Urinary System

Kidneys (2)
Ureters (2)
Urinary bladder
Urethra

 System functions to filter and remove waste products from the blood
 Main functional units of the kidneys are the nephrons
 Nephrons filter the blood and form the urine
Functions of the Urinary System
Elimination of waste Regulate -homeostasis
products – Water balance
– Nitrogenous wastes – Electrolytes
– Toxins – Acid-base balance
– Drugs – Blood pressure
– -metabolites – RBC production
– Activation of vit.D
Organs of Urinary system includes:

1) The kidneys
Two, (on its top adrenal glands)-Produce urine
2) The ureters
Transport urine from the kidneys to the bladder
3) The urinary bladder
Stores urine
4) The urethra
Eliminates urine
Functions of the Kidneys

1) filter blood plasma, separate

wastes, return useful materials
to the blood, and eliminate the
wastes.

Toxic nitrogenous wastes

- ammonia, urea, uric acid, creatine, and
creatinine
- cause diarrhea, vomiting, and cardiac arrhythmia,
convulsions, coma, and death.
Functions of the Kidneys

1) filter blood plasma,

separate wastes, return
useful materials to the
blood, and eliminate the
wastes.

2) regulate blood volume and osmolarity.

 Functions of the Kidneys

3) produce hormones
1. Erythropoietin

2. *Calcitrol (Active form of Vit-D)

3. * Renin

4) regulate acid-base balance of the body fluids.

5) detoxify superoxides, free radicals, and drugs.

 1. Erythropoietin

-is a glycoprotein acts on the bone marrow to increase the production of

red blood cells.

Stimuli such as bleeding or moving to high altitudes (where oxygen is

scarcer) trigger the release of EPO

People with failing kidneys can be kept alive by dialysis, cleanses the
blood of wastes.

Without a source of EPO, patients suffer from anemia.

--to recombinant DNA technology, recombinant human erythropoietin

(rhEPO) is available to treat these patients.
To treat AIDS, zidovudine, for example, cause anemia as a side effect.
Treatment of anemia in chronic kidney disease anemia in myelodysplasia, and
in anemia from cancer chemotherapy.
 Calcitrol

Calcitriol ,the active form of vitamin D, derived from

calciferol (vitamin D3) which is synthesized in skin exposed to
the ultraviolet rays of the sun
precursors ("vitamin D") ingested in the diet.

Calciferol in blood is converted into the active vitamin in two

steps:
calciferol is converted in the liver into 25[OH] vitamin D3

this is carried to the kidneys where it is converted into calcitriol.

This step is promoted by the parathyroid hormone.

Calcitriol Action:
-intestine to promote the absorption of calcium and phosphate
from food
-bone to mobilize calcium from the bone to the blood:
To treat rickets (children) and In adults, weakened bones
causing osteomalacia.
 Anatomy and Physiology of Kidney

• Kidney: Primary organs of the urinary system

-are bean-shaped organs that lie behind the peritoneal cavity
(retroperitoneal) on either side of the vertebral column
 Located between the 12th thoracic and 3rd lumbar vertebrae.

 Right is usually lower due to liver.

 Lie in shallow depressions against the posterior abdominal wall and

behind the parietal peritoneum – retroperitoneal

 Attached to ureters, renal blood vessels, and nerves at renal hilus

 Atop each kidney is an adrenal gland

 Coverings of the Kidneys
• Renal capsule
– Surrounds each kidney
• Adipose capsule
– Surrounds the kidney
– Provides protection to the kidney
– Helps keep the kidney in its correct location
 Regions of the Kidney

 Renal cortex – outer

region
 Renal medulla – inside
the cortex
 Renal pelvis – inner
collecting tube
Each kidney is approx. 3 cm thick, 6
cm wide and 12 cm long

Indentation on medial aspect = hilus

– where renal vessels and ureters
transverse

a hilum carrying renal nerves and

blood vessels.

