ROBBINS PATHOLOGY WWW.PATHGUY.COM GENERAL PATHOLOGY –Basic mechanisms of disease SYSTEMIC PATHOLOGY: 1. Cell injury of death 2. Inflammation 3. Liquid of hemodynamic arrangement in this 2types of edima mainly 1 by inflammation 4. Immunopathology 5. Nutritional pathology 6. Genetical developmental pathology 7. Neoplasia 8. Infectious diseases DISEASE: Loss of homeostasis PATHOLOGY: STUDY OF disease ETIOLOGY: Cause PATHOGENESIS: Events leading to the development of disease SYMPTOMS: like nausea, headache .change that you feel SIGNS: STRESS CELL-
ADAPTATION INJURY-REVERSIBLE AND IRREVERSIBLE
ADAPTATION: Hyperplasia: organ is bigger due to number of cells Hypertrophy: organ is bigger due to size of cell
1
Atrophy: decrease in size of cells Metaplasia: involves change of one kind of tissue to another but still within the general tissue type PSEUDOSTRATIFIED COLUMNAR CILIATED EPITHELIAL
STRATIFIED
SQUAMSAL EPITHELIAL
Anaplasia: a reversion of differentiation in cells that is characteristic of malignancy in tumours Cell parts /functions Vulnerable to injury: 1. Aerobic respiration 2. Membranes 3. Protein synthesis (ribosomes) 4. Genetic material (DNA) A. Hypoxia: something possess a disruption of aerobic respiration MOST COMMON REASON LEADS CELL INJURY IS HYPOXIA Causes: 1.ischemia: 2. Hypoxemia: Lack of oxygen 3. Failure of cytochromes: CYTOCHROMES SEEN IN KREBS CYCLE AND OXIDATIVE PHOSPORILATION IN THIS FAILURE OCCUR WHICH LEADS TO HYPOXIA B. Infectious agents C. Genetic disease D. Physical or chemical agents HYPOXIA Anaerobic pathway (lactic acid preparation) glycogen depleted (decrease in cell PH (acidic)) Na &k pump affected Na flows into the cell H2o enters the cell st cellular swelling (1 sign of cell injury) K leaves out Ca+2 flows into the cell detachment of ribosomes from RER enzymes leaves out of the cell bleed form myelin figures (water and lipid compounds) appear damage to nuclear 2
material Ca+2 pp+ (Ca10(po4)6OH2) Hydroxyapatite activate, proteases, phospholipase, endonucleases, ATPase lysosome membrane fracture cell dies Cellular swelling Fatty accumulation
sign of reversible cell injury
Precipitation of hydroxyapatite
Disruption of RER &
sign of irreversible injury
Rupture of lysosome membrane
MICROSCOPIC SIGNS OF CELL DEATH: 1. Pyknosis: clumping of nucleus Karyohexis: fragmentation of nucleus injury Karyolysis: dissolution of nucleus 2. Acidic cytoplasm-PINK
sign of irreversible cell
TYPES OF NECROSIS: 1. COAGULATIVE NECROSIS: -Cellular outline preserved for a short while -Enzymatic breakdown halted by acidic PH 2. LIGNEFICATION OF NECROSIS: (BRAIN) -Cells into soup -Enzymatic breakdown completed INFLAMMATION: Four primary signs TUMOR: swelling/Exudates RUBOR: Redness/vasodilation CALOR: Heat/vasodilation DOLOR: Pain Cell death followed by inflammation (stereotyped response to injury) to contain dilute destroy cause of injury repairs after damaged the part.
3
TYPES OF INFLAMMATION:
ACUTE CHRONIC Minutes/hours/days after the Months and years injury -max of 7 days Proliferative increases size of cells Vascular changes exudative –release of Monocyte/macrophage exudates Neutrophil(WBC)
3 Important Events of acute inflammation 1. Vascular changes A. vasodilation B. increases in permeability –exudate= (plenty of vascular protein and specific gravity < 1.020) 2. Cellular activity -chemo taxis: By use of chemical signals neutrophils are moved -phagocytosis: cause of injury -Degranulation: lysosome enzymes Cellular mediators: 1. 2. 3. 4.
