Exam 1 practice Flashcards
1
Q
Cell Components: Membrane Organelles
A
nucleus (double membrane), mitochondria (double membrane), RER, SER, Golgi, lysosome, peroxisome.;
2
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Cell Components: non-membrane organelles
A
non-membrane organelles: ribosomes, microfilaments, microtubule, centriole;
3
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Cell Components: Inclusions
A
melanin, glycogen, lipid, secretory granules
4
Q
What are the properties of Plasma Membrane
A
Semi-permeable, consists of three laminae, each lamina is 2-3 nm thick, made of lipids and proteins: 98% lipids (75% phospholipids, 20% cholesterol, 5% glycolipids) and 2% proteins. But make up 50% of the weight
5
Q
Phospholipid molecules
A
Phospholipid molecules are arranged in a bilayer, with hydrophilic heads facing outside and hydrophobic ends facing toward the center of the membrane. Cholesterol molecules are located amid the tails of phospholipid molecules
6
Q
Proteins
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Proteins, although 2% of the membrane molecules, constitute 50% of the membrane weight. These include: transmembrane proteins and peripheral proteins.
7
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Transmembrane proteins
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Transmembrane proteins have hydrophilic regions facing the cytoplasm and extracellular fluid and hydrophobic regions passing back and forth through the lipid of the membrane; mostly, they are glycoproteins.
8
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Peripheral Proteins
A
do not protrude through the phospholipids but adhere to one face of the membrane.
Note chains of sugars or glycolipids attached to peripheral proteins (form glycocalyx).
9
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Functions of membrane proteins: Receptors
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usually specific for one ligand;
10
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Functions of membrane proteins:Second -messenger system
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second-messenger system: e.g., cAMP that activates kinases which, in turn, activate physiological changes within a cell;
11
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Functions of membrane proteins: enzymes
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enzymes that carry out starch and protein digestion, e.g., in the intestine;
12
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Functions of membrane proteins: channel proteins
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channel proteins that are transmembrane proteins with pores, which allow passage of water and hydrophilic solutes through the membrane; some channels are always open, while others are gated and open or close in response to three types of stimuli: ligand-regulated gates, voltage-regulated gates, and mechanically-regulated gates;
13
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Functions of membrane proteins: carrier proteins
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carrier proteins that are transmembrane proteins and help transferring glucose, electrolytes and other solutes across the membrane;
14
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Functions of membrane proteins: Cell Identity markers
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cell identity markers that are glycocalyx and help the body in distinguishing between its own cells and foreign invaders;
15
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Functions of membrane proteins: cell adhesion molecules
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cell adhesion molecules that help bind cells to one another and to extracellular material
16
Q
What cell organelles/inclusions can be identified with light microscope
A
Nucleus
17
Q
describe cell organelles and processes associated with absorption phagocytosis
A
is absorption of large particles by means of pseudopods and occurs only in specialized cells, e.g., macrophages and neutrophils.
18
Q
describe cell organelles and processes associated with absorption pinocytosis
A
or cell drinking is the process of taking in droplets of ECF containing molecules of some use to all body cells, e.g., pinocytic vesicles in the epithelial cells of the intestine, kidney, gallbladder.
19
Q
Receptor-mediated endocytosis
A
Is phagocytosis or pinocytosis in which specific solutes bind to receptors on the plasma membrane and then are taken into the cell in clathrin-coated vesicles with a minimal amount of fluid, e.g., low-density lipoproteins (LDL, protein-coated droplets of cholesterol in the blood), insulin transport from the blood to the ECF (this process called transcytosis)
20
Q
Endocytosis
A
brings matter into a cell and exocytosis is the reverse
21
Q
Discuss transporting mechanisms across the cell membrane:
Vesicular transport
A
Unlike carrier-mediated transports, move large particles, droplets of fluid, or numerous molecules at cone, contained in vesicles or vacuoles
22
Q
Describe cell organelles and processes associated with steroid synthesis
A
Mitochondria contains enzymes associated with sterod synthesis
23
Q
Describe cell organelles and processes associated with ATP synthesis
A
Mitochondria
24
Q
Describe cell organelles and processes associated with cell cycle
A
Divided into four phases: G1, S, G2, and M. G1 is the pre-duplication phase during which cell performs its specific functions; S is the synthesis phase in which centrioles and DNA duplicate; G2 is the post-duplication phase during which cell finishes replicating its centrioles and synthesis of enzymes that control cell division; M is the mitotic phase, in which a cell forms two new daughter cells. Phases G1, S and G2 are collectively called interphase.
25
Nuclear degenerative changes are classified as
pyknosis (clumping of chromatin)
karyorrhexis (breaking down of chromatin)
karyolysis (dissolution of chromatin).
26
Describe cell organelles and processes associated with cell death: Apoptosis
Defined as the process of programmed cell death that occurs continuously in all organs throughout life.
Nuclear Fragmentation
Cytoplasmic blebbing
27
Discuss transporting mechanisms across the cell membrane.:
Diffusion
Movement of particles from higher concentration to lower concentration, e.g., transport of oxygen into the bloodstream, diffusion of solutes across the artificial dialysis membrane (note, diffusion does not require cell membrane).
The diffusion rate is directly affected by temperature, molecular weight, concentration gradient, and surface area, and inversely by molecular weight.
Diffusion through a cell membrane depends on how permeable it is to the particles. For example, potassium ions diffuse more rapidly than sodium; nonpolar, hydrophobic, lipid soluble substances such as oxygen, nitric oxide, alcohol, and steroids diffuse easily through the phospholipid molecules of the membrane; conversely, water and small charged hydrophilic solutes such as electrolytes do not mix with lipids but diffuse through channel proteins.
28
Discuss transporting mechanisms across the cell membrane.:
Filtration
driven by hydrostatic pressure, e.g., transport of water, salts, nutrients, and other solutes from capillaries to the tissue fluid and vice versa, and filtration of wastes from the blood in the kidneys.
29
Discuss transporting mechanisms across the cell membrane.
Osmosis
diffusion of water down its concentration gradient and it occurs through non-living membranes such as dialysis membranes, as well as through the plasma membrane. Significant amount of water even moves through hydrophobic regions of the membrane, but it occurs more rapidly through channel proteins called aquaporins.
30
Discuss transporting mechanisms across the cell membrane:
Facilitated Diffusion
Facilitated diffusion is the carrier-mediated transport through a membrane down its concentration gradient, but it does not consume ATP, e.g., transport of glucose with a carrier protein.
31
Discuss transporting mechanisms across the cell membrane.
Active Transport
Is a carrier-mediated transport of a solute through a membrane up its concentration gradient (from a lower to a higher concentration) and requires ATP; e.g., calcium pumps (transport calcium out of the cell in the extracellular fluid [ECF], which already has more calcium than within the cell), absorption of amino acids from the ECF to the cytoplasm; sodium-potassium pump, also called sodium-potassium ATPase, transfers sodium in the ECF and potassium in the cytoplasm (keeps potassium concentration higher and sodium concentration lower within the cell, this difference in sodium and potassium concentration maintains the resting membrane potential).
32
Cell membrane Transport
Membrane is selectively permeable, allowing some things to pass through (generally lipid soluble and small molecules), but prevents proteins and phosphates from entering or leaving the cell.
Two overlapping methods of moving substances across the membrane: passive, requires no energy (ATP), e.g., filtration and diffusion; active, requires ATP, e.g., carrier-mediated, and vesicular transports.
