BIOL 2402 A&P II
Lecture Notes Urinary
Dr. Weis

Urinary System Organs :: kidneys, ureters, urinary bladder, urethra.

I. Kidney :: function -->

excretion of the end products of metabolism
regulate volume & chemical composition of blood

maintain balance between

Vitamin D activation

Hormone production -->


::
location --> bean shape, superior lumbar region T12-L3, retroperitoneal.

 Right kidney is lower than the left due to the postition of the liver.

Gross Anatomy
Later surface is convex, medial is concave and forms a hilus where the renal sinus is located.
Ureters, blood vessels, nerves and lymphatics enter and leave the hilus region.

Outer support ::

1. renal capsule :: fibrous c.t., also lines renal sinus
2. adipose capsule :: cushions, maintains position
3. renal fascia :: dense fibrous c.t., surrounds all membranes for anchoring.


ANATOMY of the
Three regions --> Cortex, Medulla, Pelvis

A. Cortex......outer, lighter and more granular, contains structures for filtration of blood.

B. Medulla.....middle, darker, contains renal pyramids with the base near the cortex and apex (papilla) near medulla.


Pyramids are separated by the renal columns
The renal pyramid + cortical tissue associated at its base is called a LOBE.
Contains renal tubules to help in reabsorption and secretion

C. Renal Pelvis...funnel shaped tube, continuous with the ureter, lined with transitional epithelium.

  Pelvic extensions will branch into the Major calyces that will further branch into the Minor calyces at the papilla of the pyramids.
Fxn> to collect urine and empty into the pelvis
Inflammation : pyelitis


BLOOD Supply to the kidneys::

20-25% of Cardiac Output passes through the kidneys and this % is called the renal fraction.

Renal artery will branch to form segmental a -> lobar a -> interlobar a (between the pyramids) --> arcuate a (at the cortex/medullary junction over the base of the pyramids) C> interlobular a (in the cortex).

Veins are the reverse and will go from the interlobular v to the arcuate C> the interlobar v. ---> the renal v --> inferior vena cava. 

 Therefore, there are No lobar v. or segmental vein.

NERVE : Renal plexus :: ANS primarily sympathetic nervous system from the ciliac ganglia to regulate blood flow to control arteriole diameter, stimulate rennin release, and stimulate reabsorption of Na+ and water.


NEPHRON.... the functional units of the kidney

I. Renal Corpuscle

1. Glomerulus :Fenestrated capillaries for the production of filtrate (fluid filtered from blood), called the Glomerular filtrate

2. Glomerular [Bowman's] capsule : surrounds the capillaries, consists of two portions :

Outer parietal for support & Inner visceral that is associated with the glomerulus
The epithelial cells are podocytes that have foot processes that cling to the
Basement membrane of the glomerulus.
The spaces beteen the foot processes create filtration or slit pores (for filtration).

II. Tubules

Tubules :: filter blood to create a filtrated fluid which is converted to urine by reabsorption and secretion.

a. Renal Tubule ::

Proximal Convoluted Tubule (PCT)
Loop of Henle (LH)
Distal Convoluted Tubule (DCT)

b. Collecting Tubule ::

travel through the medullary pyramids to collect filtrate from the renal tubules and fuse to form papillary ducts that deliver the final filtrated product called urine to the minor calyces [calyx, singular] at the papillay of the medullary pyraminds.

 

Summary of anatomy ::

Glomerulus with Capsule (forms renal corpuscle) --> PCT B> LH C> DCT C> Collecting Duct --> Renal Papilla --> Renal Calyces [Minor --> Major] --> Renal Pelvis



HISTOLOGY :
:  related to filtration capabilities

1. PCT... cuboidal epithelium with microvilli and a large # of mitochondria; Fxn : absorption of H2O, solutes from filtrate

2. LH ... two parts -->

a. Descending limb

b. Ascending limb

3. DCT... simple cuboidal, NO microvilli; fxn : primarily secretory, to secrete solutes into the filtrate

4. Collecting Ducts (CD) simple cuboidal, no microvilli


NEPHRONS ::

location......

 These JM Nephrons have LONG loops of Henle and a more extensive thin segment to help in concentration of urine.

NEPRONS with their TWO Capillary Beds, which are tied together by an arterial anastomosis.

