Brihaspathi Synopsis

NEET

Concepts

Volume 01

Anatomy

Physiology

Biochemistry

DADH

HUMAN ANATOMY

Scalp

1

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SCALP

Soft tissues covering cranial vault

EXTENT

Lateral: temporal lines

Anterior: eyebrows-superior orbital margins

Posterior: superior nuchal line

Layers

Contents

Applied anatomy

S:

Skin

Thin

skin

with

sweat

and

sebaceous glands

Sebaceous cysts

C:

(dense)

Connective

tissue

Thin layer of fat and fibrous tissue

in form of locules with blood

vessels and nerves (with its walls

attached to its fibrous walls)

Injury
blood vessels walls non-collapsible

severe bleeding, inflammation
very painful

A:

Aponeurosis/

Gálea

aponeurótica

Aponeurosis

is

membranous,

tendon of fleshly bellies of

epicranial muscle (formed by

occipitalis and frontalis muscles,

each with two bellies)

Injury
(horizontal) leads to gapping of wound

by contraction of fronto-occipitalis

L:

Loose areolar

connective

tissue

Layer provides an easy plane of

separation between the upper

three layers and the Pericranium

"Danger Zone" because of the ease by which

infectious agents can spread through it to emissary

veins which then drain into the cranium.

It contains the major blood vessels of the scalp.

Safety-valve hematoma-fracture of the skull with

tear of dura, signs of cerebral compression do not

develop until this space is filled with blood.

P:

Pericranium

Periosteum of the skull bones

(continuous with endocranium at

sutural lines)

Cephalohaematoma / traumatic cephalohydrocele -

takes shape of related bone

BLOOD SUPPLY

Location

Arteries

Branches of

Anterior to auricle

Supratrochlear Artery

INTERNAL CAROTID

Supraorbital Artery

Superficial Temporal Artery

EXTERNAL CAROTID

Posterior to auricle

Posterior Auricular Artery

Occipital Artery

VENOUS DRAINAGE

Location

Veins

Drain into

Anterior to auricle

Supratrochlear vein

Join to form Angular vein, continue as Facial

vein;

join

with

anterior

division

of

Retromandibular vein
common facial vein

Internal jugular vein

Supraorbital

Superficial Temporal

Join

with

maxillary

vein,

forms

Retromandibular vein

Posterior to auricle

Posterior Auricular

Join

with

posterior

division

of

Retromandibular vein
External jugular

vein
Sub clavian vein

Occipital

Joins Sub-occipital venous plexus

NERVE SUPPLY - "Z-GLASS"

Location

Nature

Nerves

Branches of

Anterior to

auricle

Sensory

Supratrochlear

Ophthalmic division of the Trigeminal nerve

Supraorbital

Zygomatico temporal Maxillary division of the Trigeminal nerve

Auriculo temporal

Mandibular division of the Trigeminal nerve

Motor

Temporal

Facial nerve

Posterior to

auricle

Sensory

Greater Auricular

C2, C3-Cervical Plexus

Lesser occipital

C2 -Cervical Plexus

Greater occipital

C2-Cervical Plexus

Third occipital

C3-Cervical Plexus

Motor

Posterior auricular

Facial

LYMPHATIC DRAINAGE

•

Anterior to Auricle: Pre-auricular/Superficial parotid node

•

Posterior to Auricle: Post auricular/Mastoid and Occipital nodes

PHYSIOLOGY

General Physiology

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GENERAL PHYSIOLOGY

INTRODUCTION

•

The cell is the smallest structural and

functional unit of the body

•

Integrated functioning of about 100 trillion

cells forms human body

•

These cells are organized into different

organs which in turn are combined to form

system.

•

For better understanding human body can

be considered to be functionally organized

into various systems like:

1. Skin and its appendages: Skin, Hair,

Nails, Sebaceous glands, Sweat glands

2. Skeletal system: Bone, Cartilage, Joints,

Ligaments

3. Muscular system: Skeletal muscles,

Smooth muscles, Cardiac muscles

4. Nervous system:

Central Nervous system

Brain Spinal Cord

Peripheral Nervous system

Cerebrospinal Nerves Autonomic Nervous System

Supplies

Body wall and Limbs

Sympathetic Parasympathetic

Supplies

Viscera (Organs)

5. Cardiovascular system:

Heart Arteries

Arterioles

Capillaries

Blood Vessels

Veins

Small venules

Sinusoids

6. Respiratory system:

Lungs

Airway: Nasal cavity Larynx 

Pharynx  Trachea  Bronchi

Bronchioles  Alveoli

7. Digestive system:

Starts at mouth and ends at anus

Oral cavity, pharynx, esophagus,

stomach,

small

intestine,

large

intestine

Also includes liver and gall bladder

and pancreas

8. Excretory system:

Excretion is not egestion

Involves kidney, ureter, bladder and

urethra

9. Reproductive system:

Male reproductive system  Testis,

Epididymis,

Ductus

deferens,

Seminal vesicles, Prostate, Male

urethra, Penis

Female reproductive system  Right

and left ovaries, Uterine tubules,

Uterus, Vagina, External genitalia,

Mammary glands

10. Endocrine system:

Pituitary glands, Pineal glands,

Thyroid glands, Parathyroid glands,

Suprarenal

glands,

Islet

of

Langerhans, Interstitial cells of the

testis, Follicles and corpora lutea of

the ovaries, Some cells of the

kidneys, thymus and the placenta

11. Blood and Immune system

BODY COMPOSITION

In an average adult male

•

Water (60%)

•

Minerals (7%)

•

Proteins and related substances (18%)

•

Fat (15%)

Total Body Water – TBW (60 % of body weight)

•

Intracellular fluid (2/3

of TBW)

40% of body wt

•

Extracellular fluid (1/3

of TBW)

20% of body wt

Interstitial fluid (5% of body wt)

(25% of ECF)

Plasma (75% of body wt) (15% of

ECF)

Lymph

CSF

Measurement of body fluid volumes

•

Theoretically measured using formula 

ܸ =

A1 − A2

ܥ

V = Volume of fluid compartment

A1 = Area of indicator injected in the fluid

A2 = Area of indicator and removed by

excretion of metabolism

C = Concentration of indicators in the fluid

Most abundant

Cation

Most abundant

Anion

ECF

Na

_Cl

_(HCO3-)

