Ultrastructure of Nerves

The nervous system allows us to perceive, understand, and respond to our environment. It comprises two different types of cells:

Nerve cells (neurones) – these form the functional basis of the nervous system, responsible for transmitting signals as electrical or chemical signals.

Glial cells – these provide functional and structural support for the neurones. One example is a Schwann cell, which produces the lipid sheath of peripheral neurones.

In this article, we will focus on the ultrastructure of nerves. We will look at the general structure of nerves, their layers of connective tissue and finish by considering some conditions that arise when the normal structure is lost.

Neuronal Structure

There are several different types of neurones found in the nervous system. They all contain the same key structural components – the cell body, dendrites, the axon and the axon terminals.

Cell Body

The cell body holds the nucleus. It is the site of protein synthesis, which occurs on small granules of rough endoplasmic reticulum called nissl substance.

In the nervous system, many neuronal cell bodies can group together to form a distinct structure. In the CNS, this is known as a nucleus, and in the PNS as a ganglion.

Dendrites

The dendrites are elongated portions of the cell body. They extend outwards, receiving input from the environment and from other neurones.

Axons

The axon is a long, thin structure down which action potentials (the nerve impulse) are conducted. Whilst neurones have many dendrites, most cells only have one axon.

Each axon is coated in myelin – a layer of insulating lipid. Myelin is formed by cells wrapping themselves around the nerve axon. In the CNS, this is performed by oligodendrocyte cells. In the PNS, Schwann cells are responsible for this action.

There are gaps between the myelin sheaths formed by different cells. These gaps are known as nodes of Ranvier. They allow for saltatory conduction of impulses.

Axon Terminals

The axon terminal is the most distal part of the axon. It is from here that the neurone sends chemical signals to other cells – usually via neurotransmitter release. To facilitate the secretion of neurotransmitters, the axon terminals contain a large number of mitochondria.

Fig 1.0 – The components of a typical neurone.

Coverings

Fig 1.1 – Connective tissue layers of a nerve cell.

In the peripheral nervous system, the axons of neurons are grouped together to form nerves. The axons are enclosed by several connective tissue layers:

Endoneurium – Surrounds the axon of an individual neurone.

Perineurium – Surrounds a fascicle, which is a collection of neurones.

Epineurium – Surrounds the entire nerve, which is formed by a collection of fascicles. It contains numerous small blood vessels, which supply the nerve fibres. Epineurium appears on the nerve as it exits the intervertebral foramen. It is created by the fusion of arachnoid and pia mater, which are layers of the meninges.

Classification

Neurones can be classified by structure or by function. Neurones with different functions have differing structures, which is visible histologically.

Structural Classification

Fig 1.2 - Structural classification of neurones.

Neurones can be either unipolar, pseudounipolar, bipolar or multipolar.

Unipolar – Here the cell body is at one end of a single unbranched axon, and there are no dendrites. These can be found in the cochlear nucleus of the brain.

Pseudounipolar – They have one axon which is divided into two branches by the presence of the cell body. Sensory neurones are all pseudounipolar.

Bipolar – These neurones have two processes arising from a central cell body – typically one axon and one dendrite. These cells are found in the retina.

Multipolar – They have one axon and many dendrites, with a cell body displaced to one side of the axon. Motor neurones are a prime example of this.

Functional Classification

There are three broad functional classifications of nerves – sensory (afferent), intermediate and motor (efferent). There are key structural differences between these three types:

Sensory nerves – small axons and psuedounipolar structure.

Motor nerves – larger axons and multipolar structure.

Intermediate neurones – central cell body and many dendrites.

Sensory and motor nerves are located within the PNS, whereas intermediate nerves are found in the CNS.

Clinical Relevance: Disorders of Nerve Tissue

Multiple Sclerosis

Fig 1.3 - Photomicrograph of ademyelinating MS-Lesion.

In multiple sclerosis, the myelin covering of neurones in the central nervous system is lost. This means that the relay of action potentials between sensory and motor neurones is affected. This can lead to visual, motor and auditory problems.

The etiology of Multiple Sclerosis (MS) is still uncertain. However, the causes are thought to either be as a result of autoimmune destruction of myelin, or the failure of oligodendrocytes to myelinate the interneurons.

Motor Neurone Disease

Motor Neurone Disease describes a group of conditions that include Amyotrophic lateral sclerosis, better known as ALS. In these diseases, motor neurones become damaged for reasons that are not entirely clear, but are thought to include dysfunctional mitochondria.

