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INTRODUCTION TO ANATOMY AND . THE CELL

1. Aims and scope of anatomy 2. Methods of morphological examination 3. Aims and scopes of cytology, and embryology 4. Methods for microscopic observations 5. The cell – basic structural and functional unit  cellular organization and chemical composition   cell – membranous and non-membranous Aims and scope of human anatomy

Anatomy – knowledge of the structure of living things Gr. ἀνατοία anatomia = to cut apart; from ἀνατένειν ana: separate, apart from, and temnein , to cut up, cut open human anatomy  anatomy (zootomy) plant anatomy (phytotomy) Human anatomy: Aim: how is the human body organized? structure of living organism spatial organization of living matter Scope (mission): why it is so organized? regularity of the structure functional approach Prof. Dr. Nikolai Lazarov 2 Major anatomical disciplines  Systemic anatomy  Topographical (regional) anatomy  Plastic anatomy  Clinical (applied) anatomy  Dynamic anatomy (functional anatomy of the locomotor apparatus)  Comparative anatomy  the study of phylogenesis (Gr. φυλή/φ ῦλον, phyle/phylon = "tribe, race" + genesis, “ creation”, from Gr."gignesthai" = "to be born")  Embryology  the study of ontogeny, ontogenesis (ontos, present participle of “to be” + genesis, “creation”)  Anthropology – the study of human behavior (Gr. ἄνθρωπος, anthrōpos = "human")  Morphology – the study of the form or shape of an organism (Gr. morphe, “ form”) = anatomy + cytology + histology + embryology NB: Morpheus (Gr: Μορφέας, Μορφεύς, "he who forms, shapes, moulds", from the Greek morphe) is the Greek god of dreams and sleep Prof. Dr. Nikolai Lazarov 3 Systemic anatomy

 Locomotor system (apparatus) –  Osteology , scientific study of bones – Osteologia , Gr. os, ossis = bone  Arthrology , study of articulations and ligaments – Arthrologia , Gr. arthros = joint  Myology , specialized study of muscles – Myologia , Gr. myos = muscle  Internal organs, viscera – Splanchnology  alimentary system  respiratory system  urogenital system  endocrine – endocrinology  Cardiovascular system – Angiology  system – Neuroanatomy  organs and integument, Prof. Dr. Nikolai Lazarov 4 Methods of morphological investigations  Dissection, Gr. anatemnein = separate HIC MORTUI VIVOS DOCENT  Ink injection technology  Corrosion method  Plastination  Graphic and plastic reconstruction  Imaging anatomy:  Roentgen anatomy  Xray computed tomography (CT)  Magnetic resonance imaging (MRI)  Microscopic techniques:  Light microscopy  Electron microscopy  Experimental anatomy Prof. Dr. Nikolai Lazarov 5 Regional texture of the human body

 Parts of the body:  head, caput  neck, collum  trunk, truncus thorax, thorax abdomen, abdomen pelvis, pelvis  extremities (limbs) upper, membrum superius lower, membrum inferius

Prof. Dr. Nikolai Lazarov 6 Major axes and planes in the human body

 Three main axes and planes:

 sagittal axis – anteriorposterior

 transversal axis – transverse

 longitudinal axis – superiorinferior

 sagittal plane – median section

 transversal plane – axial section

 frontal plane – coronal section

Prof. Dr. Nikolai Lazarov 7 Spatial orientation in the human body

 Spatial terminology: (main axes of the human body )  frontal plane – frons,tis m.  anterior,us = ventralis,e  posterior,us = dorsalis,e  sagittal plane – sagitta,ae f.  medialis,e ↔ lateralis,e  proximalis,e ↔ distalis,e  median plane  sinister ↔ dexter  transversal (horizontal) plane  superior,us = cranialis,e  inferior,us =caudalis,e Prof. Dr. Nikolai Lazarov 8 Anatomical Nomenclature Nomina Anatomica

 End of 19 th century – over 50 000 anatomical terms  1895 – Basle Nomina Anatomica (BNA ): 5528 anatomical terms  1933 – Birmingham Revision (BR )  1935 – Jena Nomina Anatomica (JNA )  1955 – Parisiensia Nomina Anatomica (PNA, NA ): 5640 anatomical terms Revisions of Nomina Anatomica :  1960 – New York  1965 – Wiesbaden  1970 – Saint Petersburgs (formerly Leningrad)  1975 – Tokyo  1980 – Mexico City  1983 – last 5th edition of Nomina Anatomica  1985 – Nomina Histologica and Nomina Embryologica  1998 – Terminologia Anatomica (TA ) Prof. Dr. Nikolai Lazarov 9 Objective of cytology, histology and embryology

