Clinical Sciences Flashcards

Question

X-llinked recessive inheritance?

Answer 1

In X-linked recessive inheritance only males are affected. An exception to this seen in examinations are patients with Turner's syndrome, who are affected due to only having one X chromosome. X-linked recessive disorders are transmitted by heterozygote females (carriers) and male-to-male transmission is not seen. Affected males can only have unaffected sons and carrier daughters. Each male child of a heterozygous female carrier has a 50% chance of being affected whilst each female child of a heterozygous female carrier has a 50% chance of being a carrier. The possibility of an affected father having children with a heterozygous female carrier is generally speaking extremely rare. However, in certain Afro-Caribbean communities G6PD deficiency is relatively common and homozygous females with clinical manifestations of the enzyme defect are seen.

Answer 2

Vitamin D-resistant rickets is a X-linked dominant condition which usually presents in infancy with failure to thrive. It is caused by impaired phosphate reabsorption in the renal tubules

Answer 3

failure to thrive normal serum calcium, low phosphate, elevated alkaline phosphotase x-ray changes: cupped metaphyses with widening of the epiphyses

Answer 4

Diagnosis is made by demonstrating increased urinary phosphate Management high-dose vitamin D supplements oral phosphate supplements

Answer 5

Burkitt's lymphoma Hodgkin's lymphoma Post transplant lymphoma Nasopharyngeal carcinoma

Answer 6

Cervical cancer Anal cancer Penile cancer Vulval cancer Oropharyngeal cancer

Answer 7

Penetrance describes the proportion of a population of individuals who carry a disease-causing allele who express the related disease phenotype. Expressivity describes the extent to which a genotype shows its phenotypic expression in an individual. Penetrance describes 'how likely' it is that a condition will develop examples of conditions with incomplete penetrance include retinoblastoma and Huntington's disease in contrast, achondroplasia shows 100%, or complete, penetrance Expressivity describes the 'severity' of the phenotype a condition with a high level of expressivity is neurofibromatosis

Answer 8

These phenomena are thought to be due to a number of factors, including: Modifier genes Environmental factors Allelic variation

Answer 9

Riboflavin is a cofactor of flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN) and is important in energy metabolism. Consequences of riboflavin deficiency: angular cheilitis

Answer 10

upper small intestine especially the duodenum about 10% of dietary iron absorbed Fe2+ (ferrous iron) much better absorbed than Fe3+ (ferric iron) absorption is regulated according to body's need increased by vitamin C, gastric acid decreased by proton pump inhibitors, tetracycline, gastric achlorhydria, tannin (found in tea)

Answer 11

total body iron = 4g haemoglobin = 70% ferritin and haemosiderin = 25% myoglobin = 4% plasma iron = 0.1%

Answer 12

carried in plasma as Fe3+ bound to transferrin

Answer 13

stored as ferritin in tissues

Answer 14

This role in B cell activation makes IgD crucial for the initiation of immune responses. When an antigen binds to the IgD molecule on a B cell, it triggers the cell to proliferate and differentiate into an antibody-secreting plasma cell.

Answer 15

Mitochondrial disease symptoms typically develop at around the age of 30 years central scotoma → loss of colour vision → rapid onset of significant visual impairment

Answer 16

Leber's optic atrophy symptoms typically develop at around the age of 30 years central scotoma → loss of colour vision → rapid onset of significant visual impairment MELAS syndrome: mitochondrial encephalomyopathy lactic acidosis and stroke-like episodes MERRF syndrome: myoclonus epilepsy with ragged-red fibres Kearns-Sayre syndrome: onset in patients < 20 years old, external ophthalmoplegia, retinitis pigmentosa. Ptosis may be seen sensorineural hearing loss

Answer 17

inheritance is only via the maternal line as the sperm contributes no cytoplasm to the zygote none of the children of an affected male will inherit the disease all of the children of an affected female will inherit the disease generally, encode rare neurological diseases poor genotype:phenotype correlation - within a tissue or cell there can be different mitochondrial populations - this is known as heteroplasmy e

Answer 18

translation and folding of new proteins manufacture of lysosomal enzymes site of N-linked glycosylation examples of cells with extensive RER include pancreatic cells, goblet cells, plasma cells

Answer 19

steroid, lipid synthesis examples of cells with extensive SER include those of the adrenal cortex, hepatocytes, testes, ovaries

Answer 20

Modifies, sorts, and packages these molecules that are destined for cell secretion The addition of mannose-6-phosphate to proteins designates transport to lysosome

Answer 21

Aerobic respiration. Contains mitochondrial genome as circular DNA

Answer 22

DNA maintenance RNA transcription RNA splicing the process that removes the intervening, non-coding sequences of genes (introns) from pre-mRNA and joins the protein-coding sequences (exons)

