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Excretory System - Lecture notes

Human anatomy and physiology (Kerala University of Health Sciences)

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EXCRETORY SYSTEM
- Excretion is the process by which the unwanted
substances and metabolic waste are eliminated from the
body
- Various systems organs in the body are involved in
performing the excretory function

1) DIGESTIVE SYSTEM excretes food residues in the form of

faeces.
2) LUNGS remove carbon dioxide and water vapour
3) SKIN excrete water salts and some wastes
4) LIVER excretes many substances like bile pigments heavy
metals drugs toxins bacteria etc.

- Renal system includes

1) a pair of kidneys
2) ureters
3) urinary bladder
4) urethra

FUNCTIONS OF KIDNEY
1) ROLE IN HOMEOSTASIS
- Primary function of kidney is homeostasis
- It is accomplished by formation of urine
- During formation of urine, kidneys regulate various
activities in the body which are

a. Excretion of WASTE PRODUCTS

- kidneys excrete urea, uric acid, creatinine, Bilirubin,
products of metabolism

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b. Maintenance of WATER BALANCE

- kidneys maintain water balance in the body by
CONSERVING WATER, when it is DECREASED and EXCRETING
WATER, when it is EXCESS in the body.

c. Maintenance of ELECTROLYTE BALANCE

- especially sodium is in relation of water balance
- kidneys retain sodium if osmolarity of body water
decreases and eliminate sodium when osmolarity
increases

d. Maintenance of ACID BASE BALANCE

- pH of blood and body fluids should be maintained within
the narrow range for healthy living

2) HEMATOPOIETIC FUNCTION
- kidney stimulate the production of erythrocytes by
secreting ERYTHROPOIETIN
- it is the important stimulating factor for ERYTHROPOIESIS

3) ENDOCRINE FUNCTION
- hormone secreted by kidneys
i. Erythropoietin
ii. Thrombopoietin
iii. Renin

4) REGULATION OF BLOOD PRESSURE

- by regulating the volume of ECF
- Through renin angiotensin mechanism

5) REGULATION OF BLOOD CALCIUM LEVEL

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FUNCTIONAL ANATOMY OF KIDNEY

- Kidney is a compound tubular gland covered by a
CONNECTIVE TISSUE capsule
- There is a depression on the medial border of the kidney
called HILUM, through which RENAL ARTERY, RENAL VEIN,
NERVES, and URETERS pass.

DIFFERENT LAYERS OF KIDNEY

- Components of kidney are arranged in three layers
1) Outer cortex
- dark and granular in appearance
- contains renal corpuscles and convoluted tubules
2) Inner medulla
- medulla contains tubular and vascular structures
arranged in parallel radial lines
3) Renal sinus
- renal pelvis and renal calyces

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NEPHRON
- NEPHRON is defined as the STRUCTURAL AND FUNCTIONAL UNIT
of kidney.
- Each kidney consists of 1 to 1 . 3 million nephrons.

PARTS OF NEPHRON
- Each nephron is formed by two parts
1) A blind end is called RENAL CORPUSCLE or MALPHIGIAN
CORPUSCLE
2) A tubular portion called RENAL TUBULE.

RENAL CORPUSCLE
- It is a spheroidal and slightly flattened structure with
a diameter of about 200 microns
Situation of renal corpuscle and types of nephron
Renal corpuscle is situated in the cortex of the kidney either
near the periphery or near medulla.
CLASSIFICATION OF NEPHRONS
1) Cortical nephrons or superficial nephrons
2) Juxtamedullary nephrons
Structure of renal corpuscle
Renal corpuscle is formed by two portions
1) GLOMERULUS
- It is a tuft of capillaries enclosed by Bowman's capsule.
It consists of glomerular capillaries interposed between
afferent arteriole on one end and efferent arteriole on
the other end.
- After entering the bowman's capsule, the afferent
arteriole divides into 4 or 5 large capillaries.

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- Each large capillary Sub divides into many small

capillaries. The small capillaries are arranged in
irregular loops and form anastomoses.
- All the smaller capillaries finally reunite to form the
efferent arterial which leaves the Bowman's capsule

2) BOWMAN'S CAPSULE
- It is a capsular structure which encloses the glomerulus
- It is formed by two layers
INNER VISCERAL LAYER covers the glomerular capillaries.
It is continued as a PARIETAL LAYER at the visceral pole.

TUBULAR PORTION OF NEPHRON

- It is a continuation of bowman's capsule
- It is made up of three parts
• Proximal convoluted tubule
• Loop of Henle
• Distal convoluted tubule
PROXIMAL CONVOLUTED TUBULE
- PCT is coiled portion rising from Bowman's capsule
- It is situated in the cortex
- It is continued as descending Loop of Henle
LOOP OF HENLE
- It consists of
1. Descending limb
- It is made of thick and thin descending segment
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- Thick descending segment is the direct continuation of the

PCT. It descends down into the medulla.
- Thin descending segment is continued as thin descending
segment
2. Hair pin bend
- Continuation of thin descending segment
- Formed by flattened epithelial cells
3. Ascending limb
- It has two parts
a) Thin ascending segment
- It is a continuation of hairpin bend
- It is lined by flattened epithelial cells without brush
border
- Thin segment is continued as thick segment
b) Thick ascending segment
- It is about 9 mm long lined by cuboidal epithelial cells
- Terminal portion which runs between afferent and
efferent arterioles forms the MACULA DENSA
DISTAL CONVOLUTED TUBULE
- DCT is the continuation of thick ascending segment and
occupies the cortex of kidney
- It is continued as collecting duct

COLLECTING DUCT
- DCT continues as the initial or arched collecting duct
which is in the cortex
- Lower part of the collecting duct lies in the medulla.
- It is formed by two types of epithelial cells
1) Principal or P cells
2) Intercalated or I cell

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JUXTAGLOMERULAR APPARATUS
- Juxtaglomerular Apparatus is a specialised organ
situated near the glomerulus of each nephron

STRUCTURE OF JGA
- It is formed by three different structures
• Macula Densa
• Extraglomerular mesangial cells
• Juxtaglomerular cells
MACULA DENSA
- It is the end portion of thick ascending segment before
it opens into DCT
- It is situated between afferent and efferent arterioles
of same nephron
- Macula Densa plays an important role in TUBULOGLOMERULAR
FEEDBACK MECHANISM
EXTRAGLOMERULAR MESANGIAL CELLS
- They are situated in the triangular region bound by
afferent arteriole, efferent arteriole and Macula Densa
- These cells are also called AGRANULAR CELLS, LACIS CELLS or
GOORMAGHTIGH CELLS
JUXTAGLOMERULAR CELLS
- JG cells are specialised smooth muscle cells situated in
the walls of afferent arteriole just before it enters the
Bowman's capsule.
- They are also called GRANULAR CELLS because of the
presence of secretory granules in their cytoplasm

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Polar cushion or Polkissen

- JG cells form a thick cuff called Polar cushion or
Polkissen around the afferent arteriole before it enters
the Bowman’s capsule.

FUNCTIONS OF JGA
- Primary function is SECRETION OF HORMONES
- It also regulates the glomerular blood flow and
glomerular filtration rate.
Secretion of hormones
RENIN
- Renin is a peptide with 340 amino acids
- Along with angiotensins, renin forms the renin- angiotensin
system, which is a hormone system that plays an important
role in maintenance of blood pressure

RENIN ANGIOTENSIN SYSTEM

- When renin is released into the blood, it acts on the
plasma protein ANGIOTENSINOGEN/ RENIN SUBSTRATE
- By activity of renin ANGIOTENSINOGEN is converted to
ANGIOTENSIN I (DECAPEPTIDE)
- ANGIOTENSIN I is converted into ANGIOTENSIN II
(OCTAPEPTIDE) by the activity of ACE (Angiotensin converting
enzyme) secreted from lungs
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- ANGIOTENSIN II is then rapidly degraded into

ANGIOTENSIN III (HEPTAPEPTIDE) by ANGIOTENSINASES.
- ANGIOTENSIN III is converted into ANGIOTENSIN IV
(HEXAPEPTIDE)
ACTIONS OF ANGIOTENSINS
- Angiotensin I is physiologically inactive. It serves as a
precursor of Angiotensin II
- Angiotensin II is the most ACTIVE form
• Increases arterial blood pressure
• Stimulates the secretion of aldosterone
• Regulate glomerular filtration
• Inhibits baroreceptor reflex

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RENAL CIRCULATION
- RENAL ARTERY- arises directly from abdominal aorta and
enters the kidney through hilus
- SEGMENTAL ARTERY- subdivides into inter lobar address.
- INTERLOBAR ARTERY- passes between the medullary pyramids.
At the base of the pyramid, it turns and runs parallel to
the base of pyramid forming arcuate artery
- ARCUATE ARTERY- each arcuate artery gives rise to
intralobular arteries
- INTERLOBULAR ARTERY- it runs through the renal cortex
perpendicular to arcuate artery
- AFFERENT ARTERIOLE- it enters the Bowman's capsule and
forms glomerular capillary tuft
- GLOMERULAR CAPILLARIES- each large capillary divides into
small glomerular capillaries which form the loops

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Efferent arteriole
- It forms a second capillary network called peritubular
capillaries which surround the tubular portions of
nephrons
Peritubular capillaries
- They are found around the tubular portion of cortical
nephrons only
Venous systems
- Peritubular capillaries and Vasa recta drain into the
venous system

REGULATION OF RENAL BLOOD FLOW

AUTOREGULATION
- It is intrinsic ability of an organ to regulate its own
blood flow
- Renal autoregulation
- It is important to maintain the glomerular filtration
rate
- Two mechanism are involved

1) MYOGENIC RESPONSE
- Whenever the blood flow to kidneys increase, it stretches
the elastic wall of afferent arteriole.

