ic2 Flashcards
Requirements for homeostasis (IC2)
- energy from mitochondria
- compartmentalisation of organelles (importance of lipid bilayer membrane)
- control mechanism (nucleus, signalling pathway)
- quality control systems (lyosomes: autophagy, all types of biomolecules: ubiquitin, proteasome system: only protein)
- repair process
cells when stressed (ic2)
1) adaptive response: cope with stress, enable cell to cope with increased workload
2) damage (cell injury): sublethal (Reversible) / lethal (irreversible)
type of adaptive responses (ic2)
1) increase in size: hyperplasia (increase in cell no, reversible), hypertrophy (increase in cell size, reversible)
2) decrease in size: hypoplasia/aplasia (decrease in cell no, reversible), atrophy (decrease in cell size, both reversible/irreversible)
3) change in cell type: metaplasia (cell doesn’t work as well, reversible)
examples of abnormal stimulus that results in increase in size (ic2)
e.g. : increase work demand, excess endocrine stimulation, metabolic demand, persisting tissue injury
physiological:
1) dedicated workout -> skeletal muscle hypertrophy
2) physiological response to hormonal change -> uterine enlargement in pregnancy (hyperplasia & hypertrophy, small spindle shaped cells to large plump cells)
pathological
1) pressure load (hypertension) -> left ventricular hypertrophy (left ventricle increase in size, response to pressure and/or volume loads
2) androgen (older men) -> benign prostate hyperplasia (urinary retention -> urinary tract infection / obstructive uropathy -> renal failure)
3) prolonged oestrogen stimulation -> benign endometrial hyperplasia (abnormal menstrual bleeding, increased risk of developing endometrial carcinoma
decrease in size due to adaptation to loss of required stimulus (ic2)
e.g. : decreased functional demand, disuse, inadequate nutrients, poor blood supply, denervation, aging
disuse (after limb fracture/prolonged inactivity), denervation -> skeletal muscle atrophy
chronic narrowing of renal artery -> unilateral renal artery stenosis with renal atrophy
drugs, chemicals, ionising radiation, immune system attack -> marrow hypoplasia (bone marrow failure)
metaplasia (change cell type) (ic2)
. replacement of one differentiated cell type by another cell type
. most common: columnar epithelium to stratified squamos, often in bronchus of smokers
. e.g. Barrett’s oesophagus (stratified squamos epithelium to columnar epithelium, chronic acid reflux)
aetilogies (Causes) of cell injury (ic2)
. physical: trauma, cold, heat, electrical, ionising radiation, hypoxia
. chemical: therapeutic, non-therapeutic
. immunological: hypersensitivity
. biological: infectious agents (bacteria, virus, fungi)
. nutritional: effects on cells and rowth
. genetic: enzyme deficiency, abnormalities
. aging: cell lifespan, environment (chronic stress)
common mechanisms of cell injury (stimulus) (ic2)
1) decrease in ATP
2) mitochondrial damage: leakage of pro-apoptotic proteins (promote/cause apoptosis)
3) entry of Ca2+: increase in mitochondrial permeability, activation of multiple cellular enzymes
4) increase in reactive oxygen species (ROS): free radicals cause oxidative damage to proteins/lipids/DNA
5) membrane damage: plasma (loss of cellular components), lysosomal (enzymatic digestion of cellular components)
6) protein misfolding, DNA damage: activation of pro-apoptotic proteins
common sites of injury (ic2)
1) cell membrane
2) mitochondria
3) cytoskeleton
4) nuclear DNA
after onset of cell injury (ic2)
. stress exerts effect at biomolecular. molecular, ultrastructural level
. morphological change taxes take longer to become visibly exident
. cell death if unable to replace damaged components
. features of dead cell: loss of nucleolus (early), no ribosomes, swelling of mitochondria, swelling of ER, nuclear condensation, membrane blebs and holes, lysosome rupture, fragmentalisation of all inner membrane, nuclear break up
autophagy (ic2)
. removal of damaged/redundant proteins, part/whole organelles, areas of nucleus
. breakdown via lysosomal enzymes
. controlled process within autophagosome
. protect/destroy cell depending on condition
. factors that stimulate: starvation, oxidative stress, irradiation, hormonal signals, accumulation of mis-folded proteins, change in cell volume
general properties of sublethal damage (ic2)
. reversible damage
. light microscopic changes (cellular swelling, fatty change)
sublethal damage - cellular swelling (ic2)
. first visible manifestation for most injury
. pale cytoplasm
. development of intracellular vacuoles (hydropic change/hydropic degeneration), cell incapable of maintaining ionic and fluid homeostasis, increase in intracellular [Na] & accumulation of water
. organ turns pale, increase in turgor and weight
reversible if injurious situation corrected
sublethal damage - steatosis (fatty acid change) (ic2)
. cells with central role in fatty acid metabolism (common in liver cells)
. normal (brownish pink) vs bad liver (yellowish pale)
. reversible but long standing steatosis -> cirrhosis and liver failure
intracellular accumulations (ic2)
. chronic mild injury associated with other forms of intracellular accumulations
. types: pigments, environmental particles, cholesterol and cholesterol esters, proteins
intracellular accumulations - pigments (endogenous, not because of external environmental factor) (ic2)
. lipofuscin: ‘wear and tear’ pigment, in long-lived neurons, cardiac myocytes, hepatocytes
. haemosiderin: aggregates of denatured ferritin/iron complex (local/systemic excess of iron)
. melanin: freckles in light-skinned children following sun exposure
