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Everything You Need to Know (at least) for
ONN08/09
NAME
YEAR
MATRIC NO
ACADEMIC SESSION -
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EDITORIAL
Allah, tiada tuhan selain Allah Pasti Allah akan mengumpulkan kamu semua di hari kiamat,
hari yang tidak dapat diragui dan siapakah gerangan yang lebih benar perkataanya selain
Allah
(An Nisa : 87)
Dengan nama ALLAH yang MAHA PEMURAH lagi MAHA PENYAYANG
Blok asas merupakan salah satu blok daripadai kesemua 9 blok yang akan kita hadapisemasa dalam pengajian tahun 2 fasa 2 sesi 08/09 selagi tidak berubah silabusnya. Blok inisebenarnya telah pun merangkumi kesemua blok yang akan kita belajar kelak, tetapi secaraumum. Oleh yang sedemikian, blok ini amat penting bagi mencetuskan rough idea mengenaihamper kesemua perkara.
Kekuatan seseorang pelajar dalam menghadapi blok akan datang bergantung kepadakekuatan asas (basic knowledge) dalam kesemua perkara
Handout ini akan meliputi pengetahuan asas yang perlu kita tahu untuk menghadapipeperiksaan selanjar 1 dan ikhtisas 2 kelak. Objektif asas diterbitkan handout ini adalah untukmemudahkan pelajar merujuk buku ini di saat-saat peperiksaan semakin menjelang. Apapun,saya ingin mengambil kesempatan di sini untuk mengucapkan selamat berjaya menghadapipeperiksaan yang semakin hampir ini. Semoga dengan ketaqwaan kepada ALLAH di sampingusaha yang tidak pernah putus, kejayaan yang cemerlang bakal digapai bersama. Sekian,wassalam.
Onn Azli PuadeMD 420011/2012
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CAUSES OF CELL INJURY AND ITS MECHANISM
Disturbed process of OxidativePhosphorylation
Impaired sodium pump (lack of ATP)
Increase sodium and water intake,increase potassium loss
Cell swelling due to excessive anduncontrollable water intake
Loss of cell membrane integrity
Lack of glucose Lack of Oxygen
Cell injury
Reduced mitochondrial respiration(usually aerobic respiration)
Increase anaerobic respiration
Increase production of lactic acid
Reduction in pH
Nuclear changes Mitochondrial damages Lysosomal injury
Membrane damage
Physical agent
Chemical agent
Interact directlywith plasma
Weakens antioxidantdefences
Microbial infection
Cell disrupted
Insert protein intoplasma membrane
Involvement of cytotoxicT cell/ macrophages
Production of TNF-alphaGenetic disorder
Alteration of cell genes
GlossaryOxidative phosphorylation is a process in which ATP isproduced by phosphorylation of ADP, a reaction that islinked to the oxidation of reduced substances in therespiratory chain of enzymes. Two crucial substancesinclude sox en and lucose
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APOPTOSIS1
1 Apoptosis is a programmed cell death which functions as for proper development and remove the cellthat represents threat to the integrity of the organisms. It could be physiological and pathological
Internal signals; intrinsic ormitochondrial pathway
Internal damage to the cell
Causing Bcl-2 drawn from theouter mitochondria
Activates Bax
Punches holes in the outermitochondria
Cytochrome c leak out frommitochondria and bind to Apaf-1
Forming apoptosomes
Activated caspase 9
Digestion of cytoplasm degradation of the
cytosolic DNA phagocytosis of the cell
External signal; extrinsic ordeath receptor pathway
Production of TNF-alpha bymacrophages during
inflammatory responses
Bind to the TNF receptor and Fasreceptor at the surface of the
cell
Intracellular signals
Activation of caspase 8
Digestion of the cytoplasm
Phagocytosis of the cell
Apoptosis Inducing Factor orAIF
AIF located at theintermembrane spaces of
mitochondria
Death signal
AIF leaks out and migrates tonucleus
Bind with DNA
Destruction of DNA
Cell death
MORPHOLOGICAL CHANGES Cell shrinkage smaller cell, dense cytoplasm, tightly packed
organelles Externalization of phospholipid
Chromatin condensation Cytoplasmic blebs and apoptotic bodies Intense eosinophilic cytoplasm No inflammatory reaction
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CELL INJURY
NORMAL CELL (HOMEOSTASIS) Genetic program and metabolism Differentiation and specialization Constrains of neighboring cell Availability of metabolic substrate
Cell Stress
Physical agentChemical agent
Insufficient Oxygenand Nutrients
DrugsGenetic Disorder
Microbial Infection
Affecting Protein synthesis Cell membrane
integrity
