Clinical Sciences Flashcards
1
Q
HLA B27?
A
Ankylosing spondylitis Postgonococcal arthritis Acute anterior uveitis Reiter’s syndrome (reactive arthritis)
2
Q
HLA-DR2?
A
Narcolepsy
Goodpasture’s
(2 good 2 sleepy)
3
Q
HLA DR3?
A
Autoimmune hepatitis
Primary biliary cirrhosis
Diabetes mellitus type 1
Dermatitis herpetiformis
Coeliac disease (95% associated with HLA-DQ2)
Primary Sjögren syndrome
4
Q
HLA DR4?
A
Rheumatoid arthritis
Diabetes mellitus type 1 (> DR3)
(4 fingers, BM 4)
5
Q
HLA B47?
A
21-hydroxylase deficiency
(47 is life expectancy)
6
Q
HLA A3?
A
Hemochromatosis
Iron overload –> overloaded –> think cardiology, ward A3
7
Q
HLA-B5?
A
Bechet’s disease
B –> Bechet’s
8
Q
Clusters of differentiation? (CD molecules)
A
9
Q
Type I Hypersensitivity Reaction?
A
Anaphylactic
- Antigen reacts with IgE bound to mast cells
- Anaphylaxis, atopy
10
Q
Type II Hypersensitivity?
A
Cell Bound
- IgG or IgM bind to antigen on cell surface
- Autoimmune haemolytic anaemia, ITP, Goodpasture’s
11
Q
Type III Hypersensitivity Reaction?
A
Immune Complex
- Free antigen and antibody (IgG, IgA) combine
- Serum sickness, SLE, post-streptococcal glomerulonephritis, extrinsic allergic alveolitis
12
Q
Type IV Hypersensitivity?
A
Delayed Hypersensitivity
- T-cell mediated
- TB, Tuberculin skin reaction, graft vs host disease, contact dermatitis, scabies, extrinsci allergic alveolitis (chronic phase)
Think Ts
13
Q
Type V hypersensitivity reaction?
A
Stimulated Hypersensitivity
- IgG antiboides stimulate cells they are directed against
- Grave’s, Myasthenia Gravis
14
Q
IgG?
A
- IgG makes up approximately 75% of the serum antibodies.
- IgG has a half-life of 7-23 days depending on the subclass.
- IgG is a monomer and has 2 epitope-binding sites
- The Fc portion of IgG can activate the classical complement pathway.
- The Fc portion of IgG can bind to macrophage and neutrophils for enhanced phaGocytosis.
- The Fc portion of IgG can bind to NK cells for antibody-dependent cytotoxicity (ADCC).
- The Fc portion of IgG enables it to cross the placenta. (IgG is the only class of antibody that
can cross the placenta and enter the fetal circulation).
15
Q
IgA?
A
- IgA makes up approximately 15% of the serum antibodies, it has a half-life of aound 5 days.
- IgA is found mainly in body secretions (saliva, mucous, tears, colostrum and milk) as secretory IgA (sIgA) where it protects internal body surfaces exposed to the environment by blocking the attachment of bacteria and viruses to mucous membranes.
- Secretory IgA is the most immunoglobulin produced.
- IgA is made primarily in the mucosal-associated lymphoid tissues (MALT).
- IgA appears as a dimer of 2 “Y”-shaped molecules and has 4 epitope-binding sites and secretory component to protect it from digestive enzymes in the secretions
- The Fc portion of secretory IgA binds to components of mucous and contributes to the ability of mucous to trap microbes.
- IgA can activate the alternative complement pathway. (IgA = Alternate)
16
Q
IgM?
A
- IgM makes up approximately 10% of the serum antibodies and is the first antibody produced
during an immune response. - IgM has a half-life of about 5 days.
- IgM is a pentamer and has 10 epitope-binding sites
- The Fc portions of IgM are able to activate the classical complement pathway (most efficient)
- Monomeric forms of IgM are found on the surface of B-lymphocytes as B-cell receptors or sIg.
17
Q
IgD?
A
- IgD makes up approximately 1% of the serum antibodies.
