Lecture 28: Epithelial and glandular tissues

Objectives
1. Describe micro-anatomical features, which all epithelia have in common.
2. Describe the general organization of epithelia and glands.
3. Describe the micro-anatomical structure and function of various types of epithelia and glands.

Four Basic Cell types of Body

 Epithelium/ epithelial tissue
 Connective tissues
o Never form as many cell junctions as epithelial cells do
 Muscle tissue
 Nerve tissue

Epithelium
 Epithelium is composed of two parts i.e. Junctional
structure embedded on basement membrane Junctional structure Basement membrane
o Separated from the underlying connective tissues

Basement membrane
 Basement membrane is composed of basal lamina derived from
epithelium together with lamina reticularis derived from connective tissue
 All cells rest on basement membrane
 Basement membrane is mainly made of collagen IV and I
 Basal membrane can be seen under light microscope whereas basal lamina can only be seen under EM
structure
 Some cancer cells secrete substances to destroy collagen IV, which is
originally responsible for keeping the cell intact
Basal lamina
Developmental Origin
 Derived from all three germ layers
o Ectoderm
 Epidermis of skin
 Epithelial linings of sweat glands
 Duct oral surface
 Vagina
 Anal canals
o Mesoderm
 Epithelial linings of blood vessels
i.e. endothelium
 Surfaces of body cavities i.e. mesothelium
 Genital ducts
 Urinary ducts and tubules
o Endoderm
 Epidermis of oesophagus
 Epithelial linings of GI tract and lower respiratory tract epithelium
 Epithelial parts of liver and pancreas
 Functions of Epithelial Tissues
 Protection by epidermis of skin
 Complete coverage of body surfaces and cavities
 Sensory function by retina and olfactory epithelia
 Absorption by digestive epithelium and excretion
 Secretion by glandular epithelium
o Endocrine e.g. hormones
o Exocrine e.g. digestive enzymes, mucus and sweat
 Transport e.g. lining of kidney tubules
 Synthesis of various proteins
 Reduction of friction in intestines

Properties of Epithelium
 Composed of closely packed and contiguous cells with junctional structures at their lateral surfaces
 Very little or absence of intercellular matrix, which is contrast to connective tissues
o Because these cells are already closely packed
 Form membranous sheets covering
o Surfaces of the body e.g. skin and GI tracts
o Cavity of the body e.g. thoracic, pleural and abdominal cavity of body
 All cells rest on basement membrane
 Cytokeratin as intermediate filament
 Avascular i.e. no blood supply, or else cancer
o Obtain nutrients by diffusion from blood vessels in the underlying connective tissue
 Many cancers actually derive from epithelial tissue
 Epithelium with secretory function is glandular epithelium i.e. glands
 Frequently renewed and replaced

Special Type of Simple Epithelium

 Mesothelium
o Linings of pleural or abdominal cavities and surfaces of internal organs
 Endothelium
o Linings of the heart chambers, blood and lymph vessels

Classification of Epithelia

1. Number of cell layers Simple or stratified

2. Cell shape Squamous (e.g. lung alveoli), cuboidal (e.g. thyroid follicle) or
columnar (e.g. gallbladder and intestines)
3. Keratin Keratinized or non-keratinized
4. Cilia Ciliated or non-ciliated

Types of Epithelia
Simple squamous
Simple cuboidal
Simple columnar
Stratified cuboidal epithelium
Stratified columnar
Stratified squamous
(non-keratinized)
Peritoneum epithelium
Examples
Parietal layer of Bowman’s capsule
Endothelium of blood vessel
Thin segment of loop of Henle
Lung alveoli
Mesothelium of peritoneum
Lining of most ducts, thyroid follicles
Epithelium of intralobular
duct of pancreas
Absorptive epithelium of intestine and
gall bladder
Ducts of sweat gland
 Uncommon
 Present in excretory duct of
endocrine gland
Lining of large excretory ducts,
conjunctiva of eye
 Found in few places e.g.
epiglottis, urethra and some
glands
Lines moist surfaces i.e. buccal cavities
E.g. oesophagus, vagina
 Non-keratinized does not
necessarily mean the absence
of keratin but it indicates the
cells are not completely filled
by keratin
Epithelium of vagina
 Stratified squamous (keratinized) Lines dry surfaces e.g. epidermis of skin

Epidermis of skin

Pseudo-stratified columnar Multiple layers of nuclei with all cells

touching the basement membrane
E.g. linings of trachea, bronchi and
epididymis (with cilia)
Epithelium of trachea

Transitional Present in urinary epithelium in

bladder and ureter
 Cell shape changes from
cuboidal to squamous

Epithelium of urinary bladder

Metaplasia Contributes to elasticity

 Cells change from one type to the other
when faced with a chronic change of
environment
o Smoking causes squamous metaplasia
in respiratory epithelium

Renewal of Epithelial Cells Thick epithelium of bladder to prevent

 Presence of self-renewal adult stem cells diffusion of urea back into tissue
o Potential therapeutic applications
 Intestinal epithelium renews in approximately a week’s time
o Stem cells present at the base of crypts (intestinal glands)
 Skin epithelial cells renew in approximately a month’s time
o Stem cells present in stratum basale

Polarity of Epithelial Cells

 Specialization are found at various surfaces of epithelial cells
Apical surface
Lateral surface

Basal surface
Apical Specialization
 Cilia Movement of fluid in
respiratory epithelium and
lining epithelium of
oviduct

Ciliated simple columnar epithelium

Cross-section (XS) of cilia showing 9

doublets plus 2 central doublets
 This “9 + 2” pattern is universal
in all animals
 If not, the cilia will not function

Basal body

 Stereocilia Long microvilli in

epididymis

 Microvilli Absorption in GI tract Above microvilli is a layer of glycocalyx containing

 Microvilli usually brush boarder enzymes
do not move Actin

 Flagella Movement of spermatozoa from seminiferous

tubules
Lateral Specialization
 Junctional complex for adhesion and barrier to passage of materials
o Thus forces substances to go through cells instead of gaps
Tight junction

Adhering junction

Gap junction

Hemidesmosome
Desmosome

 Tight junction (Zonula occluden)

o Completely sealed off
o Non-leaky but not strong
 Adhering junction (Zona adherens)
o Strong but leaky as compared to tight junction
o Associated with actin
 Gap junction
o Achieve communication by ion transfer between adjacent cells
 The adhesion belt is composed of actin instead of keratin whereas the
lower part is associated with keratin
 Desmosome
o Associated with intermediate filament
(keratin filament)
Tonofilament (Keratin)
Basal Specialization
 Hemidesmosome
o Pemphigoird is an autoimmune disease
 Skin coming off as hemidesmosome does not attach to basement membrane
  Membrane interdigit ation
o In active absorptive cells such as kidney tubules
(up face urine, down face body tissue)

Glandular Epithelium
 Epithelial cells specialized for secretion (glandular epithelium)
 Down growth of epithelia into the underlying connective tissue
 Exocrine gland (ducted)
o With excretory duct
o Deliver secretions to epithelial surface
 E.g. sweat gland and digestive glands
 Endocrine gland Cell’s own
Mitochondria of neighbouring cells mitochondria
o Ductless
o Deliver secretions (i.e. hormones) into blood

Classification of Glands
An Overview
Cell Number Shape of gland Ducts of gland Nature of secretion Mode of secretion
 Unicellular  Tubular branched  Simple  Serous  Merocrine
 Multicellular  Tubular unbranched  Compound  Mucous  Apocrine
 Acinar  Mixed  Holocrine
 Tubuloacinar
Goblet Cells
 Single cell gland

 Absence of cilia indicates that this is not an epithelial

cell in the respiratory tract
 It is likely to be an absorptive cell in the intestine
Nature of Secretion