The damage to the motor neurones is progressive, making this a degenerative disease. It often begins with damage to peripheral nerves, and works its way up through the limbs until the central nervous system is compromised. This disease is fatal, with a median survival length of 3-5 years post diagnosis.

Ultrastructure of Blood Vessels

The average man has approximately six litres of blood in his body. This blood is carried by several different types of blood vessels, each of which are specialised to play their role in circulating blood around the body.

There are three major types of vessels; arteries, veins and capillaries. Arteries (with the exception of the pulmonary artery) deliver oxygenated blood to the tissues. At the tissues, the oxygen and nutrient exchange is carried out by the capillaries.

 The capillaries also return deoxygenated blood to the veins, which bring it back to the heart (with the exception of the pulmonary veins).

In this article, we shall follow the path that blood takes around the body, examining the structure and function of the major types of blood vessels.

Vessel walls can largely be split into three sections; tunica intima (innermost), tunica media, and tunica adventitia. Each must be considered.

The Arterial System

As a whole, the arterial system takes oxygenated blood from the heart, and delivers it to the capillaries, where oxygen and nutrient exchange can occur.

There are four main types of artery in the body, each with a distinct structure and function. 

We shall look at each in more detail (in order of decreasing size).

Large Elastic (Conducting) Arteries

These are the largest arteries found in the body, and are found closest to the heart. They function to ‘conduct’ blood from the heart to regions of the body, where it can be distributed.

Elastic arteries include most of the named vessels surrounding the heart, such as the aorta and pulmonary arteries.

Tunica Intima: Endothelial cells with a thin subendothelium of connective tissue and discontinuous elastic laminae.

Tunica Media: The tunica media is comprised of 40-70 fenestrated elastic membranes with smooth muscle cells and collagen between these lamellae. It is the thickest part of an elastic artery.

Tunica Adventitia: Thin layer of connective

 tissue containing minor vasa vasorum, lymphatics and nerve fibres.

Medium Muscular (Distributing) Arteries

From the large elastic arteries, blood enters smaller distributing arteries. 

They distribute the blood to sub-regions of the body.

Medium muscular arteries are similar in structure to large elastic arteries.

Tunica Intima: Consists of an endothelium, a subendothelial layer and a thick elastic lamina.

Tunica Media: Consists of around 40 layers of smooth muscle connected by gap junctions in order to allow coordinated contraction.

Tunica Adventitia: Thin layer of connective tissue containing minor vasa vasorum, lymphatics and nerve fibres.

Arterioles

Arterioles are part of the microcirculation. They carry blood from the muscular arteries to the metarterioles.

Structure:

Arteries with a diameter of less than 0.1mm are classed as arterioles. They generally have around 3 layers of smooth muscle cells and the internal elastic lamina is absent. The external elastic lamina is only present in larger arterioles.

Metarterioles

Arteries that supply capillary beds are known as metarterioles.

Instead of having a continuous layer of smooth muscle cells, intermediate rings of smooth muscle are located at certain points. These rings are known as known as precapillary sphincters, which contract to control blood flow to the capillary bed.

Clinical Relevance: 

Precapillary Sphincters Precapillary sphincters are very important in the control of tissue perfusion. When the body performs certain actions, these structures are able to restrict blood flow to certain regions and encourage it to others.

For example, when running, skeletal muscle requires a lot more blood than it usually would. In order to accommodate for this, precapillary sphincters in skeletal muscle relax in order to increase blood flow

The Capillaries

Capillaries consist of one layer of endothelium and its concordant basement membrane.

They are specially adapted to provide a short diffusion distance for nutrient and gaseous exchange with the tissues they supply.

There are three types of capillaries; continuous, fenestrated and sinusoidal, each of which have variably sized gaps between the endothelial cells.

These gaps act as a sieve, controlling which molecules and structures can leave the capillary. For example, in continuous capillaries (located in skeletal muscle), only water and certain ions can leave. In sinusoidal capillaries (located in the liver), larger structures such as cells and proteins are able to exit.

The Venous System

As a whole, the venous system takes deoxygenated blood from the capillaries, and delivers it to the heart (with the exception of the pulmonary veins). From the heart, blood can be pumped to the lungs and re-oxygenated.

Like the arterial system, the venous system is comprised of different vessel structures. We shall look at each in more detail (in order of ascending size, as we move away from the capillaries).

Postcapillary Venules

A postcapillary venule receives blood from capillaries and empties into venules. In addition, the surrounding tissue fluid tends to drain into them, as their pressure is lower than that of capillaries or the tissue.

