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A set pathological process with well-defined signs and symptoms
Disease
Any indication of disease perceived by the patient, usually subjective
Symptom
Any objective evidence of disease or dysfunction. An observable physical phenomenon witnesses or interpreted by the clinician
Sign
The science and study of the causes of disease and their mode of operation
Etiology
The pathologic, physiologic, or biochemical mechanism resulting in the development of a disease or morbid process. All cellular events and reactions leading up to and occurring during the disease
Pathogenesis
The etiology of any disease begins with individual _____
Cell injury
Loss/lack of blood supply. Metabolic substrates build up in the tissues, injuring them faster
Ischemia
Act of taking up oxygen by tissues
Perfusion
Tissue death
Infarction
Deprived of oxygen loss of aerobic oxidative respiration
Hypoxia
An absence of oxygen supply to an organ or tissue
Anoxia
Every human cell evolves from the _______
fertilized egg
An undifferentiated (stem) cell capable of developing into any type of body cell is said to be ____
Totipotent
During _______ cells differentiate and therefore become specialized
mitosis
This cell type typically sits on a basement membrane
Connective tissue cell?
Epithelial cells
Mesenchymal cell
What are the two types of epithelial cells?
1. Lining Epithelial
2. Secretory Epithelial
____ epithelium means there is one layer of cells
Simple
_____ epithelium means there is more than one layer of cells
Stratified
Cells that are wider than they are tall (plate-like)
Squamous cells
Boxlike cells, approximately as tall as they are wide. Cube-shaped cells
Cuboidal cells
Cells that are taller than they are wide
Columnar cells
What kind of epithelium is found in the blood vessels?
Simple squamous epithelium
What kind of epithelium is found in the stomach?
Simple columnar, non-ciliated
What kind of epithelium is found in the larynx and respiratory tract?
Stratified squamous epithelium
What kind of epithelium is found in the urinary bladder?
Transitional epthelium
An organism with a complex cell or cells, in which the genetic material is organized into a membrane-bound nucleus or nuclei
Eukaryote
An organism that have DNA and are organisms such as bacteria that lack nuclei and other complex cell structures.
Prokaryotic
Non-living obligate intracellular parasites. Made only of a nucleic acid and a protein coat
Viruses
a small, spherical to rod-shaped, membrane-bounded cytoplasmic organelle, the principal sites of ATP synthesis (Krebs Cycle) found in eukaryotic cells only.
Mitochondrion
usually created aerobically (more efficient than anaerobically)
ATP
The cell's outer membrane made up of a two layers of phospholipids with embedded proteins. It separates the contents of the cell from its outside environment, and it regulates what enters and exits the cell. Internal receptors allow the cell to communicate with the external
environment
Plasma Membrane
Certain things can pass through the Plasma Membrane either ______ and or _____
actively and or passively
The process in which a cell takes in fluid together with its contents by forming narrow channels through its membrane that pinch off into vesicles, and fuse with lysosomes that hydrolyze or break down contents
Pinocytosis (cell drinking)
The process of ingestion and digestion by cells of solid substances, for example, other cells, bacteria, bits of necrotic tissue, foreign particles
Phagocytosis (cell eating)
What are the internal factors that cause cell injury?
1. Immunologic reaction - auto immune
2. Genetic derangements - cell line specific
3. Nutritional imbalance - non essential cells first
What are external factors that cause cell injury ?
1. Hypoxia
2. Physical agents - temperature, trauma, radiation
3. Chemical agents and drugs
4. Infectious agents
What is the difference between hypoxia and ischemia?
Hypoxia is a loss of O2 and ischemia is a loss of blood supply
Which are more dangerous/lethal, internal or external causes of cell injury/death?
