finals Flashcards
0
Q
Huntingtons - chromosome, repeat, pathology
A
Chromosome 4 - cag repeat - huntingtin protein
Decreased GABA neurons in basal ganglia leads to increases stimulation of thalamus and cortex by global pallidus
1
Q
Alzheimer’s - pathology
A
Beta amyloid plaques
Neurofibrillary tangles - tau proteins
Cerebral atrophy, peri ventricular degeneration
Affects posterior parietal lobe
2
Q
Alzheimer’s drug treatment?
A
If mmse >12 - acetylcholinesterase inhibitors - donepezil, rivastigmine, galantamine
<12 - nmda receptor antagonist - memantine
3
Q
Lewy body dementia - pathology, treatment
A
Lewy bodies (eosinophilic aggregates, ubiguitin) - widespread in subcortical areas and temporal cortex No treatment - avoid antipsychotics as they may be neuroleptic sensitive - get very bad epse's
4
Q
Frontotemporal dementia - picks disease - pathology
A
Frontotemporal atrophy, knife blade atrophy, picks bodies (contain tau)
5
Q
Neurosyphilis
A
General paresis - dementia, frontal lobe dysfunction, ar pupils
Tabes dorsalis - shooting pains, ataxia
6
Q
Alcohol dependence
A
Primacy Compulsion to drink Narrowing of repertoire Increased tolerance Withdrawal symptoms Continuing drinking to avoid withdrawal Reinstatement after abstinence
7
Q
Delirium tremens
A
72 hrs after last drink
Tachycardia hypertension, tremor, fits, visual tactile hallucinations, worse at night
Rx: bdz reducing regime (chlordiazepoxide), thiamine b1
8
Q
Maintenance of alcohol detox
A
Disulfiram - Antabuse - acetaldehyde
Acamprosate - reduces cravings by enhancing GABA
Naltrexone - partial opioid receptor antagonist - reduces cravings
9
Q
Wernickes encephalopathy
A
B1 deficiency causes mammillary body damage
Nystagmus Ataxia Peripheral neuropathy Clouding of consciousness Ophthalmoplegia
Rx - pabrinex
10
Q
Korsakoffs psychosis
A
Anterograde amnesia
Retrograde amnesia
Preservation of immediate recall
Confabulation
Irreversible
Give oral thiamine
11
Q
Opioid dependence - treatment
A
Methadone
Buprenorphine - partial opioid receptor antagonist - start when not using very much meth
Naltrexone - opioid receptor antagonist - use after stopped to prevent relapse
Naloxone - for overdoses
12
Q
Benzodiazepines - how do they work
A
Enhance GABA activity
13
Q
Cocaine - neurotransmitters involved?
A
Dopamine, serotonin, noradrenaline - blocks reuptake
14
Q
Test for cystic fibrosis
A
Immunoreactive trypsinogen
15
Q
ECG changes in PE?
A
Rv hypertrophy
Sinus tachycardia
S1Q3T3
16
Q
ECG changes in left atrial hypertrophy?
A
P mitrale - broad bifid p waves - due to mitral stenosis
17
Q
ECG changes in right atrial hypertrophy?
A
P Pulmonale - peaked p wave - tricuspid stenosis or pulmonary hypertension
18
Q
What type of drug is a statin?
A
Hmg coa reductase inhibitor
Sfx - muscle pain, rhabdomyolosis, elevated lfts
19
Q
What is cushings disease?
A
ACTH excess causing high cortisol levels
20
Q
Hormonal treatment for acromegaly?
A
Octreotide - a somatostatin analogue
21
Q
What is kallmans syndrome?
A
Failure of gnrh secretion - 50% have loss of smell
22
Q
What is Hashimoto’s thyroiditis?
What are the antibodies?
A
Atrophic changes with regeneration leading to goitre formation
Thyroid peroxidase antibodies
24
Q
Graves’ disease antibodies and special features?
A
Tsh receptor antibodies
Specific eye signs - Ophthalmoplegia and exophthalmos
25
What is extramedullary haematopoeisis and when does it occur?
Haematopoesis that starts occurring in liver and spleen and places other than marrow - occurs in states where marrow has been replaced eg myelofibrosis, myeloproliferative disorders, and in excessive demand eg haemoglobinopathies
26
What cells are produced from common myeloid progenitors?
Megakaryocytes, erythrocytes, mast cells, basophils, neutrophils, eosinophils, monocytes
27
What cells are produced from common lymphoid progenitors?
natural killer cells, t lymphocytes, b lymphocytes
28
Where do lymphocytes mature?
