Last Minute Review
Physiology — Last Minute Review
Rapid Review
A last-minute review of high-yield neurophysiology facts for the RITE and board exams. Tables, key associations, and must-know one-liners — designed for a quick pass the night before.
Neurotransmitters & Receptors
| Neurotransmitter | Receptor Types | Location | Clinical Relevance |
|---|---|---|---|
| ACh (nicotinic) | nAChR (ligand-gated Na+/K+) | NMJ, autonomic ganglia, CNS | MG (anti-AChR Ab), Lambert-Eaton (anti-VGCC); succinylcholine depolarizing block |
| ACh (muscarinic) | M1 (cortex/hippocampus), M2 (heart), M3 (smooth muscle/glands) | Parasympathetic end-organs, basal forebrain → cortex | M1 loss → Alzheimer cognitive decline; anticholinergics → delirium; M2 → bradycardia |
| Dopamine | D1/D5 (excitatory, ↑cAMP); D2/D3/D4 (inhibitory, ↓cAMP) | Nigrostriatal, mesolimbic, mesocortical, tuberoinfundibular | D2 blockade → parkinsonism + hyperprolactinemia; D1 = direct pathway (go); D2 = indirect pathway (stop) |
| Serotonin (5-HT) | 5-HT1A/1B/1D (inhibitory); 5-HT2A/2C; 5-HT3 (ligand-gated ion channel); 5-HT4–7 | Raphe nuclei → diffuse cortical/subcortical projections | 5-HT1B/1D agonists = triptans (migraine); serotonin syndrome (clonus, hyperthermia, agitation); 5-HT3 = ondansetron |
| GABA | GABA-A (ligand-gated Cl− channel); GABA-B (G-protein, K+/Ca2+) | GABA-A: ubiquitous postsynaptic in cortex/cerebellum/hippocampus (targets of GABAergic interneurons); GABA-B: spinal cord, thalamus, presynaptic autoreceptors and postsynaptic Gi → K+ open | GABA-A: benzos (frequency), barbiturates (duration), alcohol; GABA-B: baclofen; anti-GAD65 Ab → stiff-person syndrome |
| Glutamate | NMDA (Ca2+; Mg2+ block; glycine co-agonist); AMPA (Na+, fast EPSP); Kainate | Ubiquitous excitatory — cortex, hippocampus, spinal cord | NMDA: LTP/memory, excitotoxicity (stroke); anti-NMDAR encephalitis; ketamine/PCP = NMDA antagonists; AMPA = fast synaptic transmission |
| Norepinephrine | α1 (Gq, vasoconstriction); α2 (Gi, presynaptic inhibition); β1/β2 (Gs) | Locus coeruleus → diffuse cortical projections | α2 agonists (clonidine) ↓ sympathetic outflow; β-blockers → tremor Rx; NE reuptake inhibitors (SNRIs, TCAs) |
| Glycine | GlyR (ligand-gated Cl− channel) | Spinal cord & brainstem (Renshaw cells) | Strychnine = GlyR antagonist → opisthotonus; tetanus toxin blocks glycine/GABA release; NMDA co-agonist |
| Histamine | H1 (wakefulness); H2 (gastric acid); H3 (presynaptic autoreceptor) | Tuberomammillary nucleus → cortex | H1 antagonists → sedation; H3 inverse agonist (pitolisant) for narcolepsy |
| Endorphins/Enkephalins | μ (analgesia, euphoria); δ; κ | Periaqueductal gray, dorsal horn, limbic system | μ agonists = opioids; naloxone = antagonist; descending pain modulation |
💎 Board Pearl
- GABA-A: benzos ↑ frequency of Cl− channel opening; barbiturates ↑ duration — mnemonic: Benzo = Frequency, Barbiturate = Duration
- NMDA requires both glutamate + glycine and membrane depolarization (to relieve Mg2+ block) — voltage-dependent AND ligand-gated
- Only 5-HT3 is an ion channel — all other serotonin receptors are G-protein coupled
- D2 blockade explains EPS (parkinsonism, akathisia, dystonia, tardive dyskinesia risk) and hyperprolactinemia (tuberoinfundibular). Other antipsychotic AEs — sedation, weight gain / metabolic effects, orthostasis, anticholinergic toxicity, QT prolongation — involve H1, 5-HT2C, α1, M1, and cardiac ion-channel effects (drug-specific), NOT D2 blockade alone
Ion Channels & Channelopathies
| Channel | Gene | Disease | Key Feature |
|---|---|---|---|
| Na+ (brain) | SCN1A | Dravet syndrome (SMEI) | LOF mutation; seizures worsen with Na+ channel blockers (lamotrigine, phenytoin) |
| Na+ (brain) | SCN2A | Benign familial neonatal-infantile seizures | GOF → early-onset epilepsy; may respond to Na+ channel blockers |
| Na+ (muscle) | SCN4A | Hyperkalemic periodic paralysis; paramyotonia congenita | HyperKPP: K+-triggered attacks, myotonia; paramyotonia worsens with cold/exercise |
| Na+ (cardiac) | SCN5A | Brugada syndrome; long QT type 3 (LQT3) | SCN5A is cardiac — NOT a periodic paralysis gene. HypoKPP type 2 is caused by SCN4A (same gene as hyperKPP type 1 + paramyotonia congenita) |
| K+ | KCNQ2 | Benign familial neonatal epilepsy (BFNE) | Seizures day 2–7 of life; usually self-limited; M-current dysfunction |
| K+ | KCNA1 | Episodic ataxia type 1 (EA1) | Brief ataxia attacks (seconds-minutes) + interictal myokymia; responds to carbamazepine |
