AG RO Flashcards
(176 cards)
1
Q
What are the differnt modalities of stem cell division?
A
Asymmetric: most common, one of the two daughter cells remains a stem cell and the other moves towards differentiation.
Symmetric: one stem cell divides in either 2 stem cells or two differentiated cells.
These modalities may coexist in the same niche based on different physiological conditions.
2
Q
How is stem cell division regulated?
A
Intrinsic: a cell polarity is defined due to the segregation caused by intrinsic determinant factors inside the cell.
Extrinsic: Signals from inside the niche promote self renewal or repress differentiation.
3
Q
What is the difference between totipotent, pluripotent and multipotent stem cells?
A
Totipotent cells for example are those in the early stages of embryo development, they give rise to all cells in the embryo as well as extra embryonic cells. Pluripotent cells for example are Embryonic Stem cells bc they can give rise to all embryonic cells but not extra embryonic. Finally Multipotent cells are those that can develop in a limited number of cells found in a specific tissue such as Keratinocytes that give rise to nervous tissue cells.
4
Q
What are some examples of post natal stem cell niches?
A
Crypts of the intestine, hair follicles, bone marrow and nervous tissue. The first two are more anatomically defined niches unlike the last two.
5
Q
What is Somatic Cell Nuclear Transfer?
A
SCNT is when you take a nucleus from differentiated somatic cell - a mammary cell - and transfer it into the cytoplasm of an egg. Of course before that you must remove the nucleous of the oocyte. The last step is to implant the egg inside a recepient mother and technically - this is not 100% efficient - she will birth a clone of the donor. This proves that the differentiated somatic cells contain the genetic information of the whole organism.
6
Q
How is reprogramming somatic cells into induced pluripotent stem cells done?
A
In this experiment they started by selecting 24 genes that qualified as possible factors that induced pluripotency in somatic cells. They inserted these genes one by one in cells with a cocktail of different TFs in a mouse fibroblast. They discovered that the cells obtained were very similar to ES colonies. They eventually were able to narrow down the number to 4 TFs and 4 genes that were very efficient in inducing PSCs.
7
Q
What are the four main types of tissues present in our bodies?
A
Connective Tissue, Epithelial Tissue, Muscle Tissue, and Nervous Tissue.
8
Q
What are some main characteristic of epithelial tissue?
A
This tissue covers all body surface, lines hollow organs and forms glands. It is very distinctive. It is polarized which will help distinguish apical, lateral and basal domains. It doesn’t have vessels so they are avascularized. There are very active stem cells that allow high turnover of the cells.
9
Q
What are some main characteristic of connective tissue?
A
Less cells and more ECM and fibers. ECM is composed of ground substance with proteins, glycoproteins. The main cell is called fibroblast. Provides overall structural support and metabolic support to all tissues and organs.
10
Q
What are some main characteristic of the nervous tissue?
A
Its main functions are that it detects, collects and analyzes stimuli from the environment. This tissue is soft, jelly like consistency. We are able to distinguish a grey and white matter.
11
Q
What is H&E staining?
A
Hematoxilyn and Eosin staining is commonly used in histological samples. H which has a bluish/purple color stains nucleic acids and E which has a pink color stains proteins.
12
Q
What is immunofluorescence?
A
We use an primary antibody that recognizes a specific molecules. Then we use a secondary antibody tagged with a flourescence tag that recognizes the primary antibody. Finally we use a flourescent microscope with a specific lamp to observe our target.
13
Q
How are epithelia classified?
A
The epithilia can either be simple or stratified and can be squamous cuboidal or columnar. There are also other two special epithelia categories called pseudostratified and transitional.
All epithelia are classified based on their morphology not on function.
14
Q
What are some main characteristic of simple squamous epithelia?
A
It is made of a single layer of flat scale-shaped cells. Most commonly found lining blood vessels and body cavities. It allows materials to pass through diffusion and filtration. Lines for example the bowman capsule in the kidney, alveoli of the lungs and a part of the cornea.
15
Q
What are some main characteristic of simple cuboidal epithelia?
A
It is a single layer of cube-like shaped cells, mainly found in duct and secretory portions of the small glands.
16
Q
What are some main characteristic of simple columnar epithelia?
A
Single layer of column shape cells, found mainly in ducts of many exocrine glands. The main function is secretion but also absorption. It can also be protective.
17
Q
What are some main characteristic of columnar pseudostratified epithelia?
A
The nuclei are not aligned. Main functions are mucus secretion, found in the trachea, much of the upper respiratory tract, duct deferens.
18
Q
What is epithelial metaplasia?
A
It means the conersion in post natal life of one cell type to another. For example going from pseudostratified columnar to stratified squamous. This conversion is used to adapt to the stress caused by the environment.
19
Q
What is cell polarity?
A
Cell polarity indicates the different domain a cell has. The apical domain is the part of the cell that faces the lumen it may support structures like microvilli, stereocilia and cilia. The lateral domain faces the lateral part of the neighboring cell and supports junctions that keep the cells together. The basal domain is is the part below of the cell, it acts as a filter controlling the movement of substances with the CT below.
20
Q
What are Occluding/Tight junctions?
A
They keep cells together like a zip. The zonula occludens is the region of contact between the two cells. Proteins like occludins and claudins help create the structure that keeps them together.
21
Q
What are Anchoring/Adherent junctions?
A
They are beneath the tight junctions and they function in an area called zonula adherens. They aswell anchor cells together. The cell adhesion is mediated by proteins called cadherins. Desmosomes, hemidesmosomes and focal ashesion are some examples of anchoring junctions. The difference is that the last two anchor the basal domain of the cell to the basal lamina.
22
Q
What are Gap junctions?
A
They are specialized intercellular connection between cells. They are formed by two hemichannels called Connexons, one provided by each cell. They aid the movement of small molecules, proteins , nucleic acids and sugars. They play key roles in many tissues such as heart, blood vessels, CNS and respiratory tract.
23
Q
What are the basement membrane and the basal lamina of a cell?
A
The basal lamina is a fine extracellular layer, the basement membrane is the entire structure beneath the epithelial cells. The basement membrane has three distinct layers; lamina lucids which is electron lucent, lamina densa which is electron dense and lamina reticularis which is associated with retivular fibers of the underlying CT.
