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EXCRETORY SYSTEM
Kidneys: Main excretory organ that remove nitrogenous wastes
(urine) from blood.They regulate the amount of water, salts &
other substances in the blood.
Renal hilum-opening to kidney; Renal sinus- space within
hilus where kidneys receive blood vessels and nerves.
Each kidney is composed of 3 sections:
Renal cortex: outer region of kidney where blood is filtered.
Renal medulla: inner region of kidney that contains the
collecting ducts which carry filtrate to the pelvis. Medulla is
divided into multiple cone-shaped masses of tissue called renal
pyramids.
Renal pelvis: a hollow funnel-shaped inner cavity where
urine accumulates and drains into the ureter. Contains renal
artery and renal vein.
Ureters: Paired muscular tubes that conduct urine from the
renal pelvis of the kidneys to the posterior wall of the urinary
bladder.
Urinary bladder: Temporarily stores urine until released
from body. Average bladder volume is 500 ml, max capacity
700-800 ml.
Urethra: Tube that carries urine from the urinary bladder to
the outside of the body.
Functions of Kidneys
Regulate blood volume and pressure by eliminating or conserving water as necessary.
Regulate osmolarity of body fluids by controlling relative amounts of water & solutes eliminated.
Function with the lungs to regulate the PCO2 and acid-base balance of the body fluids.
Secretion of hormones:
a. Erythropoietin, which controls erythrocyte production & oxygen-carrying capacity of blood.
b. Renin, which activates hormonal mechanisms that control blood pressure & electrolyte balance.
c. 1,25-dihydroxyvitamin D3 (calcitriol), which influences calcium homeostasis
Filter blood plasma, separate wastes from useful chemicals, and eliminate the wastes while
returning the rest to the bloodstream.
Detoxify free radicals and drugs with the use of peroxisomes.
In times of starvation, they carry out gluconeogenesis..
Nephrons come in 2 forms
Main difference in two types of nephron is the length to
which the loop of Henle extends into the kidney.
Cortical nephron
Cortical Nephrons: About 80% of nephrons in humans,
most numerous; Originate in outer cortex; With relatively
short loops of Henle & collecting tubules. Responsible for
most of the function of the kidneys.
Juxtamedullary Nephrons: Originate close to corticomedullary junction. Have very long loops of Henle &
collecting tubules, extending almost down to renal pelvis
ie loop of Henle extends past the cortex & into the
medulla of the kidney. Responsible for production of
concentrated urine.
Renal
cortex
Juxtamedullary
nephron
Renal
medulla
Collecting
duct
1.KIDNEY CORPUSCLE or RENAL CORPUSCLE
Each renal corpuscle consists of an epithelial cup called Bowman's capsule enclosing
glomerulus. Each renal corpuscle has 2 "poles" at opposite ends. (1)Vascular pole: receives the
afferent & efferent arterioles, which serve glomerular capillaries. (2) Urinary pole :location of
proximal tubule, the outflow for glomerular filtrate. Associated with the vascular pole is JGA.
Role of renal corpuscle: Site where the process of urine formation begins. Major function is to
produce an ultrafiltrate ie the filtrate of blood plasma except its proteins.
(A) Bowman's capsule: Outer epithelium that encloses Bowman's
space (urinary or capsular space); with 2 layers: outer parietal & inner
visceral; visceral layer is very closely applied to the loops of capillaries.
Glomerular plasma filtrate collects in the Bowman’s space as it leaves Renal
the capillaries through the filtration membrane.
tubules
(B) Glomerulus: A small knot of capillaries suspended within
Bowman's capsule, having both cellular and extracellular elements.
Role Source of initial filtrate of plasma that is eventually processed
Glomerulus
Glomerular
into urine. Blood pressure forces the liquid portion of blood minus large
capsule
proteins into capsular space. Blood cells & large proteins are not
included in this filtrate.
Cellular elements of glomerulus
(1)Capillary endothelial cells : Line the fenestrated glomerular capillaries. Fenestrations are
too small to allow blood cells through, but plasma can pass freely out of the holes & into the
filtration membrane.
(2) Podocytes: Cover glomerular capillaries, support the filtration membrane without obstructing
flow of filtrate. Each podocyte stands upon branched pedicels, or "foot processes" that rest on
filtration membrane. Between adjacent pedicels are gaps called filtration slits which permit free
passage of fluid filtrate into Bowman's space.
(3)Mesangial cells (lacis cells or cells of
Goormaghtigh): Inconspicuous cells concentrated
toward the vascular pole of glomerulus. Produce the
mesangial matrix & may contribute to maintenance of
the filtration membrane. Occupy the space between
glomerulus & macula densa of the distal tubule.