| K+ | KCNJ2 | Andersen-Tawil syndrome (ATS / periodic paralysis type 3) | Triad: periodic paralysis + cardiac arrhythmias (long QT) + dysmorphic features |
| Ca2+ (P/Q-type) | CACNA1A | Episodic ataxia type 2 (EA2); familial hemiplegic migraine type 1 (FHM1); SCA6 | EA2: hours-long ataxia, responds to acetazolamide; same gene → 3 different phenotypes by mutation type |
| Ca2+ (L-type) | CACNA1S | Hypokalemic periodic paralysis type 1 | Low-K+ triggered flaccid paralysis; most common periodic paralysis |
| Cl− | CLCN1 | Myotonia congenita (Thomsen AD / Becker AR) | Muscle stiffness without weakness; warm-up phenomenon; EMG → myotonic discharges |
| Ryanodine (RyR1) | RYR1 | Malignant hyperthermia; central core disease | Triggered by volatile anesthetics + succinylcholine; Rx = dantrolene |
💎 Board Pearl
- CACNA1A = one gene, three diseases: EA2 (LOF), FHM1 (GOF), SCA6 (trinucleotide repeat expansion)
- Dravet (SCN1A LOF): AVOID Na+ channel blockers — they worsen seizures; use valproate, clobazam, stiripentol, fenfluramine
- HyperKPP (SCN4A) = K+ triggers attacks + myotonia; HypoKPP (CACNA1S) = low K+ triggers attacks + NO myotonia
- Acetazolamide works in: EA2, hypoKPP, and some hyperKPP — it does NOT work in EA1 (use carbamazepine)
Neuromuscular Junction
| Component | Structure/Mechanism | Disorder | Key Features |
|---|---|---|---|
| Presynaptic — VGCC (P/Q-type) | Ca2+ influx triggers ACh vesicle release | Lambert-Eaton myasthenic syndrome (LEMS) | Anti-VGCC Ab; proximal weakness + areflexia + autonomic dysfunction; facilitation with exercise; RNS: ↓ CMAP + ↑increment ≥60% (classic >100%); modern AANEM threshold ≥60% at high-rate |
| Presynaptic — ACh vesicles | Vesicle docking/fusion (SNARE complex) | Botulism | Clostridium botulinum toxin cleaves SNARE proteins; descending paralysis; dilated pupils; Decrement on slow RNS + post-tetanic facilitation present but often less robust than LEMS |
| Synaptic cleft — AChE | Degrades ACh → choline + acetate | Organophosphate poisoning | Irreversible AChE inhibition; cholinergic crisis (SLUDGE + nicotinic effects); Rx: atropine + pralidoxime |
| Postsynaptic — nAChR | Ligand-gated Na+/K+ channel on muscle endplate | Myasthenia gravis (MG) | Anti-AChR Ab (85%) or anti-MuSK Ab (5–8%); fatigable weakness; RNS: ≥10% decrement (1st to 4th–5th response) at low-frequency RNS (2–3 Hz) for postsynaptic MG |
| Postsynaptic — MuSK | Organizes AChR clustering at endplate | MuSK-MG | Bulbar-predominant; poor response to AChEIs; IgG4 (not complement-mediated) |
| Postsynaptic — agrin/LRP4 | Agrin → LRP4 → MuSK signaling cascade | Congenital myasthenic syndromes; anti-LRP4 MG (rare) | CMS: genetic; onset childhood; no autoantibodies; treatment varies by subtype |
💎 Board Pearl
- Safety factor: Normally, ACh release far exceeds the threshold needed to trigger muscle AP — this “safety factor” is reduced in MG (fewer receptors) and LEMS (less ACh released)
- MG: decrement on slow RNS (2–3 Hz); LEMS: increment on rapid RNS (20–50 Hz) or post-exercise facilitation
- MuSK-MG is IgG4 → does NOT fix complement → no complement-mediated endplate destruction (unlike AChR-MG which is IgG1/IgG3)
- Botulism vs LEMS: both presynaptic with facilitation; botulism = acute + descending + pupil involvement; LEMS = chronic + proximal + autonomic + associated with SCLC
EEG Frequencies
| Frequency Band | Hz Range | Normal State | Pathological Significance |
|---|---|---|---|
| Delta (δ) | <4 Hz | Deep sleep (N3); normal in infants | Focal: structural lesion; diffuse: encephalopathy, increased ICP |
| Theta (θ) | 4–7 Hz | Drowsiness (N1); normal in children/adolescents | Focal: subcortical lesion; diffuse: mild encephalopathy |
| Alpha (α) | 8–13 Hz | Relaxed wakefulness, eyes closed, posterior dominant rhythm | Loss/asymmetry: cortical dysfunction; alpha coma (poor prognosis post-anoxia) |
| Beta (β) | 13–30 Hz | Active thinking, anxiety; frontal predominance | Excess: benzodiazepines/barbiturates; focal: breach rhythm (skull defect) |
| Gamma (γ) | >30 Hz | Cognitive processing, sensory binding | Rarely assessed clinically; may be seen with cortical activation |
💎 Board Pearl
- Alpha rhythm: posterior dominant, attenuates with eye opening (“Berger effect”) — if it does NOT attenuate, consider alpha coma
- Diffuse beta = think benzodiazepines or barbiturates on board questions
- Focal continuous delta in an adult = always think structural lesion until proven otherwise
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