Renal Physiology

 

  • Kidney structure and function

    • Roles: fluid balance, excretion, endocrine (EPO, prostaglandins, renin), vitamin D conversion.
    • Functional unit is the nephron, with around 1 million per kidney.
    • Receives 25% of cardiac output: 1 L/minute of blood, 600 ml/minute of plasma, of which 100 ml/minute (20%) is filtered (150 L/day). Ultimately, around 1-2 ml/minute (1%) is excreted as urine, amounting to 2-3 L/day.
    • Substances enter nephron via filtration (glomerulus) or secretion (into tubule), and leave via reabsorption (into peritubular capillaries) or excretion (urine).

    Passage of fluid through the nephron

    1. Glomerulus:

    • Blood enters glomerulus from afferent arteriole.
    • Some continues in efferent arteriole and the rest undergoes ultrafiltration. Glomerular filtration rate (GFR) is the rate at which ultrafiltration occurs.
    • Ultrafiltration though 3 layers: fenestrated capillary endothelium → basal lamina (glomerular basement membrane, GBM) → filtration slits of podocytes, from which it enters the lumen of Bowmen's capsule then the tubule.

    2. Proximal convoluted tubule (PCT):

    • Where most H2O reabsorbed, as it has a permeable membrane. The rest of the tubules are impermeable, except for aquaporins.
    • H2O resorption driven by reabsorption of solutes: Na+ (passive) and glucose (active via SGLT and GLUT).
    • Also site of HCO3- reabsorption.

    3. Loop of Henle (LoH):

    • Na+-K+-2Cl- cotransporter reabsorbs all 3 ions.

    4. Macula densa:

    • Lies in the early part of the distal convoluted tubule.
    • Forms juxtaglomerular (JG) apparatus as tubule passes between the afferent and efferent arterioles.
    • ↓Na+ in the macular densa – a marker of ↓GFR (and ↓BP) – triggers renin release from JG cells in the afferent arteriole, raising BP, and causes afferent dilatation (via prostaglandins) and efferent constriction (via angiotensin 2).
    • In prerenal AKI, ↑↑renin levels reverse this mechanism to ensure fluid and electrolyte retention, via ↑reabsorption and ↓GFR (afferent constriction).

    5. Distal convoluted tubule (DCT):

    • Na+ is reabsorbed via Na-Cl cotransporter in early part.
    • Late DCT and collecting ducts both contain ENaC for Na+ reabsorption and aquaporins for H2O reabsorption.

    6. Collecting duct:

    • 8 DCTs converge into 1 collecting duct.
    • Excretion of urine into papillary ducts then calyces then renal pelvis then ureters.
  • Glomerular filtration rate (GFR)

    Definition and formula:

    • GFR is approximately the volume of plasma cleared of creatinine i.e. the volume of plasma that is filtered (e.g. per minute).
    • {Urine creatinine concentration x Urine flow rate} ÷ {Plasma creatinine concentration}.

    Conceptual explanation:

    • After filtration, plasma is almost entirely (99%) reabsorbed, while the creatinine in it is not.
    • If plasma contains e.g. 0.01 mg/ml of creatinine, then each 1 ml of plasma getting filtered will leave 0.01 mg of creatinine in the tubules.
    • We want to know the total amount of creatinine being deposited in the tubules every minute, by multiplying the urine concentration by the volume per minute (urine flow rate).
    • We then divide that total amount of creatinine (e.g. 1.25 mg) by the concentration in the plasma (e.g. 0.01 mg/ml), to tells us how much plasma (e.g. 125 ml) was filtered to provide that amount of creatinine.
    • In fact, while 90% of creatinine in urine is filtered, 10% is secreted into the tubule, so creatinine GFR is around a 15% overestimate of true GFR.

    Results and BSA correction:

    • The result is given as the amount filtered by body surface area (BSA). 1.73 m2 is the BSA of the average man, so the unit for GFR is ml/min/1.73 m2.
    • 90-120 ml/min/1.73 m2 is the normal range.
    • To correct for people not having a BSA of exactly 1.73 m2, their ml/min should be multiplied by {their true BSA ÷ 1.73}. In reality, this is rarely done.

    Estimated GFR (eGFR) using plasma creatinine:

    • In simple terms ↑plasma creatinine suggests ↓elimination due to ↓GFR.
    • eGFR uses plasma creatinine levels and takes into account age, race, and sex.
    • In reality, plasma creatinine has a non-linear relationship with GFR, and rises very little until GFR <60. Therefore GFR cannot be accurately estimated if >60, with labs usually just reporting 'eGFR >60'.
    • Creatinine is made in the liver and stored in muscle, so levels are lower if there is liver disease or reduced muscle mass. This may mask kidney disease. eGFR is thus less reliable in severe malnutrition, skeletal muscle disease, para/quadriplegia, and amputees.
    • Conversely, levels in bodybuilders may be artificially high, falsely suggesting impaired kidney function.
    • Creatinine levels are raised by meat, so advise people to avoid eating meat in the 12 hours before test. Vegetarians, however, will have persistent low creatinine levels, perhaps masking kidney disease.

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