Neutrophils Monocytes Mast cells Ordinary tissue cells 4
Chemical mediators: A. arachindonic Acid metabolites(phospholipids and cell membranes) B. vasoactive chemicals C. cytokines D. lysosomal enzymes
ARACHIDONIC ACID prostaglandin (PGS)
Cyclooxygenase
Lipo
oxygenise
Leukotriene (LT)
C5a Prostaglandins
CHEMOTACTIC
Leukotriene
IgG (antidote) C3b
OPSONIZATION (necessary for phagocytosis)
Bradyokinin: Pain vasoactive (dilate permeability) Kallikrein: Chemotactic (for neutrophils) Fibrin: PLASMA
blood
clot
C3& C5a-include mast cells to release histamine & serotonin derive C5a-chemotactic 5
C3b: opsonin MAC: membrane attachment complex-------plasma derived CELL DERIVED: Histamine Serotonin (vasoactive)
from mast cells vasodilation increases permeability
LTC4 LTD4
Increase vascular permeability
LTE4 LTB4 – chemotactic TXa2- Platelet aggregation Prostacyclin-vasodilation Serotonin -vasoactive Cytokinesis Mon kinesis
chemotactic
Lymph kinesis Both neutrophils and macrophages are can degaranulate Neutrophils and macrophages/monocytes are respond chemotactic cpds. Neutrophil is the first cell type to arrive at sight of injury. CHRONIC INFLAMMATION: -More than 7 days
6
to
-cause of injury not neutralized/removed ACUTE INFLAMMATION CHRONIC INFLAMMATION Last for minutes only Lasts for weeks -acute inflammation most -in chronic inflammation most important cell is neutrophil (can’t important cell is monocytes and do mitosis) macrophages(become epitheloid cell) -Exudates more importance Exudates less importance Fibroblast are proliferate Affected part is swelling Affected part is swelling Chemotactic cpds involved
Chemotactic cpds involved
Vascular changes exudative – Proliferative release of exudates cells
increases
size
of
In chronic inflammation blood vessels are become leaky Some scaring is also developed in this chronic inflammation Macrophages are phagocytic they have huge appetite 1. They have longer life span 2. They can reproduce 3. Release chemical mediators (chemotactic chemicals) and (hydrolytic enzymes) Monocytes/Macrophages have role in tissue repair But neutrophils don’t play role in tissue repair Neutrophil can die after phagocytosis Neutrophil and macrophages are respond to chemotactic cpds Fibroblast play role inflammation and tissue repair Macrophage is a voracious phagocyte TYPES OF CHRONIC INFLAMMTION: 1. Non-specific inflammation: –acute inflammation of Macrophages of lymphocytes of fibroblasts in the site of injury -No definite arrangement of the cells 2. Granulomatous inflammation: -Granuloma 7
- Macrophages macrophages)
look
like
epitheliad
cells
(non-motile
-Giant cells (fusion of all epithelial cells) Types of granuloma cells A. Granuloma with separation: B. Granuloma with casseation (centre is occupied by dead cells that resemble cheese(dry and plenty) C. Granuloma with foreign body (Ex: splitter of wood) A.TISSUE REPAIR: Types of cells (according to ability to reproduce) 1. Labile cell (Ex: membranal and epidermal cells) 2. Stable cell (organ completing development and stable again EX: Liver cell) 3. Permanent cell (EX: smooth or skeletal muscle)
dividing
B.TISSUE REGENERATION -dead cell replaced by new but same kind of cell (type 1 of 2) C. TISSUE REPLACEMENT: (Type 3) -Replaced by scar tissue (Ex: cardiac muscle) permanent Parenchyma (type 1& 2&3) Strom function as scar Stages in fibrosis (tissue replacement): 1. Granulation tissue formation a. angiogenesis (produce new blood cells) new capillaries b. deposition of ECM, proteoglycans and macrophages (EXTRA CELLULAR MATRIX=CONNECTIVE TISSUE reproduced by fibroblast by chemotactic , Ex: Fibronectin -adhesive Hyaluronic acid 8
Fibrinogen deposits structural component of scar is collagen Proteoglycans C. deposition of collagen 2. Scar formation: Granulation tissue MPs Fibroblast Capillaries
spongy
ECM Collagen