Answer 23

Breakdown of large molecules such as proteins and polysaccharides

Answer 24

ribosome production

Answer 25

Translation of RNA into proteins

Answer 26

Catabolism of very long chain fatty acids and amino acids Results in the formation of hydrogen peroxide

Answer 27

Along with the lysosome pathway involved in degradation of protein molecules that have been tagged with ubiquitin

Answer 28

involved in the cell-mediated response and delayed (type IV) hypersensitivity secrete IFN-gamma, IL-2, IL-3

Answer 29

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

Answer 30

Cerebral calcification Chorioretinitis Hydrocephalus other features: anaemia hepatosplenomegaly cerebral palsy Up to 70% of infected and untreated children will remain clinically well at birth and will exhibit signs of the infection later in life. Chorioretinitis remains the most common presentation of congenital toxoplasmosis. It is seen as a white focal lesion with surrounding exudate located adjacent to an old scar. Small pigmented/atrophic scars can also be seen.

Answer 31

Low birth weight Purpuric skin lesions Sensorineural deafness Microcephaly Other features: Visual impairment Learning disability Encephalitis/seizures Pneumonitis Hepatosplenomegaly Anaemia Jaundice Cerebral palsy

Answer 32

Sensorineural deafness Congenital cataracts Congenital heart disease (e.g. patent ductus arteriosus) Glaucoma Other features: Growth retardation Hepatosplenomegaly Purpuric skin lesions 'Salt and pepper' chorioretinitis Microphthalmia Cerebral palsy

Answer 33

Vitamin D is a fat-soluble vitamin that plays a key role in calcium and phosphate metabolism. It is converted into the prohormone calcifediol in the liver. Circulating calcifediol is then converted into calcitriol (the biologically active form of vitamin D) in the kidneys.

Answer 34

increases plasma calcium and plasma phosphate increases renal tubular reabsorption and gut absorption of calcium increases osteoclastic activity increases renal phosphate reabsorption Vitamin D increases serum calcium primarily through raising its absorption via the small intestine

Answer 35

Osteomalacia

Answer 36

Subunits of troponin troponin C: binds to calcium ions troponin T: binds to tropomyosin, forming a troponin-tropomyosin complex troponin I: binds to actin to hold the troponin-tropomyosin complex in place

Answer 37

the same genetic defect can result in a wide range of clinical manifestations. This variability is due to factors such as heteroplasmy - the presence of both normal and mutated mitochondrial DNA (mtDNA) within a cell - and other genetic or environmental influences.

Answer 38

multiple cardiac problems may be present endocardial cushion defect (most common, 40%, also known as atrioventricular septal canal defects) ventricular septal defect (c. 30%) secundum atrial septal defect (c. 10%) tetralogy of Fallot (c. 5%) isolated patent ductus arteriosus (c. 5%)

Answer 39

face: upslanting palpebral fissures, epicanthic folds, Brushfield spots in iris, protruding tongue, small low-set 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

Answer 40

Subfertility learning difficulties short stature repeated respiratory infections acute lymphoblastic leukaemia hypothyroidism Alzheimers disease atlantoaxial instability

Answer 41

superiority: whilst this may seem the natural aim of a trial one problem is the large sample size needed to show a significant benefit over an existing treatment equivalence: an equivalence margin is defined (-delta to +delta) on a specified outcome. If the confidence interval of the difference between the two drugs lies within the equivalence margin then the drugs may be assumed to have a similar effect non-inferiority: similar to equivalence trials, but only the lower confidence interval needs to lie within the equivalence margin (i.e. -delta). Small sample sizes are needed for these trials. Once a drug has been shown to be non-inferior large studies may be performed to show superiority

Answer 42

activates macrophages

Answer 43

a rare mitochondrial disorder characterized by the triad of onset before 20 years of age, progressive external ophthalmoplegia (PEO), and pigmentary retinopathy (retinitis pigmentosa).

Answer 44

a rare genetic disorder characterized by obesity, intellectual disability, retinitis pigmentosa, polydactyly (extra fingers or toes), and hypogonadism.

Answer 45

Genetic disorder characterized by sensorineural hearing loss at birth and progressive vision loss due to retinitis pigmentosa

Answer 46

a rare metabolic disorder caused by a deficiency of phytanic acid alpha-hydroxylase enzyme resulting in an accumulation of phytanic acid in tissues. The clinical features include retinitis pigmentosa, peripheral neuropathy, cerebellar ataxia, anosmia (loss of smell), and ichthyosis (dry scaly skin).

