Histology Course for Medical Students. Dr. Sami Zaqout Faculty of medicine - IUG

Transcription

1 Histology Course for Medical Students Dr. Sami Zaqout Faculty of medicine - IUG

2 Topic Week The Cytoplasm Week 1 The Cell Nucleus Week 2 Epithelial Tissue Week 2 Connective Tissue Week 3 Cartilage Week 4 Bone Week 4 Muscle Tissue Week 5 Nervous Tissue Week 6 The Circulatory System Week 8 Blood Cells Week 8 Lymphoid System Week 9 Digestive Tract and its Associated Organs Weeks 9+10 The Respiratory System Week 11 The Urinary System Week 11 The Male Reproductive System Week 12 The Female Reproductive System Week 12 Endocrine glands Week 13 Skin Week 13 Receptors Week 14

3 The Cell

4 Types of cells Cells are the structural units of all living organisms. Prokaryotic cells are found only in bacteria. These cells are small (1 5 µm long), Typically have a cell wall outside the plasmalemma, Lack a nuclear envelope separating the genetic material (DNA) from other cellular constituents. Have no histones (specific basic proteins) bound to their DNA. Usually no membranous organelles.

5 Types of cells Eukaryotic cells are larger. Have a distinct nucleus surrounded by a nuclear envelope. Histones are associated with the genetic material. Numerous membranelimited organelles are found in the cytoplasm.

6 Cellular Differentiation Zygote Blastomeres Cell Differentiation

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8 Cell Components Cell Components Cytoplasm Nucleus

9 Cytoplasm Cytoplasm

10 Plasma Membrane Phospholipids double layer Cholesterol Proteins (integral proteins) and (peripheral proteins) Chains of oligosaccharides covalently linked to phospholipids and protein molecules.

11 Plasma Membrane Proteins, which are a major molecular constituent of membranes (about 50% in the plasma membrane), can be divided into two groups: Integral proteins are directly incorporated within the lipid bilayer. Peripheral proteins exhibit a looser association with membrane surfaces.

12 Plasma Membrane Some integral proteins span the membrane one or more times, from one side to the other. One-pass transmembrane proteins Multipass transmembrane proteins

13 Plasma Membrane Membrane cleavage occurs when a cell is frozen and fractured (cryofracture). Most of the membrane particles (1( are proteins or aggregates of proteins that remain attached to the half of the membrane adjacent to the cytoplasm (P, or protoplasmic, face of the membrane). Fewer particles are found attached to the outer half of the membrane (E, or extracellular, face).

14 Plasma Membrane For every protein particle that bulges on one surface, a corresponding depression )2) appears in the opposite surface. Membrane splitting occurs along the line of weakness formed by the fatty acid tails of membrane phospholipids, since only weak hydrophobic interactions bind the halves of the membrane along this line.

15 Plasma Membrane The ultrastructure and molecular organization (right) of the cell membrane. The dark lines at the left represent the two dense layers observed in the electron microscope; these are caused by the deposit of osmium in the hydrophilic portions of the phospholipid molecules.

16 Plasma Membrane Membranes range from 7.5 to 10 nm in thickness Exhibit a trilaminar structure after fixation in osmium tetroxide The three layers seen in the electron microscope are apparently produced by the deposit of reduced osmium on the hydrophilic groups present on each side of the lipid bilayer.

17 Plasma Membrane Membrane proteins are synthesized in the rough endoplasm reticulum, their molecules are completed in the Golgi apparatus, and they are transported in vesicles to the cell surface

18 Functions of Plasma Membrane A selective barrier that regulates the passage of certain materials into and out of the cell and facilitates the transport of specific molecule. Keep constant the intracellular milieu Carry out a number of specific recognition and regulatory functions.

19 Fluid-Phase Pinocytosis Small invaginations of the cell membrane form and entrap extracellular fluid and anything in solution in the fluid. Pinocytotic vesicles (about 80 nm in diameter) pinch off from the cell surface and most eventually fuse with lysosomes. Pinocytotic vesicles may move to the surface opposite their origin.

20 Receptor-Mediated Endocytosis Ligands, such as hormones and growth factors, bind to specific surface receptors and are internalized in pinocytotic vesicles coated with clathrin and other proteins. After the liberation of the coating molecules, the pinocytotic vesicles fuse with the endosomal compartment, where the low ph causes the separation of the ligands from their receptors.

