Cell degeneration/death (year 2) Flashcards
what is homeostasis?
cells keeping balance of physiological demands
what stimulates cellular adaptation?
response to excessive physiological stress of pathological stimuli
what does cellular adaptation affect?
the growth and differentiation of cells
what are some examples of cellular adaptation?
hypertrophy, hyperplasia, atrophy, metaplasia
what is atrophy?
decrease in size and number of cells
what is hypoplasia?
reduced organ volume because of incomplete cell proliferation
what is aplasia?
organ absence because of defective cell proliferation
define involution
a physiological atrophy
define atrophy
a pathological atrophy
give some examples of involution
uterus after parturition
thymus after puberty
senescence
give some examples of pathological atrophy
skeletal muscle disuse
denervation
inadequate nutrition
pressure atrophy
define hypertrophy
increase in size of cells - no cell division involved
what causes hypertrophy?
increased functional demand
what is an example of physiological hypertrophy?
smooth muscle in pregnant uterus
skeletal muscle with training
give an example of pathological hypertrophy
cardiac myocytes
what is hyperplasia?
increase in the total number or cells in an organ/tissue
what are the two types of physiological hyperplasia?
hormonal and compensatory
give some examples of hormonal hyperplasia
proliferation of mammary and uterine epithelium during pregnancy
give an example of compensatory hyperplasia
in symmetrical organs with functional loss of one such as kidney
partial loss of parenchyma such as partial hepatectomy
what can cause pathological hyperplasia?
excessive hormonal stimulation
attempt at regeneration
viral infection
what is metaplasia?
reversible change in which one adult cell type is replaced by another adult cell type
give an example of metaplasia
columnar epithelia replaced by stratified squamous when smoking
what are normal cellular constituents?
water, lipid, carbohydrate, protein
what are the two categories of abnormal intracellular accumulation?
exogenous and endogenous
name some exogenous abnormal intracellular substances
minerals
products of infectious agents
what is the name for intracellular accumulation of lipids?
steatosis/lipidosis
what organ is steatosis common in?
liver cells
name some causes of lipidosis
toxins, protein malnutrition, diabetes, obesity
describe the normal metabolisms of lipids
free fatty acids transported to liver where they form triglycerides, phospholipids, cholesterol, ketone bodies
triglycerides are then associated with apoproteins and form lipoproteins that enter circulation
what form of lipid accumulates in hepatocytes?
triglycerides
what may cause intracellular protein accumulation?
excess of protein presented to cell
excessive protein synthesis
defects in protein folding
where is an example of somewhere that excess proteins can be presented to the cell?
proximal renal tubules during proteinuria
where may you see excessive synthesis of proteins?
plasma cells producing high levels of immunoglobulins
what may cause abnormal folding of proteins?
genetic mutations ageing environmental factors amyloidosis Alzheimers
why might defects in protein folding occur?
defective intracellular transport and secretion of critical proteins
toxicity of aggregated abnormally folded protein
why may glycogen accumulate intracellularly?
diabetes, glucocorticoid hepatopathy, glycogen storage disease
how does glycogen appear in the cell?
clear vacuoles in cytoplasm
what are pigments?
coloured substances that can be normal or abnormal constituents of a cell
name some normal endogenous pigments of cells
melanin, lipofuscin and haemosiderin, bilirubin
name some common abnormal pigments of cells
carbon/coal dust
define anthracosis
inhalation of carbon/coal dust
where are carbon particles found?
phagocytksed by alveolar macrophages and transported to regional lymph nodes
what is is lipofuscin?
insoluble polymers of lipids that are yellow/brown colour
what colour is melanin?
brown/black
what is haemosiderin?
haemogobulin derived storage form of iron that appears gold/yellow/brown
when does haemosiderin appear?
haemorrhage (depredation of haemoglobin)
end of the lifespan of RBC
what is bilirubin?
normal major pigment of bile
what colour is bilirubin?
green/blue
what does excess bilirubin cause?
jaundice
what colour is biliverdin?
green
what are the components of bile?
water, cholesterol, bile salts, bile pigment, iron
what colour is bile?
yellow/green
what can cause jaundice?
excessive haemolysis
severe hepatic injury
obstructed bile flow
what may cause cell injury?
oxygen deprivation physical agents infectious agents immunological reactions genetic derangements nutritional imbalances chemical agents/drugs
what intracellular systems are vulnerable to injury?
cell membrane, aerobic respiration, protein synthesis, genetic apparatus
what biochemical mechanisms may lead to cellular injury?