24
Q
What are the two main types of glands? What the three types of secretion?
A
Exocrine: retain continuity with the external environment through ducts.
Endocrine: looses direct continuity with the external environment during development.
Merocrine: product is released through exocytosis. The gland can be either serous or mucous.
Holocrine: the whole cell ruptures releasinf the product
Apocrine: product released in the apical portion surrounded by thin cytoplasms and membrane.
25
What is Mesenchyme?
It is embryonic tissue found in the embryo. All CTs and other tissues derive from this tissue. They are considered multipotent stem cells. Even in adults we can find some niches of mesenchymal stromal cells and they are though to be like stem cells in adult tissue.
26
Why is ECM important and what are some of its features?
ECM provides pathway for cell migration, pathway for cell signaling and it senses the biochemical mechanical changes that occur.
27
How is connective tissue classified?
CT is classified based on the composition, organization of ECM and function. We have the Embryonic CT which contains the Mesenchyme and Whartons jelly - CT proper which is divided in loose and dense - and specialized CT such as cartilage, blood, bone, hematopoietic tissue, lymphatic tissue and adipose tissue.
28
What is the difference between an active and quiescent fibroblast?
Active: Active in the process of producing and secreting the ECM.
Quiescent: Not active in this process.
29
What is the difference between Blasts and Cytes?
A -blast every cell type in active state of proliferation and production and -cyte to every cell that is not active.
30
What are adipocytes?
They are cells found in the specialized CT of the adipose tissue. They derive from the mesenchyma and there are two types.
White: specialized in the storage of triglycerides and the main function is the storage of energy. Also involved in the synthesis of some hormones and GFs.
Brown: brownish color given by the mitochondria present, the main function is thermoregulation. They are abundant in infants and in mammals that hibernate.
Adipocytes are resident cells.
31
What are Mesenchymal stromal cells?
They are multipotent cells present in several adult tissues like bone marrow and adipose tissue. They can self renew, proliferate and differentiate in different tissues. They are probably remnants of mesenchymal cells and the most logical origin is the mesoderm.
32
What are the different connective tissue fibers?
Collagenous fibers, Reticular fibers and Elastic fibers.
33
What are collagen fibers?
Most common protein in the ECM and it is composed of glycine and hydroxyproline. Structurally three alpha chains wrap around eachother. Then they associate to form fibrils and then fibers. The synthesis starts in the RER and then they pass through the golgi for glycosylation. Histologically speaking you can see the nuclei of the fibroblasts.
Defects of collagen synthesis can cause diseases such as scurvy.
34
What are reticular fibers?
Composed of mainly type III collagen. They do not form bundle fibers but form a network that serves as a scaffold for all cells.
35
What are elastic fibers?
They are thin fibers compared to the other fiber types. They contain elastin. They also form a network. Produced by fibroblast but also muscle cells.
36
What are some features of muscle tissue and what are the different types?
Contractility is a fundemental property of muscle tissues. The contraction is performed by the sliding interaction of thick myosin filaments along thin actin filaments. The three main muscle tissue types are; skeletal, cardiac and smooth muscle.
Specific terminology is used when talking about the muscle cells; Cytoplasm is called Sarcoplasm - Smooth ER is called Sarcoplasmic Reticulum and the membrane and its lamina is called Sarcolemma.
The muscle tissue derives form the mesoderm.
37
What are some features of skeletal muscle tissue?
The fibers can be very long like in the arm or leg, but also very short like around the eye.
38
What are the stages of skeletal myogenesis?
During the embryonic stage there are inactive cells called Myoblasts, they will migrate and then fuse to become Myocytes. These primary myocytes fuse to give rise to myocytes which are multinucleated. Subsequently there is the formation of the basal lamina and the innervation.
39
What are satellite cells?
They are part of the myoblast that will fuse to give a multinucleated cell.
40
How is the skeletal muscle organized?
From the outside to the inside:
Muscle fibers are wrapped by a CT called deep fascia, then we have the epimysium. Next we have bundle of fibers called fascicles seperated by a layer of dense irregular CT called Perimysium. The next we have budles of muscle fibers surrounded by the Endomysium and finally we have the myofibrils.
41
What is the structure of the muscle fibers?
The sarcomere extends from one Z line to the other, it is symmetrical. The A band in the sarcomere is formed by myosin filamets - dark bands - and the I band is formed by actin filaments - light bands. The I bands are divided by the Z bands.
T tubules are invaginations in the sarcolemma and they are associated with two terminal cisternea of the sarcoplasmic reticulum, this structure is called Triad. This is the functional unit that is responsible for calcium release.
42
How does muscle contraction work?
An action potential in the motor neurons release Acetylcholine which binds to the nicotinic receptors of the muscle fibers which in turn cause a depolarization. This allows the calcium ions to enter the muscle fiber. Ca binds to Troponin which exposes the myosin heads which then can bind to the actin filaments. ATP is hydrolyzed and the release of ADP and P cause the myosin head to change position and cause the movement of the actin filament. This sliding of the filament causes a change in length - contraction.
43
What are the different types of muscle fibers?
Type I : Aka slow oxidative, mainly rely on aerobic metabolism, they contain mitochondria and capillaries. Also contain myoglobin. They are responsible for slow contraction over time.
Type II B : Aka fast glycolitic fibers have very few mitochondria and capillaries and mainly depend on anaerobic metabolism. They appear whitish and are responsible for the fast and short term contractions.
Type II A: Aka fast twitch oxydative, physiological and histological features intermediate between the other two types.
44
What is the gross morphology of the CNS?
Not a lot of CT, the tissue is very soft almost jelly like. It is possible to distinguish a grey and white matter.
45
How does the nervous system develop?
It develops early in the neural plate, from an invagination called the Neural Groove which generates the Neural Tube. At a certain time the cells from the neural tube detach and give rise to the Neural Crest cells which originate part of the PNS and other cell types. Cell types such as neurons, astrocytes and oligodendrocytes derive from the ectoderm of the neural tube.
46
What are neurons?
