EMBRYOLOGY: EARLY AND GENERAL

Fetal tissues-G3P2 38 weeks gestation pregnancy complicated by eclampsia

Maturation of lytic enzymes-spermatozoa with rounded heads globozoospermia
Acrosome formation-from golgi vesicles
Fertilization by a spermatozoon-required in continuation of 2nd meiotic division to produce haploid
ovum
Capacitation an acrosome reaction-husband sperm normal morphology but penetration assay 3.7
(normal 10%) spa requires
Surge of LH initiated by high estrogen titers-natural mens nearing ovulation undergo 1st meiotic division
result which hormonal stimuli
FSF and LH-produced in adenohypophysis
Theca cells- proliferate hypertrophy and produce estrogen
Cortical reaction-prevention of polyspermy
1st meiotic division-arrested prophase I during ovulation
2nd meiotic division-fusion of sperm + oocyte membrane result haploid pronucleus
5months of fetal life/5 months AOG-oogonia reach max no.of human development
7-12 weeks-primordial GC arrive at embryonic gonad of genetic female and differentiate in oogonia
6 million at 5month-number of oogonia continue to increase
7thmonth-primordial follicles
2 months –how much time for return of viable sperm to epidydimis
Normal implantation-occurs superior posterior postero lateral walls of uterus
Epiblast-cs done sent for patho which embryo source in sacrococcygeal teratoma,migrate toward
primitive streak at 2nd which form mesoderm and endoderm
Teratomas-3 germ layers ectodem, endoderm, mesoderm associated with gastrulation,arise from
remnants of primitive streak or primordial GC that fail to migrate to gonadal ridge
Mesoderm, endoderm-epiblast displace hypoblast cells at periphery give rise to muscle, bone,
cartilaginous.
2nd week of development-cells of inner cell mass (embryoblast) of blastocyst-differentiate into epiblast
and hypoblast
Epiblast-become ectodermal germ layer
Hypoblast-contribute to yolk sac
Yolk sac-primitive gut
Outer cell mass-cytotrophoblast, syncitiotropoblast
Syncitiotrophoblast-contribute formation of placenta
1st-cleavage formation of germ layer establish embryonic body
2nd or 8 weeks-organogenesis, most of internal organs begin to form
4th,6th,9th-known as fetal period
Decidual reaction-events occurs at second week of embryonic development
1st week-a.formation of blastomere,b.segregation of blastomere into embryoblast and tropholast,c.
formation of inner cell mass, d.formation of epiblast, hypoblast from embroblast, e.morula develop and
fluid cavity is transformed into blastocyst
Neuration-heart begins on day 22, formation of neural tube,establish neural groove,from neural tube
from surface ectoderm
Gastrulation- on 3rd week, establish 3 gem layers trilaminar disk, formation of primordial of major
organs systems, embryo folding occur at week 4,epibast migrate primitive streak, mesoderm, endoderm
germ layer
Lat. Folding-endo tube concentric layer mesoderm and ectoderm
Septum transversum-form central tendon of diaphragm membrane
Non gastrulated epiblast-endoderm derived directly
Common carotid artery+aortic arch+subclavian artery- highest oxygen content, directed valve of IVC
directly to foramen ovale into L.A
Oxygen depleted blood from SVC directed into R.V to pulmonary trunk
Most shunted to throcic aorta-via ductus arteriosus and lowers oxygen content occurs distal to origin of
carotid artery
PDA-1st 4 days after birth ventilator press, and fraction of inspired air oxygen are reduced,
Echocardiogram xray-diagnostic exam reveal left atrial enlargement, enlarged pulmonary artery,
increase vasculature, and continuous machine like murmur
Ductus arteriosus-in fetus lungs not involved co2 and oxygen exchange until after birth
Shunts flow from left pulmo artery to aorta
High o2 levels after birth and absence of PG allows it to close in 24 hours
Persistent F.ovale-ASD bec splitting of 2nd heart sound during expiration, result minimal or intermittent
cyanosis during crying or straining
VSD-between 1st and 2nd HS S1 and S2, holosystolic (pansystolic ) amplitude is high throughout systole
COA- harsh SEM
Thymus-from endoderm,from 3rd pharyngeal (brachial) pouches
Tonsils-from pharyngeal mesoderm
Bone marrow-either intramembranous or endochondral-mesoderm beginning 2nd month of fetal life
Spleen-CT- sk frame work from splanchnic at mesoderm in 5th week remain active until 7th month
Blood islands-extraembryonic mesoderm lining yolk sac,during 3rd week give rise vitelline vessels, major
site of RBC
Cranial folding-developing heart in presumptive thoracic region cranial to septum transversum, lies
dorsal and caudal to oropharyngeal membrane
Cells in syncitiotrophoblast-direct contact which maternal blood in lacunate and placenta
3rd thru 8th weeks-nonlethal congenital malformations
Fertilization to 1 week fetal life, 2nd week fetal life-induces spontaneous abortion
3rd month of fetal life, 3rd trimester of fetal life-teratogenic expo result retardation of organ growth

Skeletal muscle and CNS- received vitamin A treatment for acne, exogenous source of retinoic acid
Duodenal or esophageal atresia-increase back pain, AFI 27,(normal 5-24) polyGIT hydramios
Greater than 2k ml in 3rd tri- excess AF
Bilateral agenesis of kidneys-low AFI, oligohydramio, low levels AFi inhibit lung development
Formula- less than urine output-less than A.F,
Formula-less than swallowing-more AF
Ectoderm-nb born with lumbar S. bifida myeloschisis (rachisis) mass of neural plate
Endoderm-GI tract, respi
Somatopleuric Mesoderm-skin,dermis, non muscle portions of limbs, bones tendons, Ct ofextremities
and dermis
Splanchnopleuric mesoderm-heart,muscle, GI tract, urinary sys,
Hypoblast-thin layer of cell ventral to epiblast
Myeloschisis (rachishisis)-most severe form of spina bifida, neural tube fails to close leaving plate like
mass
Biceps brachi-FGFRI gene results expansion of axial skeleton most affected by deficiency in paraxial
mesoderm (muscles of extremities)
FGF- differentiation of paraxial mesoderm
Masseter- muscle of mastication from 1st brachial arch innervated by SVE from nucleus ambiguous
versus GVE biceps muscles

Telencephalon-severe infantile spasms with diagnaosis lissencephaly based on MRi or CT

Forebrain-prosencephalon-telencephalon-cerebrum-lateral ventricle
-dincephalon-thalamus-3rd ventricle
Midbrain-mesencephalon-mesencephalon-midbrain-aqueduct
Hindbrain-Rhombencepalon-metencephalon-pons and cerebellum-upper part of 4th ventricle
-myelencepalon-medulla-lower part of 4th ventricle (cavities)
Cerebrum, thalamus, midbrain,pons,cerebellum, medulla-wall

Endodermal sinus tumor/EST/yolk sac tumor/infantile embryonal Cancer-mc testicular tumor in

children
Yolksac-initial site of hematopoiesis/3-8 weeks, important source of blood until fetal liver replaces this
function in about6weeks of devt, predominantly hematoctoblasts, (stem cell) and primitive erythroblast
Vasculogenesis-initiated in yolk sac
Umbilical vein-L.teres hepatis origin
Endodermal lining of yolk sac-seminoma, derived from hypoblast of allantois 3rd or beginning of 4th
week
Chorion-outermost fetal membrane, composed somatic mesoderm cytotrophoblast and
syncitiotrophoblast,
Chorion frondosum-wherevilli form and proliferate
Smoothcorion/aka chorion laevae
GC tumors-origin primordial GC during embryodevt, detection of disease occurs decades later
Splitting early-in blastocyst stage result in splitting inner cell mass (sepaateamnion with common
chorion and placenta)
Splitting later-in blastocyst stage result in common amnion, chorion, placenta
Division of inner cell mass(embryoblast) into 2 embryonic primordial- 1 gestational sac and 2 yolk sacs
Monozygotic- arise anywhere from 2 cell (blastomere to blastocyst),arise from division of embryoblast
to form 2 embryos-1 gestational sac and 2 yolk sacs, fuse or separate placenta or separate or fused
dichorionic sacs or1 chorionic sac diamnionic sacs, fertilization of 1 oocyte by 2 sperm cant occur bec of
calcium dependent block to polyspermy,Egg cortical reaction effects
2 pellucida in 2 ways
a.hydrolysis of CHO prevents sperm binding
b.proteolytic activity hardens it
Dizygotic-splitting occurs at 2cell stage results in separate amnions, chorions,placenta,arise from
fertilization of 2 oocytes by2 sperm and are merelywomb mates, difer in genotype with different sexes
Ectoderm-include hair follicle, sweat glands, hair teeth with a diagnosis of dermoid cyst almost always
presentat birth
Dermoid cyst-mc locations-bregma(junction of coronal and sagittal suture, anterior fontanelle upper
lateral region of forehead, lateral upper eyelid, submental region lesions occur anywhere in scalp, face
or spinal axis
Myotome-form skin and trunk extremities
Sclerotome-form cartilage and bone
Intermediate mesoderm-origin of urogenital sytem and adrenal (suprarenal gland)
Lateral folding-responsible for fusion of paired dorsal aorta,fusion of endocardial heart tube
Craniocaudal folding-establish head,tail,region of embryo
Middle aortic syndrome/MAS-segmantal narrowing of abdomen,distal descending throracic
aorta,congenital failure of fusion maturation of paired embryo dorsal aorta

CELLIBOLOGY:MEMBRANES
Plasma membranes-creation of a barrier to water soluble molecules
Hydrophobic layer of cell (plasma)membrane-fundamental structure of membrane provides barrier to
water soluble molecule in ext milleu
Membrane-consist of bilayer phospholipids with non polar hydrophobic layer in central portion and
hydrophilic polar region of phospholipid in contact with aqueous component at intracellular or
extracellular surface of membrane
7um-diameterof RBC (erythrocyte)
Glycoproteins/glycosphingolipids gangliosides-terminate in sialic acid with negative charge
Glycoproteins-the negative charge on cell membraneis primary cause, diagnosis Iga deficiency
IgA deficiency-repels polyanionic harge pathogens attached more easily to cell surface leading
persistent infections
40-60 mg/dl-normal IgA levels
Polyanionic charge- by sugar sidechains of glycoproteins and glycolipids
Facing away from the cytoplasm-freeze fracture preparation of eukaryotic cell membrane
Freeze fracture-procedure in which tissue rapidly frozen and fractured with a knife
Fracture plane-occurs thru hydrophobic center plane of membrane.
2 faces, 2 interior faces of membrane
a.extracellular face( efface), protoplasmic face (pface)
cytoplasmbacking for p face which generallycontains intramembranous particles mostly protein
Cholesterol-altersmembrane fluidity ,is amphiphatic (hydrophilic, hydrophobic),reduce packing of lipid
acyl groups thru its steroid ring structure and hydro carbon tail
Blood ph-the rbc membrane band 3 binds to spectrin dimers and tetramers indirectly thru ankyrn,
decrease in absence of band 3 protein
Band 3-interacts with spectrin thru ankyrin bridge
Spectrin-exists as dimers and trimmers
Trimmers-maintain shape stabilizing RBC
In its anion exchanger role band 3 chon exchanges HCO3 ion for CL ion
HCO3-transported by band 3 out of RBC in echange forchloride permitting highly efficient transport of
CO2 to lungs as bicarbonate
In absence of band 3 CHON-HCO3 buffering of blood is reduced leading to acidosis or lowering blood ph
Binding of antibody to cell surface receptor-erythrocyte fluidity is altered in liver disease, and increase
membrane fluidity in hepatocytes in patients liver diagnosis cirrhosis
Cirrhosis-alterations in plasma lipoprotein
Increase membrane fluidity- patching and capping
Rotational and lateral movements of both proteins and lipids- contribute to membrane fluidity
Restriction-reduces membrane fluidity
Peripheral membrane proteins-on cytosolic leaflet ofmembrane bilayer
Integrins-heterodimeric receptors bind with extracellularmatrix molecule as laminin or fibronectin.
Phospholipid-capable of lateral diffusion, rapid rotation undergoes trans bilayer movement s flipflop
between bilayers in E.R
Other factors reduce membrane fluidity-increase amount of chole relative to phospholipid both
biological and artificial membranes, associated or binding of interal membranes chons with cytoskeletal
elements on interior of cell and peripheral membrane proteins on extracellular surface
Spherocytes-osmoticaly fragile bec. Decrease surface area or unit volume
Accelerated hemolysis-leads to increase bile production and jaundice
Bone marrow compensates for increase destruction of rbcs with hyperplasia of erythroid precursors
Ribsomes-both CHON and RNA, rRNA predominantly
Membrane synthesis in E.R before reaching golgi apparatus- asymmetry of cell membrane is
established primarily
CHO-associated with N terminals of transmembrane chons
CHOLE- assymetrically distributed within bilayer, on both sides of bilayer allows to flip flop
CHONS and phospholipids- limited to E.R
They can activate plasma memb. Bound enzymes or ion channels-no relief on albuterol
ALBUTEROL- a moderate selective b2 receptor agonist binds to beta receptors, multipass G protein
linked receptors, binding to G protein linked receptors activates or inactivates enzymes bound to plasma
membrane (adenyl cyclase or phospholipase C)or opens or closes ion channels using G protein
Beta receptors-as muscarinic cholinergic receptors, and rhodopsin- are multipass transmemb. Chons
Ligand binding-occurs on extracellular surface
Receptors with intrinsic enzyme activity- belong to a separate class of single pass transmembrane
chons.
Multipass G protein link receptors-transmembrane chon possess a carboxy terminus on the cytosolic
side and N linked glycosylation sites on the extracellular surface.

CELL BIOLOGY:CYTOPLASM
Fibrous stromal CT-in Salivary gland derived from mesenchyme diagnosis pleomorphic adenoma
Pleomorphic adenoma of submandibular gland-uses antivimentin antibodies with
immunocytochemistry to stain biopsy tissue expect to find vimentin
Intermediate filaments chons-in anchorage of Chons form ion channels, used by pathologist to
determine origin of tumors, has types derived from 3 embryo germ layers
Cytokeratins-aka keartins-specific for epithelial cells
Desmin-striated and most smooth muscle except vascular smooth muscle
Anti vimentin-specific for mesenchymal cells as fibroblast, macrophages, endothelial cells-smooh
muscle of vasculature
Glial fibrillary acidic protein GFAP-specific for astrocytes
Parasympathetic ganglia-stain with panneuronal markers as peripherin
Serous acini,mucous acini, striated ducts- epithelial in origin
Catalyze peptide bond formation-function of large subunit of ribosome,activation of peptidyl
transferase
Small ribosomal subunit -contain peptidyl + RNA binding P site that binds the TRNA molecule attach to
carboxyl end of growing end of polypeptide chitin, contains amino acyl TRNA binding site A site that
holds incoming RNA and AA, initiator increase RNA containing methionine provides AA to start chon
synthesis, initiate CHON synthesis
Aminoacyl +RNA binding A site-that holds incoming + RNA and AA
Actin binding CHONS-stability arrangement of actin filaments as well as properties
Roles:
a.Tropomyosin-strengthens actin filaments
b.Fibrin and villin- are actin binding chons
c.Filamin and gel solution-regulate transformation from sol to gel state
d.Members of myosin II family are responsible for sliding filaments
e.Myosin I (minimyosin)-responsible for movement of vesicles on filaments
f.Spectrin- cross links sides on actin filaments to plasma membranes
they are biochemicaly compartmentalized-weakness and paralysis of thoracic muscles leads to
progressive respi insuff.diagnosis of ALS/Lou Gehrig Disease topological compartmentalized
histochemical stains as acid phosphate and nucleoside diphosphates
2 face
Cis phase-point of entry transport vesicles COP II coated
Transphase-exit point associated with granule formation and maturation
Golgi apparatus-specific org to Golgi stacks related processing of chon, trimming oligosaccharide chains
that was initiated in RER as well as sulfation of CHONS
Keratin 5 and keratin 14-provide mechanical stability for diagnosis of epidermolysis bullosa simplex with
skin blisters with easily rubbing scratching blisters
Keratin-intermediate filaments chons, different types hve similar structure, pattern are non helical
head, tail segments with helical arrangement in center
Positive end of microtubule- oriented toward plasma membrane
Negative end toward nucleus
Positive and negative ends -works for fibroblast as well neurons
Centrosomes-carry out nucleation of microtubules
Myosin, dynein, kinesin-generate movement of motor chon
Kinesin-kicks molecule out
Dynein-drags them in
Microtubule associated chons-stabilize or destabilize microtubules, function in organellar transport
example axonal transport
Oxidative demethylation or metabolism by CP450 in hepatocyte -overdose goof balls phenobarbital,in
hepatocyte occurring in organelle
P450 oxidase system-found in SER in hepatocytes respond to phenobarbital ingestion increasing its
volume,proliferation of SER
RER- Synthesis of enzymes
Lysozymes-contain acid hydrolases
P450system+SER-involved in drug interactions
Drug metab-purpose to make more drugs more H20 soluble, easily excreted from liver thru bile
Proton translocating activity in inner membrane-mri and ct striatal and caudate atrophy with boxcar
ventricles, PCR:1normal band with 20 CAG trimester tide repeats and other with 49 CAG rpts modulation
of respi and mitochondrial memb potential and bioenergetic failure assoc. with abnormal gene diagnosis
Huntington disease
Huntington dse- assoc. with respi chain and ATP synthase,encodes for hunting chon which cause
mitochondrial dysfunction by perturbing transcription of nuclear encoded mitochondrial CHON directly
modulating a. mitochondrial respi, b. mem potential c.calcium buffering, cellular energy stored as ATP
synthesized by phosphorylation of ADP by ATp synthase
Mitochondria-use ETC or respi chain that transfers energy from NADH to O2, atrophy of caudate
nucleus causes expansion of lat ventricles to form BOX CAR ventricles
N linked glycosylation in E.R-enbloc method, electron microscopy confirm presence of fingerprint
inclusion bodies, elevated levels of of dolichol in urine normally is associated diagnosisof infantile form
of batten disease, neuronal ceroid lipofuscinoses build up lipofuschin bec absence of sp lysosomal
enzymes,
N linked ligosaccharides- MC oligosaccharides in glycochons and contain sugars, residues linked to NH2
amide nitrogen of asparagine
O linked glycosylation-occurs in golgi mech involve oligosaccharide glycosyl transferases rather than
enbloc with dolichol have sugar residues linked to hydroxyl grps on side chains of serine and theonine
Dolichol-added to CHON
Plasmalogen synthase-sole site elevated iron and copper levels in blood hepatomegaly, liver biopsy with
empty peroxisomes as peroxisome ghosts,group of glycerol based phospholipids in which aliphatic side
chains are not attached, highest in brain, s.c, liver ,kidney, diagnosis of Zellweger syndrome
Zellweger syn-peroxisomes empty bec failure of signlas system that sort CHON to perixosome
peroxisomes lack dna orsynthetic machinery ribosomes
Peroxisomes- single memb with catalase carry out oxygen by ester linkages
Diversity in oligosaccharides- is produced by selective removal of GLUCOSE and MANNOSE
RER-trimming process begins,before reaching golgi
Golgi-where final mannose residue trimming occurs
Sulfation and chon sorting-carried out in golgi apparatus
Most alcohol humans consume-broken down by alcohol dehydrogenase ADH and microsomal ethanol
oxidizing system MEOS, P450 cytochrome pathway in hepatocyte liver cell cytoplasm, remains small
percent of broken down by oxidation in peroxisomes of hepatocytes using catalase
Phagocytic activity by macrophages-inhibition of actin assembly by cytochalasins interfere
Cytochalasins-potent inhibitors of cell motility and other cellular events that depend on actin
assembly,bind to positive end filament , prevent polymeration movement of chromosome in anaphase
of cell cycle depends on disassembly of microtubules at kinetochore in anaphase A and addition at
anaphase the plus end of the polar microtubules
Cytokinosis-conducted by actin containing contractile ring phagocytosis and formation of lamelopodia
Microtubules-ciliary movement vesicular transport and structure of centrioles
Chloroquine in BMI of 30 improves glucose, inhibits conversion of proinsulin to insulin result in decrease
formation of insulin with in secretory vesicles of pancreatic b cells, a weak base neutralizes acidic
organellesas secretory vesicles
Increased proinsulin content in secretory vesicles-in pancreatic b cell has a direct effect of chloroquine
treatment,
Acidification-breakdown of phagosomes and lysosomes cleavage of prohormones to their active forms
example proinsulin to insulin
Ribosomes-less sensitive to chloroquine
Proinsulin-split into c peptide and insulin in secretory vesicles
In vivo C peptide- release used to measure production of insulin by a patients pancreatic Bcells useful in
patients who are receiving insulin,
Glucagon-syn by alpha cells and amylase an exocrine pancreatic product produced by acinar cells
Inner membrane of mitochondrion- repaeated episodes of vomiting with seizure like events p.e
hypotonia, spasticity, deafness with mild choreathetosis, with high lactate in CSF, deficiency in
cytochrome oxidase COX complex IV,where 1 expect to find enzyme localization diagnosis of Leighs
dsease (subacute necrotizing encephalopathy),
Inner membrane of mitochondrion-folded into convulsions called cristae, number of cristae directly
related to metabolic activity of cell,highly impermeable to small ions bec presence of cardiolipin,
contains chon requiredfor oxidative reactions of respi transport chain,location of cytochromes,
dehydrogenases, flavoproteins, include cytochrome C, tansmembrane complex ATP synthase
responsible for ATP synthesis
Inner membranespace-site ofcytochromeB and other unique membrane chons
Outer mito membrane-hight permeable to molecule 10 kda or less bec. Of porin a channel forming chon
membrane with enzymes in lipid synthesis and metab., mediates movement of FA into mitochondria for
use of formaton of acetyl COA
Matrix granules-represent accumulation of ca ions
Mitochondrial matrix or interstitial space matrix-conains circular DNA of mitochondrial denome also
contains enzymes responsible for Krebs citric acid cycle
Opsin-sense light kinesisn on ATPase
Microtubules-with tublinmotility principal chon n composition of axoneme core of cilum or flagellum
Microfilaments-thin filaments composed of actin mostabundant protein in cells of eukaryote,cell
motility changes in cell shape
Myosin –thick filaments binds to actin functions ATPase activated by actin
Intermediate filament-diameter 8-10 nm bet thin and thick with 5 types, important cytoskeletal
elements with specificity depends on origin of cells
5 types intermediate filaments
Type I and II-acidic and basic keratins (cytokeratins) sp in epithelial cells
Type III-vimentin,desmin, GFAP in astrocytes
Type IV-neurofilaments proyein in neurons
Type V- nuclear laminins A,B,C associated with nuclear laminar cells
Specrin heterdimers-stabilize plasma membrane connect membrane to actin
Vimentin-specific intermediate filament protein found in cells derived from mesenchyme ex fibroblast,
chondrocytes,mesenchymal origin desmin in muscle cells GFAP in astrocytes
Leighs disease-generalized systemic form of COX deficiency characterized as progressive regeneration of
brain and dysfunction of heart, kidneys,muscles, liver, loss of acquired motor skills appetite vomiting
irritability and seizure, generalized weakness, loss of muscle tone hypotonia, episodes of lactic acidosis
with lactate higher in CSF
Microtubules-rod degeneration with limited peripheral vision with pigment deposits in mid peripheral
retina as bone spicules and paleness of optic nerve with diagnosis retinitis pigmentosa
Retinitis pigmentosa- vesicle organelle move unidirectionally along microtubules from inner segment to
outer segment of photo receptor
Cop II- coat chon for vesicles transported in anterograde direction from RER to golgi with a diagnosis of
Cystic fibrosis
Cop I-important con coating of secretory vesicles from IGN to target and coated pits involved in
endocytosis
Spectrin-retrieval of membrane following exocytoss
Spectrin heterodimers- form tetramers interact with actin provide flexibility support for membrane
Ankyrin-chon anchors band 3 chon to spectrin memb skeleton indirectly binding band 3 protein to
cytoskeleton spectrin tetramers of RBC
Actin- band 3 proteins known to be anion transport chon of RBC, in thin filaments in RBC cytoplasm
Stimulate hexosaminidase production- loss of peripheral vision abnormal startle response to auditory
simuli sudden loss of coordination has cherry red spot on macula with dignosisof Tay sachs
Taysacs – LSD array of specific hydrolases, build up of GM2 ganglioside in lysosomes leading to MR,
blindness , mortality, pharma approach: reduce GM2 ganglioside levels, increase hexosaminidase A
activity
Mannose 6 phosphate and its receptor- involved in trafficking of proteins to lysosomal compartment
Removal of mannose 6 phosphate-occurs in inclusion cell (I cell) result deault of lysosomal enzymes to
secretory pathway and hexosaminidase deficiency would worsen
Lysosomal storage diseases LSD
Tay sacs- enzyme deficit: B-N- hexosaminidase A, cellular site: neurons, accumulation :glycolipid, organ
most affected: CNS
Gaucher- enzyme deficit: B-O-glycosidase, cellula site :macrophage, accumulation: glycolipid, Organ
most affected: spleen liver
Hurler- enzyme deficit:a-L-iduronidase, cellular site:fibroblast, chondroblast, osteoblast, accumulation:
dermatan sulfate, organmost affected: skeletal system
Niemann pick- enzme deficit: sphingomyelinase, cellular site:oligodendrocyte, fibroblast, accumulation:
sphingomyelin, organ most affected : CNS
Inclusion I disease- enzyme deficit: N- acetylglucosamine-phosphotransfease, celluelar site: fibroblast,
macrophage, accumulation: glycoproteins, and glycolipids, organ ost affected: nervous, skeletal system
(liver unaffected)
Lysosome for degradation- with a diagnosis of Wilsons disease- hepatic failure, kayser Fleisher rings,
mutations in ATP7B gene, mutations alter transport of cargo with in late endosomes , occurs in liver
mutation ATP 7B prevents tanslocation of cupper from cytosol to late endosome
Late endosome-part of endocytic pathway cargochon from endosome reach lysosome by development
into lysosomes transport to lysosomes via vesicles fusion
MVBs- means transport from early to late endosomes
CGN-cis golgi network- receives transitional elements in form of coated vesicles,carrying chon and lipids
from RER and participates in phosphorylation or breakdown
Clathrin coated pits and vesicles-endocytose deliver chon to earlyendosomes 1st stages of endocytic
process
Remaining golgi stacks, cis, medial, trans, TGN
Medial compartment-for removal of mannose and addititon of N acetylglucosamine
Transface-addition of sialic acid and galactose
TGN-as sortng station for chons destined for various organelles example lysosomes, plasma membrane
chon, for export from cell
Golgi apparatus-derived transport secretory vesicles,
Early endosomes-recycling of receptors to plasma membrane
RER- predominant in alzheimers disease
Golgi apprataus- where O linked glycosylation, sorting of TAU proteins sulfation of amyloid precursor
CHON occur
SER-this is where Glycogenolysis ocur , sulfation of amyloid precursor protein frequently changes in
extracellular environment

