phys - renal system

What are the 3 main functions of kidney?

• Filter blood

• Keep the good stuff (nutrients)

• Remove the waste

Why is kidney failure dangerous?

The kidneys remove substances from INSIDE the body. They take substances from your BLOOD (inside the body) and move them OUT of the body.

This makes kidney failure dangerous, bcs toxins/drugs/acids stay in blood, potassium rises and water balance fails.

Functions the kidneys regulate:

1) Water Balance: Kidneys decide how much water to keep & how much water to lose.

• Too much water retained → swelling/high BP

• Too much water lost → dehydration

2) Osmotic regulation: This is controlling salt concentration, solute concentration and osmolarity (how concentrated a fluid is).

Note:

• water moves towards higher osmolarity

• Normal body fluid osmolarity is about 300 mOsm

3) Acid-Base Regulation: Kidneys help regulate blood pH by controlling H+ ions and bicarbonate - this keeps body pH stable

4) Remove Waste & Drugs: ex// urea, creatine, toxin, medications - kidneys clean them out thru urine.

Role of Renin

Its an enzyme NOT a hormone. It helps regulate blood pressure. The kidneys release renin into blood.

Role of Erythropoietin (EPO)

This IS a hormone. It stimulates red blood cell production.

• Less kidney function → less EPO → anaemia.

Role of Vitamin D Activation

Kidneys activate vitamin D. Activated vitamin D helps absorb calcium.

What is Gluconeogenesis?

Making new glucose from NON-carbohydrate sources (such as amino acids).

What does blood use to enter / exit kidneys?

Blood enters kidneys through renal arteries.

Blood exits kidneys through renal veins.

Why does about 20% of cardiac output go to kidneys?

Because kidneys constantly filter blood.

Ureters

Ureters connect kidneys to bladder (look like string).

Once fluid enters the ureter, it is effectively already “outside” the body, bcs it’s sealed off from internal tissues.

Cortex vs Medulla

If you cut a kidney open you see:

• cortex: outer light layer

  • most filtration happens here

• medulla: inner darker layer

  • contains renal pyramids

  • This is where urine concentration is adjusted.

  • is VERY important for water balance.

Osmotic Gradient in the Medulla

As you go deeper into the medulla, osmolarity increases (starts around 300 mOsm and goes to 1200 mOsm).

This matters bcs the kidney creates this gradient so it can pull water out of filtrate when needed. This is how concentrated urine is produced.

Role of The Nephron:

• Is the functional unit of kidneys

• each kidney contains huge amt of nephrons

• Each nephron filters blood independently.

What does blood use to enter and exit the nephron?

• Blood enters through Afferent arteriole (afferent means arriving)

• Blood exits thru efferent arteriole (efferent means exiting)

Role of Glomerulus:

• Glomerulus is inside nephron.

• The arteriole forms a capillary ball called Glomerulus

• Glomerulus is where filtration occurs

• It’s surrounded by Bowman's Capsule (a.k.a glomerular capsule) which collects the filtrate

What occurs after filtration? (Tubule System)

After filtration, filtrate flows through:

• Proximal convoluted (“twisted”) tubule (PCT):

  • closer to Bowma’s capsule

  • this is where massive reabsorption occurs.

• Loop of Henle

  • Has descending & ascending limb - descending limb goes DOWN into medulla, Ascending limb comes BACK UP.

  • Imp bcs it creates the medullary osmotic gradient

• Distal convoluted tubule (DCT)

• Collecting duct:

  • Collects filtrate from multiple nephrons.

  • Final urine concentration occurs here.

Countercurrent System

The nephron sets up opposite-direction flow.

• Descending limb: fluid goes down

• Ascending limb: fluid goes up

Blood vessels nearby flow opposite directions too.

This system is CRITICAL for concentrating urine.

Components of Filtration Barrier of kidneys that does NOT just let everything through:

1. Fenestrated Capillaries: have holes for filtration

2. Basement Membrane: Acts like a selective mesh.

3. Podocytes: Special cells with “foot processes.” These create filtration slits.

What does the filtration barrier allow to pass thru and blocks?

The filtration barrier allows:

• water

• salts

• glucose

• urea

BUT blocks:

• proteins

  • healthy urine contains No albumin/other proteins. If there are proteins in urine, it indicates kidney damage.

• blood cells

What’s the Juxtaglomerular Apparatus (JGA)?

This is the nephron’s sensing system.

“Juxta” means beside.

The distal tubule loops back beside its own glomerulus. This lets the nephron monitor itself.

Role of Macula Densa Cells

These are sensory cells which detect sodium chloride concentration inside filtrate.

If sodium levels are abnormal, the nephron changes filtration, blood vessel constriction & renin release.

2 ways JGA controls BP and filtration:

1. Afferent Arteriole Constriction: Changes blood flow into glomerulus.

2. Renin Secretion: Helps regulate blood pressure.

Role of Mesangial cells:

Are supporting cells around glomerulus.They can contract. When they contract, glomerulus shrinks & filtration decreases.

