UNIT 7: THE KIDNEYS

BIOL2420 D01 Lecture Notes

 A) Kidney Functions – Overview
Ø The kidneys = main organ of urinary system and have a number of
different functions that ultimately relate to the mass balance of fluid,
electrolytes, and wastes in the body. Major functions include:
1. Regulating ECF volume and blood pressure – through release or retention
of water (maintains water balance). .
2. Regulating osmolarity of body fluids – maintains body fluids at 290 mOsm.
3. Maintaining electrolyte balance by controlling levels of specific ions such
as Na+, Cl-, K+, Ca2+, Mg2+, PO43-
4. Homeostatic control of acid-base balance to maintain pH of body fluids –
through reabsorption (retention) or secretion (release) of H+ and HCO3-.
5. Excretion/elimination of wastes, such as
Ø end products of metabolism (urea, creatinine)
Ø foreign compounds (xenobiotics) such as drugs, pesticides and other
environmental toxins.
6. Production of hormones – erythropoietin (stimulates RBC production) and Figure 19.1
renin (triggers pathway important for salt conservation).
 B) Basic Anatomy of Urinary System
Ø Urinary system consists of
1. 2 kidneys - receive ~20-25% of cardiac output (>1 L/min).
Ø Basic unit of structure and function of the kidneys is the nephron
Ø Nephrons are arranged to form two layers in the kidney”
a. renal cortex (outer layer)
b. renal medulla (inner layer) – organized into renal pyramids
(cone shaped structures that contain part of the tubular Renal
portion and collecting duct for each nephron). pyramids

ØNephrons filter plasma to form urine. Filtrate passes through the

tube of the nephron, into collecting ducts, and then into the renal
pelvis which is connected to the ureter.
ØBlood is carried to the kidney through the renal artery and is
drained from the kidney through the renal vein.
2. 2 ureters – carry urine to bladder
3. 1 bladder – stores urine until micturition
4. 1 urethra – passes urine out of body
 C) Nephron renal corpuscle proximal convoluted
tubule
Ø ~1 million nephrons per kidney Bowman’s glomerulus peritubular
Capsule capillaries
Ø site of urine formation efferent
arteriole distal
Ø functional unit of the kidney convoluted
afferent
tubule
Ø Two main structural components are necessary for arteriole

nephron function: collecting

duct
1. Vascular elements cortex
ØTwo arterioles and two sets of capillaries between them (the medulla
renal portal system). A portal system moves blood between
two capillary beds before returning it to the heart (most
circulation patterns involve only a single capillary bed).
ascending descending
Ø afferent arteriole à glomerulus (capillary bed #1) à thick loop thin loop
efferent arteriole à peritubular capillaries and vasa recta of Henle of Henle
(capillary bed #2)
ascending vasa recta
ØGlomerulus, efferent arteriole and peritubular capillaries/vasa
thin loop
recta make up the renal portal system (blood flows through
two capillary beds before retuning to heart).
of Henle
Figure 18.2
 Figure 19.1g
C) Nephron
2. Tubular elements
ØEach nephron is a twisted tube divided into different sections. Each section
of the tube has specific functions that are carried out by the specific cell
types located there.
ØParts:
a. Renal corpuscle
i. Bowman’s capsule (tubular element) - two layers of simple
squamous cells: Parietal layer
1) outer parietal layer forming exterior surface of capsule (of Bowman’s
capsule) Glomerulus
2) inner visceral layer that wraps around the surface of the
Podocytes
glomerular capillaries. These cells are modified to have short
(visceral layer)
foot-like processes or extensions and are known as podocytes.
Podocytes form the filtration slits (act like a sieve/strainer that
allows some materials to pass from the blood into capsule
and tubule, and keeps some materials (such as red blood
cells and large plasma proteins like albumins in the blood).
ii. Glomerulus (vascular element, capillary bed containing blood
to be filtered)
C) Nephron
2. Tubular elements
ØEach nephron is a twisted tube divided into different sections. Each
section of the tube has specific functions that are carried out by the
specific cell types located there.
ØParts:
b. Proximal convoluted tubule (PCT) – composed if simple
cuboidal cells with microvilli
c. Descending thin loop of Henle – small simple squamous cells
d. Ascending thin loop of Henle – larger simple squamous cells
e. Ascending thick loop of Henle – simple cuboidal cells
f. Distal Convoluted tubule (DCT) - simple cuboidal cells, no (few)
microvilli,
g. Collecting Duct – two cell types:
a. Principal cells (P-cells)
Figure 19.1g
b. Intercalated cells (I-cells).
C) Nephron
Ø Vascular and tubular elements come together to form the juxtaglomerular apparatus, a point of
contact between the arterioles and the thick ascending limb of loop Henle. Consists of:
1. Macula densa cells in thick ascending loop of Henle facing afferent and efferent arteriole.
Ø detect Na+ concentration of filtrate
2. Granular cells – surround afferent arteriole.
Ø secrete renin (enzyme and hormone involved in salt and water balance – see Unit 8).