Extracellular elements that comprise the
glomerulus
(1)Filtration membrane: Sheet of porous material made of
endothelial & podocyte basement membranes. Outside of
filtration membrane is supported by podocytes.As plasma passes
through capillary fenestrations, water, ions & small molecules
pass through the filtration membrane into Bowman's space, while
serum proteins are retained in the capillaries.
(2) Mesangium or mesangial matrix: Extracellular material
that surrounds mesangial cells. Gives some mechanical
support to the glomerular capillaries.
2. KIDNEY or RENAL TUBULE
•Renal tubule receives plasma filtrate from glomerulus & processes it into urine.
Proximal convoluted tubule (PCT): PCT is much more
common than DCT in a typical histological slide.
PCT cells: (i) Apical end with brush border of
microvilli helps to (i) reabsorb large amount of
sodium, water, glucose, amino acids & some other
constituents of tubular fluid & (ii) secrete some
substances into the tubular fluid. (ii) mitochondria
provide energy for pumping ions & molecules
against their concentration gradient.
ROLE: PCT drains filtrate away from a renal corpuscle.
Restores much of the filtrate to blood in peritubular
capillaries, by actively pumping small molecules out of
the tubule lumen into the interstitial space. (Water
then follows the concentration gradient)
Loop of Henle: Descends into medulla, makes a hairpin turn, & returns to cortex. Consists of a
descending limb, with an initial short thick segment followed by a long thin segment & an
ascending limb, with a thin segment followed by a thick segment.
Descending thick segment: structurally similar to PCT. Ascending thick segment:
structurally similar to DCT.
ROLE: Basically, the loop helps to establish a hypertonic saline environment in medulla,
which allows subsequent recovery of water from collecting ducts. The loop actively transports
sodium & potassium ions out of loop & into interstitial fluid. Resulting osmotic gradient results
in movement of water out of loop & into the interstitium where it is absorbed by vasa recta &
returned to the general circulation.
Distal convoluted tubule (DCT):
Starts at the point where the thick ascending limb ends & passes near to the original corpuscle
(at JGA) & then leads to a collecting duct.
Part of DCT passing between afferent & efferent arteriole is called macula densa (macula
densa = "dense spot“,clustering of epithelial nuclei in wall of DCT) which is part of JGA.
DCT cells: (i) Apical end without a brush border, few scattered microvilli (ii) Mitochondria to
provide energy for pumping ions & molecules against their concentration gradient; fewer
mitochondria. Plasma membranes of adjacent DCT cells extensively interdigitated (like PCT)
that increases basal membrane surface area for pumping molecules .
ROLE: DCT actively secretes ions to be removed via urine & further absorbs water & some
ions. Returns useful materials from filtrate to blood in peritubular capillaries, like PCT by
actively pumping small molecules out of the tubule lumen into interstitial space.
Juxtaglomerular complex (JGA)
JGA is a complex of structures associated with the vascular pole of each renal corpuscle.
JGA has following principal components:
Juxtaglomerular cells ("J-G cells") :Found in the wall of the afferent arteriole are specialized
smooth muscle cells containing secretory granules. Source of hormone renin.
Macula densa :Patch of densely-packed large columnar epithelial cell nuclei along DCT, adjacent
to the afferent arteriole at the vascular pole of the corpuscle from which the tubule arose. May
function as a sensor for sodium and/or chloride concentration.
Extra-glomerular mesangial cells:Juxtaglomerular region also includes extra-glomerular
mesangial cells, called lacis cells or cells of Goormaghtigh, between the two arterioles. The
fluid absorbed by macula densa cells bathe the lacis cells.
ROLE: JGA is thought to participate in the regulation of blood flow through glomerular capillaries
(& hence rate of urine formation). JGA monitors electrolyte concentration and secretes the
hormones renin and erythropoietin.
Collecting duct: Receives fluid from several
distal tubules, then passes through the
medulla and drains into the pelvis; so
named because they "collect" the urine
from distal tubules. Collecting ducts merge
& become larger as they descend through
the medulla, so different sizes of collecting
ducts may be observed at different levels in
the kidney, with the smallest in the cortex
and the largest near the pelvis.
Best way to identify collecting ducts is by
the presence of prominent lateral borders in
between adjacent cells. These well-defined
lateral borders are not found in any other
tubule segment in the kidney.
ROLE: Collecting duct epithelium has
unusual physiological property of adjustable
permeability to water (under control of
pituitary ADH). If permeability to water is
high, then water diffuses across the
collecting duct epithelium into the
hypertonic interstitium of the medulla,
resulting in a concentration of urine within
the duct. But if water permeability is low,
then water is retained in the urine and
excreted from the body.
