Extracellular matrix = ground substance + fibers

Endochondral ossification / calsification

The process where bone develop directly from cartilage The other way bone can develop is not directly from cartilage but from within connective tissue called membranous ossification Complex process

What can we see? - Mature bone - Spicules o Are lined by osteoblasts Turns to osteocytes when they get trapped up in the spicule (bone matrix / osteoid) - Marrow - White spaces are fat - Usually we can assume Zones - Reserved zone (zone of resting cartilage) mature cartilaginous cells reserved cartilage contains normal, resting hyaline cartilage - Zone of proliferation line up to form these little disks and undergo rapid mitosis - Hypertrofy zone (zone of maturation)- Chondrocytes undergo hypotrophy (become enlarged) this zone contain a lot of glycogen and begin to secrete alkaline phosphatase o WHY? Because the bone collar have formed. There is less nutritiens so they grow bigger to try to get nutrients. - Zone of calcifying cartilage - Darker and more calcified appearance and this is where cartilage calcify/mineralize last steps before it turns into actual bone - Osteoid: Proteinacous matrix that havent yet. Once it calcifies in other words osteoid + calcium = bone. Cells: - Osteoclasts o Creates the spicules Different ossifications - Formation of periosteum o Perichondreum becomes periosteum once vascularized. Contains a layer of undifferentiated cells which become osteoblasts - Formation of bone collar o The osteoblasts secretes osteoid against the shaft of the cartilage model this serves as a support for the new bone, and eventually the osteoblasts gets trapped in its own osteoid and become osteocytes. - Calcification of matrix

o Chondrocytes in the primary center of ossification begin to grow (hypertrophy). o They stop secreting collagen and other proteoglycans and begin secreting alkaline phosphatase (an enzyme important for mineral disposition) o Nutritients can no longer diffuse trough the calcified matrix and the chondrocytes will die. Invasion of the periosteal bud o The periosteal bud which consist of blood vessels, lymph vessels and nerves, invades the cavity that is left behind from the chondrocytes. The vascularization ultimately carries haemopoteic cells, osteoblasts and osteoclasts inside the cavity. The haemapoetic cells will later form the bone marrow!! o The periosteal bud is created because chondrocytes cant get enough oxygen and need blood supply. Then they release a factor that makes the vessels protrude through the bone collar and make a periosteal bud. Bone collar: A calcified perichondrium that makes the bone not able to grow in diameter (appositional) so only in length (longitudinal).

Cartilage is retained in the epiphyseal plate located between the diaphysis and the epiphysis which is commonly known as the second center of ossification. Bone increase in length from here and bone growth from this second center of ossification stops during adulthood in approx.. age 20 Intramembranous ossification (not in test) is formation of bone from the mesenchyme e.g. flat bones in skull

Bone
Spongy bones Center of long bones The darker purple part is bone trabeculae = Compact bone Purple outline is Periosteum White area outside is bone marrow that contains blood vessels The purple shit everywhere is haemopoetic tissue (Czech this haematopoetic tissue is tissue that contain undifferentiated stem cells that will end as blood elements) Higher magnification: o Can find osteon which is a part of the lamellar (compact) bone(?) o Black hole in center is Haversian canal Whole system is called Haversian system o Transverse canals from periosteum to Haversian canal (endosteum) is called Volkmanns canal. o Canaliculi is formed by the cytoplasmic processes of the trapped osteoblasts which is now called osteocytes in o The concentric circles are the black circles in the Haversian system Space between these are called interstitial lamellae NB! Lamellar bone is a combination of compact and cancellous (spongy) bone Bone is either compact or cancellous

o Cortical layer (outer layer) is compact. Cortical bone makes up a large portion of skeletal mass, BUT; because of its density, it has a small surface area. o Cancellous bone is trabecular (a open network if trabeculae) and a relative high surface area Long bones are tubular in structure (tibia) Short bones are similar to long bones but no medullar cavity (finger bones, carpals) Flat bones consist of two layers of compact bone with a zone of cancellous bone sandwiched between them (skull and ribs) Irregular bones can not be categorized in any of the superior. (vertebra)