21 Receptor-Mediated Endocytosis Membrane with receptors is returned to the cell surface to be reused. The ligands typically are transferred to lysosomes. The cytoskeleton with motor proteins is responsible for all vesicle movements described.

22 Receptor-Mediated Endocytosis Internalization of low-density lipoproteins (LDL) is important to keep the concentration of LDL in body fluids low. LDL, which is rich in cholesterol, binds with high affinity to its receptors in the cell membranes. This binding activates the formation of pinocytotic vesicles from coated pits.

23 Receptor-Mediated Endocytosis The vesicles soon lose their coating, which is returned to the inner surface of the plasmalemma: the uncoated vesicles fuse with endosomes. In the next step, the LDL is transferred to lysosomes for digestion and separation of their components to be utilized by the cell.

24 Phagocytosis Certain cell types, such as macrophages and polymorphonuclear leukocytes, are specialized for incorporating and removing foreign bacteria, protozoa, fungi, damaged cells, and unneeded extracellular constituents.

25 Exocytosis Fusion of a membrane-limited structure with the plasma membrane, resulting in the release of its contents into the extracellular space without compromising the integrity of the plasma membrane. A typical example is the release of stored products from secretory cells, such as those of the exocrine pancreas and the salivary glands.

26 Organelles Mitochondria Ribosomes Endoplasmic Reticulum Golgi Complex Lysosomes Secretory Vesicles

27 Mitochondria Are spherical or filamentous organelles µm wide that can attain a length of up to 10 µm. They tend to accumulate in parts of the cytoplasm at which the utilization of energy is more intense, such as the apical ends of ciliated cells.

28 Mitochondria In the middle piece of spermatozoa. At the base of iontransferring cells.

29 Mitochondria They are composed of an outer and an inner mitochondrial membrane; The inner membrane projects folds, termed cristae,into the interior of the mitochondrion. The compartment located between the two membranes is termed the intermembrane space. The inner membrane encloses the other compartment the intercristae, or matrix, space.

30 Mitochondria Between the cristae is an amorphous matrix,rich in protein and containing circular molecules of DNA and the three varieties of RNA. In a great number of cell types, the mitochondrial matrix also exhibits Rounded electron-dense granules rich in Ca +2 Enzymes for the citric acid (Krebs) cycle and fatty acid βoxidation

31 Mitochondria The globular structures are a complex of proteins with ATP synthetase activity.

32 Dr. Sami Zaqout JUST

33 Mitochondria Several diseases of mitochondrial deficiency have been described, and most of them are characterized by muscular dysfunction. Because of their high-energy metabolism, skeletal muscle fibers are very sensitive to mitochondrial defects. Mitochondrial inheritance is maternal. In the case of nuclear DNA defects, inheritance may be from either parent or both parents. Generally, in these diseases the mitochondria show morphological change.

34 Ribosomes Ribosomes are small electrondense particles, about 20 x 30 nm in size. They are composed of four types of rrna and almost 80 different proteins. Composed of two differentsized subunits. The RNA molecules of both subunits are synthesized within the nucleus. Ribosomes are intensely basophilic

35 Ribosomes Proteins synthesized for use within the cell and destined to remain in the cytosol are synthesized on polyribosomes existing as isolated clusters within the cytoplasm.

36 Ribosomes Polyribosomes that are attached to the membranes of the endoplasmic reticulum (via their large subunits) translate mrnas that code for proteins that are segregated into the cisternae of the reticulum. These proteins can be secreted (eg, pancreatic and salivary enzymes) or stored in the cell (eg, enzymes of lysosomes, proteins within granules of white blood cells [leukocytes]). Integral proteins of the plasma membrane are synthesized on polyribosomes attached to membranes of the endoplasmic reticulum

37 Endoplasmic Reticulum The endoplasmic reticulum is an anastomosing network of intercommunicating channels and sacs formed by a continuous membrane. Smooth endoplasmic reticulum is devoid of ribosomes. Ribosomes (the small dark dots are present in the rough endoplasmic reticulum. The cisternae of the smooth reticulum are tubular, whereas in the rough reticulum they are flat sacs.

38 Rough Endoplasmic Reticulum Rough endoplasmic reticulum (RER) is prominent in cells specialized for protein secretion, such as Pancreatic acinar cells (digestive enzymes), Fibroblasts (collagen), Plasma cells (immunoglobulins).