ICF

K

_(Mg

₎

_{Proteins (PO}

₎

ܧܥܨ

ܫܥܨ

ݎܽݐ݅݋ = ℎ݅݃ℎ

ܰܽ +

ܭ +

ݎܽݐ݅݋

VOLUMES

MEASUREMENT

TBW

• By dilution principle; used to measure other body spaces

• D

pyrine are also used (Mn: DAT)

ECF

• Most accurate method is by using Inulin, Mannitol and sucrose have

also been used

ICF (cannot be measured

directly)

• TBW – ECF (Mn: SIM)

Interstitial fluid volume

(can not be measured)

• ECF – Plasma volume

Plasma Volume

• By dyes that become bound to plasma protein Ex: Evan blue (T-1824)

Mn: PEA

• Serum Albumin labeled with radioactive iodine, I

126

_{, Na}

_{, Thio}

sulfate

Total blood volume (TBV)

•

Plasma Vol ሺPl. Vሻ x

ଵ଴଴ ଵ଴଴ି୦ୣ୫ୟ୲୭ୡ୰୧୲

Red cell volume

• TBV – Pl. V

• Measured by injecting tagged RBCs and measuring the fraction of

red cells that is tagged.

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BODY ELECTROLYTES

•

7% of total body weight

Ionic concentration in ECF and ICF

ION ICF (mMol/L) ECF (mMol/L) Total percentage available for exchange across cell membrane Na+ _{12 145 65 – 70%} K+ _{155 4 ≈100%} H+ _{13 x 10} -5 _{3.8 x 10} -5 Cl- _{3.8 120} HCO3- 8 27 Anions (proteins) 155 0

PO4 Non exchangeable

K

_{ Efflux along concentration and}

Na+  Influx electrical gradient

•

High proteins in plasma than in interstitial

fluid plays important role in maintaining

fluid balance.

•

Ca

(predominant in ECF) and Mg

(predominant in ICF) are non exchangeable.

•

Only exchangeable solutes are osmotically

active.

Functions of Electrolytes

Electrolytes are main solutes in the body

fluids for maintenance of acid base balance

Electrolytes

_maintain

_the

_proper

osmolarity and volume of body fluids

The concentration of certain electrolytes

determines their specific physiological

functions. Eg: The effect of calcium ions on

neuromuscular excitability

INTERNAL ENVIRONMENT

AND HOMEOSTASIS

•

Claude Bernarde (1949), the great French

Physiologist, introduced the term Internal

environment of the body or the Milieu interiew

for the extra cellular fluid (ECF) of the body

because all the body cells depends on ECF

for maintenance of cellular life.

•

Homeostasis is a term introduced by W.B

Cannon, refers to the mechanism by which

the constancy of the internal environment is

maintained and ensured.

•

Cell membrane and vascular endothelium

with varying permeability play an important

role in maintenance of homeostasis.

Factors involved in the maintenance of Internal

Environment

1. Maintenance of pH of ECF (acid-base

balance)

2. Regulation of temperature

3. Maintenance of water and electrolytic

balance

4. Supply of nutrients, oxygen, enzymes and

hormones

5. Removal of metabolic and other waste

products

•

All systems of the body play vital role in an

integrated manner for the maintenance of

internal environment

Mode of action of Homeostatic control system

Feedback Mechanism

1. Negative feedback mechanism

•

Most control systems of body act by this

mechanism

•

That is, in general if the activity of a

particular system is increased or

decreased a control system initiates a

series of changes that returns the activity

towards normal.

•

Stabilizes homeostatic mechanism

‘Feedback’ mechanism

Is through

Negative Positive

•

Ex:

1. When the blood pressure suddenly

rises or lowers, it initiates a series of

reactions that tries to bring the BP to

normal levels.

2. Other examples: ACTH secretion,

aldosterone K+ glucose regulation,

GH secretion.

2. Positive feedback mechanism

•

It is better known as a Vicious circle

•

Usually it is harmful and in some

instances even death can occur due to

positive feedback

•

Destabilizes homeostatic mechanism

•

Ex:

1. When a person has suddenly bled 2

liters of blood, a vicious circle of

progressively weakening of the heart

is set which ultimately cause death.

If it of mild degree can be overcome

by negative feedback mechanism.

2. Sometimes positive feedback can

serve useful purposes. Ex: child birth

(parturition)

during

labour

is

facilitated

by

progressively

increasing uterine contractions due

to positive feedback from stretching

of cervix by head of the body.

3. Other examples: Clotting blood, Ca

entry into sarcoplasmic reticulum,

LH surge during ovulation, Milk

ejection reflex, Action potential,

Shock

Adaptive Control System

•

This refers to a delayed type of negative

feedback mechanism

•

Seen in nervous system

CELL STRUCTURE

•

A typical cell as seen by the light microscope

consists of three basic components

Cell membrane

Cytoplasm

Nucleus

CELL MEMBRANE

•

Cell membrane/plasma membrane is the

protective sheath, enveloping the cell

body

•

It separates ECF from ICF

•

It is a unit membrane consisting of two

electron dense layers separated by an

electro lucent layer

•

Biochemically, cell membrane is mainly

made up of

Lipids (40%)

Proteins (55 %)

Carbohydrates (5 %)

Ratio of proteins to lipids in different

membranes

•

Inner mitochondrial membrane – 3.2 (max)

•

Sarcoplasmic reticulum – 2.0

•

Outer mitochondrial membrane

– 1.1

•

Myelin – 0.23

•

In almost all the membrane of the body

proteins are equal or exceed the quantity of

lipid. The only exception is Myelin (high lipid

content provide good insulation)

•

Two types of proteins are recognized

1.

Lipoproteins – enzymes, ion channels

2.