Answer 47

Refsum disease: AR -cerebellar ataxia, peripheral neuropathy, deafness, ichthyosis, anosmia, Usher syndrome- AR, deafness - most common form of deaf blind abetalipoproteinemia Lawrence-Moon-Biedl syndrome is a rare AR It is characterized predominantly by hypogonadism, polydactyly, retinitis pigmentosa, obesity, and mental retardation. Kearns-Sayre syndrome- mitochondria deletion, <20 year old, prog external ophthalmoplegia, assoc with heart block, cerebellar ataxia, ragged red fibre on muscle biopsy Alport's syndrome- x linked- renal (GBM t4 collagen), deafness, protrusion of lens, ret pigment

Answer 48

mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS)

Answer 49

0 - Exploratory studies I - safety assessment II - Assess efficacy III - assess effectiveness IV - postmarketing surveillance

Answer 50

Exploratory studies Involves a very small number of participants and aim to assess how a drug behaves in the human body. Used to assess pharmacokinetics and pharmacodynamics. Phase 0 trials help in determining whether it is feasible to move on to further phases.

Answer 51

Safety assessment Determines side-effects prior to larger studies. Conducted on healthy volunteers

Answer 52

assess efficacy Involves small number of patients affected by particular disease May be subdivided into IIa - assesses optimal dosing IIb - assesses efficacy

Answer 53

Assess effectiveness Typically involves 100-1000's of people, often as part of a randomised controlled trial, comparing new treatment with established treatments

Answer 54

Post marketing surveillance? Monitors for long-term effectiveness and side-effects

Answer 55

Fragile X (CGG) Huntington's (CAG) myotonic dystrophy (CTG) Friedreich's ataxia* (GAA) spinocerebellar ataxia spinobulbar muscular atrophy dentatorubral pallidoluysian atrophy

Answer 56

Homocystinuria is a rare autosomal recessive disease caused by a deficiency of cystathionine beta synthase. This results in severe elevations in plasma and urine homocysteine concentrations.

Answer 57

often patients have fine, fair hair musculoskeletal > Marfanoid body habitus: arachnodactyly etc >osteoporosis > kyphosis neurological: may have learning difficulties, seizures ocular >downwards (inferonasal) dislocation of lens > severe myopia increased risk of arterial and venous thromboembolism also malar flush, livedo reticularis

Answer 58

Fabry disease is an X-linked recessive disorder characterised by a deficiency of alpha-galactosidase A.

Answer 59

Severe neuropathic/limb pain brought on by stress, heat, or cold Angiokeratomas Renal features: proteinuria, polyuria, polydipsia Cardiac: left ventricular hypertrophy, coronary artery disease, valvular abnormalities and heart failure Cerebrovascular: TIAs/strokes

Answer 60

Enzyme replacement therapy with agalsidase alfa

Answer 61

Drugs which interfere with metabolism trimethoprim methotrexate pyrimethamine Drugs which can reduce absorption phenytoin

Answer 62

lung (most common) breast bowel skin (namely melanoma) kidney

Answer 63

Glioblastoma is the most common primary tumour in adults and is associated with a poor prognosis (~ 1yr). On imaging: Solid tumour with central necrosis and a rim that enhances with contrast. Histology: Pleomorphic tumour cells border necrotic areas Treatment is surgical with postoperative chemotherapy and/or radiotherapy. Dexamethasone is used to treat the oedema.

Answer 64

Meningiomas are typically benign, extrinsic tumours of the central nervous system. They arise from the arachnoid cap cells of the meninges and are typically located next to the dura and cause symptoms by compression rather than invasion. * They typically are located at the falx cerebri, superior sagittal sinus, convexity or skull base. * Histology: Spindle cells in concentric whorls and calcified psammoma bodies * Investigation is with CT (will show contrast enhancement) and MRI, and treatment will involve either observation, radiotherapy or surgical resection.

Answer 65

A vestibular schwannoma (previously termed acoustic neuroma) is a benign tumour arising from the eighth cranial nerve (vestibulocochlear nerve). Often seen in the cerebellopontine angle. It presents with hearing loss, facial nerve palsy (due to compression of the nearby facial nerve) and tinnitus. * Neurofibromatosis type 2 is associated with bilateral vestibular schwannomas. * Histology: Antoni A or B patterns are seen. Verocay bodies (acellular areas surrounded by nuclear palisades) * Treatment may involve observation, radiotherapy or surgery.

Answer 66

The most common primary brain tumour in children Histology: Rosenthal fibres (corkscrew eosinophilic bundle)

Answer 67

A medulloblastoma is an aggressive paediatric brain tumour that arises within the infratentorial compartment. It spreads through the CSF system. Treatment is surgical resection and chemotherapy. * Histology: Small, blue cells. Rosette pattern of cells with many mitotic figures

Answer 68

* Commonly seen in the 4th ventricle * May cause hydrocephalus * Histology: perivascular pseudorosettes

Answer 69

* Benign, slow-growing tumour common in the frontal lobes * Histology: Calcifications with 'fried-egg' appearance

Answer 70

Vascular tumour of the cerebellum * Associated with von Hippel-Lindau syndrome * Histology: foam cells and high vascularity