Thymus
29
Which white blood cells are granulocytes
basophils, eosinophils, neutrophils, nk cells
30
Role of neutrophils
```
Engulf & kill bacteria
Release cytokines (IL1, TNFalpha) and chemotaxins (adhesion molecules)
```
31
Role of eosinophils
Similar function to neutrophils
Act against parasites
Involved in hypersensitivity
32
Role of monocytes
Migrate to tissues and become either dendritic cells (present antigens) or macrophages (engulf pathogen and present antigens)
33
Role of basophils & mast cells
Mediate parasite and allergic reactions, like eosinophils
Have surface receptors for IgE
Release heparin and histamine
Mast cells = v similar but stay on connective tissue not blood
34
Role of T lymphocytes
CD4 helper cells - bind to MHCs on antigen presenting cells and produce cytokines which activate B cells and macrophages
CD8 cytotoxic cells - bind to MHCs on antigen presenting cells and kill cells infected by pathogens
35
Role of natural killer cells
Destroy native cells which are abnormal or infected by pathogens - part of innate response - important in the bodys response to cancer
36
Role of B lymphocytes
When activated by T helper cells, some become plasma cells and produce antibodies, some become memory cells which stay around after the infection and have v sensitive immunoglobulins which will detect and respond to low levels of the same pathogen in the future
37
Roles of the spleen
Phagocytosis of old RBCs
Pools WBC and platelets, can be rapidly mobilised when needed
Some first-line immunological defence
Extramedullary haematopoesis
38
Causes of massive splenomegaly
```
CML
Myelofibrosis
Chronic malaria
Leishmaniasis
Gauchers (lysosomal storage disease --> lipid accumulation)
```
39
Complications of splenectomy
Infection - vaccinations & lifelong oral Pen V
Thromobocytosis for 2-3 wks afer
Abnormal RBC morphology - Howell-Joly bodiesm Pappenheimer bodies, target cells etc
40
Causes of splenic atrophy
Sickle cell disease (infarctions)
| Coeliac disease
41
Causes of microcytic anaemia
Iron deficiency
Thalassaemia
Sideroblastic anaemia
Anaemia of chronic disease
42
Causes of macrocytic anaemia
Megaloblastic - B12 and folate def
| Normoblastic - liver disease, hypoTH, alcohol, drugs, aplastic anaemia, pregnancy, myeloma
43
Causes of normocytic anaemia
Haemorrhage, haemolysis, anaemia of chronic disease
44
What is sideroblastic anaemia?
Consider if microcytic anaemia does not respond to Fe
DIsorder of haem synthesis resulting in refractive anaemia, microcytics hypochromic RBCs, ring sideroblasts in BM
May be due to myelodysplasia, alcohol, isoniazid
45
Causes of red cell aplasia
Diamond blackfan
Transient erythroblastopenia of childhood (post viral)
Parvovirus B19
46
Causes of aplastic anaemia
```
Fanconis anaemia (AR)
Idiopathic
Cytotoxic drugs
Radiation
Infection
```
47
Investigations for Fe def anaemia
```
Low Hb, low MCV, low MCHC
Low ferritin
Low Fe
High total iron binding capacity (as liver produces more transferrin)
Endoscopy - in older people
Coeliac serology
```
48
Drugs which may cause folate deficiency?
Trimethoprim, methotrexate, phenytoin, sulfasalazine
49
Causes of haemolytic anaemia
Inherited RBC abnormalities - spherocytosis, G6PD def, thalassaemia, sickle cell
Immune - newborn, blood transfusions
Autoimmune - warm & cold
Mechanical - DIC, HUS, heart valves, marching
50
Inheritance and pathophysiology of hereditary spherocytosis
AD
| Mutation of RBC membrane protein eg spectrin - increased permeability to Na - spheroidal shape- destroyed in spleen
51
Differential diagnosis of spherocytosis
Hereditary spherocytosis
| Autoimmune haemolytic anaemia - direct Coombes test +ve
52
Inheritance and pathophysiology of G6PD deficiency
X-linked
G6PD is enzyme which maintains glutathione levels and prevents oxidative damage to RBCs - without it, oxidant-induced haemolysis occurs
53
Warm haemolytic anaemia - antibody type and causes
IgG
| SLE, lymphoma, CLL, carcinomas, drugs
54
Cold haemolytic anaemia - antibody type and causes
IGM
| Infection, paroxysmal cold haemolysis
55
Triggers for haemolysis in G6PD deficiency
Infection, fava beans, quinine, ciprofloxacin, nitrofurantion, sulphonylureas
56
Sickle cell disease pathology
```
Mutation in gene for Beta-globin chain --> HbS gene - valine instead of glutamine
If homozygous (HbSS) - nearly all Hb is HbS, which polymerises in low oxygen states, making RBCs sickle shaped and rigid and fragile
```
57
4 crises in sickle cell disease
-Vasocclusive - painful - dactylitis, pain, avascular necrosis, priapism, stroke
-Sequestration - spleen engorged
-Aplastic - due to Parvovirus
-Haemolytic (rare)
Also increased risk of infection & sepsis
58
Management of sickle cell crisis
analgesia (opioids), hydration, abx if infection, exchange transfusion if severe
59
Drug used to reduce rate of crises in sickle cell
Hydroxyurea/hydroxycarbamide - increased concentration of foetal Hb
60
B thalassaemia pathophysiology
Imbalance of production of alpha and beta chains - beta chain production decreased so cant make HbA - make more HbF and HbA2 instead
Major form - severe anaemia, need regular transfusions + iron chelation (desferrioxamide)
61
A thalassaemia pathophysiology
Problem with genes for alpha globin - fewer normal a globin genes means more b globin chains
Most severe is major (all 4 deleted) -fatal
3 deleted - mild anaemia
1/2 deleted - asymptomatic
62
Haemophilia - what is deficient in each type?