2) TUBULOGLOMERULAR FEEDBACK
- Macula Densa plays an important role in tubuloglomerular
feedback

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URINE FORMATION
Urine formation is a blood-cleansing function. Normally, about
1300ml of blood enters the kidneys. Kidneys excrete the
unwanted substances along with water from the blood as
urine.
Normal urine output – 1 to 1 . 5L/day.
Process of Urine Formation
- GLOMERULAR FILTRATION is when blood passes through
glomerular capillaries and plasma is filtered into the
Bowman’s capsule.
- Filtrate from the Bowman’s capsule passes through the
tubular portion of the nephron and undergoes changes in
quality and quantity.
Many unwanted substances like Glucose, Amino acids, water
and electrolytes are reabsorbed from the tubules. This
process is called TUBULAR REABSORPTION.
- Some unwanted substances are secreted into the tubule from
the peritubular blood vessels. This is called TUBULAR
SECRETION or EXCRETION.
Urine formation includes three processes :
A) Glomerular filtration
B) Tubular reabsorption
C) Tubular secretion

GLOMERULAR FILTRATION
It is the process by which the blood is filtered while
passing through the glomerular capillaries by filtration
membrane. It is the First process of urine formation.
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Filtration Membrane
It is formed by three layers :
1. Glomerular capillary membrane.
2. Basement membrane
3. Visceral layer of Bowman’s capsule.
Glomerular capillary membrane
It is formed by single layer of endothelial cells, which are
attached to the basement membrane.
Basement membrane
Basement membrane of glomerular capillaries and visceral
layer of Bowman’s capsule fuse together .
The fused basement membrane separates he endothelium of
glomerular capillary and the epithelium of visceral layer of
Bowman’s capsule.
Visceral layer of Bowman’s capsule.
It is formed by a single layer of flattened epithelial cells
resting on a basement membrane.
Each cell is connected with the basement membrane by
cytoplasmic extensions called pedicles or feet.
Pedicles leave small cleft-like spaces in between called SLIT
PORE or FILTRATION SLIT.
Filtration takes place through these slit pores.

Process of Glomerular Filtration

When blood passes through glomerular capillaries, all the
substances of plasma are filtered into the Bowman’s capsule
except the plasma proteins.
The filtered fluid is called GLOMERULAR FILTRATE.

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- MICROPUNCTURE TECHNIQUE that involves insertion of a

micropipette into the Bowman’s capsule and aspiration of
filtrate is the method of collection of Glomerular Filtrate .

- GLOMERULAR FILTRATION RATE (GFR) is the total quantity of

filtrate formed in all the nephrons of both the kidneys in
the given unit of time.
Normal GFR is 125mL/min or about 180L/day
- FILTRATION FRACTION is the fraction of the renal plasma,
which becomes the filtrate.
Filtration fraction = ( GFR / Renal Plasma Flow ) x 100
= 19. 2%
Normal filtration fraction varies from 15 to 20%

PRESSURES DETERMINING FILTRATION

Pressures which determine the GFR are
1. Glomerular Capillary Pressure ( GCP )
- It is the pressure exerted by the blood in glomerular
capillaries
- It varies between 45 and 70 mm Hg.
- It is highest capillary pressure in the body and favours
glomerular filtration.

2. Colloidal Osmotic Pressure. ( COP )

- It is the pressure exerted by plasma proteins in the
glomeruli.
- The plasma proteins are not filtered through the
glomerular -capillaries and develop the colloidal osmotic
pressure, which is about 25 mm Hg.
- It opposes glomerular filtration

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3. Hydrostatic Pressure in Bowman’s Capsule

- It is the pressure exerted by the filtrate in Bowman’s
capsule
- It is also called CAPSULAR PRESSURE and is about 15 mm Hg.
- It also opposes glomerular filtration.

NET FILTRATION PRESSURE is the balance between pressure

favouring filtration and pressures opposing filtration.
It is known as EFFECTIVE FILTRATION PRESSURE or ESSENTIAL
FILTRATION PRESSURE
NFP = GCP - ( COP + Hydrostatic Pressure in Bowman’s capsule )
= 60 - ( 25 + 15 ) = 20 mm Hg.
NFP varies between 15 and 20 mm Hg.
FILTRATION COEFFICIENT
It is the GFR in terms of net filtration pressure.
Filtration Coefficient = 125 mL / 20 mm Hg
= 6 . 25 mL / mm Hg.
FACTORS REGULATING GFR.
1. Renal Blood Flow
- It is the most important factor that is necessary for
glomerular filtration.
- GFR is directly proportional to Renal Blood Flow.
- Normal blood flow to both the kidneys is 1300 mL/min.

2. Tubuloglomerular Feedback
- It is the mechanism that regulates GFR through Renal tubule
and Macula Densa.
- MACULA DENSA of juxtaglomerular apparatus is sensitive to
NaCl in the tubular fluid.
- When the glomerular filtrate passes through the terminal
portion of thick ascending segment, Macula Densa detects
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the concentration of sodium chloride in tubular fluid and

alters Glomerular blood flow and GFR.
WHEN CONC. OF NACL INCREASES IN THE FILTRATE
When GFR increases, concentration of NaCl increases in the
filtrate.
• Macula Densa releases ADENOSINE from ATP.

• Adenosine causes constriction of afferent arteriole.

• Blood flow through glomerulus decreases, leading to

decrease in GFR.
• Factors increasing sensitivity of Tubuloglomerular

Feedback-
ADENOSINE, THROMBOXANE, PROSTAGLANDIN E2
• Factors decreasing sensitivity of Tubuloglomerular

Feedback
ANP, PROSTAGLANDIN I2, CYCLIC AMP, NITROUS OXIDE

WHEN CONC OF NACL DECREASES IN THE FILTRATE

When GFR decreases, conc. Of sodium chloride decreases in
the filtrate.
• Macula Densa secretes prostaglandin E2, Bradykinin and

Renin
• They cause dilation of afferent arteriole.

• Renin induces the formation of Angiotensin II which

causes constriction of efferent arteriole.

• Dilation of afferent arteriole leads to increase in

glomerular blood flow and GFR.

3. Glomerular capillary pressure

- GFR is directly proportional to GCP.
- Capillary pressure in turn depends on renal blood flow and
arterial blood pressure.

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4. Colloidal Osmotic pressure

- GFR is inversely proportional to COP.
- When COP increases, as in DEHYDRATION, GFR decreases
- When COP is low, as in HYPOPROTEINEMIA, GFR increases

5. Hydrostatic Pressure in Bowman’s capsule

- GFR is inversely proportional to this.
- HP in Bowman’s capsule increases in conditions like
obstruction of urethra and oedema of kidney beneath renal
capsule.

6. Constriction of Afferent Arteriole

- It reduces the blood flow to Glomerular capillaries, which
in turn reduces the GFR.

7. Constriction of Efferent Arteriole

- If efferent arteriole is constricted, initially the GFR
increases because of stagnation of blood in the capillaries.
- Later, further filtration does not occur.
- It is because, the efferent arteriolar constriction prevents
outflow of blood from glomerulus and no fresh blood enters
the glomerulus for filtration.

8. Systemic Arterial Pressure

- Renal blood flow and GFR are not affected as long as the
mean arterial blood pressure is in between 60 and 180 mm
Hg.
- Variation affects the Renal blood flow and GFR accordingly.

9. Sympathetic Stimulation
- Afferent and efferent arterioles are supplied by
sympathetic nerves.
- Strong sympathetic stimulation causes severe constriction of
the blood vessels by releasing NORADRENALINE.

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- The effect is more on the efferent arterioles than on the

afferent arterioles.
- So initially, there is increase in filtration, but later it
decreases.
- If the stimulation is continued for more than 30 minutes,
there is recovery of both Renal Blood Flow and GFR.

10. Surface area of Capillary Membrane

- GFR is directly proportional to the surface area of the
capillary membrane.

11. Permeability of Capillary membrane

- GFR is directly proportional to the permeability of
glomerular capillary membrane.
- In many conditions like hypoxia, lack of blood supply,
presence of toxic agents, the permeability of capillary
membrane increases.

12. Contraction of Glomerular Mesangial Cells

- They are situated in between the glomerular capillaries.
- Contraction of these cells decreases surface area of
capillaries resulting in reduction in GFR.

