Pathology Flashcards
Hipertrophy
Increase in cell size
Hyperplasia
Increase in number of cells.
May progress to displásica and cancer.
Often hormonal
Atrophy
Decrease in cell size.
Uses ubiquitin-proteasome pathway and autophagy.
Causes: denervation, loss of blood supply and hormonal stimulation, poor nutrition
Metaplasia
Replacement of one cell type by another.
Myositis Ossificans (muscle replaced by bone) or Xerophthalmia (epithel replaced by mucus) are examples of
Metaplasia
Dysplasia
Disordered precancerous epithelial cell growth.
Can become irreversible and progress to carcinoma
Dysplasia
Disordered precancerous epithelial cell growth.
Can become irreversible and progress to carcinoma
Characteristics of Dysplasia
- Pleomorphism (loss of uniformity of size and shape)
- Abnormal nuclei (large and hyperchromatic)
- Mitotic figures (cells dividing)
- Mild and moderate dysplasia can be reversible.
- Usually preceded by persistent Metaplasia or pathological hyperplasia
Neoplasia
Change in cell type and structure
It’s irreversible
Which of the following is not reversible:
Hypertrophy - Hyperplasia - Metaplasia - Atrophy - Metaplasia - Dysplasia - Neoplasia
Neoplasia
Characteristics of reversible cell injury:
- Cellular/mitochondrial swelling
- Ribosomal/polysomal detachment
- Plasma membrane blebbing
- Nuclear changes (chromatin clumping)
- Rapid loss of function
- Myelin figures/fatty change
- Disruption of cytoskeleton
Characteristics of irreversible cell injury:
- Breakdown of plasma membrane
- Mitochondrial damage/dysfunction
- Rupture of lysosomes
- Nuclear degradation (pyknosis, karyorrhexis or karyolysis)
5.Amorphous densities/inclusions in mitochondria.
Pyknosis
Nuclear shrinkage/condensation
Karyorrhexis
Nuclear fragmentation
Karyolysis
Nuclear dissolution
Hallmark of cell injury
Ca+2 inside the cell
Which enzymes are in charge of the inactivation of free radicals:
-peroxidase
-catalase
O2 (superoxide) converts to H2O2 (hydrogen proxide) via:
Superoxide dismutase
Free radicals are coverted to water via the process of
Oxidative phosphorylation
Which enzymes in drug use are responsible for cell injury?
Cytochrome P450 enzymes
In which phase can Drugs cause cell injury?
Phase 1 (drug modification)
Which zone of the liver is most affected by the free radicals of drugs?
Zone lll (centrilobular) - Damage zone
How can Paracetamol/acetaminophen cause liver damage?
Via CYP450 -> NAPQI (ROS production) -> liver damage
Which transition metals usually keep H2O2 (free radical) from forming water?
-Fe+2
-Cu+
Why are Hemochromatosis and Wilson’s disease related to free radicals?
Hemochromatosis is produced by Fe+2 excessive accumulation, just as Wilson’s disease is by Cu+, due to the failure of carrier proteins like Ferritin and ceruloplasmin. Both necessary to keep low levels of free radicals
Characteristics of Apoptosis:
- Chromatine condensation
- Non inflammatory
- Pyknosis, karyorrhexis
- Membrane blebbing
- Apoctotic bodies
- Membrane is intact
- Single cell affected
- Can be physiological
- DNA laddering
Apoptosis
ATP dependent programmed cell death
What is a sensitive indicator of apoptosis?
DNA laddering
Apoptosis intrinsic pathway is regulated by:
-Bax and Bak (proapoptotic)
-Bcl-2 and Bcl-xL (antiapoctotic)
How do Bak and Bax operate?
Ex. DNA damage -> activates P53 -> activates Bak and Bax -> create pores in the mitochondria-> release cytochrome C into cytoplasm -> activates caspases - apoptosis begins
How do Bcl-2 and Bcl-xL operate?
They keep the mitochondrial membrane impermeable -> cytochrome C inside
Consequence of Bcl-2 overexpression?
Tumerogenesis. Apoptosis is kept from happening in any case.
Ex. Follicular lymphoma
Apoptosis extrinsic pathway is regulated by:
-Ligand receptors interactions in the membrane.
Ex: FasL binding to Fas(CD95) or TNFa
What is the cause of Autoimmune lymphoproliferative syndrome?
