Lecture 7: Histology Flashcards
Functions of blood
> Body heat- circulates fluid at a constant temperature
Coagulation- seals the body to the external environment by clothing at the site of cuts or grazes
Defence- provides a network for immune cells to move
Export- remove waste during cellular metabolism
Food- ensures cells have all the nutrients they need to function
Gas exchange- supply of O2 and CO2
Hormones- moves hormones around the body
Blood an blood cells
There are three main groups of cells in blood:
> Red cells (erythrocytes)
-carry oxygen around the
body
> White cells (leukocytes)
-make up our immune
system
> Platelets (thrombocytes)
-assist blood clotting
Making new blood
> The process of making new blood is called haematopoiesis, in the bone marrow
Stem cells which form blood cells are called haematopoietic stem cells (HSCs)
A haematopoietic stem cells can differentiate into lots of different blood cells; it is multipotent
They can not differentiate into non-blood cells like fat, bone and cartilage therefore they are pluripotent
Haematopoiesis
> Haematopoiesis is a tightly controlled process involving a complex network of cell signalling
Needs to ensure a basal level of cells in blood
But also monitor and shift the population of cells such as an increase in white cells in response to injury or infection for example:
-RBCs: 3.5x10¹¹ cells per
day
-Neutrophils: 10¹¹ cells per
day
-monocytes: 8.4x10⁹ cells
per day
-Platelets: 10¹¹ cells per day
Red blood cells
> Erythrocytes make up around 95% of all blood cells
There are around 5,000 000,000 red cells in 1ml of blood
The lifespan of a red blood cell is around 100 days
Every second your bone marrow is making around 2 million new red cells
Red cells are an atypical mammalian cell as they do not contain DNA, they are also atypically small for a mammalian cell (less than 10um)
They are easily deformed which means they can squeeze into tiny capillaries
The arm of haematopoiesis in which specially red cells are formed from a haematopoietic stem cell is called erythropoiesiss
It takes a red cell about 20 seconds to do a full la of your circulatory system
White blood cells
> White blood cells are famed for their role in defending us from attack by bacteria, fungi and viruses
They are also very important in ensuring our body heals correctly when it is damaged and recovers after surgery
About 1-10 in every 1000 circulating blood cell is a leukocyte
This equates to approximately 5,000,000 per ml of blood
There are a number of different leukocyte families, each their own function during infections and inflammation
Some white cells act non selectively to destroy any material deemed as foreign to the body, they are called innate immune cells
Others target specific foreign bodies to minimise collateral damage to other cells in the body, these are called adaptive immune cells
White blood cells- Neutrophils
> Neutrophils are our first line of defence
Play an important role in directing the immune response
Most common leukocyte in circulation; approx. 3,000,000- 8,000,000 neutrophils per ml of blood
About 60% of all white blood cells are neutrophils (vary on health status)
They are short lived, and last about 4-7 days
Neutrophils contain a range of membrane bound granules in their cytoplasm
These granules contain enzymes and biochemicals capable of degrading bacterial and other foreign substances
Degranulation- a pathogen may be internalised into the cell where it comes into context with these granules, or they can be released into the extracellular environment
White blood cells- Eosinophils
> Like neutrophils eosinophils are also granulocyte
They are usually somewhere between 30,000 and 300,000 eosinophils per ml of blood
Although not considered a ‘professional’ phagocyte, eosinophils do have phagocytic capability too
Their specific function is less characterised than the neutrophil
Eosinophils are particularly common at the muscle/membrane/tissue interface of the gut
Eosinophils co tribute to protecting the body from large invading organisms such as worms, these are called helminthic infections
Also involved in the pathology of allergy and asthma, numbers increase at sites of allergic reactions
White blood cells- basophils
> Like neutrophils and eosinophils, basophils are a granulocyte
They are called basophils as their granules react with the basic dye ‘haematoxylin’ which gives them a blue/purple colour
In normal healthy individuals they are relatively rare cells; 10,000-30,000 per ml blood
Similarly to eosinophils, basophils are implicated in the body’s response to large invading microorganisms and allergic reactions
White blood cells- monocytes
They are a unipotent progenitor cell- they migrate into tissues where they become a lineage committed leukocyte called a macrophage
White blood cells- B Lymphocytes
> B cells make antibodies
Between 50,000 and 300,000 B cells per ml blood
B cells can also present antigen in a similar manner to macrophages via MHCII so can also activate T cells
Blood cells- Platelets
> The correct nomenclature is thrombocyte
Between 150,000,000 and 400,000,000 platelets per ml of blood
They are a very small cell; 1-3up in diameter
Don’t have a nucleus
Formed from cytoplasmic budding from a much larger cell called a megakaryocyte
Stops bleeding
Megakaryocyte
> Each megakaryocyte can produce up to 4000 thrombocytes during its life time
Megakaryocytes aren’t typically found in blood
They produce their thrombocytes in bone marrow, which subsequently migrate into blood
Their presence in blood may be indicative of disease
Epithelial cells
> Epithelial cells are lining cells
They line the parts of the body that come into contact with an external environment
Clearly skin, but also the insides of lungs, bladder, GI tract…….
