Pathoma Chapter 1 Flashcards
T or F. An increase in stress leads to an increase in organ size
T. Atrophy is the opposite
How can an increase in organ size occur?
Hypertrophy or Hyperplasia
How does hypertrophy result in increased cell size?
increased production of proteins, increased gene activation, and increased production of organelles
not an increase in cytoplasm
What organs can only undergo hypertrophy?
Heart, brain, nerve, skeletal muscle. These are termed permanent tissue and are terminally differentiated
caused by increased pressure and need to work harder
Pathologic hyperplasia can lead to what?
Exception?
dysplasia, and eventually cancer
exception: benign prostatic hyperplasia (BPH) does not increase the risk of prostate cancer
How does atrophy occur?
Decrease in cell size occurs via ubiquitin-proteasome degradation of the cytoskeleton and autophagy of cellular components.
Intermediate filaments of the cytoskeleton are tagged with ubiquitin and destroyed by proteosomes
How does autophagy occur?
Involves generation of autophagic vacuoles that fuse with lysosomes who’s hydrolytic enzymes break down cellular components
Barrett’s esophagus.
Metaplasia of the nonkeratinizing squamous epithelium of the esophagus for nonaffiliated, mucin-producing columnar cells
How does metaplasia occur?
re-prgramming of stem cells, which then produce the new cell type
Is metaplasia reversible?
YES, with removal of the driving stressor.
However, under persistent stress, metaplasia can progress to dysplasia and eventually cancer
Ex. barrett’s esophagus can lead to adenocarcinoma of the esophagus
Under persistent stress, metaplasia can progress to dysplasia and eventually cancer. Exception?
apocrine metaplasia of the breast
Deficiency of what can lead to metaplasia?
Vitamin A
What does Vitamin A do?
necessary for differentiation of specialized epithelial surfaces such as the conductive of the eye
In vitamin A deficiency, the goblet cell/columnar epithelium of conductive undergoes metaplasia into keratinizing squamous epithelium
T or F. Mesenchymal tissues can undergo metaplasia
T. A classic example is myositis ossificans in which connective tissue within muscle changes to bone during healing after trauma
Dysplasia
Proliferation of precancerous cells
Example of Dysplasia?
Cervical intraepithelial neoplasia (CIN) represents dysplasia and is a precursor to cervical cancer
Dysplasia often arise from what?
longstanding pathologic hyperplasia (endometrial hyperplasia) or metaplasia (eg. Barrett’s esophagus)
T or F. Dysplasia is reversible.
T. If stress persists, dysplasia can lead to carcinoma (irreversible)
What is aplasia?
failure of cell production during embryogenesis
What is hypoplasia? Example?
decrease in cell production during embryogenesis, resulting in a small organ (streak ovary in Turner’s syndrome)
What is cellular injury?
Occurs when stress exceeds the cell’s ability to adapt
The likelihood of injury depends on what?
the type of stress, its severity, and the type of cell affected.
Nerve cells are more susceptible to ischemic injury than skeletal muscle
Slowly developing ischemia (i.e. renal artery atherosclerosis) results in ____, while acute ischemia (e.g renal artery embolus) results in ____.
atrophy; injury
Common causes of cellular injury include:
inflammation, nutritional deficiency or excess, hypoxia, trauma, and genetic mutations
How does hypoxia lead to cell injury?
lack of O2= lack of ATP produced
What are some common causes of hypoxia?
ischemia, decreased O2 carrying ability of blood, hypoxemia
What is ischemia?
decreased blood flow to an organ
What are some common causes of ischemia?
1) decreased arterial perfusion (e.g. atherosclerosis)
2) decreased venous drainage (e.g. Budd-Chiari syndrome)
3) shock- generalized hypotension resulting in poor tissue perfusion
What is hypoxemia?
low partial pressure of oxygen in the blood
What causes hypoxemia?
- high altitude (decreased PaO2),
- hypoventilation (increased PaCo2, decreased PaO2),
- diffusion defect (thick diffusion barrier, e.g. interstitial pulmonary fibrosis)
- decreased O2 carrying capability of hemoglobin
What are some things that might lead to decreased ability of hemoglobin to carry O2?
- Anemia (decrease in RBC mass)- PaO2 and SaO2 normal
- CO poisoning (PaO2 normal, SaO2 decreased) because CO binds better to
- Methemoglobinemia- PaO2 normal, Sao2 decreased
Treatment for methemoglobinemia?
Treatment with methylene blue which helpers reduce Fe3+ back to normal
classic finding is cyanosis with chocolate-colored blood
Hallmarks of reversible injury?
initially injuries are reversible
cellular swelling resulting in loss of microvilli and membrane blebbing and swelling of the RER resulting in dissociation of ribosomes and decreased protein synthesis
and fatty change
Hallmarks of irreversible injury?
Eventually, the damage becomes irreversible
plasma membrane damage resulting in cytosolic enzymes leaking into the serum and additional calcium entering the cell
mitochondrial damage resulting in loss of ETC and cytochrome c leaking into the cytosol (activated apoptosis)
T or F. Necrosis can be caused by physiologic stimuli.