 Serous
o Watery with protein or enzymes
o Basophilic cytoplasm due to abundant
rough ER for protein synthesis
o E.g. pancreas
 Mucous
o Mucinous i.e. mucin (rich in proteoglycan)
o Thick and slimy (when a person is nervous,
the saliva is thicker, watery when happy)
o E.g. mucous gland along the GI tract
  Submandibular gland, the salivary gland, has a mixed secretion and its shape is tubuloacinar

S M

Mucous and Serous Membranes

 Mucosa
o Lines cavities connecting the outside of the body e.g. alimentary tract, respiratory epithelium,
genitourinary tract
o Mucous secretion
o Components
 Epithelium
 Lamina propria (connective tissue)
 Muscularis mucosae
 Serosa
o Lines the peritoneal, pericardial and pleural cavity
o Watery secretion rich in enzymes and proteins
o Components
 Mesothelium
 Connective tissues

Mode of Secretion
 Merocrine
o Secretion passed to outside by exocytosis without significant loss of cytoplasm
o E.g. pancreas, sweat gland
 Apocrine
o Loss of a portion of the apical cytoplasm as secretory product
o E.g. mammary gland
 Holocrine
o Lysis of whole cell during the secretory process
o E.g. sebaceous gland
Shapes of Exocrine Glands

Simple tubular Simple coiled tubular Simple branched Simple branched Compound tubuloacinar
e.g. intestinal e.g. sweat gland tubular e.g. acinar e.g. e.g. salivary gland
gland gastric gland sebaceous gland

Lecture 29: Connective tissues
2016-17:
-Describe the basic histological layers of the GI tract
-Describe the major histological features and functions of oesophagus, stomach, small and large
intestine
-Describe the structures and functions of major digestive glands of the GI tracts

Objectives
1. Describe the micro-anatomical features of connective tissue.
2. Describe the composition of extracellular matrix.
3. Describe the fibrous component of connective tissues.
4. Describe the common cell types in the connective tissues and their functions.

Types of Connective Tissues

 Embryonic connective tissues
o Mesenchyme in embryo
 Undifferentiated cells in viscous ground substance
 Form the mesodermal germ layer which is the origin of connective
tissues
o Mucous connective tissue in umbilical cord
 Both are loose connective tissues
 Connective tissue proper
o Loose and dense connective tissue
 Specialized connective tissue
o Cartilage and bone
o Blood, lymphatic and haematopoietic tissues
o Adipose tissue

Developmental Stages
Stem cells

Haematopoietic stem cells Undifferentiated mesenchymal cells

 Red blood cells  Mesothelial cells
 Basophils  Endothelial cells
 Eosinophils  Osteoblasts
 Neutrophils  Chondroblast
 Mast cells  Adipocyte
 Megakaryocytes  Fibroblast
 B lymphocytes
 Plasma cells
 Monocytes
 Macrophages
o Monocytes only exist in blood but not in
connective tissues, as they differentiate to form
macrophages when leaving blood vessels
o So macrophages can only be found in connective
tissues but not in blood

Specialized Connective Tissues

o Cartilage and bone Support
o Adipose tissues Storage of lipid as energy source
o Blood, lymphatic and Formation of blood cells
haematopoietic tissues
  Contain no keratin or cell junctions
Functions
 Connect tissues and organs
 Form ligaments and tendons
 Provide support to the epithelial tissues by facilitating nutrient diffusion and waste removal from avascular
epithelial tissues
 Protection, preventing spread of infection
o Secrete fibres to form physical barriers
o By immune and inflammatory responses e.g. lymphocytes, mast cells and macrophages
 Extracellular matrix (ECM) regulates the behaviour of cells such as differentiation, migration and proliferation
 Tissue repairs

Two Major Components

 Extracellular matrix (ECM)
o Ground substance i.e. proteoglycans (particularly common in connective tissues) and glycoproteins
(present in many parts of body)
o Fibrous components i.e. collagen, elastic and reticular
 Form a dynamic and interactive system to inform cells about the biochemical and mechanical changes in
their extracellular environment
 Cellular components
o Non-fibrous components e.g. fibroblasts, immune and inflammatory cell, adipocytes, lymphocytes,
macrophages, fat cells, etc.

Ground Substances
 Amorphous (shapeless), highly hydrated gel, gel-like matrix
o Resist compressive force
 For nutrient diffusion and waste removal
 Poorly preserved in histological preparations
 PAS (Periodic Acid Schiff) positive i.e. presence of sugar moiety
 Complex mixture of proteoglycans and glycoproteins

Proteoglycans
 Core protein linked with glycosaminoglycans (GAGs), formerly known as mucopolysaccharides
 E.g. syndecan, aggrecan

Glycosaminoglycans (GAGs)
 Amino sugar long, linear polymers of repeating disaccharide subunits
 Covalently linked to core protein to from proteoglycans
 Highly extended and osmotically active due to presence of negative charge and cations
o Absorb water and form a hydrated gel
 Major glycosaminoglycans
o Hyaluronic acid
o Chondroitin sulphate
o Dermatan sulphate
o Heparan sulphate
o Heparin
o Keratan sulphate  The sequence and length of GAG chains attached to the
core protein could vary among different proteoglycans
 Hyaluroran Proteoglycan
Proteoglycan aggregate
(Hyaline cartilage)

Proteoglycan
Heavily hydrated i.e.
attract water readily
because a lot of
charges are present on
proteoglycan

Glycoproteins
 Involved in adhesion of cells to their substrate
 With specialized receptors, integrins, on the cell surface
 Fibronectin
o Promotes the attachment of fibroblasts and other cells to the matrix in connective tissues
 Laminin
o Promotes the attachment of epithelial cells to the basal lamina
o Others include entactin, tenascin, chondronectin and osteopontin

Classification of Fibres
Relative abundance of fibres Arrangement of fibres Nature of fibres
Loose Irregular White for collagen
Dense Regular Yellow for elastic

Types of Connective Tissue Example

Loose (areolar) Mesentery, Wharton’s jelly in umbilical cord, lamina propria in GI tract
Dense irregular Dermis of skin
Dense regular Tendon, ligaments, aponeurosis

Fibroblasts

Collagen Elastic fibres Fibroblasts Collagen Collagen Fibroblasts

Ground substance
Fibrous Component
 There are three major types, collagen fibres, reticular fibres and elastic fibres

Collagen Fibres
 Present in all kinds of connective tissue and are major components in skin and bone
 At least 27 subtypes
 The most type is collagen type I arranged in parallel fibrils (cross striation under EM)
 Each collagen molecule (tropocollagen) is a triple helix i.e. α1, α1 and α2 peptides (I)
 Abundant hydroxyproline and hydroxylysine
 Acidophilic
 Unbranched molecules

Common Types of Collagen

Type Cells Location in body
I Fibroblasts Dermis of skin, tendons and ligaments
Osteoblasts Bone
II Chondroblasts Hyaline cartilage
III Fibroblasts Reticular fibre
IV Epithelial cells Basal lamina
V Mesenchymal cells Placenta
VII Keratinocytes Anchoring fibres in basal membrane

Reticular Fibres
 Extremely fine i.e. 0.5-2 micron
 Mainly made of collagen type III
 Form extensive network to support soft organs and tissues
o E.g. lymph node, spleen, red bone marrow, liver, kidney,
endocrine organs
 Not visible under H & E staining
 Easily visible by silver stain i.e. argyrophilic

 PAS positive due to high content of glycoproteins

o Periodic acid–Schiff (PAS) is a staining method used to
detect polysaccharides such as glycogen, and
mucosubstances such as glycoproteins, glycolipids and
mucins in tissues.

