module 17 - urinary system

7/28/2019 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

module 17 - urinary system

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