RENAL PHYSIOLOGY

The Renal system consist of:

• Kidneys
• Ureters
• Urinary Bladder
• Urethra
The Kidney
A retroperitoneal organ
T11-L3
Normal size: 11-15cm in adults.
 protected by the ribcage.
Right kidney usually shorter than the left (upper
limit of variation in length between right & left 1.5
cm)
The Nephron
Most basic microscopic structures of the kidneys

Insideeach kidney, there are about 1 million

nephrons

Physiological unit of the kidney used for filtration

of blood, reabsorption and secretion of materials
The Kidney Nephron
The Nephron
Locations for filtration,
reabsorption, secretion &
excretion
Nephron Function
Nephrons filter blood and then reabsorb useful materials
from the filtrate before eliminating the remainder as urine
This process occurs over three key stages:
• Ultrafiltration – Blood is filtered out of the glomerulus at the
Bowman’s capsule to form filtrate
• Selective reabsorption – Usable materials are reabsorbed in
convoluted tubules (both proximal and distal)
• Osmoregulation – The loop of Henle establishes a salt
gradient, which draws water out of the collecting duct
 Nephron structures and
functions
Afferent Arteriole
Transport arterial blood to glomerulus for
filtration

Efferent Arteriole
Transports filtered blood from glomerulus through
the peritubular capillaries and the vasa recta, and
to the kidney venous system
Glomerulus
• It is a network of capillaries surrounded by Bowman’s
capsule
• The site for blood filtration
• Nonspecific filtration - removes both useful and non-
useful material
• the product of the glomerulus – filtrate (primary
urine/capsular urine)

Bowman’s Capsule
• A sac that encloses glomerulus
• transfers filtrate from the glomerulus
• to the Proximal Convoluted Tubule
Ultrafiltration
Ultrafiltration is the process whereby blood plasma is
selectively filtered at the glomerulus to produce the
primary urine.
Ultrafiltration
Blood is filtered by a mesh called the basement membrane, which lies between the
glomerulus and Bowman’s capsule

Glomerular blood vessels are fenestrated (have pores) which means blood can freely exit
the glomerulus
The podocytes of the Bowman’s capsule have gaps between their pedicels, allowing for
fluid to move freely into the nephron
Consequently, the basement membrane functions as the sole filtration barrier within the
nephron

The basement membrane is size-selective and restricts the passage of blood cells and
large proteins
Hence when the blood is filtered, the filtrate formed does not contain any blood cells,
platelets or plasma proteins
Ultrafiltration
Hydrostatic Pressure

Ultrafiltration involves blood being forced at high pressure against the basement
membrane, optimising filtration

This high hydrostatic pressure is created in the glomerulus by having a wide afferent
arteriole and a narrow efferent arteriole
This means it is easy for blood to enter the glomerulus, but difficult for it to exit –
increasing pressure within the glomerulus
Additionally, the glomerulus forms extensive narrow branches, which increases the
surface area available for filtration
The net pressure gradient within the glomerulus forces blood to move into the capsule
space (forming filtrate)
Ultrafiltration
Proximal Convoluted Tubule
(PCT)
A thick, constantly active segment of the nephron

that reabsorbs most of the useful substances of

the filtrate: sodium (65%), water (65%),
bicarbonate (90%), chloride (50%), glucose
(nearly 100%)

The primary site for secretion (elimination) of

drugs, waste and hydrogen ions.
Selective Reabsorption
Selective reabsorption is the second of the three processes by which blood is filtered and
urine is formed
It involves the reuptake of useful substances from the filtrate and occurs in the
convoluted tubules (proximal and distal)

The majority of selective reabsorption occurs in the proximal convoluted tubule, which
extends from the Bowman’s capsule
The proximal convoluted tubule has a microvilli cell lining to increase the surface area for
material absorption from the filtrate
The tubule is a single cell thick and connected by tight junctions, which function to create
a thin tubular surface with no gaps

There are also a large number of mitochondria within these tubule cells, as reabsorption
involves active transport
Substances are actively transported across the apical membrane (membrane of tubule
cells facing the tubular lumen)
Substances then passively diffuse across the basolateral membrane (membrane of tubule
cells facing the blood)
Selective Reabsorption
Selective Reabsorption
The tubules reabsorb all glucose, amino acids, vitamins
and hormones, along with most of the mineral ions
(~80%) and water

