Mechanism of Urine Formation.

DR. F. L MASIKA M.D

JANUARY, 2023
 Objectives:
Students are expected to be able to:
Describe Structure and Functions of a Nephron.
List steps in the Production of Urine.
Explain Filtration process and control of
filtration rate.
Explain Tubular reabsorption and control of
tubular reabsorption.
Explain Tubular secretion.
Explain mechanism of Micturition.
 Structure and Functions of Nephron
Kidney Nephrons are the functional units of the
kidneys.
It is the Nephrons that actually perform the
kidney's main functions.
The main function of Nephron is Filtration and
Reabsorption of essential materials.
There are a million Nephrons within each kidney
There are two parts of a kidney nephron:
1. Renal corpuscle.
2. Renal tubule.
Contin…
1.Renal corpuscle
Renal corpuscle is the part of the kidney
nephron in which blood plasma is filtered.
It has two parts:
i. Glomerulus: which is a network of small blood
vessels called capillaries.
ii. Bowman’s capsule: Is the double-walled
epithelial cup within which the glomerulus is
contained.
 Contin….
Glomerulus Contains glomerular capillaries
that are located between:
(A) Afferent arteriole :bringing blood into
the glomerulus.
(B) Efferent arteriole: draining blood
away from the glomerulus.
For filtration to occur, the efferent arteriole
has a smaller diameter than the afferent
arteriole.
 Contin…
This difference in arteriole diameters helps to
raise the blood pressure in the glomerulus.
Bowman’s capsule is the blind expanded end
of a renal tubule.
It’s lined by a simple squamous epithelium on
its outer wall.
The area between the double-walls of the
Bowman's capsule is called the capsular space.
 Contin..
2.Renal tubules
Is the part of the nephron into which the glomerular
filtrate passes after it has reached the Bowman's
capsule.
Portions of the renal tubules are:
Proximal Convoluted tubule.
 Loop of Henle: Descending limb and ascending limb.
Distal convoluted tubule.
Collecting duct.
Function of Renal tubule
 Production of Urine
Nephrons are the functional units of the kidney
because they are the smallest structural
components capable of Producing urine.
Urine formation is a blood cleansing function.
Normal urinary output is 1 L/day to 1.5 L/day.
Urine is formed in three steps:
1. Filtration.
2. Reabsorption.
3. Secretion.
 Filtration Process
Filtration is movement of fluids across the
filtration membrane into the lumen of Bowman’s
capsule as results of pressure difference.
Filtration takes place through the semi
permeable walls of the glomerulus.
The renal blood flow is 1176mls/minute.
The fluid entering the nephron is called the
Filtrate.
The filtrate in the glomerulus is similar to
 Contin…..
Filtrate produced each minute is called the
Glomerular Filtration Rate (GFR) is 125mls/minutes.
Normally, GFR is about 180 L/day and tubular
reabsorption is 178.5 L/day.
 Leaving 1.5 L/day of fluid to be excreted in the
Urine.
The formation of filtrate depend on a pressure
gradient, called the filtration pressure, which forces
fluid from the glomerular capillary across the
filtration membrane into Bowman’s capsule.
 Contin….
The filtration pressure results from the sum of the
forces that move fluid out of the glomerular capillary
into the lumen of Bowman’s capsule.
The glomerular capillary pressure is the blood
pressure inside the capillary, moves fluid out of the
capillary into the Bowman’s capsule.
Opposing the movement of fluid into the lumen of
Bowman’s capsule is the capsule pressure, caused by
the pressure of filtrate already inside Bowman’s
capsule.
 Contin…
The Colloid osmotic pressure within the
glomerular capillary exists because plasma
protein does not pass through the filtration
membrane.
 Osmotic force that favor fluid movement to the
glomerular capillary from Bowman’s capsule.
 Control of Filtration Rate
The kidneys are capable of renal Auto regulation,
through the specialized activities of the
Juxtaglomerular Apparatus.
