Physiology: Renal system

Kidney functions

• Maintains H2O balanced in body

• Regulate the volume of extracellur fluid

• Regulate concentration of extracellurlar fluid

• Regulate concentration of ECF ions (Na+, Cl-, HCO3-)

• Maintains plasma volume +osmolarity

• Excretion of waste products

• Secreting hormones (erythropoietin and renin)

The nephron

• Primarily maintain plasma homeostasis and excrete

• Done via

• - filtration

• - reabsorption

• - secretion

• Vascular component vs tubular

Vascular Compartment - Afferent/Efferent arteriole + glomerulus

• Afferent arteriole (“in”) carries blood to the glomerulus

• Glomerulus - a ball like tuft of capillaries that filters blood plasma into the tubular component

• Efferent arteriole (“out”) carries blood from the glomerulus and divides into peritubular capillaries

The Tubular Compartment: Bowman’s capsule, proximal tubule, lope of Henle, distal tubule and collecting duct.

• Bowman’s capsule “cups” the glomerulus and collects glomerular filtrate.

• Proximal tubule: reabsorption and secretion of selected substances

• Lope of Henle: establishes establishes an osmotic gradient and reabsorption ions

• Distal tubule: selectively absorbed and secretes ions to maintain pH and electrolyte

• Collecting duct: collects fluid from distal tumbles, reabsrobes water/solutes

Juxtamedullary nephron

• 20% of total glomeruli in inner cortex

• Loop of Henle descends further into medulla

• Osmotic gradient

Cortical Nephron

• 80% of total glomeruli in outer cortex

• Loop of Henle dips slightly into medulla

• Involved in basic filtration and reabsorption

Renal processes to form Urine

• Glomerular filtration: non-selective filtration of protein-free plasma

• Tubular reabsorption: valued substances reabsorbed from Tubular lumen and transferred back to blood

• Tubular secretion: waste substances removed from blood to the tubular lumen via tubular cells

• Plasma constituents not reabsorbed pass into the renal pelvis → urine

Glomerular filtration

• Blood enters glomerular capillaries via Afferent arteriole

• Fluid then passes through three layers of the glomerular capillary

Three layers layers of the glomerular capillary wall are:

• endothelium; large pore allow passage of solute/fluid but not blood cells

• Basement membrane: mix of collagen (structure) and glycoproteins (repel proteins)

• Podocytes: epithelial cells which have slits between them.

Affecting glomerular Filtrtion - glomerular capillary blood pressure (A)

Can be impacted by:

• arterial blood pressure

• Afferent arteriole Fluid diameter

• Efferent arteriole diameter

Increases if:

• arterial blood pressure increases

• Afferent arteriole diameter increases (increase flow)

• Efferent arteriole diameter decreases

Osmolarity

• the concentration of the total number of solute particles per litre.

• Unit: osmolarity per L (osm/L)

• Eg: 200mmoles of glucose and 300mmoles of fructose in a litre of water= 500mosm/L

• Eg: 300mM of salt dissociates into 300mH Na+ and 300mM Cl- = osmolarity of 600mOsmol/L

Affecting glomerular filtration - plasma colloid osmotic pressure - B

• retention of blood proteins in the glomerulus increases the osmolarity of glomerular blood, compared with Bowman’s Capsule

• This draws H2O back into the glomerulus.

Hypo-osmotic

• a solution with lower osmolarity than inside a cell or another solution

Hyper-osmotic

• a solution with higher osmolarity than inside a cell or another solution

Affecting Glomerular Filtration - Bowman’s Capsule Hydrostatic pressure (C)

• Fluid already in Bowman’s capsule exerts a pressure which resists the influx of more fluid from the glomerulus - reducing filtration.

Glomerular Filtration rate calculation

• flow rate of filtration from the glomerulus into Bowman’s Capsule, (ml/min or L/min)

• Net filtration pressure = A-B-C

• Filteration coefficient (kf) = 12.5ml/min

• GFR = NFP x kf

Glomerular Filtration rate - stats

• High rate allows for rapid removal f waste and foreign chemicals.

• Normal rate is 125ml/min (180L/day) at normal mean arterial pressure (100mmHg)

Autoregulation - Renal system

• Autonomic regulation of renal blood flow occurring in response to blood pressure controlled at the local level.

• Increased MAP → autoregulation induces vasoconstriction of the Afferent arteriole

• Decreased Map → autoregulation induces vasodilation of he Afferent arteriole.

Mechanism of GFR Autoregulation

1. Myogenic

2. Tubuloglomerular feedback

Autoregulation - Myogenic Mechanism

• The process by which arteries/ arteriole react to changes in blood pressure to maintain constant blood flow

Autoregulation - Tuboglomerular feedback

1. Macula dense cells since tubular flow/NaCl levels in ascending tubule (these increase with BP)

2. Release ATP (converted to adenosine) in repsonse

3. Granular Cells respond to adenosine by contracting and reducing Afferent arteriole blood flow

Tubular reabsorption

• 99% of water is reabsorbed

• 100% of sugars

• 99.5% of salts

Sodium reabsorption locations

• 80% of energy in the kidney is for Na+ reabsorption

• Proximal tubule (67%) - obligatory

• Loop of Henle (25%) - obligatory

• Distal tubule (8%) - hormonal

• Obligatory = regardless of body needs, hormonal = in response to Na+ levels

Tubular reabsorption - All barriers

1. Luminal cel membrane

2. Cytosol

3. Basolateral cell membrane

4. Interstitial fluid

5. Capillary wall.

Tubular reabsorption of Na+: Step 1

1. Na+ - K+ ATPase pump moves Na+ from tubular epithelia cell to interstitial fluid (and K+ the other way, 1 for 1)

Tubular reabsorption of Na+: Step 2

2. The created concentration gradient allows the passive movement of Na+ from lumen to tubular epithelial cells and from interstitial fluid to capillaries

Tubular reabsorption of Na+: Step 3

3. K+ passively leaks from tubular epithelia cells back into interstitial fluid.

Reabsorption of glucose and nutrients

• specialised transport proteins (support carrier) move both Na+ and glucose/nutrients in the same direction.

• Glucose/nutrients then passively diffuse into the peritubular capillaries

Transport maximum (Tm) of glucose

• normal plasma glucose concentration: 100-125mg/dL (100ml)

• If plasma glucose increases above 300mg/100ml (e.g. in diabetes) active reabsorption mechanism max out (-375mg of glucose/min)