Glycoproteins

–

receptors,

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PHOSPHOLIPIDS

PROTEINS

Integral/Transmembrane proteins Peripheral proteins

•

Are present embedded in either the inner

or outer leaflet of the lipid bilayer and are

respectively called as

•

Intrinsic proteins or Extrinsic/Surface

proteins

•

They do not interact directly with the

phospholipids in the bilayer and do not

require use of detergents for their release

•

They

are

weakly

bound

to

the

hydrophilic region of specific integral

proteins

•

They interact with the phospholipids and

requires the use of detergents for their

solubilisaiton

•

Generally span the lipid bilayer

•

Distributed asymmetrically across the lipid

bilayer

•

Are usually globular proteins

•

On the basis of function they have been

described as

Channel proteins

Carries proteins

Receptor proteins

Antigen

Pumps

Caveolae

•

Lipid rafts + specific

protein Cavedin-I

•

Proteins

detected

in

Caveolae form various

components of signal

transduction system

Lipid rafts

•

Dynamic

areas

of

exoplasmic

leaflets

of

lipid bilayer enriched in

cholesterol

and

phospholipid

•

Involved

in

signal

transduction

Along with Cholesterol

•

Maintains

fluidity

of

membrane

•

As membrane fluidity 

its permeability to water



_{and small hydrophilic}

molecules increases

Properties of Cell Membrane

•

Membranes are asymmetrical shut like enclosed

structures with distinct out and inner

surface. This asymmetry is attributed to

Irregular distribution of protein within

the cell membrane

External location of carbohydrate

attached to membrane protein

Specific enzymes are located exclusively

on the outside or inside of membranes

Gap junction, synapses and tight

junctions occupy only smaller regions of

membrane

and

generate

local

asymmetry

•

The choline – containing phospholipids

(phosphotidylcholine and sphinomyelin) are

located mainly in the outer molecular layer;

The amino phospholipids (phosphotidyl

serine and phosphotidylethanolamine) are

preferentially located in inner leaflet

•

Membranes are dynamic structures

Major lipids in mammalian membranes

are phospholipids, glycolipids and

cholesterol.

Membrane lipids are amphipathic i.e.,

contain

both

hydrophobic

and

hydrophilic regions

Membrane lipids are bilayered

Proteins are associated with lipid bilayer

and may be integral or peripheral in

location

•

Ion channels are transmembrane proteins

that allow selective entry of various ions;

ionophores are molecules that act as

membrane

shuttle

for

various

ions;

aquaporins are proteins that form water

channels in certain molecules.

Arrangement of Carbohydrates in the cell

membrane

•

The carbohydrates are attached either to the

proteins (glycoproteins) or the lipids

(glycolipids).

•

Throughout

the

cell

membrane,

carbohydrate molecules form a thin layer of

loose covering called Glycocalyx

Functions

1. Being

negatively

charged

the

carbohydrate molecules of the cell

membrane do not allow the negatively

charged particles to move out of the cell

2. The glycocalyx helps in tight fixation of

the cells with one another

3. Some of carbohydrates molecules also

serve as receptors

Arrangement of Lipid bilayer of the cell

membrane

•

Each lipid molecule in the lipid bilayer of the

cell membrane consists of phospholipids,

cholesterol and glycolipids.

•

The lipid molecules are cloth pin shape and

consists of a head and a tail end

•

The head end/globular end of the molecules

contains

phosphate

moiety

of

phospholipid/hydroxyl

radical

of

cholesterol. It is positively charged and quite

water soluble (hydrophilic)

•

The tail end consists of two chain of fatty

acids/steroid radical of cholesterol. It is water

insoluble and is hydrophobic

•

These lipid molecules are arranged as bilayer in

such a way that their non polar hydrophobic tail

ends are directed towards the centre of

membrane, where as their polar hydrophilic head

ends are directed outwards on either sides of the

membrane

Functional significance of the Lipid bilayer

1. It is the major barrier for the water

soluble molecules like electrolytes, urea

and glucose

2. Fat soluble substance like O

and alcohol can pass through the

membrane with ease

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CYTOPLASM

•

An aqueous substance containing a variety

of cell organelles and other structures

•

In Eukaryotic cell,

Nucleus and Cytoplasm together form



_Protoplasm

Cytoplasm contains,

1. Organelles

2. Inclusion bodies

3. Cytoskeleton

1.

ORGANELLES

•

Are permanent components of the cells, participates in cellular metabolic activity as they contain

enzymes

Sl. No.

Organelle

Function

1

Mitochondria

•

Plays role as power generating unit

•

May have role in synthesizing membrane

bound proteins

2

Endoplasmic reticulum

1.

Rough ER/Granular ER

•

Characterized by presence of a

number of ribosomes on its surface

•

Ex: Russell’s bodies of plasma cells,

Nissl granules of nerve cells and

Acinar cells of pancreas

2. Smooth endoplasmic reticulum/ Agranular

ER

•

Is devoid of ribosomes on its surface.

•

In skeletal and cardiac muscle, it is

modified as sarcoplasmic reticulum

•

It transports proteins made by the

ribosomes through the cisternae

•

It is site of lipid and steroid synthesis

found in abundance with Leydig cells

and cells of adrenal cortex

3

Golgi Apparatus

•

It is particularly well developed in

exocrine glandular cells

•

It is collection of membranous vesicles,

sacs or tubules which is generally located

close to nucleus

•

Synthesis of carbohydrates

•

Packaging of proteins synthesized in the

rough ER into vesicles

•

Site of formation of lysosomal enzymes

•

Transport of the material to the other

parts of cell or to cell surface membrane

and secretion

•

Glycolysation of proteins to form

glycoproteins

4

Ribosomes

•

Spherical particles with 80 to 85 % of

cells RNA

•

The sites of protein synthesis

•

They synthesize all transmembrane

proteins, secreted proteins and most

proteins are stored in Golgi apparatus,

lysosomes and endosomes

Sl. No.

Organelle

Function

5

Lysosomes

•

Are

membrane

bound

organelles

containing powerful lysosomal digestive

enzymes

•

They are formed by Golgi apparatus

•

There are three forms of lysosomes

1. Primary lysosomes/storage vacuoles

Formed

_various

_hydrolytic

enzymes synthesized by rough

ER and packaged in the Golgi

apparatus

2. Secondary

lysosomes/autophagic

vacuoles

Are formed by fusion of primary

lysosomes

with

parts

of

damaged/worn

out

cell

components

3. Residual bodies

Are undigestible materials in the

lysosomes

6

Peroxisome

•

Are known as microbodies

•

Are

predominantly

present

in

hepatocytes and tubular epithelial cells

•

They essentially contain two types of

enzymes

1. Oxidases: which are active in

oxidation of lipids

2. Catalases: which act on hydrogen

peroxide to liberate oxygen

7

Centrosome

•

Consists

of

two

short

cylindrical

structures called centrioles

•

They are responsible in movement of

chromosomes during cell division

2.

