Module 17 - Urinary System
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Transcript of Module 17 - Urinary System
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MODULE 17: ROMANCING THE PAIN
1. Enumerate the parts of the urinary system. Describe thegross and microscopic appearance of each part.
Gross Anatomy of the urinary system
Kidneys- retroperitoneal organs/ against posterior abdominal wall- right kidney slightly lower than left due to large size of right lobe of liver- upper pole of right rest on 12 th rib- left kidney rests on 11th & 12th ribs- each gives rise to a ureter w/c runs vertically down to psoas muscle- on medial concave border is a vertical slit bounded by thick lips of renal
substance called the hilumHilum
- extends into a the Renal Sinus- passed by lymph vessels & sympathetic fibers- transmits from front backward the:
renal vein2 branches of renal artery
Ureter
3rd branch of renal arteryRenal Pelvis- renal pelvis divides into 2 or 3 major calyces- minor calyces arise from the major calyces- funnel-shaped expanded upper end of ureter- each minor calyx is indented by the apex of renal pyramid the renal
papillaRenal Papilla - indented by the apex of renal pyramid2 zones are identifiable in longitudinal section:
-cortex - outer zone
- extends into the medulla between adjacent pyramids as therenal papilla
- medulla - inner zone- composed of about a dozen of renal pyramids w/ base oriented
to cortex & its apex, renal papillae, medially- Medullary Rays - striations extending from base of pyramids into
cortex- Coverings:
1. Fibrous capsule- surrounds kidney
2. Peritoneal fat
-covers fibrous capsule
3. Renal fascia- condensation of CT- outside perirenal fat- encloses the kidneys & suprarenal glands- continuous laterally with fascia transversalis
4. Pararenal fat- external to renal fascia- often in large quantity- forms part of retroperitoneal fat
Peritoneal fat, Renal fascia & Pararenal fat- support kidneys & hold them in position on posterior abdominal
wallBlood Supply
ArteriesAorta
Renal Artery
5 Segmental Arteries
- enters each hilum- 4 in front& 1 behindrenal pelvis
Lobar Arteries
- arise from each segmental arteryone for each renal pyramid
3 Interlobar Arteries
- run toward the cortex on each side of renal pyramid
Arcuate Arteries-junction of cortex & medulla- arch over bases of pyramid
Several Interlobar Arteries
-Ascend in the cortex
Afferent Glomerular Arterioles- each intracts with glomerular portion of nephron &
breaks into capillary network
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Glomerulus
Efferent Glomerular Arterioles
Peritubular Capillaries (surrounds tubules)
- reunite to form venous channels through whichblood ultimately leaves the kidney
Veins
Left and Right Renal Vein- emerges from hilum in front of renal artery
Inferior Vena Cava
Lymph Drainage- lateral aortic lymph nodes around the origin of renal artery
Nerve Supply- Renal sympathetic plexus
-Afferent fibers that travel through the renal plexus enter the spinal cordin the 10th, 11th & 12 thoracic nerves.
Relations of the Right KidneyAnteriorly:
- Suprarenal gland- Liver- 2nd part of the duodenum- Right colic flexure
Posteriorly:- Diaphragm- Costodiaphragmatic recess of the pleura- 12th rib
-Psoas
- Quadratus lumborum- Transverses abdominis muscles- Subcostal (T12), iliohypogastric and
ilioinguinal nerves (L1) run downward and laterally
Relations of the Left KidneyAnteriorly:
- Suprarenal gland- Spleen- Stomach- Pancreas
-Left colic flexure
- Coils of jejunumPosteriorly:
- Diaphragm- Costodiaphragmatic recess of the pleura- 11th and 12th ribs
-Psoas
- Quadratus lumborum- Transverses abdominis muscles- Subcostal (T12), iliohypogastric and
ilioinguinal nerves (L1) run downward and laterally
Ureters- muscular tubes- extend from kidneys to posterior surface of urinary bladder- 10 in [25 cm] long- resembles esophagus in having 3 CONSTRICTIONSalong its course:
where renal pelvis joins the ureter
where it is kinked as it crosses the pelvic brim
where it pierces the bladder wall
Male Ureter
Cross bifurcation ofcommon iliac artery in front of sacroiliac joint
Pelvis
Lateral wall of pelvis in front of internal iliac artery
Region of ischial spine
Lateral angle of bladder- near termination, crossed by vas deferens- ureter passes obliquely through wall of bladder for about
0 .75 in [1.9 cm] nefore enteriong into bladder
Female Ureter
Crosses over the pelvic inet in front of the bifuration of the commoniliac artery
down & back in front of internal iliac artery & behind ovary
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Reaches the region of the iliac spine
Turns forward & medially beneath the base of the broad ligament, whereit is crossed by the uterine artery
Runs forward, lateral to the lateralfornix of the vagina
Bladder
Relations of Ureter
Right UreterAnteriorly:- duodenum- terminal part of ileum- right colic & ileocolic vessels- right testicular or ovarian vessels- root of the mesentery of the small intestine
Posteriorly:- right psoas muscle (separates ureter form lumbar
transverse processes)- bifurcation of right common iliac artery
Left UreterAnteriorly:- sigmoid colon- left colic vessels- sigmoid mesocoon- left testicular or ovarian vessels
Posterior:- left psoas mucle (separates ureter from lumbar transverse
proceses)- bifurcation of left common iliac artery
Blood Supply:
Artery:Upper end Renal artery
- Middle portion Testicular or Ovarian artery
- Pelvis Superior Vesical artery
Veins:- Upper end Renal vein
- Middle portion Testicular or Ovarian vein
-Pelvis Superior Vesical vein
Lymph Drainage:- lateral aortic nodes- iliac nodes
Nerve Supply:
-renal
- testicular or ovarian
- hypogastric plexuses in the pelvis- Afferent fibers travel with sympathetic nerves & enter spinal cord
in 1st & 2nd lumbar segments
Urinary Bladder- behind pubic bones within pelvis- receptacle for storage of urine- In adult: maximum capacity of about 500 mL- strong muscular wall- Its shape and relations vary according to amount of urine
-Empty bladder in adults lies entirely within pelvis
- as the bladder fills, superior wall rises up into hypogastric region- In young child, empty bladder projects above pelvic inlet- later when the pelvic cavity enlarges, the bladder sinks into the pelvis