F. Only pathologic and following acute inflammation usually
What is coagulative necrosis?
Necrotic tissue that remains firm and cell shape and structure are preserved by coagulation of proteins, but the nucleus disappears
Coagulative necrosis occurs when?
typically of an ischemic event of any organ except the brain
How does coagulate necrosis typically present macroscopically?
are of infarcted tissue often wedge-shaped (pointing to focus of vascular occlusion) and pale
What is liquefactive necrosis?
necrotic tissue that becomes liquefied by enzymatic lysis of cells and proteins
When does liquefactive necrosis occur?
common in brain infarction, abscess, and pancreatitis
What is gangrenous necrosis?
resembled mummies
dry=coagulative
wet= liquefactive
Caseous necrosis is a combo of what two types?
liquefactive and coagulative
What is fat necrosis?
necrotic adipose tissue due to chalky-white appearance due to deposition of calcium characteristic of trauma to fat and pancreatitis mediated damage of per pancreatic fat
How doe fat necrosis occur?
fatty acids are released by trauma or lipase (pancreatitis) and join with calcium via a process called saponification
What is the difference between metastatic and dystrophic calcification?
metastatic- occurs when high serum calcium or phosphate levels lead to calcium deposition in normal live tissue
dystrophic- calcium deposition in dead tissue under normal serum levels of calcium or phosphate
What is fibrinoid necrosis?
necrotic damage to a blood vessel wall characterized by a bright pink staining of the wall microscopically
When is fibrinoid necrosis common?
common in malignant HTN and vasculitis
T or F. Apoptosis is ATP dependent
T.
Describe the morphology of apoptotic cells
Dying cells shrink, leading the cytoplasm to become more eosinophilic (pink), nucleus condones and fragments in an organized manner, apoptotic bodies fall from the cells an are removed by phagocytes before inflammation occurs
How does apoptosis occur?
Mediated by caspases via:
1) intrinsic mitochondrial pathway
2) extrinsic receptor-ligand pathway
3) cytotoxic CD8+ T cell-mediated pathway (granzymes activate caspases)
Extrinsic receptor-ligand pathway
FAS ligand binds FAS death receptor on the target cells, activating capsizes (e.g. negative section of thymocytes in thymus)
How can free radicals arise physiologically?
via oxidative phosphorylation (cytochrome c oxidase and partial reduction of O2)
How can free radicals arise pathologically?
- ionizing radiation- water hydrolyzed to hydroxyl free radical
- Inflammation- NADPH oxidase generates superoxide ions
- Metals- Fe2+ generated hydroxyl free radicals (fenton reaction)
- drugs and chemicals
Free radicals cause cellular injury via what mechanisms?
peroxidation of lipids
oxidation of DNA and proteins
How does elimination of free radical occur?
1) Antioxidants (glutathione and vitamins A, C, and E)
2) Superoxide dismutase, glutathione peroxidase, and catalase
3) Metal carrier proteins (transferrin and ceruloplasmin)
What are some examples of cellular injury caused by free radicals?
1) CCl4 is converted to CCl3 by P450 system of hepatocytes resulting in swelling of RER, and ribosomal detachment
2) Reperfusion injury- return of blood of ischemic tissue results in production of O2 derived free radicals (leads to continued rise in cardiac enzymes (e.g. troponin) after repercussion
What is amyloid?
a misfolded protein that deposits in the extracellular space, damaging tissue. Multiple proteins can deposit as amyloid
Can be systemic or localized
Amyloid cannot be removed and requires organ transplant
Systemic amyloidosis
amyloid deposition in multiple organs; divided into primary and secondary amyloidosis
What is primary amyloidosis?
deposition of AL amyloid, which is derived from immunoglobulin light chain
What is secondary amyloidosis?
systemic amyloid deposition of AA amyloid, which is derived from serum amyloid-associated protein (SAA)
What genetic disease predisposes to increased SAA?
Familial Mediterranean Fever (FMF)
autosomal recessive neutrophil deficiency
What are some types of localized amyloidosis?
1) Senile cardiac amyloidosis
2) Familial amyloid cardiomyopathy
3) Non-insulin-dependent diabetes mellitus (type II)
4) Alzheimer disease
5) Dialysis-associated amyloidosis
6) Medullary carcinoma of the thyroid
Senile cardiac amyloidosis
Non-mutated serum transthyretin deposits in the heart
usually asymptomatic; present in 25% of patients over 80 y/o
Familial amyloid cardiomyopathy
Mutated serum transthyretin deposits in the heart leading to restrictive cardiomyopathy
carried in 5% AA
Non-insulin-dependent diabetes mellitus (type II)
Amylin (derived from insulin) deposits in the islets of the pancreas
Alzheimer disease
AB amyloid (derived from B-amyloid precursor protein) deposits int he brain forming amyloid plaques
Gene for B-APP is present on chromosome 21, Most patients with Down syndrome (trisomy 21) develop Alzheimer disease by age 40 (early-onset)
Dialysis-associated amyloidosis
B2-microglobulin deposits in joints
Medullary carcinoma of the thyroid
calcitonin (produced by tumor cells) deposits within the tumor
