Pathophys+Development+of+the+Cell+Theory

8/18/2019 Pathophys+Development+of+the+Cell+Theory

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The Foundations of Structure:Organelles, Cells and Tissues


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Medicine of the Ancients

• --Interpreted through the lens of animism, superstition

• --Handicapped ! lac" of an! appreciation of ph!sical or

functional anatom!

• --#estricted ! religious and social taoos $hich limited

ph!sical access to patients

• --%o tradition of e&perimentalism


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Medicine of the Egyptians

• An ailment $hich I $ill

treat

• An ailment $ith $hich

I $ill contend

• An ailment not to etreated


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The Medicine of Hippocrates of Cos

'Health is the alance of the four (ital components

that comprise the od!) *isease is the imalance

of these components to the detriment of od!

action) Therap! is the restoration of this alance

! altering humoral content+

• lood heart.

• /hlegm rain.

• 0ello$ ile li(er.

• lac" ile spleen.


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Treatment from Hippocrates to 18th Century

• Starve

• Purge

• Bleed

• If patient survives treatment and is still ill repeat

treatment until cured cautious or dead!


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The Homunculus


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• Emergence of the Cell Theory

• Identification of cells- Schleiden 1Sch$ann

• lastema-#o"itans"!


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"#mnis cellula e cellula$

%udolf &ircho' 18(8


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Implications of Cell Theor!

• 2enetics

• 3mr!olog!

• iochemistr!

• Cellular /atholog!


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Organi4ation of Structure

• Cells: smallest functional unit that a largerorganism can e di(ided into and $hich retainscharacteristics of life

• Tissues: groups of similar cells, speciali4ed in acommon direction and dedicated to performanceof a common function

• #rgans: some$hat independent portions of the

od! performing specific functions• Systems: groups of organs $hose functions are

integrated and coordinated


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Composition of the Cell

• 567 $ater • 897 protein

• 7 lipid

• 9);7 *%A

• 9)


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Ma=or Organelles

• ios!nthetic>metaolic ? %ucleus

? %ucleolus

? #3#>pol!riosomes

? S3#• ioenergetic

? Mitochondria

? 2l!cogen

• Structural ? Microtuules ? Intermediate filaments

? Microfilaments

• House"eeping ? @!sosomes

? /ero&isomes

? /hagosomes

)) /roteasomes

• arrier>Memranous ? /lasma memrane

? %uclear memrane

? Organelle memranes


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/lasma Memrane• All cells are surrounded ! a plasma memrane consisting of lipid

phospholipids, gl!colipids and cholesterol., proteins andcaroh!drates)

• @ipids are polar, possessing an uncharged, h!drophoic and a

charged, h!drophilic segment) These segments spontaneousl!

organi4e, !ielding a 'ila!ered+ memrane)

• /roteins are either anchored to a memrane lipid or fatt! acid

termed 'integral+ memrane proteins., or reside at the inner or outer

memrane surface termed 'peripheral+ memrane proteins.)

• /lasma memrane receptors are proteins on or in the plasma

memrane $hich ind to ligands such as drugs, neurotransmitters,

endogenous proteins such as hormones)

• /lasma memrane receptors can also ind infectious agents such

as specific receptors for HI present on certain l!mphoc!tes.)

• Channels are speciali4ed memrane proteins $hich allo$ mo(ement

of ions, $ater or solutes do$n their electrochemical gradient)

• /lasma memranes represent the interface $ith the e&tracellular

milieu, and are hence often the first organelle altered ! diseases)


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/lasma Memrane


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Bunctional Comple&es


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%ucleus

• All mammalian cells are eu"ar!otic or deri(ed from eu"ar!otic cells#Cs or platelets.)

• %uclei are surrounded ! t$o memranes) The outer memrane is

deri(ed from the endoplasmic reticulum, the inner is uniue to the

nucleus)

• The nucleus contains the ma=orit! of the cell+s *%A, *%A-indingproteins histones and non-histones. and supporti(e proteins)

• Histones control the translational acti(it! of the *%A and hence

man! facets of cell function epigenetics.)

• Chromatin *%A and histones. is present as uncoiled *%A

euchromatin. $hich is translationall! acti(e, and dense, highl!-coiled *%A heterochromatin., elie(ed to e largel! inacti(e)

• #%A is locali4ed to the nucleolus)

• Translated #%A lea(es the nucleus through pores in the nuclear

memrane)


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Mitochondrion• Site of most cellular energ! metaolism through o&idati(e

phosphor!lation

• Dltimate energ! product is AT/ (ia the citric acid Eres. c!cle• /roduction of AT/ is dependent upon the a(ailailit! of molecular

o&!gen) @oss of o&!gen rapidl! inhiits mitochondrial AT/production, reuiring the cell to use anaeroic sources eg),gl!cogen. for energ! production

• C!anide, caron mono&ide, );-*%/ poison mitochondria• %umer of mitochondria reflects metaolic acti(it! of cell

• Mitochondria ha(e t$o memranes

• Mitochondria contain high mM. concentrations of calcium, $hichma! e 'urped+ from cells ! mitochondrial pore transition) Also

contains c!tochrome c and proteins in(ol(ed in the apoptotic celldeath path$a!) #elease of apoptotic mediators from themitochondrion is termed the 'intrinsic cell death path$a!)+

• %ot all mitochondria $ithin a cell are acti(e at one time

• Mitochondria contain single-stranded *%A, deri(ed entirel! from thematernal line) This has special application in forensic patholog!)


