everything you need to know foundation block

7/31/2019 Everything You Need to Know Foundation Block

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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


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


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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