CELL BIOLOGY: INTRACELLULAR TRAFFICKING

Use of clathrin coated pits and vesicles-man taking atorvastatin, endocytosis of LDL differs from
phagocytosis of damaged cells
Receptor mediated endocytosis- requires invagination o cell membrane to form clathrin coated pits and
vesicles
Phagocytosis of damaged cells-evagination to engulf IgG coated surface of target
BOTH endocytosis and phagocytosis- use adification of compartments and hydrolases to uncouple
receptor and liand (receptor mediated endocytosis) or destroy engulf material (phagocytosis)
BOTH use membrane enclosed vesicles associated with hydroxylase and lysosomal activity
LDL- most cholesterol transported in blood, is an example of receptor mediated endocytosis
LDL-LDL receptor (ligand receptor) complexes-incorporated to cell in coated vesicles, acidic
environment of endosome results: cleavage of ligand from its receptor
LDL receptors-recycled to the membrane for additional exposure to LDL and LDL in endosome
brokendown to cholesterol
Statins- inhibit 3 hydroxy 3 methyl glutaryl co enzyme A HMG CoA reductase, blocking hepatic
cholesterol synthesis
Decrease in cholesterol synthesis-leads to activation of LDL receptor gene
Increase in number of LDL receptor- enchanced endocytosis of blood LDL and lower blood LDL levels
Failureof preprotein translocation into ER- diagnosis of Ehler danlos I or III EDS
Mannose 6 Phosphate receptors- regulates sorting to the lysosomes
Signal peptide-key element of signal hypothesis for preprotein translocation into cisterna of ER, usually
N terminus normally absent from mature protein, directs the ribosome to ER, where cotranslational in
section takes place, Highly hydrophobic
RER-proteins with a KDEL (lysine-asparagine-Glu-Leucine)sequence on C terminus are retained in RER or
rerouted back to RER via interaction with KDEL receptors in Golgi App,
HDEL histidine- asp-glu-leu and KDEL-immunological evidence that plants use both for targeting
proteins to the endoplasmic reticulum
Using their ATPase acetylcholine to bind and release themselves from hydrophobic regions of protein -
disease caused by chon misfolding chaperonins regulate CHON folding with diagnosis of Alzheimers
disease
Molecular chaperones- absent in alzheimers disease, and other neurodegenerative diseases,in
conjunction with calreticulin monitor the progress of folding and ensure that only properly folded chon
are secreted from the cell, they assist translocation of CHONS across int membranes (Example
mitochondria)
It is stimulatory G protein (Gs)-man begins allergic reaction reaches his inhalator filled with albuterol, a
beta adrenergic drug that binds to beta receptor on cell on respi airways
Beta receptor-mediate the tissue effects of EPI and NE and respond to pharmacological agents as
albuterol and beta adrenergic agonist
Albuterol-binds to beta receptor initiating a CAMP signal transduction cascade
Signal transduction- f ligand binding involves sp G protein ( shorthand Guanosine triphosphate GTP
binding regulatory protein)
G proteins-associated with increase CAMP levels AKA Gs because of role in enzyme activation
On inactive state- Gs is bound to GDP
Alpha subunit of activated Gs CHON exhanges GDP for GTPand activates adenyl cyclase
Intrinsic GTPase Activity of alpha subunit is increase- resulting short activation time for complex and
recycling of subunits to inactive site
PKA- activated by dissociation of regulatory subunits leading to activated PKA
Phosphorylating action of CAMP dependent CHON kinase (kinase A)- stimulated by increased
intracellular CAMP concentration which affects many aspects of intracellular metabolism and function.
Phosphorylation-stimulate exocytosis, induces nuclear change include transcriptional events
Hydrolysis of PIP2 to form DAG and IP3- retaining urine in her bladder given Bethanechol
Betanechol-a muscarinic agonist which is a ligand , binds to muscarinic receptors
Phosphoinositide cycle PI- formation of PIP2 in the inner leaflet of plasma membrane
Phospholipase C- catalyses formation of DAG, IP3 from PIP2
P1-specific phospholipase C- hydrolyzes P1P2 to form DAG and IP3
DAG and IP3- 2 molecule function differently to regulate intracellular function
IP3- functions in mobilization of calcium by binding to IP3 gated channels in ER membrane
DAG-activates protein kinase C because of dependency on calcium
Protein kinase C-phosphorylates specific serine and threonine residues alter gene transcription in
contrast
2 intracellular messenger pathways do interact in elevated calcium which translocates protein kinase
C from cytosol to inner leaflet of plasma membrane
G1-inhibitory G protein leads to 5 AMP production thru phosphodiesterase instead CAMP
Gs- involved in adenylate cyclase signal transduction
2 major secretory pathways-A-B-C-D (pathway 1) and C-E (pathway 2)
Pathway 2- albumin secretion by hepatocytes
Reduced number of functional hepatocytes-in patients with cirrhosis serum levels of albumin is
reduced with a diagnosis of cirrhosis
Cirrhosis- damage hepatocytes leading reduction synthesis of serum proteins
Albumin secretion- by heaptocytes is used by fibroblast for synthesis of proteoglycans, fibronectin and
collagen serum CHONS ( albumin, transferrin, and lipoCHON) which is synthesized by hepatocytes and
plasma cell derived Ig,
Pathway 1-/ regulated secretion-resulting in secretagogue receptor binding, 2 pathways similar until
golgi pathway are clathrin coated and contains a receptor involved in concentration of secretory product
Pathway 2/constitutive pathway-shuttles CHON as integral membrane CHONS and lipids in vesicles to
apical and basolateral membranes, vesicles are non clathrin example is RAS superfamily, GTpases
members of CHON kinase D family
Exocytosis- requires vesicle fusion with membrane both regulated and constitutive
Secretion of lysosomal enzymes into the blood -mean weight height for 6 months old are 17 pounds 4
oz and 26.5 in respectively, he has I Inclusion cell disease and missing N acetylglucosamine undine
diphospho (UDP)- N-acetylglucosamine 1 phosphotransferase
Inclusion (I ) cell disease (mucolipidosis type II/ ML II-absence or def. of N acetylglucosamine
phosphotransferase and absence of mannose 6 phosphate M6P on lysosomal enzymes
Failure to add M6P in cis golgi- results in appropriate vesicular segregation by M6P receptors in trans
Golgi network TGN
Peroxisomal enzymes- which are assorted by presence of 3 sp AA located at C terminus, ser-lys-leu-
COO not affected
KDEL-signal used for retrieval of proteins from golgi back to ER
SNARES-receptors for SNAPS ( soluble N ethylmaleimide SN factor NSF attachment CHONS bind vesicles
to membrane
Trafficking to other structure as nucleus and mitochondria-is regulated by nuclear localization signals
NLS or an N terminal signal peptide respectively

CELL BIOLOGY: NUCLEUS

Transcription of ribosomal CHONS-treacher Collins franceschetti syndrome 1 TCOF gene encode protein
treacle
TCOF 1 gene-encodes treacle, critical in early embryo devt that forms bones and other facial structure
Treacle- active in nucleus regulates ribosomal DNA
Nucleolus- site of ribosomal CHON transcription and site of ribosomal synthesis
Cytoplasm- complete assembly maturation of ribosomes require transport to cytoplasm
Ribosomal proteins or all proteins- that function in nucleus are synthesize in cytosol transported in
nucleus
Nuclear chons-translated on ribosomes in cytoplasm and targeted to nucleus thru nuclear pores by sp
nuclear localization signals
Cytosolic CHONS- synthesize on isolated ribosomes
Lysosomes- degeneration of organelles
Disruption, reaarangement of cellular actin-dolastatin (actin) promising chemotherapeutic has
mechanism
Actin and myosin- force for cytokinesis generated by action
Dolastatin II-causes rapid disruption of the actin microfilament network
Lengthening of the kinetochore microtubules-attach the kinetochore apparatus, shorten pull the
chromatids to opposite poles in anaphase
Cytokinesis-cleavage of cytoplasm to form 2 cells occurs after completion of nuclear division example
nuclear condensation and separation of chrmosomes which are mediated by microtubules
Growth of polar microtubules- results in separation of spindle poles in anaphase B
M-cdk complex (MPF)- regulates metaphase thru phosporylaton
Antitubulins antibodies-block movement of chromosome
Tubulin- important in separation of chromosomes and nuclear division

Events of cell cycle phases

Phase of cell cycle Defining events
Interphase G1 S1 G2 -duplication of centrioles, DNA Syn (S phase)
Prophase -nucleolus disappears
Prometaphase -nuclear envelopebreaksdown
Metaphase -alighment of chromosomes in metaphase plate
Anaphase -separation of sister chromatids, initiation of cytokinesis
Telophase -nuclear envelope reforms, completion of cytokinesis

Packaging of genetic material in a condensed form- facial rash malar rash, butterfly rash thatis
accentuated by sun exposure labs crea 1.7 normal 0.5-1-1 mg/dl, high titer antinuclear auto antibodies,
smith antigen, antinucleosome, antibody in serum diagnosis SLE
SLE-chronic auto immune dsd autoabs against nucleosomes (ANA) are sensitive markers
Nucleosomes-basic structural packaging units of chromatin
Chromatin strands-treated to unpack chromatin structure, appearance beads on a string
Beads-form by core of histones as an octamer 2 of each of 4 nucleosomal histones H2A,H2B H3 H4 and 2
turns DNA
Transcription of DNA- carried out by RNA polymerase I and II, and III responsible for transcription of
different type of genes
Nuclear pores- are perforations in nuclear envelope each with nuclear pore complex
Nuclear matrix- intranuclear cytoskeleton forms scaffolding for nuclear structure
Chromatids- held together at centromere
Lamins will be phosphorylated in G1 cell-g1 phase and M pase cell are fused together with sendai virus
G1 phase cell- quickly pulled or driven to mitosis as chromosome condense
m-cdk- cause phosphorylation of lamins
lamins-(nuclear lamina) subclass of intermediate filaments 3 nuclear chons Lamins A,B,C, nuclear import
signal
phosphorylation of intermediate filaments- disassembly of lamins result dissolution of nuclear
envelope in prometaphase of cell cyle
lamins-roles maintenance of shape of nucleus,
dephosphorylation of lamins-reassembly of nuclear envelopein telophase
inhibition of tubulin polymerization- borderline high uric acid, drinks 2 liter of water soda at race and 2
or more liters at home, he is anuric for 10 to 12 hours was prescribed with colchicine functions and
mechanism
colchicine tubulin complex-added at positive end of kinetochore but inhibits further addition of tubulin
result in biochemical capping of tubulin at growth end preventing further tubulin addition
metaphase – cells are blocked
at higher doses of colchicine-cytosolic microtubules depolymerize
actin and myosin- involvedin cytokinesis (division of cytoplasm) whereas tubulin and microtubules
regulate separation of daughter nuclei and contents
Taxol-like colchicine inhibits mitosis binds and stabilizes microtubules causing disruption of microtubule
dynamics and inhibition of mitosis
Taxol and colchicine-similar in binding only to a beta tubulin dimers and microtubules
Friedrich ataxia- caused by DNA triplet repeat expansion leading to silencing of frataxia (FXN gene)
etiology or cause is condensation of chromatin (heterochromatin and gener silencing associated with
large blocks of repetitive DNA sequences, on light microscope heterochromatin is visible as condensed
basophilic clumps
Interphase-it is transcriptionaly inactive genetic material is normally duplicated
Heterochromatin-1 of 2 subclass of chromatin on morphologic basis
Euchromatin-actively transcribe chromatin visible on electron microscope
Position effect variegation-euchromatin genes reposition to near the heterochromatin become silenced
Nucleolus-site of ribosomal RNA synthesis
Tritiated (H) uridine- may be localized to nucleolus by use of autoradioraphy, marker of RNA syn bec,
uridine is incorporated to RNA
RNA- packaged with ribosomal chons to form ribosomes
Nuclear envelope-shields nucleus from cytoplasm, allows sequestration of genetic material from
mechanical cytoplasmic forces, with 2 concentric unit membrane, highly selective, with nuclear import
signals and receptor recognition
a.outer membrane-continious with RER
b.inner nuclear membrane- associated with fibrous chons
cytoplasm-translation of mRNA
intermediate filament chons( lamins)- regulate assembly and disassembly of nuclear envelope during
mitosis
nuclear pores-interruptions in nuclear envelope functions in aqueous channels for passage of soluble
molecule from nucleus to cytoplasm
increase transcription of gene regulatory proteins as E2F-accelerating PSA has radical prostatectomy
with diagnosis of prostate carcinoma with gleason score of 7, rb, p53 and bcl 2 genes involved in
development of prostate cancer
E2F-regulated thru phosphorylation and dephosphorylation of retinoblastoma protein Rb a key negative
regulator of cell cycle
Cells that enter G1- have dephosphorylated Rb protein that is phosphorylated allowing passage of cells
from G1 to S
Dephosphorylated Rb-inhibitory bec it sequesters E2F
Phosphorylation or absence of Rb-E2F is released and induces expression of various genes associated
with initiation of cell cycle, facilitates E2F binding to DNA
BcL 2- antiapoptotic gene accumulation has associated with increase incidence and severity of prostate
cancer in afican amerikan males
Cell division kinase inhibitors-block activation of cyclic cdk cyclin dependent kinase complexes and cell
cycle progression
P53 and Rb-tumor suppressor genes
P53- increases presence of DNA damage, resulting in inhibitors as p21 resulting in uncontrolled cell
division, its absence permits proliferation of damaged cells
Absence of Rb and P53 and tumor suppression and normal control are lost
Pachytene-man with oligozoospermia, with meiotic recombinations both diminished frequency result
high frequency of aneuploidy sperm md explains meiosis and recombination attributing the problem, it
begins soon as synapsis is complete, include period of crossover
Chiasmaforms- each point where crossover occurred between 2 chromatids of homologous
chromosomes
Meiosis-to generate gametes
Gametes- cell with haploid number of chromosomes
DNA syn- occurs before meiotic prophase I begns and followed by G2 phase cell then enter meiotic
prophase I
During meiotic prophase I- maternal and paternal chromosomes precisely paired and recombination
occurs in each pairs of homologous chromosomes
5 substages of 1st meiotic prophase-leptotene, zygotene, pachytene,diplotene, diakinesis
Metaphase I-random segragation of maternal paternal chromosomes, homologous chromosomes
aligned on metaphase plate of meiotic spindle
2nd meiotic division-reduction in chromosome content of cell by 50 %,
Metaphase- consists of daughter chromatids of single homologous chromosomes aligned on a
metaphase plate ( metaphase II)
Leptotene-condensation of chromatids
Zygotene-synaptonemal complex begins to form assoc. bet chromosomes AKA synapsis
Bivalent-form bet 2 set homologous chromosomes 1 set maternal 1 set paternal= a pair of 4 chromatids
form a tetrad ( bivalent) maternal chromatids and a pair of paternal chromatids
Diplotene-formation of chiasma and desynapsing separation of axes of synaptonemal complex
Diakinesis-intermediate phase bet diplotene and metaphase of 1st meiotic division
Male with mild to moderate learning problems and infertility- chorionic villous sampling CVS and
karyotype concerned about D.S and diagnosis is Klinefelter syndrome
Klinefelter syndrome- occur as 47xxy, 48 xxxy ,49 xxxxy genotype have inactive chromosome, ratio 1:
500 male due to meiotic non disjunction, male with mild to moderate learning problem and infertility,
abn body proportions long legs short trunk, shoulders equal to hip size gynecomastia, less than normal
amount of pubic, axillary, facial hair, small testicles and penis and height taller than paents or siblings,
genotypic sex of KS and xxx individual would be male and female respectively as determined by
presence or absence of testis determining Y chromosome or Tdy chromosome
Non dysjunction- in oogenesis occurrence proportional to increasing maternal age
Turner syndrome- XO genotype and no inactive chromosome
Superfemales xxx-possess 2 inactive chromosomes and 1 active chromosome
Either amniocentesis or CVS –is used to obtain fetal cells for karyotyping
Aberrations in nuclear architecture-20 month old male with Hutchinson Gilford progerial syndrome or
HGPS, with some areas of tight hard skin, normal genetic analysis mutation in codon 608 of LMNA gene
HGPS huchinson Gilford progerial syndrome-abnormal chon progerin is generated has dominant negatve
effect on function of lamins, dramatic abnormal in architecture of ucleus shape loss of heterochromatin
(unable attach lamins)
Lamins-intermediate filament chons egulate nuclear envelop maintain its stability and are
phosphorylated (prometaphase) and dephosphorylated (telophase) during cell cycle
Laminins-binds to integrins on cell surface to facilitate attachment of cells to BM
DNA degradation- by endonucleases- hallmark of programmed cell death apoptosis, newborn with
aperts syndrome has cranosnostosis hypoplasia of middle part of face with retrusionof eyes , syndactyly
with fusion of skin CT and muscle of 1st middle ring fingers
Necrosis- response to cell injury or toxins,random DNA degradation inflammation and cell nuclear
swelling,
Bax and BcL-2-members of bcL 2, family of apoptosis regulatory CHONS
Bax- proapoptotic member of that CHON family inhibits antiapoptotic actions of BcL 2, down regulated
BcL-upregulated in syndactyly where apoptosis has failed
Apoptosis- works thru different several pathway and ultimately thru action of caspases
Import of macro molecules to the nucleus-led to triple A syndrome,all groove triple A syndrome include
the clinical triangle of adrenal failure, achalasia, alacrima, patient with neuro impairment CN IX, X, XI, XII,
optic atrophy, upper and lower limb muscle weakness and Horner syndrome, causative mutations for
disease have been identified in gene that encode protein ALADIN
All groove syndrome- a 12 neuroendocrinological dse caused by mutation in a gene that encodes the
nucleoporin aladin compo of nuclear pore complex ,have: adrenocorticotropic (ACTH) resistant adrenal
failure, achalasia (abnormal esophageal motility) due to inability of esophageal sphinter to relax,
alacrima (reduced ability to produce tears, some consider autonomic neuropathy, proposed name $ A
syndrome autonomic disturbance include horner syndrome and orthostatic hypotension
Immediate effect of mutations in nucleoporins-decreased import of macromolecules from the
cytoplasm
Nucleolus- site of RNA synthesis
Phosphorylation ( breakdown)
Dephosphorylation ( reconstitution) of lamins- regulate nuclearenvelope stability during cell cycle

EPITHELIUM
Increase in surface area for absorption- boy with normal structure of refractory diarrhea dependent on
parenteral nutrition with dx of microvillus inclusion dse or MID
MID microvillus inclusion dse- absence of microvilli in I absorptive cell (enterocyte), inability to absorb
simple nutrients, presents as refractory diarrhea in early postnatal period with chronic dependency on
TPN
Microvilli- increase surface area for specialized uptake of molecules by pinocytosis, receptor mediated
endocytosis and phagocytosis, with brush border enzymes as lactase and ALP, capable of movement
Cilia- function involve in substance as mucus foreign material over surface
Cell involvement- controlled by interaction bet cytoskeleton and extracellular matrix
Mictotubules-organellar movement within cytoplasm
Transitional epithelium-urinary system facilitate distensibility and stretch
Contraction of microfilament bundles assoc with zonula adherens desmosomes- primary neuralation
mechanism for neural tube
In apical part of cells actin filaments bundles contract narrowing cells at the apical end
Desmosomes- resisting shear forces
Z. occludens-prevent leakage between cells
Gap junctions- facilitate communication between cells to cell thru heart provide rhythmic cxn of heart
beat
Cardiac arrhythmias- to occur in presence of loss of function mutations, abnormal in spatial distribution
of gap junctions or proteins (connexins) with connexons will lead to this
Connexins-play role in obstructive coronary hear dse or MI or cardiac dse
Freeze fracture- illustrate a gap junction, connexons in circular arrangements on the P face of the
membrane
Gap junction- composed of connexons that traverse intracellular gap essential role in conduction with
cardiac muscle, maintain electrical or chemical coupling bet cells
mutations in connexins- slow down normal impulse conduction
normal peristalsis-requires normal gap junctions bet smooth muscle in SI
hemidesmosomes and integrins- adherence of EC to BM
molecular filtering- function of basement membrane
Epith cell-require BM as structural support
BM- prevents penetration from L. propia into epith pathway for migrating cells during devt and repair
processes healing skin wounds, in kidney BM of renal glomerulus forms selective barrier for filtration of
plasma
Reticular lamina-composed collagen fibrils formed by CT below epithelium
Basement membrane- basal lamina and reticular lamina
Lamina lucida or L. rara - biopsy a split with in Lamina Lucida of epidermal BM and junctional
epidermolysis bullosa (JEB) aka epidermolysis bullosa the layer affected , with primarily laminin its
connections with integrins, lamina rara contain laminin, proteoglycan and adhesive chons
Lamina densa- deep to lamina rara, with its electron dense type 4 collagen
JEB-disruption bet laminin sp beta and gamma chains and integrins
Na- K –Atpase-congestive HF given digoxin to increase myocardial contractility, target of digoxin and
characterizes basolateral membrane of cardiomyocyte and all eukaryotic cells and is responsible for
gene ating NA- K- gradient of cell
Sodium- pumped out of cell
Potassium- into cell by this ATP dependent pump
Digoxin-inhibit cardiomyocyte Na K atpase reducing transport of sodium from cell and leading to
increased intracellular sodium
Higherintracellular sodium levels- cause decrease in calcium efflux and increase in calcium influx
In response to rise in intracellular calcium- the Sarcoplasmic reticulum of digoxin exposed
cardiomyocyte sequesters more calcium
When cardiomyocytes exposed to digoxin- it depolarize in response to an action potential there are
more calcium available to bind troponin C and stronger cxn is facilitated,
Decrease active transport- dentist observe firm mass on the anterior right side of floor of mouth, the
calcification blocks the submandibular duct leading to atropy of acini and ducts with reduce secretory
function, and changes in basal folds of striated duct cells
Distal tubule cells of kidney and striated duct cells of Submandibular glands- possess prominent basal
infoldings
Basal fold- modifications of basal region of cell
Deep infoldings of basal plasma membrane- increase surface area provide energy for tonic and water
transport
Primary isotonic saliva- formed by acinar cells and modified by striated duct cells which resorb na and
excrete K
Macula adherens/ desmosomes- form spot weld/ rivet bet adjacent cells, resist shearing forces on
epithelium
Zonula occludens- provide tight seal between epithelial cells
Zonula adherens-interact with actin that comprise the terminal web
Microvilli- brush border covered by glycocalyx and SI contains enzymes involve in degradation of food in
lumen
Abnormalities occur in organization of axonemal ciliary dynein arms that bridge the 9 outer doublet
microtubules to each other- male with ciliary dyskinesia sinusitis, shows dextrocardia with diagnosis
kartagener aka immotile cilia syndrome
Kartagener /aka immotile cilia syndrome- don’t function normal lead to chronic infections otitis media
infertility (immotile sperm or sub optimal oviductal ciliary function in females, abnormalities occur in
organization of axonemal ciliary dynein arms that bridge the 9 outer doublet microtubules to each
other,uncoordinated dyskinesia more prevalent, primary ciliary dyskinesia
Dynein-high molecular weight ATPAse when activated it produces sliding motion of microtubules
Protein nexin- links outer microtubular doublex creating strap like arrangement of paired microtubules
Inner sheaths- surround the central microtubule doublet
Radial spokes- restrain the sliding movement of outer doublets
Basal body- anchors microtubules converting sliding of outer microtubules into the bending of cilum
Bronchiectasis- irreversible abn. Dilation of 1 or more bronchi associated with various lung conditions
with chronic infection
Dextrocardia- cardiac apex to right occurs in mild case.
Situs inversus- in more severe cases, morphologic right atrium is on Left and morphologic left atrium is
on Right, pulmo structures right or left lungs as abdominal organs may also be reversed in mirror image ,
devt of right to left asymmetry is at least partially regulated by ciliary beat at hensen node
Saccharin test-test for nasal mucociliary clearance carried out placing small amount of saccharin behind
anterior end of turbinate
In mucociliary action- saccharin will be swept backward to nasopharynx a sweet taste perceived
Failure of sweetness to ne detected in about 20 minues-indicates delayed mucociliay clearance
Restriction of the microtubule doublets b radial spokes nexin and basal bodies- conversion of sliding to
bending in the cilium is accomplished
Nexin,radial spokes, and basal body –all play role in restricting the sliding moton and converting it to
the bending of the axoneme in relation to basal body, it links outer microtubular doublets creating strap
arrangement,
Basal body- anchors microtubules plays essential role in converting the sliding of the outer microtubules
into bending of cilium, itresit sliding movement generated by dynein activation
Radial spokes- hold microtubule doublets in place and sliding is limited lengthwise, are rigid do not slide
against nexin
Macula adherens/desmosomes-there is positive nikolsky sign, sera analysis indicates auto antibodies to
a sub family of cadherins with diagnosisof P. vulgaris
P.vulgaris-autoantibodies to desmogleins, amember of cadherin protein family result in disruption of
macula adherens (desmosomes), autoantibodies specific to desmoglein, which begin as oral lesion
appear cutaneously, positive nikolsky sign at edge of blister ext to adjacent skin
Desmogleins-transmembrane linker chons of desmosomes
Specific desmogleins- target of auto antibodies in diff. form of the dse.
Cadherins-critical molecule in maintainance of zonula adherens, are calcium dependent transmembrane
linker molecule essential for cell to cell contact so their disruption n pemphigus leads to severe blistering
of skin because of disrupted cell to cell interactions early in differentiation of keratinocytes (epidermal
cells) and excessive fluid loss.
Subepidemal dse bullous pemphigoid (BP)- BP Ag (BPAG ) and BPAG2) cause separation of epith for
basal lamina- negative nikolsky sign
Epidermolysis bullosa acquisita (EBA) distinct blistering dse EBA ag is localized within subjacent to L.
densa
Hemidesmosomes, basal lamina- L. densa of basal lamina
Centrioles- where triplet arrangement of microtubules is found, consist of microtubule triples linking
chons to form a cartwheel arrangement
Microtubules- in different structural pattern
Basal body- has 9 triplet arrangement
Flagella- 9 plus 2 arrangement as cilia limited to 1 per cell only in sperm
Axoneme- classic 9 plus 2 arrangement of microtubules
Stereocilia-large modified microvilli in epidydmis hair cells n organ of corti

