Functions of kidney

1. Role in homeostasis:
a- Regulation of water and electrolyte balance.
b- Regulation of blood pressure:
Kidneys play an important role in the long-term regulation of arterial blood
pressure by two ways:
• By regulating the volume of extracellular fluid
• Through renin-angiotensin mechanism.
c- Regulation of acid base balance
2. Excretion of Waste Products through Urine formation:
– Urea (end product of amino acid metabolism)
– Uric acid (end product of nucleic acid metabolism)
– Creatinine (end product of metabolism in muscles)
– Bilirubin (end product of hemoglobin degradation)
– Products of metabolism of other substances.
3. Hemopoietic function (erythropoietin, thrombopoietin)
4. Endocrine function
(erythropoietin, thrombopoietin, renin, 1,25 dihydroxycholicalciferol,
prostaglandins)
5. Gluconeogenesis: synthesis of glucose from amino acids during prolonged fasting.
Functional unit of the kidney (Nephron)
Nephron is the functional unit of the kidney, where the processes of urine
formation take place. There are about 1-1.3 million of nephrons in each kidney.
After age of 40, nephrons are decreased 10% each 10 years due to aging. When
there is only 30 % of nephrons remained, renal failure may develop.
Nephron is composed of:
1- Vascular component: Afferent arteriole, glomerular capillaries, efferent arteriole,
and peritubular capillaries.
- Glomerular capillaries and Bowman's capsule together are called renal
corpuscule.

- The efferent arteriole has lesser diameter than that of the afferent arteriole.
This is an important factor in glomerular filtration as we will see later.
2- Tubular component: Glomerular capillaries are involved in Bowman's capsule,
which continues in the proximal tubule, loop of Henle, distal tubule, collecting
tubule, and collecting duct multiple nephrons may share the same collecting duct.
There are two types of nephrons:
1- Cortical (superficial) nephrons:
Found in the superficial layer of the
renal cortex, and forms about 80% of
the whole nephrons. These nephrons
have shorter loop of Henle that does
not dip into the medulla.
2- Juxtamedullary nephrons: Also found in the renal cortex, but close to the
medulla. They form about 20% of the whole nephrons. They dip deeply in the
medulla. The loop of Henle of juxtamedullary nephron is surrounded by special
peritubular capillaries that are straight and known as Vasa Recta.
Juxtaglomerular apparatus:

- The juxtaglomerular apparatus is a specialized organ situated near the glomerulus