33
Cytoplasmic Inclusions
Are metabolic byproducts and are of two kinds: endogenous and exogenous. Endogenous inclusions include pigments (melanin, lipofuscin), glycogen, lipid, and secretory granules. Exogenous inclusions include dust, bacteria, and viruses. While secretory granules are surrounded by cell membrane; melanin granules, glycogen granules, and lipid droplets are not.
34
Mitochondria
Double membrane, cristae, matrix contains circular DNA (maternal origin), ribosomes, and calcium ions. Function: Powerhouse (ATP synthesis, Krebs Cycle), also contain enzymes associated with steroid synthesis; synthesize 13 mitochondrial proteins. Mitochondria are thought to be derived from bacteria because of similarities in DNA and ribosomes. Also, both can self-duplicate.
35
Endoplasmic reticulum: SER
Smooth ER lacks ribosomes; both are continuous with each other and with the nuclear membrane.
SER synthesizes steroids (testosterone, Leydig cells), detoxifies alcohol and drugs (liver), stores and releases calcium (skeletal and cardiac muscle).
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Endoplasmic reticulum
Network of interconnected channels called cisternae enclosed by a membrane
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Endoplasmic reticulum: RER
Rough ER cisternae are covered with ribosomes;
RER synthesizes proteins that are destined for other organelles such as lysosomes or secreted extracellularly such as enzymes, antibodies, and hormones.
38
Ribosomes
Composed of ribosomal proteins and ribonucleic acids; three types of RNA:
Transfer RNA (tRNA) carries amino acids to ribosomes;
mRNA carries a code for amino acid sequence; and
rRNA (ribosomal RNA) produces ribosomes with the ribosomal proteins that are organelles responsible for mRNA translation.
39
Golgi complex
Consists of a stack of flat cisternae with an inner face (cis, forming) and outer face (trans, maturing); cisternae of cis phase receive newly synthesized proteins from RER in the form of vesicles; after Golgi processing, these molecules are released from the trans face in larger vesicles to constitute secretory vesicles, lysosomes, or other cytoplasmic components.
While lysosomes remain within the cell, secretory vesicles leave the cell by fusing with the cell membrane.
The Golgi complex in most epithelial cells, especially simple epithelium, is supra-nuclear, and it can be stained in paraffin sections with silver stain.
The cisternae of Golgi forming a stack. It has two faces: CIS (forming) and TRANS (maturing).
40
Lysosome
Lysosomal enzymes are synthesized in RER and packaged in the Golgi complex.
are divided into three types:
Primary lysosomes are homogenous (virgin, newly synthesized),
secondary lysosomes are heterogeneous (Heterophagosomes), and
tertiary lysosomes contain undigested material and are also called lipofuscin pigment or residual body. The latter are more numerous in neurons and cardiac cells because these cells are not replaced.
Lysosomal enzymes are acidic in pH and thus they can be stained in paraffin sections for acid phosphatase.
All cells use lysosomes to digest old organelles, the process is called autophagy; neutrophils and macrophages use lysosomes to digest and dispose of foreign materials such as bacteria; liver cells use them to break down glycogen; the uterus after pregnancy uses them to shrink its size, the process is called autolysis.
Lysosomal enzymatic failure leads to diseases because of accumulation of undigested material in different cell types.
41
Peroxisome
Spherical bodies, 0.5 to 1.2 m in diameter; like mitochondria, they utilize oxygen, but this is used to oxidize organic molecules, which produces H2O2, which is broken to water and oxygen by catalase enzyme. They are present in all cells but are abundant in liver and kidney cells, where they neutralize free radicals and detoxify alcohol, drugs, and blood-borne toxins.
42
Cytoskeleton
includes: microfilaments (actin and intermediate filaments) and microtubules.
43
Actin
6 nm thick, form a part of the cytoplasmic skeleton in all cells; however, in muscle cells, they form integration with myosin filaments. In other cells, they are associated with membrane activities such as pinocytosis, endocytosis, exocytosis, and cell’s migratory activities.
44
Intermediate filaments
10 nm thick, resist stress placed on a cell, form a part of the junctions between cells, especially developed in epidermal cells where they are also called tonofilaments. (Fig. 1-14). Types of intermediate filaments, depending upon protein composition, differ among tissue types: keratin (epithelium), vimentin (mesenchymal cells), desmin (muscle), glial fibrillary acidic protein (glial cells), and neurofilaments (neurons).
45
Microtubules
Microtubules are cylindrical structures, 25nm in diameter, lumen is surrounded by 13 protofilaments of globular proteins called tubulin. Microtubules provide support to the cell and participate in moving organelles and other cytoplasmic contents within the cell. Microtubules are parts of the centriole, basal body, cilium, and flagellum. They can be easily assembled and disassembled, depending upon the cell’s requirements. The anti-mitotic alkaloids arrest microtubule formation and are used in preparing karyotypes (colchicine) and cancer chemotherapy (Taxol, vinblastine).
46
Centrioles
Short cylindrical bodies consisting of nine groups of peripherally arranged three microtubules each; two centrioles lie at right angle to each other within the cytoplasm, usually above the nucleus, called centrosome. Centrioles play a role in cell division, are the source of basal bodies, which migrate to the plasma membrane and give rise to cilia or flagella (the process is called ciliogenesis).
47
Nucleus
Largest organelle and usually the only one visible with the light microscope, spherical to elliptical in shape and about 5 um in diameter,
without nucleus in the case of mammalian RBC,
multinucleate in the case of skeletal muscle, osteoclast (bone eating cell), giant cell;
surrounded by two unit membranes, which are perforated by 30-100 nm nuclear pores, which are sites of transport between the nucleus and the cytoplasm (e.g., raw materials for RNA and DNA synthesis, certain enzymes and hormones that activate DNA enter the nucleus; RNA and ribosomes leave the nucleus); the nuclear material is called nucleoplasm, which includes chromatin (fine thread-like material composed of DNA and protein) and one or more dark-staining bodies called nucleoli where ribosomes are produced.
Chromatin is classified into two types: heterochromatin appears as basophilic clumps at the LM or coarse granules in the EM; euchromatin is visible as lightly basophilic areas in the LM or finely dispersed particles in the EM.
Sex chromatin is one of the two X chromosomes in the female nucleus. Nucleoli are composed of nucleolar organizer DNA, pars fibrosa, and pars granulosa.
Note, the nucleolus synthesizes ribosomes, but not proteins.
48
Body cells, based upon the length of cycles can be divided into following types
1) Static Cells: never divide, stem cells not present (e.g. Neurons and Cardiac cells, come out of the cycle, G0 phase for life).
2) Stable Cells: normally don’t divide but can divide in response to disease and/or injury (e.g., liver cells, remain in G0 phase until injured).
3) Renewing Cells: are continuously replaced at a fixed interval. Examples: Blood cells are replaced after 120 days, leukocytes are replaced every 2-3 days, gastrointestinal epithelial cells are replaced every 2-3 days, skin cells are replaced every 2-3 weeks.
Note: Only stem cells can divide. Differentiated cells do not divide.
