introduction to anatomy and cell biology. the...

INTRODUCTION TO ANATOMY AND CELL BIOLOGY. THE CELL

1. Aims and scope of anatomy

2. Objective of cytology, histology and embryology

3. The cell – basic structural and functional unit

cellular organization and chemical composition

cell membrane

cell organelles – membranous and non-membranous

the cell nucleus

cytoplasmic inclusions

cell physiology

Prof. Dr. Nikolai Lazarov 2

Aims and scope of human anatomy

human anatomy

animal 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

Anatomy – knowledge of the structure of living things

Gr. ἀνατομία anatomia = to cut apart;from ἀνατέμνειν ana: separate, apart from,and temnein, to cut up, cut open

Locomotor system (apparatus) –

Osteology, scientific study of bones –

Osteologia, Gr. os, ossis = bone

Arthrology, study of articulationsand 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 glands – endocrinology

Cardiovascular system – Angiology Nerve system – Neuroanatomy

sense organs and integument, skinProf. Dr. Nikolai Lazarov

Systemic anatomy

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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


Major axes and planes in the human body

Three main axes and planes:

sagittal axis – anterior-posterior

transversal axis – transverse

longitudinal axis – superior-inferior

sagittal plane – median section

transversal plane – axial section

frontal plane – coronal section


Prof. Dr. Nikolai Lazarov

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

Objective of cytology, histology and embryology

Histology: (Gr. ἱστός, histos, web or tissue + logos)

general histology

special histology = microscopic anatomy of organs

Embryology: (Gr. έμβρυον, embryon + logos)

general embryology (embryogenesis)

special embryology (organogenesis)

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Levels of organization

Levels of organization:cell tissue organ

organ system

organism

The cell: the basic structural

and functional unitof all known living organisms

the smallest unit of life – the building block of body

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Prokaryotic cells(Gr. πρό- (pro-) "before" + καρυόν(karyon) “nut or kernel", referring to the cell nucleus)

bacteria and archaea

Eukaryotic cells – "true nucleus"(Gr. eυ- (eu), "good", "true") multicellular organisms internal compartmentalization

The cell –evolutionary levels

The biological universe consists of two cell types:

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200 different cell types that come in an astounding

assortment of shapes and sizes:

size – 5-200 µm

small-sized – up to 10 µm

medium-sized – 10-20 µm

large-sized – > 20 µm

shape – related to their function:

spherical

spindle-shaped

squamous, cuboidal ...

color: colorless

pigmented

The cell –external morphology

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essential elements: macroelements – 98-99%

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 – 70-80% exogenous – ⅔ endogenous – ⅓

inorganic molecules: free – ions bound with

organic molecules

organic compounds: carbohydrates lipids proteins nucleic acids

The cell –chemical composition

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nucleus (Lat., nux, nut)

cytoplasm (Gr. kytos, cell + plasma, thing formed)

organelles (“little organs”) universal and specialized membranous

(membrane-limited) nonmembranous

cytoplasmic inclusions deposits of carbohydrates,

lipids, and pigments

cytosol (cytoplasmic matrix)

Basic cellular architecture

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Plasma (cell) membrane

Plasma membrane, synonym: plasmalemma (Gr. lemma = 'husk')

thickness – 8-10 nm (EM)

asymmetrical

Chemical composition: lipids – 20-40%

phospholipids

steroids (cholesterol)

glycolipids – 2-10%

proteins – ~50% hydrophobic – structural

hydrophilic – receptors andenzymes >30

carbohydrates – 10% glycoproteins

glycolipids

glycocalyx

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Fluid mosaic model

Lipid-protein mosaic model

structural skeleton –phospholipid double layer

globular proteins:

integral membrane proteins, (single-pass and multi-pass transmembrane proteins)

peripheral proteins

SeymourJonathan

Singer

(1924-2017)

Garth L. Nicolson

(1943-)

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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 Golgi apparatus

transported in vesicles to the cell surface

Functional categories: transport proteins

structural proteins (membrane-anchored)

receptor proteins

enzymes

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Cell coat (glycocalyx)

First description – Yamada (1955)