CYTOPLASMIC INCLUSIONS

•

These are temporary components of certain cells

•

These may or may not be enclosed in the membrane

•

Ex:

Lipid droplets: seen in cells of adipose tissue, liver and adrenal cortex

Glycogen: seen in the cells of liver and skeletal muscles

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NUCLEUS

•

Nucleus is present in all the eukaryotic cells

•

It controls all the cellular activities including

reproduction of the cell

•

DNA replication occurs in nucleus

•

Most are uninucleated cells except few like

skeletal

muscle

cells

which

are

multinucleated cells

•

It

consists

of

Nuclear

Membrane,

Nucleoplasm and Nucleolus

1.

Nuclear membrane

Double layered structure with 40-70 nm

wide space in between called perinuclear

cistern, which is continuous with the

lumen of ER

Exchange

_of

_materials

_between

Nucleoplasm and cytoplasm occurs

through this membrane

2.

Nucleoplasm

Is Matrix – gel like ground substances

with large quantity of genetic material in

the form of Deoxyribose Nucleic Acid

(DNA)

When cell is not dividing, nuceloplasm

contains dark staining thread like

material called chromatin, while cell

division it is converted to rod shape

structures, the chromosomes.

All somatic cells contains 23 pairs/46

chromosomes while gamete cells (sex

3.

CYTOSKELETON

•

This is a complex network of fibres that maintains the structures of the cell and allows it to change

shape and move

•

It primarily consists of microtubules, intermediate filaments and micro-filaments along with

proteins which anchor and tie them together

Microtubules

Are long hollow tubular structures with limiting membrane and are about 25 nm in diameter

Kinesis and dynein known as molecular motors help in the movement of molecules through the

microtubules

The cilia and flagella which projects from surface of certain cells are also composed of

microtubules enclosed in the plasma membrane and are active in the locomotion of the cells.

Intermediate filaments

Is about 10 nm diametric filamentous structures

Main function of intermediate filament is to mechanically integrate the cell organelles within

the cytoplasm

In their absence, cell ruptures more easily

When they are abnormal in human., blistering of the skin is common

Microfilaments

Are long solid filamentous structures of 6-8 nm diameter

These are made up of contractile proteins  actin and myosin

Actin is the most abundant protein in the Mammalian cell

Extension of microfilament along with plasma membrane on the surface of the cells form

microvilli which increases the absorptive surface of the cells

cells) contains only 23 (haploid) number

of chromosomes

Chromosomes

composed

of

two

chromatids connected at the centre to

form ‘X’ configuration by centromere

Chromosomes are composed of three

components - DNA, RNA and Nuclear

proteins

3.

Nucleolus

Nucleus may contain one or more

nucleoli. They are the sites of synthesis

of ribosomal RNA (r RNA).

These are present mainly in cells activity

synthesizing proteins and in growing

cells

CELL CYCLE

•

The sequence of cell cycle is

G

or resting phase

G

Maximum part of cell cycle remain in G1

S phase (6-8 hrs): DNA synthesis phase

G2 phase (4 - 5 hrs):

_{Premitotic phase,}

Cytoplasmic enlargement; preparation

for cell division, DNA repair can occur.

M Phase (2 hrs): Mitotic phase, Stages of

mitosis are Prophase  Metaphase 

Anaphase  Telophase  Interphase

•

The duration of cell cycle and its stages

varies greatly between cell types

•

The time taken for S, G2 and M phases are

similar for most cell types, whereas the

duration of G1 shows considerable variations

•

Because in this phase, cells are not

committed to DNA replication, can enter

resting state or progress to next cell division

•

In mammals, because of the time required

for a cell to progress of S-phase through

mitosis from beginning is typically 12-24 hrs

irrespective of duration of G1 phase; almost

all the variation in proliferation rates are

attributable to the amount of time spent in

G1/G0 state.

•

Cells cycle arrest due to P

occurs in late G2

phase

Site ‘a’

G1  S G2  M  G1  G0

Site ‘b’

•

Cell cycle regulators in cell growth: cyclins

and kinases

•

In block prior to G2 phase (Site ‘a’) by TGF β

will lead to increase in cell size (and thus cell

hypertrophy).

•

In block after mitosis (Site ‘b’) if cell not

enters quiescent phase it leads to increase in

number of cells (i.e., cell hyperplasia)

•

Growth factors are most effective in G1 phase

•

In Mitosis – spindles are formed in late

Prophase and chromosomes are attached to

spindles in Metaphase

•

In Meiosis – crossing over and chiasmata

formation in Pachytene stage of 1

_meiotic

division; Genetic shuffling occurs in 2

meiotic division

Radiation injury to the cell

•

If cells are irradiated in G1 phase,

chromosomal abnormally may result

•

It cells are irradiated in G2 phase, chromatid

aberration may result

•

Cells are most radiosensitive in G2 - M

interface and most resistant towards the end

of S phase.

•

Series of radio sensitivity  M > G2 > G1 > S

Drugs acting in various phases of cell cycle

•

G1 – Vinblastine

•

S – Doxorubicin, Methotrexate, Cytarabine,

6-TG, 6-MP, Hydroxyurea, Mitomycin – C

•

G2 – Bleomycin, Etoposide, Daunorubicin,

Topotecan

•

M – Vincristine and Vinblastine (breaks

microtubules),

Paclitaxel

(stabilizes

microtubules), Colchicines

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TRANSPORT ACROSS CELL MEMBRANE

•

The physiological activity of a cell depends

on the substances like nutrients, oxygen and

water which must be transported into the

cell and at the same time metabolic waste

must be transported out of the cells

•

Various

process

of

transport

across

membranes are

1.

Passive transport

Is

_along

_the

_gradient

_without

expenditure of any energy

It depends on physical factors like

concentration

gradient,

electrical

gradient and pressure gradient

Transport occurs along the gradient

(down hill movement)

Types

i.

Diffusion

a. Simple diffusion

b. Facilitated diffusion

o

Carrier mediated

o

Uniport, Symport and Antiport

ii.

Osmosis

2.

Active transport

Is transport of substances against the

chemical and or electrical gradient with

the expenditure of energy which is

liberated by breakdown of high energy

compounds like ATP

Types

i.

Primary active transport

o

Energy is derived directly by

breakdown

of

high

energy

compounds (ATP)

o

Ex: sodium, potassium pump,

calcium pump, potassium- hydrogen

pump

ii.