Figure 19.7
C) Nephron
Ø Two categories of nephrons based on structure,
location and function:
1. Cortical Nephrons (two sub-types)
Ø ~80% of nephrons
Ø Corpuscle is located in the outer layer of the cortex.
Ø Loop of Henle is short and extends towards the
medulla, reaching to either the cortex/medulla
boundary or just passing the boundary and having a
small portion in the the medulla.
2. Juxtamedullary nephrons:
Ø Corpuscle is located deep in the cortex, with long
loops of Henle that extend deep into the medulla
Ø Important for production of dilute or concentrated
urine depending on the needs of the body. Help to
control water balance.
Ø Has vasa recta capillaries that run parallel to the
nephron loop. Figure 19.1e
 C) Nephron
Ø Processes in the nephron that lead to urine formation:
1. Glomerular Filtration
Ø Plasma in glomerular capillaries is filtered into the lumen of
Bowman’s capsule to form the filtrate that will become urine
Ø Filtrate is similar in composition to plasma, but is almost
protein free (only the smallest proteins can move past the
filtration membrane into Bowman’s capsule).
Ø ~ 20% of plasma is filtered per pass (= filtration fraction)
2. Tubular Reabsorption
Ø Selective movement of certain substances from the tubular
lumen back into the venous system via peritubular capillaries.
Ø ~99% of filtrate is typically reabsorbed
3. Tubular secretion
Ø Selective transfer of certain substances from the peritubular
capillaries (and tubular cells) into the tubular lumen (i.e. into
the filtrate). Provides a mechanism for rapid elimination of Figure 19.2
unwanted substances.
 C) Nephron
Ø Anything filtered or secreted but not reabsorbed is
excreted. Therefore:

