Respiratory System and Cardiovascular System Histology PDF

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Respiratory System and Cardiovascular System HistologyRespiratory SystemFunctions of the Respiratory System:  Supply oxygen to the blood for delivery to cells throughout the body  Removes carbon dioxide that has been accumulated (via metabolism) in the blood from the tissues of the body  Phonatio...

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Respiratory System and Cardiovascular System Histology Respiratory System Functions of the Respiratory System:  Supply oxygen to the blood for delivery to cells throughout the body  Removes carbon dioxide that has been accumulated (via metabolism) in the blood from the tissues of the body  Phonation – speaking  Olfaction – smelling  Lungs function – blood pressure control via renin-angiotensin system (angiotensin I > angiotensin II via angiotensin-converting enzyme (ACE) in lung capillaries). Anatomy of the Respiratory System Air flows through a series of conducting passageways that branch. Air enters the nose/mouth travels via the pharynx  larynx  trachea which branches into  principal bronchi to convey the air to  lungs. In the lung each bronchus  smaller bronchi  smaller bronchioles. These bronchioles terminate in the alveolar sacs where gas exchange occurs. The Nasal Cavity (1) The nasal cavity provides an extensive area for:  Warming inspired air  Moistening inspired air  Filtering inspired air (nasal hairs) Also, in the roof it contains an area of specialised olfactory epithelium. Lining of the Nasal Cavity (1) The initial part of the nasal cavity is the vestibule (2-3cm), and it is lined by keratinised stratified squamous epithelium. Deeper into the nasal cavity, the keratin is lost, and the nasal cavity is lined with (non- keratinised) stratified squamous epithelium. Deeper still the lining changes to the epithelium that lines nearly all of the rest of the conducting part of the respiratory system: pseudostratified ciliated columnar epithelium with goblet cells, or respiratory epithelium. Respiratory Epithelium Respiratory epithelium is made up of: 1. Pseudostratified columnar epithelium ciliated with goblet cells (respiratory epithelium) 2. Goblet Cell 3. Basal Cell (stem cell) 4. Cilia 5. Submucosa Goblet cells produce mucus-y fluid which floats on a thin layer of serous tissue fluid above the cilia. The cilia beat in one direction very fast and slowly back in the opposite direction, the net effect of this is to move the mucus across the surface. The fast stroke is directed up towards the pharynx. This current/mechanism is called the mucociliary rejection, any trapped particles in the mucus gets wafted upward to the pharynx where it can be swallowed in order to remove particulate material from the respiratory tract.

Scanning electron micrograph looking down at the surface of respiratory epithelium. Notice the many cilia projecting above the surface and the rounded goblet cells (G).

The Nasal Cavity (2) Stratified squamous epithelium in the anterior portion of the vestibule (partially keratinised, partially non-keratinised). Olfactory mucosa epithelium at the very apex of the nasal cavity but the rest is respiratory epithelium, as is nasal pharynx. Oropharynx (cavity experiencing passage of food) has stratified squamous epithelium which extends down into the oesophagus. The opening to the larynx has respiratory epithelium, continues down essentially to the alveoli. (Epithelium gets shorter as we make that journey) – one exception is the vocal fold in the larynx.

Lining of the Nasal Cavity (2) Underneath the respiratory epithelium (RE) is the lamina propria, a band of connective tissue containing seromucous glands (M and S) and a rich venous plexus (V) which can quickly engorge with blood and ‘block’ the nose. The Oropharynx and Epiglottis The oropharynx transmits both air and swallowed food, so it must resist abrasion. Its lined by non-keratinized stratified squamous epithelium, as is the anterior (lingual) surface and upper part of the posterior surface of the epiglottis. The posterior (respiratory) surface of the epiglottis is largely covered by respiratory epithelium. Elastic cartilage allows the epiglottis to be a very flexible structure.

The Larynx The walls are made up of cartilage and muscles with respiratory epithelium lining its inner surfaces (with the exception of the vocal folds and adjacent structures which are covered with stratified squamous epithelium). Has cricoid cartilage that goes all round the airway. Vocal folds are not covered in respiratory epithelium as it would mean they wouldn’t stand up to the abusive movement . Section through the larynx.

The Trachea The trachea is continuous with the larynx and terminates by dividing into the main bronchi. It contains 15-20 ‘C’ shaped cartilages, the open side of the ‘C’ of the cartilage is spanned by fibroelastic tissue and smooth muscle (trachealis muscle). The wall of the trachea is lined by respiratory epithelium, backed by a basal lamina, lamina propria of connective tissue with abundant elastic fibres and a submucosa of loose connective tissue that includes numerous seromucous glands. Ducts take mucus secretion up to the surface to supplement to the product of the goblet cells.