- IgD is a monomer and has 2 epitope-binding sites.
- IgD is found on the surface of B-lymphocytes (along with monomeric IgM) as a B-cell receptor or sIg where it may control of B-lymphocyte activation and suppression.
- IgD may play a role in eliminating B-lymphocytes generating self-reactive autoantibodies.
18
Q
IgE?
A
- IgE makes up about 0.002% of the serum antibodies with a half-life of 2 days.
- Most IgE is tightly bound to basophils and mast cells via its Fc region.
- IgE is a monomer and has 2 epitope-binding sites.
- IgE is made in response to parasitic worms (helminths) and arthropods. It is also often made in
response to allergens. - IgE may protect external mucosal surfaces by promoting inflammation, enabling IgG,
complement proteins, and leucocytes to enter the tissues. - The Fc portion of IgE can bind to mast cells and basophils where it mediates many allergic
reactions. Cross linking of cell-bound IgE by antigen triggers the release of vasodilators for an
inflammatory response. - The Fc portion of IgE made against parasitic worms and arthropods can bind to
eosinophils enabling opsonization. This is a major defense against parasitic worms and
arthropods.
19
Q
Most common targets of pANCA and cANCA?
A
cANCA
- Serine protease 3 (PR3)
- Wegener’s +ve in 90%
pANCA
- Myeloperoxidase (MPO)
- Immune crescentic glomerulonephritis (+ve in 80%)
- Microscopic polyangiitis (+ve in 50-75%)
- Churg-Strauss (+ve in 60%)
- Wegener’s (+ve in 25%)
- Others = IBD (UC > Crohn’s), CTD, Autoimmune hepatitis
20
Q
Complement Deficiencies?
A
C1
- Causes hereditary angioedema
C1q, C1rs, C2, C4
- Predisposes to immune complex disease
- SLE, HSP
C3
- Causes recurrent bacterial infections
C5
- Predisposes to Leiner disease
- Recurent diarrhoea, wasting and seborrhoeic dermatitis
- Disseminated meningococcal infection
C5-9
- Encodes for the MAC
- Prone to Neisseria meningitidis infection
21
Q
Anion gap?
A
(Na+ + K+) - (Cl- + HCO-3)
22
Q
Causes of normal anion gap metabolic acidosis (hyperchloraemic)
A
- Gastrointestinal bicarbonate loss: diarrhea, ureterosigmoidostomy, fistula
- Addison’s disease
- Renal tubular acidosis
- Drugs: e.g. Acetazolamide
- Ammonium chloride injection
GARDA
HCO3 loss and replaced with Cl- -> anion gap normal
23
Q
Causes of HAGMA?
A
Accumulation of organic acids or impaired H+ excretion
LKTR
- Lactate - shock, hypoxia
- Ketones - DKA, alcohol
- Toxins - salicyclates, methanol
- Renal - high urea
24
Q
Lactic acidosis types?
A
Type A
- Shock, hypoxia, burns
Type B
- Metformin
25
Causes of metabolic alkalosis?
Loss of hydrogen ions or gain of bicarbonate
* Vomiting / aspiration (e.g. Peptic ulcer leading to pyloric stenosis, nasogastric suction)
* Diuretics
* ECF depletion --\> Na+ and Cl- loss --\> activation of RAAS --\> raised aldosterone --\> reabsorption of Na+ in exchange for H+ in DCT
* Liquorice, carbenoxolone
* **Hypokalemia** - K+ shifts into ECF, H+ shifts into cells to maintain neutrality --\> alkalosis
* Primary hyperaldosteronism
* Congenital adrenal hyperplasia
* Cushing's syndrome
* Bartter's syndrome
* Defect in thick ascending loop of Henle
* Hypokalaemia, alkalosis, and normal to low blood pressure
26
Interpretation of urinary sodium in hyponatraemia?
