Pathophysiology Midterm 1

Syndemic Factors

2 or more concurrent factors exacerbate prognosis or burden of disease

Epigenetics

Behaviour and environment can change gene expression (DNA/his tone modification, chromatin remodelling, post translation modification)

Pathogenesis

development of disease

Ethiology

Cause/causes of diseases

Diagnosis - Definition + Methods

determination of disease and cause of illness - clinical history, physical examination, differential diagnosis

Prognosis

Eventual outcome of disease, probable outcomes/survivability

Clinical history

History of current illness, medical history, family history, social history, review of symptoms

Differential Diagnosis

Consideration of various diseases/conditions which may also explain patients symptoms

General Diagnostic Test Considerations

Cost, invasive/noninvasive, appropriate for question being asked, false-positive/false-negative ratio

Specificity

People without disease, diagnosed as having it

Sensitivity

People with disease, diagnosed as NOT having it

Clinical Laboratory Tests

Determine concentration of substances altered by disease in BLOOD or URINE

X-Ray

high-energy radiation waves at lower doses to produce images to help diagnose disease

Radiopaque

appears white on film, high density tissues such as bone absorb most of rays

Radiolucent

appears dark on film, low density tissues allow rays to pass through

Contrast media used to outline structures in x-rays:

Barium sulfate, radiopaque oil, intravenous dye, radiopaque tablets, arteriogram, cardiac catheterization

CT Scan

radiation detectors record amount of x-rays or ionizing radiation absorbed by body and feed data into a computer to reconstruct data into an image

Use of CT Scans

Cancer in asymptomatic, abnormalities in internal organs

MRI (magnetic resonance imaging)

computer constructed images of body based on response of hydrogen protons in water molecules when placed in a strong magnetic field

MRI Advantages of CT

no ionizing radiation, detects abnormalities in tissue surrounded by bone (ex. spinal cord), more detailed images

Use of MRI

multiple sclerosis, SUPERIOR to mammogram in detected breast cancer

PET Scans

biochemical functions in brain used to determine metabolic function of organ/tissue. Evaluate changes in blood flow in heart muscle, distuinguish benign from malignant tumor.

PET Scans Disadvantages

very expensive, not widely available, requires special facilities for incorporating isotopes into biochemical compound

Combined PET and CT Scan

pinpoint abnormal metabolic activity, my be better then 2 scans on their own.

Radioisotope

evaluate organ function through uptake and excretion of substances labelled with a radioisotope

Radioisotope Uses

Anemia, Hyperthyroidism, Pulmonary Blood Flow, Cancer Spread, Heart Muscle Damage

Cytology and Histology

Pap smear - identifies abnormal cells in fluids/secretions. Biopsy - tissue samples to determine abnormal structural/cellular patterns (liver, kidney, bone marrow)

Electrical Activity

measures electrical impulses associated with body functions and activities

Types of Electrical Activity

ECG - heart, cardiac cycle.

EEG - brain, brain waves.

EMG - skeletal muscle during contraction and at rest.

Endoscopy

Examine body using rigid/flexible tubular instruments equipped with lens/light source.

ex.

- bronchoscope: trachea and major bronchi

- cytoscope: bladder

- laparoscope: abdomen

Ultrasound

Mapping echoes produced by high frequency sound waves, reflect change in tissue density to produce images

Ultrasound Uses

- Study uterus during pregnancy

- Study structure and function of heart valves

Preventative treatment example

ex. statins to reduce risk of cardiovascular incidents

Specific treatment example

antibiotics to treat an infection

Symptomatic treatment example

Alzeiheimers treatment to manage cognitive and behavioural symptoms

Lecture 1 Summary

- Diseases persist along a continuum

- Prevention is important in all stages (self/public health guidance)

- Complex interplay of genetics, environment, behaviours, syndemics, epigenetics which contribute to disesase risk and prognosis

- Examination, screening, testing diagnosis and treatment are provided by health care system

- Should be targeted, evidence based

- Benefits/harms, costs/effectiveness, invasiveness need to be weighted when choosing a test

Nucleus

Contains genetic information, directs metabolic function, has nuclear membrane which allow cytoplasmic communication

Cytoplasm

surrounds nucleus, carry out directions of nucleus

Cell

basic structural/functional unit of human body

Tissues

group of cells performing the same functions

Organs

group of tissues

Organ Systems

group of organs functioning together

Functioning organisms

integrated organ systems

Organization of Cells

Cells

Tissues

Organs

Organ systems

Functioning organisms

(abnormality at any level can cause disease)