CONNECTIVE TISSUE
Aorta-most affected bec of extensive elastin in wall and dissecting aortic aneurysm, in cardiovasc there
is valve problems, aortic aneurysm, in skin there is abnormal height, severe chest deformities, ocular
system,molecular basis : mutations in fibrillin gene, lens often affected, result in dislocation of lens loss
of elasticity in suspensory ligament, 27 yearold 5 ft and 10 inch tall with pneumothorax scoliosis pectus
excavatum, and stretch marks in buttocks,with dx of marfan syndrome
Marfan syn- AD elastic tissue, decrease elasticity of lung tissue causes increase tendency toward
spontaneous pneumothorax aka collapsed lung
Integrins-extracellular matrix and cytoskeleton communicate across cell membrane , are
transmembrane heterodimers (integral membrane proteins ) acts as membrane receptors ex fibronectin
receptor, laminin receptor
Intermediate filaments and microtubules-intracellularly constitute cytoskeleton
Proteoglycans-located extracellular surface of plasma membrane throughout extracellular matrix
Cadherins- function as transmembrane glycoprotein in the formation of parts of intercellular junctional
are components of desmosomes and zonula adherens complexes
Cell attachment and adhesion-type 2 dm taking humulin 3x a day for decades complain floaters
difficulty nightdriving fundoscopy with proliferative diabetic nephropathy, fibronectin ishisto marker
ofdiabetic microangiopathy which is the primary function of fibronectin in basement membrane
Fibronectin- adhesive glycochon impt in cell attachment and adhesion, for modulaton and cell migration
in adult during devt,neural crest and othercells guided here,contain cell binding domain (RGD sequence)
collagen binding domain and heparin binding domain
Has 3 forms:
a. plasma form- in blood clotting
b. cell surface-binds to cell surface transiently
c. matrix- fibrillar in arranement
elastin and type III collagen- elasticity in large artery pinna of ear
cell to cell interactions-both transient and long term stable process
cell adhesion-mediaed b transmemebrane chons (cell adhesion molecule) include Calcium, magnesium,
dependent selectins integrins and cadherins and non calcium dependent Ig superfamily
Zonula adherens-stable adhesion junction links the cytoskeleton of adjacent cell thru cadherins
(transmembrane linker chons) to actin filaments inside the cell
Crosslinking tropo elastin-serum alpha 1 antitypsin AAT conc is below normal indicating a copy of S and
1 of Z (SZ) mutation and 40 percent abnormal AAT protein production, desmosine, isodesmosine are
elevated in the urine and both contribute to elasticity of lung with this mechanism and dx is AAT def.
emphysema A1 antirypsin defieceincy
AAT- protects lung from neutrophil derived elastase which breaks down elastic fibers
Desmosine, isodesmosine- are AA unique to elastin, for covalent binding of elastin to each other
Lysyl oxidase-catalyses cross linking of tropoelastin, microfibrils composed of fibrillin facilitate formation
of elastin molecules
Elastase- serine proteasesp degrades elastin,occur between type III collagen and elastic fiber
Collagen- elasticity is conferred thru highly hydrophobic nature of elastin
½ of elastin- composed of hydrophobic AA Glycine randomly distributed throughout elastin molecule in
contrast to even distribution of glycine in collagen, random distribution of glycine makes elastin
hydrophobic,overall hydrophobicity of elastin molecules allows for their distensibility, facilitates their
capacity to slide over 1 another
Ascorbic acid def. result In insufficient hydroxylation of collagen-endency with bruising, bleeding
periodontium
Vitamin C- cofactor reducing agent in hydroxylation of proline, lysine by prolyl and lysyl hydroxylase
espectively
Scurvy-def of ascorbic acid result insufficient hydroxylation of collagen and abnormal collagen fibrils
Prolyl and lysyl hydroxylase-2 enzymes carry out hydroxylation of proline, lysine 2 AA caract of collagen
Hydroxyproline-10 percent of collagen used to determine collagencontent of various tissues
Hydroxylation of proline-stabilizes triple helix thru interchain Hydrogen bonds
Hydroxylation of lysine- critical for cross linking stage of collagen assembly
Presence of non helical registration peptides at ends of triple helix-reason ropocollagen is not
assembled in cell
Cell- RER, golgi app , secretory vesicles
Collagen-synthesis as pro a- chain assembled into procollagen molecule triple helix in RER
Procollagen- transported in transfer vesicles togolgi for packaging into secretory vesicles
Transport of secretory vesicles- energy andmicrotubule dependent process
Outside cell- N terminal and C terminal sp prcollagen peptidases cleave non helical registration peptides
result form troprocollagen
Tropocollagen- assembles stagger array form collagen fibrils
Lysyl oxidase- extracellular enzymeform covalent cross links bet trpocollagen molecule
Fibrils- form collagen fibers under influence other extracellular matrix constituents as proteoglycans,
glycoproteins
Collagenases- sp cleave tropocollagen in extracellular matrix
Laminin to collagen- butteryfly rash after sun exposure her wbs 3.2 normal >4 hct 25% normal 3% esr
120 normal <20, serumcrea is 1.6 normal 0.8-1.4 mg/dl, urine protein to crea is 2.1 normal < 0.1 and 24
hoururine crea is 2500normal 500-2000 with positive ANA test and DNA antibodies autoantibodies
detectedto entactin (nidogen) with dx of SLE
SLE- major criteria leukopenia, nephritis, (+) ANA, (+)anti Ds DNA, arthritis,
Entactin (nidogen)- primary function to cross link laminin to type 4 collagen
Basal lamina- formed by interactions bet type4 collagen and lamin, entactin and proteoglycan
Integrins-like lamin receptors bind cells to basal lamina
Lysyl oxidase-deaminates lysine and hydroxylysine to form aldehyde
Actin- crosslink into bundles by binding chons as bundling chon a- actinin a gel forming chon ( fibrin)
Fibronectin receptors- bind cells to extracellular matrix
Laminin receptor in cell membrane- organize assembly of basal lamina
Collagen-cross linked by covalent intramolecular intermolecular cross links bet non helical segments at
ends of collagen molecule
Rupture of intestinal or aortic walls- abnormal secretion of type III procollagen a mutation on COL3A1
gene with dx ehelerdahlos syndrome 4/ EDS 4
EDS 4- of vascular type improperly formed type III collagen responsible for elasticity of intestinal and
aortic walls,errors in transcription of type III collagen in RNA
EDS 6- hypeextensible skin hydroxylation of AA lysine
EDS 7 sp def. of AA terminal procollagen peptidase that alter propeptide sequence that molecular
oeientation cross linking are adversely affected, result hypermotility of synovial joints
OA- increase degradation of proteoglycans
Type I collagen-in dentin
Use of FA to produce heat-biopsy of subq tissue necrosis of tissue in photo which differ with white
adipose tissue dx is SCFN subcutaneous fat necrosis of nb
SCFN- firm erythematous nodulespalques on FT. NB in 1st few weeks of life, induced by cold stress
induced in injury to immature fat
Both types fat tissues brown and white) are highly vascularized and function in protection from cold
Brown fat- heat production, non shivering thermogenesis for developing organs in fetus and
neonate,Brown adipose tissue-multilocular in fetus and neonate, FA are used with in the cell, Result –
solidification +necrosis,
White fat-thermal insulator,lipid storage, shock absorber, unilocular single large lipid droplet in
cytoplasm provides signet ring appearance,in white adipocytes are released FA and glycerol are
exported from cells
Heat-by extensive capillary networks in brown adipose
Shivering-caused by hypothermia mobilization of lipid in white adipose bec requires energy
Electron transport- is uncoupled from oxidative phosphorylation, results in production of heat insteadof
ATP
In fat NE- activates CAMP cascade thru adenylate cyclase
CAMP-activates hormone SN lipase which removes TG from stored lipid hydrolyzes free FA
Leukocytosis-NB with delayed umbilical cord separation normal 3-45 days mean 10 days with elvated
WBC > 20 x 10 in absence of infection with dx of primary immunodef leukocyte adhesion def . a loss of
function mutation in integrin expression on lymphocytes (beta 2 integrin CD 18) is identified
Leukocytosis-mutation loss of integrin function increase lymphocytes in blood
LAD leukocyte adhesion Dse-rare congenital immunodef from recurrent bacterial infections in which
leukocytes fr children fail to adhere to endothelial cells, defects of leukocyte integrin CD 18 subunit
LAD cascade: rolling, integrin activation, firm adhesion of leukocytes- all necessary prerequisite to
transendothelial migration
Initial dx work up- blood test ff failure separation of umbilical cord
Inflammatory bowel dse crohns and UC-alterations of lymphocyte integrins
Formation of unstable collagen helices-dums from others with bleeding under skin around hair follicles
with bruises on arms with dx vitamin c def
Vitamin C def- cause scuvy woman smokes diet deficient in freshfruits vegetables, result inability to
form normal collagen triple helices
Collagen- not normally hydroxlated at proline and lysine residues bec absence of vitamin C
Absence of vitamin C-sp cofactor for hydroxylation of proline and lysine , general tissue instability,
periodontal bleeding, ulceration common symptom scurvy
Intramolecular and intermolecular cross links-with DM since child with Charcot foot neuroarthropathy
and weakness in his calf muscles
Fibrillar collagens- establish tensile strengths
Covalent binding- occurs thru OH groups of hydroxyl lysine and hydroxyproline to stabilize triple helix
Triple helix-to resist tensile forces ex, in tendons varies onfunction from layered appearance in bone to
axial parallelbundles
Interaction with fibril associated collagens-important in establishing tissue org. and flexibility
Lysine and hydroxylysine- substrate for lysyl oxidase catalyses the formation of cross links
In adherence of epithelial to the BM-genetic analysis mutational defect in laminin 5 laminin functions
and dx is JEB
Junctional epidermolysis bullosa-blisters form at level of L. lucida with in B. lamina
Laminin in L.rara (lucida) of B. lamina binds to laminin receptor (integrin) of the EC
Cell to cell interaction- modulated by cell adhesion molecule ex calcium dependent cadherin and
selectins and calcium independent CAMS as neural cell adhesion molecules (N- CAM)
Laminin-glycoprotein, major component of BM, involved in cell adherence to basal lamina, contains cell
binding site as well binding site for collagen entactin (nidogen) and heparin sulfate proteoglycan
Type 4 collagen- insoluble scaffolding of B. lamina
Highly charged GAGS- for filtration characteristics of BM ex renal glomerular BM
Edema-malewith 100 oval round red brown macles on her back with a (+) dariers sign, stained with
toluidine blue with metachromatically stained cells dx is urticarial pigmentosa induced by mastocytosis
Mastocytosis-excessive production mast cells by bone marrow cell in biopsy mast cells that stain
metachromatically from blue to purple, like basophils they synthesize and secrete heparin and
histamine, as result excessive release of bioactive products contained in mast cells granules like
hitamine, heparin eosinophil chemotactic factor ofanaphylaxis SRS-A and leukotrines, they induce
urticarial pigmentosa wth edema caused by increased vascular permeability induced by histamine and
SRS A, infiltration of eosinophil attracted ECF Acause itching, excessive production of acid by parietalcell
of stomach bec of over stimulation of histamine result peptic ulcer and gastritis
Lower GIT- increase motility diarheaa due to stimulation by mast cells contents
Osteoporosis, anemia- occur in multiple myeloma plasma cytosis there is excessive number of plasma
cells
Periportal fibrosis of liver –in systemic mastocytosis de to extensive infiltration of mast cells in liver,
excessive production of plasma cells in bone marrow disrupts normal hematopoiesisinclude production
of RBCs causing plasma cell release IL1,IL6,TNF alpha then induce osteoporosis
(+) dariers sign- red wheal and surround erythema around lesion after rubbing due to release of
histamine
Acceleration of chemotaxis of monocytes macrophages- MOA of PDGF ,man with dm1 with foot ulcers
wasprescribed with becaplermin gel, which contains latelet derived growth factor PDGF
PDGF-stimulate chemotaxis of monocytes and macrophages as well as fibroblast to site of wound,
induce proliferation of vascular smooth muscle,induce proliferation of vascular smooth muscles in blood
vessel repair and fibroblast to synthesis type I collagen, stimulate granulation tissue with new CT and
small BV
Type II collagen- synthesized by chondrocytes in hyaline and elastic cartilage
Wound healing-complex process initiated by damage to capillaries in dermis
Clot- forms thru interaction of integrins on surface of blood platelets with fibrinogen and fibronectin.
Scar-formed as a very dense region of type I collagen fibers
Macrophages-remove debris at wound site and involved in remodeling of scar
All wound healing- slower in diabetics and presenced of advanced glycation end products (AGE) and
interaction with receptor for AGE (RAGE) as well as endogenous ligand for RAGE (ENRAGE)
AGE-produced by non enzymatic glycation and oxidation of CHON or lipids and alter those molecules
and therefore function and structure of tissue organs as kidney (diabetic nephropathy) peripheral nerve
(neuropathy and retina) diabetic retinopathy
IgA-patient with right sided muscular weakness xray revealed 2wedge thoracic vertebrae with dx of
multiple myeloma
Multiple myeloma-increase in number of plasma cells for production of immunoglobulin, Plasma cell-
eccentric nuclei with coarse granules of hetro chromatin arranged in radial pattern about the nuclear
envelope,produced all Ig IgG,IgA,IgM,IgD,IgE are derived from B lymphocytes
Membrane bound ribosome- intense basophilia
Ribosomes-involve in antibody production IgG
Differentiation of plasma cells requires Ag presenting cells (macrophages, dendritic cells or B cells)- that
pahgocytose and present Ag MHCII complex and T helper (T14) cells
Fibroblast-synthesize collagen
Mastcell- synthesize heparin and histamine
Eosinophils- synthesize histaminase
Neutrophil- synthesize myeloperoxidase
Increase release of NE from Nerve terminals in adipose tissue-patient allergic to erythromycin, patient
has family history of HPN and DM and stroke, in this patient period of weight gain, is responsible
Leptin-chon hormone by adipocytes binds receptors in hypothalamus has multiple effects include
increase release of NE from sympathetic nerve terminals that innervate adipose tissues, inhibits
hypothalamic synthesis and secretion of neuropeptide Y an appetite (orexigenic peptide)
Adipocyte adrenergic receptors- bind NE leading to increase metab of FA with dissipation of energy as
heat
Serum levels of leptin are increased- as weight increase adipocyte accumulate TG the obese OB gen is
upregulated n adipocytes and leptin synthesis
Leptin receptors in hypothalamus- upregulated as leptin levels increase,
Metalloproteinases- exposed to second hand smoke both home (his wife smokes)biopsy shows
transitional cell carcinoma 4.5 cm in diameter staged as T3N1M2 which is involved in M2 classification
Metalloproteinases- as serine, cysteine, metalloproteinases (MMPs) include type 4 collagenase MMP-2,
also play key role in freeing tumor cells to migrate to metastatic sites
Transitional cell carcinoma-tumor cell adhere to BM, to undergo mets, must dissolve BM and
extracellular matrix in order to reach blood stream and migrate to new site
Lysyl oxidase-responsible for cross linking of collagen by deamination of lysne and hydroxylysine
residues to form aldehydes
Aldehydes- interact with each other lysyl side chains and form collagen cross links
Synthesis of elastin has similar process
Plasminogen-inactive form of plasmin occurs in plasma converted to plasmin by organic solvents
Serpins-serines protease inhibitors memvers of that gene family regulate cell division and migration,
neurite ext tumor cell mets and blood coagulation, are specific inhibitors of cell surface and extracellular
matrix, are serine proteases that participate in cascade mechanisms
TIMPS- tissue inhibitors of metallproteinases like serpins inhibit degradation of extracellular matrix

SPECIALIZED CT AND BONE AND CARTILAGE

Microenvironment in which ossification occurs or bone formation occurs-intramembranous
ossification differs from endochondral ossification
Intramembranous and endochondral ossification BOTH has bone development, same process
synthesis of collagen and other matrix components by osteoblasts and calcification of matrix tru action
of ALP from osteoblasts
Bone devt occurs 2 different locations which differ in presence or abscense of cartilage models
Example
Intramembranous ossification- ex. Flat bones of skull-bone formation occurs thru differentiation of
osteoprogenitor cell from mesoderm and accompanied by vascularization
Endochondral chondrocytes- establish cartilage model ex.long bone subsequently replaced by bone
humerus and femur- used as scaffolding for bone formation
Decrease interstitial growth of chondroblasts in the epiphyses-prominent forehead frontal bossing,
radioexam by MRI reveals caudal narrowing of interpedicular spaces of T1 and T2 vertebrae and spinal
stenosis of L2-L4, gene analysis, gain of function mutation, G1138A in fibroblast growth actorreceptor3
(FGFR3) band 4p16.3, with a diagnosis of Achondroplasia
Achondroplasia- common mutation cause a gain of function of FGFR3 gene result in decrease in
endochondral ossification inhibited proliferation of chondroblast in, growth plate cartilage, with
decrease cellular hypertrophy and decrease cartilage matrix production
Secondary ossification centers of epiphyses- Growth in length of long bones AFTER Birth (postnataly)-
occurs thru cell proliferation of chondroblasts (immature chondrocytes)
Diaphysis of cartilage model(primary ossification center)-BEFORE birth growth of length of long bone
occurs primary thru proliferation of chondroblasts
Growth in width of longbones- occurs by add on of osteoblast by periosteumand deposition of
periosteal example collar- this is appositional growth with a a cartilage intermediate (intramembranous
ossification)
Primary ossification centers close soon after birth
Cartilage model is replaced by bone Fetal devt of long bones- occurs by process of endochondral
ossification
Osteoblasts- deposit bone matrix and secret ALP
Hydration of GAGs-molecular basis for shock absorption within articular cartilage , role shock
absorption and enchances resilency of cartilage, role important which is articular cartilages which
receive pressure during joint movement required to resist strong compressive forces
Proteoglycans-major component of ground sites of cartilage, possess large an aionic charge because of
sulfate hydroxyl carboxyl groups with in Gags with in GAGs which join to form proteoglycan subunits by
linking with a core chon
Proteoglycan (monomers)-linking non covalently to hyaluronic acid with type II collagen
Negative charge of GAGs- binding of cations and transport electrolytes and water with in matrix,
important aspect of cartilage metabolism because chondrocytes depend on diffusion to obtain nutrients
Calcitonin receptors- are found in osteoclasts,long term responses of elevated calciumare mediated
lowering of PTH levels, and is exemplified in patients with absence of calcitonin secretion after
thyroidectomy example : medullary thyroid cancer –normal bone metabolism- calcitonin measurement
important
ARF cycle-links osteoblast , osteoclast presence high calcium- calcitonin is synthesized released from C
interfollicular, parafolicular) cells of thyroid with decreases rufled border activity
Alkaline phosphatase-webbed neck , low levels of estrogen, short stature linked to reduced protein
expression of the short stature homeobox gene (SHOX ) with dx of turner syndrome
Turner syndrome-gonadal dysgenesis in which 45 x karyotypes result multiple medical problems, region
in box zone of chondrocyte hypertrophy where chondrocytes synthesize ALP which calcifies the cartilage
matrix leading to chondrocyte death bec dependence on diffusion to obtain oxygen and nutrient from
matrix
Angiogenesis-bone formation action of osteoblasts forming type I collagen non collagenous CHONS (
osteocalcin, osteopontin, and osteonectin) and ALP which play in mineralization of osteoid.
Acid phosphatase- synthesize by osteoclasts and type I collagen
Osteocalcin- synthesized by osteoblasts
During long bone development- specific zones established as cartilage model of long bone converted to
mature bone.
Zones from epiphysis toward center of shaft ( diaphysis ) and resting zone proliferative zone,
hypertrophyzone and zone of calcified cartilage- is used as scaffolding for deposition of bone
Periosteal bud- represents ingrowth of blood vessel ( angiogenesis ) bringing bone marrow precursors
and osteoprogenitor cells into diaphysis
Proton pump activity similar to a parietal cell- history of recurrent fracture of humerus and femur,
umerous dental caries associated with ascesses. Serum acidphosphatase is 4 units normal .5-2 and hct is
35 normal 41-50percent mean 47 %, complains joint pain, sandwich vertebra with thickening of
vertebral end plates and abnormal thickening of long bones and basilar sclerosis with diagnosis type II A
osteopetrosis (type II ADO ) aka as albert Schonberg dse which is the radiological image sandwich
vertebrae
Albert Schonberg dse-targets osteoclast which function is altered in osteopetrosis, function by release
of lytic enzymes and protons derived from carbonic acid
Bone compartment around ruffled border of osteoclast- analogous to secondary lysosome in function
Osteoclasts- use protons derived from carbonic acid anhydrase in similar to parietal cells of stomach
ALP-synthesize by osteoclast
PTH and vitamin D receptors- on osteoblast
Osteoclast with its distinctive ruffled border, multinucleate cells in small depressions in bone (howships
lacunae)
PTH- major regulator osteoclastic activit, increase osteoclast and ruffled
Osteoclast- respond to low serum calcium by removing calcium from bone
PTH receptors-in osteoblast which release RANK-L and M- CSF
Vitamin D receptors- present on osteoblast
Calcitonin-transient changes in bone formation resorption
Heterologous auto antibody directed against the synovium- pain is seropositive for anti cyclic
citrullinated peptide ( anti CCP) antibodies, Pe shows decrease abduction and extension rotation on
right and left shoulders has swelling in her right and left metacarpal phalangeal jont with full range of
motion, with diagnosis of R.A
R.A- auto immune disease in which rheumatoid factor composed of heterologous autoantibody directed
against serum ama globulin IgG
Arthritis- inflammatory changes in joint appears
Anti CCP antibodies-use to diagnose R.A superiorover IgM RF in predicting erosive dse., RF 85 to 90 % of
patients with RA,
Alteration of synovial membrane- results a pannus inflammatory hypertrophic synovial villus
Presence of pannus and release lysosomal enzymes from pannus results-degradation of cartilage ff by
hypertrophy hyperplasia of articular cartilage which leads to bone formation across the joint with
welding bones together (ankylosis)
Because of inflammation in RA- elevated leukocytes n particular PMNs in synovial fluid, also fbrinogen
is another indicator inflammatory response elevated
Calcitonin- use as nasal spray for osteoporosis when cant tolerate bisphosphonates
Biphosphonates- analogous of pyrophosphate primary means treating osteoporosis and pagets disease,
inhibit osteoclstic activity thru apoptosis of osteoclast
Osteoarthritis-begins loss of hydrated GAGs ff by death of chondrocytes and fibrillation and devt of
fissures in articular cartilage matrix, severe wear and tear increase with age, during breakdown of
articular cartilage width of bone increase, formation of reactive bone spurs osteophytes which may
break off to form foreign bodies (joint mice), in fingers affect DIP primarily, with painful nodular
enlargement called heberdens nodes, large weight bearng joints, with eburnation in late stage with
result osseous articular cartilage
Clot-placing hand out to save herself in process her wrist is forced backward with xray on micrograph 1st
step in healing the injury, which is organized into a callus by granulation tissue and diagnosis is Colles
fracture
Colles fracture- MC wrist fracture 2 cm from wristjoint where radius narrows from cancellous bone
forming the joint of cortical bone of shaft
Granulation tissue- consists of fibroblast, osteogenic cells and budding capillaries
Internal bony callous- forms where local bone factors most active close proximity to periostium and
endosteum retain osteogenic potential
External cartilaginous callus- forms bone by endochondral ossification ff initial chondrogenesis, involved
histiogenesis of bone
Bone graft- more impt temporary bridge
Other methods electrical forces and bone morphogenic protein (BMP)- a bone growth factor obtained
from decalcified bone matrix
BMD-stimulates bone when implanted at fracture site
Pannus formation- inflammation event with in synovial membrane in R.A
Pagets dse aka osteitis deformans-man with increase warmth over right thigh ALP 656 normal 23-110
elevated 24 hr urine hydroxyproline and osteocalcin 13 normal 6 ng ml, xray of hips and pelvis with
osteolytic lesions and regions with excessive osteoblastic activity, bone scan with significant uptake in
Right proximal femur
Pagets dse aka osteitis deformans- example skull, femoral head enlargement, serum calciumis normal
but increase ( osteolytic lesions and proline), increase osteoblastic activity ( elevated osteocalcin and
ALP), exhibit marked increase osteoid and bone enlarges, bone scan shows significant uptake of labeled
bisphosphonates
Bisphosphonates- into newly formed osteoid during bone formation,her prox femur is enlarged no
longer fit acetabulum result in hip pain
Osteoclasts- synthesis tartrate resistant acid phosphatase so increase osteoclastic activity is reflected
Hydroxyproline- good marker of bone metabolism, because its released in urine as collagen breakdown
Pyridinoline crosslinks- involved in bundling of type I collagen used for measurement of bone resorption
Markers of bone formation- osteocalcin, ALP, extention peptides of type I collagen
Osteocalcin- vitamin K dependent y- carboxy glutamic acid CHON synthesis by osteoblast secreted in
serum in unchanged state, its serum conc is proportional related to osteoblastic activity, more sp organs
as liver, kidney produce that enzyme
Xray-use to detect osteoporosis only after 30-50 percent bone mass
Dual beam photon absorptiometry-accurate dx of loss of bone mass
Increase IL-1,IL6, TNF alpha by plasma cells-abnormal serum chon electrophoresis with a monoclonal
IgG spike,urine (+) bence jones protein and abnormal bone marrow smear, xray reveal lytic lesions of
skull and pelvis and compression fracture of lumbar vertebrae with diagnosis of Multiple myeloma
Multiple myeloma-increase plasma cell activity and anemia hgb data and increase fatique, plasma cells
produce elevated IL 1
IL-1 functions as osteoblast activation factor resulting in elevated serum calcium
Compression fracture of spine-depletion of bone calcium result lytic lesion of skull, pelvis
Bence jones chon-free Ig light chains featue (bence jones proteinuria) in urine in patients with MM
RANK-on osteoclasts, stimulates osteoclastic activity
Mastcells- upregulated in MM
Osteoprotegerin- are decrease in MM
Osteomalacia-lab test show low levels of 1,25 hydroxy vitamin D, calcium and phosphorus and elevated
ALP, related to malnutrition specific with vitamin D deficiency, 2nd biopsy was not decalcified shows
uncalcified osteoid on all bone surface, being formed not undergoing mineralization, correlates with low
25 hydroxy vitamin D levels, vitamin D replacement and calcium supplement is prescribed
Osteoporosis-1st biopsy calcified,induce by excess glucocorticoid, example cushings syndrome increase
level corticosteroids interfere bone metabolism, prolong steroid therapy result increase bone resorption
compared with bone deposition, 6th decade and 7th decade problem with normal aging both sexes, bone
deposition and bone resorption is lost, prevalent in post menopausal women because protective effect
of estrogen is no longer present
Bone fragility resulting from excess bone resorption- etiology of osteoporosis induced by cushing
syndrome
Intestinal calcium absorption- inhibited and PTH levels may be increase
Tetany-chromosome 22q112 leading to diagnosis of anomaly which results from failure of normal
development of 3rd or 4th brachial pouches during embryo development with diagnosis of di George
anomaly
Di George anomaly- absence of thymus and parathyroid land arise from 3rd 4th pairs of
brachial(pharyngeal pouches)
Absence of thymus-result deficiency in T. lymphocytes- dependent areas of immune system
Dependent areas- deep cortex of lymph node,PALS of spleen, intefollicular areas of peyers patches
PTH- stimulates devt of osteoclasts and form ruffled borders of osteoclasts
Absence of PTH results- drastic reduction of numbers and activity of osteoclasts, reduced calcium levels
in blood, denser bone,spastic cxns of muscled tetany, excessive excitability of N.S
Parafollicular cells (C cells)- arise from ultimo brachial body migrates into thyroid gland and should form
normally
Accumulation of calcium and phosphate in form of hydroxyapatite crystals-MOA for matrix vesicles
which are derived from cell membrane of osteoclasts hypertrophied chondrocytes, ameloblast,
odontoblast depending on location
Exposure of seed crystals to ECF-leads to seeding of osteoid between spaces in collagen fibrils located in
matrix
Osteoprotegerin-inhibits osteoclastic activity
Osteoblasts- synthesis type I collagen
Formation of 3D lattice of matrix- the collagenous chon in bone subserous
Type I collagen- for 3D fiber structure of matrix synthesis by osteoblasts and amount 85 % to 90 % of
total bone chon
Non collagenous bone chon- primarily synthesized by osteoblasts 10-15 % of bone CHON, include
cytokines, growth factors, which are synthesized endogenously and become trapped in matrix, are also
cell attachment chons as fibronectin, osteopontin, proteoglycans, example chondroitin 4 sulfate,
chondroitin 6 sulfate both play a role in collagen fibrille genesis GLA ( containing y-carboxyglutamic acid)
chons as osteocalcin which bind calcium mineral component to matrix
Some plasma chons-absorbed by bone matrix
Site of near tear damage- halmark of OA dse begins with production of metalloproteinases as
collagenases that proteolytically destroy cartilage matrix
Erosion of articular cartilage- leads to release of proteoglycans and collagen fragments into synovial
fluid, joint architecture is altered, it induces bone overgrowth in response to stabilize the joint
Joint cavity- lined by ext fibrous layer
Synovial fluid- form from synovial capillary ultrafiltrate as mucins, hyaluronic acid, glycoproteins by
fibroblast like cells in synovial epithelium that lines fluid filled joint cavity
Diarthrosis- it is freely movable joint
Synarthroses-limited or no movement and classified by uniting CT
Hyaline cartilage- syndesmoses, covers ends of bones, lacks a pericondrium
Macrophage like cells perform phagocytic function
Synovial fluid-reduced protein content, as lubricant becomes more viscus with age, use to diagnose
joint disorder as arthritis
R.A-autoimmune infiltration of cells from immune system to destruction of synovial capsule and
articular cartilages.
Inflammation of synovium- formation of pannus to changes in articular cartilage converting it to fibro
cartilaginous structure
Apoptosis of osteoclasts- dual energy absorptiometry DXA is -2 for spine -2.5 for hip, MOA of
bisphosphonates with diagnosis of osteoporosis
DXA- increase chance of 4x spine fracture than person with BMP normal bone mineral density
Bisphosphonates- most effective treatment osteoporosis, target is mitochondria, analogs of
pyrophosphates, suppress bone resorption by osteoclasts
Increase RANK- L secretion by osteoblast, increase M-CSF secretion by osteoblasts- increase all
osteoclastic activity
Inhibition of osteoblastic activity block new bone deposition inhibit production of RANK-L (receptor for
activation of nuclear factor Kappa beta-ligand) and M-CSF macrophage colony stimulating factor by
osteoblasts
M-CSF-stimulate M-CSF diffentiation of monocytes into osteoclasts
RANK-L binds to RANK on osteoblasts stimulate osteoclastic activity
ALP-bone forming cells in lungs once osteosarcoma cells reach the lungs, enter parenchyma and clonally
expand they producebone synthesis with diagnosis of osteosarcoma cells which metastasize to lungs
synthesize bone and functionlike osteoblasts from which it is derived
Osteoblasts and osteosarcoma cells-synthesize ALP which is critical in increasing local calcium
phosphate ratio inducing calcification of osteoid (prebone) to form one
Osteoblast-synthesize type I collagen
Fibroblast highly cellular organs; spleen- synthesize type III collagen, primary component of reticular
fibers
Chondrocytes in hyaline and elastic cartilage-synthesize type II collagen
Acid phosphatase- synthesize by osteoblasts for dissolution of bone and its resorption
Elastin- synthesize by smooth musclecells, endothelial, microvascular cells, chondrocytes, and
fibroblasts
Upregulation of tissue inhibitors of matrix metalloproteinases (TIMPS) at primary tumor site- a
laboratory to prevent spread of tissue inhibitors of matrix metalloproteinases (TIMPS) at primary tumor
site- a laboratory successful approach to prevent spread of metastatic osteosarcoma
To reduce metastasis is to below- target for therapy of metastatic tumors as osteosarcoma
TIMPS-inhibit proteolytic activityof matrix metalloproteinases(MMPS), inhibiting tumor invasion of BM
or restraining tumor angiogenesis, they modulate tumor growth and apoptosis of tumor cells
Enchance tumor growth-down regulation of anti antiangiogenic peptides angiostatin endostatin
Angiostatin- cleavage product of plasminogen
Endostatin-cleavage product of type XVIII collagen
Antibodies to fibronectin, integrins and lamin-interfere with metastasis
Enchancement of integrin-integrin receptor interaction- facilitate metastasis
Overexpression of selectins on endothelial cells- enchance sticking of tumor cells to endothelium and
eventual extravasation
Type II-in nasal septum
Type I-ubiquitous
Type III- collagen forms reticular network in highly cellular organs
Type IV-in basement membrane
Type VII-in basement membrane of skin and anchoring fibrils

MUSCLE AND CELL MOTILITY

Differentiation of satellite cells-tear n gastrocnemius muscle will regenerate
Satellite cells-in muscle proliferate reconstitute the damage part of myofibrils they are supportive cells
fro maintenance of muscle and source of new fibers after injury or after increase load
Hypertrophy-occurs in existing myofibers response to increase
Proliferation of fibroblast-in damage area lead to fibrosis
Fibroblast- not differentiate into myocytes
Multinucleate organization of sk muscle-derived developmentally by fusion
Mitotic activity- terminated after fusion occurs
Myocyte cell division-ceases soon after birth
Myoblasts-are mononucleate cells fuse with each other end to end to form myotubes
1.50um- length of A band after shortening produced by muscle contraction

