Respuesta al daño celular Flashcards
Cuál es el mecanismo de acción de la inhalación de monóxido de carbono?
Previene el transporte de oxígeno
Mecanismo de daño de los accidentes traumáticos y térmicos
Disrupción y desnaturalización de proteínas –> trombosis vascular local –> isquemia –> muerte celular.
Mecanismo de daño del congelamiento
Los cristales de hielo perforan las membranas.
El mecanismo de acción de los virus es romper la membrana celular de las células que infectan. Que virus es una excepción de este mecanismo?
Hepatitis B, el daño tisular de la enfermedad es causado principalmente por la reacción inmune del huésped.
En qué vía metabólica interfiere el cianuro, y cómo lo hace?
En la respiración celular. El cianuro se une a los citocromo oxidasa –> interrumpe la utilización de oxígeno. Los miocitos son de los más vulnerables, ya que son células de alto requerimiento metabólico.
Células que son altamente dependientes de la glucosa para su funcionamiento
Neuronas
Agentes o medicamentos que afectan la síntesis de proteínas (a nivel de traducción)
Ricina y antibióticos como streptomicina, cloramfenicol y tetraciclina.
Physiopathology of ischemia and reperfusion injury
Impaired blood flow→ ceasing of mitochondrial ATP production→ anaerobic glycolysis→ accumulation of lactate → acidosis and calcium influx → disruption of mitochondria’s inner membrane (it exceeds its calcium storage capacity), activation of calcium-dependent proteases, leakage of endoplasmic reticulum’s calcium storage into the cytosol → necrosis
Physiopathology of free radicals
Damage to polyunsaturated fatty acids (essential components of cell membranes) and damage of lysosomal membranes → release of proteases (cathepsin) → damage of DNA → cell death .
Mechanisims of failure of membrane integrity (4)
Complement- mediated cytolysis, perforin - mediated cytolysis, specific blockage of ion channels and failure of membrane ion pumps and free radicals attack.
Result of ion pump failure
Cell swelling (oncosis or hydropic change) → may progress to cell death
The non-lethal DNA damage can be inherited by daughter cells, resulting in clone cells with abnormal growth characteristics → neoplastic transformation → tumors. (T or F)
True
Types of DNA damage (3)
Strand brakes, base alterations (nonsense/ missense) and cross-linking.
“Unreadable” mutation
Nonsense
“Read incorrectly” mutation
Missense
Type of DNA damage used by some radiotherapies
Cross-linking.
Cross-linking (physiopathology)
ROS cause linkage between complementary strands → inability to separate and to make new copies → DNA replication is blocked → “reproductive death”
Mutated ERCC6 gene → extreme skin sensitivity to sunlight → tumors (disease)
Xeroderma pigmentosum
Some people are more susceptible to ionizing radiation or ultraviolet light due to defective DNA repair mechanisms, such as enzymes. Name 2 diseases caused by this defect
Ataxia telangiectasia and xeroderma pigmentosum
Impair excision repair of double strand breaks due to a loss of function mutation of the ATM gene (disease)
Ataxia telangiectasia
Pattern of cellular injury in which the cytoplasm becomes pale and swollen due to accumulation of fluid. Generally caused by hypoxia or chemical poisoning.
Hydropic change (oncosis)
Pattern of cellular injury in which occurs vacuolation of cells due to accumulation of lipid droplets as a result of ribosomal dysfunction and uncoupling of lipids from protein metabolism. Liver is commonly affected this way by hypoxia, alcohol or diabetes
Fatty change
Cellular response to stress in which
cell components are isolated into intracellular vacuoles → these are processed through to lysosomes.
Autophagy
Main difference between apoptosis and necrosis
In apoptosis the cell membrane remains intact, there is NO inflammatory reaction and it follows a lower dose or shorter duration of damage.
Result of the failure of ATP production
Ineffective ion pumps → loss of homeostasis, influx of water, oncosis, lysis and cell death
Which cells are most affected by ischemia
Cortical neurons and cardiac myocytes will be most affected
Physiopathology of the reperfusion injury
When the blood supply is restored → burst of mitochondrial activity → excessive release of free radicals (ROS).
Physiopathology of TNF
Stimulates mitochondrial ROS production → necrosis
Causes of autophagy
cellular stress (ex. deficiency of nutrients, growth factor- mediated effects or organelle damage)
Most common form of necrosis. The cell’s proteins coagulate, maintaining a ghost outline. Initially the tissue texture is normal or firm but later becomes soft due to digestion of macrophages.
Microscopic examination: Loss of nuclear staining and cytoplasmic detail.
Coagulative necrosis
Type of necrosis that occurs in the brain because of its lack of substantial supporting stroma. Site of necrosis will eventually be marked by a cyst.
