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158 Cards in this Set

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What does hypokalemia do to cause altered consciousness?
Increases incidence of ectopic beats.
What is a premature ventricular contraction (PVC)/ Ectopic/ extra-systole?
A relatively common event where the heart beat is initiated by the heart ventricles rather than the SA node. May be perceived as a "skipped beat" or felt as palpitations. Several PVCs in a row form ventricular tachycardia which is dangerous. They are likely to cause a 'flip flopping' sensation, due to the pause that occurs after the premature contraction, and then a powerful contraction after the pause.
What is the cAMP theory of PVCs?
One explanation is increased cAMP in the ventricular myocytes, leading to increased flow of Ca2+ into the cell. Can be caused by anxiety/ stress, or hypovolemia caused by dehydration/ haemorrhage. Can also be caused by amphetamines or cocaine. Cause release of NA. Caffeine inhibits the enzyme (PDE) that breaks down cAMP, leading again to increased levels in the cell. Potassium ion is a major determinent of the magnitude of electrochemical potential of cells, and hypokalemia makes it more likely that cells will depolarize spontaneously. Hypercalcemia has a similar effect, and magnesium is necessry for maintaining potassium levels, so hypomagnesemia also makes spont depolarization more likely.
What is the treatment for PVCs?
Treatment is removing the trigger eg caffeines, or restoring the balance of magnesium, calcium and potassium within the body.
As well as disturbed cAMP levels, what else can cause PVCs?
Existing damage to the myocardium eg of MI or surgical repair of congenital heart disease can disrupt the conduction system and also irritate surrounding viable ventricular myocytes making them more likely to depolarize spontaneously. Simlarly inflammation such as in myocarditis or surges in cytokines can potentially cause irritability of myocytes.
What does hypokalemia do to cause altered consciousness?
Increases incidence of ectopic beats.
What is a premature ventricular contraction (PVC)/ Ectopic/ extra-systole?
A relatively common event where the heart beat is initiated by the heart ventricles rather than the SA node. May be perceived as a "skipped beat" or felt as palpitations. Several PVCs in a row form ventricular tachycardia which is dangerous. They are likely to cause a 'flip flopping' sensation, due to the pause that occurs after the premature contraction, and then a powerful contraction after the pause.
What is the cAMP theory of PVCs?
One explanation is increased cAMP in the ventricular myocytes, leading to increased flow of Ca2+ into the cell. Can be caused by anxiety/ stress, or hypovolemia caused by dehydration/ haemorrhage. Can also be caused by amphetamines or cocaine. Cause release of NA. Caffeine inhibits the enzyme (PDE) that breaks down cAMP, leading again to increased levels in the cell. Potassium ion is a major determinent of the magnitude of electrochemical potential of cells, and hypokalemia makes it more likely that cells will depolarize spontaneously. Hypercalcemia has a similar effect, and magnesium is necessry for maintaining potassium levels, so hypomagnesemia also makes spont depolarization more likely.
What is the treatment for PVCs?
Treatment is removing the trigger eg caffeines, or restoring the balance of magnesium, calcium and potassium within the body.
As well as disturbed cAMP levels, what else can cause PVCs?
Existing damage to the myocardium eg of MI or surgical repair of congenital heart disease can disrupt the conduction system and also irritate surrounding viable ventricular myocytes making them more likely to depolarize spontaneously. Simlarly inflammation such as in myocarditis or surges in cytokines can potentially cause irritability of myocytes.
What is the approach to an unconscious patient in regard to patient history? (it has a 5 letter pneumonic, that could be used to describe your bosom)
AMPLE: Allergies, Meds, PMHx, Last ate, Event/ environment.
In GCS, what constitutes a severe score/ coma?
<8
In general examination of the unconscious patient, what things are you looking for in general inspection?
Skin texture + hydration status. HEAD TO TOE: Signs of cyanosis, trauma, needle marks, ears and nose for blood, per rectal --> anal tone/ bleeding (in cirrhotic pt with hepatic encephalopathy).
Resp- smell breath for ketones/ alcohol and assess for Kussmauls (deep sighing hyperventilation- DKA/uremia). And finally circulation, for colour, perfusion, warmth, cap refill, peripheral pulses.
When doing the neuro exam, what are the implications of the following pupil changes: fixed enlarged, pinpoint, and midpoint + reactive.
Fixed enlarged: brain death, barb intox or hypothermia.
Pinpoint: opiate OD, or pons lesion cutting sympathetic input.
Midpoint & reactive: metabolic LOC.
What are the 4 steps of rapid sequence induction eg intubation of a conscious patients who needs advanced airway support.
1. Sedate with eg IV medazolam/ ketamine.
2. Muscle relax with suxamethonium, an AcH analog that isn't broken down and causes depol block and widespread muscle relaxation.
3. Cricoid pressure, to displace cartilage posteriorly and compress oesophagus.
4. Intubate.
What are the criteria for schizophrenia?
Characteristic Symptoms: At least 1 month of 2 or more of the following: hallucinations, delusions, speech disorder, negative symptoms, catatonic behaviour. Only one symptom is required if the delusions are grossly bizarre, of if hallucinations are auditory and consist of a running commentary or 2 people holding a conversation.
Social/ occupational dysfunction. Duration of disturbance spanning 6 months, and exclusion of mood disorder/ substance-general medication abuse.
What is the most common type of schizophrenia?
Paranoid- delusions of persecution, relative preservation of cognitive functioning. Onset tends to be later in life, and carries the best prognosis.
What is the clinical course of schizophrenia?
Prodrome- patient begins to withdraw socially, their grades begin to fall, or odd thoughts/ behaviours begin. Shorter prodrome= better prognosis.
Acute active phase- mainly positive symptoms.
Recovery or/ Chronic Phase: positive sx remain and -ve sx emerge- greatest cause of disability and can dominate patients life.
PROGNOSIS:
20%- complete recovery.
30%- multiple episodes with reasonable inter-morbid functioning.
50%- significant ongoing impairment in functioning.
What defines a brief psychotic disorder?
Symptoms from 1day-1month: can occur after stressful life event, but resolves rapidly and comletely, often without anti-psychotics. Treatment involves secure environment/ anxiolytics. Self-limiting.
Delusional Disorder
Persistent holding of non-bizarre delusions (may be jealous/ grandiose/ somatic/ mixed), but normal functioning is un-impaired and otherwise appear quite normal.
What are the criteria for schizophrenia?
Characteristic Symptoms: At least 1 month of 2 or more of the following: hallucinations, delusions, speech disorder, negative symptoms, catatonic behaviour. Only one symptom is required if the delusions are grossly bizarre, of if hallucinations are auditory and consist of a running commentary or 2 people holding a conversation.
Social/ occupational dysfunction. Duration of disturbance spanning 6 months, and exclusion of mood disorder/ substance-general medication abuse.
What is the most common type of schizophrenia?
Paranoid- delusions of persecution, relative preservation of cognitive functioning. Onset tends to be later in life, and carries the best prognosis.
What is the clinical course of schizophrenia?
Prodrome- patient begins to withdraw socially, their grades begin to fall, or odd thoughts/ behaviours begin. Shorter prodrome= better prognosis.
Acute active phase- mainly positive symptoms.
Recovery or/ Chronic Phase: positive sx remain and -ve sx emerge- greatest cause of disability and can dominate patients life.
PROGNOSIS:
20%- complete recovery.
30%- multiple episodes with reasonable inter-morbid functioning.
50%- significant ongoing impairment in functioning.
What defines a brief psychotic disorder?
Symptoms from 1day-1month: can occur after stressful life event, but resolves rapidly and comletely, often without anti-psychotics. Treatment involves secure environment/ anxiolytics. Self-limiting.
Delusional Disorder
Persistent holding of non-bizarre delusions (may be jealous/ grandiose/ somatic/ mixed), but normal functioning is un-impaired and otherwise appear quite normal.
What does strychnine and tetanus do?
Block glycine activity, and block glycine release respectively --> myoclonus, and violent muscle spasms.
What are the three dopaminergic pathways?
Nigrostriatal (substantia nigra to corpus striatum - Extrapyramidal system, coordination).
Mesolimbic/ cortical: mid-brain to limbic system (nucleus accumbens, amygdala and frontal cortex).
Neuroendocrine control of pituitary: PRL suppression.
