Exam #2 patho

Genetics

study of hereditary, focused on single gene

Gene

unit of heredity

• sequence of nucleotides

• determined structure or has regulatory function in a cel

Chromosome

• linear arrangement of genes within the cell nucleus

• Normal = 23 pairs (22 pairs of autosomes) 1 pair of sex chromosomes XX or XY

Homozygous

possessing pair of identical genes

Heterozygous

different genes on a pair of chromosomes

Genomics

study of all genes, genetic inter-relationship and their influence on growth and development.

Congenital Disorder + (types)

abnormalities of body structure, function, or metabolism and present at birth, irreversible damage to the cell’s DNA.

• chromosomal disorder

• single gene disorder

• multifactorial disorder

Medalion disorder

inherited from Mom and Dad

Denobo disorder

new genetic disorder, not passed on from parents

Chromosomal disorder

Numerical disorders and structural disorders

Numerical disorders

Euploidy and Aneuploidy

losses are more lethal and result to stillborn and dye shortly after birth

Euploidy

normal # (46) in all cells (23 pairs)

Aneuploidy and causes

abnormal, where cells do not have the multiples of 23 (because you have an additional one)

causes: nondisjunction

• failure of chromatid pairs to separate

• results in unequal number of chromosomes in daughter cell

Types of Aneuploidies

autosomal and monosomy

Autosomal

abnormal # of chromosomes in the somatic cells, usually on 13, 18, 21 (extra one on it)

Trisomy - when a cell contains one extra copy of the chromosomes, they have 3

Ex: Down Syndrome has a 3rd chromosome on 21

CM: facial abnormalities, intellectual disability/low IQ, poor muscle tone, short stature, systemic disorders, mortality. flattened nose and face, slanting eyes, large tounge, small ears

• increased risk with increased maternal age (35 and up)

Monosomy

when a cell contains only 1 copy of any of the chromosomes instead of two (loss)

22+23=45 instead of 46

• generally a lethal condition, miscarriage, still born, or die shortly after birth.

Sex chromosome

change in number of chromosomes but found on the sex chromosomes

Ex: Klinefelter Syndrome and Turner Syndrome

Klinefelter Syndrome

(polysomy X) - extra x’s

• at least two Xs and one Y

• Ex: XXY or XXXY

• CM: male appearance, but female features; moderate IQ. long legs small testis, less pubic hair, wide hips, have a penis but female features.

• usually male but more female features pull through

Turner Syndrome

• X chromosome monosomy = only females with only 1 X chromosome. No Y, its a loss. they live but have short lives.

• CM: webbed neck, shield-like chest, faulty ovary development, short stature, narrow aorta, some IQ impairment. Not a strong female outward appearance.

Polyploidy

more than 2 sets of chromosome pairs but still in sets of 23.

• Tetraploidy - 92 chromosomes

• Triploidy - 69 chromosomes

  ( both of thease lead to misscarages) spontanulosly aborted.

Structural disorders (5)

physical rearrangement of chromosomes

1. deletions

2. duplication

3. inversion

4. translocation

5. fragile sites

deletions

loss of portion of a chromosome, section comes off, gone, rest of the chromosome comes together.

EX: Cir Du Chat Syndrome - missing part of chrome #5, decreased birth weight, microcephaly, heart defects

Duplication

presence of a repeated gene or gene sequence

Inversion

reversal of gene order, can be a part of the gene or the entire gene (flip flop)

Translocation

transfer of one part of a chromosome to another.

Fragile sites

chromosome parts that develop distinctive breaks and gaps

Ex: Fragile X syndrome, only on X chromosome, its X linked only in males. intellectual disability, 2nd most common disability that causes intellectual. (#1 down Syndrome)

Single gene disorder (2)

one single gene has an alteration, and it can be autosomal, or sex linked

1. autosomal dominant

2. autosomal recessive

Autosomal dominant

abnormal gene is dominant and normal gene is recessive

Ex: Marfan’s Syndrome: connective tissue disorder involving skeletal, ocular, and cardiovascular systems. Passed from parents to children, they are thin and tall and arm span is greater than height. short life with a weak aorta and other arteries because of the CT.

