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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