Synonym = glycolemma thickness – up to 100 nm renewal – 6-8 h PAS-positive

Chemical composition: glycolipids

cerebrosides gangliosides

glycoproteins proteoglycans

hyaluronic acid

Functions:

defense absorption immunologic role cell recognition cell adhesion

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Cell surface modifications

(Gr. mikros, small + Lat. villus, tuft of hair)

4 types structural specializations:

Microvilli:

cytoplasmic processes, 1 µm high;0.08 µm wide

brush (striated) border

core of actin filaments

terminal web

Basal cell surface folds:

interdigitations

Stereocilia:

non-motile microvilli of unusual length

ductus epididymis

hair cells of the ear

Cilia & Flagella 16


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Membrane-limited organelles

Endoplasmic reticulum

Annulate lamellae

Mitochondria

Golgi apparatus

Lysosomes

Proteasomes

Secretory vesicles

Transport vesicles

Peroxisomes

Coated vesicles

Nucleus17


18protein synthesis

roughendoplasmic

reticulum

Endoplasmic reticulum:

rough

smooth

Endoplasmic reticulum

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Structure: cisternae – 7-8 nm ribosomes

Functions: protein synthesis and

segregation: intracellular utilization

extracellular export

initial glycosylationof glycoproteins

phospholipid synthesis

Prominent in protein-

synthesizing cells: blast cells exocrine gland cells plasma cells neurons

Rough (granular) endoplasmic reticulum

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Structure: tubular cisternae – 6-7 nm

lacks the associated ribosomes

Functions: lipid absorption and metabolism glycogen metabolism synthesis of steroid hormones regulation of Ca2+ concentration drug detoxification

Well-developed in: steroid-producing cells:

cells of adrenal cortex interstitial cells of gonads

other cell types: liver cells (hepatocytes) skeletal and cardiac muscle cells

– sarcoplasmic reticulum nerve cells (neurons) glandular cells

Smooth (agranular) endoplasmic reticulum

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Golgi Apparatus

ital. – apparato reticolare interno:

Cammillo Golgi, 1886, 1898

Synonyms: Golgi complex

Golgi zone

Golgi bodies

Ultrastructure: A. Dalton, M. Felix, 1953

Dictyosome:

stacks of smooth membrane-limited:

3-12 flattened cisternae (50-200 nm)

vesicles (30-50 nm)

large, clear vacuoles (200-300 nm)

Cammillo Golgi

(1843-1926)

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Golgi Apparatus – structure

both morphologically and functionally polarized structure:

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Golgi Apparatus –functional polarity

glycosylation, sulfation, phosphorylation,

and limited proteolysis of proteins

initiates packing,

concentration, and storage

of secretory products

trafficking and sorting of proteins:

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Zymogen granules – digestive enzymes

Secretory vesicles

Secretory granules: shape – spherical

diameter – 0.15 µm->1 µm

clathrin-coated vesicles

core – histamine, chromogranin В, secretogranin ІІ

Neurosecretosomes – hormones

Synaptic vesicles – transmitters

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Lysosomes

Discovered by Christian de Duve, 1955

Spherical organelles:

Christian de Duve

(1917-2013)

(Gr. lysis, dissolution or destruction + soma, body)

size – 0.05-0.5 μm

single layer (unit) membrane – 6 nm

lysosomal matrix – pH 5 favorable for enzymatic activity

more than 40 hydrolytic enzymes

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Lysosomes – stages

Primary lysosomes:

inactive enzymes

Secondary lysosomes

(phagosomes, phagolysosomes):

heterolysosomes

(heterophagosomes)

autophagosomes

(autophagic vacuoles)

residual bodies

(telolysosomes)

lipofuscin droplets

pinocytotic vesicles

multivesicular bodies

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Lysosomes –"suicide-bags" or "suicide-sacs"

autophagic cell death – a form of programmed self destruction

(autolysis)

(autophagy – self digestion, Gr. auto, self + phagy, to eat)

the cells' garbage disposal system27


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Gr. peroxide + soma, body microbodies: Rhodin, 1954

Peroxisomes (microbodies)

Spherical organelles: 70-100/cell

size – 0.5-3 μm (macroperoxisomes) microperoxisomes – 0.1-0.3 μm

homogeneous matrix(crystalloid core or nucleoid)

marginal plate single layer membrane – 6-8 nm

identified by EM as organelles by Christian de Duve, 1967

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Peroxisomes –structure and function

