Lecture Notes: Controlling Internal Environment: Excretion and Kidneys, Chpt 44

I. Function of Excretion

A. Mechanism for removing undesirable molecules.
B. Mechanism for maintaining water balance.
C. Energy is stored in bonds, what is left over after metabolism is passed out.

1. Metabolic Waste Products

- Sugar to CO₂ and H₂O
- Amino acids to NH₃, CO₂, S
- Nucleotides to P, CO₂, NH₃ (PO₄, Sugar, base)
- Fats to Krebs Cycle to CO₂

2. Discharge

- CO₂ - respiration
- rest - excretion

3. Nitrogenous Waste: Toxicity of NH₃

- NH₃ is biproduct of amino acid metabolism, it's toxic

-- toxicity: elevation of pH >> tertiary structure of proteins
-- interferes with iron (Fe) transport
-- 3x10^-5 M fatal in rabbits

- many aquatic animals - NH₃ is diluted in aqueous environment
- terrestrial - urea (less toxic - 2 nitrogens per molecule)

- uric acid: birds, reptiles, most terrestrial arthropods

D. Toxin Ingestion (natural products); Selective removal of such agents.

Evolution of Excretion: Detoxification and Water Balance

In General: Filtration, Active Secretion and Resorption (F-S-R)

Diversity of anatomical structures, all accomplishing F-S-R in the context of the above "evolutionary" overview.

III. Mammalian Urinary System

A. Parts overview

1. Renal Artery, Renal Vein
2. Kidney - Urine Formation
3. Ureter
4. Bladder
5. Urethra

B. Urine Formation - Kidney - Nephron is the functional Unit

1. Nephron is the functional unit

a. Glomerulus / Bowman's capsule
b. Proximal Tubule
c. Loop of Henle

- unique to birds and mammals
- establishes & maintains salt gradient from 300-1200 mosmol

d. Distal Tubule
e. Collecting Duct


2. Activities

a. Glomerulus / Bowman's capsule

- Filtration of blood

b. Proximal Tubule

- NaCl, H₂O recovery
- recovery of glucose, amino acids, vitamins, ions, etc
- synthesis and secretion of NH₃
- secretion of toxins

c. Loop of Henle

- establishes salt concentration gradient which removes H₂O from urine

d. Distal Tubule

- similar to Proximal Tubule

e. Collecting Duct

- final concentration of urine (H₂O removal).


C. Glomerulus / Bowman's Capsule: Filtration

1. High Pressure in Capillaries
2. "holes" in walls of capillaries making them leaky
3. Cells (Podocytes) cover capillaries - junctions make very fine holes

a. Blood retains cells, most plasma proteins
b. filtrate contains small molecules

desirable: amino acids, glucose, ions, etc.
undesired: toxins (nicotine, pesticides), urea, etc.
180 liters every 24 hrs (-->> 1.5 liters urine / 99% recovered)


D. Proximal Tubule: Selective Resorption / Secretion

1. Cells: microvillous inner surface, mitochondria rich (much ATP)
2. Active transport and facilitated diffusion selectively remove...

a. transport - saturate / maximum rate

- active transport: a pump requiring ATP energy, transport against concentration gradient
- facilitated transport: biochemical pump, but utilizing conc. gradient

b. Selective recovery of glucose, amino acids, vitamins,

Na⁺, Cl^-, HCO₃^-, K⁺, etc.

c. ~ 65% of H₂O follows by osmosis
d. mechanism: Na⁺ coupled transport

- Active transport of Na⁺ out of cell / out of tubule
- Na⁺ transported into cell from lumen down a gradient
- Solute movement into cell coupled with Na⁺ transport
- Solute exits cell by facilitated diffusion, down conc. gradient
- The active transport of Na⁺ out of cell drives bulk transport.


3. NH₃ synthesis and secretion from amino acids.

a. picks up H⁺ to form ammonium ion NH₄⁺
b. charged form cannot pass out but is trapped in urine for excretion.

4. HPO₄^2- lost with filtrate

a. picks up H⁺ to form H₂PO₄^-
b. charged form cannot pass out but is trapped in urine for excretion.