WHere is 5HT localised and what is it produced from?
5-hydroxy trypaphan, synthesises from tryptophan... localised in the raphe nuclei (pons/ upper medulla), has a distribution similar to NA.
What 4 functions is 5HT involved in?
1. Hallucinations (LSD).
2. Sleep/ awake cycles, arousal.
3. Feeding (blockage with anti-psychotics can reduce feelings of satiety --> weight gain).
4. Control of sensory transmission.. 5HT receptors found in the dorsal horn?
What is the distribution and role of Ach?
Widely distributed across fore, mid and hindbrain (little in cerebellum). Excitatory role- arousal, learning, memory and movement.
How does caffeine (methylxanthines) case wakefulness?
They are adenosine antagonists (adenosine receptors have sedative effects). As well as neuroprotective and anti-convulsant effects... so caffeine overdose can actually be fatal due to convulsions, as well as palpitations and cardiac arrhythmia secondary to the increased cAMP in the cells (also a PDE inhibitor).
5HT controls sleep/ wake cycles. How?
Melatonin is synthesised from 5HT in the pineal gland, with secretion controlled by light intensity (low in day, high by night). Melatonin causes sedation.
What constitutes substance abuse? Think alcohol pattern. (1 or more of the following in last 12 months)
1. Failure to fulfil obligations.
2. Use when hazardous (driving)
3. Legal implications (loss of licence)
4. Interpersonal problems.
And what constitutes drug dependence. (3 or more of the following in last 12)
1. tolerance
2. withdrawal
3. Taken in larger amounts than intended.
4. Persistent desire to cut down
5. a lot of time spent using or obtaining
6. Important activities sacrifieed.
7. Continued use despite physical or psychological problems.
What is addiction then, and are dependent and adddicted the same thing?
Addiction is the recurrent psyhcoactive drug use, where obtaining drug is the primary goal and the personas ability to function normally is disrupted. Only a fraction of dependent users go on to become addicted and there are large individual dffferences in vulnerability to addiction.
Does the psychocological or the physical dependence lead to relapse?
The psychological dependence is the major factor, and usually outlasts the physical dependence. The long-lasting effects are mediated via the limmbic system, and result in mood changes, agitation and anxiety.
What is tachyphylaxis?
Acute tolerance- the de-senstization of a receptor by the first dose. This is compared to chronic tolerance, which is at a cellular level (neuro-adaptive changes/ receptor invagination etc), and at a metabolic level (increased metabolism due to enzyme induction.
What constitutes the dopaminergic reward pathway, and how do addictive drugs use this pathway?
Ventral tegmental area (tip of the brain stem) --> nuc accumbens --> amygdala --> PFC. Most projection neurons are dopaminergic.
Most addictive drugs increase Dopamine in this pathway, essentially hijacking the reward system and conditioning re-use of the substance, leading to pathological reinforcement, further drug consumption and addiction. THe addictive and pleasurable quality of the drug is NOT from the subjective appreciation of the diverse effects of the drug eg alertness, disinhibition, but from the activation of this pathway (mesolimbic pathway).
What is Addiction?
A Disease of Maladaptive Learning.
What are the three molecular effects of alcohol?
1. Enhancement of GABA
2. Inhibition of NMDA activity.
3. Blockage of VG Calcium channels.
What are the three chronic effects of alcohol?
1. Ventricular enlargement leading to dementia.
2. Peripheral neuropathy.
3. Cerebellar degeneration (alcoholic gait)
How does cellular tolerance to alcohol occur?
Increased membrane lipid fluidity, requires increased alcohol concentration to cross the membrane and cause intoxication. There are pharmacokinetic changes in chronic alcoholics.
What are the three phases of alcohol withdrawal?
Phase 1 (<1day): Nervous, apprehensive, TREMOR, nausea.
Phase 2 (2-4day): nausea/ vomiting, muscle cramps, tachycardia, insomnia, agitation.
Phase 3 (>4days): confusion, disorientation, convulsions (can be fatal).
What is the presentation of alcoholic overdose?
Hypoglycemia, metabolic acidosis, increased blood osmolality, acute renal failure. Management is glucagon or IV glucose for the hypoglycemia, and haemodialysis in severe cases (esp with severe metabolic acidosis).
What drugs can be used in the management of alcohol dependence?
To alleviate the acute abstinence syndrome: benzo's. clonidine (alpha-2 agonist, decreases sympathetic tone and the acute symptoms), propanolol (also decreases SNS activity- manages tachycardia, hypertension, sweating, tremor of withdrawal).
Disulfiram (aldehyde dehydrogenase inhibtor and accumulation of acetaldehyde), naltrexone (blocks opiate receptors, blocks alcohol-induced reward), and acamprosate to decrease cravings (NMDA-R antag).
What is the main pitfall with the use of barbiturates as anxiolytics/ sedatives?
Tolerance develops rapidly to their sedative/ anxiolytic/ anti-convulsant effects, but less tolerance to the respiratory depression. Dangerous for overdose --> CVS depression.
List the benzodiazapines in order of half-life, and what their clinical use is.
Midazolam (short acting, 6 hrs) -general anaesthetic.
Oxazepam, temazepam (short acting, 12-18hrs) - sedative, anxiolytic.
Diazepam (valium- long acting (12-48hrs) - muscle relaxant and anxiolytic.
Clonazepam - long acting anticonvulsant used in mania.
What three structures in the brain do amphetamines act on and what effect does this cause?
Nucleus accumbens - pleasure and euphoria.
Hypothalamus - temperature, decreased appetite.
Reticular formation- alertness.
Amph causes release of DA, NA and 5HT in these areas, and inhibition of DA transporter/ MAO at high doses.
What are the consequences of amphetamine over-use?
Repeated admin to maintain the high can trigger a state of 'amphetamine psychosis', closely resembling an acute schizophrenic attack, with hallucinations/ paranoia/ aggressive behaviour. The cellular tolerance is to the peripheral effects and anorexia, and psychosis emerges if dose is increased after tolerance develops to the euphoria.
Is there dependence to amphetamines?
YES- powerful psychological dependence.
What is the presentation of amphetamine overdose?
Convuslsion, BP changes, hyperthermia, cardiac arrhythmia's, DIC, rhabdomyelosis and renal failure. Death can occur.
Where does cocaine act in the brain? How are the effects of cocaine different to amphetamines?
Same places as amphetamines: NA, HTH, RF.
Inhibits NA, DA and 5HT uptake enzymes, potentiating the effects of catecholamines and 5HT centrally. Also enhances peripheral effects of SNS activity.
Similar effects to amphetamines, but less tendency to produce delusions, hallucinations, paranoia and the stereotyped behaviour (gnawing, licking etc).
What are the four effects of caffeine?
1. CNS stimulation - less fatigue, insomina, improved concentration.
2. Cardiac muscle stimulation.
3. Bronchial muscle relaxation.
4. Diuresis.
What is the definition of a manic episode?
Persistent and abnormally elevated, irritable or expansive mood, for a period of at least a week, with 4 of the 7 following addional symptoms:
1. Inflated self esteem/ grandiosity
2. Flight of ideas
3. Motor agitation/ restlessness
4. More talkative than usual
5. Decreased need for sleep.
6. Distractibility
7. Risky goal-directed activities eg excessive credit-card spending.
What is the deal with adjustment-depressive disorder?
Must be within 3 months of a loss or change, and cuases significant impairment to social or occupational functioning.
Often a divorce, or loss of a loved one. The patient is angry, which turns to guilt, and develops into either mild sadness and worry, to more severe feelings, indistinguishable from major depression.
What are the differences between depression and dysthymia?
Dysthymia; more chronic, but less severe. Must be present for at least 2 years, no suicidal ideation.
What is the difference between bipolar disorder and hypomania?
Hypomania has a lesser degree of mania. Delusions and hallucinations are not present, patient does not require hospitalisation, and has a fairly normal level of social and occupational functioning.
What is cyclothymia?
Chronic low-grade mood cycling. Alternate between periods of hypomania, and clusters of depressive symptoms that fail to meet criteria for major depression. Fluctuations should be present for at least 2 years before Dx made.
What is the title for episodes of major depression and hypomania?
Bipolar II
How many episodes of mania/ depression/ hypomania must there be per year to constitute rapid cycling bipolar?
4+
What is the differential diagnosis of mania?
- Stimulants.
- Sympathomimetics
- Organic disorder: hyperthyroidism, AIDS (?), Huntington's (chorea), Wilson's disease or CVA.
N.b WIlson's disease involves deposition of excess copper in the liver and the brain --> liver disease & neuropsychiatric symptoms.