39 Rough Endoplasmic Reticulum The principal function of the RER is to segregate proteins not destined for the cytosol. Additional functions include The initial (core) glycosylation of glycoproteins The synthesis of phospholipids The assembly of multichain proteins, and certain posttranslational modifications of newly formed polypeptides.

40 Smooth Endoplasmic Reticulum Found in cells that synthesize steroid hormones (e.g., cells of the adrenal cortex), SER occupies a large portion of the cytoplasm and contains some of the enzymes required for steroid synthesis.

41 Smooth Endoplasmic Reticulum SER is abundant in liver cells, where it is responsible for the oxidation, conjugation, and methylation processes employed by the liver. SER contains the enzyme glucose-6-phosphatase, which is involved in the utilization of glucose originating from glycogen in liver cells.

42 Smooth Endoplasmic Reticulum Synthesis of phospholipids for all cell membranes. The phospholipid molecules are transferred from the SER to other membranes (1) by vesicles that detach and are moved along cytoskeletal elements by the action of motor proteins. (2) through direct communication with the RER. (3) by transfer proteins.

43 Smooth Endoplasmic Reticulum SER participates in the contraction process in muscle cells, where it appears in a specialized form, called the sarcoplasmic reticulum, that is involved in the sequestration and release of the calcium ions that regulate muscular contraction.

44 Golgi Complex (Golgi Apparatus) The Golgi complex completes posttranslational modifications and packages and places an address on products that have been synthesized by the cell. This organelle is composed of smooth membrane-limited cisternae.

45 Golgi Complex (Golgi Apparatus) In highly polarized cells, such as mucussecreting goblet cells the Golgi complex occupies a characteristic position in the cytoplasm between the nucleus and the apical plasma membrane.

46 Golgi Complex (Golgi Apparatus) Through transport vesicles that fuse with the Golgi cis face, the complex receives several types of molecules produced in the rough endoplasmic reticulum (RER). After Golgi processing, these molecules are released from the Golgi trans face in larger vesicles to constitute secretory vesicles, lysosomes, or other cytoplasmic components.

47 Dr. Sami Zaqout JUST

48 Dr. Sami Zaqout JUST

49 Lysosomes Lysosomes are sites of intracellular digestion and turnover of cellular components. Lysosomes are membrane-limited vesicles that contain a large variety of hydrolytic enzymes (more than 40) whose main function is intracytoplasmic digestion

50 Lysosomes Lysosomal enzymes are capable of breaking down most biological macromolecules. Lysosomal enzymes have optimal activity at an acidic ph. The enveloping membrane separates the lytic enzymes from the cytoplasm, preventing the lysosomal enzymes from attacking and digesting cytoplasmic components.

51 Lysosomes Synthesis occurs in the rough endoplasmic reticulum (RER), and the enzymes are packaged in the Golgi complex. Secondary lysosomes. Heterophagosomes, in which bacteria are being destroyed, Autophagosomes, with RER and mitochondria in the process of digestion.

52 Lysosomes The result of their digestion can be excreted, but sometimes the secondary lysosome creates a residual body, containing remnants of undigested molecules. Large quantities of residual bodies accumulate and are referred to as lipofuscin, or age pigment. In some cells, such as osteoclasts, the lysosomal enzymes are secreted to the extracellular environment.

53 Lysosomes Lysosomes play an important role in the metabolism of several substances in the human body, and consequently many diseases have been ascribed to deficiencies of lysosomal enzymes.

54 Proteasomes Multiple-protease complexes that digest proteins targeted for destruction by attachment to ubiquitin. Proteasomes deal primarily with proteins as individual molecules Lysosomes digest bulk material introduced into the cell or whole organelles and vesicles.

55 Peroxisomes Peroxisomes are spherical membrane-limited organelles whose diameter ranges from 0.5 to 1.2 µm Peroxisomes oxidize specific organic substrates by removing hydrogen atoms that are transferred to molecular oxygen (O2). This activity produces hydrogen peroxide (H2O2), a substance that is very damaging to the cell. However, H2O2 is eliminated by the enzyme catalase, which is present in peroxisomes

56 Peroxisomes Peroxisomes contain enzymes involved in lipid metabolism. Probably the most common peroxisomal disorder is X- chromosome-linked adrenoleukodystrophy, caused by a defective integral membrane protein that participates in transporting very long-chain fatty acids into the peroxisome for β oxidation. Accumulation of these fatty acids in body fluids destroys the myelin sheaths in nerve tissue, causing severe neurological symptoms.

