Exam 1

What is cellular adaption?

cells adapt to the environment to avoid injury

Cell decreasing in size

cell atrophy

cell increasing in size

hyperplasia

cell disorderly growth

dysplasia

conversion of one cell type to another

metaplasia

cell injury

body is unable to maintain homeostasis

reversible cell injury

cells can recover

irreversible cell injury

cell death

Four causes of cell injury

physical agents, radiation, chemicals, biological agents

ischemia

reduced blood supply/oxygen. blood flow is diminished from the tissue

hpoxia

lack of sufficient oxygen within cells

what is the 2nd most common cause of cell injury

hypoxia

anoxia

total lack of oxygen

necrosis cell death results from

hypoxia secondary to severe ischemia

autolysis

autodigestion and necrotic cell contents leak into surrounding intracellular spaces

Liquefaction necrosis

cells digested by own hydrolases, triggered by bacteria

fat necrosis

lipase enzymes break down intracellular triglycerides to free fatty acids. opaque, chalky, white

caseous necrosis

liquefication/coagulative. pulmonary TB, cottage-cheese

coagulative necrosis

interruption of blood flow

coagulative necrosis

interruption of blood flow. protein denaturation

gangrene is caused by:

severe hypoxic injury, impaired blood flow and bacteria

gangrene is common in:

GI tract and legs

dry gangrene

results from coagulative necrosis
dry/shrivled
slow spreading

wet gangrene

liquefication necrosis
extremities and internal organs
clostridium
cold, swollen, black, odor
rapid spread, can lead to death very quickly

gas gangrene

presence of Clostridium (anerobic bacterium, found in soil, releases toxins)
produces enzymes that destroy tissue
progresses rapidly, death in 12 hours

Metastasis

spread of cancer from the site of origin

Clinical Manifestations (CAUTION)

Change in bowel or bladder habits
A sore that doesn't heal
Unusual bleeding or discharge
Thickening or lump in the breast or elsewhere
Indigestion or difficulty swallowing
Obvious change in a wart or mole
Nagging cough or hoarseness

Screening methods for cancer:

routine exams, investigation of symptoms, x-rays, CT, MRI, ultrasound, PET scans

Tumor staging by TNM system:

T: tumor spread
N: node involvement
M: distant metastasis

Cancer staging:

size
degree of invasion
extent of spread
stages 1-4

what are tumor markers

Substances in the body produced by cancer cells that can be found in blood, spinal fluid, or urine.

3 goals for cancer treatment

Curative - cure
Palliative - comfort
Prophylactic - prevent

6 types of cancer treatments

surgery
combination therapy
radiation
chemotherapy
immunotherapy
targeted disruption of cancer

Karyotype

A display of the chromosome pairs of a cell arranged by size and shape.

Phenotype

physical expression

patterns of inheritance

homozygous - identical
heterozygous - different
dominant
recessive

autosomal dominant disorders

- Transmitted from an affected parent to offspring regardless of gender
- Delayed onset
- Examples: Marfan syndrome (1 in 5k) and neurofibromatosis

Marfan Syndrome

- genetic connective tissue disorder
- chromosome 15 - fibrillin (decrease in elasticity)
- no cure

neurofibromatosis

neurogenic tumors
treatment: removal of tumors - palliative

Type 1 Neurofibromatosis

chromosome 17 - cutaneous lesions on skin

type 2 neurofibromatosis

chromosome 22 - tumors of the acoustic nerve + hearing loss

autosomal recessive disorders

- rare
- transmitted from parent regardless of gender
- homozygous allele pairs
- onset early
- deficient enzyme
- PKU and Tay-Sachs

Phenylketonuria (PKU)

- deficiency of liver enzymes phenylalanine hydroxylase - toxic levels accumulate in blood and tissues
- Progressive neurological decline
-Mental retardation
- ALL infants are screened at 3 days old
Dietary restrictions - restrict phenylalanine. eggs, milk, cheese, nuts, chicken, pork or beef
- 1 in 10-15k

Tay-Sachs

- mutation of hexosaminidase A
- lipids accumulate, destroying demyelinating nerve cells
- mental and motor destruction
- rapid decline at 6-10mo. age
- death by 4-5 years
- no cure

x-linked disorders

- females have 50% more chance of being carriers
- men with defected X are affected