RENAL VASCULATURE
Kidneys are supplied by renal arteries &
drained by renal veins. Renal artery brings
blood, wastes & nutrients into kidneys for
waste disposal. Renal veins connect the
kidney to inferior vena cava & carry the blood
purified by the kidney.
Peritubular
capillaries
envelope
convoluted tubules of cortex & return blood
to the interlobular veins. Vasa recta
("straight vessels"): Thin vessels (larger
than capillaries) which carry blood into & out
of medulla. Vasa recta return blood to
arcuate veins.
Urinalysis
HORMONAL CONTROL OF KIDNEY FUNCTION
Renal endocrine regulation of erythropoiesis occurs by secretion of erythropoietin in response
to hypoxia & O2 tension in afferent arteriole.
Norepinephrine & Epinephrine: constrict afferent and efferent arterioles, causing reductions
in GFR and renal blood flow.
Hormones control urine concentration: Aldosterone –produced by adrenal cortex,
reabsorbs sodium ions and water but loses potassium ions. It works at DCT. ADH-released by
posterior pituitary gland; increases water permeability in DCT & collecting duct; water absorbed
Atrial Natriuretic Peptide is released by cardiac atrial cells in response to atrial stretch due to
increased circulating blood volume. ANP opposes the actions of aldosterone. Actions of ANP
include inhibition of sodium channels & sodium pump in inner medullary collecting duct cells,
inhibition of aldosterone release by adrenal cortex, inhibition of renin release (which will ultimately
reduce aldosterone release) & increase in GFR. All these actions will contribute to an increased loss
of sodium in the urine.
Hormonal Control of Kidney Function
reduced blood pressure and glomerular
filtrate
JGA
angiotensinogen
renin
angiotensin I
angiotensin II
Angiotensinconverting
enzyme
adrenal cortex
aldosterone
convoluted tubules
FORMATION OF URINE
(1) Glomerular filtration or ultrafiltration of plasma to form an
ultrafiltrate in the lumen of the Bowman's capsule.
(2) Tubular reabsorption of approximately 99% of the water &
most of the salts from the ultrafiltrate leaving behind &
concentrating waste products such as urea.
(3) Tubular secretion of a number of substances via active
transport in nearly all instances.
Final product is a hypertonic urine, whose composition
differs from that of blood.
Step1: GLOMERULAR FILTRATION
Blood pressure forces plasma through capillary walls in glomerulus to remove impurities. The
main force that moves substances by filtration through glomerular capillary wall is hydrostatic
pressure of the blood inside. GFR is about 180 L/day.
Glomerular filtrate: Fluid that filters through glomerulus into Bowman’s capsule & contains
essentially all constituents of blood except for blood cells & nearly all blood proteins. Also
calcium & fatty acids are not freely filtered as they are bound to plasma proteins.
Step 2: TUBULAR REABSORPTION
As filtration is non-selective, it is important that small molecules essential to the body be returned
to blood fluid. Substances move from renal tubules into interstitial fluid where they then diffuse
into peritubular capillaries.
Tubular Reabsorption Is Selective & Quantitatively Large:
Some substances like glucose & amino acids are almost completely reabsorbed from the
tubules. Many of the ions in plasma, like sodium, chloride & bicarbonate are also highly
reabsorbed, but their rates of reabsorption & urinary excretion are variable, depending on
body need. Certain waste products like urea & creatinine are poorly reabsorbed from the
tubules & excreted in relatively large amounts.
Tubular Reabsorption Includes Passive and Active Mechanisms:
Transport that is coupled directly to ATP is termed primary active transport. Eg: sodiumpotassium ATPase pump that functions throughout most parts of the renal tubule.
Passive water reabsorption by osmosis is coupled mainly to sodium reabsorption.
Reabsorption of chloride, urea & other solutes occurs by passive diffusion.
(A) Proximal Convoluted Tubules: Proximal tubules have a high capacity for active &
passive reabsorption (70%).
In the first half of the proximal tubule, sodium is reabsorbed by co-transport along with
glucose, amino acids, and other solutes. In the second half of the proximal tubule, little
glucose and amino acids remain to be reabsorbed. Instead, sodium is now reabsorbed
mainly with chloride ions.
Reabsorption of creatine, lactic, citric, uric & ascorbic acids, phosphates, sulfate,
calcium,potassium by active transport.
Reabsorption of water by osmosis.
(B) Loop of Henle: Consists of 3 functionally distinct segments: thin descending, thin ascending
& thick ascending segment.
