ESA 1 Clinical Conditions Flashcards
Amyloidosis
Misfolding of proteins leading to insoluble form of normally soluble protein. Effects vary dependent on location – in brain -> Alzheimer’s/dementia
Sickle Cell Anaemia
Autosomal Recessive - A -> T, Glu -> Val, Hydrophilic -> Hydrophobic, leads to creation of hydrophobic knob that can join with natural hydrophobic pocket (in B chains only) when Hb is in T state. Polymerised Hb causes cell to adopt sickle shape. Can block microvasculae and cause sickle cell crisis (lots of pain, downstream ischaemia). Crisis precipitated by factors that reduce O2 availability (so promote T state): smoking, obesity, cold, infection etc.
Haemolytic anaemia as a result of spleen removing sickled RBCs. Jaundice as a result of excess bilirubin from excess breakdown.
Can have trait, mainly no symptoms of SCA but conveys protection against malaria, very common in Sub-Saharan Africa.
Cystic Fibrosis
Autosomal Recessive – Defective cystic fibrosis transmembrane regulator (CFTR) gene (most commonly one codon deletion), leading to impaired ability to transport Na+/Cl-. Osmosis means this causes thick mucus across the body: in the respiratory tract means the ciliary escalator no longer works, bacteria aren’t cleared and cause infections. In the pancreatic duct this means mucus blocks the duct, causing pancreatitis and stopping fat digestion. In sweat this creates abnormally salty sweat. Also causes vas deferens to never form in males -> infertility. No genetic cure so treat symptoms: prophalaxis for lung infections, lipase tablets to digest fats, can recover sperm from testes (bypassing vas deferens).
Thalassaemias
A thal – Decreased or absent A chains in Hb, appears before birth.
B thal – decreased or absent B chains in Hb, appears after birth (fetal Hb is A and Y chains). Neither can form stable tetramers. Reduced Hb -> reduced O2 capacity -> usual symptoms of anaemia.
Haemophilia A
Recessive X Linked – No/reduced factor VIII production -> blood can’t clot as well (factor Xa production down 50%). Treat with recombinant factor VIII, avoid thrombolytics/blood thinners.
Scurvy
Vit C deficiency, prolyl hydroxylase can’t convert proline -> hydroxyproline, reduced H bonds, less cross links, weakened structure, “wobbly” collagen.
Down’s Syndrome
Trisomy 21 -Extra 21st chromosome due to meiotic division error or Robertsonian translocation. Characteristic facial features, impaired intelligence, heart defects, inc prevalence leukaemia, inc early onset alzheimers. Can be screened during pregnancy.
`Edward’s Syndrome
Trisomy 18 – Extra 18th chromosome due to meiotic division error or Robertsonian translocation. ‘Rocker bottom’ feet, overlapping fingers, small lower jaw. Live one or two weeks.
Patau’s Syndrome
Trisomy 13 – Can be due to meiotic division error or Robertsonaian translocation. Congenital heart defects, cleft lip etc. Median survival is 2.5 days.
Turner’s Syndrome
Monosomy X – Only occurs in women, single sex chromosome, so missing one copy of the small autosomal region at the start of the sex chromosomes. Short stature, heart defects, mild learning difficulties, neck webbing, infertility.
Klinefelter’s Syndrome (XXY)
Occurs in men, extra X chromosome -> smaller testes -> reduced testosterone production -> lack of male sex characteristics at puberty. Hypogonadism, infertility, no coarse body hair, gynoacomastia etc. Treat with testosterone (doesn’t reverse infertility).
Ectopic pregnancy
Implantation of embryo in fallopian tube, leads to rupture of tube, miscarriage and haemorrhage.
Placenta praevia
Implantation of embryo in lower segment of uterine wall, placenta blocks cervix – c section required
Marfan’s Syndrome
Autosomal Dominant - Misfolding of fibrillin leading to more elastic connective tissue. Very tall, long digits, death usually around 40 from aortic rupture (arteries too elastic, just snap.)
Ethlers-Danlos disease
Type 3 collagen deficiency leading to loss of structure (reticulin = scaffold). Presents as stretchy skin, unstable joints, easy bruising etc
Vitiligo
Autoimmune destruction of melanocytes, leads to depigmentation, psychosocial problems for dark skinned people (not very noticeable on fair skin)
Alopecia areata/universalis
Autoimmune destruction of hair follicles. Can occur anywhere and everywhere, on head creates psychosocial problems, particularly for women. Worsened by stress
Psoriasis
Extreme overproduction of skin cells, eventually leading to too much corneum when it reaches that part of the cycle – manifests as “scaling”. Genetic link but cause unknown, treat with steroids.
Malignant melanoma –
UV damage induces mutations that give rise to malignant cancer – prognosis good if not penetrated basement membrane, poor if has. Uncommon with dark/black skin, melanin provides protection against this damage
Osteogenesis imperfecta
Autosomal Dominant - Disease resulting in type 1 collagen deformity/deficiency, major component in ground substance of bone. Most severe case leads to no conversion of feotal (hyaline) skeleton, incompatible with life. In most cases, repeated fractures lead to bowed long bones, and can be confused with NAI. Blue sclera due to unknown cause, possibly thinning of cornea due to issues with collagen that forms it.
Rickets/osteomalacia
Deficiency in vit D, less absorption of Ca2+ by small bowel -> less rigid bones. Rickets in kids – bowed bones as they’re still growing. Osteomalacia in adults – bone/back ache, and can be secondary to impaired hepatic/renal function (less absorption). Both more common in dark skinned people as fair skin synthesises vit D better than dark skin.