There are about 100 billion neurons which account for about 10% of total brain cells. Neuron is composed by a cell body, an axon and a dendrite. Mature neurons are not mitotically active, as of now neural stem cells are still under question. Multipolar neurons have one axon and a dozen dendrites and are the most common. Bipolar neurons have one axon and one dendrite and are found in the retina and olfactory mucosa. Pseudounipolar neruons are T shaped, and have a single short process that functions as an axon. Based on connection and function we can distinguish motor neurons, sensory neurons and interneurons.
47
What is a synapse and how does it work?
It is the site where one neuron transmits info in the form of an electric impulse to another target cell. The chemical synapse relies on the secretion of neurotransmitters in the space between the two cells called synaptic cleft. The binding of the neurotransmitter causes conformational chnage and the opening of a channel. The electric synapse makes use of gap junctions which align and allow the movement of small molecules and ions. They are faster but less specific.
48
How does the action potential work?
The resting potential is characterized by a greater concentration of ions outside the cell, when ions move inside the membrane depolarization occurs. Voltage gated calcium channels opens and allow calcium to enter the membrane causing depolarization. This causes the release of neurotransmitters which then bind on the postsynaptic membrane. Ligand gates ion channels are then opned resulting in the repolarization of the membrane.
49
What are some neurotransmitters and their functions?
Each neuron releases on type of NT. Acetylcholine is important in cognitive memory and movement, its dysfunction is associated to alzheimers and huntigtons disease. Dopamine is involved in reward, motivation, and motor function and is associated with parkinsons disease. Seratonin is involved in mood, memory processing, sleep and cognition.
50
What is the neuro muscular synapse?
It is the junction between a muscle fiber and an axon of a motor neuron. Two molecules of Ach bind to a nicotinic AchR.
51
What are astrocytes?
They have a star shaped morphology and many branches, they can be found both in gray and white matter. They retain the ability to proliferate. They regulate synapse info, elimination and function - they participate in the formation of the BBB.
52
What is the Blood Brain Barrier?
The BBB serves to prevent the migration of cells and other large molecules from the blood to the CNS. It is a specialized neurovascular unit evolved to maintain homoestasis, it is formed by endothelial cells connected to tight junctions surrounded by a basal lamina. It is highly selective semipermeable membrane, it also protects the brain from pathogens. Non-lipophilic molecules are not able to pass and this is of clinical relevance when dealing with drugs.
53
What are oligodendrocytes?
They are branched cells with many processes which are found both in white and gray matter. One of the main characteristics is that that it is very hard to see the nucleus. They are myelinating cells in the CNS. In gray matter they are poorly myelinated unlike in white matter.
54
Which are the myelinating cells of the PNS?
Schwann cells
55
What are microglia?
They are resident macrophage like immune cells of the CNS, they account for 5/15% of brain cells. They proliferate inside the tissue. They are very plastic and can undergo changes of shape in order to adapt to various needs. They are critical regulators of the CNS development and homoestasis. Since they are able to change their genetic signature they are really difficult to mark and detect. From their “ base “ shape - small body with many branches - they change shape retracting the branches so to be more motile.
56
What are ependymal cell?
These cells form the Ependyma which is a thin epithelial lining of the ventricular system of the brain and the spinal cord. They are similar to the mucosal epithelium and their main roles are protections, regulation of CNS and production of CSF.
57
What is the cerebro spinal fluid?
It is an aqueous solution with Na+, K+ and Cl- with very little proteins and few cells. It fills all the cavities of the CNS and has the function of protection from shocks and other types of damage.
58
What is the PNS?
The PNS consists of nerves and ganglia that reside outside the brain and spinal chord. There are three types of nerves: Afferent ( sensory ), Efferent ( motor ), and Mixed ( both sensory and motor ).
59
What are the two categories of astrocytes?
Protoplasmatic: They serve as transporters of nutrients and act as a barried. Found in gray matter.
Fibrous: Respond to injury and facilitate neural remodeling.
60
What is the choroid plexus?
It is a highly vascularized tissue located in the brain ventricle. It is a folded tissue which projects into the ventricles. It removes water and blood, also it helps produce CSF.
61
What is the function of the skin and what are the different layers?
The skin is the largest organ in our body. It is divided in Epidermis which is epithelium, Dermis which is the CT and Hypodermis which is loose CT, adipose tissue and vessels. Its functions are protection from the outside environment, sensory function bc of sensory receptors and mechanoreceptors, thermoregulation, and metabolic function.
62
What are the layers of the epidermis?
Starting from the dermis and moving outwards:
Statum basale, stratum spinosum, stratum granulosum, stratum lucidum and stratum corneum.
Also, if the skin has the stratum lucidum it is defined thick skin, if it lacks it it is considered thin skin. Another difference between them is that the stratum corneum in the thick skin is much thicker compared to the thin skin.
The epidermis is not vascularized, all the nutrients come from the dermis.
63
What are some characteristic of the layers composing the epidermis?
Stratum basale: Single layer of cuboidal and columnar cells, we also have the presence of melanocytes and innervated Merkel cells which are responsible for sensing light touch.
Stratum spinosum: Spiny appearance due to the extension of the desmosomes. Cells have a polyhedral shape, they actively produce keratins. Contains langerhans cells which are fundemental for immunity.
Stratum granulosum: Flattened cells, composed of 3 to 5 layers of these cells. We find lamellar granules which contain lipids and glycolipids.
Stratum lucidum: Found only in thick skin, composed of flattened keratinocytes. No nuclei.
Stratum corneum: Can be made up of up to 20 layers of squamous flattened dead cells filled with keratins. Every two weeks the layers are sheded.
64
What is the structure of the dermis?
It is the layer beneath the epidermis, it is made of CT. The connection between the dermis and epidermis is very irregular. Dermal Papillae reinforce this junction. In the dermis we find innervation and vascularization. The dermis can be divided into Papillary dermis and Reticular dermis. The first is where the dermal papillae are found, the latter is in contact with the subcutaneous tissue. In the dermis two different types of plexuses can be found. The subpapillary plexus with venules and arterioles. The cutaneous plexus found in between the dermis and hypodermis which has veins, arteries and lymphatic vessels.
65
What is the structure of the hypodermis?
It is also called the subcutaneous layer or superficial fascia. It is no longer considered part of the skin. It is composed of loose CT and many adipocytes which act as fat storage, insulators and protectors from mechanical stress,
66
What are the different receptors and how is the skin innervated?