Amount of solute Amount Amount Amount

= − +
excreted filtered reabsorbed secreted

Figure 19.3
 D) Glomerular Filtration
Ø Urine formation begins with glomerular filtration.
Ø A 3-layer filtration membrane is formed by the interface
between the glomerulus and Bowmans’s capsule (“filtration
barriers” that act like a sieve). Consists of:
1. Fenestrated endothelium (capillary wall) of glomerulus –
porous simple squamous epithelium that is >100x more
permeable than capillaries in other parts of the body (so
very leaky).
Ø Large pores allow most solutes to pass between these cells
(paracellular route), but endothelium still physically blocks
platelets, blood cells, and most proteins.
2. Basement membrane – An acellular glycoprotein/collagen
layer (basal lamina). Most glycoproteins here are anionic
(negatively charged), and so repel most anionic plasma
proteins. Filtration of much smaller anions (such as Cl-,
HCO3-, HPO42-) is not affected
Figure 19.5
 Figure 19.5
D) Glomerular Filtration
3. Podocytes of Bowman’s capsule – layer of specialized capsular cells
that surround the glomerular capillaries. Have finger-like processes
that extend off the cell body. These projections interdigitate with
those of neighboring podocytes, covering the capillary and forming
filtration slits for fluid to pass through (like sieve)
Ø Filtration membrane allows for complete extracellular filtration (all
materials pass via paracellular routes out of the capillary, through
the basement membrane, through the filtration slits in between
podocyte cell processes and into the lumen of Bowman’s capsule.
Ø Any material that cannot make it past one of these 3 filtration
barriers remains in the blood.
Ø Filtrate is nearly protein-free and is isosmotic to the plasma.
 D) Glomerular Filtration
Ø Filtration is a passive mechanical process in which pressure differences (ΔP) on either side of the
filtration membrane drive the plasma across the membrane via bulk flow. Similar hydrostatic and
osmotic pressures involved as in regular capillary exchange.
Pressure Name P (mmHg) Effect See Figure 19.6
1. Glomerular capillary hydrostatic 55 Favours NOTE: Because
pressure (blood pressure), Pc filtration 55
the filtration
membrane
2. Plasma Colloid Osmotic Pressure 𝜋c 30 Opposes keeps most
filtration 30 proteins in the
blood, the total
3. Bowman’s Capsule Hydrostatic 15 Opposes protein in
Pressure, PB filtration 15 Bowman’s
capsule is very
low, and so the
4. Bowman’s Capsule Colloid Osmotic 0 Favours
0 colloid osmotic
Pressure, 𝜋B filtration pressure of the
capsule (𝜋B) is
4. Net filtration pressure (NFP +10 Favours
10 usually taken as 0
(55 + 0) – (30+15) = mmHg filtration
 E) Regulation of Glomerular Filtration Figure19.6
Ø The body uses homeostatic control to maintain glomerular
filtration rate (GFR) within narrow limits despite short-term and
long-term changes in mean arterial blood pressure.
ØGFR is dependent upon both the net filtration pressure (NFP)
and the filtration coefficient Kf of the glomeruli.
GFR (ml/min) = Kf × NFP
ØWhere, Kf = permeability of glomeruli x total surface area
ØGFR is primarily controlled by by changing the glomerular
capillary blood pressure. This can be accomplished by changing
the diameter of mainly the afferent and (to a lesser extent) the
efferent arterioles (i.e. changing the resistance of these vessels).
ØIn a healthy person, ~900 L of blood per day passes through
the afferent arteriole and ~180 L/day (20%) is filtered into the
nephrons, which is an average GFR of 125 mL/min.
E) Regulation of Glomerular Filtration Figure19.6
Ø GFR is maintained at ~125 mL/minute by both intrinsic and
extrinsic mechanisms that stop GFR from changing when
blood pressure changes (otherwise any increase in MAP
would lead to an increase in GFR and any decrease in MAP
would decrease GFR).
Ø Mechanisms of regulation:
1. Intrinsic mechanisms (autoregulation) – most important for
control of GFR in normal healthy conditions.
a. The Myogenic Response
Ø Increased pressure in the afferent arteriole induces
vasoconstriction à decreases flow into the glomerulus,
decreasing Pc, and therefore GFR.
Ø Decreased pressure in the afferent arteriole induces vasodilation
à more blood into glomerulus, increases capillary hydrostatic
pressure ( Pc) and therefore GFR).
E) Regulation of Glomerular Filtration
b. Tubuloglomerular feedback
Ø Mediated by macula densa cells of juxtaglomerular region of
the thick ascending loop Henle.
Ø Changes in GFR affect the flow rate through the nephron
(increasing GFR, increases flow rate of filtrate though nephron),
and hence the [NaCl] moving past macula densa cells.
Ø If [NaCl] is elevated (indicating increased flow through tubules):
i. macula densa cells are stimulated and release local chemical
messages (paracrines)
ii. Paracrines cause vasoconstriction of the smooth muscle
cells surrounding the afferent arterioles.
iii. Vasoconstriction increases resistance and reduces blood
flow into the glomerulus.
iv. Reduced blood flow decreases net filtration pressure and
GFR (less blood in the glomerulus results in lower
glomerular capillary hydrostatic pressure, so the force
pushing plasma across the filtration membrane is lower and
less filtrate is formed). Figure19.7
E) Regulation of Glomerular Filtration
Ø NOTE: the net effect of autoregulation (intrinsic mechanisms) on GFR is that it mostly
compensates for any changes in mean arterial pressure (MAP) between MAPs of 80 mm Hg
and 180 mmHg. At very high or very low MAP, autoregulation fails and GFR will
increase/decrease proportionally with changes in MAP.

Figure19.7
E) Regulation of Glomerular Filtration
2. Extrinsic mechanisms (neural and hormonal control)
a. Sympathetic Nervous System (SNS) input
i. Stimulates 𝛼1-receptors on smooth muscle of afferent and efferent arterioles and causes vasoconstriction.
Ø Vasoconstriction in afferent arteriole reduces flow into glomerulus (decreases GFR)
Ø Vasoconstriction of efferent arteriole causes blood to back up in the glomerulus (increases GFR)
Ø Under moderate SNS activation, both balance and GFR is mostly held constant.
Ø SNS is most important in reducing GFR during severe acute disturbances (e.g. heavy exercise, severe
hemorrhage).