A - factor VIII
| B - factor IX
63
Clotting function test results in haemophilia and VW disease
Haemophilia - prolonged APTT
VW - prolonged APTT, prolonged bleeding time (as platelet function abnormal as well as decreased factor VIII)
Both have normal prothrombin time
64
Treatment of haemophilia and VW disease
Replace deficient factor
| Desmopressin
65
Polycythaemia rubra vera pathophysiology
Excess proliferation of RBC ± platelets and other cells
| 95% due to JAK2 mutation --> activates tyrosine kinase
66
Treatment of polycythaemia rubra vera
venesection
chemo - hydroxycarbamide & busulfan to decrease plt count
low dose aspirin
allopurinol
67
WHO definition of osteporosis
BMD at least 2.5 standard deviations below the mean (between -1 and -2.5 is osteopenia)
68
Risks associated with oestrogen
```
Breast cancer
Endometrial cancer (if unopposed)
Venous thromboembolic disease
Stroke
Vaginal bleeding
```
69
What is raloxifene?
Selective oestrogen receptor modulator - acts on oestrogen receptors in bone to increased BMD, but does not affect receptors in endometrium and breast - which is good!!
Sfx - increases menopausal symptoms, increased risk of VTE
70
What is denosumab?
Fully human monoclonal antibody to RANKL - for osteoporosis
71
What is strontium ranelate?
dual action bone agent for osteoporosis - increases bone formation AND decreases bone resorption
72
Risk factors for osteomalacia
Lack of sunshine, dark skin, anticonvulsants, malabsorption, CKD
73
RA + splenomegaly = ?
Feltys syndrome
74
Extra-articular features of Ank spond?
Anterior uveitis
Aortitis/aortic regurg
Apical lung fibrosis
Amyloidosis
75
Which crystals are present in gout and pseudogout?
Gout - monosodium urate - negatively birefringent
| Pseudogout - calcium pyrosphosphate - positively birefringent
76
Side effects of corticosteroids
```
Weight gain
Osteoporosis
Think skin, bruising, poor wound healing
Hypertension/oedema
Infection
Hyperglycaemia
Psychosis
Cataracts
Muscle weakness/myopathy
Adrenal/pituitary suppression
Pancreatitis
Impaired growth
```
77
What is rituximab?
Anti-CD20 antibody - causes lysis of B cells
78
What are the anti TNF drugs?
Infliximab - monoclonal antibody against TNF
Etanercept - TNF receptor fusion protein
Adalimumab - monoclonal antibody against TNF
79
What are complications of blood transfusion? Early & late
Early - ABO incompatibility, fluid overload, febrile reaction, urticarial reaction, transmission of infection
Late - RhD and other sensitisation, delayed transfusion reaction, Iron overload, transmission of infection
80
Causes of red eye
Conjunctivitis, keratitis, scleritis, episcleritis, uveitis, acute glaucoma, endophthalmitism subconjunctival haemorrhage
81
What is the 4th generation test for HIV?
ELISA or western blot for HIV antibodies
| Test for p24 antigen
82
Treatment of urge incontinence
Anticholinergics - oxybutynin, tolterodine
Sacral neuromodulation
Intravesical botox
Surgery - detrusor myomectomy, cystoplasty
Physiotherapy
Behavioural therapy
83
Treatment of stress incontinence
Pelvic floor exercises, vaginal cones
Weight loss
Surgery - TVT, TOT
Duloxetine (SNRI)
84
What are the most common types of testicular tumour?
90% are germ cell tumours
- seminomas 48%
- non-seminomatous 42% - teratoma, yolk sac, choriocarcinoma
85
What are the tumour markers for testicular ca?
beta hcg, afp, palp (placental ALP), LDH
86
Which drug can reverse the effects of benzos?
Flumazenil (benzodiazepine antagonist)
87
What are the beta lactam abx?
Penicillins, cephalosporins and carbapenems
They inhibit cell wall synthesis
Bacteriocidal
88
What are the aminoglycoside antibiotics?
Gentamycin, streptamycin, neomycin
They inhibit protein synthesis
Bacteriocidal
89
What are the macrolide antibiotics?
clarithromycin, azithromycin, erythromycin,
They inhibit translocation of proteins
Bacteriocidal/static
90
What are the tetracycline antibiotics?
Doxycyline, oxytetracycline
Inhibits protein synthesis
Bacteriostatic
91
What is trimethoprim?
A folic acid inhibitor
| Bacteriostatic
92
What is the innervation to the pupil?
Afferent - CN2 (optic nerve) - chiasm --> optic tracts --> synapses in lateral geniculate nucleus --> optic radiations --> occipital cortex
Efferent
-Parasympathetic - with CN3 (oculomotor) - arises from Edinger-Westphal nucleus
-Sympathetic - from cervical spinal cord
93
Causes of miotic pupil
```
Old age
Opiates
Pilocarpine
Horner's
Pontine lesion
Argyll Robertson pupil (neurosyphilis)
```
94
Causes of mydriatic pupil
Arousal
Damage to eye eg acute glaucoma, trauma, iritis
Anticholinergics - atropine, oxybutynin, antidepressants
Sympathetic stimulants - cocaine
3rd nerve palsy - eg DM
Midbrain lesion
Holmes Adie pupil
95
What is Bell's palsy?