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3ndoplasmic #eticulum• T$o general t!pes: rough #3#., $hich is

in(ol(ed in protein s!nthesis, and smooth S3#.,

in(ol(ed in s!nthesis and metaolism ofsteroids, drug metaolism and regulation ofcalcium

• Consists of net$or"s of tuules and (esicles

• #3# is decorated $ith riosomes $hich arepresent on the outside of the organelle) @oss ofriosomes $ill distur protein s!nthesis,particularl! of proteins destined for e&port fromthe cell

• S3# consists of aggregates of small (esicles)S3# can proliferate $hen stimulated, as occursfreuentl! $ith use of drugs reuiring metaolicacti(ation or deto&ification


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2olgi Apparatus

• Stac" of (esicular memranes in(ol(ed in

posttranslational modification phosphor!lation,

gl!cos!lation. and pac"aging of proteins and

lipids follo$ing s!nthesis• /roteins lea(ing #3# are transferred to 2olgi for

modification

• 2olgi apparatus produces (esicles destined for

e&tracellular release and l!sosomes


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2olgi Apparatus


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@!sosomal S!stem

• @!sosomes arise from the 2olgi apparatus and areassociated $ith the digestion of cellular deris and

e&tracellular in(aders eg), acteria.

• @!sosomes contain acid h!drolases, lipases, proteases,

nucleases and am!lase

• @!sosomal en4!mes are largel! inacti(e at ph!siologic

pH


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@!sosome


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/roteasome>Diuitin S!stem

• #elati(el! ne$l! descried s!stem critical for the proteol!tic

degradation of proteins and other 'house"eeping+ chores

• /rotein destruction is a multistep process in(ol(ing 'tagging+ of

protein $ith uiuitin ! means of a uiuitin ligase

• Tagged protein is directed to the proteasome) The proteinundergoes proteol!tic destruction $hile the uiuitin tags are

rec!cled

• *efects in the proteasome>uiuitin s!stem are implicated in man!

diseases, notale those in $hich misfolded proteins accumulate

eg), Al4heimer+s disease., and in the process of apoptotic cell death• /roteasome inhiiting drugs are used in cancer chemotherap!


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/roteosome


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C " l


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C!tos"eleton• %et$or" of filamentous proteins seen in all eu"ar!otic

cells• Comprised of three road classes of proteins:

microtuules, intermediate filaments and microfilaments,

differing ! molecular structure and si4e

• Microtuules are the largest and most d!namic) Man!MTs ha(e a lifespan measured in seconds to minutes)

MTs are critical for cell di(ision, transport of materials

$ithin the cell and cell motilit!

• Intermediate filaments help maintain cell structure,transport and d!namic functions such as contraction

• Microfilaments ser(e to reinforce the plasma memrane

and as a scaffold for internal structure) The! also

function in cell contraction


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http://upload.wikimedia.org/wikipedia/commons/0/09/FluorescentCells.jpg


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Organ 3lements

• 3pithelia: cells $hich perform the asic function ofan organ) *eri(ed from ectoderm or endoderm) Situated

on asement memrane, epithelia generall! lac" an

independent lood suppl!)

• Stroma: cells that pro(ide support and maintenance ofepithelia) *eri(ed from mesoderm)


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3mr!onic Origin of Tissues


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Functions of 3pithelia

• /rotection-epidermis

• Transport-ronchi

• Secretion-s$eat glands

• 3&cretion-"idne!

• Asorption-gastrointestinal tract

• @urication-rectum

• Sensor! input-touch endings

• #eproduction-o(aries>testes


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Connective Tissues

• Connective

? *oose

? Strong

? Hematopoietic

• Muscle

? S+eletal

? Cardiac

? Smooth


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H t i ti Ti


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Hematopoietic Tissue


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%eural Cells and *eri(ati(es

• %eurons the parench!mal unit of the

ner(ous s!stem.

• 2lial cells

? Astroc!tes

? Oligodendroglia

? Microglia

? 3pend!ma


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Terminolog! in Medicine

• /rimaril! 2ree" and @atin roots-eg), nephro-,pneumo-, osteo-

• Suffi& defines process prefi& is descriptor, core isthe organ>structure

• eg) ?oma tumor. lipoma, m!&oid liposarcoma --itis inflammation. ronchitis, nephritis

--iasis process. cholelithiasis

--plasia gro$th>formation. neoplasia

--orrhea flo$. diarrhea, d!smenorrhea

Pathophys+Development+of+the+Cell+Theory

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