Physiology Exam #4a: Urinary/ Kidneys

6 Major Functions of Urinary System

1. Excretion of Wastes

2. Regulating Blood Volume and Pressure

3. Balancing Electrolytes

4. Acid-Base Balance

5. Removing Drugs & Toxins

6. Producing Hormones

Excretion of Wastes

• KIDNEYS remove from bloodstream

  • urea (from protein breakdown)

  • creatinine (from muscles)

  • uric acid (from nucleic acids)

Regulating Blood Volume & Pressure

• By controlling how much water the body loses in urine, kidneys help maintain blood pressure

  • dehydrated= conserve water

  • hydrated= excrete more

  • Hormones such as ADH, aldosterone, and renin-angiotensin-aldosterone system (RAAS) fine-tune

Balancing Electrolytes

• Kidneys carefully regulate key ions

• essential for nerve signals, muscle contraction, normal cell function

  • sodium (Na⁺)

  • potassium (K⁺)

  • calcium (Ca²⁺)

  • chloride (Cl⁻)

Maintaining Acid–Base Balance

• To keep blood pH in healthy range (7.35–7.45)

  • kidneys remove excess hydrogen ions and reabsorb bicarbonate (HCO₃⁻)

  • keeps body fluids from becoming too acidic/ basic

Removing Drugs & Toxins

• Kidneys help clear medications, toxins, and other foreign chemicals

  • filtering them into urine=

Producing Hormones (3 main)

Kidneys= endocrine organs

• Erythropoietin (EPO)

  • tells bone marrow to make more RBCs when oxygen is low

• Renin

  • regulates blood pressure

• Calcitriol

  • active form of vitamin D

  • essential for calcium absorption and bone health

4 Organs of Urinary System

1. Kidneys

2. Ureters

3. Urinary Bladder

4. Urethra

Kidneys

• 2 bean-shaped organs located below the ribs

  • Each contains about a million tiny nephrons (functional units that filter blood and form urine)

  • make hormones like EPO and renin

  • activates vitamin D (calcitriol)

Ureters

• Muscular tubes that carry urine from kidneys to bladder

  • Peristalsis move urine downward and prevent backflow!

Urinary Bladder

• Hollow, stretchy organ that stores urine until you’re ready to pee

  • can hold about 400–600 mL before stretch receptors signal the need to urinate

Urethra

• Tube carries urine from bladder to OUTSIDE of body

  • longer in males (passage for semen)

  • shorter in females (only carries urine)

is Urination muscle control voluntary or involuntary? (trick question)

• BOTH!!

• Urination (or micturition) involves both involuntary and voluntary muscle control

Afferent vs. Efferent Arteriole

• Afferent: carries blood TO glomerulus capillaries

• Efferent: carries blood AWAY from glomerulus capillaries

Define Filtrate

• Fluid filtered out of blood

  • contains water, ions, glucose, amino acids, and wastes

  • NO proteins or cells

3 Core Processes

1. Glomerular Filtration

2. Tubular Reabsorption

3. Tubular Secretion

1) Glomerular Filtration

in renal corpuscle (glomerulus and Bowman’s capsule)

• Blood enters glomerulus through AFFERENT arteriole (carries blood TO glomerulus capillaries)

  • high pressure in capillaries force water and small molecules through membrane into Bowman’s capsule

  • forming the initial FILTRATE!!

  • osmolarity= 300mOsm/L

Glomerular Filtration is driven by… and excludes…

• blood pressure

• large proteins and cells

2) Tubular Reabsorption

in proximal tubule (most), loop of Henle, distal tubule, and collecting duct

• Returns valuable substances to BLOODSTREAM:

• water, glucose, amino acids, ions

  • active transport, diffusion, or osmosis

  • Regulated by hormones such as aldosterone (Na⁺ and water reabsorption) & ADH (water reabsorption)

Most of reabsorption is where?

Proximal Convoluted Tubule

3) Tubular Secretion

in distal tubule and collecting duct

• Removed unwanted wastes, drugs, and excess ions from blood BACK INTO tubular fluid/ filtrate

• becomes part of urine

• H+, K+, drugs, creatinine

  • opposite of reabsorption

  • Helps regulate blood pH, potassium levels, and toxin removal

  • between tube/ filtrate and blood, must pass thru interstitial fluid first!!

