Pathology I Flashcards
The tendency of the body to seek and maintain a condition of balance or equilibrium within its internal environment, even when faced with external changes
Homeostasis
Refers to the mechanisms of development and progression of disease, which account for the cellular and molecular changes that give rise to the specific functional and structural abnormalities that characterize any particular disease
Pathogenesis
Refers to why a disease arrises
Etiology
Describes how a disease develops
Pathogenesis
Metabolism, differentiation and specialization, neighboring cells, availability of substrates are all?
Constraints on a cell
Reversible functional and structural responses to changes in physiologic and some pathologic stimuli to maintain homeostasis
Adaptations
If the limits of adaptive response are exceeded, we see
Reversible injury, irreversible injury, and cell death
New cells from proliferating mature cells & stem cells
Hyperplasia
Non-dividing permanent cells (muscle, nerve) get bigger
Hypertrophy
What is an example of
- ) Physiologic hypertrophy?
- ) Pathologic hypertrophy?
- ) Skeletal muscle
2. ) Cardiac muscle
Endometrial & prostatic hyperplasia is an example of
Pathologic hyperplasia
An increase in the size of cells => increase in size of
Organ
Occurs in tissue whose cells have a limited capacity to divide
Hypertrophy
Turn on signal transduction pathways => induction of genes => protein synthesis
Mechanical and trophic triggers of hypertrophy
The normal adult prostate gland shows compound tubulo-acinar glands lined by pseudostratified columnar and/or cuboidal epithelium and separated by a supporting
Stroma
The supporting stroma consisting of bundles of smooth muscle cells separated by bands of
Fibrous tissue
An extremely common condition seen in men over the age of 50 years
Benign Prostatic Hyperplasia
The histologic hallmark of BPH is the
Expansile Nodule
The cause of BHP is most likely related to excess stimulation of the prostate gland by
Testosterone or DHT
A proliferation of cells in organs whose cells can replicate
Hyperplasia
Hyperplasia is controlled: remove stimulus and proliferation
Ceases
Decrease in stress or trophic factors => decrease in organ size
Atrophy
Atrophy can be caused by an increased degredation due to
Ubiquitin-proteosome degradation
A reversible change whereby one adult cell type is replaced by another one
Metaplasia
A cell type vulnerable to a particular stress is replaced by one that is less vulnerable in
Metaplasia
The drawbacks of metaplasia is the loss of
Specialized function, and growth deregulation
Change in metaplasia results from altering the maturation program of
Stem cells
In a smoker’s bronchi, ciliated columnar cells => tougher squamous cells. This is an example of
-But protective mucus secretion and ciliary clearance is lost
Metaplasia
As the stress continues to affect the metaplastic epithelium, we may see
Malignant transformation
Characterized by generalized swelling of the cell and its organelles; blebbing of the plasma membrane; detachment of ribosomes from the endoplasmic reticulum; and clumping of nuclear chromatin
Reversible injury
Characterized by increasing swelling of the cell; swelling and disruption of lysosomes; presence of large amorphous densities in swollen mitochondria; disruption of cellular membranes; and profound nuclear changes
Irreversible injury
Nuclear condensation (pyknosis), followed by fragmentation (karyorrhexis) and dissolution of the nucleus (karyolysis) is an example of
Irreversible injury
Laminated structures (myelin figures) derived from damaged membranes of organelles and the plasma membrane first appear during the
Reversible stage
Can cause direct membrane damage
Ischemia
What are the earliest, i.e. reversible changes seen in cell injury?
Decreased ATP and cell swelling
What are two signs of irreversible cell injury?
Extensive membrane injury and severe mitochondrial damage
On a microscopic scale, reversible injury shows
Swelling and fatty change
Lysosome rupture and mitochondrial amorphous densities are signs or
Irreversible damage
One of the events that occurs in hypoxic or ischemic injury is
Cellular swelling
The decrease of oxygen tension in the cell results in impairment of mitochondrial
Oxidative phosphorylation
Since ATP is used to maintain the cellular ion pumps, the lack of ATP leads to an influx of
Sodium and water
There is also an efflux of calcium. However, we still see a net increase in
Osmotic load
In addition inorganic phosphates, lactate, and purine nucleosides accumulate in the cell and contribute to the
Osmotic load
The microvilli (mv) are lost and have been incorporated in apical cytoplasm; blebs have formed and are extruded in the lumen (L). Mitochondria are slightly dilated in a proximal tubule with
Reversible injury
Markedly swollen mitochondria containing amorphous densities, disrupted cell membranes, and dense pyknotic nucleus are seen in a proximal tubule with
Irreversible damage
Oxygen deprivation such as hypoxia and ischemia are major agents of
Cell injury
Anaphylaxis and autoimmune disease are both agents of
Cell injury
With cellular injury, ATP levels drop to
5-10% of normal
What are the three major causes of the ATP depletion seen in cellular injury?
