8/ growth Flashcards
what is cell hypertrophy
- type of tissue growth
- cells enlarge (without necessarily dividing)
what is cell proliferation
- type of tissue growth
- daughter cells half the volume, need hypertrophy to get back to same volume as parent
what is growth by accretion
- type of tissue growth
- cells excrete extracellular matrix around them - eg cartilage
cell cycle outline
- G1: very long or permanent
- S: DNA replication
- G2: cell doesn’t function well at this stage - temp gap
- M: nuclear and cytoplasmic division
cell cycle checkpoints
- end of G1: start checkpoint, checks for favourable environment. activates by FGF and IGF, inhibited by TS gene Rb (mutated in retinoblastoma)
- G2/M: enter mitosis. check for all DNA replicated, favourable environment
- metaphase to anaphase checkpoint: trigger anaphase and proceed to cytokinesis. checks chromosomes attached to spindle
3 negative feedback loops affecting GH and skeletal growth
- somatostatin inhibits GH, GH activates somatostatin
- GHRH activates GH, GH inhibits GHRH
- circulating IGF-1 inhibits GH
how does GH cause skeletal growth
- stimulates liver to produce IGF-1
- circulating IGF-1 reaches bone and drives proliferation
- local IGF-1 synthesis drives bone proliferation
what do IGF, GH and GHRH stand for and where are they released
- Growth hormone releasing hormone. hypothalamus, with somatostatin
- Growth hormone. pituitary gland
- Insulin like growth factor. liver and local tissue (muscle etc)
organ with poor sense of its size and experiment
- pancreas
- transgenic mouse is generated that expressed diphtheria toxin under control of tetracycline - genetic ablation, kills cells of interest
- pancreas reduced to 36% of its normal size and only recovered to 40-50% of its normal size
organ with good sense of its own size and experiment
- liver
- transgenic mouse is generated that expressed diphtheria toxin under control of tetracycline - genetic ablation, kills cells of interest
- liver reduced to 33% of its normal size and regenerated to 86%
regulation of organ size by TOR pathway
- activates cell growth which increases cell size
- cell hypertrophy
regulation of organ size by hippo pathway
- hippo inhibits cell proliferation, which would have activated cell proliferation, which would have activated cell number
- hippo activates cell death which inhibits cell number
- so hippo shrinks tissue - mutations cause overgrowing/tumours
apoptosis
- deliberate suicide
- careful coordination of cell shut down, followed by engulfment of remnants by other cells
- caused by stresses like starvation or DNA damage
- used development for unneeded cells (eg webbing between fingers)
- in adult tissue, mainly used for homeostasis (mammary gland-breast shrinks back after breastfeeding) and health (get rid of virally infected cells or genetically compromised tumour cells)
necrosis
- cause by injury, infection, cancer, infarction, inflammation
- disorderly dying off, w/o signalling to neighbouring cells
- cells split open and empty contents into surrounding tissue - dangerous, bacteria can start feeding on nutrients
effects of myostatin
- activates Rb, which inhibits proliferation of myoblasts
- inhibits MyoD which would activate transition from myoblasts to multinucleate myotube
- secreted by muscle fiber - negative feedback on muscle growth
- mutations in myostatin cause increased muscle growth
cartilage to bone
- chondrocytes secrete cartilage matrix in the shape of the skeleton
- over time bone is formed on the cartilage matrix by osteoblasts (ossification)
- during ossification chondrocytes die by apoptosis
- cartilage remains in joint areas as adult - shock absorber
how to look at skeleton vs cartilage in an embryo
- bone matrix is red when treated with alizarin red
- cartilage matrix is blue when treated with alcian blue
postnatal growth in long bones
- long bones while growing have cartilage on either end and bone forms on the long part (in middle)
- ossification centers inside joints where bone is forming
- growth plates between cartilage and bone drive growth: contain chondrocytes that proliferate, hypertrophy and then die, remaining cartilage matrix turned into bone by osteoblasts
- growth plates close when you stop growing
examples of long bones
clavicle, humerus, radius, ulna, metacarpus, phalanges, femur, tibia, fibula, metatarsus, phalanges
sex specific differences
- girls have earlier growth spurt
- in embryo, high levels of androgens in ring finger (4D) promote growth
- high levels of oestrogens in ring finger (4D) repress growth