Clinical Sciences Flashcards
Rough ER Functions
- translation and folding of new proteins
- manufacture of lysosomal enzymes
- n-likned glcyosylation
Smooth ER functions
-Steroid and lipid synthesis
Golgi apparatus functions
- Modifies and packages molecules for secretions
Mitochrondria functions
Aerobic respiration
Mitochrondria DNA
Circular DNA
Nucleus functions
- DNA maintenance
- RNA transcription
- RNA splicing
Lysosome function
Breakdown of latge molecules
Nucleolus function
Ribosome production
Ribosome function
Translation of RNA into proteins
Peroxisome function
Catabolism of long fatty acids and amino acids
Formation of hydrogen peroxide
Proteasome function
Degradation of protein molecules
Southern Blotting
Detects DNA
Northern Blotting
Detects RNA
Western Blotting
Detects proteins
e.g. HIV test
ELISA
Detects antigens and antibodies
Reverse Transcriptase PCR
Amplify RNA
Study designs: Ia
Evidence from meta-analysis of RCTs
Study designs: Ib
Evidence from at least x1 RCT
Study designs: IIa
Evidence from at least x1 well designed controlled trial not randomised
Study designs: IIb
Evidence from at least x1 well designed experimental trial
Study designs: III
Evidence from case, correlation and comparative studies
Study designs: IV
Evidence from panel of experts
Left ventricular ejection fraction: formula
(stroke volume / end diastolic LV volume) * 100
Stoke volume: formula
end diastolic LV volume - end diastolic LV volume
Cardiac output: formula
stroke volume x HR
Alkaptonuria: deficiency
- Homogentisic dioxygenase
Alkaptonuria: features
Pigmented sclera
Black urine in air
Disc calcification
Renal stones
Alkaptonuria: Rx
High dose vitamin C
Dietary restriction
Cell surface proteins: CD4, TCR, CD3, CD28
helper T cell
Cell surface proteins: CD8, TCR, CD3, CD28
Cytotoxic T cells
Cell surface proteins: CD4, CD25, TCR, CD3, CD28
Regulatory T cell
Cell surface proteins: CD19, CD20, CD40, MHC II, B7
B cell
Cell surface proteins: CD14, CD40, MHC II, B7
Macrophage
MHC molecule that presents lipid molecules
CD 1: function
Thymocytes, T cells and NK cells
Act as ligand for CD58 and. CD59
CD 2: function
Signalling component of TCR
CD 3: function
Th cells
Co-receptor for MHC II
Used by HIV to enter cells
CD 4: function
Found in mantle cell lymphoma
CD 5: function
Tc cells
Co-receptor for MHC I
CD 8: function
Found on Reed-Sternberg cells
CD 15: function
Bind to IgG
CD 16: function
Oncogenes: ABL
CML
Oncogenes: c-MYC
Burkitt’s lymphoma
Oncogenes: n-MYC
Neuroblastoma
Oncogenes: BCL-2
Follicular lymphoma
Oncogenes: RET
MEN II and MEN III
Oncogenes: RAS
Pancreatic cancer
Oncogenes: erb-B2 (HER2)
Breast and ovarian cancer
Nitric oxide: effects
Vasodilation
Inhibits platelet aggregation
Nitric oxide: receptor
acts on guanylate cyclase raising intracellular cGMP and decreasing Ca
Tumour suppressor: p53
Li-Fraumeni syndrome
Tumour suppressor: APC
CRC
Tumour suppressor: BRCA1/2
Breast and ovarian cancer
Tumour suppressor: NF1
Neurofibromatosis
Tumour suppressor: Rb
Retinoblastoma
Tumour suppressor: WT1
Wilm’s tumour
Tumour suppressor: MTS-1
Melanoma
Vitamin B1: Name
Thiamine
Vitamin B1: deficiency
Alcohol XS and malnutrition
Vitamin B1: Wernicke’s
Nystagmus, ophthalmoplegia and ataxia
Vitamin B1: Korsakoff’s
Amnesia, confabulation
Vitamin B1: dry berbiberi
Peripheral neuropathy
Vitamin B1: wet berbiberi
Dilated cardiomyopathy
Standard error: formula
standard deviation / (root of samples)
Bohr effect
Increased acidity (or CO2) means O2 binds less well to Hb
Haldane effect
Increase in O2 means CO2 binds less well to Hb
Prader-Willi syndrome: cause
15q11-13 paternal deletion