Bronchi The trachea divides into two primary bronchi which divide further within the lung. The ‘plates’ of hyaline cartilage are replaced by irregularly shaped cartilage plates. The wall of the bronchus is made up of respiratory epithelium (RE), a lamina propria (LP), a muscularis consisting of a ring of smooth muscle and a submucosa (SM) with adipose tissue and some seromucous glands. The epithelium gets shorter as you go down the airway from the trachea  bronchioles.

The Bronchial Tree As bronchi branch and become smaller the cartilage becomes more discontinuous, its finally lost when the airway is about 1mm in diameter. These smaller airways lacking cartilage are called bronchioles. First part of the airway is referred to as the conducting airway, that extends down to where we enter the respiratory bronchioles. Then this is the portion involved in gas exchange. How do the cells of the wall of the conducting airways obtain O2, nutrients, etc.? The diffusion distance to the bronchi is too large for them to receive oxygen, deoxygenated blood from the right heart (pulmonary artery) is delivered to the lungs. They are always supplied with oxygen and nutrients as there is a small left blood supply to the lungs, to the bronchial arteries. Bronchioles Bronchioles are less than 1mm in diameter and lack cartilage and glands but may contain a few goblet cells in their initial portion. The epithelium decreases in height from columnar to cuboidal as you progress down the respiratory tree to the smallest bronchioles. The lamina propria is composed of smooth muscle and elastic and collagenous fibres. The smallest bronchioles that lack respiratory function (gas exchange) are referred to as terminal bronchioles and these branch smaller to give rise to the first part of the respiratory tree that has respiratory function, the respiratory bronchioles. Respiratory bronchioles have a cuboidal epithelium but the walls are interrupted by alveoli. The smooth muscle (SM) of the bronchioles respond to parasympathetic innervation, histamine and other factors by contracting and constricting the diameter of the bronchiole. This mechanism plays a significant role in asthma attacks and allergic reactions. Terminal and Respiratory Bronchioles Terminal Bronchioles are lined with cuboidal ciliated epithelium and contain non-ciliated club cells that project above the level of adjacent ciliated cells. Club cells have several roles:  Act as stem cells  Have enzymes that can detoxify certain chemicals (detoxification)  Immune modulatory  Surfactant production Alveoli interrupt the continuity of the respiratory bronchioles and the low cuboidal epithelium is replaced by discontinuous squamous type I alveolar cells. Conducting vs Respiratory Airways The conducting portion of the airways extends from trachea to the terminal bronchioles. No exchange of oxygen/CO2 with blood occurs in these airways. The respiratory bronchioles are the beginning of the respiratory portion of the airways. Gas exchange does occur in the alveoli, which are found associated with respiratory bronchioles, alveolar ducts and alveolar sacs. Alveoli

The alveoli are the terminal portions of the bronchial tree and are responsible for the spongy nature of the lungs. They resemble thin-walled pockets similar to a honeycomb. Within them oxygen and CO2 are exchanged. There are about 300 million alveoli in each lung. The alveoli are lined by an epithelium that consists of two cell types:  Type I alveolar cells (type I pneumocytes) – gas exchange barrier.  Type II alveolar cells (type II pneumocytes) – surfactant production. Type I cells: simple squamous epithelium that lines the alveolar surfaces covering over 90% of the alveolar surface, permeated with vasculature (capillaries). These cells provide a barrier of minimal thickness that is permeable to gases. Type II cells: polygonal in shape, the free surface is covered by microvilli and the cytoplasm displays dense membrane bound lamellar bodies which contain surfactant. The surfactant is released by exocytosis and spreads over the pulmonary surface to reduce the surface tension at the air-fluid interface. This reduces the tendency for the alveoli to collapse at the end of expiration. The problem is that type II pneumocytes are one of the last cells to form during foetal development (not using lungs, don’t need alveoli to open), meaning that premature infants lack of surfactant in their lungs. Difficult to get their lungs inflated, as their lungs subsequently collapse easily. Lamellar bodies in the type II pneumocyte secrete the surfactant. Also the

present in the alveoli are alveolar macrophages (dust cells): free cells either in septa or migrating over the luminal surfaces of the alveoli, phagocytosing inhaled particles that may have escaped entrapment by the mucous lining of the airway. They typically migrate up the bronchial tree, transported by ciliary action, to the pharynx where they are swallowed or will move into the septal connective tissue where they will remain.