1. Glomerulus......for filtration

2. Peritubular capillaries.....for reabsorption and secretion

Capillary Beds -->

1. Glomerular

     AFFERENT ARTERIOLE from the interlobular a. (in cortex) will lead to glomerular capillaries.

a. high resistance arterioles
b. larger diameter than efferent arterioles

therefore :: force fluid/solutes out of glomerular capillaries into the glomerular capsule. 
The high pressure allows for filtration

  The EFFERENT arteriole leaves the glomerulus and gives rise to ::

            2. Peritubular capillary Bed      

will surround all the tubules, low pressure and porous, adapted for reabsorption of water and solutes and these will empty into the renal venous system.

For the juxtamedullary nephrons there are additional  vessels called the VASA RECTA. 
A portion of the peritubular capillaries descend and run parallel with the longer loops
of Henle
Blood flow is minimal & sluggish, role in formation of concentrated urine.


Juxtaglomerular Apparatus :: (JGA)

The distal tubule lies against the afferent arteriole, before the glomerulus.

 Two cell populations are important in regulating filtrate and systemic blood pressure.

a. In the arteriole :: cells enlarge & have granules that contain rennin.

b. In distal tubule :: modified tall smooth muscle cells (chemoreceptors and osmoreceptors) are responsive to chemical changes related to solute concentration. 

In addition, mesangial cells, located between the capillaries in the renal corpuscle and between the arterioles and JGA, have phagocytic and contractile properties to help regulate blood pressure, which ultimately effects glomerular filtration rates.

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REMEMBER the difference between FILTRATE and URINE

1) Filtrate is like blood plasma except for no large proteins, like albumin
2) Urine is what remains of the filtrate once it passes through the nephron tubular regions. 
Water, ions, nutrients will have most likely been removed (put back into the blood).

The remaining fluid is urine and is primarily made up of water, metabolic wastes, and unneeded substances.


KIDNEY PHYSIOLOGY ::

Three processes ...       Glomerular Filtration

 Tubular Reabsorption
 Tubular Secretion

I. Glomerular Filtration....passive, nonselective, as it allows free passage of water and most solutes.

 Form filtrate -- fluid filtered through glomerulus into capsule, like plasma only decreased amounts of large proteins and no RBCs. 
Fluids/solute are forced through capillaries by
hydraulic (old term was hydrostatic) pressure.

Filtration membrane is more permeable and the higher pressure will increase filtrate.

Filtration membrane is between the blood and internal part of the glomerular capsule, consists of three layers

a. fenestrated capillary endothelium
b. visceral membrane of the capsule (podocytes)
c. fused basement membrane (the basal lamina), which is primarily collagen.

The capillary pores size allow for selective sizes and prevent RBC passage

The basement membrane of the glomerular endothelium restricts protein size, allowing only the smallest sized solutles through (glucose, AA, H2O, urea) & keeping larger proteins in to create a capillary colloid osmotic pressure to prevent loss of all water. Basement membrane is also negatively charged, so anions are repelled by electrostatic repulsion.

Spaces between the podocytes are called filtration slits that are controlled by mesangial cells.

Problem :: with filtration membrane: allowing large proteins and blood into urine, sometimes a problem with mesangial cells.


4 FILTRATION PRESSURES ::

Two pressures deal with hydraulic (hydrostatic) pressures (HP) and two pressures deal with osmotic pressures (OP)....

1. Glomerular Hydraulic (Hydrostatic)  (HPg) ..push H2O and solutes out
2. Capsular Hydraulic (Hydrostatic)   (HPc) .....fluids into glomerulus
3. Glomerular Osmotic (OPg).. osmotic gradient in capillaries brings H2O in
4. Intracapsular Osmotic  (OPc) ......essentially zero

Creates a NET FILTRATION PRESSURE (NFP).... [out-in]

HPg - [HPc + OPg]  = 60-[28+15]= 17 mm Hg out and is the  pressure involved in forcing H2O/materials out of the glomerular capillaries into the capsular space to form the filtrate.

Another example: 55-[30 +15] = 10 mm Hg.

Therefore, the minimum net filtration pressure is 10 mmHg.

GLOMERULAR FILTRATION RATE  (GFR)

Amount of fluid filtered from blood into glomerular capsule each minute.