**_\>20mmol/L_**
* Sodium depletion due to renal loss
* If hypovolaemic
* Diuretics, diuretic stage of renal failure, Addison's
* If euvolaemic
* SIADH (urine osmolality \>500)
* Hypothyroidism
**_\<20mmol/L_**
* Sodium depletion, extra-renal loss
* If hypovolaemic
* Diarrhoea, vomiting, sweating
* Burns, adenoma of rectum
* If overloaded
* Secondary hyperaldosteronism, CCF, cirrhosis
* Low EGFR with volume overload
* IV dextrose, psychogenic polydipsia
27
Causes and consequences of hypophosphataemia?
**_Causes_**
* Alcohol excess
* Acute liver failure
* Diabetic ketoacidosis
* Refeeding syndrome (like in anorexia nervosa management)
* Primary hyperparathyroidism
* Osteomalacia
**_Consequences_**
* Red blood cell hemolysis
* White blood cell and platelet dysfunction
* Muscle weakness and rhabdomyolysis
* Central nervous system dysfunction
28
Actions of PTH and vitamin D?
**_PTH_**
* Increases plasma calcium, Decreases plasma phosphate
* Increases renal tubular reabsorption of calcium
* Increases osteoclastic activity
* Increases renal conversion of 25-hydroxy vitamin D to 1,25 dihydroxy vitamin D
* Decreases renal phosphate reabsorption
**_Vitamin D_**
* Increases plasma calcium and Increases plasma phosphate
* Increases renal tubular reabsorption and gut absorption of calcium
* Increases osteoclastic activity
* Increases renal phosphate reabsorption
29
Causes of hyper and hypocalcaemia?
**_Hypercalcaemia_**
* Sarcoidosis
* Vitamin D intoxication
* Acromegaly
* Thyrotoxicosis
* Milk-alkali syndrome
* Drugs: thiazides, Ca++ containing antacids
* Dehydration
* Addison's disease
* Paget's disease of bone
**_Hypocalcaemia_**
* Vitamin D deficiency (osteomalacia)
* Chronic renal failure
* Hypoparathyroidism (e.g. Post thyroid/parathyroid surgery)
* Pseudohypoparathyroidism (target cells insensitive to PTH)
* Rhabdomyolysis (initial stages)
* Magnesium deficiency (due to end organ PTH resistance)
30
Hyperuricaemia?
Associated with hyperlipidaemia and HTN - seen in metabolic syndrome
**_Increased synthesis_**
* Lesch-Nyhan disease
* Myeloproliferative disorders
* Diet rich in purines
* Exercise
* Psoriasis
* Cytotoxics
**_Decreased Excretion_**
* Drugs: low-dose aspirin, diuretics, pyrazinamide
* Pre-eclampsia
* Alcohol
* Renal failure
* Lead
31
Acute phase reactants and negative acute phase reactants?
**_Increase_**
* CRP
* Ferritin
* Fibrinogen
* Alpha-1 antitrypsin
* Caeruloplasmin
* Serum amyloid A
* Serum amyloid P component
* Haptoglobin
* Complement
**_Decrease_**
* Albumin
* Transthyretin (formerly known as prealbumin)
* Transferrin
* Retinol binding protein
* Cortisol binding protein
32
RF - what is it? Conditions with +ve RF?
IgM antibody against own IgG
Detected by
* Rose-Waaler test: sheep red cell agglutination
* Latex agglutination test (less specific)
**_Conditions_**
* Sjogren's syndrome (around 100%)
* Felty's syndrome (around 100%)
* Infective endocarditis (= 50%)
* SLE (= 20-30%)
* Systemic sclerosis (= 30%)
* General population (= 5%)
* Rarely: TB, HBV, EBV, leprosy
33
Effects of nitric oxide?
* Acts on guanylate cyclase leading to raised intracellular cGMP levels and therefore decreasing Ca++ levels
* Vasodilation, mainly venodilation
* Inhibits platelet aggregation
34
Actions of atrial natriuretic peptide?
Secreted by both atria (R\>L) and ventricle in response to increased blood volume
Acts via guanylate cyclase and cGMP
* Natriuetic (promotes excretion of sodium)
* Lowers BP
* Antagonises angiotensin II, aldosterone
35
BNP actions?