SCAR FORMATION: reduction in ECM, capillaries of other components -increase collagen deposition which leads formation of scar WOUND HEALING: 1. Inflammatory stage After the 48 hours Macrophages more into the site of injury 2. Proliferative stage : a. granulation tissue formation b. re-epithelialization 3. Remodelling: a. scar formation b. Contraction 1st intention healing: -narrow gap little granulation tissue - No infection -slight contraction -minimize scaring 9
2nd intention healing: -Exagarent granulation -keloid formation -Excessive contraction
2. FLUID OF DEARRANGEMENTS:
HEMODYNAMIC
1. Non-inflammatory edema 2. Thrombosis 3. Shock First physical force is plasma hydrostatic pressure Force exerted by H2o plasma against blood vessel wall is called hydrostatic pressure. This has the tendency to exert the fluid from the wall of the vessel Plasma is refers to fluid portion of blood. Plasma osmatic pressure: Attract fluid into the blood vessel Plasma albumin (made by liver) Is a protein is responsible for plasma osmatic pressure. Transudate is low in plasma protein or without plasma protein& Specific gravity is less than 1.012. Exudates is with plasma protein for this the specific gravity is greater than 1.012. 10
Causes of non-inflammatory edema: 1. Increase in plasma hydrostatic pressure (HP) EX: venous thrombosis 2. Right side heart failure 3. Decrease in plasma osmotic pressure (plasma albumin from liver) a. Liver disease b. Kidney disorder c. Malnutrition- kwashiorkor FLUIDS ARE NOT ENTERED INTO VENULE INFLMMATION OCCUR 3. BLOCK IN LYMPHATIC DAMAGE: a. Surgical removal of lymph nodes of vessel b. Colonies of malignant cells in lymph vessels c. Presence of parasites in lymph vessels leads to eg- filariasis
4. Reduction in plasma protein concentration PHP
PHP > POP Causes fluid escape from blood vessel POP >POP causes fluid to enter into blood vessel 11
PRINCIPLES OF HEAMOSTASIS 1. Vascular spam 2. 1ST (primary) haemostasis Van wille brand factor (released by injured endothelium) activate platelets platelets degranulte ADP and Thromboxane A2 (Txa2)-make platelets sticky, platelet plug formation, PF3 (platelet factor no 3= PHOSPHOLIPIDS)-helps in blood clot formation. 3. Blood clot formation (HEMOSTASIS). Interna = endothelium (intact) Media= collagen (healthy layer) Externa Lumen (Platelets are prostacyclin) PLASMA CLOTTING FACTORS: 1. Fibrinogen 2. Prothrombin (blood clot) 3. Tissue thromboplastin 4. Ca+2(nerve signalling) 5. proaccelerin (muscle contraction) 7. Proconvertin 8. Anti-haemophilic factor (haemophilia-a) 9. Plasma thromboplastin component (haemophilia-b) 10. Stuart prower factor 11. Plasma thromboplastin antecedent 12. Hageman factor 13. Fibrin Stabilizing factor Blood must remain fluid while inside A blood must become solid outside a blood vessel
12
Virchow’s triad: 1. Endothelial injury 2. Disturbance in the blood flow 3. Hypercoagulability CIRCULATORY (SHOCK): Systemic hypo perfusion (blood flow to the organs which leads to hypoxia) Due to: 1. Reduced cardiac output 2. Reduction in blood volume: (Stroke volume heart rate)=cardiac output 4. Widespread peripheral vasodilation: seen in both progressive and non-progressive shocks Blood will pool in (microcirculation) synonym for systemic is widespread
When doing exercise: 13
Volume of blood in brain-normal Digestive organ-reduced Muscles-increased
STAGES OF SHOCK: 1. compensated stage :(non-progressive) best for correction still in able to function reduction in cardiac filling reduction in cardiac output reduction in arterial blood pressure a. vasoconstriction (tachycardia=rapid heartbeat ) b. Oliguria: (Reduction in urine formation to conserve body fluids) Patient skin turns grey, cool to touch, sweating rapid heartbeat and reduction in urine these are symptoms for compensated shock. In this shock B.P is maintained 2. Progressive stage: systemic hypoxia (if there is no oxygen) cells shift to anaerobic respiration accumulation of lactic acid (decrease in Ph acidic) reduction of vasomotor control area of brain (which controls fluid levels of body) arterioles dilates venules remain constricted (vicious circle/cycle appears) In first stage microcirculation is affected In second stage arterioles are dilated and venules are constricted. Blood is trapped in microcirculation because arterioles are dilated and less will be leaving venules are constricted