of each nephron (juxta = near) at a point where the initial part of the distal tubule
passes through the fork formed by the afferent and efferent arterioles of the same
nephron.
- It Consists of 3 specialized cells that involves:
1- Granular cells (juxtaglomerular cells), located in the media of afferent
arteriole (Baroreceptors, Renin-secreting cells),
2- Macula densa of distal nephron (Chemoreceptors, sensitive cells to sodium
chloride concentration) close to afferent and efferent arterioles
3- lacis cells (extraglomerular mesangial cells). are situated in the triangular
region bound by afferent arteriole, efferent arteriole and macula densa
- Functions of juxtaglomerular apparatus:
1- Secretion of hormones (Renin, Prostaglandin).
2- Regulation of the glomerular blood flow and glomerular filtration rate. Macula
densa of juxtaglomerular apparatus plays an important role in the feedback
mechanism called tubuloglomerular feedback mechanism, which regulates the
renal blood flow and glomerular filtration rate
3- Secretion of other substances
1. Extraglomerular mesangial cells of juxtaglomerular apparatus secrete
cytokines like interleukin-2 and tumor necrosis factor
2. Macula densa secretes thromboxane A2.
Renin:
- Secreted by Juxtaglomerular cells.
- Along with angiotensins, renin forms the renin-angiotensin system, which is a
hormone system that plays an important role in the maintenance of blood pressure.
- Secretion of renin is stimulated by four factors:
i. Fall in arterial blood pressure
ii. Reduction in the ECF volume
iii. Increased sympathetic activity
iv. Decreased load of sodium and chloride in macula densa
Renin-angiotensin system:
- When renin is released into the blood, it acts on a specific plasma protein called
angiotensinogen.
- By the activity of renin, the angiotensinogen is converted into angiotensin I.
- Angiotensin I is converted into angiotensin II, by the activity of angiotensin-
converting enzyme (ACE) secreted from lungs.
- Most of the conversion of angiotensin I into angiotensin II takes place in lungs.
- Angiotensin II has a short half-life of about 1 to 2 minutes. Then it is rapidly
degraded into angiotensin III by angiotensinases, which are present in RBCs and
vascular beds in many tissues.
- Angiotensin III is converted into angiotensin IV.
Actions of Angiotensins:
Angiotensin I: is physiologically inactive and serves only as the precursor of
angiotensin II.
Angiotensin II: Angiotensin II is the most active form. Its actions are: On blood
vessels:
i. Angiotensin II increases arterial blood pressure by directly acting on the blood
vessels and causing vasoconstriction. It is a potent constrictor of arterioles.
ii. It increases blood pressure indirectly by increasing the release of noradrenaline
from postganglionic sympathetic fibers.
On adrenal cortex:
It stimulates zona glomerulosa of adrenal cortex to secrete aldosterone.
Aldosterone acts on renal tubules and increases retention of sodium, which is also
responsible for elevation of blood pressure.
On kidney:
i. Angiotensin II regulates glomerular filtration rate.
ii. It increases sodium reabsorption from renal tubules. This action is more
predominant on proximal tubules.
 On brain:
i- Angiotensin II inhibits the baroreceptor reflex and thereby indirectly increases
the blood pressure. Baroreceptor reflex is responsible for decreasing the blood
pressure.
ii. It increases water intake by stimulating the thirst center iii. It increases the
secretion of corticotropin-releasing hormone (CRH) from hypothalamus. CRH in
turn increases secretion of adrenocorticotropic hormone (ACTH) from pituitary
iv. It increases secretion of antidiuretic hormone (ADH) from hypothalamus.

Renal
circulation:
• Renal artery →segmental arteries, → interlobar arteries → arcuate artery →
interlobular arteries → afferent arterioles → glomerular capillary tuft → efferent
arteriole, → peritubular capillaries, vasa recta → peritubular venules →
interlobular veins → arcuate veins → interlobar veins → segmental veins → and
finally the renal vein (it leaves the kidney through the hilus and joins inferior vena
cava)
- Measurement of renal blood flow: Blood flow to kidneys is measured by using
plasma clearance of para-aminohippuric acid (PAHA) (see later)
- Regulation of renal blood flow:
Renal blood flow is regulated mainly by autoregulation. The nerves innervating
renal blood vessels do not have any significant role in this.
Autoregulation:
- Autoregulation is the intrinsic ability of an organ to regulate its own blood flow.
- Autoregulation is present in some vital organs in the body such as brain, heart and
kidneys.
- It is highly significant and more efficient in kidneys.
- Renal autoregulation is important to maintain constsnt glomerular filtration rate
(GFR) and to allow continuous control of renal functions.
- Blood flow to kidneys remains normal even when the mean arterial blood pressure
varies widely between 60 mm Hg and 180 mm Hg. This helps to maintain normal
GFR.
- Two mechanisms are involved in renal autoregulation:
1. Myogenic response
2. Tubuloglomerular feedback.
1. Myogenic Response:
A- Whenever the blood flow to kidneys increases, it stretches the elastic wall of the
afferent arteriole.
- Stretching of the vessel wall increases the flow of calcium ions from extracellular
fluid into the cells.
- The influx of calcium ions leads to the contraction of smooth muscles in afferent
arteriole, which causes constriction of afferent arteriole. So, the blood flow is
decreased.
B- At low blood pressure, relaxation of the smooth muscles of the afferent arterioles
→ decrese of vascular resistance → maintain constant blood flow.
2. Tubuloglomerular Feedback
- Macula densa plays an important role in tubuloglomerular feedback, which
controls the renal blood flow and GFR.
- When the glomerular filtrate passes through the initial portion of DCT, macula
densa acts like a chemoreceptor. It detects the concentration of sodium chloride in
the tubular fluid and accordingly alters the glomerular blood flow and GFR.
A- When GFR increases → the concentration of sodium chloride increases in the
filtrate → macula densa releases adenosine (a vasoactive substance) → causes
constriction of afferent arteriole → the blood flow through glomerulus decreases
leading to decrease in GFR back to normal.
B- When GFR decreases → the concentration of sodium chloride decreases in the
filtrate → Macula densa secretes prostaglandin (PGE2 ), bradykinin and renin →
PGE2 and bradykinin cause dilatation of afferent arteriole, renin induces the
formation of angiotensin II, which causes constriction of efferent arteriole. The
dilatation of afferent arteriole and constriction of efferent arteriole leads to increase
in glomerular blood flow and GFR.
Renal Plasma clearance:
 - Is defined as the volume of plasma that is cleared off a substance in a given unit
of time. It is also known as renal clearance.
- Determination of clearance value for certain substances helps in assessing the
following renal functions:
1. Glomerular filtration rate
2. Renal plasma flow
3. Renal blood flow.
- Formula to calculate clearance value:
C = UV/P
Where, C = Clearance, U = Concentration of the substance in urine, V = Volume
of urine flow, P = Concentration of the substance in plasma.
1. Measurement of Glomerular Filtration Rate:
- A substance that is completely filtered but neither reabsorbed nor secreted should
be used to measure glomerular filtration rate (GFR).
- Inulin is the ideal substance used to measure GFR. It is completely filtered and
neither reabsorbed nor secreted. So, inulin clearance indicates GFR.
 - Inulin clearance:
A known amount of inulin is injected into the
body. After sometime, the concentration of
inulin in plasma and urine and the volume of
urine excreted are estimated.
- For example, Concentration of inulin in
urine = 125 mg/dL, Concentration of inulin in
plasma = 1 mg/dL, Volume of urine output =
1 mL/min
- Thus, GFR = UV/P = 125 X 1 / 1 =
125 mL/min