Dysfunction of CN7 (facial nerve) --> unilateral facial weakness
(LMN so does NOT spare forehead like a UMN problem would)
96
What is mild non-proliferative diabetic retinopathy?
At least 1 microaneurysm
97
What is moderate non-proliferative diabetic retinopathy?
Microaneurysms or dot/blot haemorrhages ± cotton wool spots, venous beading, IRMAs, hard exudates
98
What is severe non-proliferative diabetic retinopathy?
Blot haems + microaneurysms in 4 quadrants
Venous beading in at least 2 quadrants
IRMA in at least 1 quadrant
99
What is proliferative diabetic retinopathy?
```
Retinal neovascularisation (may cause vitreous haem)
Fibrous tissue forms anterior to retinal disc
```
100
What is maculopathy?
Any background changes, haemorrhage, oedema or ischaemia of the macula --> may affect vision
101
Management of diabetic retinopathy
Glycaemic & risk factor control
Focal or panretinal photocoagulation
Anti-VEGF - Pegaptanib, bevacizumab and ranibizumab
Intravitreal steroids
102
Hypertensive retinopathy - grades
1 - barely detectable arterial narrowing (silver wiring)
2 - arterial narrowing & focal irregularities (AV nipping)
3 - + flame haemorrhages, exudates, cotton wool spots
4 - + disc swelling
May also get Elschnig spots & Siegrist streaks
103
Management of glaucoma
Decrease secretion - topical beta blockers, topical/PO carbonic anhydrase inhibitors (acetazolamide)
Increase outflow - topical prostanoids, topical alpha agonists
Laser - trabeculoplasty, iridotomy
Surgical - trabeculectomy
If acute closed angle - IV acetazolamide, beta blockers, pilocarpine (parasympathomimetic, constrict pupil to open angle), iridotomy
104
Prevention of thyroid eye disease in Grave's?
Stop smoking!
105
What are the symptoms and signs of chronic open angle glaucoma?
May be no visual changes
May get loss of peripheral fields, starting nasally, ending up with tunnel vision
O/e - optic disc cupping with notched rim
With gonioscopy lens - open angle visible at iridocorneal angle
106
What are the symptoms and signs of acute closed angle glaucoma?
```
Sudden onset severe eye pain - worse with mydriasis
Blurred vision
Watering
Photophobia
Visual haloes
N, V, abdo pain
Fixed semidilated pupil
Cloudy cornea
```
107
SIgns and symptoms of retinal artery occlusion
Sudden painless visual loss
| PALE retina, cherry red spot at fovea
108
Signs and symptoms of retinal vein occlusion
Sudden painless loss of vision
| Severe haemorhages, tortuous dilated retinal veins, macular oedema, cotton wool spots - cheese and tomato pizza!
109
Causes of anterior ischaemic optic neuropathy
Arteritis - eg temporal!
| Atherosclerosis
110
How to manage a pregnant woman exposed to chicken pox?
```
If >20wks gestation - v low risk of transmission
If <20wks...
-Check antibodies
-If not immune, give VZ immunoglobulin
-If rask present, give aciclovir
```
111
Classification of hypertension in pregnancy
Pre-existing hypertension = 140/90 before 20 wks
Pregnancy-induced hypertension = 140/90 after 20 wks, no proteinuria
Pre-eclampsia = 140/90 after 20 wks + proteinuria >0.3g/24hrs
112
What is Meig's syndrome?
Benign ovarian tumour (normally fibroma) + ascites + pleural effusion
113
Most common benign ovarian tumour in young women
Dermoid cyst (teratoma)
114
Most common cause of ovarian enlargement in women of reproductive age
Follicular cyst
115
Which HPVs are associated with cervical ca?
16,18, 33
| 6 and 11 are warts
116
Risks associated with HRT?
Increased risk of breast ca, endometrial ca (reduced by adding progestogen), VTE, stroke, ischaemic heart disease
117
What is Fitz Hugh Curtis syndrome?
RUQ pain and perihepatitis caused by PID
118
Treatment of chlamydia?
Single dose azithromycin or 7 days doxycycline
119
Benefits of HRT?
Alleviates vasomotor symptoms (flushing, headaches etc)
Prevents osteoporosis
Reduces risk of colorectal ca
120
Why can you get symptoms of thyrotoxicosis with hydatiform moles?
Because the high levels of hCG can mimic TSH
121
What disease does Coxsackie A16 virus cause in children?
Hand foot and mouth disease = sore throat, fever, vesicles in mouth and on palms and soles
122
What is Scarlet fever?
Reaction to erythrogenic toxins produced by Group A haemolytic streptococci
Fever, malaise, tonsillitis
'Strawberry' tongue
Rash - fine punctate erythema sparing face
Rx - Pen v
123
How does Rubella infection in a chid present?