Produced by LV in response to strain
* Vasodilator
* Diuretic and natriuretic
* Suppresses both sympathetic tone and the renin-angiotensin-aldosterone system
Useful marker of prognosis in HF, useful in guiding treatment.
36
Actions of endothelin?
* Potent, long-acting vasoconstrictor and bronchoconstrictor.
* Secreted by vascular endothelium as a prohormone then converted to ET-1 by endothelin converting enzyme.
* Acts via a G-protein coupled receptor --\> phospholipase C --\> calcium release
**_Promotes_**
* Angiotensin II
* ADH
* Hypoxia
* Mechanical shearing forces
**_Inhibits_**
* NO
* Prostacyclin
37
Conditions with raised endothelin levels?
* MI
* Heart failure
* ARF
* Asthma
* Primary pulmonary hypertension (endothelin antagonists now used)
38
Actions of TNF?
Pro-inflammatory cytokine
Secreted by macrophages
* Activates macrophages and neutrophils
* Acts as a costimulator for T cell activation
* Key mediator of response to gram -ve septicaemia
* Similar properties to IL-1
* Anti-tumour effect (phospholipase activation)
39
Endothelial and systemic effects of TNF?
**_Endothelial_**
* Increased expression of selectins
* Increased production of platelet activating factor, IL-1 and prostaglandins
* Promotes proliferation of fibroblasts and production of protease and collagenase
**_Systemic_**
* Pyrexia
* Increased acute phase proteins
* Disordered metabolism leading to cachexia
40
TNF blockers?
**_Infliximab_**
* MAB, IV administration
* Used in Crohn's unresponsive to steroids
**_Etanercept_**
* Fusion protein, binds soluble TNF receptors; SC administration
**_Adalimumab_**
* Monoclonal antibody, SC administration
Adverse effects = reactivation of latent TB and demyelination
Used in severe RF
41
Interferons?
Cytokines released in response to viral infections and neoplasia. Classified by cellular origin and type of receptor they bind to.
**_IFN-aLpha_**
* Produced by **_L_**eukocytes
* Antiviral action
* Useful in hepatitis B & C, kaposi's sarcoma, metastatic renal cell cancer, hairy cell leukemia
* Adverse effects include fLu-Like symptoms and depression
**_IFN-Beta_**
* Produced by fibro**B**lasts
* Antiviral action
* Reduces the frequency of exacerbations in patients with relapsing-remitting MS
**_IFN-gamma_**
* Produced by T lymphocytes & NK cells
* Weaker antiviral action (inhibit viral duplication), more of a role in immunomodulation particularly macrophage activation
* May be useful in chronic granulomatous disease and osteopetrosis
42
Leukotrienes?
* Fatty molecules of the immune system that contribute to inflammation in asthma and bronchitis
* Secreted by leukocytes; Formed from arachadonic acid by lipoxygenase
* Mediators of inflammation and allergic reaction
* Cause bronchoconstriction, mucous production
* Increased vascular permeability, attract leukocytes
* NSAID incuded bronchospasm in asthma secondary to express production of leukotrienes due to inhibition of prostaglandin synthetase
43
Interluekin-1?
* Mediator of immune response
* Secreted by macrophages and monocytes
* Costimulator of T and B cell profileration
* Increases expression of adhesion molecules on endothelium
* Stimulates release of vasoactive factors (PAF, nitric oxide, prostacyclin) --\> vasodilation and increased vascular permeability --\> **_mediator of shock in sepsis_**
44
T helper cells?
**_Th1_**
* Involved in the cell mediated response and delayed (type IV) hypersensitivity
* Secrete IFN-gamma, IL-2, IL-3
**_Th2_**
* Involved in mediating humoral (antibody) immunity
* e.g. Stimulating production of IgE in asthmA
* Secrete IL-4, IL-5, IL-6, IL-10, IL-13
45
Components of thin and thick filaments?
**_Thin Filaments_**
* Troponin
* Tropomyosin
* **Actin**
**_Thick Filaments_**
* Myosin
Depolarisation --\> Ca2+ release from sarcoplasmic reticulum --\> Ca2+ binds troponin --\> Troponin/tropomyosin undergo a conformational change --\> myosin binding sites on actin exposed --\> actin/myosin form link --\> myosin pulls actin inward --\> sarcomere shortening
46
Cardiac enzymes?