Cytology – now Cell Biology: (Gr. κύτος, kytos, a hollow + logos, study)

Histology: (Gr. ἱστός , histos, web or tissue + logos ) general histology special histology = microscopic anatomy of organs

Embryology: (Gr. έβρυον, embryon + logos ) general embryology (embryogenesis) special embryology (organogenesis)

Prof. Dr. Nikolai Lazarov 10 Levels of organization

 Levels of organization: cell  tissue  organ   organism  The cell:  the basic structural and functional unit of all known living organisms  the smallest unit of life – the building block of body  Major cell abilities:  reproduction by cell division  the functioning of a cell depends upon its ability to extract and use chemical energy stored in organic molecules  response to stimuli such as changes in temperature, pH or levels of nutrients  cell contents are contained 11 within a cell surface membrane Prof. Dr. Nikolai Lazarov 11 The cell – evolutionary levels The biological universe consists of two cell types:

 Prokaryotic cells (Gr. πρό (pro) "before" + καρυόν (karyon) “nut or kernel", referring to the )  and archaea  Eukaryotic cells – "true nucleus" (Gr. eυ (eu), "good", "true")  multicellular organisms  internal compartmentalization

Prof. Dr. Nikolai Lazarov 12 The cell – external morphology  200 different cell types that come in an astounding assortment of shapes and sizes:  size – 5200 µm  smallsized – up to 10 µm  mediumsized – 1020 µm  largesized – > 20 µm  shape – related to their function:  spherical  spindleshaped  squamous, cuboidal ...  color:  colorless  pigmented

Prof. Dr. Nikolai Lazarov 13 The cell – chemical composition

 essential elements:  macroelements – 9899% of the cell mass C, N, O, H  microelements – up to 0.000001% Cu, Zn, Mg  ultra trace elements – ≤0.000001% Hg, Ag, U, Ra  water – 7080%  exogenous – ⅔  endogenous – ⅓  inorganic molecules:  free –  bound with organic molecules  organic compounds:   lipids  proteins 14  nucleic acids Prof. Dr. Nikolai Lazarov 14 Basic cellular architecture

 nucleus (Lat., nux, nut)  (Gr. kytos , cell + plasma , thing formed)  organelles (“little organs”)  universal and specialized  membranous (membranelimited)  nonmembranous  cytoplasmic inclusions  deposits of carbohydrates, lipids, and pigments  (cytoplasmic matrix )

Prof. Dr. Nikolai Lazarov 15 Plasma (cell) membrane

 Plasma membrane , synonym: plasmalemma (Gr. lemma = 'husk')  thickness – 810 nm (EM)  asymmetrical  Chemical composition:  lipids – 2040%   steroids (cholesterol)  – 210%  proteins – ~50%  hydrophobic – structural  hydrophilic – receptors and >30  carbohydrates – 10%   glycolipids  glycocalyx 16

Prof. Dr. Nikolai Lazarov 16

 Lipidprotein mosaic model  structural skeleton – double layer  globular proteins: Seymour  integral membrane proteins, Jonathan Singer (singlepass and multipass (1924-) transmembrane proteins)  peripheral proteins  freezefracture:  Pface (protoplasmic)  Еface (extracellular)

Garth L. Nicolson (1943-)

Prof. Dr. Nikolai Lazarov 17 Membrane proteins – structure and functions

 Membrane proteins:  ~50% w/w in the plasmalemma  synthesized in the rough endoplasm reticulum  their molecules are completed in the  transported in vesicles to the cell surface  Functional categories:  transport proteins  structural proteins (membraneanchored)  receptor proteins  enzymes

Prof. Dr. Nikolai Lazarov 18 Cell coat (glycocalyx)

 First description – Yamada (1955)  Synonym = glycolemma  thickness – up to 100 nm  renewal – 68 h  PASpositive  Chemical composition:  glycolipids  cerebrosides  gangliosides  glycoproteins   hyaluronic acid  Functions :  defense  absorption  immunologic role  cell recognition  Prof. Dr. Nikolai Lazarov 19 Cell surface modifications