Decreased O2 nutrients, mitochondrial damage, and toxins (ex: cyanide)
ATP depletion, mitochondrial damage, loss of Ca2+ homeostasis, oxidative stress, defects in plasma membrane, and protein/DNA damage are mechanisms of
Cellular injury
The loss of Ca2+ homeostasis can be seen by initial release of Ca2+ from intracellular stores. Followed later by influx across the
Plasma membrane
Some diseases such as Alzheimer’s, Huntington’s, Parkinson’s, and +/- type II diabetes are the result of
Protein/DNA damage
Unregulated cell death from damage to cell membranes, loss of ion homeostasis, and denaturation of cellular proteins
Necrosis
A passive response to injury, i.e. there is no energy required
Necrosis
Necrosis is always
Pathologic
There is no individual cell phagocytosis with
Necrosis
What are the 5 types of Necrosis?
- ) Coagulative
- ) Liquefactive
- ) Gangrenous
- ) Caseous
- ) Fat
Underlying tissue architecture is preserved
–Characteristic of infarcts (ischemic necrosis)
Coagulative necrosis
Focal bacterial/fungal infections
–Characteristic of CNS infarcts
–Liquid, viscous mass
Liquefactive Necrosis
Clinically, an ischemic limb with coagulative necrosis.
–Called “wet” if bacterial superinfection => liquefaction
Gangrenous necrosis
Tissue architecture & cell outlines obliterated
–Surrounded by distinctive inflammation: granuloma
Caseous necrosis
Caseous necrosis is mainly due to
Tuberculosis
Shows vague outlines of necrotic fat cells
Fat necrosis
Typically from release of activated pancreatic lipases in acute pancreatitis
Fat necrosis
Since the etiology of coagulative necrosis is often ischemia, the infarct occurs in a vascular distribution that is wedge-shaped with a base at the
Organ capsule
Outline of the myocardial cells are preserved, but the fibers have a “smudgy” appearance with increased eosinophilia and decreased numbers of nuclei
Coagulative necrosis due to MI
In coagulative necrosis the necrotic process is due mainly to
Protein denaturation
When hypoxic injury leads to cell death, it often results in coagulative necrosis except in the
Brain (where we see liquefactive necrosis)
Usually the result of a bacterial or fungal infection, because these processes evoke a massive influx of inflammatory cells, which release various degradative enzymes
Liquefactive necrosis
For unclear reasons, a hypoxic insult to the brain (as opposed to most other organs) results in
Liquefactive necrosis
As this infarct in the brain becomes organized and resolved, the liquefactive necrosis leads to resolution with
Cystic spaces
Often the result of mycobacterial or fungal infection
Caseous necrosis
Characterized by acellular pink areas of necrosis
Caseous necrois
Necrosis of the acinar cells of the pancreas releases lipase and proteases that in turn lead to injury and death of
Adipose cells
If fat necrosis is extensive, sufficient calcium may be deposited to result in hypocalcemia and in some cases even
Tetany
Programmed cell death
-a rational way of getting rid of cells
Apoptosis
In apoptosis, activation of caspase cascade => catabolism of
Proteins and DNA
Results in: chromatin condensation, cytoplasmic blebs/apoptotic bodies, phagocytosis
Activation of caspase cascade
What are the two pathways for apoptosis?
Intrinsic and extrinsic
In the intrinsic pathway, cell injury leads to
- ) Activation of?
- ) Inhibiton of?
- ) Bax and Bak
2. ) Bcl-2
This causes mitochondrial membrane channels to release
Cytochrome c
Cytochrome c release into the cytoplasm leads to activation of
Caspase cascade
Cell surface death receptors (Type I TNF receptor, Fas) bind their ligands => activate caspase cascade in
Extrinsis Apoptosis
Most apoptosis is actually
Physiologic
However, DNA damage, misfolded protein response, and certain infections are three types of
Pathologic apoptosis
Proteolytic enzymes that are important in the chain of intracellular events that lead to apoptosis
Caspases
The extrinsic pathway functions through the
Death receptor
The death receptor binds
Fas and TNF
Members of the TNF receptor family
Death receptors
The death domains bind to the
Adapter proteins
Too little apoptosis leads to increased cell survival which can cause
Cancer and autoimmune diseases
Mutated cells survive without apoptosing in
Cancer
Increased apoptosis leads to excessive cell death. This can result in
Neurodegenerative diseases, ischemic injury, and death of virus infected cells
Failure to eliminate self-reactive lymphocytes
–failure to eliminate dead cells, a source of self-antigens
Autoimmune diseases