There are two categories of receptors in the skin: Free nerve ending and Encapsulated mechanoreceptors. The first are non capsulated and may have contact with merkel cells. The latter includes Pacinian corpuscule, meissner corpuscule, ruffini endings and krause end bulbs.
67
What are some appendages of the skin?
Sweat glands, sebaceous glands, hair follicles and nails. They all come from the down growth of epidermal cells into the dermis during the development of the organism.
68
What are sebaceous glands?
They are in close contact with the hair follicle and they discharge their product in it. It uses holocrine secretion, the cells break and release the content called the Sebum which is a mixture of lipids and lubricates the hair follicles.
69
What are sweat glands?
The most abundant sweat gland is the Eccrine sweat gland. It is tubular coiled exocrine gland. There is a duct which secretes sweat outside. Sweat is composed of water, salts and lactic acid. The Apocrine sweat glands are less common and only present in specific parts of the body, like the perineal regions. They mature around puberty and it secretes a milky protein rich serum.
70
What are hair follicles?
The three main parts are the Bulb which is the terminal part inserted into the dermis and epidermis, the Root which is the intermediate part in which we have the growth of the hair and the Shaft the external part of the hair.
71
Describe the functions of the GI tract from the upper part.
Ingestion, mastication, motility, secretion, hormone release, chemical digestion, absorption and elimination.
72
What is the general structure of the GI tract?
Starting from the lumen we have mucosa which is divided in epithelium, lamina propria and muscolaris mucosa , then following we have the submucosa, muscolaris propria and adventitia.
73
What characterizes the mucosa layer of the GI tract?
First we have the epithelium. Then we have the lamina propria which is loose CT with blood vessels, lymphatics, macrophages and lymphocytes. Following we have the muscolaris mucosae which is a thin layer of smooth muscle.
Each part of the GI tract may have a slight difference in layer function.
The lymphoid cells present in the mucosa are called GALT, gut associated lymphoid tissue.
74
What are Peyers patches and M cells?
Peyer patches are clusters of lymphoid cells found in the small intestine, more specifically the ileum.
M cells are specialized epithelial cells that resemble langerhans cells in the skin, they are able to sense antigens and pathogens.
75
What characterizes the submucosa of the GI tract?
It is made of CT, mainly loose, blood and lymph vessels, nerves both free and organized - submucosal Meissner plexus - and glands.
76
What characterizes the Muscolaris propria of the GI tract?
It is a thick smooth muscle layer and it is organized in internal sublayer - circular - and external sublayer - longitudinal. This is bc it is crucial to the movement and contraction called peristalsis.
Myenteric/Auerbach nerve plexus is also present, it is formed by autonomic neurons, they are also important in the contraction of the muscles.
77
What characterizes the serosa/adventitia of the GI tract and what is the difference?
The serosa is the outermost layer in GI tract sections that are suspended in the abdominal cavity, those which are continuous with mesenteries and the peritoneum. Other sections not suspended in cavity such as the esophagus have the adventitia layer instead.
The serosa is a thin layer of loose CT rich in blood vessels, lymphatics and adipose tissue - also with simple squamous covering epithelium.
The adventitia si a more fibrous and/or adipose CT.
78
What characterizes the Oral cavity of the GI tract?
The oral cavity is the first section of the GI tract, it is important for sensory detection, mechanical processing, initial lubrification and enzymatic digestion and immune surveillance. It contains the oral mucosa, the lips and the tongue.
79
What is the oral mucosa composed of?
Mainly composed by protective stratified squamous epithelium. The three main types of mucosa are lining mucosa 60%, masticatory mucosa 25%, and specialized mucosa 15%. Its main layers are a stratified squamous epithelium followed by the lamina propria - CT - and the submucosa made of CT and adipose tissue.
The epithelium is always stratified but can be keratinized - gums - partially keratinized - hard palate and non keratinized.
There is also the presence of salivary, sebaceous and lymphoid glands.
80
What are the lips of the oral cavity composed of?
The inner facing part of the lips are composed of nonkeratinized thick epithelium. The top part is called vermilion border made of thin keratinized stratified squamous epithelium. The outer facing part is similar to the skin.
81
What is the tongue composed of?
It is made up of skeletal muscle, CT, adipose tissue and some glands. It is covered in oral mucosa, both partially and non keratinized. The lingual papillae can be either fungiform, filiform or circumvallate in mophology. The filiform have keratinized tips, they provide a rough surface that facilitates the movement of the food. The fungiform and circumvallates have structures called taste buds, they are ovoid in form and sample the composition of ingested material.
82
How do we sense different tastes?
Taste receptors associate different molecules to certain tastes. From the taste buds there is a sensory cascade that leads to the brain.
83
What characterizes the esophagus?
It is a muscular tube, about 25 cm long in adults, it transports swallowed material from the pharynx to the stomach. Starting from the lumen: we have epithelium, CT divided in mucosa and submucosa, a muscle layer and then the adventitia.
The esophageal mucosa has nonkeratinized stratified squamous epithelium. The first third of the esophagus has skeletal muscle in the muscolaris propria which means that the movement is voluntary. The other 2/3 are composed of smooth muscle.
84
What characterizes the stomach?
The main functions are to continue digestion of carbs, to add acidic influx, to begin digestion of proteins and lipids. The cardia is the region between the esophagus and the stomach. Then there is the fundic region defined by a horizontal plane through the gastro-esophageal junction. Then we have the body. Followed by the pyoric region defined by a oblique plane that goes through the intermediate sulcus. The fundus and body are identical in microscopic structure, they contain glands that release gastric juice.
The pylorus secretes to types of mucus and the cardia releases the hormon gastrin.
85
What characterizes the gastro-esophageal junction?
The stratified squamous epithelium is repaced by the simple columnar epithelium of the stomach. It is an abrubt transition called metaplasia.
86
What characterizes the mucosa of the stomach?
The gastric mucosa contains invaginations called gastric pits that lead to the gastric glands. These structures are lined with simple columnar epithelium and contain five different functional cells. Surface mucous cells, mucous neck cells, parietal cells, chief cells and G cells. These cells have a specific position along the gastric pit.
87
What functions do the five functional cells in the gastric pits have?