49
What stains Carbohydrates
Periodic acid Schiff (PAS)
50
What stains glycogen
PAS (Best carmine, glycogen only)
51
What stains lipids
Oil red/Sudan black (frozen section); Osmium (paraffin section)
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What stains Mitochondria
Succinate dehydrogenase enzyme
53
What stains lysosome
Acid phosphatase enzyme
54
What stains golgi body
Silver nitrate
55
What stains peroxisomes
Catalase enzyme
56
What stains elastic fibers
Wiegert’s elastic stain
57
What stains Reticular fibers
Silver nitrate
58
Steps involved in the synthesis of protein granules and lysosomes. ( protein synthesis)
1: Synthesis of mRNA, rRNA and tRNA in the nucleus.
2: Polyribosomes docking with RER.
3. Fusion of protein-containing vesicles with cis phase of Golgi.
4. Processing of molecules within Golgi cisternae, including glycosylation.
5. Release of packaged and condensed vesicles from trans phase of Golgi
6. Fusion of condensed vesicles with cell membrane for exocytosis.
Note: Lysosomes are sorted out and remain within the cell.
59
Autophagosomes ( another secondary lysosome)
are lysosomes fused with cell’s own old organelles (mitochondria, SER, RER, etc.).
60
Lipofuscin/ residual bodies
Are un-digestible products of lysosomal digestion. These are excreted outside the cell or stored within cells, e.g., neurons or cardiac cell.
61
How is melanin synthesized and transferred
Melanocytes synthesize melanin, which is then transferred to keratinocytes (skin cells).
Note melanocytes are present in the basal layer of the epidermis.
62
Liver Hepatocytes
Have an aggregation of glycogen granules near the central vein
63
Significance of lipid droplet outer layer
They are not surrounded by a membrane
64
Brush border
A group of microvilli collectively
65
What is the juntional complex (JC)
(called terminal bar at LM) is membrane-associated structures that function in cell-to-cell attachment of simple epithelia.
zonula occludens (ZO),
zonula adherens (ZA) and
macula adherens (MA, also called desmosome).
Both ZO and ZA form a belt around the cell apex, whereas MA makes spot-like plaques.
ZA and MA have 10-20 nm intercellular spaces.
66
Zonula occludens
No intercellular space because outer laminae of adjacent membranes are fused.
ZO surrounds the entire apical circumference of adjacent cells and is formed by fusion of the outer leaflets of the plasma membrane.
Function: prevents movement of substances into the intercellular space from the lumen or vice versa.
67
Zonula adherens
ZA surrounds the entire circumference of adjacent cells, is located next to the ZO, and is characterized by 10-20 nm intercellular space occupied by filamentous material.
A variation of ZA is fascia adherens (FA), which is a ribbon like fusion between adjacent endothelial cells (does not cover the entire circumference). FO is also present between adjacent cardiac muscle cells.
Function: binding of adjacent cells
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Desmosomes (macula adherens)
Are seen as dense bodies between adjacent skin cells (arrows).
is a small, discrete, disk-shaped adhesive site. It is characterized by dense plaque of intermediate keratin filaments (tonofilaments) loops in the cytoplasm. Function: Provides firm binding between cells; desmosomes are well developed in stratified epithelia, especially in the skin).
A variation of desmosome is hemidesmosome (half desmosome), which binds the epithelium with the underlying connective tissue.
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Gap Junctions
are spot-spot like structures with 1-2 nm gap.
They can be found along with JC, or independently, such as, in smooth and cardiac muscles.
is not a part of the junctional complex, but is present in all tissues, except skeletal muscle.
Gap junctions couple adjacent cells metabolically and electrically (sites of low electrical resistance), is composed of six proteins called connexins, which leave a gap of 2 nm between opposing plasma membrane.
Gap junctions permit between cells the exchange of signaling molecules such as ions, hormones, AMP and GMP, so that cells can act as a coordinated manner rather than as independent units (important in nervous system, smooth muscle and cardiac muscle).
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Cell Cycle
Divided into four phases: G1, S, G2, and M.
G1 is the pre-duplication phase during which cell performs its specific functions;
S is the synthesis phase in which centrioles and DNA duplicate;
G2 is the post-duplication phase during which cell finishes replicating its centrioles and synthesis of enzymes that control cell division;
M is the mitotic phase, in which a cell forms two new daughter cells.
Phases G1, S, and G2 are collectively called interphase.
71
Epithelial tissue
General information: covers the body surface or lines the body cavities; epithelial cells are closely placed with little intercellular space; cells lie on a layer of connective tissue, with the bottom layer of cells lying on a basal lamina; avascular, but cells derive nutrients via diffusion from blood vessels in the underlying connective tissue; cells perform various functions, depending upon the location: absorption (intestine), secretion (glands), protection (skin), sensory (neuroepithelium), and contractility (myoepithelial).
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Classification of epithelia
Simple:
Cuboidal, columnar, squamous
Stratified:
Cuboidal, columnar, squamous
Pseudostratified
Transitional
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Simple epithelium
all cells lie on the basal lamina; stratified: more than one layer, cells of the bottom layer lie on the basal lamina
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Pseudostratified epithelium
all cells lie on the basal lamina but appear stratified because their nuclei lie at different location
Pseudostratified epithelium is usually columnar and ciliated with goblet cells.
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Transitional epithelium
Transitional between squamous and cuboidal, depending upon the stress on epithelial cells
Note dome-shaped (outward bulging) appearance of cells in the outermost layer (stars).
Transitional epithelium changes from many layers in empty bladder to a few layers in full bladder (appears as stratified squamous).
Example: in the urinary tract
76
What is the most prevalent epithelium and its function
The most prevalent epithelium is stratified squamous, which can be keratinized or non-keratinized.
Keratinized: skin
non-keratinized: esophagus
77
Changes in epithelium (Physiological Process)
A continuous abrasion or irritation can change the epithelium from one type to the other, usually stratified squamous non-keratinized to keratinized, as is the case in the esophagus when milk diet is replaced by roughage in young animals
78
Changes in epithelium (Pathological): Metaplasia
pseudostratified columnar ciliated to stratified squamous in the respiratory tract because of continuous smoke inhalation
79
Basement Membrane
separates the epithelial tissue from the connective tissue; too thin to be seen at the light microscope; basal lamina and the adjoining connective tissue components, including collagen, glycoproteins (laminin and fibronectin), and a large proteo-glycan complex called heparin sulphate, form a layer called the basement membrane, which is PAS-positive and can be seen with a light microscope.
80
Renewal of epithelia
Epithelial cells are continuously replaced, but the rate of replacement is variable. For example, replaced every week in the intestine, every 3-4 weeks in the skin, and very slow in the liver and pancreas.
81
Cell surface specializations
The apical cell surface modifications include: microvilli, stereocilia, cilia, and flagella.
82
Microvilli
are 1um high, 80 nm wide, extensions of the plasma membrane, increase the surface area of absorptive cells such as intestine and kidney by 15-40 times. An individual microvillus is difficult to see with the light microscope (LM), but they are grouped together and form a brush border (also called striated border) that is visible at the LM.
83
Stereocillia
are long (10-20 um) and irregular microvilli, present in the epididymis, where their function is to absorb testicular fluid.
84
Cillia
are hair like processes, 7-10 um high and 0.2 um diameter. Each cilium consists of 2 central microtubules and 9 peripheral microtubule pairs, which are surrounded by a cell membrane. Each peripheral microtubule pair has two little dynein arms, a motor protein that uses energy from ATP to hook up to the next pair of microtubules.
85
Clinical significance of cillia
Patients with Kartagener syndrome, also called immotile cilia syndrome, genetically lack dynein arms and thus are infertile and more prone to respiratory infections).