Prader-Willi sydrome: features (8)
Hypotonia Dysmorphic features Short Hypogonadism Infertility LD Obesity Behavioural problems
MELAS syndrome
Mitochondrial encephalomyopathy lactic acidosis and stroke like episodes
MERRF syndrome
Myoclonus epilepsy with ragged-red fibres
Kearns-Sayre syndrome
External ophthalmoplegia, retinitis pigmentosa
PKU: Defect
Phenylalanine hydroxylase
Chromosome 12
PKU: Features (6)
Developmental delay Fair hair and blue eyes LD Seizures Eczema Musty urine and sweat
PKU: Diagnosis
Guthrie test
Hyperphenylalaninaemia
Phenylpyruvic acid in urine
Respiratory physiology: hypoxia
- Vasoconstriction of pulmonary arteries
Leukotrienes: Function
- Mediators of inflammation and allergic reaction
Leukotrienes: Effect
Bronchoconstriction
Mucus production
Increased vascular permeability
Leukotrienes: Production
Secreted by leukocytes
Hypersensitivity reactions: 1
anaphylaxis
IgE mediated
Hypersensitivity reactions: 1 examples
Anaphlyaxis
Atopy
Hypersensitivity reactions: 2
Cell mediated
IgG and IgM bind to cell membrane
Hypersensitivity reactions: 2 examples (5)
Goodpastures, ITP, rheumatoid fever, autoimmune haemolytic anaemia, pernicious anaemia
Hypersensitivity reactions: 3
Immune complex
Free antigen and antibody combine
Hypersensitivity reactions: 3 examples
SLE, post strep GN, acute extrinsic alveolitis
Hypersensitivity reactions: 4
Delayed hypersensitivity
T cell mediated
Hypersensitivity reactions: 4 examples (6)
TB skin reaction, contact dermatitis, graft vs host, scabies, MS, GBS
Hypersensitivity reactions: 5
Antibodies bind and stick to cell surface
Hypersensitivity reactions: 5 examples
Myasthenia gravis, Graves
Acute inflammation and fevers
Source; macrophages
IL 1
Stimulates growth and proliferation of T cells
Source; Th1
IL 2
Stimulates differentiation and proliferation of myeloid lineage cells
Source; activated Th cells
IL 3
Differentiation of T cells
Source; Th cells
IL 4
Eosinophil production
Source; Th cells
IL 5
Differentiation of B cells and fevers
Source; Th cells
IL 6
Neutrophil chemotaxis
Source; macrophages
IL 8
Anti-inflammatory. Inhibits Th synthesis
Source; Th2 cells
IL 10
Stimulates maturation of immature T cells
Source; dendritic cells, B cells, macrophages
IL 12
Increased renin secretion
Hypotension, hyponatraemia, sympathetic nerve stimulation, catecholamines, erect position
Decreased renin secretion
Beta blockers, NSAIDs
TNF-a
induces fever and neutrophil chemotaxis
Source; macrophage
HLA A3
Haematochromatosis
HLA B51
Bechets
HLA B27
Ankylosing spondylitis, anterior uveitis, reactive arthritis
HLA DQ2/8
Coeliac
HLA DR2
Narcolepsy, Goodpasture’s
HLA DR3
Dermatitis herpetiformis, PSC, Sjogrens
HLA DR4
RA, T1DM
Cell cycle: G0
Resting phase
Cell cycle: G1
Cells increase in size
Under influence of p53
Determines length of cycle
Cell cycle: S
Synthesis of DNA, RNA and histones
Cell cycle: G2
Cells increase in size
Homocystinuria: deficiency
Cystathionine beta synthase
Homocystinuria: features
tall, long fingered, Marfanoid, downward lens dislocation, DVT, learning difficulties
Homocystinuria: management
Vitamin B6
Complement deficiencies: C1
Hereditary angioedema
Complement deficiencies: C1q, C1s, C2, C4
Immune complex disease
Complement deficiencies: C3
Recurrent bacterial infections
Complement deficiencies: C5
Lenier disease (recurrent diarrhoea, wasting and seborrhoeic dermatitis)
Complement deficiencies: C5-9
Prone to N. meniginitdes infections
Non REM 1 sleep
Light sleep. Associated with hypnic jerks
Non REM 2 sleep
Deeper sleep
Non REM 3 sleep
Deep sleep
Parasomnias
REM sleep
Dreaming. Loss of muscle tone and erections
