RENAL PHYSIOLOGY

 INTRODUCTION: Body Tissues are constantly involved in metabolic activities that produce several
waste products e.g. undigested food materials, heavy metals, toxins, pathogenic organisms, etc. in
order for the body to remain healthy, these substances have to be excreted. The digestive system
excrete food residues in faeces, the skin excretes water and salts in sweat, the liver excretes toxins
and bile pigments in bile while the renal system serves as the principal screening system which helps
to filter metabolic waste products from the plasma and excrete them in urine, thereby maintaining
homeostasis.

 FUNCTIONS OF THE KIDNEY:

1. Homeostatic function: The kidneys play a great role in maintenance of the fairly constant
internal environment by;

(a) Excretion of waste products: Waste products of metabolism such as urea and creatinine and
toxins are excreted in urine.

(b) Maintenance of water balance: The kidneys either conserves or excretes water as the body
demands.

(c) Maintenance of electrolyte balance: The kidneys retains sodium when the osmolarity is low
and excretes it when the osmolarity is high.

(d) Maintenance of acid-base balance: The kidneys eliminate excess acids from the body
thereby preventing occurrence of acidosis.

2. Hemopoietic function: Kidneys stimulate the production of erythrocytes by secreting

erythropoietin and thrombocyte production by secreting thrombopoietin.
3. Endocrine function: apart from erythropoietin and thrombopoietin, the kidney secretes other
hormones such as prostaglandins and renin.
4. Regulation of arterial blood pressure: The kidney is involved in long-term regulation of arterial
blood pressure by either regulating the volume of ECF or through the renin-angiotensin system.
5. Regulation of blood calcium level: The kidney does this by activating 1, 25-
dihydroxycholecalciferol into vitamin D which is required for calcium absorption from the
intestine.

 GROSS STRUCTURE OF THE URINARY SYSTEM: Macroscopically, the renal or urinary system is made
up of a pair of bean-shaped organs known as the kidneys. Urine produced by the kidneys is conveyed
by long ducts known as the ureters to the urinary bladder which stores it until it is ready for voiding.
The urethra arises from the urinary bladder and opens to the exterior. The urethra in females is
shorter than in males. The male urethra serves the dual function of providing both a route for
eliminating urine from the bladder and a passageway for semen from the reproductive organs.
 Fig 1: The urinary system.

 MACROSCOPIC AND MICROSCOPIC STRUCTURE OF THE KIDNEYS: the kidneys lie in the abdominal
cavity, on either side of the vertebral column below the diaphragm and the liver. Each adult kidney
weighs about 160g and is about 11cm long and 5-7cm wide. A longitudinal section of the kidney
shows two distinct regions: The outer cortex which is reddish brown and granular in appearance
because of its many capillaries and the inner medulla that is striped in appearance due to the
presence of microscopic tubules and blood vessels. The medulla is composed of 8 to 15 conical renal
pyramids separated by renal columns. Each pyramid projects into a small depression called a minor
calyx. Several minor calyces unite to form a major calyx. The major calyces then join to form the
funnel-shaped renal pelvis. The renal pelvis collects urine from the calyces and transports it to the
ureters and urinary bladder.

Fig 2: Longitudinal section of the Kidney.

Microscopically, each renal pyramid contains numerous specialized structures known as nephrons.
Hence, each kidney consists of about 1 million nephrons, which are bound together by connective
tissues.
Since the main function of the kidneys is to produce urine thereby maintaining constancy in the ECF
composition, a nephron is the smallest structural and functional unit of the kidney.
 Structure of the nephron
Structurally, the nephron can be divided into two portions: the renal (malpighian) corpuscle and
the renal tubule. The renal corpuscle is made up a bulb-like tuft of capillaries known as the
glomerulus which is enclosed within the Bowman’s capsule. The glomerulus consists of
glomerular capillaries interposed between afferent arteriole on one end and efferent arteriole
on the other end. Glomerular capillaries arise from the afferent arteriole (a division of the renal
artery). After entering the Bowman capsule, the afferent arteriole divides into 4 or 5 large
capillaries. Each large capillary subdivides into many small capillaries. These small capillaries are
arranged in irregular loops that finally reunite to form the efferent arteriole, which leaves the
Bowman capsule. Blood not filtered into the tubular portion leaves the glomerulus through the
efferent arteriole. The efferent arteriole subdivides into peritubular capillaries that are
intertwined around the tubular system, which supply the renal tissue with blood. The
peritubular capillaries rejoin to form venules that drain into the renal vein through which blood
leaves the kidney.
The renal tubule runs from the Bowman’s capsule to the renal pelvis. It is formed by a single
layer of epithelial cells. It is further subdivided into three: Proximal convoluted tubule, Loop of
Henle and the distal convoluted tubule.
i. Proximal convoluted tubule: Proximal convoluted tubule is the coiled portion arising
from Bowman capsule. It is situated in the cortex. It continues as descending limb of
loop of Henle. The wall of the proximal convoluted tubule consists of a single layer of
cuboidal cells containing millions of microvilli; these microvilli increase the surface area
for reabsorption.

