Pathophysiology

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Pathophysiology
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Study Tips

• Frequent quizzes
• Understand the material
• Read the text
• Study frequently for short periods
• Find a study buddy

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• Turn off cell phones !
• No chewing gums
• Be considerate of others
• Take out what you bring in.
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  5-10m
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• phone or internet.

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Academic Integrity

• Use Professional ethics
• NO
• Plagiarism
• Cheating
• Allowing others to copy from you
• Penalties can be severe !!

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Terminology

• Pathology focus on physical changes in diseased
  organs and tissues
• Pathophysiology abnormal functioning of
  diseased organs and how it applies to medical
  treatment and client care

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• Disease loss of homeostasis, or when physical
  or mental capacities cannot be fully utilized
  (interuption, cessation or disorder in the
  function of an organ or system).
• Etiology cause of the disease
• When the etiology is unknown, the disease is said
  to be idiopathic.

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Categories of etiology

• Genetic disease genes are responsible for a
  structural or functional defect
• Congenital disease genetic information is
  intact, but the intrauterine environment
  interferes with normal development
• Acquired disease disease is caused by factors
  encountered after birth (biological agents,
  physical forces, and chemical agents)

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• Clinical manifestations indications that the
  person is sick
• Symptoms unobservable effects of a disease
  reported by the patient
• Signs observable or measurable traits
• Syndrome - a characteristic combination of signs
  and symptoms associated with a particular disease.

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• Diagnosis identification of the specific
  disease
• Therapy the treatment of the disease to either
  effect a cure or reduce the patients signs and
  symptoms
• Prognosis prediction of a diseases outcome

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Normal Functioning of Cells
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Structural Levels
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Cell
The cell is the building block of each living
organism. Each cell is a self-contained system
that undergoes the functions of energy production
and usage, respiration, reproduction, and
excretion
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Cellular Functions

• Organization
• Metabolism
• Catabolism
• Anabolism
• Responsiveness
• Conductivity
• Movement

• Reproduction
• Growth
• Differentiation
• Respiration
• Secretion
• Excretion

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Cell continued

• All cells composed internally of cytoplasm and
  nucleus, and surrounded externally by cell
  membrane.
• The cytoplasm includes everything inside the cell
  but outside the nucleus

• mitochondria energy
• endoplasmic reticulum and ribosomes protein
  synthesys
• Golgi apparatus secretion of proteins
  synthesized on the ribosomes.
• lysosomes digestive enzymes.
• Cytoskeleton.

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Boundary Cell membrane(plasma membrane)
Composed of lipid molecules in bilayer Phospholip
ids have hydrophobic tail Phospholipids have
hydrophilic heads Also contains embedded
proteins proteins are important for
cell-cell communication receptors for
hormones cell recognition also important for
metabolic processes inside the
cell channels pumps enzymes
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Cellular Components

• Phospholipid bilayer
• Membrane proteins
• Cytoplasm
• Nucleus
• Ribosomes
• Endoplasmic Riticulum
• (protein synthesis and fat metabolism)

• Mitochondria
• Golgi Apparatus holds enzyme helps in metabolism
• ATP fuel made by methochondria
• Lysosomes enzymes that allow cytoplasmic
  digestion to be completed

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Generic Eukaryotic Cell
Generic Cell
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Cell Membrane
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Cytoplasm
Cytosol aqueous gel-like medium Important
metabolic processes occur here Organelles
membrane bound structures Membranes provide
compartments for separation of chemical
reactions
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Rough Endoplasmic ReticulumContains ribosomes
make proteins
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Smooth ERsynthesizes phospholipidsdetoxifies
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Golgi ApparatusPackages protein for export
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MitochondriaThe cells power plant
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Nucleus

• large, membrane-bound organelle that contains
  deoxyribonucleic acid (DNA), the genetic material
  of the cell.
• the DNA is folded up inside the nucleus

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NucleusDNA codes for proteins
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• Movement Through the Membrane
• Lipid-soluble substances, such as oxygen, carbon
  dioxide, alcohol, and urea, move across the lipid
  bilayer by simple diffusion
• Other substances thatnot lipid soluble, i.e most
  small ions, glucose, amino acids, and proteins,
  move between the extracellular and the
  intracellular compartments through pores provided
  by the integral proteins or through
  carrier-mediated transport systems.
• Simple diffusion osmosis,

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• Cell division and reproduction
• Individual cells dont live as long as the
  organism theyre a part of.
• Cell reproduction occurs in two stages
• mitosis, the nucleus and genetic material divide
• cytokinesis, the cytoplasm divides, beginning
  during late anaphase or telophase.
• At the end of cytokinesis, the cell produces two
  daughter

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• The great divide
• Before division, a cell must double its mass
  and content (interphase).
• Chromatin, the small, slender rods of the nucleus
  that give it its granular appearance, begins to
  form.
• Replication and duplication of DNA occur during
  the four phases of mitosis
• Prophase, metaphase, anaphase, and telophase.
  Most cells reproduce as quickly as they die.