to take up adult position- Empty bladder is pyramidal with the ff:
having an apex, base & neck
1 superiorand 2 inferolateral surfaces
Male Urinary BladderApex
- points anteriorly
-behind upper margin of symphysis pubis
- connected to umbilicus by MEDIAN UMBILICAL LIGAMENT [remainsof urachus]
Base / Posterior Surface- faces posteriorly & triangular- superolateral angles joined by ureters- inferior angle gives rise to urethra- 2 vasa deferentia lie side by side on posterior surface of bladder &
separate seminal vesicles from each other- upper part covered by peritoneum, w/c forms anterior wall of
rectovesical pouch- lower part is separated from rectum by vasa deferentia, seminal
vesicles,
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- peritoneum is reflected onto lateral pelvic wallsSuperior Surface
- covered with peritoneum- related to coils of ileum or sigmoid colon- along lateral margins of this surface, peritoneum is eflected onto lateral
pelvic wallsInferolateral Surface- related in front to retropubic pad of fat and pubic bones- more posteriorly, they lie in contact with the obturator internus muscle
above & the levator ani muscle belowNeck- lies inferiorly & rests on upper surface of prostate- here, smooth muscle fibers of bladder wall are continuous with those of
prostate- held in positionby the: thickenings of the pelvic fascia
PUBOPROSTATIC LIGAMENTS in the male
PUBOVSICAL LIGAMENTS in the female
Trigone- the area of mucous membrane- covers internal surface of base of the bladder- here, mucous membrane is always smooth, even when viscus is empty- mucuos mebrane over the trigone is firmly adherent to underlying
muscular coat- SUPERIOR ANGLEScorrespond to openings of ureters- INFERIOR ANGLEto internal urethral orifice- limited above by a muscular ridge (runs from the opening of one
ureter to that of the other & is known as the INTERURETERIC RIDGE)- UVULA VESICAE is a small elevation behind urethral orifice, produced
by underlying median lobe of prostate
Muscular Coat of the Bladder- composed of smooth muscle & is arranged as 3 layers of interlacing
bundles known as the DETRUSOR MUSCLE- at the neck of bladder, the circular component of the muscle coat is
thickened to form the SPHINCTER VESICAEFemale Urinary Bladder- due to absence of prostate,- lies at a lower level than in male pelvis- neck rests directly on upper surface of urogential diaphragm
Apex lies behind the symphysis pubis
Base separated by the vagina from the rectumSuperior surface
-related to uterovesical pouch of peritoneum & to body of uterus
Inferolateral surface- related in front of retropubic pad of fat & pubic- most posteriorly, lie in contact with obturator internus muscle
above & levator ani muscle below
Neck -rest on upper surface of urogenital diaphragmBlood Supply
Arteries- superior & inferior vesical arteries- branches of the internal iliac arteries
Veins- form VESICAL VENOUS PLEXUS, w/c communicates below with
prostatic plexus- drained into internal iliac vein
Lymph Drainage- drain into internal & external iliac nodes
Nerve Supply
-Inferior Hypogastric Plexus
Sympathetic postganglionic fibers- originate in the 1st & 2nd lumbar ganglia & descend to the bladder via
the hypogastric plexuses
Parasypathetic preganglionic fibers- arise as the pelvic splanchnic nerves from the 2nd, 3rd, & 4th sacral
nerves
UrethraMale Urethra
- about 8 in [20 cm] long- extends from the neck of the bladder to the external meatus of the
glans penis3 parts: 1)Prostatic, 2) Membranous, 3) Penile
Prostatic Urethra- about 1 in [3 cm] long- begins at the neck of the bladder- passes through the prostate from base to apex, where it becomes
continuous w/ membranous part of urethra- wider & most dilatable portion of entire urethraurethral crest - longitudinal ridge on post. wallprostatic sinus - groove on each side of urethral crest
- where the prostate glands openprosatic utricle - depression on summit of urethral crest
- analog of uterus & vagina in femalesOpenings of 2 ejaculatory ducts
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- on ridge of mouth of utricle
Membranous Urethra (about in [1.25 cm])- lies within urogenital diaphragm surrounded by sphincter
urethrae muscle- least dilatabe portion of urethra
Penile Urethra (about 6 in [15.75 cm])- enclosed in bulb & corpus spongiosum of penisexternal meatus - the narrowest part of urethrafossa terminalis - lies within the glans penisbulbourethral glands - open into penile urethra below
urogenital diaphragmFemale Urethra- 1 in [3.8 cm],prone to UTIdue to shortness/nearness to vagina- extends from neck of bladder to externak meatus, where it opens into
vestibule about 1 in below clitoris- traverses sphincter urethrae- lies immediately in front of vagina
-openings ofducts of parauretral glands
sides of external urethral meatus- dilated relativley easy
Microscopic Appearanceof the urinary system
Kidneys
- Divisions:
OuterCortex
InnerMedulla- Consists of 10-18 conical or pyramidal structures/medullary pyramids- From base of each medullary pyramid, parallel arrays of tubules called
medullary rays penetrate cortex- Each kidney is composed of 1-4 million nephrons
Each nephron consists of:
- dilated portion renal corpuscle- proximal convoluted tubule- thin & thick limbs of Henles loop- distal convoluted tubule- collecting tubules & ducts
The nephron is the functional unit of the kidneyRenal Corpuscle ( IN CORTEX)
- Consists of a tuft of capillaries called the glomerulus- glomerular (Bowmans) capsule
double-walled epithelial capsule surrounding glomerulus
- 2 layers:Internal (visceral layer)- envelopes capillaries of glomerulus- cells are called podocytes & have a cell body from which arise
several primary processes
Each primary process gives rise to numerous secondaryprocesses called pedicels, that embrace capillaries of theglomerulus
At adistance of 25 nm, secondary processes are in directcontact with basal lamina & interdigitate, defining elongatedspaces about 25 nm wide called the filtration slits
The cell bodies of podocytes and their primary process do nottouch basement membrane
External (parietal) layer- outer limit of renal corpuscle- simple squamous epithelium supported by basal lamina and a