During contractio :
Sarcomere-distance between adjacent Z lines decrease in length and length of A band is almost
constant, degree of thick and thin filament is altered
Thin filament or I band and anchored to Z line- pulled toward center of sarcomere
As it occurs I band decrease in length and H band-no longer visible
Filaments- do not decrease length they slide past 1 another in sliding filament model of muscle
contraction
12.5 um- average length of sarcomere measured from Z line to Z line
1.5um-length of A band
1.0 um- length of T band
10% contraction of muscle ( contraction to90 % of its length)
Sarcomere – is reduced in length from 2.5 to 2.25um
Size of A band- remains unchanged
Length of I band-is reduced from 1.0 to 0.775 um and compensates from 0.25 um reduction in length
during muscle contraction
Absence of ATP preventing detachment of the myosin heads from actin or insufficient- patient with MI
dies at night man had already rigor mortis, small production ATP after death thru anaerobic and
phoshagen pathways
Calcium ions continue to leak- from ECF, SR, SR is no longer to retrieve calcium ions
Tropomyosin and troponin- disengaged from myosin active sites
Lactic acid- in rigor mortis thru anaerobic pathways have high levels deterioration of sk muscle end is
rigor mortis
Cellular calcium storage-function of sarcoplasmic reticulum of skeletal muscle
Calcium-for coupling of excitation contraction in skeletal muscle, concentrated at lumen of SR, pass thru
open ryanodine receptor channel, travel from lumen of SR into muscle cell cytoplasm
When calcium is in muscle cell cytoplasm- it binds to troponin complex binding calcium to troponin
complex SR, conformational change in complex allowing myosin to interactwith actin which produce
force, calcium pump back to lumen of SR by calcium ATPase as its pump back calcium in cytoplasm drops
and dissociates from troponin complex
Troponin complex-reverts conformational state in which troponin complex blocks interaction of myosin
with actin
SR- modified SER
Depolarization of muscle cell membrane during action potential-triggers opening of ryanodine receptor
channel in membrane of SR
Glycogen-stored as particles or droplets which contains enzymes for synthesis and breakdown of
glycogen
Transverse tubule system or T system- ext of plasma membrane of myofiber ( sarcolemma), allows for
simultaneous contraction of all myofibrils, it encircles A-I bands in each sarcomere of every myofibril, in
combination with paired terminal cisternae, it froms a triad
2 triads- in each sarcomere of sk muscle 1 at each junction of dark A and light I bands, depoarizaton of T
system during contraction is transmitted to SR at triad
Cardiac muscle-also has t system not elaborated and well organized example Diads with fewer T tubules
in atrial compared to ventricular muscle
Red muscle fibers-strong staining reaction for succinic dehydrogenase, also shows mitochondria in rows
between myofibrils and underneath the sarcolemma
Red oxidative fibers type I slow-reductive process based on fact that sample must be sk muscle or
cardiac muscle due to cross striations, with high cytochrome and myglobin and beneath containing
mitochondria for high metabolism of cells, can physiologically do continuous contraction high
concentration of myosin ATPAse in capable rapid contraction, has large concentration of myoglobin,
colored oxygen binding chon
Type II fast white glycolytic muscle fibers- fast twitch in function stain very lightly for succinic
dehydrogenase and myosin,ATPase and few mitochondria visible at ultrastructural level, capable rapid
contraction, unable continuous heavy work, it is larger than red fiber, with more prominent innervation
and little myoglobin
Intermediate oxidative-glycolytic type II a fast fibers-intermediate between red and white,
Mitochondria- surround myofibrils if numerous provides strong straining reaction with use of
cytochemical stain as succinic dehydrogenase
Realease of P1 from myosin heads leading to tight binding of actin and myosin- in which muscle
contraction powerstroke is initiated
Tight binding- induces conformational in myosin head,occurs only when P1 or powestroke is release
from myosin heads leading to powerstroke
Myosin head- pull against actin filament to cause powerstroke of myosin head walking along actin
filament
Walking process-unidirectional based on polarity of actin filament, it occurs from minus to plus end of
actin filament
Cycle of ATP actin-myosin during contraction-begins with resting state
Quiescent period- ATP binds to myosin heads, hydrolysis occurs slowly and only allows weak binding of
myosin heads to actin filaments
Recycling-occurs thru release of ADP and addititon of ATP molecule and detachment of myosn
headfrom actin
Rigor-lack of ATPbecause 1 ATP molecule required for each myosin molecule present in muscle
Rigor mortis-absence of ATP in sk muscle phosphorylation of light chain not required for binding to actin
Loss of binding of I and M bands to cell membrane-protein dystrophin is absent or defective structure
to spectrins I and IIand a actinin which of most tooccur
Dystrophin-like actinin and spectrin I, and II an actin- binding chon binds to sk muscle membrane and
binds the I and M bands to cell membrane, it is absent in Duchene muscular dystrophy, in ability to bind
actin to plasma membrane of sk muscle result indisruption of contraction process weakness of muscles
abnormal running hopping and jumping, if its lost may cause destabilization and decraes contractility, 1
in 3500 male birth , it is found n all muscle types regulate interaction of sarcolemma with extracellular
matrix thru associated glycchon (dytrophin-glycoprotein)
Gower maneuver- by persons sffering from muscular dystrophy to stand from a sitting position
Respiratory failure- disruption of diaphragmatic function
Becker muscular dystrophy- less severe which dystrophic is defective,synthesis of actin not reduced in
sk muscle hypertrophy and pseudohypertrophy ( replacement of muscle with CT and fat) occurs
Intermediate filament- form intracellular connection in desmosomes
Phagocytosis, cytokinesis, cell locomotion-PMNs has increaseactivity as measured by oxidative burst of
F actin assays, which increase in peripheral blood PMNs from patient
Actin- maintains much strength of cytoplasm of cell essential for cellular function requires surface
motility
Minimyosin ( myosin I)- movement of vesicles along filamnts
Microtubules-movement of vesicles and organelles, chromosomal movements occur thru mcrotubular
kinetics
Dynein-movement of chromosomes as well as cilia and flagella
Troponin-absent in smooth muscle cells ,
Smooth muscle- least specialized type, no troponin, contractile process similar to actin myosin
interactions occur in motility of non muscle cells, actin and myosin attached to intermediate filaments at
dense bodies in sarcolemma and cytoplasm,SR not well developed, no T tuble,endocytic vesicles called
caveolae function similar to T tubule system of skeletal muscle, ( vascular smooth muscle cells fibroblast
they are capable of collagen, elastin,proteoglycan synthesis
When intracellular calcium increased- calcium bound to calcium binding chon, calmodulin, calcium-
calmodulin is required bound to myosin light chain kinase to form calcium calmodulin kinase complex
and this complex catalyses phosphorylation of 1 and 2 myosin light chains on myosin heads that
phosphorylation allows binding of actin to myosin
A specific phosphatase- dephosporylates myosin lght cain which returns actin and myosin to inactive
resting state,
Actin- tropomyosin interaction- similar in smooth and sk muscle
Dense bodies- contain a- actinin and resemble Z lines of sk muscle
Contraction- shortening change from elongate to globular, slidingfilament action, mechanism used by
thick and thin filaments in striated muscles
Connection to plasma membrane- allows all smooth muscle cell in same region to act as functional unit
Myofibrils- composed of sarcomeres which are repeating units that extend from z disc
I band-consist of thin filaments without overlap of thick filaments, located on adjacent A bands
A band- at center of myofibril consist of thick filament which interdigitates with I band, this is the width
of thick myosin filaments
Each I band- bisected by Z disc
Z disc- composedmostly intermediate filaments Chon desin a actinin, filamin, amorphin and Z protein
H band- in center of A band lighter staining only thick rodlike portions of myosin, located between ends
of thin 9 actin filaments
M line-lateral connections occur between adjacent thick filament in regon of M line which bisects H
zone composed primarily of CK
CK- enzyme catalyse formation of ATP
I zone/band- found adjacent A band
F zones- ends of thin ( actin filament)
Kinesin- mechanochemical enzyme found on surface of cellula organelles movement toward (+) end of
microtubules, this moves vesicles unidirectionally from (-) end to (+) end of microtubule kicks out ex.
From cell body to axon terminus
Myosin (myosin II), minimyosisn (myosin I), dynein, filamin- all mechanochemical enzymes molecular
motors hydrolyze ATP undego conformational change
Dynein-movement toward negative end of microtubules, motor which cause sliding between
microtubules with in axoneme as whole which convertto ciliarybending, drags in
Ciliary or flagella bending- classic model of microtubule motility
Dynamin -other ATPase motor mediates sliding betweenadjacent cytoplastic microtubules
Filamin- other actin cross linking chons, forms gel network in cell cortex, changes in cell shape
Sarcomere- extends from Z disc ( line to ) z disc
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SYSTEMS
NERVOUS SYSTEM
Subventricular zone-mri showed significant reduction in total gray matter volume with localized gray
matter reduction in frontal, striatl, parietal and ventral and superior emporal gray matter
Marginal zone- most peripheral zone (myelinated axons of developing motor neurons)
Adult white matter- axons of development motor neurons
Intermediate zone, mantle zone,- where all bodies of differentiatings
Sulcus limitans-separate alar ( sensory ) and basal ( motor ) plate in development brainstem
Limbic striatal system- abnormal in ANA and connectivity of cortical region or social brain region
Lmbic striatal system- behavioral and brain metabolism different in autism
Cerebral cortex-origin from ventricularand subventricular zone
Layer I to VI- from deep to superficial layers
Cell proliferation- predominant process before neural tube closure,
neurons differentiate- after neural tube closure
3 layers differentiate- from wall of neural tube
Ventricular zone- where mitotic activity occus closes to lumen
Marginal and mantle zone-in spinal cord layers it differentiate into peripheral white mater with a
central H shape reion of gray matter
Macroglia ( astrocytes and oligodendrocytes) arise from neural epithelium
Microglia ( macrophages of brain)- bone marrowderived from monocytes
Cerebral and cerebellar cortices- peripheral gray matter formed thru a 2nd wave of cell proliferation
Cerebellar devt- 2nd wave comes from external granular layer
Opening of sodium channels- action potential neuron is initiated
Restins state- Na/ K/ ATpase- builds up high ionic gradient across axolema, there is more na onoutside
of axon, inside o axon is negative relative to outside(-70- MV resting potential)
Action potential- exchange of ions across axonal membrane will displace membrane potential toward 0
Steps of action potential
a. presence of stimulus causes na gated channels to open
b. na ions flow thru channel into neuron
c. positive charge of na makes axon more postivive and depolarized
d. delay in opening of K channels
e. opening K channels causes flow of K out of cell reversing depo
f. na channels start to close at about this time causing AP to return toward -70 mv and repolarizing
the membrane
membrane- hyperpolarizes as potential passes -70 mv
K channels-serve bring membrane potential to hyperpolarized state
Inward influx of K combined with closing of Na channels- important in return to RMP
AP in all or none phenomenon- occurs with constant amplitudes and duration for given axon
Myelination –increases conduction AP
Myelination of CST by oligodenrocytes- 18 th month old foot other toes fan out after sole frimly
stroked, change in response is due to postnatal event
Maturation of cerebellar cortex-in 2nd trimester continue after several years
Myelination of lumbar spinal nerve by schwann cells- completed by oligodendrocytes in CNS
Babinsky sign/external plantar reflex- indication of immaturity of ST which is myelinated after birth,
infantile reflex in children until 2 years old but abnormal in older children or adults
Ataxia-acute inflammation reaction after suffering from chiken pox, acute child with infection
cerebellum ( cerebelitis) or inability to coordinate voluntary muscle movement unsteady movementsand
staggering gait, it is classified as Axial ( trunk ) or limb ataxia, in sitting position childs trunk move side to
side or back to front then resume vertical position in jerky motion Nystagmus(jerky eye movement) also
occur
Limb ataxia- manifest itself loss offine motor control of hands or legs appears as person able to
coordinate his movement ex hand sway back and forth when reaching object
Cerebellar ataxia- follows viral infection subsides without treatment over period of weeks to months
Amnesia- cortical injury damage
Perirhinal entorrhinal hippocampal-mamillary body thalamus circuit fornix or temporal lobe
Reflexive actions-level of ventralhorn cells is spinal cord
Dorsal root or trigeminal ganglion, sensory, frontal cortex, limbic system, and thalamus- loss of pain
sensation
Cortical injury- total or partial loss of ability to use or understand language ( aphasia)
Different types of memory
Working memory- affected by prefrontal lesions to sp tempero parietal regions subserving modality
being used
Aphasia- several areas of cortex frontal, parietal, or temporal lobes
3 layers forming cerebellar cortex
molecular layer at left or top
large purkinjie cell layer
granular layer MPG
white matter- is inside 3 layers of gray matter- basket cells,purkinjie cells, granule cells which compose
several cerebellar cortex
a.basket cells- make profuse inhibitory dendritic contents with flask shaped purkinjie cells
b.each purkinjie cell- receives 2x10raise to 5 synapses onto its dendritic spines which splay out across
molecular layer
c.granule cell- small neurons on vicinity of purkinjie cell, its axonsfrom parallel fibers make excitatory
synapse onto purkinjie cell dendrites
each parallel fiber- synapses 200 purkinjie cells creating excitation strip across cerebellum
minus end to plus end kinesin -glucocorticoid treatment, with sharp pain dermatomal level nipple to
right side of back, vesicular lesion not cross midline tzanck test is Positive, cause of illness is movement
of virus with dx of shingles
shingles- caused by herpes virus known as VZV, this begins as erythematous macupapular eruptions
rapidly evolves to vesicles with positive fever, patient had history chicken pox also caused VZV stored in
DRG primarily in satellite cell surrounding perkarya ( cell Bodies)
Kinesin- walks along microtubule toward the plus end of microtubule, motor chon uses energy from ATP
hydrolysis to move vesicles (- to +) from cell body in DRG which is anterograde direction toward axon
terminal
Dynein -minus end microtubule motors move organelles inclu vesicles in retrograde direction toward
cell body of DRG ganglia, involved in axonal transport are cytoplasmic dyneins as compared to axonemal
dyneins seen in cilia and flagella
Myosin II- actin based motor chon generates force of muscle cxn
Tzanck test- testing for virus in presence of herpes virus lesion, although it cannot detect between HSV
and VZV
PCR- for absolute detection
Shingles- T4 which surrounds nipple which is midlle of T4 although T5 also is innervated
Dermatome- area of skin supplied by Nerve origin from single spinal nerve
Occurs by a mechanism that is dependent on proliferation of schwann cells- injury to radial nerve during
motorcycle crash an advancing tinel sign, this is the regeneration of axons after injury, if tinel sign is
absent its poor prognosis
Tinel sign- when tapping nerve trunk that is damaged is regenerating ff trauma causes sensation of
tingling and pain in distribution up to site of regeneration
Regeneration-depends on proliferation of schwann cells which guide sprouting axons from prox
segment toward target organ
Wallerian orthograde degeneration- injury distal to level of injury proximal axonal degeneration to at
least the next node of ranvier
Proximal degeneration –in more severe traumatic injuries, extent beyond next node of ranvier, electro
diagnostic studies MUP motor unit potential
Axonal regeneration- distal to wound include myelin is phagocytosed and removed by macrophages,
rate of 1mm per day or 1 in per month, monitored with an advancing tinel sign
Macrophages- also produce cytokines activate nerve growth fctor and other neutrophils in schwann
cells
Proximal segment- capable of regeneration remains in continuity with perikaryon
Chromatolysis (literaly disintegration of color)-is 1st step in regenertin process , breakdown of nissl
substance ( RER , ribosomes) sweliing of perikaryon and migration of nucleus peripherally
Degeneration of perikarya and neuronal process- extensive neuronal damage
Axonal regeneration- in PNS more successful than in CNS
Sequestration of na entry into axon-progressive degeneration of fibularis muscle foot drop walking gait
foot bone abnormalities high arches and hammertoes problem with balancehand function, forearm
muscle cramping, scoliosis with dx of Charcot marie tooth syndrome, with reduced normal conduction
velocity with alteration in characteristic of nodes of ranvierwhich increase the efficiency of neural
transmission
Nodes of ranvier- increase efficiency of nodal conduction because restriction ( sequestration) of energy
dependentna influx to the node, they also represent space between adjacent units of myelination area
is bare in CNS where PNS axons in nodes partially coveredby cytoplasmic tongues of adjacent schwann
cells, most of sodium gated channels are located in bare areas
Saltutory conduction-jumps from node to node spread of depo from nodal region along axon until it
reaches next node
HIV infected monocytes passing thru occluding junctions between endothelial cells-AIDS dementia
complex include aseptic meningitis, encepethalopath, leukoencephalopath, myelopathy, neuropathy
myopathy
HIV entry to the brain-by infected CD4 and lymphocytes and monocytes enter thru occluding junction of
BBB
Barrier function of BBB- is formed by occluding (tight junctons) (Z. occludens) between endothelial cells
that comprise lining of brain capillaries
Astrocytes- form foot processes around brain capillaries that induce and maintain BBB, surrounding
CNS is basal lamina with a lining of astrocyte foot processes that form Glia limitans
Microglia-macrophages of the brain phagocytose dying infected CD4 and lymphocytes or endocytose
free viral particles
Pathologically HIV enceph characteristics-diffuse myelin damage ( spongy myelinopathy) gliosis, neuro
half loss, vascular damage, microglial nodules and lymphocytic infiltrates
HIV envelope glycoCHONS- cause mebanes of HIV infected macrophages to fuse forming multinucleate
giant cells which is the hallmark of HIV enceph
Gap junctions- communication between cells
Calcium gated channels-man with dysphonia, dysarthria, on PE hoffmans sign, Babinski sign and clonus
MRI, dx is ALS,
Calcium entry thru sp. Channels- result fusion of AcTH containing synaptic vesicles with presynaptic
membrane ultimately release NT
Neuromuscular ( myoneural ) junctions-represent site at which end feet (Boutons teminaux)
proportional surface of skmuscle cell, arrangement is similar to synapse NM jxn can be considered best
studied synapse
Na gated channels and K gated channels voltage gated- in transmission of nerve impulses but don’t
couple AP ( electrical signal ) to NT release ( chemical alteration)
Calcium influx into end feet- have direct effect on phosphorylation of synapsin I which is a vesicular
membrane CHON which in its non phosphorylated state blocks vesicle fusion with presynaptic
membrane
ALS- continuous denervationand e nnervation does not allow sufficient time for maturation of newly
formed NM junction, patients with sporadic ALS have antibodies against boltage gated calcium channels
Left pyramidal cells-vehicuar accident transported with motor deficits on right side unable to move right
arm and leg has slurred speech
Motor neurons- large amount f euchromatin distinct nucleoli and nissl if stained characteristic is high
synthetic activity
Left hemisphere- regulate language and speech
Right hemisphere- controls verbal, spatial skills as ability to draw and play music
If right side cerebellum damaged- movement in left arm and leg vision to left or hearing in left ear may
be affected
If injury to left side cerebellum- affects speed and movement on right side of body
Axon- from axon illock
RER- dispersed in soma and dendrites
Dendrites- generally wide than axons non uniform diameter
Perinerium-loss of sensation in her hands feet, a lepromin test is (+) with dx of leprosy, layer of 2-3
fibroblast like cells with contractile properties that surround individual fasciles cells have are joined by
tight junctions and form a barrier to macro molecule, individual sk muscle identifiable by its striation
and peripheraly located nuclei
Epinerium- dense irregular CT part of epineurium surrounding entire Nerve
Perimysium- with numerous nerve fibers by myelin sheath produced by schwann cell ( nucleus visible)
Fibroblast-which secrete reticular CT elements
Leprosy- with infection of peripherl nerve by M. leprae
Perineural inflammation of cutaneous nerve- leads to distal anesthesia and paralysis which are major
clinical features in early stage leprosy, neuropathic change, social stigma
Neuropathy of leprosy- primarily affects facial, ulnar , radial and fibular nerve with ascending
degeneration of nerve
Later stages- endoneurial inflammation , infection of schwann cells, demyelination and reduced
conduction velocity occurs
Sensory neurons of cranial ganglia- with hearing impairment poliosis white sock of hair, a low hairline
with eyebrows that touch in middle, white pigmentation on skin
Neural crest- forms most of PNS
Neural tube-which embryonic source of CNS
Sensory neurons of cranial and spinal sensory ganglia –e x DRG sympha chain ganglia post ganglionic
sympa and para fibers of ANS cells of pia and arachnoid, schwann cells, satellite cells of DRGanglia are
elements derived from neural crest,
Non neuronal structure- formed from neural crest include melanocytes of skin, odontoblast in teeth,
derivatives of brachial arch cartilage ( pinna of ear) and adre medulla not cortex ex Z. glomerulosa
Adrenal medulla- represent post ganglionic sympa fibers respond to inputs from pre ganglionic sympa
fibers in splanchnic nerve
Block parasympa pathways- with left sided hemiplegia, shes treated with atropinefor her sialorrhea
best description of of atropine with dx of cerebral palsy
Sialorrhea-impeds social integration
Parasympathetic ganglia- located in close proximity to wall of organs they innervate
Form a glial scar following damage-memory loss mood swings clinical depression cd4 counts 170 normal
500-1200 cd4 percentage 12 percent normal 40 percent viral load 12k copies, was treated pneumocystis
carini with anti glial fibrillary acidic protein GFAP with dx of neuro aids
Neuro AIDS- infxn lead to change in gene expression of cells and some release produtcts have deletions
affects neurons
GFAP-activated astrocytes
Astrocytes- most abundant cell in human brain, activated in CNS damage and form glial scar source of
MC glioma, astrocytoma, infected with AIDS virus, impt function: regulation of microenvironment,
include conc of ions, metabolites and NT glutamate,establish maintain BBB control entry of compounds
into brain parenchyma, during devt are critical to normal migration of developing neurons, infected with
HIV 1 only limited replication, exhibit calcium excitability and communicate bidirectionally with
neighboring neurons and synapses, NOT synapses with neurons
Glial cells- interact with neurons BV and pia matter by stellate processes
Microglia-present antigen, hagocytose dying neurons in CNS
Oligodenrocytes- form myelin in CNS, barrier fxn of BBBis established by tight jxn (z.occludens) bet endo
cells in BV of brain
NT reuptake in synaptic vesicles- treated with fluoxetine HCL for clin depression, MOA with dx of clinical
depression
Clinical depression-assoc reduced levels monoamines as 5 hydroxytrptamine ( serotonin 5HT) in CNS
SSRI as fluoxetine HCL Prozac-bind 5 HT reuptake in presynaptic membrane, blocking re uptake and
degradation of serotonin in synaptic cleft, there is serotonin increase in synaptic cleft result of ssri
treatment
Mitochondria- binding of NT to postsynaptic receptors
Membrane permeability- other regions of synapse
Recycling of synaptic vesicle membrane-at presynaptic membrane inconjunction with NT release by
exocytosis
Post synaptic surface- typically denser than presynaptic membrane
NT release- induced by membrane depo leading transient opening of calcium channels following calcium
influx,
transmission from neuron to neuron-occurs by chemical transmission form of NT release
NT from synaptic vesicles- crosses synaptic cleft between pre and post synaptic membrane interacts
with receptors on post synaptic membrane which result in changes in permeability of membrane
Oligodendrocytes-increase in csf protein, elevated gamma globlin moderate pleiocytosis, MRI confirms
areas of demyelination in ant. Corpus callosum, imaging identifies palques which are hyperintense on T2
weighted and fluid attenuated inversion recovery FLAIR images and hypodense on T1 weighted
scanswith dx of Multiple sclerosis /MS
MS- demyelinating dse in which both CD4 andCD8 T cells as well autoantibodies are targeted against
oligodendrocytes, are twice prevalent in males and demyelination is MC in anterior corpus callosum,
main identifying feature on histopath is paucity of oligodenrocytes, with astrocytic proliferation and
gliosis may increase with duration
Alterations in CSF shows pleocytosis- increase number of mononuclear cells abovenormal, increase in
protein, elevated gama globulin ( antibodies to oligodendrocytes as represented by oligoclonal bands on
gel elephoresis
Schwann cells- myelination in PNS
On Autopsy-lymphocytes, monocytes infiltrates areound small veins aka perivascular cuffing
Junctional folds- on pe with bilat ptosis, difficult pronouncing many words. With stable waddling gait,
SOB, labs (+) edrophonium CL tensilon test and auto antibodies to acetylcholine receptors, dx is M.
gravis
Junctional folds-site of Acetylcholine receptors which are reduced in number in MG, normal NM
junction releases Ach fr motor nerve terminal in discrete packages quantal
Ach quanta diffuse- across synaptic cleft bind to receptors on folded muscle end plate
Edphoronium CL tensilon test- USES as rapid acting and degrading acetylcholinesterase inhibitor, causes
neuromuscular transmission to be increase in pt, procedure injection tensilon looks rapid relief of
symptom on eyelids and diplopia