Examples of secreted substances that move from blood back into tubules (step 3)

• Hydrogen ions (H⁺)- regulate blood pH

• Ammonium (NH₄⁺)

• Creatinine

• Drugs/ toxins

• Potassium ions (K⁺)

Glomerular Filtration Rate (GFR)

• Volume of fluid filtered into Bowman’s capsule per minute (mL/min)

  • ~125 mL/min in adults

  • Indicator of kidney function!!

  • decline signal possible renal disease
    

Factors Influencing GFR

• HIGH GFR

  • ↑ bp

  • afferent arteriole dilation (more blood!)

  • efferent arteriole constriction

• LOW GFR

  • ↓ bp

  • less blood

  • afferent arteriole constriction (less blood!)

  • efferent arteriole dilation

  • ↑ capsular/ oncotic pressure

Autoregulation maintains stable GFR via:

• Myogenic Response

  • (smooth muscle adjusts arteriole diameter)

  • HIGH GFR= (more blood) afferent dilation, efferent constriction

  • LOW GFR= (less blood) afferent constriction, efferent dilation

• Tubuloglomerular feedback (TGF) & JGA!

  • maintains blood pressure and GFR

  • negative feedback

  • connects tubules and arterioles

Juxtaglomerular apparatus (JGA)

• Communication point between DISTAL tubule and AFFERENT arteriole

  • allows nephron to sense changes in the filtrate

Tubuloglomerular feedback (TGF)

Enables nephron to adjust its own glomerular filtration rate (GFR)

3 Components of the Juxtaglomerular Apparatus (JGA) and Tubuloglomerular Feedback (TGF)

(Where distal convoluted tubule contacts afferent arteriole)

• Macula Densa

  • in distal convolute tube

  • senses NaCl in tubular fluid

  • negative feedback!!

  • ↑ GFR= high salt (low bp, dehydration, less water)

    • releases adenosine & ATP

    • (constricts afferent arterioles, lowers back down)

  • ↓ GFR= low salt 

    • releases nitric oxide & prostaglandins

    • (dilates afferent arterioles, brings back up)

• Juxtaglomerular Cells

  • modifies afferent arteriole

  • ↓ bp or salt= secretes renin (RAAS)

• Extraglomerular Mesangial Cells

  • coordinate signaling

The Juxtaglomerular Apparatus (JGA) and TGF Mechanism

• HIGH NaCl

  • adenosine/ ATP → afferent constriction → ↓ GFR

• LOW NaCl

  • (low bp, dehydration, less water)

  • NO/ prostaglandins → afferent dilation → ↑ GFR

What does Renin do in Juxtaglomerular Cells?

• RAAS

Renin → angiotensinogen → angiotensin I → angiotensin II →

(stimulates adrenal cortex which will release aldosterone)

Angiotensin II is a…

• Strong vasoconstrictor

  • raises blood pressure!!

What does adrenal cortex release in response to low bp?

• Aldosterone

  • ↑ sodium & water reabsorption!!

  • ↑ bp

Net Filtration Pressure (NFP 3 pressures)

• Positive forces drive fluid out capillaries into capsule

  1. Glomerular Blood Pressure (pushes out)

  2. Capsular Hydrostatic Pressure (pushes back)

  3. Blood Colloid Osmotic Pressure (pulls back)

NFP Equation

NFP = Glomerular – Capsular – Blood Oncotic pressure

NFP = 55 −15 − 30 = +10 mmHg

Glomerular Blood Pressure

• PUSHES OUT

  • main outward force that drives water and solutes
    into Bowman’s capsule

  • 55mmHg

  • maintained by afferent and efferent arterioles

  • Directly related to body’s bp!

    • systemic bp ↑, glomerular pressure ↑, filtration ↑

    • systemic bp ↓, glomerular pressure ↓, filtration ↓

Capsular Hydrostatic Pressure

• PUSHES BACK

  • fluid in Bowman’s capsule resists new fluid entering

  • opposes filtration

  • (like a balloon resists being filled further)

  • 15mmHg

• Relatively stable unless something blocks urine

  • when urine can’t drain, fluid backs up in kidney

  • ↑ “push back”

  • ↑ pressure in capsule

  • ↓ GFR

Blood Colloid Osmotic (Oncotic) Pressure

• PULLS BACK

  • Plasma proteins remaining in the blood draw water back into the capillaries by osmosis

  • opposes filtration

  • 30mmHg

• Affect by plasma proteins

  • ↑ plasma proteins, ↑ pressure, ↓ filtration (GFR)

  • ↓ plasma proteins, ↓ pressure, ↑ filtration (GFR)

Factors Influencing Blood Colloid Osmotic (Oncotic) Pressure

• INCREASE Blood Osmotic Pressure

  • dehydration (water loss concentrates plasma proteins)