Functions:

a compartment for oxidation reactions:

decomposes H2O2 to H2O and O2 and eliminates it

degrades several toxic molecules and prescription drugs

involved in lipid biosynthesis

important role in cellular respiration

Enzymes: >50

catalase – 40%

peroxidase

β-oxydase of very long-chain fatty acids

D- and L-amino oxydases

urate oxidase

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Gr. mitos, thread + chondros, granule:

Carl Benda, 1898

First observations:

Kölliker, 1850

Flemming, 1882

R. Altman, 1890: bioblasts

Size: 0.5-1 μm wide

length up to 10 μm

Number – varying: fibroblasts – 100

hepatocytes – 800 (25%)

oocytes – 300 000

Mitochondria vitally staining – Janus green B

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Mitochondria – structure

Ultrastructure: G. Palade, F.S. Sjöstrand, 1952

two mitochondrial membranes:

outer (6-7 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) space31


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Mitochondria –structure and function

Mitochondrial matrix: (intercristal space; inner chamber)

rich in proteins, DNA, RNA

matrix granules: 30-50 nm; storage site for divalent cations –Ca2+, Mg2+

mitoribosomes (mrRNA): 15-20 nm

mitochondrial mRNA, tRNA

circular DNA: 2-3 nm

RNA- and DNA-polymerases

Krebs cycle enzymes

enzymes for lipid synthesis

enzymes for protein synthesis

Origin of mitochondria: evolutionary from an ancestral aerobic

prokaryote adapted to an endosymbiotic life (intracellular symbiosis)

new mitochondria – from preexisting mitochondria by growth and subsequent division (fission)

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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

external morphology: shape – species-diversified

size – 10% of the cell volume;5 µm (spermatozoon), 40 µm (oogonium)

Cell Nucleus

RobertBrown

(1773-1858)

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Structural components:

nuclear envelope

chromatin

nucleolus

nuclear matrix (nucleoplasm)

Nucleus – structure

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Ultrastructure: outer nuclear membrane – 6 nm

ribosomes rER

vimentin filaments

inner nuclear membrane – 6 nm

nuclear lamina – 100-300 nm lamins A, B, C chromatin

perinuclear space – 10-40 nm

nuclear pores

Nuclear envelope

First description: M. Watson, 1955

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Heterochromatin (condensed) – 90%Gr. heteros, other + chroma, color: marginal chromatin – nuclear membrane

chromocenters – nucleoplasm

nucleolar-associated 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:

Chromatin

First description: W. Flemming, 1882

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

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synonym: Barr body – only in females

Barr, Bertram, 1949 tightly packed inactive Х chromosome localization:

adhering to the nuclear envelope “drumstick-like” appendage to the nuclei

Medical application: diagnostics in endocrinology forensic medicine practice study of inherited chromosome anomalies

– Klinefelter's and Turner syndromes etc.

disclosure of the genetic sex – in hermaphroditism and pseudohermaphroditism

Sex chromatin

Murray L. Barr

(1908-1995)

diameter – 1 µm

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Number: 1- max. 10: metabolically active cells embryonic cells during proliferation rapidly growing malignant tumors

External morphology: non-membrane bound structure shape – spherical; compact,

reticular, annular etc. diameter – 1-3 µm

Formation: nucleolar organizers – short arms of

chromosomes 13, 14, 15, 21 and 22 (the acrocentric chromosomes)

Nucleolus First description: Fontana, 1774

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a highly dynamic structure Composition – amorphous:

proteins + RNA – nucleoskeletonnuclear lamina – lamins A, B, C

numerous enzymes

metabolites

ions

crystalline inclusions viruses and other inclusions

Nuclear matrix synonyms: nucleoplasm, karyoplasm

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

Ribosomes

1943 – Albert Claude “microsomes” 1955 – George Palade Palade granules1958 – Richard B. Roberts “ribosomes”

65% rRNA and 35% ribonucleoproteins

George Emil Palade

(1912-2008)

The Nobel Prize in Physiology or Medicine 1974

small electron-dense particles, 20 x 30 nm in size

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free ribosomes proteins for use within the cell monosomes and polyribosomes (polysomes)

bound ribosomes (ribophorins І and ІІ)

secretory proteins (Ig, collagen, hormones)

Ribosomes

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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