CVS BLOOD AND BONE MARROW

Coronary artery- analogous to Vasa vasorum, fulfill similar function for myocardium
Vasa vasorum-vessels in a vessel primarily in adventitia of large artery and vein provide nutrition and
oxygenated blood to thick media and adventitia of these vessels which unable to obtain nutrition by
diffusion from lumen
Basophils- may be bilobed or segmented but with larger and more irregular granules that obscure the
nucleus in wright stained blood smears
Lineage eosinophilic devt in bone marrow
MYELOBLAST------PROMYELOCYTE--------EOSINOPHILIC MYELOCYTE--------METAMYELOCYTE-------
EOSINOPHILIC BAND-------MATURE EOSINOPHIL
Myeloblast-1st stage in granulopoeisis, a large cell with prominent light staining nucleoli with only little
cytoplasm generally without granules
Promyelocyte- next cell in line age larger than myeloblast nucleoli less visible, primary granules present
in cytoplasm,
Myelocyte -granule specificity is attained with flattening of nucleus
Eosinophilic myelocyte- diffentiates to eosinophilic metamyelocyte .
Metamyelocyte-invagination of nucleus begins
Invagination- leads to formation of eosinophilic band and ultimately mature eosinophils
Eosinophil-bilobed nucleus and plays important role in allergic and parasitic infections, its granules stain
with eosinophilic dyes and contain major basicprotein MBP,histaminase, peroxidase and some
hydrolytic enzymes, have affinity for antigen antibody complexes although phagocytic, its not active
against as neutrophil
Histaminase secreted by eosinophil- counteracts release of histamine from basophil and mast cells
essential in hypersensitivity reactions
B lymphocytes- differentiate into antibody producing plasma cells
T lymphocytes- responsible cell mediated response include graft rejection
Neutrophils- responsible phagocytosis of bacteria
Bone marrow-primary familial erythrocytosis or familial polycythemia during 7th to 9th month of fetal
devt primary effect was on rbc production
Bone marrow –predominant hematopietic site during 3rd trimesterof gestation
Yolk sac – 1st site of blood cell devt ( hematopeisis) extraembryonic, produces hemangioblast
Hemangioblasts- precursors of hematopeitic stem cells (HSCS) primitive erythroblast from 3rd week to
2nd month of gestation, young liver synthesize blood
Hepatic erythropoiesis or liver- active in 2nd trimester
Spleen- produce RBC orerythropoietin from 2 months to 7 of gestation continue postnatally, is the
minor extramedullary source of monocytes and lymphocytes throughout life
From 2nd month of gestation- LN produce lymphocytes
Thymus- responsible for education of T cells
T lymphocyte- seeded to T dependent areas as deep cortex of LN and periarteriolar lymphoid sheath of
spleen
Iliac crest- bone marrow and aspiration and biopsy best place, best location of bone marrow sampling
with dx of CL MC in elderly adults not in sternum cause damage thoracic duct
Scapula- hematopoiesis occurs in flat bone and other bones in adult
Marrow of sternum, rbs, vertebrae, iliac crest, skull and proximal femur- are primary sites of blood cell
devt by time sk maturity is achieved, also occurs in long bones as humerus, tibia during devt but in
adulthood become dominated by yellow marrow contain fat cells ( adipose tissue)
Continuous type with few vesicles-organs as bain, thymus have more effective BBB because capillaries
as in basal lamina
Blood thymus barrier- provides appropriate microenvironment for education of T cells without
exposure to self
Capillaries- surrounded by perivascular CT and EC and their basement membrane
In BBB- a continous endothelium with a basal lamina and absence of fenestrations
Foot process of astrocytes- surround basal lamina in brain, they form glia limitans, important to note
that barrier function of BBB is form specific by endothelial cell occluding junctions with many sealings
strands, other capillary endothelial in bodyare fenetrated ( transcellular openings)or discontinue (
sinusoids )
Fenestrae- are transcellular openings which occur in visceral capillary
In hematopoietic organs-large gaps in endothelium and capillaries classified as discontinuous
Diaphragms- ( thinner cell membrane )-produce intermediate level molecular transit, they have pore
like structure which contain proteoglycan high in heparin sulfate, which results in numerous anionic
sites that repel an ionic chon, they also facilitate passge of h20 and small molecule dissolved in fluid
physiologically.
Large pores 50-70 nm of endothelia- represented by pinocytic vesicles
Intercellular junctions particularly tight junctions- function as small endothelial pores 10 nm in
diameter
Plasmalemmal vesicles and channels- neutral charged rich in galactose and N acetylglucosamine
Vesicular and chanel pathway- for transport of anionic chons as insulin, transferrin, albumin and LDL
Injury to endothelium-exercise induced angina serum chole 277 normal less than 200, LDL 157 normal
less than 100 HDL 43 normal greater than 35 TG 170 normalless than 150, bmi 34 coronary risk ratio
6.84 normal less than 5, on cardiac catheter there is occlusion of LAD and origin of RCA the dse process
is initiated with this
3 Sites at which coronary artery occluded are:
a. LAD – which affect both ventricles anteriorly
b. Origin of RCA- affect both Right atrium and ventricle and disrupting cardiac rythym
c. Circumflex branch – affecting both left atria and ventricle
Atherosclerosis- damage to endothelial cell which exposes subjacent CT,there is loss of antithrombotic
endo which results in aggregation of platelets,and 1 form or arteriosclerosis (hardening of artery) that
involves deposition of fatty material primarily in wall of conducting artery
Intima and media-infiltrated with lipid
Intimal thickening-addition of collagen and elastin with abnormal pattern of elastin cross linking
Thickening of intima aka atheromatous plaque and worsens with repeated damage to endothelium,
most dangerous in small vessels coronary artery where occlusion can result in MI
Platelets- release mitogenic substance stimulate proliferation of smooth muscle cells
Atherosclerotic plaques- lead to thrombi and aneurysms
Adventitial proliferation-occurs during atherosclerosis
Distribution of blood with in an organ-type 2 dm 10 years, has weak tibial pulse on both sides, poor skin
filling for capillaries which function primarily affected in blood vesse
Arteriole small artery-in intraorgan blood flow, only 1 layer smooth muscle, internal elastic membrane
present
Venule-no visible internal elastic membrane
Capillary-lacks smooth muscle in single layer endothelial cells
Aota and large artery-extensive elastic fibers permit rapid arterial stretch response to force of
ventricular contraction during systole 120-160 mmhg following by sudden relaxation 60-90 mmhg during
diastole, blood ejected from left ventricle into large artery only during systole
Muscular distributing artery-regulate blood flow to organs
Muscular medium artery-more smooth muscle than arteriole distribute blood to organs
Contraction of muscular artery- is sympathetic, when tunica media of muscular artery is contracted less
blood flow to organ versus in more relax state there is increase bloodflow to same organ
Thoracic duct-complete disorganization in wall, no distinct media or adventitia, returns lympho from
lymphoid compartment to circulation
Large vein-as vena cava return blood to heart with smooth muscle,bundles in adventitia 1 sees both
circulatory and longitudinal arranged smooth muscle
Plasma buffy coat and packed erythrocytes-in presence of heparin as anticoagulant to obtain
hematocrit result
3 layers
plasma-upper
buffy coat- with leucocytes beneath plasma
packed erythrocyte-bottom
after blood is removed from blood clot forms-clot contains platelets, erythrocytes, leukocytes, clear
yellow fluid aka serum
hematocrit-vol. of erythrocytes per unit vol of blood 40-50 % in adult human males
abnormal bruising- with idiopathic ITP
ITP- primarily disease of peripheral platelet destruction and reduction in platelet production by bone
marrow, main symptom are bleeding include bruising (ecchymosis) and tiny red dots on skin or mucus
membrane petechiae, in some instance bleeding from nose periodontalligaments and gums urinary GIT
occur,is an auto immune dse most have autoantibodies to sp platelet membrane of glycoproteins
Acute ITP-follows an acute infection or response to pharmaceutical administration, during pregnancy
and chronic diseases as hepa c, HIV and Lupus
RBC and WBC- are normal platelets count range 10k to 30k/ml raise to 3 with 150,000 ml as normal or
higher than 100k ml raise to 3 is safe, reduction in the number in decrase platelets, increase clotting
time, decrease coagulation and result in heavier mens and bleeding
Progressive decrease in normal condition-small peripheral nerve with outer covering of perineuriom,
with his diet fast food and junk food with dx of diabetic retinopathy
Small lymph vessels- single layer of endothelium
Schwann cells- dark nuclei with in cross section belong
Microcytic hypochromic anemia with smaller mature erythrocytes- blue tinge in her sclerae, always
tired fighting colds with dizziness, lightheadedness, hgb is 11.0 normal 11.7-13.8, hct 33.9 serum normal
36-46, serum ferritin 12 normal greater than 15, what erythrocyte shape expected
Iron def- leads to anemia with presence of smaller pale staining erythrocytes (microcytic, hypochromic)
Hyperchromatic, macrocytic anemia- results from vit B12 def
Spherocytosis- spherical rather than biconcave, rbc membrane undergoes deformation due to inability
of ankyrin to bind spectrin, trapping splenic sinusoids excessive destruction of RBC in organ
Poikolocytosis- generic term abnormally shaped erythrocytes
Hereditary elliptosis and hereditary poikilocytosis-rbc membrane fragility and abnormal shape due to
spectrin mutation in band 3 (anion exchanger 1 ) result in RBC that are hyperchromati with
poikolocytosis
Decrease renal eryhthropoetin production leading to reduce RBC production- dm for 30 years, with
increase serum creatinine 3.0 normal 2.0
Normal hct for female-37-47
Renal failure to diabetic retinopathy- cause anemia
DM-alters glomerular BM cause glycation of CHON resulting in advanced glycation end products induces
glomerular hypertrophy contributing to glomerulosclerosis
Renal insuff- decrease production of kidney derived rbc growth factor, EPO
Initial stages of Renal failure
EPO- is increase As continuation peritubular capillary cells that produced EPO are destroyed there is
increase levels of reticulocytes ( immature RBC) in blood stream then reversed low production of retic is
hallmark of anemia associated with renal disease, platelet is decrease, estrogen levels, decrease
hematocrit
Pregnancy in 3rd tri has decrease hematocrit -37 plus minus 6 3rd trimester versus 40 plus minus 6 adult
woman and 42 plus minus 6 post menopausal the treatment is admin of recombinant EPO for anemia
advanced renal dse
EPO- administered if hct less than 30, synthesize by peritubular interstitial cells of kidney cortex, and
stimulate differentiation of cells from erythrocyte CFU and differentiation release of retic from bone
marrow
CFUs-distinct cell lineage from pluripotential stem cells in bone marrow
Endothelial cells-Synthesis of plasminogen activator which synthesize no. of antithrombogenic factors
include plasminogen activator and prostacyclin, also synthesize basal lamina include type 4 collagen
Prostacyclin-functions thru cyclic AMP to inhibit thromboxane production by platelets
Firbroblast- synthezise collagen type I and III
Receptors for endothelin- most potent VC plasminogen inhibitor (a coagulant) and nitric oxide (NO) aka
EDRF
Serotonin- for platelets and enteroendocrine cells
ACE on endothelial cells surface- converts angiotensin I to angiotensin II ( a potent VC) also an
inactivation enzyme ( bradykininase for bradykinin AVD
Von willibrand factor factor VIII- in weibel palade granules localized in endothelial cells of vessels larger
than capillary
Def of factor VIII- decrease platelet aggregation and hemophilia
Peripheral VC-research use knock out mouse what is the gene for ANP is deleted which it is elevated
ANP- important diuretic and natriuretic molecule that is released from the atria in response to atrial
stretch and or endothelial I stimulation, in the absence of ANP peripheral VC increase due to absence
induced relaxation of vasc smooth muscle and increase in aldosterone levels, its main targets are the
kidneys , vascular smooth muscle, it decreases BP due to direct relaxation of vascular smooth muscles, it
also counteracts RAAS, if increase ANP levels are detected in CHF there is Chronic renal failure and
severe essential hypertension
Natriuretic effect- results from a direct inhibition of na absorption in renal collecting duct and increase
GFR and inhibited aldosterone production and secretion
Excretion of urine , na, and capillary permeability- all decrease in absence of ANP
Aldosterone- increase sodium permeability of lumina membrane in distal renal tubule and activity of
sodium pumps, - angiotensin II, endothelin, renin, vasopressin
Increase salt- causes water retention and expanded blood volume and elevated BP, it enchance capillary
permeability
ACE- coverts angio I to angio II a potent VC
Neutrophil- still pus remaining at wound site, or formation of pus, in acute phase inflammation and for
phagocytosis of invading bacteria, it has lysosomes and ALP with in their granules, they die soon after
phgocytosing bacteria and are added to pus which consists dead neutrophils, serum and tissue fluids, if
they mature aka PMN have 3-5 lobes, and phagocytose bacteria, dead neutrophils are major constituent
of pus
Basophils- have same size as neutrophils with granules variable size and obscure nucleus in attraction o
eosinophil to site of infection, it occurs in parasitic and non parasitic infections and involves
chemoattraction by histamine and eosinophil chmoatractant factor for anaphylaxis, also involved in
inflammation thru relase of histamine and heaparin
IgE- by plasma cells found to cell surface of mast cells and basophils on 1st exposure
Secondary exposure- antigen binds to IgE and stimulate degranulation of mast cells and basophil
granules and relaesing histamine and heparin
Basophils and mast cells- in anaphylactic and immediate hyper sensitivity reactions
Eosinophils-are bilobed with more regular granules than basophil, have less phagocytic ability tha
neutrophils, may kill parasites by phagocytosis or exocytotic release of granules, they contain MBP
histaminase and acid phosphatase and other lysosomal enzymes, they are essential for destruction of
parasites as trichinas , schistosomes, are granules contain number of important substance including
histaminase, eosinophil, peroxidase, eosinophilic cationic CHON , MBP, they do not release IL 1 and IL
2,phagocytose parasites
Monocytes-eccentric nucleus kidney shaped chromatin has rope like appearance with less condensed
than chromatin of lymphocytes, has phagocytic activity in blood , its majorrole source of macrophages
throughout bod include langerhans cells skin , microglia brain and kuppfer cells liver
Megakaryocytes- large cells with multilobar appearance source of platelets, fragments to form platelets
which are key elements of blood
Lymphocyte- considered agranular cell with ovoid nucleus and scanty cytoplasm, its shape and
arrangement of chromatin vary depending on class of lymphocyte small,medium, large, either T or B
cells are based on their education in thymus or bone marrow
Small and medium lymphocytes- chronic inflammation involved
Large lymphocytes- are source of T and B cells
Plasma cells- diffentiate from B lymphocyte that undergo mitosis and form a plasma cell and a memory
cell after exposure to appropriate antigen
Antigen presenting cells and sp subtype of t lymphocytes- are called helper T cells which are required
for B cell differentiation into antibody producing plasma cells
Contain a toxin for parasites- vomiting with diarrhea, now with large worms in vomitus an had
visibleworm in his stool in Colorado, patient had parasitic infection like eosinophils
IL-5- they stimulate the production and maturation of eosinophils
MBP- forms the core of eosinophilic granules is a toxin for parasites they binds and disrupts membrane
of parasite, causes basophils to release histamine
Binding-is mediated by Fc receptor
IL-1 and IL-2- carry out functions of activating APCs and stimulating proliferation of B and T cells
respectively

LYMPHOID SYTEM AND CELLULAR IMMUNOLOGY

Create optimal immune response to specific antigen- function of clonal selection,
Clonal selection-immune system way of fine tuning the immune response means by which immune
system makes antigen receptor sites ( T cells) or antibodies ( B cell) more and more specific to create the
optimal response to 1 specific antigen, not lead to form CFU
Honing receptors for lymphocytes-important part of naïve T cell and B cell maturation in thymus and
bone marrow cell
Ig class switching- during maturation of B cells after antigen stimulation, a clone of lymphocyte is
commited to respond to a particular antigen
Antigenic determinants- consist specific AA or monosaccharides induce clones, and wide variety of
humural and cell mediated responses, during devt , maturation of immune system responsible for
specificity of lymphocyte cells surface receptors for antigen
Regulatory T cells T Reg- actively suppress activation of immune system and inhibit pathological self
reactivity and auto immune dse
T lymphocytes are cells that Tacrolimus- (FK506)is prescribed for a pt who received allogeneic liver
transplant its MOA is blockage of signal transduction pathways
Tacrolimus-blocks signal transduction leading to IL2 production and preventing T cell activation
Transplant acute graft rejection-mediated by action of T cells
Helper T (Th) cells- recognize peptides assoc with MHC antigens from donor tissue and become
activated
Plasma cells, monocyte, eosinophils, mast cell- in rejection process
Activated (th) cells- release IL-2 and IFN –y- which activate cytotoxic Tc cells, B cells and macrophages
Tc cells-primary agents of transplant rejection in acute graft rejection response
Preformed antibodies recognize CHO on endothelial cells in the graft-rejection of a pig pancreas
transplanted into a human occur primarily
Xenotransplantation-main potential solution obtaining donor organs, induces hyperacute graft rejection
Human preformed antibodies-recognize (alpha) Gal (1-3) (beta) Gal terminal CHO present on anima
endothelial cells in the graft
Old world monkeys and humans- don’t express that xenoantigen on their endothelial cells
Thymus- site of production of CD4 and CD 8 cells which produces CD4 helper an CD8 cytotoxic T cells,
function generation of self or non self discrimination bet. Reactive T cells are deleted and self MHC
restricted cells expanded during their education with in the thymus
Tcell receptor TCR for antigen- develop during education of T cells in thymus
T cells develop homing receptors from subsequent seeding to T dependent areas of LN , spleen and
other lymphoid tissues thruougout the body
Thymus- at low magnification from lobulations with cortex and medulla in each lobule , absence of
germinal centers, at high magnifications presence of hassal thymic corpuscles an identifying
characteristic, derived from 3rd, 4th brachial pouches, this is where T cell gene rearrangement occurs
during educ. Of T cells in thymus in fetal and early neonatal devt
Hassal corpuscles- contain degenerating EC in concentric arrays increases with age and instruct thymic
dendritic cells to induce development of regulatory T cells T reg.
Secondary lymphoid oragns- production of memory B cell as well as effector and memory T cells
Plasma cells- production of antibodies which arise from B lymphocytes found in germinal centers of LN
throughout body as well as spleen and tonsils
LN- filter lymph and blood
Spleen- site erythrocyte degradation and bilirubin recycling
TCR or T cell receptors- composed of alpha and beta chains, are antibody like heterodimers
Gene rearrangement in B and T cell edc- involves similar V(D)J recombinations
Alpha and beta chains- contains variable amino terminal portion of a constant carboxy terminal portion,
are encoded by V, D, J,C genes segments which undergo rearrangement during devt in thymus
3 types of T cells-
Cytotoxic T cells , T regulatory (T1)cells and helper T cell
Helper T cell-posses sp cell membrane marker, primary gene products of class MHC II present antigenic
peptides
CD8- MHC1
CD4-MHCII
CD4- regulator and cytotoxic subgrps have CD8 on all surface
T cells- require close contact with other cell to perform cell mediated function
B cells- where antibodies are secreted into blood stream
B cell rearrangement- in bone marrow during B cell education
Cytotoxic T cells, antigen presenting cells , B cells, plasma cells- fragments of antigen associated with
class MHC II glycoproteins recognized by helper T cells
Activation of helper T cell- early step in immune response
Helper T cells are required- for B and Tc cells to respond to most antigens
B cells respond to antigen in absence of helper T cell-in caseof bacterial polysaccharides
Macrophage or dendritic cels APC- primary cell for expression of class II MHC
CD8 t lymphocytes- cytotoxic T cells- possess of CD8 cell surface marker
B cells, CD4 T lympho, plasma cell, macrophage- recognized foreign antigen in association with class I
MHC molecules
Cytotoxic T cells- effective killing virus infected cell that express fragments of viral chons combined with
MHC I molecules
Helper T cells (CD4)- recognize antigen in association with class II MHC molecules
MHC Class I- present on most cells
MHC class II- possess APC ( including B lymphocyte )and thymic EC
CD4 T lymphocytes- IL 2 is produced
IL2- produced by helper T cells ( cell surface marker CD4), cytokinine affects the proliferation and
differentiation of other cells including T and B cells
APCs- synthesize IL 1 with helper T cells as primary target
Helper T cells- diminished during immunodeficiency following AIDS
NK cells -10-15 % of circulating lymphocytes, are produce products that kill tumor cells
IL1- critical role in inflammation and immune response mediating pathogenic events, mainly secreted by
monocytes, macrophages and binds T cells that have been activated by exposure to antigenic or
mitogenic stimuli
Binding of IL1- induces activated T cells to produce 2 forms of IL 1 and IL2 which are a. keratinocytes-
secrete IL-Ia, and monocytes or macrophages which secrete IL-IB
IL-1- binds to receptors on activated T cells to induce production and release IL 2, wide varietof other
effects include induction of chemokine expression ( monocyte chemoattractant CHON I), IL has up
regulation of vascular adhesion molecules ( selectin ) by capillary endothelium up regulation of matrix
metalloproteinases that degrade extrcellular matrix, IL is required for IFN –y production
Abcense of T cells- yong boy with positive persistent otitis media, oral candida albicans, a red diaper
rash in diaper area, (+) hepatomegaly, (+)P. aeroginosa on nasal culture,with blood worked WBC 480
normal 5-10k, absolute lympho ct.760 normal 3k, 99 % of his lympho bound antibody against B cell mol
CD20 and 1% were natural killer cell reacting with anti CD16, IgA and IgM levels were at low end of
normal range for his age, blood mononuclear cells were completely unresponsive to
phytohemagglutinin PHA specific antigen to sp antigen to which been previously exposed by
immunization or infection tetanus and diphtheria toxoid and candida antigen, B lymphocytes did not
react with antibody to y chain of IL2 receptor IL2Ry
CD3- antibody- recognizes a group of 5 cons associated with a and b chains of TCR
Tcells (TH or Tc) and their partner ligands on APCs target cells- provide a second signal to stimulate T
cells
Histological structure of spleen-presence of CT capsule with extension into parenchyma forming
trabeculae
Parenchyma-consists of red pulp and white pulp represents lymphocytes involved in filtration of blood
Germinal centers with in whitepulp- are B dependent regions of spleen
Sheath surround central artery- known periarterial lymphoid sheath (PALS)
PALS- analogous to deep cortex (paracortex )of LN interfolliculaer zone of paeyers patches, the other T
dependent regions with in the lymphoid tissue, are the dependent regions
Germinal center of lymph node IgE-rash with swelling in his face had difficulty swallowing, breathing
followed tummy pain, cramping with diarrhea cells treated with Fluorescein labeled anti human
Immunoglobulin wiith dx of peanut allergy
Peanut allergy- involve in IgE produced by plasma cells in germinal centers of LN or spleen
Allergens like peanut antigen-originally recognized by tcrS ON Th2 cells
Th2 cells- produce IL4 which stimulate B cells to differentiate into plasma cells which synthesize and
secrete IgE
Thymus- site of T cells education and deep cortex of LN
IgE-binds specifically to high affinity receptor Fc epsilon R1 on mast cells ad basophils, presence of IgE
primes the mastcell, its presence of IgE is on allergic response secreting histamine and heparin when
child exposed to allergen (peanut antigen)
Histamine-alters vascular permeability lead to edema and in severe to anaphylaxis
Differentiation of IgE plasma cells- regulated by low affinity IgE receptor Fc epsilon R11 aka CD23
Ig producing cells- on germinal cells of white puld of spleen and other secondary lymphoid organs (
germinal centers in cortex of spleen and tonsils and lymphoid follicles in MALT and SALT)
B lymphocytes- identifiable by presence of Ig on surface membrane differentiate to antibody secreting
plasma cell under appropriate conditions
Germinal centers-primary site of heavy class or isotope switching from IgM to IgG,most antibody
production occurs of LN tonsils and spleen
IgM to IgG-formerly called Ig switching normally occurs in germinal centers during maturation of B cells,
synthesis of B cell antibody begins as IgM inserted into cell membrane then switches to membrane
bound IgM and IgD, after Antigen stimulation, switch to surface IgM, IgA, IgE –occurs an antibody are
secreted
Germinal centers of LN, spleen, tonsils-occurs lesser extent in bone marrow
Splenic red pulp- site of RBC breakdown
Thymus- education of T cells
Bone marrow-functions in education of B cells represent major site of hematopoiesis in adult
Recognition of antigen by B cells – is accomplished by expression of Igm molecule on cell surface
Term pre b cell or virgin B cell- distinguish B cells that not yet synthesis IgM from synthesis and inserted
IgM to cell membrane
IgD- produced later by maturing B cells serves as antigen receptor
Secretion of IL that promote T cell proliferation-assist (+) tuberculin skin test Helper T cells
Tuberculin skin test- T cell proliferation increase by secretion of IL
IL-1- synthesize by APCs and macrophages with helper T cells as targets
Memory Helper T cells- react to tuberculin and secrete IL2 which upregulates IL 2 receptors
IL-2 binding to IL-2 receptors on same cell is example of autocrine regulation
Autocrine regulation- which cell secretes a ligand that bunds to a receptor on its own surface which
Result of upreglation and ligand receptor binding- increase in T cell proliferation
TNF alpha and beta- T cell derived cytokines, induce leukocyte recruitment
Production of gamma(y) interferon (y-IFN ) by helper T cell- attracts and activates macrophages
y-IFN- converts other cells ( as endothelial cells ) to APC by induction of class II MHC
result of activity of helper T cells- is a dramatic increase in number of lymphocyte and macrophages at
test site which produce swelling
formation of memory T and B cells-occur during influenza infection
cell mediated immunity- key in some viruses in which antibody mediated immunity is critical to prevent
ion or recovery
B cell differentiation- requires presence of CD4 helper T cells and APCs
APCs- phagocytose virus and present it to helper T cells in presence of MHC class II molecules
B cells- also presents antigen during viral infections
Lymphocyte passage from efferent lymphatic vessel to thoracic duct and subsequently the venous rom
lymphoid compartment
Passage of lymphocytes- involves passage efferent lymphatic vessel to thoracic duct to venous sytem at
junction of left brachiocephalic and subclavian vein
Hilus of LN- classic bean shape contains artery and vein it involves specific homing receptors on
lymphocyte which are complementary to addressing on posterior capillary high endothelial venules
(HEVs)
HEVs- explain specificity of lympho homing cells that line HEVs permit selective passage of lymphocyte
by diapedesis thru intercellular junctions
Lymphocyte- have sp homing receptors on their cellsurface that provide entry for mucosal seeding
HEVs High endothelial venules-to leave the blood stream and enter sp areas of LN, in peyers patches
during inflammation of tissue ( synovium in RA), in normal condition: in T dependent areas of LN,
spleen,and peyers patches
Circulation and recirculation of lymphocytes- constant process function allow lymphocyte to continue
monitor presence of antigen
Plasma cells- not enter blood stream under normal conditions but secrete antibodies into circulation
from medulla of LN or marginal zone of spleen
Medullary sinus-where efferent lymph vessel drains the node
Macrophage- presentation of antigen and synthesize IL 1, they arise from bone marrow( monocytes)
and include kuppfer cells of liver , Langerhans cell of skin, microglia of CNS
Macrophages,dendritic cells, and B cells- phagocytose antigen partially degrade the antigen in the
endosomal system, portions of antigen with type II MHC as a complex,are required for differentiation of
plasma cells from b cells, they are not directly involved in antibody production
B cell- can present antigen in add on to move traditional APCs
IL-1- activates helper T cell
NK cells and cytotoxic T cells- carry out tumor specific killing of tumor cells
Primary response generates memory B and T cells-immunological basis for vaccine
Goal of vaccines- to promote primary immune reaction so when organization is again exposed to
antigen a much strongersecondary immune response will be elicited
Vaccines- more effective long lived when live attenuated virus is used to develop the vaccine
Live attenuated virus- undergoes limited replication in host cell resulting in a strong site specific
response to antigen
Anthax vaccine- made to inactivated virus, requires boosters at yearly intervals
Primary immune response-IgM
Secondary immune response-IgG antibodies,involve memory T cels, helper cells, specificity is retained,
involve memory T cells, helper cells, macrophages and memory B cells, proliferate of either B or T cell
during 1st exposure to antigen result is production of memory cells, example: introduction of different
new antigen which induce primary rather than secondary response, exposure to antigen produce
secondary immune response
Secondary response- any subsequent longer immune response to antgen
Secondary immune response- more rapid of longer duration, more intense than primary, more specific
to invading antigen because of generation of memory cells produced during primary response
Humoral immunity and cell mediated immunity-involved retention of immunologic memory thru
memory B and T cells respectively

RESPI SYTEM
Neutrophilic infirtration leading to destruction of bronchiolar and septal elastic fibers-malesmoke 2
packs cigarettes per day, discomfort during breathing is using extra effort involve accessory muscles to
lift sternum, diminished lung sounds in patient is primarily cellular event with dx of emphysema
Emphysema- neutrophilis enters lungs parenchyma secrete elevated levels of elastase leading to
destruction of bronchiolar and alveolar septal elastic tissue support, destruction of elasticity leads to
diminished breath sounds, with faint high pitched rhonchi at end of expiration and hyper resonant
percussion notes, rhonchi are adventitious sounds high pitched notnormally present general because of
bronchospasm or low pitched generally bec of presence of airway secretion
Emphysema- not associated with adventitious breath sounds, due to cigarette smoking with always
chronic bronchitis, rhonchi can be auscultated, are with genetic and environment causes smoking air
pollution, deficiency in alpha 1 antitrypsin antiprotease activity genetic cause of dse, balance bet normal
elastas- elastin production and protease antiprotese activity is altered
Emphysema- person with deficiency with alpha 1 antitrypsin ( antiprotease ) activity , lack sufficient
protease activity to counteract neutron derived elastase, when increase entry and activation of
neutrophil in alveolar space more elastase is released and elastic structure is destroyed
Smoking- increase number of neutrophils and macrophages in alveoli, and increase elastase activity
from neutrophils and macrophages
Increase protease activity- causes breakdown of alveolar walls and dissolution of elastin in bronchiolar
walls, there is loss of tethering of bronchioles to lung parenchyma which leads to collapses
Bronchioles- have no hyaline cartilages, thick layer but tethered to lung parenchyma by elastic tissue
Like trachea , bronchi- have hyaline cartilage
Elastic tissue- stretch recoil of lungs during exhale and inhale
Alveolarduct and alveolus-tripod position noted with liver enzymes elevated and liver biopsy shows
fibrosis cirrhosis dx is alpha 1 antitrypsin def
Alveolar duct and alveolus- initially distenstion of peripheral structure later extend to respi bronchiole
or even emphysema as panacinar ( panlobular) pan refers to damage to entire acinus
Centriacinar emphysema- targets respi bronchiole
Smoking- aggravates panacinar emphysema causing a decade of acceleration of onse of major smptoms
Macrophages containing hemosiderin granules-3 plus pitting edema, bilat rhonchi, crackles, wheezes,
pleural effusion with elevated neck veins, this is congestive heart failure cell
CHF cell-alveolar macrophage containing hemosiderin granules presence of large number of cells is an
indicator of edematous lung changes
Edema results-microhemorrhages leakageof erythrocytes into alveoli
Transferrin and hemoglobin- also present in edematous fluid released from capillaries, are 2 products
phagocytosed by alveolar macrophages which convert those products to hemosiderin
The cells of sweat duct fail to resorb na cL while in the airway there is decrease in CL secretion and
Increase in waterand na resorption – ear infecton and salt crytlas in boys skin, gene analysis detects
AF508 mutation, boy has increase CL in sweat not secrete CL properly in pancrease lungs and salivary
glands
CF- sweat glands produce a normal secretion but duct cells with defective CFTR cant resorb the na CL, an
airway have decrase CL secretion and increase Na and water resorption leading to dehydration of mucus
laye coating EC defective mucociliary action and mucus plugging of airways
CFTR- lacks an exit code its degraded in ER of both airways GI gland duct cells and sweat duct cells, it
regulates multiple ion channels including ENaC on apical surface of sweat duct airway and exocrine cells
ENaC epeithelialsodium channels-inhibitted by normal functioning CFTR
In airways of CF patients- EnaC activity increase markedly augmenting na transport across apical surface
Opposite occurs in sweat ducts where EnaC decrease activity asresult of CFTR mutations there are
luminal fluid containing high Na CL is formed
Differentiate suffieciently during gestation- Transient tachypnea of newborn infants 1 and 5 minutes
APGAR scores are 8 and 9 respectively has respi distress
Differentiation of type II penumocytes in EM- occurs in late in gestation therefore incomplete at birth
in premature infant
NB premies- have def of surfactant – bec of immaturity of type II penumocytes
Def of surfactant- inhibits normal expansion of alveoli results in idiopathic RDS hyaline membrane dse
Lecithin / sphingomyelin ratio- test performed on sample of Amniotic fluid obtained by amniocentesis
L/S ratio- used to determine whether typeII pneumocytes are mature and synthesizing and secreting
surfactant
Maternally administered glucocorticoids- used to induced surfactant production prior to birth and
exogenous surfactant may be given intratracheally to premature infantsto reduce the severity of RDS
Surfactant-release of lamellar bodies by exocytosis, produced by type II pnemocytes in lung and stored
in form of lamellar bodies whorls seen in EM, they consists of aqueous layer or hypophase that contains
CHONS and mucopolysaaccharides, its layer is covered by functional layer ofphospholipid that consists
of predominantly of dipalmitoyl phosphatidylcholine ( lecithin)
Tubulomyelin- consist of criss cross lipidbilayer that covers type II pneumocytes,
SAPS surfactant aassociated proteins-stabilize surfactant activate surfactant recycling enchance
surfactant induced reduction of surface tension and possess antiviral and anti bacterial activities
Turnover – occurs both endocytosis (typeI and typeII) pneumocytes and phagocytosis ( macrophages) 90
% of surfactant is recycled
Blood air barrier- formed by type I pneumocyte capillary endothelium cell and fused basal laminae
Mast cells in BALT, edema-cough wheezing , indicates attacks in past winter with dx asthma attack
Asthma attack probably allergen induced
Mast cells- key player in airway dse, if in bronchioles are stimulated to release histamine and heparin
Histamine and heparin- induce cxn of smooth bronchiolar muscle ( bronchoconstriction) and edema in
wall
If bronchoconstriction is chronic long term it result thickening of bronchiolar musculature, there is no
cilia in alveoli
Alveolar macrophages ( dust cells)- ingest particulate matter that enters the alveoli, airway epithelial
respond to mediators
Hypersecretion of viscus mucus from goblet cells in bronchi -they obstruct airways
Eosinophils, neutrophils,, lymphocyte, macrophages- signal to each other thru a complex cytokine
network using a variety of mediators, bradykinin, leukotrienes and prostaglandins- which enchance
bronchoconstriction, vascular congestion and edema
Eosinophils- relaes CHONS that destroy airway epith ( releasing Creola bodies) arerounded cack sloghed
off ciliated columnar epith cells
T lymphocytes- present in more severe attacks and along with B lymphocytes
B Lymphocytes- play role in initiation of allergic asthma, release cytokines that activate cell mediated
immunity pathways
Stimulation leading to depolarization- tremor rigidity bradykinesia, gait disturbance anosmia with dx of
idiopathic parkinsons dse
Idiopathic parkinsons dse- 1st sign is decrease olfactory function, response of rod cells to light cause
hyperpolarization whereas olfactory stimuli result in depolarization
Olfactory epith and rod cells- are 2 examples of signal transduction that bypass a CHON kinase system
In case of the rod- the cyclic nucleotide involved is CGMP
In case of olfactory epith- an odorant molecule binds to an odor sp trans membrane found on modified
cilia at apical surface,
Binding- activates an odorant specific G protein , golf which binds result in dissociation of alpha subunit
Dissociation of alpha subunit- stimulates adenylate cyclase to produce CAMP
CAMP—directly stimulates opening of cation channels on membrane of bipolar olfactory receptor cells
leading to sodium influx, resulting membrane depolarization is transmitted from modified cilia to
olfactory vesicle thru neuron at basal axon
Axonal process- traverse the Lamina propia as olfactory nerve and pass thru cribriform plate of ethmoid
to terminate in olfactory bulb
Fused basal lamina of epithelial cell and endothelial cells- testicular germ cell tumors removed and
cisplatin, etoposide, and bleomycin chemotherapy to affect alveolar capillary wall
Oxygen- moving from alveolar air to capillary blood
Carbon dioxide- diffusing in opposite direction pass thru a 3 component blood air barrier consists of a.
type I pneumocytes b. endothelial cells, and c fused basal lamina
Pulmonary capillaries- indirect contact with alveolar wall in other locatin alveolar wall and capillaries
are separated by cells and extracellular fibers
Areas of direct contact- are location of gas exchange whereas other ares represent sites offluid
exchange bet intersitiumand air spaces
Macrophages- present for phagocytosis of debris and surfactant
Pores of kohn- connections from 1 alveolus to another and macrophage travel thru these passageways,
they normally equalize air pressure bet alveoli and can in dse state provide collat circulation of air in
event that a bronchiole is blocked, it also provides a passageway forspread of bacteria
Type II pneumocytes and smooth muscle cells- not part of minimal blood air barrier
IgM and IgG activation of complement in alveolar fluid-had kidney transplant receiving prednisone,
cyclosporine azathioprine for post transplant immunosuppression
IgM and IgG- serum antibodies in alveolar fluid that activate complement by classic pathway
Classic pathway- fixation of C1 to antibody combined with antigen leads to activation of C3B
Cb- which binds to bacterial cell walls and enchances opsonization
Neutohils and macrophages- have C3b receptors that facilitate the opsonization
IgG- also functions as opsonin
Type II pneumocytes-resorb as well as secrete surfactant and surfactant associated proteins that
haveantiviral and antibacterial function
CD8 T cells- carry out cell specific killing
Mucociliary action- critical component of immune fxn of respiratory sytem but clearance occurs in the
bronchiole to bronchi to trachea
Trachea- part of mucociliary apparatus
Microorganism- entrapped in mucus, cilia, propel them to oropharynx, phagocytosed in alveolineed to
be transported to bronchioles to ride on mucociliary escalator
IgA- functions prevent attachment of microorganism to epithelium in URT, overall defense mechanism
of respi sytem include nasal clearance of material with occurs thru sneezing
Mucociliary or tracheobronchial escalator- mucociliary action with in trachea and bronchi
Neutrophils- attracted by chemokines and factors derived from macrophages and phagocytose bacteria
In bronchi- there is extensive associated lymphoid tissue BALT
BALT- which is analogous to mucosa associated lymphoid tissue MALT of gut ( GALT) and skin associated
lymphoid tissue (SALT)
B cell and Tcell- areas thoughout BALT
B cells- precursors of plasma cells synthesize Ig as IgA associated with bronchial secretion
Helper T cell- recognized foreign antigen in association with class II MHC molecule
Cytotoxic T cells- recognize fragments of antigen ( sp. Viral fragments) on surface of viral infected cells
in association with Class I MHC
APC ( alveolar macrophages) –also function in similar fashion to found else where in body- present
antigen to helper T cells in conjunction with class II MHC
Endostatin- bronchoscopic evaluation reveals cavitary lesion of a proximal bronchus,tumor vascularity
assessed by bronchial arteriography and immunocytochemistry indicates a highly vascular tumor with
many micro vessels, vascularity of tumor is inhibited by upregulation
Angiostatin and endostatin-are cleavage products of plasminogen and type XVIII collagen respectively
and function as angiogenic peptides
VEGF- stimulates recruitment growth of endothelial cells thru VEGF-R located on endothelial cells
precursors as well as endothelial cells
PDGF- recruits smooth muscle cells and TGF- B stimulates and stabilizes extracellular matrix production
Recruitment proliferaton of periendothelial cells smooth muscle cells, pericytes, fibroblasts- required for
devt and maturation of new BV
Angiopoetins ( ang) 1 and 2- bind their receptor
Tic2- a receptor tyrosine kinase which regulates endothelial cells proliferative status
Angiotensin 1 binds Tie2- leading to periendothelial cell recruitment and therefore vascular maturation
Angiotensin 2- found in organs of female reproductive tractand blocks angiotensin II effects when VEGF
is absent which result in regression of BV
Angiotensin 2- in presence of VEGF leads to loosening of surrounding cells permitting multiplication of
endothelial cells and angiogenesis