86
Flagellum
is much larger than cilium (100 um long or longer) and is present in the sperm tail.
87
Intracellular Junctions
Provide adhesions between cells and restrict movement of materials into and out of lamina.
88
Glands
Are epithelial invaginations into the underlying connective tissue.
Examples:
Exocrine glands
Endocrine glands
89
Exocrine Glands
Exocrine glands secrete via a duct on the epithelium of its origin;
90
Endocrine Glands
disconnect from the parental epithelium; so, they do not have a duct; secrete into the bloodstream. Paracrine and autocrine glands are endocrine glands, but they secrete into the local extracellular space;
Examples: Pituitary, adrenal, thyroid, parathyroid.
91
Paracrine secretion
paracrine secretion acts on nearby cells other than those cells which produce them;
Example: Immune cells
92
Autocrine secretion
autocrine secretion acts on the same cell that secretes it.
Example: Liver regeneration in response to injury.
93
Classification of exocrine glands
Based on number of cells: Unicellular: composed of a single cell (e.g., goblet cell), Multicellular: composed of many cells and is further classified according to duct branching: simple (duct does not branch), compound (duct branches). Further classification is based upon shape of the secretory unit: acinar or alveolar (sac or flask-like) or tubular (straight, branched, coiled). Examples include simple tubular, simple coiled tubular, simple branched tubular, simple branched acinar, compound tubular, compound acinar, compound tubular acinar. In the salivary gland
Based on the nature of secretion: Mucus is a viscous material that protects or lubricates cell surfaces; serous is watery secretion that is often rich in enzymes; mixed secretion contains both mucus and serous.
Based on how the secretion leaves the cell: Merocrine cells release only secretory granules by exocytosis with no loss of cytoplasm; apocrine cells release secretory product with some apical cytoplasm; holocrine cells release secretory product with all cytoplasmic contents (in other words, holocrine cells die).
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Myoepithelial cells
are epithelial in organization (lie between the epithelial cells and the basal lamina) and are muscular in function (contain both actin and myosin). Hence, they are called myoepithelial cells.
95
Simple squamous
examples
All blood vessels are lined by simple squamous epithelium (called endothelium).
lining body cavities (peritoneum, pleura, pericardium) is called mesothelium
96
Simple cuboidal
examples
lining thyroid follicles
97
Special example of pseudostratified columnar
Epididymis is another example where epithelium is pseudostratified columnar, but cells have stereocilia, not cilia, at the apical surface.
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Simple columnar example
Stomach
99
Stratified cuboidal epithelium
example
glands
100
2 cells which secrete by apocrine
Apocrine secretion is characterized by the discharge of the secretion product, along with a part of the cytoplasm.
Sweat gland in animals
Mammary gland
101
Holocrine gland example
Sebaceous gland
102
mucus cells example
in the esophagus
103
Serous secretion example
in pancreas
104
How is connective tissue formed
CT is formed by three components: cells, fibers, and ground substance. Unlike epithelial tissue, which is mainly cellular (very small intercellular space), avascular (receive nutrients by diffusion from blood vessels in the CT), and its cells are arranged in layers; CT is fibrous, less cellular, vascular, and its cells are randomly dispersed in the ground substance. The connective tissue originates from the mesenchyme, an embryonic tissue made of mesenchymal cells.
105
Functions of connective tissue
Functions of CT: binding of organs, support, physical protection, immune protection, movement, storage, temperature regulation, transport, repair, or regeneration of damaged organs
106
Classification of CT
loose irregular, dense irregular, dense regular, embryonal (mesenchymal and mucous), reticular, elastic, and adipose (note, cartilage, bone, and blood are also considered CT, but they are described separately).
107
Connective tissue cells
CT cells include those that are formed locally and remain in the CT (mesenchymal, fibroblasts, pericytes, mast, adipocytes) and those that are formed elsewhere and remain in the CT transiently (macrophages, lymphocytes, plasma cells, neutrophils, eosinophils) or permanently (macrophages).
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Mesenchymal
Undifferentiated stem cells present throughout the body.
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Fibroblasts
‘blast’ means metabolically active and ‘cyte’ means inactive; most prevalent CT cell type, synthesize fibers and ground substance, spindle-shaped with long tapering ends and thus cytoplasm is difficult to discern in tissue sections stained with H&E; associated with wound healing.
110
Active fibroblast vs Quiescent fibroblast
Fibroblasts that are actively engaged in synthesis are richer in mitochondria, lipid droplets, Golgi complex, and rough endoplasmic reticulum than are quiescent fibroblasts (fibrocytes).
111
Macrophages
Originate in the bone marrow as monocytes, which circulate in the blood and then migrate to the CT, where they mature into functional macrophages.
They are mononuclear cells, are abundantly rich in lysosomes, have a huge phagocytic activity, can remove large particles and form a second line of defense in the body.
Their surface contains IgG and IgM receptors and thus they play an important role in body’s immune system.
Macrophages may fuse to form a giant cell, which is multinucleated and is capable of phagocytosing larger foreign bodies.
Macrophages may encircle the foreign body and form epithelioid cells (like epithelial cells), which ward off the foreign body (e.g., Mycobacterium tuberculosis).
Macrophages are distributed throughout the body and constitute the mononuclear phagocytic system, including :
monocytes in the blood, Kupffer cells in the liver, microglia cells in the nervous system,
Langerhans cells in the skin, dendritic cells in the lymph node,
osteoclasts in the bone, giant cells in the CT (note, all of them have their origin from blood monocyte).
Macrophages have flat nuclei, similar to fibroblasts, but they must have cytoplasm with some granularity or vacuoles.
112
How to dye macrophages
only macrophages are able to phagocytose trypan blue
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Giant Cells
Are multinucleated and are formed by merging of number of macrophages
114
Macrophages ( antigen-presenting cell) in the immune system
1) Macrophages phagocytose bacteria and present bacterial antigen to B lymphocytes;
2) B lymphocytes differentiate into Plasma cells, which secrete antibodies;
3) Antibodies circulate in the body and attach to antigen of bacteria (opsonization);
4) Opsonized bacteria are phagocytosed by macrophages and removed from the body
115
Mast Cell
Cytoplasmic granules are usually difficult to identify in H&E slides because of water solubility.
Granules contain: heparin, histamine, eosinophilic chemotactic factor, and leukotriene C.
Mast cell surface contain IgE receptors, which play a role in mediating immediate hypersensitivity reaction (anaphylactic response).
Basophils are similar to mast cells (contain IgE receptors and secrete heparin, histamine).
Found in groups near blood vessels, their granules are water-soluble and thus are difficult to see with H&E, but are metachromatic which means they change the color of metachromatic dyes (blue dyes to red or purple); granules contain histamine, heparin, eosinophil chemotactic factor, and leukotriene C.
Outer surfaces of mast cells contain Ige receptors, which mediate hypersensitivity reactions (anaphylactic shock) as follows: the first exposure to foreign antigen (e.g., plant pollens, insect venoms, certain drugs) leads to the production of Ige antibodies, which bind to receptors on the surface of mast cells, which then become sensitized to the antigen. The second exposure to the same antigen triggers mast cells to de-granulate and release histamine and leukotriene C.
Histamine increases the permeability of blood vessels and contraction of smooth muscle cells, especially in the lungs, which then can lead to dyspnea (difficulty in breathing; hopefully, you now understand why your doctor asks you if you are allergic to any medicine).