thin layer of reticular fibers
Urinary space- between two layers w/c receives fluid filtered through capillary
wall & visceral layer- each has 2 poles:
Vascular pole where afferent arteriole enters &efferentarteriole leaves
Urinary pole proximal convoluted tubule begins- epithelium changes to a simple cuboidal or low columnar
(epithelium characteristic of proximal tubulePodocytes
- have bundles of actin microfilaments in their cytoplasm that givethem a contractile capacity
Pedicels - secondary processes of podocytes which are incontact with basal lamina
- interdigitate to form filtration slits
Basement membrane- fusion of capillary- podocyte produced basal laminae- between the fenestrated endothelial cells of glomerular capillaries
&podocytes that cover their external surfaces- believed to be the filtration barrier that separates urinary space and
blood in capillaries- Derived from fusion of capillary & podocyte-produced basal lamina
-filtration barrier where:
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lamina densa- as physical filter- network oftype IV collagen and laminin- larger than d= 10 nm do not readily cross- negatively-charged proteins with a molecular mass greater
than that of albumin (69 kDa) pass across sparinglylamina rarae- as charge barrier- composed offibronectin
Note:- Blood flow in the 2 kidneys of an adult amounts to 1.2 to 1.3 L of
blood per minute- This means that all the circulating blood in the kidney passes
through the kidneys every 4-5 minutes- The glomeruli are composed of arterial capillaries in which the
hydrostatic pressure about 45 mmHg is higher than that found inother capillaries
Glomerular filtrate formed in response to:- Hydrostatic pressure in glomeruli- Osmotic/oncotic pressure of plasma colloids- Hydrostatic of fluids in Bowmans capsule- has a chemical composition similar to blood plasma but contains
almost no protein because macromolecules do not readily cross theglomerular filter
- The largest protein molecules that can cross glomerular have amolecular mass of about 70 kDa, and small amounts of plasmaalbumin appear in the filtrate
Endothelial cells of glomerular capillaries- are of fenestrated variety-
but lack thin diaphragm that spans openings of other fenestratedcapillariesMesangial cells
- adhere to glomerular capillaries- contracts and have receptors for angiotensin II; when these receptors
are activated, glomerular flow is reduced
- also have receptors for natriuretic factor increase blood flow- other functions:
structural support to glomerulus
synthesize ECM
endocytose & dispose normal & pathogenic molecules trapped byglomerular basement membrane
produce chemical mediators such as cytokines andprostaglandins
Extraglomerular mesangial cells
In the vascular pole but outside the glomerulus
Form part of juxtaglomerular apparatus
RENAL TUBULESProximal convoluted tubules (IN CORTEX)
- longer than distal- cuboidal or low columnarepithelium- acidophilic cytoplasm due to numerous elongated mitochondria- absorbs all glucose and amino acids and 85% NaCl and H2O,
phosphate and calcium- secrete creatinine, PAH, penicillin
cell apex- abundant w/ microvilli forming brush border
cell base
-abundant with membrane invaginations & lateral interdigitations w/neighboring cells
- mitochondra concentrated here
Henles Loop (IN MEDULLA)- consists ofthick & thin descending & ascending limbs
- thick limbs similar to distal- 60 m, squamous epithelial cells whose nuclei protrude into lumen
- thin limbs 12 m- 1/7 of nephrons are located nearjuxtamedullary nephrons, others
are cortical- Juxtamedullary nephrons ( bent to hairpin loop)
Prime importance in establishing gradient of hypotonicity inmedullary interstitium basis of kidneys ability to producehypertonic urine
Very longHenles loops- short, thick descending limbs- long thin descending and ascending limbs- thick ascending limbs
- cortical nephrons (no order/ gubot kaau)
long segments, 85%
very short thin descending limbs
no ascending limbs- water retention
- descending limb - permeable to water
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- ascending limb - impermeable to waterDistal convoluted tubules (IN CORTEX)
- simple cuboidal epithelium- no brush border- no apical canaliculi-
smaller cells- more nuclei- elaborate basement membrane invaginate- associated mitochondria indicative of ion-transporting fxn- in juxtaglomerular region, cells become columnar & nuclei are closely
packed, most have Golgi complex in basal regions macula densaMacula densa
- sensitive to ioniccontent & H20 volume of tubular fluid- producing signals that promote liberation of rennin in circulation
Collecting Tubules and Ducts (IN MEDULLA)- cuboidal epithelium- become more columnar deep into medulla-
in medulla, are major component of urine concentrating mechanism- epithelium is responsive to arginine, vasopressin (or ADH)
Juxtaglolmerular (JG) Cells- Modified smooth muscle cells of T. media of afferent arteriole, adjacent
to renal corpuscle- Have a cytoplasm full of secretory granules- Secretions play a role in the maintenance of BP- Show characteristic of protein-secreting cells, including
Abundant rough endoplasmic reticulum
Highly developed Golgi complex- Secretory granules of 10-40 nm in diameter- Produce enzyme rennin, which acts on a plasma protein angiotensin
to produce an inactive decapeptide angiotensin I
Juxtaglomerular (JG) Apparatus (IN MEDULLA)- Formed by region of afferent arteriole that contains the JG cells and
macula densa of the distal convoluted tubule- modified smooth muscle cells in tunica media of afferent arteriole
adjacent to renal corpuscle
- cytoplasm is full of secretory granules secretions for maintenance ofBP
- secretes rennin- composed of JG cells + macula densa + extraglomerular mesangial
cells or lacis cells
Renal Insterstitium- The space between uriniferous tubules,blood&lymph vsl.- Occupies a very small volume in cortex but s in medulla- small amount of CT with fibroblasts, some collagen fibers and
(mainly in the medulla) a highly hydrated ground substance rich in
proteoglycan- In the medulla, interstitial cells (secreting cells) are found
Contain cytoplasmic lipid droplets
Implicated in the synthesis of prostaglandins and prostacyclin