“Normal”

“Afferent constriction” “Effeerent constriction” Constriction of Both

E) Regulation of Glomerular Filtration
2. Extrinsic mechanisms (neural and hormonal control)
a. Sympathetic Nervous System (SNS) input
ii. Causes podocyte foot processes (of filtration
glomerular capillary
membrane) to contract/flatten which decreases the size
of the filtration slits (and therefore decreases the basal lamina
podocytes
filtration coefficient, Kf).
Ø Decreasing Kf, results in a decrease in GFR
sympathetic stimulation filtration slits
(filtration membrane is less permeable, so less
filtrate forms).
b. Hormonal and Paracrine regulation
Ø Norepinephrine and epinephrine cause arteriolar
vasoconstriction - ↓GFR
Ø Angiotensin II causes vasoconstriction of efferent
arteriole – helps to maintain GFR when pressure drops
and flow through afferent arteriole is reduced
Ø Prostaglandins causes arteriolar dilation - ↑GFR
 F) Tubular Reabsorption
Ø Most filtered nutrients, H2O, and electrolytes are returned to the
blood in order to maintain nutrient, electrolyte and water balance.
Ø Reabsorption is a highly selective process (compared to filtration
which is less selective) that also helps to concentrate nitrogenous
wastes and excess ions for excretion.
Figure 19.8
Ø The magnitude of tubular reabsorption is extremely large:
Ø 1 - 1.5 L/day of urine produced but 180 L/day is filtered, therefore
transepithelial
most of filtrate is reabsorbed from tubules of nephrons into peritubular
+ vasa recta capillaries. Reabsorption includes: transepithelial
paracellular
Ø >99% of the filtered H2O (~17.8 L/day)
Ø 100% of the filtered “sugars”, e.g. glucose (~180 g/day)
transepithelial
Ø ~99.5% of the filtered salt (~625 g/day) paracellular

Ø ~50% of the filtered urea is reabsorbed on a daily basis

transepithelial
Ø Reabsorption occurs by transepithelial transport (across cells) or via paracellular

the paracellular pathway (in between cells)

 F) Tubular Reabsorption
Ø Both active and passive transport processes are involved:
1. Active Reabsorption
a. Na+ Reabsorption
Ø Active transport of Na+ is critically important as it sets up
electrochemical and concentration gradients that will
influence the transport of almost all other molecules/ions.
Ø With the exception of the thin descending and ascending
Loop of Henle, Na+ reabsorption is primarily accomplished by
energy dependent Na+-K+- ATPase transport across the
basolateral membrane of tubule cells.
Ø Actively pumping Na+ across the basolateral membrane from
the tubule cells into the interstitial fluid decreases the [Na+] in
tubule cells while increasing the [Na+] in the ISF. This
establishes two electrochemical gradients for Na+ diffusion:
i. From lumen into tubular cells (Na+ enters tubule cells by
diffusion down this gradient through Epithelial Na+ Modified from
Channel proteins, also known as ENaC.
Figure 18.8
ii. From the ISF into the peritubular capillaries
 F) Tubular Reabsorption
Ø Both active and passive transport processes are involved:
1. Active Reabsorption
a. Na+ Reabsorption
Ø 80% of total energy requirement of the kidneys is
used for Na+ reabsorption, indicating the
importance of this process
Ø Na+ is reabsorbed to varying extents throughout
the nephron:
Ø ~65% from proximal convoluted tubule
Ø ~25% from the ascending limb of the
loop of Henle
Ø 8 – 10% from the late DCT and cortical
collecting ducts.
Ø As a result, only up to ~2% of the filtered
Na+ can be excreted (15 g of Na+ and 15g Cl- Modified from
= 30g of NaCl excreted per day)
Figure 18.8
 F) Tubular Reabsorption
Ø Both active and passive transport processes are involved:
1. Active Reabsorption
b. Glucose and amino acids
Ø Symport via secondary active transport (cotransport) with Na+. Na+ moves down its concentration gradient
which moves glucose and amino acids against their concentration gradients.
Ø E.g. Glucose moves into the cell with Na+ through the SGLUT transport proteins in the apical membrane, and
then diffuses into the ISF via a GLUT protein in the basolateral membrane.