Secondary active transport

o

Energy is derived secondarily from

the energy which has been stored in

the form of ionic concentration

difference between two sides of

membranes, created in the first place

by primary active transport

Types of Secondary Active Transport

1. Co-transport – carrier protein transports

secondary substances in the direction of

primary substances

2. Counter transport – carrier protein

transports secondary substances in the

opposite direction of primary substances

Examples

1. Sodium Co-transport: substances carried

are like glucose, aminoacids, chloride

and iodine. Carrier protein acts as

symport

2. Sodium Counter transport: sodium ion is

exchanged for some other substances

like calcium, hydrogen, potassium,

magnesium. Carrier protein acts as

antiport.

3. Calcium - Magnesium counter transport

system

4. Chloride - Bicarbonate counter transport

system

3.

Vesicular transport

This mechanism is involved in the

transport of macromolecules such as

large protein molecules which can

neither pass through the cell membrane

by diffusion nor by active transport

mechanism

Types

i.

Endocytosis

o

Process by which the substances is

transported into the cell by in

folding of cell membrane around the

substances and internalizing it

Sub Types

Pinocytosis  cell drinking  for liquid

substances. Ex: reabsorption by renal

tubular epithelial cells

Phagocytosis  cell eating  for solid

substances.

Ex:

In

cell

defense

mechanism

Receptor

mediated

endocytosis.

Ex:

transport of iron and cholesterol into the

cells

ii.

Exocytosis

o

Reverse of endocytosis.

o

Ex: Release of hormones and

enzymes by secretory cells of the

body occurs by exocytosis.

o

This process of exocytosis requires

Ca

_{and energy along with docking}

proteins

iii.

Transcytosis

o

Is vesicular transport within the cell

o

Is also called

cytopemisis

iv.

Other transport process

o

Transport

across

epithelial

membrane

o

Ex: Ultra filtration

MEMBRANE POTENTIAL

•

Potential difference across the cell membrane

of all living cells with the inside being

negative in relation to the outside is named

Membrane Potential

•

Membrane potential is basically due to

unequal distribution of ions across the cell

membrane

•

Factors involved in the genesis of membrane

potential are

Selective permeability of the cell

membrane

Gibb’s Donnan Equilibrium

Nernst equation

Constant field Goldman equation

Sodium – Potassium ATPase pump

Equilibrium Potential

Equilibrium potential of an ion is

defined by Nernst equation.

It is the membrane potential at which

efflux and influx of the ions are equal

Formula

ܧሺ݉ሻ =

ܴܶ

ܼܨ

Ln

ሾܿ݋݊ܿሿ݅

ሾܿ݋݊ܿሿ݋

Em = Equilibrium potential

R = Gas constant  8.316 Joules/degree

T = Absolute temperature

F = Faraday constant = 96,500 coulomb/mole

Z = Valency of the ion

Ln = Logarithm symbol

ܧሺ݉ሻ = ±61 log

ሾܿ݋݊ܿሿ݅

ሾܿ݋݊ܿሿ݋

Equilibrium potential for important ions in a

mammalian spinal motor neuron

Ion

Concentration

(in mmol/L of H2O)

Equilibrium

potential

(in MV)

Outside

cell

Inside

cell

Na

₁₅₀

₁₅

_{+ 60}

K

_5.5

₁₅₀

_{- 90}

Cl

₁₂₅

₉

_{- 70}

BIOCHEMISTRY

Carbohydrates

1

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CHEMISTRY OF CARBOHYDRATES

DEFINITION

Carbohydrates are polyhydroxy aldehydes or polyhydroxy ketones or compounds that can be

hydrolyzed into these compounds. General formula is CnH2nOn..

FUNCTIONS

1. Major source of energy in most organisms

2. Serve as metabolic intermediates

3. Constituents of nucleotides that form DNA & RNA

4. Give structure to cell membranes & cell walls

5. Play a role in immunity, joint lubrication & cell to cell communications

COMMON DISEASES associated with carbohydrates include diabetes mellitus, galactosemia, glycogen

storage diseases and lactose intolerance.

CLASSIFICATION OF CARBOHYDRATES

A.

SIMPLE – ONLY CARBOHYDRATE MOIETY

1.

Monosaccharides

i. Aldoses [glucose (6C), glycerose (3C), erythrose (4C), ribose (5C)]

ii. Ketoses [fructose (6C), dihydroxyacetone (3C), erythrulose (4C), ribulose (5C)]

2. Disaccharides (sucrose, maltose, lactose)

3. Oligosaccharides (3-9 residues; Eg. raffinose, stachyose)

4.

Polysaccharides (>/= 10 residues; Homopolysaccharides- starch, inulin, cellulose and

Heteropolysaccharides- heparin, chondroitin sulphate)

B.

COMPLEX – SUGAR + LIPID or PROTEIN MOIETY

•

proteoglycan, glycoprotein, glycolipid

HAWORTH (OPEN CHAIN) STRUCTURE OF CARBOHYDRATES

PYRANOSE RING STRUCTURES

HAWORTH (OPEN CHAIN) STRUCTURE OF CARBOHYDRATES

FRUCTOSE STRUCTURE

ISOMERISM

•

Same molecular formula but different

Types

1. Optical

2. Functional

3. Stereoisomerism

i. Anomerism

ii. Epimerism

iii. Enantiomerism

iv. Diastereoisomerism

Optical isomerism

•

Same molecular formula but differs

•

‘d / + ’: dextrorotatory

•

‘l / - ’: laevorotatory.

Stereoisomerism

•

Same molecular formula but differs

carbon atoms.

•

OH on the right side- D form. Eg

•

Asymmetric carbon atom- C atom with 4 different groups attached to it.

Same molecular formula but different physical or chemical properties

formula but differs in their physical property of turning the plane polarized light.

formula but differs in spatial configuration of H & OH groups at penultima

D form. Eg- D-glucose & OH on left side- L form. Eg- L-glucose.

C atom with 4 different groups attached to it.

BIOCHEMISTRY

Carbohydrates

3

in their physical property of turning the plane polarized light.

in spatial configuration of H & OH groups at penultimate

glucose.

•

No of isomers = 2

_{(n = no of asymmetric carbon atoms).}

Epimerism

•

Differ in orientation of H & OH groups around single C atom. Eg- Glu & Gal at C4, Glu &

Mannose at C2.

