- Site: nephron
Process: Reabsorption and secretion of ultrafiltrate are monitored carefully and influenced by plasma concentrations as well as hormones (e.g., aldosterone, ADH, PTH).
- Blood flows via the afferent arterioles into the glomerular capillaries
- Plasma components are filtrated from the glomerular capillaries across the into the urinary space within the Bowman capsule → primary ultrafiltrate is formed
- 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 flows into the collecting ducts → renal pelvis → ureter → bladder → urethra
|Substance||Reabsorption||Secretion||Regulation / Mechanism||Clinical relevance|
|Chloride|| || |
|H+ ions|| || || |
|Magnesium|| || |
|Glucose|| || || |
|Bicarbonate|| || |
|Phosphate|| || |
|Afferent arteriole||Renal cortex|| |
|Proximal convoluted tubule||Renal cortex|| |
|Loop of Henle||Thin descending loop of Henle||Renal medulla|| || |
|Thick ascending loop of Henle|| || |
|Distal convoluted tubule||Renal cortex|| || |
|Connecting tubule and collecting duct||Renal cortex and renal medulla|| |
|Efferent arteriole||Renal cortex|| |
Renal blood supply
- Renal arteries (from the aorta) → segmental arteries → interlobar arteries → arcuate arteries → interlobular arteries → afferent arterioles → glomeruli → efferent arterioles → vasa recta and peritubular capillaries → renal veins (merge into the inferior vena cava)
Renal blood flow (RBF): the blood volume that flows through the kidney per unit time
- Normal: ∼ 20% of cardiac output, 1.2 L/Min
Renal plasma flow (RPF): the volume of plasma that flows through the kidney per unit time
- RPF = RBF × (1 - Hct)
- Para-aminohippuric acid (PAH): nearly 100% of PAH that enters the kidney is also excreted (completely filtrated and secreted) → clearance rate is used to estimate RPF
- Effective renal plasma flow (eRPF) = (urine concentration of PAH) × (urine flow rate / plasma concentration of PAH)
Regulation of renal blood flow
- Description: renal arteries maintain a constant blood pressure (between 80–180 mm Hg)
- Description: renal hypoperfusion (particularly renal medulla) → stimulate prostaglandin synthesis → vasodilation of renal vessels → increased renal perfusion
- Description: feedback system between the tubules and glomeruli that adjusts the GFR according to the resorption capacity of the tubules
- Mechanism: (of the ) monitors the NaCl concentration in the DCT
- Description: hormonal system that regulates arterial blood pressure and sodium concentration
- Mechanism: renal hypoperfusion (e.g., hypotension, hypovolemia), hyponatremia or increased sympathetic tone → kidneys release renin (produced in the ) → renin converts angiotensinogen (produced in the liver) to angiotensin I → conversion of angiotensin I to angiotensin II through angiotensin-converting enzyme (ACE, mostly produced in the lungs) → Angiotensin II acts as a strong vasoconstrictor and induces the secretion of aldosterone by the adrenal cortex → aldosterone increases renal reabsorption of sodium (and water) and augments the excretion of potassium and protons → ↑ extracellular fluid, ↑ blood pressure, ↓ K+, ↑ pH
- Systemic: ↑ arterial blood pressure
- Renal: maintains GFR during renal hypoperfusion
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.
- Atrial natriuretic peptide (ANP): volume overload → dilation of atria → secretion of ANP by myocytes
- BNP): volume overload → dilation of ventricles → secretion of ANP by myocytes (
- Increases contraction of smooth muscle in blood vessels via V1 receptor → increased blood pressure → increased kidney perfusion
- Increases free water reabsorption in the collecting duct ; (stimulation of adenylate cyclase → ↑ cAMP → incorporation of aquaporins in the luminal membrane of collecting ducts)
- Increases urea resorption (↑ incorporation of urea transporters in the collecting duct)
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 production → acute renal injury
- 60% of body mass is composed of water.
- Two-thirds of body water (i.e., 40% of body mass) is intracellular fluid (ICF), which is mainly composed of potassium, magnesium, and inorganic phosphates.
- One-third of body water (i.e., 20% of body mass) is extracellular fluid (ECF), which is mainly composed of sodium, chloride, bicarbonate, and albumin.
- ICF and ECF are separated by capillary walls and cellular membranes.
- H2O can move between fluid compartments by osmosis or in response to pressure differences.
Total blood volume is ∼ 6 L. Blood is composed of ∼ 45% cellular components (99% of which are red blood cells) and ∼ 55% plasma.
- Serum osmolarity: 285–295 mOsm/kg H2O
The 60–40–20 rule refers to total body water (60% of body mass), ICF (40% of body mass), and ECF (20% of body mass).
Think of HIKIN to help you remember the main intracellular ion: HIgh K+ INtracellularly.
- 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)
- Definition: the rate at which fluid is filtered by the kidneys
- Normal GFR
- ♂ 95–145 mL/min/1.73m2
- ♀ 75–125 mL/min/1.73m2
- After the age of 29, a physiological decrease in the GFR of about 10 mL/min/1.73m2 occurs every 10 years.
- GFR depends on the effective filtration pressure
- Glomerular filtration is driven by the difference between hydrostatic and osmotic pressure
Used to estimate GFR (eGFR)
- The 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.
- 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 (plasma glucose level at which glucose is first excreted in urine): 180 mg/dL
- The fraction of the renal plasma flow (RPF) that is filtered from the capillaries into the Bowman space
- FF = GFR/RPF → FF = (creatinine clearance / PAH clearance)
- Normal: 20%
- 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)
: (FeNa): percentage of the glomerular filtered sodium that is excreted in the urine
- Used in a clinical setting to establish the cause of acute kidney injury
- FeNa = Na excreted / Na filtered = (urine flow rate x urine concentration of Na) / (GFR × plasma concentration of Na)
- Reabsorption rate = filtered load (GFR × plasma concentration of X) - excreted load (urine flow rate x urine concentration of X)
- Secretion rate = excreted load - filtered load