Congenital Rubella
Sensorineural deafness, cataracts, congenital heart disease, glaucoma
Congenital Toxoplasmosis
Cerebral calcification, chorioretinitis, hydrocephalus
Congenital CMV
Growth retardation, purpuric skin lesions
Clinical Trial: 1 purpose
Determines pharmacokinetics and pharmacodynamics
Clinical Trial: 2 purpose
Assesses efficacy and dosing
Clinical Trial: 3 purpose
Assesses effectiveness
Clinical Trial: 4 purpose
post marketing surveilance
Parametric tests
T test and Pearson’s
Mann Whitney
Compares ordinal, interval or ratio scales of unpaired data
Wilcox Rank
Compares 2 observations on a single sample e.g. before and after
Chi Squared
Compare proportions or percentages
Fabry’s disease: deficiency
Alpha-galasosidase A
Fabry’s disease: features
paraesthesia, angiokeratomas, lens opacities, proteinuria, early CVD
Niacin deficiency: features
Dementia, dermatitis, diarrhoea
Li Fraumeni syndrome
Mutation of p53
Early onset of cancers
Sensitivity
TP / (TP + FN)
Proportion of those with condition who test positive
Specificity
TN / (TN + FP)
Proportion of those without condition who test positive
PPV
TP / (TP + FP)
Chance of having condition if tests positive
NPV
TN / (TN + FN)
Chance of not having the condition if tests negative
Likelihood ratio for positive
sensitivity / (1 - specificifty)
Likelihood ratio for negative
(1-sensitivity) / specificity
IF - a: production
Produced by leukocytes
IF - a: viruses
HBV, HCV, Kapsosi’s, metastatic RCC, hairy cell leukaemia
IF - a: SE
Flu like illness
Depression
IF - B: production
Fibroblasts
IF - B: Uses
Relpasing-remitting MS
IF - gamma: Production
NK and Th cells
IF - gamma: action
Macrophage activation
Th1 cells secrete
IFN-gamma, IL 2, IL 3
Th2 cells secrete
IL 4 / 5 /6 / 10 / 13
Positive skewed
mean > median > mode
Negative skewed
mean < median < mode
Type 1 error
Rejection of null hypothesis when it is true
False positive
Type 2 error
Acceptation of null hypothesis when it is false
False negative
Power
Probability of correctly rejection null hypothesis when it is false
Cardiac conduction: rapid depolarisation
rapid Na influx
Cardiac conduction: early repolarisation
K efflux
Cardiac conduction: plateau
slow Ca influx
Cardiac conduction: final repolarisation
K efflux
Cardiac conduction: restoration
slow Na influx
NNT
1 / (CER - ER)
Epidermal corneum
flat, dead, scale like cells with keratin. Continually shed
Epidermal lucidum
clear layer, thick skin only
Epidermal granulosum
cells link with neighbours
Epidermal spinosum
squamous cells begin keratin synthesis
thickest layer
Epidermal germinativum
basement membrane. Single layer of columnar cells. Gives rise to keratinocytes and melanocytes
Di George syndrome: CATCH-22
Cardiac abnormalities (ToF and Truncus arteriosus) Abnormal facies Thymic aplasia / T cell deficiency Cleft palate Hypocalacaemia / PTH Chromosome 22 deletion
Turner’s Syndrome: features
Short stature, wide spaced nipples, webbed neck, coarctation of aorta, bicuspid aortic valve, amenorrhoea, cystic hygroma, hypothyroid, horse shoe kidney
Vitamin K dependent clotting factors
2
7
9
10
Prometaphase
Nuclear membrane breaks down allowing microtubules to attach to chromosomes
Metaphase
Chromosomes aligns at middle
Anaphase
Chromosomes separate and move to opposite sides
Telophase
Chromatids arrive at opposite sides
Cytokinesis
Product of x2 daughter cells
Urinary casts: RBC
GN, renal ischaemia / infarction
Urinary casts: WBC
Acute PN, interstitial nephritis
Urinary casts: granular
ATN
Urinary casts: Hyaline
common follow exercise or dehydration
Urinary casts: epithelial
ATN
Urinary casts: waxy
CKD