57 Peroxisomes Deficiency in peroxisomal enzymes causes the fatal Zellweger syndrome, with severe muscular impairment, liver and kidney lesions, and disorganization of the central and peripheral nervous systems. Electron microscopy reveals empty peroxisomes in liver and kidney cells of these patients.

58 Secretory Vesicles and Granules Secretory vesicles are found in those cells that store a product until its release is signaled by a metabolic, hormonal, or neural message (regulated secretion). These vesicles are surrounded by a membrane and contain a concentrated form of the secretory products.

59 Secretory Vesicles, or Granules Secretory vesicles containing digestive enzymes are referred to as zymogen granules.

60 The Cytoskeleton Microtubules Actin filaments Intermediate filaments

61 Functions of the Cytoskeleton Shaping of cells Movements of organelles and intracytoplasmic vesicles. Participates in the movement of entire cells.

62 Microtubules Found within the cytoplasmic matrix. Also found in cytoplasmic processes called cilia and flagella. It is a polarized structure has an alternation of the two subunits α and β of the tubulin molecule. Tubulin molecules are arranged to form 13 protofilaments.

63 Microtubules Changes in microtubule length are due to the addition or loss of individual tubulin subunits. Polymerization of tubulins to form microtubules in vivo is directed by a variety of structures collectively known as microtubuleorganizing centers. Cilia Basal bodies Centrosomes.

64 Microtubules Cytoplasmic microtubules are stiff structures that play a significant role in the development and maintenance of cell shape. They are usually present in a proper orientation, either to effect development of a given cellular asymmetry or to maintain it. Microtubules also participate in the intracellular transport of organelles and vesicles. Axoplasmic transport in neurons Melanin transport in pigment cells Chromosome movements by the mitotic spindle Vesicle movements among different cell compartments

65 Microtubules Microtubules provide the basis for several complex cytoplasmic components: Centrioles Basal bodies Cilia Flagella

66 Centrioles Centrioles consist of nine microtubule triplets linked together in a pinwheel-like arrangement. In the triplets, microtubule A is complete and consists of 13 subunits, whereas microtubules B and C share tubulin subunits. Under normal circumstances, these organelles are found in pairs with the centrioles disposed at right angles to one another.

67 Centrosome Close to the nucleus of nondividing cells is a centrosome made of a pair of centrioles surrounded by a granular material. In each pair, the long axes of the centrioles are at right angles to each other.

68 Cilia and flagella Cilia and flagella are motile processes, covered by cell membrane, with a highly organized microtubule core. Ciliated cells typically possess a large number of cilia, each about 2 3 µm in length. Flagellated cells have only one flagellum, with a length close to 100 µm. In humans, the spermatozoa are the only cell type with a flagellum. The main function of cilia is to sweep fluid from the surface of cell sheets. Both cilia and flagella possess the same core organization.

69 Cilia and flagella A cross section through a cilium reveals a core of microtubules called an axoneme. The axoneme consists of two central microtubules surrounded by nine microtubule doublets. In the doublets, microtubule A is complete and consists of 13 subunits, whereas microtubule B shares two or three heterodimers with A.

70 Cilia and flagella When activated by ATP, the dynein arms link adjacent tubules and provide for the sliding of doublets against each other. At the base of each cilium or flagellum is a basal body essentially similar to a centriole, that controls the assembly of the axoneme.

71 Actin Filaments Contractile activity in muscle cells results primarily from an interaction between two proteins: Actin Myosin. Actin is present in muscle as a thin (5 7 nm in diameter) filament composed of globular subunits organized into a double-stranded helix.

72 Actin Filaments 1) In skeletal muscle, they assume a paracrystalline array integrated with thick (16-nm) myosin filaments. 2) In most cells, actin filaments form a thin sheath just beneath the plasmalemma, called the cell cortex. These filaments appear to be associated with membrane activities such as endocytosis, exocytosis, and cell migratory activity. 3) Actin filaments are intimately associated with several cytoplasmic organelles, vesicles, and granules. The filaments are believed to play a role in moving and shifting cytoplasmic components (cytoplasmic streaming.