5. Acid balance:

a. NH₄⁺ and H₂PO₄^- remove extra H⁺ from fluid
b. H⁺ removal reduces body acidity


E. Loop of Henle: Concentration Mechanism: more below

1. Establishes Concentration Gradient that concentrates Urine

a. Descending Loop: perm to H₂O, imperm to NaCl
b. Ascending Loop-lower: imperm to H₂O, perm to NaCl
c. Ascending Loop-upper: imperm to H₂O, active transport of NaCl


F. Distal Tubule: Selective Reabsorption / Secretion

1. Many of the same events as in the proximal tubule.
2. Secretion of K⁺ and H₂O reabsorption are hormonally regulated


G. Collecting Duct: Final Concentration

1. upper region, active transport of NaCl
2. lower regions:

H₂O leaves by osmosis
NaCl and urea can diffuse out,

- contributing to interstitial salt concentration
- increased salt concentration draws out more H₂O conc. urine


H. Final urine

1. high concentration of urea
2. secreted toxins, some NH₄⁺, H₂PO₄^-
3. 99% of NaCl & H₂O recovered from primary filtrate
4. glucose, etc, present if reabsorption mechanisms are saturated

IV. Mech. of urine formation: Filtration, selective secretion / reabsorption.

A. Filtration: Glomerulus / Bowman's Capsule

1. High Pressure in Capillaries
2. "holes" in walls of capillaries making them leaky
3. Cells (Podocytes) cover capillaries - junctions make very fine holes

a. Blood retains cells, most plasma proteins
b. filtrate contains small molecules

desirable: amino acids, glucose, ions, etc.
undesired: toxins (nicotine, pesticides), urea, etc.
180 liters every 24 hrs (-->> 1.5 liters urine / 99% recovered)

B. Selective Resorption / Secretion: Proximal Tubule.

1. Cells: microvillous inner surface, mitochondria rich (much ATP)
2. Active transport and facilitated diffusion selectively remove...

a. transport - saturate / maximum rate

- active transport: a pump requiring ATP energy
- facilitated transport: biochemical pump, utilizing conc. gradient

b. Selective recovery of glucose, amino acids, vitamins,

Na⁺, Cl^-, HCO₃^-, K⁺, etc.

c. ~ 65% of H₂O follows by osmosis
d. mechanism: Na⁺ coupled transport

- Active transport of Na⁺ out of cell / out of tubule
- Na⁺ transported into cell from lumen down a gradient
- Solute movement into cell coupled with Na⁺ transport
- Solute exits cell by facilitated diffusion, down conc. gradient
- The active transport of Na⁺ out of cell drives bulk transport.

3. NH₃ synthesis and secretion from amino acids.

a. picks up H⁺ to form ammonium ion NH₄⁺
b. charged form cannot pass out but is trapped in urine for excretion.

4. HPO₄^2- lost with filtrate

a. picks up H⁺ to form H₂PO₄^-
b. charged form cannot pass out but is trapped in urine for excretion.

5. Acid balance:

a. NH₄⁺ and H₂PO₄^- remove extra H⁺ from fluid
b. H⁺ removal reduces body acidity

C. Selective Reabsorption / Secretion: Distal Tubule.

1. Many of the same events as in the proximal tubule.
2. Secretion of K⁺ and H₂0 reabsorption are hormonally regulated

V. Mechanism of urine concentration: Loop of Henle

A. Concentrations

1. Osmolarity

a. Solute molarity
b. 1 osmol = 6x10²³ solute molecules per liter
c. example: 150 mM NaCl = 300 mosmol solute (150 mM Na⁺ + 150 mM Cl^-)

2. Blood: ca. 300 mosmol
3. In Kidney: concentration gradient from 300 - 1200 mosmol along Loops


B. Counter Current Exchange

1. A concentration gradient can be established and maintained between two currents

if the two currents are running in opposite directions


C. Following Events...

1. Na⁺ is actively transported out of upper, ascending loop

This elevates interstitial NaCl

2. H₂O moves out by osmosis in upper descending loop

driven by elevated interstitial NaCl

3. Loss of H₂O elevates lumen [NaCl]; as this condition enters

ascending loop, [NaCl]lumen > [NaCl]interstitial
NaCl passively diffuses down conc. gradient, maintaining a high
[NaCl]interstitial

4. Descending filtrate confronts ever increasing [NaCl]interstitial;

driving out more H₂O by osmosis / increasing [NaCl]lumen

5. This condition develops spontaneously from three conditions:

a. Initial elevated source of NaCl: Na⁺ active transport
b. Descending loop permeable only to H₂O, imperm to NaCl
c. Ascending loop permeable to NaCl, imperm to H₂O

VI. Hormonal Regulation

A. Antidiuretic Hormone (ADH)

1. brain peptide, hypothalamus, stored released from pituitary
2. Action

a. Osmoreceptors in hypothalamus
b. Osm above 300, ADH release
c. acts on distal tubules and collecting ducts
d. increased H₂O permeability (increased recovery)