13. Hormonal and Other Factors

Factors INCREASING GFR by VASODILATION
- Atrial Natriuretic Peptide
- Brain Natriuretic Peptide
- cAMP
- Dopamine
- Endothelium derived NO
- PGE2

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Factors DECREASING GFR by VASOCONSTRICTION

- Angiotensin II
- Endothelin
- Noradrenaline
- Platelet- activating factor
- Platelet- derived growth factor
- PGF2

TUBULAR REABSORPTION
- It is the process by which water and other substances are
transported from renal tubules back to the blood.
- When the glomerular filtrate flows through the tubular
portion of nephron, both Qualitative and Quantitative
changes occur.
- Large quantity of water, electrolytes and other substances
are reabsorbed by the tubular epithelial cells.
- The reabsorbed substances move into the interstitial fluid
of renal medulla. And, from here, the substances move into
the blood in peritubular capillaries.
- Since the substances are taken back into the blood from
glomerular filtrate, the entire process is called TUBULAR
REABSORPTION.
MICROPUNCTURE TECHNIQUE and STOP-FLOW METHOD are the two
methods to collect the tubular fluid for analysis.
Tubular reabsorption is known as SELECTIVE REABSORPTION
because the tubular cells reabsorb only the substances
necessary for the body.
- ESSENTIAL SUBSTANCES like glucose, amino acids and
vitamins are completely reabsorbed from renal tubule
- UNWANTED SUBSTANCES like metabolic waste products are
not reabsorbed and excreted through urine.

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MECHANISM OF REABSORPTION
Basic transport mechanisms involved in tubular reabsorption
are of two types-
1. ACTIVE REABSORPTION
- It is the movement of molecules against the
ELECTROCHEMICAL (UPHILL) GRADIENT.
- Substances reabsorbed actively from the renal tubule
are Na, Ca, K, phosphates, sulfates, bicarbonates,
glucose, amino acids, uric acid and ketone bodies.

2. PASSIVE REABSORPTION
- It is the movement of molecules along the ELECTROCHEMICAL
(DOWNHILL) GRADIENT.
- This process does not need energy.
- Substances reabsorbed passively include Chloride, urea
and water.

ROUTES OF REABSORPTION
Reabsorption of substances from tubular lumen into the
peritubular capillary occurs by two routes:
1. Transcellular route
Substances move through the cell.
It includes transport of substances from
- Tubular lumen into tubular cell through apical surface of
the cell membrane.
- Tubular cell into interstitial fluid.
- Interstitial fluid into capillary.

2. Paracellular route
Substances move through intercellular space.
It includes transport of substances from
- Tubular lumen into interstitial fluid.
- Interstitial fluid into capillary
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SITE OF REABSORPTION
1. Proximal Convoluted Tubule ( PCT )
Substances reabsorbed are glucose, amino acids, Na, K, Ca,
bicarbonates, chlorides, phosphates, urea, uric acid and
water.
2. Loop of Henle
Substances reabsorbed are sodium and chloride.
3. Distal Convoluted Tubule ( DCT )
Na, Ca, bicarbonate and water are reabsorbed from DCT.
4. Collecting duct.
Substances reabsorbed are sodium (in the presence of
aldosterone), water ( in the presence of ADH ) and urea.

REGULATION OF TUBULAR REABSORPTION

Tubular reabsorption is regulated by three factors.
1. Glomerulotubular Balance
- It is the balance between filtration and reabsorption of
solutes and water in the kidney.
- When GFR increases, tubular load of solutes and water in
PCT is increased.
2. Hormonal factors
- ALDOSTERONE - ± Sodium reabsorption in ascending limb, DCT
and collecting duct.
- ANGIOTENSIN II - ± sodium reabsorption in proximal
tubule, thick ascending limb, distal tubule and collecting
duct.
- ATRIAL NATRIURETIC FACTOR - ³ sodium reabsorption.
- BRAIN NATRIURETIC FACTOR - ³ sodium reabsorption
3. Nervous factor
- Activation of sympathetic nervous system increases the
tubular reabsorption from renal tubules.

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THRESHOLD SUBSTANCES
Depending upon the degree of reabsorption various substances
are classified into three categories :
1. High threshold substances
- The substances which do not appear in urine under normal
conditions.
- The food substances like glucose, amino acids and
vitamins are completely reabsorbed from renal tubules
and do not appear in urine under normal conditions.
- They can appear in urine only if their concentration in
plasma is abnormally high or in renal diseases when
reabsorption is affected.

2. Low threshold substances

- The substances which appear in urine even under normal
conditions like urea, uric acid and phosphate that are
reabsorbed to a little extent.

3. Non threshold substances

- The substances which are not at all reabsorbed and are
excreted in urine irrespective of their plasma level.
Example : Creatinine

TRANSPORT MAXIMUM – Tm VALUE

It is the rate at which the maximum amount of a substance is
reabsorbed from the renal tubule.
For every actively reabsorbed substance there is a maximum
rate at which it could be reabsorbed.
For example : the transport maximum for glucose ( TmG ) is
375mg/min in adult males and 300mg/min in adult females.

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REABSORPTION OF IMPORTANT SUBSTANCES

1. Reabsorption of Sodium
- From the glomerular filtrate, 99% of sodium is
reabsorbed.
- 2/3rd of Na is reabsorbed in PCT
- 1/3rd in other segments ( except descending Limb ) and
collecting duct.
Sodium reabsorption occurs in three steps .
i. Transport from lumen of renal tubule into the tubular
epithelial cells.
Active reabsorption of sodium ions from lumen into
tubular cells occurs by two ways
a) In exchange for hydrogen ion by ANTIPORT – in PCT
b) Along with other substances by SYMPORT – in other
segments and collecting duct.
ii. Transport from tubular cells into the interstitial
fluid
Sodium is pumped outside the cells by SODIUM POTASSIUM
PUMP. It moves three Na ions from the cell into
interstitium and two K ions from interstitium into the
cell.
iii. Transport from interstitial fluid to the blood.
From the interstitial fluid, Na ions enter the
peritubular capillaries by CONCENTRATION GRADIENT.
In DCT, the Na reabsorption is stimulated by
aldosterone.

2. Reabsorption of water
It occurs from PCT, DCT and in collecting duct ( CD ).
i) From PCT – OBLIGATORY WATER REASBSORPTION
- It is secondary to sodium reabsorption
- When Na is reabsorbed from the tubule, osmotic pressure
decreases.
- It causes osmosis of water from renal tubule.
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ii) From DCT and CD – FACULTATIVE WATER REABSORPTION.

- It occurs by the activity of antidiuretic hormone (ADH).
- Normally, the DCT and CD are not permeable to water.
- In presence of ADH, they become permeable to water so it
is reabsorbed.
iii) Mechanism of action of ADH – AQUAPORINS
- ADH increases water reabsorption in DCT and CD by
stimulating the water channels called AQUAPORINS.
- ADH combines with vasopressin (V2) receptors in the tubular
epithelial membrane and activates ADENYL CYCLASE, to form
cyclic AMP.
- This activates aquaporins, which increase the water
reabsorption.

3. Reabsorption of Glucose.
- Glucose is completely reabsorbed in the PCT.
- It is transported by sodium cotransport mechanism.
- Glucose and sodium bind to a common carrier protein
called SODIUM – DEPENDENT GLUCOSE COTRANSPORTER 2 (SGLT2).
- From tubular cell, glucose is transported in medullary
interstitium by another carrier protein called GLUCOSE
TRANSPORTER 2 ( GLUT2 ).
- SPLAY means DEVIATION
With normal GFR of 125 mL/min and TmG of 375 mg/min in an
adult male the predicted renal threshold for glucose
should be 300 mg/dL, But actually its only 180 mg/dL .
This type of deviation is called Splay.
It is because of the Nephrons do not have the same
filtering and reabsorbing capacities.

4. Reabsorption of Amino acids

They are also reabsorbed completely in PCT, by the
secondary active transport mechanism.

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5. Reabsorption of bicarbonates
- It is reabsorbed actively in proximal tubule in the form
of carbon dioxide .
- Bicarbonate is mostly present as sodium bicarbonate in
the filtrate.
- It dissociates into sodium and bicarbonate ions in the
tubular lumen.
- Na diffuses into tubular cell in exchange of hydrogen.
- Bicarbonate combines with hydrogen to form carbonic
acid.
- Carbonic acid dissociates into carbon dioxide and water.
- They enter into the tubular cell.
- In tubular cell, carbon dioxide combines with water to
form carbonic acid.
- It immediately dissociates in to hydrogen and
bicarbonate.
- Bicarbonate from the tubular cell enters the interstitium.
- There it combines with sodium to form SODIUM BICARBONATE.

TUBULAR SECRETION
- It is a process by which the substances are transported
from blood into renal tubules.
- It is also called TUBULAR EXCRETION.
- DYE PHENOL RED was the first substance found to be
secreted in renal tubules in experimental conditions.
- Later many other substances like Penicillin, Diodrast, Amino
derivatives were found to be secreted.
Substances secreted in different segments of renal tubules
1. POTASSIUM is secreted actively by sodium potassium pump
in PCT, DCT and CD.
2. AMMONIA is secreted in the PCT.
3. HYDROGEN IONS are secreted in PCT and DCT
4. UREA is secreted in LOOP OF HENLE.