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• Meiosis, another type of cell division, occurs in
  the reproductive cells, the egg and sperm.
• Meiosis involves two cell divisions resulting in
  a total of four daughter cells produced, each
  containing 23 single chromosomes rather than 23
  pairs.

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• Pathophysiologic concepts
• The cell faces a number of challenges through
  its life. Stressors, changes in the bodys
  health, disease, and other extrinsic and
  intrinsic factors can alter the cells normal
  functioning.
• Adaptation
• Cells generally continue functioning despite
  challenging conditions or stressors. However,
  severe or prolonged stress or changes may injure
  or destroy cells. When cell integrity is
  threatened, the cell reacts by drawing in its
  reserves to keep functioning, by adaptive changes
  or by cellular dysfunction.

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• If cellular reserve is insufficient, the cell
  dies. If enough reserve is available and the body
  doesnt detect abnormalitiesgt
• The cell adapts by
• atrophy,
• hypertrophy,
• hyperplasia,
• metaplasia, or
• dysplasia.

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Cells change to adapt to their environment
Atrophy shrinkage decrease in cell size.
Reversible Due to decreased use
(disuse) decreased blood supply decreased
nutrition denervation, or reduced endocrine
stimulation Of tissues or organs may be due to
cell shrinkage or due to cell death.
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Atrophy
? Workload (or disease state)
? Efficiency -OR-
? Functionality in disease state
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Hypertrophy an increase in the size of a cell due
to an increased workload. It may be normal or
abnormal. Hypertrophy is primarily seen in
cells that cannot adapt to increased work by
increasing their numbers through mitosis (cardiac
and skeletal muscle cells).
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There are three main types of hypertrophy
-Physiologic hypertrophy (i.e., increased
muscle bulk through exercise). -Pathologic
hypertrophy( hypertrophy of the left ventricle in
response to longstanding hypertension)
. -Compensatory hypertrophy (the loss of one
kidney causes the cells of the remaining kidney
to undergo hypertrophy).
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Hypertrophy
? Size ? of organelles
? Workload (or disease state)
? ability to meet demands! -OR-
? Functionality in disease state
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Hyperplasia Hyperplasia, an increase in the
number of cells, caused by increased workload/
hormonal stimulation. It can only occur in cells
that undergo mitosis ( liver, kidney, and
connective tissue cells). Hyperplasia may be
Physiologic (monthly in uterine endometrial
cells) . Pathophysiologic (with excessive
hormonal stimulation, which is seen
in acromegaly) . Compensatory (cells of a
tissue reproduce to make up for a
previous decrease in cells liver cells
after surgical removal of sections of liver
tissue).
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Hyperplasia
? Workload Physiological state
? tissue size by ? of cells
2 types Compensatory Hormonal
? ability to meet demands! ...
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Hyperplastic endometrium
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• Metaplasia
• is the replacement of one adult cell with another
  adult cell that can better endure the change or
  stress.
• Its usually a response to chronic inflammation
  or irritation the change in the cells of the
  respiratory passages from ciliated columnar
  epithelial cells to stratified squamous
  epithelial cells in response to years of
  cigarette smoking.
• Stratified epithelial cells are better able to
  survive smoke damage. Unfortunately, they do not
  assume the vital protective role of ciliated
  cells.

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Metaplasia
Ex Cigarette Smoking
Pathological
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Dysplasia In dysplasia, deranged cell growth of
specific tissue results in abnormal size, shape,
and appearance.adaptive and potentially
reversible, they can precede cancerous changes.
The most common sites of dysplasia are the
respiratory tract (especially the squamous cells
present as a result of metaplasia)and the
cervix. Cervical dysplasia usually results from
infection of the cells with the human papilloma
virus (HPV). Dysplasia is usually rated on a
scale to reflect its degree, from minor to
severe.
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Dysplasia
Epithelial Tissue
Pathological
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Cerical Dysplasia
Normal Tissue
Abnormal Tissue
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• Cell injury A persons state of wellness and
  disease is reflected in the cells.
• Injury to any of the cells components can lead
  to illness.
• One of the first indications of cell injury is a
  biochemical lesion that forms on the cell at the
  point of injury.
• This lesion changes the chemistry of metabolic
  reactions within the cell. Consider, for example,
  a patient with HIV. The cells of the immune
  system may be altered, making the patient
  susceptible to infection.