14
15
Low blood pressure leads to hypoxia damage cells increase vasodilation and then low blood pressure from hypoxia increase in fluid ion increase in vascular permeability damage to capillaries hypoxia. TYPES OF CIRCULATORY SHOCK: 1. Hypovolemic shock: reducing in effective blood volume. Ex: blood loss, vomiting with diarrhoea. Burns also cause loss of body fluids 2. Cardiogenic shock: reducing cardiac output (arrhythmias) 3. Neurogenic shock: peripheral vasodilation. is from nerves especially from medulla oblongata 4. Septic shock: infection by gram negative bacteria. This is also peripheral vasodilation. 5. Anaphylactic shock: very severe to allergies. This is also peripheral vasodilation.it is normal just small part effected. It is systematic, allergies become very serious leads to death.
IMMUNITY (IMMUNITY SYSTEM): INNATE IMMUNITY 1 Non-specific response 2 Exposure leads maximum response
ADAPTIVE IMMUNTY Pathogen of antigen specific response to Time lag exposure of response
between maximum
3 Cell mediated of humoral Cell mediated of humoral response response 4 No immunological Develops immunological memory develops memory develops 5 Ex: some living things
Ex: only for man
Functions of innate immune system: 1. It recruits wbc to site of injury 2. Remove foreign cells of foreign substances 1 and 2 are part of acute immune system 3. Activate the complement (plasma proteins)system 16
4. Activate adaptive immune system there antigen precipitation Cells of innate immunity: 1. Mast cells: -release histamines -vasodilation and increase inflammation
vasopermiability
2. Phagocytes: - eat foreign cells +neutrophils -Infected cells + monocytes/MP 3. Dendritic cell/Langerhans cells -phagocytosis - On epidermis 4. Nature killer cells (NK) -tumour cells -viral infected cells Anatomical barriers: 1. Skin :include sweating Degranulation 2. Gastro intestinal tracts Hydrochloric acid – stomach (digestive enzymes) Bile -small intestine (peristalsis) 3. Respiratory tract: (sneezing/coughing) Cilia 4. Urinary tract:
(urination)
17
in
acute
It’s not so effective
18
Model for cell Action in the immune response 1. Recognition (auto immune disorder) 2. Defence PRRs: Pattern recognition receptors PAMPs: Pathogen associated molecular pattern Lipopolysaccharides: Lipoteichoic acid + peptide glycan In human flagella bacterial flagella flagellin Nucleic acid variants is (double standard RNA) then it is in humans if it is single standard the in other organisms DAMPs: damage associated molecular pattern Proteins ATP DNA
Outside the cells these are damage.
Adaptive immunity: 1. Humoral antibody response 2. Cell mediated response First kind of lymphocyte (WBC) IS: B cell (naive, Plasma memory produce immunoglobulin (Ig antibody) Second kind of cell: T cell start life cycle, (bone marrows –thymus) Helper T cell (Th/CD4) Cytotoxic T (Tc/CD8) 19
Suppressor T (Ts/ Trecg) [Cluster designation number CD- 20] ANTIGEN: Foreign cells is called antigen is responsible for immune system. Usually antigen is a protein. Poly saccharide Glycoprotein Lipid+protein -bigger the molecule have more antigen. Immunoglobulin/antibodies: - Also proteins -produced by plasma (active B) cells
20
Ig classes (immunoglobulin classes): 1. IgG – 85% -internal body fluids - can
placental barrier
- Into foetal circulation -activate complement 21
2. IgA – -external secretion -mucosa 3. IgM- First response Ig - Active complement 4. IgD –receptors on B cell membranes 5. IgE – attracts to mast cell -membranes release histamine
FUNCTIONS OF IgS: 1. 2. 3. 4.