Thin descending limb: Highly permeable to water & moderately permeable to most solutes,
including urea & sodium. About 20% of filtered water is reabsorbed in the loop of Henle, and
almost all of this occurs in the thin descending limb.
Ascending limb (both thin & thick portions) is virtually impermeable to water:
Thick ascending limb: Most of water delivered to this segment remains in the tubule. Capable
of active reabsorption of sodium, chloride & potassium + calcium, bicarbonate, magnesium. An
important component of solute reabsorption in thick ascending limb is Na-K-ATPase pump.
Thin ascending limb: With much lower reabsorptive capacity & does not reabsorb significant
amounts of any of these solutes.
(C) Distal Convoluted Tubule: Very first portion of DCT forms part of JG complex. Reabsorbs
most ions, including sodium, potassium & chloride, but is virtually impermeable to water and urea.
Hence it is referred to as the diluting segment as it also dilutes the tubular fluid.
(D) Late Distal Tubule and Cortical Collecting Tubule: Second half of distal tubule &
subsequent cortical collecting tubule have similar functional characteristics. Principal cells
reabsorb sodium & water from the lumen while the intercalated cells reabsorb potassium ions.
Almost completely impermeable to urea, similar to diluting segment of early distal tubule. So
almost all urea that enters these segments passes on through & into the collecting duct to be
excreted in urine, although some reabsorption of urea occurs in the medullary collecting ducts.
(E) Medullary Collecting Duct: Reabsorb less than 10% of filtered water & sodium, but they are
the final site for processing urine & so play an extremely important role in determining the final
urine output of water & solutes. Permeability of medullary collecting duct to water is controlled by
level of ADH. With high levels of ADH, water is avidly reabsorbed into the medullary interstitium,
thereby reducing the urine volume and concentrating most of the solutes in the urine.
Step 3: TUBULAR SECRETION
Substances move from peritubular capillaries into fluid of
renal tubules.
(A) Proximal Tubules: Counter-transport: active
secretion of H+ coupled to sodium reabsorption in
luminal membrane of PCT.
PCT: important site for secretion of organic acids &
bases like bile salts, oxalate, urate & catecholamines.
Many of these substances are end products of
metabolism & must be rapidly removed from the body.
Active secretion of substances like penicillin, histamine, creatinine. Another compound rapidly
secreted by PCT is para-aminohippuric acid (PAH).
(B) Loop of Henle: Thick ascending limb secretes H+ into tubular lumen.
(C) Late Distal Tubule and Cortical Collecting Tubule: Principal cells secrete potassium ions
into lumen while intercalated cells actively secrete H+ ions into the tubular lumen. H+ secretion
by intercalated cells is mediated by a hydrogen-ATPase transport mechanism. Thus, intercalated
cells play a key role in acid-base regulation of the body fluids.
(D) Medullary Collecting Duct: Secreting H+ ions against a large concentration gradient, as also
occurs in the cortical collecting tubule.
Hormonal Control of Kidney Function
reduced blood pressure and glomerular
filtrate
JGA
angiotensinogen
renin
angiotensin I
angiotensin II
Angiotensinconverting
enzyme
adrenal cortex
aldosterone
convoluted tubules
COUNTERCURRENT MECHANISM-How
does body conserve water & excrete a
hyperosmotic urine? The ability of the
collecting ducts to concentrate urine depends
on salinity gradient of the renal medulla.
I. COUNTERCURRENT MULTIPLIER:
Loop of Henle as Countercurrent
Multiplier:
Fluid entering the loop from PCT flows
down the descending limb & then flows up
the ascending limb. The opposing flows in
two limbs is termed a countercurrent flow,
the entire loop functions as a countercurrent
multiplier system to create a hyperosmotic
medullary interstitial fluid (osmolarity of
~1400).
Called multiplier as it multiplies salinity
deep in medulla. Nephron loop continually
recaptures salt & returns it to the deep
medullary tissue. Mechanism works in
Henle’s loop to increase water reabsorbed
from descending limb (high water
permeability) due to salt reabsorbed from
ascending limb (impermeable to water). This
magnifies effect of transport from one limb
on transport from other limb.
1. Thin segment of descending limb is very permeable to water but not to NaCl. So, as tubular
fluid descends into the increasingly salty medulla, more & more water leaves the descending limb
while NaCl remains in the tubule. As the fluid reaches the lower end of loop, it has a concentration
of ~1,200 mOsm/L. Thus water moves across the tubular wall into the medullary space, making
the urine hypertonic.
