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Biology 233
Human Anatomy and Physiology
Chapter 26 Lecture Outline
URINARY SYSTEM
kidneys – filter blood and form urine
ureters – carry urine from kidneys to bladder
urinary bladder – stores urine
urethra – voids urine to outside
FUNCTIONS OF URINARY SYSTEM
1) Filtration and Reabsorption of Blood – wastes are excreted and nutrients
are reabsorbed
Excretion of Wastes – excreted in urine
nitrogenous wastes
urea and ammonia – from amino acids
uric acid – from nucleic acids
bilirubin – from hemoglobin
creatinine – from creatine phosphate
foreign drugs and toxins
Regulation of Blood Osmolarity, Ion Concentration, and pH
osmolarity = number of solute particles / liter of solution
ions (electrolyte balance) – Na+, K+, Ca+2, Cl-, phosphate
pH – H+, bicarbonate ions
water – maintains blood volume and pressure
regulated by ADH and aldosterone
2) Secretion of Hormones and Enzymes
calcitriol (vitamin D) – increases absorption of dietary calcium
erythropoetin – stimulates RBC production
renin (enzyme) – RAA pathway; increases blood pressure
RENAL (KIDNEY) GROSS ANATOMY
paired; kidney bean-shaped (11cm X 6cm)
retroperitoneal; superior abdomen
Protected by connective tissues:
renal capsule (on surface of kidney) – dense irregular CT; protects and
shapes kidney
adipose capsule – cushions kidney
renal fascia – dense irregular CT; anchors kidney to abdominal wall
1
Renal Hilus (Hilum)
renal artery and nerves enter
renal vein and ureter exit
Renal Parenchyma – functional tissues of kidney
renal cortex – superficial; pale reddish-brown
renal columns – extend toward hilus
renal medulla – deep portion; dark reddish-brown
renal pyramids (8-18)
renal papilla – apex of pyramid
renal lobes (8-18)
1 pyramid + surrounding cortex
filter blood and form urine
urine drains into minor calyx (8-18)
major calyces (2-3)
renal pelvis – connects calyces to ureter
RENAL HISTOLOGY
NEPHRON – basic functional unit of kidney
renal corpuscle – site of filtration
renal tubule – collects filtered fluid, site of reabsorption & secretion
Blood Supply to Nephron
renal artery – branches extensively
afferent arteriole – supplies one renal corpuscle
glomerulus – capillary bed in renal corpuscle (filtration site)
efferent arteriole – drains renal corpuscle
peritubular capillaries & vasa recta – surround renal tubules
(site of reabsorption into blood)
renal vein
Renal Corpuscle – lies in cortex; 2 divisions
1) glomerulus – fenestrated capillary bed
endothelial cells with many pores
2) glomerular (Bowman’s) capsule – surrounds glomerulus
2 layers:
1) visceral layer – lines glomerulus
podocytes – modified simple squamous epithelium
pedicels – foot-like processes
wrap around glomerulus
filtration slits – spaces between pedicels
2) parietal layer – lines wall of capsule
simple squamous epithelium
capsular space – between layers of capsule
fluid (filtrate) filters out through glomerulus and
collects in capsular space
2
Renal Tubule – filtrate from corpuscle flows through
some solutes reabsorbed into blood, others secreted into urine
3 divisions:
1) proximal convoluted tubule (PCT) – in cortex
drains glomerular capsule
simple cuboidal e. w/ microvilli
2) Loop of Henle
descending limb – enters medulla
ascending limb – returns to cortex
thick segment – simple cuboidal e.
thin segment – simple squamous e.
3) distal convoluted tubule (DCT) – in cortex
simple cuboidal e.