Renal pelvis – expansion of the ureter that

further divides into calyces
 Frontal section through the kidney
– Renal cortex
– Renal pyramids
– Renal pelvis
 Major caliyx
 Minor calicies
Gross vasculature
– Renal arteries
– Branch into segmental arteries

Renal cortex – outermost portion of the kidney that covers the pyramids
and dips down between them

Renal medulla – middle portion that also divides into renal pyramids
 KIDNEY ANATOMY
Renal parenchyma
Renal pyramids-extensions of cortex (renal columns) divide medulla
into 6 – 10 renal pyramids

– Pyramid + overlying cortex = Lobe

– Point of pyramid = Papilla
– Papilla nested in cup (minor calyx)
– 2 – 3 minor calices  Major calyx
– 2 – 3 major calices  Renal pelvis
– Renal pelvis  Ureter

pyramids consist mainly of tubules that transport urine from the cortical to the
calyces, or cup-shaped cavities in which urine collects before it passes through the
ureter to the bladder.
papilla is the location where the renal pyramids in the medulla empty urine into
the minor calyx
 Blood supply of the kidneys
Blood enters into the kidney via the renal artery, which then splits up to form
the interlobar arteries.

The interlobar arteries each in turn branch into arcuate arteries, which in turn
branch to form interlobular arteries, and these finally reach the glomeruli.

At the glomerulus the blood reaches a highly disfavourable pressure gradient and
a large exchange surface area, which forces the serum portion of the blood out of
the vessel and into the renal tubules.

Flow continues through the renal tubules, including the proximal tubule, the Loop
of Henle, through the distal tubule and finally leaves the kidney by means of
the collecting duct, leading to the renal pelvis, the dilated portion of the ureter
 Blood supply of the kidneys
Pathway of blood flow to the kidneys:
– Renal artery – renal arteries deliver blood to the kidneys
– Segmental artery – renal arteries branch to segmental arteries
– Interlobar artery - Segmental arteries divide into a series of interlobar
arteries
– Arcuate artery - interlobar arteries supply blood to the arcuate arteries
– Interlobular artery - Each arcuate artery gives rise to a number of
interlobular arteries
– Afferent arterioles - interlobular artery branch to number of afferent
arterioles
– Glomeruli – afferent arteries deliver blood to capillaries called glomeruli.
Glomeruli is network of capilaries found in the corpuscle of nephrone
Renal venules follow similar opposing pattern ending with renal
veins
The Blood Supply to the Kidneys
 The Nephron
The kidney contains 1.2 million nephrons, functional units of the kidney

The nephron consists of :

– 1) Renal corpuscle
– 2) Renal Tubule
Renal corpuscle:– the head of the nephron, a knot of capillaries
– The renal corpuscle is the part of the kidney nephron in which blood
plasma is filtered.
– The renal corpuscle of each kidney nephron has two parts - they are
the Glomerulus, which is a network of small blood vessels
called capillaries,

– and the Bowman's Capsule, which is the double-walled epithelial cup

within which the glomerulus is contained.
The fluid that is filtered into the Bowman's Capsule is called the glomerular filtrate.
GFR= 130-150 ml/min
The renal tubule part of nephron into which the glomerular filtrate passes after it has
reached the Bowman's capsule. consists:
-Proximal convoluted tubule (PCT)
-Loop of Henle
-Distal convoluted tubule

The first part of the renal tubule -called

the proximal convoluted tubule

The water and solutes that have passed

through the PCT-enter the Loop of Henle:

-which consists of two portions - first

the descending limb of Henle, then
the ascending limb of Henle.
The water, urea, and salts contained within the ascending limb of Henle eventually
pass into the distal convoluted tubule (DCT).

-The DCT of many individual kidney nephrons converge onto a single -CD
-Many CD join together to form several hundred papillary ducts

-There are typically about 30 papillary ducts per renal papilla (the renal papillae
being the tips of the renal pyramids - which point towards the centre of the kidney).
The Nephron
– The tubular passageway of the nephron is responsible for:
1. Reabsorbing organic substrates and vitamins
2. Reabsorbing water and electrolytes
3. Secreting waste products

 From the tubular passageway -fluid enters into the collecting system
 Collecting ducts carry the fluid to papillary ducts and Papillary ducts carry the
fluid to the minor calyx
 Minor calyx carry the fluid (urine) to major calyx
– Number of minor calyces join together to form a major calyx
 Major calyx deliver the fluid to renal pelvis
 Renal pelvis is connected to the ureter
 Ureter transports the urine to the bladder
The Nephron
 The Nephron
There are two types of nephron
– 1) Cortical nephrons
• ~85% of all nephrons
• Located in the cortex
– 2) Juxtamedullary
nephrons
– Closer to renal medulla
– Loops of Henle extend
deep into renal pyramids
 Cortical and Juxtamedullary Nephrons

The main difference in the two types of nephron is the length to which
the loop of Henle extends into the kidney.