Fig 3: Structure of the nephron

 ii. Loop of Henle: Fluid passes from the proximal convoluted tubule to the loop of Henle.
This fluid is carried into the medulla in the descending limb of the loop and returns to
the cortex in the ascending limb of the loop.
iii. Distal convoluted tubule is the continuation of ascending limb of the loop and occupies
the cortex of kidney. It is continued as collecting duct. The distal convoluted tubule is
shorter than the proximal tubule and has relatively few microvilli.
A collecting duct receives fluid from the distal convoluted tubules of several nephrons.
Fluid is then drained by the collecting duct from the cortex to the medulla as the collecting
duct passes through a renal pyramid. This fluid, now called urine, passes into a minor calyx.
Urine is then funneled through the renal pelvis and out of the kidney in the ureter.

Fig 4: Parts of a nephron.

 Types of nephron: Nephrons are classified into two based on their position in the kidney and
the length of Henle’s Loop.
(a) Cortical nephrons or superficial nephrons: Nephrons having the corpuscles in outer cortex
of the kidney near the periphery. In human kidneys, 85% nephrons are cortical nephrons.
(b) Juxtamedullary nephrons: they are nephrons that have their corpuscle in the inner cortex.
Their loop of Henle goes deep into the medulla. These nephrons play a significant role in
urine concentration.
 RENAL BLOOD VESSELS: Arterial blood enters the kidney through the renal artery, which divides
into interlobar arteries. Arcuate arteries branch from the interlobar arteries at the boundary of
the cortex and medulla. A number of interlobular arteries radiate from the arcuate arteries into
the cortex and subdivide into numerous afferent arterioles. The afferent arterioles deliver blood
into glomeruli capillary networks that produce a blood filtrate that enters the urinary tubules.
The blood remaining in a glomerulus leaves through an efferent arteriole, which delivers the
blood into another capillary network—the peritubular capillaries surrounding the renal tubules.
Blood from the peritubular capillaries flow through the interlobular, arcuate and interlobal veins
into the renal vein that empties into the inferior vena cava.
 THE JUXTAGLOMERULAR APPARATUS (JGA):
 Definition: the JGA is a specialized structure near the glomerulus of a nephron. It is
made up of the macula densa, extraglomerula mesangial cells and the JG cells.
i. Macula densa: it is situated between the afferent and efferent arterioles.
ii. Extraglomerula mesangial cells (lacis cells) are situated in the triangular region
bound by afferent and efferent arteriole plus the macula densa.
 iii. Juxtaglomerular cells: they are situated in the wall of afferent arteriole before it
enters the Bowman’s capsule.

Fig 5: The Juxtaglomerular apparatus

Fig 6: Scheme of renal blood flow.

  Function: the major role of JGA is secretion of hormones namely: Renin and
prostaglandins.
Renin with angiotensin and aldosterone form the Renin Angiotensin Aldosterone System
which regulates arterial blood pressure. Secretion of renin is stimulated by: fall in
arterial blood pressure or decrease in Extracellular fluid volume. Once released, renin
activates angiotensinogen (a plasma protein) into angiotensin I. Angiotensin I is
converted to angiotensin II in the presence of Angiotensin Convertase/Angiotensin
Converting Enzyme from the lungs. Ag II acts on:
i. Blood vessels to cause vasoconstriction thereby increasing ABP
ii. Post ganglionic sympathetic fibres to trigger release of noradrenaline which in
turn causes vasoconstriction.
iii. The adrenal gland to secrete aldosterone which facilitates sodium retention.
iv. The hypothalamus to increase ADH secretion.
 URINE FORMATION PROCESS: the kidneys receive about 25% of the cardiac output (about
1300ml) per day. It excretes unwanted substances and water in urine leading to production of
about 1-1.5L of urine per day.
Blood received by the kidneys is filtered into Bowman’s capsule by the glomerular capillaries in a
process known as glomerular filtration. Glomerular filtrate passes down the tubular portion of
the nephron to allow reabsorption of vital substances such as glucose, amino acids, water,
electrolytes in a process known as tubular reabsorption while unwanted substances are
secreted into the tubule from the peritubular capillaries through tubular secretion.
(a) Glomerular filtration: it is the first step of urine formation which involves filtration of
protein free plasma into the Bowman’s capsule. Average of 125mL of glomerular filtrate
is formed by all glomeruli per minute which amounts to 180L per day.
 The glomerular membrane: this is the structure that is well suited for filtration. It is
made up of; glomerular capillary wall which consists of a single layer of endothelial
cells with filtration pores, the basement membrane situated between the
glomerulus and the Bowman’s capsule and the visceral layer of Bowman’s capsule
made up of podocytes that interdigitate to form filtration slits.
 Glomerular filtration pressure: the forces involved in glomerular filtration include:
glomerular capillary blood pressure, plasma colloid osmotic pressure and Bowman’s
capsule hydrostatic pressure.
i. GCP is the pressure exerted by blood within the glomerular capillaries. It is
about 55mmHg and favour filtration.
ii. PCOP is pressure build up due to presence of plasma proteins. It is about
30mmHg and opposes filtration.
iii. BCHP is exerted by fluid in the Bowman’s capsule. It is about 15mmHgand
opposes filtration.
In order for filtration to occur, sum of supporting forces must be greater than the sum of opposing
forces. Hence, net filtration pressure is obtained as sum of supporting – sum of opposing forces i.e.
55 – (30+15) = 10mmHg. Hence, filtration is favoured.
(b) Tubular reabsorption: Although the kidney filters about 180L per day, it does not
excrete all filtered substances in urine. Hence, the kidneys reabsorb certain substances
in the appropriate quantity necessary for maintaining homeostasis. The tubules
reabsorb 99% of filtered water, 100% of filtered sugar and 99.5% of filtered salt.
(c) Tubular Secretion: it is the process by which substances are transported from the blood
into renal tubules. Examples of substances secreted are: hydrogen ions, potassium ions,
urea etc.
  URINE CONCENTRATION PROCESS:
(a) Role of ADH: ADH is released from the anterior pituitary gland in response to decrease
in ECF volume. Once released, it binds its receptors on the cells of Distal Convoluted
Tubule to activate specialized water channels known as aquaporin. Aquaporin is
involved in passive transport of water from the DCT into the interstitium by a process
known as facultative water reabsorption.
(b) Role of the countercurrent system: in order for concentrated urine to be formed, there
has to be establishment of medullary osmotic gradient. This gradient serves as the
driving force for water reabsorption from the renal tubules. Cortical interstitial fluid is
isotonic to plasma with the osmolarity of 300mOsm/L. this is also the osmolarity of
glomerular filtrate. However, osmolarity increases as the nephron runs from the cortex
into the medulla reaching about 1200mOsm/L.
The counter current system is a system of U-shaped tubes that is involved in the
development and maintenance of medullary osmotic gradient. It is formed by the
descending and ascending limbs of Henle’s loop and vasa recta.