Autosomal Recessive

abnormal gene is recessive and normal gene is dominate

homozygous, both parents have to carry the recessive gene for kid to get it. If they don’t both express, it the kid is a carrier.

• consanguinity (inbreeding)

Ex: Phenylketonuria (PKU) and Cystic Fibrosis

PKU

• Inability of body to convert Phenylalanine atyrosine = elevated levels of phenylalanine and deficient tyrosine.

• accumulation in the blood and excess causes alterations in nervous system development Metabolic system disturbances.

• tests now available for detection.

Cystic Fibrosis

passed on from parents that are carriers

Sex Chromosomes

Present on the X in females and Y in males

• most are X linked but you need 2 for females and one for males.

• EX: Fragile X syndrome and Duchenne Muscular Dystrophy (progressive muscle degeneration)

Sex-limited

trait only occurs in 1 gender

females - can only have uterine disorders

males - are the only ones that can have testicular defects

Sex- influenced

trait is that occurs more often in 1 gender than the other

males - baldness and colorblindness

females - breast cancer

Multifactorial

• interaction between genetic susceptibility and environment

• occur more frequently in families (the way they live)

• EX: cleft lip palate, neural tube defects (spinabifida), club feet, some congenital heart defects, diabetes mellitus, hypertension, some types of cancer.

Environmental Alterations in Fetal development (in utro)

Teratogen - which is an enviromental agent that harms a developing fetus

EX:

1. medications

2. smoking

3. alcohol/drugs

4. mothers’ health status - diabetes, hypothyroidism, hypertension

5. radiation

6. malnutrition - folic acid: CNS, Iron: blood, Ca+:bones

7. microorganisms

Developmental factors (timing, stage of development: 5 weeks, %50 not expected)

outcome: congenital defect

TORCH

extra harmful to the fetus, can cross the placenta barrier causing birth defects

T: Toxoplasmosis - protozoen infections, unpasterized milk, undercooked meat, cat pee

O: other - hepatitis, syphilis, HIV

R: Rubella (measles) - first trimester will be deff

C: Cytomegalovirus (CMV) - body secretions like breast milk, hearing loss

H: Herpes

Transmission

Recurrence Risk - probability an individual will develop a genetic disease

No history of disease in family + child with autosomal dominant disease = probable new mutation of a parent’s gene.

Delayed age of onset - symptoms of genetic disorder do not manifest until age 40 or later

Autosomal Dominant

affected parent + Normal parent = %50 risk

affected parent + Affected parent = %75 risk

Autosomal Recessive

Heterozygous parent (carrier) + Heterozygous parent (carrier) = 25% risk

Heterozygous parent (carrier) + affected parent = 50% risk

Lines of defense

skin and mucous membranes, inflammation, specific immune response

Inflammatory Response

• usually, beneficial response to invasion by microorganisms or to tissue injury

• remove stimulus and work to move that injury to its pretissue state.

Tissue reaction to injury: 2 phase

Involves vascular and cellular responses working together to destroy substances recognized as foreign to the body

Followed by tissue repair or restoration

Vascular Phase

involves chemical mediators from either plasma or cells

CComplement: major mediator

a. Proteins, sequential activation (complement cascade)

b. Enhances chemotaxis, increases vascular permeability and causes cell lysis (three part of the inflammatory process)

Kinins (bradykinin

Contribute to pain and fever

b. Vasodilation - vessels dilate, providing larger diameter for more blood flow

Histamine: Vasodilation

wide distribution of inflammation through the body

a. Major mediator of capillary permeability

b. Role of mast cell/basophils - release histamine

c. Degranulation of mast cell - process of molecules being realsed from inside of cell, histamine is released to.

