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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

SH

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