Defective Fas-FasL (extrinsic apoptosis pathway) necessary in thymic medullary negative selection.
How do Immune cells activate apoptosis?
Virus infection-> CD8T cells can:
1. Produce FasL -> bind to CD95 -> activate caspases -> apoptosis
2.MHC1 binds to them -> produce perforin and granzymes B-> activate caspases -> apoptosis
Characteristics of Necrosis:
- Immflamatory
- Cell swelling, membrane blebs
- Random fragments of DNA (no laddering)
- Damaged membrane (leakage of content)
- Affects many cells
- Always pathological
Coagulative necrosis
Occurs due to Ischemia/infarcts in most tissues. Characteristics:
1. Enzymes affected
2. Cell architecture preserved
3. Nuclei lost
4. Red-pink color (eosinophilia)
Liquefactive necrosis
Associated to bacterial abscesses and CNS infarcts (brain). Characteristics:
1.Architecture lost
2. Neutrophils
3. Enzymes are intact
4. Early: cellular debris and macrophages
5.Late: Cystic spaces and cavitations (CNS)
Caseous necrosis
Associated to Tuberculosis and systemic fungi. Characteristics:
1. Cheese like appearance (due to mycolic acid)
2. Granular debris
3. Granuloma formation (debris surrounded by lymphocytes and macrophages)
4. Necrotic center
Fat necrosis
Associated to acute pancreatitis and trauma. Characteristics:
1. Release of lipase (pancreas damage)
2. Saponification/chalky white color (trauma)
Fibrinoid necrosis
Associated to vascular reactions. Fibrin leaks in blood vessels.
-Polyarteritis nodosa (immune disease) -> type lll sensibility
-severe Hipertension/preclamsia (non-immune disease) -> fibrin leakage
Gangrenous necrosis
Associated to chronic isquemia in Distal extremities and gastrointestinal tract. Characteristics:
-Dry: ischemia (coagulative)
-Wet: superinfection (liquefactive)
Primary amyloidosis has
Fibril protein AL (Ig Light chains)
Ex: multiple myeloma
Secundary amyloidosis
Fibril protein AA (serum Amyloid A)
Seen in chronic inflammatory disease
Alzheimer’s disease has
Beta-amyloid protein and it’s localized
Most susceptible organs to isquemia
- Brain (ACA/MCA/PCA)
- Heart (subendocardium LV)
- Kidney (straight segment of proximal tubule and think ascending limb)
- Liver (zone lll)
- Colon (splenic flexure and rectosigmoid junction)
Free radical injury occurs via
Lipid peroxidation -> membrane damage
Free radicals can be eliminated by
- Enzymes: catalase, superoxide dismutase, glutathione peroxidase.
- Antioxidants: vitamin A, C, E.
- Transferrin/ferritin/lactoferrin (keep Fe+2 from linking to H2O2)
- Ceruplasmin (keeps Cu+ from linking to H2O2)
- Spontaneous decay
Chronic Granulomatose disease is connected to free radicals because of
The loss of NADPH oxidase, which allows phagocytes to engulf bacteria via the production of H2O2 (free radicals).
This is no problem if bacteria are catalase (-), however if they are catalase (+) there will be recurrent infections.
Dystrophic calcification is different to metastatic calcification because
-occurs in previous diseased tissue
-tends to localized
-Ca+2 levels are normal
-associated to granulomatous infections like TB
-2nd to injury (chronic inflammation) or necrosis
-Has psammoma bodies
Tumors usually associated to psammoma bodies:
- Papillary thyroid carcinoma
- Meningioma
- Ovarian carcinoma (serous)
- Mesothelioma
- Prolactinoma - milk
Remember as: Please MOM don’t forget the Milk
Metastatic calcification is different to dystrophic because
-occurs in healthy tissue
-there hyperCa+2 or hyperphosphatemia (typical in chronic kidney disease)
-associated to tissue that produces acid.
Repetitive hemolysis associates to
G6PD deficiency-> limited supply of glutathione -> less capacity to inactivate H2O2 -> red blood cell damage
Why can myocardial reperfussion associate to cell damage?
Sudden increase in O2 -> increase of free radicals-> cell damage
Lipofuscin
-accumulates with aging
-is NOT pathological
-looks yellow-brown in tissue
