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 cortical interneurons; GABA-B: spinal cord, thalamus | 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 |
- 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 receptor blockade explains ALL antipsychotic side effects: parkinsonism (nigrostriatal), hyperprolactinemia (tuberoinfundibular), akathisia
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/muscle) | SCN5A | Brugada syndrome; hypokalemic periodic paralysis type 2 (rare) | Cardiac arrhythmias + periodic paralysis overlap |
| 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 |
- 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 >100% at high-rate |
| Presynaptic — ACh vesicles | Vesicle docking/fusion (SNARE complex) | Botulism | Clostridium botulinum toxin cleaves SNARE proteins; descending paralysis; dilated pupils; RNS similar to 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: ↓decrement >10% at 2–3 Hz |
| 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 |
- 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 |
- 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
EEG Patterns & Associations
| Pattern | Description | Clinical Association |
|---|
| FIRDA (frontal intermittent rhythmic delta) | Bilateral, frontal, 2–3 Hz rhythmic delta | Metabolic/toxic encephalopathy; increased ICP; deep midline lesions |
| TIRDA (temporal intermittent rhythmic delta) | Unilateral temporal rhythmic delta | Strongly associated with temporal lobe epilepsy |
| LPDs (lateralized periodic discharges) / PLEDs | Lateralized, periodic sharp waves/complexes at 1–2 Hz | Acute destructive lesion (stroke, herpes encephalitis, tumor); seizure risk ↑ |
| GPDs (generalized periodic discharges) | Bilaterally synchronous periodic discharges | Anoxic injury, CJD (1 Hz triphasic morphology), status epilepticus |
| Burst suppression | Alternating bursts of high-amplitude activity and suppression (<10 μV) | Deep anesthesia/coma; severe anoxic injury; neonatal: Ohtahara syndrome |
| Triphasic waves | Generalized, frontally-predominant, positive-negative-positive morphology with AP lag | Hepatic encephalopathy (“classic”); also uremic, other metabolic encephalopathies |
| GRDA (generalized rhythmic delta) | Generalized, continuous/semi-continuous rhythmic delta | Non-specific; metabolic encephalopathy; may indicate non-convulsive status if evolving |
| Breach rhythm | High-amplitude sharply contoured activity over skull defect | Post-craniotomy; NOT epileptiform — do not overread as spikes |
| Wicket spikes | Arciform, 6–11 Hz, temporal, μ-shaped | Benign normal variant; do NOT treat as epileptiform; seen in adults during drowsiness |
| 14 & 6 Hz positive bursts | Positive sharp transients at 14 or 6 Hz, posterior temporal, drowsiness | Benign normal variant; no clinical significance; do NOT overread |
Board Trap
- Triphasic waves vs GPDs in CJD — morphology overlaps significantly; clinical context is essential (hepatic failure vs rapid dementia)
- Breach rhythm is NOT epileptiform — do not mistake sharply contoured activity over a craniotomy site for spikes
- TIRDA is the only intermittent rhythmic delta pattern that has a strong association with epilepsy; FIRDA does NOT indicate epilepsy
NCS/EMG Patterns
| Parameter | Axonal Neuropathy | Demyelinating Neuropathy | Myopathy | Presynaptic NMJ (LEMS) | Postsynaptic NMJ (MG) |
|---|
| CMAP amplitude | ↓ Reduced | Normal or mildly ↓ | Normal or mildly ↓ | ↓↓ Reduced (low baseline) | Normal or mildly ↓ |
| Conduction velocity | Normal or mildly ↓ | ↓↓ Slowed (<70–80% LLN) | Normal | Normal | Normal |
| Distal latency | Normal | ↑ Prolonged | Normal | Normal | Normal |
| F-wave latency | Normal or mildly ↑ | ↑ Prolonged or absent | Normal | Normal | Normal |
| Conduction block | Absent | Present (hallmark) | Absent | Absent | Absent |
| Temporal dispersion | Absent | Present | Absent | Absent | Absent |
| Fibrillations/PSWs | Present (denervation) | Present if secondary axonal loss | Present (active/inflammatory) | Absent | Absent |
| Motor unit morphology | Large, polyphasic (reinnervation) | Normal or large | Small, short, polyphasic | Normal (may vary) | Normal (may vary) |
| Recruitment | Reduced (neurogenic) | Reduced (neurogenic) | Early (myopathic) | Normal to reduced | Normal to reduced |
| RNS (2–3 Hz) | N/A | N/A | N/A | Decrement (low baseline CMAP) | Decrement >10% |