* Myoglobin is the first to rise
* CK-MB is useful to look for reinfarction as it returns to normal after 2-3 days (troponin T remains elevated for up to 10 days)
47
Causes of raised ALP?
* Liver: cholestasis, hepatitis, fatty liver, neoplasia
* Paget's
* Osteomalacia
* Bone metastases
* Hyperparathyroidism
* Renal failure
* Physiological: pregnancy, growing children, healing fractures
48
Causes of raised ALP according to calcium level
**_Raised ALP, Raised Calcium_**
* Paget's
* Bone mets
* Hyperparathyroidism
**_Raised ALP, Low Calcium_**
* Osteomalacia
* Renal Failure
49
Causes of raised and low ESR?
**_High_**
* Temporal arteritis
* Myeloma
* Other connective tissue disorders e.g. Systemic lupus erythematosus
* Other malignancies
* Infection
* Other factors which raise ESR: increasing age, sex, anemia
**_Low_**
* Polycythemia
* Afibrinogenemia/hypofibrinogenemia
50
Summary of autosomal and recessive?
* Autosomal **RECESSIVE** conditions are 'METABOLIC' - exceptions
* inherited ataxias
* Mucoplysaccharidoses - Hunter's (X-linked recessive)
* G6PD (X-linked recessive)
* Autosomal **DOMINANT** conditions are 'STRUCTURAL' - exception: hyperlipidemia type II, hypokalaemic periodic paralysis
51
Mnemonic for autosomal recessive disorders?
**_ABCDEFGH_**
* Albinisim
* Beta thalessaemia
* CF
* Deafness
* Emphysema (Alpha-1-antitrypsin)
* Freidrich's ataxia
* Gaucher's disease
* Homocystinuria, Haemochromatosis
Others:
52
X-linked recessive inheritence?
* Only males affected (except Turner's syndrome)
* No male to male transmission, only from heterozygote female carriers
* Male child of heterozygous female carrier has 50% chance of being affected
* Female child of heterozygous carrier had 50% chance of being a carrier
* Daughters of affected males are 100% carriers
53
X-linke recessive conditions?
* Androgen insensitivity syndrome
* Becker muscular dystrophy
* Color blindness
* Duchenne muscular dystrophy
* Fabry's disease
* G6PD deficiency
* Hemophilia A,B
* Hunter's disease
* Kallman Syndrome (X-Linked Trait)
* Lesch-Nyhan syndrome
* Nephrogenic diabetes insipidus
* Ocular albinism
* Retinitis pigmentosa
* Severe combined immunodeficiency
54
X-linked recessive conditions?
* Androgen insensitivity syndrome
* Becker muscular dystrophy
* Color blindness
* Duchenne muscular dystrophy
* Fabry's disease
* G6PD deficiency
* Hemophilia A,B
* Hunter's disease
* Kallman Syndrome (X-Linked Trait)
* Lesch-Nyhan syndrome
* Nephrogenic diabetes insipidus
* Ocular albinism
* Retinitis pigmentosa
* Severe combined immunodeficiency
55
X-linked dominant inheritance?
* If a child has inherited the mutation from the X chromosome from one of their parents they will have the condition
* Affected mother --\> 50% chance of having affected daughter or son
* Affected father --\> sons will not get it as X comes from mother, daughters will all be affected
56
X-linked dominant conditions?
* Vit D resistant Rickets
* Alport syndrome (85% XLD)
* Rett syndrome
57
Anticipation? Trinucleotide repeat disorders?
* Anticipation = earlier onset in successive generations (also increased severity)
* Trinucleotide repeat disorders = mutations caused by abnormal number of expansions of repetitive seqeunce of three nucleotides
* Expansions are unstable and may enlarge --\> anticipation
58
Examples of trinucleotide repeat disorders?