Rash: pink maculopapular, initially on face before spreading to whole body, usually fades by the 3-5 day
Lymphadenopathy: suboccipital and postauricular
124
What is seborrhoeic dermatitis?
Common benign greasy scaling rash caused by yeast (Malassezia sp) - may cause cradle cap in infants
125
Combined test for Downs?
Beta hcg + PAPPA + nuchal translucency - at 11-14 weeks
126
Consequences of congenital rubella
Sensorineural deafness
Congenital cataracts
Congenital heart disease (e.g. patent ductus arteriosus)
Glaucoma
127
Consequences of congenital toxoplasmosis
Cerebral calcification
Chorioretinitis
Hydrocephalus
128
Consequences of congenital CMV
Growth retardation
| Purpuric skin lesions
129
Treatment of threadworm (pinworm)?
Mebendazole & hygiene measures for child & all family
130
What are muscle fibres made up of?
Many myofibrils - which have thick myosin and thin actin filaments - actin filaments have troponin and tropomyosin attached for linking to cross bridges on myosin
131
What receptors monitor how much a muscle fibre is being stretched?
Muscle-spindle stretch receptors - wrapped round intrafusal muscle fibres
132
Which receptors monitor how much tension a muscle is under?
Golgi tendon organs
133
Pathophysiology of Parkinsons
Degeneration of substantia nigra in brainstem --> less dopamine released in basal ganglia --> motor cortex activated less
134
Drugs for Parkinsons?
Dopamine agonists - ropinirole
Monoamine oxidase B (enzyme breaks down Da) inhibitors - selegeline
Dopamine precursors - Levodopa + peripheral decarboxylase inhibitor
135
What are the amine hormones?
Thyroid hormones, catecholamines and dopamine
136
What are the steroid hormones?
Cortisol, aldosterone, testosterone, estradiol, 1,25-dihydroxyvitamin D
137
What are the majority of hormones?
Peptides
138
What hormones are secreted by each part of the adrenal glands?
Cortex
ZG - aldosterone
ZF/ZR - DHEA, androstenedione, cortisol
Medulla - adrenaline, noradrenaline
139
Enzyme necessary for producing thyroid hormones from iodine and thyroglobulin
```
Thyroid peroxidase (TPO)
nb anti-TPO antibodies are present in Hashimotos thyroiditis
```
140
Actions of thyroid hormone
Increased basal metabolic rate
Regulate bone growth and neural maturation
Increase bodys sensitivity to catecholamines
Increase body temperature
Fat mobilisation & breakdown
Carbohydrate metabolism
Growth & development in children
Increase heart rat, contractility and cardiac output
Allow normal fertility
141
What is Addisons?
Primary adrenal insufficiency
142
What is Conns?
Aldosterone producing adenoma
143
What is Cushings disease?
Cushings syndrome due to ACTH-secreting tumour of pituitary gland
144
Major effects of growth hormone?
Induces secretion of IGF-1 from liver, chondrocytes and other tissues. IGF-1 --> cell division
Stimulate protein synthesis, esp in muscle
Anti-insulin effects
145
Which hormones favour bone formation and which favour resorption?
Bone formation: insulin, GH, IGF-1, oestrogen, testosterone, calcitonin
Bone resorption: PTH, cortisol, thyroid hormones
146
What is released in hypercalcaemia of malignancy?
PTH-related peptide
147
What is the cause of secondary hyperparathyroidism?
Failure to absorb Vit D in gut or decreased 1,25dihydroxyvitamin D production --> increased PTH --> restores calcium levels but at expense of bone
148
What is the cause of pseudohypoparathyroidism?
End-organ resistance to PTH (PTH levels are high but ineffective)
149
What is atrial natriuretic peptide?
A peptide hormone and powerful vasodilator secreted in the atria in response to high blood volume
Increases GFR, decreases sodium reabsorption, inhibits renin, inhibits aldosterone, vasodilates, increases release of free fatty acids from adipose tissue
150
What is Cushing's phenomenon?
Traumatic head injury leads to increased intracranial pressure, decreased brain blood flow, and a large increase in arterial blood pressure
(because the pressure exerts force on blood vessels so slow is reduced and metabolites build up in brain interstitial fluid causing powerful stimulation of sympathetic neurons controlling systemic arterioles
151
Typical causes of AF
```
Thyrotoxicosis
Mitral stenosis
Ischaemic heart disease
Pulmonary embolism
Pneumonia
Sepsis
Alcohol
Cardiomyopathy and other structural / valvular heart diseases.
```
152
Which hormones are lipid soluble and where are their receptors?
Steroids, thyroid hormones and 1,25-dihydroxy Vit D
Bind to intracellular receptor proteins - in nucleus or in cytosol - these receptors act as transcription factors or suppressors
153
Which hormones are water soluble and where are their receptors?
Most hormones, neurotransmitters, paracrine/autocrine messengers (apart from Steroids, thyroid hormones and 1,25-dihydroxy Vit D)
Bind to proteins on extracellular surface of plasma membrane - these may be ligand gated ion channels, enzymes or G-protein-coupled receptors - may activate second messengers inside cell
154
How do steroids work?
