Lecture Objectives

The function of the respiratory system is to bring oxygen to the blood and to remove the carbon dioxide.  The system is composed of two parts:

(a)               Conducting Portion.

(b)               Respiratory Portion.

The Conducting Portion consists of a series of cavities and tubes conducting air to the lungs.  It is composed of :

Nose

Nasopharynx

Larynx

Trachea

Bronchi

Bronchioles (terminal and respiratory).  The respiratory bronchioles constitute an area of transition between the conducting and respiratory systems.

Some of these structures lie outside the lungs (extrapulmonary) and need cartilaginous supports in their walls, which provide rigidity and flexibility.  Some of the structures are inside the lungs (intrapulmonary), where the need for structural support is less.

The Respiratory Portion consists of:

Alveolar ducts

Alveolar sacs

Alveoli.

The exchanges of gases (respiration) only occurs in the alveoli.

The functions of the conducting portion are to provide a route for the air to reach the lungs and also for conditioning the air. Air-conditioning during its passage through the conducting portion includes:

filtration (by hairs)

cleansing (by mucus and ciliary action)

moistening (by mucus)

warming or cooling (by heat exchange via blood vessels). 

These air-conditioning functions are performed by a specialized epithelium, the "respiratory epithelium", which lines much of the surface of the conducting portion.

Respiratory epithelium is a pseudostratified columnar ciliated epithelium with goblet cells. The epithelium lining the smaller tubes of the bronchial tree becomes simple cuboidal epithelium.  The goblet cells of the respiratory epithelium secrete mucus, which traps dust and particulate matter, which is propelled by the ciliary action towards the pharynx.  This mucus moistens and lubricates the ciliary surface and provides a barrier to prevent much of the dust entering the lungs. The amount of mucus increases greatly in cases of infections of the respiratory tract.

NOSE AND NASAL CAVITY

The external nostrils (nares) and vestibule have coarse hairs to filter large particles.  The nose is divided by the nasal septum into two chambers.  Three incomplete plates of bone (conchae or turbinates) divide each chamber into three smaller chambers (superior, middle and inferior).  The surface of these chambers is lined with respiratory epithelium, apart from the superior chamber, which is lined by a specialized olfactory (smell) receptor (Regio olfactoria).

Regio olfactoria

The olfactory region (about 10 cm²) is lined by a highly specialized sensory "epithelium", which is in fact composed of neurons and glia.  This is unique as neurons are usually not in direct contact with the external environment.

The components of the olfactory "epithelium" consist of :

(1) Olfactory cells.  These are bipolar neurons.  The apical part of the neuron is a modified dendrite, which has a terminal globular vesicle (olfactory vesicle) with 6-8 non-motile cilia, which are very long (150-200mm).  The perikaryon is located in the middle of the "epithelium" and leads to the axon, which enters the underlying connective tissue.  The axons in this connective tissue are present in small bundles (fila olfactoria) surrounded by an envelope of dense connective tissue.  These axons are non-myelinated, lack endoneurial sheaths, and belong to the central nervous system.

(2) Supporting cells.  These are columnar cells (really glia) and contain a yellow pigment in their cytoplasm.

(3) Basal cells.  These are small cells situated close to the basal lamina.  It is possible that these are replacement cells for the supporting cells.

The lamina propria, in addition to the fila olfactoria, possesses epithelial tubulo-alveolar glands of Bowman.  These produce secretions that are conveyed to the free surface of the epithelium via secretory ducts.  These secretions are believed to function to moisten and refresh the sensory surface of the chemoreceptors.

Most food that we eat is "tasted" by chemoreception of the olfactory organ. The taste buds of the tongue can only distinguish between sweet, bitter, acid and salty.  People suffering from colds are unable to distinguish the aromas of food and typically do not have an appetite.

The lamina propria of the conchae, including those of the Regio olfactoria, possesses large vascular venous plexuses.  These blood vessels are thin-walled and possess both longitudinal and circular smooth muscle.  These vessels can engorge with blood (similar to erectile vessels of the penis). Erotic stimulation can cause engorgement.  Many animals, such as dogs, where the sense of smell is much greater than that of humans, have much more extensive olfactory areas and typically use their olfactory sense to detect hormonal secretions in other dogs.  It is possible that in humans this function no longer plays a significant role as we hide our natural smells by bathing and use of deodorants.

These blood vessels (also known as "swell bodies") engorge periodically on alternate sides of the nose to reduce the rate of airflow and protect the epithelium from desiccation.

