A/6-11 CELL INJURY, ACCUMULATIONS, PIGMENTS, CALCIFICATION (Leiel) Flashcards
What separates reversible cell injury from irreversible cell injury?
“point of no return” = irreversible cell injury.
The points of no return:
- Ca++ influx
- Profound disturbance in membrane function
- Inability to reverse mitochondrial dysfunction
The 2 main morphologic changes in the reversible cell injury include:
- cellular swelling / hydronic degeneration
- Fatty changes (steatosis)
What are the 5 reasons for fat accumulation?
- Starvation
- Hypoxia
- Toxins, alcohol
- Protein malnutrition
- Obesity
The microscopical changes of reversible cell injury include:
- Plasma membrane alteration such as blebbing and loosening of intercellular attachments
- Mitochondrial swelling, appearance of phospholipid-rich amorphous densities
- Dilation of ER with ditachment of ribosomes and dissociation of polysomes
- Nuclear alterations with clumping of chromatin
Examples of fat accumulation diseases
- Hepatic steatosis (fatty liver)
- Nutmeg liver (hepar muscolutum adiposum)
- Tiger heart (degeneration adipose insularis myocardii)
What is Atherosclerosis?
a chronic inflammatory response of the vascular wall to a variety of insults including endothelial injury, accumulation of lipids in smooth muscle cells and macrophages and thrombosis
What makes atherosclesrosis?
It is an intimal plaque
(lipid/necrotic core, fibrous cap, shoulder) So
Plaque = lipid core + fibrous cap + 2 shoulder
What are the 3 groups that the risk factors of atherosclerosis are divided into?
-
Major constitutional risk factors
- Age, Gender, Genetics
-
Major modifiable factors
- Hyperlipidemia/hypercholesterolemia (LDL, HDL, Lipoprotein A), Hypertension, Cigarette smoking, Diabetes mellitus
-
Additional risk factors
- Inflammation, Hyperhomocystinemia, Obesity, Lack of exercise, Stressful life, Competitive personality
What is the pathogenesis of atherosclerosis?
Chronic endothelial injury →
Accumulation of lipoproteins in the vessel wall →
Monocyte adhesion to the vessel wall →
Platelet adhesion and activation →
Production of growth factor ⇒
Lipid accumulation
What are the possible morphologies of atherosclerosis?
- Fatty streaks
- Primary plaques (lipid/necrotic core, fibrous cap, shoulder)
- Complicated plaque: (rupture, thrombi incorporation, hemorrhage, atheroembolism, aneurysm, calcification)
Prevention of atherosclerosis
-
Primary prevention:
- prevent the disease or lead to its regression
- stop smoking, control of hypertension, exercise, lowering LDL and increasing HDL
-
Secondary prevention:
- prevent MI or stroke
- Usage of statins, aspirin, b-blockers, surgical intervention like coronary bypass.
What is Amyloidosis?
A condition associated with a number of inherited and inflammatory disorders in which extracellular deposits of fibrillar proteins are responsible for the tissue damage and functional compromise.
The abnormal fibrils are the result of aggregation of misfolded proteins.
Protein accumulation might occur in the following cases:
- Excess of protein in presented to the cell.
- Increased protein synthesis
- Cell injury.
- Abnormal folding of proteins
Describe the pathogenesis of Amyloidosis
misfolded proteins → aggregate to form fibrillar protein → 4-6 fibrils crossed in β-pleated configuration ⇒ amyloid.
(System: there are precursor proteins for each of the 23 amyloid types. When those proteins are misfolded, they accumulate and lead to amyloidosis)
What is used to identify amyloid structure in a tissue (histology?*)?
Congo staining (red dye) binds to the fibrils and if we use a polarization light it gives a green color.
The most important amyloid types are:
-
AL = amyloid light chain protein
- The precursor of it are complete immunoglobulin light chains
-
AA = amyloid associated fibril
- Its precursor is SAA (serum amyloid associated protein)
-
Aβ amyloid
- Its precursor is APP (amyloid precursore protein)
-
Transthyretin
- A serum protein that binds thyroxine and retinol.
Classification of amyloidosis
-
Immune dyscrasia associated amyloidosis
- Systemic amyloidosis, AL type, primary.
-
Reactive systemic amyloidosis
- Systemic amyloidosis, AA type, secondary
-
Familial amyloidosis
- AA type
-
Localized amyloidosis (or: plasma cytoma)
- Neoplastic disease in one organ only
-
Endocrine amyloidosis
- APUD-OMAS
- Amyloid of aging
General macroscopic morphology of amyloidosis
- It may or may not be apparent in macroscopic examination.
- Often small amounts are not recognized until the surface of the organ is cut and painted with iodine and sulfuric acid (brown staining).
- When accumulated in larger amount: enlarged organ, graish color, waxy, firm.
General microscopic morphology of amyloidosis
- the deposit is extralcellular and begins between the cells.
- As it accumulates it presses the cells and leads eventually to pressure atrophy.
- We use congo red dye which under light gives a red/pinkish color and under the polarized light show greenish color.
Organ morphology of amyloidosis*
- Kidney: deposits are usually found in the glomeruli, tubular cells, interstiatial peritubular tissue.
- Liver: Disses space and then progresses to the parenchyma and sinuses.
- Spleen: nodular or trabecular
- Heart: subendocardial elevations
- The GI is frequently involved in the systemic cases, thus, biopsy of the gingiva, intestine and rectum is good for diagnosis.
Clinical correlation (symptoms and outcome)
Symptoms:
- Difficult to recognize.
- Non-specific complains: weakness, fatigue, weight loss, then by: kidney disease, heart abnormality, enlarged liver and spleen. Proteinuria and the resultant kidney failure
- Conduction disturbances Make biopsy and congo red staining
Outcomes
- Death 1-3 years after diagnosis because the amyloid cannot be removed.
- The primary is the most frequent.
- The occurance of the secondary depends on the treatment of the inflammation.
Give examples for Exogeneous pigments
- Carbon
- silicium
- tattoo
Describe what happens to the lung in urban life.
Carbon is inhaled → phagocytosed by alveolar macrophages → transported through the lymphatics to a regional tracheobronchial lymph node ⇒ aggregation of it blackens the lymph node and the parenchyma ⇒ !!!anthracosis!!! <3 ™
Describe the pathogenesis of coal workers pneumoconiosis
Pneumoconiosis describes a non-neoplastic lung reaction to inhalation of mineral dusts.
Substances are inhales like SiOH which is dangerous.
Inhaled particles → impacted in the alveolar dust bifurcation → macrophages accumulate and phagocytose → reactive particles (like SiOH) kill the macrophages → leakage of lysosomal enzymes. through the macrophage system the active substances activate interleukins, TNF etc.
consequences: in the lung the macrophages produces necrosis → the necrosis is replaced by fibrosis → the alveoli and capillary are destroyed → the resistance of the lung increases → cor pulmonale chronicum: the work of the right heart side is increased (-> Heart failure**)