Inhibit phospholipase A2 - which inhibits the formation of arachidonic acid (the origin of prostaglandins, prostacyclin, thromboxane and leukotrienes)
In contrast, NSAIDs inhibit COX, and so inhibit formation of prostaglandins, prostacyclin and thromboxane only
155
Which cells produce the myelin sheath of nerves?
CNS - oligodendrocytes
| PNS - Schwann cells
156
What produces CSF?
Ependymal cells of choroid plexus lining ventricles
157
Where does CSF go in the brain?
Subarachnoid space (between arachnoid and pia mater)
158
Where is CSF absorbed?
Arachnoid granulation & lymphatic channels
159
What controls the shape of the lens in the eye?
The ciliary muscles, and the tension they apply to the zonular fibres
Parasympathetic control
160
What is presbyopia?
Lens loses elasticity with age - less able to accommodate for near vision
161
What are the muscles which protect the inner ear from very loud sounds?
Tensor tympani (attaches to malleus and TM) and stapedius (attaches to stapes) - contract reflexively to dampen movements of middle ear bones and transmit less sound to inner ear
162
What is the uvea?
Choroid, ciliary muscles and iris
163
What neural pathway is involved in rewards and motivation?
Mesolimbic dopamine pathway
164
Alzheimers drug rx?
Mild-mod: acetylcholinesterase inhibitors - donepezil, rivastigmine, galantamine
Mod-sev: NMDA receptor antagonist - memantine
165
Causes of long QT
```
Hypocalcaemia, hypokalaemia, hypomagnesaemia
MI/ischaemia
Myocarditis
Hypothermia
Amiodarone, sotalol, Class 1a's
TCA, fluoxetine
Jervell-Lange-Neilsen, Romano-ward
```
166
Antiplatelet mechanism of aspirin?
Inhibits the production of thromboxane A2
167
Mechanism of action of clopidogrel
Antiplatelet - inhibits ADP binding to its platelet receptor via inhibition of P2Y12 receptor
168
Mechanism of action of enoxaparin and fondaparinux
Activates antithrombin III, which in turn potentiates the inhibition of thrombin and coagulation factors Xa
169
Mechanism of action of bivalirudin
Reversible direct thrombin inhibitor
170
Mechanism of action of heparin
Activates antithrombin III, which in turn potentiates the inhibition of thrombin and coagulation factors Xa
171
Management of NSTEMI/unstable angina?
```
GRACE score (6 month mortality risk)
if > 1.5% clopidogrel for 12 months
if > 3% angiography within 96 hours + GIIb/IIIa antagonist
```
172
Antipsychotics - side effects
Typicals - Antidopaminergic - EPSEs (ADAPT)
Atypicals - Antiserotoninweight gain
Either type
- Antihistaminic - drowsy
- Hyperprolactinaemia - galacttorhea, gynaecomastia, amenorrhoea, impotence
- Antiadrenergic - postural hypotension
- Antimuscarinic - dry mouth, const, blurred vision, retention, increased intraocular pressure
- Prolonged QT
- Neuroleptic malignant syndrome
Clozapine - agranulocytosis
173
What drug can be used to lessen the dystonia sfx of antipsychotics?
Procyclidine (antimuscarinic)
174
Side effects of tricyclic antidepressants?
```
Sedative (esp amitriptyline)
Toxic in overdose
Arrhythmias
Anticholinergic
Antiadrenergic
```
175
Side effects of SSRIs?
```
GI upset
Headache
Sexual dysfunction
Withdrawal symptoms (dizzy, lethergy, nausea, headache)
Safe in overdose
```
176
Side effects of Lithium?
Narrow therapeutic range - check twice weekly then every 3 months
Excreted by kidney - check renal ftn before & every 6m
Can cause hypoTH - check TFTs before & every 6m
Teratogenic
Nausea, metallic taste, thirst, weight gain, oedema, tremor
177
Define 'opportunity cost'
The sacrifice in terms of the benefit forgone from not allocating the resources to the next best activity
178
Define equity
Fairness or justice of distribution of costs and benefits
179
Define economic evaluation
Comparative study of costs and effectiveness/benefits of different health care interventions
Analysed in terms of increments - eg are the incremental benefits of this new rx worth the incremental costs?
Simplest form is cost-effectiveness analysis, or can use cost-utility analysis
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What is cost-utility analysis?
Form of economic evaluation
Measures health in terms of QALYs (utility x life expectancy)
Incremental cost effectiveness ratio (ICER) must be <20,000 to be funded by NICE
ICER = incremental cost/incremental QALY = £X per QALY gained
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How do you calculate NNT?
1/Absolute risk reduction
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Valve most often involved in infective endocarditis
Tricuspid
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ECG signs of digoxin toxicity
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Reverse tick (down-sloping ST depression)
Short QT
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Enlarged heart on CXR without pulmonary oedema?
May be pericardial effusion - often a/w malignancy eg lung tumour
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Complications of Paget's
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Bone pain
Pathological fractures
Nerve deafness
Spinal cord compression
High-output cardiac failure and
Osteosarcoma.