73 Actin Filaments 4) Actin filaments are associated with myosin and form a "purse-string" ring of filaments whose constriction results in the cleavage of mitotic cells. 5) In most cells, actin filaments are found scattered in what appears to be an unorganized fashion within the cytoplasm.

74 Intermediate Filaments Cells contain a class of intermediate-sized filaments with an average diameter of nm. Several proteins that form intermediate filaments have been isolated and localized by immunocytochemical means.

75 Intermediate Filaments The presence of a specific type of intermediate filament in tumors can reveal which cell originated the tumor, information important for diagnosis and treatment

76 Cytoplasmic Deposits Cytoplasmic deposits are usually transitory components of the cytoplasm, composed mainly of accumulated metabolites or other substances. Lipid droplets Glycogen Proteins

77 Cytoplasmic Deposits Deposits of pigments are often found in cells. Lipofuscin Carotene Melanin

78 Cytosol The final supernatant produced by centrifugation, after the separation of organelles, is called the cytosol. The cytosol constitutes about half the total volume of the cell. The cytosol coordinates the intracellular movements of organelles and provides an explanation for the viscosity of the cytoplasm. It contains thousands of enzymes that produce building blocks for larger molecules and break down small molecules to liberate energy. All machinery to synthesize proteins (rrna, mrna, trna, enzymes, and other factors) is contained in the cytosol.

79 Cell Components & Diseases

80 The Cell Nucleus The nucleus contains a blueprint for all cell structures and activities encoded in the DNA of the chromosomes. It also contains the molecular machinery to replicate its DNA and to synthesize and process the three types of RNA:- ribosomal (rrna) messenger (mrna), transfer (trna).

81 The Cell Nucleus The nucleus frequently appears as a rounded or elongated structure, usually in the center of the cell.

82 The Cell Nucleus Nuclear envelope Chromatin Nucleolus Nuclear matrix

83 Nuclear Envelope The nuclear envelope is composed of two membranes of the endoplasmic reticulum, enclosing a perinuclear cisterna. Where the two membranes fuse, they form nuclear pores. Ribosomes are attached to the outer nuclear membrane.

84 Nuclear Envelope Heterochromatin clumps are associated with the nuclear lamina, whereas the euchromatin (EC) appears dispersed in the interior of the nucleus. Closely associated with the internal membrane of the nuclear envelope is a protein structure called the fibrous lamina which helps to stabilize the nuclear envelope.

85 Nuclear Envelope Nuclear pores provide controlled pathways between the nucleus and the cytoplasm. The pores are not open but show an octagonal pore complex made of more than 100 proteins.

86 Chromatin Chromatin, in nondividing nuclei, is in fact the chromosomes in a different degree of uncoiling. According to the degree of chromosome condensation, two types of chromatin can be distinguished with both the light and electron microscopes.

87 Chromatin Heterochromatin which is electron dense, appears as coarse granules in the electron microscope and as basophilic clumps in the light microscope. Euchromatin is the less coiled portion of the chromosomes, visible as a finely dispersed granular material in the electron microscope and as lightly stained basophilic areas in the light microscope.

88 Chromatin The chromatin pattern of a nucleus has been considered a guide to the cell's activity. In general, cells with light nuclei are more active than those with condensed, dark nuclei. In light-stained nuclei (with few heterochromatin clumps), more DNA surface is available for the transcription of genetic information. In dark-stained nuclei (rich in heterochromatin), the coiling of DNA makes less surface available.

89 Sex chromatin The X chromosome that constitutes the sex chromatin remains tightly coiled and visible, whereas the other X chromosome is uncoiled and not visible. Evidence suggests that the sex chromatin is genetically inactive.

90 Nucleolus The nucleolus is a spherical structure that is rich in rrna and protein. It is usually basophilic when stained with hematoxylin and eosin.

91 Nucleolus Nucleolar organizer DNA sequences of bases that code for rrna. Pars fibrosa, which consists of primary transcripts of rrna genes. Pars granulosa consists of 15- to 20-nm granules (maturing ribosomes). Nucleolus-associated chromatin Heterochromatin is often attached to the nucleolus

92 Nuclear Matrix The nuclear matrix is the component that fills the space between the chromatin and the nucleoli in the nucleus. It is composed mainly of proteins (some of which have enzymatic activity), metabolites, and ions.

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