Leukotriene C also induces contraction of smooth muscles, but at a slower rate.
116
How to see the difference between mast cell and macrophages
The skin injected with toluidine blue to differentiate between macrophages and mast cells.
Note macrophages with blue toluidine granules (did not change the dye color).
Note mast cells with pink granules (changed the dye color from blue to pink).
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Steps in mast cells-induced immediate hypersensitivity
1) First injection of penicillin induces IgE antibodies production against penicillin.
2) IgE antibodies bind with IgE receptors on the mast cells surface (response is mild).
3) Second injection of penicillin triggers massive release of mast cell’s granules, leading to anaphylactic shock.
118
Mast cell secretions
1) Heparin: anticoagulant;
2) Histamine: increases vascular permeability leading to edema, and stimulates smooth muscle contraction, especially in the lungs, leading to dyspnea.
3) Eosinophil chemotactic factor (ECF): attract eosinophils at the edema site, which secrete a factor that breaks down histamine and thus the anaphylactic response becomes less severe.
4) Leukotrienes: induces mild contraction of smooth muscle cells.
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Lymphocyte
Originate from lymphoid stem cells of the bone marrow; structurally two types: small and large, based upon the size of the nucleus and the amount of cytoplasm; functionally two types: B and T, based upon the surface receptors.
Both B and T lymphocytes increase in number in viral infection, surgical transplantation, and leukemia.
Another type of lymphocytes is called null cells, which lack surface receptors characteristics for T and B cells but may have cytotoxic activity against tumor cells.
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How to tell if its a lymphocyte
Lymphocytes have round heterochromatic nucleus and a very little cytoplasm,
Plasma cells have round nucleus with cart-wheel like chromatin arrangement, basophilic cytoplasm with a distinct halo (negative image of Golgi) above the nucleus.
Plasma cells differentiate from B lymphocytes and produce antibodies (immunoglobulins).
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B cells
B cells originate and differentiate in the bone marrow (note differentiation occurs in the cloacal bursa in birds and that is the reason for their name).
B cells differentiate into plasma cells, which produce antibodies and thus B cells are called to mount a humoral immune response because antibodies circulate throughout the body; B cells only account for 5-15% of blood lymphocytes (most remain in the lymphoid organs).
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T cells
T cells originate in the bone marrow but differentiate in the thymus; both cells circulate back and forth between the CT and blood.
T cells secrete cytokines, which attack foreign cells directly and thus T cells are called to mount a cell-mediated immune response; T cells account for 80-90% of blood circulating lymphocytes; subtypes of T lymphocytes: helper, suppressor, and killer.
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Plasma Cells
Are antibody producing cells that arise from activated B lymphocytes and thus are responsible for humoral immunity; these cells are characterized by a cartwheel-like nuclear chromatin pattern, basophilic cytoplasm with a ‘halo’ above the nucleus and aggregates of RER (called Russell bodies at the TEM).
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Three characteristics of plasma cells
Round nucleus with a cart-wheel like chromatin arrangement (one chromatin dot in the middle of the nucleus and many chromatin dots in the periphery);
Basophilic cytoplasm due to RER aggregation; and
Lightly-stained area above the nucleus, representing a large Golgi complex (white arrows.)
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Neutrophils
Originate in the bone marrow, circulate in the blood and then migrate to the connective tissue (process called diapedesis), do not re-circulate after leaving blood and thus CT is their action site and graveyard (true for all granulocytes); multilobed nucleus, cytoplasm is rich in lysosomes that are neutral in color (that is the reason for their name), phagocytic, first-line of defense, their numbers increase in bacterial infection.
(not visible in H&E Slides)
Numbers are increased in blood and CT in inflammation, especially bacterial infection; phagocytose bacteria.
First-line of defense, whereas macrophages are second-line of defense.
Neutrophils create a mess, macrophages clear the mess at the site of inflammation
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Eosinophils
bilobed nucleus, cytoplasm contains eosinophilic granules, mildly phagocytic, phagocytose antigen-antibody complexes, their numbers increase in parasitic infestation and allergic reaction; in the latter case, their role is to cleave histamine and thus they moderate the allergic reaction.
Eosinophils (arrows): Bi-lobed nucleus, eosinophilic granules in the cytoplasm.
Numbers are increased in the blood and CT in parasitic infestations and allergic reactions.
Mildly phagocytic, phagocytose antigen-antibody complexes.
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Basophils
The lobed nucleus that is obscured by large basophilic granules.
Basophils are less than 1% in the blood and thus are difficult to identify in a blood smear.
Basophil granules are metachromatic and contain heparin and histamine similar to mast cells.
Basophil cell membrane has IgE receptors similar to mast cells.
Also note plasma cells, eosinophils, and fibroblasts in this picture
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Pericytes
undifferentiated stem cells located adjacent to the basal lamina of capillaries and thus can be confused with endothelial cells, present throughout the body.
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Adipose Cells
Are described under adipose tissue.
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Collagen
They are made of protein tropocollagen are tough and flexible and resist stretching, most abundant fiber in the body (about 25% of the body’s protein); it is the base of such animal products as gelatin, leather, and glue; they are often called white fibers because of their glistening white appearance such as in tendons, ligaments, and aponeurosis; in tissue sections, they form wavy bundles and stain eosinophilic with H&E; they are extracellular, non-living, and continuously replaced by new fibers synthesized by fibroblasts.
Most abundant in the body (25% of body protein); tropocollagen molecules polymerize to form collagen fibrils, which are cross linked to form fibers, which are grouped to form bundles.
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Types of Collagen
Collagen I, II, III, IV
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Collagen I
Most abundant, consists of bundles of fibers; present in skin, tendons, bone, and dentin.
Most common, form bundles, eosinophilic, high tensile strength (stronger than steel fiber of the same width); examples: skin, tendon, ligament, aponeurosis.
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Collagen II
Loose aggregates of fibrils; present in hyaline cartilage and vitreous body. Consist of fibrils in the hyaline cartilage.
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Collagen III
Thin reticular (argyrophilic) fibers; present in skin, blood vessels, lymphoid tissue.
Consists of supporting fibers (Reticular) in lymphoid organs, bone marrow.
Reticular (collagen III): Form a supporting network of fibers in lymphoid organs, bone marrow; PAS+ve, argyrophilic (silver positive).
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Collagen IV
Invisible, amorphous, detected by special stains; present in basement membrane.
Consists of anchoring fibrils in the basement membrane.
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Reticular connective tissue
Consists of branched reticular fibers; present in the bone marrow, lymphoid organs, surrounding liver sinusoids and smooth muscle cells.
They are thin type III collagen fibers coated with glycoprotein, form a sponge-like framework of organs such as spleen and lymph nodes; do not stain with H&E, but can be stained with special stains such as PAS (because of their glycoprotein coating) and silver stain and thus are also called argyrophilic fibers.
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Elastic CT
They are thinner than collagen, branch, made of elastin protein whose coiled structure allows elastic fibers to stretch and recoil like a rubber band (properties of the skin, arteries and lungs to spring back after they are stretched); and fresh elastic fibers are yellowish and are called yellow fibers, do not stain with H&E, but can be stained with special stains such as Van Gieson or Wiegert’s elastic.