Genetic apparatus ATP generation
Success repairprocess
Cellular Adaptation Hypertrophy Hyperplasia
Atrophy Metaplasia
Removein urious stimuli
Cell injury
Severity based upon Type of injury Cell type Adaptation
respose
Unable to cope with changes
Reversible cell death
Membraneblebs
Mitochondrialswelling
ER dilation Fatty change
Point of no return
Irreversible cell death
Necrosis Apoptosis
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ACUTE INFLAMMATION3
3 Inflammation can be defined as a body protective mechanism to remove causative agent that cancause tissue injury as well as to remove tissue injury and facilitate tissue healing and repair process
Physical agentChemical agent
Hypersensitivity reaction
Microbial InfectionHypersensitivity reaction
Tissue necrosis
Release of Chemical mediatorsuch as bradykinin, histamine,
serotonin
Transient vasoconstrictionfollowed by vasodialation
[erythema]+
Increase membrane permeability
Vascular Component
Accumulation of Neutrophils andfibrin element to the periphery
[MARGINATION]Expression of E and P selectinat the endothelial wall
Neutrophils sticks and roll all the way onE and P selectin
[ROLLING]
Squeezing of neutrophils throughintercellular junction into extravascular
space and aided by CAM and PECAM
[ADHESION ANDTRANSMIGRATION]
Chemical attractions are; Soluble bacterial product Interleukin 8
Arachidonic Acidmetabolites B4 Complement C5a
Chemotaxis process Activates more Leukocytes
Phagocyosis Mannose and scavenger receptor Aided by opsonin IgG Alternative Pathway
Killing bacteria reactive O 2 speciesDigest bacteria acid hydrolases
Termination by tight regulationof chemical mediators
Outcomes Bacterial resolution Complete healing Fibrosis Chronic inflammation
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Stimulate pain receptor(kinin system)
Ascending via lateral
spinothalamic tract
Ascend to brain stem
Ascend via thalamus
Reach the sensory cortex
Pain is appreciated here
DOLOR3
CARDINAL SIGNS OF INFLAMMATION
1 redness of the skin due to the vasodialation2heat due to the increase blood supply to the injured area3edema because of the extravasation of the body fluid to the extravascular space4the inability of the injured part to function normally5pain due to the bradykinin system
Body protectivemechanism
Prevent ActionPotential reaching the
motor nerve at theinjured site
Unable to move theinjured site
FUNCTIO LAESA4
Physical agentChemical agent
Hypersensitivity reactionMicrobial Infection
Hypersensitivity reactionTissue necrosis
Release of Chemical mediatorsuch as bradykinin, histamine,
serotonin
Transient vasoconstrictionfollowed by vasodialation
[erythema]
Increase membrane permeability
RUBOR1
Exudation of fluid and inflammatory cellto the extravascular space
TUMOUR5
Increase blood flow
Blood carries significantamount of heat
CALOR2
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TISSUE HEALING PROCESS
Regeneration replacement of injured ordeath tissue with the same type of tissue
Tissue injury
Induction of the acute inflammation
Regeneration of the parenchymal cell
Migration and regeneration of parenchymaland connective tissue
Deposition of Extracellular Matrix
Remodeling
Acquisition of the wound strength
Fibrosis replacement of injured or death tissuewith the connective tissue
Angiogenesis (development of the blood vessel)
Migration and proliferation of the fibroblast
Deposition of the extracellular matrix
Remodeling (fibrogenesis)
Fibrinolysis mediated by matrix metalloproteases(MMP)
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NEOPLASIA4 MOLECULAR BASIS
4 Is a new (neo) growth (plasia) of the tissue in which occurs after cessation of normal growth controlmaking it exceeding growth limit, uncoordinated and enjoy certain degree of autonomy
Normal cell
DNA damage
DNA mutation
Mutation in Genome
Activation of Growth Promoting
Oncogenes* (oncogenic product class1, 2 and 3 )
Carcinogenic agents Acquired DNA
damaging substance
Apoptosis Gene Alteration*
(hereditary)Cancer suppressing gene alteration*
(hereditary)
Oncogenic product class 4 and 5 Expression of altered gene product Loss of regulatory gene product
Malignant Neoplasia
Successfully repaired
Alteration in gene thatregulates DNA repair*
CANCER RELATED GENES1. Oncogenenic Products class 1 to class 52. Tumour Supressing genes p53,pRb genes
3.