Elastic Fibres
 Stretchable with cross-linked molecules
o Loss of elastic fibres is responsible for wrinkles
o Elastin, a protein that is rich in glycine and lysine, allows
many tissues in the body to resume their shape after stretching or contracting
 Many tropoelastin molecules e.g. desmosine and isodesmosine covalently bind together
with crosslinks to form elastin
 With uniform diameter 4-5 microns
 Consist of an amorphous core of elastin surrounded by microfibrils
 o Mutation may cause misfolding of fibrillin that leads to Marfan’s syndrome
 Branched and re-joined to form a loose network in
loose connective tissue
 Fenestrated sheets in walls of large arteries
 When abundant, appears yellow in colour (aorta)
 Difficult to stain with H & E
o Selectively stained by Weigert’s
resorcin-fuchsin method

Cells
 Fibroblasts, macrophages, mast cells, plasma cells,
leukocytes and adipose cells
Elastic fibres Smooth muscle cells & collagen
Fibroblasts
 Most common cell type in connective tissue
 Synthesize the fibrous components and the ground substance
 Respond to tissue damage and synthesis of new matrix
 Fibroblast is the active state while fibrocyte is the quiescent
 Some fibroblasts may be precursor cells for smooth muscle cell, adipocyte,
chondroblast and osteoblast

Macrophages
 Phagocytic, derived from circulating monocytes
 Distributed throughout the whole body and present in most organs
 Irregular surfaces
 Constitute the mononuclear phagocyte system
o Küpffer cells in liver
o Microglial cells in CNS
 10 to 30 μm in size
 Oval or kidney-shaped nuclei eccentrically located
 Contains many lysosomes
 Long-living (moths or even years)
 Form multi-nuclear giant cells in pathologic conditions
 Surface receptors for Fc (antibody) and C3 (complements) i.e. opsonisation
o An opsonin is any molecule that enhances phagocytosis by marking an antigen for an immune
response
 Functions
o Ingestion of particles and their digestion by the lysosomal enzymes
o Involved in immune defence
 Antigen presentation i.e. engulf and digest antigens and present the antigens
recognizable to lymphocytes to initiate immune response
 Secretion of growth factors and cytokines
Mast Cells
 20 to 30 μm in size
 Oval to round in shape
 Nucleus obscured by the cytoplasmic granules
 Specific surface receptors IgE (similar to basophils)
 Mast cell granules are metachromatic Mast cell
 Metachromasia
o The stained material takes on a different colour from the colour of
the applied dye (e.g. with Toluidine blue dye, they are stained
purple red), due to the presence of heparin
 Other contents of mast cell granules
o Histamine
o Neutral proteases
o ECF-A (Esosinophil chemotactic factor of anaphylaxis)
o Leukotriene
 Release of the granules triggered by binding of antigen to IgE
 Involved in immediate hypersensitivity reactions e.g. anaphylactic shock
o Anaphylaxis is a serious allergic reaction that is rapid in onset and may cause death
o Typically causes a number of symptoms including an itchy rash, throat swelling, and low blood
pressure

Plasma Cells
 Differentiated from B lymphocytes cells
 Few in connective tissues
 Eccentrically placed nucleus (clock-face)
 Synthesis of antibody
 Prominent juxta nuclear (near the nucleus) Golgi complex
 Large ovoid cells with basophilic cytoplasm due to abundant rough ER involved in antibody synthesis

Leukocytes
 Migratory cells from blood (more during inflammation)
 Major types
o Neutrophils Plasma cell
 Polymorph
 Multilobed nucleus
 o Eosinophils (eosinophilic granules)
o Basophils (contents of granules similar to mast cells)
o Lymphocytes
 Condensed nucleus
 Thin rim of cytoplasm

Adipose Cells
 Two types of adipose tissue
o Unilocular (yellow) adipose tissue
 Cells have only one large fat vacuole
 Common form in adult as the main energy source
o Multilocular (brown) adipose tissue
 Cells have several fat vacuoles
 Numerous mitochondria
 Transformed into heat efficiently
 Large number of blood capillaries
 More abundant in hibernating animals
 Important mainly in the first few months of postnatal
life

Thick skin
Lecture 30: Introduction to the gastrointestinal system
Objectives
1. Describe the basic histological layers of the GI tract
2. Describe the major histological features and functions of esophagus, stomach, small and large intestine
3. Describe the structures and functions of major digestive glands of the GI tract.

Histological Layers in Digestive Tract  Mucosa

o For absorption, secretion and protection
Mucosa o Lamina propria
Submucosa  Muscularis mucosae
 Submucosa
Muscularis externa
o Support, nervous and blood supply and lymphoid tissues
Serosa/ Adventitia o Submucosal plexus for regulating secretion
 Muscularis externa
o Two layers of smooth muscle
 Inner circular
 Outer longitudinal
o Myenteric plexus for regulating peristalsis
 Serosa or adventitia

Muscularis mucosae Submucosa Epithelium

Mucosa

Lamina propria

Adventitia
Submucosal gland Lymph nodule Muscularis

Stratified squamous
epithelium
(Non-keratinizing)

Muscularis mucosae

Submucosa
Submucosal gland Lamina propria
Mucosa
Epithelial Lining
 Oesophagus Stratified squamous non-keratinizing epithelium
 Stomach Simple columnar epithelium
 Predominantly mucus-secreting for protection
 Intestine Simple columnar epithelium
 Absorptive cells and mucus-secreting cells
Laminar Propria
 A thin layer of loose connective tissue which lines beneath the epithelium
o Allowing it to be cell rich e.g. fibroblasts, lymphocytes, plasma cells, leukocytes
 Together with epithelium, constitutes the mucosa
 Supports and nourish the epithelium
 Contains lymphatics and fenestrated blood capillaries
 Accommodates the mucosal gland i.e. Epithelial invagination
o Secretes mucus and other secretions
 Unencapsulated lymphoid nodules and plasma cells for protection

Muscularis Mucosae
 Thin layers of smooth muscle oriented in different ways
 For local movement and folding of the mucosa
o Controlled by Meissner's plexus and some paracrine hormones
 Modulates the height of villi in small intestine

Submucosa
 Loose connective tissue
 With larger blood vessels and lymphatics
 Contains submucosal plexus of ANS ganglia and nerve fibres
o Controlled by Meissner's plexus
 Contains mucus-secreting glands in duodenum and oesophagus only

Muscularis Externa
 Two layers of smooth muscle
o Inner circular
o Outer longitudinal
 Regulate the luminal diameter of the intestine
 Moves luminal contents along the tract i.e. Peristalsis
 Peristaltic waves coordinated by Auerbach's (Myenteric) plexus (between
the circular and longitudinal muscle layers) and by paracrine hormones

External Layer
 Serosa
o Visceral peritoneum
 Mesothelium
 Connective tissues
 Adventitia
o Loose connective tissue in oesophagus and retroperitoneal segments of
intestines
Oesophagus
 Muscular walls to convey chewed food from pharynx to the stomach

Layers
 Stratified squamous non-keratinizing epithelium to withstand abrasion
 Oesophageal cardiac glands (simple tubular and mucous) in lamina propria at the upper and submucosal
esophageal glands eases the passage of ingested food
 Substantial muscularis mucosae
 Muscularis externa
o Striated muscles in the upper third
o Smooth muscles in the lower third
o Mixed in the middle third
o Physiologic sphincters at two sites
 Pharyngoesophageal
 Gastroesophageal
 Adventitia as the outermost layer

Stomach
 Beginning of digestion where food is partially digested and
converted to chime
 Rugae
o Gastric mucosa raised into folds
o Simple columnar epithelium
o Allows the stomach to expand when needed
 Mucosal simple tubular glands secrets hydrochloric acid (HCl),
mucus, digestive enzymes and hormones
 No submucosal glands are present except in regions close to
the duodenum
 Three layers of muscle in muscularis externa
o Innermost (oblique)
o Middle (circular)
o Outermost (longitudinal)
 Serosal covering
o Continuation of mesogastrium