 4 types structural specializations: (Gr. mikros, small + Lat. villus, tuft of hair)  Microvilli: cytoplasmic processes, 1 µm high;0.08 µm wide brush (striated) border core of filaments terminal web  Basal cell surface folds: interdigitations  : nonmotile microvilli of unusual length  ductus epididymis  hair cells of the

 Cilia & Flagella Prof. Dr. Nikolai Lazarov 20 Intercellular junctions  3 types intercellular junctions:

 Barrier (impermeable) junctions: , zonula occludens occluding strip, fascia occludens occluding spot, macula occludens

 Adhering (anchoring) junctions: punctum adhaerens belt , zonula adhaerens spot desmosome, macula adhaerens (Gr. desmos, band + soma, body)  Communicating junctions: , nexus synapse 21  Junctional complex Prof. Dr. Nikolai Lazarov 21 Membrane-limited organelles

  Annulate lamellae  Mitochondria  Golgi apparatus    Secretory vesicles  Transport vesicles   Coated vesicles 22

 Nucleus Prof. Dr. Nikolai Lazarov 22 Endoplasmic reticulum

 Endoplasmic reticulum:  rough  smooth

rough endoplasmic reticulum

protein synthesis 23 Prof. Dr. Nikolai Lazarov 23 Rough (granular) endoplasmic reticulum

 Structure:  cisternae – 78 nm   Functions:  protein synthesis and segregation:  intracellular utilization  extracellular export  initial glycosylation of glycoproteins  phospholipid synthesis  Prominent in protein synthesizing cells:  blast cells  exocrine cells  plasma cells

 neurons Prof. Dr. Nikolai Lazarov 24 Smooth (agranular) endoplasmic reticulum

 Structure:  tubular cisternae – 67 nm  lacks the associated ribosomes  Functions:  lipid absorption and metabolism  glycogen metabolism  synthesis of steroid  regulation of Ca 2+ concentration  drug detoxification  Welldeveloped in:  steroidproducing cells:  cells of adrenal cortex  interstitial cells of gonads  other cell types:  cells ()  skeletal and cardiac muscle cells – sarcoplasmic reticulum  nerve cells (neurons)  glandular cells Prof. Dr. Nikolai Lazarov 25 Golgi Apparatus

 ital . – apparato reticolare interno: Cammillo Golgi, 1886, 1898 Cammillo  Synonyms: Golgi  Golgi complex (18431926)  Golgi zone  Golgi bodies  Ultrastructure: A. Dalton, M. Felix, 1953 Dictyosome:  stacks of smooth membranelimited:

 312 flattened cisternae (50200 nm)

 vesicles (3050 nm)

 large, clear (200300 nm) 26 Prof. Dr. Nikolai Lazarov 26 Golgi Apparatus – structure

 both morphologically and functionally polarized structure:

Prof. Dr. Nikolai Lazarov 27 Golgi Apparatus – functional polarity

 trafficking and sorting of proteins:  glycosylation, sulfation, phosphorylation , and limited proteolysis of proteins  initiates packing, concentration, and storage of secretory products

Prof. Dr. Nikolai Lazarov 28 Secretory vesicles

 Secretory granules:  shape – spherical  diameter – 0.15 µm>1 µm  clathrincoated vesicles  core – histamine, chromogranin В, secretogranin ІІ

Neurosecretosomes – hormones

Zymogen granules – digestive enzymes Synaptic vesicles – transmitters

Prof. Dr. Nikolai Lazarov 29 Lysosomes  (Gr. lysis , dissolution or destruction + soma , body)  Discovered by Christian de Duve, 1955

Christian de Duve (1917)

Spherical organelles:  size – 0.050.5 m  single layer (unit) membrane – 6 nm  lysosomal matrix – pH 5  favorable for enzymatic activity  more than 40 hydrolytic enzymes

Prof. Dr. Nikolai Lazarov 30 Lysosomes – stages

 Primary lysosomes: inactive enzymes  Secondary lysosomes (, phagolysosomes):  heterolysosomes (heterophagosomes)  autophagosomes (autophagic vacuoles)  residual bodies (telolysosomes)  lipofuscin droplets  pinocytotic vesicles  multivesicular bodies

Prof. Dr. Nikolai Lazarov 31 Lysosomes – "suicide-bags" or "suicide-sacs"  (autophagy – self , Gr. auto , self + phagy , to eat)

 autophagic cell death – a form of programmed self destruction (autolysis)

 the cells' garbage disposal system Prof. Dr. Nikolai Lazarov 32 Peroxisomes ()

 identified by EM as organelles by Christian de Duve , 1967  Gr. peroxide + soma, body  microbodies: Rhodin, 1954 Spherical organelles: 70100/cell  size – 0.53 m (macroperoxisomes)  microperoxisomes – 0.10.3 m  homogeneous matrix (crystalloid core or nucleoid)  marginal plate  single layer membrane – 68 nm