Depends on Net filtration pressure (NFP) which reflects mean arterial pressure.

Other Factors for GFR:

total surface area for filtration
permeability of filtration membrane
changes in net filtration pressure (incr/decr)

Regulation of GFR:

Intrinsic regulation

a. Renal autoregulation --> regulates blood flow by regulating diameter of afferent arteriole to maintain constant pressure

b. Myogenic - vascular smooth muscle of afferent arterioles maintain pressure along their walls.

c. Macula Densa provides chemical control for vasoconstriction/vasodilation

Extrinsic regulation

a. Rennin/Angiotensin system B> juxtaglomerular cells release rennin to initiate the system, which involves angiotensinogen [from liver] AT I --> lungs to be converted to AT II --> to Adrenal Cortex Zona Glomerulosa to simulate Aldosterone formation --> targets the kidneys mesangial cells to contract and the DCT / CD to reabsorb sodium.

b. Sympathetic N.S. --> epinephrine to constrict arterioles --> decrease filtrate formation

   --> Sympathetic N.S. --> N.Epi that will stimulate the JG cells

 c. Other factors :: Hormones

prostaglandins :  either vasoconstrict or vasodilate
adenosine  : renal vasoconstrictor
nitric oxide: vasodialator

endothelin
: vasoconstriction

  Therefore the affects of Renal Blood Flow ::

Increased Pressure --> Increases GFR, but increased resistance will slow blood, so protein leaks and ultimately will decrease GFR.


II. Tubular Reabsorption ::

Filtrate like plasma except for decreased proteins enters the tubular portion of the nephron

Urine is the metabolic waste and end process of filtration, reabsorption, secretion

Mostly occurs via transepithelial transport due to the tight junctions that form between the cells lining the tubules.
Transepithelial movement involves going through three layers. (Two layers involve the tubular cells, on luminal, the other basal, and the third is
the endothelium of the capillaries).
Reabsorption via transepithelial movement begins at the proximal tubule.

Reabsorption may be passive (no Energy), or active (E)

a. Active Tubular Reabsorption ::

against a concentration gradient, need ATP to go across Basement membrane.

ie : glucose, AA, vitamins, ions, most involved w/ cotransport with Na+ threshold --> transportation maximum, carriers are saturated, with excesses excreted in urine

b. Passive Tubular Reabsorption ::

along concentration gradient, involves diffusion, facilitated diffusion, osmosis for water (osmosis) through aquaporins in the PCT that form water channels, linked with Na+ movement. In the DCT/CD, ADH must be present for the aquaporins to form and allow water to move by osmosis.

HCO3-, Cl- :: absorbed depending on pH

c. Nonreabsorbed ::

end products of metabolism --> urea, creatinine, uric acid

not reabsorbed due to lack of carriers, nonlipid soluble, too large

NOTE: some urea is reabsorbed passively by diffusion since it is a small molecule.


 *** Regional Absorption ***

1. PCT : most active, ~ 60% - 80%  reabsorbed

glucose/AA.....facilitated diffusion, CoTransport with Na +

ions ....by ions pumps, regulated by concentration and hormones

        Na+ : paracellular, passive, electrochemical

Cl-, K+, Ca++, Mg++, SO4= : passive

HCO3- : paracellular, passive, electrochemical, or possible Co-transport with Na+

vitamins

H2O......osmosis

urea.....freely permeable

creatinine.... not reabsorbed since it is too large


2. Loop of Henle : changes permeability

a. descending loop.... H2O permeable (goes out) via osmosis

b. thick ascending loop ...
Na/Cl/ K+ active transport via a symporter
H2O impermeable,  urea impermeable
Ca++, Mg++ : paracellular, passive
Na+ / H+ antiporter


3. Distal Convuluted Tubule : two parts

a. diluting segment :: like the thick ascending L.H.

b. Late distal tubule :: responsive to ADH


4. Collecting Ducts ::


III. Tubular Secretion :

move substances from capillaries through cells into filtrate

Occurs in the Distal Tubule and collecting ducts, primarily

Fxn :    to eliminate undesirable substances, rid K+ excess and to control pH

Also removes certain drugs and other substances (neurotransmitters)
Secretion of substances such as H+, K+, NH3, creatinine, ammonia
pH control --> involve secretion or retention of H+/HCO3-
Regulation of Urine :: Concentration and Volume

Osmolarity B> number of solute particles dissolved in 1 liter (1000g) of water.

solutions that are able to cause osmosis are measured in osmoles, milliosmoles (= .001 osmol)

Body fluids are normally at 300 mosmoles [300 mOsm]

Counter Current Mechanism : opposite flow of fluids.

