1 + 2 - Renal System

What are the 2 major compartments in which body fluids are housed in

Extracellular Fluid (ECF) - Volume : 15L , 20% of Body weight

• Interstitial fluid (IF) - Volume : 12L - 80% of ECF

• Plasma - Volume : 3L - 20% of ECF

• Na+ and Cl- key ions in ECF

Intracellular Fluid (ICF) - Volume : 25L , 40% of body weight

• K+ and phosphates in ICF

What are the gross features of the kidneys

Two functional regions:

• Cortex - outmermost layer

• Medulla - inner part

Renal pyramids house tubular structures that process filtrate and collect urine (nephrons)

Hillman - point of insertion of vessels, nerves and the uterus into which kidney excretions (urine) drain

What are the nephrons briefly

Structural and functional units of the kidney

Rich network of tubules and vasculature across cortex and medulla through which filtrate is formed

Two functional parts:

• renal corpuscle - glomerus & capsule

• Rena tubules - Proximal convoluted tubule (PCT), nephron loop, distal convoluted tubule (DCT)

Describe the path of blood flow through the kidney

1. RENAL ARTERY : oxygen rich blood, solutes + waste

2. Branches toward renal cortex → CORTICAL RADIATE ARTERY → AFFERENT ARTERIOLE

3. GLOMERULUS : fluid leaves capillary bed, moves into the tubules

4. EFFERENT ARTERIOLES brands into the capillary network, supplying the nephron tubules

5. Reclaimed water, nutrients returned to systemic circulation via the RENAL VEIN

What are the cortical and juxtamedullary nephrons

CORTICAL NEPHRON

• short nephron loop

• Glomerulus further from the cortex medulla junction

• Efferent arteriole supplies peritubular capillaries

JUXTAMEDULLARY NEPHRON

• long nephron loop

• Glomerulus closer to the cortex-medulla junction

• Efferent arteriole supplies vasa recta

How do the capillary beds reclaim filtrate

EFFERENT ARTERIOLE branches into the capillary networks supplying the nephron tubules.

PERITUBULAR CAPILLARIES:

• low-pressure, porous capillaries adapted for absorption of water and solutes

• Wrapped around cortical renal tubes

VASA RECTA:

• long, thin-walled vessels, run parallel to long nephron loops of juxtamedullary nephrons

• Contribute to formation of concentrated urine

What are the specialised cells involved in regulation of filtration rate and blood pressure

MACULA DENSA: proximal portion of the DCT lies adjacent to arterioles, modified epithelial cells:

• Chemoreceptors monitor Na+ content of fluid in DCT

• Sensory cilia detect fluid flow rate

• secrete Paracrine agents (ATP, adenosine) when these increase.

GRANULAR CELLS: modified smooth muscle cells lining afferent arteriole

• vasoconstriction of afferent arteriole in response to increase in arteriole BP, via Paracrine signalling from macula densa Paracrine.

• Secretes renin - enzyme involved in systemic blood pressure regulation

EXTAGLOMERULAR MESANGIAL CELLS:

• pass Paracrine signals between macular densa and granular cells

What are the 3 functional regions of the renal tubules & collection ducts

Proximal convoluted tubule -

• majority of reabsorption ; some acid-base balance

• Apical surfaced lined by microvili - increases surface area for water & solute reabsorption, and secretions

Nephron Loop -

• descending (thin) & ascending libs alter filtrate osmolarity by reabsorbing water and NaCl

Distal convoluted tubule -

• regulated reabsorption of ions, passive diffusion of water follows

• Secretion of H+ contributes to acid- base balance

What are the 2 cell types in the collecting ducts

PRINCIPAL CELLS -

• more numerous

• Blunt, fewer microvili

• Receptors for antidiuretic hormone (ADH) and aldosterone for water and Na+ reabsorption

INTERCALATED CELLS -

• more microvili

• Used for acid-base balance

What is the first major renal process

Glomerular Filtration -

Glomerular Filtration Rate (GFR): volume of plasma filtered (filtrate formed) per minute by both kidneys.