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Thus, urine is formed in nephron by the process of glomerular

filtration, selective reabsorption and tubular secretion.

SUMMARY OF URINE FORMATION

1. Glomerular filtration
Plasma is filtered in glomeruli and substances reach the
renal tubules along with water as filtered.
2. Tubular reabsorption
The 99% of filtrate is reabsorbed in different segments
of renal tubules.
3. Tubular secretion
Some substances are transported from blood into the
renal tubule.
With all these changes, the filtrate becomes URINE.

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CONCENTRATION OF URINE
- Everyday 180 litre of glomerular filtrate is formed with
large quantity of water.
- Osmolarity of glomerular filtrate is same as that of
plasma and it is 300 mOsm/L.
- Normally urine is concentrated and its omolarity is 4
times more than that of plasma, i.e., 1200 mOsm/L
Factors determining osmolarity of urine.
- Osmolarity of urine depends upon two factors
1) water content in the body
2) antidiuretic hormone (ADH)

FORMATION OF DILUTE URINE

- When water content in the body increases, kidney excretes
dilute urine.
- This is achieved by inhibition of ADH secretion from
posterior pituitary
- So, water reabsorption from renal tubules does not take
place leading to excretion of large amount of water.
- This makes the urine dilute.

FORMATION OF CONCENTRATED URINE

- Formation of concentrated urine is not as simple as that
of dilute urine.
- It involves two processes:
1) Development and maintenance of Medullary Gradient by
countercurrent system
2) Secretion of ADH

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MEDULLARY GRADIENT
- MEDULLARY HYPEROSMOLARITY
• Cortical interstitial fluid is isotonic to plasma
osmolarity of 300 mOsm/L.
• Osmolarity of medullary interstitial fluid near the
cortex is also the same
• While proceeding from outer part towards the inner
part of medulla the osmolarity increases gradually and
reaches the maximum at the innermost part of medulla
near the renal sinus.
• This type of gradual increase in the osmolarity of the
medullary interstitial fluid is called the Medullary
Gradient which plays an important role in the
concentration of urine.
DEVELOPMENT AND MAINTENANCE OF MEDULLARY GRADIENT
• Kidney has a unique mechanism called countercurrent
mechanism which is responsible for the development and
maintenance of medullary gradient and hyperosmolarity
of interstitial fluid in the inner medulla.

COUNTERCURRENT MECHANISM
COUNTERCURRENT FLOW
• Countercurrent system is a system of U- shaped tubules in
which the flow of fluid is in opposite direction in two
limbs of the U- shaped tubules.
• divisions of countercurrent system
1) countercurrent multiplier formed by loop of Henle
2) countercurrent exchanger formed by Vasa recta

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COUNTERCURRENT MULTIPLIER
• Loop of Henle functions as countercurrent multiplier.
• it is responsible for development of hyperosmolarity of
medullary interstitial fluid and medullary gradient

Role of loop of Henle in development of medullary gradient.

- Loop of Henle plays a major role as countercurrent
multiplier because loop of these nephrons is long and
extends up to the deeper parts of the medulla.

- Main reason for the HYPEROSMOLARITY of Medullary

interstitial fluid is the active reabsorption of sodium
chloride and other solutes from ascending limb of Henle's
loop into the medullary interstitium.

- The sodium and chlorine ions are repeatedly recirculated

between the descending limb and ascending limb of
Henle's loop through medullary interstitial fluid leaving a
small portion to be excreted in the urine.

- Apart from this, there is regular addition of more and

more new sodium and chloride ions into the descending
limb by constant filtration.

- The reabsorption of sodium chloride from ascending limb

and addition of new sodium chloride ions into the
filtrate increase or multiply the osmolarity of medullary
interstitial fluid and medullary gradient. Hence, it is
called COUNTERCURRENT MULTIPLIER

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OTHER FACTORS RESPONSIBLE FOR HYPEROSMOLARITY OF MEDULLARY

INTERSTITIAL FLUID
1) Reabsorption of sodium from collecting duct
- it adds to the osmolarity of inner medulla
2) Recirculation of urea
- 50% of urea filtered in glomeruli is reabsorbed in PCT.
- Almost an equal amount of urea is secreted in the Loop of
Henle.
- Collecting duct is impermeable to urea. However, due to the
water reabsorption from DCT and collecting duct in the
presence of ADH, urea concentration increases in collecting
duct.

COUNTERCURRENT EXCHANGER
- Vasa recta functions as countercurrent exchanger and is
responsible for the maintenance of medullary gradient
which is developed by countercurrent multiplier.
Role of Vasa recta in the maintenance of medullary gradient
- Vasa recta acts like countercurrent exchanger because of
its position.
- The sodium chloride reabsorbed from ascending limb of
Henle's loop enters the medullary interstitium.
- from here it enters the descending limb of Vasa recta.
- A large quantity of NaCl flows slowly towards ascending
limb.
- The increased concentration of sodium chloride causes
diffusion of it into the medullary interstitium.
- Water from Medullary interstitium enters the ascending
limb of Vasa recta and the cycle is repeated.
- Thus, sodium chloride and urea exchanged for water
between the ascending and descending limbs of Vasa
recta , hence this system is called COUNTERCURRENT
EXCHANGER
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ROLE OF ADH
- Final concentration of urine is achieved by the action of
ADH
- Normally, DCT and collecting duct are not permeable to
water.
- The presence of ADH makes them permeable resulting in
water reabsorption
- Water reabsorption induced by ADH is called FACULTATIVE
REABSORPTION OF WATER

SUMMARY OF URINE CONCENTRATION

- When the glomerular filtrate passes through renal tubule
its osmolarity is altered in different segments as
described below

1) BOWMAN'S CAPSULE
- Glomerular filtrate collected at the Bowman's capsule is
ISOTONIC TO PLASMA.
- This is because it contains all the substances of plasma
except proteins
- Osmolarity of the filtrate at bowman's capsule is 300
mOsm/L

2) PROXIMAL CONVOLUTED TUBULE

- When the filtrate flows through proximal convoluted
tubule, there is active reabsorption of sodium and
chloride followed by OBLIGATORY REABSORPTION OF WATER.
- So, the osmolarity of fluid remains the same as in the
case of Bowman's capsule that is 300 mOsm/L.
- In PCT, the fluid is ISOTONIC TO PLASMA

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3) THICK DESCENDING SEGMENT

- When the fluid passes from PCT into the thick ascending
segment, water is reabsorbed from tubule into outer
medullary interstitium by means of osmosis.
- It is due to the increased osmolarity in the Medullary
interstitium.
- Osmolarity of fluid inside the segment is between 450 and
600 mOsm/L.
- That means the fluid is SLIGHTLY HYPERTONIC TO PLASMA.

4) THIN DESCENDING SEGMENT OF HENLE'S LOOP

- As the thin descending segment of Henle's loop passes
through the inner medullary interstitium more water is
reabsorbed.
- This segment is highly permeable to water and so the
osmolarity of tubular fluid becomes equal to that of the
surrounding Medullary interstitium.
- In the short loops of cortical nephrons, osmolarity of
fluid at the hair pin bend of loop become 600 mOsm/L
- Thus, in this segment the fluid is HYPOTONIC TO PLASMA.

5) THIN ASCENDING SEGMENT OF HENLE'S LOOP

- When the thin ascending segment of loop ascends upwards
through the Medullary region, osmolarity decreases
gradually.
- Due to concentration gradient sodium chloride diffuses out
of tubular fluid and osmolarity decreases to 400 mOsm/L.
- The fluid in this segment is SLIGHTLY HYPERTONIC TO PLASMA.

6) THICK ASCENDING SEGMENT

- This segment is impermeable to water but there is active
reabsorption of sodium and chloride from this.
- Osmolarity is between 150 and 200 mOsm/L.
- The fluid inside becomes HYPOTONIC TO PLASMA

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7) DISTAL CONVOLUTED TUBULE AND COLLECTING DUCT

- In the presence of ADH, DCT and collecting duct become
permeable to water resulting in water reabsorption and
final concentration of urine.
- In the collecting duct, PRINCIPAL CELLS (P) are responsible
for ADH induced water reabsorption
- Osmolarity increases to 1200 mOsm/L.
- The urine becomes hypertonic to plasma
APPLIED PHYSIOLOGY
1) OSMOTIC DIURESIS
- Dialysis is the excretion of large quantity of water
through urine.
- Osmotic diuresis is the diuresis induced by osmotic
effects of solutes like glucose
- It is common in diabetes mellitus

2) POLYURIA
- It is the increased urinary output with frequent voiding
and is common in diabetes insipidus.
- The renal tubules fail to re absorb water because of ADH
deficiency.

3) SYNDROME OF INAPPROPRIATE HYPERSECRETION OF ADH (SIADH)

- It is a Pituitary disorder characterized by
hypersecretion of ADH and causes water retention which
decreases osmolarity of ECF.

4) BARTTER SYNDROME
- It is a genetic disorder characterized by dysfunction of
thick ascending segment and distal convoluted tubule.
- this causes decreased reabsorption of sodium potassium
and chloride resulting in loss of large quantity of it
through urine.