| RNS (20–50 Hz) / post-exercise | N/A | N/A | N/A | Increment >100% (facilitation) | No significant increment |
- Axonal = amplitude loss; Demyelinating = velocity slowing + conduction block — the single most tested NCS concept
- Myopathy: small, short, polyphasic MUPs with early recruitment (full interference at low force) — opposite of neurogenic
- Conduction block = >50% CMAP amplitude drop between proximal and distal stimulation without temporal dispersion — pathognomonic for demyelination
- LEMS: low baseline CMAP → decrement at slow RNS → >100% increment at fast RNS or post-exercise — this triad is classic
CSF Analysis
| Condition | Opening Pressure | WBC (cells/μL) | Protein (mg/dL) | Glucose (mg/dL) | Special |
|---|
| Normal | 10–20 cm H2O | <5 (lymphocytes) | 15–45 | 50–80 (or >60% serum) | Clear, colorless |
| Bacterial meningitis | ↑↑ (>25) | 1,000–10,000+ (PMNs) | ↑↑ (>100) | ↓↓ (<40) | Positive Gram stain/culture; lactate ↑ |
| Viral meningitis | Normal or mildly ↑ | 10–500 (lymphocytes) | Normal or mildly ↑ | Normal | PCR for HSV, enterovirus; early may show PMNs |
| TB/Fungal meningitis | ↑ | 50–500 (lymphocytes) | ↑↑ (100–500) | ↓ (<40) | TB: AFB smear, adenosine deaminase ↑; Fungal: India ink (crypto), antigen testing |
| GBS | Normal | <10 (albuminocytologic dissociation) | ↑↑ (>45, often >100) | Normal | High protein + normal WBC = albuminocytologic dissociation (classic) |
| MS | Normal | 0–50 (lymphocytes) | Normal or mildly ↑ | Normal | Oligoclonal bands (CSF-specific); ↑ IgG index; >50 WBC should question MS diagnosis |
| SAH | ↑ | RBCs (non-clearing across tubes) | ↑ | Normal | Xanthochromia (yellow supernatant after centrifugation) — appears >6–12 hrs |
| Carcinomatous meningitis | ↑ | Lymphocytes + atypical cells | ↑↑ | ↓ | Positive cytology (may need repeated LPs); flow cytometry for lymphoma |
- Albuminocytologic dissociation (high protein, normal WBC) = GBS until proven otherwise
- CSF glucose <40 mg/dL (or <60% serum glucose) = bacterial, TB/fungal, or carcinomatous — NOT viral
- MS: if WBC >50 or protein >100, strongly reconsider the diagnosis
- SAH: xanthochromia distinguishes true SAH from traumatic tap — must centrifuge and examine supernatant
Sleep Stages
| Stage | EEG Pattern | Features | Clinical Relevance |
|---|
| Wakefulness | Alpha (8–13 Hz) posteriorly; beta with eyes open | Posterior dominant rhythm; attenuates with eye opening | Absence of alpha = cortical dysfunction or alpha coma |
| N1 (NREM Stage 1) | Theta (4–7 Hz); vertex waves (V-waves) | Lightest sleep; 5% of total sleep; slow rolling eye movements | Vertex waves = sharply contoured central — normal variant, NOT epileptiform |
| N2 (NREM Stage 2) | Sleep spindles (12–14 Hz) + K-complexes | ~50% of total sleep; thalamocortical circuits generate spindles | Spindles arise from thalamic reticular nucleus; K-complexes = largest normal EEG waveform |
| N3 (NREM Stage 3) | Delta (<4 Hz, >75 μV); high-amplitude slow waves | Deep/slow-wave sleep; 15–20% of total; GH release peaks | NREM parasomnias: sleepwalking, sleep terrors, confusional arousals (arise from N3) |
| REM | Low-amplitude, mixed-frequency (resembles wakefulness); sawtooth waves | Muscle atonia; rapid eye movements; dreaming; 20–25% of total | REM behavior disorder (RBD): loss of atonia → dream enactment; strong predictor of synucleinopathy (PD/DLB/MSA) |
- Sleep spindles = thalamic reticular nucleus; K-complexes = vertex, biphasic, largest normal waveform
- NREM parasomnias (N3): sleepwalking, night terrors, confusional arousals — vs REM parasomnias: RBD, nightmares
- Narcolepsy type 1: hypocretin/orexin deficiency → direct REM entry (SOREMP); cataplexy is pathognomonic
- RBD → synucleinopathy conversion rate >80% over 10–15 years (PD, DLB, MSA)
- GH secretion peaks during N3 (slow-wave sleep); cortisol peaks in early morning
Nerve Fiber Types
| Type | Diameter (μm) | Myelination | Function | Conduction Velocity (m/s) |
|---|
| A-alpha (Ia, Ib) | 12–20 | Heavy myelination | Proprioception (muscle spindle Ia, Golgi tendon Ib); motor to extrafusal muscle | 70–120 |
| A-beta (II) | 5–12 | Myelinated | Light touch, pressure, vibration | 30–70 |
| A-gamma | 3–6 | Myelinated | Motor to intrafusal muscle fibers (muscle spindle) | 15–30 |
| A-delta (III) | 2–5 | Thinly myelinated | Fast/sharp pain; temperature; first pain response | 12–30 |
| B | <3 | Lightly myelinated | Preganglionic autonomic fibers | 3–15 |