INTEGUMENTARY SYSTEM
Holocrine-cyst on labia majora with foul smell discharge with dx of epidermoid or sebaceous cyst
Holocrine-secretion from sebaceous gland shedding of disintegrated cell along with sebum into hair
follicles
Sebaceous gland, hair follicles-not found thick skin, located in dermis associated with a hair follicle
Cyst formation-blockage of sebaceous gland ducts from injury , infection, and irritation
Sebaceous cyst-prone to infection have foul drainage with inflammation, pain, lesion consist enlarged
sebaceous gland with numerous lobules grouped around a centrally located sebaceous cyst
Difference between thick and thin skin-virtual absence of Stratum lucidum in thin skin
2 types sweat glands
merocrine-release secretion thru exocytosis with conservation of membrane
apocrine- in anal, areolar, axillary regions sweat glands, apical part of cell is released with secretion
endosecretion- into blood
autocrine secretion- self stimulation example is activated T cells
activated T cells- stimulate their own proliferation by secreting IL-2 and synthesizing Il-2 receptors that
bind the IL-2
2 point discrimination- diagnosis is merkel cell carcinoma merkel cells are modified epidermal cells that
function primarily
Transient vibratory stmuli-detected by pacinian corpuscles
Meckel cell Carcinoma-rare tumor rapidly increasing incidence
Source of granules that form part of water impermeability barrier of the skin- layer at tip
Keratohyalin granules-located in stratum granulosum, produce lamellar granules which form
bidirectional lipid bilayer barrier to penetration of substance
Epidermis- has 4to 5 strata from BM to skin surface
stratum Basale or basal layer,germinativum, or cylindrical layer- most of mitotic cells attached to BM
with hemidesmosomes
stratum spinosum- cell with numerous cytoplasm tonofilaments and intercellular desmosomes, nodes
of bizozar
stratum granulosum-keratohyaline granules
Stratum basale plus stratum spinosum equals stratum malphingii- those layers are hyperproliferative
in psoriasis
Stratum basale- where new cells producedas differentiate
stratum Lucidum- translucent layer typical of thick skin, its clear or elaiden
stratum corneum- contains as many as 20 layers of flattened cells
in deep wounds- new EC obtained from Epithelium of hair follicles and sweat glands located in dermis
Pacinian corpuscle-suspeced schwanomma soft tissue mass with,dumbell configuration with
components lateral to neural foramen a waist in foramen itself and a component the spinal canal to the
right of the culdesac, she asks the patient to close her eyes and then tell her whether tuning fork
vibrating or not, vibration sense is impaired on right side test for painand temperature indicate
impairment on the left side using tuning fork the neurologist is primarily testing function of sensory
receptors with a dx of schwannoma
Schwannoma- a nerve sheath tumor arising from schwann cells which results in impairment of
proprioception or position sense and vibration sense, ipsilateral , white pain and temperature impaired
contralaterally
Pacinian corpuscle-primary sensory receptor for vibratory sensation
Ruffinis endings-simplest encapsulated receptor associated with collagen fibers
Mechanical stress- results in displacement of collagen fibers and stimulation of the receptor
Meissner and merkel corpuscle- respond to texture and 2 point discrimination respectively
Free nerve endings- detect light pressure and touch
Scwanoma-compressing SC from its lateral or antero lateral aspect causing impairment of pain and
temperature sensation on contralateral side with weakness, spasticity, loss of proprioception, vibratory
sense on ipsilateral side to tumor
DAMAGE TO ANTEROLATERAL SYSTEM ALS, SPINOTHALAMIC TRACT OF SPINAL CORD-causes
impairmet or loss of pain and temperature sensation contralateral to lesion EX.SCHWANOMMA
DAMAGE TO CORTICOSPINAL TRACT IN SPINAL CORD (LATERAL CORTICOSPINAL TRACT LCST-results
uppermotor neuron syndrome ipsilateral to lesion EX. BROWN SEQUARD SYNDROME, AMYOTROPHIC
LATERALSCLEROSIS/ALS
Macula adherens-blisters on back and buttocks has auto antibodies to 1 of cadherins with dx of
Pemphigus
Pemphigus-basal layerof epidermis remains attached to basal lamina, there is disruption of macula
adherens in s. spinosum, autoantibodies to desmogleins ( a member of cadherin CHON family ) result in
disruption of macula adherens/ desmosomes
Bullous pemphigoid/BP-antigen develop that are specific for hemidesmosomes, entire epithelium
separates from basal lamina,in which BPag are produced to chon specific to hemidesmosomes, entire
epidermis separates from basal lamina, with severe blistering over her buttocks, with numerous
neutrophils present underlying cell biological mechanism
Desmogleins- transmembrane linker chons of the desmosome
Sp. Desmosomes- targetof autoantibodies different forms of dse
Cadherins- are calcium dependent transmembrane linker molecule essential to cell to cell contact so
their disturbance in pemphigus leads to severe blistering of skin, bec of disrupted cell to cell interactions
early in differentiation of keratinocytes ( epidermal cell) and excessive fluid loss
Hemidesmosomes- contain different chons than desmosomes not affected in pemphigus
Production of cytokines by infiltrating inflammatory cells- with patches of raised red skin covered by
flaky white build up on her knees and elbows with dx of psoriasis
Psoriasis- chronic dse affects both epidermis and dermis, there is hyperplasia of epidermis
andabnormal microcirculation in dermis as venules predominate in cappilaries which results in increase
extravasation of inflammatory cells, the underlying cause is infiltration of inflammatory cellsinto dermis
with further migration of neutrophils into epidermis
Psoriasis- those inflammatory cells are cytokines that induce inflammatory response, there is
hyperplasia of epidermis as keratinocytes traverse cell cycle in a shortened period of time
Autoantibodies to desmoglein I- cause of pemphigus Foliaceus
Autoantibodies to BPAG- are cause of Bullous Pemphigoid
Mutations in keratins 5and 14- -result in epidermolysis bullosa which is a group of inherited bullous
disorder characterized by blister formation in response to mechanical trauma
Mutation in Laminin 5 subunits- cause junctional epidermolysis bullosa
Gap junctins- are comminucation jxn
z.occludens- prevents material from flowing between cells
z. adherins- belt like component of jxntional complex links to actin cytoskeleton
MEMORY GRID: component of junctional complexes and their attachment to cellmove down or across
no diagonal
cadherin integrins
actin adhesion belts focal adhesions no plaque
intermediate fil desmosomes cell-cell hemidesmosomes plaque
cell-matrix
competitive inhibition of phenylalanine for tyrosine in melanocytes-a phenyl kentonuria test in boys is
positive with lighter skin and hair with dx of PKU
PKU- with diffuse pigmentary dilution dueto elevated levels of L phenylalanine resulting from a
deficiency in L-phenylalanine hydroxylase that converts L phenylalanine to L tyrosine
High levels of phenylalanine- provide competitive inhibition for tyrosinase, characteristic blonde hair of
PKU can go darkening when pt is onlow phenylalanine diet, number of melanocytes that differentiate
from neural crest would be normal

GIT AND GLANDs

Keratin- man drinking 6 pack beer each day with increase alanine aminotransferase or serum glutamic
pyruvic transaminase (ALT/SGPT) and aspartate amino transferase or serum glutamic oxaloacetic
transaminase (AST/SGOT), sclera is jaundiced , serum bili 2.5 normal 0.3-1.9, biopsy shows eosinophilic
intracytoplasmic inclusions ( Mallory bodies) derived from iintermediate fil chons source of Mallory
bodies
Mallory bodies- derived from keratin intermediate fil with in hepatocytes
Hepatic stellate cells- secrete collagen replaces normal liver parenchyma in cirrhosis
Kuppfer cell- macrophages of liver
Vimentin-intermediate fil protein in cells of mesenchymal origin
Liver and hepatocytes- epithelial in origin
Desmin-intermediate fil chon associated with muscle
ALT/SGPT and AST/SGOT-hepatic aminotransferase when their blood vessel are elevated indicates liver
damage
H,K ATPase is sequestered in tubulovesicles- resting parietal cell not secrete acid because of this
reason, proton pump (H,K ATPase) is found in tubovesicle membrane located intracellularly
Sequestration of proton pump intracellular tubulovesicles- is the resting state which prohibits
secretion
On activation of parietal cell- thru calcium to diacylglycerol 2nd messengers the tubulovesicle membrane
fuse with plasma membrane by exocytosis
Histamine- along with gastrin and actylcholine- activate parietal cell
NA,K ATPAse- located in basal membrane
Cl channels- of apical plasma membrane maintains appropriate ionic gradients to facilitate acid
secretion
Carbonic anhydrase- cytoplasmic enzyme catalyses formation of carbonic acid
(H2CO3) from CO2- which is source of protons in parietal cell and other types as osteoclast, that depend
on proton pump.
Enteroendocrine cells-identified by stain response to silver or chromium stains, aka argentaffin cells
respective older term
Direction of release of secretion-H2 blocker the parietal cell returns to resting state by recycling (
endoctytosis) of membrane to reform tubulovesicular arrangement in cytoplasm dx with carcinoid after
an appendectomy dx carcinoid tumors
Carcinoid tumors- arise from enteroendocrine cells
Enteroendocrine cells- release peptides from their basal surface ( domain),secrete to bloodstream or
paracrine function nearby cells, are derived from same stem cell, turnover slower rate, fnctionin local
paracrine regulation of mucosa ( acid secretion in stomach mucosal growth, small intestinal secretion
and turnover)
Goblet cells- secrete mucus from their apical surface ( domain), are unicellular mucus secreting glands
analogous to entero endocrine cells that are unicellular endocrine glands
Eneteroendocrine and goblet cells- release granules by a regulated exocytotic secretion, both cells
formed stemcells in crypt base of small and large intestinal glands of lieberkuhn,
They secrete similar peptides throughout GIT -enteroendocrine cells and cells comparing enteric
nervous sytem of gut which applies to both types of cells
Cells that compose enteric NS- neurons derived from neural crest
Enteric NS- particularly myenteric or aurbach plexus respon intrinsic rhythmicity of gut and peristalsis
CN VII-damage structre in antrio 2/3 oftongue which is specific for chorda tympani in tongue piercing
which result from pain, numbness,loss of tatste when eating associatedwith damage to taste buds,
innervated by taste bud at anterior 2/3
CN V- trigeminal CN respond transmitting general sensation from ant 2/3 of tongue
Taste buds from post 1/3 of tongue-innervated by CNIX
CN X-innervates taste bus on epiglottis and palate
CN XII- hypoglossal – innervates intrinsic musculature of tongue
Hirsprung dse and chagas dse with disruption of muscularis externa- result in disturbance of
intestinalmotility
Hirshprung dse ( congenital megacolon) and chagas dse- have dif etiologies both inhibit intestinal
motility affecting myenteric (auerbach) plexus located between layers of muscolaris externa,
Hirshsprung dse aka aganglionic megacolon- result in failure of migration of neural crest cells to colon
result aganglionic segment both myenteric and submucosal plexus are affected
Submucosal ( meissner) plexus- more involved in regulation of luminal size and will affect defecation
but will be less involved in peristalsis
Myenteric plexus-primarly regulator of intrinsic gut rhymicity
Chagas dse- caused by protozoan T cruzi, severe infection result in extensive damage to myenteric
neurons
4 layers and walls of Gi tract- mucosa, submucosa, m. externa, serosa
l.propia- loose CT layer immediately beneath epithelium
m.mucosa- last part of mucosaa double layerof smooth muscle cells
nest of parapostganglionic neurons- forming part of meissners plexus
submucosa-inner circular and outer longitudinal layer of smooth muscle cells is discernible, a thick layer
of dense irregular CT the submucosa separates m. mucosa from m. externa
m. externa- consist inner circular and outer longitudinal layers of smooth muscle cells,respi, urinary,
integumentary, reproductive differ in epithelium and arrangement of tissue
sodium-frequent mouth sores, lab test (+) ANA and Rheumatoid factor levels of 70, with CT damage to
acinar cells and striated ducts, in this case resorption of which of the ff be most altered by destruction of
striated ducts with dx of sjogrens syndrome
sjogrens syndrome- much more common in women
striated ducts-resorbs sodium and secrete potassium from isotonic saliva converting it to hypotonic
state, its primary secretion is produced by acinar cells comprise of amylase, mucus, ions in same conc as
those extracellular fluid
Na independent CL, HCO3, anion exchanges-appear to be involve in these processes by generating ion
fluxes into salivary secretion
in duct system-sodium actively absorbed from lumen of ducts
CL- passively absorbed although tight junctions between striated duct cells inhibit CL from ff sodium
HCO3- secreted
Calcium transport- not a factor result hypotonic NA and CL conc and hypertonic K concentration
Autonomic NS-primary regulator of Salivary gland secretion and function is contradiction to pancreas
which is regulated primarily by hormones ( cholecystokinin and secretion)
Parasympathetic fibers- carry neural signals origin in salivar nuclei of medulla and pons
Sympathetic NS-origin from superior cervical ganglion of sympathetic chain and stimulates acinar
enzyme production
Elevated aldosterone levels- affect amount and ionic concentration of saliva result in decrease NaCL
secretion and increase potassium concentration
Cholecystokinin (pancreozymin) an secretin- hormones regular acinar and ductal secretion
respectivelyin exocrine pancreas
ADH- modulate SG production
Glycogen- child with hepatomegaly, renomegaly FTT stunted growth, hypoglycemia, def in glucose 6
phosphatase on dx of Von gierkes dse dx is type I Hepatorenal Von gierkes glycogenosis
Type I ( hepatorenal,von gierkes glycogenosis GSD- is caused by defect inG-6-phosphate and glycogen in
liver
C.M- at basal surface of hepatocytes less dense than glycogen
Hepatocyte-under regulation of insulin and glucagon stores glucose in its polymerized form of glycogen
In EM glycogen- appears as 15-25 nm
Lipid droplets- are spherical , homogenous structure of varying density diameter is larger than glycogen
granules
Ribosomes- on RER or as free structure not clusters like glycogen
Mitochondria- contain distinctive cristae much larger (0.5-1.0 mm ) in diameter than glycogen
Bile flow- in 2 adjacent hepatocytes,
Bile cannaliculi- compose space bet lat surfaces of adjacent hepatocytes and tansport bile
Microvilli-line bile canaliculi visible protruding into lumen
Membrane- between cells are connected by tight ( Z. ooccludens ) and gap junctions
Z. occludens- preentmaterial from passing bet. Hepatocytes
Desmosomes- when present bet cells funtions as spot welds
Islet of Langerhans- in pancreas function both exocrine ( secretion of pancreatic juice), and endocrine(
secretion of insulin and glucagon) gland, they have heterogenous distribution with in pancreas they
decrease from tail to head of gland, used to distinguish pancreas from parotid gland
Submandibular and sublingual glands-can ber uled out bec of purely serous nature of acini with in
exocrine portion of gland
Centroacinar cells- modified intralobular duct cells from intercalatd duct are present in lumen of each
acinus
Duct- distinguish by presenceof cuboidal epithelium the absence of blood and blood cells from lumn and
absence of characteriticvascular wall
Anal canal and rectum- normal tissue sample taken from region
Cervical mucosa- contains extensive cervical glands
Vaginal epihelium- is keratinized
Crypts ( without vlii ) in rectum
Anus- has valves and absence of m.mucosa
Esophagus cardiac jxn- represents jxn between stratified squamous and simple columnar epithelium
Cardiac portion of stomach-forms mucus secreting cardiac glands with no goblet cells
Jxn of stomach, pylorus and duodenum- represent juncture of 2 simple columnar epithelia
Pylorus- contain short pyloric glands andduodenum with crypts and villi as well as submucosal brunners
gland
Mucus and HCO3- dx of celiac dse presents bout of diarrhea, which secrete brunner glands in
submucosa
Celiac dse- allergic response to gliadin which result in villous atrophy and cryot and brunner gland
Enterokinase- made by duodenal mucosa nd instrumental in conversion of pancreatic zymogens to teir
active form example trypsinogen to trypsin
Brunnel glandsecretion- function to neutralize acidic ph n stomach establish appropriate ph for function
of enzymesin pancreatic juice
Parietal cells- unique to stomach synthesize acid and intrinsic factor required for vitamin B1 absorption
for SI
Chief cells-on fundic glands produce pepsinogen activated by acini to form pepsin
Paneth cells- in base of crypts make lysosome and modulate flora of SI
Top of right shoulder- inflammation of organ with referred pain organ is GB
GB-stones and concentrates bile, inflammation lead to pain referred to top of right shoulder
Diaphragmatic pain- felt in neck
Stomach pain- refer to spine bet scapulae
Kidney pain- in groin area
Intestinal dysfunction- felt middle or low back
Umbilical pain-refered to appendix, finger like extension of GB resemble villi represent changes that
occur in mucosa with increasing age, thinnest of wall notable characteristic of GB
Bile- is synthesis by hepatocytes transported from liver to GB where its store and concentrated
Small intestinal epithelium-immune defense mechanism
Mast cells- synthesize and secrete histamine and heparin
Intraepithelial lymphocyte- are lymphocyte that crossed the basal laminamay respond to antigen in
lumen of small bowel
In peyers patches of ileum-lymphocyte in lamina propia respond antigen that has been sampled from
lumen and transported by m cells in peyers patches
Enetrocytes- absorptive cells of gut, possess numerous microvilli on apical surface
Goblet cells- synthesize and secrete mucins
Paneth cells—eneteroendocrine cells contain granules but secrete lysozyme ( regulation of flora and
endopetides respectively)
Elevated bilirubin levels- in hemolytic jaundice
Bile duct- contain elevated levels of bilirubin ff hemolytic jaundice
Hemolytic jaundice- associated with unconjugated hyperbilirubinemia,
Overproduction of bilirubin- occurs because of accelerated intravascular erythrocyte destruction or
resorption of a large hematoma
When hepatic uptakeexcretion of urobilinogen are impaired or production of Bilirubin -is greatly
increased xample hemolysis- daily urinary urobilinogen ecretion may increase significantly
Cholestasis- ( arrested flow of bile due to obstruction of bile ducts ( intrahepatic) or extrahepatic
obstruction
Extrahepatic biliary obstruction-interferes with intestinal phase of bilirubin metab and leads to
significantly decreased production and urinary excretion of urobiinogen
Diapedesis of lymphocytes- across endothelium of post capillary high endothelial venules of lymphoid
organs ( eg L.N ) increase during inflammation
Bile- formed by hepatocytes is released intobile canaliculi which are located bet lat surfaces of adjacent
hepatocytes, direction of flow from hepatocytes toward bileduct which drains bile from liver on its path
to the GB where bile is stored and concentrated, synthesized by hepatocytes using SER and consists of
bile acids and bilirubin
Portal triad- hepatic artery , hepatic portal vein, bile duct, blood flows from triad- toward central vein,
whereas bile flows in opposite direction toward the triad
Bile acids-90 % recycycled from distal small and large intestinal lumen and 10% newly synthesized by
conjugation of chilic acid, glycine, and taurine in SER
Bilirubin- breakdown product of hgb derived from action of kuppfer cells in hepatic sinusoids and other
macrophages particularly lining sinusoids of spleen
Lining sinusoids of spleen- where degradation of RBC is prominent
Deficiency of enzymes regulating bilirubin solubilty- skin, sclerae icteric blood test with elevated
unconjugated bilirubin in serum
Jaundice (neonatal unconjugated hyperbilirubinemia )- commonly initial low levels of glucoronyl
transferase in underdeveloped SER of hepatocytes in NB
Neonatal small intestinal epithelium- has increase capacity for absorption of unconjugated bilirubin
Bilirubin- product of free iron heme , liberated during destruction of old erthycytes by mononuclear
macrophages of spleen and to lesser extent of liver and bone marrow
Hepatic portal system- brings splenic bilirubin to liver where its made soluble fro excretion b
conjugation with glucoronic acid
Increase plasma levels of bilirubin ( hyperbilirubinemia)- result increase bilirubin turnover, impaired
uptake of bilirubin or decrease conjugation of bilirubin
Increase turnover occurs in both dubin Johnson and rotor syndrome B2 or conjugated bilirubin CDR
Dubin Johnson- impairment of transfer of bilirubinglucoronide into bile canaliculi
Rotor syndrome-impairment of excretion of bilirubin glucoronide into bile canaliculi
B1 or unconjugated bilirubin in:
Gilbert syndrome- impaired uptake of bilirubin into hepatocyte and defect in Glucoronyl transferase
Crigler najar syndrome-defect in glucoronyl transferase occurs in neonate
Ability of mature hepatocytes to take upand conjugate bilirubin- may be exceeded by abnormal
increase in erythrocyte destruction ( hemolytic jaundice)or by hepatocellular damage ( functional
jaundice) as in hepatitis
Finally obstruction of duct system between liver and duodenum ( usuallyof CBD in adult and rarely
from aplasia of duct system in infants)- results in back up of bilirubin ( obstructive jaundice)
Gallstone obstructing CBD- 42 yr old female, sudden onset severe pain Right upper abdomen, bowel
sounds tender throughout the abdomen esp. RUQ, icteric urine darker than usual, with indigestion
referd to Right upper abdomen radiating to shoulder after eat fried foods after eating a meal ff long
period of fasting has no fever but anxious and tachycardic, blood test are CBC, blood chem, liver
enzymes, ALP, bilirubin, wbc 10k hepatic enzymes increase AST /SGOT 52 normal 3-33 increase ALT
/SGPT 70 normal4-44 increase ALP300 normal 17-91 increase bilirubin 6.3 normal 0.2 -1.0 dx is gall
stones
Gallstones- (+) pain in RUQ radiate to shoulder after eating fried foods, or similar pain when they not
eaten long period of time then eat large meal, pain is caused by obstruction of cystic duct, CBD produces
increase luminal pressure in bile vessels which cannot be compensated for by cholecystokinin- induced
cxn
Gallstone pneumonic: 4F( female, forty, fat fertile)
Enzyme obstructive parenchymal
Liver enzymes (AST, ALT) 1x increase 3x increase
ALP 3x increase 1x increase
Bilirubin 3x increase 3x increase
It contains mineralized collagen secreted by cells derived from neural crest- dentin, with abnormaly
large in her teeth with wide vascular channels with dx of dentiogenesis imperfect
Type II Dentigenesis imperfecta- AD disorder by mutation in DSPP gene result is defective dentin ,
discoloration of translucent teeth, blue gray or yellow brown color, teeth is weaker thannormal making
them prone torapid decay wear , breakages and loss occursabout 1/6k to 8k births
Type I- occurs in conjunction with O.I with mutations in type I collagen children have typical blue sclerae
with defects in bone and dentin
Dentin- synthesize by odontoblast- derived from neural crest
Pulp of mature tooth- consists primarily of loose CT rich in vessels and nerves
Odontoblast-lie at edge of pulp cavity and secrete collagen and other molecules which mineralizeto
become dentin
Mineralization- of matrix occurs around odontoblast processese and forms dentinal tubules
Ameloblast- ectodermal derivatives lay down an organic matrix and secrete enamel initially onto surface
Hydroxyapatite crystals-form at apices of ameloblast (tomes) processeces rods of enamel grow
peripherally and ameloblast resorb organic matrix so that enamellayer is almost entirely mineral
Ameloblast- contains unique chons as amelgenins and enamelins
On eruption of tooth- enamel deposition is complete, and ameloblast shed
Cementum- similar to bone by similar appearance as osteocytes and covers dentin of root
Periodontal ligament- consist coarse collagenous fibersrunning bet alveolar bone and cementum of
tooth,separate tooth from alveolar socket,is the site of inflammation in diabetic pts. It is affected in
scurvy
Body of stomach-dyspnea, fatique, pallor, tachycardia anosmia diarrhea abnormal stage 1of schilling
test autoantibodies are detected to a cell dx of pernicious anemia
Pernicious anemia- resulting from auto antibodies to parietal cells that synthesize intrinsic factor as well
as HCL
Abnormal stage I of schilling test- indicative of def of intrinsic factor or IF
Chief cells and parietal cells- in fundus
Chief cells- synthesize pepsinogen
Gastric fundic glands- contain mucus cells , chief cells , parietal cells
I.F- for absorption of vit B12 from SI
Food entering pylorus- stimulates release of gastrin
Gastrin- stimulates HCL production by parietal cells
Pylorus- connectto duodenum contains mucus and HCO3 neutralize secretion of brunners gland
Wall of stomach- consists of mucosa ( epithelial, l.propia, and m.mucosa) submucosa, m. externa and
serosa lined by mesothelium
ADP ribosylationof Gs of the GTP binding CHON in enterocytes- which leads to elevated CAMP and
opening of CL channels dx secretory diarrhea
Secretory diarrhea –by cholera toxin, the exit of CL thru open channels ff by passage of Na and water
dehydration
Dehydration-off set by IV feeding or oral rehydration therapy
Pancreatic secretion- regulated by hormones secretion regulates ductal secretion
Cholecystokinin- regulate release of enzymes ( amylase, lipase , DNASE, RNASE and other enzymes that
compose pancreatic juice
Zymogens- are inactive preursors, number of pancreatic secretions released to pancreatic duct system
are activated only when they arrive in SI lumen
Enetrokinase-brush border enterocyte enzyme responsible for activation of chymotrypsinogen,
proelastase, procarboxypeptidase, A and B to their active forms: ( chymotrypsin, elastase,
carboxypeptidase A and B
Specific dissacharidase activity- cramping abdominal pain,meteorism, diarrhea with excessive flatulence
is decrease in ff. and dx is lactase def.
Lactase def-has adult onset since lactate activity is decrease after childhood,absence of lactase or
reduce activity results in passageof undigested lactose in colon, bloating, cramping, abd pain are due to
breakdown of lactose and production of H gas
Glycocalyx ( brush border) – consist of microvilli of SI epithelium,location of brush border enzymes
include lactase
Microvilli- site of glucose or galactose transporter
Other brush border enzymes are- monosaccharides, eneterokinase which are imp t for cleavage of
pancreatic enzymes ex trypsinogen to their active form
Digestion of lipids- occrs hru action of bile
From liver and bile duct and lipase from pancreas
Bile- emulsify lipid to form micelles whereas
Lipase- breaks down lipid from TG to FA , glycerol and monosaccharides
FA, glycerol, monosaccharides- those 3 beakdown products difuse freely across microvilli to enter apical
portion of enterocyte by passive diffusion
TG- resynthesize in RER
CHON- synthesize in RER and combined with sugar lipid portions in golgi to form glycoproteins and
lipoproteins
Glycochons and lipochons- 2 types of molecules form coverings of TG cones of chylomicra
Chylomicra- released at basolateral membrane by exocytosis into lacteals
From lacteal chylomicra- travel into cisterna chili and eventually into venous system by way of thoracic
duct
Digestion of fat- occurs to a greater extent in duodenum and jejenum than in ileum
Sugars- broken down by amylase in oral cavity with continued digestion by brush border
monosaccharides
CHON- breakdownby pepsinogen on stomach with continu breakdown in SI by enzymes of pancreatic
juice ( trypsin, chymotrypsin and carboxypeptidase) products ofCHON digestion also located in brush
borders