Mineral ions and vitamins are actively transported by

protein pumps and carrier proteins respectively
Glucose and amino acids are co-transported across the
apical membrane with sodium (symport)
Water follows the movement of the mineral ions
passively via osmosis
The Loop of Henle
U-shaped tube that consists of a descending limb
and an ascending limb.

begins in the cortex, receiving filtrate from the

PCT, extends into the medulla, and then returns
to the cortex to empty into the distal convoluted
tubule(DCT).
Its primary role is to concentrate urine and
conserve water and sodium chloride from the
filtrate, creating a hypertonic interstitium in the
medulla.
Osmoregulation
Osmoregulation is the control of the water balance of the
blood, tissue or cytoplasm of a living organism

Osmoregulation occurs in the medulla of the kidney and

involves two key events:

The loop of Henle establishes a salt gradient

(hypertonicity) in the medulla
Anti-diuretic hormone (ADH) regulates the level of water
reabsorption in the collecting duct
Osmoregulation
Establishing a Salt Gradient

The function of the loop of Henle is to create a high solute (hypertonic)

concentration in the tissue fluid of the medulla
The descending limb of the loop of Henle is permeable to water but not salts
The ascending limb of the loop of Henle is permeable to salts but not water
This means that as the loop descends into the medulla, the interstitial fluid
becomes more salty and hypertonic
Additionally, the vasa recta blood network that surrounds the loop of Henle
flows in the opposite direction (counter-current)
This means that salts released from the ascending limb are drawn down into
the medulla, further establishing a salt gradient
Osmoregulation
Water Reabsorption
As the collecting duct passes through the medulla, the hypertonic conditions of the
medulla will draw water out by osmosis
The amount of water released from the collecting ducts to be retained by the body is
controlled by anti-diuretic hormone (ADH)
ADH is released from the posterior pituitary in response to dehydration (detected by
osmoreceptors in the hypothalamus)
ADH increases the permeability of the collecting duct to water, by upregulating
production of aquaporins (water channels)
This means less water remains in the filtrate, urine becomes concentrated and the
individual urinates less (i.e. anti-diuresis)
When an individual is suitably hydrated, ADH levels decrease and less water is
reabsorbed (resulting in more dilute urine)
Remember: ADH is produced when you Are DeHydrated
Water Reabsorption
Distal Convoluted Tubules (DCT)
• Similar to the proximal convoluted tubule (PCT), the
DCT is composed of simple cuboidal epithelium but has
very few microvilli
• Reabsorption and secretion still occur in the DCT, albeit
to a lesser degree than in the PCT. The DCT selectively
reabsorbs ions such as sodium, chloride and calcium
from the tubular fluid, while potassium is secreted. The
DCT also regulates pH levels by reabsorbing
bicarbonate and secreting hydrogen ions.
Peritubular Capillaries
Transport reabsorbed materials from the PCT and
DCT into kidney veins and eventually back into the
general circulation.

Help complete the conservation process

(reabsorption) that takes place in the kidney
 Juxtaglomerular apparatus

• The juxtaglomerular apparatus (JGA) is a specialized region of the

nephron formed by three different types of cells:
• macula densa, juxtaglomerular granular, and extraglomerular
mesangial (Lacis) cells.
• The tightly packed macula densa is situated at the transition between
the ascending limb of the nephron loop and the distal tubule, where it
comes into contact with the juxtaglomerular granular cells, which are
modified smooth muscle cells in the afferent (and sometimes efferent)
arteriole.
• Enclosed in the triangular space between the afferent and efferent
arteriole and the macula densa of the distal tubule are the
extraglomerular mesangial cells.

• The JGA functions to regulate systemic blood pressure and glomerular

blood flow and filtration rate via RAAS (renin-angiotensin-aldosterone
system)
Juxtaglomerular apparatus
RAAS (renin-angiotensin-aldosterone
system)
Urine Formation
The main processes of Urine
formation are:

• Glomerular Filtration

• Tubular Reabsorption

• Tubular Secretion
1. Glomerular filtration

• This takes place in the renal corpuscle.

• Blood pressure forces water and solutes (e.g.,
glucose, amino acids, electrolytes, urea) through
the glomerular capillaries into Bowman’s capsule,
forming the glomerular filtrate (also called primary
urine).
• Primary Urine Volume: The volume of glomerular
filtrate formed per day is about 180 liters in an
average adult.
 2. Tubular Reabsorption

• This is the process of selectively moving substances from

the filtrate back into the blood.
• Mainly in the proximal convoluted tubule (PCT), loop of
Henle, distal convoluted tubule (DCT), and collecting
ducts.
• Essential substances (e.g., glucose, amino acids,
sodium, water) are reabsorbed from the filtrate into the
blood via active and passive transport mechanisms.
3. Tubular secretion

• This is the process of selectively moving substances

from the blood into the filtrate.
• Primarily in the distal convoluted tubule (DCT) and collecting
duct.