Serotonin and Leukotrienes

• similar to histamine

• it works slower, causes vasodilation and Bronco-constriction

Prostaglandins

Increase effect of histamine - vasodilation (pain response)

b. Promotes platelet aggregation

Hemostatic-fibrinolytic system

Clotting cascade: fibrin clot formation in damaged vessels

b. Clot breakdown to resort patency of vessel, to ensure it remains open

Vascular changes resulting from mediator

a. Brief vasoconstriction - minimize bleeding

b. Vasodilation

c. Increased capillary permeability, exudate (protein rich fluid) moves into the vascular space causing edema. leading to a decrease in proteins, decrease in capillary pressure, increase in intestinal osmotic pressure.

d. Leakage of fluid from the capillary membrane and into the interstitial space

e. Edema

f. Stimulation of pain receptor

Role of Other Inflammatory Substances → Cytokines (regulators)

a. Interleukins - stimulates liver to make plasma protein

b. Interferon: anti-viral effect @ receptor site, protein against invasion, does not destroy the virus though.

c. Tissue Necrosis Factor (TNF) - increases the Pagasitic activity of neutrophils and causes fever.

Cellular Phase

Characteristics of WBC response

margination, emigration, phagocytosis, formation, fibrin

Margination (pavementing)

a. Movement of phagocytes to periphery of BV

b. Granulocytes: neutrophils, eosinophils, basophils (early cells that respond)

c. Monocytes → macrophages (seen with chronic inflammation because they can survive longer)

Emigration (diapedesis) of leukocytes:

chemotaxis, it pulls WBC into the tissue. the inflammation cite pulls the leukocytes

Phagocytosis: begins with recognition of the target

a. Neutrophils and macrophages - primary phagocytes that destroy the target

b. Engulfment of foreign material - cytoplasm flows around target

c. Ingestion through fusion with lysosomes within the phagocyte - receptor cites for attachment are used

d. Destruction by lysosomal enzyme - tissue slumps off

Formation of exudate (drainage)

It is a product of phagocytosis

Initially plasma-like (edema)

b. Purulent as cellular debris accumulate - becomes thicker, smell, discolored with infection

Fibrin barrier formation

Activated at the cite and walls off the area to limit speed

framework for tissue formation

Chronic Inflammation: Inflammatory process persists, Stimulus not clear

More macrophages, less neutrophils

2. Lack of control of plasma protein systems

3. Natural inhibitors ineffective

4. May cause scar formation and organ dysfunction

Clinical Manifestation of immflaortory response

local responses and systemic effects

local response (at cite)

Redness, heat, edema (vasodilation)

b. Pain

c. Formation of exudate

d. Body’s removal of exudate

Ex. cough. lymphatic system, GI, urine

Systemic Effects (throughout the whole body)

fever, increase in circulating plasma proteins, CRP, ESR, Leukocytosis, Lymphadenopathy

Fever

initiated by release of pyrogens that act on hypothalamus & raise thermos

CRP

(C-reactive protein) you see an increase in circulating plasma proteins. 0-3mg

ESR

(erythrocyte sedimentation rate) 0-20 men, 0-30 women

Leukocytosis

elevation in white blood cell count (neutrophils)

• “left shift” - increase in bands, immature cells, bone marrow is responding to release more WBC

Lymphadenopathy

enlarged lymphnodes

more severe, localized infection in attempt to drain exudate

Resolution of Inflammation (3)

1. simple resolution

2. regeneration

3. repair by scar formation

Simple resolution

• no destruction of tissue

• Neutralization and destruction of agent, the vessels return to normal permeability, fluid is absorbed.

Regeneration

• replacement of lost or necrotic tissue by tissue of same type

• Surrounding cells replace dead cells

Repair by scar formation

• : Replacement of dead cells by cells of a different type

Necrotic tissue and exudate

• replaced by granulation tissue (vascular in nature)

• Enhanced by angiogenesis, development of new BV, and capillary growth

Collagen formation

to strengthen healing wound (vessels become smaller), color fades

Healing by first (primary) intention

: minimal tissue loss with well approximated wound edges, nice line

• sutured or stapled wound, lacerations, surgery

Healing by second (secondary) intention

: deep or large wounds that heal from inside, scar formation and looks like a crater, not nice

Proliferative (reconstructive) phase - 3-4 days after injury, up to 2 weeks and scar tissue is formed

 Remodeling (maturation) phase - weeks to years, contraction and fading of tissue, tissue strengthens.