Anomerism

•

Differ in orientation of H & OH groups around first C atom. Eg- α- OH to the right of 1

_C.,

α-glucose

β - OH to the right of 1

_{C., β-glucose.}

GLYCOSIDES

Sugar + Aglycone

Phlorhizin- glucose + phloretin; renal damage

Digitonin- glucose+ digitogenin; cardiac stimulant

Ouabain- Na

_-K

_{ATPase inhibitor}

Amino sugars

Glucosamine- in hyaluronic acid, heparin & blood group substances

Galactosamine- in chondroitin of cartilage, bone & tendons

Mannosamine, N-acetylated glucosamine & N-acetylated galactosamine- in glycoproteins

Erythromycin- Diethyl amino sugar; antibiotic

Deoxysugars

L-fucose- 6-deoxy β L-galactose - in blood group antigens

Deoxyribose- in nucleic acid. Feulgen staining is specific for DNA

PENTOSES

•

D-Ribose- constituent of RNA, ATP & NAD

•

Deoxyribose- in DNA

•

D-Ribulose- in HMP shunt

•

D-Xylose- in proteoglycans

•

D-Lyxose- in heart muscle

KEY POINTS ABOUT GLUCOSE

•

Aldo-sugar with 6 membered pyranose ring

•

β-D glucopyranose is the most common form

•

C1 carbon is the anomeric carbon

•

Ring closure occurs between C1 & C5

•

D-glucose is dextrorotatory

•

Forms 16 stereoisomers

•

Glucose is oxidized to gluconic acid, glucuronic acid & glucosaccharic acid

•

Reduced to sorbitol (mechanism in diabetic cataract)

BIOCHEMISTRY

Carbohydrates

5

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KEY POINTS ABOUT FRUCTOSE

•

Keto-sugar with predominant furanose ring structure

•

C2 carbon is the anomeric carbon. D-fructose is laevorotatory

•

Forms 4 isomers

•

It is a major constituent of honey

•

Component of inulin

KEY POINTS ABOUT GALACTOSE

•

Component of lactose

•

Epimer of glucose at C4

•

Constituent of glycolipids & glycoproteins

•

Oxidized to galactonic acid, galacturonic acid & mucic acid

•

Reduced to dulcitol

KEY POINTS ABOUT MANNOSE

•

Occurs in glycoproteins

•

Epimer of glucose at C2

IMPORTANT POINTS ABOUT DISACCHARIDES

Sucrose

•

α (1, 2) is not reducing since both anomeric carbons of glucose & fructose are involved in

glycosidic linkage

•

It is called invert sugar as sucrose being dextrorotatory (+66.5

) becomes laevorotatory (- 19.5

) on

hydrolysis

•

Honey contains invert sugar

Maltose

•

α (1, 4) contains 2 glucose units

•

Forms sunflower shaped crystals of maltosazone

Isomaltose

•

α (1, 6) contains 2 glucose units produced by partial digestion of glycogen and starch

Lactose

•

β (1, 4) is sugar present in milk.

Contains glucose & galactose

Hedgehog or powder puff appearance of lactosazone crystals

Digested by separate enzyme, lactase

HOMOPOLYSACCHARIDES

Structural Homopolysaccharides

•

Cellulose made up of glucose residues linked by β (1,4) linkages., so its not digestible in humans

•

Inulin is a fructosan

•

Chitin- the constituent of exoskeleton of crustaceans is made up of amino sugar N-acetyl

glucosamine

Storage Homopolysaccharides

•

Starch- 2 components- amylose, unbranched form with α (1, 4) linkages [300-400 glucose units]

and amylopectin, highly branched with α (1, 4) along straight lines and α (1, 6) along branch

points [each branch at interval of 24-30 glucose units]

•

Glycogen – highly branched, formed on a protein core- glycogenin to which glucose molecules are

attached with α (1, 4) linkages along straight line & α (1, 6) along branch points [each branch at

interval of 12-18 glucose units]. Each branch has 11 residues & the whole molecule is arranged in

12 concentric circles.

HETEROPOLYSACCHARIDES

Mucopolysaccharides

Features of glycosaminoglycans (GAG)-

GAG / Proteoglycans are composed of an uronic acid & amino sugar. Exception – keratan

sulphate doesn’t have uronic acid, instead it has galactose.

Normally, they prefer to have glucuronic acid & N-acetyl glucosamine. Exception- Iduronic acid

in Heparin & Dermatan sulphates. Galactosamine in chondroitin & dermatan sulphate.

COMPLEX POLYSACCHARIDES

Proteoglycans

•

It has a core protein, to which the GAGs (unbranched, repetitive units) are linked by ‘O’ linkage.

•

Exception is keratan sulfate type 1, which is N-linked and, hyaluronic acid is not linked to the core

protein directly at all.

•

All GAGs are sulfated so that they get a negative charge, but hyaluronic acid is not sulfated.

Functions

Constituents of extracellular matrix providing negative charge which is important for basement

membrane’s charge selectivity for proteins.

Helps in morphogenesis and metastasis in cancer.

Keratan sulfate is responsible for corneal transparency.

Dermatan sulfate is responsible for shape of the cornea.

Glycoproteins

•

Glycosylated protein but the side chains are branched, non repetitive carbohydrate moieties-

carbohydrates less than proteoglycans

•

Eg- plasma proteins, Igs, hormones, enzymes, transport proteins etc

•

It helps in maintaining receptor function, protein folding, determining protein solubility.\

•

Types- N-linked, O-linked & GPI anchored.

•

GPI anchored glycoprotein- carboxy terminal of amino acid is linked to the carbohydrate chain,

ethanolamine & inositol. Eg- Decay acceleration factor is a GPI anchored protein which prevents RBC

lysis by complement pathway product, mutation of which causes PNH.

BIOCHEMICAL TESTS

1. Molisch test- for carbohydrates

2. Benedict’s test- for reducing sugars

3. Barfoed’s test- for distinguishing between monosaccharides & disaccharides

4. Bial’s test- for pentoses

METABOLISM OF CARBOHYDRATES

DEFINITIONS

Metabolism- process by which we assimilate energy from the food we intake (

building up macromolecules (Anabolism).

Oxidative Phosphorylation- The energy obtained by oxidation of substrates is trapped in the f

equivalents NADH or FADH2 which passes thro’ mitochondria to generate ATP.

