Ch 2- Cell Responses and Adaptations (Dobson Lect) Flashcards
Define:
Disease
“Any deviation from or interruption of the normal structure or function of a part, an organ, or system of the body as manifested by characteristic symptoms and sign ; the etiology, pathology, and prognosis may be known or unknown”
Define:
Disorder
“A derangment or abnormality of function; a morbid physical or mental state/condition”
Define:
Neoplasm
“Any new and abnormal growth; specifically a new growth of tissue in which the growth is uncontrolled and progressive”
Define:
Syndrome
“A set of symptoms that occur together; a symptom complex; the sum of signs of any morbid state”
What is an adaptation?
Adaptations are reversible functional and structural responses to changes in physiologic states and some pathologic stimuli
What are 4 examples of adaptation that were discussed in lecture?
Hypertrophy
Hyperplasia
Atrophy
Metaplasia
Is cell injury reversible?
UP TO A CERTAIN POINT IT IS
If the stimulus persists or is severe enough, the cell will suffer from irreversible injury
Define:
Hypertrophy
Increase cell and organ size
*Hyper-trophy = you always want a BIG trophy*
Define:
Hyperplasia
Increased cell numbers
Define:
Atrophy
Decreased cell and organ size
Define:
Metaplasia
Change in phenotype of differentiated cells
What does the difference in heart size reveal?
What was the mechanism of this?
Hypertrophy
Increased production of cellular proteins
This comparitive image demonstrates what type of hyperplasia?
Physiologic hypertrophy of the uterus
A hallmark of cardiac metabolism before birth is?
The predominance of carbohydrate use for energy
After birth, cardiac metabolism switches energy source to the utilization of?
Oxidation of fatty acids
Why is it important to know the differences in fetal vs adult cardiac metabolism energy sources?
(*reminder: fetal uses carbohydrates, adult uses fatty acid oxidation)
It’s important because in several pathophysiologic conditions [ex: hypoxia, ischemia, hypertrophy, atrophy, diabetes, and hypothyroidism] the postnatal heart returns to “fetal” gene program
What is this image an example of?
(Left : Normal kidney)
(Right: (Physiologic compensatory hyperplasia)
***This is physiologic because it was due to loss of sister kidney. This kidney developed more renal cells to compensate.
What is one of the most concerning outcomes from repetitive hyperplasic events?
Transformation to malignancy
Where are the most common sites for developing cancerous malignancy?
Sites where hyperplasia are common!!!
Examples Include:
Breast
Endometrium
Prostate
What is this image revealing?
Hyperplasia can become cancerous if checkpoints go unregulated
What is this a picture of?
A patient with ALS that shows atrophy of the thenar eminence
What are the common reasons for atrophy? (6)
- Decreased workload
- Loss of innervation
- Diminished blood supply
- Inadequate nutrition
- Loss of endocrine stimulation
- Pressure
What is the mechanism of atrophy?
Atrophy results from:
Decreased protein synthesis (due to reduced metabolic activity) and increased protein degradation in cells (proteosomes and/or autophagy)
What is the mechanism of metaplasia?
Result of a reprogramming of stem cells in normal tissues, or of undifferentiated mesenchymal cells present in connective tissue
The influences that predispose to metaplasia, if persistent, can intiate _______________
Malignant transformation
Which tissues do NOT have stem cells in them?
What does that mean in terms of metaplasia?
Heart & Brain
Cannot undergo metaplasia!!!
*Likely a test question* cough cough
What is this histologic slide revealing?
Bronchus Metaplasia!!!
Notice the difference in cell types that are directly adjacent to each other
What are the microscopic features of reversible cell injury?
Cell swelling
Fatty change
Features of Necrosis and Apoptosis
Feature: Cell size
What happens with necrosis vs. apoptosis?
Necrosis: Enlarged (swelling)
Apoptosis: Reduced (shrinkage)
Features of Necrosis and Apoptosis
Feature: Nucleus
What happens with necrosis vs. apoptosis?
Necrosis: Pyknosis –> Karyorrhexis –> Karyolysis
Apoptosis: Fragmentation into nucleosome-size fragments
Features of Necrosis and Apoptosis
Feature: Plasma membrane
What happens with necrosis vs. apoptosis?
Necrosis: Disrupted
Apoptosis: Intact; altered structure
Features of Necrosis and Apoptosis
Feature: Cellular contents
What happens with necrosis vs. apoptosis?
Necrosis: Enzymatic digestion; may leak out of cell
Apoptosis: Intact; may be released in apoptotic bodies
Features of Necrosis and Apoptosis
Feature: Adjacent Inflammation
What happens with necrosis vs. apoptosis?