ENDOCRINE GLANDS
Secretion of glucocorticoids into intraadrenal circulation-adre cortex influences secretion of adrenal
medulla
Metabolism of adrenal medulla- regulated by glucocorticoids because they induce enzyme
phenyethalomine-N_ methyl transferase which catalyses methylation of NE to EPI
Most of blood supply entering medulla- passes thru cortex
Glucocorticoids- synthesize in Z, fasciculate of adrenal released into sinusoids and enter medulla
Monoamine oxidase-mitochondrial enzyme regulates storage of catecholamines in peripheral sympa
nerve endings
Adrenal glands- functions as 2 separate glands
Adrenal cortex-derived from mesoderm
Adrenal medulla- from neural crest
BLOOD SUPPLY of adrenal is derived from 3 adrenal artery
Superior adrenal ( suprarenal ) from inferior phrenic
Middle adrenal from aorta
Inferior adrenal from renal artery
Paroxysms-pheochromocytoma common tumor of adrenal medulla, paroxsyms is the hallmark of this
tumor, seizure like catecholamine induced attacks include headache, prouse seating,palpitations and
overall anxiety
Pheochromocytoma- common tumor of adre medulla that leads to excess release of NE ( noradrenaline)
EPI ( adrenaline) which causes HPN and hyperglycemia
VC of arterioles- occurs in conjunction with increase BP
Hirsuitism- due to action of androgen dihydrotestosterone (DHT) that acts on hair follicles to produce
terminal hair,
Markedly elevated plasma catechcholamine- levels known to increase metabolism rate
Pineal gland aka epiphysis cerebri- It influences the rhymicity of other endocrine glands, used as a
radiological landmark by its calcifications, which arises as an out growth of diencephalon has 2 main cell
types
Pinealocytes- secrete melatonin in response to light dark cycle and influence the ryhmicity of other
endo organs, in a sense functions as biologic clock
Neuroglia- to be modified astrocytes
Pineal gland –is innervated by post ganglionic sympathetic fibers in similar to other organs in head ,
neck region, ( salivary glands), not contain melanocytes or secrete MSH are age related changes in pineal
in which number of concretions and degree of calcification of brainsand increase
Adre medulla- innervated by pre ganglionic sympa fibers
Corticotrophs- in anterior pituitary produce MSH
A defect in cortisol pathway-NB genitalia are female, but masculinized genotype be 46 xx dx with
adrenogenital syndrome aka congenital virilizing hyperplasia aka female pseudohermaphroditism which
leads in def in pathway that leads cortisol synthesis
Androgen insensitivity- cause testicular feminization
In ability to synthesis cortisol- leads to production of high levels of ACTH and ACTH releasing factor
from hypothalamus
hypertrophy of fetal adrenal cortex result- critical fetal endocrine organ produces
dehydroepiandrosterone
Excess production of androgen by fetal adrenal result-leads to masculination of female genitalia
Increase secretion of cortisol- cannot occur becaue metabolism defect in pathway therefore negatve
feedback control is not functional
Fetal cortex- part of maternal fetoplacental unit because dehydroepiandrosterone is used by placenta
to produce estradiol
Fetal adrenal cortex- involve birth causing overall reduction in size of adrenal
Adult cortex- (Z.glomerulosa. Z. fasciculate< Z.reticularis) repaces fetal adrenal cortex
Z.fasciculata and Z. reticularis- produce androgens after birth
Vasopressin (AVP) aka ADH- released by post pituitary and regulates flid balance
ADH- increases permeability of collecting duct thru aquaporin mediated mechanism
TSH receptors- easy to anger, eyes protrude feeling dry p.e revelas asthenia, tachycardia, pretibial
myxedema and tremor in her right arm, biopsy in organ showed increase lymphoid cells with dx of
graves dse
Graves dse, hyperthyroidism- autoimmune dse tha t occurs much more frequently in women,accounts
approximately 85 %of x hyperthyroidism, pts produced auto antibodies to TSH receptors
CD8 T cells- generated against TSH receptor leading to their destruction
Myxeda – hypothryroidism versus pretibial myxedema which is hyperthyroidism
Increase TST produced by anterior pit with concommitant increase thyroid hormones production ( T4
tetra iodothyroxine, thyroxine ) and T3 tetraiodothyronine from the thyroid
Elevated thyroid hormone secretion leads to nervousness, weight loss, extreme mood changes
Permeability-is electromagnetismis the measure of ability of material to support the formation
ofmagnetic field itself
Graves dse- no auto antibodies to C cells
Destruction of C cells- lead to absence of calcitonin and high serum calcium levels
Thyroid gland – most often confused histologically with lactating mammary gland which differs from
thyroid in presence of duct system
Thyroid- composed of follicles, with colloidal material surrounded by follicular C cells aka interfollicular
or parafollicular cells are clear found outside follicular cells
C cells- synthesize calcitonin dereived embryologially from ultimobrachial bodies 4th and possibly 5th pair
of brachial pouches
Calcitonin- decraes elevated calcium levels transiently inhibiting osteoclastic activity thru receptors on
osteoclasts
Autoantibodies- to principal cells of parathyroid- lead to decrease serum calcium levels as PTH synthesis
and secretion would be reduced
PTH- increase osteclastsresorption, stimulates calcium uptake from gut, and calcium reabsorption by the
kidneys
Thyroid gland-is under direct regulation of TSH (thyrotropin) production by anterior pituitary which
inturn is regulated by TSH releasing actor (TSH RF) released from hypothalamus
TSH RF-transported by hypothalamushypophyseal pit portal system to anterior pituitary
Autoantibodies to TSH RF- result in elevated TSH, T3, T4 receptors located in anterior pituitary on
thyrotrophs
Autoantibodies to thyroglobulin and thyroid peroxidase- result in hashimotos thyroiditis
Asthenia-loss of strength and tachycardia is accelerated HR
Pretibial myxedema-presents as orange peel like rash on shins in some ps with graves dse
Thyroid follicular EC-import iodide and AA from capillary lumen
Follicular cells- synthesize thyroglobulin fr AA
When iodide enters follicular cells- it undergoes oxidation
Thyroglobulin is iodinated while in the colloid and iodinated thyroglobulin- is the storage products of
thyroid colloid
Thyroid follicular cells- process iodinated thyroglobulin and activity of lysosomes breaks own colloid to
form thyroxine (T4) and T3, MIT, and DIT
Most of secretion of human thyroid gland- composed of thyroxine although triiodothyronine more
potent
Elevated TSH levels in the serum-always being tired temperature skin very dry, with dense lymphocytic
infiltration with germinal centers throughout the parenchyma with dx of hashimotos thyroiditis
Hashimotos thyroiditis- extensive lymphocytic infiltration of thyroid gland, auto antibodies develop to
thyroglobulin and thyroid peroxidase an iodide transporter and TSH receptor,in cases where
autoantibodies to TSH receptor, TSH receptor activity is blocked resulting in hypothyroidism
CD8 T cells- directed against that site
T3 and T4- elevated early in dse due to disruption of follicles and release of hormones overalleffect
hypothyroidism
Destruction of thyroid hormone receptors- lead to hyperthyroidism
Calcitonin- secreted by C cells in thyroid not affected by thyroiditis

Herring bodies- derived embryologically from neuroectoderm

Neurohypophysis—contains herring bodies is formed from neuroectoderm as an extension of
developing diencephalon
Pars nervosa- consists of pituicytes ( supportive glia) herring bodies,dilated axons whichoriginate in
supraoptic and paraventricular nuclei
Supraoptic and paraventricular nuclei- produce oxytcin and vasopressin that are stored in herring
bodies
Pit gland ( hypophysis cerebri)- formed from 2 types of ectoderm an outgrowth of oralectoderm, overall
is derived from ectoderm of oral cavity( rathkes pouch) and floor of diencephalon
Rathkes pouch-forms structures that compose adenohypophysis, pars distalis, pars intermedia, pars
tuberalis
Cleft of rathkes pouch- represents lumen of thestructure formed originally from oral cavity,
Anterior intermediate lobes, pars tuberalis- derived from oral cavity whereas remainder of pituitary
Anterior pituitary- unique bec. It sepends on presence of H-H sytem portal
Pars distalis-contains coticotrophs,thyrotrophs, lactorophs, gonadotrophs,that synthesize trophic
hormones which regulate other endocrine organs,includes classic histo cell types: chromophils (
acidophils, basophils) and chromophobes ( acidophils and basophils) that are depleted of secretory
product, and regulated by stimulatory and inhibitory hormones produced by hypothalamus
Releasing and inhibitory factors- are transported from cell bodies in hypothalamus along axons into
median eminence to secondary capillary plexus where it interacts with corticotrophs in pars distalis
Median eminence- where secretion is release in primary capillary plexus
H-H portal sytem- carries blood from primary plexus to secondary plexus comprises sinusoids of pars
distalis, system brings hypothalamic hormones into close proximity with appropriate cell types in pars
distalis
Example: CTH-RH ( corticotropin releasing factor , CRH is synthesize in hypothalamus released into
primary capillary plexus in median eminence subsequently carried in portal system
Acidophils- include lactotrophs ( prolactin) somatotrophs (growth hormone)
Basophils- ncludecorticotrophs ( ACTH), a-lipotropin, B-MSH alpha – endorphin, thyrotrophs ( TSTH and
gonadotrophs (FSH and LH)
Pars intermedia-form also from oral ectoderm is rudimentary in humans may produce
preproopiomelanocorticotrophic peptide
Pars tuberalis- forms a colar around pit stalk also derived from oral ectoderm
Pars nervosa-major cell type present in pituicyte( include herring bodies) and remainder of pit stalk (
infundibular stem and median eminence) are formed from a down growth of the diencephalon,neutrally
connectedportion of pit, contains dilated axons of hypothalamic cell bodies produce vasopressin and
oxytocin,
Axons that originate in supraoptic and paraventricular nuclei of hypo- descend into pars nervosa
Pituicyte- supportive glial cell
Pars nervosaand pit stalk- is derived from a neuroepithelium origin,
Posterior pituitary ( pars nervosa and stalk)- retains this close rel. with the brain ( hypo) throughout
life,stores oxytocin, vasopressin in dilated axonal terminals
Cushing syndrome- pituitary adenoma result from ant pituitary specific corticotroph
Adenoma- cause increase levels of ACTH stimulate excessive production of corticosteroid from adrenal
cortex ( cushing syndrome)
Prolactinoma- MC of pituitary adenoma result in infertility galactrorrhea 9 excessive production of milk
and amenorrhea)
Oxytocin-regulates milk ejection reflex and vasopression (AVP) aka (ADH), regulates collecting duct
permeability
Oxytocin and vasopressin- are stored in dilated endings in pars nervosa called herring bodies, those
secretions therefore synthesize in hypothalamus and stored in pars nervosa
Thyroid- secretes T3, T4 regulated by TSH from thyrotrophs in anterior pituitary
PTH- not regulated by anterior pituitary
LH and FSH producing gonadotrophadenomas- occur but result in hypogonadism
Somatotropic tumors- produce GH cause gigantism
D.I- cause absence of vasopressin ( arginine , vasopressinAVP) leading t excretion of large quantity of
dilute fluid (hypotonic polyuria)
Overproduction of PTH- leads to osteoporotic changes
Diabetes- tumor in specific region
Tumor of glucagon secreting alpha and A cells delineated – resuls in hyperglycemia and diabetes
Pancreatic exocrine tissue-throughout pancreas with round aggregations light stains cells forming islet
of Langerhans
More numerous 70 % of total B or B cells- are centrally located secreteinsulin that issecreted after a
meal results in lowering of blood sugar
Small popn of A or a cells located at periphery of islet secrete glucagon
Glucagon- secreted in response to low blood sugar and raises blood sugar levels
Glucagonama- produce excesive amount of glucagon that result in hyperglycemia and diabetes
Interaction of b and a cells is based on blood supply
Blood entering islet- initially pass a cells result is blood reaching a cells already contains insulin which
contains insulin which regulates glucagon production
Type I DM- absence of normal glucagon, regulation by insulin is this, complication :insulin not produced
Other celltypes (D, and F) are variable in location secrete somatostatin, pancreatic polypeptide
respectively
Somatostatin-regulates insulin, glucagon , release
Pancreatic polypeptide- appears to regulate exocrine chon and HCO3 secretion
Exocrineportion of pancreas- consists of acinar andductal cells
Acinar cells- are pyramidal in shape, posses very basophilic basal cytoplasm indicating presence of
abundant RER an acidophilic apical cyto due to presence of numerous secretory ( zymogen) granules
Other tumors- ofilet of langerans include Insulinomas-
Insulinomas- wich is elevated levels of insulin, secreted into blood stream result in hypoglycemia as
blood sugar levels drop
Insulin- removes sugar frombood n liver either stores it as glycogen or metabolizes it thru glycolysis,
inhibit glycogen phosphorylase which catalyses breakdown of glycogen to form glucose and activates
glycogen synthase in both muscle and liver result in increase storage of glycogen
Addisons dse-loss of appetite, depressed with irregular mens, and hot flashes, histo on pic is adrenal
gland with hypertrophy, progressive destruction ( hypertrophy of adrenal cortex)
Asthenia- result bec of lack of strength overall weakness fatique, anorexia, nausea , vx , weight loss,
hpotension, low blood sugar
Adrenal gland ( cortex or medulla)- releases stress related hormones ( glucocorticoids and
catecholamines NE or EPI)
Adrenal cortex- orign intermediate mesoderm
Adrenal medulla- forms from neural crest
Hyperpigmentation-result in elevated ACTH stimulation on melanocytes
Adrenocortical cells-under influence of corticotrophs in anterior pituitary, import cholesterol, acetate,
produce hormones
z. glomerulosa-immediately beneath the capsule
z. fasciculate, z. reticularis- ffolow as 1 moves toward medulla
steroid hormone-released by diffusion thru plasma membrane without use of exocytotic preces used by
most glands including adrenal medulla
cells of the adrenal medulla- considered as modified post ganglionic sympathetic neurons, synthesize ,
secrete NE, EPI, enkephalins in response to stimulation of preganglionic sympathetic fibers that travel
thru abdomen in splanchnic nerve and innervate the gland
adrenal cortical hormone- essential for life bec of their regulation of metabolism
it lacks function when separated from the hypothalamus hypophyseal portal system-not a good
candidate for transplantation compared with endocrine glands
the liver and kidney- convert T4 and T3peripherally
T4- thyroxine-primary serum thyroid hormones is produced only by thyroid gland
20% of T3- produced by Thyroid gland, is formed in liver and kidney by action of sp . enzyme 5’
deiodinase that converts T4 to T3
5’deiodinase- converts T4 to T3, converts T4 to metabolically inactive thyroid hormone rT3 ( reverse T3)
T3- 3-5x more physiologically active than T4
Both T4 and T3- are bound to thyroxine binding globulin ( TBG ) , transthyretin, and albumin with only 1
% of free circulating hormone
Levels of available binding chons- affect measurable levels of total T4 and T3
When those binding proteins are found in high concentrations-total T4,T3 levels also high both free
T4,T3 values remains normal
Free fractions of T4 and T3-responsible for feedback mechanism at level of hypothalamus and
thrytrophs in anterior pituitary
T3 and T4- regulated by TSH from thyrtrophs, there is some cross reactivity of all immune asays , but not
a reason of extra polating from serum T3 levels to thyroid function

REPRODUCTIVE SYSTEMS
Increase ciliation of epithelial cells of the oviduct-physio changes of elevated estrogen levels during
menstrual cycle result
Estrogen levels- increase during maturation of ovarian follicles which result concomitant increase in
ciliation and height of oviductal lining cells, also increase in estrogen levels results in decrease FSH
levels, and cause LH surge, increase estrogen levels result in increase secretion of lytic enzymes , PGs,
plasminogen activator, and collagenase, estrogen to facilitate rupture of ovarian wall and released of
ovum and the attached corona radiate, it upregulates FSH receptors on granulosa cell membrane, it
enchances synthesis and storage of glycogen in vaginal epithelium
Increase in number of cilia- serve to facilitate movement of ovum
Following ovulation- during luteal phase of cycle
Theca and granulosa cells-transformed into corpus luteum under the influence of LH
Ovulation- occurs near the middle of menstrual cycle is associated with increase BBT that appears to be
indirectly regulated by elevated estrogen levels with IL1, functioning as endogenous pyrogens
Leydig cell ( interstitial cell )- regulated or stimulated by LH formerly known as ICSH interstitial cell
stimulating hormone secreted by gonadotropin in anterior pituitary, are located in seminiferous tubules
and responsible for production of testosterone, normally synthesize and release testosterone in
response to LH produced by gonadotropins in anterior pituitary
Leydig cell tumors-in males 20-60 yr produce androgens, estrogen, sometimes glucocorticoids
Calcitonin- synthesize by C cells in thyroid
Androgens-tumor as originating from cell delineated with the star tumor on picture
Progesterones- synthesized by corpora lutea under influence of LH
FSH-physio role in both males ( spermatogenesis ) and female ( regulation of follicular growth) and is
produced released by gonadotrophs in anterior pituitary, stimulate maturation of ovarian follicles
FSH treatment of humans- result devt of more than usual number of mature follicles , increase number
of mature gametes, critical for sperm production, supports function of sertoli cells which serve as
nutritive role in sperm cell maturation
PTH- synthesized and released from principal cell of parathyroid glands
Sertoli cell- function in nutritive and supportive role some what analogous to glial cells of CNS, produce
inhibin which feeds back on anterior pituitary and hypothalamus to regulate FSH release, have extensive
tight occluding junctions between them form blood testis barrier, they communicatewith adjacent cells
thru gap junctions, they extend from outside the blood testis barrier ( basal portion) to lumnal ( apical
portion)
Testosterone- binds to androgen binding CHON ( ABP) which is synthesized by sertoli cells, for
maintenance of spermatogenesis as well as male ducts and accessory glands
Androgen binding protein is regulated by FSH, testosterone, and inhibin
During spermatogenesis preleptotene spermatocytes-cross from basal to adlumina compartment across
Z. occludens between adjacent sertoli cells, each of sertoli cells associated with multiple spermatogenic
cells
Testis- composed of seminiferous tubules contain number of spermatogenic cells undergoing
spermatogenesis and spermiogenesis
Spermatogia- derivatives of embryonic primordial GC
Spermatocytogenesis- undergo mitosis to form primary spermatocytes which have distinctive clumped
or coarse chromatin
Secondary spermatocytes- formed during 1st meiotic div. exist for short time, no LAG period before entry
into second meiotic division which results from formation of spermatids
Spermatids- round structure elongate form of flagellum, last part of SF tubules function is
differentiation of sperm from spermatids ( sperm iogenesis)complete with release of mature sperm into
lumen of tubule
Efferent ductules or ductuli efferentis- with waxy epithelium, tall ( ciliated ) short ( non ciliated)
Mediastinum testis- contain rete testis
Sperm leave SF tubules thru short tubuli recti into straight tubules of rete testis which subsequently
drain into efferent ductules
Passage of sperm from epididymid to urethra- fxn of reproductive sytem in photo
Vas deferens ( ductus deferen)- conducts sperm from epididymis to urethra
Thick muscular wall—unique in presence of inner longitudinal, middle circlar and outer longitudinal
layer of smooth muscle
Ureter – 2 thin layers are inner longitudinal and outer circular
Male and female urethra- contain extensive vascular channels
Epididymis- consist of CT stroma and stores sperm resorbs fluid and produces sperm maturation factors
Male urethra ( penile)- possess primarily pseudostratified columnar type of epith,distinguishing features
are thick walled artery of penile and cavernous sinuses of penile erectile tissue
Helicine artery- supply sinuses
Action of parasympathetic NS- mediates dilation of these vessels during erection
Female urethra- surrounded less erectile tissue
Glands of littre- produces mucus also observed in section, not present n oviduct, ureter, seminal vesicle,
Outer peripheral glands- malignant most frequently arise from this portion of prostate
Organ is prostate-70 % of cancer arise from main ( ext gland ) aka outer peripheral gland
3 parts of prostate gland
Small mucosal ( inner periuethral gland)
Transition zone- consist submucosal ( outer peripheral ) gland
Peripheral portion- akamain or ext . gland, because its location of most prostate cancer
Primarily adenocarcinoma- remainundiagnose until later symptom of back pain and blockage of urethra
are detected
DRE- identify some tumors earlier
BPH- aka benign nodular hyperplasia- occurs in mucosal submucosal gland which are rarely sites of
cancer, cause urethral obstruction in early stages bec its locaton in mucosal and submucosal glands
surrounding urethra
Main prostate gland- sensitive to androgens
Periurethral glands- sensitive to androgens and estrogens
Acid phosphatase and PSA levels- used to dx of prostatic cancer and its mets, breast cancer in 1/10
females in US
A cancer is ductal in origin
Breast cancer- mets to brain, lungs bones, easy access of tumor cells to extensive axillary BS and lymph
drainage facilitates spread of cancer into blood and lymphy supplies
Breast self exam and mammography- to early diagnose with a reduced mortality
Sperm is found in lumina
Spermiogenesis- occurs in testis
GC of testis( testi neoplasms)- classified as seminomas ( germinomas ) of pure germ cells, more
heterogenous cell types example is teratomas, embryonal cancer
Seminal vesicle – an organ where Proteins that coagulate semen, they also produce fructose, ascorbic
acid, PG, chonsresponsible to produce 50 % of seminal fluid orcoagulation of semen on a volume basis
and comprises most of ejaculate, wall consists, thich smooth muscle, mucosa of anastomosisng villus
like folds in comparison
Prostate- composed of 15-30 tubuloalveolar galandssurrounded by fibro muscular tissue with
concretions in lamina, secretes thin opalescent fluid primarily to 1st part of ejaculate include acid
phosphatase, spermine ( a polyamine) fibrinolysin, amylase and zinc
Spermine oxidation- result is musky odor of semen and fibrolysis- responsible for liquefaction of semen
after ejaculate
Acid phosphatase and PSA- important for dx of mets
Thyroid- synthesis T3 and T4
Lactation mammary gland- produces milk
Epididymis-Phagocytosis of sperm, function as storage, maturation of sperms, involved in absorption of
testicular fluid and secretion of glycochons involved in inhibition of capacitation
Epith of epididymis-pseudostatifed with stereocilia ( long microvilli) and wall contains extensive CT
Fetal testisdevt from an indifferent gonad- independent of testosterone or other androgens, which
depends on presence of testis determining factor TdF a gene shortarm of y chromosome
Milk production-occurs in lactating mamry gland which contains alveoli and lactiferous ducts
Implantation- occurs in uterus lined by simple columnar eepithelium with endometrial glands that
differe in arrangement depending on phase of cycle ( long and straight in proliferative phase and S
shaped in secretory phase
Myometrium- composed of smooth muscle, hormone sensitive and undergoes both hypotrophy and
hyperplasia
During pregnancy and atrophy- after menopause result in shrinking of uterus in postmenopausal
women
During fetal devt-production of androgens by developing testis results in masculination of indifferent
gonadal ducts and indifferent genitalia
In absence of androgens- female genitalia and ducts ( vagina, oviducts, uterus ) develop
In mature male- testosterone is required for initiation maintenance of spermatogenesis as well as
structural and functional integrity of accessory glands and ducts of male repro system
Testosterone- bound to ABP, synthesis by sertoli cells under influence of FSH
ABP- impt both storage and delivery of androgens in male ducts and accessory glands
Neurohumoral reflex-involved in suckling milk ejection response
Placental lactogen- last trimester of normal pregnancy synthesis of milk in her mammary glands
specifically requires this
Mammary gland- enlarge during pregnancy in response to several hormones including prolactin
synthesize by anterior pituitary
Estrogen and progesterone- synthesize by corpus luteum and placental lactogen
Alveoli- at end of duct system respond to those hormones by cell prolifereation which increase size of
mammary glands
Growth- continue throughout pregnancy
Secretion most notable late in pregnancy
Milk- synthsize in alveoli and stored in their lumina before passage thru lactiferous ducts to nipples
Secretion ofmilk lipid- occurs b apocrine mechanism whereby some apical cytoplasm include with
secretory product in comparison
Milk proteins- as caseins are secreted by exocytosis