The Juxtaglomerular apparatus is a microscopic
structure in the kidney, which Regulates the function
of each Nephron.
The juxtaglomerular apparatus is named for its
Proximity to the glomerulus.
This location is critical to its function in regulating
renal blood flow and Glomerular Filtration Rate.
 Contin…
The three cellular components of the apparatus
are:
1. Macula densa cells.
2. Mesangial cells.
3. Juxtaglomerular cells.
 Are modified pericytes of glomerular
arterioles.
 Juxtaglomerular cells.
Juxtaglomerular cells secrete Renin in response
to:
Beta1 adrenergic stimulation.
Decrease in renal perfusion pressure.
Decrease in NaCl absorption in the Macula
Densa.
Decrease in glomerular filtration rate or GFR.
This stimulate Mechanism of Action of Renin-
Angiotensin-Aldosterone.
 Macula Densa Cells
Macula densa cells are columnar epithelium
thickening of the distal tubule.
The macula densa senses Nacl concentration in
the distal tubule.
 Secretes a locally active vasopressor which acts
on the afferent arteriole to decrease glomerular
filtration rate (GFR).
 Contin…
Adenosine vasoconstricts the afferent arteriole
via A1 receptors and vasodilates efferent
arterioles via A2 receptors which decreases
GFR.
When macula densa cells detect higher
concentrations of Na and Cl they inhibit Nitric
Oxide (decreasing renin release) o A decrease in
GFR means less solute in the tubular lumen
 Mesangial cells
Mesangial cells are structural cells in the
glomerulus.
Under normal conditions serve as anchors for the
glomerular capillaries.
 The mesangial cells within the glomerulus
communicate with mesangial cells outside the
glomerulus (extraglomerular mesangial cells).
 Tubular Reabsorption
It is the process by which certain substances that are
required by the body ( Glucose, Amino acids,
Vitamins and Water) are Reabsorbed.
As only certain substances are reabsorbed, it is
known as Selective reabsorption.
Selective reabsorption takes place in the Proximal
Convoluted Tubule of the kidney.
In this way, many useful solutes salts and water that
have passed, return in the circulation.
 Contin…
Solutes are reabsorbed Isotonically , in that the
osmotic potential of the fluid leaving the proximal
tubule is the same as that of the initial glomerular
filtrate.
About 65 per cent of the filtered load of Sodium,
Water and Chloride are reabsorbed by the Proximal
tubule.
However, glucose, amino acids, inorganic phosphate,
and some other solutes are reabsorbed via Secondary
Active Transport.
 Contin….
Loop of Henle is highly permeable to water and
moderately permeable to most solutes, including
Urea and Sodium.
About 20 per cent of the filtered water is reabsorbed
in the Loop of Henle.
 It is essential to maintain a precise balance between
tubular reabsorption and glomerular filtration.
There are multiple nervous, hormonal, and local
control mechanisms that regulate tubular
reabsorption.
 Control of Tubular Reabsorption
Hormones That Regulate Tubular Reabsorption:
1.Aldosterone:
Increases Sodium Reabsorption and Increases
Potassium Secretion.
Activation of the sympathetic nervous system can
decrease sodium and water excretion by constricting
the renal arterioles thereby reducing GFR.
Sympathetic activation also increases sodium
reabsorption in the proximal tubule.
 Contin…
2. Antidiuretic Hormone
 Is a powerful feedback system for regulating
Plasma Osmolarity and Sodium concentration.
When osmolarity of the body fluids increases
above normal,
The posterior Pituitary gland secretes more
ADH,
Which increases the permeability of the distal
tubules and collecting ducts to water.
 Contin….
This allows large amounts of water to be reabsorbed
and decreases urine volume.
When there is excess water in the body and
extracellular fluid osmolarity is reduced.
The secretion of ADH by the posterior pituitary
decreases.
