Cell Injury + Cell Death Flashcards
Examples of physiological hypertrophy
Skeletal, cardiac muscle (increased workload)
Uterine smooth muscle (increased estrogenic activity)
Examples of pathological hypertrophy
Cardiac muscle hypertrophy due to pressure overload
Arterial smooth muscle hypertrophy due to hypertension
Bowel smooth muscle hypertrophy due to colon obstruction
Examples of hyperplasia
Glandular proliferation in breast at puberty
Benign prostatic hyperplasia
Liver regeneration
Hypertrophy is?
Increase in cell size
Hyperplasia is?
Increase in cell number
Examples of physiological atrophy
Thymus involution (shrinking of thymus with age)
Closure of ductus arteriosus and foramen ovale
Brain, muscle atrophy with age
Causes of pathological atrophy
Disease
Ischemia
Malnutrition
Examples of pathological atrophy
Poliomyelitis causing musclular atrophy
Renal artery stenosis causing affected kidney atrophy due to decreased workload
Types of metaplasia (3)
Columnar to Squamous
Squamous to Columnar
Connective tissue metaplasia
Examples of columnar to squamous
Smoking, ductal stones
Example of squamous to columnar
Barrett esophagus
Esophagus normally lined with nonkeratinising squamous epithlium suited to handle friction from food bolus. Acid reflux from the stomach causes metaplasia to nonciliated, mucin-producing columnar cells, better able to handle the cellular stress of gastric acid.
Connective tissue metaplasia
Formation of bone, cartilage or adipose in tissue that does not normally contain them (e.g. myositis ossificans - calcium deposition in muscle during bruise healing causes hard bone like structure within the muscle)
Other examples of metaplasia
Squamous metaplasia is common in the transformation zone between ectocervix and endocervix - it can be either physiological: metaplasia as cervix becomes more everted during puberty OR pathological: Cervical Intraepithelial Neoplasia (CIN), and development of cancer
Intestinal metaplasia due to increased gastric acidity (could be due to gastrinoma), H. pylori or bile reflux from small intestine
Causes of cell injury (7)
Oxygen deprivation, physical agents, chemical agents, infectious agents, immunlogic reactions, genetic derangements, nutritional imbalances
Mechanisms of cell injury (4)
Cell membrane damage
Mitochondrial damage (leading to insufficient aerobic respiration)
Ribosomal damage (leading to altered protein synthesis)
Nuclear damage
Cell membrane damage caused by
Complement-mediated lysis by MAC (membrane attack complex)
Bacterial toxins
Free radicals
Mitochondrial damage caused by
Hypoxia
Cyanide poisoning
Ribosomal damage caused by
Alcohol in liver
Antibiotics in bacteria (protein synthesis inhibitors like macrolides/aminoglycosides LOL)
Nuclear damage caused by
Viruses
Radiation
Free radicals
Early changes caused by cell injury
*Reversible
Cytoplasmic swelling
Mitochondrial & ER swelling
Chromatin clumping
Late changes caused by cell injury
*Irreversible
Change in densities of mitochondrial matrix t
Cell membrane disruption
Nuclear shrinking (pyknosis)
Nuclear dissolution (karyolysis)
Nuclear fragmentation (karyorrhexis)
Lysosome rupture
Subcellular responses to cell injury
Unfolded protein response
Autophagy
What is unfolded protein response? And what is the side effect?
Increased expression of protective (cell stress/heat shock) proteins including:
Small proteins (molecular chaperones) that protect proteins from further damage
Ubiquitin (cofactor in proteolysis) which tags damaged proteins for removal via proteosome
BUT this may lead to aggregates of ubiquitin and damaged proteins presenting as inclusion bodies such as:
Mallory hyaline bodies in hepatocytes due to alcoholic liver damage
Lewy bodies in neurons in Parkinson’s disease
What is autophagy?
Cell stress > cell eats its own organelles > atrophy
*this forms residual bodies which may accumulate as lipofuscin
Eliminate abnormal toxic molecules
Allows recycling of molecular components > survival mechanism
What is autolysis?
Death of cell after death of organism/after cell is surgically removed from the organism
Degraded by post-mortem release of digestive enzymes from lysosomes
What is apoptosis?
Programmed cell death
Examples of physiological apoptosis
In embryogenesis: apoptosis of limb buds (precursors to limbs) and organ involution
Immature lymphocytes in lymph organs to prevent autoimmunity
Endometrial cells in menses
Crypt regeneration in GIT
Examples of pathological apoptosis
Viral infection, such as Hepatitis (hepatocytes) and HIV (CD4 T helper cells)
Atrophy in parenchymal organs due to duct obstruction (e.g. pancreas, kidney, parotid)
Loss of apoptosis can lead to
Neoplastic lymphoid proliferation - follicular lymphoma, low grade: t(14, 18) and BCL2 gene rearrangement
Characteristics of necrosis
Always pathological, large number of cells in one area. Death of cells in living tissues characterised by breakdown of cell membrane. Digestion and denaturation of proteins caused by hydrolytic enzymes released from damaged lysosomes.
Causes of necrosis
Organ/tissue lose function, intracellular enzymes released, initiate inflammation
Examples of release intracellular enzymes
Cardiac muscle cells - troponin T, creatine kinase (CKMB) after acute myocardial infarction
Hepatocytes - ALT, AST
Skeletal muscle cells - creatine kinase (CKMM)
Pancreatitis - release of pancreatic enzymes causing fat necrosis
Types of necrosis (7)
Coagulative
Liquefactive
Caseous
Haemorrhagic
Suppurative
Fat
Gangrene
Coagulative necrosis?
Necrotic tissue remains firm
Secondary to hypoxia (ischemia, infarction) EXCEPT brain
Ghost cell - no nuclei, paler region
E.g. AMI, renal infarct
**RED INFARCTION: when blood re-enters a loosely organised tissue
Liquefactive necrosis?
Necrotic tissue is liquefied
E.g. cerebral infarct, post-stroke
Caseous necrosis?
Cheesy
Granuloma (enclosed within distinctive inflammatory border with epithelioid cells, lymphocytes, AFB in langerhan giant cells seen in Ziehl-Neelsen stain)
Typical of tuberculosis
Haemorrhagic necrosis?
Dual blood supply or secondary to venous congestion
E.g. Volvulus of intestine leading to venous occlusion, congestion of intestinal veins
Chronic obstruction of hepatic portal vein (Budd-Chiari syndrome/hepatic vein thrombosis) or vena cava (heart failure)
Suppurative necrosis?
Seen in abscess formation - collection of neutrophils and pus
E.g. Occurs in entamoeba histolytica infection (parasite) - trophozoites or amoebiasis can be seen, resemble large foamy histiocytes but with small single round eccentric nucleus and ingested RBCs
Fat necrosis?
Appears chalky white due to deposition of calcium in a process called saponification (fatty acids join w calcium)
Acute pancreatitis, pancreatic enzymes digest retroperitoneal fat
Gangrenous necrosis?
Characteristic of lower limb and GIT ischemia
Differences between apoptosis and necrosis
Apoptosis: membrane preserved, single cell, non-inflammatory, active process
Necrosis: membrane breached, many cells, inflammatory, passive process
What is senescence?
In germinal cells, telomerase is present, so the length of the telomeres can be maintained (the cell can replicate endlessly)
However, in somatic cells, telomerase is absent, so telomere is shortened with every round of DNA replication and chromosomes become unstable. As the chromosome becomes more unstable, it eventually reaches senescence, a point where apoptosis occurs.
