Human Physio Renal function and fluid balance
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
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
Urinary excretion of substance depends on its filtration, reabsorption and secretion.
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
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.
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
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
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.
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
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 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
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)
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.
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)
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
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 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
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
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
Urinary excretion of substance depends on its filtration, reabsorption and secretion.
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
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.
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
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
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.
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
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 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
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)
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.
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)
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
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 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