Substrate Level Phosphorylation

•

ATP is generated directly from the substrate.

•

Eg- Phosphoglycerate kinase

Pyruvate kinase

Succinyl thiokinase

Creatine kinase

EXAMPLES OF

Catabolic Pathways- Glycolysis, glycogenolysis, fatty acid oxidation,

Anabolic Pathways- Glycogen synthesis, FFA synthesis, protein synthesis

Amphibolic Pathways- TCA cycle

KEY POINTS IN GLYCOLYSIS

METABOLISM OF CARBOHYDRATES

process by which we assimilate energy from the food we intake (Catabolism) &

building up macromolecules (Anabolism).

The energy obtained by oxidation of substrates is trapped in the f

equivalents NADH or FADH2 which passes thro’ mitochondria to generate ATP.

ATP is generated directly from the substrate.

Glycolysis, glycogenolysis, fatty acid oxidation, amino acid oxidation

Glycogen synthesis, FFA synthesis, protein synthesis

BIOCHEMISTRY

Carbohydrates

7

Catabolism) & utilize the same for

The energy obtained by oxidation of substrates is trapped in the form of reducing

Irreversible Steps

•

Hexokinase or glucokinase

•

Phosphofructokinase

•

Pyruvate kinase

Rate Limiting Step

•

Phosphofructokinase

Substrate Level Phosphorylation Steps

•

Phosphoglycerate kinase

•

Pyruvate kinase

Products

•

Pyruvate

•

Lactate- For the regeneration of NAD- NAD is required for the G3PDH step when it’ll be

converted to NADH. In aerobic glycolysis, NADH will enter into respiratory chain & we get back

the NAD, but if its happening anerobically, LDH step converts it back to NAD to convert pyruvate

to lactate.

ANAEROBIC GLYCOLYSIS- occurs in RBC, white muscle fibres, lens, retina, brain, renal medulla. Only

2 ATP is produced.

RBC- glycolysis is the only energy generating pathway as it lacks mitochondria & hence dependent on

anaerobic pathway.

RAPPAPORT LUEBERIN CYCLE- a deviation of the normal glycolysis whereby phosphoglycerate kinase

step is bypassed & phosphoglycerate mutase generates 2, 3-DPG which is essential for decreasing the

affinity of RBC for oxygen, thereby facilitating unloading in tissues.

PASTEUR EFFECT- Body attempts to prevent anaerobic glycolysis whenever there is high ATP level,

which is obtained by lipolysis & fatty acid oxidation.

FATES OF PYRUVATE

•

Aerobic Condition- forms acetyl Co A

•

Anaerobic Condition- forms lactate

•

Well Fed State- forms alanine by transaminase

•

Starvation- forms oxaloacetate for gluconeogenesis

PYRUVATE DEHYDROGENASE COMPLEX (PDH)

•

Multi enzyme complex, mitochondrial enzyme with PDH, dihydrolipoyl tranacetylase, dihydrolipoyl

DH & coenzymes: TPP, CoA, Lipoic acid, NAD, FAD

•

Generates 3 ATP.

REGULATION

•

Allosteric inhibition by acetyl Co A(glucose sparing effect), NADH, ATP

•

COVALENT MODIFICATION-activated by phosphorylation & vice versa.

•

Activated by insulin.

KEY POINTS IN GLUCONEOGENESIS

•

Formation of glucose from non carbohydrate sources

•

ORGANS INVOLVED- liver & kidney

•

Conversion of pyruvate to phosphoenolpyruvate consumes CO2 & ATP generating inorg

phosphate.

Enzymes Involved

•

Pyruvate carboxylase

•

PEPCK

•

Fructose 1,6 bis phosphatase (rate limiting step)

•

Glucose-6-phosphatase

Substrates

•

Glucogenic amino acids, lactates, glycerol & propionate

Regulation

•

Regulated by PFK-2

•

PFK-2 on phosphorylation acts like fructose 2,

dephosphorylated, it behaves like PFK

•

Fructose 2,6 bisphosphate is an allosteric activator of PFK

TCA CYCLE

•

Occurs in mitochondria

•

Only aerobic pathway

•

Amphibolic

KEY POINTS IN GLUCONEOGENESIS

e from non carbohydrate sources

liver & kidney

phosphoenolpyruvate consumes CO2 & ATP generating inorg

(rate limiting step)

lactates, glycerol & propionate

2 on phosphorylation acts like fructose 2, 6 bisphosphatase (glucagon) & when it gets

behaves like PFK-2 synthesizing fructose 2,6 bisphosphate.

Fructose 2,6 bisphosphate is an allosteric activator of PFK-1 (glycolysis)

BIOCHEMISTRY

Carbohydrates

9

phosphoenolpyruvate consumes CO2 & ATP generating inorganic

•

Catabolic- generates 12 ATP from acetyl Co A

•

Anabolic- forms various intermediates like glutamate from alpha-KG, aspartate from oxaloacetate,

fatty acids from acetyl Co A.

Regulation of TCA Cycle

Depends on the type of the cell

In skeletal muscle- main purpose is energy production, the cycle generates ATP. The

dehydrogenases are all activated by calcium ions & the ATP/ADP ratio will be very low: inhibition

on PDH is overcome.

In Liver- cycle is anabolic. Citrate synthase is inhibited by high energy level, so oxaloacetate

accumulates, which can be utilized for aspartate synthesis. Similarly ATP allosterically inhibits DH

to help in glutamate & other synthesis. Succinyl CoA is used in heme synthesis.

In adipose tissue- aconitase inhibited-citrate accumulates & helps in FA synthesis.