Internal are more dangerous (immunologic reactions, genetic derangements, nutritional imbalances). This is because external factors are easier to control
Ubiquitin is one of the most highly conserved __________. It is found in the ________, ___________ and __________
eukaryotic proteins
nucleus, cytoplasm, cell-surface membrane
What is the purpose of ubiquitin?
to protect itself from itself
Ubiquitin is a small _________ that is involved in ___________ and is a marker for __________ and __________
polypeptide
histone modification
intracellular proteins transport
breakdown
________ have been found to produce proteases that denature "bad proteins" when Identified by Molecular Chaperones.
Lysosomes
what do lysosomes denature?
What do they produce to do this?
bad proteins
proteases
Failure of the ubiquitin system has been linked to ____, ____, ____ and _____
Alzheimers, Parkinson's, ALS, cataracts
Hyperactive ubiquitin system has been linked to _____ and _____
Non-insulin dependent diabetes mellitus (NIDDM)
muscle wasting in aging
What are the adaptive responses of the cell?
Atrophy
Hypertrophy
Hyperplasia
Metaplasia
Dysplasia
Atrophy is reduced _____ or ______ of cells or organ in response to different situations
function or size
4 causes of atrophy
1. interruption of trophic signals
2. persistent cell injury
3. increased pressure
4. chronic disease
Atrophy due to persistent cell injury is MC caused by ____
Inflammation
Example: atrophy of gastric mucosa with chronic gastritis
What is an example of atrophy secondary to interruption of trophic signals?
Endometrium atrophies after menopause secondary to decreased estrogen production
Where is atrophy caused by increased pressure is most commonly located?
sacral decubitus
What are some chronic disease that can cause atrophy?
1. Cancer
2. AIDS
3. CHF
Increase in cell size and function, typically in response to increased demand or increased trophic signals
Hypertrophy
Increase in number of cells in an organ or tissue
Hyperplasia
This often happens together with hypertrophy but also can happen individually as well.
Hyperplasia
Give some examples of normal hyperplasia (3)
Hormone stimulation causing an increase in endometrial/uterine cells during puberty or early menstrual cycle
Increase in O2 demand at high altitudes, causing polycythemia
long standing inflammation
Chronic injury such as long standing inflammation or chronic physical or chemical. Ex: injury- tight shoes can lead to a corns/callous. This is any example of?
Hyperplasia
Why is it dangerous for a patient with sickle cell disease travel to Denver without slowly acclimating ?
Due to the high altitude, the patient will become hypoxic and start producing more Hb S polymers that can cause acute chest syndrome (basically their lungs fill up with blood)
Conversion of one differentiated cell to another
Metaplasia
Barrett's esophagus forms as a result of long-term exposure of gastric acid in the esophagus. Esophageal cells are differentiated to gastric cells. This is an example of ?
Metaplasia
A patient with chronic GERD who has Barrett's esophagus, their normal _______ epithelium is replaced with ______ metaplasia.
Stratified Squamous epithelium
Simple Columnar metaplasia
In the early stages of Barrett's esophagus, is it reversible?
YES! *
Disordered growth and maturation of the cellular components of a tissue. Occurs in response to a ________ and will usually regress
Dysplasia
persistent injurious influence
Dysplasia is the first step in __, ___ and __ cancers
Bladder, cervical and prostate cancer
Occurs when environmental changes exceed the cells capacity to maintain normal homeostasis. This is the "point of no return".
Cell injury
Inability to adapt to stress, a cell will suffer severe damage leading to death
NECROSIS
Failure of the Na+/K+ pump leads to _____, which is reversible
Cloudy swelling
Cloudy swelling leads to ____, which is also reversible
Hydropic degeneration (cellular swelling) (reversible if insult is removed in time)
Hydropic degeneration (cellular swelling) leads to ____, which is irreversible
Necrosis
This is usually due to decrease blood flow, ATP is produced anaerobically under these conditions and its usually reversible.