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Prof. Dr. Nikolai Lazarov 33 Peroxisomes – structure and function

 Enzymes : >50 catalase – 40% peroxidase βoxydase of very longchain fatty acids D and Lamino oxydases urate oxidase

 Functions :  a compartment for oxidation reactions:

 decomposes H 2O2 to H 2O and O 2 and eliminates it  degrades several toxic molecules and prescription drugs  involved in lipid biosynthesis

 important role in cellular respiration Prof. Dr. Nikolai Lazarov 34 Mitochondria  vitally staining – Janus green B  Gr. mitos , thread + chondros , : Carl Benda, 1898  First observations:  Kölliker, 1850  Flemming, 1882  R. Altman, 1890: bioblasts  Size:  0.51 m wide  length up to 10 m  Number – varying:  fibroblasts – 100  hepatocytes – 800 (25%)

 oocytes – 300 000 Prof. Dr. Nikolai Lazarov 35 Mitochondria – structure

 Ultrastructure: G. Palade, F.S. Sjöstrand, 1952  two mitochondrial membranes:

outer (67 nm) ~50% proteins and lipids: transport proteins (porin) enzymes: oxidases, hydrolases, transferases, enzymes of fatty acid metabolism, cytochromes inner : 80% proteins and cardiolipin reductases, oxidases, dehydrogenases, ATP synthase, transferases, cytochromes enzymes for oxidative phosphorylation and for electron transport system (cytochromes) forms cristae (tubules) – intracristal space attached elementary particles  intramembranous space (outer chamber) – 4-10 nm  matrix – intercristal (matrix) space Prof. Dr. Nikolai Lazarov 36 Mitochondria – structure and function

 Mitochondrial matrix: (intercristal space; inner chamber) rich in proteins, DNA, RNA  matrix granules: 3050 nm; storage site for divalent cations – Ca 2+ , Mg 2+  mitoribosomes (mrRNA): 1520 nm  mitochondrial mRNA, tRNA  circular DNA: 23 nm  RNA and DNApolymerases  Krebs cycle enzymes  enzymes for lipid synthesis  enzymes for protein synthesis  Origin of mitochondria:  evolutionary from an ancestral aerobic adapted to an endosymbiotic life (intracellular symbiosis)  new mitochondria – from preexisting mitochondria 37 by growth and subsequent division (fission) Prof. Dr. Nikolai Lazarov 37 Mitochondria – the power plants of the cell

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Prof. Dr. Nikolai Lazarov 38 Cell Nucleus

 R. Brown, 1831 – (Lat. nucleus, kernel; Gr. karyon , nut)  in all eukaryotic cells – with exception of Er  number – uninuclear , binuclear , multinuclear cells  localization – centrally or peripherally Robert Brown  external morphology: (17731858)  shape – speciesdiversified  size – 10% of the cell volume; 5 µm (spermatozoon), 40 µm (oogonium)

Prof. Dr. Nikolai Lazarov 39 Nucleus – structure

 Structural components:   chromatin   nuclear matrix (nucleoplasm)

Prof. Dr. Nikolai Lazarov 40 Nuclear envelope

 First description : M. Watson , 1955  Ultrastructure:  outer nuclear membrane – 6 nm  ribosomes  rER  vimentin filaments  inner nuclear membrane – 6 nm  nuclear lamina – 100300 nm lamins A, B, C  chromatin  perinuclear space – 1040 nm  nuclear pores

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Prof. Dr. Nikolai Lazarov 41 Chromatin

 First description: W. Flemming, 1882  Heterochromatin (condensed ) – 90% Gr. heteros, other + chroma , color:  marginal chromatin – nuclear membrane  chromocenters – nucleoplasm  nucleolarassociated chromatin:  perinucleolar  intranucleolar  constitutive heterochromatin – inactive, around the chromosome centromere and near telomeres  facultative heterochromatin  euchromatin and sex chromatin  Euchromatin (extended) – 10% Gr. eu, good, true:  a lightly packed form of chromatin (DNA, RNA and protein)  comprises the most active portion of the genome within the cell nucleus – replication and transcription Prof. Dr. Nikolai Lazarov 42 Sex chromatin

 synonym: Barr body – only in females Barr, Bertram, 1949  tightly packed inactive Х chromosome  localization:  adhering to the nuclear envelope diameter – 1 µm  “drumsticklike” appendage to the nuclei Murray L.  Medical application: Barr  diagnostics in endocrinology (19081995)  forensic medicine practice  study of inherited chromosome anomalies – Klinefelter's and Turner syndromes etc.  disclosure of the genetic sex – in hermaphroditism and pseudohermaphroditism

