Disorders of growth, differentiation and morphogenesis Flashcards
Types of growth
Multiplicative: increase in number of cells by mitosis.
Auxetic: increased size of individual cells (skeletal muscle)
Accretionary: increase in intracellular tissue components (bone)
Combined patterns: embryological development.
Cell types based on regenerative ability
Labile (very high reg.) intestine
Stable (good regen, low turnover) hepatocytes
Permanent (no) neurones
What does the M phase comprise of?
Nuclear division (mitosis) + cytoplasmic division (cytokinesis)
Totipotent
Able to form all of the cells of the embryo and placenta
Pluripotent
Producing all cells from endo-, meso-, and ectoderm.
Multipotent + Unipotent
Generates small number of cell types or only one.
Hypertrophy
Increase in cell size without cell division
Hyperplasia
Increase in size by increasing the number of cells by mitosis.
Also a decrease in apoptosis.
Physiological examples of hypertrophy
Muscles in athletes (skeletal and LV)
Physiological examples of hyperplasia
Bone marrow cells in high altitudes.
Breast tissue in pregnancy.
Thyroid - increased metabolic demand (pregnancy)
Physiological example of hypertrophy and hyperplasia (mixed)
Uterine smooth muscle by oestrogens.
Disease marked by epidermal hyperplasia
Psoriasis
Hyperplasia of osteoblasts and osteoclasts resulting in thick but weak bone
Paget’s disease
Autonomous proliferations of myofibroblasts - forming tumour like masses
Fibromatoses
Angiogenesis can take place by…
Sprouting
Intussusception
Circulating stem cells recruited to the site of hypoxia.
VEGF and MMP
Vascular endothelial cells and myofibroblast hyperplasia…
Important components of repair and regeneration.
Athropy
Decrease in size of an organ or cell
Atrophy may be..
Physiological - post menopause
Pathological - immobilisation of limbs = muscle atrophy. Loss of innervation etc.
Pressure atrophy
Bed sores (exogenous)
Tumour compresses against BV (endogenous)
Cachexia
Severe starvation (systemic atrophy) influenced by CKs and TNF.
Hypoplasia
Failure of development of an organ.
Related to atrophy
Failure of morphogenesis
Example of hypoplasia
Failure in the development of the legs in severe spina bifida PTs.
Metaplasia
Acquired form of altered differentiation (one mature differentiated cell into another)
Response to altered cellular environment.
Affects epithelial and mesenchymal cells
Increased risk of malignancy.
Examples of metaplasia
Respiratory epithelium of trachea and bronchi to squamous epithelium.
Bladder epithelium to simple squamous in the presence of stone and ova of Schistosoma haematobium.
Example of glandular metaplasia
Barrett’s oesophagus from squamous epithelium to columnar glandular epithelium (glandular metaplasia).
Examples of mesenchymal metaplasia
Osseous metaplasia
- Ca deposition in atheromatous arterial walls
- bronchial cartilage
Congenital disorder
Present at birth.
Autosomal chromsome trisomy
21 Down’s syndrome
18 Edward’s syndrome
13 Patau’s syndrome (microcephaly, cleft lip and cleft palate) die in first year.
Sex chromosomal abnormalities
Klinefelter’s 47 XXY: testicular atrophy, geynaecomastia (varients 48 XXXY, 49 XXXXY, 48 XXYY)
Double Y males 47 XYY
Turner’s syndrome 45 X: short stature, amenorrhoea and infertility.
Multiple X females: 47 XXX, 48 XXXX mental retardation.
Hermaphrodites (true) 46 XX, 46XX, 47XXY both testicular and ovarian tissue.
Loss of part of a chromosome
Cri-du-chat syndrome (46XX 5p-) deletion of short arm of chromosome 5.
Three categories of single gene disorders
Enzyme defects: albinism lack of melanin, galactose-1-phosphate uridyl transferase deficiency.
Receptor or cellular transport defect: lack on androgen receptor = insensitivity. CF no membrane transport.
Non-enzyme protein defects: sickle cell anaemia. Marfan’s and Ehlers-Danlos defective collagen production.
Deformation or disruption
Anomalies of normal development caused by extrinsic physical forces.
Malformations
Intrinsic failures of morphogenesis, differentiation or growth.
Kartagener’s syndrome
Defect in ciliary motility due to absent or abnormal dynein arms -> situs inversus.
Hirschsprung’s disease
Marked dilation of the colon and failure of colonic motility = absence of Meissner and Auerbach’s nerve plexuses.
Cryptorchidism
Failure of testis to migrate to its normal position.
Agenesis
Failure of development of an organ or structure within it.
Renal - few days of survival
Thymic - DiGeorge (poor T-cell production)
Anencephaly - lethal
Atresia
Failure of the development of a lumen in a normally tubular structure.
Oesophageal - fistulae
Biliary atresia - obstructive jaundice in early childhood.
Urethral atresia.
Hypoplasia
Failure of an organ to attain its normal size.
Osseous nuclei of the acetabulum= congenital dislocation of the hip due to the flattened roof to the acetabulum.
Maldifferentiation (dysgenesis)
Failure of normal organ differentiation or presistence of primitive embryological structures.
Ectopia
Development of mature tissue in an inappropriate site.
Endometriosis
Merkel’s diverticulum
Neural tube defects are due to what?
Dietary deficiency of folate.
Spina bifida
During 4th week the neural tube is formed by invagination of the dorsal ectoderm.
Failure of the neural tube to invaginate fully / the overlying ectoderm to close afterwards results in defects = exposed cord.
Cleft palate
Occur in the first 9 weeks = from about 5 weeks the maxillary processes grow anteriorly and medially - fuse with the fronto-nasal process at two points just below the nostrils= upper lip.
Palate develops from palatal processes of maxially processes and fuse with the nasal septum.
Failure of this results in cleft palate.