Fragile X syndrome

Single trinucleotide gene (FMR1) sequence on the X chromosome

◦Plays a role in synapse development

No cure - supportive care

Male and Female

2nd most common genetic-caused intellectual disability after Down syndrome.

long face and ears

multifactorial inheritance disorders

between environmental and genetic disorders

less predictable

extremely common

ex: cleft lip, clubfoot, heart defects, cancer, hypertension

chromosomal disorders

May be related to an abnormality in chromosomal number and/or structure that occurs in meiosis

Account for most early abortions

More than 60 syndromes

Occur in utero - 15-60 days of gestation is the most vulnerable time for a fetus

Down Syndrome (Trisomy 21)

Risk increases with maternal age (upper 40s) & and environmental exposures (drugs, alcohol, smoking)
Prenatal screening tests

- 4D ultrasounds and checking hormonal levels

- in ultrasound: small square head, upper slant of eyes, and low-set ears.

congenital heart disease

Increased susceptibility to leukemia

Alzheimer's similarities by age 40

Life expectancy 60 years
◦20% die before age 10

tuner syndrome

45 Chromosomes
◦45, X

Females - short, sterile, no ovaries
Coarctation of the aorta
Sterile

◦Gonadal streaks rather than ovaries
Short stature, neck webbing, widely spaced nipples

Not considered intellectually disabled

Treatment - growth hormones or female sex hormones, estrogen

Also called: Monosomy X

Klinefelter Syndrome (XXY)

Males
◦Sterile & gynecomastia

◦Small testicles
High-pitched voice
Sparce body hair

Moderate degree of mental impairment

High-pitched voice
Risk of osteoporosis and breast cancer

Treatment: Testosterone, mastectomy

3 general adaption syndrome stages

1. alarm
2. resistance
3. exhaustion

alarm reaction

initial/emergency
sympathetic
fight-or-flight
releases catecholamines and cortisol

resistance reaction

adapts or alters

exhaustion reaction

adaption failing
disease develops
the body is depleted and damage occurs

Local Adaption System (LAS)

involves only one specific body part
Reflex pain response.
body attempts to limit damage associated with stressors by confining the stressor to one location

adaptive coping

◦Positive - exercise, meditation, good quality sleep, having friends, family, and classmates to talk to, healthy diet.

maladaptive coping strategies

◦Negative - abusing drugs, over-gambling, over-eating, over-shopping

◦Reduce stress to help the immune system

thee lines of immune defense mechanisms

First Line: Innate Immunity - defense

Second Line: Inflammation -attack

Third Line: Adaptive Immunity

innate immunity

Defense mechanisms present at birth and provide an initial response to invasion and injury

Physical, Mechanical, Biochemical Defenses:

◦Epithelial cells of skin, linings of GI, GU, and respiratory tracts
◦Mucus, perspiration, saliva, tears, earwax
◦Normal Flora

Inflammation (2nd line of defense)

◦1. Occurs in vascularized tissues

◦2. Activation is rapid after damage occurs

◦3. Includes both cellular and chemical components

◦4. The response is nonspecific - happens the same way regardless of the past

Acute vs Chronic

Vascular Response (third line)

Hemostasis (coagulation)
◦Clotting cascade
◦Platelets

Vasodilation
◦Increased blood volume
◦More time for fluid movement

Increased vascular permeability
◦Blood vessels become porous
◦Exudation and edema

White blood cell adhesion
◦Phagocytes

Acute Inflammation

self limiting

8-10 days from onset of injury to healing
May lead to chronic inflammation

Local Manifestations
◦Swelling, pain, heat, redness, loss of function

Systemic Manifestations
◦Fever, leukocytosis (presence of inflammation and swelling), increased levels of circulating plasma proteins

chronic inflammation

dense infiltration of lymphocytes and macrophages

would healing phases:

Phase I: Hemostasis or bleeding

Phase II: Inflammation

Phase III: Proliferation and New Tissue Formation. Macrophage cells are cleaning up the wound site

Phase IV: Remodeling and Maturation

Adaptive immunity (acquired or specific immunity)

Immunity that develops over the lifetime of an individual and provides long-term protection against specific invaders

"Memory"