Cortical nephron, which are about eighty percent of the nephron in humans,
have a loop of Henle that does not extend past the cortex of the kidney.

Juxtamedullary nephron, on the other hand, have a loop of Henle that

extends past the cortex and into the medulla of the kidney.
Nephron Function: URINE FORMATION

The principle processes that determine the

urinary excretion of drugs are:
1. Glomerular filtration.
2. Passive or active tubular re-absorption.
3. Active tubular secretion

6/12/2021 BITS, Pilani 26

 Basic processes of urine formation
1) Filtration – this is the first process, and it occurs in corpuscle of
nephron
– Filtration occur because blood pressure forces fluid and dissolved
solutes out of the glomerular capillaries and into the capsular space
2) Reabsorption – occurs in tubular passageway of the nephron
– filtrate produced in the corpuscle contain organic substrates,
vitamins and other beneficial material.

3) Secretion – occurs in the tubular passageway of the nephron

– Transport of solutes from the peritubular fluid into the tubular fluid
Glomerular Filtration Rate (GFR)
-Hydrostatic pressure pushes a portion of blood to be filtered
across a semi-permeable memb into the Bowman’s Capsule.
- is the amount of filtrate formed per minute by the
two kidneys - is about 125-150 ml/min.

- This amounts to a rate of 180 L/day.

- An average of 99% of the filtrate is reabsorbed,

so that only 1-2 L of urine per day is excreted.

 Blood cells, platelets, and plasma proteins, retained in

the blood and not filtered.
GFR is be precisely controlled –

If GFR is too high then-

- increase in urine output
- threat of dehydration and electrolyte depletion.

If GFR is too low then

- insufficient excretion of wastes and may results
serious consequences

The only way to adjust GFR from moment to

moment is to change glomerular blood pressure.
The nephron has two ways to
prevent drastic changes in GFR
when blood pressure changes:

1) Constriction of the afferent

arteriole to reduce blood flow into the
glomerulus

2) Dilation of the efferent arteriole to

allow the blood to flow out more
easily.

 Change in an opposite direction if blood pressure falls-RAAS

 When blood pressure is law, the amount of filtrate in the corpuscle decreases, stimulates production of renin by JG
 Renin converts angiotensin to angiotensin I - to angiotensin II
Angiotensin II affects the/ or acts on:
1) Angiotensin II stimulates constriction of blood vessel and increases production of aldosterone.
2) Aldosterone increases sodium and water retention.
3) CNS: stimulates thirst, increases production ADH, increases water reabsorption by the collecting system.
1) Glomerular Filtration

2) Tubular Reabsorption

3) Tubular Secretion

4) Concentrating Urine by Collecting Duct

Reabsorption in Proximal
Convoluted Tubules

About 99% of Water and other useful

small molecules in the filtrate are
normally reabsorbed back into plasma by
renal tubules.

PCT reabsorbs about 65% of the glomerular

filtrate and return it to the blood.
Mechanisms of Proximal Tubular
Reabsorption

1) Solvent drag
2) Active transport of sodium.
3) Secondary active transport of glucose, amino
acids, and other nutrients.
4) Secondary water reabsorption via osmosis
5) Secondary ion reabsorption via electrostatic
attraction
6) Endocytosis of large solutes
Active transport of sodium
 Sodium pumps (Na-K ATPase) in basolateral membranes
transport sodium out of the cells against its concentration gradient
using ATP.

Na+ Na+

K+

capillary PCT cell Tubular

lumen
 There are also pumps for other ions

Ca++ Ca++

capillary PCT cell Tubular

lumen
 Secondary active transport of glucose, amino
acids, and other nutrients

- Various cotransporters can carry both Na+ and other solutes.

For e.g, the sodium-dependent glucose transporter
(SDGT) can carry both Na+ and glucose.

Na+

Na+
K+

Glucose
capillary PCT cell
 Secondary active transport of glucose, amino
acids, and other nutrients

Amino acids and many other nutrients are

reabsorbed by their specific cotransporters
with sodium.