Urinary Bladder and Ureter
- transitional epithelium
- lamina propria loose to dense CT surrounded by dense wovensheath of smooth muscle
- muscular layers in calyce, renal pelvis and ureters in helicalarrangement
- muscular layers in bladder in longitudinal arrangement In Tunica
Muscularis:Inner longitudinal
Distal to bladder neckMiddle circular layer
around prostatic urethra & prostatic parenchymaOuter longitudinal layer
end of prostate & external urethral meatus in womenintravesical ureter- only longitudinal muscle fibersurinary passages
-covered externally by adventitial membrane, except upper partof bladder which is covered by a serous peritoneum
Male Urethra
- Consists of 4 parts:
Prostatic,Membranous,Bulbous,Pendulous- Initial part passes through prostate(close 2 bladder) & ducts that
transport secretions of prostate open into prostatic urethraProstatic Urethra
- In dorsal and distal part, there is an elevation called verumontanumthat protrudes into its interior
-A closed tube called the prostatic utricle opens into tip ofverumontanum; tube has no known function
- The ejaculatory ducts open sides of verumontanum- seminal fluid enters proximal urethra through these ducts to be stored
just before ejaculation
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- Lined with transitional epitheliumMembranous Urethra
- Extends for only 1 cm- stratified or pseudostratified columnar epithelium- Surrounding this part of urethra is a sphincter of striated muscle, the
external sphincterof urethra- The voluntary striates sphincteradds further closing pressure to that
exerted by the involuntary urethral sphincter(formed by continuationof internal longitudinal muscle of the bladder)
Bulbous and Pendulous Urethra- Located in corpus spongiosum of penis- The urethral lumen dilates distally, forming fossa navicularis
- The epithelium is mostly pseudostratified and columnar, withstratified& squamous areas
Littres Gland- Mucous glands found along entire length of urethra but mostly in
pendulous part-
secretory portions of some of these glands are directly linked to theepithelial lining of the urethra; others have secretory ducts
Female Urethra
- 4-5 cm long- stratified squamous epithelium and areas of pseudostratified columnar
epithelium- Mid part surrounded by external striated voluntary sphincter
BLADDER AND URINARY PASSAGES- Store urine formed in kidneys& conduct it to exterior- Calyces, renal pelvis, ureter, and bladder have the same basic
histologic structure with the walls of the ureters becoming thicker asproximity to the bladder increases
- Mucosa of these organs consists of transitional epithelium and alamina propria ofloose to dense CT
- Surrounding the lamina propria of these organs is a dense wovensheath of smooth muscle
- The transitional epithelium of the bladder in distended state is 5 or 6cells in thickness; the superficial cells are rounded and bulge intothe lumen
- Cells are frequently polyploidy or binucleate- When epithelium is stretched, epithelium is only 3 or 4 cells in
thickness, and the superficial cells become squamous
- The superficial cells of the transitional epith. have special membraneof thick plates separated by narrow bands of thinner membraneresponsible for osmotic barrier between urine & tissue fluids
- When bladder contracts, the membrane folds along the thinnerregions, and the thicker plates invaginate to form fusiform cytoplasmic
vesicles- The muscle fibers of the bladder run in every direction (without
distinct layers) until they approach the bladder neck, where 3 distinctlayers can be identified:
Internal longitudinal layer- distal to bladder neck- Becomes circular around the prostatic urethra and prostatic
parenchyma in men
Middle layer (middle circular layer)- Ends at the bladder neck
Outer longitudinal layer- Continues to end of prostate in men and to external urethral
meatus in women- Urinary passages are covered externally by adventitial membrane,
except for upper part of bladder, which is covered by serousperitoneum
2. Identify the functions of the kidney.
FUNCTIONS of the kidney
Process the plasma portion of blood by removing substances from it andadding substances to it. Resulting to following functions:
1. Regulation of water and inorganic-ion balance- H20 concentration, inorganic-organic composition, & volume of
internal environment by excreting just enough water& inorganic
ions to keep amounts of substances in body relatively constant.2. Removal of metabolic waste products from the blood and their
excretion in the urine- excrete metabolic waste products into urine as far as they are
produced- These keeps toxic waste products from accumulating- The metabolic wastes include:
urea from the catabolism of protein
uric acid from nucleic acids
creatinine from muscle creatine
end products from hemoglobin breakdown (which give urinemuch of its color)
many others
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3. Removal of foreign chemicals in the blood and their excretion inthe urine.- drugs, pesticides & food additives & metabolites
4. Gluconeogenesis- During prolonged fasting, kidneys synthesize glucose from amino
acids& other acids% release it into blood.- kidneys can supply approx. 20%as much glucose as the liver does
at such times.5. Secretion of hormones ( as endocrine glands)
- synthesize and secrete the following:
Erythropoietin - controls erythocyte production
Renin - controls formation of angiotensin- influences BP and sodium balance- BP regulation
1,25 dihydroxyvitamin D3 - influences calciumbalance
vasopressor renal medullary lipids (Vitamin E)
Maintainance of acid-balance of the bloodmaintenance of Blood Osmolality
- Osmolality = SolutesSolvent
- ex. H20 in blood, osmolality
3. Discuss glomerular filtration, taking into consideration thefollowing:
a. Relationship of structural characteristics of theglomerulus to glomerular filtration
Blood from the afferent arteriole enters the glomerulus located
within the Bowmans capsule
Glomerulus consists of a coil of approximately eight capillarylobds referred to as the capillary tuft
Glomerulus serves as a nonselective filter of plasma substances
with molecular weights of less than 70,000
Factors influence the actual filtration process.