Muscularis
externa
Division of Stomach
Cardia
 Epithelium changed drastically from the stratified
squamous type in oesophagus to simple columnar
type in cardiac region
 Contains mucosal cardiac gland
 Secretory cells secrets mucus and lysozyme
 Few parietal cells secrets HCl

Fundus and Body

 They are histologically similar
 Simple mucous columnar cells without goblet cell as surface epithelial lining
 Gastric pits are tiny epithelial recesses where gastric glands open into
o Lined by mucous columnar cells
 Gastric/ Fundic glands
o Straight and branched at the base
o Secrets gastric juice containing water, HCl,
mucus, digestive enzymes and electrolytes
Pylorus
 Pyloric glands
o Deeper pits
o Shorter gland and more branched
o Proximal region secrets HCl and mucus
o Other regions are entirely mucous secreting
o Fewer enteroendocrine cells are responsible for secretion of serotonin, gastrin and somatostatin
 Substantial circular middle layer of the muscularis externa at the outlet of stomach i.e. pyloric sphincter

Gastric Glands
 Simple branched mucosal gland in lamina propria
o Isthums
o Neck
o Base
 Germination zones
o Isthums and neck
o Replace all cells in gastric glands, gastric pits
and luminal surface
 Regulated by vagus nerve and by several hormone
secreted by cells in gastric and duodenum
o E.g. Somatostatin, gastrin and serotonin
Hormone Function
Gastrin Stimulates HCl secretion
Stimulates secretion of pepsinogen
Somatostatin Inhibits release of gastrin
Urogastrone Inhibits HCl secretion
Serotonin Regulation of mood and apppetite
 Gastric pits
Gastric glands
An Overview
Location Name
Isthums Mucous neck cells
Neck Parietal (Oxyntic) cells
Base Chief (Zymogenic) cells
Base Enteroendocrine cells
Undifferentiated cells
For vitamin B12 absorption
Zymogen
(Inactive enzyme precursor)
Enteroendocrine cells
Description Secretion Staining
In gastric pits Mucus gel layer Clear
Isthums refers to the opening into
the gastric pits
Large oval cells stain that stain HCl and intrinsic factors Acidophilic
deeply with eosin
Studded throughout the tube at
intervals, giving the tube a beaded
or varicose appearance
Short columnar, granular cells that Pepsinogen, rennin Basophilic
constrict the lumen to turn it into a
fine channel below
G cells, a type of enteroendocrine Hormones /
cell that secrete the hormone E.g. serotonin, gastrin
gastrin and somatostatin
 Gastrin promotes the
secretion of pepsinogen by
chief cells and HCl by
parietal cells
 Gastrin also promotes
gastric contractions to mix
the content
Cell Types in Gastric Glands
Mucous Neck Cells
 Located in the neck region
 Mucus secreting and mitotic

Parietal (Oxyntic) Cells

 Large pale-staining, pyramidal cells
 Concentrated in the upper and middle part of gastric glands
 Canaliculus
o A deep folding, Intracellular channel which serves to increase
surface area for secretion
o Produce HCl
o Lined by numerous smooth ER as well as mitochondria to supply energy for active transport of H+
ions
 Account for acidophilic property in H & E staining
 Numerous interdigitating and long microvilli
 Mucous coating to protect the gastric lining
 Secret gastric intrinsic factor for vitamin B12 absorption in small intestine
 Deficiency will lead to impaired erythrocyte production in myeloid tissue i.e. pernicious anaemia

Chief (Zymogenic) Cells

 Concentrated at the lower half of the gland
 Contain many zymogen granules
o Enzyme precursors of pepsinogen and the
precursor of rennin and lipase
o Pepsinogen converted to pepsin by acidic pH
 Extensive rough ER makeing them basophilic
 Basally located nucleus
 Prominent Golgi complex

Enteroendocrine Cells
 Present in small number
 Numerous variety
 Produce peptide hormones e.g. somatostatin, motilin,
serotonin and cholecystokinin
o Referred to as the Diffuse Neuroendocrine System (DNES)
o Some GI peptides and amines are neurotransmitters
o Paraneurons
 Neurotransmitter secreting cells
o Many of them belong to the Amine Precursor
Uptake and Decarboxylation (APUD) cells system

Undifferentiated Cells
 Located at the neck and isthmus
 Germination region
 High rate of mitosis
 Epithelium replaced in 4 to 6 days
Small Intestine
 Duodenum, jejunum and ileum
 Functions
o Completes digestion
o Absorbs nutrients
o Produces a variety of GI hormones

Secretions in Small Intestine

Brunner’s glands
 Digestive juices in small intestine are released from pancreas
o Pancreatic juice is alkaline which counteracts gastric acidity
o Digestive enzymes in pancreatic juice assist digestion
o Bile from liver augments pancreatic lipase
 Mucus in small intestine are secreted by
o Brunner's glands in duodenum
 Compound tubular submucosal glands found in the duodenum
o Mucosal glands in lamina propria of mucosa in the GI tract
 Crypts of Lieberkühn/ Intestinal crypts in small and large intestine
o Goblet cells of the mucosal epithelium Crypts of Lieberkühn

Amplification of Absorptive Surface

A. Convolution
B. Plicae circulares
C. Villi
D. Microvilli
E. Oligosaccharide chains of
integral protein

 Absorptive surface expanded by

o Plicae circulares Approximately 2-3X surface area
 Numerous in the upper part of small intestine
o Intestinal villi Approximately 10X surface area
o Microvilli Approximately 20X surface area
 Collectively increased the surface area by 400 to 600 folds

Villi
 Tall absorptive columnar cells with abundant goblet cells and occasional enteroendocreine cells interspersed
between them
 Contain a profuse network of fenestrated blood capillaries for the absorption of nutrients
 Smooth muscle cells extend into villi from muscularis mucosae, which modulate the height of villi
 Contain numerous cell types in lamina propria e.g. lymphocytes, plasma cells and eosinophils
 Absorption of Fats by Lacteals
1. Absorbed products of fat in forms of monoglycerides and free fatty acids
2. Lipid synthesis in the smooth ER of the villous columnar cells
3. Lipid containing vesicles fuse with the lateral borders of villous columnar cells and liberate their lipid
content into the intercellular spaces between cells in the form of chylomicrons
4. Chylomicrons enter the lacteals in lamina propria reach blood chiefly via the thoracic duct

Intestinal Glands
 Also known as crypts of Lieberkühn
 Main cell types includes goblet cells and paneth cells

Peyer's Patches
 Aggregated lymphoid nodules, particularly prominent in lowest portion of the small intestine, the ileal walls
and extended to submucosa
o Thus differentiate the ileum from the duodenum and jejunum
o The duodenum can be identified by Brunner's glands
o The jejunum has neither Brunner's glands nor Peyer's patches
 Gut-associated lymphoid tissue (GALT) is responsible for mucosal
immunity
 Antigen presenting epithelial cells (M cells) overlying the
aggregated lymphoid nodules ingest the foreign antigen and deliver
them to macrophages or lymphocytes
 B-cells develop into IgA producing plasma cells
o IgA is secreted onto the free surface of epithelia and this is the
primary defence against mucosal infection

Cell Types in Small Intestine

 All the cell types are believed to derive from the small crypt base columnar stem cells
 Epithelial cells on villi are renewed about every 5 to 6 days

Villous Columnar Cells

 For absorption
 Presence of microvilli, striated or brush border
 Produce disaccharidases and peptidases for completing digestions of carbohydrates and proteins
o These enzymes are integral membrane glycoprotein of the cell membrane
o They are the brush border enzymes
 Form junctional complexes
o Tight junctions
o Adhering junctions

Paneth Cells
 At the lower part of the crypts
 Large acidophilic zymogen granules
 Extensive rough ER and prominent Golgi apparatus
 Major source of lysozyme (antibacterial enzyme)

Paneth cells
 Goblet Cells
 In both villi and crypts
 Increase in number from the duodenum to ileum

Enteroendocrine Cells:
 GI hormones including secretin and cholecystokinin-pancreozymin

Regional Variations in Small Intestines

Duodenum Jejunum Ileum
Plicase circulares Present Present Proximal half
Villi Broad, tongue-like Narrow Narrow
Submucosal gland Brunner’s gland Absent Absent
Lymphoid nodules Present Present Extensive as Peyer’s patches
Outermost layer Adventitia (Mostly Serosa Serosa
retro-peritoneal)
Large Intestine
Columnar epithelial cells (absorptive)

Villus Goblet cells

Plicae circulares
Intestinal glands Lumen of intestinal
Brunner’s glands glands
in duodenum Muscularis
mucosae

Villus Capillary Lacteal

Mucosa
Columnar epithelial cells

Lamina propria

Intestinal crypts

Lymphatic nodule
Submucosa

Muscularis externa

Serosa
Large Intestine
 Colon, rectum, anal canal and appendix

Functions
 Complete absorption and retrieves water from the luminal contents
 Produces abundant protective mucus, some GI hormones with no digestive enzymes secreted
 House bacteria that produce vitamin B12 and vitamin K

Histology
 Surface epithelium
o Tall absorptive columnar cells with a striated border
 Epithelium replaced every 6 days by new cells arising from lower parts of the crypts
o Goblet cells
 Increase in number from ascending colon to rectum
 Enteroendocrine cells
 No villi or submucosal glands
 Absence of paneth cells in most parts of the large intestine
 Retroperitoneal segment of the colon and rectum have adventitia

Glands openings

Glands
Mucosa

Submucosa

Muscularis externa

Serosa/ Adventitia

Features
1. Taeniae Coli
 In cecum and colon, longitudinal muscles in muscularis externa are arranged
mostly as three longitudincal bands i.e. taeniae coli
o Continuous contraction causes the sacculation (formation of pouches)
of the colon, forming small pouches called haustra, which give the
colon its segmented appearance
o Haustra are absent in the appendix
 2. Appendix Epiploica
 Presence of appendix epiploica
o Small pouches of the peritoneum filled with fat, situated along the colon but not in the rectum
o Function is unknown
o The appendages can become inflamed, a benign but painful process known as epiploic
appendagitis, which can mimic acute appendicitis

Appendix/ Vermiform Appendix

 Blind end appendage of the caecum
 Microscopically resembles large intestine
 Prominent lymphoid nodules which involve deep into submucosa
o Confluent and surround the entire lumen

Appendicitis
 Obstruction of lumen with bacterial infection
 Perforate and leads to peritonitis
 Appendectomy – removal of the inflamed appendix

Anus
 At anus, circular smooth muscle in muscularis externa form the internal anal sphincter
 Inferior part of anal canal
o Simple columnar epithelial lining changes to stratified squamous non-keratinized and to keratinized
epidermis of skin
 External anal sphincter
o Circular band of skeletal muscle which provide voluntary control of defecation

Haemorrhoids (Piles)
 Mucosal lining of the anal canal that lacks crypts
 Raised into longitudinal ridges (anal columns) joined to
form anal valves
 Discontinuous muscularis mucosa
 Terminate at anal valve
 Contain a plexus of small vein
o Anastomosis (Reconnection of two previously
branched streams) between the portal venous system
and the systemic venous system

Sequence of Development
1. Chronic congestion of anal venous plexus cause it to dilate and varicose
2. Anal mucosa bulges – Internal haemorrhoids
3. Protrude under the anal skin – External haemorrhoids
Comparison of Small Intestine and Large Intestine

Small Intestine

Large Intestine

Summary
Lecture 31: Scientific basis of medicine
Objectives
1. Identify the historical development and scientific background of modern medicine.
2. Describe observed patterns in diseases as real or apparent.

Inaccuracy
 In general, there are three possible reasons why the association may not be real
o Chance
o Bias
o Confounding

Chance
 When we treat patients, every patient can have a slightly different outcome
 Usually in medical research we will try to study a larger number of patients and look at average outcomes,
to minimise the role of chance in our findings
 Statistical analysis explicitly allows for variability in outcomes and can help us to determine whether
differences between groups of patients are significant or not

Bias
 Biases are caused by systematic rather than random variation leading to inaccurate estimates of the
actual effects of treatments or interventions
 There could be systematic errors in the way we select patients, measure outcomes, or analyse data
o Selection bias
o Information bias
o Analysis bias

Confounding
 Whereas bias involves error in measuring an association, confounding involves misinterpretation of an
association
 Confounding is a major problem in medical research

Limitations of Experiment
 It is not always feasible or ethical to allocate treatments to patients randomly
 The effects of treatments under controlled conditions may differ from their effectiveness in real-life
 Experiments often include well-behaved motivated patients, with single rather than multiple conditions,
with intensive follow-up
o This is a type of selection bias
 Chance can also affect the results of experiments

Summary
 Scientific progress often hindered by prevailing “wisdom” and vested interests
 Limited scientific data to support many treatments and interventions but evidence base is growing every
year
 Experimental evidence is usually the strongest
 Be alert to possibility of chance, bias and confounding when distinguishing real from apparent effects
Lecture 32: Structural organization of the respiratory system
Objectives
1. Describe the anatomy of the nasal cavity.
2. Identify the structures and know the functions of the pharynx.
3. Describe of the anatomy of the airways and lungs.

General Features
 The respiratory system provides the pathway for the entry of oxygen into the body and the excretion of
carbon dioxide into the atmosphere
 The organs of the respiratory system are
o Nose
o Pharynx and larynx
o Trachea, bronchi, lungs
o Muscles of respiration and diaphragm

Glabella

Alar cartilage

Nasal bone

Septal cartilage
Alar fibrofatty tissue

Anterior nasal spine

Nasal Cavity
The Upper and Lower Respiratory Tracts
 The nasal cavities are considered to be the upper part of the respiratory tract
 The lower respiratory tract consists of the larynx, trachea, bronchi, bronchioles and alveoli of the lungs
 The pharynx separates the upper and the lower respiratory tracts

Nasal Septum
 The nose is divided into right and left nasal cavities by nasal septum
 The nasal septum is made up of partly bone and partly cartilage
o Perpendicular plate of the ethmoid bone
o Vomer
o Septal cartilage

Structure of the Nasal Cavity

 The nose opens anteriorly as an aperture called anterior nares and opens posteriorly as an aperture
called posterior nares aperture
 Behind the posterior nares aperture is the nasopharynx
  The nose is an immovable bony bridge supported by
o Nasal bones
o Frontal processes of the maxillae
o Nasal part of the frontal bone
 The roof of the nasal cavity is formed by frontonasal, ethmoidal and sphenoidal bones
 The floor is formed by palatine process of the maxilla and horizontal plate of the palatine bone
 The medial wall of the nasal cavity is formed by nasal septum

Conchae and Meatus

To nasopharynx

 The lateral wall is formed the three curvature plates known as conchae or turbinates
 These plates are called superior, middle and inferior nasal conchae
 Underneath each curvature plate, there is a potential space called meatus for the drainage of the
paranasal sinuses and nasolacrimal ducts
 The meatus is named according to the curvature plate above i.e. superior meatus, middle meatus and
inferior meatus

Functions
1. Respiration
2. Olfaction (Smell)
3. Filtration of dust
4. Humidification of air
 5. Drainage of paranasal sinuses (air-filled extension of the nasal cavities)

Epithelium and Nerve

 The nasal cavities and paranasal sinuses are lined by pseudostratified ciliated columnar epithelium
 Near the roof of the nasal cavities, the lining is different and being formed by olfactory epithelium
o This contains the cell bodies of olfactory nerve (Cranial nerve I), which convey the sense of smell
to the brain
o The other parts are supplied by branches of trigeminal nerve (Cranial nerve V)
 Three major branches are the ophthalmic nerve (V1), maxillary nerve (V2) and
mandibular nerve (V3)

Blood Supply
1. Branches of maxillary artery (External carotid artery)
2. Branches of the facial artery (External carotid artery)
3. Branches of ophthalmic artery (Internal carotid artery)
 Blood is drain into pterygoid plexus, facial vein, infraorbital vein and ophthalmic vein

Paranasal Sinuses
 The paranasal sinuses are air-filled extension of the nasal cavity
o Frontal sinuses, located in the frontal bone
o Ethmoid sinuses, located in the ethmoid bone
o Sphenoid sinuses, located in the spheoid bone
o Maxillary sinuses, located in the maxilla
 The paranasal sinuses drain into the meatus
 The function is not well defined but they are involved in adding resonance to the voice
 The sinuses also serve to lighten the skull
 The mucosal lining of the paranasal sinuses is innervated by branches of the trigeminal nerve
 The blood supply is from branches of maxillary (External carotid artery) and branches of ophthalmic arteries
(Internal carotid artery)

Pharynx and Soft Palate

 The pharynx is about 12 - 14 cm in length and commences at the base of the skull and ends at the level of C6
 It is divided into three segments
o Nasopharynx
o Oropharynx
o Laryngopharynx
 The pharynx is composed of three layers of tissue
o Mucous membrane lining
 Ciliated columnar epithelium at the nasopharynx
 Stratified squamous epithelium at the oropharynx and laryngopharynx
o Fibrous tissue
o Muscle tissue
 This is composed of several muscle groups of constrictor muscles which is involved in swallowing

Nasopharynx
 The nasopharynx lies above the soft plate and behind the nasal cavity
 At its roof lies a collection of adenoid tissue called pharyngeal tonsils i.e. adenoids
 o These are lymphoid tissues that are prominent in children up to the age of 7 years old
 The auditory tube opens on the lateral wall
o This allows connection between the nasal cavity and middle ear
o Middle ear infection (Otitis Media) is common amongst children and they get infected via this
route
o The elevated part of the auditory tube is called tubal elevation
o Behind it, there is a space called pharyngeal recess (a common site of origin for nasopharyngeal
carcinoma)
 The palate is divided into hard and soft palate
o The hard palate forms the floor of the nasal cavities
o The soft palate is a mobile fold of tissue attached to the posterior part of the hard palate
o There is a conical projection in the midline of the soft palate known as uvula
 There are five muscles that regulate the movement of the soft palate
o Their general functions are to elevate and tense the soft palate
o These muscles are attached to the bones and aponeurosis of the pharynx
o They are innervated by a group of nerves known as pharyngeal plexus

Oropharynx
 The oropharynx is located behind the mouth and extends below the level of C3
 Anteriorly, there are each pair of folds of mucosa enclosing a collection of lymphoid tissue known as
palatine tonsils
 During swallowing, the nasal and oral cavities are separated by the soft palate

Laryngopharynx
 The laryngopharynx extends from the level of C3 to C6
 It starts at the lower level where the oropharynx ends and continues down with the esophagus at the
level of C6
 Functions
o Pathway for air and food
o Taste (CN I nerve endings are found at the oral and pharynx)
o Hearing
 Auditory tube allows air to flow into the middle ear and balance the pressure across the
ear drum or tympanic membrane
o Warming and humidifying
o Protection (Done by the lymphoid tissue)
o Speech (By acting as a resonating chamber)

Larynx
 The larynx is located ate the level of C3 to C6
 It consists of several irregularly shape cartilages bounded by ligaments
 Superiorly, it is related to the hyoid bone and inferiorly, it is continuous with the trachea
 Anteriorly, there are group of muscles attached to the hyoid bone known as the supra- and infra-hyoid
muscles
 Posteriorly, the laryngopharynx is behind the larynx that is continuous with the esophagus
 Laterally, there are two lobes of the thyroid gland
 The primary function of the larynx is for the production of sound
Trachea
 The trachea is the continuation of the larynx
 It extends from the level of C6 to the level of T4 - T5 where it bifurcates into two main bronchi
 Posteriorly, the esophagus separates the trachea from the vertebral column
 Laterally, the trachea is related to the lungs and thyroid gland
 The trachea is made up of C-shaped cartilages and behind it consists of ciliated columnar epithelium and
smooth muscle layer
 Functions
o Support the patency of the airway
o Excretion of particles
o Assists in cough reflex and humidification
o Warming and filtration of air
 The blood supply comes from the inferior thyroid artery (a branch of subclavian artery) and bronchial artery
(from the thoracic aorta) and drains into the inferior thyroid vein and brachiocephalic veins
 The nerve supply comes from the recurrent laryngeal nerve and vagus nerve and sympathetic cervical ganglia

Bronchi
 The two primary bronchi are formed when the trachea divides at the level of T4 - T5
 It further divides into
o Lobar bronchus
 Distributed to the lobes
o Segmental bronchus
 Goes into the bronchpulmonary segment of the lobes
o Bronchioles
 Gas exchange occurs
o Alveolar ducts
 The alveolar ducts opens into the alveolus
 Gas exchange occurs
 The function of air passages not involved in gaseous exchange is for control of airflow whereas the
respiratory bronchioles and alveoli are involved in external respiration (exchange of gas), immune defense,
warming and humidification of air

Lungs
 The lungs are located in the thoracic cavity
The right lung has three lobes

o Upper, middle and lower lobes
 The left has two lobes
o Upper and lower lobes
 The lungs are enveloped by the pleura
Lecture 34: Blood cells
Objectives
1. Describe the fluid phase and formed elements of blood.
2. Describe the histological features of red and white blood cells in blood smear.
3. Describe the functions of peripheral blood cells.
4. Describe the inflammatory and immune cells found in tissues including mast cells, plasma cells, macrophages,
Kupffer cells and dendritic cells.

Functions of Blood
 Transport
o Oxygen, carbon dioxide, nutrients, metabolic wastes, stem cells,
hormones and heat
 Protection
o Roles in inflammation
o WBC destroy invading microorganisms, cancer cells and
pathogenic substances
o Antibodies and proteins neutralize toxins and destroy
pathogens
o Blood clotting assisted by blood platelets to minimize blood loss
 Regulation
o Capillaries for stabilizing fluid distribution
o Blood proteins for stabilizing pH of ECF
o Help with water balance and body temperature

Blood Composition
 Blood is considered as a connective tissue
 It is 8% of body weight
 Average blood volume of an adult is around 4-6L (Around 8%
of body weight)
 Composed of cells submerged in extracellular matrix, where
the matrix refers to the plasma
 Plasma
o Accounts for 55% of blood
o 92% of plasma is water
o Clear and light yellow in colour
 Formed elements
o Red blood cells (45% in volume)
o White blood cells (Less than 1%
by volume)
o Platelets (Less than 1% by
volume)
 Albumin primarily for viscosity and osmolarity
Globulins primarily for fat soluble vitamins and lipids and
Plasma immune responses
 Clotting, defence and transport
Consists of
 Water 92% by weight
 Proteins Serum albumin (60%), globulins (36%), fibrinogen (4%), clotting factors, enzymes
and others
 Nutrients Glucose, amino acids, lactic acids, lipids (Cholesterol, triglycerides, fatty acids,
phospholipids and lipoprotein), iron, trace elements and vitamins
 Electrolytes Salts of sodium, potassium, calcium, magnesium, chloride, bicarbonate, phosphate
and sulphate (Na+, K+, Ca2+, Mg2+, Cl-, HCO3-, PO43-, SO42-
 Nitrogenous wastes Urea, uric acid, creatinine, creatine, bilirubin and ammonia
 Gases Oxygen, carbon dioxide and nitrogen

