Physiology of the kidney

Abstract

Urine production

  • Site: nephron
    • The functional unit of the kidney.
    • Consists of:
      • A glomerulus (the major filtration structure)
      • Tubules (major absorbing and concentrating structure)
  • Process: Reabsorption and secretion of ultrafiltrate are monitored carefully and influenced by plasma concentrations as well as hormones (e.g., aldosterone, ADH, PTH).
    1. Blood flows via the afferent arterioles into the glomerular capillaries
    2. Plasma components are filtrated from the glomerular capillaries across the glomerular filtration barrier into the urinary space within the Bowman capsule → primary ultrafiltrate is formed
    3. Ultrafiltrate flows from the glomerulus through the tubular system (then referred to as tubular fluid) finely-tuned reabsorption and secretion of plasma components → Approx. 99% of the ultrafiltrate is reabsorbed into the bloodstream. → Urine is formed.
      • Urine osmolality: 50–1400 mOsmol/L
      • pH: 5.5 (between 4.5–8.2)
    4. Urine flows into the collecting ductsrenal pelvisureterbladderurethra
  • Function
    • Excretion of waste products (e.g., urea, creatinine, drugs)
    • Regulation of electrolytes, serum osmolality, and acid-base balance within narrow limits

Homeostasis

Substance Reabsorption Secretion Regulation / Mechanism Clinical relevance
H2O
  • Osmosis in proximal tubule, descending loop of Henle
  • Collecting duct (aquaporins)
Sodium
  • 65–80% in proximal tubule
  • 10–20% in thick ascending loop of Henle
  • 5–10% in distal tubule
  • 3–5% in collecting duct
  • Na/H antiporter
  • Na-Glucose symporter
  • Na-K-2Cl channel
Chloride
  • Follows sodium
  • Na-K-2Cl channel
Potassium
  • Na-K-2Cl channel; H+/K+ antiporter in α intercalated cells
H+ ions
  • -
  • H+ ATPase
Calcium
  • -
Magnesium
  • -
  • Competes with calcium
Glucose
  • Proximal tubule
  • -
  • Glucosuria
Urea
Bicarbonate
  • -
  • Acid-base balance
Phosphate
  • 85% in proximal tubule
  • -

Physiology of the tubular system

Segments

Location

Function Regulation Clinical relevance
Afferent arteriole Renal cortex
  • Regulation of blood flow
  • Na+ loss → volume loss
  • NSAIDs block prostaglandin synthesis → inhibit dilation of the afferent arteriole → decrease GFR and RPF
Proximal convoluted tubule Renal cortex
  • Resorption of most of the ultrafiltrate
    • Glucose
    • Amino acids
    • Uric acid
    • Na+(65–80% of Na+ is reabsorbed in this segment), Cl-,K+, HCO3, PO43-, and H2O
  • Forms NH3 and secrets into lumen (→ facilitates H+ secretion)
  • PTH decreases PO43- reabsorption
  • Angiotensin II increases Na+, HCO3, and H2O reabsorption
Loop of Henle Thin descending loop of Henle Renal medulla
  • Concentration of the ultrafiltrate: medullary hypertonicity (impermeable to Na+) → passive reabsorption of H2O
Thick ascending loop of Henle
  • Impermeable to H2O
  • Reabsorption of Na+(10–20% of Na+ is reabsorbed in this segment), K+, Cl-
  • K+ shift creates a positive lumen potential → facilitates paracellular reabsorption of Mg2+, Ca2+
  • Ultrafiltrate becomes less hypertonic
Distal convoluted tubule Renal cortex
  • Resorption of ions: 5–10% of Na+ is reabsorbed in this segment, Cl- and Mg2+
  • Impermeable to H2O
  • Urine becomes hypotonic
Connecting tubule and Collecting duct Renal cortex and renal medulla
  • Resorption of Na+ (3–5%): aldosterone stimulates epithelial Na channel and apical K+ transport, Na+/K+ ATPase
  • Selective water permeability (ADH integrates apical aquaporin in principle cells)
  • H+ and HCO3- secretion (H+ ATPase and HCO3-, Cl- exchanger)
Efferent arteriole Renal cortex
  • Regulation of blood flow
  • Angiotensin II causes vasoconstriction → increase in GFR
  • Juxtaglomerular feedback

Renal blood flow

Renal blood supply

  • Renal arteries (from the aorta) → segmental arteries → interlobar arteries → arcuate arteries → interlobular arteries → afferent arterioles → glomeruli → efferent arteriolesvasa recta and peritubular capillaries → renal veins (merge into the inferior vena cava)

Renal blood flow

Regulation of renal blood flow

The kidney has multiple mechanisms to regulate its own blood flow, and thus, the rate of glomerular filtration if fluctuations in systemic blood pressure occur.