Complement activation Neutralization Opsonisation of antigen Agglutination
22
5. Precipitation MHC (major histocompatibility complex) MHC1 – all cells MHC 2- APCs (macrophages) Antigen presentation: APC – macrophage Infected cell – by virus on a tumour cell
Hypersensitivity actions: damage.
inflammations
1. 2. Anaphylactic /reaginic 3. Antibody cell-mediated immediate 4. Immune (antigen-antibody) complex 5. Delayed hypersensitivity hours takes)
23
pain
involves antibodies
involves in T cell (48 – 72
Mast cell release histamine which increase vasodilation or vascular permeability. And cause smooth muscle contraction ex: asthma in this bronchioles of lungs are contracted ANTIGEN = Allergens Stimulus/antigen is called by several names i.e. Coz type 1 hypersensitive reactions also called allergy reactions. 2nd Allergy + sensitive mast cell
histamines
Symptoms: vasodilation, vascular permeability, smooth muscle contraction. It is local certain parts are allergic (or) systemic whole body effects 2) ANTIGEN CELL MEDIATED:
B. organ transplant rejection C. Auto immune haemolytic anaemia (reduction of no of RBC)
24
3) IgG Ig A
antibody combine with antigen form antigen-antibody
complex
Ig M ANTIGEN > ANTIBODY EX: R.A IgM attaches IgG
4) T cell delayed hyper sensitivity:
Bruton’s X-linked a gammaglobulinemia. - Genetic disorder: inability in produce T- cells -Defective X- chromosome 25
- No B- cells Thymic hypoplasia: -under developed thymus -defective T cells severe combined immunodeficiency (SCID) - No B & T cells. AIDS: - Target on Cd4 - Not a genetic disorder Auto immune diseases: -Systemic lupus Erythematous (SLE) -IgS Against own DNA -no cure Diabetic mellitus type 1: antibodies against beta cells.
INFECTIOUS DISEASES: Parasite –host relationship (co evolutionary relationship) between pathogen and human Bacteria Virus Protozoans Parasite: extract nutrient material from host Parasite – host Commensalism
symbiosis
26
Important pathogen principles:
Asexual reproduction: -cell division - (A mitosis/binary fission)
27
Sexual reproduction: Gathering new genetic material 1. Conjugation 2. Lysogenic conversion or may be transduction Requires bacteriophage it is a virus 3. Transformation
Virion (complete viral particle): N.A – DNA ONLY 28
-RNA only Capsid – protein Envelope – lipids of proteins -Cell membrane of host
VIRAL Multiplication 1. 2. 3. 4. 5. 6.