Nucleus Structure

two types of nucleic acid (DNA + RNA) combined with protein + nuclear membrane

Cytoplasm Structure

Protoplasm surrounded by selectively permeable membrane with pores/channels + contains organells

Mitochondria

Rod shaped structures convert food into energy to make ATP to fuel reactions in cell

Endoplasmic Reticulum

Network of tubular channels enclosed by membranes

Rough ER with ribosomes, smooth ER with lipids

Golgi Apparatus

Membrane-like sacs near nucleus to synthesis large carbohydrate molecules

Lysosomes

Cytoplasmic vacuoles with digestive enzymes + peroxisomes with enzymes to decompose hydrogen peroxide

Centrioles

Short cylinders adjacent to nucleus, move to opposite poles of cell during division to form mitotic spindle

Cytoskeleton

Intermediate filaments to reinforce cell's interior and keep shape

Identification and characterization can help diagnose disease - ex. destruction of cytoskeleton for Alzheimers or cell of origin for cancer

Cell Membrane Structure

selectively permeable membrane, lipid bi-layer, contains many different proteins/glycoproteins/glycolipids

Movement of materials in and out

Oxygen/nutrients (Na+, K+, Ca2+) must come in, and waste must go out, through the selectively permeable membrane

Diffusion

solutes move from concentrated to dilute solution

DCD

Osmosis

Water molecules move from dilute to concentrated solution

ODC

Tonicity

Hypertonic (high concentration), hypotonic (low concentration), isotonic (normal)

Hypertonic and hypotonic can cause disease

Active transport

movement from low concentration to high concentration; requires cell to expand energy due to concentration gradient

Na+/K+ pump

Na+ is predominant in plasma

K+ is predominant in cells

Phagocytosis

Ingestion of particles too large to pass across cell membrane

cytoplasmic processes fuse to engulf particle within a vacuole into cytoplasm

Endocytosis

internalization materials by engulfing (small particles)

receptor median

Pinocytosis

ingestion of fluid and very small molecules/ions

Exocytosis

remove wastes/products (hormones, enzymes, etc.) from cells through secretory vessels from Golgi

make membrane proteins

Types of tissue

Epithelium, connective/supporting, muscle, nerve

Epithelium

protection, absorption, gladular secretes mucus/sweat/oil/enzymes/hormones

exocrine/endocrine glands

endothelium = layer of simple squamous epithelium inside of heat/blood vessels

mesothelium = layer of simple squamous epithelium that lines pleural, pericardial and peritoneal cavities

Types of Epithelia

Simple: squamous (capillary walls, alveoli walls), cuboidal (kidney, pancreas), columnar (stomach, colon, rectum)

Stratified:

pseudo (upper airways, trachea),

transitional (bladder, urethra), squamous (esophagus, mouth, vagina)

Connective and Supportive Tissues

hematopoietic (blood), lymphatic (lymphocyte), adipose (insulation, energy, padding)

Cartilage: hyaline, elastic, fibrocartilage

Bone

Subcutaneuous tissue (deepest skin layer, support/protect organs and muscles)

Types of Connective Tissue Fibers

collagen fibers (joints, skin) connect and support tissues, contain collagen fibers

elastic fibers (blood vessels, lungs, skin) responsible for distensibility of arteries, contain elastin protein but not as elastic as collagen

reticular fibers form framework of organs (liver, spleen, LN), similar to collagen BUT thin/delicate

Muscle Tissue

Muscle cells contain filaments of actin (cytoskeleton) and myosin (motor protein to pull actin filaments together through contraction)

Striated Muscle moves skeleton and moves under conscious control

Types of Muscles

Smooth muscle = located in walls of hollow internal organs (gastrointestinal, biliary, reproductive tracts, blood vessels) and functions automatically NOT under conscious control

Cardiac Muscle is found only in heart, resembles striated muscle but has feature common to both smooth and striated muscles

Nerve Tissue

Neurons = nerve cells that transmit nerve impulses

Central body:

dendrites (transmit toward cell body)

axos (transmit away from cell body)

Neuroglia (nerve tissue)

supporting cells more numerous than neurons

astrocytes = star shaped cells which provide structure/support and nourishment to neurons

Oligodendrocytes (nerve tissue)

small cells surrounding nerve cells (myelin)

schwann (PNS)

oligodendrocytes (CNS)

Microglia (nerve tissue)

phagocytic cells for immune protection

macrophages of NS

Organs and Organ Systems

Parenchymal cells (primary functional cells of an organ)

Parenchyma (functional cells of an organ)

Stroma (tissue that forms the supporting framework of an organ)

**parenchyma is more inside, stroma more outside)

Fertilized ovum differentiates into...