Cognition can also be affected in Wilson's disease. This comes in two, not mutually exclusive, categories, frontal lobe disorder (may present as impulsivity, impaired judgement, promiscuity, apathy and executive dysfunction with poor planning and decision making) and subcortical dementia (may present as slow thinking, memory loss and executive dysfunction, without signs of aphasia, apraxia or agnosia).
When are mood stabilisers contraindicated?
Pregnancy & breastfeeding/ lactation.
What are the three main mood stabilisers used in acute mania?
Lithium carbonate (lithicarb), Sodium valproate (valpro), and carbamazepine.
Chronic diseases like Rheumatoid arthritis, MS & heart conditions, have a high risk of what.
Depression.
List three drugs that can cause depression (acutely/ chronically):
1. Reserpine: decreases NA and 5HT in the CNS (anti-psychotic and anti-hypertensive).
2. Steroids
3. OCP (hormonal effects, supporting increased frequency in women/ post-partum etc)
4. Methyldopa/ clonidine (anti-hypertensives).
5. Levodopa (anti-PD).
What 2 drugs should be given with L-DOPA?
A dopa-decarboxylase inhibtior such as carbidopa or benserizide... and vitamin B6 in the form of pyridoxine can be given, as pyridoxal phosphate (its derivative) is a required cofactor in the DOPA decarboxylation.
What happens if you administer pyridoxine without a Dopa-decarb inhibitor?
Co-administration of pyridoxine without a DDCI negates the effects of L-dopa, due to the rapid peripheral decarboxylation & depletion of L-DOPA.
Where in the brain do abnormalities have associations with mood disorder?
Limbic system & the temporal and frontal lobes.
What will a lesion in the hypothalamus result in?
1. Extreme passivity and loss of drive.
2. Excessive eating and drinking.
3. Rage and violent behaviour.
What three brain changes are associated with depression? (all decreases in volume)
1. Reduced PFC volume.
2. Decreased hypothalamic volume.
3. Reductions in the caudate and putamen.
What drugs are used to wean someone off opioid addiction?
Clonidine (3-5 days), Methadone, Buprenorphine.