Three types of muscles

Read on z-band what it consist of actin, myofilaments etc? Without striations: Smooth muscles With striations o Parallel fibers: Skeletal /voluntary muscles o Interconnected fibers: Cardiac muscles Skeletal muscles - Striated usually have to be a longitudinal cut - Arranged very longitudinally - Nuclei are located in the periphery => Skeletal voluntary striated muscle o Can sometimes look like its not in the periphery if fiber is cut in crosssection, but this is just a geometrical artifact Smooth muscles - No striations - Cigar shaped nuclei if you cut them longitudinally - Round shaped nuclei if you cut them transversely - Can have a hard time differentiate this from irregular or regular dense connective tissue but if you did a trichrome stain the fibroblasts of the cytoplasm and the collagen stain very clearly or greenish-blue and the muscle fibers would not pick up the greenish at all - Nuclei is located in center Cardiac muscle - Also striations - Differential diagnosis from skeletal voluntary muscles: o Nuclei are clearly in the center of the fiber o Fibers are not stacked up nicely they branch o You have an abundance of areas where you can see little lines called intercalated disks which -

Lip (labium ris)

Epidermis o Stratified squamous keratinized epithelium with surface cells that constantly falls off (desquamating) Dermis o Here we can find: Sebaceous glands with hair follicles (can we??) Which have a holocrine secretion secrete sebum that has a protective and waterproof function for both hair and skin Simple tubular sweat glands (eccrine secretion apocrine is only found in axilla and pubic region) Arrector pilli muscles smooth muscles attached to hair follicle that is responsible for goose bubs and also helps during extrusion of sebum. Core of lip o Orbicularis oris Muscle Striated muscle: Large cylindrical muscle fibers arranged in a parallel. o Multinucleated numerous of flattened nuclei just beneath the sarcolemma / in the periphery. o Cross-striated myofibrils Transition zone o Zone between skin epithelia and oral epithelia. (stratified squamous nonkeratinized) Here a mucocutaneous junction are seen o Transition zone also has a free vermilion border Here is hair and sweat glands absent and free sebaceous glands can be seen. (free = not associated with hair follicles) In deeper CT o Here can we find tubuloacinar mucus secreting labial glands Secretion from these glands is oral mucosa Underlying CT o Here we can simply find adipose cells, blood vessels and capillaries

Tounge
One side is a non-keratinized squamous stratified mucosa a smooth side which is propably the underside of the tounge because it doesnt contain any papilla Other side is a bumpy squamous mucosa o All of the bumps are papilla The papilla are hyper-keratinized and to a nice point are filiformed papilla which are the things that scrape the food and do not contain taste-buds Smoother ones are the fungiform papilla These contain tastebuds Can see that the most of it consist of vessels, nerves, connective tissue and skeletal muscles

o Once again we know it is skeletal muscles because when you look at them you see that the nuclei is located at the periphery of the fiber, and some small striations as well o Can also see nerve cells with schwanns cells o Can aslo see a fibroblast every now and then o Can see loose connective tissue of the lamina propria