• Additional waste products (e.g., hydrogen ions, potassium,

drugs, toxins) are secreted from the blood into the tubular
fluid.
Urine Concentration and Excretion
• The amount of water reabsorbed depends on the
body's hydration status and the action of hormones like
antidiuretic hormone (ADH) and aldosterone.
• After reabsorption and secretion, about 1.5 to 2 liters of
urine is excreted daily.
Summary of Urine Volumes:
• Primary Urine Volume (Glomerular Filtrate): ~180
liters/day
• Secondary Urine Volume (Final Urine Output): ~1.5 to 2
liters/day
 Glomerular Filtration Rate (GFR)
• The GFR is the measurement of volume filtered through the
glomerular capillaries and into the Bowman's capsule per unit of
time.
• The gold standard measurement of GFR involves the injection of
inulin and the subsequent measurement of its clearance by the
kidneys.
• However, the use of inulin is invasive, time-consuming, and
expensive. Alternatively, the biochemical marker creatinine found in
serum and urine is commonly used to estimate GFR (eGFR)
• Creatinine is a breakdown product of dietary meat and creatine
phosphate found in skeletal muscle.
• Creatinine is not eliminated extra-renally, and under steady-state
conditions, urinary excretion equals creatine production, regardless
of the serum creatinine concentration, the glomerulus freely filters
creatinine.
Glomerular Filtration Rate (GFR)
 Normal GFR
• The GFR in an average-sized normal man is
approximately 125ml/min.
• It is about 10% lower in women.
• Its magnitude correlates with surface area.
 Regulation of Glomerular
Filtration

• 1. Intrinsic Controls

• 2. Extrinsic Controls
 Intrinsic Controls: Renal Autoregulation

• Renal autoregulation is the process by which the

kidney adjusts its own resistance to blood flow.
• This helps the kidneys to maintain a nearly constant
GFR despite fluctuations in systemic arterial pressure.

• The 2 mechanisms used for renal autoregulation are;

• (i) Myogenic Mechanism

• (ii) Tubuloglomerular feedback mechanism

 Myogenic Mechanism
• The vascular smooth muscles in the walls of the
arterioles constrict when there is an increase in
systemic blood pressure.
• this constriction limits the blood flow into the
glomerulus and keeps the GFR at a normal level.

• Conversely a falling systemic blood pressure causes

dilation of afferent arterioles and raises the
glomerular hydrostatic pressure
 Tubuloglomerular Feedback
Mechanism
• This is directed by the macula densa cells of the
juxtaglomerular complex.

• These cells are in the ascending limb of the nephron

loop.

• They respond to filtrate NaCl concentration.

Tubuloglomerular Feedback
Mechanism
• When the filtrate NaCl concentration is high, the macula
densa cells release vasoconstrictor chemicals.

• This causes intense constriction of the afferent arteriole

and reduces blood flow into the glomerulus.
 Tubuloglomerular Feedback
Mechanism
• The reduction in blood flow reduces the GFR and
allows more time for NaCl reabsorption.

• In contrast, low NaCl concentration inhibits the

macula densa cells, causing vasodilation of the
afferent arterioles.

• This allows more blood to flow into the glomerulus

and increases the GFR.
Extrinsic Controls: Neural and
Hormonal Mechanisms
• The extrinsic controls regulate the GFR by
maintaining systemic blood pressure.

• They include;

• (i) Sympathetic Nervous Controls

• (ii) Renin-Angiotensin- Aldosterone Mechanism

Sympathetic Nervous system
• When blood pressure falls, Norepinephrine is
released by the sympathetic nerve fibres as well as
Epinephrine released by the adrenal medulla.

• These cause constriction of vascular smooth

muscles, increases peripheral resistance and brings
blood pressure back to normal.

• The afferent arterioles also constrict and helps

restore blood volume and pressure back to normal.
Renin-Angiotensin-Aldosterone Mechanism

• This is the body’s main mechanism for increasing

blood pressure.

• Low blood pressure stimulate cells of the JG

complex to release Renin.

• Renin splits Angiotensinogen into Angiotensin I.

• Angiotensin is converted into Angiotensin II which

is a vasoconstrictor.
•THANK YOU 