Attachment Penetration Uncoating Biosynthesis Assembly Release
VIRULENSE Bacteria: 1. Exoenzymes: (dissolve collagen) Coagulase fibrinogen fibrin (blood clot) Kinase dissolve fibrin Hyalurinidase hyaluronic acid (cement of cells) Lecithinase lecithin (attach to phospholipids of cell membranes) Necroting enzyme Tissue destruction 2. Toxins: 29
Endotoxin Lipopolysaccharides of gram -ve bacteria Exotoxin (dissolved in plasma) (attacks nerve cells,form of antignantibody complex) Neurotoxin Enterotoxin 3. Others (bacterial structure) Capsule Attachment Pilli Flagella
VIRAL INFLUENCE DIRECT effective in cell 1. Lysis of infected cells 2. Infected cell becomes an APC affected by immune system 3. Infected cell becomes malignant – Hepatitis-B liver cancer Effect Indirect effect in cell
4. Kills cells without the support of other cells Polio virus Motor neurons
control skeletal muscles
(atrophy) 5. Opportunity for secondary infections
30
Pathogenesis of an infection: 1. Entry: a. faecal oral route b. genital urinary tract d. inoculation 2. Attachment (receptors must be present on target cell) 3. Multiplication 4. Spread incubation period [2&5] 5. Erasion 6. Damage to host
1. INSUFFICENT MEMBERS: 10 vibrio cholera 100 Giardia 2. Lands in the place 3. No Receptors 4. Indigenous micro flora 5. Overall health status and nutrition 6.1’ innate immunity
7.2’ innate immunity
EVADING THE IMMUNE RESPONSE: 1. Antigen a. Shielding of antigens – schist soma b. Changing of antigens- Neisseria c. Many variants – Rhino virus d. Mimicry- streptococci group A 2. Phagocytosis a. Resistance - capsule of pneumococcus
31
b. Surviving phagocytosis- mycobacterium tuberculosis inside Macrophage 3. Immune system A. accessibility to the immune system----Skin epidermis-Papilloma virus Get Lumina - Clostridium B. Kill immune cells – pseudomonas------- secondary neutrophils C. immune suppression: HIV/AIDS
NUTRITIONAL PATHOLOGY: 1. Obesity 2. PEM 3. Vitamin deficiency
Obesity: having too much, too little Cal input > Cal output Genetics Social study Glands Hormones Thyroxin Pathological conditions Associated Obesity 1. Osteo arthritis - Weight bearing joints 2. Insulin resistance Ex: diabetes mellitus type 2
32
3. Hypertension
Brain stroke, myocardial infraction, kidneys
BMI: BODY MASS INDEX: Weight (lbs.) Height
703
Height (m)
Metric: Weight (kg) Height (m)
Height (m)
Under wt.: <18.5 Normal wt.: 18.5-24.9 Over wt.: 25- 29.9 Obesity >30 BODY FAT
Description Essential fat Athletes Just average Excess fat
Male 8-12% 14-20% 25-32% 32% +
Female 3-5% 6-13% 18-24% 25%+
Anorexia, Nervous (starving) Bulinia (overheating) PEM: protein energy malnutrition Marasmus Skin &bones Lack of calories
Kwashiorkor Non-inflammatory edema Orange hair colour
VITAMINE DEFICIENCIES: 33
B1 (Thiamine) B3 (Niacin) Water soluble C D A Fat soluble B1 (thiamine): Needed for: 1. CHO catabolism Amino acid catabolism 2. Production of acetylcholine
Deficiency disorder- BERI BERI A. Dry Beri-Beri Peripheral neuropathy Damage to peripheral nervous system If it’s mild tingling of matured examities---------severe Wrist drop Central nervous system------------ Dementia B. wet Beri-Beri -
Edema (swelling)
B3 (Niacin): 1. Component of NAD of NADP 2. DNA repair 3. Production of steroid hormones Deficiency disorders: Pellagra Diarrhoea Dermatitis
34
Dementia Death Vitamin C (Ascorbic acid) 1. Antioxidant 2. Collagen synthesis 3. Natural anti-histamine Deficiency disorders: Scurvy Lethargy Witness Muscle pain Vitamin D (cholicaliciferol): Allow body to absorb Dietary Ca Increasing blood Ca levels Deficiency disorders: Osteomalacia- in adults Rickets- in children
weak Skelton
Bowlegs VITAMIN A (retinol) 1. Proper development of cells 2. Component of rhodopsin (for might vision) Deficiency disorders: Night blindness Xeropthalmia (dry eyes) of keratomalcia 35