Factors Affecting Healing

Insufficient Inflammatory Response

Abnormal Wound Healing

Insufficient Inflammatory Response

1.Poor nutrition - vitamins, minerals, proteins

2. Poor blood flow - lack of O2, and nutrients

Abnormal Wound Healing

1. Dehiscence - reopening of a wound, college inadequate or excessive swelling

2. Wound contractures - scars prevent movement, not as elastic, decrease range of motion

3. Adhesions - scar tissue that binds to adjacent structure

• Ex: abdominal cavity, excessive fibrin

Neoplasia

• Abnormal growth

• Proliferation of cells independent of normal growth control or unresponsive to growth control mechanisms

• Accelerated or uninhibited formation of genetically altered cell

Cancer

• A group of diseases that share common features

• Characterized by abnormal growth, poor differentiation, and invasion of cells

Neoplasm (tumor)

New growth

Metastasis

• Establishment of secondary tumor growth

• New Location from primary tumor

• Through blood or lymphatic system

Epidemiology

• statistical incidence - its the 2nd leading cause of death to heart disease, breast and prostate cancer have the highest chance

• Environmental Risk Factors

  1. chemical carcinogens (Tabacco, vaping, alcohol), radiation (uv rays), pollution (air, soil) diet (food additives), reproductive/sexual behavior, pharmaceutical agents, obesity, chronic inflammation (chronic bronchitis, pancreatitis, HIV)

Genetic Risk Factors

inherited genetic mutations, alterations, and chromosome changes

Ex: breast cancer (bronco 1 and 2 gene) = show if they have a higher risk for cancer.

Types of Tumors

1. Benign

2. malignant

3. Carcinoma In Situ (CIS)

Benign

grow slowly, well differentiated cells, not invasive (remain localized), nonfatal

• similar to tissue of origin, look like the cell before. they stay in the same spot that they started in and can be encapsulated.

Malignant

grow rapidly, poorly differentiated cells, do not remain localized invade surrounding tissues, can spread distantly (metastasis), death possible. Away from the original site.

Signs:

1. anaplasia - no differentiated cells, can’t tell what they are and can’t carry out normal function.

2. Pleomorphic - varied size and shape of cell

Carcinoma In Situ (CIS)

• not malignant, non-invasive

• could be early stages that can lead to more advance stages

Process of carcinogenesis

Initiation  Promotion  Progression  Metastasis

Initiation

cells are exposed to something causing the cells to change or there is a genetic mutation or alteration. Chemical exposure, STD’s

Promotion

chemical promotes the cell to continue the process of change mutated cell changes more and more.

Progression

cells were changed into actual cancer cells and they continue to promote, multiply, they start to form there own unit into a mass, no longer individual cells

Metastasis (5 phases)

4th step, cells break away from the primary cite and go to another part of the body.

5 phases of Metastasis:

1. primary site invasion - original site

2. cell detachment - enter blood or lymphatic system. only way cancer can spread to another part of the body.

3. dissemination - enough builds up that it can get past the WBC and blood to get somewhere else.

4. secondary site attachment - settles in at another cite

5. proliferation - cancer grows at new cite and process starts all over again.

cell changes in neoplasia’s cell membrane

Changes result in failure to respond to normal growth control

Involves the breakdown of any of the following:

1. appropriate cell recognition

2. cellular adhesion - loss of the ability of the healthy cells to adhere

3. intercellular communication

4. uncontrolled proliferation/autonomy - lack of independence

Intercellular communication

• Growth formation

• Continue to divide and migrate into layer - cells don’t look like there tissue origin anymore

cell changes in Neoplasia Nucleus

• Genetic changes inherited by subsequent tumor cells

• Oncogene

• Tumor suppressor genes

• Angiogenesis

angiogenesis

• growth of new blood vessels to supply advanced cancers with oxygen and nutrients, Cancer gets its own blood supply so it can grow. if it gets bigger than 1 mm it gets its own blood supply and gets there own vasculature

Classifications of neoplasms

epithelial origin, CT origin, Neural tissue origin, lymphomas, leukemias, historical

Epithelial Origin

• Papillomas

• Adenomas

• Polyps

• Adenocarcinomas

Connective Tissue Origin

• Sarcomas - Muscle-cell; malignant (grows overtime but could be noticed)

• Osteoma – bone; benign