Structure:

The wall is an endothelial lining with associated pericytes and a diameter of 10-30 micrometres. This is similar to the structure of capillaries, but postcapillary venules are more permeable, making them the preferred site of white blood cell migration (e.g. to sites of infection).

Clinical Relevance: Inflammation and Postcapillary Venules

During inflammation pressure in the venules actually becomes higher than that of the surrounding interstitium. This allows fluid to leak into the site of inflammation along with inflammatory cytokines and white blood cells.

Venules

Venules are continuous with the post-capillary venules. They continue to move blood away from the capillary beds. Many venules unite to form a vein.

Structure:

The endothelium is associated with pericytes or thin smooth muscle cells (the beginning of a tunica media) to form a very thin wall. Venules can have a diameter of up to 1mm. They also contain valves that press together to restrict retrograde transport of blood.

Veins

Veins are the major vessels of the venous system. They are the final step in the return of blood to the heart.

Structure:

Veins generally have a larger diameter and a thinner wall than the accompanying artery. The vessel wall contains more connective tissue, with less elastic and muscle fibres.

Veins vary slightly in structure according to their size:

Small and medium veins have a well developed tunica adventitia and a thin tunica intima and media.

Large veins have diameters greater than 10mm and a thicker tunica intima. They have well developed longitudinal smooth muscle in the tunica adventitia. The media has circular smooth muscle, which is usually not prominent, except for the superficial veins of the legs.

Veins contain valves that primarily prevent the back-flow of blood. They also act together with muscle contraction, squeezing the veins to propel blood towards the heart.

Fig 3 – Structure of a vein wall.

Venae Comitantes

Venae comitantes are deep paired veins wrapped together with an artery in one sheath. The pulsations of the artery promote venous return within the paired veins.

Ultrastructure of Bone

Bone is a specialised type of connective tissue. It has a unique histological appearance, which enables it to carry out its numerous functions:

Haematopoiesis – the formation of blood cells from haematopoietic stem cells found in the bone marrow.

Lipid and mineral storage – bone is a reservoir holding adipose tissue within the bone marrow and calcium within the hydroxyapatite crystals.

Support – bones form the framework and shape of the body.

Protection – especially the axial skeleton which surrounds the major organs of the body.

In this article, we shall look at the ultrastructure of bone – its components, structure and development. We shall also examine how disease can affect its structure.

Protection – especially the axial skeleton which surrounds the major organs of the body.

In this article, we shall look at the ultrastructure of bone – its components, structure and development. We shall also examine how disease can affect its structure. 

Components of Bone

Bone is a specialised form of connective tissue. Like any connective tissue, its components can be divided into cellular components and the extracellular matrix.

Cellular Components

There are three types of cells in bone:

Osteoblasts – Synthesise uncalcified/unmineralised extracellular matrix called osteoid. This will later become calcified/mineralised to form bone.

Osteocytes – As the osteoid mineralises, the osteoblasts become entombed between lamellae in lacunae where they mature into osteocytes. They then monitor the minerals and proteins to regulate bone mass.

Osteoclasts

– Derived from monocytes and resorb bone by releasing H+

ions and lysosomal enzymes.

They are large and multinucleated cells.

The balance of osteoblast to osteoclast activity is crucial in the maintenance of the tissue’s structural integrity. 

It also plays a role in conditions such as osteoporosis.

Extracellular Matrix

The extracellular matrix (ECM) refers to the molecules that provide biochemical and structural support to the cells.

The ECM of bone is highly specialised.

 In addition to collagen and the associated proteins usually found in connective tissue, bone is impregnated with mineral salts, in particular calcium hydroxyapatite crystals. These crystals associate with the collagen fibres, making bone hard and strong. 

This matrix is organised into numerous thin layers, known as lamellae.

Fig 1 – Cellular components of bone and their functions.

Structure of Bone

Under the microscope, bone can be divided into two types:

Woven bone (primary bone) – Appears in embryonic development and fracture repair, as it can be laid down rapidly. It consists of osteoid (unmineralised ECM), with the collagen fibres arranged randomly. It is a temporary structure, soon replaced by mature lamellar bone.

Lamellar bone (secondary bone) – The bone of the adult skeleton. It consists of highly organised sheets of mineralised osteoid. This organised structure makes it much stronger than woven bone. Lamella bone itself can be divided into two types – compact and spongy.

In both types of bone, the external surface is covered by a layer of connective tissue, known as the periosteum. A similar layer, the endosteum lines the cavities within bone (such as the medullary canal, Volkmann’s canal and spongy bone spaces).