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ACID-BASE BALANCE
- Acid base balance is very important for the homeostasis
of the body and almost all the physiological activities
depend upon the acid-base status of the body.
- An ACID is the proton donor and a BASE is the proton
acceptor

HYDROGEN ION AND PH

- The hydrogen ion shows severe effects on the physiological
activities of the body even at low concentrations.
- Normal H+ concentration in the extracellular fluid is
between 30 and 42 nM/L.
- The pH is another term for H+ concentration that is
generally used nowadays instead of hydrogen ion
concentration.
- The pH scale was introduced in order to simplify the
mathematical handling of large numbers.
- negative logarithm of H+ concentration is taken for
calculating the pH
pH= log 1/H+
- An increase in H+ ion concentration decreases the pH
(acidosis) and reduction in H+ concentration increases the
pH (alkalosis)
- In a healthy person the pH of ECF is 7.40 and it varies
between 7.38 and 7.42.
- The maintenance of acid base status is very important for
homeostasis because even a slight change in pH below 7.38
or above 7.42 will cause serious threats to many
physiological functions.

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REGULATION OF ACID BASE BALANCE

- Body is under constant threat of acidosis because of the
production of large amount of acids.
- Generally two types of acids are produced in the body

1) Volatile acids
- They are derived from carbon dioxide that is produced
in large quantities during the metabolism of
carbohydrates and lipids and it is not a threat because
it is almost totally removed through expired Air by lungs

2) Non - volatile acids

- Produced during metabolism of other nutritive substances
- proteins.
- Acids that are real threat to the acid base status of
the body
- E.g. sulfuric acid is produced during metabolism of
sulphur containing amino acids such as cysteine and
methionine

Compensatory mechanism
- Whenever there is a change in pH beyond the normal range,
some compensatory changes occur in the body to bring the
pH back to normal level.
- The body has three different mechanism to regulate acid
base status
1) Acid base buffer system
2) Respiratory mechanism
3) Renal mechanism

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*REGULATION OF ACID BASE BALANCE BY ACID BASE BUFFER SYSTEM

- An acid base buffer system is the combination of a weak
acid (protonated substance) and a base- the salt
(unprotonated substance)
- Types of buffer systems

1) BICARBONATE BUFFER SYSTEM

It is present in ECF and consists of the protonated
substance carbonic acid (H2CO3) which is a weak acid and
the an protonated substance, HCO3-, which is a weak base.

MECHANISM OF ACTION OF BICARBONATE BUFFER SYSTEM

- It prevents the fall of PH in a fluid to which strong acid
like hydrochloric acid is added
- Normally when HCL is mixed with the fluid, pH of that
fluid decreases quickly because a strong HCL dissociates
into H+ and Cl-
- But if bicarbonate buffer system is added to the fluid
with HCl, the pH is not altered much.
- This is because of the H+ dissociated from HCL combines
with HCO3- of NaHCO3 and forms a weak H2CO3.
- This in turn dissociates into CO2 and H2O
- Bicarbonate buffer system also prevents the increase in
pH in a fluid to which a strong base like sodium
hydroxide is added.
Importance of bicarbonate buffer system
- it is not powerful like the other buffer systems because
of the large difference between the pH of ECF and the pH
of bicarbonate buffer system but it plays an important
role in maintaining the pH of body fluids than the other
buffer systems

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2) PHOSPHATE BUFFER SYSTEM

- This system consists of a weak acid the dihydrogen
phosphate (H2PO4) in the form of sodium dihydrogen
phosphate (NaH2PO4) and the base hydrogen phosphate in
the form of disodium hydrogen phosphate (Na2HPO4)
- Phosphate buffer system is useful in intracellular fluids,
in red blood cells or other cells as a concentration of
phosphate is more in ICF than ECF
- Mechanism of phosphate buffer system
When a strong acid like hydrochloric acid is mixed with
the fluid containing phosphate buffer sodium dihydrogen
phosphate is formed.
HCl + Na2HPO4 ² NaH2PO4 +NaCl
- If a strong base such as sodium hydroxide is added to
the fluid containing phosphate buffer, a weak base
called disodium hydrogen phosphate is formed.
Importance of phosphate buffer system
- It is more powerful than bicarbonate buffer system as it
has a pH of 6.8 which is close to the pH of body fluids
that is 7.4
- It is useful in tubular fluids of kidneys as well

3) PROTEIN BUFFER SYSTEM

- They are present in the blood both in plasma and
erythrocytes
Protein buffer systems in plasma
- Elements of protein which form the weak acids in the
plasma are
1) C terminal carboxyl group
2) Side chain amino group of lysine
3) Imidazole group of histidine.

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Protein buffer system in erythrocytes

- Haemoglobin is the most effective protein buffer and the
major buffer in blood
- Due to its high concentration than plasma proteins
haemoglobin has about 6 times more buffering capacity
than plasma proteins
- The deoxygenated haemoglobin is a more powerful buffer
than oxygenated haemoglobin because of the higher PH

*REGULATION OF ACID BASE BALANCE BY RESPIRATORY MECHANISM

- Lungs play an important role in the maintenance of acid-
base balance by removing CO2, which is produced during
various metabolic activities in the body.
- This CO2, combines with water to form carbonic acid.
- Since carbonic acid is unstable, it splits into H+ and HCO3-,
CO2+ H2O ² H2CO3 ² H+ + HCO3-
- Entire reaction is reversed in lungs when CO2 diffuses
from blood into the alveoli of lungs.
H+ + HCO3- ² H2CO3 ² CO2 + H2O
And CO2, is blown off by ventilation.

*REGULATION OF ACID BASE BALANCE BY RENAL MECHANISM

APPLIED PHYSIOLOGY- DISTURBANCE OF ACID BASE STATUS

a) ACIDOSIS
- Acidosis is the reduction in pH below normal range
- It is produced by
❖increase in partial pressure of carbon dioxide in the
body fluids particularly in arterial blood
❖Decrease in bicarbonate concentration

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b) ALKALOSIS
- It is increase in pH above normal range
- It is produced by
❖Decrease in partial pressure of carbon dioxide in the
arterial blood
❖Increase in bicarbonate concentration

The acid base disturbances are

RESPIRATORY ACIDOSIS
- It is the acidosis that is caused by alveolar
hypoventilation
- During hyperventilation the lungs failed to expel carbon
dioxide which is produced in the tissues.
- Carbon dioxide accumulates in blood where a reacts with
water to form carbonic acid which is called RESPIRATORY
ACID.
- Hypoventilation is a primary cause for excess carbon
dioxide in the body

RESPIRATORY ALKALOSIS
- It is the alkalosis that is caused by alveolar
hyperventilation.
- Hyperventilation causes excess loss of carbon dioxide from
the body.
- Loss of carbon dioxide leads to decrease formation of
carbonic acid and decreased release of H+
- Hyperventilation is primary cause for loss of excess
carbon dioxide from the body because during
hyperventilation lot of carbon dioxide is expired through
respiratory tract leading to decreased partial pressure
of carbon dioxide.

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METABOLIC ACIDOSIS
- It is the acid base imbalance characterized by excess
accumulation of organic acids in the body which is
caused by abnormal metabolic processes
- Organic acid such as lactic acid, ketoacids and uric
acids are formed by normal metabolism
Causes of metabolic acidosis
LACTIC ACID
- the amount of lactic acid increases during anaerobic
glycolysis in some abnormal conditions such a circulatory
shock
- the amount of ketoacid increases because of insulin
deficiency as in the case of diabetes mellitus
URIC ACID
- The amount of uric acid increases in the body due to the
failure of excretion

METABOLIC ALKALOSIS
- Metabolic alkalosis is acid base imbalance caused by
loss of excess H + resulting in increased HCO3-
concentration
- Some of the endocrine disorders renal tubular disorders,
etc. cause metabolic disorders leading to loss of H +

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ACIDIFICATION OF URINE AND

ROLE OF KIDNEY IN ACID- BASE
BALANCE
- Kidney plays an important role in maintenance of acid
base balance by excreting hydrogen ions and retaining
bicarbonate ions
- Normally urine is acidic in nature with the pH of 4.5 to 6
- Metabolic activities in the body produce large quantity of
acids which threaten to push the body towards acidosis
- However kidneys prevent this by two ways

1) Reabsorption of bicarbonate ions

- About 4320 mEq of HCO3- is filtered by the glomeruli
everyday
- It is called filtered load of HCO3-
- Excretion of this much bicarbonate in urine will affect
the acid base balance of body fluids

2) Secretion of hydrogen ions

- Reabsorption of filtered HCO3- occurs by the secretion of H+
in the renal tubules.
- Secretion of H+ into the renal tubules occurs by the
formation of carbonic acid.
- H+ is secreted into the lumen of PCT, DCT and collecting
duct have a special type of cells called INTERCALATED
CELLS (I CELLS) that are involved in handling hydrogen and
bicarbonate ions.
- Secretion of H+ occurs by two pumps

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a) SODIUM HYDROGEN ANTIPORT PUMP

- When sodium ion is reabsorbed from the tubular fluid
into the tubular cell, H+ is secreted from the cell into the
tubular fluid in exchange for sodium
- The sodium hydrogen antiport pump present in the tubular
cells is responsible for the exchange of sodium and
hydrogen
- This type of sodium hydrogen counter transport occurs
predominantly in the DCT.

b) ATP DRIVEN PROTON PUMP

- This is an additional pump for H+ secretion in distal
convoluted tubule and collecting duct
- This pump operates by energy from ATP.

