2018B08 Briefly outline the functions of the kidney.

Overall function

·  Control water content

·  Control water partitioning (ECF vs ICF)

·  Control osmolality

Summary of renal handling

·  Free glomerular filtration water (180L/day) and electrolytes

·  Selective tubular reabsorption

·  Urine output only ~2L/day and variably concentrated

Autoregulation

·  Glomerular filtration rate:

o Constant 125mL/min at mAP 70-170mmHg

o Mechanism: ↓stretch -> ↓afferent arteriolar constriction

·  Glomerulotubular balance:

o Constant fraction of Na⁺/Cl^-/H₂O reabsorbed from proximal tubule

o Mechanism: ? ↑glucose and amino acid absorption -> ↑osmosis

·  Tubuloglomerular feedback:

o ↓NaCl load to macula densa -> afferent arteriolar dilation -> ↑GFR

o Mechanism: ↑PGE₂, ↓adenosine

Hormonal control

·  RAAS:

o Renin source: granular cells of juxtaglomerular apparatus

o Renin release stimuli: a) hypoperfusion b) SNS stimulation c) low Na⁺Cl^- load to distal tubule

o End result: ↑reabsorption of Na⁺, H₂O -> ↑ECF volume

·  ADH:

o Source: hypothalamus

o Release stimuli: ↑osmolality (∆2%) ↓mAP, ↓blood volume (∆10%), angiotensin 2

o End result: ↑H₂O reabsorption only -> ↑total body water and ↓osmolality

·  ANP:

o Source: right atrium

o Release stimuli: distension

o End result: ↑GFR, ↓Na⁺/H₂O reabsorption from distal nephron (natriuresis)

Na⁺ reabsorption

H₂O reabsorption

Proximal tubule

65%

65%

Thin descending loop of Henle

-

10%

Thick ascending loop of Henle

25%

-

Distal convoluted tubule

5%

-

Collecting duct

4-5%

5-24.7%

Potassium

·  Free filtration: 180L/day x 4mM = 720mmol per day

·  Fixed reabsorption 95% (proximal tubule 65%, loop of Henle 30%)

·  Compulsory excretion 5%

·  Variable secretion (stimulated by aldosterone)

Calcium

·  Proximal tubule: PO₄^3- reabsorption

o ↑: Vit D

o ↓: PTH, calcitonin

·  Distal tubule: Ca²⁺ reabsorption

o ↑: Vit D, PTH

o ↓: Calcitonin

Reabsorption of HCO₃^-

·  4000-5000mmol/day

·  85% prox tubule, 10% thick ascending LOH, 5% distal tubule and collecting duct intercalated cells

·  ↑ECF HCO₃^- -> shift in carbonic acid equilibrium (H₂O + CO₂ <-> H⁺ + HCO₃^-)

Excretion of titratable acid

·  Phosphoric acid 30mmol/day (up to 60mmol/day)

·  H₂PO₄ <-> H⁺ + HPO₄^- pKa 6.8

Excretion of ammonia

·  70mmmol/day (up to 300)

·  60% deamination of glutamine, 35% filtered by glomerulus, 5% deamination of other amino acids

·  Glutamine -> 2NH₄⁺ + 2HCO₃^- + oxoglutarate

·  HCO₃^- reabsorbed

·  NH₄⁺ secreted by Na⁺/NH₄⁺ antiporter. 70% reabsorbed in LOH, recycled

Gluconeogenesis

·  Glutamine -> oxaloacetate -> glucose (?)

·  Supplies obligate glucose users (brain, RBCs)

·  Important in starvation

Detoxification

·  CYP450 enzymes

·  e.g. CYP2E1 metabolises 70% methoxyflurane

Exogenous waste

·  Creatinine as creatinine

·  Amino acids as urea

Drug metabolites

·  Especially if large, water-soluble

·  e.g. morphine-6-glucuronide

·  e.g. pancuronium

(accumulation in renal failure)

In health

·  ↓pO₂ in interstitium -> ↑EPO secretion by interstitial fibroblasts -> ↑differentiation of pluripotent haem stem cells to erythroblasts

In renal failure

·  ↓Renal metabolic rate -> ↑pO₂ in interstitium -> ↓Epo -> anaemia