Cellular structure of the capillary walls and BowmanscapsuleHydrostatic and oncotic pressureFeedback mechanisms of the rennin-angiotensin-aldosterone system
Plasma filtrate must pass through three cellular layer
Capillary wall membraneThe endothelial cells of the capillary wallmembrane differ from those in other capillaries bycontaining pores and are referred to asfenestrated. Fenestra 600-1000 Angstroms in
diameter
Basement membrane ( basal lamina)- Homogenous and acellularConsists of glycoprotiens and mucopolysaccharides
Visceral Epithelium of the Bowmans capsule- Capsular epithelial cells are called podocyteswhich posses foot processes called pedicels.Pedicels interdigitate with each other and reducethe diameter of the path through which solutespass to about (240 Angstrom). Pedicels coatedwith a thick layer glycosialprotiens with furtherocclude the pathExtremely thin diaphragm bridge the slits at thesurface of the basement membrane. In order tobe freely filtered a solute must be lesser than 100
Angstroms
Glomerular membranes are freely permeable to water and to
crystalloids but are relatively impermeable to colloids, especiallyplasma proteins. This is sometimes called steric hindrance
Electrical change is also important in the process of movement of
a solute across the glomerular capillary. The cell coats of the
epithelium, the basement membrane, and the cell coats of thepodocytes are polyanions. Negatively charged molecules arerestricted from entering and moving through the filtration barrier.This is called electrical hindrance
Every minute approximately 120mL of water containing low-
molecular weight substances are filtered through the 2 millionglomeruli
Filtration is nonselective
Filtrate has a specific gravity of 1.010
Difference between compositions of filtrate and plasma is
absence of:Plasma protein
Any protein bound substance
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Cellsb. Factors affecting:
i. Glomerular plasma flow rateGlomerular plasma flow rate
Changes in blood pressure lead to changes in glomerularfiltration rate by changing capillary hydrostatic pressure, Howeverbecause of autoregulation, arterial pressure changes have verylittle effect on glomerular filtration rate.Autoregulation is broughtabout by 2 mechanisms:
Myogenic mechanismAn increase in arterial pressure causes stretch of the
smooth muscles of the renal arteries, which respond to thestretch contraction. The renal artery constricts and as a result, thepossibility of increased filtration is minimized
Tubuloglomerular feedback
More popular mechanism, which explains autoregulation of renalblood flow.
Increased blood pressure
Increased renal arterial pressure
Increased glomerular filtration rate
Increased rate of fluid flow to the proximal tubule and loop ofHenle
Increased rate of fluid flow to the macula densa
Stimulation of macula densa cells
Release of adenosine
Adenosine constricts the renal arteries
Adenosine constricts the renal arterioles
Decreased glomerulus filtration rate
ii. Glomerular Ultrafiltration CoefficientAt any given net filtration pressure, glomerular filtration rate isproportional to the glomerular ultrafiltration coefficient ( theproduct of hydraulic water permeability of glomerular membranes
and the surface area available for filtration). Any factor thatdecreases glomerular ultrafiltration coefficient reduces glomerularfiltration rate.
Substances that decreas glomerular ultrafiltration
coefficient
o Angiotensin II
o ADH
o PG E and PG 12
o Acetylcholine
o Bradikinin
o Histamineo Parathyroid hormone
o Papaverine
o High plasma levels of calcium
o Low plasma levels of protein
i ii. Starlings ForcesThe net filtration pressure (NFP) across the glomerular capillariesis the algebraic sum of the forces that induce filtration (hydrostaticpressure in the glomerular capillaries and osmotic pressure in thebowmans capsule), and the forces that oppose filtration(hydrostatic pressure in the Bowmans capsule and the osmoticpressure in the glomerular capillaries).
At the region of the afferent arteriole, the net filtration pressure ishigh, and allows fluid to be filtered into the Bowmans capsule. Atthe region of the efferent arteriole, the net filtration pressure iszero, and fluid is not filtered. Thus, fluid is only filtered at thecapillary near the region of the afferent arteriole.
iv. Podocyte structure
Glomerular filtration rate is measured using a test substance.Such substance must posses the following criteria
o It must be freely filtered at the glomerulus
o It must be reabsorbed at the tubules
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o It must not be secreted by the tubules
o It must not be synthesized by the tubules
o It must not be degraded by the tubules
The substance used inulin meets all the criteria
The amount of inulin secreted per unit time must be equal to the
amount of the substance filtered per unit time. Quantitation of inulin is technically difficult so clinically other
substances are used as substitutes.