collecting ducts – collect urine from several renal tubules
papillary ducts – collect urine from several collecting ducts
Flow Summary
glomerular capsule ---> proximal convoluted tubule ---> Loop of Henle
---> distal convoluted tubule ---> collecting duct ---> papillary duct --->
minor calyx ---> major calyx ---> renal pelvis --->ureter
Types of Nephrons
cortical nephrons
corpuscles in outer cortex
short Loop of Henle
juxtamedullary nephrons
corpuscle near medulla
long Loop of Henle, extends deep into medulla
juxtaglomerular apparatus – (DCT near glomerulus)
endocrine cells involved in blood pressure regulation
macula densa – densely packed cells in wall of DCT
juxtaglomerular (JG) cells – modified smooth muscle cells in wall of
afferent arteriole
RENAL PHYSIOLOGY
3 Processes Involved in Production of Urine:
1) Glomerular Filtration – blood filters through walls of glomerular
capillaries into glomerular capsule
filtrate – water and smaller plasma solutes
average production – 180 liters/day (50 gal)
2) Tubular Reabsorption – filtrate passes through renal tubule and
99% of water and many useful nutrients are reabsorbed into blood
(1-2 liters of urine/day excreted)
3
3) Tubular Secretion – renal tubule cells secrete additional solutes from
from blood into urine
(nitrogenous wastes, excess ions, drugs)
GLOMERULAR FILTRATION
Filtration Membrane – thin, leaky membrane that filters blood
3 layers:
glomerular endothelium – large fenestrations
water and all solutes pass through
blood cells and platelets retained in capillaries
lamina densa (basement membrane)– acellular layer
prevents filtration of large plasma proteins
filtration slits – between pedicels of podocyte cells
acellular layer
prevents filtration of most plasma proteins
Composition of Filtrate – plasma minus plasma proteins
water, glucose, amino acids, lipoproteins, nitrogenous wastes,
ions, bilurubin, creatinine, vitamins
Filtration Pressure (FP) = GHP – (CsHP + BCOP)
GHP – glomerular hydrostatic pressure
blood pressure that promotes filtration
normally high – efferent arteriole smaller that afferent
CsHP – capsular hydrostatic pressure
resistance in glomerular capsule that opposes filtration
BCOP – blood colloid osmotic pressure
pressure due to plasma proteins that opposes filtration
GLOMERULAR FILTRATION RATE (GFR) – total amount of filtrate
formed/minute (average 125ml/minute)
high GFR – urine formed so quickly, needed substances may not have
time to be reabsorbed (nutrients and water lost in urine)
low GFR – wastes filtered out slowly and slow movement of urine in
tubules may allow too much reabsorption
(wastes accumulate in blood)
Regulation of GFR
CsHP – constant if urine outflow is unobstructed
BCOP – constant if blood volume and plasma protein content are normal
GHP – regulated by altering blood flow and pressure in glomerulus
altering diameter of afferent and efferent arterioles
mesanglial cells – cells in glomerulus that open or close filtration
slits
4
3 GFR REGULATORY MECHANISMS – can maintain normal GFR for mean
arterial blood pressures between 80-180mmHg
1) Renal Autoregulation – kidneys regulate own GHP in response to changes in
local blood flow and blood pressure
decreased blood pressure and blood flow in glomerulus triggers
dilation of afferent arteriole = increases blood flow
constriction of efferent arteriole = increases GHP
opening of glomerular filtration slits = more filtration
increased blood pressure – stretches afferent arteriole
reflex vasoconstriction of afferent arteriole
decreases blood flow = decreases GHP = decreases GFR
2) Neural (Autonomic) Regulation
sympathetic stimulation (fight or flight)
norepinephrine causes vasoconstriction of afferent arterioles
decreases blood flow = decreased GHP = decreased GFR
3) Hormonal Regulation
Returning Reduced GFR to Normal:
RAA pathway – begins with secretion of renin by JG cells
(angiotensinogen --> angiotensin I --> angiotensin II)
3 Triggers for RAA Pathway: (all related to reduced GFR)
1) decreased GHP (< BP, < blood volume, blocked renal arteries)
2) sympathetic stimulation
3) decreased solute concentration of filtrate detected by macula
densa (slow GFR causes more reabsorption)
Effects of Angiotensin II:
nephron – constriction of efferent arteriole = >GHP
> reabsorption of Na+ and water in PCT = > blood volume
adrenal glands – aldosterone secretion
> reabsorption of Na+ and water in DCT and collecting
duct = > blood volume
CNS – thirst = > blood volume
secretion of ADH = > reabsorption of water in DCT and
collecting duct = > blood volume
> CO, venoconstriction, vasoconstriction = >BP
capillary beds – vasoconstriction = >BP
Returning Increased GFR to Normal:
natriuretic peptides (ANP, BNP) (high BP or volume)
increased stretching of heart = release of ANP, BNP
opening of filtration slits = more filtration
dilation of afferent arteriole = > blood flow
constriction of efferent arteriole = >GHP