  • hyperproteinemia

• DECREASE Blood Osmotic Pressure

  • overhydration (extra water dilutes proteins)

  • hypoproteinemia

Order of 3 Key Fluids

1. Blood plasma

2. Glomerular Filtrate

3. Urine

Blood Plasma

• Starting fluid that carries nutrients, electrolytes, hormones, and wastes through the body

  • 90% water (liquid part of blood)

  • 55% of blood volume

  • includes proteins, electrolytes, nutrients, hormones waste products

  • 3 liters in body

Glomerular Filtrate

• FILTERED PLASMA that enters Bowman’s capsule

  • (similar to plasma but lacks proteins and cells)

  • result of glomerular filtration!!

  • includes water, electrolytes, glucose, amino acids, and small waste molecules

  • almost all is reabsorbed, small portion becomes urine

  • 180 liters filtered/ day

Urine

• Final product LOL

• mostly (95%) water with dissolved wastes such as urea, creatinine, and excess ions

  • 1.5 liters excreted/ day

  • (kidney filters 180 liters of plasma/ day)

Nephrons

• Kidney’s functional unit!!

  • each kidney contains about one million

  • filter→ reabsorb→ secrete → excrete

2 Parts of a Nephron

• Renal corpuscle

• Renal tubules

Renal Corpuscle

part of nephron

• Glomerulus (capillaries)

• Bowman’s capsule around it

  • filters blood creating filtrate!

  • enters tubules

Renal Tubules

part of nephron

• Proximal Convoluted Tubule (closer to renal corpuscle)

• Loop of Henle

• Distal Convoluted Tubule (further from renal corpuscle)

  • filtrate is modified

  • forms urine!

Proximal Convoluted Tubule (PCT)

majority of reabsorption

• Where 2/3 of filtered water and solutes are reabsorbed!

• (Na⁺, Cl⁻, glucose, amino acids)

  • Water follows solutes by osmosis

  • osmolarity= 300 mOsm/L

  • isosmotic—reabsorbs water and solutes in proportion

• REABSORBS:

  • 65-70% of Na⁺ (NHE3, SGLT2)

  • 65-70% of water (AQP1, paracellular)

  • all glucose

  • all amino acids

  • 80-90% of bicarbonate

  • large amounts of Cl⁻, K⁺, Ca²⁺

Descending Limb of the Loop of Henle

• Permeable to WATER but NOT to solutes

• WATER EXITS

  • As filtrate descends into the hyperosmotic medulla, water leaves by osmosis

  • CONCENTRATES filtrate!!

  • Osmolarity increases from 300 → 1200 mOsm/L (depending on hydration status and medullary gradient strength)

Ascending Limb of the Loop of Henle

• IMPERMEABLE to WATER but actively transports Na⁺, K⁺, and Cl⁻ out of filtrate

• SOLUTE EXITS

  • Solutes are reabsorbed while water stays

  • DILUTES filtrate!!

  • osmolarity falls to 100 mOsm/L (hypoosmotic)

Distal Convoluted Tubule (DCT)

• Continues reabsorbing Na⁺ and Cl⁻

• May secrete K⁺ and H⁺

  • Normally impermeable to water unless ADH is present!!

  • Without ADH: diluted filtrate stays ~100 mOsm/L

  • With ADH: ↑ water permeability, ↑ osmolarity (concentration) as water is reabsorbed

Collecting Duct

• FINAL site of osmolarity adjustment

• strongly regulated by ADH!!

  • Without ADH: Duct stays water-impermeable → urine stays dilute (~100 mOsm/L)

  • With ADH: Water leaves filtrate and enters the hyperosmotic medulla → urine becomes concentrated (up to 1200 mOsm/L)

Importance of Nephron Loop (Loop of Henle)

• Establishes medullary osmotic gradient

• Interacts with renal medulla

  • U shaped extends from renal cortex into renal medulla

    • Descending: water exits; filtrate concentrated

    • Ascending: solutes exit; filtrate dilute

Filtration begins at the… producing…

• Renal corpuscle (Glomerulus)

• Filtrate

Reabsorption and secretion occur along the… MODIFYING that filtrate.

tubule system (proximal, loop, distal)

Final fluid that enters the renal pelvis is… ready for excretion.

