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8/7/2019 IMMS weeks 6 and 7
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IMMS weeks 7 and 8 8.11.10 19.11.10
1. Protozoa
y Describe what protozoa are
y Identify key diseases caused by protozoa
y Describe the transmission and basic lif e cycle of plasmodia spp.
y Recognise how a patient may present in the UK with Malaria
y List the initial critical steps in investigating and managing a potential case of Malaria Protozoa are single celled eukaryotic organisms which consume bacteria. Very diverse:
Body shapes & sizes
Motility mechanisms
Lif e cycles
Reproductive strategies
Nutritional strategies
Hosts
5 main groups:
i. Mastigophora (f lagellates): Reproduce by binary fission.
Intestinal f lagellates:
Giardia lamblia Loose stools, diarrhoea, f latulence, abdominal
cramps. Giardiasis
Haemof lagellates:
Trypanosoma spp. insect bite 2 years previous, f ever, lethargy,
myalgia, weight loss, personality change, daytime somnolence, coma.
African
Trypanosomiasis
(sleeping sickness)
Other body sites:
Trichomonasvaginalis
ii. Sarcodina (Amoebae): move by means of f lowing cytoplasm
E.g. E ntamoeba histolytic holiday, bloody diarrhoea, increasing
right hypochondrium pain, liver abscess.
Amoebiasis
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iii. Apicomplexa (Sporozoans): all species parasitic
P lasmodium spp. transmitted by bite of f emale Anopheles
mosquitoes, lie dormant and cause late relapse by reactivating months later,
f ever, haemolysis, anaemia, jaundice, hepatoslenomagaly, dark urine,
coma, renal failure, ARDS, Hypoglycaemia, shock.Children: non-specific, anaemia, hypoglycaemia.
Malaria
Five species cause human disease:
P . falciparum- cerebral malaria, matures in RBCs, Parasite matures in
RBCs knobs on RBC surface, bind to receptors on endothelial
cells in capillaries &venules, bind to non-inf ected RBCs = Rosetting,
Sequestration in small vessels (including brain, lung),
microcirculation obstructed: tissue hypoxia. chills and sweats,
myalgia, fatigue, nausea and vomiting, diarrhea.
Children: coma, extended limbs, fixed screaming, convulsions.
P . ovale
P . vivax
P . malariae
( P . knowlesi)
300-500 million cases per year, increasing incidence (resistance of parasite,
resistance of mosquito, climate change, travel)
Lif espan of f emale: 3-4 weeks
Night biting indoors mainly
Merozoites released into blood stream
P .falciparum
Complicated falciparum malaria: IV Q uinine Un complicated falciparum malaria: PO Q uinine
Non-falciparum malaria: PO Chloroquine
Fever + exotic travel = Think Malaria!
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Other:C ryptosporidium spp.
Toxoplasma gondii - Recent HIV +ve diagnosis, 2-week history of progressive
left sided weakness, headaches, visual disturbance.
Toxoplasmosis
iv. Ciliophora (Ciliates): 2 types of nuclei
Balantidium coli severe diarrhoea, ulceration of colon
v. Microsporidia: production of spores
E nterocytozoonbieneusi diarrhoea and immunocompromisation
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2. Histology of bone and cartilage
y Rigid forms of connective tissue
y Both derived from undiff erentiated mesenchymal cells
y Cartilage : 3 types
Hyaline Elastic
Fibrous
: cells are embedded in a dense glycosaminoglycan rich matrix containing
elastic tissue and collagen (f lexible, compressible and hardwearing)
: formed by chondroblasts, these become trapped in the matrix and mature
in chondrocytes.
: surrounded by a fibrous capsule perichondrium. (can diff erentiate into
chondroblasts if needed)
Hyline = contains fine fibrils of collagen and elastic. Appears as glassy. (rings
of trachea, larynx and articular surfaces)
Elastic = irregular fibres of elastic in matrix. (epiglottis and pinna of ear)
Fibrous = distinct bands of collagen (inter-vertebral discs)
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y Bone: synthesised by osteoblasts which initially secrete a collagen matrix (type 1)
osteoid, which becomes mineralise
dwith crystals of hy
droxyapetite, trapping the
cells within the bone and causing them to become less synthetically active.