< reabsorption of Na+ and water = increased urine volume
= < blood volume = < BP
5
TUBULAR REABSORPTION AND SECRETION
filtration forms 180 liters/day
total blood volume is only 5 liters
Tubular Epithelium
tight junctions between cells – prevent leakage
apical membrane – faces tubular fluid
basolateral membrane – faces interstitial fluid
peritubular capillaries lie nearby
apical and basolateral membranes have different permeabilities due
to different transport proteins in their membranes
Mechanisms of Reabsorption and Secretion
Passive Transport
diffusion – ion leakage channels
facilitated diffusion – eg. glucose
osmosis – aquaporin channels; water follows solutes
obligatory water reabsorption – 90%
facultative water reabsorption – final 10%
regulated by antidiuretic hormone
occurs in DCT and collecting duct
Active Transport
primary – Na+/K+ pumps
apical membrane – none
basolateral membrane – many
Na+ is pumped out of tubule cells into interstitial space
creating a concentration gradient
(high Na+ in filtrate, low in tubular cells)
secondary – use energy from Na+ concentration gradient
cotransport – solutes cross with Na+
countertransport – solutes cross opposite to Na+
Proximal Convoluted Tubule
all organic nutrients reabsorbed – glucoses, amino acids, lipids
majority of water and ion reabsorption (65%)
Primary Active Transport
Na+/K+ pumps in basolateral membrane pump Na+ out of tubular
cells into interstitial space
Passive Transport
Na+ diffuses into tubule cells from tubular fluid
water follows by osmosis
less water in tubule = osmolarity of tubule fluid increases
other solutes diffuse down their concentration gradients
6
Secondary Active Transport
Na+ cotransport – glucose, amino acids, bicarbonate reabsorbed into
blood
+
Na countertransport – H+ secreted into urine
(buffered by bicarbonate in tubules)
Loop of Henle – 25% of reabsorption
countercurrent multiplication
ascending limb – no aquaporins – impermeable to water
Na+-K+-2Cl- cotransporters – ions are reabsorbed without
water following
osmolarity in interstitial fluid increases
descending limb – aquaporins – water flows out by osmosis
osmolarity in descending limb increases
more ions to be pumped out in ascending limb
+
Na and Cl become concentrated in interstitial space of medulla
creates a concentration gradient in the medulla
Distal Convoluted Tubule
filtrate entering from loop of Henle has low osmolarity
amount of reabsorption varies
Na-Cl cotransport
site of PTH activity – promotes reabsorption of Ca+2
site of aldosterone activity – promotes reabsorption of Na+ and
secretion of K+
(opposed by natriuretic peptides)
Na-H+ countertransport – secrete variable amounts of H+ to maintain pH
(reabsorb bicarbonate – related to H+ concentration)
Collecting Duct
site of aldosterone activity – same as DCT
urea reabsorption
highly concentrated in tubules – diffuses into interstitial space
adds to concentration gradient in medulla
site of regulation of body pH
secretes or reabsorbs H+ and bicarbonate as needed
Water Reabsorption
obligatory reabsorption – 85% of water reabsorption
occurs in PCT and loop of Henle
water always follows reabsorbed solutes by osmosis
facultative reabsorption – remaining 15% of water reabsorption
occurs in DCT and collecting duct
variable amounts of water reabsorbed depending on number of
aquaporin channels present
facultative reabsorption is regulated by ADH
no ADH = no aquaporins = no water reabsorbed
more ADH = more aquaporins = more water reabsorption
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Summary of Hormones Regulating Renal Function
1)RAA Pathway – initiated by factors that reduce GFR
increases blood volume
increases blood pressure
increases GFR, but mildly decreases urine production
also increases K+ secretion
2) Antidiuretic Hormone (ADH)
released due to increased blood osmolarity and RAA pathway
increases water reabsorption
decreases urine production
diabetes insipidus – hyposecretion of ADH
up to 20 liters of urine/day
3) Natriuretic Peptides (ANP, BNP)
secreted due to increased stretch of heart (high preload)
decreases Na+and water reabsorption
suppresses aldosterone and ADH secretion
decreases GFR and increases urine production
PRODUCTION OF DILUTE OR CONCENTRATED URINE
kidneys maintain body fluid volume and osmolarity
regulated mainly by ADH
increased water intake – increases blood volume and decreases osmolarity
less ADH is secreted = fewer aquaporins in DCT and collecting duct
solutes are reabsorbed in renal tubule
water cannot follow due to lack of aquaporins
large volume of dilute urine produced
dehydration – decreases blood volume and increases osmolarity
more ADH secreted = more aquaporins in DCT and collecting duct
water reabsorbed by osmosis
high solute concentration gradient in medulla
Na+ and Cl- pumped out in ascending loop of Henle
urea diffusing out of distal collecting duct
large volumes of water can be reabsorbed if enough aquaporins