A further function for the rich vascular blood system of the lamina propria is to warm inspired air, especially in cold climates.

The nose leads to the nasopharynx, the first part of the pharynx.  The development of the palate in evolution was of utmost biological significance as it enabled the separation of the route for air (nasopharynx) from the route for feeding (oropharynx).  People with incomplete palates (cleft palate) suffer from many clinical problems and palate malformations need to be surgically corrected as soon as possible.

THE EPIGLOTTIS

The epiglottis is a flexible flap-like structure forming the uppermost part of the larynx. It is thought to have a passive role in preventing food or fluids from entering the larynx.

The epiglottis is lined by stratified squamous epithelium.  The epithelium of the upper (lingual) surface is usually thicker, than the lower (laryngeal) surface, which continues as respiratory epithelium.  The main support for the epiglottis is a plate of elastic cartilage, surrounded by perichondrium.  Small exocrine glands are common in the lamina propria.

THE LARYNX

The larynx is an irregular tube connecting the pharynx to the trachea.  The larynx has two functions:

(1) phonation (creation of sounds for speech).

(2) controlling the air pathway so that only air (and not food or foreign objects) reaches the lower respiratory passages. During swallowing the larynx moves upwards and directs the food to the esophagus. If anything other than air enters the larynx there is a cough reflex (responding to fluids or food to prevent them entering the trachea).  In cases of drowning, the cough reflex may cause uncontrolled layngeal spasm, preventing oxygen reaching the lungs and death by asphyxiation.  Autopsies of bodies after drowning commonly reveal lungs that are virtually free of water.

The mucosa of the larynx has two pairs of folds.  The false vocal cords (upper folds) are separated from the true vocal cords (lower folds) by the laryngeal ventricle.  The true vocal cords, by modifying the slit-like opening (rima glottidis) enable us to produce sounds.

The true vocal cords consist of:

(1)               stratified squamous epithelium

(2)               vocal ligament (connective tissue, which is mainly elastic bundles)

(3)               vocal muscle (skeletal muscle, which regulates the tension of the folds).

The false vocal cords consist of:

(1)               respiratory epithelium

(2)               lamina propria with many exocrine glands

Irregular plates of hyaline cartilage provide support and protection for the larynx.

Lymphatic nodules are common in the lamina propria of the larynx, especially in the area of the false vocal cords.

TRACHEA

The trachea is a short tube (about 10 cm long) extending from the larynx to the bifurcation at the beginning of the two primary bronchi. The trachea is lined with typical respiratory epithelium. In the lamina propria there are about 20 C-shaped rings of hyaline cartilage (the open ends are posterior). The open ends of each ring are connected by a bundle of smooth muscle. A dense fibroelastic ligament continuous with the perichondrium of each ring connects adjacent rings. This ligament prevents overdistention of the lumen. In histological preparations as a result of contraction of the smooth muscle, the muscle may be displaced and the C-shape of the rings may be distorted.

BRONCHIAL TREE

The tubes bringing air to the lungs continually divide into smaller tubes (trachea, primary bronchi, secondary bronchi, terminal bronchioles) and are often described as the bronchial tree. In humans this has the general appearance of an oak tree. The bronchial tree can be well demonstrated if latex casts are made of the respiratory tubes and ducts.

BRONCHI

The trachea divides into the two primary bronchi, which enter the lung at the hilum. These primary bronchi divide into smaller secondary bronchi (3 in the right lung, 2 in the left lung). The extrapulmonary bronchi have a similar histological appearance to that of the trachea. The intrapulmonary bronchi (lobar bronchi) have irregular plates of hyaline cartilage (instead of C-shaped rings). In transverse section these appear as small oval or crescent-shaped plates or islands of cartilage. As the bronchi become smaller, the bands of smooth muscle in the wall become more prominent. Contraction of this smooth muscle after death typically causes the mucous membrane of the bronchi to appear to have longitudinal folds. The lamina propria of the bronchi has abundant elastic fibers.

BRONCHIOLES

Terminal bronchioles

The first and larger bronchioles are the terminal bronchioles. These have a diameter less than 1mm and lack cartilage in their walls. They lack glands in the mucosa. Goblet cells are virtually absent and if present are only found in very small numbers in the initial segments.  A simple ciliated columnar or cuboidal epithelium lines the terminal bronchioles. (In the initial segments of the largest bronchioles, it may be pseudostratified). Clara cells (non-ciliated secretory cells) are dome-like cells located between the ciliated cells. The function of Clara cells is still unknown. They secrete glycosaminoglycans in response to chemical irritation (xenobiotics).

