na⁺/K⁺ ATPase actively pumps Na⁺ out → blood

  • HCO₃⁻ is reabsorbed → blood via Cl⁻/HCO₃⁻ exchanger

  • NaHCO3 regenerated and reabsorbed

• H+ pumped apically

  • H⁺-ATPase (Proton pump)

  • H⁺/K⁺ exchanger (H⁺/K⁺ ATPase) (H+ out, K+ in)

• H+ combines with negative ion → SO4^2- PO4^3-

Glutamine → NH3 (in DC epithelium) → NH4+ (ionised and trapped in lumen)

Glutamine is a source of HCO3- & NH3

Acidotic

Respiratory → high pCO2 → compensation → high HCO3-

Metabolic → low pCO2 → respiratory trying to correct acidosis but failing as HCO3- still high

Respiratory → acute, acts faster