Goes one direction for the filtrate in the L.H. and goes the opposite direction for blood in the Vasa Recta

Needed to maintain osmotic gradient

Multiplication : effect of osmotic gradient is increased as Na+ is re-circulated


Descending Loop of Henle ::

relatively impermeable to solutes

freely permeable to water

Osmosis of water out of the tubules into the medulla since concentration in tubule is less hypertonic compared to that in the medulla

Ascending Loop of Henle ::

impermeable to water
permeable to Na/Cl
Active Na/Cl pump (ATP is used) to pump Na+ into the ICF of the medulla
 creates hypotonic state in tubule

Collecting Tubules ::

Dilute urine from the ascending loop enters

Permeable to urea, will leak out and increase the osmolarity in the medullary region and add to the osmotic gradient

Vasa Recta :: helps maintain the osmotic gradient
freely permeable to Na/Cl and water
passive exchange to maintain equilibrium with medulla ICF

blood flows from thick to thin region, opposite of filtrate flow in the loops.

     In the deep medulla region : loses water, gains salt to become more concentrated

     In the cortex : gains water and loses salt to be less concentrated


Dilute Urine is in the ascending loop and will flow into the DCT and CD.

If NO ADH, then the distal tubule and collecting ducts remain impermeable to water and no further water is reabsorbed.
At this pont, the filtrate osmolarity is about 100 mOsm/l

 Some reabsorption of salt/ions can still take place to further dilute the urine to about 65 mOsm/ l


Concentrated Urine : Involves the counter current/multiplication mechanisms created with the JXM-LH and the Vasa Recta and the increase in osmolarity in the medulla ICF

1. Active transport of Na+ out of the thick ascending Loop of Henle into the ICF

2. Na+ diffuses into the thin descending loop of Henle and into the capillaries of the vasa recta.
This movement creates the countercurrent multiplier as Na+ diffuses
out at the papilla of the renal pyramids, some remains in the medulla, some diffuses into the thin ascending loop of Henle, some diffuses into the blood and adds to the Na+ already in the vasa recta.

3. Collecting duct transports ions into medullary ICF

4. Urea permeability in collecting duct allows for it to diffuse to equilibrium with the medulla ICF and adds to the osmotic gradient.

Therefore, water flows into the medulla because of the osmotic gradient created by Na+ and urea when ADH is present.

ADH opens aquaporin pores by activating adenyl cyclase for cAMP to change the lumen side membrane of these ducts. 
This  increases
water permeability in the distal tubules and  collecting ducts and the high medullary osmotic gradient causes osmosis and the flow of water into the medulla as the
filtrate passes through these tubular structures.

Medullary blood flow is slow and minimal (1%), so this will minimize the washout of solutes since it is the site of the counter current exchanger as the ascending and descending limbs of these vessles are in close proximity to one another and can exchange fluid and solute freely.


Diuretics :: chemicals that enhance urine output

Renal Clearance :: tests used to determine GFR and the function of kidney tissue.

 Measured against a standard and relates to the urine concentration of the substance, urine flow and the plasma concentration of the substance.  RC values of zero are for substances that are completely reabsorbed


URINE ::
Composition reflects filtration/absorption/secretion, so that it is normally composed of

 Color :: clear-pale-yellow-deep yellow as the pigment comes from Hemoglobin destruction (urochrome)

If  more concentrated, the darker in appearance, also Abnormal pigments due to blood, bile, food, dyes
urine
concentration depends on osmotic movement of water

Specific Gravity ::   concentration, depends on solute conc.

  water is the standard at 1.000, urine specific gravity  will range from 1.001 - 1.035.