The lamina propria of the terminal bronchioles contains relative large amounts of smooth muscle and elastic fibers. These smooth muscles contract and severely restrict air-flow during asthmatic attacks. Asthmatics use drugs that stimulate the sympathetic innervation of the smooth muscle and cause their relaxation resulting in distention of the bronchiolar diameter.

Respiratory bronchioles

These are short tubes regarded as areas of transition between the conducting and respiratory portions of the respiratory system. The diameter of the respiratory bronchioles is about 0.5mm. The lining epithelium is simple cuboidal and non-ciliated. They have no cartilage in their walls. They lack goblet cells.

Respiratory portion of the lung

The functional unit of the lung (primary lobule) includes the :

·         Alveolar ducts

·         Alveolar sacs

·         Alveoli

These form sponge-like, elastic, thin-walled air-filled structures with extensive capillary beds, where respiratory gas exchange occurs.

The alveolar ducts are short tubes into which open numerous alveoli. "Knobs" of smooth muscle can be seen separating adjacent alveoli. The only support for the alveolar ducts and alveoli is a rich matrix of elastic and collagen fibers.
The terminal part of the alveolar duct opens into an atrium (alveolar sac) into which open many alveoli. The sac-like alveoli are the final elements of the bronchial tree. Each alveolar sac is surrounded by a rich network of blood capillaries. It has been estimated that each adult lung has about 300 million alveoli, with a total surface area for gas exchange of 70-80 square meters.

Adjacent alveoli may be connected by small openings with diameters of about 10-15um (alveolar pores). These pores may help equalize air pressure in adjacent alveoli.

The alveolar "wall"

The alveolar "wall" is composed of three main cell types :

·         Endothelial cells of blood capillaries (continuous, non-fenestrated)

·         Squamous epithelial cells (Type I)

·         Secretory cells (Type II, great alveolar cells)

The alveolar "wall" is extremely thin. The total thickness of the alveolar "wall" for gas exchange is only about 0.2-0.6um. A common basal lamina is found between the alveolar cells and the endothelial cells.
The squamous epithelial cells, which constitute the main cell type of the alveoli, are as the name implies extremely thin.
The alveolar secretory cells (Type II) are large rounded cells, which synthesize and secrete surfactant. Surfactant is a phospholipid (dipalmitoyl lecithin), which reduces the surface tension of alveoli. Without surfactant the alveoli collapse and cannot function. Surfactant is only produced and secreted towards the end of gestation. Premature babies lack surfactant and suffer from respiratory distress syndrome. At the ultrastructural level the surfactant is seen in the type II cells as multilamellar bodies (about 0.2um diameter).

Alveolar macrophages

Alveolar macrophages ("dust cells") are mobile phagocytic cells in the lung that seek and collect particulate matter that has managed to reach the lungs. These belong to the Mononuclear Phagocyte System. Alveolar macrophages are much more prominent in lungs or smokers or people from cities with industrial pollution.
 

URINARY SYSTEM

The urinary system consists of:

Kidneys (2)

Ureters (2)

Urinary bladder

Urethra

KIDNEYS

Functions of the kidneys include:

1.                    Urine production

2.                    Excretion of metabolic waste

3.                    Homeostasis of body fluids (regulation of total body water and volume of extracellular fluid)

4.                    Homeostasis of electrolytes

5.                    Hormone production : 

(a) active metabolites of vitamin D3

(b) renin

(c) erythrogenin (precursor of erythropoietin)

6.                    Control of acid-base balance (pH of the body)

  7.   Role in blood pressure control.

Renal Morphology (Macroscopic)

The kidneys are bean-shaped retroperitoneal structures.  The area of the concave surface of the kidney where the nerves, blood and lymph vessels enter and leave is known as the hilum (or hilus).  The kidney is covered with a capsule composed of dense connective tissue.  If a whole kidney is sliced vertically it can be seen to be composed of an outer cortex and an inner medulla. The main structures seen in the medulla are 10-18 medullary pyramids. The areas of connective tissue between the pyramids are known as Columns of Bertin. (This is cortical tissue situated in the medulla).