| C (IV) | 0.4–1.2 | Unmyelinated | Slow/burning pain; temperature; postganglionic autonomic (sympathetic) | 0.5–2 |
- Conduction velocity is proportional to fiber diameter — largest/most myelinated fibers conduct fastest
- A-delta = first (sharp) pain; C fibers = second (burning/aching) pain — classic double pain response
- Small fiber neuropathy (A-delta + C fibers) = burning pain + autonomic dysfunction; NCS is NORMAL (too small to measure); diagnose by skin biopsy (IENFD)
- Large fiber neuropathy (A-alpha/beta) = loss of proprioception/vibration + areflexia; NCS abnormal
Must-Know Numbers
Membrane & Ion Physiology
| Parameter | Value | Notes |
|---|
| Resting membrane potential | −70 mV (neurons); −90 mV (skeletal muscle) | Determined mainly by K+ leak channels; closest to EK |
| Na+ equilibrium potential (ENa) | +60 mV | Na+ intracellular ~15 mM; extracellular ~145 mM |
| K+ equilibrium potential (EK) | −90 mV | K+ intracellular ~140 mM; extracellular ~4 mM |
| Ca2+ equilibrium potential | +120 mV | Intracellular ~0.0001 mM; extracellular ~2 mM |
| Action potential threshold | −55 mV | Voltage-gated Na+ channels open; all-or-none response |
| Na+/K+ ATPase ratio | 3 Na+ out : 2 K+ in | Electrogenic pump; contributes −3 to −5 mV to resting potential |
Normal NCS Values (Upper Limb Reference)
| Parameter | Normal Value | Notes |
|---|
| Motor conduction velocity | >50 m/s (upper limb); >40 m/s (lower limb) | Slowing <70–80% LLN = demyelinating |
| CMAP amplitude | Varies by nerve; typically >4–6 mV | Reduced in axonal neuropathy or NMJ disorder |
| SNAP amplitude | Varies; typically >10–20 μV | Normal SNAPs + abnormal CMAPs = preganglionic lesion or NMJ disorder |
| Distal motor latency (median) | <4.4 ms | Prolonged in carpal tunnel syndrome |
| F-wave latency (upper limb) | <32 ms | Tests proximal segments; prolonged in GBS, radiculopathy |
Normal CSF Values
| Parameter | Normal Value |
|---|
| Opening pressure | 10–20 cm H2O (up to 25 in obese) |
| WBC count | <5 cells/μL (all lymphocytes/monocytes) |
| Protein | 15–45 mg/dL |
| Glucose | 50–80 mg/dL (or >60% serum glucose) |
| Volume (adult) | ~150 mL total; ~500 mL produced/day |
| IgG index | <0.7 |
- Resting potential is closest to EK (−90 mV) because resting membrane is most permeable to K+
- Normal SNAPs + abnormal CMAPs → think preganglionic lesion (radiculopathy, motor neuron disease) or NMJ disorder — dorsal root ganglion intact preserves SNAPs
- CSF protein rises ~1 mg/dL per 1,000 RBCs in traumatic tap
- IIH (pseudotumor cerebri): elevated OP (>25 cm H2O) with NORMAL CSF composition
Classic Board Traps
Board Traps — Do Not Get Caught
- Dravet + lamotrigine: SCN1A LOF → Na+ channel blockers WORSEN seizures; if a child with febrile seizures progressing to epilepsy gets worse on lamotrigine → think Dravet
- Small fiber neuropathy + normal NCS: NCS only measures large myelinated fibers; small fiber neuropathy (burning pain, autonomic sx) needs skin biopsy (intraepidermal nerve fiber density)
- Breach rhythm ≠ epileptiform: Sharply contoured beta/alpha over craniotomy site is breach rhythm — a normal finding, not spikes
- Wicket spikes ≠ temporal spikes: Benign variant in drowsy adults; arciform, temporal, monophasic — no treatment needed
- MG + aminoglycosides: Aminoglycosides block presynaptic Ca2+ channels and postsynaptic AChR — can precipitate myasthenic crisis
- Succinylcholine + hyperkalemia: Depolarizing blocker → K+ release; CONTRAINDICATED in burns, denervation, upper motor neuron lesions, crush injury → risk of fatal hyperkalemia
- LEMS vs MG on RNS: Both show decrement at slow RNS; LEMS shows >100% increment at fast RNS or post-exercise — MG does NOT
- Triphasic waves vs NCSE: Triphasic waves (hepatic/metabolic) vs nonconvulsive status epilepticus — look for anterior-posterior lag (triphasic) and clinical context; trial of benzodiazepine may clarify
- GBS + normal NCS early: NCS may be normal in the first 1–2 weeks of GBS; F-wave prolongation/absence may be the earliest finding
- Anti-MuSK MG + pyridostigmine: MuSK-MG often worsens with AChE inhibitors; first-line is immunotherapy (rituximab, PLEX)
- Alpha coma: Unreactive, diffuse alpha in a comatose patient post-cardiac arrest = poor prognosis; do NOT confuse with normal wakefulness alpha
- RBD → synucleinopathy: Isolated RBD precedes PD/DLB/MSA by years-decades; conversion rate >80% — essential prognostic counseling point