The top cells are the surface mucous cells which secrete an alkaline fluid containing mucin. The mucous neck cells secrete acidic fluid also containing mucin. The parietal cells produce HCL and intrinsic factor. The chief cells have on their apical domains zymogen granules which release pepsinogen and lipase. Finallt G cells secrete gastrin in the blood.
88
What characterizes the small intestine?
The small intestine is the longest part, is is divided in three segments: duodenum, jejunum and ileum. The main functions are digestion, absorption and production of gastrointestinal hormones. The mucosa is highly folded, Plicae circulares are large circular folds. Smaller folds like villi and microvilli are also present.
89
What are the cells of glands of the small intestine?
Enterocytes absorb nutrients, Goblet cells secrete mucin and protect the epithelium, Paneth cells secrete antimicrobials, Enteroendocrine cells secrete hormones, M cells sense pathogens, Tuft cells trigger type 2 immunity and stem cells. Each of these cells has a specific location.
90
What is the structure of the salivary gland?
The structure is quite large as there is a connective capsule that enwraps the gland. The septa divides the gland in lobules. The functioning units are called Acinar. In serous secreting glands the cells are pyramidal with a nuclei at the center or base. The mucous secreting glands also have pyramidal shape but the nuclei is flattened and usually at the base of the cell. Serous cells appear darker than mucous cells. The smaller ducts are called Intercalated ducts and the epithelia is mostly columnar and white in color.
91
What are the main characteristics of the pancreas?
It is a gland, a mix of endocrine and exocrine. It produces both digestive enzyme and hormones. It is surrounded by a capsule of CT, with septa going inside. Inside there is a complex system of ducts, the endocrine cells are not scattered but clustered together and these clusters are called Islets of Langerhans. The septa is whit and the islets or paler in color.
92
What are the main characteristics of the Liver?
The liver deals with the synthesis of molecules, detoxification, storage of molecules and bio-transformations. It has important metabolic functions such as glycogenesis. The different functions are almost exclusively performed by Hepatocytes. The functional unit of the liver are the hepatic lobules, they have a polygonal sort of shape. They are organized around a central vein. At the periphery of the lobules there are three to six whitish spots called portal areas or portal triads, they are made of dense CT and may contain venules, arterioles or bile ducts.
93
What are Kupffer cells?
They are found in the liver, specifically in the sinusoidal spaces between the hepatocytes. They are macrophages and have therefore an immune role.
94
What is bile and how is it transported?
Bile is produced by hepatocytes. It is a mixture of acids, salts and bilirubin, it is fundemental in the emulsification of lipids. The first canniculi where the bile is transported is called Canal of Hering, and then you have larger ducts. The ducts are lined by Cholangiocytes, they are though to be a population of stem cells.
95
What is the parotid gland?
They are located in each cheek near the ear, they are branched acinar glands with exclusively serous acini. They secrete abundant alpha-amylase.
96
What are the submandibular glands?
They produce 2/3 of all salive. They are branched tubuloacinar glands having primarily serous acini. The mucous cells have large granules unlike the serous cells which have small dense granules.
97
What are sublingual glands?
They are branched tubuloacinar glands, it is mainly mucous secreting.
98
What is the gallbladder?
It is a hollow, pear shaped organ attached to the lower surface of the liver. It stores bile. The wall of the gallbladder consists in a highly folded mucosa with simple columnar epithelium. Then it has lamina propria followed by a muscolaris and an external adventitia.
99
What is the structure of the tooth?
The two main areas are the crown and the root. There are three layers: enamel, denitn and pulp chamber. The crown is protected by a layer of enamel which is highly mineralized and hard. Under the enamel there is the dentin which is a special calcified tissue made of odontoblasts. The pulp cavity at the center contain all the vessels and lymoh.
100
How is enamel made and what is it composed of?
It is composed of 96% calcium hydroxyapatite and 2/3% organic material. It is made by ameloblasts.
101
How is the cardiac muscle composes? What are some key features?
It has three layers, starting from the outer layer: Epicardium - simple squamous with some thin CT and nerves - Myocardium - muscle fibers and CT - and Endocardium - endothelium with CT and smooth muscle.
Cardiac muscle is only found in the myocardium. Cardiac muscle fibers are made of individual ramified cells joined end to end by a structure called Intercalated disks. The disks have abundant desmosomes, anchoring and gap junctions. The cardiac muscle is rich in mitochondria and has a central nuclei, visible striated banding pattern.
102
What is the turnover of myocardium?
It has a high turnover rate of endothelial cells throught life. Damage to the heart muscles are usually replaced by proliferating fibroblasts and CT called Myocardial scars.
103
What are some key feature of smooth muscle?
SM is found in walls of hollow organs throughout the body. It is a major component of digestive, respiratory, urinary sytems and blood vessels.
It is specialized in slow and steady contraction under the influence of autonomic nerves and various hormones. The individual cells of SM are spindle shaped, unstriated and with a central oval nucleus.
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What is the histological sample preparation?
First is sample collection, consists in slicing a thin layer of the chosen organ.
Fixation: The sample must be stabilized and preserved, this is done freezing the sample and using fixatives such as methanol or free nitrogen.
Inclusion: The tissue must be incorporated into a solid matrix, like paraffin, once it is incorporated it can be sliced.
Cut: The biopsy is cut into consecutive slices so that it is possible to observe different stacks.
Staining: The tissue slide is stained to assign specific colors to certain structures.
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What is an optical light microscope?
It uses normal light coming from a light bulb which will go through the sample and be captured by the lens. It allows for a magnification up to 1000 times the original size. It is suitable for objects uìfrom 1 micrometer to 1 mm.
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What are some different methods of staining?
H&E dyes do not recognize structures but different chemical properties. H is basic and will stai acidic substances and E is acidic so it will stain basic substances.
Trichrome staining is when 2 or more dyes bind specificallt to certain structures. For example: Azan-Mallory binds to CT and epithelia, Masson stains CT and Periodic Acid Schiff reacts with C-C bonds typically found in carbs.
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What is confocal microscopy?
It allows to reconstruct a 3D image from multiple slides. This is a particular type of immunoflourescence.
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What is tissue clarification?
Uses electrophoresis to remove lipids making it more transparent.
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What is Flow Cytometry?