. bilirubin: deposits in tissue result in jaundice
intracellular accumulations - environmental particles (ic2)
. carbon deposits from cigarette smoking
. colour pigments from tattooing
intracellular accumulations - cholesterol and cholesterol esters (ic2)
. atherosclerosis: in smooth muscle cells & macrophages of arteries
. xanthomas: in macrophages in sub epithelial connective tissue in skin and tendons
intracellular accumulations - proteins (ic2)
. misfolded proteins in neurons of patients with Alzheimer disease
. aggregates of abnormal protein: some form of Amyloidosis (build up in organs, interfere with function)
apoptosis (ic2)
. physiological & programmed (for elimination of unwanted cells)
. pathological when abnormally activated
. tidy & systematic, minimal inflammatory response
. intrinsic (withdrawal of growth factors/hormones affect mitochondria) vs extrinsic (receptor-ligand interactions, cytotoxic T lymphocytes), both lead to activation of caspases that break down cells into fragments -> formation of cytoplasmic bud and apoptotic body
initiators of apoptosis (ic2)
1) binding of specific ligands
2) cell damage pathway
3) DNA damage/p53-p73 pathway
4) cell membrane damage pathway
pathology of apoptosis (ic2)
1) death of native cells in acute inflammation
2) death induced by cytotoxic T cells
3) viral diseases (e.g. vial hepatitis)
4) apoptosis-necrosis overlap
necrosis (ic2)
. form of cell death, morphological changes seen following cell death, always pathological
. denaturation of intracellular proteins and/or enzymatic digestion in dead cells
. common features: no nuclei, cytoplasmic eosinophilia
types of necrosis (ic2)
1) coagulative necrosis: occurs in infarction, necrotic cells retain cell outlines, cytoplasm eosinophilic, loss of nuclei
2) liquefactive necrosis: pathological lesion (cerebral infarct, infective abscess), brain full of myelin and fatty material after tissue dies, necrotic area semi-fluid, no visible cell outline (release of powerful hydrolytic enzymes that degrade cellular components and extracellular material)
3) caseous necrosis: TB infection, macroscopically: gray-white, soft, cheese-like material, microscopically: dead cells persists as solid but eosinophilic amorphous material, cell outline not retained, no tissue-architecture seen
4) fibrinoid necrosis: follow damage to blood vessels, plasma proteins accumulate in wall -> resemble blood clot
necrosis - calcification (ic2)
large amount of Ca enter necrotic tissue/cell -> complex with phosphates within mitochondria -> hydroxyapatite crystals
intracellular/extracellular
can occur in normal tissue/cell associated with hypercalcemia
apoptosis vs necrosis (ic2)
1) single/scattered cells involved vs groups of cells affected
2) programmed by cell vs triggered by injury
3) cell shrink cytoskeletally vs cell swell hydropically
4) orderly fragmentation of nucleus vs haphazard DNA turnover
5) fragments released as apoptotic bodies, rapidly phagocytosed vs rupture
6) tidy and systematic vs messy and disorganised
7) minimal inflammatory response vs debris trigger inflammation
8) require ATP vs triggered by depletion of ATP
cellular aging mechanisms (ic2)
1) decrease in replication (telomere shortening due to Hayflick limit)
2) accumulative damage (genetic & environmental insult, DNA repair effects)
3) abnormal growth factor signalling
hyperaemia (ic2)
. vessels of microcirculation contain more blood than normal
. active hyperaemia: increase blood flow to organ cuz of nervous impulse (blushing) or functional demand (muscles durin exercise, acute inflammation)
. passive hyperaemia: decrease blood flow out of organ cuz of congestion, caused by local (obstructed vein)/general (congestive heart failure)
oedema (ic2)
. excessive extravacular accumulation of fluid in interstitial tissues/body cavities
. primary causes due to change in Starling’s forces:
1) increase hydrostatic pressure
2) decrease oncotic/osmotic pressure
3) increase endothelial permeability
4) lymphatic obstruction
types of oedema (ic2)
1) localised: impaired venous draining, increase vascular permeability and hyperaemia, obstruction/destruction of lymphatics
2) generalised: cardiac oedema (fluid in lung -> pulmonary oedema), renal oedema (nephrotic disease, protein loss in urine due to glomerular disease/decrease in plasma oncotic pressure -> fluid to extravascular compartment -> RAA system activated -> kidney retain Na+ and H2O
exudate vs transudate (ic2)
1) protein content: high vs low
2) types of protein: plasma fibrinogen vs albumin, no fibrinogen
3) specific gravity: high (1.018) vs low (1.012)
4) cells: many vs little inflammatory cells
haemorrhage (ic2)
. causes: traumatic, spontaneous (abnormal blood vessel/platelets (thrombocytopenia (low blood platelet count, bruise and bleed excessively), qualitative platelet defect), coagulation factor deficiency)
. response to blood loss:
1) initial: maintenance of BP and flow, sympathetic response
2) compensation for volume loss: fluid retention, redistribution of blood to vital organs
3) replacement of red cells (Depends on function of bone marrow)
shock (ic2)
. state of inadequate perfusion of cells and tissues leading to reversible hypoxic injury and, if severe or prolonged enough, to irreversible cell and organ injury and death
. types:
1) hypovolemic shock (hemorrhage, severe burns, vomiting & diarrhea)
2) cardiogenic shock (pump failure)
3) distributive shock (generalised vasodilation, septic shock, anaphylactic shock, neurogenic shock)
4) obstructive shock (pulmonary embolism, pericardial tamponade, mechanical obstruction to heart)