The appendix
At inner surface you see mucous-secreting cells which are simple, columnar epithelium with goblet cells that secrets mucous Also notice that there is a lot of lymphoid connective tissue between the surfaces and in some areas lymphoid tissues forms actual follicles, or secondary follicles where you have lighter areas on the inside of the circle and darker area on the outside. o Primary follicle Dark all over o Secondary Light inside (germinal center) and dark on the outside The mucous layer contain mainly the lymphoid area The submucous layer contain mainly the rest explained underneath The lymphoid area is actually the majority of the thickness of the appendix itself, and its all mucous and submucousal lymphoid tissue The lymphoid tissue can sometimes have a abrupt end, where you can find very few small muscle fibers o In direction towards surface to that is very loose loose connective tissue, fat, veins, arteries which is the classical submucosa Then you have layers of muscle cells arranged very circulary, nuclei look spindly Then you have a longitudinal layer of muscle fibers where nuclei will look round just because theyre cut transversely to their fibers Then we can find a small layer of LCT again, and the appendix is clearly intraperoteneal which means it is inside of the peritoneal sack. This allow you to find mesothelial cells in the outermost layer covering the surface of peritoneum. Funfact: o In the muscle layers in the periphery of the appendix, you cant find any inflammatory cells, especially neutrophils that if they were there, we could diagnose the appendix with acute appendicitis. o Can see vessels in the muscular layers

Appendix #2 maybe a bit easier explained

NO villi, no plicae circularis Similar to colon Consist of 4 layers o 1st Mucosa

Epithelia Simple columnar epithelium Contains mucous filled goblet cells which increase in number towards terminal end of colon Lamina propria Many lymphatic nodules with germinal centers Dispersed lymphatic tissue often present Less developed intestinal glands Muscularis mucosa Longitudinal smooth muscle o 2nd submucosa Lymphatic nodules Dispersed lymphatic tissue Dense irregular CT Blood vessels (visible) Lymph vessels (not visible) o 3rd muscularis externa Outer layer made of: Longitudinal smooth muscle layer Inner layer of circular smooth muscle Between the two is another CT layer containing nerve plexus that control the movement of the smooth muscle in muscularis externa th serosa o 4 Layer of LCT covered by a thin outer layer of squamous epithelium called mesothelium. Mesothelium covers organs that lie intraperitonealy with abdominal cavity Adipose cells

THE SALIVARY GLANDS:

Most important: o Parotid Only sereous o Submandibular A mix o Sublingual Only mucous And the ducts o Are in all exocrine glands (which have ducts for transport their secretion) and lined with simple columnar epithelium non stratified and non ciliated

Parotid gland
Exocrine gland Loose fibrous capsule in the periphery The gland in separated into lobules by strands of connective tissue Contain a acinar/alveolar (secretory portion of gland) compartment as well as ducts o NB! The part of any exocrine gland that secrete the product is an acinar or alveolar part!

o The transportation portion of the secreted material is the ducts Ducts o Ducts can be intralobular located inside of a lobule. Two types: Striated ducts with thickened, lighter cytoplasm The most common ducts simple columnar cells Intercalated ducts - Other one with simple cuboidal cells no striations called o Ducts can be interlobular located between lobules inside the connective tissue

Secretory portions o Almost all of them are sereous (secreting saliva) rather than mucous glands (secreting mucous) We can distinguish between sereous and mucous gland by looking at the staining: Sereous aciny stain darker because of the secretory granules o And you can find nuclei in the basal third of the cytoplasm. Mucus tubules stain lighter because of lipids o And you can find nuclei in the periphery o Sereous acinous parts of secretory portion smallest functional unit Divided into small groups 5-20 cells Aciny nuclei are the actual nuclei of the pure sereous gland THIS IS THE ONLY GLAND THAT IS 100% SEREOUS AND SECRETE ONLY SALIVA

Submandibular gland
Also a sereous gland but not 100% sereous Contain whitish areas which stains paler like mucin and the nuclei placed more towards the base o Is mucous glands So its a mix of sereous and mucous gland, someplace they say its 50/50 but in many cases the ratio will be more like 2:1 where there is twice as much sereous aciny Also a lot of intralobular ducts like in the parotid gland o With bright red, slightly striated cytoplasm Morphology o Capsule o Connective tissue septae consist of collagen which separates the actual lobules o Intralobular ducts within the lobules which of almost all of them are striated o And you have the acinies in the lobules

Many areas the aciny are 100% sereous, but some areas they are mucinous. Some areas you even get acinies that are half sereous and half mucinous This would be called and identified as a demilune or crescents of Gianuzzi