Urine

Aldosterone

↑ sodium (Na⁺) & water reabsorption

Antidiuretic Hormone (ADH)

↑ water reabsorption in collecting duct

Renal Equation for Excretion

E = F − R + S

Excreted= filtered - reabsorbed + secreted

Total Reabsorption

• Solute is completely reclaimed by tubule cells and returned to the blood

  • none appears in the urine

  • ex: glucose, amino acids

Partial Reabsorption

• Part of filtered amount is taken back to blood

  • rest is excreted

  • ex: sodium, chloride, urea

Examples of substances that are filtered and excreted without reabsorption

• insulin

• creatine

Examples of substances that undergo no handling because they are too large to be filtered

• plasma proteins

• blood cells

3 Layers of Filtration Barrier

• between glomerulus and Bowman’s capsule (nephron’s renal corpuscle)

• determine what can/ can’t leave bloodstream

  • Endothelium

  • Glomerular Basement Membrane (GBM)

  • Podocyte (Visceral) Layer

Filtration Barrier: Fenestrated Endothelium

INNERMOST layer of glomerular capillaries

• Contains pores (≈70–100 nm) that allow water, ions, glucose, and small solutes to pass.

  • Blocks blood cells

  • negative charge repels plasma protein

Filtration Barrier: Glomerular Basement Membrane (GBM)

MIDDLE layer

• made of type IV collagen, laminin, and proteoglycans

• Thick, acellular

• Acts as both a physical and electrostatic filter

  • Molecules < 4 nm pass easily

  • protein/ albumin (≈ 7 nm) mostly restricted

  • Overall negative charge limits movement of negatively charged proteins

Filtration Barrier: Podocyte (Visceral) Layer

OUTERMOST layer

• formed by Podocytes with Foot Processes (pedicels) extended from them

  • spaces between them form filtration slits (nephrin, podocin, CD2AP)

  • Provides final size- and charge-selective barrier

  • Blocks large macromolecules

Filtration Selectivity depends on what 2 things?

1. Molecule size (too large)

2. Electrical charge (negative)

Filtration Selectivity Permits and Restricts:

• Permits

  • water, Na⁺, K⁺, Cl⁻, glucose, amino acids, small peptide

• Restricts

  • large proteins (albumin)

  • blood cells

  • size cutoff= 4 nm

  • negative molecules are repelled

Osmolarity

• Measures how concentrated solutes are

  • osmoles per liter (Osm/L)

  • changes depending on how much water and
    solute are reabsorbed or secreted

• In nephron

  • reflects concentration of ions and molecules like sodium (Na⁺), chloride (Cl⁻), and urea

Tubule Lumen

• Space inside tubule where filtrate is

  • where substances become urine or are reabsorbed in blood/body

Tubule Epithelial Cell

Cells deciding what substances are reabsorbed into the blood or secreted into filtrate (becomes urine)

Apical (Luminal) Side

• Faces FILTRATE (tubule lumen)!!

• Direct contact with filtrate

  • reabsorption: move from filtrate → into the cell

  • secretion: move from the cell → into the filtrate

Basolateral Side

• Faces Interstitial Fluid and Peritubular Capillaries!!

• FACES BLOOD

  • Reabsorption: move from cell → into the blood

  • Secretion: move from blood → into the cell

Interstitial Fluid

• surrounds tubules

• reabsorbed substances pass through here before they get to blood

Peritubular Capillaries

blood vessels that pick up reabsorbed solutes and return them to blood

Active Transport

• Uses ATP to move substances uphill (low → high)

  • Ex: Na⁺/ K⁺ pump on basolateral membrane

Osmosis

• Water moves through AQUAPORINS from (low → high)

  • Ex: PCT water movement via AQP1

Aquaporins

• Special water channels

• allow water to move in and out of cells

Facilitated Diffusion

• Downhill movement using carrier/channel (high→ low)

  • take no energy

  • uses transport protein

  • Ex: Glucose exiting PCT cells via GLUT2

Electrochemical Gradients

• Ions move based on concentration + electrical charge!!

  • Ex: Na⁺ entry into PCT cells

• Concentration Gradient

  • difference in IONS on each side of membrane

  • high → low

• Electrical Gradient

  • difference in CHARGE across membrane

  • (+) ions attracted to negative regions

  • (-) ions attracted to positive regions

Receptor-Mediated Endocytosis

• Highly selective cell uptake using receptors

  • “lock and key”

  • molecule binds to specific receptor, cell membrane folds in and brings molecule into cell

  • Ex: Reabsorbing filtered proteins/peptides

Transcytosis

Vesicles transport macromolecules cross the entire cell

Transcellular Transport

• THROUGH the cell (apical → cytoplasm → basolateral)

  • Highly selective and regulated

  • Uses specific channels/ pumps

Paracellular Transport

• Shortcut BETWEEN cells, through tight junctions

  • Less selective!