Clonidine- sympatholytic, alpha-2 agonist (auto-inhibitory). Treats anxiety and panic disorder, ADHD, and opiod detoxification. Can also be used for high blood pressure: decreases cardiac output and peripheral vascular resistance, by it's specificity for a2 receptors in the vasomotor centre of the brainstem; decreases calcium levels, inhibits release of NA.
In opiate withdrawal, combates the SNS response eg tachycardia and HTN in the initial days of withdrawal; takes away the sweating, hot cold flushes and general restlessness.
Buprenorphine = semi-synthetic opiod, used to treat addiction.
What does promethazine do?
A first generation H1 receptor antagonist (phenothiazine class), used medically as an anti-histamine. Can be prescribed for insomnia. Also used as an anti-emetic eg in motion sickness, or morning sickness.
Has 1/11'th of the anti-psychotic potency of chlorpromazine (weak dopamine block, on top of the histamine antagonism).

Can be used in opiate withdrawal, to manage the nausea and vomiting.
Acamprosate?
Treating alcohol dependence:
NMDA block, GABAa Activation.

alcoholism- camper's fate, acamprosate, block glutamate, GABA activate!
Naloxone vs Naltrexone?
Naloxone- immediate use, short term full antagonism of opiod receptors, high affinity.
Naltrexone- competitive antagonists at mu and kappa, half-life of ~ 4h. Blocks effects of opiods.