Oxytocin-required for release of milk from mammary gland thru action of myoepithelial cells that
surround alveoli and proxima ( closer to alveolus) portion of duct system
Arginine, vasopressin, (AVP,ADH)-binds to receptors in collecting tubules of kidneys and promotes
resorption by stimulating insertion of aquaporins waterchannels into membrane of kidney tubules
Aquaporins- transport solute free water thru collecting duct cells and into blood leading to decrase
plasma osmolarity and increase osmolarity in urine
Sperm coated withautoimmune antibodies are unable to fertilize an egg-reattachment of severed vas
deferens ( vasovasostomy) as successful, greater than 99 % unsuccessful due to the following reason,
Attempt to counteract or repair effects of vasectomy ( vasovasostomy)-unsuccessful because of devt
of antisperm antibodies, this lack of success occurs despite fact 90 % of pts undergo vasostomy have
sperm to ejaculate
Case of vasectomy- sperm that leaked from male reproductive tract are viewed s foreign by immune
surveillance and antibodies develop
Phagocytosis of sperm by macrophages- plays arole in devt of antisperm antibodies that occurs
following ligation or removal of segment of vasdeferens
Sperm- immunologically foreign because of number of factors
Spermatogenesis- begins at puberty long after devt of self recognition in immune sytem
Blood testis barrier- protects developing sperm from exposure to systemic factors
Basal compartment- containing spermatogonia and preleptotene spermatocytes is exposed to plasma
Adluminal compartment- contains primary and secondary spermatocytes spermatids and testicular
sperm- prevent those antigens from entering blood
Inability of cryptorchid testis to produce fertile sperm is related to higher temperature inn abdomen
than in normal scrotal location
It depends on progesterone secretion by corpus luteum-trying to become preg, with irregular
menstrual cycles heavy prolonged ireular uterine bleeding and done endometrial biopsy
Secretory phase of menstrual cycle- depends on progesterone secretion and follows the proliferative
(follicular )phase
Approximately days (16-25)-charaterized by high progesterone levels, from corpus luteum a tortous
appearance of uterine glands apocrine secretion by gland cells, maximum endometrila thickness occurs
at secretory phase
Earlysecretory phase- which shows edematous endometrium that is 4mm thick wit glands that are large
beginning to sacculate in deeper mucosa and coiled for their entire length
Late secretoryphase- endometrium becomes 6-7 mm thick
menstrual phase-occurs after secretory phase, approximately days 26-30, characterized by decrease
glandular secretion and eventual gradual degeneration because of decrease production of both
progesterone and estrogen by theca lutein cells
contraction of coiled arteries and arterioles- leads to ischemiaandnecrosis of stratum functionale
follicular phase- approximately days 14 -16 estrogen produced by ovaries drives cell proliferation in
base of endometrial glands and uterine stroma, during this phase cells undergo mitosis to form multiple
granulosa layers ( primary follicle) in response to elevated levels of FSF and LH from anterior pituitary
proliferative phase- culminates with ovulation
bacterial metabolism of glycogen to form lactic acid- the low ph in vagina is maintained, the low 4.0 ph
of vagina is maintained by bacterial metabolism of glycogen to form lactic acid
vagina- stratified squamous epith. With accumulations of glycogen
in the proliferative phase-endometrium only 1-3 mm thick glands are straight with spiral areries only
slightly coiled
glycogen-released to vagnal lumen, metabolized to lactic acid by commensal lactobacilli
low ph- inhibits growth ofvariety of microorganism but not Sexually transmitted pathogen as T.vaginalis
Treatment for vagina infections-acidified carriers to reestablish a more acidic ph, usually seen in mid
menstrual cycle
There are detectable levels of hcg in her serum and urine-woman withaverage menscycle of 28days
comes with routine papsmear it has been 35 days since startof her LMP and vaginal smear reveals
clumps of basophilic cells
Pregnant- delay in menstruation coupled with presence of basophilic cells in vagina smear are clues
Ovulation- mid point of cycle not greater than a few days away
Vaginal epithelium- varies little with normal mens cycle
Exfoliative cytology- diagnosis cancer, and determine if epitelium under stimulation of estrogen and
progesterone
Basophilic cells- in smear with paps stain method, indicate presence both estrogen and progesterone,
data suggest maintenance of corpus luteum ( pregnancy)
Formation of a corpus albicans- where absent 12-14 days after ovulation, in a human female,
Corpus luteum- in absence of hormones necessary for maintenance of corpus luteum LH or HCG, it
regresses to form corpus albians which consist primarily of fibrous CT,it forms from ganulosa and these
layers of follicle follow ovulation
Without LH or HCG- uterine epithelium which undergoes glandular proliferation in preparation for
implantation collapses and degenerates as part of menstruation
Luteal phase-2nd half of memstrual period and follows follicular phase during with follicles mature
Corpus luteum- synthesize progesterone in response to hig LH levels
In each reproductive cycle- production of LH- stimulates devt and maintenance of corpus luteum which
well formed by 12-14 days following ovulation
In case of fertilization and implantation- corpus luteum of pregnancy is maintained by HCG which is
produced by the embryo
Reduced progesterone spasmodic cxn- regular menstrual period pairings of hormonal change function
nd best describes response
Spiral artery of endometrium- depend on the specific Estrogen or progesterone ratios for their devt
during menstrual cycle, they pass thru basalis layer of endometrium,into functional zone and their distal
ends are subject to degeneration with each menses
Specifically reduction of progesterone- induces spasmodic cxns leading to ischemia sloughing of
stratum functionalis
Basal layer – not affected bec basal straight arteries provide independent BS to area
Straight arteries- not subject to hormonal change

Breakdown of the basement membrane bet the thecal and granulosa layers facilitating ovulation-
secrete plasminogen activator and collagenase is required for this
Granulosa cells- produce plasminogen activator and collagenase, those molecues along with plasmin
and PG- facilitate rupture of ovarian follicle leading to ovulation
Increase in LH in midcycle- induces production of collagenase and plasminogen activator
Collagenase and plasminogen activator-those proteases facilitate ovulation by initiating CT remodeling
include breakdown of BM bet thecal and granulosa layers
Ct remodeling- involved in process of follicular atresia occurs throughout life involves death of follicular
cells as well as oocytes no Basement membrane bet theca interna and externa, there is absence of clear
delineation between thece interna and externa
Devt of ovarian follicles—begins with primordial follicle that onsists flattened follicular cells surround
primary oocyte
Glycoproteinase coat- surround oocyte and calledzona pellucida
CT- around follicle differentiates into 2 layers theca externa and interna
Theca externa-closes to ovarian stroma consists of hughly vascular CT
Theca interna- synthesize androgens ex androstenedionein response to LH
Androgens- converted to estradiol by action of aromatase enzyme synthesis by granulosa cells under
influence of FSH
Increase levels of Estrogen from ovary- feedback to decrease FSH secretion from gonadotrophic in
anterior pit.
Liquor foliculi- produced by granulosa cells secreted beween cells, when cavities 1st formed by devt of
follicular fluid bet cells folliclecalled secondary
When antrum completely formed follicle called mature ( grafian follicle and antrum completely filed wth
liquor folliculi)
Granlosa cells- forms 2 structure
corona radiate- represent those granulosa cells that remain attached to zona pellucida
Cumulus oophorus- represent granlosa cells surround the oocyte cunned it towall
Transfer ofmaternal antibodies to suckiling neonate- secretion from organ carry this
Lactating mammry gland- synthesizs milk include antibodies from IgA secreting plasma cells in CT of
gland, presence of lactiferous ducts for exocrine secretion compared to endocrine secretion of thyroid
Placenta- removes waste products dring gestation
Secretion from seminal vesicle, (fructose, PG and other chons)- facilitate clotting of ejaculate semen
Prostatic secretions- zinc, citric acid
Citric acid- antibiotic like molecule and enzmes, enchance sperm function
Occlusion of the fallopian tubes-unable to conceive, cause of couples infertility dx is PID
PID-leads to scarring of oviducts ( fallopian or uterine tubes) which result of sperm that cant reach the
oocyte and a zygote that cant reach uterine cavity for implantation
IVF- best method assisted reproductive technology (ART), for overcoming couples infertility problem
GIFT and ZIFT- place gametes
GIFT or zygote ZIFT respectively in fallopian tubes site of structural problem
TET- an ART synonym for ZIFT drugs as clomid or gonadotropin treatment is effective when ovary is
source of infertility
IVF- requires gonadotropin treatment
Ectopic pregnancy-if a woman conceives naturally following multiple episodes of PID this is the
complication
10x higher than in women with no previous hx of PID- rate of ectopic pregnancy in women with previus
known PID

URINARY SYSTEM
Decrease HCO3 in pancreatic juice- occurs after treatment with acetozlamide
Acetozalamide- a member of sulfonamide family of antibacterialdrugs which blocks carbonic anhydrase
activity, it is diuretic
Carbonic anhydrase or Ca critical enzyme plays essential role in number of cells by catalyzing
hydrationof CO2 and dehydration of HCO3
In pancreas- blocking CA results in reduction in secretion of HCO3 into pancreaticjuice by pancreatic
duct cells
Blockage of Carbonic anhydrase- result in “alkalinazation of urine and metabolic acidosis”, not alkalosis,
beca loss of HCO3 and decrease in renal tubular excretion of H ions from kidney
In osteoclasts- blockageof CA- result decrease bone resorption
In parietal cells- blockage of CA activity result in reduction of in protons moving toward lumen and
HCO3 toward blood
Mesangial cell-recent URT BP increasesteadily over course of his annual PE and serum IgA elevated
renal biopsy show IgAdeposits
Mesangial cell- synthesisze extracellular matrix supports capillary wall, morphological similar to
pericytes in association with other systemic blood vessels, surround glomerular capillaries and function
as phagocytes and regulators of glomerular blood flow, synthesize cyclooxygenase 2 COX2
COX 2- critical enzyme in PG synthesis and nitric oxide
PG and NO- 2 molecules involved in vasoactive regulaton
Mesanglial cell also proliferation and matrixaccumulation are major contributor to devt of
glomerulosclerosis, like endo cells synthesize endothelin
Endothelial cells-are anti thrombogenic with in glomerular capillary
Podocyte with its processes- in close association with glomerular capillary is observed below mesangial
cell, from visceral layer of bowmans capsule and possess processeses that interd
Igitate to form pedicels
Outer layer of bowman capsule- formed parietal cells one of which is located in lower
Urinary space and blood- separated by GBM formed fro fusion of capillary and podocyte produced basal
laminae
Alport syndrome-adolescent with hematuria,hearing , lens discoloration cataracts,genetic analysis
shows mutation of COL4A5 gene,leads to defect n alpha drains that compose type IV collagen in Lamina
densa of basement membrane, mutation of a 5 chain of type IV collagen
GBM-showns abnormal splitting and thinning in lamina densa and overall thickening
Hematuria-results to breakdown of basal lamina allowing passage of RBC eventually protein(
proteinuria)
Type IV collagen- consists of 3 alpha chains forming triple helixNC1 or non collagenous C terminal and &
SN terminal- particular important in crosslinking of type IV collagen
Crosslinking- forms scaffolding necessary for normal filtration properties of basal lamina
Proliferation of mesanglial cells and increase production of mesanglial matrix- are typical of later
stages of alport syndrome when glomerulonephritis is a prominent feature of the dse
Glomerular filtration barrier-consists of pedicel of podocyte, basal lamina ( L.rara, L.densa) synthesis by
odocytes and endothelial cell
Podocyte- consist of cell body of cytoplasm with long processes encircle GBM,
Filtration slits- are located between adjacent pedicels ( foot processes of podocytes)
Remainder of filtration barrier- formed by GBM which contains type IV collagen and heparin sulfate
3 distinct layers of GBM-
electron dense L. densa ( type IV collagen)angle in center surrounded by
L.rara-externa-on glomerular side by
L.rara interna-on capillary endothelial side
Glomerular filtration barrier- physical and charge barrier exhibits selectively based on molecular size
and charge, presence of collagen type IV in L.densa on BM present a physical barrier to passage of large
chons from blood to urinary space
GAGS particularly heparin sulfate- produce polyanionic chargethat binds cationic molecules
Foot processes- coated with glycoprotein called podocalyx in which is rich in sialic acid and provides
mutual repulsion to maintain structure of filtration slits, also possess large poyanionic charge for
repulsion of large anionic chons,patients with mutation in gene encoding for nephrin, are dx with
congenital nephritic syndrome characterize by proteinuria resulting in excessive edema
Nephrin-key chon comprisisng slit diaphragm functions to inhibit passage of molecules thru filtration
slits, integral membrane protein anchored by other CHON to cytoskeleton of pedicel of podocyte
Primary site for reduction of tubular fluid volume-serum gamma globulin as well as Ig: IgG,IgA,IgM are
all elevated dx is bilatereal photophobia as result of non granulomatous uveitis.her serum creatine is 1.4
normal 0.6-1.2 mg/dl glucose and potein 2+ on dipstick test electron microscopy lumphocyte, plasma
cells, and eosinophils found with in infiltrates with patho change in tubular BM
Tubulointerstitial nephritis uveitis (TINU)-autoimmune dse which autoantibodies are targeted against
renal tubular cells
PCT cell- primary site for reduction of tubular fluid volume by reabsorption from glomerular filtrate,
microvilli at apical surface and extensive endocytic vacuoles are deisgned for chon reabsorption and
distinguishing features of PCT cells, in basal folds provide energy for transport, distal tubule very few
microvilli
Afferent arterioles- contain JG cells modified arterial smooth muscle cells produce renin
Renin- a major factor in BP regulation
Thin loop of henle-for production of counter current multiplier which allows kidneys to produce a
hyperosmotic medulla
Multiplier- moves sodium and chloride out of ascending limb ( which is impermeable to water ) and into
medullary interstitial fluid
Descending limb- permeable to water takes up sodium and chloride from interstitium
Vasa recta- adjust their osm to that of medulla
DCT- has highest concentration of Na, K, ATpase, pumps Na against a concentration gradient and
relatively impermeable to water leading to production of hypotonic tubular fluid
Distal tubules- empty into conncting and collecting ducts which are permeable to water under
regulation of ADH
ADH stimulation- increases collecting duct permeability to water allowing production of hyperosmotic
urine
Without ADH- urine leaving kidney would be hypoosmotic
Collecting duct principal cells- are the ADH responsive cells and contain fewer mitochondria and basal
infoldings than occur in cells in DCT
Aldosterone- acts on principal cells and secondarily on thick ascending limb of henle to increase
reabsorption of sodium chloride
Regulates size selectively and GFR-a renal biopsy dx with nephrotic syndrome and Focal segmental
Glomerulosclerosis dse is caused by mutations in TRPC6 gene leading to malfunction in cell with dx of
focal segmental glomerulosclerosis
Podocyte- visceral epithelial cell- along with other factors regulate size selectively and filtration rate of
GBM, each has foot processes called pedicels that
Extend around glomerular capillaries and interdigitate with pedicels from adjacent podocytes,
Filtration slits- space between adjacent pedicels
Diaphragms-comprised of nephrin
Basement collagen type IV- is synthesize by podocytes and glomerular endothelial cells
Mesanglial cells- involve in turnover of glomerular basal lamina and phagocytose Ig trapped in basal
lamina, they contract in response to angiotensin II inding this regulating blood flow thru glomerular
capillaries and synthesis mesangial matrix
Endothelial cells-line glomerular capillaries and possess many aquaporin water channels
Angiotensin II receptors- found on mesangial cells, are formed from angiotensin I by endothelial cells in
lung
Patients with focal segemental glomerulosclrosis- result in mutation TRPC6 cation channel chon found
in pedicels,mutation leads to impaired channel function and decrease adaptation to physiological
challenges
Macula densa- portion of distal tubule specialized for determination of distal tubular osmolarity
Glycation of proteins in basal lamina- in patients with DM of 30 years duration complication related to
kidney function
Long term DM patients-glycation ( non enzymatic addition of sugar to chons and other molecules)
occurs in response to high blood glucose levels
Critical renal changes
a. thickening of GBM elimination of separation of L.rara and densa,
b. loss of anionic repulsion of sugar groups
c. obliteration of filtration slits
Renal changes known as nephrotic syndrome- lead to loss of selectivity of filtration barrier and increase
permeability to chons,nephrotic syndrome-loss of protein from blood to urine ( proteinuria)
Liver- adjusts to proteinuria by producing more chons (ex. albumin)after continued proteinuria, unanle
to produce sufficient chons which results in hypoalbuminemia
Hypoalbuminemia- leading overall decrease in osmotic pressure
Edema- occurs as fluid leaves vasculature to enter tissues, movement of fluid from vasculature to tissue
results plasma volume and decrease GFR, this is the over all effect because of compensatory release of
aldosterone coupled with reduced GFR and already existing edema
Glycation- results production of advanced glycation end products AGE which alters properties of GBM
, cellular receptor for AGE is RAGE is multiligand member of Ig superfamly of cell surface molecule
RAGE-interacts with molecular pathways that regulate homeostasis and devt inflammation, plays role in
pathologic conditions as alzheimers dse and DM
Binding ligand to RAGE-activates key cell signaling pathways as P21 (ras MAP kinases and NF- kappa B
NFKB) thereby reprogramming cellular characteristics
Interactions and terminology- complicated by presence of ENRAGE ( extracellular newly identified RAGE
binding protein)- interacts with cellular RAGE on endothelial cells, macrophages, lymph and oher cells to
activate proinflammatory mediators
Interactions between AGE, RAGE, ENRAGE- explain many diabetic complications including delayed
wound healing
AGE derivatization-is problem non specific involves not only basal lamina specific molecules but also
vast array of extracellular, intracellular chons ( transcription factors, structural chons and membrane
transporters)
Hence cellular coordination or communication- becomes slowly but hampered in kidney and other
organs
DM –dangers to diabetic thyperglycemia

Glucose----- amino acids ----- reactive intermediates

I Degradation I circulating chons or matrix
I Metabolism I chons in Basement membrane, CT
V I
Hemiacetatal----------------aldehyde I
AGE receptor
Decrease potential (RAGE)
Lower conduction-----------------------------advanced glycated end products (AGE)
Speeds generation I
Of reactive oxygen I
Species endothelial leakage thicker BM, generation of immunogenecity
I
apoptosis

Thin loops of henle-with nephrolithiasis process of calcium oxalate stone formation as seen in patient
with Bandall plaques in Basement membranein renal medulla only,only exclusive in medulla
collecting ducts- both cortex and medulla
cortical collecting ducts- in medullary rays
medullary collecting ducts- in medulla lead into papillary duct
convoluted portions of proximal and disal tubules-exclusively in cortex
afferentarterioles- in adjacent to vascular pole of cortex
plaques- sites of interstitial crystal deposistion at near papilla tip, in kidneys of calcium oxalate stone
formers
decrease refraction of light by cornea-underwent LASIK for myopia in both eyes, shape of cornea is
flattened with result
LASIK-laser assisted in situ keratomileusis- largely replaced radial or refractive, after corneal anatomy to
create new shape, most of lasik patients have myopia, the purpose is to reduce myopia eliminate need
for corrective lenses, reduction in curvature of central portion of cornea which result in decrease
refractive power of cornea, removal of tissue and degree of correction required is estimated by
computer simulations, it is used to correct nearsightedness or myopia , farsightedness or hyperopia and
astigmatism, but not presbyopia
Presbyopia-age related progressive loss of ability to focus at near
Keratotomy- both methods can be used to decrease refraction of light by cornea
That’s more flattened in center and higher at periphery of cornea-it occurs becauseintraocularpressure
will causereshaping of cornea due to induced weakness produced by laser removal of tissue.
Presbyopia-age related progressive loss of ability to focus at near
Fluid accumulation between retina andretinal pigment epithelium (RPE)-retinal detachment MC results
In type I of detachment and rhegma togenous retinal detachment- fluid accumulates after a break
occurs in retina
Non rhegmatogenous or serous detachment- detachments without breaks in retina
Vitreous degeneration- prerequisite for retinal detachment result breaking of retina, breakdown
produce traction on retina which already has inherent area of weakness
Site of retinal detachment-is bet inner and outer layersof embryonic optic cup and represents weak
area of adherence bet retinal and RPE layers
Closing of sodium channels-has given up night driving also describes a prolonged adaptaion period
going from light to dark her day vision as tunneled as walks into furniture. There is single point mutation
in Rhodopsin gene leads to disruption of signal transduction, visual transduction involves this dx of
retinitis pigmentosa RP
Retinitis pigmentosa-most prevalent hereditary retinal degenerative dse, linked to over 30 diff gene
mutations, theres a final common pathway leading to death of rods
Nyctalopia ( night blindness)-is 1st symptom followed b progressive loss of peripheral vision
Visual transduction- involves closing of sodium channel in rod cells in response to photon s of light
Rhodopsin- visual pigment in outer segment of rod cells composed of retinal vitamin A derivative bound
to opsin
When photons strike rhodopsin 11 cis retinal is isomerized to 11 trans retinal as a result in bleaching
which represents dissociation from opsin, conformationally altered opsin acts on transducing
Transducin- a Gprotein couple bleaching to CGMP thru actionsofphosphodisterase
Phosphodiesterase- enzyme cleaves CGMP to GMP
Breakdown of CGMP result – in closing gated sodium channels a reduction in permeability to sodium
and hyperpolarization of cell membrane
Signal spreads to inner segment and thru gap junctions to nearby photoreceptor cells,
In presence of CGMP sodium channels- remains open
In absence of channel – closes and cell hyperpolarizes
Therefore ROD and CONES- differe from other receptors in that hyperpolarization of cell membrane
occurs rather than depolarization that occurs in other neural systems
Closing the channel- slows down release of visual transmitter
Phagocytosis of worn out component of photoreceptor cells- RPE or retinal pigment epithelium
characterization with single layer of cells that phagocytose old component of photoreceptor cells,
derived from outer layer of optic cup continuous from or serata retinae to optic nerve
RPE-also synthesize melanin and stores vitamin A for photoreceptor cells
Microvilli- prominent on apical surface of RPE, play important role in maintenance of blood retinal
barrier
Rod and cone preikaryaand amacrine cells- found in photosensitive retina derived from inner layer of
optic cup
Aqueous humor- synthesize by non pigment epith of ciliary body
Microaneurysms- experience floaters blurred vision dx of diabetic retinopathy this is the complication
Diabetic retinopathy- patho changes begins with thickening of Basement membrane of small retinal
vessels, it occurs with prematurity when initial retinal vascularization is disturbed,Abnormal vessels
develop microaneuysms- which leak and hemorrhage with resultant ischemia of retinal tissue,New
vessels proliferate in response to ischemia and production of angiogenic factors as vascular endothelial
growth factor VEGF,There is loss of phagocytic capacity of RPE in retinal dystrophy
Site of blockage in glaucoma-in figure is iridocorneal angle
Sinus venosus sclerae ( canal of schlemnn)- which carries aqeuos humor to scleral veins and systemic
vasculature, blockage to canal of schlegmn, trabecular meshwork ( schleral vein ) result in – Glaucoma
Iridocorneal angle- and other associated structure in eye- important in production and outflow
ofaqeous humor in distribution of zonule fibers to lens
Iris-contains both sphinter and dilator muscles which work in opposition to 1 another, innervted by
parasympathetic and sympathetic fibers respectively
Pupil- center of iris a hole
Ciliary body- contains ciliary muscles
Ciliary muscles- stretch the chorid relax the lens which is essential for process of lens accommodation
Ciliary processes- extend from ciliary body and produce aqeoues humor, origin from zonule fibers
Zonule fibers- involve in accommodation, which anchor the lens
When ciliary muscle contract-causing forward displacement of ciliary body tension of zonule fibers is
reduced which lead to increase in lens thickness and maintenance of focus
Aqueous humor- produced by ciliary processes is transported into posterior chamber and flows into
anterior chamber thru the pupil
Outflow from anterior chamber- occurs thru trabecular meshwork at iridocorneal angle and flows thru
canal of sclemn
Cornea- forms transparent, avascular anterior portion of eye,outer anterio surface is covered by
epithelium
Beneath epithelum- is bowman membrane, corneal stroma, decement membrane
Endothelium- ( at posterior surface of cornea) lines anterior boundary of anterior chambers
Lens- form embryologically from a thickening of surface ectoderm calledlens placode which eventually
forms a lens vesicle
Lens fiber production- continue throughout life new fibers are addd under anterior epithelium
Anterior epithelium-contain nuclei and other light scattering organelles which disappear toward center
of lens
Lens specific cytoskeletal prteins- maintains lens fiber conformation and transparency are crystalline (
members of lenticular chaperone family ) and beaded filament structural proteins, filensin, phaknin
(P49) members of intermediate filament protein family, inteactions between these uniques proteins and
cytoskeleton, they also maintain normal lens fiber structure an are modified during normal aging leading
to decrease flexibility and onset of presbyopia, mutations in genes transcribing those chons are-
associated with cataract gormation
Lens- surrounded by a capsule
3 compartments of eye muscle
Posterior and anterior chambers-filled with aqeous humor
Vitreus body- filled with gel consist of hydrated hyaluronic acid and other GAGS,
Conjunctiva-is the mucosa or lining of eyelid
Innernuclear layer of retina-is data from photoreceptors are integrated
Blood supply of retina-derived from choriocapillaries of choroid
Inner nuclear layer of retina- responsible for integration of data from adjacent photoreceptors
Retina layers
Retina pigment epithelium- derived from outer wall of optic cup
Function is phagocytosis of rod disks
Photoreceptor layer- consist of rods and cones is the outer layer of retina
Sclera- layer of relatively avascular dense CT
Outer limiting membrane-formed by junctional complexes between mulle cells and membrane of
photoreceptor cells
Outer nuclear layer- contain nuclei rods and cones cells and surrounding cytoplasm perikarya
Outer plexiform layer- contain rod and cone synapses as well cell synapses of bipolar , horizontal
photoreceptor cells
Inner plexiform layer- consist amacrin cells dispersed between processes of bipolar and ganglion cells
respond for modulation of signals from ganglion to photoreceptor cells
Ganglion cell layer-contains cells separated by cytoplasm of astrocyte like glia ( muller cells)
Nerve fiber layer- consist axons of ganglion cells willform optic nerve
Internal limitingmembrane- located between vitreous body and retina
2 types of photoreceptors- rods and cones
Nuclei of rods and cones- found in outer nuclear layer extend across outer limiting membrane in 1
directionand toward outer plexiform layer in other direction
Outer segment is photon sensitive portion of rod and cone-contain membranous disks
Rhodopsin-composed of opsin and retinal, responsible for transduction of light ( photons)into
hyperpolarization of cell membrane, they present in disks of outer segment of rod
Inner segment- contain numerous mitochondria, glycogen, CHON synthetic apparatus
Rods-responsible night vision
Cones- responsible for color vision, rest resolved at fovea
Fovea- center of macula, composed exclusively of cones site of optimal resolution
Choroid- highly vascular layer
With 3 parts: stroma, choriocappillaris, brush membrane
Determines whether cells are depolarized or hyperpolarized-direction in which vestibular hair cell
stereocilia are deflected is important
Vestibular hair cells-sensory transduction system of inner ear, responsible for conversion of mechanical
energy into electrical signal for N VIII, called hair cells because of surface contains sterocilia
Stereocila-modified microvilli contain large number of actin filaments and extend from surface of cell,
are different lengths,arranged in order by size with large kinocilum at 1 end, arrangement very
important because bending in 1 direction (toward kinocilium)
Toward kinocilium- depolarizes cell and leads to excitation whereas
Bending them in other direction (away from kinocilium)-result in hyperpolarization and inhibition
Class of type of hair cell
I or II- is based on pattern of efferent and afferent innervation
Movement of the tectorial membrane resulting in hair cell depolarization and the release of NT onto
afferent endings of auditory VIII CN lead to initiation AP-episodes otitis media, there is decreasevisibility
of landmarks of middle ear, myringotomy is carried out of her hearing returns normal, this is involve in
normal soundtransduction
Sound waves-directed toward tympanic membrane by pinna and xternal auditory canal of external ear
Vibration of tympanic membrane- transmitted to oval window by way of ossicles of middle ear
Induction of wavs in perilymph- result movement of basilar and vestibular membrane toward scala
tympani and cause round window to bulge outward
Movement of hair cells- facilitated bec tectorial membrane is rigid and pilar cells form a pivot
Scala tympani- where perilymph is normally found
Endolymph- similar to ECF high potassium, low sodium found in utricle, saccule, semicircular canal, s.
media ( cohlear duct), synthesize by highly vascular stria vascularis in lateral wall of S. media
Scala media ( cohlear duct)-parts of membranous labyrinth
Endolymphatic sac and duct- responsible for absorption of endolymp and endocytosis of molecule from
endolymph
Overproduction of endolymph-audiometry electrocochleagraphy detect sensorinneural hearing loss
and endolymphatic hydrops dx of menieres dse
Menieres dse- with triad vertigo, sensorineural hearing loss, and tinnitus result in overproduction of
endolymp, and distention of endolymph filed sytem of cochlea
Stria vascularis- on lateral wall of cohlear duct (s. media)
Organ of corti- wit in cochlear duct contains hair cells that are responsible for transduction of sound to a
normal impulse, rests on basilar membrane which sepates it from epithelial lining oftympanic cavity
Inner tunnel of organ of corti-separates the outer from inner hair cells
Outer hair cells-possess microvilli attached to tectorial membrane in contrast
Inner hair cells- unattached
Supportive cells- include phalangeal and pillar cells
Spiral lamina-bony structure protrudes from modiolus
Spiral limbus-CT structure superior to unattached edge of spiral lamina
Along outer wall of canal or organ of corti- a thickened projection of periostium known as spiral
ligament
Spiral ganglion- contain biplar cells
Peripheral processes of spiral ganglion cells- reach organ of corti
Central processes terminate in nuclei located in medulla
Cristae ampullaris of semicircular canals- detection of angular acceleration
Semicircular canals-extend from utricle contain cristae ampullaris
Cristae ampullaris- detect angular aceeration
Utricle- represent dorsal portion of otocyst derived inner ear
Saccule- ventral portion
Both utricle and saccule- contain maculae that detect linear acceleration
Maculae of utricle and saccule- are perpendicular to 1 another, contain type I and II hair cells, these
maculae- contain type I and II haircells which differ in innervation
Hair cells- have stereocilia and kinocilium embedded in membrane contain otocoia ( statoconia)
composed of calcium carbonate
Stereocili, kinocilia- embedded in cupula which does not contain otoconia , found in maculae,
Endolymph- turns right when head turns left and vice versa
Movement stimulate stereocilia, induces depolarization
Interdental cells- produced by tectorial membrane, essential for devt of hearing force for sound
transduction in organ of corti
Hair cells of organ of corti- detects sound vibration responsive to variation in frequency of sound waves
2 types of pilar cells- inner and outer
Pillar cells- along with inner and outer ( deiters ) phalangeal cells- provide cellular mechanical coupling
between mechanosensory hair cells and basilar membrane