* Fragile X (CGG)
* Huntington's (CAG)
* Myotonic dystrophy (CTG)
* Friedreich's ataxia\* (GAA)
* Spinocerebellar ataxia
* Spinobulbar muscular atrophy
* Bulbospinal Neuropathy
* Dentatorubral pallidoluysian atrophy
Note mostly neurological disorders
59
Mitochondrial Diseases?
* Small amount of double stranded DNA found in mitochondria
* All children of affected *males* **_will not_** be affected
* All children of affected *females* **_will_** be affected
* Generally rare neurological disorders
Muscle biopsy usually shows 'red, ragged fibres' due to increased number of mitochondria
60
Examples of mitochondrial diseases?
* **Leber's optic atrophy**
* **MELAS syndrome**: mitochondrial encephalomyopathy lactic acidosis and stroke-like episodes
* **MERRF syndrome**: myoclonus epilepsy with ragged-red fibres
* **Pearson syndrome**: characterized by sideroblastic anemia and exocrine pancreas dysfunction. It is usually fatal in infancy. The few patients who survive into adulthood often develop symptom of Kearns-Sayre syndrome.
* **Kearns-Sayre syndrome**: onset in patients \< 20 years old, external ophthalmoplegia, retinitis pigmentosa. Ptosis may be seen
* Sensorineural hearing loss
* Neuropathy, ataxia, and retinitis pigmentosa (NARP)
61
Tumour suppressor genes?
P53
APC: colorectal cancer
NF-1: neurofibromatosis
RB: retinoblastoma
62
P53 gene and Li-Fraumeni Syndrome?
* Tumour suppressor gene on Ch 17p
* Most commonly mutated gene in breast, colon and lung cancer
* Prevents entry into the S phase until DNA has been checked and repaired
**_Li-Fraumeni Syndrome_**
* Rare AD disorder
* Mutation in p53
* Early onset of sarcomas and breast cancer
63
Clinical features in Down's syndrome?
* Face: upslanting palpebral fissures, epicanthic folds, Brushfield spots in iris, protruding tongue, small ears, round/flat face
* Flat occiput
* Single palmar crease, pronounced 'sandal gap' between big and first toe
* Hypotonia
* Congenital heart defects (40-50%, see below)
* Duodenal atresia
* Hirschsprung's disease
* **Females** - subfertility
* **Males** - infertility
64
Cardiac defects in Down's syndrome?
* Endocardial cushion defect (40%, also known as atrioventricular septal canal defects)
* Ventricular septal defect (30%)
* Secundum atrial septal defect (10%)
* Tetralogy of fallot (5%)
* Isolated patent ductus arteriosus (5%)
65
Later complications in Down's syndrome?
* Subfertility
* Learning difficulties
* Short stature
* Repeated respiratory infections (+hearing impairment from glue ear)
* Acute lymphoblastic leukemia
* Hypothyroidism
* Alzheimer's
* Atlantoaxial instability
66
Risk of Down's syndrome with increasing maternal age?
* Risk at 30 years = 1/1000
* 35 years = 1/350
* 40 years = 1/100
* 45 years = 1/30
One way of remembering this is by starting at 1/1,000 at 30 years and then dividing by 3 (i.e. 3 times more common) for every extra 5 years of age
67
Cytogenetics of Down's syndrome?
68
Turner syndrome? Features?
45X
* Short stature
* Shield chest, widely spaced nipples
* Webbed neck
* Bicuspid aortic valve (15%), coarctation of the aorta (5-10%)
* Primary amenorrhoea
* High-arched palate
* Short fourth metacarpal
* Multiple pigmented naevi
* Lymphedema in neonates (especially feet)
High incidence of autoimmune disease (autoimmune thyroiditis and Crohn's)
69
Klinefelter Syndrome?
Hypogonadotrophic Hypogonadism (47XXY)
* Often taller than average
* Lack of secondary sexual characteristics
* Small, firm testes (hypogonadism)
* Infertile
* Gynaecomastia - increased incidence of breast cancer
* Elevated gonadotrophin levels
LH and FSH raised (in Kallman's --\> low to normal)
70
Kallman Syndrome?