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Ground substance
This is a featureless substance occupying in life empty spaces appearing in tissue sections; it is composed of three large molecules: glycosaminoglycan (GAG), proteoglycans, and adhesive glycoproteins; it absorbs compressive forces and thus protects the cells from mechanical injury.
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GAG
Composed of long polysaccharide molecules, negatively charged and thus attract sodium and potassium, which in turn enables GAG molecules to absorb and retain water and thus play an important role in regulating and water and electrolyte balance; examples of GAGs include: chondroitin sulfate that is abundant in blood vessels, cartilage, and bone; heparin (anticoagulant) and hyaluronic acid, which is very viscous serves as a barrier for organisms in the skin and as a lubricant in joints.
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Proteoglycan
Consist of a core protein from which many GAGs extend. In the skin, the entire proteoglycan may be attached to hyaluronic acid and thus forming a very large molecule, which slows the spread of organisms through the tissue, also help to hold cells together.
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Glycoproteins
Are protein-carbohydrate complex that bind plasma membrane proteins to collagen and proteoglycans outside the cell; they bind all the components of a tissue together and mark pathways that guide embryonic cells to migrate to their destinations in a tissue.
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Loose irregular CT compared to dense irregular and dense regular
Loose irregular Ct has fewer fibers, more cells, more vascular, more abundant, and less resistant to stress than dense CT, which is further classified as dense irregular CT that constitutes most dense CT, e.g., dermis and capsules of organs, and dense regular CT that has fewer cells, fewer vessels, and more densely arranged fibers than dense irregular CT, e.g., tendons (explain why tendons are harder to heal than the dermis).
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Mucous CT
Consists of a jelly-like matrix with some collagen fibers, stellate shaped mesenchymal cells, e.g., umbilical cord.
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Mesenchymal CT
Gel-like amorphous matrix containing mesenchymal cells and a few reticular fibers; present in the umbilical cord and embryos.
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Elastic CT
Comprised of branching elastic fibers with a few collagen fibers; present in lungs, external ear, glottis, ligamentum nuchae, large blood vessels.
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Adipose CT
two types: white and brown.
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White Adipose CT
Consists of unilocular adipose cells, constitutes almost all the adipose tissue in adults and is found throughout the body, each adipose cell is seen as a large vacuole with its nucleus and cytoplasm pushed to one side as a signet ring in tissue sections stained with H&E; function is to store fat.
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Brown Adipose CT
Consists of multilocular adipose cells, which contain numerous mitochondria and many fat droplets that appear small empty spaces with H&E; found in hibernating animals and infants, function is to produce heat.
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Tissue Fluid
In addition to the ground substance, the CT contains a small amount of tissue fluid that is like blood plasma, except that it contains a smaller quantity of proteins. It is continuously exchanged at the level of the capillary wall.
Two forces act on the capillary wall: hydrostatic pressure (HP) that is generated by the pumping action of the heart and the colloid osmotic pressure (COP) that results mainly from blood plasma proteins. These two forces oppose each other; whereas the HP forces fluid out of the capillary wall, the COP draws water back into the capillaries. Normally, water moves out at the arterial end of the capillary because the HP is greater than the COP, and the fluid moves back at the venous end of the capillary because the COP is higher than HP. The reason for the decrease in the HP at the venous end of the capillary is that the luminal diameter of the capillary increases; similarly, the reason for the increase in the COP is that the concentration of proteins increases (note, when fluid moves out at the arterial end of the capillary, blood becomes relatively denser because of increased concentration of proteins). So, it is not surprising that increased blood pressure or hypoproteinemia (low proteins due to malnutrition or parasitic infection) leads to increased fluid in the CT (edema). Normally, not all fluid that leaves at the arterial end of the capillary returns to blood at the venous end of the capillary. However, whatever fluid is left does return to blood via lymph vessels. Hence, it is not surprising that the blockage of lymph vessels due to pressure (e.g., during pregnancy) or parasites (elephantiasis, a roundworms infection that blocks lymph vessels) and a decreased tone in the valves of lymph vessels (due to old age) result in accumulation of fluid in the tissue.
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Classification of principal types of connective tissue
Connective tissue
- loose (areolar) - Dense
- regular or irregular
Connective tissue with Special Properties
- Adipose tissue
- elastic tissue
- mucous tissue
- Hematopoietic (lymphatic and myeloid) tissue
Supporting connective tissues
- Cartilage
- Bone
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Components of Loose or Dense Connective Tissue
A) Cells:
A-1) Locally produced and always present:
Mesenchymal, fibroblast, mast, pericyte
A-2) Produced elsewhere in the body and remain transiently (Wandering cells)
Macrophage, lymphocyte, plasma, neutrophil, eosinophil
B) Fibers:
Collagen, elastic, reticular
C) Ground Substance:
Glycosaminoglycans (GAG), proteoglycans, glycoproteins
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What is the first line of defense? What is the second line of defense
First line of defense is neutrophils Macrophages are the second line of defense
They originate from monocytes in da blood
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The names of mesenchymal stem cells in different locations
They serve as stem cells for fibroblasts in the connective tissue, chondroblasts in the cartilage, osteoblasts in the bone, hemocytoblasts in the bone marrow.
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c
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Differences between cartilage and CT
Cartilage, compared to CT, is harder due to chondromucoid in the matrix, avascular, and cells (chondrocytes) lie in lacuna.
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Cartilage Types
Hyaline, elastic, and fibrous
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Hyaline
covered by perichondrium that consists of an outer fibrous layer and an inner cellular layer called chondrogenic that contains stem cells, which, in the absence of blood vessels (in an environment of low oxygen tension), differentiate into chondroblasts.
The latter cells synthesize cartilage matrix that is rich in chondromucoid (proteoglycan and glycoprotein), in which are embedded type II collagen fibrils (also synthesized by chondroblasts).
The chondroblast entrapped in its own matrix is called chondrocyte, which lies in a space (just like the space surrounding a candle in a cake) called lacuna.
Nests of chondrocytes (all originate by division of the same chondrocyte) surrounded by large lacunae and dense matrix called territorial matrix are the hallmarks of hyaline cartilage in H&E-stained section.
Type II collagen fibrils are not visible in these sections because they have the same refractive index as that of the matrix in which they are embedded.
Examples of hyaline cartilage include most long bones in the fetus and young animals until they are ossified, articular cartilage in adult bones (note, articular cartilage is not covered by perichondrium), and walls of respiratory passages (nose, trachea, larynx, bronchus).
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Elastic
Like hyaline cartilage, except the matrix contains elastic fibers that impart flexibility and yellowish color to it; examples: pinna of the ear, auditory tube, epiglottis.
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Fibrous
Essentially like dense connective tissue because it contains type I collagen fibers, which are densely packed and longitudinally arranged as in the tendon, except that chondrocytes lies in lacunae and are arranged in rows; examples: intervertebral disks, pubic symphysis, and insertions of some tendons.
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Growth of cartilage: Interstitial
results from cell division of preexisting chondrocytes and occurs in early stages of cartilage formation, articular cartilage, and epiphyseal plates of long bones. Appositional: results from differentiation of chondrogenic cells in the perichondrium to form new chondroblasts, which lay down a new layer of cartilage matrix at the periphery.
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Degeneration of Cartilage
Chondrocytes hypertrophy and matrix becomes calcified; normal process in endochondral ossification (replacement of cartilage by bone), but it can abnormally occur in an environment of hypercalcemia. Regeneration: very poor, except in young animals, results from the activity of chondrogenic cells in the perichondrium.