 The descending limb is permeable to water but not sodium.

 The ascending limb is impermeable to water but actively transports sodium out of the
tubular lumen into the interstitial fluid.

Fig 7: Counter current multiplier.

The CCS is made up of the countercurrent multiplier (CCM) and the countercurrent exchanger (CCE).
 i. CCM: it comprises of the two limbs of Henle’s Loop that are in constant
interaction. It helps to create the medullary osmotic gradient required for water
reabsorption to occur as follows:
 Fluid reaching the ascending limb is isotonic to plasma (300mOsm/L).
 Ascending limb actively pumps out sodium chloride into the interstitium.
 Interstitial fluid becomes slightly hypertonic due to the presence of Nacl.
 Hyper tonicity of interstitial fluid causes flow of water from the descending limb into the
interstitium.
 Filtrate within the tubules become slightly hypertonic on getting to the ascending limb.
 Increase in Nacl load in the ascending limb causes more Nacl to be further pumped out
into the interstitium.
 Concentration of interstitial fluid is raised causing more water to be drawn out of the
descending limb via osmosis.
 Concentration of filtrate further increases.
 Steps are repeated until maximum concentration is reached.
ii. CCE: the CCE helps to maintain the medullary osmotic gradient established by the
CCM. It is constituted by the vasa recta (U-shaped long thin-walled vessels lying
parallel to the Henle’s Loop).
The vasa recta is permeable to water, Nacl and urea but not plasma proteins.
Hence, the colloid osmotic pressure is higher in the vasa recta than interstitium.
This causes movement of water from the interstitium into the vasa recta.
Therefore, vasa recta maintains medullary osmotic gradient by helping to remove
water from the renal medulla.

Fig 8: Counter Current Exchanger

 MICTURITION: this is the process by which urine is voided from the urinary bladder. It can also
be referred to as urination. Of 180L of plasma filtered per day, about 1.5L of urine is excreted
(Excess urine is expelled in Diabetes insipidus).
The bladder is a large capacity storage organ that holds urine formed by the kidneys. Transfer of
urine from the urinary bladder into the urethra is controlled by the opening of the urethral
sphincters. Internal urethral sphincter (a ring of smooth muscles under involuntary control)
opens when the bladder contracts to allow flow of urine into the urethra while the external
urethral sphincter (under somatic control) has to be opened to allow voiding of urine to the
exterior.
Micturition reflex:
i. Buildup of urine to about 400ml within the bladder activates stretch receptors.
ii. Afferent fibres from stretch receptors convey impulses to the spinal cord.
iii. Parasympathetic supply to the bladder is stimulated while the motor neuron to the
external sphincter is inhibited.
iv. Parasympathetic stimulation to the bladder causes it to contract thereby opening the
internal urethral sphincter.
v. Inhibition of the motor neuron to external sphincter causes it to relax.
vi. Urine is expelled.
However, the process of micturition is voluntarily controlled by the cerebral cortex in
adults thereby allowing an individual to have influence on micturition timing by
voluntarily tightening the external urethral sphincter.

Urinary Incontinence: Occurs when the voluntary control to micturition is lost as in

spinal cord injury.