Cause of delayed puberty secondary to hypogonadotrophic hypogonadism
X-linked recessive trait
Failure of GnRH secreting neurons to migrate to hypothalamus
* 'Delayed puberty'
* Hypogonadism, cryptorchidism (including undescended tests)
* Anosmia
* Sex hormone levels are low
* LH, FSH levels are inappropriately low/normal
* Patients are typically of normal or above average height
* Cleft lip/palate and visual/hearing defects are also seen in some patients
71
Marfan's syndrome?
Autosomal dominant connective tissue disorder. It is caused by a defect in the fibrillin-1 gene on chromosome 15
* Tall stature with arm span \> height ratio \> 1.05
* High-arched palate
* Arachnodactyly
* Pectus excavatum
* Pes planus
* Scoliosis of \> 20 degrees
* Heart: dilation of the aortic sinuses (seen in 90%) which may lead to aortic regurgitation, mitral valve prolapse (75%), aortic dissection
* Lungs: repeated pneumothoraces
* Eyes: upwards lens dislocation (superotemporal ectopia lentis), blue sclera
72
Noonan syndrome?
Male Turner's
AD; defect in chromosome 12
Some features similar to Turner's
* Webbed neck, widely spaced nipples, pectus carinatum and excavatum, short stature
Other signs
* Cardiac: pulmonary valve stenosis
* Ptosis
* Triangular-shaped face
* Low-set ears
* Coagulation problems: factor XI deficiency
73
Fragile X?
Trinucleotide repeat disroder with complex X-linked inheritence
**_Features in Males_**
* Learning difficulties
* Large low set ears, Long thin face, High arched palate
* Macroorchidism (Large testes)
* Hypotonia
* Autism is more common
* Mitral valve prolapse
**_Features in Females_**
* Normal to mild (because one fragile chromosome and normal X chromosome)
74
Patau syndrome?
Trisomy 13
* Mental & motor challenge
* Polydactyly (extra digits)
* Microcephaly
* Low-set ears
* Holoprosencephaly (failure of the forebrain to divide properly).
* Heart defects
* Structural eye defects, including microphthalmia, peters anomaly, cataract, iris and/or fundus (coloboma), retinal dysplasia or retinal detachment, sensory nystagmus, cortical visual loss, and optic nerve hypoplasia
* Cleft palate
* Meningomyelocele (a spinal defect)
* Omphalocele (abdominal defect)
* Abnormal genitalia
* Abnormal palm pattern
* Overlapping of fingers over thumb.
* Cutis aplasia (missing portion of the skin/hair)
* Prominent heel
* Kidney defects
* Deformed feet known as "rocker-bottom feet"
75
Prader-Willi syndrome?
Deletion on chromosome 15 (15q11-13)
* Prader-Willi if gene deleted from father
* Angelman syndrome if deleted from mother
**_Features_**
* Hypotonia during infancy
* Dysmorphic features
* Short stature
* Hypogonadism and infertility
* Learning difficulties
* Childhood obesity
* Behavioural problems in adolescence
* Acanthosis nigricans
76
Edward's syndrome?
Trisomy 18
Presence of three—as opposed to two—copies of chromosome 18
Low rate of survival
**_EDWARDS_**
* Eighteen
* Digit overlapping flexion
* Wide head
* Absent intellect
* Rocker bottom feet
* Diseased heart/kidney
* Small lower jaw
77
Vitamin deficiencies?
78
Pellagra?
Vitamin B3 (Niacin) Deficiency
Features (Ds)
* Dermatitis (scaly rash on sun exposed sites)
* Dementia
* Diarrhoea
79
Vitamin B12 deficiency - causes? Features?
**_Causes_**
* Pernicious anemia
* Post gastrectomy
* Poor diet
* Disorders of terminal ileum (site of absorption): crohn's, blind-loop etc
* Metformin
**_Features_**
* Macrocytic anemia
* Sore tongue and mouth
* Neurological symptoms: e.g. Ataxia
* Neuropsychiatric symptoms: e.g. Mood disturbances
80
Vitamin D-resistant rickets?
