Robbins Pathology Notes

1 ROBBINS PATHOLOGY

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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

2 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 STRATIFIED

EPITHELIAL 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 cellular swelling (1st 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

3

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 sign of irreversible cell injury

Karyolysis: dissolution of nucleus 2. Acidic cytoplasm-PINK

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.

4 TYPES OF INFLAMMATION:

ACUTE

Minutes/hours/days after the injury -max of 7 days  Vascular changes exudative –release of exudates  Neutrophil(WBC) CHRONIC

Months and years

 Proliferative increases size of cells

 Monocyte/macrophage

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. Neutrophils 2. Monocytes 3. Mast cells

5 Chemical mediators:

A. arachindonic Acid metabolites(phospholipids and cell membranes) B. vasoactive chemicals

C. cytokines

D. lysosomal enzymes

ARACHIDONIC ACID Cyclooxygenase prostaglandin (PGS) 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: blood clot PLASMA

C3& C5a-include mast cells to release histamine & serotonin derive

6 C3b: opsonin

MAC: membrane attachment complex---plasma derived CELL DERIVED:

Histamine

Serotonin from mast cells vasodilation increases permeability (vasoactive)

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 to chemotactic cpds.

 Neutrophil is the first cell type to arrive at sight of injury.

CHRONIC INFLAMMATION:

7 -cause of injury not neutralized/removed

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

ACUTE INFLAMMATION CHRONIC INFLAMMATION Last for minutes only Lasts for weeks

-acute inflammation most important cell is neutrophil (can’t do mitosis)

-in chronic inflammation most important cell is monocytes and 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 –

release of exudates

Proliferative increases size of cells

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- Macrophages look like epitheliad cells (non-motile macrophages)

-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 dividing again EX: Liver cell)

3. Permanent cell (EX: smooth or skeletal muscle) 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

9

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

10 2nd _{intention healing:} -Exagarent granulation -keloid formation -Excessive contraction

2.

FLUID

OF

HEMODYNAMIC

DEARRANGEMENTS:

 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.

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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

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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

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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

14 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

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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

ADAPTIVE

IMMUNTY

1 Non-specific response Pathogen of antigen specific response

2 Exposure leads to maximum response

Time lag between exposure of maximum response

3 Cell mediated of humoral response

Cell mediated of humoral response

4 No immunological memory develops

Develops immunological memory develops

5 Ex: some living things Ex: only for man

Functions of innate immune system:

2. Remove foreign cells of foreign substances 1 and 2 are part of acute immune system

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4. Activate adaptive immune system there antigen precipitation Cells of innate immunity:

1. Mast cells:

-release histamines

-vasodilation and increase vasopermiability in acute inflammation

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

18 It’s not so effective

19 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)

20 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

21

I

1. IgG – 85%

-internal body fluids - can placental barrier - Into foetal circulation -activate complement

22 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. Complement activation 2. Neutralization

3. Opsonisation of antigen 4. Agglutination

23 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: inflammations pain damage.

1.

2. Anaphylactic /reaginic

3. Antibody cell-mediated involves antibodies immediate

4. Immune (antigen-antibody) complex

5. Delayed hypersensitivity involves in T cell (48 – 72 hours takes)

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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)

25

3)

IgG

I

A

complex

IgM

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

26 - 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

27 Important pathogen principles:

Asexual reproduction:

-cell division

28

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):

29

-RNA only Capsid – protein

Envelope – lipids of proteins

-Cell membrane of host

VIRAL Multiplication 1. Attachment 2. Penetration 3. Uncoating 4. Biosynthesis 5. Assembly 6. 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:

30 Endotoxin

Lipopolysaccharides of gram -ve bacteria

Exotoxin (dissolved in plasma) (attacks nerve cells,form of antign-antibody 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)

31 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

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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

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3. Hypertension Brain stroke, myocardial infraction, kidneys BMI: BODY MASS INDEX:

Weight (lbs.) 703 Height 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 Male Female

Essential fat 8-12% 3-5%

Athletes 14-20% 6-13%

Just average 25-32% 18-24%

Excess fat 32% + 25%+

Anorexia, Nervous (starving) Bulinia (overheating)

PEM: protein energy malnutrition

Marasmus Kwashiorkor

Skin &bones Non-inflammatory edema

Lack of calories Orange hair colour

34 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

35 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

36 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 Powerful effect &environmental negligible

a. Autosomal dominants AA: very (dead)

Aa: sick (heterozygous)

aa: normal /not affected (homozygous) Aaxaa

Offspring is affected

50% have the normal condition AaxAa

AA-Aa-Aa 75% are sick

Familial hyper cholestrolemia: 1/500 Short arm of chromosomal no 19 Huntington’s cholera: 1/15000 4P A A A Aa Aa A A A AA Aa 7a Aa Aa

37 -50% for children

-followed by Death

B. Autosomal recessive AA – normal

Aa – normal but carrier aa - affected

Aaxaa (not very common) Aa x Aa Aaxaa 3. Cystic fibrosis:

1/2500 exocrine gland disorders 7of9

4. Sex-linked recessive disorders A/a = xy/xx

x/a female male

A A A Aa 50% Carriers Aa 50% Affected A A A AA 25% Aa 50% A Aa 50% Aa 25%

38

XAxA = normal

Carrier

XAxa = normal

XAy =normal

XaXa affected/sick

Xay Sick/affected

Haemophilia type A:



XAXa XAy

Characteristics of multifactorial genetic disorders:

1. Controlled by many genes ,each gene of small effect (additive effect)

XA

Xa

XA

XAXA

XAXa

Y

XAY

Xay

39

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

1. Progressive 2. Purposeless

-regardless of surrounding tissue -regardless of needs to the body 3. Parasitic

Pathological Effect: Benign: oma

40 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 MALIGNANT

Cells are well And not well differentiated -pleomorphic

-variations in the shapes and sizes Differentiated and mature Anaplasia is immature

-ratio between nuclease of cytoplasm

41 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. Metastasis-

It 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

42 -stop cell division

- Guardian of the genome MSH2- Chromosome 2 MLH1- Chromosome 3 Hallmarks of malignancy:

1. Self-sufficiency in growth regulators 2. Insensitivity to growth inhibitions 3. Erasion of apoptosis

4. Limitless reproductive potential due to telomerase production 5. Sustained angiogenesis

6. 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

43 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

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