Colliquative necrosis
Tuberculosis characterized by this type of necrosis. The dead tissue is structureless. Amorphous eosinophilic area stippled by haematoxyphilic nuclear debris
Caseous necrosis
Necrosis with putrefaction of tissues. The affected tissue appears black due to deposition of iron sulphide from degraded hemoglobin.
Gangrene
Microorganism (present in the bowl) that causes wet gangrene necrosis
Clostridia
Type of gangrene usually seen in toes due to gradual arterial or small vessel obstruction (atherosclerosis or diabetes)
Dry gangrene
Microorganism that causes gas gangrene
Clostridium perfringens
Type of necrosis seen in malignant hypertension arterioles that are under such pressure → necrosis of smooth muscle wall → leakage of plasma and fibrin deposition. With haematoxylin and eosin the vessel wall is bright red.
Fibrinoid necrosis
Direct trauma to adipose tissue and extracellular liberation of fat → inflammatory response → fibrosis. Type of necrosis?
Fat necrosis
Type of necrosis seen in acute pancreatitis.
Fat necrosis
Enzymatic lysis of fat due to release of lipases → release of pancreatic lipase → release of fatty acids → combined with calcium → in severe cases causes hypocalcemia.
Cell classification according to their potential for renewal (3)
Labile, stable and permanent
Examples of labile cells
Surface epithelial cells
Examples of stable cells
Hepatocytes and renal tubular cells
Examples of permanent cells
Nerve cells and striated muscle
Type of cell that is present in labile and stable cells population. When they go into mitosis, one of the daughter cells progress to differentiation and the other daughter retains the stem cell characteristics
Stem cell
Consequence of radiation to stem cells
Loss of stem cells or mutations that are propagated to daughter cells → risk of neoplastic transformations
What is contact inhibition in healing?
When the cells form a confluent layer, the stimulus to proliferate is switched off.
Process whereby tissues are repaired by formation of mature fibrovascular connective tissue.
Organization.
Tissue that is formed in early stages of healing. It is the combination of the capillary loops and myofibroblasts. It contracts and accumulates collagen to form the scar.
Granulation tissue
Diseases in which organization process is a common. The organized area is firmer than normal, shrunken and puckered
Pneumonia and an infarct
Process in which capillary endothelial cells proliferate and grow into the area to be repaired. Simultaneously, fibroblast secrete collagen and other matrix components and acquire bundles of muscle filaments (myofibroblasts) → fundamental in wound contraction.
Granulation tissue formation
Name of an excessive granulation tissue protruding from a surface
Proud flesh
Important function of granulation tissue that reduces the volume of tissue for repair.
Wound contraction and scarring. The granulation tissue as a whole contracts and indraws the surrounding tissue
Possible complication of the wound contraction in the granulation tissue.
Can lead to stenosis or obstruction in case of damage around a lumen tube (such as the gut)
Excessive fibroblast proliferation and collagen production. They are genetically determined and are prevalent among blacks
Keloid nodules
Leer
Hypoxia and release of growth factors by platelet degranulation → production of epidermal growth factor (EGFs) and keratinocyte growth factor (KGF) from platelets, macrophages and dermal fibroblast →keratinocytes and macrophages produce vascular endothelial growth factor (VEGF) → angiogenesis. Platelet-derived growth factor (PDGF) activates macrophages, proliferation of fibroblasts and matrix production. TGF-beta controls myofibroblasts and collagen production.
Steps of bone fracture healing (3):
- Removal of necrotic tissue and organization of the hematoma.
- Capillaries are accompanied by fibroblasts and osteoblasts → they deposit bone in a woven pattern.
- Woven bone is replaced by lamellar bone, which is remodeled according to the direction of mechanical stress.
Name of the mass of woven bone deposited by fibroblast and osteoblasts in bone fracture
Callus
Problems with fracture healing (5)
- Movement → results in pain and excessive callus and prevents tissue union → formation of false joints at fracture site.
- Interposed soft tissues
- Gross misalignment → increase risk of osteoarthritis.
- Infection: more common on compound fracture (exposed)
- Pre-existing bone disease.
Is the result of imbalance of hepatocyte regeneration and failure to reconstruct architecture
Cirrhosis
Damage of tubular epithelium following ischaemic episode or exposure of toxins can be reversible (T or F)
True
Damage to renal glomerulus can be reversible (Tor F)
False. Damage to glomerulus is likely to be permanent → loss of filtration capacity.
Process in which glial cells can proliferate in response to injury
Gliosis
Modifying influences in the healing process (8)
- Age
- Disorders of nutrition
- Neoplastic disorders
- Cushing’s syndrome and steroid therapy: immunosuppression
- Diabetes mellitus: affects polymorph function, occlusion of small blood vessels → neuropathy.
- Vascular disturbance
- Denervation
Type of vitamin that is important in the healing process due to hydroxylation of proline (step of collagen synthesis).
Vitamin C
Capillary consequences of vitamin C deficiency (escorbuto)
Deficiency of vitamin c → fragile capillaries → hemorrhage