trophoblast (peripheral group of cells which forms placenta and other structures to support and nourish embryo)

inner cell mass (inner group of cells; will give rise to the embryo, arranged in 3 distinct germ layer: ectoderm, mesoderm, endoderm

3 types of Germ Layers

ectoderm: outer layer which becomes external covering of body that interacts with external environment (skin, nervous system, ears, eyes)

mesoderm: middle layer (CT, muscle, bone, cartilage, heart, blood, blood vessels, and major portions of urogenital system)

endoderm: inner layer (epithelium of pharynx, respirtaory tract, liver, biliary tract, pancreas, some parts of urogenital tract)

Atrophy

reduction in cell size in response to diminished function, inadequate hormonal stimulation, reduced blood supply

ex. shrinkage of breasts/genitals following menopause due to less estrogen

Hypertrophy

increase in cell size without increase in cell number

ex. muscles of a weightlifter

Hyperplasia

increase in both cell size and number in response to increased demand

ex. glandular tissue of breasts during pregnancy in preparation for lactation

Cell necrosis

irreversible damage causing cell damage and leads to cell death

Apoptosis

programmed cell death

all normal cells have a predetermined life span, number of functional cells determined by the balance between cell growth and cell death

ex. virus infected cells

Aging and the cell

genetic and environmental factors play role in cell longevity

Hayflick limit: normal cells have a fixed number of divisions before they die

Lecture 2 Summary

Cells (organelles) - tissues - organs - organ systems - functioning organism

Cells = controlled movement of materials, active/passive transport, diffusion/osmosis, phagocytosis/pinocytosis, adaptiation - atrophy/hypertrophy, hyperplasia/metaplasia/dysplasia, apoptosis/necrosis

Tissues (4 types): epithelium (protection, absorption, gladular tissues), connective (bone, cartilage, adipose, hematopoietic/lymphatic), muscle (striated, smooth, cardiac), nerve (neurons and neuroglial cells in CNS/PNS)

Derived from germ layers:

ectoderm (outer layer becomes external covering of body that will interact with external environment), mesoderm (middle layer of CT, muscle, bone, cartilage, heart, blood/blood vessels), endoderm (epithelium of pharynx, respiratory tract, liver, biliary tract, pancreas)

Parenchyma/stroma: organized to form organs/organ systems to carry out various bodily functions

Human genome

20,000 genes, 46 chromosomes in 23 pairs

all non-germinal cells are diploid (46 chromosomes)

germinal cells (sperm/ovum) are haploif (23 chromosomes, no pairs)

Aneuploidy

extra/missing chromosome

ex. trisomy 21 - down syndrome

Genotype

sequence of DNA

Phenotype

expressed traits derived from genotype

Expression of genes

dominant gene expressed in either homozygous or heterozygous state (ex. Aa or AA - brown eyes) both have capital letter

recessive gene expressed in only homozygous state (ex. aa - blue eyes) does not have capital letter

Factors of Epigenetics

diet, obesity, physical activity, alcohol consumption, environmental pollutants, pyschological stress, depression, shift work

Karyotype

used to study composition and abnormalities in chromosomes in terms of number/structure

use human blood and culture

Chromosomes

double coils of DNA combined with protein

in pairs, 1 from male parent 1 from female

23 pairs in humans (22 autosomes + 1 sex)

Nucleosomes

chromosomes wrapped around histone

Structure of DNA molecule

DNA helix wraps around histone molecules to form a chromatin fibre

DNA Structure in Chromosome

CGAT

phosphate group, deoxyribose

nitrogen containing base (CGAT)

purine bases: adenine, guanine (A, G)

pyridine bases: thymine, cytosine (T, C)

CGAT forms different patterns of DNA nucleotides

*only 1-2% of CGAT codes for proteins, the others code for other stuff*

Semi-conservative replication

used to replicate DNA molecules

both chains seperate and act as templates for copies to form 2 new identical strands of DNA

Translation of DNA into Protein

DNA directs synthesis of enzymes and other proteins by ribosomes

DNA for expressed genes transcribes into mRNA

pre mRNA processed to remove non-coding regions (introns) and splice remiaing exons (coding regions)

mRNA exported to ER to allow for translation in ribosomes

rRNA carries out protein synthesis in ribosomes

tRNA transfers amino acids in sequence (anticodon) according to mRNA codons to produce proteins

Mitochondrial Genes

mitochondria contains small amounts of DNA

code for ATP generating enzymes

inherited differently than genes on chromosomes

NOT transmitted from parent to child

Cell division

mitosis - somatic cells

meiosis - germ cells

Mitosis

no reduction in chromosomes

each of 2 new daughter cells receive same # of chromosomes as parent cells