Figure 18.8b
 F) Tubular Reabsorption
Ø Both active and passive transport processes are involved:
1. Passive reabsorption (indirectly linked to Na+ reabsorption)
a. Chloride (Cl-) reabsorption
Ø Mostly occurs via the paracellular route following the electrical gradient established by the active
transport of Na+. [Na+] in the ISF is high, resulting in a build up of positive charge that attracts Cl- to
enter via the paracellular pathway.

Modified Figure
18.8
 F) Tubular Reabsorption
Ø Both active and passive transport processes are involved:
2. Passive reabsorption (indirectly linked to Na+ reabsorption)
b. Water reabsorption
Ø Removal of solutes from the tubular lumen decreases the lumen
osmolarity, while increasing the ISF osmolarity tubule create a
concentration gradient for urea.
Ø However tubular epithelium in most locations is not permeable to water – so diffusion of H2O from lumen to
ISF is primarily via osmosis through channels in the apical and basolateral membranes called aquaporins
(AQs).
Ø 6 different aquaporin isoforms in kidney.
Ø In PCT and thin descending tubules aquaporins are always present, so get obligatory reabsorption of ~75% of filtered
H2O in this region.
Ø Numbers of the specific aquaporin AQ2 in the late DCT and collecting ducts can be increased under the influence of the
hormone vasopressin. This allows these structures to modify water reabsorption in response to need (facultative water
reabsorption). We will look at this more in Unit 8.
Ø Plasma entering peritubular capillaries has a high colloid osmotic pressure (as 20% of fluid was removed during
filtration at glomerulus), and so it “pulls” water into the plasma (see text Figure 19.11)
 F) Tubular Reabsorption
Ø Both active and passive transport processes are involved:
2. Passive reabsorption (indirectly linked to Na+ reabsorption)
c. Urea reabsorption
Ø Solute and H2O reabsorption in the proximal convoluted tubule create
a concentration gradient for urea.
Ø There are no channels for urea, but “leaky” tight junctions of the
paracellular pathway are moderately permeable to urea in the PCT
(~50% reabsorbed)
Ø Tight junctions in the loop of Henle, DCT and cortical/outer medullary
collecting ducts are not permeable to urea, however urea uniporters in
the cells of the thin regions of the Loop of Henle passively secrete an Figure 19.13
equivalent amount back into the lumen.
Ø Up to half of the urea secreted in the Loop of Henle is again
reabsorbed by urea transporters in the distal (inner medullary)
collecting ducts. Trapping of urea in the medulla contributes to the
vertical osmotic gradient in the medulla (more on this in Unit 8)
F) Tubular Reabsorption
Ø Summary of steps in tubular Reabsorption:
1. Active transport of Na+ by Na+/K+-ATPase out of tubule cells (across the basolateral
membrane) and into ISF.
2. Na+ passively diffuses into tubule cell down its electrochemical gradient through ENaC
(replaces Na+ that was moved out of the cell in step 1)
3. a) Anions (e.g. Cl-, HCO3-) move into the cell or ISF (following Na+).
b) Secondary active transport (cotransport) of glucose and amino acids into the cell followed
by diffusion through channel proteins in the basolateral membrane into the ISF
4. Water follows the solutes (osmosis) moving from the tubule lumen into the ISF mostly via
aquaporins..
5. Loss of water from tubule lumen increases the concentration of the solutes remaining in the
tubule (Ca2+, urea, K+, etc) which creates a concentration gradient favoring their
movement via the paracellular pathway (through tight junctions between cells).
6. Diffusion and Bulk flow of water and solutes from the ISF into the peritubular capillaries.