Can also be used to MODULATE THE DOPAMINERGIC-MESOLIMBIC PATHWAY in alcohol dependence- block the reward associated with alcohol.
Bupropion?
NA-DA reuptake inhibtior: binds selectively to the DA transporter. Anti-depressant, increases concentration in the synapse.

Also a nAchR antagonist... used in smoking cessation (Zyban). Can also use SSRI's in management of smoking.
What happens to a patient on methadone, when they take a hit of morphine/ heroin?
- Don't get same euphoria
- Don't get physical abstinence syndrome; makes it possible to wean them off.
What is the use of Buprenorphine?
semi-syntheti opioid, partial mu-receptor agonist... longer duration of action, minimal withdrawal symptoms, low potential for OD and the ability to block heroin effects. Used in abstinence-maintenance.
What is a complication of Naloxone?
In large doses, can cause HYPERalgesia, by blockage of endogenous opioids.
Also only lasts 2-4 hrs, may need to be given repeatedly.
What happens to someone who has been given disulfirum, when they drink alcohol?
Acetaldehyde build up --> flushing, sweating, tachycardia, distressed. = aversion therapy.
What 4 groups of drugs are used in alcohol dependence mangagement?
- blunt acute withdrawal --> benzodiazepines, clonidine (alpha 2 antagonist, blocks SNS response and NT release), propanolol (beta blocker- same effect).
- Make alcohol unpleasant - disulfiram
- Decrease alcoholic reward- Naltrexone
- Re-balance the chemical changes in the brain, reduce cravings - Acamprosate (block glutamate, GABA activate).
Presentation of opioid OD?
- Miosis
- Hypoglycemia
- Convulsions
What is pethidine? Compared to morphine?
SE
Synthetic mu agonist, not chemically related to morphine. Decreased resp depression, decreased constipation, better oral activity.
SE = convulsions, from a metabolite.
Red nucleus?
Rubrospinal function?
The two eyes in the middle of the tegmentum, activate rubrospinal pathway which activates flexor muscles. If severed above the red nucleus, lose cortical inhibition --> decorticate position, arm flexion. If sever below, then lose rubrospinal arm flexor activatin --> decerebrate.
Ventral tegmental area?
Neurons located close to the midline of the midbrain, is the origin of the dopaminergic cell bodies that distribute to the mesocorticolimbic pathway... = the MOTHERSHIP of the reward pathway. Mu receptors are localised here and activated by opioids. Projections to various locations, such as the nucleus accumbens for euphoria/ reward (+ amygdala, hippocampal complex). The PAG for analgesis, the area postrema of the third ventricle including CTZ (nausea vomiting), and thee brainstem/ rticular formation (sedation and resp depression).

Location: medial to the substantia nigra, rostral to the red nuclei/ oculomotor nuclei.

Has glutamatergic afferents that activate.
From the following drugs, rate the dependence liability.
1. Narcotics
2. CNS depressants eg ethanol, barbiturates.
3. Anxiolytics eg benzo's.
4. Psychomotor stimulants eg amphetamines, cocaine, nicotine.
5.PSychomimetics (LSD, mescaline, cannabis, PCP).
1. opiods-Very strong
2. CNS depressants eg alcohol, barbs --> moderate.
3. Anxiolytics (benzo's)- moderate.
4. Stimulants (cocaine, nicotine, amphetamiens)- strong/ very strong.
(caffeine- weak).
5. Psychomimetics- weak or absent.
Presentation of amphetamine overdose
convulsions
hyperthermia
hyper/hypotension
cardiac arrhythmia's
DIC/ rhabdomyolysis
renal failure/ death.

