L36 Irreversible response to cell injury necrosis and apoptosis.

Question 1

define necrosis?

Answer 1

early associated with leakage of intracellular proteins through damaged plasma membrane into the circulation, this sets the biochemical basics of early detection of tissue specific cell injury by blood testing.

Question 2

give 3 examples of proteins used in blood testing to detect necrosis

Answer 2

1- damaged cardiac muscles expresses specific contractile protein TROPONIN
2-damaged liver cells expresses transaminases
3-damaged bile duct expresses alkaline phosphatases.

Question 3

Phenomenas consistently characterized by irreversibility?

Answer 3

1- inability reverse mitochondrial dysfunction
2-disturbance of the membrane integrity with lysosomal enzymes leakage
3-nuclear changes

Question 4

define coagulative necrosis?

Answer 4

Its a form of necrosis where the architecture of dead tissue is preserved for a couple of days. Caused by ischemia or impairment of arterial supply, area of localized coagulative necrosis is called INFARCT.

Question 5

pathogenesis of coagulative necrosis?

Answer 5

the injury damages structural proteins and enzymes therefore disrupts the proteolysis of the dead cell’s. Leading to intensely eosinophilic cells with distinct outline and indistinct or reddish nuclei that’s preserved for somedays or weeks. the necrotic cells are broken-down by the action of lysosomal enzymes and the remains of cell debris is removed by phagocytosis.

Question 6

clinical implications of coagulative necrosis?

Answer 6

myocardial infarctions under the effect of ischemia due to narrowed or occluded coronary arteries in context of atherosclerosis sclerosis and kidney is similar.

Question 7

define liquifactive necrosis?

Answer 7

its characterized by the release of hydrolytic enzymes digestion the cells into viscous liquid

Question 8

abscess with pus formation ?

Answer 8

focal bacterial or fungal infection that stimulate the accumulation of leukocytes and liberation of digestive enzymes transforming the tissue into yellow creamy pus containing the bacteria and dead cells.
hypoxic death of central nervous system cells offend manifest liquifactive necrosis without a known reason.

Question 9

Define gangrenous necrosis?

Answer 9

a clinically used term to describe necrosis with superadded putrefaction infection. usually occurs in the lower leg where it has lost its arterial blood supply and had already undergone necrosis on several different pannels
###coagulative necrosis———> dry gangrene of foot due to diabetes mellitus
when there is venous and arterial occlusions due to bacterial infection more liquifactive necrosis occur due to the action of digestive enzymes and attraction of leukocytes
###liquifactive necrosis ——–> wet gangrene of the small intestine due to vascular occlusion.

Question 10

define caseous necrosis?

Answer 10

it combines both coagulative and liquifactive necrosis where its encountered in the foci of tuberculosis and some fungal infections. it occurs in reaction of lipids of the cell wall of these organisms, resembles dry cheese that’s soft yellow and granular. on microscopic examinations the necrotic area appeared as a structureless collection of fragmented/lysed cells and amorphous granular debris contained with a distinctive inflammatory border. GRANULOMA.

Question 11

define fibrinoid necrosis?

Answer 11

its a specific pattern of cell death that occurs when antigen and antibody complexes are deposited in the walls of blood vessels along with fibrin. its common in the immune mediated vasculitis which are a result of type 3 hypertension

Question 12

Whats the fate of necrosis

Answer 12

# within living patients most necrotic cells and their content disappear due to enzymatic digestion and phagocytosis of the debris by leukocytes 
#if necrotic cells and cellular debris are not promptly destroyed and reabsorbed they provide a nidus for the deposition of calcium salts and other minerals thus classified as dystrophic calcification

Question 13

what’s meant by apoptosis in general?

Answer 13

programmed cell death tightly regulated suicide program cell activates intrinsic enzyme activity that degrade genome nuclear proteins and cytoplasmic proteins it occurs in 1 or few cells

Question 14

apoptosis in physiological conditions?

Answer 14

cells undergo apoptosis because they are deprived from necessary survival signals such as growth factors and interaction with extracellular matrix or the have received pro-apoptotic signals from neighboring cells or surrounding environment.

Question 15

during embryo genesis?

Answer 15

its critical for the involution of primordial structure and remodeling of maturing tissue example the formation of the digits during embryogenesis in the fetus occurs be=y the apoptosis of interdigital tissue

Question 16

hormone dependent involution of tissue ?

Answer 16

during menstrual cycle the sloughing of the endometrium after withdrawal of oestrogen and progesterone, ovarian follicular atresia in menopause and regression of lactating breast after weaning

Question 17

cell turnover?

Answer 17

in proliferating cell population is maintained a constant cell number such as immature lymphocytes in the bone marrow and thymus.

Question 18

elimination of potentially harmful/dangerous cells?

Answer 18

as virus infected cells are eliminated by cytotoxic T cells
cells with DNA damage that fail to repair by P53 activation then will undergo apoptosis to protect cells from risk of mutation

Question 19

auto reactive T cells

Answer 19

in thymus they are killed by apoptosis

Question 20

apoptosis in PATHOLOGICAL conditions?

Answer 20

the main purpose is to eliminate cells that have been injured beyond repair without eliciting host cell reaction thus limiting colorectal tissue damage dysregulated apoptosis may prolong the survival or reduce the turnover of abnormal cells

Question 21

TUMORGENESIS?

Answer 21

radiations and cytotoxic drugs can damage the DNA either directly or via production of free radicals if repair mechanisms unable to correct the damage the cells triggers intrinsic enzyme mechanisms to induce apoptosis as a protecting effect to prevent survival of muted cells that can lead to malignant transformations in case of muted apoptosis genes chemicals and radiations and viruses can damage P53 tumor suppressor gene that lead to inhibition of apoptosis and immortalizes abnormal cells and development of malignant cells

Question 22

accumulation of abnormal proteins?

Answer 22

cell death triggered by improperly folded intracellular proteins and the subsequent endoplasmic reticulum response ———–>neurodegenerative disorders

Question 23

autoimmune disease?

Answer 23

decrease in apoptosis of self reactive immune cells can lead to the development of auto immune diseases

Question 24

Infectious conditions?

Answer 24

elimination of viral infected cells (e.g., hepatitis), is mediated by apoptosis induced mechanisms. Dysregulation of this pathway , will fail the body ‘s defensive mechanisms.

Question 25

Morphologic features of apoptosis

Answer 25

Involves single isolated cells or small clusters of cells within a tissue.
● Lack of inflammatory response
● Blebbing of plasma membrane
● Cytoplasmic and cellular shrinkage
● Chromatin condensation and fragmentation
● Budding of cell and Fragmentation into apoptotic bodies (membrane-bound segments)
● Phagocytosis of apoptotic bodies by adjacent healthy cells or macrophages.