It is a method that consists in pouring cells inside a tube which will be hit by a light source. The data of the amount of light deflected and the amount of light that went through is used to understand the size and granularity of a cell.
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What are some features of the blood?
Blood is a specialized CT bc it has a liquid matrix and it is mobile. The main functions are transportation of: solutes, nutrients, metabolites, hormones, oxygen and electrolytes - maintaining and restoring homoestasis after tissue damage - coagulation - fighting infections.
It is composed of 45% of Corpuscular components, 55% plasma which is an aqueous solution that does not contain cells.
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What is the Hematocrit?
It is the percentage of RBC based on volume.
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What does the plasma of the blood contain? What are some key features?
It contains the aqueous and soluble components of the blood, this includes albumins, globulins and fibrinogen which is essential for coagulation. When it flows outside of vessels it coagulates.
It contributes to the maintenace of osmotic pressure in a cell.
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What is coagulation and how is it initiated?
It is mainly initiated by the cleavage of fibrinogen which creates fibrin and together with platelets leads to the formation of clots. After coagulation we are left with what is called Serum, which is similar to plasma but contains many proteins, it does not contain fibrinogen.
When blood is drawn in the hospital, anticoagulants are added to prevent the cleavage of fibrinogen.
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What are some features of red blood cells?
RBC aka Erythrocytes are the most abundant blood cell - 95%. They are round in shape but they concave in the center, this is bc it increases the surface area to transport O and CO2. They do not have a nucleus, they are filled with hemoglobin. They have a well defined size about 6.5/7.5 micrometer diameter. Their life cycle is around 120 days after they are released.
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What is hemocateresis?
After RBC loose function they are phagocytosed by macrophages in the spleen and liver.
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How are red blood cells formed?
The differentiation of RBCs progresses together with the acquisition and expression of proteins that are relevant for the correct functioning. They are constantly produced in the bone marrow by hematopoietic stem cells.
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Why is oxidative stress relevant in red blood cells?
The cytoplasm of RBCs is full of hemoglobin which transports oxygen. The cells are subject to a high degree of oxidative stress, which mitigates the oxygen transport. The life of RBCs is maintained by mechanisms called Antioxidant systems which aim to reduce oxidation. For example: the oxidation of hemoglobin will lead to the formation of a superoxide anion, O2- -, which is very reactive. The RBCs use SOD, super oxide dismutase which catalyzes the conversion of the superoxide anion in H2O2 which is less reactive. It is then converted to water by enzymes like catalase.
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Why is relevance of gene CD47 with the life span of RBCs?
CD47 interact with the SIRP-alpha receptor in macrophages, this blocks phagocytosis. Due to aging CD47 is not expressed on the surface of old RBCs, resulting in the phagocytosis of the RBC.
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What is the Splenic open circulation?
In the red pulp of the spleen, capillaries at some point terminate in an open end. When the RBCs are released in the open circulation they must be fully functional to “ escape “ the macrophages to re-enter closed circulation. This occurs in a specific structures called Splenic sinuses or sinusoids. Here the macrophages act as quality control of the RBCs.
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What is the general classification on blood cells?
RBCs are the mast majority. The remaining are called white blood cells or Leukocytes. Leukocytes are divided in Agranulocytes which contain Lymphocytes and Monocytes - and Granulocytes which contain Basophils, Eosinophils, Neutrophils and mast cells.
Classification of abundance of leukocytes : Never Let Monkeys Eat Bananas.
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What are platelets?
Traditionally they were not considered cell although now there is increasing evidence that they are capable of performing autonomous functions. They are produced by Megakaryocytes. They are discoid in shape and anucleated. Their main function is dictated by granules that contain enzymes important in the coagulation cascade and that contain histamines and other agents ivolved in modulating the vascular tone. They are produced in the bone marrow from hematopoietic lineage.
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What is innate immunity?
The goal is to protect the organism from pathogens and alert the damage and integrity of tisues. The immune system works in two main ways; Avoidance so it aims to avoid pathogens mediated by barriers such as skin, mucose and antimicrobial proteins; Resistance aims to reduce and eliminate pathogens by activating a mechanism.
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What are the two types of immunity?
Innate immunity : It is the first line of defence and it is characterized by having all the cells and components generated in the germline.
Adaptive immunity : It is the type that is most linked to T and B lymphocytes and requires the generation of immune mechanisms not encoded in the germ line.
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How does innate immunity work?
The first phase is called Recognition, it is mediated by Pattern Recognition Receptors, PRRs, they are proteins that are expressed by immune system cells that recognize certain pathogens and other non selfs. Pathogens have certain specific structures called Pathogen Associated Molecular Patterns, PAMPs, these PAMPs are recognized by the immune systems PRRs. The second phase is the response of the immune system.
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What are some examples of PAMPs.
Lipopolysaccharides (LPS) are major components of gram negative bacteria, flagellin found in bacteria, Beta-glucans which are found only on fungi and yeast, double stranded RNS found in viruses during replication and single stranded DNA which is the genome of some viruses.
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What are Toll Like Receptors?
TLRs are a family of PRRs discovered in the 80s. The most famous one is TLR4, the receptor for LPS.
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How is tissue damage recognized by the immune system?
PRRs are not only able to recognize PAMPS but also DAMPs. DAMPs are Damage Associated Molecular Patterns, and include extracellular ATP, HMGB1, urate crystals and others.
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What happens after PRRs recognize PAMPs or DAMPs?
The recognition initiated the production and release of Cytokines and Chemokines. These are molecules which mediate inflammatory response. In particular Interleukin1 is a very potent cytokine bc it activates other immune cells. It also leads to the production of Interleukin6 which is a molecule that mediates fever. TNF-alpha is another one that facilitates the recruitment of other immune cells.
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What are type I interferons?
They are a class of inflammatory cytokines liek TNF-alpha, IL-1 and IL-6. They are critical for antiviral immune response. When a viral infection is sensed the cells produce type I interferons and they act in an autocrine and paracrine way allerting the nearby cells. They also promote apoptosis of infected cells.
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Why are RIG-1 and MDA5 PRRs important?
They typically recognize RNA. They are cytosolic. They patrol the cytosol for the presence of nuclei acids. They are important viral detectors.
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What are some features of eosinophils?