Figure 18.3c
 F) Tubular Reabsorption Figure 19.9
Ø NOTE: Tubular cells possess a limited number of co-
transport protein carriers (for glucose, amino acids, and
most other molecules). When all carriers are occupied
(saturated) with solute, the maximum rate of transport of
those substances is reached. The rate of transport at
saturation is referred to as the transport maximum (Tm).
Ø Renal threshold = the plasma concentration at which the Figure 19.10
substance first appears in the urine.
Ø E.g. glucose: Tm= 375mg/min;. Under normal conditions,
plasma levels of glucose never reach renal threshold or
the Tm (glucose gets taken up by skeletal muscle cells,
liver cells etc. via the action of insulin).
Ø Because renal threshold/Tm is not reached, no glucose is excreted,
and it is 100% reabsorbed. In conditions like untreated diabetes
mellitus, plasma levels of glucose do reach or exceed renal
threshold and excess glucose is excreted in the urine (glucosuria).
 G) Tubular Secretion
ØSimilar process as reabsorption, but in opposite direction
(from peritubular capillaries into the lumen of nephron).
Amount secreted is of lower magnitude than amount
reabsorbed.
ØSubstances that are selectively secreted include:
1. K+ – important for normal nerve and muscle function.
Ø Most filtered K+ is first reabsorbed in PCT (via the leaky tight junctions) and in the
thick ascending Loops of Henle (via NKCC cotransport – Na+, K+, Cl- Cotransport,
involves a symport protein that moves Na+, K+, and Cl- together from the tubule
lumen into the tubule cell, and they can then be transported to the ISF/capillary.
2. H+ and HCO3- ions – regulates plasma acid-base balance (see Unit 8). Figure 19.13
3. Waste products such as creatinine (waste product of muscle metabolism) and
urobilin (waste product of heme breakdown that gives urine its yellow colour).
4. Foreign substances – e.g. drugs (penicillin).~ 80% secreted in 3-4 hours, (which
is why when prescribing many drugs, the dosage can be several times a day at
regular intervals to maintain effective concentrations in the blood).
H) GFR, Renal Handling, &Renal Clearance
Ø Renal handling – describes whether or not a substance is filtered and reabsorbed and/or
secreted by the kidney.
ØRenal clearance = rate at which a solute disappears from the body by excretion or by metabolism.
Ø represents the volume of plasma cleared of a substance in one min.
ØCan be used to estimate the time a substance remains in the blood (e.g. drugs)
ØCan be used to estimate GFR (if look at the clearance of a substance that is known to not be reabsorbed or secreted
in the nephron).
Urine Flow Rate (UFR)
ØCalculated as:
Together, this is the
Urine volume produced per Concentration of X in
Clearance of X = unit time (mL/min)
× the urine (mg/mL)
excretion rate of X

Concentration of X in the plasma (mg/mL)

ØTo determine the urine volume produced per unit time in clinical situations, a 24 hour urine collection would be
taken (urine collected over a 24 hour period and its volume measured). You can then determine the volume of urine
produced per minute.
H) GFR, Renal Handling, &Renal Clearance
Ø Inulin (a carbohydrate found in some plants) can be
used to estimate GFR since
ØIt is filtered but not reabsorbed, secreted, or metabolized,
therefore the amount excreted = the amount filtered by the
glomerulus.
Ø As a result Renal Clearance = GFR
Ø for example if UFR = 4 mL/min, [inulin] in urine =
62.5mg/mL and [inulin in plasma = 2 mg/mL then clearance
(and GFR):
4 mL/min x 62.5 mg/mL
= = 125 mL/min
2 mg/mL

Figure 19.14
100 mL/min x 4 mg/mL
= = 100 mL/min
4 mg/mL
 H) GFR, Renal Handling, &Renal Clearance
ØClinically, using inulin injections to measure GFR is not very feasible, so we estimate
GFR using creatinine (naturally and constantly produced in the body as a result of
muscle metabolism). However, this is not as perfect a match for GFR as inulin, since
there is some secretion of creatinine into the filtrate. Therefore, measurements of GFR
using creatinine will be a 10-20% overestimate of GFR.
Ø Sample calculation:
H) GFR, Renal Handling, &Renal Clearance
Ø If RC < GFR – substance is reabsorbed
from filtrate.
ØE.g.1: urea has a renal clearance ~50 mL/min
(50% reabsorbed), based on an average GFR
of 125 mL/min.
ØE.g.2: glucose RC = 0 (100% reabsorbed)

ØIf RC > GFR – substance is secreted

into filtrate.
ØEg.1: penicillin
ØE.g.2: H+

Figure 19.14
 I) Micturition
Ø Micturition is the process of urination.
ØOnce it has left the collecting ducts, there is no change in
the composition of the urine (this can only be done in the
nephron).
Ø Once filtrate leaves collecting ducts, it is transferred to the
renal pelvis, into the ureter and down to the bladder where
the urine is stored.
ØThe bladder wall is a smooth muscle (called the detrusor muscle)
that is under PSNS control.