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Prof. Dr. Nikolai Lazarov 43 Nucleolus

 First description: Fontana, 1774  Number: 1 max. 10:  metabolically active cells  embryonic cells  during proliferation  rapidly growing malignant tumors  External morphology:  nonmembrane bound structure  shape – spherical; compact, reticular, annular etc.  diameter – 13 µm  Formation:  nucleolar organizers – short arms of chromosomes 13, 14, 15, 21 and 22 (the acrocentric chromosomes)

Prof. Dr. Nikolai Lazarov 44 Nuclear matrix

 synonyms : nucleoplasm, karyoplasm  a highly dynamic structure  Composition – amorphous:  proteins + RNA – nucleoskeleton nuclear lamina – lamins A, B, C  numerous enzymes  metabolites  ions  crystalline inclusions  viruses and  other inclusions

Prof. Dr. Nikolai Lazarov 45 Ribosomes

 small electrondense particles, 20 x 30 nm in size

George Emil 1943 – Albert Claude  “microsomes” Palade 1955 – George Palade  Palade granules (19122008) 1958 – Richard B. Roberts  “ribosomes” The Nobel Prize 65% rRNA and 35% ribonucleoproteins in Physiology or Medicine 1974

"for studies of the structure and function of the " Prof. Dr. Nikolai Lazarov 46 Ribosomes

free ribosomes  proteins for use within the cell monosomes and polyribosomes (polysomes) bound ribosomes (ribophorins І and ІІ)  secretory proteins (Ig, collagen, hormones) Prof. Dr. Nikolai Lazarov 47 Protein synthesis

 2 principal stages:

transcription – in the cell nucleus

translation – in the cytoplasm: initiation elongation termination  Signal hypothesis for the synthesis of secretory proteins

Prof. Dr. Nikolai Lazarov 48

 Gr. kytos, cell + skeleton, dried body , ‘misshapen', amorphos

Paul Wintrebert 1931

Prof. Dr. Nikolai Lazarov 49  nonbranching, elongated hollow cylinders, made of protein  Gr. micros , small + tubulus , tubule  a left handed , formed by FActin polymers

outer diameter = 2425 nm, varying length = several µm  seen only under EM – first described in 1963  dynamic instability – after :  stabile  labile

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Prof.Prof. Dr.Dr. NikolaiNikolai LazarovLazarov 50 Microtubules – structure

 arranged as a ring of 13 protofilaments  main component – dimeric tubulin (alpha&beta)  isolated in 1975

wall – 5 nm thick; hollow core – 14 nm wide Prof. Dr. Nikolai Lazarov 51 Microtubules – functions

 component of the cytoskeleton – development and maintenance of cell shape  intracellular transport of other organelles: motor proteins (kynesins and dyneins)  formation of the mitotic spindle

 antimitotic alkaloids – experimental inhibition of mitosis:  colchicine  vinblastine treatment (chemotherapy)  vincristine  basis for formation of , basal bodies,

cilia and flagella Prof. Dr. Nikolai Lazarov 52 Cilia and flagella

 and basal bodies – highly organized core

Prof. Dr. Nikolai Lazarov 53 Cell center

 synonym:

Oscar Hertwig  first observation: Oscar Hertwig , 1875 18491922  ЕМ description: Bessis , 1955

 diplosome (a pair of centrioles)  centrosphere

Prof. Dr. Nikolai Lazarov 54 – structure  barrelshaped cell structure composed of microtubules

 diameter: 0.150.2 µm  length: 0.30.7 µm  structure: 9 triplets (9 x 3) + 0  centriolar satellites: 4070 nm microtubule organizing centers

Prof. Dr. Nikolai Lazarov 55 Centriole – functions

 role in cell division:  formation of mitotic spindle

 role in generation of the cell's cytoskeleton:  formation of cilia and flagella  building of their basal bodies