They are phagocytic. They have abundant granules and peculiar structures. The content of the granules is Cationic proteins, they are stimulated by IL-5 and are produced in the bone marrow.
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What are some features of Basophils?
They are very rare in circulation (0.5/1.5%). They have large purple granules. The main difference with eosinophils is that they are not phagocytic and they contain histamine.
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What are some features of mast cells?
They do not circulate, are tissue resident and are non phagocytic. They are found in mucosal cellls and CT. They contain high levels of histamine.
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What are Granulocytes?
They are a family of white blood cells that contain: Neutrophils (60%), Eosinophils (1-5%), Basophils (0.1%) and Mast cell (unkown). The main characteristics are: They are granulated, Polymorphonuclear which means their nucleus is multi lobed. They are fundamentally involved in the inflammatory response as well as other effector mechanism.
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What are Agranulocytes?
They are characterized by a single lobed nucleus, but it is large. They function as phagocytic cells and are involved in the long term clean up of the injury area. They are lymphocytes and monocytes. Lymphocytes have a round nucleus while monocytes have a U shaped nucleus.
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What is extravasation?
It is a process where white blood cells leave the circulation in the blood to go to the CT where the infection has been sensed. This takes place in four steps.
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What is Oxygen dependent microbial killing?
It is the killing of pathogens within phagosomes, it requires Reactive Oxygen Species. ROS are formed in this case by a dedicated enxymes called NADPH Oxidase. This method is used for small pathogens that can be phagocytosed.
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What are neutrophil extracellular traps?
When neutrophils cannot use oxygen dependent killing they undergo a special death called NETosis. This consists in the active distruption of the membrane causing the release of all internal molecules. NET filaments trap and kill pathogens acting extracellularly. This method is effective but not efficient bc many autoinflammatory disorders are associated to to much activation of NETs.
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What are the main features of neutrophils?
They are abundant, have a single nucleus with a peculiar shape with many lobes. They have many large granules: Primary granules have high cytotoxic abilities, Secondary and Tertiary granules are later released and have less cytotoxic abilities, and Secretory granules contain receptors and other functional proteins to terminate inflammation.
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How is the life cycle of neutrophils regulated?
Neutrophil life cycle is very regulated bc they are extremely abundant and have a very short half life. Neutropoiesis is the process of differentiation of hematopoietic stem cells, it takes place in the bone marrow. They mature in the bone marrow and are found in the blood only fully differentiated.
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Where do macrophages come from?
It was discovered that macrophages do not come from monocytes but are instead from a distinct lineage. They are generated with the developing tissue.
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What are the three general layers of arteries and veins?
Tunica Intima: inner portion of the vessel
Tunica Media: surrounds the tunica intima
Tunica Adventitia: outer layer of the vessel
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What are the components of the tunica intima of blood vessels?
Composed by three sublayers, going from the inside out:
Endothelial cells: specialized squamous single layer
Basal lamina: on which the cells rest on
Subendothelial layer: Loose CT in arteries some elastic fibers but not in veins.
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What are the components of the tunica media of blood vessels?
It is mostly composed of smooth muscle cells. In arteries it is more elastic and contractile compared to veins.
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How is the tunica adventitia composed in blood vessels?
It provides structural support, it is particularly developed in big arteries and veins. It hosts the Vaso Vasorum which are smaller vessels which bring oxygen to the smooth muscle cells and endothelial cells.
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How are arteries classified?
Large elastic arteries for example the aorta have a very big tunica media.
Medium arteries have the same organization but slightly less.
Small arteries and arterioles have less layers and almost to elastic fibers.
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What are capillaries and what are the different types?
It is microvasculature, often the dm of a capillarie is smaller the RBCs. We dont have a tunica media or adventitia since there is no need for elasticity or contraction. There are three types:
Continous: Enable the exchange of gases, liquid and small molecules. Typically found in muscles and skin.
Fenestrated: Have fenestrae which permit the passage of macromolecules in a controlled way, they have a continous basement membrane.
Discontinous: Ensure the highest level of exchange as well as the exit and entry of cells. They are found in the spleen, liver, BM. They also have a continous basement membrane.
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How are veins generally composed?
The organization is basically the same but there is less elasticity and the tunica media is smaller but the tunica adventitia is bigger. Arterioles do not have elongated nuclei which leads into a non regular lumen with bulging. The venules have elongated nuclei which leads to a more regular lumen.
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How are innate and adaptive immunity connected?
The main connection between the two is Dendritic cells which are innate immune cells aka antigen presentinf cell because they recognize the pathogen and activate T and B lymphocytes.
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What are the two main types of antigen specific lymphocytes?
T lymphocytes: T bc generated in the thymus, they don’t make antibodies but mediate cellular immunity by killing directly infected cells. Activated by T cell receptor.
B lymphocytes: Generated in the BM, they produce antibodies and therefore mediate the humoral immunity. Activated by B cell receptor.
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What are the two lymphocytes receptors?
B cell receptors: BCR composed of 2 heavy and 2 light chains which is the variable region, Y shaped, and a constant region.
T cell receptors: TCR composed of side to side alpha and beta chains, the bottom complex is the constant region and the top is the variable region
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What is lymphocyte receptor diveristy?
A segment of immunoglobulin locus contains up to 4 V segments, and 5 J segments. We get the variability by joining a V to J. The variable region is determined by the DNA. Similar process for the heavy chain but there are also D segments.
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What are RAG1 and RAG2 genes?
They are genes which are expressed selectively in lymphocytes. They encode for enxymes that are Recombinases. They work by recognizing sequence signals which flank the V J D segments and bind to the sequences and make a loop to cut and join different segements. This mechanism increases diversity.
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What are autoreactive lymohocytes?
The recombinating mechanisms can randomly generate BCRs and TCRs that will recognize self molecules like albumin or insulin. This can cause autoimmunity. In this case Clonal deletion occurs before it can mature.
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What is the role of the thymus in immunity?
The thymus is the site of maturation of T cells. After childhood, in adulthood most of the parenchyma of the thymus is being replaced by adipose tissue as our repertoire of T cells is mostly made in early life.
The thymus has a capsule of dense CT and it has mutiple lobules and septa which are called thymic lobules. The cortex is mostly composed of Thymocytes which are developing T cells. Its main function is to support the correct maturation of T cells. Positive selection produces funtional TCR and negative selction eliminates possible autoreactive TCRs.