Myogenic autoregulation (Bayliss effect)

  • Description: renal arteries maintain a constant blood pressure (between 80–180 mm Hg)

Prostaglandins

  • Description: renal hypoperfusion (particularly renal medulla) → stimulate prostaglandin synthesis → vasodilation of renal vessels → increased renal perfusion

Tubuloglomerular feedback

  • Description: feedback system between the tubules and glomeruli that adjusts the GFR according to the resorption capacity of the tubules
  • Mechanism: macula densa (of the juxtaglomerular apparatus) monitors the NaCl concentration in the DCT
    • Hypotonic urine (↓ Intraluminal Cl- concentration) → vasodilation of afferent arteriolesGFR↑ Cl- intraluminal concentration
    • Hypertonic urine (↑ Intraluminal Cl- concentration) vasoconstriction of afferent arteriolescapillary pressureGFR↑ Intraluminal Cl- concentration

Renin-angiotensin-aldosterone system (RAAS)

ACE inhibitors inhibit the conversion of angiotensin I to angiotensin II. Angiotensin receptor blockers inhibit the effect of angiotensin II. Both drug classes are used to treat arterial hypertension.

Hormonal

Autonomic regulation

Hypovolemic shock with severe hypotension activates the sympathetic nervous system. Subsequently, the hypovolemia and noradrenaline-induced vasoconstriction result in low renal blood flow → low GFR → low urine productionacute renal injury

Measurement of renal function

This section focuses on the basics of glomerular filtration and tubular secretion. For more information on kidney function tests, see Diagnostic evaluation of the kidney and urinary tract.

Clearance

  • Definition: the volume of plasma that is cleared of a substance X per unit time
  • Clearance of X (mL/min) = (Urine concentration of X (mg/mL) × (Urine flow rate (mL/min)) / Plasma concentration of X (mg/mL)

Glomerular filtration rate

GFR is directly proportional to the renal plasma flow!

The GFR is used to estimate kidney function → stages of chronic kidney disease.

Inulin clearance

Creatinine clearance

  • Used to estimate GFR (eGFR)
    • The Cockcroft-Gault equation is used to estimate GFR.
    • Typically slightly overestimates actual GFR because small amounts of creatinine are secreted by the renal tubules.
    • There is an age-related increase in serum creatine levels secondary to an age-related reduction in GFR. This must be taken into consideration when interpreting lab values in patients of advanced age.

Para-aminohippuric acid (PAH)

  • Used to estimate effective renal plasma flow (eRPF)
  • PAH is freely filtered in the glomerulus and secreted into the tubular lumen, but not reabsorbed→ results in almost 100% excretion
    • Secretion is dependent on an organic anion transporter that is located on the basolateral membrane of the proximal tubule.
    • If the concentration of PAH surpasses the transport capacity of the anion transporters; (or if there is damage to the PCT ) secretion is impaired → reduction in total excreted amount → underestimation of renal plasma flow.
  • Clearance depends on the plasma concentration of PAH; approx. 650 mL/min
    • If the plasma concentration of PAH is low, it gets completely excreted from the plasma through filtration and secretion.

Glucose clearance

  • Used to assess for glucosuria
  • Glucose is completely filtrated and completely reabsorbed in the proximal convoluted tubule through sodium-glucose cotransporters (SGLT2), it is not secreted → clearance is normally 0 mL/min
  • Glucose threshold: 180 mg/dL, above the threshold glucose clearance is proportional to the plasma concentration until the maximum secretion rate (Tm, 380mg/min) is reached

Filtration fraction (FF)

RPF FF Possible cause
GFR
GFR
  • Decreased plasma protein concentration (e.g., cirrhosis, malnutrition)
↑↑

Fractional excretion

  • Definition: the proportion of the glomerular filtered substance X that is excreted in the urine
  • Fractional excretion = excreted load (urinary concentration of X) / filtered load (GFR × plasma concentration of X)
    • FE < 1: a large proportion of the filtered substance is reabsorbed in the tubules (e.g., water, glucose, amino acids, sodium chloride)
    • FE > 1: a small proportion of the filtered substance is reabsorbed or additional tubular secretion occurs (e.g., PAH, atropine)
  • Woodcock T. Plasma volume, tissue oedema, and the steady-state Starling principle. BJA Education. 2017; 17(2): pp. 74–78. doi: 10.1093/bjaed/mkw035.
  • Corrigan G, Ramaswamy D, Kwon O, et al. PAH extraction and estimation of plasma flow in human postischemic acute renal failure. Am J Physiol Renal Physiol. 1999; 277(2): pp. F312–F318. doi: 10.1152/ajprenal.1999.277.2.f312.
last updated 11/25/2018
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