Odor  :: some, older urine will have ammonia smell (NH3)

 pH    :: changes with the diet and metabolism, usually pH = 6 [with a pH range of 4-8]

 

 Abnormal --


Nephron Summary ::

1. Glomerulus  --> filtration into the glomerular capsule


2. PCT
B> primary reabsorption

cotransport : Na+ with glucose, AA, PO4=, Cl-, H+
 active transport of ions (Ca++, Mg++, Cl-, I, Fe, Na+, K+)
passive transport (osmosis) for water
passive facilitated diffusion for ions, glucose, AA
secretion : nitrogenous wastes, H+
active countertransport : Na+ with H+  therefore reabsorbing Na+ and secreting H+


3. Loop of Henle
B>

a. Descending limb :: loses water by osmosis due to water permeability concentrates solutes due to impermeability
b. Ascending limb :: Na+/Cl- pump out into medulla ICF filtrate is more dilute due to H2O impermeability


4. DCT --> Early and Late regions

Early = forms part of the JGA
Late = primarily secretion of substances into filtrate

            countertransports

                        Na+ for H+

                        Cl- for HCO3-

                        Na+ for NH4+

                        Na+ for K+

                        Na+ for Ca++

Active absorption

            with ADH ::  H2O permeability and passively reabsorb urea

            with Aldosterone:: Na+, passively reabsorb Cl-

            with ANP:: reabsorb K+ and secrete Na+


5. Collecting Duct -->

pH homeostasis with regulation of K+, H+, HCO3-  can be secreted or absorbed
urea permeable, diffusion to equilibrium with medulla and adds to the osmotic gradient in the medulla
Impermeable to H2O unless ADH is present
Water impermeability will lead to dilute urine
Water permeability will causes osmosis, water will go into medullary ICF and concentrate filtrate to form a concentrated urine.

Each substance requires specific transport in the tubules.

 When transport is at the maximum, the excess is lost in the urine

This transport maximum [Tm] is called the renal threshold and is defined as the plasma concentration at which a specific compound/ion will begin appearing in the urine.


GFR regulation ::

1. change in the diameter of the arterioles.

 Mechanical control of blood volume :: if increase blood volume --> incr CO --> incr Pressure --> incr GFR --> incr urine

output --> decrease blood volume


2. Hormonal ....

Rennin/Angiotensin :: vasoconstriction,  aldosterone release for Na+ reab

Erythropoietin :: stimulate bone marrow for RBC prod.

ADH :: from supra optic/paraventricular nuclei of the hypothalamus for change in water permeability at the distal tubules and collecting ducts

  will also stimulate angiotensin II to help with vasoconstriction.


3. ANS...sympathetic stimulation of beta receptors in the JGA
will respond by releasing rennin, and ultimately affect angiotensin/aldosterone release.


REGULATION of ELECTROLYTES

ECF Na+ determines most of the osmotic pressure in the ECF and therefore control to regulate Na+ concentrations is based on

1. ADH...

Increased Na+ affects osmoreceptors in hypothalamus and stimulates
ADH release from the nuclei.  ADH will change the permeability of
water and therefore conserve H2O, while still having Na+ loss

2. Thirst ... osmoreceptors in thirst center of the hypothalamus will be stimulated due to decreased blood volumes

3. Appetite... craving for salt, tied to thirst  center in hypothalamus

Most Na+ reabsorbed in PCT and LH

some reabsorbed in DCT/Collecting Ducts depending on release of aldosterone from the zona glomerulosa of the adrenal cortex.  Secretion of aldosterone is based on

stimulation by

a. angiotensin II
b.Increased K+ concentrations
c. Decreased Na+ concentrations in ECF

Urea excretion is based on concentration and is re-circulated in the medulla and adds to the osmotic gradient due to the collecting ducts permeability and establishing equilibrium with the medulla.  Rate of excretion of urea is determined by GFR.


URETERS : Fxn :: urine transport from the kidneys to the urinary bladder

Is a continuation of the renal pelvis and will enter at an oblique angle into the urinary bladder.

Histology of the tube

1. mucosa ... transitional epithelium + lamina propria
2. muscularis .. sm. m in 2 layers :inner long, outer cir
3. Adventitia .. fibrous C.T.

Urine entering causes distention --> peristaltic waves --> to propel urine to the urinary bladder

Problems :: renal calculi obstruct ureter & urine outflow

       Ectopic ureter (abnormal opening)


URINARY BLADDER : Body and neck, supported by 2 lateral ligaments and 1 medial ligament. 