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General functions of bone
Support, protection, movement, electrolyte balance, and blood formation
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Differences between cartilage and bone
Compared to cartilage, bone is harder due to calcification, vascular, canalicular, and grows only by appositional mechanism.
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Macroscopic structure of a long bone
Shaft, diaphysis; extremities, proximal and distal epiphyses; epiphyseal plate or growth plate, located between epiphysis and diaphysis; metaphysis, a small actively growing area between epiphysis and diaphysis; marrow cavity, a central space that contains bone marrow cells; articular cartilage, the joint surface between two bones; periosteum, an outer covering that consists of an outer fibrous layer and an inner osteogenic layer of stem cells; and endosteum, a layer of bone cells that lines bone marrow, as well as all marrow spaces within a bone.
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Macroscopic structure of a cranial bone
Consists of three parts: outer plate, diploe, and inner plate; the outer surfaces of both plates are covered with periosteum, although the periosteum of the inner plate is fused with the dura-mater of the cranial cavity; the inner surfaces of both plates face marrow spaces of the diploe and thus are lined by endosteum.
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Microscopic structure of a typical compact bone
Consists of ground substance containing inorganic calcium and phosphate salts; four cell types: osteoprogenitor, osteoblasts, osteocytes, and osteoclasts; and type I collagen embedded in the matrix, which is arranged in the form of lamellae, which, based upon their location, are classified as: outer circumferential, under the periosteum; inner circumferential, under the endosteum; concentric, a part of osteons (also called Haversian systems); and interstitial, between osteons.
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Structure of an Osteon (Haversian system)
These are cylinders that run parallel to the diaphysis, just like pillars in a house; have a central space called Haversian canal (also called central canal) that contains blood vessels and is surrounded by 4-20 circumferential lamellae, which contains bone cells, osteocytes;
adjacent Haversian canals are connected with each other by Volkmann’s canals, which also connect to the periosteum and endosteum and thus bring blood vessels and nerves to the bone.
Three types of osteons, depending upon the type of bone cells that line the Haversian canal:
mature osteons are lined by osteoprogenitor cells, forming osteons are lined by osteoblasts, and resorption osteons (also called resorption cavities) are lined by osteoclasts.
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Bone cells
Osteoprogenitor
Osteoblasts
Osteocytes
Osteoclasts
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Osteoprogenitor
Osteoprogenitor: stem cells, found in the endosteum, inner layer of periosteum, and Haversian canal; they multiply and some of them become osteoblasts at sites where new bone must be synthesized; may become chondroblasts in an environment of low oxygen tension.
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Osteoblast
bone forming cells, found in the same locations where osteoprogenitor cells are; synthesize osteoid (uncalcified matrix made of type I collagen and osseomucoid) that is subsequently calcified; stress and fractures stimulate osteoprogenitor cells to differentiate into osteoblasts, which build new bone.
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Osteocytes
mature osteoblasts surrounded by their own matrix, therefore, osteocytes do not line the bone surface; like chondrocytes, they also lie in tiny cavities called lacunae, which are interconnected by slender channels called canaliculi; thus neighboring osteocytes in a mature osteon connect with each other via cytoplasmic processes that lie in canaliculi; this canalicular arrangement allows osteocytes to get nutrients from distant vessels (for example, vessels of the central canal), which cannot penetrate the calcified matrix.
Functions of osteocytes: maintenance of bone density and blood concentration of calcium and phosphate; calcium is continuously renewed by osteocytes (osteolytic homeostasis, do not confuse this with bone resorption that occurs at the level of osteoclasts).
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Osteoclasts
Bone eating cells, found on the bone surface (periosteum, endosteum, central canal), multinucleated cells that are derived from monocytes, often lie in pits called Howship's lacunae, the side of osteoclasts facing the bone surface has ruffled border that is composed of finger-like projections of the cell membrane extending into the Howship’s lacunae, thus increasing the surface area of bone resorption.
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Spongy Bone
Is composed of interconnected trabeculae, which surround cavities filled with bone marrow. Each trabecula is lined by endosteum containing osteoprogenitor cells, osteoblasts, and osteoclasts (remember all marrow spaces are lined by endosteum); the bony matrix contains osteocytes and may or may not form osteons (note, only thicker trabeculae have osteons).
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Immature bone or woven bone
It is the primary bone formed for the first time, regardless of when and where; contains more osteocytes and irregularly arranged collagen bundles; is remodeled and replaced by mature bone with time.
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Bone Marrow
Is a general term for soft tissue present in the marrow cavity of a long bone and in the spaces of a spongy bone; two types: red and yellow;
red: marrow cavity of all bones in young animals are filled with red marrow (myeloid tissue, also called hematopoietic tissue); in adults, however, red marrow turns into fatty yellow bone marrow, except in the skull, vertebrae, sternum, pelvic girdle.
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Ossification
Ossification: The bone formation is called ossification, which is two types: intramembranous and endochondral.
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Intramembranous bones
bones develop in fibrous sheets called trabeculae; mesenchymal cells lining the trabecula in the presence of blood vessels differentiate into osteoblasts, which synthesize osteoid, which is subsequently calcified. The trapped osteoblasts in a calcified matrix are called osteocytes. Adjacent trabeculae join and form a spongy bone consisting of many trabeculae separated by wide spaces. Trabeculae at the surface of the bone continue to grow and calcify until the spaces between them are filled in, converting the spongy bone to compact bone; examples of intramembranous ossification include flat bones of the skull, part of the scapula and pelvic girdle.
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Endochondral
bone develops from a preexisting model of hyaline cartilage; steps include: formation of periosteal collar in the periphery (note, with the invasion of blood vessels in the perichondrium, chondrogenic cells become osteoblasts and synthesize bone, the perichondrium is now called periosteum), hypertrophy of cartilage cells in the center of the cartilage models, calcification of cartilage matrix, degeneration of cartilage cells, infiltration of periosteal bud carrying blood vessels and osteoblasts in the middle of the cartilage matrix (establishment of primary ossification center in the diaphysis), deposition of woven bone on the calcified cartilage matrix, replacement of woven bone by lamellar bone, repetition of the above sequence of events until the entire cartilage is replaced by bone, except the epiphyseal plate (growth plate), which is responsible for growth in length of the bone. Different zones of the epiphyseal plate are zone of reserve cartilage cells (resting), zone of cell proliferation, zone of hypertrophy, zone of calcification, and zone of ossification. Thus, bone elongation is really the result of interstitial growth of hyaline cartilage, which is continuously replaced by bone until the epiphyseal plate fuses (in other words, becomes bone). Note, bone cannot grow by interstitial mechanism because cells cannot multiply in a calcified matrix; however, bone grows by appositional mechanism, where new bone is formed under the periosteum or endosteum; appositional growth allows bone to grow in width.
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Bone Remodeling
In addition to growth, bone is continuously remodeled throughout life by the absorption of old bone and deposition of new bone. Remodeling does not cause any significant changes in its structure, geometry, or size. Conversely, modeling determines the size, shape and structure of the bone and is limited to the growing bone, no modeling after maturity.
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Role of hormones in bone formation/resorption:
Parathyroid hormone
Calcitonin
Growth hormone
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Parathyroid Hormone
Activates osteoclastic activity and thus elevates blood calcium level; excess calcium loss renders bone susceptible to fracture, and the resulting hypercalcemia can calcify arteries and certain organs such as the kidney.