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What type of antiemetic are cyclising and promethazine?
Antihistamines - block h1 receptors in vomiting centre
| Sfx - antimuscarinic, sedative
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Skin rashes caused by Malassezia?
Seborrhoeic dermatitis
Dandruff
Pityriasis versicolor
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What type of antiemetic are haloperidol, chlorpromazine, metoclopramide and domperidone?
Dopamine receptor antagonists - block da receptors in chemoreceptor trigger zone
Sfx - epse, sedation, long QT
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Causes of erythema nodosum?
infection: streptococci, TB, brucellosis
systemic disease: sarcoidosis, inflammatory bowel disease, Behcet's
malignancy/lymphoma
drugs: penicillins, sulphonamides, combined oral contraceptive pill
pregnancy
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What type of antiemetic is ondansetron?
5ht3 receptor antagonist - block 5ht3 receptors in chemoreceptor trigger zone and gut
Sfx - qt prolongation, headache, flushing, constipation
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Rheumatoid arthritis - antibodies
RF, anti-CCF
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RA X ray changes
JS narrowing, periarticular osteopenia & erosions, soft tissue swelling, subluxation
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Treatment of RA & psoriatic arthritis?
Methotrexate + a DMARD (steroids for acute attacks)
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When dont you use DMARDS?
disease of the spine
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Features of sle?
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Hair loss
butterfly rash
discoid rash
livedo reticularis
photosensitivity
depression
glomerulonephritis
pleuritis
pericarditis
ulcers
raynauds
antiphospholipd - CLOTS
seizures
Libman sacks endocarditis
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SLE antibodies
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ANA
Anti-dsDNA - best
Anti-Sm
Anti Ro, Anti La
Anti-histone - esp drug induced
Also low C3, C4
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Treatment of SLE
Cyclophosphamide, steroids, sun cream, hydroxychloroquine, NSAIDs, rituximab
Don't use TNF blockers
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Pathology of Sjorgrens
Abnormal B cell activity - antibodies (Ro and La RF, ANA) attack exocrine glands
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Pathology of scleroderma
Overactive fibroblasts --> too much collagen --> vascular damage, inflammation
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Antibodies for systemic slerosis
Limited - anticentromere
| Diffuse - Anti topoisomerase
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Clinical features of scleroderma
Cutaneous - linear and morphea skin fibrosis
Systemic
-Limited - CREST, pulm htn, renal crisis
-Diffuse - myocardial fibrosis, pulm htn, renal etc
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What is polyarteritis nodosa
Medium vessel vasculitis - necrotising arteritis --> aneurysms - a/w Hep B
Clinical features all related to ischaemia eg post prandial abdo pain, acute tubular necrosis
Arteriography --> aneurysms
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Risk factors for gout
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Alcohol Seafood meat (with purines in)
Male
Obesity
Diabetes
Thiazide diuretics
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Gout investigations
Joint aspirate - strongly negatively birefringent monosdium urate crystals
X -ray - erosions, punched out lesions, sclerosis
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Treatment of acute gout (and pseudogout)
NSAIDs, colchicine, steroids
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Prevention of gout
Allopurinol (xanthine oxidase inhibitor)
| Lifestyle - low purine diet, look at drugs
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Pseudogout investigations
Joint aspirate - weakly positive rhomboidal calcium pyrophosphate crystals
X - ray - chondrocalcinosis
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Bisphosphonates - mechanism
Adhere to hydroxyapatite - inhibit osteoclasts
| Alendronate is first line in osteoporosis
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Strontium ranelate - mechanism
Dual action - inhibit osteoclasts & promote osteoblasts
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Raloxifene - mechanism
SERM
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What is denosumab
Monoclonal antibody against RANK - used in osteoporosis
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What is teriparatide
Recombinant PTH - used in osteoporosis - anabolic mechanism
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Pagets - X-ray?
Sclerosis or lytic lesions, thickening of trabeculae, lose distinction of cortex
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Risk factors for osteomalacia
Low vit d or calcium or phosphate
Anticonvulsants
Renal tubular acidosis, renal failure
Malabsorption
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What is azothioprine
Purine analogue - inhibits DNA synthesis
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What is cyclosporin
Inhibits T lymphocytes and IL2
| Monitor kidney function
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What are the 5ASA (aminosalicylates)
Sulfasalazine, mesalazine
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What hormone in pregnancy causes gestation diabetes?
Human placental lactogen
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Causes of microcytic anaemia
Fe deficiency, sideroblastic, thalassaemia
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What is sideroblastic anaemia
Can't use iron in bone marrow --> get ring sideroblasts
Microcytic anaemia not responding to iron!
Low total iron binding capacity
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Causes of normocytic anaemia
Haemolytic anaemias
| Chronic disease
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What is wrong with the beta chain in sickle cell
Replaced glutamic acid with valine
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Treatment of spherocytosis
Splenectomy
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What is myelodysplasia
Defect in stem cells --> bone marrow failure --> tends to evolve into AML
Old people
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Which pathway does prothrombin time measure
Extrinsic - used for warfarin monitoring (INR)
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Which pathway does APTT measure
Intrinsic - used for monitoring heparin - increased in haemophilia & VW disease
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How do GPIIb/IIIa antagonists work?