Urinary casts: fatty
nephrotic
ANP: secretion
secreted by myocytes in left side of heart in response to increase blood volume
ANP: action
Natriuretic
Lowers BP
Antagonises angiotensin II/aldosterone
IgG
Enhances phagocytosis, passes placenta
Most abundant
IgM
First responder
Anti-A b-blood antibodies (haemolytic reaction)
IgA
Found in breast milk and secretions
Most commonly produced
IgD
Activation of B cells
IgE
Type I hypersensitivity reactions
Parasitic immunity
Ligand gated ion channel receptors
Mediate fast response
Ligand gated ion channel receptors: eg
ACh, GABA-A, GABA-C glutamate
Tyrosine kinase receptors: eg
Insulin, PRL, erythropoietin
Guanylate cyclase receptors
Contain intrinsic enzyme activity
Guanylate cyclase receptors: eg
ANP, BNP
G-protein coupled receptors
Slow transmission and metabolic processes
G-protein coupled receptors: Gs
Stimulates adenylate cyclase
E.g. B-1, B2, H-2, D1
G-protein coupled receptors: Gi
Inhibits adenylate cyclase
E.g. M2, a-2, D2, GABA-B
G-protein coupled receptors: Gq
Activates phospholipase C
E.g. a-1, H-1, V1, M1 and M3
Endothelin: function
Powerful vaso/bronchoconstrictor
Endothelin: promotion
Angiotensin II, ADH, hypoxia, mechanical shearing forces
Endothelin: inhibition
NO, prostcyclin
Renal stones: calcium oxalate
Most common
Hypercalcaemia RF
Renal stones: calcium phosphate
Associated with RTA
Radio-opaque
Renal stones: Uric acid
Associated with malignancies
Renal stones: Struvate
Urease producing bacteria
Renal stones: Cystine
Multiple stones
Oncoviruses: EBV
Burkitt’s lymphoma, Hogkin’s lymphoma, post transplant lymphoma, NP cancer
Oncoviruses: HPV 16/18
Cervical, anal, penile, vulval, OP cancer
Oncoviruses: herpes 8
Kaposi’s
Oncoviruses: HBV, HCV
HCC
Oncoviruses: t-lymphotropic virus 1
tropical spastic paraparesis, adult T cell leukaemia
Erythropoiesis: haematocytoblast
Multipotent stem cell
Erythropoiesis: proerythroblast
Committed to developmental pathway
Erythropoiesis: basophilic erythroblast
Ribosomes start to accumulate and nucleus shrinks
Erythropoiesis: polychromatophillic erythroblast
Nucleus and total cell volume shrink
Erythropoiesis: normoblast
cell nucleus is ejected
Erythropoiesis: reticulocyte
enters circulation
Collagen I
Bone, skin and tendons
Condition: osteogenesis imperfecta
Collagen II
Hyaline cartilage, vitreous humour
Collagen III
Reticular fibre, granulation tissue
Condition; Ehlers-Danlos syndrome
Collagen IV
Basal lamina, lens, basement membrane
Condition: Alport’s, Goodpasture’s
Collagen V
Interstitial and placental tissue
Condition: Ehlers-Danlos
Increased lung compliance
Age, emphysema
Decreased lung compliance
Pulmonary oedema, pulmonary fibrosis, pneumonectomy, kyphosis
Kidney histology: nodular glomerulosclerosis and hyaline arteriosclerosis
Diabetic nephropathy
AKA Kimmelstiel-Wilsom
Kidney histology: apple green birefringence
Amyloidosis
Kidney histology: enlarged hypercellular glomeruli
Acute post-strep GN
Kidney histology: crescent moon shaped glomeruli
Rapidly progressive crescentic GN
Kidney histology: wirelooping of capillaries
Diffuse proliferative GN e.g. SLE
Zona glomerulosa
Outside
Aldosterone
GFR-ACD
Zona fasciculate
Middle
Cortisol
GFR-ACD
Zona reticularis
Inside
Dehydroepiandrosterone
GFR-ACD
Study design: Superiority
Requires large sample size to show significance
Study design: Equivalence
If new drug lies within equivalence margin then assumed to have similar effect
Study design: Non-inferiority
Small sample size
Fragile X: inheiritance
CGG repeat
Huntington’s: inheiritance
CAG repeat
Myotonic dystrophy: inheiritance
CTG repeat
Friedreich’s ataxia: inheiritance
GAA repeat