Similar to cocaine OD: tremor, convulsions, arrhythmia, resp/ cvs depression.
What is the progression of symptoms in paracetamol overdose?
Phase 1: up to 24 hrs. Ano, nausea, vomting.
Phase 2: RUQ pain from liver damage, Elevated LFTS.
Phase 3: Sequelae of hepatic damage: jaundice, coagulopathy, hep encephalopathy/ confusion, renal failure, DCM/ death.
Phase 4: recovery, with complete resolution, or continued deterioration and death.
What is the acute management of paracetamol overdose?
Gastric lavage
N-acetylcysteine
What are three consequences of a hypothalamic lesion?
1. passivity
+ 2. loss of inhibition:
Rage and violence
Excessive eating and drinking.
What roles are the following NTs related in, in regard to mood regulation.
5HT
NA
DA
5HT- sleep, aggression (rage and violence), appetite (excessive eating and drinking).
NA: Mood, appetitie, drives (passivity)
DA: pleasure, sex, psychomotor activity.
What brain changes are seen in depression?
decresed PFC
Decrease hippocampus
Decreased caudate and putamen
Depression neurophysiology?
dysregulation of NA and 5HT.
What personality traits carry an increased risk for depression?
Low self esteem, perfectionism, neuroticisism, self-criticism, dependency.
What factors are evolved in the regulation of mood/ depression
1. Childhood experiences: develop an internal working model, based on 'attachment' experiences. If childhood relationships are devient, patient will have low self esteem, poorly developed sense of entitilement. Develop "schema" based on core beliefs- self defeating attitudes/ theory of learned helplessness.
2. Social factors eg unemployment, daily life hassles, chronic medical condition.
3. Personality traites: perfectionism, neuroticism, dependency etc.
4. Gender differences: females 2-3x more likely than males. Multifactorial.
What is the lifetime risk of unipolar, and bipolar depression?
MDD 15%
Bipolar 1%
RFs for a mood disorder?
female
age- in your 20s
low SES
lack of a confiding relationship
family history
childhood sexual abuse or violence
adverse life events in adulthood
drug abuse
sleep deprivation
Adjustment disorder?
WIthin 3 months of stressor, continued sig impairment of soc/occ functioning.
Stressor = death, divorce, financial crisis.
Anger --> guilt.
Post-partum depression.
2 weeks- 6 months after the birth.
Most women (80%) experience a mild let down, but ~15% progress to full severity of major depression.
Obsessive thoughts about child's safety, and inability to care + hormonal vulnerability.
Dysthymia- Milder but more chronic form of depression. What are the main 2 differences?
depressive symptoms for >2 years
suicidal ideation not present.
Hypomania.
Lesser degree of mania, more common.
No delusions or hallucinations.
No need for hospitalisation.
Good soc/occ functioning.
Cyclothymia.
2 years of low grade mood cycling. Episodes of hypomania, and then clusters of depressive symptoms that fail to reach definition of major depression (mild depression).
2 years.
What conditions can cause mania eg differentials for a manic episode.
Stimulants
Sympathomimetics
Organic conditions:
- Wilsons
- CVA
- Hyperthyroidism
- AIDS... get both depression and mania.
What is the link between stroke and depression?
one third of stroke patients develop minor depression, with a proportion of them developing major depression.
An interplay of neurological changes eg in frontal lobe, temporal lobe, and the psychosocial issues associated with the stroke.
What are the three drugs of treatment for manic episodes?
1. Lithicarb: 80% response rate in acute mania.
2. Sodium valproate:
What drugs can cause depression?
Corticosteroids (directly lower serotonin levels)
OCP
Reserpine- NA and 5HT depletion (anti-psychotic and anti-hypertensive)
Methyldopa, guanidine (antihypertensives)
Levidopa
Alcohol, sedatives, opiates.
Withdrawal of stimulants.
How does reserpine work? indications?
Anti-hypertensive and anti-psychotic.
Centrally, works by blocking VMAT, the transporter needed to move newly synthesised NTs into the synaptic vesicle for release. If not taken up into vesicle, will be degraded by neuronal MAO. --> depression, NA and 5HT depletion.
SAD A FACES: symptoms of depression.
Sleep changes
Anhedonia
Dysthymia/ depressed mood.
Appetite or weight changes.
FATIGUE
Agitation/ retardation.
Concentration impairment.
Esteem (low)
Suicidal ideation.
RFs for suicide: SAD PERSONS
Sex (male)
Age
Depressed
Previous attempts
Ethanol
Rational thinking gone
Social support- none
Occupation eg pharmacists, vet, access!
No past times
Sickness (chronic illness)
Is there inheritance of depression?
There is strong genetic basis:
70% concordance in monozygotic twins. 20% in dizygotic.

Parent with depression- 10% risk.
2 parents with depression- 20% risk.
What is the association between depression and cortisol?
Corticosteroids --> depression.
Cushing's syndrome is the most potent cause of 'organic' depressive illness; ~80% suffer depression.
1/2 of all patients with depression also have raised cortisol levels and enlarged adrenal glands = stress hormone, inactivates hypothalamus (defective monoamine synthesis), allows overactivity of the fear/ anxiety centre, the amygdala.
Depression: limbic system + frontal and temporal lobes. NA and 5HT inputs. How do these systems intersect to mediate depression?
Functional deficit in NA and 5HT, who interact in these systems to mediate
- arousal, mood, appetite drives (NA)
- Sleep, aggression, appetitie (5HT).
dysregulation.
Increasing NA- increases 'get up and go' - risk of suicide in adolescents.
Increasing 5HT- improve affect.
Outline the pathway of depression in medical illness.
Multiple stressors of illness. Result depends on life-experience, coping strategies + personality, social support. + PERSONAL MEANING eg an 80 year old vers 25 year old with cancer.
Then, manifest as either sadness, anxiety, somatic distress. and progress to either sub-threshold depressive symptoms, or depression.
What are some key presentations of depression to look for?
Fatigue
Irritability (may be prominent feature)
Dysfunctional sleeping habits.
Somatic: headache, abdo pain, weight change.
Elderly- confusion, decline in functioning.
Children- irritability, decline in school performance, social withdrawal.
And be extra perceptive in a patient with a chronic medical ilness.
DSM IV criteria for major depression:
Symptoms present for 2 weeks, persistent.
5 symptoms needed: at least one must be either DYSTHYMIA OR ANHEDONIA.
4+ of others, on most days, including:
sleep changes
appetite changes
agitation/ retardation
fatigue
alexithymia
concentration difficulties
esteem/ excessive guilt
suicidal ideation..
Symptoms must not be due to drug/ medical condition (thyroid screening)
Should not be better accounted for by another transient problem.
In differentials of depression, what should you ask about, keeping in mind organic conditions that could be responsible.
Cushings- Are you on corticosteroids? Does the patient look cushingoid? Hirsute?
Thyroid- Cold intolerance? voice change? weight gain? Sluggish reflexes? O/e, look for cool, dry hands, slow pulse, sluggish reflexes, skin pigmentation and thickening, alopecia.
Brain tumor- look for focal neuros, ask about fever/ night sweats/ weight loss.
Hyperparathyroidism- the symptoms are mostly related to hypercalcemia: bones, stones, groans and psychic moans. eg bone fracture? osteoporosis? Kidney stones, have you noticed any blood in your urine, or pain on urination, or flank pain. Groans- Constipation? Psychic moans- weakness, fatigue, depression. Inquire about all!

