- 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
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.
- 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