Lymphocytes

Active vs. Passive

active immunity

Develops in response to antigen

Disease and vaccinations
Long lasting;

long-term

passive immunity

Receiving antibodies from external sources
Maternal-fetal transfer

Short-lived - not actively producing the antibodies themselves

IgM

◦Largest antibody
◦First produced in response to antigen

IgG - immunoglobin

◦Most abundant class (80-85%)
◦Provides most protection
◦Protects newborn for first 6 months of life

IgA

◦Found in blood and bodily secretions
◦Tears, saliva, mucus, breast-milk

IgD

◦BCR antigen receptor on the surface of early B cells

IgE

◦Low concentrations in circulation
◦Specialized functions
◦Mediator or allergic responses

Hypersensitivity

Inflated or inappropriate response to antigen

Can be immediate or delayed

Sensitization against antigen

Four types of hypersensitivity

◦Type I: IgE Mediated
◦Type II: Tissue Specific
◦Type III: Immune Complex Mediated
◦Type IV: Cell Mediated

Type I: IgE mediated

Immediate development

Environmental antigens

EX: seasonal allergic rhinitis, peanuts, milk, fish

Most common allergic reactions are type 1

Type II, tissue specific

Immune reaction against specific cell or tissue

Antigen on target cell bind with antibody and are destroyed
Immediate

Type III, Immune complex

◦Formation of antigen-antibody immune complexes in bloodstream
◦Later are deposited in vessel walls or other tissues
◦Immediate
EX:
Systemic lupus erythematosus

Type IV, Cell Mediated

Delayed response
◦24-72 hours
◦Time for T-cells to travel to site
Examples:
◦Contact with poison ivy
◦Metals
◦Late

xHypertensives
A
C
I
D

I \= Allergic Anaphylaxis

II \= antiBody (cytoxic)

III \= immune Complex

IV \= Delayed

4 types of transplants

◦Allogenic - most common, same species. Not identical, but similar tissue type.
◦Syngenic - identical twin to host
◦Autologous - host is donor
◦Xenogenic - another species

Hyperacute tissue rejection

◦Immediate or 3 days after
◦Complement response
◦Tissue becomes permanently necrotic
◦Make antibodies

acute tissue rejection

◦Most common
◦Treatable
◦Between 4 days and 3 months
◦Inflammatory process
◦Impaired function

chronic tissue rejection

◦4 months to years after transplant
◦Likely antibody-mediated response
◦Ischemia

Host Vs. Graft & Graft Vs. Host

Host fights the graft, and the immune system tries to eliminate donor cells

Autoimmune disorders are the most prevalent in \__________

females

Systematic Lupus Erthematosus

•Remission and exacerbations

•Progression varies from mild to severe

•More common in women ages 15-50, Asians, and African Americans

- Affects connective tissue

Chronic inflammatory autoimmune condition

Systemic Lupus Erythematosus
must have 4 or more of the following:

◦Serositis
◦Oral ulcers
◦Arthritis
◦Photosensitivity

◦Blood disorders
◦Renal involvement
◦Immunological phenomena
◦Antinuclear antibody
◦Neurological disorders
◦Malar rash
◦Discoid rash

Malar rash

butterfly rash on face

discoid rash

redness on the fingers

diagnosis for SLE

Blood work for inflammation
◦Erythrocyte sedimentation rate
◦C-reactive protein
◦Antinuclear Antibody
Urinalysis
Diagnostic Criteria

treatment for SLE

No cure

Stress management, exercise, sleep

Pharmacological
◦Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)
◦Corticosteroids
◦Disease-modifying antirheumatic drugs (DMARDs)

plasmapheresis

remove antibodies and immune substances in the body

Human Immunodeficiency Virus (HIV)

•Two primary types
•Type 1 is the most common strain in US
•Type 2 is more common in Africa
•Transmission - blood, bodily fluids

35 million people worldwide
1.2 million in the united states

Phases of HIV

Acute HIV
Chronic HIV
AIDS

stage 2 - a person may not know they have it

acute HIV

flu-like symptoms that occur days to weeks after contracting HIV

Chronic HIV

also known as latent or asymptomatic stage; can last for several years

AIDS

occurs when CD4 cell count falls below 200 cells. makes a person vulnerable to opportunistic infections, and AIDS-defining conditions

HIV symptoms

fever, sore throat, swollen lymph nodes, rash, muscle aches, night sweats, mouth ulcers, chills, fatigue