  • Driven by concentration/ electrical gradients

Glucose

completely reabsorbed

Sodium

• tightly regulated

• mostly reabsorbed

Potassium

• reabsorbed early

• secreted later

Creatinine

filtered and excreted

Nephron PATHWAY: Proximal Convoluted Tubule (PCT)

• “Bulk Reabsorption Zone”

• Microvilli ↑ surface area

  • 65-70% of Na⁺ (NHE3, SGLT2)

  • 65-70% of water (AQP1, paracellular)

  • all glucose

  • all amino acids

  • 80-90% of bicarbonate

  • large amounts of Cl⁻, K⁺, Ca²⁺ (paracellular)

• Secretion

  • H⁺ (via Na⁺/H⁺ exchanger

Nephron PATHWAY: Descending Loop of Henle

water leaves

• “Concentrate”

  • Reabsorbs water only (AQP1)

  • No significant solute reabsorption

  • Filtrate becomes concentrated

Nephron PATHWAY: Ascending Loop of Henle

solute leaves

• “Dilute”

  • Reabsorbs Na⁺, K⁺, Cl⁻ (NKCC2)

  • Impermeable to water → filtrate becomes dilute

  • Helps create the salty medulla

Nephron PATHWAY: Distal Convoluted Tube (DCT)

highly regulated, hormones make decisions

• EARLY

  • Reabsorbs Na⁺ and Cl⁻ (NCC transporter)

  • Reabsorbs Ca²⁺ (TRPV5), ↑ by PTH

  • Impermeable to water= dilute

• LATE

  • Reabsorbs Na⁺ (ENaC)

  • Secretes K⁺ (ROMK)

  • Secretes H⁺ (H⁺-ATPase in intercalated cells)

  • Water reabsorption only with ADH (AQP2)

Nephron PATHWAY: Collecting Duct

“Final Decision”

• PRINCIPLE Cells

  • Reabsorb Na⁺ (ENaC; ↑ aldosterone)

  • Secrete K⁺ (ROMK; ↑ aldosterone)

  • Reabsorb water (AQP2 insertion with ADH)

• INTERCALETD Cells

  • Secrete H⁺ (H⁺-ATPase)

  • Reabsorb or secrete HCO₃⁻ depending on acid–base needs

How Much Filtrate Is Reabsorbed in Each Nephron Segment?

• PCT: ~65–70%

• Loop of Henle: ~20–25%

• DCT: ~5%

• Collecting Duct: ~4–5% (variable with ADH)

What is Clearance?

Measurement

• HOW WELL kidneys remove/ filter a solute from the blood

• what’s filtered out= urine

  • HIGH: removes a lot

  • LOW: removes a little

  • ZERO: none removed, all gets reabsorbed

• evaluating using creatinine!!

How is Clearance evaluated?

• Creatinine

  • freely filtered by kidneys, and is not reabsorbed

  • clinicians measure serum creatinine level and use it to estimate the glomerular filtration rate (eGFR)

    • ↑ creatinine= ↓ clearance

    • ↓ creatinine= ↑ clearance (filtering well)

• Insulin

  • freely filtered by kidneys, and is not reabsorbed

  • good for measuring GFR

What is Renal Handling?

Mechanism

• Describes HOW the kidney processes that solute

• Options:

  1. Filtration (solute moves from glomerulus to Bowman’s)

  2. Reabsorption (moves from tubule/ filtrate to blood)

  3. Secretion (moved from blood back to tubule/ filtrate)

  4. Excretion (solute moved from body as urine)

• ex: glucose= filtered and reabsorbed

• ex: creatinine= filtered and secreted

How Inulin & Creatinine Help Measure GFR

• Insulin

  • gold standard

  • (filtered, not reabsorbed or secreted)

• Creatinine

  • used clinically

  • (filtered, not reabsorbed, slightly secreted)

Sodium (Na⁺) Reabsorption in PCT

proximal convoluted tubule

• Apical Side

  • (sodium naturally wants to move into cell, bc the concentration is low in there)

  • Na⁺ enters through SGLT2 (move Na⁺ and glucose in together)

  • Na⁺ also enters via NHE3 (exchanges Na⁺ for H⁺)

• Basolateral Side

  • ^^Low Na⁺ inside cell bccc Na⁺/ K⁺ ATPase pump is constantly pumping Na⁺ out into blood