Lecture 1

Overview of Renal Function

 The kidneys are both excretory and regulatory organs. By excreting water and solutes, the
kidneys rid the body of excess water and waste products.
 They also regulate the volume and composition of the body fluids within a very narrow
range, despite wide variations in the intake of food and water.
 Because of the kidney's homeostatic functions, the tissues and cells of the body are able to
carry out their normal functions in a relatively constant environment.
 Thus, the kidneys have several major regulatory functions, which include:

1. Regulation of water and electrolyte balance:

For regulation of homeostasis, excretion of water and electrolytes must be precisely
matched to intake.

2. Excretion of metabolic waste products:

The kidneys are the primary means for eliminating waste products of metabolism. These
products include urea, uric acid, creatinine, metabolites of various hormones and
bilirubin.

3. Excretion of foreign chemicals, e.g. drugs, food additives and pesticides.

4. Endocrine functions of the kidney:
a) Regulation of erythrocyte production:
The kidneys secrete erythropoietin hormone, which stimulates the production of
R.B.Cs. The kidneys account for almost all the erythropoietin secreted into the
circulation. Severe anaemia develops in people with severe kidney disease as a result
of decreased erythropoietin production.
b) Regulation of 1,25-Dihydroxy vit. D3 production:
The kidneys produce the active form of vitamin D: 1,25-dihydroxycholecalciferol by
hydroxylating this vitamin at the number "1" position. Active vitamin D plays an
important role in calcium and phosphate homeostasis.
c) Renin secretion.
5. Regulation of arterial blood pressure:
I. Short-term regulation: renin-angiotensin aldosterone system.
II. Long-term regulation: through excreting variable amounts of sodium and water.
6. Regulation of acid-base balance by:
a) Elimination of acids produced from the metabolism of proteins such as sulphuric and
phosphoric acid.
b) Regulation of the buffer stores in the body.
7. Gluconeogenesis:
The kidneys synthesize glucose from amino acids during prolonged fasting and add it to
the blood. This helps to maintain blood glucose concentration.
8. Secretion of prostaglandins (PGE2, PGl2) and bradykinins.
These act as paracrine hormones that play important role in regulation of the renal blood
flow.
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Nephron as a functional Unit:
The functional unit of the kidney is the nephron. There are approximately 1.3 million
nephrons in each human kidney. Each nephron is capable of forming urine, i.e. acts as a
functional unit. The parts of the nephron are shown in Fig. (1).

Figure (1): The main histologic features of the cells that make up each portion of the tubules.

Each nephron is composed of:

1. GIomerulus:
 It is formed of a tuft of capillaries (glomerular capillaries) contained within the dilated
blind end of the renal tubule known as (Bowman's capsule).
 The capillaries are supplied by an afferent arteriole and drained by a smaller efferent
arteriole.

 The glomrulus is a high pressure capillary bed, the hydrosatic pressure in glomerular
capillaries'is 60 mmHg.
2. Renal tubule:
 It is a thin tube, which is subdivided into functionally and morphologically distinct
segments:

a) Proximal Convoluted Tubule: It is about 15 mm long that lies in the cortex. The wall
of the proximal convoluted tubule is made up of a single layer of cells that are united
by apical tight junction. Between the bases of the cells, there are extensions of the
extracellular space called the lateral intercellular space. The luminal edges of the cells
have a brush border due to the presence of many microvilli (Fig. 1)

b) Loop of Henle: It is a U - shaped extension of the proximal convoluted tubule that dips
in the renal medulla. Each loop consists of:
i) Descending limb.
ii) Ascending limb.

The walls of the descending limb and the lower half of the ascending limb are thin
and therefore are called the thin segment of the loop of Henle. After the ascending
limb of the loop has returned part of its way back to the cortex, its wall becomes
thick. The thin segment of the loop of Henle has an epithelium made up of
attenuated flat cells. The thick ascending limb of the loop of Henle is lined by
cuboidal cells with extensive invaginations of the basilar portion.
c) The Distal Convoluted Tubule: It lies in the cortex and is about 5 mm long. Its
epithelium is lower than that of the proximal tubule. There is no distinct brush border, but
there are few microvilli.

3. Collecting Ducts:
 The distal tubules coalesce to form collecting ducts that are about 20 mm long and pass
through the renal cortex and medulla to empty into the pelvis of the kidney at the apexes
of the medullary pyramids.
 The collecting duct is lined by two types of cells:
1) Principal cells (P cells):

 These are the predominant cells and are relatively tall.

 They are involved in:
- Sodium reabsorption.
- Water reabsorption, which is controlled by ADH.

2) Intercalated cells (I cells):

 They are present in smaller number and are also found in the distal convoluted tubule.
They have more microvilli, mitochondria and cytoplasmic vesicles.

 They are concerned with acid secretion and bicarbonate reabsorption.

Types of Nephrons
There are two types of nephrons according to the location of the glomeruli in the cortex:

1) Cortical Nephrons: with their glomeruli in the outer cortex.

2) Juxtamedullary Nephrons: their glomeruli lie deeper in the renal cortex, near the medulla.
(Fig. 2)

The following table shows the differences between the two types of nephrons:

Cortical nephrons Juxtamedullary

nephrons
Percentage of the
85% 15%
total number

In the outer portion of the renal cortex. Deep in the renal cortex near
Glomeruli the medulla.

Short & penetrate a short distance into the Long & dips deeply into the
medulla no further than the junction medullary pyramids.
Loop of Henle between the inner & outer medulla.
 The tubule is surrounded by a network of Vasa recta which are
peritubular capillaries. specialized U - shaped
Vascular peritubular capillaries that lie
structures side by side with loop of
supplying tubule Henle. In addition to the
peritubular capillary network

Plays an important role in the

Special functions process of urine
concentration.

Fig.2
 Juxta Glomerular Apparatus
JGA is a combination of specialized tubular and vascular cells located at the vascular pole
where the afferent and efferent arterioles enter and leave the glomerulas.

Fig. (3): Juxta Glomerular

Apparatus

 It consists of :
1- Macula densa: These are modified tubular cells in the initial portion of distal tubule that
comes in contact with the afferent and efferent arterioles. The macula densa is in close
proximity to the JG cells. These cells monitor the composition of the fluid in the tubular
lumen at this point, i.e. function as chemoreceptors that are stimulated by a decrease of
NaCl load.
2. Juxtaglomerular cells: There are epithelioid granular cells located in the media of the
afferent arterioles and to a lesser extent the efferent arteriloes as they enter the glomeruli.
These cells secrete renin. These cells act as barorecptors and respond to changes in
perfusion pressure and are stimulated by a decreased renal perfusion pressure or by
hypovolemia, to release rennin.
.
The Juxtaglomerular apparatus plays an important role in auto- regulation of the renal
blood flow and GFR during changes in arterial pressure and is important for regulation of
arterial blood pressure through renin-angiotensin aldosterone system.