Ø Two sphincters control urine flow from the bladder:

ØInternal urethral sphincter – under PSNS control
ØExternal urethral sphincter – skeletal muscle under somatic motor
control (this is the muscle that you are learning how to use during
potty training).
Figure 18.3c
 Figure 19.15
I) Micturition
Ø Micturition is a simple spinal reflex
ØWhen the bladder is full, stretch receptors in bladder
wall send signals to the spinal cord.
ØParasympathetic (PSNS) fibers in the sacral spinal
cord are stimulated and induce detrusor muscle
contraction and internal urethral sphincter relaxation.
ØSomatic neurons to external urethral sphincter are
inhibited, causing relaxation and opening so that
urine can exit the body.
ØIf you need to wait to urinate, the reflex can be
overridden by the cortex (voluntary control of
external urethral sphincter, prevents inhibition of the somatic neurons).
ØPotty training children teaches them how to control the external urethral sphincter muscle. As
we age, this muscle weakens causing urinary incontinence.
ØIf you wait too long, and the volume of urine exceeds 500mL, the spinal reflex overrides
the voluntary control, and you will urinate whether you want to or not.
I) Micturition
Urine into bladder

stretch receptors

sacral spinal cord Cortex

micturition center “gotta pee” feeling Figure 19.15

PSNS
external urethral “Gotta wait”
sphincter relaxes If urine volume
Detrusor muscle of and opens >500 mL, “oops”
bladder wall external urethral
contracts, sphincter contracts (closes)
internal urethral
sphincter opens
urine expelled no micturition
J) Urine Composition
Ø Properties of urine under normal homeostatic conditions:
1. Contains Water – urine is normally 91-96% water.
2. Contains Nitrogenous wastes:
a) Urea – from metabolism of amino acids - ~50% of all urea filtered is reabsorbed.
b) Uric acid – from breakdown of nucleic acids. These are secreted into the nephron
and ~10% are reabsorbed. They are poorly water soluble and an accumulation of
uric acid crystals in body fluids can cause:
i. Gout – accumulation of crystals in joints resulting in a severe form of
inflammatory arthritis
ii. Kidney stones – accumulation of uric acid (or other crystal forming compounds
like calcium phosphate) in kidney, ureter or bladder
c) Creatinine – from breakdown of creatine phosphate in skeletal muscles. Filtration
and secretion are constant and there is no reabsorption, so creatinine is often used
to measure GFR and can indicate kidney disease before there are any physical
symptoms.
3. Contains Regulated Substances (such as ions: Na+, K+, Cl-, Ca++, Mg++, etc.)
4. Has a pH of 4.5 – 8.0 (average = 6.0).
J) Urine Composition
Ø Abnormal Properties of urine:
1. Proteinuria – presence of protein in urine, also known as
albuminuria. Due to an increase in permeability of the glomerulus
Can be caused by:
a) Glomerulonephritis – inflammation of the glomerulus and nephron.
b) High blood pressure – leads to glomerular huypertension and increased
pressure in the glomerulus forces proteins out of the capillary.
c) Heavy metal toxicity (e.g. mercury poisoning).
2. Glycosuria – glucose in urine. Normally 100% of filtered glucose is
reabsorbed into the blood by the proximal convoluted tubule.
Caused by:
a) Diabetes – Especially Type I since there is no insulin production at all,
but can also be seen in advanced stages of untreated Type II.
b) Genetic mutations in SGLTs (sodium glucose transporters responsible for
reabsorption.
J) Urine Composition
Ø Abnormal Properties of urine:
3. Hematuria – blood in urine. Also due to increase in permeability of
glomerulus, but an even greater increase than seen in proteinuria
(proteins are smaller so they will get filtered first, red blood cells are
larger so they require increased permeability in order to make it past
the filtration membrane). Caused by:
a) Advanced glomerulonephritis
b) Viral or bacterial infection (urinary tract infection) that causes
inflammation in the kidney, ureter, bladder and/or urethra.
c) Etc.
4. Ketonuria – ketones in urine. Occurs when the body is metabolizing
more fatty acids and proteins than carbohydrates. Causes include:
a) Diabetic ketoacidosis (potentially fatal).
b) Starvation, Fasting and Low-carb diets. Ketone levels in these cases are
typically not as severe as would be observed in diabetic ketoacidosis, but
should be monitored to prevent complications.
c) Hyperthyroidism.