REMOVAL OF HYDROGEN IONS AND ACIDIFICATION OF URINE

Role of kidney in preventing metabolic acidosis
- Excretion of H+ occurs by three mechanisms

1) Bicarbonate mechanism
- All the filtered HCO3- in the renal tubules is reabsorbed.
- About 80% of it is reabsorbed in the proximal convoluted
tubule 15% in the Henle's loop and 5% in the distal
convoluted tubule and collecting duct
- The reabsorption of HCO3- - utilizes the hydrogen ion
secreted into renal tubules
- H+ secreted into the renal tubule combines with filtered
HCO3- forming carbonic acid
- Carbonic acid dissociates into carbon dioxide and water
in the presence of carbonic anhydrase
- In the tubular cells carbon dioxide combines with water
to form carbonic acid
- It immediately dissociates into H+ and HCO3- from the
tubular cells and enters the interstitium.
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- Simultaneously sodium is reabsorbed from the renal tubule

under the influence of aldosterone.
- HCO3- combines with sodium to form sodium bicarbonate
- For every hydrogen ion secreted into lumen of tubule one
bicarbonate ion is reabsorbed from the tubule
- In this way kidneys conserve bicarbonate ion

2) Phosphate mechanism
- In the tubular cells, carbon dioxide combines with water
to form carbonic acid.
- It immediately dissociates into H+ and HCO3-.
- HCO3- from the tubular cell enters the interstitium.
- Na is reabsorbed from renal tubule under the influence
of aldosterone. Na enters the interstitium and combines
with HCO3-.
- H+ is secreted into the tubular lumen from the cell in
exchange for Na
- H+ which is secreted into renal tubules, reacts with
phosphate buffer system.
- It combines with sodium hydrogen phosphate to form
sodium dihydrogen phosphate which is excreted in urine.
- The H+, which is added to urine in the form of sodium
dihydrogen phosphate, makes the urine acidic.

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3) Ammonia Mechanism
- This is the most important mechanism by which kidneys
excrete H+ and make the urine acidic.
- In the tubular epithelial cells, ammonia is formed when
the amino acid glutamine is converted into glutamic acid
in the presence of the enzyme glutaminase.
- Ammonia (NH3) formed in tubular cells is secreted into
tubular lumen in exchange for sodium ion.
- Here, it combines with H+ to form ammonium (NH4).
- The tubular cell membrane is not permeable to ammonium.
- Therefore, it remains in the lumen and then excreted into
urine.
- Thus, H+ is added to urine in the form of ammonium
compounds resulting in acidification of urine.
- Thus, by excreting H+ and conserving HCO3- kidneys produce
acidic urine and help to maintain the acid base balance
of body fluids.

APPLIED PHYSIOLOGY
- Metabolic acidosis occurs when kidneys fail to excrete
metabolic acids.
- Metabolic alkalosis occurs when kidneys excrete large
quantity of hydrogen

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RENAL FUNCTION TESTS

- Renal function tests are the group of tests that are
performed to assess the functions of kidney.

- Renal function tests are of three types

1. Examination of urine
2. Examination of blood alone
3. Examination of blood and urine.

EXAMINATION OF URINE- URINALYSIS

- Routine examination of urine is a group of diagnostic tests
performed on the sample of urine
- Urinalysis is done by
1. Physical examination
2. Microscopic examination
3. Chemical analysis

PHYSICAL EXAMINATION
1. Volume
- Increase in urine volume indicates increase in protein
catabolism and renal disorders such as chronic renal
failure, diabetes insipidus and glycosuria

2. Color
- Normally urine is straw coloured.
- Abnormal coloration of urine is due to several causes such
as jaundice, hematuria, hemoglobinuria, medications,
excess urobilinogen, ingestion of beetroot or color added
to food.

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3. Appearance
- Normally urine is clear.
- It becomes turbid in both physiological and pathological
conditions.
- Physiologycal conditions causing turbidity of urine are
• precipitation of crystals,
• presence of mucus or
• vaginal discharge.
- Pathological conditions causing turbidity are presence of
blood cells, bacteria or yeast

4. Specific Gravity
- Specific gravity of urine is the measure of dissolved
solutes (particles) in urine.
- It is low in diabetes insipidus and high in diabetes
mellitus, acute renal failure and excess medications.

5. Osmolarity
- Osmolarity of urine decreases in diabetes insipidus.

6. pH and Reaction
- Measurement of pH is useful in determining the metabolic
or respiratory acidosis or alkalosis.
- The pH decreases in renal diseases.
- In normal conditions, pH of urine depends on diet.
- It is slightly alkaline in vegetarians and acidic in non-
vegetarians

MICROSCOPIC EXAMINATION
- Microscopic examination of centrifuged sedimented urine
is useful in determining the renal diseases

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1. Red Blood Cells

- Presence of red blood cells in urine indicates glomerular
disease such as glomerulonephritis

2. White Blood Cells

- The number of WBCs increases in acute glomerulonephritis,
infection of urinary tract, vagina or cervix

3. Epithelial Cells
- Normally few tubular epithelial cells slough into urine.
- Presence of many epithelial cells suggests nephrotic
syndrome and tubular necrosis

4. Casts
- Casts are the cylindrical bodies that are casted in the
shape of renal tubule Casts may be hyaline granular or
cellular in nature.
- Hyaline and grunular casts, which are formed by
precipitation of proteins, may appear in urine in small
numbers -The number increases in proteinuria due to
glomerulonephritis.

5. Crystals
- Several types of crystals are present in normal urine
Common crystals are the crystals of calcium oxalate,
calcium phosphate, uric acid and triple phosphate
(calcium, ammonium and magnesium)
- Abnormal crystals such as crystals of cystine and
tyrosine appear in liver diseases.

6. Bacteria
- Bacteria are common in urine specimens because of normal
microbial flora of urinary tract, urethra and vagina and
because of their ability to multiply rapidly in urine.

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CHEMICAL ANALYSIS
- Chemical analysis of urine helps to determine the presence
of abnormal constituents of urine or presence of normal
constituents in abnormal quantity.
- Both the findings reveal the presence of renal
abnormality.
- Following are the common chemical tests of urine.

1. Glucose
- Glucose appears in urine when the blood glucose level
increases above 180 mg/dl
- Glycosuria (presence of glucose in urine) may be the first
indicator of diabetes mellitus

2. Protein
- Presence of excess protein (proteinuria) particularly
albumin (albuminuria) in urine indicates renal diseases.
- Urinary excretion of albumin in normal healthy adult is
about 30 mg/day.
- It exceeds this level in glomerulonephritis.

3. Ketone Bodies
- Ketonuria (presence of ketone bodies in urine) occurs in
pregnancy, fever, diabetes mellitus, prolonged starvation
and glycogen storage diseases.

4. Bilirubin
- Bilirubin appears in urine (bilirubinuria) during hepatic
and post- hepatic jaundice

5. Urobilinogen
- Normally, about 1 to 3.5 mg of urobilinogen is excreted in
urine daily.
- Excess of urobilinogen in urine indicates hemolytic
jaundice.
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6. Bile Salts
- Presence of bile salts in urine reveals jaundice.

7. Blood
- Presence of blood in urine (haematuria) indicates
glomerulonephritis, renal stones, infection or malignancy
of urinary tract.
- Haematuria must be confirmed by microscopic examination
since chemical test fails to distinguish the presence of
red blood cells or haemoglobin in urine

8. Haemoglobin
- Haemoglobin appears in urine (haemoglobinuria) during
excess haemolysis

9. Nitrite
- Presence of nitrite in urine indicates presence of in urine
since some bacteria convert nitrate into nitrite in urine.
EXAMINATION OF BLOOD
Estimation of Plasma proteins
- Normal values
a) Total proteins: 7.3 g/dL (6.4 to 8.3 g/dL)
b) Serum albumin: 4.7 g/dL
c) Serum globulin :23 g/dL
- Level of plasma proteins is altered during renal failure

Estimation of Urea, Uric acid and Creatinine

- Normal Values
a) Urea : 25 to 40 mg/dL 25 mg/dL
b) Uric acid : 2.5mg/dl
c) Creatinine : 0.5 to 1.5 mg/dL
- The blood level of these substances increases in renal
failure

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EXAMINATION OF BLOOD AND URINE

PLASMA CLEARANCE
- Plasma clearance is defined as the amount of pasta that
is cleared off a substance in a given unit of time.
- It is also known as renal clearance.
- It is based on Fick principle.
Determination of clearance value for certain substances helps
in assessing the following renal function
1. Glomerular filtration rate.
2. Renal plasma flow.
3. Renal blood flow
Value of following factors is required to determine the
plasma clearance of a particular substances
1. Volume of urine excreted
2. Concentration of the substance in urine
3. Concentration of the substance in blood.