Of the plasma volume entering the afferent arteriole:

• 20% filtered by glomerulus and enters renal tubules

• 80% continues back out efferent arteriole into capillaries

• >99% of filtrate reabsorbed.

Glomerular filtration is passive, nonselective process.

What pressures affect glomerular filtration

Filtrate formation is determined by net filtration pressure across the capillary membrane

OUTWARD PRESSURES (promote filtrate formation)

• hydrostatic (blood) pressure in glomerular capillaries (HP)

• Major force pushing water and solutes out of the blood

• Higher than usual for capillaries

INWARD PRESSURES (inhibit filtrate formation)

• Hydrostatic (filtrate) pressure in capsular space (HP)

• Colloid osmotic pressure in glomerular capillaries (OP), pressure exerted by proteins in blood ‘sucks’ water into capillaries.

Increase blood volume at afferent arteriole → increase HP → increase filtrate

How is renal blood flow regulated

1. SYMPATHETIC innervation of afferent arteriole smooth muscle

• at rest, minimal sns input → arterioles dilated, increased glomerular flow

• Under stress, increase sns input → vasoconstriction + reduction in flow and GFR; blood shunted away from kidneys

2. MYOGENIC STRETCH of afferent arteriole smooth muscle

• volume/pressure of fluid entering arterioles alters arteriole diameter

• Vascular smooth muscle contracts when stretched, relaxes when not stretched

• High blood pressure stretches arteriole walls triggering vasoconstriction → decrease flow of blood entering glomerulus, maintain appropriate GFR.

3. TUBULOGLOMERULAR FEEDBACK

• macula densa cells monitor filtrate flow rate and NaCl in DCT

• High GFR reduces time for solute reabsorption at PCT, osmolarity stays high by DCT

• Vasoactive Paracrine (ATP, adenosine) secreted → vasoconstriction of afferent arterioles to reduce blood flow and GFR.

Describe what Tubular reabsorption is

Substances moved by passive/active transport mechanisms along, sometimes against, their concentration gradient

From TUBULES → CAPILLARIES

Movement of water from tubules→nephron capillary beds influenced by osmolarity and concentration gradients

• osmosis by aquaporins and obligatory water reabsorption with Na+

Sodium is actively transported against/with concentration gradients

• glucose, amino acids, vitamins, ions, co-transported out of lumen alongside various Na+ transporters

Describe what secretion is

From CAPILLARIES/INTERSTITIAL SPACE → TUBULES

What is ADH and what does it do

Antidiuretic Hormone (AD) regulates renal water and solutes handling to maintain blood osmolarity, volume and pressure

ADH - synthesized in hypothalamus, released from posterior pituitary

• increased osmolarity detected by hypothalamic osmoreceptors → secretion of ADH

• Fall in blood volume/pressure → loss of baroreceptor stimulation → secretion of ADH

Effects:

• ADH binds to receptors on principle cells of collecting ducts

• Aquaporins inserted, increased water reabsorption

• Reduced volume and more concentrated urine

What does aldosterone do

Aldosterone regulates renal water and solutes handling to maintain blood osmolarity, volume and pressure

Initiated by RENIN SECRETION FROM GRANULAR CELLS of afferent arterioles (3 ways this can occur) :

1. Decrease in renal perfusion detected by granular cells of afferent arterioles

2. Drop in blood volume/pressure → reduced GFR (slow movement of glomerulus) → more time for NaCl reabsorption at PCT, nephron loop, DCT → macula densa cells signal granular cells

3. Increased sympathetic activity directly stimulates granular cells

Effect:

• renin release → RAAS cascade → Na+ reabsorption (+water follows)

• Decrease Na+ and water loss in urine

How does the osmolarity gradient adjust urine composition

At nephron loop…

DESCENDING LIMB :

• water moves out by osmosis into the increasingly hyperosmotic medulla; filtrate becomes more concentrated

ASCENDING LIMB :

• NaCl pumped out into the medullary interstitium (limb impermeable to water); filtrate becomes more dilute

At the collection duct…

UREA

• some moves from the collecting duct into the deep medullary institium, contributing to the osmotic gradient