3. EtOH inhibits ADH release, leads to dehydration.


B. JGA: juxtaglomerular apparatus

1. Center located near afferent arteriole which supplies blood to glomerulus
2. Three hormones

a. renin
b. angiotensin II (from plasma peptide angiotensinogen)
c. aldosterone

3. Action

a. blood pressure drop >> renin release from JGA
b. angiotensinogen converted to angiotensin II in blood

- constricts arterioles, restricting blood flow, raising pressure
- increase NaCl and H₂O reabsorption in proximal tubules

-- increases blood volume and hence blood pressure

c. angiotensin II stimulates adrenal glands to release aldosterone

- increase Na and H₂O reabsorption by distal tubules

-- increases blood volume and hence blood pressure


C. Atrial Natriuretic Factor (ANF)

1. Peptide from heart atrial cells;

a. released in response to increase blood volume and pressure

2. Action

a. inhibits renin release from JGA
b. inhibits NaCl reabsorption by collecting ducts
c. reduces aldosterone release from adrenal glands

Review Summary Tables...

EXCRETION:

1. Problematic Metabolic End Products 2. Toxins 3. Water Balance	Amino Acids: NH3 (Urea, Uric Acid)
Filtration // Reabsorption & Filtration	Water recovery: ... aquatic, salt water (NH3) ... aquatic, fresh water (NH3) ... terrestrial (Urea)
Concentration above body Osmolarity	Mammals (urea) and Birds (uric acid)

PARTS:

SYSTEM	KIDNEY	NEPHRON
Renal Artery / Vein	Renal Cortex	Glomerulus
Kidney	Renal Medulla	Bowman's Capsule
Ureter	Renal Pelvis	Proximal Tubule
Bladder		Loop of Henle
Urethra		Distal Tubule
		Collecting Duct

Nephron is functional unit of kidney.

Over 1,000,000 nephrons per human kidney (80 km of tubules).
Several nephrons per collecting duct (many collecting ducts per medulla).

NEPHRONIC ACTIVITIES:

Glomerulus & Bowman's Capsule	Glomerulus is "ball" of blood capillaries embedded in "ball-like" end of Proximal Tubule; this Ball-like end is called Bowman's Capsule. Capillaries are surrounded by special cells called "Podocytes" which have specialized joinings which act as filters, excluding blood cells and proteins from entering the Proximal Tubule
Proximal Tubule	Active transport "OUT" of Na+. Na+ co-transport of glucose, amino acids, vitamins, etc. H2O out by osmosis (65% of entering). Toxin excretion.
Loop of Henle	Establishes Na+ concentration gradient which "extracts" H2O from urine (by osmosis) as it descends through this gradient in the collecting ducts.
Distal Tubule	Similar to Proximal Tubule. Hormonally regulated K+ secretion and H2O recovery.
Collecting Duct	"Descends" from cortex, through medulla, emptying into Renal Pelvis. "Descends" through increasing Na+ concentration H2O removed by Osmosis. Final urine is what drips out of collecting duct.

ESTABLISHING THE GRADIENT: THE LOOP OF HENLE.
Pre-Conditions:

1. Descending loop permeable to H₂O, impermeable to Na⁺
2. Ascending loop permeable to Na⁺ , impermeable to H₂O
3. Distal tubule, H₂O permeability is regulated.
4. Collecting duct: permeable to H₂O, Na⁺ permeability is regulated.

HORMONAL REGULATION:

ADH: Antidiuretic Hormone ...Brain Peptide ...released in Posterior Hypothalamus ...Osm detectors in Hypothalamus	above 300 mOsm, ADH released. Acts on Distal Tubules Increases H2O permeability ... increase H2O recovery ...decrease H2O loss Dilute blood, lower Osmolarity.
JGA - Juxtaglomerular Apparatus ...cells around renal arteriole ...BP drop >> secrete Renin.	Renin stimulates conversion of Angiotensinogen >> Angiotensin II in blood. Angiotensin II acts on: .. Arteriole Construction ......close capillary beds ..Proximal Tubules ......increase Na+, H2O reabsorption ......increase blood volume ..Adrenal Gland >> Aldosterone ......Distal Tubules .........increase N+, H2O reabsorption .........increase blood volume BP rises.
Atrial Natriuretic Factor (ANF) ..Peptide Hormone ......released from heart atrial cells ......BP increase >> release ANF	ANF acts on: ..JGA ......Inhibits release of Renin ..Collecting Duct ......Inhibit Na+ reabsorption ..Adrenal Gland ......Inhibits release of Aldosterone BP drops.

Vocabulary