The two lateral ligaments were once patent  fetal structures called the umbilical arteries. 

Sits posterior to pubic symphysis and lies retroperitoneal.

Trigone :: 3 openings in the region of the neck of the urinary bladder that form a triangle created by the 2 ureter openings (right, left) and the urethra opening, distally.

Histology :: three layers

1. Mucosa...transititional epithelium with lamina propria, folded into rugae when relaxed

2. Muscularis .. smooth muscle in three layers, inner longitudinal, middle circular, outer  longitudinal.
Muscle layers collectively called the Detrusor muscle of the urinary bladder
Stretch for expansion and will allow increase storage of urine.

3. Adventitia ... connective tissue

In males, the prostate gland is associated with the neck region of the urinary bladder.

Inflammation of the u. bladder is called CYSTITIS


URETHRA :: fxn.. drains urine from the bladder

Histology

1. Mucosa will change

near bladder is transitional epithelium
in middle section will become pseudostratified columnar
at opening will become stratified squamous


2. Muscularis...

Creates two sphincters

a. internal urethral sphincter at the junction of the bladder and urethra Sm.M, involuntary to keep urethra closed and prevent leakage of urine
b. external urethral sphincter at the opening of the urethra Sk. m. & under voluntary control


3. Adventitia... connective tissue

Difference in length of the urethra ::

Females :: short, close to anal opening

 transport of urine only
 more problems with ascending bacterial infections to cause
inflammation in this area --> Urethritis

Males :: longer, has three regions

1. prostatic urethra
2. Membranous urethra
3. Spongy urethra

  fxn to transport semen and urine

Opening of the urethra at the body is called the external urethral orifice


Micturition :: urination or voiding

The urinary bladder at rest is in a contant filling state. The internal sphincter smooth muscle is passively contracted, while the external skeletal muscle is in a contracted state via somatic innervation from CNS stimulation.

As the urinary bladder fills, stretch receptors in bladder wall trigger a reflex arc sensory afferents to spinal cord segment S2-S3 and motor efferents to bladder from the pons.  Under ANS control involving primarily the parasympathetic fibers in the pelvic nerve for sensory via the splanchnic nerves and the somatic nervous system via the pudenal nerves for motor to the sphincter muscle.
Parasympathetic nerurons in the bladder wall will be excited to contract and therefore increase the pressure on the contents of the urinary bladder. This will cause the detrusor m. of the u. bladder to contract and relaxation of the smooth muscle of the internal urethral sphincter, since pressure that is exerted by the urine will force the internal sphincter to open.
.At the same time, somatic motor effernt neurons of the pudendal nerve will be inhibited to allow relaxation of the sphincter.

Urine passes into the urethra and out of the body via peristaltic contractions and aided by gravity.

CNS impulses received from ascending tracks to the pons and cortex to monitor the urinary bladder functions, degree of fullness, and appropriateness of when to void. Centers in the brain stem and cerebral cortex can override the basic micturition reflex by direct inhibition of parasympathetic and reinforcing the contraction of the external urethral sphincter via somatic efferents in the pudendal nerve.

Problems with micturition:

Urinary Incontinence: inability to control micturition
Urinary Retention: unable to expel urine due to musclular problems
Urinary Obstruction : unable to expel urine due to physical blockage [stone, tumor, enlarged prostate]

Problems with the Kidneys ::

1. acute renal failure... shutdown of the nephrons

example of causes --> abnormal immune system, toxins, ischemia

2. Chronic renal failure... progressive destruction of nephron

due to obstruction, cystic disease, chronic inflammation

3. Hypertensive kidney dsdue to hypertension in glomerulus

4. Nephrotic Syndrome... increased permeability of the glomerulus, and proteins are lost

5. Tubular abnormalities.. change in reabsorption either abnormal reabsorption or lack of reabsorption

especially for glucose, AA, urate, P, H+

Aging changes in the urinary system ::

1. decrease number of nephrons

2. decreased GFR due to decrease blood flow, decr nephrons

3. Decreased ADH sensitivity, so less H2O reabsorbed

4. Changes in micturition due to

a. decreased sphincter tone
b. decreased neural control
c. prostatitis

.