: also present are osteoclasts
:Compact bone is laid down as concentric layered cylinders called osteons
or Haversian systems. At the centre of osteons is anHaversian canal
containing blood vessels which carry nutrients and oxygen to the living
bone.
:Bones are surrounded by a fibrous capsule (collagen) called the periosteum
which contains progenitor cells capable of diff erentiating into osteoblasts
should the need arise.
:Mature (secondary) bone is well organised. It is laid down in layers with the
long axis of the hydroxyapetite crystals lying parallel to the collagen
framework. The collagen fibres of succeeding layers run at right angles to
each other thereby providing "plywood-like" strength to the bone.
:Internally many bones can be seen to consist of osteons. These are
cylindricals units composed of concentric layers of bone with a Haversian
canal at their centre. This canal contains blood vessels and nerves that
supply the osteocytes trapped within the bone. Osteones are continually
being eroded and replaced throughout lif e. Between osteons is interstitial
bone, the remnants of previous generations of osteons.
:Bones are surrounded by a fibrous capsule (mostly collagen) called the
periosteum. This contains progenitor cells capable of diff erentiating into
osteoblasts or condroblasts. These play an important part in bone healing
following a fracture.
3. Cellular regeneration
Due to:
y Wear and tear
y Continual loss of cells
y Hazardous environment
y Sub-lethal damage
y DNA damage
If not causes:
y Osteoarthritis
y Atheroma
y Osteoporosis
y Dementia
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y Neoplasia
y Aging
y Death
Not:
y Permanent cells (skeletal muscle, neurones)
y Stable cells (hepatocytes, smooth muscle cells, renal tubular cells) y Labile cells (epidermal skin cells, gut enterocytes, bone marrow cells)
Stem cells:
y One daughter cell becomes a stem cell
y One daughter cell becomes a transit amplifying cell
y Fetal stem cells are pluripotent
Cell signalling:
y Autocrine acts on itself
y Paracrine acts on neighbouring cells
y Endocrine acts on distant cells (hypothalamus, pituitary, thyroid, pancreas, ovaries,
testes, adrenals, parathyroids, kidney)
Cell surface receptors:
y Ion channels ligand binding alters conformation of receptor, allows specific ion
movement (Ach at neuromuscular junctions)
y With intrinsic kinase activity extracellular binding site, ligand binding causes
dimerization and phosphorylation of receptor, receptor binds to other proteins,
signal cascade.
y G-protein coupled receptors 7 transmembrane segments, ligand binding causes
association with intracellular GTP-hydrolysing proteins (drug receptors)
y Without intrinsic enzymatic activity monomeric transmembrane molecules, ligand
biding causes intercellular conformational change
4. Wound healing and fibrosis
y Fibrosis?
y Forming a fibrous scar
y Healing incised wounds
y Healing after tissue loss
" Fibrosis=scarring
Damage to parenchymal cells
Damage to stromal framework
Parenchymal regeneration cannot repair def ect
Formation of granulation tissue (loops of capillaries surrounded by
myofibroblasts, gradually contracts)
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I w s
" Forming a scar Help remove debris¡ f ig¢
t inf ection and stimulate f ibroblast
prolif eration
Inf lux of macrophages¡ mast cells¡ lymphocytes
Angiogenesis (breakdo£
n of parent vessel basement membrane¤
endothelial cell migration and prolif eration, lumen f ormation,
maturation and gro
£
th inhibition¥
Stimulated by basic f ibroblast gro
£
th factor, vascular endothelial gro£
th factor¥ P
¦ ODUCED BY
ST¦
OMAL CELLS)
Migration and prolif eration of f ibroblasts (stimulated by basic
f ibroblast gro§
th factor, platelet derived gro§
th factor,
transf orming gro§
th factor)
Deposition of extracellular matrix (f ibroblasts synthesise collagen,
induced by PDGF, bFGF, TGF, TNF, interleukin 1)
Remodelling (removal of collagen by matrix
metalloproteinaseseg ̈interstitial collagenases, gelatinases,
stromeolysins. Inhibited by Tissue inhibitors of mms (TIMPS) wound
contraction)
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IMMS weeks 7 and 8 8.11.10 19.11.10