Also psychiatric diferentials eg alcohol, drug use (esp amphetamines), recent bereavement.
Will someone with alcoholic depression have symptoms lasting >2 weeks?
no.
Questions to ask about a patient with 'fatigue and low mood'-
Appetitie, weight change, energy levels.
Do you have any recreational activities or hobbies you enjoy? Are you still finding you enjoy these?
What are the risks of recurrence with a single, two and three depressive episodes?
50% with 1
70% with 2, and
90% with 3.
After a depressive episode, what are the indications for long-term anti-depressants?
1. Female
2. Never married
3. Multiple prior episodes
4. Residual sub-threshold symptoms
5. Longer duration of depression before initiation of treatment.

35% of patients have a CHRONIC COURSE.
What is the most common CNS malformation?
Neural tube defect.
What 2 diseases is tuberous sclerosis associated with?
Epilepsy and dementia.
TS is an autosomal dominant condition, characterised by the development of hamartoma's and benign neoplasms, involving brain and other tissues.
Malar erythematous nodular rash.
Tubers = hard nodular areas of the brain - broadened gyri.
Compare Chiari I and Chiari II (arnold)
Chiari I: low lying cerebellar tonsils, protrude into the vertebral canal. Sx of obstructive hydrocephalus and medullary compression (tonsils- incoordination).

Chiari II: more complicated. Small posterior fossa, distorted/ misshapen midline cerebellum, with downward extension of the vermis through the foramen magnum (vermis- central postural control, balance, gait). Invariably associated with lumbar myelonemeningocele, and hydrocephalus.
Myelomeningocele.
Extension of CNS tissue and meninges, through a defect in the vertebral column. Most commonly in the lumbo-sacral region, manifests as lower limb motor and sensory dysfunction, including poor bowel and bladder control.
When can microencephaly occur? (a reduction in brain volume- far more common than macroencephaly)
HIV infection in utero
FAS (fetal alcohol syndrome)
Chromosomal abnormalities.

An example of microencephaly is LISSENCEPHALY- where there is incomplete number of neurons, causing flattening of and reduced number of gyri- small head, with a smooth cerebral surface.
Dandy-Walker Malformation.
Hint- enlarged posterior fossa.
Cerebellar vermis is absent, replaced by a large midline cyst lined by ependyma, that represents the expanded roofless fourth ventricle in the absence of a normally formed vermis.
Syringomyelia-
formation of a fluid-filled, cleft like cavity in the inner portion of the spinal cord = 'hole'/ syrinx.
Can be associated with chiari I malformation, or intraspinal tumors/ trauma.

Hydromyelia: expansion of the ependyma-lined central canal of the SC.

Both are associated with destruction of the surrounding grey and white matter, and a dense feltwork of reactive gliosis. Cervical cord is most often affected. Begins as progression of small wasting of the hands/ loss of pain and temporary sensation in the upper extremities.
What conditions is Von Hippel Lindau associated with
Haemangioma's of the cerebellum, spinal cord, kidneys and retina.

Cafe au lait spots
RCC
Ralph is 9 months old, and keeps bumping into walls when he's crawling and is struggling to recognize his father. He has quite a big head, compared to his older sister even. What could be going on with Ralphy?
Macrocephaly + vision impairment.... Tay-Sachs disease, the hereditary lipid storage disease. Also presents with mental deterioration. Head is large due to deposition of lipids in the neurons.
What percentage of meningitis is accounted for by N.Meningitis, and what percentage by S.pneumoniae?
30% S.pneumoniae
50% N.Meningitides.
What parts of the brain are most commonly affected by cerebral abscesses?
Frontal - parietal - cerebellum.
Where in the brain is tubercular meningitis concentrated?

What is the most serious complication?
The base of the brain. Presents with fibrinous, gelatinous exudate in the subarachnoid space, florid cases demonstrate caseating granuloma's.