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• Draw on your reserves, adapt, or die
• When cell integrity is threatened (toxins,
  infection, physical injury, or deficit injury),
  the cell reacts in one of two ways
• by drawing on its reserves to keep functioning
• by adapting through changes or cellular
  dysfunction.
• If enough cellular reserve is available and the
  body doesnt detect abnormalities, the cell
  adapts.
• If there isnt enough cellular reserve, cell
  death (necrosis) occurs. Necrosis is usually
  localized and easily identifiable.

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Mechanisms of Injury

• Hypoxic
• Chemical
• Structural
• (traumatons next semester!)
• Infectious
• Immunologic / Inflammatory

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Hypoxic Injury
? Atmospheric Oxygen
? Respiratory Function
Loss of Hb
? Cardiovascular Function
? Hb function (CO)
? erythropoiesis
Most Common Cause of Cellular Injury!
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Hypoxic Injury (pathway 1)
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Hypertrophy increase in cell size We'll see
this in heart, kidney (and others) w/
pathology NOT due to increased cell volume or
fluid Rather, due to increased protein synthesis
within the cell, or decreased protein
breakdown Result is increased protein in
organelles
Hyperplasia increase in cell number Due to
increased cell division Uterus and breast
tissue Parathyroid gland in kidney
failure Liver (compensatory hyperplasia)
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Metaplasia replacement of one cell type with
another Reversible An example ciliated
columnar epithelium replaced by stratified
squamous epithelium
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Dysplasia change in cell resulting in abnormal
cell size, shape or organization We'll see this
in respiratory tract, cervix w/ pathology In
mature cells only Immature cells would be
expected to change in size, shape as they grow
and mature Considered a reversible
change Neoplasia associated with a malignant
tumor
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Intracellular accumulations

• Buildup of substances the cell cant use or
  dispose of.
• Normal body substances
• Abnormal products from inside the body (inborn
  errors of metabolism)
• Substances from outside the body (transient or
  permanent)

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Cellular injury cell unable to maintain
homeostasis

• Causes of cell injury
• Deficiency lack of a substance necessary to the
  cell
• Intoxication or poisoning presence of a toxin
  or substance that interferes with cell
  functioning
• Trauma physical injury and loss of cells
  structural integrity

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Deficiencies Deficiency in oxygen most
important
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Hypoxia deficiency in oxygen at cell Due to
Decreased oxygen in air Decreased hemoglobin
or decreased oxygen transported to
cells Diseases of the respiratory and/or
cardiovascular system
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Important to cell because of oxidative
phosphorylation, which results in the
production of ATP Oxidative need oxygen to
produce ATP ATP needed by cell for metabolism,
cell life
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Cellular response to hypoxia Decreased
mitochondrial reactions ? decreased ATP
produced ? decreased energy Ion pumps cease,
so can't regulate ions into/out of cell (ATP
needed for this) Can't pump Na and water out of
cell, so get cell swelling ? organelle swelling
? cell death
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• Ischemia is inadequate blood supply to a cell or
  tissue.
• Ischemia can cause hypoxia.

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Intoxication (or introduction of toxins into the
cell) Effect on cell depends on toxin and on
cell Some examples Lead -- injures nervous
system CO -- deprives body of oxygen Ethanol --
effects central nervous system
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Trauma -- physical disruption of cells Ex
abrasion, cutting, burns, microorganisms etc.
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Free radicals uncharged atom or group of atoms
with an unpaired electron Formed by
radiation, redox reactions, chemicals Atom is
unstable needs to gain or lose an electron can
alter chemical bonds in proteins, lipids,
carbohydrates and nucleic acids can cause chain
reaction in cell
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Apoptosis

• fallen apart
• Regulated cell death
• During development
• Worn out cells
• Diseased cells (tumor suppressor p53 gene,
  natural killer or Tc cells)

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Necrosis

• Messy cell death
• Initiates inflammation
• Gangrene large mass of tissue undergoes necrosis

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Infections agents Microorganisms can invade and
harm cells Cell injury can have effects on the
entire body Examples fever, pain, increased
heart rate