Formula to calculate Clearance Value

C= UV/P
Where, C= clearance,
U= Concentration of substance in urine
V= Volume of urine flow, P= Concentration of the substance in
plasma
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

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Inulin Clearance
- A known amount of insulin 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,
Glomerular filtration rate = UV/P
= 125 mL/min

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 aminohippuric acid (PAH)
- Renal plasma flow= UV/P
= 660 mL/min

MEASUREMENT OF RENAL BLOOD FLOW

- Values of factors necessary to determine renal blood
flow are:
1. Renal Plasma Flow
- Renal plasma flow is measured by using PAH clearance.

2. Percentage of Plasma Volume in Blood

- Percentage of plasma volume 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.

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Calculation of Renal Blood Flow

- Renal blood flow is calculated with the values of renal
plasma flow and percentage of plasma in blood by using
a formula given below.
- Renal blood flow =
Renal plasma flow / % of plasma in blood

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RENAL FAILURE
- Renal failure refers to failure of excretory functions of
kidney.
- It is usually characterized by decrease in glomerular
filtration rate (GFR)
- So GFR is considered as the best index of renal failure.
- If 50% of the nephrons are affected, GFR decreases only
by 20 to 30%.
- It is because of the compensatory mechanism by the
unaffected nephrons.
- The renal failure may be either ACUTE OR CHRONIC

- COMPLICATIONS OF RENAL FAILURE

1. Deficiency of calcitriol (activated vitamin D) resulting in
reduction of calcium absorption from intestine and
hypocalcemia. Deficiency of calcitriol and hypocalcemia
may cause secondary hyperparathyroidism in some
patients.
2. Deficiency of erythropoietin resulting in anemia
3. Disturbances in acid-base balance.

ACUTE RENAL FAILURE

- Acute renal failure is the abrupt or sudden stoppage of
renal functions.
- It is often reversible within few days to few weeks.
- Acute renal failure may result in sudden life-threatening
reactions in the body with the need for emergency
treatment.

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CAUSES
1. Acute nephritis (inflammation of kidneys) which usually
develop by immune action
2. Damage of renal tissues by poisons like lead, mercury and
carbon tetrachloride.
3. Renal ischemia, which develops during circulatory shock
4. Acute tubular necrosis
5. Severe transfusion reactions.
6. Blockage of ureter due to the formation of calcium (renal
stone) or tumor

FEATURES
1. Oliguria (decreased urinary output)
2. Anuria (cessation of urine formation) in severe cases.
3. Proteinuria (appearance of proteins in urine) including
albuminuria (excretion of albumin in urine)
4. Haematuria (presence of blood in urine)
5. Oedema due to increased volume of extracellular fluid
(ECF) caused by retention of sodium and water.
6. Hypertension
7. Acidosis
8. Coma

CHRONIC RENAL FAILURE

- Chronic renal failure is the progressive, long standing
and irreversible impairment of renal functions.
- When some of the nephrons lose the function, the
unaffected nephrons can compensate it
- However, when more and more nephrons start losing the
function over the months or years, the compensatory
mechanism fails and chronic renal failure develops.

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CAUSES
1. Chronic nephritis
2. Polycystic kidney disease
3. Renal calculi (kidney stones).
4 Urethral constriction
5. Hypertension.
6. Atherosclerosis
7. Tuberculosis
8. Slow poisoning by drugs or metals

FEATURES
1. Uremia
- It is characterized by excess accumulation of end
products of protein metabolism such as urea, nitrogen and
creatinine in blood.
- There is also accumulation of some toxic substances like
organic acids and phenols.
- Uremia occurs because of the failure of kidney to excrete
the metabolic end products and toxic substances.

Common features of Uremia

1. Anorexia (loss of appetite)
2. Lethargy
3. Drowsiness
4. Nausea and vomiting.
5. Pigmentation of skin.
6. Muscular twitching, tetany and convulsions
7. Confusion and mental deterioration
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2. Acidosis
Uremia results in acidosis, which leads to coma and
death.

3. Edema
Failure of kidney to excrete sodium and electrolytes
causes increase in extracellular fluid volume resulting
development of edema.

4. Blood Loss
Gastrointestinal bleeding accompanied by platelet
dysfunction leads to heavy loss of blood.

5. Anemia
Since, erythropoietin is not secreted in the kidney during
renal failure, the production of RBC decreases resulting
In normocytic normochromic anaemia.

6. Hyperparathyroidism
Secondary hyperparathyroidism is developed due to the
deficiency of calcitriol bones results in osteomalacia.

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MICTURITION
- Micturition is a process by which urine is voided from the
urinary bladder. It is a reflex process.
- The functional anatomy and nerve supply of urinary
bladder are essential for the process of micturition

FUNCTIONAL ANATOMY OF URINARY BLADDER AND URETHRA

URINARY BLADDER
- Urinary bladder is a triangular hollow organ located in
lower abdomen..
- It consists of a body and neck.
- Wall of the bladder is formed by smooth muscle.
- It consists of three ill-defined layers of muscle fibers
called detrusor muscle,
• the inner longitudinal layer
• Middle circular layer and
• Outer longitudinal layer.
- Inner surface of urinary bladder is lined by mucus
membrane
- In empty bladder, the mucosa falls into many folds
called rugae.
- Lower part of the bladder is narrow and forms the neck.
It opens into urethra via internal urethral sphincter.
URETHRA
- Male urethra has both urinary function and reproductive
function. It carries urine and semen.
- Female urethra has only urinary function and it comes only
urine.
NERVE SUPPLY TO URINARY BLADDER AND SPHICTERS is by
sympathetic and parasympathetic nerve supply.

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FILLING OF URINARY BLADDER

- Urine is continuously formed by nephrons and it flows into
urinary bladder drop by drop through ureters.
- When urine collects in the pelvis of ureter, the contraction
sets up in pelvis.
- This contraction is transmitted through rest of the ureter
in the form of peristaltic wave up to trigone of the
urinary bladder.
- Peristaltic wave usually travels at a velocity of 3 cm/sec
and moves the urine into the bladder.
- After leaving the kidney, when peristaltic wave pushes the
urine towards bladder, this valve opens towards the
bladder.
- The position of ureter and the valvular arrangement at
the end of ureter prevent the back flow of urine from
bladder into the ureter when the detrusor muscle
contracts.
- Thus, urine is collected in bladder drop by drop.
CYSTOMETROGRAM
- It is the technique used to study the relationship between
intravesical pressure and volume of urine in bladder.
- It is the graphical registration of pressure changes in
urinary bladder in relation to volume of urine collected
in it.
MICTURITION REFLEX
- Micturition reflex is the reflex by which micturition
occurs.
- This reflex is elicited by the stimulation of stretch
receptors situated on the wall of urinary bladder and
urethra.
- When about 300 to 400 mL of urine is collected in the
bladder, intravesical pressure increases.

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- This stretches the wall of bladder resulting in

stimulation of stretch receptors and generation of sensory
impulses.
Filling of urinary bladder
↓
Stimulation of stretch receptors
↓
Afferent impulses pass via pelvic nerve
↓
Sacral segments of spinal cord
↓
Efferent impulses via pelvic nerve
↓
Contraction of detrusor muscle and relaxation of internal
sphincter
↓
Flow of urine into urethra and stimulation of stretch
receptors
↓
Afferent impulses via pelvic nerve
↓
Inhibition of pudendal nerve
↓
Relaxation of external sphincter
↓
Voiding of urine
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APPLIED PHYSIOLOGY
1. ATONIC BLADDER - EFFECT OF DESTRUCTION OF SENSORY NERVE
FIBERS
- Atonic bladder is the urinary bladder with loss of tone
in detrusor muscle.
- It is also called flaccid NEURO- GENIC BLADDER OR
HYPOACTIVE NEUROGENIC BLADDER.
- It is caused by destruction of sensory (pelvic) nerve
fibers of urinary bladder.
- Due to the destruction of sensory nerve fibers, the
bladder is filled without any stretch signals to spinal
cord
- Due to the absence of stretch signals, detrusor muscle
loses the tone and becomes flaccid.
- So, the bladder is completely filled with urine without
any micturition.
- Now, urine overflows in drops as and when it enters the
bladder.
- It is called overflow incontinence or over flow dribbling.
- Spinal injury and syphilis are the conditions of
destruction of sensory nerve fibres

2. AUTOMATIC BLADDER
- It is the urinary bladder characterized by hyperactive
micturition reflex with loss of voluntary control.
- So, even a small amount of urine collected in the bladder
elicits the micturition reflex resulting in emptying of
bladder.

3. UNINHIBITED NEUROGENIC BLADDER

- it is the urinary bladder with frequent and
uncontrollable micturition caused by lesion in midbrain
- it is also called spastic neurogenic bladder or
hyperactive neurogenic bladder

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4. NOCTURNAL MICTURITION
- it is the involuntary voiding of urine during night.
- it is otherwise known as enuresis or bedwetting.
- it occurs due to the absence of voluntary control of
micturition
- it is a common and normal process in infants and children
below 3 years.
- it is because of incomplete myelination of motor nerve
fibres of the bladder.
- if it occurs after three years of age it is considered
abnormal and occurs due to neurological disorders like
lumbosacral vertebral defects.