Prof. Dr. Nikolai Lazarov 56  up to 10% of the total protein of some nonmuscle cells

 Actin filaments – thin filaments: the thinnest filaments of the cytoskeleton located close to the cell membrane grouped as bundles or networks linear polymers of actin subunits

cytochalasin: blocks actin polymerization phalloidin: promote actin polymerization ; stabilize actin polymers Prof. Dr. Nikolai Lazarov 57 Intermediate filaments

• Nuclear lamins: А, B, C

Prof. Dr. Nikolai Lazarov 58 Cytoplasmic inclusions

 small particles of insoluble substances suspended in the cytosol

 synonyms: deutoplasm, paraplasm  Cytoplasmic deposits:  proteins: secretory granules  glycogen granules  lipid inclusions (fat droplets)  crystalline inclusions  pigments: exogenous endogenous

Prof. Dr. Nikolai Lazarov 59

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Prof. Dr. Nikolai Lazarov 60

 Gr. ἔξω , out + κύτος , cell

 secretion of:  modes of secretion:  components of extracellular  matrix (collagen)   protein hormones ()  serum proteins  Prof. Dr. Nikolai Lazarov 61

 the process by which cells absorb molecules from outside the cell  Gr. endon , within  three main types of endocytosis:  phagocytosis (literally, celleating)  pinocytosis (literally, celldrinking)  receptormediated endocytosis

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Prof. Dr. Nikolai Lazarov 62

 a complex system of information signals:  communication designed for:  perceiving of cell integrity  maintenance of optimal tissue homeostasis  coordination of cell actions

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Prof. Dr. Nikolai Lazarov 63 Ways of signaling

Prof. Dr. Nikolai Lazarov 64 Kinds of communication

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Prof. Dr. Nikolai Lazarov 65 Cell cycle

G0 phase: a specialized resting state  cycle duration – 1520 h  mitosos (M phase) – 3060 min  interphase:

 G1 phase (presynthetic) – 510 h  S phase (synthetic) – 68 h

 G2 phase (postsynthetic) – 25 h

Prof. Dr. Nikolai Lazarov 66 Cell division

 the process by which a parent cell divides into two or more daughter cells

 Mitosis: somatic cells  Endomitosis:megakaryocytes (polyploid amitosis)  Amitosis: osteoclasts  Meiosis: gametes (reductional division)

Prof. Dr. Nikolai Lazarov 67 Mitosis

 Gr. mitos, a thread

 Mitotic (M phase) of the cell cycle:  prophase: 1060 min  metaphase: 1020 min  anaphase: 58 min  telophase: 2030 min  cytokinesis

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Prof. Dr. Nikolai Lazarov 68 Meiosis

 Gr. meiosis, a lessening

 Phases of meiosis – two consecutive cell divisions:  Іst meiotic division: (reduction in chromosome number) – prolonged phophase:  leptotene (leptos =thin)  zygotene (zygon =yoke): bivalents  conjugation  pachytene (pachy =thick): tetrads  crossingover  diplotene (diplos =double)  diakinesis (dia =through )  ІІ nd meiotic division: (reduction in the amount of genetic material (DNA) – similar to mitosis:  without Sphase 69

 haploid chromosome number Prof. Dr. Nikolai Lazarov 69 Cell proliferation

 Fr. proliferer, to increase

 Proliferation: a rapid increase in the number of cells

Prof. Dr. Nikolai Lazarov 70 Cell differentiation

 Differentiation: structural and functional specialization of the cell  Three categories of specialized cells:  fully differentiated, nondividing cells  potentially dividing cells  not terminally differentiated, renewal by stem cells:  unipotent cells  pluripotent (multipotent) cells potency – the capacity to differentiate into specialized cell types71 Prof. Dr. Nikolai Lazarov 71 Necrotic cell death

 Gr. nεκρός, death

 Necrosis – cell death caused by external factors, such as infection, toxins or traum:  karyopyknosis (Gr. pyknos = thick)  karyorrhexis (Gr. rhexis = to tear)  karyolysis (Gr. lysis = dissolution)

Prof. Dr. Nikolai Lazarov 72 Programmed cell death

 Gr. apo, from + ptosis , falling

 or programmed cell death – death of a cell, mediated by an intracellular program

 Pathways – caspases :  receptor pathway  mitochondrial pathway

 Phases :  latent  executive Prof. Dr. Nikolai Lazarov 73 Thankyou74… Prof. Dr. Nikolai Lazarov