are present
small volume of concentrated urine produced
diuretics – drugs that inhibit reabsorption of water in kidneys = more urine
diuresis – production of large volumes of urine
used to treat hypertension (high BP) and edema
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URINE STORAGE AND ELIMINATION
Ureters – carry urine from kidneys to urinary bladder
12 inches long, 1-10mm wide
retroperitoneal; enter bladder posteriorly
physiological sphincter – pressure in bladder blocks backflow
Histology of Ureters
mucosa – very elastic; secretes mucus to protect epithelium from
wastes in urine
transitional epithelium – changes appearance
round and many layers when empty
flat and few layers when stretched
lamina propria – areolar CT; many elastic fibers
muscularis – smooth muscle
longitudinal and circular layers
peristalsis aids flow of urine down ureters
adventitia
areolar CT + blood & lymph vessels and nerves
Urinary Bladder – stores urine
trigone – smooth, triangular area in floor of urinary bladder
2 ureteral openings – posterior wall
internal urethral orifice (neck) – opening to urethra
internal urethral sphincter – smooth muscle, involuntary
rugae (folds) in lining of empty bladder
Histology of Urinary Bladder
mucosa
transitional epithelium
lamina propria
muscularis – detrusor muscle
3 layers of smooth muscle:
inner and outer longitudinal layers
middle circular layer
serosa – visceral peritoneum lining superior surface
adventitia – surrounds other surfaces
Urethra – carries urine from bladder to exterior
Female Urethra – 4cm long; posterior to pubic symphysis
external urethral orifice – anterior to vagina
Histology
mucosa
transitional epithelium near bladder
stratified squamous at external orifice
9
muscularis – circular smooth muscle
external urethral sphincter – skeletal muscle
surrounds urethra at pelvic outlet
voluntary control over urination
Male Urethra – also carries reproductive secretions
3 regions:
1) prostatic urethra – passes through prostate gland
mucosa – changes from transitional to stratified columnar
muscularis – circular smooth muscle
2) membranous urethra – passes through urogenital diaphragm
(muscles and connective tissue across pelvic outlet)
mucosa – stratified columnar e.
external urethral sphincter – skeletal muscle
3) spongy urethra – passes through penis
mucosa – stratified columnar e. for most of length
stratified squamous e. near external urethral orofice
MICTURITION REFLEX – autonomic reflex
micturition – urination
stretch receptors in wall of bladder
Micturition Center – S2-S3 spinal cord segments (spinal reflex)
parasympathetic motor fibers to smooth muscles
contraction of detrusor muscle (bladder wall)
cerebral cortex perceives fullness – has voluntary control
contraction of skeletal muscles in external urethral sphincter and
pelvic floor can prevent urination
relaxation of external urethral sphincter also relaxes internal sphincter
urinary incontinence – lack of voluntary control over urination
CLINICAL EVALUATION OF RENAL FUNCTION
Composition of Urine
95% water
5 % solutes – ions, urea, creatinine, uric acid, ammonia,
pigments, enzymes, hormones, drugs
URINALYSIS – examining urine
Volume
normal 1-2 liters/day
Color
normal – yellow-amber
urobilin from breakdown of hemoglobin
pale – dilute urine
dark – concentrated urine
Turbidity
normal – transparent when fresh
becomes turbid (cloudy) as it sits
10
Odor
normal - mild ammonia
pH
normal – 4.5-8 (average 6)
protein diet – more acidic
vegetarian diet – more alkaline
Specific Gravity (density compared to water) – indicates solute
concentration
(specific gravity of water = 1.0)
normal – 1.001-1.035
increases when solutes are high
Test Strips
albuminuria (albumin) – glomerular damage, high BP
glucosuria (glucose) – diabetes mellitus
hemoglobinuria (hemoglobin) – destruction of RBCs
ketonuria (ketones) – diabetes, fasting
bilirubinuria (bilirubin) – liver disease
Microscopic Examination
hematuria (RBCs) – inflammation, kidney stones, trauma
pyuria (WBCs) – infection
casts – clumps of material (cells)
crystals
microbes – infection
RENAL FUNCTION TESTS – blood tests
blood urea nitrogen (BUN)
rises when GFR is low (renal disease, urinary obstructiion)
plasma creatinine
rises when GFR is low
creatinine clearance test
all creatinine is normally excreted in urine
creatinine excreted / minute
= GFR
plasma concentration of creatinine
Dialysis – artificial cleansing of blood through a semipermeable membrane
hemodialysis – blood flows through a dialysis membrane
wastes diffuse into surrounding dialysis solution
solutes removed from blood depend on permeability of dialysis membrane
and concentrations of solutes in dialysis solution
continuous ambulatory peritoneal dialysis
peritoneum is the dialysis membrane
peritoneal cavity is filled with dialysis solution
solution is drained following exchange
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