Block binding of fibrinogen to platelets
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How does heparin work
Inactivates thrombin and factor Xa
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How does clopidogrel/tacegralor work
P2y12 receptor inhibitors - block platelet activation
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How do alteplase, retaplase etc work
Recombinant tissue plasminogen activator - activates plasmin from plasminogen - plasmin breaks down fibrin
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Features of PKD?
Hypertension, infections, abdo pain, compression, hepatic cysts, berry aneurysms
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Where does renal cell carcinoma arise?
Proximal tubule
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Causes of CKD
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Congenital disease eg pkd
Glomerular disease
vascular disease
tin
urinary obstruction
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Complication of CKD
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Polyuria
Itching
Gout
Hyperprolactinaemia
Polyneuropathy
ED, amenorrhoea
Anaemia
renal osteodystrophy
uraemic encephalopathy/pericarditis
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How do you treat someone with vit d deficiency and CKD?
Calcitriol (activated vit d)
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What do HHV 6 & 7 cause
Roseola infantum
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What do the paramyxoviridae cause?
Measles & mumps
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What are cestodes?
Tapeworms - from pork and beef
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What are nematodes?
Roundworms - hookworm, pinworm, threadworm, whipworm
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What are trematodes?
Schistosomiasis
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Treatment of schistomiasis?
Praziquantel
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What are adrenaline & noradrenaline
Direct sympathomimetics
Adrenaline --> act on beta and alpha - used in anaphylaxis, in CPR, with local anaesthetic, in croup
Noradrenaline --> vasoconstriction via alpha 1 receptors - used to increased systemic vascular resistance
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Treatment of whooping cough
Erythromycin
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What are phenylephrine and metaraminol?
Alpha agonists - vasoconstriction - sympathomimetics - like noradrenaline but less direct
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Treatment of status epilepticus
Ensure safety, ABC, high flow o2
Give buccal midazolam, rectal diazepam or iv lorazepam --> up to 2 doses --> then iv phenobarbitol or phenytoin
If refractory --> iv propofol or thiopentol
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What is ephedrine
Mixed alpha and beta agonist sympathomimetic
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What is dobutamine
Directly acts on beta1 receptors (heart) --> so is an ionotrope - used in heart failure, pulmonary oedema
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Timilol?
Decreases aqueous secretion of ciliary body - used in primary open angle glaucoma
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What are alpha 1 receptors?
Causes vasoconstriction of non vital organs & contraction of bladder sphincter (sympathetic nervous system)
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What are beta 1 receptors?
Increase contraction of cardiac muscle (sympathetic nervous system)
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What are beta 2 receptors?
Relax smooth muscle of bronchus, vasculature and uterus (sympathetic nervous system)
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What is digoxin?
Positive ionotrope - used in heart failure and AF
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How do nitrates work?
Increase cyclic GMP
Vasodilates veins --> reduce preload (also vasodilate coronary arteries)
GTN - short acting
Isosorbide mononitrate - long acting
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How verapamil & diltiazem work?
Block AV node
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Histamine antagonists
H1 = antiallergy
Sedating - chlorphenamine, promethazine, cyclizine (also antiemetics)
Non-sedating = cetirizine, loratidine
H2 = parietal cells
Ranitidine, cimetidine
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Pathophysiology of paracetamol overdose
Paracetamol usually metabolised by liver conjugation
In overdose the liver conjugation becomes inundated so paracetamol is metabolised by an alternate pathway, creating toxic NAPQ - this is inactivated by glutathione
When glutathione stores are depleted, NAPQ causes necrosis of liver and kidney cells
Rx - N acetyl cysteine
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Carbon monoxide poisioning mgmt
High flow oxygen
| sats are normal
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TCA overdose - mgmt
Charcoal, gastric lavage
| IV diazepam, IV sodium bicarbonate
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Aspirin overdose - mgmt
Charcoal, gastric lavage
Urinary alkalinisation
Haemodialysis
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Ethylene glycol poisoning - mgmt
ethanol or fomepizole - inhibit alcohol dehydrogenase
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Digoxin toxicity - mgmt
FAB antibody
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Insecticide poisoning - mgmt
Atropine
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How to prove someone negligent?
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Must be a duty of care
Must be a breech of duty of care
Are their action supported by others?
Did pt come to harm?
Did the breech cause the harm?
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Effect of lithium on thyroid function?
Inhibits production and release of T3 and T4 -->hypothyroidism
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What can cause hypernatraemia with a high urine output?
Osmotic diuresis
| Impairment of ADH function (diabetes insipidus)
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Causes of diabetes insipidus
Nephrogenic - lithium, CKD, ATN, hypercalcaemia, hypokalaemia
Cranial - trauma, infection, tumours
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Diagnosis of diabetes insipidus
Water deprivation - failure to raise urine osmolality to 650 mmol/kg
Give desmopression - if cranial, osmolality will rise to >650, if nephrogenic, it won't