Sublingual gland
Almost all mucinous - Capsule - Connective tissue septae creating lobules - Some ducts within septae interlobular duct - Majority of ducts within lobules intralobular o Abundance of cytoplasm and maybe striations / Striated ducts (first type and abundant red stained cytoplasm) - Some ducts have almost no cytoplasm at all qualify as a intercalated ducts, which is the second type of intralobular ducts o The rest of the structures are chiefly mucinous-aciny Where the nuclei of the mucous aciny cells are placed in the periphery, and the cytoplasm are very watery o Differential diagnosis to sereous-aciny: Nuclei are not placed at the base, and the cytoplasm are more stainable and less watery

Nasal ala
Identification: Sebaceous glands Epidermis: Thinly keratinized stratified squamous epithelium Sebaceous glands: Numerous, branched in 2 holocrine (sebum) secretory portions o Ducts: Ope into hair follicles o Sebum: Protective and waterproof function for both hair and skin Eccrine sweat glands: May find a few ones Cartilage: Hyaline cartilage chondrocytes are in isogenic groups of 4-8. o Consist of: Isogenic groups (result of interstitial growth) Fibers type II collagen- thin (not visible because they are embedded in ground substance this is the reason why hyaline look glossy!!) Ground substance non-cellular components if extracellular matrix Consist of glycoaminoglycans and hyalinuronic acid Muscles: Skeletal wide long fibers, multinucleated with striations Connective tissue: Dense connective tissue less cells, more fibers (thickness of fibers) than LCT (which has more cells, more ground substance (hyaluronic acid and glycoaminoglycans) and less fibers.) Adipose cells

Epiglottis
You can clearly see that the body of the structure is cartilage On both sides you have a non-keratinized stratified epithelium. o Lower part can be seen as respiratory epithelium pseudostratified ciliated columnar epithelium with goblet cells o The submucousa on each sides are quite rich in blood vessels etc Can also find glands o Mostly of sereous type but also some mucous glands as well No other part of the body that can look like that The cartilage can look like hyaline cartilage, but it is really elastic cartilage. Not well-visible in the H&E stain, can only perhaps see the beginning of fibers o If we did an elastic stain with Weigert-resorsin-Fuchsin, dense elastic fibers would be clearly visible

Trachea
Part of upper respiratory tract Large space filled with air Cartilage surrounding the space almost completely Thin single / pseudostratified mucousa Can see some fat Inner lining o 1. Innermost Consist of a columnar mucousa Filled with ciliated pseudostratified columnar epithelium with goblet cells A nice row of cilia is visible and some goblet cells o 2. Second innermost Little layer of connective tissue directly underneath it called lamina propria (LCT) o 3. Layer Glands called submucosal glands which are mucous-secreting, and this layer also is rich with blood vessels o The adventitia Connective tissue o Hyaline cartilage Remember though, if we didnt know that this was trachea we would have to do an elastic stain to be sure that this wasnt elastic cartilage o Fibrous connective tissue o Smooth muscle Because of their long, spindly cigarshaped nuclei cut longitudinally and no striations o The cartilage ring that surrounds the trachea, have on the posterior side a discontinuation. Here we can find a smooth muscle, which is the trachialis muscle. This part doesnt need cartilage because it doesnt need protection anteriorly More posterior to this we can find the esophagus