X-linked dominant
Presents in infancy with failure to thrive
Impaired phosphate reabsorption in renal tubules
**_Features_**
* Failure to thrive
* Normal serum Ca2+, low phosphate, high alk phos (increased urinary phosphate)
* X-ray - cupped metaphyses with widening of epiphyses
81
Folate - drugs which interefere with metabolism, drugs which reduce absorption, foods containing?
**_Contained in..._**
* Liver
* Green vegetables
* Nuts
**_Drugs which interfere with metabolism_**
* Trimethoprim
* Methotrexate
* Pyrimethamine
**_Drugs which reduce absorption_**
* Phenytoin
82
Iron - absorption, distribution, transport/storage?
**_Absorption_**
* Absorbed in duodenum
* Increased by vitamin C, gastric acid
* Decreased by PPIs, tetracyclines, gastric achlorhydria, tannin
**_Distribution_**
* Hb 70%, Ferritin/Haemosiderin 25%, Myoglobin 4%
**_Transport_**
* Carried in plasma as ferric iron bound to transferrin
* Stored as ferritin in tissues
83
Features of zinc deficiency?
* Perioral dermatitis: red, crusted lesions
* Acrodermatitis
* Alopecia
* Short stature
* Hypogonadism
* Hepatosplenomegaly
* Geophagia (ingesting clay/soil)
* Cognitive impairment
84
Cell organelles summary?
85
Cell cycle summary? Where does P53 act?
P53 acts at G1 - checks DNA before duplication. This phase determines length of cycle
S = DNA synthesis
86
Membrane receptor summaries?
1. **_Ligand Gated Ion Channel_**
* Mediate fast responses
* nACh receptors, GABA-A/GABA-B, glutamate receptors
2. **_Tyrosine Kinase Receptors_**
* Contain intrinsic enzyme activity
* Insulin, growth factors, interferon
3. **_Guanylate Cyclase Receptors_**
* Contain intrinsic enzyme activity
* ANP, Nitric oxid receptors
4. **_G-Protein Coupled Receptors_**
* Mediate slow transmission and affect metabolic processes
* Ligand binding --\> conformational change to the receptor
* mACh, adrenergic receptors, GABA-B
87
Pathways of adrenoreceptors?
All are G-protein coupled
* alpha-1: activate phospholipase C --\> IP3 --\> DAG
* alpha-2: inhibit adenylate cyclase
* beta-1: stimulate adenylate cyclase
* beta-2: stimulate adenylate cyclase
* beta-3: stimulate adenylate cyclase
88
Alpha 1 receptors - actions? Agonist?
* Vasoconstriction
* Relaxation of GI smooth muscle
* Salivary secretion
* Hepatic glycogenolysis
Agonist = Phenylephrine
89
Alpha 2 recetor - actions? Agonist?
* Mainly presynaptic: inhibition of transmitter release (inc NA, Ach from autonomic nerves)
* Inhibits insulin
* Platelet aggregation
Agonist = clonidine
90
Beta 1 receptors - actions? Agonist?
* Mainly located in the heart
* Increased heart rate + force
Agonist = dobutamine
91
Beta 2 receptors - actions? Agonist?
* Vasodilation
* Bronchodilation
* Relaxation of GI smooth muscle
Agonist = salbutamol
92
Beta 3 receptors - action?
Lipolysis
Agonists being developed - may have a role in preventing obesity
93
Second messenger overview?
Allow amplification of external stimulus
1. Cyclic AMP
* Adrenaline, noradrenaline, glucagon, LH, FSH, TSH, calcitonin, parathyroid hormone
2. Cyclic GMP
* ANP, nitric oxide
3. Protein Kinase Activity
* Insulin, growth hormone and factor, prolactin, oxytocin, erythropoietin
4. Calcium and/or phosphoinositides
* ADH, GnRH, TRH
94
Molecular biology techniques?
SNOW DROP
* **S**outh - **NO**rth - **W**est
* **D**NA - **R**NA - **P**rotein
Southern, Northern and Western Blotting - western detects and quantifies, southern and northern just detect
95
Skull Foramina summary?
96
Renal anatomy summary?
97
Skin Layers
98
Cardiac action potential?