Inhibitors of TCA cycle

•

Fluoroacetate- inhibits aconitase

•

Malonate- inhibits succinate dehydrogenase

ENERGY YIELD (NO OF ATP GENERATED) PER MOLECULE OF GLUCOSE THROUGH

GLYCOLYSIS PLUS CITRIC ACID CYCLE, UNDER AEROBIC CONDITIONS

PATHWAY

SOURCE

NO OF ATPs GAINED

GLYCOLYSIS

Hexokinase

- Minus 1

Phosphofructokinase

- Minus 1

Glyceraldehyde-3-P-DH

NADH

3 X 2 = 6

1, 3-BPG Kinase

ATP

1 X 2 = 2

Pyruvate kinase

ATP

1 X 2 = 2

PYRUVATE TO ACETYL CO A

Pyruvate dehydrogenase

NADH

3 X 2 = 6

TCA CYCLE

Isocitrate dehydrogenase

NADH

3 X 2 = 6

Alpha-KG DH

NADH

3 X 2 = 6

Succinate thiokinase

GTP

1 X 2 = 2

Succinate DH

FADH2

2 X 2 = 4

Malate DH

NADH

3 X 2 = 6

Net generation in Glycolysis

10 - 2 = 8

Generation in PDH reaction

= 6

Generation in TCA cycle

= 24

Net generation of ATP from 1 molecule of glucose = 38

BIOCHEMISTRY

Carbohydrates

11

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KEY POINTS IN GLYCOGEN METABOLISM

•

Occurs in 2 tissues- liver & muscle

•

Total glycogen is higher in muscle than liver

•

Liver glycogen gives rise to plasma glucose whereas muscle glycogen does not since

glucose-6-phosphatase is absent in muscle

•

Key enzyme for glycogen synthesis- glycogen synthetase

•

Key enzyme for glycogenolysis- glycogen phosphorylase

•

Regulation of glycogen metabolism- by cyclic AMP

•

Total ATP utilized in glycogen synthesis- 2

KEY POINTS IN GLYCOGEN SYNTHESIS

Enzymes-

•

Hexokinase in skeletal muscle & glucokinase in liver

•

Glucokinase has got high Km & low affinity for glucose

•

UDP glucose pyrophosphorylase

•

Glycogen synthase adds glucose subunits in straight chains until 11 residues are attached

•

Branching enzyme (1->4)->(1->6) transferase

GLYCOGENOLYSIS

KEY POINTS IN GLYCOGENOLYSIS

•

Enzymes involved are phosphorylase & debranching enzyme (amylo 1, 6 glucosidase)

•

Rate limiting step is phosphorylase- pyridoxine dependent enzyme

•

Gives rise to glucose-1-phosphate

•

Energy from glucose obtained by glycogenolysis- 9 ATP

•

Liver glycogen phosphorylase is activated by glucagon & epinephrine, whereas muscle GP is only by

epinephrine & not glucagon

HEXOSE MONO-PHOSPHATE SHUNT

KEY POINTS IN HEXOSE MONOPHOSPHATE SHUNT

•

Occurs in cytosol of liver, mammary glands, adipose tissue & fetal heart

•

2 PHASES-

•

Oxidative- production of NADPH (used for reductive synthesis of lipid derivatives)

•

Non oxidative- production of ribose-5-phosphate (used for purine biosynthesis, nucleoside synthesis)

•

No ATP is generated

•

Prevents RBC hemolysis by assisting glutathione peroxidase

GALACTOSE METABOLISM

GALACTOSEMIA

•

Defect in the following enzymes

Galactose-1-P- uridyl transferase : classical type

Galactokinase : minor type

Epimerase : rare

•

Clinically manifest with failure to thrive, lethargy,

retardation.

•

Biochemically- increased blood galactose, decreased blood glucose, galactosu

aminoaciduria

FRUCTOSE METABOLISM

Defect in the following enzymes-

uridyl transferase : classical type

Clinically manifest with failure to thrive, lethargy, hypoglycemia, hepatomegaly, cata

increased blood galactose, decreased blood glucose, galactosu

___THE END___

•

Fructose intolerance

B deficiency

•

Clinically- hypoglycemia, liver

damage, hyperuricemia, lactate

acidosis.

BIOCHEMISTRY

Carbohydrates

13

hypoglycemia, hepatomegaly, cataract, mental

increased blood galactose, decreased blood glucose, galactosuria, albuminuria,

intolerance- Aldolase

hypoglycemia, liver

damage, hyperuricemia, lactate

ORAL MUCOUS MEMBRANE

• The moist lining of the oral cavity that is in continuation with the exterior surface of skin on one end and esophagus on the other end is called Oral Mucous Membrane

Origin and Development

• The mouth is derived partly from the stomatodaeum and partly from the foregut; hence its epithelial lining is partly ectodermal and endodermal. Functions 1. Protection 2. Sensation 3. Thermal regulation 4. Secretion 5. Absorption 6. Excretion 7. Aesthetics CLASSIFICATION

Based on the functional criteria

1. Masticatory mucosa – lining the gingiva and hard palate

2. Lining or reflecting mucosa – lining the cheek, vestibular fornix, alveolar mucosa, floor of mouth and soft palate

3. Specialized mucosa – Dorsum of the tongue, taste buds and vermillion border of lip

Based on structure of surface layers

1. Keratinized mucosa – Hard palate and gingiva (COMEDK-05)

2. Nonkeratinised mucosa – Cheek, soft palate, vestibule, floor of mouth

Based on location 1. Buccal mucosa 2. Palatal mucosa 3. Lingual mucosa 4. Labial mucosa 5. Alveolar mucosa 6. Gingival mucosa MASTICATORY MUCOSA

• It is present in the areas of high compression and friction and characterized by keratinized and parakeratinised epithelium (AP-05)

• The lamina propria is thick, tightly bound to the underlying bone and does not stretch • It bears the masticatory forces

LINING OR REFLECTING MUCOSA

• It is distensible over the musculature and covers adapting itself to the contraction and relaxation of cheeks, lips and tongue

• It makes up all the surfaces of the mouth except the dorsum of the tongue and the masticatory mucosa

• is not subjected to high levels of friction and must be mobile and distensible

• It is nonkeratinised and has loose lamina propria

• It is not exposed so much to masticatory forces • Mucosa covering the lip cheek vestibule, alveolar mucosa, floor of the mouth and soft palate

SPECIALIZED MUCOSA

• Dorsum of the tongue has gustatory type of specialised mucosa

• It is so called because it bears the taste buds which have a special sensory function in addition to general sensory function

GENERAL FEATURES

• Oral mucosa is situated anatomically between the skin and intestinal mucosa. Hence it shows some properties of both

• The oral mucosa like skin and intestinal mucosa consists of two separate tissues competent

A covering epithelium

An underlying connective tissue • It is considered an organ

• Oral cavity is divided into
Oral cavity proper
_{Oral vestibule} • Different from skin

Moist surface

_{Absence of appendages present in skin}

ORAL EPITHELIUM

• Oral mucosa is made up of stratified squamous epithelium derived from embryonic ectoderm • Stratification occurs as a result of cell