Bronchus
Epithelia o Pseudostratified ciliated columnar epithelium with goblet cells Lamina propria o Loose connective tissue (more nuclei of macrophages, fibroblasts, monocytes) elastic fibers Lamina muscularis o Hyaline cartilage circle /plate surrounded by perichondrium (like in trachea?) (DCT contains fibrocytes) Contains isogenic groups of 4-8 chondrocytes in their lacuna. o Has a seromucus bronchial glands with excretory duct These may have serous demilunes / crescents of gianuzzi (the half moon) o Adipose cells are present in larger bronchi Hyaline cartilage o The plates of hyaline cartilage becomes smaller and further apart as the bronchi continue to divide and decrease in size o Between the cartilage plates the submucosa blends with the adventitia(!!) so here it is almost impossible to distinguish o Hyaline cartilage consist of isogenous groups of chondrocytes in lacunae (look kind of like circles, 4-8) Surrounded by matrix. Outer layer of cartilage = perichondrium = which is made up by dense connective tissue and contain fibroblasts o Bronchial blood vessels and bronchiole arteriole are visible in CT around bronchus The glands: o Sereous acini Formed by: Pyramidal sereous secretory cells Cytoplasm: Dark due to zymogen granules that are basophilic Thin, contractile myoepithelial cells surroudns acini contract and release secretion. Nucleus is rounded and placed in the bottom 1/3 of the cell o Mucous tubuli Formed by: Cuboidal / columnar cells Appear white Mucinogen granules fill cytoplasm of mucous cells Therefore; all organelles and nucleus are pushed agains the base of the mucous cell Nuclei are flattened and dark in the base o Elastic cartilage for comparison

Urinary bladder
Nice thing to remember: o The mucosal cell / non-keratinized endothelium(?) (inner layer no serosa!!) are bluer stained because they have nuclei and cytoplasm and no connective tissue

They mucosal cell layer have a wavy appearance, not as a papillary layer but still similar. Majority of thickness of the bladder is smooth muscles arranged in a way that makes it possible for them to do their job to press out the urin Top layer of bladder has some connective tissue, and is covered by serosa o Mesothelial cells Can also find: o Arteries, veins, smooth muscle bundles, connective tissue of serosa / adventitia Can be hard to differentiate between the fibroblasts of CT and the nuclei of smooth muscle tissue The epithelium of whole urinary system is transitional. It is stratified, just like squamous is, and these cells have a columnar appearance at the base, and more cuboidal appearance at the surface o But if the bladder was distended (oppblst) then the cuboidal cells in top would look more squamous. Therefore the name transitional Now it is more commonly called urothelium The layer underneath is called submucousa or lamina propria o Contains a lot of collagen bundles and fibroblasts Quickly underneath lamina propria we can find spindly bundles of smooth muscles

Skin thin skin

1. Stratum corneum a. Keratinized, is thinner than the full thickness of the epidermis to be called thin skin b. No nucleus. The keratinize-parts are adhered with adhering desmosomes 2. Epidermis a. Stratified keratinized squamous epithelium b. Granular layer on top filled with kerato-hyalin granules which makes it stain darker c. Spinosum layer underneath with large pale stained nuclei and prominent nucleoli d. Stratum basala: Basement cells resting on basal lamina is columnar shape i. Towards middle of epithelium they become cuboidal ii. At the top they are squamous And we always name epithelium of the uppermost layer therefore this is squamous 3. Basement membrane a. Dividing the epidermis from the connective tissue of dermis 4. Papillary dermis a. Have papillas / fingerlike configuration that kind of protrude into the epidermis 5. Reticular dermis a. Contain denser connective tissue and are very rich in elastic fibers contain skin appendages i. E.g. hair follicles, sweat glands, ducts, blood vessels, nerves, etc

b. Can find small acinar or tubular structures which are eccrine sweat glands i. Clear cytoplasm ii. Ducts are darker and have a double layer of cuboidal epithelium iii. Can also find myoepithelial cells which are the contractile cells that assist in the extrusion of sweat from the eccrine sweat gland. iv. Small lumen, and if we look higher we can see ducts leading upwards until we reach the thing called pores 6. Hypodermis a. Loose connective tissue b. Contain a lot of fat cells c. Can find nerves (axons surrounded by scwhanns cells), arteries, veins. Myoepithelial cells - IMPORTANT You have myoepithelial cells in all glands except the sabecous gland so the way of secretion for the sabecous gland is first of all by filling the whole cell up with cells and perform a holocrine way of extrusion and also the smooth muscle arrector pilli helps pressing out the sebum REMEMBER WITH SKIN Wandering and fixed cells in connective tissue