Urea is one substituteo Does not fill all the criteria since it is reabsorbed
Creatinine and para-amino hippurate are also usedo However they are both secreted by the tubules
o Descripancy isnt large so they are frequently used
Using inulin the normal GFR (assuming the bodysurface area is 1.73 sq. meters
o Male 125ml/min
o Female 110ml/min
c. Measurement of Glomerular Filtration Rate (GFR)Clearance = Urine w( measured substance concentration) X Volume(24 hour urine)
Plasma w (measured substanceconcentration)
Clearance= UwX V . 1.72m2Pw A
Normal value: 125 ml/min for adult male 110ml/min foradult female
1.73m2 1.73m2
Glomerular Filtration Rate (GFR) is measured using a testsubstances. Such substance must process the following criteria:
1. It must be freely filtered at the glomerulus2. It must not be reabsorbed at the tubules3. It must not be synthesized by the tubules4. It must not be degraded by the tubules
If there is such substance, then the amount of the substanceexcreted per unit time must be equal to the amount of the substancefiltered per unit time. Fortunately, a such test substance exists, inulin.However, quantitation of inulin is technically difficult, and so clinically,
other substances are used as substitutes. One test substance usedas a substitute is urea. Urea does not fulfill are the criteria for testsubstance since urea is reabsorbed. Two other substances used assubstitutes are creatinine and paraaminohippurate. These twosubstances are however, secreted by the tubules. Nevertheless,
since the discrepancy is not large, they are frequently used a ssubstitute for inulin.
d. The test substances involved in measurement of GFRand their characteristics
Inulin
Is a polymer of fructose that can be used to measure GFR
It is not produced by the body, thus should be administeredintravenously
It is freely filtered across the glomerulus into the Bowmans spaceand not reabsorbed, secreted, or metabolized by the cells of thenephron
The amount of inulin excreted in the urine per minute equals theamount on inulin filtered at the glomerulus each minute
Quantitation of inulin is technically difficult
Urea
A substitute test substance
Does not fulfill one criteria for test substance since it isreabsorbed
Creatine
Used to estimate the GFR in the clinical practice
Creatine is a by product of skeletal-muscle creatine metabolism
Creatine has advantage over inulin because it is produced
endogenously and thus obviates the need for intravenous infusionas is required for inulin
However, it is not a perfect substance to measure GFR becauseit is secreted to a small extent in the proximal tubule
Para-amino Hippurate- Secreted by the tubules
4. Discuss the tubular reabsorption, taking into considerationthe following:
a. Relationship of structural characteristics of thedifferent parts of the tubule to tubular reabsorption
Bowmans capsule
cells of the epithelium are calledpodocytes
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pedicels of podocytes interdigitate with each other to form
filtration slits along the capillary wallProximal tubule
lining epithelium is made up of cuboidal cells connected by tight
junctions
Luminar border of cells due to the presence of numerousmicrovilli
Loop of Henle
Descending limb
o epithelium consists of flat cells
o impermeable to ions but permeable to water
Ascending limb
o epithelial cells are cuboidal
o impermeable to water but permeable
Distal Tubule
lining epithelium- cells lower than that of the proximal tubule
few microvilli; no dense brush border
reabsorption is less
Collecting ducts
epithelium is of two cell types:
o Principal cells
tall, with few organelles
involves in H2O and Na
H2O reabsorption is ADH-dependent; Na isaldosterone- dependent
o Intercalated cells
possess microvilli
concerned primarily w/ acid-base balance
b. Characteristics of:i. Passive tubular reabsorption
transport of subs without the use of energy
may occur via diffusion, w/c requires anelectrochemical gradient
diffusion may occur via water filled channels betweencells, or if the solute is lipid soluble, via the plasmamembrane of the cells
ii. Active Tm-limited tubular reabsorption
o involves transport maximum: the maximum amt of
subs. that can be absorbed by the tubuleo TL- the maximum amt of subs that reaches the tubule
if Tm is equal to TL, the subs is completelyreabsorbed
if Tm is greater than TL, the subs is completelyreabsorbed
if Tm is less than TL, the subs is partly reabsorbed,partly excreted
iii. Active gradient-time tubular reabsorptiono time at w/c the subs is in the tubule
o involves the transport of solute against an
electrochemical gradient
primary active transport
the energy comes directly from the splitting
of ATP
secondary active transport 2 or more subs interact simultaneously w.
the same carrier and both are translocatedacross the membrane
one of the subs undergoes only downhill
transport, while the other manifests uphillmovement against an electrochemicalgradient
c. The substances reabsorbed by the above-mentionedmechanisms
MECHANISMS SUBSTANCES
Passive Tubular Reabsorption - Water- Chloride- Urea
Active Tm Limited TubularReabsorption
- Glucose- Phosphate- Sulfate- Amino Acids- Vitamin C- Uric Acid- Protein
Active Gradient Time Tubular
Reabsorption
- Sodium-
Chloride
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d. Splay and its mechanismsSPLAY occurs when reabsorb able substance may appear in the urinebefore Tm value is reached or exceeded
2 mechanisms:1.Carrier-mediated mechanisms kinetic similar to enzyme
systems so that maximal activity is substrate dependent2.Not all nephrons have the same Tm value for a particular
solute, so that actually, the Tm value is an average rather thanan absolute value
5. Discuss tubular secretion, taking into consideration thefollowing:
a. Relationship of structural characteristics of thedifferent parts of the tubule to tubular secretion
Tubular secretory processes transport substances from thecapillary lumen to the tubular lumen (opposite the direction oftubular reabsorption).
The overall secretory process for any given substance beginswith its diffusion out of the peritubular capillaries into theinterstitial fluid.
The substance makes its way into the tubular lumen via:o Paracellular route crosses the tight junctions (between
the cells)o Transcellular route via the basolateral and luminal
membrane of the cell (across the cell) Secretion from the interstitial space into the tubular fluid (which
draws substances from the peritubular capillaries) is amechanism to improve the efficiency of the kidney to dispose ofsubstances at a higher rate than the filtered load.
b. Characteristics of:i. Passive tubular secretion
Passive since energy is not utilized in the process of thetransport
1. Simple diffusion
Passive tubular secretion via SIMPLE DIFFUSION
Involves movement of a solute down its concentrationgradient, from the interstitium to the tubular lumen.
Substances secreted via this type of secretion:o Potassium (K+)
2. Diffusion trappingPassive tubular secretion via DIFFUSION TRAPPING
Involves transport of weak acids and weak bases
Luminal membrane of the tubular cell is permeable too weak acids when the urine is alkaline, and to
o weak bases when the urine is acidic
Substances secreted:o Weak acids salicyclic acid or aspirin
o Weak bases ammonia
Mechanism:Once within the tubular lumen, the weak acid/base
is converted to ionic formsby interaction with Hydrogen ions.