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

Paul Wintrebert

1931

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Gr. micros, small + tubulus, tubule outer diameter = 24-25 nm

varying length = several µm

Microtubules

seen only under EM – first described in 1963

dynamic instability – after fixation:

stabile

labile

nonbranching, elongated hollow cylinders, made of protein

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arranged as a ring of 13 protofilaments

main component – dimeric tubulin (alpha&beta)

isolated in 1975

Microtubules – structure

wall – 5 nm thick; hollow core – 14 nm wide

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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

colchicine vinblastine vincristine

antimitotic alkaloids – experimental inhibition of mitosis:

cancer treatment (chemotherapy)

basis for formation of centrioles, basal bodies, cilia and flagella 46


Cilia and flagella axoneme and basal bodies – highly organized microtubule core

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Cell center

synonym: centrosome

first observation: Oscar Hertwig, 1875

ЕМ description: Bessis, 1955

Oscar Hertwig

(1849-1922)

diplosome

(a pair of centrioles)

centrosphere

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Centriole – structure

diameter: 0.15-0.2 µm

length: 0.3-0.7 µm

structure: 9 triplets (9 x 3) + 0

centriolar satellites: 40-70 nm

microtubule organizing centers

barrel-shaped cell structure composed of microtubules

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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

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Microfilaments

cytochalasin:

blocks actin polymerization

phalloidin:

promote actin polymerization;

stabilize actin polymers

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

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Intermediate filaments

• Nuclear lamins: А, B, C

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Cytoplasmic inclusions

synonyms: deutoplasm, paraplasm

Cytoplasmic deposits:

proteins: secretory granules

glycogen granules

lipid inclusions (fat droplets)

crystalline inclusions

pigments:

exogenous

endogenous

small particles of insoluble substances suspended in the cytosol

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Membrane transport

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Exocytosis

secretion of: components of extracellular

matrix (collagen) protein hormones (insulin) serum proteins

modes of secretion: merocrine apocrine holocrine

Gr. ἔξω, out + κύτος, cell

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Endocytosis the process by which cells absorb molecules from outside the cell

Gr. endon, within

three main types of endocytosis: phagocytosis (literally, cell-eating)

pinocytosis (literally, cell-drinking)

receptor-mediated endocytosis

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Cell signaling

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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Ways of signaling

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Kinds of communication



Cell cycle

cycle duration – 15-20 h mitosos (M phase) – 30-60 min

interphase:G1 phase (presynthetic) – 5-10 h

S phase (synthetic) – 6-8 h

G2 phase (postsynthetic) – 2-5 h

G0 phase: a specialized resting state

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Cell division

Mitosis: somatic cells

Endomitosis:megakaryocytes

(polyploid amitosis)

Amitosis: osteoclasts

Meiosis: gametes

(reductional division)

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

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Mitosis

Mitotic (M phase) of the cell cycle:

prophase: 10-60 min

metaphase: 10-20 min

anaphase: 5-8 min

telophase: 20-30 min

cytokinesis

Gr. mitos, a thread

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Meiosis

Іst meiotic division:(reduction in chromosome number)

– prolonged phophase: leptotene (leptos=thin)

zygotene (zygon=yoke): bivalents conjugation

pachytene (pachy=thick): tetrads crossing-over

diplotene (diplos=double)

diakinesis (dia=through)

ІІnd meiotic division:(reduction in the amount of

genetic material (DNA)

– similar to mitosis: without S-phase haploid chromosome number

Phases of meiosis – twoconsecutive cell divisions:

Gr. meiosis, a lessening

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Cell proliferation

Proliferation: a rapidincrease in the numberof cells

Fr. proliferer, to increase

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Differentiation:structural and functional

specialization of the cell

Cell differentiation

Three categories of

specialized cells:

fully differentiated,

non-dividing cells

potentially dividing cells

not terminally differentiated,

renewal by stem cells:

unipotent cells

pluripotent

(multipotent) cells

potency – the capacity to differentiate into specialized cell types65


Necrotic cell 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)

Gr. nεκρός, death

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Programmed cell death

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

Phases: latent executive

Pathways – caspases: receptor pathway mitochondrial pathway

Gr. apo, from + ptosis, falling

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68Thank you…

introduction to anatomy and cell biology. the...

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