Na+

Na+
K+

amino acids
capillary PCT cell
- Fluid arriving in the
DCT still contains about
20% of the water and
10% of the salts of the
glomerular filtrate.

- A distinguishing feature
of these parts of the renal
tubule is that they are
subject to hormonal
control.
Aldosterone

a. secreted from adrenal

gland in response to a 
Na+ or a  K+ in blood

b. to increase Na+ absorption

and K+ secretion in the DCT
and cortical portion of the
collecting duct.

c. helps to maintain blood

volume and pressure.
Atrial Natriuretic Factor
- secreted by the atrial
myocardium in response to
high blood pressure.

- It inhibits sodium and water

reabsorption, increases the
output of both in the urine,
and thus reduces blood
volume and pressure.
1) Glomerular Filtration

2) Tubular Reabsorption

3) Tubular Secretion

4) Concentrating Urine by Collecting Duct

Tubular Secretion

- Renal tubule extracts chemicals from the blood and secretes

them into the tubular fluid.

- serves the purposes of waste removal and acid-base balance.

H+
H+

capillary PCT cell Tubular

lumen
 Active tubular secretion of drugs

Therapeutic advantages of competition:

 Probenecid is used to block renal tubular secretion of some acidic drugs
(e.g. penicillin) and thus prolong its duration.

Therapeutic disadvantages of competition:

 probenecid inhibits renal tubular secretion of nitrofurantoin thus
decreases its efficacy in urinary tract infections (UTIs).

6/12/2021 BITS, Pilani 44

1) Glomerular Filtration

2) Tubular Reabsorption

3) Tubular Secretion

4) Concentrating Urine by Collecting Duct

 Water and solute loss is regulated by aldosterone and ADH

 Reabsorption
-Sodium ion, bicarbonate, and urea are resorbed
 Secretion
-pH is controlled by secretion of hydrogen or bicarbonate ions
1. The collecting duct
(CD) begins in the Cortex
cortex, where it
receives tubular fluid
from numerous
nephrons.

2. CD reabsorbs water. collecting

duct

urine
1. Driving force
The high
osmolarity of extracellular
fluid generated by NaCl
and urea, provides the
Cortex
driving force for water
reabsorption. medulla

2. Regulation
The medullary
portion of the CD is not
permeable to NaCl but
permeable to water,
depending on ADH.
mOsm/L
urine
 Control of Urine Concentration depends on the
body's state of hydration.

 In a state of full hydration,

antidiuretic hormone (ADH) is
not secreted and the CD
permeability to water is low, Cortex
leaving the water to be excreted. medulla

 In a state of dehydration, ADH is

secreted; the CD permeability to
water increases.
 With the increased reabsorption
of water by osmosis, the urine
becomes more concentrated.
mOsm/L
urine
 Urine Properties

Composition and Properties of Urine

Fresh urine is clear, containing no blood cells and little

proteins.

If cloudy, it could indicate the presence of bacteria,

semen, blood, or menstrual fluid.
Substance Blood Plasma Urine
(total amount) (amount per day)
Urea 4.8 g 25 g
Uric acid 0.15 g 0.8 g
Creatinine 0.03 g 1.6 g
Potassium 0.5 g 2.0 g
Chloride 10.7 g 6.3 g
Sodium 9.7 g 4.6 g
Protein 200 g 0.1 g
HCO3- 4.6 g 0g
Glucose 3g 0g
Urine Volume

An average adult produces 1-2 L of urine per day.

a. Excessive urine output is called polyuria.

b. Scanty urine output is oliguria. An output of less

than 400 mL/day is insufficient to excrete toxic wastes.
Diabetes - Diabetes mellitus features high glucose in the blood
(hyperglycemia),polyuria,polyphagia resulting from various
metabolic disorders, including Diabetes mellitus-
(Type-1 and Type-2-DM)
and the Diabetes insipidus

1) Autoimmune –destruction of beta cells-Insulin deficiency-IDDM

2) Type-II, Insulin receptors –resistance, desensitization -NIDDM

 high glucose
- When glucose in
tubular fluid exceeds
the transport maximum
(180 mg/100 ml), it
appears in urine high glucose
(glycosuria). in filtrate
- Glucose in tubular Retain H2O by
fluid hinders water osmosis
reabsorption by
osmosis, causing
polyuria.
high
urine
volume
Diabetes insipidus

- is caused by inadequeate ADH

secretion.