Luminal membrane is impermeable to the ionicforms of weak acids & bases
Ionic form is now trapped in the tubular lumenand is then eliminated
H+
NH3
H+
+
NH3
NH4-
Tubular
lumen
Tubular cell
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5.2.2 Active Tm-Limited tubular secretion
-Involves transport of solutes via a mechanism similar toactive Tm-limited tubular reabsorption
- Different only from Tm-limited tubular reabsorption interms of the following:
Direction of movement of the solute
Carriers are less specific
Only 1 carrier for all organic anions
Only 1 carrier for all organic cations1. Bile salts2. Fatty acids3. Hippurtaes
4. Hydroxybenzoates5. Drugs:- Acetazolamine- Chlorthiazide- Ethacrynate- Furosemide
6. Oxalate7. Prostaglandins8. Urate
PenicillinProbenecidSaccharin
Sulfonamides
Organic cations; endogenous substancessuch as:
1. Acetycholine2. Choline3. Creatinine
4. Dopamine5. Epinephrine6. Drugs:
Atropine
Isoproterenol
Cimetidine
Meperidine
Morphine
Procaine
Quinine
Tetraethylammonium7. Guanine
8. Histamine9. Serotonin10. Norepinephrine11. Thiamine
5.2.3 Active-Gradient time limited tubular secretion
Involves hydrogen (H+)
Transport of a substance depends upon the time the
intraluminal fluid (which contains the substance) is in contactwith the tubular epithelium
c. The substances reabsorbed by then above-mentioned mechanisms
Mechanisms Substance(s) Reabsorbed
Simple Diffusion Potassium
Diffusion Trapping 1. weak acids (exemplified by salicylic acid oraspirin)
2. weak bases (exemplified by ammonia)
Tm-limited secretion 1. organic anions:Endogenous substances such as bilesalts, fatty acids, hippurates,hydrobenzoates, oxalate, prostaglandins,urates; and drugs such as acetazolamide,chlorothiazide, ethacrynate, furosemide,penicillin, probenecid, saccharin,sulfonamides
If no buffers exist in the lumen, H+ pump willcontinue
The moment H+ pump stops, renal tubularcell will secrete ammonia (NH3) reacting withhydrogen forming ammonium ion (NH4
-).
Although it is PERMEABLE to ammonia (aweak base) it is IMPERMEABLE to ionic ion(ammonium). Hence it is trapped (ionic formof weak acids and bases) and is thereforeELIMINATED.
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2. organic cations:Endogenous substances such asacetylcholine, choline, creatinine,dopamine, epinephrine, guanine,histamine, serotonin, norepinephrine,
thiamine, and drugs such as atropine,isoproterenol, cimetidine, meperidine,morphine, procaine, quinine, andtetraethylammonium
3. carboxylic or sulfonic acid4. EDTA
Gradient-time limitedsecretion
Hydrogen
Passive tubularreabsorption
1. water2. Chloride3. Urea
6. Discuss the reabsorption of sodium, chloride and water atthe proximal tubule, Loop of Henle, Distal tubule andcollecting duct, taking into consideration the following:
a. Permeability characteristics of the part of the tubuleb. Osmolarity changes in the fluid in that part of the
tubulec. Amount of sodium, chloride and water reabsorbed at
each partProximal Tubule
Site of greatest Na+ and H2O reabsorption
Approximately 65% of the filtered Na+, H2O and Cl- is reabsorbed
by the time the fluid reaches the end of the proximal tubule Na+ is actively transported
Cl- and H2O are passively transported as a result of active Na+
reabsorption
Fluid osmolarity remains the same as that of plasma (isosmolar)
Loop of Henle
Reabsorbs about 25% of filtered Na+ and Cl- (ascending limb) and15% of filtered H2O (descending limb)
Descending Limb:
impermeable to ions, permeable to H2O
fluid becomes hypertonic as H2O moves into the
hypertonic interstitium
Ascending Limb:
permeable to ions, impermeable to H2O
Cl- is actively absorbed while Na+ is reabsorbed passively
Fluid becomes more dilute and is hypotonic to plasma
when it reaches the top because Na+
and Cl-
movementout of the tubular lumen
Osmolarity decreases (hypo-osmolar)
Distal Tubule
Only about 10% of Na+ & Cl- and 20% of H2O remains in thetubule as it enters distal tubule
Na+ and Cl- reabsorption continues, but H2O is reabsorbed more.
Fluid that leaves the distal tubule to enter the collecting duct isisosmolar
Collecting Duct
Na+ and Cl- continue to reabsorbed at the principal cells in the
presence ofaldosterone Reabsorption of H2O at the principal cells also continues in the
presence ofADH
Changes in osmolarity and volume depends on the amount ofADH and aldosterone acting on the duct
Fluid that leaves the collecting duct to enter the ducts of Bellinimay be either:
Hyperosmolar
ADH and aldosterone present
Concentrated urine, volume
Hypo-osmolar
ADH and aldosterone absent Dilute urine, volume
7. Explain briefly the following:a. Countercurrent multiplication of osmolar
concentrationConcentration of urine takes place at the medullary collecting ducts, in thepresence of ADH. Such action of ADH however, can only take place inthe hyperosmolarity is called the countercurrent multiplier system, andtakes place at the loop of henle of juxtamedullary nephrons.
Assume that a loop of henle is filled is filled with isosmolar fluid.At the ascending limb, chloride and sodium reabsorption takes place. In
the process, there is a decrease in osmolarity of the fluid within the
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ascending limb, but there is an increase in osmolarity of the fluid at theinterstitium. This increase in osmolarity at the interstitium causes waterfrom the descending limb to move towards the interstitium.