The upper expanded area of the ureter is known as the renal pelvis.  This further divides into 3 or 4 major calyces, each of which subdivides into 2-3 minor calyces.  The apex of each medullary pyramid fits into a minor calyx and has 10-25 openings through which the urine produced in the kidney is excreted before passing through the ureter to accumulate in the urinary bladder.

From the base of each pyramid, 400-500 medullary rays extend radially into the cortex. These medullary rays are straight collecting ducts into which nephrons open.

Renal lobes are defined as a medullary pyramid and the surrounding connective tissue.  The human kidney is described as being multilobar (10-18 lobes). 

Renal lobules are defined as single medullary rays and surrounding tissue i.e. all the structural elements that drain into a common collecting duct.

The morphofunctional unit of the kidney is the nephron.  There are an estimated 1.3 million nephrons in each kidney.  Each nephron is about 50-55 mm long and it is estimated that the total length of all the nephrons of both kidneys is about 100 km.

The nephron

Each nephron consists of:

1.         Renal corpuscle (Renal body, Malpighian body)

2.         Proximal convoluted tubule

3.         Loop of Henle

4.         Distal convoluted tubule

5.         Collecting duct  (Some authors do not include the collecting duct as a part of the nephron owing to its different embryologic origin).

All the components of the nephron are epithelial structures, with a continuous basal lamina and surrounded by a delicate reticular fiber network.

1.  Renal corpuscles (Malpighian bodies)

The renal corpuscles (renal bodies) are round or ovoid structures (about 150-200mm diameter) located in the cortex.  They have a double-walled epithelial capsule (Bowman's capsule).  The outer or parietal layer of Bowman’s capsule is composed of very flattened (squamous) epithelial cells.  The inner or visceral layer of Bowman's capsule is composed of specialized epithelial cells known as podocytes. An afferent arteriole enters the renal corpuscle at the vascular pole and forms a complex capillary bed (glomerular tuft), before leaving the vascular pole as an efferent arteriole. The podocytes are associated with and surround the capillaries of the glomerular tuft and form part of the filtering apparatus.

The structure of the podocytes can only be properly visualized by electron microscopy.  The podocytes are specialized epithelial cells with a large cell body, the site of the nucleus, and cytoplasmic processes.  The primary processes divide into smaller secondary processes. The processes are known as pedicels, which contain abundant microfilaments and microtubules. The secondary processes have numerous fingerlike projections that interdigitate with similar projections from adjacent processes to form filtration slits (about 25mm). A thin diaphragm (similar to that of fenestrated endothelium) is found between the slits.  The secondary processes lie on a thickened basal lamina (about 0.1mm), which is common with that of the underlying fenestrated capillaries (large fenestrae 70-90nm without diaphragms).  The basal lamina contains Type IV collagen (non-fibrous) and laminin (lamina densa) with associated heparan sulfate (glycosaminoglycan). During filtration, particles larger than 10nm or negatively-charged proteins larger than albumin (MW 69,000) do not pass the filter.  The heparan sulfate impedes the passage of negatively charged proteins across the filter.

The fluid that passes from the capillaries through the filter into the capsular space is known as ultrafiltrate, which enters the start of the proximal convoluted tubule at the urinary pole.

Mesangial cells are cells associated with the capillaries of the glomerulus. They are found in sites where the basal lamina forms a common sheath shared by two or more capillaries.  It is thought that mesangial cells may function as a sort of pericyte, or may function as macrophages, which engulf particulate matter by phagocytosis and help to keep the filter clean. In recent years mesangial cells have also been considered to be contractile and to be specialized vascular smooth muscle rather than connective tissue cells.

Glomeruli are commonly classified into two categories according to their location in the cortex (a) capsular glomeruli (closer to the capsule)  (b) juxtamedullary glomeruli (closer to the medulla).

2.  Proximal Convoluted Tubules

These tubules originate at the urinary pole of the renal bodies.  They consist of simple cuboidal epithelium, which is very acidophilic (owing to the activity of the numerous mitochondria). These epithelial cells are relatively large.  Their nuclei are regular and fairly central. The apical membrane of each cell is covered in large numbers of microvilli to form a distinct "brush border", which is coated with a PAS-positive glycocalyx.  The lateral membranes of the cells are modified to form numerous lateral processes, which interdigitate with similar processes from adjacent cells. The basal region of the cells have many invaginations of the basal plasmalemma.  Numerous large mitochondria are situated between the basal invaginations.  These mitochondria and invaginations result in basal striations, which are very well seen in histological preparations stained with iron hematoxylin. Lysosomes and peroxisomes are common in the apical regions of the cells.