 Thereby reducing the permeability of the distal
tubule and collecting ducts to water.
Contin…
Which causes large amounts of
dilute urine to be excreted.
 Thus, the rate of ADH secretion
determines, to a large extent, whether
the kidney excretes a dilute or
concentrated urine.
 Tubular Secretion
• Tubular secretion is the transfer of materials
from peritubular capillaries to the renal tubular
lumen.
• Glomerular filtrate enters the renal tubules, it flows:
i. Proximal tubule.
ii. Loop of Henle.
iii. Distal tubule.
iv. Collecting tubule.
• Finally, the collecting duct-before it is excreted as
 Composition of Urine
Normal urine is clear and amber in colour due to
the presence of urobilin.
The specific gravity is between 1020 and 1030.
pH is around 6 (normal range of 4.5 to 8).
The healthy adult passes 1000-1500mls per day.
Composition;
 Water 96%, urea 2% and others like Ammonia,
Potassium ,Sodium 2%
 Mechanism of Micturition
Urination, also known as Micturition, voiding,
peeing, or emiction:is the process of disposing of
urine from the urinary bladder through the urethra
to the outside of the body.
 In healthy humans the process of urination is
under voluntary control.
 In infants, elderly individuals and those with
neurological injury, urination may occur as an
involuntary reflex.
Contin…
Physiologically, micturition involves
coordination between the central, autonomic
and somatic nervous systems.
Brain centers that regulate urination
include the pontine micturition center,
periaqueductal gray, and the cerebral
cortex.
 Contin…
In healthy individuals, the lower urinary tract
has two discrete phases of activity:
1. Storage phase: when urine is stored in the
bladder.
2. Voiding phase: when urine is released through
the urethra.
At low bladder volumes: Afferent firing is low,
resulting in Excitation of the Sphincter and
Urethra and Relaxation of the Bladder.
 Contin…
At high bladder volumes: Afferent firing
increases, causing a conscious sensation of
urinary urge.
When the individual is ready to urinate,
consciously initiates voiding, causing the
bladder to contract and the outlet to relax.
Voiding continues until the bladder empties
completely, at which point the bladder relaxes
and the outlet contracts to re-initiate storage.
 Contin…
The muscles controlling micturition are
controlled by the Autonomic and Somatic
nervous systems.
During the Storage phase the Internal urethral
sphincter remains tense and the Detrusor muscle
relaxed by Sympathetic stimulation.
During Voiding phase, the detrusor muscle
contract and the internal urethral sphincter
relax by Parasympathetic stimulation.
 Contin
The external urethral sphincter is under
somatic control and is consciously relaxed
during micturition.
The impulses are sent to the spinal cord is
modified by centres in the cerebral cortex.
 In the adult, the volume of urine in the
bladder that normally initiates a reflex
contraction is about 300-400 ml.
 Contin…
The impulses from the brain cortex are sent
back as efferent nerve impulse to the sacral
region of the spinal cord
 Then to the external urinary sphincter
muscles, which relaxes and thus urine flow from
the bladder to urethra.
Injury to any of these leads to involuntary
micturition (Incontinence).
Urinary Bladder
 Volumetric of Urine
The amount of urine produced depends on:
State of hydration.
Activities.
Invironmental factors. e.g Temperature.
Age.
Health of Individual.
 Contin…
Polyuria is a condition of excessive production
of urine more than 2.5 L/day.
Oliguria where less than 400 mL are produced
per day.
Anuria with a production of less than 100 mL
per day.
 Pollakiuria is defined as an abnormal
urination frequency.
 Molecules absent in normal Urine

Carbohydrates
Proteins
Blood
Bile salts
Fats
References
 Guyton and Hall textbook of medical
th
physiology 13 edition 2015
 Ross and Wilson Anatomy and
Physiology in health in health and illness
13th edition 2018
 Essentials of medical physiology
Sembulingam 6th edition in 2012