Since the loop of henle of juxtamedullary nephrons are long, it islogical to assume that intratubular fluid becomes progressivelyconcentrated as it flows down the descending limb, and that medullaryinterstitial fluid also progressively becomes concentrated to the samedegree. Although a gradient of 200 m0sm/L is maintained across theascending limb at any given horizontal level in the medulla, there is muchlarger osmotic gradient from the top of the medulla to the bottom. In otherwords, the gradient of 200 m0sml/L established by active chloridetransport has been multiplied because of the countercurrent flow.
The moment the loop countercurrent multiplier system causes theinterstitial fluid of the medulla to become concentrated, in the presence ofadequate ADH, fluid is drawn out of the collecting ducts, and the fluidwithin the collecting ducts thud becomes concentrated
b. Countercurrent exchangeOne characteristic feature of the peritubular capillaries of the
juxtamedullary nephrons is their peculiar arrangement- that of hairpinloops- which run parallel to the loops of henle and medullary collectingducts, and are called the vasa recta.
Blood that enters the vasa recta at an osmolarity of 300 m0sm/L,and as it flows down the capillary loop deeper into the medulla, sodiumand chloride diffuse into, and water out of, the capillary loop. However,after the bend of the loop, as blood flows up the ascending capillary loop,the process is now reversed. Sodium and chloride diffuse out of thecapillary, while water diffuses into the capillary.
Thus, the capillary loop acts as a countercurrent exchanger whichprevents the gradient at the interstitium from being dissipated. Since the
capillary loop does not create the medullary gradient itself but onlyprotects it. It is therefore completely passive. And is thus the reason whyit is called an exchanger instead of multiplier.
8. Explain briefly the mechanisms involved in concentrationand dilution of urine. State the cells of the collecting ductinvolved in the concentration of urine.
In the presence of ADH, the principal cells of the collecting ductbecome permeable to watero Water moves out of the collecting duct, attracted by a
hyperosmolar interstitium, and eventually is absorbedby the vasa recta
o As a result of water movement out of the collecting duct,
the fluid within the collecting duct progressivelybecomes hyperosmolar, and thus, concentrated
In the absence of ADH, the principal cells of the collecting ductare impermeable to watero
Water accumulated in the collecting duct and is notreabsorbedo Fluid in the collecting duct becomes dilute
9. Discuss micturition, taking into consideration the following:Definition:
Micturition refers to the periodic complete emptying of the urinarybladder, under voliuntary control, except during infancy (up to 2-3 years ofage). The act of micturition involves the coordinated activity of thedetrusor muscle, the muscles of the abdominal wall, muscles of the pelvicfloor, fixation of the chest wall and diaphragm and relaxation of theinternal and external sphincter.
a. Physiological processes involved and relationship ofthese processes to structural characteristics
End of micturition, urinary bladder is empty and intra vesicle pressureis equal to the intraabdominal pressure
Bladder slowly fills with urine coming from the urethra viaperistaltic wave motion.
Discoidal vesicle at the mucosa of the bladder are reinserted into the
membrane at the luminal surface (mucosal fold unfold)
Intravesical volume rises and the pressure remains low
Bladder volume reaches 100 150 ml (sensation of bladder fillingis experienced)
Bladder continues to be filled with urine
Bladder volume reaches 150 250 ml (first desire to void)
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Afferent impulses are sent to the cerebral cortex
If access to the toilet is difficult, afferent impulses are sent by thecerebral cortex to the spinal cord (S2 S4)
Efferent impulses are sent to the pudendal nerve
Contraction of the external vesical sphincter
Bladder continues to fill with urine
Bladder volume reaches 450 ml (max. bladder volume)
Involuntary micturition occurs when bladder volume exceeds 450ml for most individuals
Involuntary relaxation of the external urinary sphincter, followedby the internal sphincter (also relax)
Small amount of urine reaches the proximal urethra
Afferent impulses signals the cerebral cortex that voiding isimminent
Voluntary control of micturition by the cerebral cortex is lifted
Suprapontine and pontine centers no longer inhibitparasympathetic fibers that innervate the detrusor
Detrusor muscles of the bladder contract causing expulsion of the
urine
Voluntary contractions of abdominal muscles raise bladderpressure and further enhance emptying
b. When micturition is involuntary and when it becomesa reflex.
When micturition is involuntary and when it becomes a reflex?
- for majority of individuals, the maximum amount of urine thatcanbe tolerated without discomfort is 250 450 ml, beyond thisamount involuntary control of micturition becomes a reflex.
-micturition is normally controlled by micturition reflex. Stretch andcontraction of muscles of bladder wall causes excitement ofmechanoreceptors in the wall. The accumulation of urine brings aboutdistention of the wall of the urinary bladder, then mechanoreceptorsbegin to discharge. Pressure in the urinary bladder is low during filling( 5 -10 cmH2O), but increases abruptly when micturition begins.
Bladder afferent fibers1. excite neurons projecting to the brainstem and activate the
micturition center (rostral pons barringtons center)2. inhibit sympathetic preganglionic neurons that prevent voiding
SPINAL REFLEX PATHWAY- operational in newborn infants- maturation: supraspinal control pathways take on dominant role in
triggering micturition- spinal cord injury: human adults lose bladder control(urinary
incontinence) and may lead to urinary infections.
Micturition through spinal reflex
Bladder fills with urine
Pressure within bladder increases
Stimulation of the stretch receptors in the bladder wall
Afferent fibers from the receptors enter the spinal cord
Stimulation of the parasympathetic neuron
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Pelvic nerve
Detrusor muscle contracts
Reflex inhibition of the sympathetic neurons to the internal urethral
sphinchter (hypogastric nerve)
Reflex inhibition of the somatic motor neurons to the externalurethral sphincter (pudendal nerve)
Opening of the external urethral sphincter