Lamellar bone can be divided into two types. The outer is known as compact bone – this is dense and rigid. The inner layers of bone are marked by many interconnecting cavities and is called spongy bone.

Compact Bone

Compact bone forms the outer ‘shell’ of bone. In this type of bone, the lamellae are organised into concentric circles, which surround a vertical Haversian canal (which transmits small neurovascular and lymphatic vessels). This entire structure is called an osteon and is the functional unit of bone.

The Haversian canals are connected by horizontal Volkmann’s canals – these contain small vessels that anastomose (join) with the arteries of the Haversian canals. The Volkmann’s canals also transmit blood vessels from the periosteum.

Osteocytes are located between the lamellae, within small cavities (known as lacunae). The lacunae are interconnected by a series of interconnecting tunnels, called canaliculi.

Spongy Bone

Spongy bone makes up the interior of most bones and is located deep to the compact bone. It contains many large spaces – this gives it a honeycombed appearance.

The bony matrix consists of a 3D network of fine columns, which crosslink to form irregular trabeculae. This produces a light, porous bone, that is strong against multidirectional lines of force. The lightness afforded to spongy bone is crucial in allowing the body to move. If the only type of bone was compact, they would be too heavy to mobilise.

The spaces between trabeculae are often filled with bone marrow. Yellow bone marrow contains adipocytes and red bone marrow consists of haematopoietic stem cells.

This type of bone does not contain any Volkmann’s or Haversian canals

Ossification and Remodelling

Ossification is the process of producing new bone. It occurs via one of two mechanisms:

Endochondral ossification – Where hyaline cartilage is replaced by osteoblasts secreting osteoid. The femur is an example of a bone that undergoes endochondral ossification.

Intramembranous ossification – Where mesenchymal (embryonic) tissue is condensed into bone. This type of ossification forms flat bones such as the temporal bone and the scapula.

In both mechanisms, primary bone is initially produced. It is later replaced by mature secondary bone.

Remodelling

Bone is a living tissue and as such constantly undergoes remodelling. This is the process whereby mature bone tissue is reabsorbed, and new bone tissue is formed. It is carried out by the cellular component of bone.

Osteoclasts break down bone via a cutting cone. The nutrients are reabsorbed, and osteoblasts lay down new osteoid. Remodelling occurs primarily at sites of stress and damage, strengthening the areas affected

Clinical Relevance – Disorders of Bone

Bone has a unique histological structure, which is required for it to carry out its functions. Alterations to this structure, secondary to disease, can give rise to several clinical conditions.

Osteogenesis imperfecta is a condition in which there is abnormal synthesis of collagen from the osteoblasts. Clinical features include fragile bones, bone deformities and blue sclera. It is a rare disease and genetic in aetiology, with an autosomal dominant inheritance pattern. The fragility of the bones predisposes them to fracture – this has a medicolegal importance, as in children it can be mistaken for deliberate injury.

Osteoporosis refers to a decrease in bone density, reducing its structural integrity. This is produced by osteoclast activity (bone reabsorption) outweighing osteoblast activity (bone production). The bones are fragile, and at an increased risk of fracture. There are three types:

Type 1: Postmenopausal osteoporosis – Develops in women after the menopause, due to decreased oestrogen production. Oestrogen protects against osteoporosis by increasing osteoblast and decreasing osteoclast activity.

Type 2: Senile osteoporosis – Usually occurs above the age of 70.

Type 3: Secondary osteoporosis – Where osteoporosis occurs due to co-existing disease (e.g. chronic renal failure).

Risk factors include age, gender, diet (vitamin D and calcium), ethnicity, smoking and immobility. It is usually managed by bisphosphonates which are taken up by osteoclasts causing them to become inactive and undergo apoptosis. This limits further degradation of bone

Rickets is Vitamin D or calcium deficiency in children with growing bones. This means that the osteoid mineralises poorly and remains pliable. The epiphyseal growth plates can then become distorted under the weight of the body, potentially leading to skeletal deformities.

Osteomalacia is a Vitamin D or calcium deficiency in adults with remodelling bones. Here the osteoid laid down by osteoblasts is poorly mineralised leading to increasingly weak bones, increasing their susceptibility to fracture.

Note: Vitamin D deficiency can be due to poor diet, lack of sunlight or a metabolic disorder. For example, kidney failure could interfere with the second hydroxylation of vitamin D or an intestinal disorder may prevent sufficient absorption. A calcium deficiency can be caused by diet or low vit. D.