Necrosis: Frequent
Apoptosis: NONE!!!
Features of Necrosis and Apoptosis
Feature: Physiologic or pathologic role
What happens with necrosis vs. apoptosis?
Necrosis: Invariably pathologic
Apoptosis: Often physiologic, means of eliminating unwanted cells, may be pathologic after some forms of cell injury, especially DNA damage
Define:
Karyolysis
Nuclear fading
Define:
Pyknosis
Nuclear shrinkage
Define:
Karyorrhexis
Nuclear fragmentation
Go read morphology box pages 42-44 of robbins
now
What are these blue lines indicating?
Patterns of necrosis
Pie shaped/wedge shaped
(right: liquifactive necrosis of the brain)
What type of necrosis is this?
Caseous necrosis
(Cheese like)
Caseous necrosis is associated with what infection?
TB (mycobacterium tuberculosis)
Caseous necrosis is described as?
Yellow-white and “cheese like”
Caseous necrosis is described as:
“…the necrotic area appears as a structureless collection of fragmented or lysed cells and amorphous granular debris enclosed within a distinctive inflammatory border; this appearance is characteristic of a focus of inflammation known as a _____________”
Granuloma
What are the principal biochemical mechanisms and sites of damage in cell injury?
Mitochondrial damage
Entry of Ca2+
Membrane damage
Protein misfolding, DNA damage
Reduction in ATP levels is a fundamental cause of ______________
Necrotic cell death
Increased production or decreased scavenging of ROS may lead to an excess of these free radicals, a condition called _________________
Oxidative stress
Oxidative stress has been implicated in the following:
- Cancer
- Cell injury
- Aging
- Alzheimers disease
ROS are produced in large amounts by ____________________
Activated leukocytes
Why are ROS generated by neutrophils and macrophages?
Produced during inflammatory reactions aimed at destroying microbes and cleaning up dead cells and other unwanted substances
Where are the most important sites of membrane damage during cell injury?
Mitochondrial membrane
Plasma membrane
Lysosomal membranes
The release of _____________ into the bloodstream occurs by different sources, including primary tumor, tumor cells that circulate in peripheral blood, metastatic deposits present at distant sites, and normal cell types.
cfDNA (cell free DNA)
What are the arrows pointing at?
Apoptotic bodies
What are the two major mechanisms of apoptosis?
Which of the two is most common?
Mitochondrial (intrinsic) pathway ***more common***
Death receptor (extrinsic) pathway
The process of apoptosis may be divided into two phases. What are they?
Initiation phase
Execution phase
Caspases are associated with?
APOPTOSIS
What are the major players in the mechanism of apoptosis?
BCL2 family
Cytochrome C
Caspases
Apoptosome
What is the MAJOR anti-apoptotic protein?
BCL2
What are the MAJOR pro-apoptotic proteins?
BAX and BAK
Describe the death receptor (extrinsic) apoptotic pathway
This pathway is initiated by engagement of plasma membrane death receptors on a variety of cells with the ligand for Fas.
FasL is expressed on T cells that recognize self antigens and on some cytotoxic T lymphocytes.
The death receptor (extrinsic) apoptotic pathway can be inhibited by a protein called?
FLIP
What are specific examples of diseases caused by misfolding of protein?
Cystic Fibrosis
Familial hypercholesterolemia
Tay-Sachs disease
Alpha-1 antitrypsin deficiency
Creutzfeldt-Jacob disease
Alzheimer disease
What is the purpose of autophagy?
Autophagy functions as a survival mechanism under various stress conditions, by maintaining the integrity of cells by recycling essential metabolites and clearing cellular debris.
Dysregulation of autophagy can result in?
Cancer, IBS, neurodegenerative disorders
What are the two examples of exogenous accumulations?
Anthracosis (carbon pigment)
Tattoo (pigment)
What are the three examples of endogenous accumulations?
Lipofuscin
Melanin
Hemosiderin
What are the two types of calcifications?
- Dystrophic
- Metastatic
Where is dystrophic calcification found?
Areas of
Necrotic, damaged or aging tissue
What causes metastatic calcification?
What are some disease states where you would find metastatic calcification? (4)
Hypercalcemia
- Hyperparathyroidism
- Resorption of bone due to bone tumors
- Vitamin D related disorders
- Renal failure
What are the arrows pointing at?
Psammoma bodies
(a round collection of calcium)
–> Associated with benign and malignant lesions
*HE LOVED TALKING ABOUT THIS