We’ve spoken about endothelial cells, which line blood (and also lymphatic) vessels
Endothelial cells are considered to be a specialised type of epithelial cell, specialised molecularly and physically to coordinate blood homeostasis
Epithelial cells are present in a wide range of anatomical locations so come in a range of shapes and organisations to allow them to carry out their roles more effectively
Epithelial cells are kept in place by adhesion to an underlying layer of proteins and glycoproteins, which act as a ‘underlay’
This underlay is called the basement membrane and is an integral part of all epithelial structures
Epithelial cells are polar
Their sides, tops and bottoms all have distinct roles, and therefore display expression of specific proteins which allow them to perform their function
Functions of epithelial cells
> Barrier/protection
-They provide a barrier from our internal tissues and the harsh external environment, preventing unregulated movement of microbes and macromolecules into our bodies from the outside world
Absorption
-Epithelial cells transport the substances we do need from the external environment into our bodies tissues, such as the epithelial cells that line the intestine for instance
Lubrication
-Epithelial cells secrete mucus and/or other fluids which minimise the sheer stress our internal tissues are subject to, either by external factors such as food moving down the oesophagus, or internal organs sliding over one another
Movement
-Some epithelial cells contain specialised structures called cilia which act like a conveyor belt to such as those in the trachea which move foreign particles and microbes away from the lungs
Epithelial cell junctions
> Epithelial Cells keep a tight ship, passage from the outside to the inside environment are tightly regulated
Passage can occur via two pathways; paracellular and transcellular
Epithelial cells need to tightly regulate the passage of substances from the lumen of a vessel to the tissue
The proteins that stick epithelial cells together in their lateral membranes are called tight junctions
Tight junctions control the passage of substances between cells
They are a complex mixture of proteins, the assembly of which is very tightly regulated
Tight junctions are probably the strongest cell/cell interaction in nature
The composition of the tight junctions can vary depending on anatomical area, making some membranes leakier than others
Epithelial Cells need to move substances across the large sheets that they form
Trafficking of substances between cells occurs using gap junctions
These junctions are about 1.5-2nm in diameter
This means they can allow passage of ions and small molecules up to a molecular weight of around 1000 Daltons
They are composed of proteins called connexins
Types of epithelial cells
> Simple: one cell thick
Stratified: layered
Cuboidal: square
Columnar: tall
Squamous: ‘scale like’/flattened
Pseudostratified: false layered
Transitional: changeable/dynamic
Simple squamous
> Simple squamous is the thinnest of all epithelia
Cells are flat and spread out, meaning they have a large surface area in contact with the exterior environment and the basement membrane
They are present in areas where easy transmembrane movement is advantageous
This could include the alveoli to support efficient gas exchange
And bowman’s capsule of the kidney to support rapid filtration of blood
Endothelium is a simple squamous epithelium which supports efficient movement of substances into and out of the blood
Simple squamous epithelium do not provide much protection from mechanical abrasion
Simple cuboidal
> Cuboidal epithelial cells are an intermediate between squamous and columnar epithelium
Simple cuboidal epithelia have an increased cytoplasmic volume to their squamous counterparts
This means they are capable of fulfilling some more complex roles such as secretion and can withstand more trauma
They are found in glands which specialise in secretion including salivary glands
And also in tissues that specialise in diffusion including the tubules of the kidney
They also line small ducts, such as the bile and pancreatic ducts
Simple cuboidal epithelium often form the lining of small ducts and glands
Simple columnar
> Cells are taller then they are wide
Cell nucleus is polarised towards the basement membrane