Plasma vs Urine Concentrations

Potassium: Low in plasma, higher in urine. (meaning filtered and secreted into filtrate)

Glucose: normaly filtered, COMPLETELY reabsorbed (so healthy urine has no gluose)

• glucose in urine suggests diabetes mellitus

Bicarbonate: filtered, almost fully reabsorbed

• bcs bicarbonate is important for pH regulation.

Creatinine: Filtered, but barely reabsorbed.

What does freely filtered mean?

A substance is “freely filtered” if dissolved in plasma/small enough to pass filtration barrier easily. (ex// glucose, urea, ions).

3 core functions of nephrons:

1. Filtration: Blood → filtrate

• Occurs in renal corpuscle

2. Reabsorption: Filtrate → back into body

• Keeps useful substances.

3. Secretion: Body → into filtrate

• Adds extra waste/toxins.

How does filtration occur in the glomerulus?

Filtration happens in the: glomerulus + Bowman's capsule = renal corpuscle

• Blood enters glomerular capillaries.

• Pressure pushes fluid out of blood and into Bowman's capsule.

  • That fluid becomes filtrate

    • Small dissolved substances pass through easily, but large proteins don’t

Do reabsorption & secretion use active/passive transport?

Because filtrate and plasma concentrations start equal, Reabsorption CANNOT happen just by diffusion alone, because there is no concentration gradient yet. So, reabsorption and secretion must use ACTIVE TRANSPORT.

Primary & Secondary active transport:

Primary active transport: Uses ATP directly. (ex// Na/K+ pump)

Secondary active transport: creates low sodium inside cell & high sodium outside cell.

• So, sodium rlly wants to come back into cell. That sodium gradient stores energy. The kidney uses that energy to move other molecules.

What are kidney tubules lined by and what’s significant abt that lining?

Kidney tubules are lined by epithelial cells.

Epithelial cells have polarity:

• means one side faces lumen (Apical membrane)

  • apical membrane contains cotransporters

• one side faces blood/interstitial fluid. (Basolateral membrane)

  • Basolateral membrane contains sodium-potassium pumps

Why does the organisation of kidney tubules lined by epithelial cells (relating to polarity) work for reabsorption?

1. Na⁺/K⁺ pump lowers intracellular Na⁺

2. Na⁺ rushes back in from lumen (wants to go down it conc grad)

3. Glucose hitches a ride with Na⁺ using cotransporters

4. Glucose then leaves cell into blood

Result:

• glucose is reabsorbed

• sodium is reabsorbed

The key idea is: the Na⁺ gradient made by the Na⁺/K⁺ pump provides the energy to move glucose.

Symport VS Antiport

Symport: Both substances move SAME direction. (ex// sodium + glucose together)

Antiport: Substances move OPPOSITE directions. (ex// sodium enters + H leaves)

Formula for Net Filtration Pressure:

Net Filtration Pressure = Filtration forces - Reabsorption forces

Starling forces in kidney:

FORCE 1 — Blood Hydrostatic Pressure: It pushes water OUT from capillary into Bowman’s capsule (This is the main filtration force.)

FORCE 2 — Capsular Hydrostatic Pressure: pull water BACK into capillary. Opposes filtration.

FORCE 3 — Blood Oncotic Pressure: Proteins remain in blood. Proteins pull water back into capillary. Opposes filtration. (Oncotic pressure increases along capillary - This gradually opposes filtration more strongly.)

What’s the Glomerular filtration rate (GFR)?

GFR = volume of plasma filtered per minute

Normal: ~125 mL/min

What are 2 examples of ideal GFR markers to measure GFR?

1) Inulin: Ideal GFR marker, bcs its freely filtered, not reabsorbed, not secreted, not metabolised, so urine amount exactly reflects filtration.

2) Creatinine: Not perfect, as a tiny amount is secreted, but close enough.

Renal Clearance formula:

Clearance = (urine concentration × urine flow rate) ÷ plasma concentration

• If clearance = GFR, Substance only filtered (ex// inulin)

• If clearance < GFR, Substance is being reabsorbed, because less appears in urine than expected. (ex// urea)

• If clearance > GFR, Substance is being secreted, because extra was added into filtrate. (ex// penicillin)

MYOGENIC MECHANISM

If arteriole stretches, smooth muscle contracts automatically.

More pressure → more stretch → more constriction (This stabilises blood flow.)

What occurs if GFR becomes TOO HIGH?

Flow through tubule increases. More NaCl reaches macula densa. Macula densa signals constrict afferent arteriole.

This lowers:

• glomerular pressure

• GFR

So the nephron self-corrects.

Constriction of afferent arteriole:

↓ glomerular hydrostatic pressure
↓ GFR

Because less blood enters glomerulus.

Two Intrinsic (Local) Control Mechanisms to keep renal blood flow & glomerular filtration rate (GFR) stable:

1. Myogenic Mechanism: This controls renal blood flow.

Blood vessels contain smooth muscle. If pressure inside the vessel increases: