Human Physio Renal function and fluid balance

Structure & Function of the Urinary System

Functions
  • Regulation of extracellular fluid volume & blood pressure   * works with CVS to ensure tissues get enough O2 and BP within normal values
  • Regulation of plasma osmolarity
  • Maintenance of ion balance   * in response to diet intake, urinary loss helps to maintain proper levels of Na+, K+, Ca2+ ions
  • Homeostatic regulation of pH   * remove or conserve either H+ or HCO3- (bicarbonate ions) as needed
  • Excretion of waste   * removes metabolic wastes dissolved in plasma e.g. uric acid and creatine
  • Secretion of hormones and enzymes   * erythropoietin (RBC production), renin (sodium balance and BP homeostasis) & vit D conversion to control Ca2+ balance
Structure of nephron

the nephron is the functional unit of the kidney

Renal corpuscle filters blood plasma:

  • Glomerulus capillary network
  • Glomerular (Bowman’s) capsule double walled up surrounding glomerulus

Renal tubule filtered fluid passes into:

  • proximal convoluted tubule
  • descending, loop of henle (nephron loop) and ascending
  • Distal convoluted tubule

Distal convoluted tubule of several nephrons empty into single collecting duct

Renal exchange processes

 

  • Urinary excretion of substance depends on its filtration, reabsorption and secretion.

 

Glomerular filtration

Filtration barriers:

  • Glomerular capillary endothelium
  • Basal lamina
  • Epithelium of Bowman’s capsule- podocytes

 

 

Forces that influence glomerular filtration:

  • Hydrostatic/blood pressure (55 mmHg)   * pressure of flowing blood in glomerular capillaries   * favors movement of filtrate into Bowman’s capsule
  • Colloid osmotic pressure (30 mmHg)   * plasma proteins entering capsule create a gradient that favors movement back into capillaries
  • Hydrostatic fluid pressure (15 mmHg)   * in fluid up in enclosed Bowman’s capsule   * creates a gradient that favors movement back into capillaries
Glomerular filtration rate (GFR)
  • volume of fluid that filters into Bowman’s capsule per unit time
  • average GFP 125mL/min or 180L/day
  • Factors influencing GFP   * Net filtration pressure   * Filtration coefficient     * surface area of glomerular capillaries     * permeability between capillary & Bowman’s capsule
  • 20% of plasma volume that pass through glomerulus is filtered
  • <1% of filtered fluid is excreted

   

  • Autoregulation of glomerular filtration rate takes place over a wide range of blood pressures.
Regulation of glomerular filtration rate

Myogenic response

  • Intrinsic ability of vascular smooth muscle to respond to pressure changes
  • ↑afferent arteriole resistance →↓GFR
  • ↑efferent arteriole resistance → ↑GFR

Tubuloglomerular feedback

  • Paracrine control through loop of Henle

 

Hormones and autonomic neurons

  • By changing resistance in arterioles
  • By altering the filtration coefficient
  • ==Angiotensin II== - vasoconstrictor
  • ==Prostaglandins== - vasodilators

Reabsorption

  • movement of filtered solutes and water from lumen of tubule back into plasma
  • takes places in proximal tubule and distal segment of nephrons

 

Principles governing tubular reabsorption of solutes & water:

  • active transport to create concentration of electrochemical gradient
  • water osmotically follow solutes
  • Transepithelial transport (passing through cells)   * substances cross both apical and basolateral membrane
  • Paracellular pathway (passing around cells)   * substances pass through junction between two adjacent cells
Principles governing the tubular reabsorption of solutes:

Some solutes and water move into and then out of epithelial cells (transcellular or epithelial transport); other solutes move through junctions between epithelial cells (the paracellular pathway). Membrane transporters are not shown in this illustration.

 

 

Secretion

Transfer of molecules from extracellular fluid into lumen of nephron:

  • dependent on membrane transport proteins to move organic compounds
  • active process move substrates against concentration gradient & use secondary active transport to move into lumen
  • secretion of K+ and H+ is important in homeostatic regulation
  • enables nephron to enhance excretion of substance   * adds to substances collected during filtration, making excretion more effective

Fluid & Electrolyte Homeostasis

Water balance in the body

  • Water makes up 50-60% of total body weight
  • main entry of water is through food & drink
  • most lost water in urine
  • homeostasis maintains water balance unless there is pathology or an abnormal ingestion of water

Kidneys in water balance

  • Kidneys cannot replenish lost water; only preserve or get rid of excess amounts
  • volume loss replaced from the environment
  • renal filtration will stop if there is a major loss causing extremely low blood pressure and blood volume

Urine concentration

  • Osmolarity of urine measure of how much water is excreted by kidneys
  • osmolarity changes as filtrate flows through nephron
  • Diuresis - removal of excess water in urine   * diuretics: drugs that promote urine excretion
  • Kidney controls urine concentration   * varying amounts of water and Na reabsorbed in distal nephron (distal tubule & collecting duct)
Osmolarity changes through nephron

 

Countercurrent multiplier system

Exchange is enhanced by active transport of solutes

 

  • Two components:   * loops of Henle that leave the cortex, dip down into the more concentrated environment of the medulla, then ascend into the cortex again.   * peritubular capillaries - vasa recta, also forming hairpin loops.
Water reabsorption
  • Distal tubule and collecting duct cells alter permeability to water
  • process involves adding or removing water pores (aquaporins) in apical membrane
  • depends on secretion of vasopressin/antidiuretic hormone (ADH)

 

Control of vasopressin secretion

 

3 stimuli controlling vasopressin secretion:

  • {{Plasma osmolarity > 280mOsM{{   * higher the osmolarity, more vasopressin released by posterior pituitary   * osmoreceptors in hypothalamus detect changes in osmolarity
  • {{Blood pressure{{
  • {{Blood volume{{

Renin-Angiotensis-Aldosterone System (RAAS)

 

  • Angiotensis II (ANG II) is the usual signal controlling aldosterone release from the adrenal cortex
  • The RAS pathway begins when afferent arterioles secrete renin
  • Renin converts inactive angiotensinogen, into angiotensis I (ANG I)
  • ANG I converted into ANG II by angiotensis-converting enzyme (ACE)
  • ANG II → adrenal gland → synthesis and release of aldosterone
  • Aldosterone reabsorb Na+ at collecting duct
ACE2 & SARS-CoV-2 (COVID-19 Virus)
  • ACE2 is present in many cell types and tissues including the lungs, heart, blood vessels, kidneys, liver and gastrointestinal tract.
  • ACE2 is highly abundant on type 2 penumocytes in alveoli
  • When the SARS-CoV-2 virus binds to ACE2, it prevents ACE2 from performing its normal function to regulate ANG II signalling
  • ANG II increases blood pressure and inflammation, death of cells in alveoli

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