These cells are very capable of dealing with wear and tear and as such line fairly harsh internal environments including the stomach and intestines
In the stomach the mucus they secrete protects them from the harsh acidic external environment
Also capable of absorbing large quantities of material, again which explains their prevalence throughout lower GI tract
Stratified squamous
> Multi-layered epithelium in which the cells on the outermost layer are flat and scale-like (squamous)
Cells in the more basal layers may be cuboidal, or vary in shape more generally. Choose a name based on the appearance of the most apical layer
Only the initial layer of the cells is in contact with the basement membrane
Found in surfaces that are subject to high levels of mechanical abrasion
Cells on the top layers are continually replaced by those underneath, which become increasingly more specialised as they migrate up the strata from the base layer
Cells at the base of the layer are very mitotically active / regularly dividing
Two varieties of stratified squamous: Wet (non-keratinising) and Dry (keratinising)
Keratinising stratified squamous epithelium
> Keratinising epithelial cells produce a tough protein called keratin, these specialised epithelial cells are given the name keratinocytes
The top layer of keratinising epithelial cells are dead
This produces a dry surface, which protects underlying delicate tissues from external forces e.g. Skin
Non-keratinising stratified squamous epithelium cells
> Non-Keratinising epithelial cells occur in wet/moist environments where abrasion is likely
The top layer of keratinising epithelial cells are alive
This produces a moist surface, which protects underlying delicate tissues from external forces e.g. Oesophagus, inside of the mouth
Pseudostratified Columnar
> The presence of misaligned nuclei in this epithelium gives the impression it is stratified, but it is not
All of the cells in the layer are in touch with the basement membrane, meaning no stratification (where only the base layer would be in contact with the BM)
The cells are different heights, some of which do not reach the lumen of the organ they are lining, giving the impression of a multi-layered structure
Common in the upper respiratory system
Flexibility of a columnar cells allows the these cells to move with the ins and outs of breathing
Mucus secretion also helps trap microbes and foreign particles in the respiratory system
Transitional epithelium
> This is a stratified epithelium in which the shape of the cells at the luminal layer may be difficult to discern
This is because this epithelium changes shape to allow an organ or tube to increase in size and shrink
Cells may appear rounded/cuboidal when the organ is relaxed, and flattened /squamous when it is stretched
Common in the urinary tract (allows the bladder to increase/decrease in size as it fills with fluid)
Specialised epithelial cells
> Epithelial Cells are a diverse group of cells, found as part of organs all over the body
Therefore there functions may vary dependant on their anatomical location
As a result of this some epithelial cells have undergone a degree of modification to make them more adapted to their role
Ciliated epithelial cells
> Some epithelial cells contain hair like projections on their surface
These projections are called cilia
Each ciliated cell may have over 200 cilia
Ciliation is most commonly seen on columnar epithelial cells
Common in the respiratory tract where they move mucus laden with dust or microbes away from the lungs
And in the fallopian tubes where they move ova
Cilia move to help substances migrate across the epithelial layer
Epithelial cells with microvilli
> Some epithelial cells contain finger like protrusions on their surface
These projections are called microvilli
Not to be confused with Cilia, microvilli don’t move, and have the main role of absorption rather than locomotion
Microvilli are shorter and wider than cilia
Microvilli are often so tightly packed they give the appearance of a fuzzy band. In histology this is referred to as a brush boarder
The epithelium within the intestine is famous for its microvilli which increase the surface area for absorption of nutrients from the Gut lumen
Goblet cells
> Modified columnar epithelial cells
Synthesise & secrete mucous
Respiratory and gastrointestinal tracts
Named because their shape resembles that of a drinking goblet
What does connective tissue do?