Genes regulates apoptosis Bax, Bcl-2, bad, Bcl-xL4. Genes regulates DNA repairAny defect in this gene, commonly inherited will increase the chances of gettingcancer 4-5 folds
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CARCINOGENESIS5
5 Is a multi-step process of conversion from proto-oncogenes to oncogenes which acquires multiple riskand reason to occurs (multi-hit theory)
Proto-oncogenes
Initiation mutation of one cell
Activates the mutation of oncogenes i.e. RAS
Promotion Carcinogenicagents*
Activates protein kinase Cand Growth factor secretion
Induction of cell proliferation
Progression growth becomeautonomous and sufficient mutation have
accumulated to immortalized the cell
Oncogenes
M
u
L
T
I
-
s
t
e p
Multi hit theory
CARCINOGENIC AGENTSChemical
direct acting requires no chemical changes to induce carcinogenicity and aregenerally weak carcinogens like acylating and alkylating agents(cyclophosphamide)
indirect acting requires chemical changes to induce carcinogenicity andassociated with smoking, diet and alcohol intake (polycyclic aromatichydrocarbons)
Physical radiation, ultraviolet
Viruses
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DIFFERENCES BETWEEN BENIGN AND MALIGNANT TUMOUR
Aspects of Benign MalignancyName Suffix name oma
i.e fibroma, lipomaSuffix name
Sarcoma messenchymal cell
Carcinoma epithelial cellTeratoma totipotential cell
Growth Slow and expansive Rapid and invasiveOuter border Capsulated Encapsulated
Metastasis No Via 3 ways Haematogenous route Lymphocytic route Seeding within body cavity
Size Small to large Small to largeMorphological cell Well differentiated cell, resemble
tissue of origin
Poorly differentiated, anaplastic cell
Nucleus Normal size and shape Hyprchromatic and increasenucleolar:nuclear ratio
Prognosis Usually good except CNSinvolvement
Usually poor
Benign Malignant
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CLINICAL MANIFESTATION FOR FOUNDATION BLOCK
1. Do you smoke?
Smoking is very closely related to Cardiovascular and Pulmonary disease. It is also one of the factor contribute to the lung carcinoma, chronic obstructive pulmonary disease andsudden death infant syndrome if the mother is a smoker
2. Do you take alcohol?Ethanol metabolism produces toxic effects to our body. It is very-very related to theliver disease such as fatty change and cirrhosis. It is also becoming the risk factor of getting several of disease involving gastrointestinal system, cardiovascular system,central nervous system as well as reproductive system. Furthermore, it increases the
incidence of getting cancer like oral cavity, pharynx, liver, breast and esophagus.
3. Did anyone in your family have suffered from cancer?Genetic factor is the most cardinal factor as any defects of the genes which passes fromgeneration to generation increase the risk of getting cancer up to 5 folds
4. What kind of work did you do?Several occupation expose workers to the harmful substances such as asbestos(asbestosis), silica (silicosis), cadmium (prostate cancer) etc
5. Did you take any drugs?Certain drugs such as cocaine and amphetamines stimulate CNS and some suppressesthe CNS. Theophylline causing cardiac arrhythmia while isoniazid and halothane cancause diffuse hepatocellular damage
6. Did you take Oral Contraceptive Pills (OCP)?Taking OCP will increase the risk of getting cervical and endometrial carcinoma. It willalso increase the risk of getting hypertension, hepatic edema and gall bladder disease
The examination question may come out as further history you
would l ike to ask the patient regarding his symptoms and itssignificant. You may take one or two questions from above
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Saya ingin mengucapkan jutaan terima kasih kepada nama-nama dibawah yang telah menyemak danmembuat sedikit pembetulan mengenai penulisan dan fakta yang telah diterbitkan
1. DR VENKATESH R NAIK2. DR THIN THIN WIN @ SAFIYA3. ASSOCIATES PROFESSOR OTHMAN MANSOR4. DR SAMARENDA S MUTUM
Reference
1. Lecture Notes, School of Medical Sciences, year 2008/2009 2 nd Year session2. Pathologic Basis of Disease, 7 th Edition, year 20073. Textbook of Medical Physiology, Guyton4. www.wikipedia.com
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