2. Most or all of ascending limb (its thick segment) is impermeable to water, but actively
transports Na+, K+ & Cl- into ECF of medullary space, making the filtrate hypotonic. This keeps
osmolarity of renal medulla high. Since water remains in the tubule, the tubular fluid becomes
more & more dilute as it approaches the cortex. It is ~100 mOsm/L at the top of the loop.
Essence of countercurrent
mechanism is that the two limbs
of the nephron loop are close
enough to influence each other
through a positive feedback
relationship.
Collecting duct also helps to
maintain the osmotic gradient.
Urea accounts for about 40% of
high osmolarity deep in medulla.
II. VASA RECTA -COUNTERCURRENT EXCHANGER
OF SALT:
Vasa recta serve as countercurrent exchangers,
minimizing washout of solutes from the
medullary interstitium. Vasa recta has
descending & ascending limbs too.
Blood flowing into medulla in descending limb
picks up salt from the hypertonic medulla. As
the surrounding medullary fluid becomes more
& more salty toward the papilla, the gradient
increases & more & more salt is picked up by
the descending vasa recta limb. But as the
blood heads back up to the cortex in the
ascending limb of vasa recta, the interstitial
fluid becomes less & less salty. This causes the
gradient to reverse & salt diffuses back out of
the vasa recta into the medulla. This helps to
conserve salt & keep medulla hypertonic.
Vasa recta give the salt back & do not subtract
from the osmolarity of the medulla. Vasa recta
are arranged as a countercurrent exchange
system that enables them to supply blood to the
medulla without subtracting from its salinity
gradient.
Ureter: Transports urine from renal pelvis to the bladder in the pelvic cavity
Urinary Bladder: Urine leaves urinary bladder by micturition or urination reflex
•Trigone: triangular area between openings of ureters & urethra. Muscular layer of trigone forms
mechanisms for closing & opening ureteral orifices & for internal urethral orifice at the bladder
neck.
• Bladder muscle (detrusor) lined internally by mucosa (transitional epithelium with a surface
differentiated to protect against the urine).
•If full: bladder is spherical & extends into abdominal cavity.If empty: bladder lies entirely within
pelvis like upside-down pyramid.
Urethra: Tube that conveys urine from urinary bladder to outside. Wall lined with a mucous
membrane. In male with 3 sections: Prostatic, Membranous & Penile urethra.
•Two urethral sphincters regulate urine flow into the urethra- (i) internal urethral sphincter:
involuntary smooth muscle; relaxes when fullness is experienced. (ii) external urethral sphincter:
voluntary striated muscle; relaxes with voluntary stimuli from the cerebral cortex.
Urinary
bladder
Ureter
Openings of
ureters
Ureter
Detrusor
muscle
Trigone
Prostate gland
Internal urethral sphincter
Urethra
Region of external urethral
sphincter
Urethra
Micturition (Urination) reflex
Urinary bladder distends as it fills with urine (200 ml). Stretch receptors in bladder wall are
stimulated, which triggers the micturition reflex.
Sensory impulses from the stretch receptors signal the micturition reflex center located in
the sacral portion of the spinal cord.
Parasympathetic nerve impulses travel out to the detrusor muscle, which contracts
rhythmically in response. The need to urinate is urgent.
Voluntary contraction of external urethral sphincter & inhibition of the micturition
reflex by impulses from brainstem & the cerebral cortex prevents urination.
Following decision to urinate, the external urethral sphincter is relaxed & impulses
from pons & hypothalamus facilitate micturition reflex.
Detrusor muscle contracts & urine is expelled through urethra. That part of the detrusor
muscle at the base of the bladder where the urethra begins functions as a sphincter called
the internal urethral sphincter.
Neurons of micturition reflex center get fatigued, detrusor muscle relaxes & the bladder
begins to fill with urine again.
UTI (Urinary Tract Infection): If
the bladder has become
infectedcystitis. If the urethra is
infectedurethritis.
GlycosuriaPresence of glucose in
urine
Polyuriaexcessive or abnormally
large production of urine (at least 2.5 or
3 L over 24 hours in adults).
Oligourialow output of urine,
clinically classified as an output below
300-500ml/day.
Anuria nonpassage of urine,
passage of <50 ml of urine in a day.
Dysuria painful urination.
Proteinuria (albuminuria)Presence of
protein (especially albumin) in
urine.Hematuria Presence of blood in
urine.
Kidney InfectionsResult when an infection reaches kidneys & is called pyelonephritis.
Kidney Stones (renal calculi)Form when chemicals in urine precipitate out & form crystals
(hard granule of calcium, phosphate, uric acid and protein).They form in renal pelvis & get lodged
in pelvis or ureter; caused by UTI, dehydration, pH imbalances, or an enlarged prostate gland.