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What are the stages of T cell development?
T cell progenitors are formed in the BM and then at the very early stage they migrate to the thymus. There they are exposed to notch signaling which promotes differentiation. Within a week they are called Double positive bc they express both CD4 and CD8 which relate to the ability to interact with major histocompatibility class. At this point if they are not cable of reacting or to strongly react they are eliminated, this happens in the Cortex. Later in the medulla thymocytes decide whether they will express CD4 or CD8 and here they are called single positive thymocytes.
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Why is the Autoimmune regulator gene important?
It is a gene that ensures that no TCR will react toward tissue specific antigens of other parts of the body.
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How are B cells developed?
They undergo the same maturation as T cells but the maturation happens in the BM and ends in the spleen.
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What are secondary lymph organs?
They are sites where circulating lymphocytes and antigens that come from the lymph or blood congregate. These sites maximizes the probability between rare circulating cells and their target molecules. Some examples are lymph nodes, spleen, mucosa associated lymphoid tissue , tonsils, appendix…
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What is the difference between CD8 and CD4 expressing T cells?
CD8 expressing T cells recognizes MHC class 1, if the specificity is correct they are able to mediate the direct killing of infected cells. Bc of this they are also called Cytotoxic T cells.
CD4 expressing cells interact with MHC class 2 and they are called Helper T cells bc functionally they do not kill but produce potent inflammatory cytokines that help other cells activate.
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What are lymphoid follicles?
Lymph nodes are easily recognizable by these very specific structures. They are circular structures made mainly of proliferating B cells, they are typically found within the outer cortex of the lymph nodes.
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What is the spleen?
It is a parenchymous organ. It does not have lobes, a cortex or medulla but we find a distributed organization of white and red pulp. It has a capsule of dense CT and has trabeculae of dense CT for structural support.
The white pulp is lighter in color, it contains less cells. In the spleen the follicles are associated and form in proximity of a central arteriole.
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What are the main characteristics of cartilage?
It is a specialized CT which has multiple functions. It acts like a cushioning system that prevents damage of the bone extremities. It also provides elasticity. Sparse chondrocytes and an abundant ECM. There are three types: Hyaline, elastic and fibrocartilage.
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What is hyaline cartilage?
The cells are located in lacunae surrounded by a capsule. It provides a low friction surfave and lubrification for joints. A typical structure found in this type of cartilage is called Isogenous groups, basically multiple chondrocytes that have proliferated and divided. The more superficial area of hyaline cartilage is made of dense CT which acts as a capsule of protection. Under we find the Perichondrium which contains chondroblasts the progenitors of chondrocytes, so it aids the growth of the cartilage.
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What is the matrix of hyaline cartilage composed of?
Glycosaminoglycans which are long polymers of disaccharides containing a modified sugar and a uronic acid.
Proteoglycans which contain sulfated GAGs linked to a protein via serine.
Chondrocytes which produce type II collagen.
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What is articular hyaline cartilage?
It is a type of hyaline cartilage which is found in the articular surfaces of movable joints. This type of hyaline cartilage has no perichondrium, the transition between the articular hyaline cartilage and the bone is the calcification of the cartilage itself.
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What is elastic cartilage?
Nothing more except the presence of elastic fibers. We find this type of cartilage in th external ear, auditory tube and walls of the external auditory tube.
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What is fibrocartilage?
It is mostly found in the vertebral disks and it is easily identifiable bc it is a mix of hyaline cartilage and dense regular CT. It lacks a perichondium and is very resistant.
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What is Bone?
Bone is a specialized CT in which the matrix is crystallized. The defining feature of the matrix is crystals of hydroxyapatite. It is important for resistance, support, anchoring and insertions. It is also a storage site for calcium and phophate.
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What is the structure of long bones?
The two terminal ends are called Epiphysis and theu are connected by the Diaphysis. The periosteum lines the outer surface, it acts as a capsule made of dense CT, it also hosts the progenitors of the bone cells and produces the matrix. The Endosteum is the same but it lines the luminal sides.
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What are the differnt types of bone?
The bone that makes the diaphysis is called Compact bone composed of tightly connected and continous lamellae which provide rigidity and stability.
The Epiphysis si made of trabecular bone aka spongy bone, it is made of thin connections that generate a network where stem cells reside.
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What is the lamellar organization of the bone?
Lamellae are calcified units of the matrix and are the structural unit of the bone. In compact bone the lamellae are organized in a concentric manner while in the spongy bone they are parallel.
The Osteon is a cylindrical unit made of lamellae organized in a concentric manner. In the center of the osteon we have the Osteonal/Haversian canal whihc contains vessels and nerves. Adjacent osteons communicate through a canal called Volkamann canal. The osteons do not fill the entire compact bone, the lamellae that connect the osteons is called Interstitial Lamellae and Circumferential Lamellae.
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What are the cells of the bone?
They are called Osteocytes and reside in structures called Lacunae. One lacunae contains one osteocyte. The osteoblast that reside within the periosteum or endosteum synthesize the matrix. Osteoclasts instead are bone residing macrophages, they degrade the bone using enzymes.
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What are the two mechanisms of ossification of the bone?
Intramembrous ossification: Typically happens in flat bones of the skull, it does not start from cartilage but directly from osteoblasts. The osteoblast progenitors and osteoblasts form the primary ossification center and start to generate the calcified matrix
Endochondral ossification: Here the first cells differentiate into chondroblast producing a cartilage mold of the bone. Then some cells of the perichondrium whill differentiate into osteoblast which will start the production of the diaphysis.
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What is the structure of the bone marrow?
It is made of Trabeculae which are filled with cells in their vascular spaces called Sinusoids. The sinuoids are filled with RBCs, the sinusoids are lined with endothelial cells and macrophages. Megakaryocytes are giant nucleated cells which produce platelets.
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How do we study Bone marrow? What is seen in a sample?
The marrow is drawn just like blood and smeared on the glass slides. There are RBC and many nucleated cells. There are cells called Blasts that are actively growinf and should only be found in the BM. The cells in the smear have different levels of maturation. You can observe the Myeloid series, which is the white blood cell lineage - and the Erythoid series which are the lighter cells and it represents the RBC lineage.