The cells of the proximal convoluted tubules are involved in active ion-transport, with large energy demands.  In particular they are involved in reabsorption of water and other components of the ultrafiltrate.

3.  Loops of Henle

Each proximal convoluted tubule continues as the descending thick segment of the Loop of Henle, which continues as the thin segment.  The thin segment of the loop is characterized by its extremely flattened epithelial cells, which possess relatively few organelles. The site of the U-shaped loop is an area of extremely concentrated urine.  The loop of Henle continues as an ascending thick segment.

4.  Distal Convoluted Tubules

The epithelial cells of the distal convoluted tubule are smaller and less acidophilic (fewer mitochondria) than the proximal convoluted tubule cells.  They lack basal striations and also lack brush borders on their apical surfaces.

Juxtaglomerular Apparatus (JGA)

Each distal convoluted tubule comes into contact with the vascular pole of the renal corpuscle of its own nephron and with the afferent arterioles.  At this site the distal tubule cells become modified to form a macula densa.  The macula densa consists of tall (columnar) epithelial cells with the most prominent feature being their tall and elongated nuclei.  The function of the macula densa is unknown though it is thought to transfer data concerning the osmolality of the fluid in the distal convoluted duct.

At the site of contact with the macula densa the smooth muscle cells of the Tunica media of the afferent arterioles have been modified and become rounded and packed with cytoplasmic granules.  These cells, known as juxtaglomerular cells, are described as epithelioid (epithelium-like) and are the site of synthesis and accumulation of the peptide hormone, renin. Renin plays an important role in control of sodium and blood pressure.  Sodium deficiency (low salt) causes renin secretion (part of the Renin-Angiotensin-Aldosterone hormonal pathway).

Extraglomerular mesangial cells (Lacis cells) are also found in the juxtaglomerular region, though their function is still unknown.

5.  Collecting tubules

In the cortex these are seen as the medullary rays, but the collecting tubules dominate in the medulla (in the pyramids). They consist of straight tubules of cuboidal epithelium with central nuclei. The cells stain weakly and the borders between adjacent cells are distinct.  Near the apex of the pyramid the cuboidal epithelium becomes a columnar epithelium and the ducts are much larger and typically ovoid.  These are known as the papillary ducts of Bellini, and open into the minor calyces.

BLOOD CIRCULATION OF THE KIDNEY

Arterial system:

1.  Renal artery (elastic artery from aorta, enters at hilum)

2.  Interlobar arteries (between the lobes in the columns of Bertin)

3.  Arcuate arteries (arched vessels at cortico-medullary junction)

4.  Interlobular arteries (in cortex, parallel to medullary rays)

5.  Afferent arterioles

6.  Glomerular tuft (and filter in renal corpuscle)

7.  Efferent arterioles (surround proximal and distal tubules for reabsorption)

Venous system:

The venous vessels accompany the arterial vessels.

1.  Interlobular veins

2.  Arcuate veins

3.  Interlobar veins

4.  Renal vein (at hilum).

The pyramids of the medulla are composed mainly of straight collecting tubules.  Each tubule is accompanied by straight arterioles and venules (known as vasa recta) that originate in the arcuate arteries and return to the arcuate veins.

THE URETER

The ureters are fibromuscular tubes that conduct the urine to the urinary bladder.

They are composed of three layers:

1.   Mucosa

(a) transitional epithelium

(b) lamina propria

          2.  Muscularis

              (a) inner longitudinal muscle

                     (b) outer circular muscle

               (This muscle arrangement is the opposite of that found in the gut)

3.  Adventitia

                     Fibroelastic connective tissue.

After fixation, the mucosa is usually thrown into longitudinal folds giving a star-like appearance when seen in transverse sections.

URINARY BLADDER

1. Mucosa

(a) transitional epithelium

(b) lamina propria

2.  Muscularis

               Well-developed thick muscular coat of smooth muscle in three layers (hard to distinguish from each other)

3.  Serosa

URETHRA

The urethra is the urinary tube leading from the bladder to the external orifice (in the male via the penis, in the female it is a fairly straight short muscular tube, 2-6cm)

1.  Mucosa

Most of the urethra has stratified or pseudostratified columnar epithelium.  Transitional epithelium is only found near the bladder.

2.  Muscularis

                   The muscle arrangements are like those of the ureter

                     (inner longitudinal, outer circular).

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