Ischemia
Injury to tissue that occurs after blood flow is restored
Ischemia/Reperfusion injury
Explain the pathophysiology being reperfusion injury
Decreased oxygen to an area leads to generation of free radicals. Reperfusion of the area brings oxygen to these free radicals to form reactive oxygen species (ROS)
Short term ischemia=
Longer=
Too long=
reversible
ROS could lead to death of cell
death of cell
Nectrosis is accidental, passive secondary to _________ which causes (4 things and) Leads to eventual cell death.
hostile environment
cell/organelle swelling, ATP depletion, increased plasma membrane permeability, release of macromolecules.
Fat necrosis can be seen in end stage _____
Pancreatitis
Liquefactive necrosis can be due to ____
Abscess
What is an example of caseous necrosis?
TB
Coagulative necrosis is the most common that involves the shrinkage of the nucleus caused by condensation of chromatin
Pyknosis
Pyknosis involves shrinkage of the ____ caused by condensation of ______
Nucleus
chromatin
Destructive fragmentation of the nucleus
followed by disintegration (_______)
Karyorrhexis
Karyolysis
List the steps in the swelling stage of the necrosis pathway
1. Decreased blood supply
2. Decreased delivery of O2 and glucose
3. Anaerobic glycolysis
4. Increased lactate
5. Decreased intracellular pH
6. Decreased ATP production
7. Distortion of the plasma membrane pumps skews the ionic balance of the cell
8. Calcium accumulates inside the cell
9. Cell swelling results (cloudy)
List the steps in the definitive necrosis pathway (irreversible)
1. Decreased blood supply
2. Decreased delivery of O2
3. Impairs mitochondria electron transport
4. Decrease in ATP production
5. Increased production of ROS
6. Release of Cyt C to cytosol
7. Initiate apoptotic cascades
8. Cell death
This pathway ensues if no intervention is made to stop it
Programmed cell death, a signaling mechanism by which cells commit suicide
Apoptosis
Inflammation is not seen in the vicinity of ____ cells, but is often seen in areas of ____
No inflammation with apoptotic cells
Inflammation present in areas of necrosis
Apoptosis triggered from activation of certain membrane receptors by their ligands
Extrinsic pathway of apoptosis
Apoptosis triggered by diverse intracellular stresses and is characterized by a central role for mitochondria
Intrinsic pathway of apoptosis
perforin/granzyme pathway of apoptosis: Caused by the _________ with their cellular target. This pathway is activated by the transfer of _______ from the _______ to its _______
interaction of cytotoxic T cells
granzyme B
killer cell
intended victim
Give two examples of initiation of apoptosis at the cell membrane
1. Binding of tumor necrosis factor-alpha to its receptor (TNFR) triggers apoptosis
2. Recognition of FasL by its receptor Fas
Apoptosis pathways are not rigid but most intermediate enzymes that transduce proapoptotic signals belong to a family of cysteine proteases called ______.
Capsids
What are two death receptors on the surface of cell membranes which are activated upon binding to their ligands and trigger a downstream series of events that end in apoptosis?
1. TNFR
2. Fas
This gene preserves the viability of an injured cell when DNA damage can be repaired, but propels it toward apoptosis in the presence of irreparable damage
P53
System of local reaction of tissues and microcirculation to a pathologic insult. Its a protective response to minimize the initial addicts of the injury.
Inflammation
What are the two types of inflammation?
1. Acute
2. Chronic
Inflammation that lasts minutes to days and is characterized by an accumulation of neutrophils
Acute inflammation
inflammation that lasts weeks to months or longer can be due to prolonged infections, exposures to toxic agents or autoimmune.
chronic inflammation
What are the 5 cardinal signs of inflammation?
Rubor (redness)
Tumor (swelling)
Dolor (pain)
Calor (heat)
Loss of function
What is the main blood cell line associated with acute inflammation?
Neutrophils
What are the main cells of chronic inflammation?
Macrophages and lymphocytes (B and T)
What is the role of fibroblasts in the inflammatory process?
Fibroblasts are important in wound healing (lead to fibrosis)
Cells that reside in the tissue and release chemicals important in the inflammatory response
Mast cells
(I think M and M , for Muscle (because thats a tissue) and Mast cell)