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DIALYSIS AND ARTIFICAL

KIDNEY
- Dialysis is the procedure to remove waste materials and
toxic substances and to restore normal volume and
composition of body fluid in severe renal failure.
- It is also called hemodialysis

ARTIFICIAL KIDNEY
- Artificial kidney is a machine that is used to carry out
dialysis during renal failure.
- It is used to treat the patients suffering from-
1. Acute renal failure.
2. Chronic or permanent renal failure.

MECHANISM OF FUNCTION OF ARTIFICIAL KIDNEY

- The term dialysis refers to diffusion of solutes from an
area of higher concentration to the area of lower con
centration through a semipermeable membrane.
- This forms the principle of artificial kidney.
- Patient's arterial blood is passed continuously or
Intermittently through the artificial kidney and then
back to the body through the vein.
- Heparin is used as an anti- coagulant while passing the
blood through the machine.
- Inside the artificial kidney, the blood passes through a
DIALYZER called HEMOFILTER, which contains minute channels
interposed between two cellophane membranes
- The cellophane membranes are porous in nature.
- The outer surface of the membranes is baked in the
dialyzing fluid called dialysate.

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- Urea, creatinine, phosphate and other unwanted substances

from the blood pass into the dialysate by concentration
gradient.
- total amount of blood in the dialysis machine at the time
is about 500 ml.

FREQUENCY AND DURATION OF DIALYSIS

- It depends upon the severity of renal dysfunction
- It is done usually THRICE A WEEK in severe uremia
- Each time the artificial kidney is used for about 6 HOURS

PERITONEAL DIALYSIS
- It is the technique in which peritoneal membrane is used
as a semipermeable membrane.
- A catheter is inserted into the peritoneal cavity through
anterior abdominal wall and sutured.
- the dialysate is passed through the catheter under
gravity.
- unwanted substances diffuse from blood vessels into
dialysate.
COMPLICATIONS OF DIALYSIS
- it depends upon the patient’s condition, age, existence of
diseases other than renal failure and many other factors.
- common complications of dialysis in individual having only
renal dysfunction are
1. Sleep disorders
2. Anxiety
3. Depression

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DIURETICS
- Diuretics or Diuretic agents are the substances which
enhance the urine formation and output.
- They are generally used for the treatment of disorders
involving increase in extracellular fluid volume like
1. Hypertension
2. Congestive cardiac failure
3. Edema
- Adverse effects of diuretics include dehydration,
electrolyte imbalance, potassium deficiency, headache,
dizziness, renal damage, heart palpitations

TYPES OF DIURETICS.
1. Osmotic diuretics
- they are the substances that induce osmotic diuresis.
- osmotic diuresis occurs because of increase osmotic
pressure.
- examples include urea, mannitol, sucrose and glucose

2. Diuretics which inhibit active reabsorption of

electrolytes
- this type inhibit the active reabsorption of electrolytes
like sodium and potassium from the renal tubular fluid
a. LOOP DIURETICS- diuretics which inhibit the electrolyte
reabsorption in thick ascending limb of loop of henle.
Eg. Furosemide, bumetanide
b. Diuretics which INHIBIT ACTIVE TRANSPORT OF ELECTROLYTES
in proximal part of DCT
E.g. chlorothiazide, metolazone
c. Diuretics which INHIBIT ACTIVE TRANSPORT OF ELECTROLYTES
in distal part of DCT and collecting duct.
Eg. Amiloride, Triamterene

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3. Diuretics which inhibit action of aldosterone

- they are also called the potassium retaining diuretics or
aldosterone antagonist
- E.g. spironolactone

4. Diuretics which inhibit activity of carbonic anhydrase

E.g. Acetazolamide

5. Diuretics which increase glomerular filtration rate

E.g. Caffeine, theophylline

6. Diuretics which inhibit secretion of ADH

E.g. water, ethanol

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SKIN
- Skin is the largest organ of the body. It is made up of an
outer epidermis and inner dermis.
- Epidermis is the outer layer of skin it is formed by
stratified epithelium.
• it does not have blood vessels
• it is formed by five layers
i) stratum corneum/horny layer that consists of
dead cells called corneocytes
ii) stratum lucidum made up of flattened epithelial
cells
iii) stratum granulosum with 2 to 5 rows of flattened
rhomboid cells
iv) stratum spinosum possess spine like protoplasmic
projections
v) stratum germinativum is a thick layer made up of
polygonal cells.

- Dermis is the inner layer of skin.

- It is made up of superficial papillary layer and deeper
reticular layer

APPENDAGES OF SKIN include hair follicles nails sweat glands

sebaceous glands and mammary glands
COLOUR OF SKIN depends upon pigmentation of skin and
haemoglobin in the blood
GLANDS OF SKIN
SEBACEOUS GLANDS
- they are simple or branched alveolar glands situated in
the dermis of skin
- it secretes and oily substance called sebum.
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- it contains free fatty acids, sterols, paraffin

- acne is the localised inflammatory condition that occurs
because of over activity of sebaceous glands
SWEAT GLANDS
- it is of two types
Eccrine glands
- are distributed throughout the body.
- the glands function throughout life since birth.
- The secrete a clear watery sweat
- play an important role in regulating body temperature
Apocrine glands
- they are situated only in areas of body like axilla, pubis
areola and umbilicus.
- these glands are non-functional till puberty
- the secretion of these glands is thick and milky.
- Pheromones are a group of chemical substances that are
secreted by apocrine glands.
- They are mostly present in urine, vaginal fluid and other
secretions of mammals.
FUNCTIONS OF SKIN
1) PROTECTIVE FUNCTION
- protection from bacteria and toxic substances
- protection from mechanical blow
- protection from UV rays

2) SENSORY FUNCTION
- skin is the largest sense organ in the body having many
nerve endings.

3) STORAGE FUNCTION
- it stores fat water chloride and sugar

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4) SYNTHETIC FUNCTION
- vitamin d3 is synthesized in skin by the action of UV rays
from sunlight on cholesterol

5) REGULATION OF BODY TEMPERATURE

6) REGULATION OF WATER AND ELECTROLYTE BALANCE
7) EXCRETORY FUNCTION
8) ABSORPTIVE FUNCTION
9) SECRETORY FUNCTION

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BODY TEMPERATURE
- Normal body temperature in human is 37 °C (98°F) when
measured by placing the clinical thermometer in the
mouth.

VARIATIONS OF BODY TEMPERATURE

- PHYSIOLOGICAL VARIATION includes that of age,
sex (less in females),
diurnal variation (1°C less in early morning),
after meals (0.5°C increase)
exercise (increases)
sleep (decreases by 0.5°C)
emotion (increases)
and menstrual cycle

- PATHOLOGICAL VARIATIONS
• abnormal increase – hyperthermia
• abnormal decrease- hypothermia

HEAT BALANCE
HEAT GAIN OR HEAT PRODUCTION IN THE BODY
1. Metabolic activities
- major portion of heat produced in the body is due to the
metabolism of foodstuffs. It is called heat of metabolism.

2. Muscular activity
- heat is produced in the muscle both at rest and during
activities.

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3. Role of hormones
- thyroxine and adrenaline increase the heat production

4. Radiation of heat from the environment

- body gains heat by radiation

5. Shivering
- compensatory physiological mechanism during which
enormous heat is produced

HEAT LOSS FROM THE BODY

1. Conduction
- 3% of heat is lost from the surface of body to other
objects such as chair or bed, by means of conduction.
2. Radiation
- 60% of heat is lost by means of radiation, transfer of
heat by infrared electromagnetic radiation from body to
other objects
3. Convection
- 15% of heat is lost from body to the air by convection,
heat is conducted to the air surrounding the body and
then carried away by air currents
4. Evaporation
- 22% of heat is lost through evaporation that is insensible
perspiration
5. Panting
- rapid shallow breathing associated with dribbling of
more saliva.

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REGULATION OF BODY TEMPERATURE

APPLIED PHYSIOLOGY
1. HYPERTHERMIA – FEVER
- Elevation of body temperature above the set point is
called hyperthermia, fever or pyrexia.
- Fever is classified into low grade, moderate and high
grade fever
- Causes include infection, hyperthyroidism, brain lesions
and diabetes insipidus
- Signs and symptoms depend upon the cause that include
headache, sweating, shivering, muscle pain, dehydration,
confusion, hallucination, irritability.

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2. HYPOTHERMIA
- Decrease in body temperature below 35°C (95°F) scald
hypothermia.
- It is the clinical state of subnormal body temperature
when the body fails to produce enough heat to maintain
the normal activities.
- It is classified as mild, moderate and severe
hypothermia
- Causes include exposure to cold water, immersion in cold
water, drug abuse, hypothyroidism, hypopituitarism, lesion
in hypothalamus and haemorrhage in certain parts of the
brain stem
- signs and symptoms include
• mild hyperthermia (uncontrolled intense shivering),
• moderate hypothermia ( muscles become stiff) and
severe hypothermia (person feels very weak and
exhausted with incoordination and physical
disability)

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