- Creatinine clearance is also used to measure GFR accurately. It is easier than

inulin clearance, because, creatinine is already present in body fluids and its
plasma concentration is steady throughout the day. It is completely filtered and
being a metabolite, it is neither reabsorbed nor secreted. The normal value of GFR
by this method is approximately the same as determined by inulin clearance.
2. Measurement of Renal Plasma Flow:
 - To measure renal plasma flow, a substance,
which is filtered and secreted but not
reabsorbed, should be used.
- Such a substance is Para-Amino-hippuric
acid (PAHA) is used.
- PAHA clearance indicates the amount of
plasma passed through kidneys.
- A known amount of PAHA is injected into
the body. After sometime, the concentration

of PAHA in plasma and urine and the volume of urine excreted are estimated.
- For example, Concentration of PAH in urine = 66 mg/dL, Concentration of PAH
in plasma = 0.1 mg/dL, Volume of urine output = 1 mL/min
Renal plasma flow (PAHA clearance) = UV/P
= 66 X 1 / 0.1 = 660 ml/min
- Diodrast clearance also can be used to measure this.
3. Measurement of Renal Blood Flow:
- Values of factors necessary to determine renal blood flow are:
i. Renal plasma flow, measured by using PAHA clearance.
ii. Percentage of plasma volume in blood, is indirectly determined by using
packed cell volume (PCV).
- For example, If PCV = 45%, Plasma volume in the blood = 100 – 45 = 55%.
That is 55 mL of plasma is present in every 100 mL of blood.
- Calculation of renal blood blow Renal blood flow:
Renal blood flow = Renal plasma flow / % of plasma in blood
For example, Renal plasma flow = 660 mL/min, Amount of plasma in blood =
55%, Renal blood flow = 660 / 55/100 = 1,200 mL/min
- Urea Clearance Test:
- assess renal function by using clearance of urea from plasma by kidney every
minute.
- Normal value of urea clearance is 70 mL/min.
- Urea is a waste product formed during protein metabolism and excreted in urine.
So, determination of urea clearance forms a specific test to assess renal function.