Skin thick skin

The stratum corneum is thicker than the thickness of the rest of the epidermis No hair follicles o Therefore no sebaceous glands either Will se (since this usually is in fingers etc) nerve-like structures (circles). These are though modified nerves (with a weird name, psendian corpuses??) Ducts of eccrine sweat glands (dark stained) o Very rich in sweat glands Acini of sweat gland is also of course present, but lighter stained Blood vessels, nerves are visible Thick DCT with fibroblasts and collagen bundles = Dense reticular dermis o Also rich in elastic fibers that we cant see because we dont have an elastic stain In the papillary dermis there would be no reticular fibers o This is the dermis with papillas of loose connective tissue sticking up and make a uneaven base of epithelia Rete pegs = Inward projections of the epidermis into the dermis in transverse section. The opposite is papillas, which is loose connective tissue going from dermis to epidermis Can se subcutaneous fat in hypodermis Usually very visible stratum granulosum which is the layer between keratinized and non-keratinized epithelium. They stain dark because have a high amount of kerato-hyalin granuels. Meissners corpuses (sensory cells) in top of the papillary layer

Skin of palm
1. Epidermis a. Stratified squamous thickly keratinized epithelium b. Following layers does the epidermis consist of: i. Stratum basale 1. Single layer of columnar cells attached to basement membrane by hemidesmosomes ii. Stratum spinosum 1. Several layers of large polygonal cells, paled stain nuclei and prominent nucleoli) connected by desmosomes 2. Stratum basale and spinosum contain cells that undergo mitotic division the 2 layers are referred to as the balpighian germinal layer iii. Stratum granulosum 1. Flattened keratinocytes containing basophilic keratohyalin granules stains dark!! iv. Stratum lucidum 1. NOT present in AXILLA!! v. Stratum corneum 1. Thickest layer in the thick skin epidermis 2. Formed by squamous fully differentiated cells (keratinized squamous). 3. Nuclei is gone and it is filled with mature keratin that increase the mechanical resistance in the skin

Cerebrospinal (peripheral) nerve

Epineurium o DCT (derived from dura mater of spinal cord + brain) surrounds the entire peripheral nerve Perineurium o Several layers of dark flattened cells connected with zonula occludentes (analogue of the arachnoid membrane) surface of each bundle Endoneurium o LCT surrounding each nerve fiber (analogue of pia mater). Contains blood capillaries with endothelial cells sealed with zonula occludentes, like BBB Nerve bundle contains nerve fibers (myelinated + non-myelinated) Nerve fibers is formed by axon of nervous cells + its coverings (myelin sheath + Schwann cells) Longitudinally sectioned myelinated nerve fibers: o Axon is located centrally, it is surrounded by whitish myelin sheath o Interval of myelin formed by a single Schwanns cell are separated by nodes of Ranvier => Internodium

The peripheral nervous system or PNS is part of the nervous system and consists of the nerves and neurons that reside or extend outside the central nervous system to serve the limbs and organs. Contains the autonomic nervous system There is two types of autonomic ganglia:

o Sympathetic ganglia o Parasympathetic ganglia Myelin o Outgrowth of glial cells: Schwann cells that supply the myelin for neurons of PNS while oligodendrocytes supply it to those of the CNS.

Sympathetic ganglion
Can se a lot of neurons Considered as multipolar rather than pseudo- or unipolar Can see modified scwhann cells which is satellite cells Also see Schwann cells that are located all around The Satellite cells are just located around the cell body So thats the characteristics: o Multipolar neurons surrounded by satellite cells In nucleus of neuron: o Nucleus are a little to the side o Can see some Nissl substance in cytoplasm(collections of rER) this is the pink inside the body of ganglion o The brown stuff inside the body of ganglion is lipfuchsin