A dense fibrous adhesive arachnoidits may develop in the base of the brain --> hydrocephalus, and obliterative endarterits/ end artery occlusion and infarction.
In what disease can you find cerebral gumma's, and what is a cerebral gumma.
Neurosyphilis. Tertiary stage of syphilis. A gumma is a plasma cell-rich mass lesion, that can occur in the meninges, and spread to the cerebral hemispheres/ diencephalon/ SC.
What is tabes dorsalis?
Slow degeneration of the sensory axons that carry information into the dorsal column (proprioception, vibration). It is caused by demyelination, secondary to untreated syphilis infection.
--> sensory ataxia, loss of deep tendon reflexes, joint degeneration due to inadequate response to change in position, "lightning pains".
What two spirochetal organisms can cause meningitis?
Treponema pallidum (syphilis)
Borrelia burgdorferi (Lyme disease)
What are the three histologic features of viral encephalitis?
1. Perivascular and parenchymal mononuclear cell infiltrate.
2. Gliosis
3. Neuronophagia. (digestion of neurons).
Changes in alzeimer's?
Senile amyloid plaques- amyloid core with dystrophic neurite tangle.
NFTs
Amyloid deposition in blood vessels.
What is the abberant protein in PD and what is the characteristic lesion?
alpha-synuclein.
Lewy Bodies
Who gets MS, and what are 2 common presenting symptoms.
Women in their 20's-50's.
Acute visual impairment (optic neuritis) or bilateral lower limb weakening.

Symptoms disappear within days-weeks, only to recur at a later date.
What are the four major consequences of head injury/ trauma?
Epilepsy
CSF leak
Intra-cranial infection
Permanent neurological deficits.
In a contre-coup injury, where are the most common sites of injury?
Crests of gyri of temporal lobes.
Inferior frontal lobe
Occipital pole
What does 'plaque jaune' refer to.
The retracted yellow, discoloured scars at the tip of gyri after a contre-coup injury. Can be the focus of epileptic activity (post-traumatic, neuron network sprouting forms a more hyperexcitable network).
What is the clinical presentation of an extradural haematoma?
Usually a period of lucidity, before descending into a deep unconsciousness. There is no bleeding into the parenchyma, rather cerebral compression by the expanding extradural football of blood.

A surgical emergency; a trephine needle is inserted into the temporal bone, and drainage of the middle meningeal artery haematoma.
Why might extradural haemorrhage be acute, and subdrual haemorrhage allow a more chronic development?
Extradural = middle meningeal tear = arterial, high flow, rapid haemorrhage.
SUbdural = tearing of the bridging veins. At venous pressure, a slower bleed, with more progressive onset of neuro symptoms.
Recurrent haemorrhages can arise in the vessels of the granulation tissue.
A 4 month old girl is having recurrent seizures, despite high doses of anti-convulsant therapy. She had quite a long and difficult delivery. What investigation would you order, and what might you see?
CT head scan.
Birth injury might have caused subdural haematoma, which continues to rebleed from the granulation tissue vessels, causing recurrent seizures that could not be controlled by anti-convulsants.
Is there a risk of a benign schwannoma transforming into a malignant schwannoma?
No. Malignant schwannoma's arise de novo.
What are the three local and 2 general effects of brain tumors.
Epilepsy (gain of function)
Loss of function
Haemorrhage

Raised ICP
Herniation
What is the physical difference between a shwannoma and a neurofibroma?
Neurofibroma is intricately involved with the nerve and cannot be removed.

The neurofiboma involves neurons, perineural cells and fibroblasts. If it is plexiform, it is involved along the course of a nerve trunk, and entrapped, and imossible to separate from the nerve. Schwannoma, can be removed.
What is the difference in location, between childhood and adult tumors?
Children: posterior cranial fossa.
Adults: above tentorium cerebelli.
Tumors in children:

Adults:
Children: Low grade astrocytoma, high grade medulloblastoma.

Adults: high grade astrocytoma or benign meningioma's.
What is herniated in subfalcine herniation?
smelly c!
Cingulate gyrus.

TU - Trans-tentorial herniation = uncal herniation.
How common are brain tumors in children?
Not common, but represent 20% of childhood cancers.
Oligodendroglioma's:
5-10% of glioma's.
Slow growing, often calcified.
Where do ependymoma's occur in the child and in the adult.
child- 4th ventricle.
adult- spinal cord.

slow growing, but cause hydrocephalus, poor prognosis.
What is the putamen circuit involved in, and what is the caudate?
Putamen- complex motor patterns.
Caudate- cognitive motor response, eg subconscious response to seeing a lion- turn, run, climb before brain even has time to make conscious commands.
What are the three types of UMN lesions.
1. posture regulating pathways - spastic paralysis.
2. Lesions limited to corticospinal + corticobulbar tracts - weakness.
3. Cerebellar lesions- incoordination.
When does the babinski reflex appear and why?
Not present when <2yrs, as myelination has not developed. Toes curl upwards with plantar pressure. After then, myelination of descinding inhibtiory motor pathways, suppress this reflex.
If reflex is abnormal, indidcates damage to higher centres (UMN) or descending tracts.
Why does an UMN lesion cause hyperreflexia?
Normally, there are higher centre descending inhibtiroy tracts that suppress the myotatic spinal reflex. Decreased inhibtion of gamma-MNs --> hyperreflexia.
LMN lesion will remove / depress it.
What 5 changes are present in an oculomotor nerve palsy?
Ptosis (paralysis of levator palpebrae superioris)
No pupillary light reflex
No convergence/ accomodation for near vision
dDilated (interuption of PSNS fibres to iris)
Down and out.