- Due to the shortage of ADH, water

reabsorption in CD is compromised,
leading to polyuria.

 urine
Diuresis : refers to excretion of large amount of urine.

Diuretics
-are chemicals that increase urine volume.
-used for treating hypertension and CHF because they
reduce overall fluid volume e.g-furasemide

Natriuresis

refers to enhanced urinary excretion of sodium and water-

ANP and BNP
Renal disease and Renal Test

1: Glumerulous Nephritis: inflammation of the glomeruli

2: Renal Acute failure
3: Renal End Stage Failure
4: Kidney Stone
Proteinuria – asymptomatic
Haematuria – asymptomatic
Hypertension
Nephrotic syndrome

Dialysis
 Renal Test
GFR and Creatinine Clearance

The perfect filtration marker: is not protein bound, is freely filtered by the
glomerulus, is without any tubular secretion, is not metabolised by the kidneys,
and is physiologically inert.

Very few substances fulfil these criteria: the gold standard has been a plant
polysaccharide called inulin, an exogenous substance requiring injection and a
complex collection protocol;

-alternatives involve administration of radionuclides such as 125I-

iothalamate, 51Cr-EDTA or 99mTc-DTPA, which are labour-intensive procedures
and too costly for routine use.

Chronic kidney disease is identified by a blood test for Creatinine.

Higher levels of creatinine indicate a lower glomerular filtration rate and as a

result a decreased capability of the kidneys to excrete waste products
Measurement of Glomerular Filtration Rate
Normal GFR's for males are about of 150 mL/min per
1.73 m2 and 130 mL/min per 1.73 m2 for females

a. Measuring GFR requires a substance that is not

secreted or reabsorbed at all. Inulin, a polymer of
fructose, is suitable.

b. Inulin filtered by the glomeruli remains in the renal

tubule and appears in the urine; none is reabsorbed,
and the tubule does not secrete it.
c. For this solute, GFR is equal to the renal clearance.
 Measurement of Creatinine
endogeneous compound that is freely filtered at the glomerulus and has
relatively minor absorption and secretion by the renal tubules.

Even though serum creatinine determination remains the most commonly

used renal marker for estimation of GFR, it is known to have a number of
inherent difficulties which limit its clinical reliability.

These include the fact that measurement of GFR by creatinine is influenced

by multiple non-renal factors including diet, gender, muscle mass and
tubular secretion which can result in an overstatement of GFR up to 20%.

Creatinine clearance rate (CCr or CrCl) is the volume of blood plasma that
is cleared of creatinine per unit time and is a useful measure for
approximating the GFR
The GFR is typically recorded in units of volume per time, e.g., milliliters per
minute mL/min. Compare to filtration fraction.
Creatinine clearance and drugs excretion
 Creatinine clearance rate (CCr or CrCl) is the volume of blood that
is cleared of creatinine per unit time.

 CrCl is a useful measure for approximating the GFR because

creatinine is produced from muscle and freely filtered (low MW,
water soluble, and is not protein bound).

 Drugs that are primarily excreted by the kidney

(> 60%) needs dose adjustment.

6/12/2021 BITS, Pilani 61

Estimation of Creatinine Clearance
The Cockcroft-Gault equation for creatinine clearance
estimation

Female: CrCl = 0.85 (140 − age) X body weight

serum creatinine × 72

Male: CrCl = (140 − age) X body weight

serum creatinine × 72

6/12/2021 BITS, Pilani 62

Example: A person has a plasma creatinine concentration of 0.01 mg/ml
and in 1 hour produces 60ml of urine with a creatinine concentration of
1.25 mg/mL.

Estimated creatinine clearance rate (eCCr) using

Cockcroft-Gault formula
Conc. of creatinine can be within the normal range even with a GFR of around 40
mL/min/1.73 m2 resulting in a so called "creatinine blind" range.

National Kidney Disease Education Program has advocated the use of GFR estimates
calculated from serum creatinine levels.