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Alveolar Wall: The Air-Blood Barrier Note that the septa between alveoli are permeated by capillary networks, indicated here by the arrows. The thin tissue is at these points between air and blood – this is referred to as the air-blood barrier. The air- blood barrier consists of the Type I cell, the endothelial cell and the basal lamina of each (cytoplasm->basal lamina->cytoplasm). It can be as thin as 200-600nm (0.2-0.6µm).

Visceral Pleura The lung is surrounded by a visceral pleura that is multilayered. There is an outer layer of simple squamous epithelium called mesothelium backed by layers of fibrous and elastic connective tissue. This would face the parietal pleura which is a similar but generally simpler membrane lining the thoracic cavity. Between the two would be a pleural cavity containing a small amount of lubricating fluid.

Cardiovascular System Roles of the Cardiovascular System The circulatory system consists of two related systems:

1. 2.

The cardiovascular system (blood vascular system) – Closed system consisting of the heart, arteries, capillaries and veins The lymphatic vascular system – Open system of lymphatic vessels present to drain excess tissue fluid, eventually returning it to veins in the base of the neck.

Roles of the cardiovascular system include:  Transport of oxygen and nutrients to the tissues.  Transport of CO2 and other metabolic waste from the tissues.  Temperature regulation.  Distribution of hormones and immune cells.  Reproductive function in males: penile erection. What is the Blood Found in the Body?  65% in the peripheral veins  40% in the heart and lungs  10% in the peripheral arteries  5% in the capillaries Note: The cumulative volume of the capillaries is rather small, but their cumulative surface area is huge (estimated at 600m2). Blood Vessels Blood Vessel Layers There is a basic 3 layer structure to the blood vessels:  Tunica intima (Inner layer) – a single layer of squamous epithelial cells termed endothelial cells supported by a basal lamina and a thin layer of connective tissue.  Tunica media (Middle layer) – made up predominately of smooth muscle. Thickness of this layer varies.  Tunica adventitia (Outer layer) – made up of supporting connective tissue. Has fairly dense connective tissue on the outside of the blood vessel. There are two layers of elastic tissue in the muscular artery:  Internal elastic membrane – Separates the tunica intima is from the tunica media  External elastic membrane – Separates the tunica media rom the tunica adventitia Elastic fibres are not stained using most common stains (including H&E) but can be visualized with special stains like the one shown here – here the elastic fibres stain black. Elastic Arteries The very largest arteries (e.g. aorta) are termed elastic arteries because they have many sheets of elastic fibres (stained black here) in their tunica media to provide elastic recoil (systole and diastole). In large vessels, only the inner part of the wall can obtain nutrients from the lumen, therefore these vessels will have their own vascular supply: the vasa vasorum.

Arterioles Arterioles have only one or two layers of smooth muscle (as a result of artery division) in their tunica media and almost no adventitia. Typical diameter: 30-200µm. These are particularly important in controlling blood flow in a tissue. Artiorles are essentially composed of endothelial cells, a basal lamina, smooth muscle and epithelial cells.

Capillaries Arterioles divide even more and when they have given up their musculature entirely, this is what we call a capillary. Capillaries are essentially composed of endothelial cells and a basal lamina. They have a diameter of 4-8 µm and they often have pericytes at intervals just outside the basal lamina. These are connective tissue cells that have contractile properties (regulate flow through cap. networks) and act as stem cells.

Arrows pointing at endothelial call nuclei

3 Types of Capillary 1. Continuous Capillaries – most common type, found in: muscle, connective tissue, lungs, skin and nerves. Have simple squamous endothelial cells, continuous basal lamina. 2. Fenestrated Capillaries – in areas where we need easy access to the bloodstream, have 50nm pores in their wall, found in: mucosa of the gut, endocrine glands and glomeruli of kidney. 3. Sinusoidal or Discontinuous Capillaries – most open capillaries, lack a (continuous, complete) basal lamina and so have large gaps between cells which allow macromolecules to pass, found in: liver, spleen and in bone marrow (places where there is intimate contact between the fluid element of blood and the cells) Capillary network is an interconnected structure.