3 major types of protein (all produced by liver except δ-G):

 Albumin (60%): most abundant, for solute transport; buffers pH; contributes to viscosity and osmolarity
 Globulins (36%): α, β, δ; for solute transport; clotting; immunity
o δ -Globulin produced by plasma cells
 Fibrinogen (4%): clotting protein

Blood viscosity and osmolarity

 Viscosity
o Resistance of fluid to flow, i.e. thickness of fluid
o Governs blood flow
 Blood 4-5x viscous than water
 Plasma 2x viscous than water
 Osmolarity
o Total molarity of dissolved particles that cannot pass through wall of blood vessel

Haematopoiesis

Ratio of red to yellow bone marrow

 Haematopoiesis takes place in
red bone marrow in long bones decreases as we age

Final maturation
happens in thymus
Haematopoiesis
 The production of blood and its formed elements
o Primitive stem cells -> bone marrow, liver, spleen, thymus
o Stem cells multiply and form blood cells
o Around birth – liver stops producing blood cells
o After birth – spleen stops producing RBC
 Bone marrow main source of blood cell production
 Lymphocytes also produced by thymus, tonsil, LN, spleen and mucous membranes (lymphoid
patches)
 Blood plasma is replaced continually
Erythrocytes (Red Blood Cells)
 Most abundant in blood; Most critical for survival
 Devoid of organelles
o Uses anaerobic fermentation to produce ATP
o Cytoplasm contains haemoglobin
o Contains no nucleus (anucleate) and mitochondria
 Glycoproteins/ Glycolipids on plasma membranes determine blood types
 Discoid with thick rim and thin centre, biconcave in shape and has high surface area to volume ratio
 Haemoglobin gives colours to cell: Heme group binds O2, globin binds CO2
 Cytoskeleton proteins provides resilience and durability: spectrin and actin
 Normally circular and fairly uniform in size
 Transport oxygen from lungs to tissues and carbon dioxide from tissues to lungs but will not take up oxygen
by itself as only anaerobic respiration takes place in it
 Life span is around 120 days

Haemoglobin
 Fe-containing gas transport protein.
 Consists of
o 4 globins (protein chains)
o Heme group (non-protein)
 Bound to each protein chain
 Ferrous ion at center of each heme group
 Binding site for Oxygen
 transporting four oxygen molecules
 Iron is required for haemoglobin production
 CO2 bound to globin
 Low haemoglobin count or iron deficiency result in anaemia

General Properties of Blood

Mean fraction of body weight 8%
Haematocrit (% of RBC by volume) Female: 37%-48% Male: 45%-52%
Haemoglobin Female: 12-16 g/dL Male: 13-18 g/dL
Mean RBC Count Female: 4.2-5.4 million/ µL Male: 4.6-6.2 million/ µL
Platelet Count 130,000-360,000 /µL
Total WBC Count 5,000-100,000 /µL

i.e. Haematocrit = the ratio of the volume of red blood cells to the total volume of blood.
Erythrocyte death
 RBC dies in spleen
 Haemolysis
o Heme + Globin
o Globin -> amino acids
o Heme -> bile pigments

Erythropoiesis *no test on steps, but the hormones involved

Lose their nuclei after entry into blood

 Erythrocyte production
 3-5 days’ process
 Erythroblast multiply and synthesize haemoglobin
o Iron is required for haemoglobin production
 Major steps
1. Reduction in cell size
2. Increase in cell number when erythroblasts develop into reticulocytes
3. Synthesis of haemoglobin
4. Loss of nucleus and organelles
 Phagocytosed by macrophages in liver and spleen after around 120 days since release from bone marrow
o Around 2.5 million are destroyed per second
 Regulated by Erythropoietin
o Bone marrow
o Requires iron, vitamin B12 and folate
o Steps:
 Oxygen deficiency in the blood
 Kidneys detect and release EPO
 3-4 days later, RBC count rises
 e.g. high altitude, exercise, emphysema
 Regulation of Erythropoiesis
(Hypoxia)

Contributes to 90% of the secretion

Iron
metabolism

Blood Types
 4 different types
o A, B, AB, O
 AB – universal recipient
 O – universal donor
 Genetically determined
 The Rh positive antigen is made upon the first exposure
to the Rh +ve blood (sensitisation)
 ABO and Rh systems are highly immunogenic
o ABO alleles on chromosome 9
 o Rh+ and Rh- (referring to Rh D antigens specifically)
 Blood plasma contains antibodies against incompatible antigens on foreign RBCs – Agglutination
 Chemical composition of glycolipids on the RBC surface act as antigens for immune activation
 49 antigens of the Rh blood groups
o D, C, E, c and e are among the most significant

Anaemia
 A reduction in the total number of circulating erythrocytes or a decrease in the quality or quantity of
haemoglobin in the blood
 Leads to generalized hypoxia
 It is a symptom of other conditions, not a disease
 The clinical manifestations are primarily due to the body’s attempts to compensate for the lack of oxygen
 Reduces the oxygen-carrying capacity of the blood
o Haematocrit < 35%

Symptoms depends on:

 Severity
 Rapidity of development
 Affected person’s age and health status
Causes
 Haemorrhage and diseases
 Iron deficiency
 Nutritional; decreased production of RBCs-
hypoproliferative (deficiency in folic acid, Vitamin
B12, iron)
 Increased destruction – haemolytic (e.g. thalassaemia)
 Heavy menstrual periods
 Bleeding in the digestive or urinary tract
 Surgery, trauma, pregnancy

Iron-deficiency anaemia
 􀂾Inadequate iron for haemoglobin synthesis

Causes:
o Blood loss (most common cause in adults)
o Dietary deficiencies
o Decreased absorption
o Increased metabolic requirements
o Chronic haemoglobinuria
Characterized by:
o Low Hb and Haematocrit
o Decreased iron stores
o Low serum iron and ferritin levels
o RBC are microcytic and hypochromic
Polycythaemia
 A disease state in which the proportion of blood volume that is occupied by red blood cells increases
 Primary
o Intrinsic to red blood cell precursors (inherited)
o Myeloproliferative disease
 Secondary
o Natural or artificial increases in erythropoietin production under chronic hypoxia
o E.g. Chronic obstructive pulmonary disease (COPD), high altitudes, tumors

Sickle-cell Anaemia
 Chronic disorder resulting in anaemia, pain and organ failure due to vessel occlusion
 Affected persons suffer severe haemolytic anaemia, chronic hyperbilirubinaemia
and vaso-occlusive crisis.
 Autosomal recessive inherited disorder caused by an abnormal HbS, which upon
deoxygenation causes the deformity of red blood cells into a sickle shape
 Common in African and middle eastern populations
 Red blood cells get stuck in small blood vessels, increasing risk of infection
 Can be treated by bone marrow transplant or cord blood stem cells transplant

Thalassemia
Bone Marrow Transplant
 A group of inherited disorders of
Hb synthesis due to absent or defective  Can treat leukaemia, lymphoma, sickle-cell anaemia, some
forms of anaemia and other disorders
synthesis of the alpha and beta chains
of adult Haemoglobin  Replace cancerous or defective marrow with donor stem
cells
o Alpha Thalassemia (4 genes)
o Beta Thalassemia (2 genes)  Aided by chemotherapy or radiation to first kill existing
cells to eliminate immune response on transplanted tissue
 Abnormal formation of haemoglobin
 Mild or severe anaemia
 Slowed growth and delayed puberty
 Bone problem associated i.e. brittle bones, expanded bone marrow and enlarged spleen
 More common in some populations thalassaemia is also called Mediterranean anaemia (southern Italy and
Greece)
 Alpha thalassaemia is more common in Asia
 Both kinds are common in Africans and African Americans