NKDEP Classification
of Kidney Disease
Normal Healthy kidneys GFR > 90 mL/min per 1.73 m2

Stage 1 Kidney damage with normal or elevated GFR GFR > 90 mL/min per 1.73 m2

Stage 2 Kidney damage and mild decrease in GFR GFR of 60 -89 mL/min per 1.73
m2
Stage 3 Moderate decrease in GFR GFR of 30 – 59 mL/min per 1.73 m2

Stage 4 Severe decrease in GFRGFR <16 – 29 mL/min per 1.73 m2

Stage 5 Kidney failure - End Stage Renal Disease (ESRD) GFR of <15 mL/min per
1.73 m2

Severe reduction in GFR (16–29 ml/min/1.73 m2) Preparation for renal

replacement therapy.
 Dialysis is the artificial process of eliminating waste (diffusion)
and unwanted water (ultrafiltration) from the blood

 In patients if failed or damaged kidneys which cannot carry out

the function properly –GFR-less than 30 ml/min, they may need
dialysis

Hemodialysis
 artificially clearing wastes from the blood
1) Dialysis
machine

- efficient

- inconvenient

AV fistula
A surgeon connects an artery to a vein, usually in your arm, to create an AV
fistula.
When the surgeon connects an artery to a vein, the vein grows wider and
thicker, making it easier to place the needles for dialysis.
The AV fistula also has a large diameter that allows your blood to flow out and
back into your body quickly.
The goal is to allow high blood flow so that the largest amount of blood can pass
through the dialyzer.
2) Continuous
ambulatory
peritoneal
dialysis (CAPD)
Dialysis
fluid
- The peritoneal
membrane is a natural
dialysis membrane

- convenient

- less efficient
The Ureters

The ureters are muscular tubes leading from the

renal pelvis to the lower bladder.
 Urinary Bladder
-is a muscular sac, highly distensible and expands superiorly
The inner lining of the urinary bladder is a mucous membrane of transitional
epithelium
2nd layer is composed of connective tissue with elastic fibers, The next layer
is the muscularis called the detrusor muscle,Contraction of this muscle expels
urine from the bladder

-the mucosa has numerous folds

called rugae. The rugae and
transitional epithelium allow the
bladder to expand as it fills.
 The openings of the two ureters and the urethra mark a triangular area
called the trigone, formed by 3 openings in the floor of the urinary
bladder.

 Two of the openings are from the ureters and form the base of the trigone.

 Small flaps of mucosa cover these openings, act as valves that allow urine
to enter the bladder but prevent it from backing up from the bladder

 The 3rd opening, at the apex of the trigone, is the opening into
the urethra.

 A band of the detrusor muscle encircles this opening to form the internal
urethral sphincter.

 When a person urinates, the detrusor muscles contract to squeeze the

urine out of the bladder while the sphincter relaxes to open the opening of
the bladder and urethra
 Bladder disorder/diseases
 Benign hypertrophy of Prostate: - frequent urination at nights and
incomplete bladder emptying due to an enlarged prostate causing
obstruction of bladder emptying- Prazocin

 Cystitis: Inflammation or infection of the bladder -chronic pain,

discomfort, or urinary frequency or hesitancy
- A dipstick test: be used to see if the urine has WBC, or the presence
of nitrates which may indicate an infection

 Overactive bladder: The bladder muscle (detrusor) squeezes

uncontrollably, causing some urine to leak out.

 Hematuria: Blood in the urine-due to infection/cancer

 Dysuria (painful urination): Pain or discomfort during urination due to

infection, irritation, or inflammation of the bladder, urethra, or external
genitals.
The Urethra
- conveys urine from the urinary bladder to the outside
of the body.

Females male
3-4 cm ~18 cm

greater risk of urinary tract infections

-Sexually transmitted disease
 The male urethra has three
regions:

1) prostatic urethra

2) membranous urethra

3) penile urethra.

Difficulty in voiding urine

with enlarged prostate
In both sexes:
- internal urethral sphincter- under involuntary control.
- external urethral sphincter - under voluntary control

internal urethral sphincter

external urethral sphincter

Voiding Urine in infants : micturition reflex

200 ml of urine in bladder, stretch receptors in the wall send impulses to spinal cord.

Parasympathetic signals return to stimulate contraction of the bladder and relaxation

of the internal urethral sphincter.
Once voluntary control has developed, emptying of the bladder is controlled predominantly by
a micturition center in the pons.
This center receives signals from stretch receptors and integrates this information with cortical
input concerning the appropriateness of urinating at the moment.

It sends back impulses to stimulate relaxation of the external sphincter.