Microvascular Networks The microvasculature in tissues varies. Some tissues have metarterioles that will then lead into capillary networks, been described in the brain but its not certain whether most tissues are served by these. Small arterioles connect to a postcapillary venule through a network made up of metarterioles, thoroughfare channels and capillaries. Precapillary sphincters, composed of smooth muscle, at the beginning of the capillary help control flow through the network. In thoroughfare channels, if the flow through the capillary network is restricted then these channels will become more prominent and blood flows directly from the arterial to venule (otherwise, blood flows through the capillaries and feed the tissue). The first vessel after the capillary is the postcapillary venule, it has greater connective tissue and has a larger lumen than a capillary, but not smooth muscle. In the venule is where we begin to pick up scattered smooth muscle.

Postcapillary Venule Capillary networks drain into post-capillary venules (10-30µm diameter), endothelial cell-lined and contain a thin layer of connective tissue and occasional pericytes (has thick connective tissue layer on the outside). These are important sites for exchange, e.g. cells moving into the tissue in inflammation.

Once the vessel begins to acquire intermittent smooth muscle cells in a tunica media layer, they are referred to as venules (generally >50µm). Vein Veins, in addition to the tunica intima, have a relatively thin but continuous tunica media typically consisting of a few layers of smooth muscle. The tunica media is markedly thinner than would be found in a muscular artery. Veins also have endothelial cells on the inner surface and some connective tissue. The largest veins (e.g. vena cava or hepatic portal vein) have a thick tunic adventitia which incorporates bundles of longitudinally oriented smooth muscle. Veins are flexible and can accommodate expansion and thus contain most of the blood in the body. Valves Most small to medium sized veins have valves that are inward extensions of the tunica intima. Valve can be seen by the endothelial cells in the image. Prevent the backflow of blood by flipping back, the ‘leaves’ come together. Artery – Vein Comparison Two similar sized vessels. Tunica media of the artery is much thicker than that of the vein – artery under high pressure, vein under low pressure. The Heart Cardiac Microstructure The heart is made up of 3 layers. From inside to outside these are: 1. Endocardium – inner layer 2. Myocardium – middle layer 3. Epicardium – outer layer Layers of the Heart Very thin endocardium  Thick myocardium (muscular wall of the heart)  Relatively thin pericardial cavity (contains fluid)  Pericardial sac forming the visceral and parietal portions of the serous pericardium (contains fluid which prevents/lubricates the movement of the heart within the pericardial sac.). Endocardium Lines the entire inner surface of the heart, including the valves. Structure:  Endothelium (simple squamous epithelium)  Basal lamina  Thin layer of collagen fibres  Layer of denser connective tissue  In some areas there is also a subendocardium of loose connective tissue containing small blood vessels and nerves and the branches of the impulse conducting system. Subendocardium In some areas, instead of the fibrous connective tissue of the endocardium neighbouring the contractile muscle, there is a subendocardium. Subendocardium contains elements of the conducting system of the heart: Purkinje fibres. Subendocardium is tissue specialised for conduction in the heart, found in the subendocardial compartment.

Myocardium Thick middle layer. Structure:  Bundles and layers of contractile cardiac muscle fibres.  Individual muscle fibres are surrounded by delicate, collagenous connective tissue with a rich network of capillaries (aerobic tissue). Cardiac muscle cells have a single central nucleus (sometimes 2) and they have intercalated discs passing across the fibres at irregular intervals, allows the cardiac muscle cells to contract in a wave-like pattern so that the heart can work as a pump. Intercalated Disc: Ultrastructure The intercalated disc has many inter-cellular junctions to anchor the cells together.  Macula adherens/desmosomes and zonula adherens (fascia adherens in this particular tissue) are actin filaments to actin filaments in terms of connection.  Gap junctions allow the electrical excitation to spread from cell to cell, however heart cells are not innervated like skeletal muscle cells and so a pulse of electricity/depolarisation passes in a wave across the heart causing a contraction across the cells of the heart. Epicardium Outer layer of the heart:  Single layer of flattened epithelium called mesothelium.  Basal lamina  Fibroelastic connective tissue and, in some places, adipose tissue. In many areas the epicardium is relatively simple. In many areas there is considerable adipose tissue on the surface of the heart and the coronary vessels are typically embedded in this. When we look at the most outer layer to the right, we can see mesothelium, simple squamous epithelium with relatively dense fibrous connective tissue and then a deep layer of adipose tissue. In the heart. Cardiac Microstructure: Pericardium Pericardium on the outside is made up by two parts: 1. Fibrous pericardium – a sac of tough fibrocollagenous connective tissue. 2. Serous pericardium – made up of a layer of simple squamous epithelium (mesothelium), b...