GENETIC DISORDERS: 1. mendelian inheritance A. autosomal dominant disorders B. autosomal recessive disorders C. sex –limited recessive disorders 2. Non-mendelian inheritance -multifactorial disorders 3. Chromosomal aberrations Single- gene disorders negligible
Powerful effect &environmental
a. Autosomal dominants AA: very (dead) Aa: sick (heterozygous) aa: normal /not affected (homozygous) Aaxaa A
A
A
Aa
Aa
Offspring is affected 50% have the normal condition AaxAa A
A
A
AA
Aa
Aa
Aa
7a AA-Aa-Aa 75% are sick Familial hyper cholestrolemia: 1/500 Short arm of chromosomal no 19 Huntington’s cholera: 1/15000 4P 36
-50% for children -followed by Death B. Autosomal recessive AA – normal Aa – normal but carrier aa - affected Aaxaa (not very common) A A
A
Aa 50% Aa Carriers 50% Affected Aa x Aa Aaxaa A
A
A
AA 25%
Aa 50%
A
Aa 50%
Aa 25%
3. Cystic fibrosis: 1/2500 exocrine gland disorders 7of9 4. Sex-linked recessive disorders A/a = xy/xx x/a female
male 37
XAxA = normal Carrier XAxa = normal
XAy =normal
XaXa affected/sick
Xay
Sick/affected
Haemophilia type A:
XAXa
XAy
XA Y
XA XAXA XAY
Xay
Xa XAXa Xay
XAXA XA
Xa
XAxa 100% carrier xAy100% normal
Y
Xay
xAxa
Xa
xA xAxa
Y
XAy
Xa rare Xaya haemophilic xay
Characteristics of multifactorial genetic disorders: 1. Controlled by many genes ,each gene of small effect (additive effect) 38
2. Environment plays a trigger role in determining expression 3. Risk of expression 5%-10% 4. The more severe the symptoms greater chance of transmission greater off springs Hypertension Diabetes mellitus type 2 CHROMOSOMAL ABBERATIONS: Usual problem is wrong no of chromosomes EX: Trisomy 21 Downs’ syndrome Monogolodism
Neoplasia/Neoplasm Characteristic of Neoplastic growth: 1. Progressive 2. Purposeless -regardless of surrounding tissue -regardless of needs to the body 3. Parasitic Pathological Effect: Benign: oma Malignant (cancer) - sarcoma, carcinoma
39
1. Location: 2. Function: -B-normal function
- M- no function
Increasing production
Decreasing production
-Pituitary gland - GH
3. Bleeding of infection: 4. Cachexia: - generalized weakness of wasting in body -Usually malignant - Due to parasitism of the neoplasm
Difference between benign/malignant BENIGN Cells are well Differentiated and mature
MALIGNANT And not well differentiated -pleomorphic -variations in the shapes and sizes Anaplasia is immature -ratio between nuclease of cytoplasm - frequent abnormal mitosis
40
2. Rate of growth: B-slow M- Fast Local invasion: B local Stays in place of origin Expansive growth 3. Malignant - Infiltration, invasion, dysfunctions: surrounding tissue 4. MetastasisIt can establish secondary growth centre elsewhere in the body a. Haematogenous special b. Lymphatic c. Rupture thin layer MOLECULAR BASIS FOR CARCINOGENESIS: 1. Caused by non-lethal Genetic damage to the cell 2. Monoclonal expansion/growth of malignant cell 3. Genes affected by the mutations. A. proto oncogenes---------------oncogenes For cell growth (Cell division) B. Tumour suppressor genes: inhibit cell division -RB (retina blast in) - RB1 gene – Chromosome 13 (ressive) - RAS at chromosome: 12 C. Gene that regulates apoptosis DCC (deleted colour carcinoma) Chromosome 18 D.Gene for DNA repair P53 – chromosome 17 41
-stop cell division - Guardian of the genome MSH2- Chromosome 2 MLH1- Chromosome 3 Hallmarks of malignancy: 1. 2. 3. 4. 5. 6.
Self-sufficiency in growth regulators Insensitivity to growth inhibitions Erasion of apoptosis Limitless reproductive potential due to telomerase production Sustained angiogenesis Obesity to invade of metastasize a. Loss of contact inhibition b. Loss of serum of anchorage c. Resistance of antiquities
7. Defects in DNA repair 8. Warburg effect
42
Hay flick limit Telomerase: T-T-AGGG [non-coding] Telomerase – replenishes Telomeres Cancer cell is virtually immortal Hela cell line (Henrietta lacks: 2/8/51) Telomerase replies telomeres Normal cell: -aerobic respiration Met -aerobic glycolysis -glucose hungry
43
44
45
46
47
48