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Calcitonin
produced by parafollicular cells of the thyroid gland, inhibits osteoclastic activity, and stimulates osteoblastic activity and thus prevents the release of calcium from the bone.
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Growth Hormone
produced by the anterior pituitary gland, stimulates overall growth of the body, especially that of the epiphyseal plate; excess growth hormone during growing years causes gigantism and in adult causes acromegaly; deficiency of growth hormone during growing years causes dwarfism.
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Clinical considerations: Osteoporosis
Decrease in bone mass associated with a normal ratio of mineral to matrix, results from decreased bone formation, increased bone resorption, or both; commonly occurs in old age, postmenopausal women, and immobile patients.
Osteopetrosis is a genetic disorder characterized by heavy bones due to defective osteoclastic activity. Acromegaly, dwarfism, and gigantism are discussed above.
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Clinical considerations: Osteomalacia
Results from calcium deficiency in adults, is characterized by deficient calcification of newly formed bone and decalcification of already formed bone.
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Clinical considerations:
Rickets
results from calcium deficiency (vitamin D deficiency is the common cause) in children, characterized by deformed epiphyseal plates.
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cartilage ppt
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General characteristics of muscles
Mesodermal origin, muscle fiber,
parts of a muscle fiber:
sarcolemma, sarcoplasm, sarcoplasmic reticulum, and sarcosomes.
Types of Muscle Fibers: Smooth, skeletal, cardiac.
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Organization of the Skeletal muscle
Fasciculus, fibers, myofibrils, myofilaments (actin, myosin).
Connective Tissue Coverings: Endomysium, perimysium, and epimysium.
Coverings supply blood vessels, nerves and muscle spindles, and provide a means by which contractile forces are transmitted to other tissues.
Structure:10-110 µm in diameter, up to 50 cm in length, nuclei peripheral and many, myofilaments create light and dark bands.
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Function Unit of the muscle
Skeletal?
Sarcomere
0.5-1.00 µm in diameter, 2.00 micrometers long. Consists of the following parts: I band, only thin filaments; A band, thick and thin filaments; H band, pale area in the center of the A band; M line, runs down the center of the H band; and Z line, dark band in the center of the I band. Note, a sarcomere extends from one Z line to the next Z line.
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T Tubule
Sarcolemma invagination at the A-l band junction in mammals and at the Z line in amphibians. Triad: T tubule and two SER cisternae (one on each side of the T tubule), SER stores Ca++ that is released during contraction
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Types of skeletal muscle fibers
Red ( type I)
White (type II)
Intermediate
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Red (type 1) muscle fiber
large amount of myoglobin, numerous mitochondria, energy from oxidative pathway, contract, and fatigue slowly, slow-twitch fibers.
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White (Type II) muscle fiber
Larger, fewer mitochondria, more extensive SER, energy from anaerobic glycolysis, contract and fatigue more rapidly, fast-twitch fibers.
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Intermediate
Share characteristics of both fibers.
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Regeneration of Skeletal cells
Limited, satellite (stem) cells present; most injured skeletal muscle cells are replaced by connective tissue.
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Motor Unit
A nerve fiber and the muscle cells it innervates.
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Motor end plate
Point of attachment of a nerve with a skeletal muscle fiber Modifications: Axon: dilation, loss of myelin sheath, and presence of mitochondria and acetylcholine (Ach) vesicles. Muscle Fiber: Sub-neural clefts, aggregation of mitochondria, and loss of striations.
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Events of Impulse Conduction
Skeletal
Depolarization of axolemma, release of Ach, binding of Ach with Ach receptors present on sarcolemma, depolarization of sarcolemma, extension of depolarization wave to the T tubule and SER cisternae (triad), release of Ca++, contraction of myofilaments, inactivation of Ach by cholinesterase enzyme present in sub-neural clefts, active transport of Ca++ back into SER, relaxation of myofilaments.
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Results of Contraction
Skeletal
I band reduces in length, sarcomere reduces in length, H band disappears, and no change in the length of the A band or of actin and myosin filaments. Huxley's Sliding Filament Theory of Muscle Contraction: Thick and thin filaments maintain the same length but slide past each other.
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Diseases of Neuro-Muscular Junctions
skeletal
Organophosphorus toxicity
Myasthenia Gravis
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Organophosphorus toxicity
Cholinesterase enzyme is phosphorylated, results in initial stimulation followed by depression. Botulism: Caused by toxins secreted by Clostridium botulinum, blocks the release of Ach, results in flaccid tetraparesis
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Myasthenia Gravis
(skeletal muscle)
Caused by deficiency of Ach and/or antibodies against Ach receptors; results in weakness in muscles.
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Cardiac Muscle
Ten to fifteen µm in diameter, 100 µm long; one or two nuclei per cell, centrally located; fibers branch, point of anastomosis shows intercalated discs, which at the E/M levels consist of gap junctions, desmosomes, and fascia (or zonula) adherens; autogenic, however, rate of contraction can be modified by nervous system; involuntary; striations and events of contraction are similar to skeletal muscle, except T tubules are located at the Z line and take the form of dyads rather than triads.
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Cardiac Muscle regeneration
Does not have stem cells so no regeneration
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Cardiac Muscle: Purkinje Fibers
Impulse conducting, modified cardiac fibers; located in the interventricular septum, moderator band (septomarginal trabecula), and beneath the endocardium. Compared to cardiac muscle cells, Purkinje fibers occur in groups, are larger in diam. (50 micrometers), and contain fewer, peripherally located myofibrils, less developed striations, and more glycogen.
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Smooth muscle
Spindle-shaped; single, centrally located nucleus; 5-20 µm in diameter, 20 µm to 1 mm or more in length; surrounded by an external lamina (basal lamina) except at sites of gap junctions; contains actin and myosin filaments, but lacks striations and troponin protein which are present in striated muscle; myofilaments are attached to dense bodies, which are analogous to Z lines of striated muscle; communicate with each other via gap junctions; actively divide and regenerate.
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Contraction of smooth muscle
Occurs more slowly and lasts longer than that of skeletal muscle; steps: increase in cytosolic Ca++, binding of Ca++ with calmodulin protein (note, Ca++ binds with troponin in striated muscle), activation of myosin kinase, phosphorylation of myosin, interaction of phosphorylated myosin with actin, contraction. Note, de-phosphorylation of myosin prevents myosin-actin interaction and leads to relaxation.
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Differences in contraction among smooth muscle cells:
Unitary smooth muscle: triggered by stretching of the muscle (myogenic), spreads from cell to cell by gap junctions, generates low level of rhythmic contraction (peristalsis), increased or decreased by autonomic nervous system rather than actually initiating the contraction, examples include viscera of the digestive system.
Multiunit smooth muscle: triggered by a nerve impulse, precise contractions due to autonomic innervation of each muscle cell, lack gap junctions, examples include constrictor and dilator muscle cells of the iris.
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Mast cell secretions
1) Heparin: anticoagulant;
2) Histamine: increases vascular permeability leading to edema, and stimulates smooth muscle contraction, especially in the lungs, leading to dyspnea.
3) Eosinophil chemotactic factor (ECF): attract eosinophils at the edema site, which secrete a factor that breaks down histamine and thus the anaphylactic response becomes less severe.
4) Leukotrienes: induces mild contraction of smooth muscle cells.