> Transport
-Blood
Defence
-Immune cells move
through blood. Also
connective tissue provides
a medium for immune
cells to get inside a tissue
or organ to take on an
infection
Mechanics
-Connective tissue confers
the mechanical properties
a tissue needs to perform.
Bone – Hard, Cartilage –
Softer, Adipose – Really soft,
Blood - Liquid
Energy store
-Adipose (Fat) is a
connective tissue –
mechanical resistance and
protection + energy store
Connecting/linking
-Connective tissue provides
a means of joining
anatomical structures
together, and ensuring
they stay where they need
to be in the body
Connective tissue is the structural framework which holds tissue together
> Cells do not simply float about inside a tissue
They need a network of ‘scaffolding’ to keep them in place
This scaffolding is called the extracellular matrix (ECM)
The constituents of ECM
> Proteins
-The proteins of ECM
provide the scaffolding
material and tensile
strength
Carbohydrates
-Large sugar molecules
called glycosaminoclycans
associate with water and
form a gel which resists
compressive forces
-Glycosaminoglycans and
proteins often interact in
ECM to form large
branched structures called
proteoglycans
Water
-In addition to contributing
to the mechanical
properties of the tissue
provides a soluble
signalling medium
Connective tissue
> The space occupied by the glycosaminoclycan/proteoglycan/water component of ECM is called ground substance
Generally this is appears as transparent space in histological sections as it does not survive the harsh processing of fixation and embedding
It’s properties can vary hugely depending on the tissue that it is found
For example:
-Blood:
Completely liquid (in blood the ground substance is plasma)
-Cartilage:
Spongy, Gel like, Shock Absorbing
* The cells of connective tissue can be either:
-Resident:
>Cells which are permanently based inside the connective tissue and generally produce the matrix that forms it, e.g. fibroblasts
-Wandering/Migratory/Transient
>These cells move through connective tissue either to fulfil a role within it, or on their way to somewhere else, e.g. neutrophils, lymphocytes
The fibroblast
> Fibroblasts are THE ULTIMATE connective tissue cell
Secrete a wide range of fibres and ground substance
Collagen producing machines, secrete large amounts of tropocollagen
Very important in wound healing and tissue regeneration; matrix reconstruction after injury
Often spindle shaped/elongated, but due to the dynamic nature of these cells and their roles in different tissues, they can appear a diverse range of shapes
Very easy to grow in vitro
The fibre component of connective tissue is largely made up of three types:
> Collagen fibres
Elastic fibres
Reticular fibres
Collagen
> Collagen is the most abundant protein in mammals
About 25% of all protein in the body is collagen
It helps tissues resist tensile stress (being pulled apart). It is estimated that a collagen fibre 1mm in diameter can suspend a 10Kg weight
Fibroblast cells are collagen secreting machines!!! (made in other cells too)
Produced inside cells although secreted before final production is finished
Leaves the cell in a precursor form called tropocollagen. This polymerises outside of the cell to form mature collagen fibrils
Synthesis in this way prevents cells becoming filled with huge mature collagen molecules
Collagen assembly
- Hydroxylation of Pro and Lys residues; assembly of triple helix in endoplasmic reticulum
- Packaging in Golgi and secretion
- Cleavage of N- and C- terminal non helical segments
- Cross- linking at lysine and hydroxylysine residues and assembly into fibrils
- Aggregation of fibrils into collagen fibres
Types of collagen
> There are several types of collagen which differ slightly in their structures and subsequent function
There are 28 different types of collagen
These are usually denoted like this Collagen I, Collagen II, Collagen III, Collagen IV etc.
Most collagen is type I, II or III
Collagen types and their tissue location
Type I- Bone, skin, dentin
Type II- Cartilage
Type III- Scars, Blood vessels
Type IV- basement membranes
Type V- Smooth muscle
Type VIII- Cornea
Type X- Hypertrophic cartilage
Elasticity and flexibility
> Collagen fibres give the ECM great tensile strength but are not well suited to elasticity and flexibility required by some tissues.
-Lung
-Heart
-arteries
Elastic fibres
> Formed in fibroblasts as tropoelastin
Once secreted it polymerises & X-links are formed
Composed of a, fibrillin plus elastin
Fibres may be branched (skin, lungs) or form flat sheets (arteries)
Elastin fibres
> Elastin fibres change organisation based to achieve optimal elasticity in the tissue they are found in
Reticular fibres
> Reticular fibres are a type of fine collagen; type III collagen
They form a meshwork structure called reticulin
Meshwork structure is random
Fibres are around 2μm in diameter, which are made up by several fibrils 20-40nm in diameter
Connective tissues
> Connective tissue can be classified into different types based on the proportion of cells, ground substance and fibres in addition to the conformation of the fibres
Dense connective tissue Contains a relatively high proportion of fibres and smaller amounts of ground substance
Loose connective tissue Contains a higher proportion of ground substance and smaller proportion of fibres
Dense connective tissue can also be described as dense regular connective tissue
Fibres are aligned relative to one another
Dense irregular connective tissue
No obvious fibre orientation exists
Loose connective tissue
> Loose connective tissue can be further categorised into three types:
-Areolar Connective Tissue
-Adipose Connective Tissue
-Reticular Connective
Tissue
Areolar connective tissue
> The most abundant connective tissue in the body
A mixture of fibre types (collagen generally predominates)
No easily identifiable structure or conformation
Fibroblasts are the predominant cell type
Substances can move easily from cell to cell and from the blood vessels
Found throughout the body, common beneath epithelial layers and surrounding blood vessels
Adipose connective tissue
> Contains a particular type of connective tissue cell called adipocytes (fat stores)
May appear fairly homogenous or may be interspersed in other tissue such as muscle
Adipose is the body’s main energy store
Also provides a layer of insulation and acts to protect internal structures within the body from external impacts
Reticular connective tissue
> Similar in appearance to areolar connective tissue
Made up of short, branched collagen fibres composed of type III collagen
Found in lymphoid tissues such as lymph nodes, thymus, tonsils, spleen, bone marrow and liver.
Difficult to visualise with ‘conventional’ histologic stains, so special techniques are used
Dense regular connective tissue
> Extremely strong
Most of the tissue space is occupied by fibres
Fewer cells than loose connective tissue
Fewer types of cells, with fibroblasts predominating
The direction of fibre alignment of collagen fibres is typically parallel to the direction of force which is placed upon it
Great at resisting tensile strength in one direction
Common in tendons and ligaments
Dense irregular connective tissue
> Also very strong
Found where resistance to tensile strength is required, but may not be applied from a single direction
Like regular dense connective tissue fibroblasts are the predominating cell
Contains densely packed Collagen fibres that are randomly aligned to form a meshwork
Common in the lower layers of skin (dermis)
Specialised connective tissue
> Cartilage
Bone
Blood
Cartilage
> Atypical connective tissue as it is avascular (does not contain any blood vessels). Not very good at repairing itself.
The resident cells within cartilage are called Chondrocytes
Typically chondrocytes produce type II Collagen
Cartilage is often coated in a film of dense irregular connective tissue called perichondrium
More rigid then muscle, less rigid than bone
Cartilage can be categorised into one of three types:
-Hyaline cartilage
-Elastic cartilage
-Fibrocartilage
Hyaline cartilage
> Colourless, transparent or ‘glassy’. Hyalos is Greek for glassy.
Often found in joints where it protects from bone-on-bone friction
When present on ‘articulating’ surface of bone like joints, it is referred to as ‘articular cartilage’
Found in other places including the trachea, nose, larynx and between the ribs and sternum
Chondrocytes produce collagen and ground substance
Collagen fibres are thin, and have similar optical properties to the ground substance, so are difficult to resolve with light microscopy
Chondrocyte cells
> Chondrocyte cells live in spaces within the cartilage matrix called lacunae
Relatively abundance of glycosaminoglycans in hyaline cartilage matrix gives it its slippery properties
Elastic cartilage
> Elastic cartilage contains some collagen but also an abundance of Elastic Fibres
The tissue has the ability to withstand repeated deformation and return to its original shape
Like hyaline cartilage, the resident cells are chondrocytes
Found in the tissue which forms the lobe of the ear, and also the epiglottis
Fibrocartilage
> Toughest type of cartilage- useful at resisting compressive forces
Found in the intervertebral disk
Contains densely packed collagen fibres which may include type I
An intermediate between dense connective tissue and cartilage and can be difficult to distinguish
Chondrocytes may be spotted in distinct rows, they are also a characteristically ‘round’ and still occur in lacunae
Bone
> Bones themselves are organs containing bone tissue and other structures such as blood vessels, nerves and marrow
There are two types of bone tissue:
-Cortical Bone Tissue
>Hard, compact exterior
of bone
-Cancellous/Trabecular
Bone Tissue
>Spongy, porous interior
of bone
The cells which produce bone are called Osteoblasts
The rounded end section of a long bone is called the Epiphysis
The long section between the Epiphyses is called the Diaphysis
Bone is lined on the outside by a layer of dense irregular connective tissue called periosteum
Osteoblasts produce type I Collagen
About 70% of bone by weight is hydroxyapatite
They also produce a calcium and phosphate containing mineral called hydroxyapatite.
This precipitates onto the collagen matrix to give it it’s strength
Cortical bone
> Also referred to as compact bone
Makes up about 75% of the weight of the skeleton
It is made up of smaller subunits of bone called Osteons
An osteon is a series of concentric rings of calcified extracellular matrix containing cells called osteocytes
Through the middle of each osteon runs a canal called the Haversian canal
The Haversian canal contains the bones blood and nerve supply
Like cartilage, the pockets in tissue in which the osteocytes live are called lacunae
Trabecular bone
> Also referred to as cancellous bone
The lattice work series of struts/rods which forms the architecture of this sort of bone are called trabeculae
Trabeculae give the interior of bone a very high surface area
Much greater vascularity than compact bone
Houses the bone marrow, which is the main source of blood cell formation in the body
Greater porosity than cortical bone (porosity between 50-90%)
Makes up about 20% of the total bone weight of an adult human
Muscle tissue
> There are three types of muscle tissue:
-Skeletal muscle
-Smooth muscle
-Cardiac muscle
The cells of muscle are called myocytes
Skeletal muscle (voluntary)
> Bring about movement of bones, hence the term skeletal muscle
Made up of large cells with multiple nuclei
The cytoplasm (sarcoplasm) of muscle tissue contains 2 important proteins; Actin and Myosin, which work together in muscle contraction and relaxation
The arrangement of these proteins in skeletal muscle in repeated subunits parallel to the direction of force, gives the muscle a lined appearance (striated)
The membrane of skeletal muscle cells has a specialised name too; the sarcolemma
Skeletal muscle cells are multinuclear
Nuclei are peripheral
Smooth muscle
> Involuntary muscle, under the control of the autonomic nervous system
Forms the inside of hollow organs such as bladder, blood vessels and the GI tract, respiratory tract, uterus……
Cells are spindle shaped, and may be easily be mistaken for fibroblasts in some tissue sections
It has no striations as the Actin and Myosin are arranged less predictably in the cell cytoplasm; hence the designation of ‘smooth’
Cardiac muscle
> Found exclusively in the walls of the heart
Striated like skeletal muscle
One or two nuclei
Nuclei are central, not peripheral
Cells arranged in a branched, tubular structure, held together by areolar connective tissue
The cell/cell junctions in cardiac muscle are referred to as intercalated disks which may be visible in histological sections