ATP depletion oxygen derived free radicals loss of Ca homeostasis defects in membrane permeability irreversible mitochondrial damage
what is hypoxia?
a deficiency in oxygen reaching tissue
what does lack of oxygen to a tissue result in?
decrease aerobic respiration meaning less ATP leading to reduced activity of the sodium pump
what happens as a result of the decreased sodium pump activity?
accumulation of sodium meaning water accumulates in the cell causing swelling
what are the consequences of increased intracellular calcium?
activates enzymes such as ATPase, phospholipase, endonuclease, protease
what does increased activity if ATPase mean?
less ATP
what does increased activity if phospholipase mean?
decreased phospholipids
what does increased activity if endonuclease mean?
nuclear chromatin damage
what does increased activity if protease mean?
disrupts membranes and cytoskeleton
what are some examples of irreversible cell injury?
mitochondrial changes, extensive plasma membrane damage, prominent swelling of lysosomes, massive calcium influx
when is cell injury characterised as irreversible?
inability to reverse mitochondrial dysfunction
profound disturbance in membrane function
what are some potential causes of membrane damage resulting in irreversible injury?
loss of membrane phospholipids, cytoskeleton abnormalities, toxic oxygen radicals, lipid breakdown
what is a free radical?
extremely unstable highly reactive chemical species with a single unpaired electron in an outer orbit
what is the main source of free radicals?
hydrolysis of water into OH and H by ionising radiation
redox reaction
what injuries do free radicals cause?
lipid per oxidation of membranes
lesions in DNA
cross-linking of proteins
what is reperfusion injury?
death of cells after the resumption of blood flow
why does reperfusion injury occur?
increased generation of oxygen free radicals
cytokines and adhesion molecules expressed by hypoxic cells - inflammation
what are two types of reversible cellular injury?
cellular swelling
fatty change
what are two examples of irreversible cellular injury?
necrosis
apoptosis
what is the medical term used for jaundice?
icterus
what is amyloidosis?
pathological accumulation of proteinaceous substance deposited between cells
what are the main categories of amyloid?
AA - amyloid associated
AL - amyloid light chain
beta amyloid protein
islet amyloid polypeptide
where is AA synthesised?
liver
what amyloid is deposited in spongiform encephalopathies?
beta amyloid protein
where are islet amyloid polypeptides deposited?
pancreatic islets
what are the classification categories of amyloidosis?
systemic
localised
primary
secondary
when does primary amyloidosis occur?
with immunocytic disorder
when does secondary amyloidosis occur?
with complications of chronic inflammation (AA)
define pathological calcification
abnormal deposition of calcium salts
define dystrophic
relating to non-viable or dying tissue - necrosis
is dystrophic calcification intra or extracellular?
can be either
what are the serum calcium levels of animals with dystrophic calcification?
normal
what are the two steps of dystrophic calcification?
initiation and propagation
what occurs during the initiation phase of dystrophic calcification?
intracellular - Ca accumulate in mitochondira
extracellular - Ca accumulates by phospholipids in membrane bound vesicles
when and where does metastatic calcification occur?
normal tissue with hypercalcaemia
when may hypercalcaemia be seen?
increased PTH secretion
bone tissue destruction
vitamin D intoxication
renal failure
why is calcium deposited during metastatic calcification?
depending on the pH of a specific area
what are the two end points of irreversible cell injury?
apoptosis
necrosis
define necrosis
morphological changes that follow cell death
what are the two processes occurring during necrosis?
enzymatic digestion of cell - autolysis or heterolysis
denaturation of protein
what are the two outcomes of necrosis?
phagocytosis
dystrophic calcification
what is autolysis of a cell?
lysosomal enzymes of the dying cell itself
what is the gross morphology of necrosis?
focal discoloured (red/white) areas within tissue
what are the three appearances of nuclei undergoing necrosis?
pyknosis, karyorrhexis, karyolysis
what is pyknosis?
chromatin collapses - nucleus becomes round and condensed
define karyorrhexis
fragmentation of the nucleus
define karyolysis
complete dissolution of the nucleus
what are the types of necrosis?
coagulative
liquefactive
caseous
fat
what is the dominant feature of coagulative necrosis?
denaturation
when does coagulative necrosis occur?
in hypoxic cell death
what type of necrosis preserves the cell outline?
coagulative
what is the dominant feature of liquefactive necrosis?
enzymatic digestion
when does liquefactive necrosis occur?
focal material/fungal infections
what is the end result of liquefactive necrosis?
complete digestion of cells forming a liquid masss
when does caseous necrosis occur?
coagulative necrosis in tuberculosis
what is fat necrosis?
focal destruction of adipose tissue
what is fat necrosis usually due to?
release of pancreatic enzymes with pancreatic necrosis
how does fat necrosis appear?
chalky white - fat combines with calcium
define apoptosis
programmed cell death
what are the biochemical steps of apoptosis?
protein cleavage
protein cross-linking
DNA breakdown
phagocytic recognition
what are the phases of apoptosis?
initiation (signalling pathway)
control and integration
execution phase
phagocytosis
what are the two ways apoptosis is initiated?
signals transmitted across plasma membrane to intracellular regulatory molecules
signals addressed within target cells
what are examples of apoptotic stimuli external to the cell?
hormones, growth factors, cytokine
what are intracellular apoptotic stimuli?
heat, radiation, hypoxia, viral infection, glucocorticoids
does inflammation occur with apoptosis?
no
when may apoptosis occur?
embryogenesis tumours neutrophils in inflammation lymphocyte death cell death by cytotoxic T cells viral disease pathological atrophy ageing