Leukaemia
 Is described as a malignant disorder of the blood and blood-forming organs, causing an accumulation of
dysfunctional cells and loss of cell division regulation
 Bone marrow is replaced by unregulated, proliferating, immature neoplastic cells
 There is an uncontrolled proliferation of WBC
 Abnormal cells are seen in the blood and may infiltrate the spleen, liver, lymph nodes and other tissues
 Because leukaemia cells are immature and poorly differentiated they proliferate rapidly and have a long life
span
o The do not function normally
o They interfere with maturation of normal blood cells
o They circulate in the bloodstream, cross the blood-brain barrier and infiltrate many body organs
  Types of leukaemia
o Named according to type of blood cells involved and whether acute or chronic:
 Acute lymphocytic (ALL)
 Lymphocytes
 Chronic lymphocytic (CLL)
 Acute myeloid / myeloblastic (AML)
 Granulocytes, erythrocytes, thrombocytes
 Chronic myeloid (CML)
Blood Smear
 Mixture of acid (Eosin) and basic (methylene blue) dyes
o Nucleic acids are stained by methylene blue
o Proteins (lysosomal enzymes in the granules) are stained by eosin

May-Grunwald Giemsa stain, Giemsa stain and Wright’s stain

Nuclei Purple to violet Granulocytes
Lymphocytes Plasma blue  Neutrophil Violet granules
Monocytes Plasma blue  Eosinophil Red-violet granules
Thrombocytes (Platelets) Violet  Basophil Strong violet granules
Erythrocytes Weak red
Acidic substances are stained better by basic dye, and vice versa
White Blood Cells
 5,000-10,000 /µL Agranulocytes also have granules but only the primary ones
Granulocytes Agranulocytes
 Neutrophil  Lymphocytes (B and T cells)
 Eosinophil  Monocytes
 Basophil  Natural killer cells
 Dendritic cells

Neutrophils
 Most abundant; 60-70% of total white blood cell count
varying shapes of the nucleus,
 Circulate in blood for 6-10 hours
which is usually lobed into three
 High in bacterial infection
segments
 Cytoplasm contains few organelles apart from granules
 Polymorphonuclear leukocytes (PMNs)

Functions
 Acute inflammatory responses to bacterial infections
o Phagocytose microorganisms and other substances
o Release toxic chemicals lethal to invaders as well as
neutrophils itself.
 Contain specific granules filled with enzymes e.g. lysozyme,
collagenase and elastase
 Azurophilic granules
o E.g. Lysosomes and antimicrobicidal
o Readily stained with an azure stain
 Types of Granules
 Primary granules
o Non-specific granules similar to lysosomes
 Secondary granules
o Specific to neutrophils and twice as numerous as primary granules but smaller
o Involved in inflammatory response (secretory)
 Tertiary granules
o Contain enzymes secreted by cell into the extracellular environment

Basophils
 Rarest (1%); Count is relatively stable
 Increase in viral infections, inflammation etc.
 Immediate hypersensitivity reactions, releases histimine
 IgE receptor on surface (Similar to mast cells but mast cells are found in
tissue whereas basophils are found in blood)
 High in allergic reactions Intensely stained granules
Hard to spot the nucleus
Functions
 Structurally and functionally similar to mast cells
 Accumulate at sites of infection
 Degranulation i.e. release histamine to increase blood flow and
promote inflammation
 Secrete heparin, which promotes mobility of other WHCs in the area
 Release chemical signals to attract eosinophils and neutrophils to the site of infection

Eosinophils
 Only 2-4% of WBC and count fluctuates
 Increase in parasitic infections, allergies, collagen diseases and diseases of
spleen and CNS
 Recruited by basophils in immediate hypersensitive late-phase reactions

Functions
 Phagocytose antigen-antibody complexes, allergens and inflammatory
chemicals
 Secrete enzymes that weaken or destroy parasitic worms
 Contain anti-histamine granules to eliminate effect of basophils

Lymphocytes
 Smallest
 20-50% of WBC
 involved in specific immunity
 Differentiate into B cells and T cells

T Lymphocytes
 Mature in thymus; thymus-dependent
  Cell-mediated immunity (adaptive immunity)
 Differentiate into 3 types
o Helper T cells (CD4+)
 Responds to antigens and assist other cells in activating immune response.
o Cytotoxic T (CD8+) cells
 Attack and kill infected or cancerous cells
o Memory T cells
 Re-exposure results in immediate response to antigen.

Functions
 Destroy cancer cells, infected cells and foreign cells
 Coordinate actions of other immune cells to regulate the immune system
 Suppress immune responses

B Lymphocytes
 Antigen presenting cells
 Mature in red bone marrow
 Differentiate into
o Plasma cells
 Secrete antibodies
o Memory B cells
 Similar to memory T cells

Natural Killer Cells

 Attack and lyse bacteria, transplanted tissue, non-self cells (cancer cells and infected cells)
 Immune surveillance
 Innate defence
 Contain small granules such as perforin and proteases (granzymes)

Monocytes
 Largest; 2-10% of WBC
 Phagocytic (Engulf bacteria), known as Antigen-presenting cells
Functions
 Circulating as the precursor of tissue macrophages
 Circulate in blood for 1-3 days and then migrate into body tissues to
become macrophages
 Count increases in viral infections and inflammation

Macrophages
 Tissue-based
 Highly phagocytic
 Phagocytose pathogens, dying or dead cells and foreign cells
 Antigen-presenting cells
 Survive longer at sites of inflammation
 Specialized Macrophages in Different Organs
 Kupffer cells in liver sinusoids
 Alveolar macrophages in the lungs
 Microglia in CNS
 Osteoclasts in bones

Platelets (Thrombocytes)
 Megakaryocytes
 Most abundant; second to RBCs; very small
 Produced through thrombopoiesis
 Fragments of cytoplasm derived from megakaryocytes
 Lasts for 8-10 days
 Contains no nucleus but a complex internal structure
o Lysosomes, mitochondria, microtubules, microfilaments, granules and open canalicular (small passage
way) system
 If number is higher than normal, there will be unnecessary clotting which can lead to strokes and heart
attacks

Haemostasis
 The process stops bleeding, as opposite to haemorrhage
 Actions of platelets
1. Secrete vasoconstrictors
2. Form temporary platelet plugs
3. Promote blood clotting
4. Initiate formation of clot-dissolving enzyme (Secrete procoagulants/ clotting factors)
5. Secrete chemicals that attract neutrophils and monocytes
6. Secrete growth factors to help to maintain and repair blood vessels
7. Secrete Factor XII to dissolve old blood clot.

Plasma Cells
 Terminally differentiated anti-body-secreting B cells
 Abundant in rough endoplasmic reticulum
 Secrete antibodies up to 2000 molecules per second
for 4-5 days
 Come from germinal centres
o Sites within secondary lymphoid organs where
mature B lymphocytes proliferate, differentiate
and mutate their antibody genes
o Mostly stored in lymph nodes but not in blood
Dendritic Cells
 Professional antigen-presenting cells found in blood and tissue
 Immature before sensing antigens and once activated, migrate to lymph nodes to activate T cells
 Present in tissues that are in contact with the external environment e.g. skin
o Langerhans cells are specialized dendritic cells at the skin
Types of Dendritic Cells
 Myeloid dendritic cells
o Most similar to monocytes
 Plasmacytoid dendritic cells

Mast Cells
 Immature form in blood and mature in tissue
 Major effector cell of immediate hypersensitivity actions i.e. allergy
 Reside in most tissues adjacent to blood vessels
 Granules rich in histamine and heparin
 Similar in both appearance and function to basophils
 Recent studies suggest that they may have a role in controlling infection

Type I Hypersensitivity Reaction

 Pollen has IgE which triggers type I hypersensitivity reaction

 Mast cells and eosinophils are sensitized
Other Types of Hypersensitivity Reactions

Summary of Formed Elements in Blood